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Sidana, Abhinav, Amit L. Jain, Meet Kadakia, Spencer Krane, Julia C. Friend, Akhil Muthigi, Martha Ninos, Joanna H. Shih, and Ramaprasad Srinivasan. "Predictors of mortality in metastatic papillary renal cell cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 509. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.509.
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509 Background: While studies have established several prognostic factors determining mortality in metastatic clear cell renal cell cancer patient, similar analysis has been lacking in metastatic papillary renal cell cancer (pRCC) patients. We aim to determine the predictors of mortality in metastatic pRCC patients. Methods: Retrospective evaluation of the medical records of patients with metastatic pRCC seen at National Cancer Institute (2000-2014) was undertaken. Patient demographics, tumor characteristics, and outcomes were studied. Kaplan-Meier Survival analysis was done to estimate overall survival (OS). Cox proportional-hazards regression analysis was done to identify predictors of All cause mortality (ACM) in this population. Results: 106 consecutive patients with metastatic pRCC were identified. The median age and follow up time after the diagnosis of metastases was 50 years (11-80) and 33.8 mon (2.3-246.7) respectively. Twenty one (19.8%) and 42 (39.6%) patients had papillary type 1 and papillary type 2 renal cancers respectively; in 43 (40.5%) patients, tumors were classified as papillary, not otherwise specified. Half (53) of patients had hereditary origin of pRCC. Median estimated OS of entire cohort was 37.5 mon. There was no difference in survival between patients with hereditary or sporadic pRCC (p = 0.80) or among patients with different subtypes of pRCC (p = 0.79). On univariate analysis, elevated serum corrected calcium elevated lactate dehydrogenase, Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and presence of malignant ascites significantly affected the patients’ prognosis. Corrected Calcium (p = 0.03) and NLR (p = 0.004) were found to be independent predictors of ACM on multivariate analysis. Conclusions: To our knowledge, this is the largest single center series evaluating survival and predictors of survival in metastatic pRCC. Metastatic pRCC patients with elevated NLR and serum corrected calcium are significantly associated with relatively poor OS when compared to patients without these findings. If validated in larger multi-institutional cohorts, it might be reasonable to incorporate corrected calcium and NLR in nomograms predicting ACM in metastatic pRCC.
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Carlo, Maria Isabel, Nabeela Khan, Yingbei Chen, James Hsieh, A. Ari Hakimi, Chung-Han Lee, Darren R. Feldman, Robert J. Motzer, and Martin Henner Voss. "The genomic landscape of metastatic non-clear cell renal cell carcinoma." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 474. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.474.
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474 Background: Non-clear cell renal cell carcinoma (nccRCC) encompasses about 20% of RCC cases and includes a number of subtypes that vary clinically and molecularly. Compared to ccRCC, these tumors have more limited sensitivity to conventional anti-VEGF agents and mTOR inhibitors, and there is clear need for better therapies. Analysis of genomic alterations in potentially targetable pathways may lead to novel therapeutic development strategies. Methods: We retrospectively analyzed tumors from 112 patients with metastatic nccRCC with targeted next-generation sequencing (NGS) across a panel of >340 cancer-relevant genes. Matched tumor and normal was used to facilitate somatic calling. We report on recurrent alterations observed for nccRCC variants. Results: Median age was 53 years (range 12-77), 67% were male; 47% presented with metastatic disease and 53% with localized disease that later metastasized. NGS was performed on tissue from primary tumors (57%) or metastatic sites (43%). Subtype classifications included unclassified (44%), papillary (21%), chromophobe (13%), translocation (12%), and other (9%). The most frequently altered genes by subtype are included in table. 36% of unclassified or papillary tumors had a mutation in a putative driver gene amenable to targeted therapies, including MET, NOTCH1, SMARCB1, TSC1, TSC2, PIK3CA, and FGFR3. 3 chromophobe tumors and 1 translocation tumor had a mutation in a potentially targetable pathway. Conclusions: The mutation profiles of metastatic nccRCC vary by papillary, chromophobe, and translocation subtype, with unclassified tumors most approximating papillary subtype. Unclassified and papillary subtypes harbor frequent mutations in potentially targetable pathways that merit further investigation. [Table: see text]
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Graham, Jeffrey, Connor Wells, Frede Donskov, Jae-Lyun Lee, Anna Paola Fraccon, Felice Pasini, Camillo Porta, et al. "Cytoreductive nephrectomy in metastatic papillary renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)." Journal of Clinical Oncology 36, no. 6_suppl (February 20, 2018): 581. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.581.
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581 Background: There is evidence that cytoreductive nephrectomy (CN) may be beneficial in metastatic renal cell carcinoma (mRCC), but the role of CN in patients with papillary histology is unclear. Methods: Using the IMDC database, a retrospective analysis was performed on patients with papillary mRCC treated with or without CN. Baseline characteristics and IMDC risk factors were collected. Median overall survival (OS) was determined for both patient groups. Multivariable Cox regression analysis was performed to control for imbalances in individual IMDC risk factors. Results: In total, 353 patients with papillary mRCC with (n = 75) or without (n = 278) a component of clear cell histology were identified. Median follow-up time was 57.1 months (95% CI 32.9-77.8) and the OS from the start of first-line targeted therapy for the entire cohort was 13.2 months (95% CI 12.0-16.1). Baseline characteristics are in Table 1 and patients who had CN were more likely to be younger, with better KPS, and have sarcomatoid histology. Median OS in patients with CN was 16.3 months (95% CI 13.1-19.2), compared to 8.6 months (95% CI 6.1-12.2; p < 0.0001) in the no CN group. When adjusted for individual IMDC risk factors, the hazard ratio (HR) of death for CN was 0.62 (95% CI 0.45-0.85; p = 0.0031). Conclusions: The use of CN in patients with mRCC and papillary histology appears to be associated with improved survival when compared to no CN after adjustment for risk criteria. A clinical trial in this rare population may not be possible but this data does corroborate with clear cell literature. [Table: see text]
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Dudani, Shaan, Guillermo de Velasco, Connor Wells, Chun Loo Gan, Frede Donskov, Camillo Porta, Anna Fraccon, et al. "Characterizing sites of metastatic involvement in metastatic clear-cell, papillary, and chromophobe renal cell carcinoma." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 5071. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5071.
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5071 Background: There exists considerable biological and clinical variability between histologic variants of metastatic renal-cell carcinoma (mRCC). Data reporting on sites of metastatic involvement in less common histologies of mRCC are sparse. We sought to characterize the frequency of metastatic site involvement across the three most common histologies of mRCC: clear-cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Methods: Using the International mRCC Database Consortium (IMDC) database, patients with mRCC starting systemic therapy between 2002-2019 were identified and sites of metastases at the time of systemic therapy initiation were documented. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. The primary outcomes were prevalence of metastatic site involvement and overall survival (OS). Patients with mixed histology were excluded. Results: 10,105 patients were eligible for analysis. Median age at diagnosis was 60, 72% were male and 79% underwent nephrectomy. 92%, 7% and 2% of patients had ccRCC, pRCC, and chrRCC, respectively. Frequency of metastatic site involvement across the histologic subtypes is shown in Table. Lung, adrenal, brain and pancreatic metastases were more frequent in ccRCC, lymph node involvement was most frequent in pRCC, and liver metastases were most frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (brain/pleura) and 50 months (pancreas). OS by site of metastatic involvement was compared between histologies for the four most common sites of metastases (lung, lymph nodes, bone, liver). As compared to patients with ccRCC, patients with pRCC had lower OS regardless of site of metastasis (p < 0.05). Power was limited and thus differences in OS between ccRCC and chrRCC were not detectable. Conclusions: Sites of metastatic involvement differ based on histology in mRCC. These data highlight the clinical and biologic variability between histologic subtypes of mRCC and constitute the largest cohorts of patients with metastatic pRCC and chrRCC to report on sites of metastases. Sites of Metastatic Involvement by Histology. [Table: see text]
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Motzer, Robert J., Jennifer Bacik, Tania Mariani, Paul Russo, Madhu Mazumdar, and Victor Reuter. "Treatment Outcome and Survival Associated With Metastatic Renal Cell Carcinoma of Non–Clear-Cell Histology." Journal of Clinical Oncology 20, no. 9 (May 1, 2002): 2376–81. http://dx.doi.org/10.1200/jco.2002.11.123.
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PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies. PATIENTS AND METHODS: Sixty-four patients with metastatic non–clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database. RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years. CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non–clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non–clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.
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Ronnen, Ellen A., G. Varuni Kondagunta, Nicole Ishill, Lesley Spodek, Paul Russo, Victor Reuter, Jennifer Bacik, and Robert J. Motzer. "Treatment outcome for metastatic papillary renal cell carcinoma patients." Cancer 107, no. 11 (2006): 2617–21. http://dx.doi.org/10.1002/cncr.22340.
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Elabbady, Ahmed, Ryan Boudreau, and Vahid Mehrnoush. "Rapid metachronous bladder metastasis of type 2 papillary renal cell carcinoma." Archive of Clinical Cases 10, no. 2 (May 18, 2023): 93–96. http://dx.doi.org/10.22551/2023.39.1002.10249.
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Renal cell carcinoma (RCC) frequently spreads to distant organs like the lung, lymph nodes, bone, and liver. However, there have been some reports of RCC bladder metastasis. We present a case of a 61-year-old man presented with total painless gross hematuria. The patient had a history of right radical nephrectomy for papillary (type 2) RCC, high-grade, pT3a with negative surgical margins. There was no evidence of metastases on 6-month surveillance CT. After one-year post-operation, at this current admission, the cystoscopy discovered a solid bladder mass away from the trigone in the right lateral bladder wall. The resected bladder mass was metastatic papillary RCC with PAX-8 positive but GATA-3 negative on immunostaining. A positron emission tomography scan confirmed multiple lung, liver, and osseous metastases. This case report can highlight the importance of having bladder metastasis in RCC mind, although rare, and may necessitate the surveillance measures like urine analysis at more frequent interval and CT Urography instead of regular CT to detect the RCC metastatic bladder cancer at early stage.
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Steiner, T., J. Roigas, H. Kirchner, C. Doehn, H. Heynemann, M. Siebels, S. Loening, et al. "Clinical course of patients with metastatic papillary renal cell carcinoma." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14591. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14591.
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14591 Background: For a long time it has been discussed, whether patients (pts.) with metastatic papillary renal cell carcinoma (mRCC pap) demonstrate different behaviour compared to those with clear cell mRCC. Methods: Clinical data of 61 pts. with mRCC pap were retrospectively assessed at 8 treatment centres. Results: Median follow-up was 20 (1–114) months, median age at time of diagnosis was 62 (24–85) years. Men were affected predominantly (50/61 pts.; 82%). 21 pts. (34%) showed metastases at time of diagnosis. The remaining 40 pts. had metachroneous metastatic disease. Mean time to metastases development was 30.4 (3–143; median 16.5) months. Metastatic sites were: lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%). Local recurrences occurred in 17 pts. (28%). Others sites of metastatic disease were brain in 6 pts. (10%), peritoneal carcinosis in 5 pts. (8%) and others. A surgical approach was performed primarily in 11 pts. (18%): lung 2; local recurrence and lymphomas 7; liver 1; brain 1. 26/61 pts. with metastatic disease received an immuno- (interferon-a ± interleukin-2) or immunochemotherapy (in combination with vinblastine or 5-fluorouracile) as first line treatment. In total, 42/61 pts. (69%) received an interferon- or interleukin-based immunotherapy. No treatment at all was performed in 12 pts. (20%) because of poor performance status. 5/42 pts. (11.4%) achieved an objective response to immuno(chemo)therapy. In the Kaplan-Meier-analysis, median overall survival after diagnosis of metastatic disease was estimated to be 13 ± 1.5 (95% CI 9.9–16) months for the entire study group and 12 ± 2.5 (95% CI 7.1–16.3) from the beginning of systemic treatment. Conclusions: Clinical data of a large population of pts. with mRCC pap have been assessed in this retrospective analysis for the first time. Compared to pts. with clear cell mRCC, these patients are characterized by: I) more frequent local recurrences; II) lower remission rates to immuno(chemo)therapeutic approaches; III) poorer prognosis with regard to overall survival. These findings should be taken into account when planning future studies. No significant financial relationships to disclose.
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Yonese, Ichiro, Masaya Ito, Kosuke Takemura, Takao Kamai, and Fumitaka Koga. "A Case of Metastatic Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome-Associated Renal Cell Carcinoma Treated with a Sequence of Axitinib and Nivolumab Following Cytoreductive Nephrectomy." Journal of Kidney Cancer and VHL 7, no. 2 (July 20, 2020): 6–10. http://dx.doi.org/10.15586/jkcvhl.2020.148.
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Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) associated renal cell carcinoma (RCC) is an aggressive form of type 2 papillary RCC caused by deficiency of the fumarate hydratase gene. For patients with metastatic disease, no standard treatment has been established with dismal prognosis. We report a case of metastatic HLRCC-associated RCC in a 65-year-old Japanese male whose clinical features mimicked advanced renal pelvic cancer. A durable response was achieved with a sequence of axitinib and nivolumab after cytoreductive and diagnostic nephrectomy. Their potential therapeutic roles in the management of metastatic HLRCC-associated RCC have been discussed based on its molecular and biological backgrounds.
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Schrader, A. J., S. Rauer-Bruening, P. J. Olbert, A. Hegele, J. Rustemeier, and R. Hofmann. "Incidence and long term prognosis of papillary renal cell carcinoma." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16020-e16020. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16020.
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e16020 Background: Papillary renal cell carcinoma (pRCC) represents the largest subgroup of non clear-cell kidney cancer. In this study we assessed tumour characteristics and long-term prognosis of patients with pRCC in comparison with conventional clear-cell cancer (ccRCC). Methods: We evaluated 744 patients who had undergone renal surgery for RCC between 1990 and 2005. The mean follow-up was 5.6 years. Results: Both groups pRCC and ccRCC were alike concerning age, body mass index, and the incidence of regional lymph node or distant metastasis at diagnosis. The percentage of male patients was higher in pRCC than in ccRCC (73.8 vs. 60.3%, p = 0.006). Even though patients with pRCC presented more often with smaller (p = 0.039) and low grade tumours (p = 0.006), there was no statistically significant difference in tumour recurrence or tumour related death. Moreover, looking at the whole cohort Kaplan-Meier curves revealed no differences regarding tumour specific survival between pRCC and ccRCC (p = 0.94; 5-year survival 78% vs. 77%). However, we observed a trend towards an improved outcome for organ confined (pT1–2) cancer, but a significantly inferior prognosis for locally advanced stage (pT3–4) and/or metastatic papillary tumours at the time of renal surgery. However, applying multivariate analysis including age, sex, and tumour grade, histology could neither be retained as a significant independent prognostic marker in the metastatic setting (p = 0.068, cox regression analysis) nor in a subgroup analysis focussing on patients with advanced cancer (pT3–4 and/or N+/M+; p = 0.064, cox regression analysis). Conclusions: Even though pRCC and ccRCC differ significantly in many aspects including histology and genetic alterations, in all, their long term prognosis is comparable. As we could not confirm a favourable clinical course for pRCC in general, standardized aftercare programmes and - if necessary - systemic treatment, especially in the era of novel targeted drugs, are also needed for this common RCC subtype. In addition, routine histologic subtyping of pRCC is strongly recommended. No significant financial relationships to disclose.
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Friend, Julia C., Daniel Su, Rashmi Thimmapuram, James Peterson, Geri Hawks, Martha Ninos, W. Marston Linehan, and Ramaprasad Srinivasan. "Malignant ascites as a manifestation of advanced papillary renal cell cancer (pRCC)." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 465. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.465.
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465 Background: Peritoneal carcinomatosis and ascites are frequent and clinically challenging complications associated with several malignancies such as ovarian cancer. Although ascites is rarely reported in patients with advanced renal cell carcinoma (RCC), its true incidence, particularly in non-clear cell variants, remains poorly defined. Here, we describe the incidence of and clinical characteristics associated with ascites in patients with pRCC. Methods: Patients with metastatic renal cell carcinoma (RCC) seen at the NCI Urologic Oncology Branch were identified in a review of our clinical database. The incidence of radiologically and/or cytologically evident ascites, relevant associated clinical characteristics, and survival were evaluated as was the incidence of ascites in a contemporaneous clear cell RCC (ccRCC) cohort. Results: 241 patients with metastatic RCC were seen between 2002 and 2014, including 109 with pRCC and 125 with ccRCC. Seventeen patients with metastatic pRCC (17/109,15.5%) had evidence of malignant ascites, while only 1/125 pts (0.8%) with ccRCC developed this complication. Median age of PRCC patients with ascites was 45.8 years (range: 26.1 to 76.6 years). Ascites was seen in both patients with type 1 (15.6%, 10/64) and those with type 2 pRCC (15.5%, 7/45). Median time to development of ascites from initial diagnosis of metastatic disease was 16 months (95% CI 7-23 months). Median survival from diagnosis of metastatic disease was 25 months (95% CI 13-41months) in patients with ascites, compared to 20 (95% CI 14-31 months) in those without this complication. (p = 0.59). Conclusions: To our knowledge, this is the largest series evaluating the incidence of and outcome associated with ascites in RCC. Although rare in ccRCC, malignant ascites is a fairly common manifestation of metastatic pRCC. In our cohort, patients with ascites appeared to have outcomes comparable to patients with metastatic pRCC without ascites.
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Wells, J. Connor, Frede Donskov, Anna Paola Fraccon, Felice Pasini, Georg A. Bjarnason, Jennifer J. Knox, Benoit Beuselinck, et al. "Characterizing the outcomes of metastatic papillary renal cell carcinoma (papRCC)." Journal of Clinical Oncology 34, no. 15_suppl (May 20, 2016): 4554. http://dx.doi.org/10.1200/jco.2016.34.15_suppl.4554.
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Somorácz, Áron, Levente Kuthi, Tamás Micsik, Alex Jenei, Adrienn Hajdu, Brigitta Vrabély, Erzsébet Rásó, et al. "Renal Cell Carcinoma with Clear Cell Papillary Features: Perspectives of a Differential Diagnosis." Pathology & Oncology Research 26, no. 3 (October 26, 2019): 1767–76. http://dx.doi.org/10.1007/s12253-019-00757-3.
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Abstract Thirty-one cases of low-grade renal cell carcinoma (RCC) with clear cells and tubulopapillary/papillary architecture were analyzed retrospectively with immunohistochemical and genetic markers to gain more experience with the differential diagnosis of such cases. All samples coexpressed CK7 and CA9; the TFE3 or TFEB reactions were negative; the CD10 and the AMACR stainings were negative in 27 cases and 30 cases, respectively. The FISH assays for papillary RCC, available in 27 cases, and deletion of chromosome 3p, available in 29 cases, gave negative results. The results for 3p deletion, VHL gene mutation or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no 3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no 3p loss, VHL abnormality mutation/hypermethylation present). In CCPRCCs, the representative growth pattern was branching tubulo-acinar, commonly accompanied by cyst formation. The linear nuclear arrangement or cup-shaped staining of CA9 did not necessarily indicate CCPRCC, and the absence of these did not exclude the diagnosis of CCPPRC. One tumor infiltrated the renal sinus; the others exhibited pT1 stage; and metastatic outcome was not recorded. The CCRCC cases were in pT1 stage; 6 exhibited cup-shaped staining of CA9, and 1 displayed lymph node metastasis at the time of surgery. Distant metastatic disease was not observed. In summary, the VHL abnormalities distinguished the subset of CCRCC with diffuse CK7-positivity and no 3p loss from cases of CCPRCC.
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Barua, Sasanka K., Sarbartha K. Pratihar, Pranab K. Kaman, Atul Garg, Rajeev T. P., Saumar J. Baruah, Puskal K. Bagchi, Debanga Sarma, and Mandeep Phukan. "Cervical lymphadenopathy as initial presentation of genito-urinary cancer." International Journal of Otorhinolaryngology and Head and Neck Surgery 5, no. 6 (October 23, 2019): 1739. http://dx.doi.org/10.18203/issn.2454-5929.ijohns20194964.
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<p class="abstract">Head and neck cancers rank fifth amongst the most affected cancers in the world. Metastasis to cervical lymph nodes is primarily from sites in head and neck. About 1% of all malignant cervical adenopathies are encountered as metastasis from remote primary site. We present here our experience of four cases in last five years. Patients presented as cervical lymphadenopathy with unknown primary, which on evaluation was found to be of genitourinary source from different sites. It is a single centre retrospective study. We reviewed cancer registry. We found four cases of genitourinary cancer with cervical lymph node metastasis. Patients presented as cervical lymphadenopathy of unknown primary. Among those one papillary renal cell cancer with rhabdoid differentiation, one testicular cancer, two prostate cancer. One case was a 67 year male patient, who revealed papillary renal cell carcinoma with rhabdoid features. Another patient was a male of 31 years, who had left testicular mass with retroperitoneal and cervical lymphadenopathy. Two patients of 68 year and 74 year respectively had metastatic prostate cancer. All patients underwent proper treatment and regularly followed up. Although rare, malignant cervical lymphadenopathy may be the first clinical manifestation of metastasis from genitourinary tumors. Evaluation of genitourinary system must be included in the protocol for uncovering the primary tumor site in cases of isolated cervical adenopathy.</p><p class="abstract"> </p>
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Stenman, Maria, Andreas Demetrios Nearchou, Per Sandström, Magnus Lindskog, and Ulrika Harmenberg. "Metastatic papillary renal cell carcinoma: A retrospective study from two large academic centers in Sweden." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 535. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.535.
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535 Background: Non-clear cell renal cell carcinoma (nccRCC) constitute about 10-15% of all metastatic renal cell carcinoma (mRCC) and typically include papillary, chromophobe and collecting duct histologies. Despite differences in clinical behavior between subtypes they are often grouped as one due to small patient numbers. Hence, there is a lack of knowledge on type-specific prognosis and treatment options. Methods: Patients diagnosed with metastatic nncRRC (56 out of 526 patients; 10.8%) during the years 2005-2013 were retrospectively identified using data from medical records at two large academic centers in Sweden. The characteristics and outcome of those with papillary subtype (n = 44; 79% of nccRCC) was analyzed. Results: Metastatic papillary RCC patients were more often male (82%), had a median age of 69 years and 48% had M1 disease. 9% were type I, 41% type II, 4% mixed and 41% papillary NOS. 89% had a nephrectomy and 56% received at least one line of systemic therapy. The median overall survival (OS) of all papillary patients was 10.1 months. Factors associated with OS included performance status (PS; OS 25.8 months for ECOG PS 0-1 patients vs OS 3.1 months for ECOG PS > 1 patients, p = 0.00002), and systemic therapy (OS 23.4 months vs 3.8 months for patients not treated systemically, p = 0.002). Systemic therapies (ST) included VEGF targeting agents (88%), mTOR inhibitors (50%), or interferon (21%) for all lines. The most common first line ST was VEGF targeting agents (75%). 42% received one line, 33% two lines, and 25% three or more lines of ST. Characteristics of patients treated with ST included lower age at diagnosis, higher proportion of M1 disease and better PS. The reasons for not giving systemic treatment were primarily poor performance status or comorbidities. ECOG PS > 1 (p = 0.04) and poor MSKCC risk group (p = 0.02) were predictive of OS among patients treated with ST. Conclusions: Patients with metastatic papillary RCC and good performance status (ECOG PS 0-1) seem to benefit from systemic therapy using drugs primarily evaluated for clear cell RCC. However, patients not eligible for systemic therapy due to poor performance status or other reasons have a dismal prognosis.
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Park, Sang Hyun, Taek Sang Kim, Jae Young Joung, Sung Han Kim, and Jinsoo Chung. "Postoperative long-term prognosis of localized renal cell carcinoma after partial or radical nephrectomy: Analysis of cancer metastasis and deaths during a more than five-year follow-up." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 604. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.604.
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604 Background: We performed a long-term follow-up study to evaluate the survival and metastatic outcomes of non-metastatic renal cell carcinoma (RCC) after curative removal of tumor. Methods: We retrospectively reviewed the clinical and pathological features of 5434 patients with localized renal cell carcinoma admitted to five Korean tertiary-care institutions between 2000 and 2012, who had undergone curative surgeries with partial or radical nephrectomy with/without lymph nodal dissection. The patients below the age of 19 years (N=9) with benign histology (N=24), and with no follow-up records (N=540) were excluded. A total of 4861 patients, followed-up for at least 1 year after the surgery, were enrolled finally. The deaths were defined as intraoperative, postoperative or RCC-related deaths. We analyzed the metastasis-free survival, cancer-specific survival, and overall survival outcomes according to the pathological stages. Results: The median age of patients at the time of surgery, male-to-female ratios, median follow-up duration, overall survival and metastasis-free survival times were 56 years (range: 19-94 years), 3471/1390 (71.4%/28.6%), 33.7 months (range: 12-297 months), 175.1 months (12-297.1 months), and 61 months (range: 12-94 months), respectively. A total of 518 (10.7%) deaths, including 338 (7.0%) RCC-related death and 164 (3.3%) deaths related to other causes were reported. Metastasis and recurrences were observed in 140 (2.9%) and 462 (9.5%) patients, respectively. The respective pathologic T1/2/3/4/x and N1 stages, namely, 3757/389/644/57/6 (77.3/8.0/13.3/1.2/0.1%) and 133 (2.7%) were observed. The rates of histological types of clear cell papillary/ chromophobe/ collecting duct/ unclassified/ MLCRCCLMP/ mixed cell papillary/ unknown were 83.4%/ 1.5%/ 7.1%/ 0.4%/ 1.1%/ 0.5%/ 0.2%/ 0.3%/ 0.1%/ 5.3%. The 10-year metastasis-free survival rate was 86.0% including 100%, 91.0%, 64.1%, and 11.8% incidence for stages I, II, III, and IV, respectively. Conclusions: The long-term survival was seen among patients who underwent nephrectomy for non-metastatic renal cell carcinoma.
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Zielli, Teresa, Letizia Gnetti, and Sebastiano Buti. "Activity of lenvatinib plus everolimus combination in a heavily pretreated patient with papillary renal cell carcinoma: a case report." Tumori Journal 106, no. 6 (May 27, 2020): NP79—NP83. http://dx.doi.org/10.1177/0300891620924472.
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Background: Papillary renal cell carcinoma (pRCC) represents the second most common histologic subtype of renal cell carcinoma and comprises 2 subtypes. Prognosis for type 2 is associated with poor clinical outcome. Current guidelines are based on phase II trials, phase III trials in patients with clear cell histology, or retrospective data. Case description: To our knowledge, we describe for the first time a case of a patient with heavily pretreated metastatic pRCC who benefited from the combination of lenvatinib plus everolimus for more than 2 years. Conclusion: According to immunohistologic and biological findings in our patient both on primary tumor and liver metastasis, we hypothesize that selected patients with metastatic pRCC, progressed to standard/available treatments (including angiogenic drugs, mTOR inhibitors, and immunotherapy) and dissociated response to everolimus, could benefit from adding lenvatinib to everolimus.
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Armstrong, Andrew J., Susan Halabi, Tim Eisen, Walter Michael Stadler, Robert R. Jones, Ulka N. Vaishampayan, Jorge A. Garcia, et al. "ASPEN: A randomized phase II trial of everolimus versus sunitinib in patients with metastatic non-clear cell renal cell carcinoma." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): TPS4590. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.tps4590.
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TPS4590 Background: Currently no level 1 evidence exists to guide therapeutic decisions in patients with metastatic non-clear cell renal cell carcinoma. Case series and retrospective analyses suggest that strategies targeting either the VEGF or mTOR/TORC1 pathways have clinical activity in papillary, chromophobe, or poorly differentiated histologic subtypes. Methods: We are conducting an international, randomized phase 2 trial of patients with metastatic non-clear cell RCC; either papillary, chromophobe, or undifferentiated histology; any Motzer risk group; and who have had no prior systemic therapy. All patients contribute tissue to an international biorepository for correlative genomic, genetic, and protein biomarker studies, along with companion longitudinal plasma and urine angiome studies. Patients are randomized to either everolimus or sunitinib (1:1) at FDA approved dosing until progression. The primary endpoint is progression free survival. Trial status: Seventy-three out of a planned 108 subjects have been enrolled at the time of abstract submission: median age 64, 59 white, 10 black, 4 unknown race, and includes 42 papillary and 31 chromophobe/undifferentiated histologies, 49 men and 22 women. Accrual is anticipated to be completed by December 2013. Accrual distribution by country is currently 43 (USA), 27 (UK), and 3 (Canada). The first DSMB meeting was conducted after 40 subjects completed at least 6 months of therapy and concluded that there were no unexpected safety signals and that the study should proceed. Tissue (primary, some metastatic, urine, plasma, whole blood) has been collected on all patients to date through the Duke Center for Human Genetics Biorepository. Clinical trial information: NCT01108445.
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Shuch, Brian, Lambros Stamatakis, Clara Chen, Rabindra Gautam, Maria Merino, Peter L. Choyke, W. Marston Linehan, and Ramaprasad Srinivasan. "Utility of 2-(18F) fluoro-2 deoxy-D-glucose PET/CT in advanced papillary renal cell carcinoma." Journal of Clinical Oncology 32, no. 4_suppl (February 1, 2014): 419. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.419.
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419 Background: 2-(18F) fluoro-2 deoxy-D-glucose (FDG) PET/CT is used infrequently in renal cell carcinoma (RCC) based on modest sensitivity in patients with clear cell kidney cancer. We evaluated the ability of FDG PET/CT to identify metastatic kidney cancer in patients with the second most common variant, papillary RCC. Materials and Methods: Patients with papillary RCC who underwent FDG PET/CT in conjunction with anatomic imaging were identified in a review of our clinical database. The ability of FDG PET/CT to detect malignant lesions (categorized by radiographic criteria) was evaluated. Results: Imaging studies from 42 patients with metastatic papillary RCC were reviewed. A total of 215 lesions were characterized as metastatic based on radiologic features. The median lesion size and lesions per patient were 2.0 cm and 5, respectively. Of these, 200 lesions were correctly classified as malignant by PET/CT (sensitivity, 93.0%, 95% confidence interval (CI) 88.8-95.7%). Of histologically confirmed lesions, 35 of 39 were PET positive (sensitivity, 89.7%, CI-76.4-95.9%). FDG PET/CT sensitivity did not appear to differ by lesion size, site, or papillary subtype. In a patient based analysis, all 42 patients had evidence of at least one FDG PET/CT avid lesion (sensitivity 100%, (95% CI 91.6-100%). Conclusions: FDG PET/CT is a highly sensitive modality for identifying extra-renal disease associated with papillary RCC. These data suggest that FDG PET/CT might be a clinically useful modality in the staging and surveillance of this patient population.
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Didwaniya, N., R. J. Edmonds, X. Fang, P. T. Silberstein, and S. Subbiah. "Survival outcomes in metastatic renal carcinoma based on histological subtypes: SEER database analysis." Journal of Clinical Oncology 29, no. 7_suppl (March 1, 2011): 381. http://dx.doi.org/10.1200/jco.2011.29.7_suppl.381.
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381 Background: Renal cell cancer (RCC) represents a heterogeneous group of tumors with distinct histopathologic, genetic, and clinical features. This study was conducted to evaluate the prognostic value of histology in RCCs. Methods: 3,062 patients with metastatic RCC from year 1998-2007 were identified from Surveillance Epidemiology and End Results (SEER) database. Data regarding their age, sex, race, treatment modality utilized and cancer specific survival was extracted and analyzed. Results: Clear cell, sarcomatoid, adenocarcinoma NOS, papillary, collecting duct, chromophobe and cyst associated renal carcinoma accounted for 2,166 (70%), 433 (14%), 216 (7%), 160 (52%), 47 (1.5%), 35 (1.14%), and 5 (0.01%) respectively. The mean age of presentation was 63.5 in clear cell RCC and 62.7 years in non-clear cell RCC. Surgery was performed in 57.23% of all clear cell cancers and 50.84% in non-clear cell-RCC group. 27.34% of all clear cell cancer patients received radiation in contrast to 34.53% in the other group. Both clear cell RCC (64.54%) and non-clear cell RCC (69.52%) occurred commonly in males. Incidence of clear cell RCC was 4.67% in Asians, 7.01% in Blacks, 88.32% in Whites. The incidence of non-clear cell RCC was 3.81% in Asians, 14.78% in Blacks, and 81.41% in Whites. Cancer-specific survival was calculated in all histologic subtypes. Median survival for clear cell RCC was 8 months, 3 months for adenocarcinoma NOS, 7 months for cyst associated renal carcinoma, 8 months for papillary carcinoma, 7 months for chromophobe type, 4 months for sarcomatoid and 4 months for collecting duct RCC. Median overall survival was significantly better for clear cell cancer as compared to non-clear cell RCCs (8 months vs. 4 months; p< 0.0001). Conclusions: Non-clear histology RCCs represent 30% of metastatic RCC and are associated with poor prognosis when compared to clear cell RCC.While development of novel targeted therapies has improved survival in clear cell RCC, it has not made a impact in survival of non-clear RCCs. An indepth understanding of the genetic and molecular changes associated with non-clear cell RCCs is important to improve their prognosis. No significant financial relationships to disclose.
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de Vries-Brilland, Manon, Nathalie Rioux-Leclercq, Maxime Meylan, Jonathan Dauvé, Christophe Passot, Elena Spirina-Menand, Ronan Flippot, et al. "Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma." Journal for ImmunoTherapy of Cancer 11, no. 11 (November 2023): e006885. http://dx.doi.org/10.1136/jitc-2023-006885.
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BackgroundPapillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.MethodsWe performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.ResultsUnsupervised clustering identified two “TME subtypes”, in each of the cohorts: the “immune-enriched” and the “immune-low”. Within AXIPAP trial cohort, the “immune-enriched” cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the “immune-enriched” group (adjusted p<0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations.ConclusionFor the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This “immune-enriched” group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies.Trial registration numberNCT02489695.
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McKay, Rana R., Pedro C. Barata, Andrew Elliott, Mehmet Asim Bilen, Earle F. Burgess, Sourat Darabi, Nancy Ann Dawson, et al. "Molecular alterations across sites of metastasis in patients with renal cell carcinoma (RCC)." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 287. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.287.
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287 Background: RCC has a distinct pattern of metastatic spread with common sites of metastasis including the lung, bone, and liver. Less common sites include the brain, adrenal gland, and pancreas. While the pattern of metastatic spread has prognostic significance, the biology driving tropism to specific organ sites has not been fully characterized. We utilized a multi-institutional real-world dataset to examine genomic alterations and transcriptional signatures across the spectrum of metastatic sites in patients with RCC. Methods: RCC tissue specimens derived from the kidney and distant metastatic sites were sequenced utilizing a commercially available Clinical Laboratory Improvement Amendments (CLIA)-certified assay by Caris Life Sciences. Whole exome and transcriptome sequencing was performed. Molecular subgroups were defined according to the IMmotion151 metastatic RCC subtypes, with subgroups determined by a weighted average of gene expression levels. Molecular analysis and PD-L1 expression (SP142) were described by metastasis site. Results: 657 RCC samples from 653 patients underwent molecular profiling. The median age was 62 years (range 14-90) and the majority were male (70.6%). The most common histology was clear cell RCC (n = 509, 77.5%), followed by papillary (n = 63, 9.6%), chromophobe (n = 30, 4.6%), medullary (n = 8, 1.2%), collecting duct (n = 6, 0.9%), and mixed (n = 41, 6.2%). Specimen source included the kidney (n = 340, 51.8%), lung (n = 75, 11.4%), bone (n = 45, 6.8%), lymph nodes (n = 34, 5.2%), liver (n = 28, 4.3%), endocrine glands (adrenal, pancreas, and thyroid; n = 23, 3.5%), brain/CNS (n = 16, 2.4%), and other metastatic sites (n = 96, 14.6%). Compared to kidney, several genes were mutated at higher rates for select metastatic sites, including PBRM1 (59.5% bone, 59.1% endocrine, and 45.9% lung vs 33.8% kidney, p< 0.05) and KDM5C (27.8% endocrine, 29.2% lymph nodes, and 35.3% soft tissue vs 9.3% kidney, p< 0.05). When evaluating metastatic specimens versus kidney specimens, bone metastases had a significantly higher proportion of tumors classified as ‘Angio/stromal’ (n = 19, 42.2%; vs n = 52, 15.4%; p< 0.0001), while liver metastases had a higher proportion of the ‘complement/Ω-oxidation’ subgroup (n = 17, 60.7%; vs n = 48, 14.1%; p< 0.0001). PD-L1 expression in metastatic sites (range 6.8%-21.7%, with exception of 0% in GI; p= 0.09 to 0.99) was not significantly different from the kidney (16.6%). Conclusions: In our contemporary real-world analysis, we demonstrate differential patterns of molecular alterations among sites of metastasis in RCC. Our observations elucidate the biology underlying heterogeneous disease outcomes associated with site of metastasis. Application of predictive signatures by site of metastasis may help inform personalized therapy strategies in advanced RCC. Further studies are warranted to validate our findings.
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Bambury, Richard Martin, Claire Brady, Aoife McCarthy, Stewart Fleming, Nicholas J. Mayer, and Derek Gerard Power. "Translocation renal cell carcinomas: An evolving entity." Journal of Clinical Oncology 30, no. 5_suppl (February 10, 2012): 472. http://dx.doi.org/10.1200/jco.2012.30.5_suppl.472.
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472 Background: Translocation renal cell carcinomas (RCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. As these neoplasms are only recently recognised, outcome data are premature. We report 2 cases of translocation RCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: In our recent practice, 2 renal cell carcinomas were suspected to be translocation tumours based on morphology and immunohistochemical features (RCC+/CK7-/EMA-). Using immunohistochemistry we tested for expression of TFE3 and TFEB. Results: Both tumours were translocation RCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 renal cell carcinoma with papillary architecture and eosinophillic hyaline nodules within many of the papillae. Staining for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She remains disease free 6 months post surgery. The second case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen performed after a new diagnosis of haemochromatosis. Staging CT imaging revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. Staining for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 5 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and identification of new cases to determine the clinical behaviour of these rare cancers in the Irish setting.
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Eldessouki, Ihab, Ola Gaber, Mahmoud A. Shehata, Tariq Namad, Joseph Atallah, Harsha Masineni, and Nagla Abdel Karim. "Papillary renal cell carcinoma: what is missing in research? A case report and a review of literature." SAGE Open Medical Case Reports 7 (January 2019): 2050313X1986947. http://dx.doi.org/10.1177/2050313x19869475.
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The incidence of renal cell carcinomas in adults ranges has been increasing over the past decades in both men and women. Once the incidence was 2.9%, now is reported to have increased to 3%–5% with male predominance according to the most recent reports of cancer statistics. The disease typically describes a group of different histopathological subtypes; the most common is clear cell carcinoma which accounts for 70%–80% of the diagnosed cases, while papillary renal cell carcinoma and chromophobe types represent 20% and 5%, respectively. In 1996, the renal cell carcinomas Heidelberg classification was introduced by Delahunt et al. It divides renal cell tumors into benign and malignant parenchymal neoplasms, excluding Wilm’s tumor and secondary metastases and limiting each subcategory to the most commonly documented genetic abnormalities, if applicable. In this report, we discuss a case of metastatic type I papillary renal cell carcinoma treated with the anti-vascular endothelial growth factor receptor sunitinib and showing marked long-term clinical response. Through this case, we highlight the importance of re-classifying papillary renal cell carcinoma subtypes to prioritize the clinical management of these cases.
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Su, Daniel, Chinonyerem Okoro, Arvin George, W. Marston Linehan, and Adam R. Metwalli. "Bilateral multifocal papillary type I renal cell carcinoma: Clinical characteristics and association with chronic renal insufficiency." Journal of Clinical Oncology 32, no. 4_suppl (February 1, 2014): 482. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.482.
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482 Background: Patients with bilateral multifocal (BMF) RCC are at risk for multiple surgeries, progressive loss of renal tissue and chronic renal insufficiency. Although BMF papillary type I RCC is commonly associated with Hereditary Papillary Renal Cell Carcinoma (HPRC), with mutation of the MET proto-oncogene, sporadic (non-familial) BMF Pap1 RCC is far more common. Here we describe the histologic and clinical phenotype as well as clinical management of a population of patients with BMF RCC that has papillary type I histology that is distinct from the HPRC population. Methods: From 2000 to 2013, patients who were evaluated at the National Cancer Institute and were diagnosed with BMF on cross sectional imaging were included. Patients who tested negative for MET proto-oncogene mutation, who have a pathologic diagnosis of papillary type I were included. Phenotypic manifestations and clinical management were analyzed. Results: 61 patients with an average age of 54.3 years were identified. A disproportionate number (22, 36%) of these patients were of African American descent. Fifty seven (93%) were male. Two patients were found to have had metastatic disease on presentation (3%); 17 patients underwent unilateral radical nephrectomy for renal mass (28%) even though the average largest tumor diameter was only 2.9 cm. 12 patients (19%) underwent partial nephrectomy. The average preoperative serum creatinine was 1.48 mg/dl and average eGFR 62.2 ml/min, there was no difference between in eGFR in African American patients and Caucasian patients (62.09 ml/min and 63 ml/min). This population had an average of 2 tumors per side, many patients also had numerous cysts on both kidneys. Conclusions: BMF papillary type I RCC represents a novel entity which disproportionally affects African Americans. These patients often present with renal insufficiency and are at significant risk for further renal deterioration. As a small percentage of these patients with BMF papillary type I will present with metastatic disease, active surveillance until the largest renal tumor reaches 3 cm is recommended.
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Agarwala, Vivek, Anant Ramaswamy, Amit Joshi, Vijay Maruti Patil, Vanita Noronha, Santosh Menon, B. Palak Popat, Sable Nilesh, and Kumar Prabhash. "Treatment outcomes of metastatic nonclear cell renal cell carcinoma: A single institution retrospective analysis." South Asian Journal of Cancer 07, no. 04 (October 2018): 226–30. http://dx.doi.org/10.4103/sajc.sajc_22_18.
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Abstract Introduction: Nonclear cell (NCC) metastatic renal cell carcinoma (mRCC) is a biologically heterogeneous entity. We report the outcomes of NCC mRCC treated with first-line vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin (mTOR) inhibitors at our institute. This is first such report from India. Methods: This is a retrospective analysis of the 40 consecutive patients of NCC mRCC treated between January 2013 and June 2015 in routine clinical practice at our institute. The primary endpoint analyzed was overall survival (OS) with respect to the type of first-line treatment and tumor histology. Results: The most common histological subtype was papillary in 25 patients (62.5%) followed by sarcomatoid in six (15%), chromophobe in 5 (12.5%), translocation-associated in one patient, and other nonspecified in three patients. First-line treatment was sorafenib in 14 (35%), sunitinib in 9 (22.5%), pazopanib in 8 (20%), everolimus in seven (17.5%), and best-supportive care (BSC) in two (5%) patients. Partial response, stable disease, and progression was observed in six (15%), 13 (32.5%), and nine (22.5%) cases, respectively, as the best response to first-line treatment. The median OS was 11.7 months and median event-free survival was 6.1 months in the whole cohort. The median OS in months for different first-line treatments were as follows: sorafenib (16.2), sunitinib (11.7), pazopanib (not reached, mean-23.9 ± 6.0), everolimus (4.1) and BSC (0.6) and for different histological subtypes were as follows: papillary (9.8), chromophobe (not reached, mean-30.3 ± 8.4), sarcomatoid (4.1), and others (7.9). Conclusions: Chromophobe histology has a better outcome compared to other histological subtypes, and anti-VEGF tyrosine kinase inhibitors are preferable first-line agents compared to mTOR inhibitors.
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Essam, Abdul Monem, Ajit Venniyoor, Suresh Nagdev, Itrat Mehdi, and Bassim Al Bahrani. "Long-term survival in a case of metastatic papillary renal cell carcinoma." South Asian Journal of Cancer 06, no. 01 (January 2017): 019–34. http://dx.doi.org/10.4103/2278-330x.202562.
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Yamazaki, Haruhiko, Takeshi Kishida, Go Noguchi, Hiroyuki Iwasaki, Nobuyasu Suganuma, Katsuhiko Masudo, Hirotaka Nakayama, et al. "Nephrectomy for Metastatic Kidney Tumor in Patients with Differentiated Thyroid Cancer: A Report of Two Cases." Case Reports in Endocrinology 2018 (November 11, 2018): 1–5. http://dx.doi.org/10.1155/2018/7842792.
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The occurrence of renal tumors originating from thyroid cancer is extremely rare with a few effective treatments for renal metastases. Here, we report the cases of two patients with differentiated thyroid cancer who underwent nephrectomy for a metastatic kidney tumor. Case 1 was a 74-year-old man who was diagnosed with right kidney tumor 10 years after initial surgery for papillary thyroid cancer (PTC). Right nephrectomy was performed, and the pathology was metastatic PTC. Case 2 was a 68-year-old woman who was diagnosed with left kidney tumor 24 years after surgery for follicular thyroid carcinoma (FTC). Left nephrectomy was performed, and the pathology was metastatic FTC. Nephrectomy for single renal metastasis could be considered a treatment option if the patients’ general condition is positive.
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Voss, Martin Henner, Yingbei Chen, Joshua Chaim, Devyn Taylor Coskey, Kaitlin Woo, Sujata Patil, Ana M. Molina, James Hsieh, Robert J. Motzer, and Darren Richard Feldman. "A phase II trial of everolimus and bevacizumab in advanced non-clear cell renal cell cancer." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 411. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.411.
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411 Background: VEGF- and mTOR-directed therapies achieve inferior outcomes in patients (pts) with advanced non-clear cell renal cell cancer (ncRCC) as compared to clear cell RCC. Limited effectiveness of monotherapy supports the study of combination regimens, and a phase II trial of everolimus (E) + bevacizumab (B) was conducted in pts with metastatic ncRCC. Methods: Treatment-naïve pts received E + B at standard doses until progression or intolerance to therapy. The primary endpoint was progression free survival (PFS) with the goal to see 22 of 34 pts progression-free on treatment >6 months (mo). Correlative analyses include next generation sequencing (NGS) from tumor and germline across 341 genes of interest, as well as immunohistochemistry (IHC) for markers of mTOR activation and vessel density. Results: 34 pts were enrolled, all are evaluable (median follow up 11.2 mo). The most common histologic subtype was unclassified RCC (URCC, n=23), the majority of which had papillary growth as a major component (URCC with papillary features, n=14). Other variants included chromophobe (n=5), papillary (n=4), and medullary RCC (n=2). 19 pts achieved PFS >6 mo; 8 continue on treatment. PFS varied by histology (p<0.001), and objective response rates (ORR) were higher in pts with significant papillary (7 of 18) or chromophobe (2 of 5) elements, than for the remaining pts (1 of 11). Presence of a major papillary component was associated with treatment benefit across the entire cohort (Table), particularly in the subgroup of URCC, where this feature correlated with ORR (43 vs. 11%), median PFS (12.9 vs. 1.9mo) and OS (18.5 vs. 9.3 mo) (p<0.001). IHC markers did not correlate with treatment effect. NGS was performed on 33 cases. Conclusions: ncRCC represent a heterogeneous group of malignancies. This study did not reach its primary endpoint, yet it suggests efficacy for E+B in patients with ncRCC characterized by papillary features. Genomic tumor and germline analysis is being performed to help define the underlying biology. Clinical trial information: NCT01399918. [Table: see text]
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Lam, J. S., R. H. Goel, A. J. Pantuck, R. A. Figlin, and A. S. Belldegrun. "Long-term survival following nephrectomy for renal cell carcinoma: The 15 year University of California-Los Angeles experience." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14532. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14532.
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14532 Background: Significant advances in the diagnosis, staging, and treatment of patients with renal cell carcinoma (RCC) during the last 2 decades have resulted in improved survival of a select group of patients and an overall change in the natural history of the disease. We describe the pathologic characteristics and long-term survival in patients treated for localized and metastatic RCC at a single tertiary care institution. Methods: Between 1990 and 2005, 1431 patients diagnosed with a renal mass underwent surgical resection and were evaluated for differences in clinicopathologic characteristics and survival based on the University of California-Los Angeles Integrated Staging System (UISS). Data were analyzed using standard statistical methods. Results: Following surgical resection, RCC was found in 1269 patients at pathologic evaluation. Of these patients, 473 had evidence of metastatic dissemination at time of surgery. The primary tumor in patients with metastatic disease was more likely to be clear cell (78.8% vs. 72.9%, p = 0.02), collecting duct (1.3% vs. 0.1%, p = 0.01), or undifferentiated (4.8% vs. 1.6%, p = 0.002) RCC, and less likely to be papillary (12.0% vs. 18.7%, p = 0.002) or chromophobe (3.1% vs. 6.7%, p = 0.006) RCC compared to patients with non-metastatic disease, respectively. The 2-year, 5-year, and 10-year survival was significantly higher in non-metastatic patients compared to patients with metastatic disease present at time of surgery (87.0% vs. 42.4%, 70.0 vs. 21.8%, 50.0% vs. 16.5%, p < 0.001, respectively). Conclusions: Over the last 15 years, patients with non-metastatic disease at the time of surgery have improved survival rates and are more likely to have papillary or chromophobe primary tumors than patients with metastatic disease. UISS stratification of patients with RCC provides a unique tool for risk assignment and outcome analysis to help determine follow-up regimens and eligibility for clinical trials. [Table: see text] No significant financial relationships to disclose.
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Peters, Inga, Christel Reese, Natalia Dubrowinskaja, Wiebke Inga Antonopoulos, Martin Krause, Tu Nghi Dang, Alexander Grote, et al. "DNA methylation signature for the assessment of metastatic risk in primary renal cell cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 516. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.516.
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516 Background: Transition from localized renal cell cancer (RCC) to metastatic disease is associated with an immense mortality. Beside clinicopathological risk estimation, a molecular prediction of metastatic risk from primary cancers with a sufficient diagnostic accuracy is not available. We biometrically identified a candidate metastasis associated methylation signature (MAMS) in a genome-wide in silico DNA methylation analysis of TCGA data and carried out a double evaluation study using tissues from localized RCC, primary metastatic RCC, and distant metastases. Methods: Candidate MAMS was identified by genome-wide random forest analyses of TCGA methylation level 3 data aiming for classification of 230 primary RCC without distant metastases and 52 metastasized tumors. Forty-nine pyrosequencing and/or quantitative methylation specific PCR analyses were established for a total of 20 candidate methylated loci. For evaluation of MAMS, DNA was isolated and bisulfite converted from the primary RCC tissue cohort (n=187) as well as 99 distant metastases. Localized RCCs consisted of 92 pT1a/b tumors (clear cell, 73; papillary, 16; chromophobe, 2; not classified, 1) without lymph node or distant metastases. RCC samples of primary metastatic disease were obtained from 31 patients. Results: Single candidate loci showed specific hypermethylation when metastatic tissues were compared to primary RCC samples. Random forest analysis showed that MAMS including nine methylation loci achieved a sensitivity of 93% and a specificity of 89% (AUC 0.95) for differentiation of localized RCC and metastases (chi square, p = 3.4*10-29). Positive, negative likelihood, and diagnostic odds ratios were 8.6, 0.08, and 108. Using this random forest model for prediction of primary RCCs associated with distant or lymph node metastases revealed a sensitivity of 58% and specificity of 94% (AUC 0.84, p = 1.0*10-9). Positive, negative likelihood, and diagnostic odds ratios were 9.2, 0.45, and 20.5. Conclusions: A negative MAMS test result retrospectively reduced the probability of metastasis 15-fold in the localized disease cohort, suggesting a prospective evaluation for a possible clinical translation of MAMS in handling RCC patients.
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Choueiri, Toni K., Anne Plantade, Paul Elson, Sylvie Negrier, Alain Ravaud, Stephane Oudard, Ming Zhou, Brian I. Rini, Ronald M. Bukowski, and Bernard Escudier. "Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma." Journal of Clinical Oncology 26, no. 1 (January 1, 2008): 127–31. http://dx.doi.org/10.1200/jco.2007.13.3223.
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Purpose Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non–clear cell histologies has not been evaluated. Patients and Methods Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions. Response rate and survival were documented. Fisher's exact test was used for categoric variables, and the Kaplan-Meier method was used to estimate survival. Results Fifty-three patients were included. The number of patients with papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively. Response rate, progression-free survival (PFS) time, and overall survival time for the entire cohort were 10%, 8.6 months, and 19.6 months, respectively. Three (25%) of 12 ChRCC patients achieved a response (two patients treated with sorafenib and one treated with sunitinib), and PFS was 10.6 months. Two (4.8%) of 41 PRCC patients achieved a response (both patients were treated with sunitinib). PFS for the whole cohort was 7.6 months. Sunitinib-treated PRCC patients had a PFS of 11.9 months compared with 5.1 months for sorafenib-treated patients (P < .001). Conclusion Patients with PRCC and ChRCC may have prolonged PFS from sunitinib and sorafenib, although clinical responses remain overall low in PRCC. Additional prospective trials with these agents in non–clear cell RCC will further clarify their use in the future.
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Voss, Martin H., Ana M. Molina, Ying-Bei Chen, Kaitlin M. Woo, Joshua L. Chaim, Devyn T. Coskey, Almedina Redzematovic, et al. "Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non–Clear Cell Renal Cell Carcinoma." Journal of Clinical Oncology 34, no. 32 (November 10, 2016): 3846–53. http://dx.doi.org/10.1200/jco.2016.67.9084.
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Purpose The decreased effectiveness of single-agent targeted therapies in advanced non–clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.
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Power, Derek Gerard, Jodie E. Battley, Aoife McCarthy, Claire Brady, John P. Sweeney, Stewart Fleming, Nicholas J. Mayer, and Richard Martin Bambury. "Translocation renal cell carcinomas: An evolving entity." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e15078-e15078. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15078.
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e15078 Background: Translocation renal cell carcinomas (tRCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. These neoplasms are only recently recognised and outcome data are premature. We report 2 cases of tRCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: : Approximately 70 new cases of RCC are referred to our centre annually. Recently, 2 renal cell carcinomas were suspected to be tRCCs on morphology and immunohistochemical(IHC) features (RCC+/CK7-/EMA-). Using IHC we tested for expression of TFE3 and TFEB. Results: : Both tumours were tRCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 RCC with mixed clear cell and papillary architecture. IHC for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She relapsed 9 months later with local recurrence, retroperitoneal adenopathy and lung metastases. She commenced sunitinib and response assessment is pending. The 2nd case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen. Staging CT revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. IHC for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 9 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and will also report 3 further cases suspected to be tRCCs based on morphology and IHC. Confirmatory TFE3/TFEB IHC is awaited.
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Tsimafeyeu, Ilya, Alexandra Naumova, Evgenia Stepanova, Alfia Khasanova, Ilya Varlamov, Nigel Wynn, Anton Snegovoy, and Lev V. Demidov. "FGFR2 expression to predict survival outcome in patients with metastatic papillary renal cell carcinoma." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 506. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.506.
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506 Background: In our previous study we showed that fibroblast growth factor receptor 2 (FGFR2) mutations are rare across papillary types of renal cell carcinoma (pRCC). The aim of the present study is to test FGFR2 expression for association with survival outcome in the largest patient cohort to date. Methods: Formalin-fixed, paraffin-embedded specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody (Santa Cruz Biotechnology). Expression was quantified by consensus of two independent observers using a four-value intensity score (0, 1+, 2+, and 3+) and the percentage (0-100%) of the extent of reactivity. Expression was scored according to the percentage of positive cells present among all tumor cells in the section. The cytoplasmic and nuclear expression score was obtained by multiplying the intensity and reactivity extension values (range, 0-300). FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response. Results: Expression of FGFR2 was observed in 23% (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. 2 of 214 (1%) patients had nuclear FGFR2 expression. Intensity was 3+ in all cases. Expression of FGFR2 was significant lower in the normal tissue of kidney (1%, P=0.001). FGFR2 expression was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0-1), type 2 of pRCC, lower nucleolar grade (P<0.001). FGFR2-positive patients had significantly shorter OS and PFS in first-line therapy (P<0.05; Table). On multivariate analysis, FGFR2 expression, MSKCC risk group, and type of pRCC were found to be independent predictors of survival. Conclusions: In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. Clinical trial information: rosoncoweb2011. [Table: see text]
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Nicaise, Edouard, Benjamin Schmeusser, Adil Ali, Eric Midenberg, Arnold Raul Palacios, Ethan Kearns, Sriram Ambadi, et al. "Linear muscle segmentation for metastatic renal cell carcinoma." Journal of Clinical Oncology 42, no. 4_suppl (February 1, 2024): 380. http://dx.doi.org/10.1200/jco.2024.42.4_suppl.380.
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380 Background: Baseline sarcopenia and postoperative changes in muscle mass are independently associated with overall survival in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN). Here we examine the relationship between preoperative (baseline) and postoperative changes in muscle quantity with survival outcomes following CN as determined by linear segmentation, a fast and clinic-friendly tool. Methods: Our nephrectomy database was reviewed for patients with clear cell, papillary, or chromophobe mRCC who underwent CN. Linear segmentation of bilateral psoas/paraspinal muscles was completed for baseline imaging within 60 days of surgery and imaging up to 1 year postoperatively. ANOVA for numerical and chi-square for categorical variables were used to test for differences according to change in linear muscle index (LMI, cm2/m2). Multivariable models estimated COX hazard ratios for cancer-specific survival (CSS) and overall survival (OS). Kaplan Meier curves estimated CSS and OS. Results: From 2004-2020, 190 patients were identified 48 stable LMI (25.3%; <5% change [0Δ]), 54 increase LMI (28.4%; +5% change [+Δ]), and 88 decrease LMI (46.3%; -5% change [-Δ]). Median time from baseline imaging to surgery was 18 days, while time from surgery to postoperative imaging was 119 days. Patients with +Δ had lower baseline LMI than -Δ or 0Δ (28.5 vs. 32.4 vs.32.5 cm2/m2; p=0.003). 0Δ LMI had lower rates of pN1 disease than other groups (27.1% [0Δ] vs. 42.6% [+Δ] vs. 45.5% [-Δ]; p=0.019). No other differences in pathology were noted. Median CSS and OS were highest among patients with 0Δ LMI (CSS: not reached [0Δ] vs. 61.9 [+Δ] vs. 37.4 [-Δ] months; p=0.0018 || OS: 67.2 [0Δ] vs. 48.5 [+Δ] vs. 26.4 [-Δ] months; p=0.0007). Median follow-up was 56 months for survivors. The table lists factors associated with increased risk of cancer-specific mortality. Conclusions: Change in muscle mass after CN, as measured by the linear muscle segmentation technique, is independently associated with OS and CSS in patients following CN. Of note, lack of change demonstrated greatest survival, potentially secondary to high baseline muscle mass. [Table: see text]
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Morinaga, Ryota, Takashi Kawahara, Yasuhide Miyoshi, Masahiro Yao, and Hiroji Uemura. "Longer Control of Nivolumab in Metastatic Renal Cell Carcinoma Patients with End-Stage Kidney Disease on Dialysis." Case Reports in Oncology 12, no. 2 (August 6, 2019): 608–12. http://dx.doi.org/10.1159/000501768.
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Introduction: Nivolumab has been introduced for metastatic renal cell carcinoma (mRCC) as a second-line therapy for years. However, despite widespread evidence of its utility, few reports have described the efficacy of nivolumab for mRCC patients on hemodialysis. Case Presentation: A 68-year-old man with a 20-year history of dialysis due to chronic glomerulotubular nephritis was referred to our department for bilateral renal tumors in 2015. In February 2015, contrast-enhanced CT revealed findings suggestive of RCC, so we performed right nephrectomy. The pathological diagnosis was clear cell carcinoma and papillary renal cell carcinoma. In July 2015, we consequently performed left nephrectomy, and the pathological diagnosis was metastatic RCC. In February 2016, because follow-up CT revealed a right adrenal tumor with time-dependent growth, sunitinib (25 mg/body) was introduced. In January 2017, although sunitinib had controlled the adrenal metastasis for 9 courses (11 months), liver metastasis was observed, so nivolumab was introduced as a second-line chemotherapy in March 2017. Nivolumab was able to control the mRCC for 15 months (32 courses). While CT showed no metastatic sites except for the liver and adrenal glands, his general condition gradually decreased, and he died in October 2018. Conclusion: We herein report a patient with RCC on hemodialysis with long-term cancer control by nivolumab.
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Albiges, Laurence, Daniel Yick Chin Heng, Jae-Lyun Lee, Stephen Walker, Anders Mellemgaard, Lone Ottesen, Melanie M. Frigault, et al. "MET status and treatment outcomes in papillary renal cell carcinoma (PRCC): Pooled analysis of historical data." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19321-e19321. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19321.
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e19321 Background: PRCC accounts for 10–15% of RCCs, but there are limited biomarker-based data to inform targeted treatment. Treatments for patients (pts) with advanced/metastatic PRCC include those approved for clear cell RCC such as sunitinib or everolimus, however their activity in PRCC can be limited. A subset of PRCCs are MET-driven, and it has been suggested that this may be a negative prognostic factor, although the role of MET activation in advanced/metastatic disease is unclear. We explored the prevalance of MET status in pts with advanced/metastatic PRCC treated with targeted therapies and impact on clinical outcomes. Methods: This large, international, retrospective, observational study included pts with previously treated, locally advanced/metastatic PRCC. MET status was determined retrospectively by NGS of archival tissue. MET-driven disease was defined as MET and/or HGF amplification, chromosome 7 gain (requiring > 30% tumor content) and/or MET kinase domain mutations. Study objectives included progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS) by MET status. Results: 305/308 pts (International Metastatic RCC Database Consortium, n = 72; The Asan Genito-Urinary Cancer Center, n = 40; Groupe Français d’Etude des Tumeurs Uro-Génitales, n = 196) received first-line (1L) treatment; sunitinib was most common (68%). 214 (69%) pts received 2L therapy; everolimus was most common (20%). Of 179 pts with valid NGS results, 38%, 49% and 13% had MET-driven, MET-independent (ind) tumors and chromosome 7 ploidy unevaluable, respectively. Baseline demographics were mostly balanced among groups. In sunitinib-treated pts, PFS and TTF were numerically longer in pts with MET-driven tumors vs pts with MET-ind tumors, but OS was similar (Table). In everolimus-treated pts, PFS and TTF were similar for both MET groups; however the sample size was small. Conclusions: MET alterations are frequent in advanced/metastatic PRCC and have potential to impact PFS and TTF, although our results show limited effect on OS. These data show that MET-driven tumours may not predict for poorer outcome vs MET-ind tumours and there is a need for suitable therapies for MET-driven PRCC. [Table: see text]
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Moreira, Raphael Brandao, Rana R. McKay, Wanling Xie, Daniel Yick Chin Heng, Guillermo de Velasco, Daniel E. Castellano, Andre Poisl Fay, et al. "Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC)." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 482. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.482.
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482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component > 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]
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Heng, Daniel Y. C., and Toni K. Choueiri. "Non–Clear Cell Renal Cancer: Features and Medical Management." Journal of the National Comprehensive Cancer Network 7, no. 6 (June 2009): 659–65. http://dx.doi.org/10.6004/jnccn.2009.0046.
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The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically with the introduction of targeted therapies against vascular endothelial growth factor and the mammalian target of rapamycin. Because patients with clear cell histology account for more than 80% of patients with RCC, little evidence is available on treating patients with non–clear cell histologies. Most clinical trials have excluded them from enrollment, except for a randomized study investigating temsirolimus. Many retrospective studies on the use of sunitinib, sorafenib, and temsirolimus in patients with non–clear cell histology have shown response rates ranging from 3.7% to 16%. Prospective studies in non–clear cell histologies are ongoing. Although response rates may not be as high as those in patients with clear cell histologies, targeted therapy may provide a clinically meaningful response. New investigational therapies are on the horizon for papillary RCC—the most-common non–clear cell RCC histology—targeting pathways specific to this histology, such as the c-MET pathway.
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Bodard, Sylvain, Idris Boudhabhay, Charles Dariane, Christophe Delavaud, Sylvain Guinebert, Dominique Joly, Marc-Olivier Timsit, et al. "Percutaneous Thermal Ablation for Renal Tumors in Patients with Birt–Hogg–Dubé Syndrome." Cancers 14, no. 20 (October 11, 2022): 4969. http://dx.doi.org/10.3390/cancers14204969.
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BHD syndrome is characterized by an increased risk of bilateral and multifocal renal cell carcinoma (RCCs), but is rarely metastatic. Our report aims to analyze the outcome of patients with BHD syndrome who underwent percutaneous thermal ablation (TA). The present report included six BHD syndrome patients (five men) with a mean age of 66 ± 11 (SD) years who had a proven germline FLCN gene mutation and underwent TA for a renal tumor. Nineteen renal tumors (median two tumors per patient; range: 1–3), including seven chromophobe RCCs, five clear-cell RCCs, four papillary RCCs, two clear-cell papillary RCC, and one hybrid oncocytic/chromophobe tumor were treated in 14 ablation sessions. The mean size of the tumors was 21 ± 11 (SD) mm (median: 20 mm; interquartile range (IQR): 14–25 mm) for a mean volume of 7 ± 11 (SD) mL (median: 3; IQR: 1–5 mL). Technical success was achieved in all ablation sessions (primary success rate, 100%). The procedure was well tolerated under conscious sedation with no significant Clavien–Dindo complication (grade 2, 3, 4). All patients were alive with no distant metastasis during a median follow-up period of 74 months (range: 33–83 months). No local tumor progression was observed. The mean decrease in estimated glomerular filtration rate was 8 mL/min/1.73 m2. No patients required dialysis or renal transplantation. In this case series, percutaneous TA appeared as a safe and efficient nephron-sparing treatment for treating RCCs associated with BHD syndrome, even in the case of advanced chronic kidney disease.
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von Klot, Christoph A. J., Natalia Dubrowinskaja, Jörg Hennenlotter, Mario W. Kramer, Axel S. Merseburger, Arnulf Stenzl, Inga Peters, Hossein Tezval, Markus A. Kuczyk, and Juergen Serth. "Rho GDP dissociation inhibitor beta ARHGDIB in renal cell cancer." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 474. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.474.
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474 Background: Rho GDP dissociation inhibitor 2 (ARHGDIB) is an important mediator of cellular signaling. The expression of ARHGDIB correlates with tumor growth and metastasis in a variety of non genitourinary cancers, however the role of ARHGDIB in renal cell cancer (RCC) has not yet been evaluated. Methods: Tissue samples from 106 patients undergoing surgery for RCC were obtained. The expression of ARHGDIB mRNA in normal kidney tissue and in corresponding cancer tissue was analyzed by means of quantitative real time PCR. Differences in mRNA expression levels were assessed using paired two-sample tests. Associations of relative mRNA expression levels and clinicopathological parameters were statistically analyzed using an univariate logistic regression model. Relative mRNA expression levels in healthy renal tissue compared to cancerous tissue from the same kidney was assessed using a paired t-test. Results: When comparing 74 tissues from kidney tumors with adjacent histologically normal appearing paired tissues, mRNA expression of ARHGDIB was significantly higher in the tumor tissue (p < 0.001). Paired analysis did not only show significantly higher mRNA expression levels for ARHGDIB over all RCC but also for the subgroup with clear cell RCC (ccRCC). The mRNA expression of ARHGDIB was also more pronounced in ccRCC when compared with papillary RCC (p < 0.001). When looking at clinicopathological parameters in univariate logistic regression analysis ccRCC was significantly associated with nodal involvement (p = 0.03) and also with tumor grade (p = 0.05). For all RCC there was no association with clinicopathological parameters. A bivariate Cox regression model, adjusted for metastatic status (p = 0.001), tumor diameter (p = 0.043), state of advanced disease (p = 0.030) and lymph node metastasis (p = 0.006) identified ARHGDIB mRNA expression as a candidate positive prognosticator for RFS. Conclusions: Increased ARHGDIB mRNA expression is significantly associated with RCC tissues. Higher relative expression observed within tumor tissues represents a candidate prognosticator for better RFS of patients.
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Tsimafeyeu, I., A. Khasanova, E. Stepanova, M. Gordiev, D. Khochenkov, A. Naumova, I. Varlamov, A. Snegovoy, and L. Demidov. "FGFR2 overexpression predicts survival outcome in patients with metastatic papillary renal cell carcinoma." Clinical and Translational Oncology 19, no. 2 (July 5, 2016): 265–68. http://dx.doi.org/10.1007/s12094-016-1524-y.
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Sawyer, Reed, and Harris Wayne B. "Clinical implications of epigenetics in Renal Cell Carcinoma." Archives of Renal Diseases and Management 7, no. 1 (July 27, 2022): 008–13. http://dx.doi.org/10.17352/2455-5495.000040.
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Renal Cell Carcinoma (RCC), is the 9th most common cancer in the United States. The major classifications of RCC include clear cell (ccRCC), papillary (pRCC) and chromophobe (chRCC). Treatment for the localized disease includes resection or ablation with curative intent, or surveillance if these procedures are not feasible. Unfortunately, about one-third of patients will present with metastatic disease at the time of diagnosis and there are currently no reliable biomarkers to guide clinical decision-making. There is growing evidence that epigenetics plays a role in kidney cancer tumorigenesis and aggressiveness and new strategies for biomarker development are emerging. For example, DNA methylation patterns may be useful in distinguishing different types of RCCs and for distinguishing malignant kidney neoplasms from benign tumors. Epigenetic changes in RCC have also been associated with poorer response to treatment and have the potential to be novel drug targets in the treatment of mRCC. Here we discuss the epigenetics of RCC and the corresponding clinical implications.
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Marchand Crety, Charles, Estelle Vigneau, and Camille Invernizzi. "Stereotactic Body Radiotherapy of a Solitary Metachronous Sphenoid Metastasis from Renal Cell Cancer: A Case Report." Case Reports in Oncology 14, no. 1 (March 2, 2021): 269–73. http://dx.doi.org/10.1159/000513743.
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Nasosinus metastases from kidney cancer are an unusual clinical presentation although some cases are reported in the literature. Among these cases, sphenoidal metastases are even rarer. Here we report a case of lone sphenoid metastasis in patients with papillary renal cell cancer. Eight months after radical nephrectomy, the patient presented with progressively worsening diplopia. Magnetic resonance imaging showed a mass in the right sphenoid sinus. Histopathological examination of the biopsy sample confirmed diagnosis of sinonasal metastasis from papillary renal cell carcinoma. The patient was declined for surgical management and received stereotactic body radiation therapy. Reassessment MRI at 4 months showed a complete response of the treated sphenoid lesion.
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Ahrens, Marit, Bernard Escudier, John B. A. G. Haanen, Ekaterini Boleti, Marine Gross Goupil, Marc-Oliver Grimm, Sylvie Negrier, et al. "A randomized phase II study of nivolumab plus ipilimumab versus standard of care in previously untreated and advanced non-clear cell renal cell carcinoma (SUNIFORECAST)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): TPS4597. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.tps4597.
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TPS4597 Background: Non-clear cell renal cell carcinomas (nccRCC) account for approximately 25% of RCC patients (pts.). Data on treatment strategies for this heterogenous group of RCC are still limited, since most clinical trials focus on clear-cell RCC (ccRCC) histology. Recently combination therapies with immune checkpoint inhibitors (IO, avelumab or pembrolizumab) and tyrosinekinaseinhibitors (TKI) (axitinib) have been approved for treatment in RCC in all International Metastatic RCC Database Consortium (IMDC) risk groups. Additionally nivolumab and ipilimumab (IO/IO) has been approved for treatment in intermediate and high risk pts. showing a significant improvement in overall response rate (ORR), progression free (PFS), and overall survival (OS) compared to sunitinib. Moreover retrospective analysis in nccRCC pts. have shown promising results for IO-based therapies as well in these entities. Methods: In this prospective randomized phase-II multicenter European trial adults with advanced or metastatic nccRCC without prior systemic therapy are eligible. Other key inclusion criteria include: available tumor tissue, Karnofsky >70% and measurable disease per RECIST 1.1. All histological diagnoses are reviewed by a central pathologist. The study plans to randomize ̃306 pts. stratified for papillary or non-papillary non-clear cell histology and by the IMDC risk score. Pts. will be randomized 1:1 to either i) nivolumab 3mg/kg intravenously (IV) plus Ipilimumab 1mg/kg IV every 3 weeks for 4 doses followed by nivolumab fixed dose 240mg IV every 2 weeks or fixed dose 480mg IV every 4 weeks or ii) standard of care therapy according to the approved schedule. Treatment will be discontinued in case of unacceptable toxicity or withdrawal of informed consent. Pts may continue treatment beyond progression, if clinical benefit is achieved and treatment is well tolerated. Primary endpoint is the OS rate at 12 months. Secondary endpoints include OS rate at 6 and 18 months, median OS, PFS, ORR and quality of life. The trial is in progress and 214 patients (132 pts with papillary, 76 pts with non-papillary histology) have been enrolled until now. Clinical trial information: NCT03075423.
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Ahrens, Marit, Bernard Escudier, Ekaterini Boleti, Marc-Oliver Grimm, Marine Gross-Goupil, Philippe Barthelemy, Gwenaelle Gravis, et al. "A randomized phase II study of nivolumab plus ipilimumab versus standard of care in previously untreated and advanced non-clear cell renal cell carcinoma (SUNIFORECAST)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): TPS5103. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.tps5103.
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TPS5103 Background: Non-clear cell renal cell carcinomas (nccRCC) are a heterogeneous group of tumors accounting for approximately 25% of RCC patients (pts.). Since most clinical trials focus on clear-cell RCC (ccRCC) only, data on treatment strategies for nccRCC are limited. The combination of Nivolumab and Ipilimumab (IO/IO) has recently been approved for treatment in RCC showing a significant improvement in overall response rate (ORR), progression free (PFS), and overall survival (OS) in intermediate and high-risk pts. compared to sunitinib in a phase-III trial. Furthermore retrospective analysis in nccRCC patients have shown promising results for IO/IO as well in these entities. Methods: In this prospective randomized phase-II multicenter European trial adults with advanced or metastatic nccRCC without prior systemic therapy are eligible. Other key inclusion criteria include: available tumor tissue, Karnofsky > 70% and measurable disease per RECIST 1.1. All histological diagnoses are reviewed by a central pathologist. The study plans to randomize ~306 pts. stratified for papillary or non-papillary non-clear cell histology and by the International Metastatic RCC Database Consortium (IMDC) risk score. Pts. will be randomized 1:1 to either i) Nivolumab 3mg/kg intravenously (IV) plus Ipilimumab 1mg/kg IV every 3 weeks for 4 doses followed by Nivolumab fixed dose 240mg IV every 2 weeks or ii) standard of care therapy according to the approved schedule. Treatment will be discontinued in case of unacceptable toxicity or withdrawal of informed consent. Pts may continue treatment beyond progression, if clinical benefit is achieved and treatment is well tolerated. Primary endpoint is the OS rate at 12 months. Secondary endpoints include OS rate at 6 and 18 months, median OS, PFS, ORR and quality of life. The trial is in progress and 122 patients (78 pts with papillary, 37 pts with non-papillary histology) have been enrolled until now. Clinical trial information: NCT03075423 .
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Casuscelli, Jozefina, Andrew G. Winer, Eduard Reznik, Jianing Xu, Brandon Manley, Jyoti Chouhan, Victor E. Reuter, et al. "Single-institutional analysis of patients with clear-cell papillary renal cell carcinoma." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 512. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.512.
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512 Background: Recently clear cell papillary renal cell carcinoma (cpRCC) has been recognized as new histologic subtype with immunohistochemical profiles that differentiate it from clear cell (ccRCC) and papillary (pRCC) RCC. Several previous studies highlighted the indolent behaviour of this entity in the reported cases. Our primary objective is to further elucidate the genomic and clinical characteristics of cpRCC. Methods: 44 patients with cpRCC were selected from the MSKCC database with surgery performed between 2007 and 2014. Only tumors with appropriate histological configuration and immunohistochemically confirmed CAIX and CK7 positivity and CD10 negativity were included. Whole exome sequencing (WES) was performed on 5 cpRCC tumor samples and one sample was analyzed by next-generation sequencing (MSK-IMPACT). A further comparison was made to 825 ccRCC and 219 pRCC tumors with initial pT1 diagnosis from our institutional database. Differences in the variables across groups were analyzed with the Chi-Square and the Kruskal–Wallis tests. To visualize and test the survival distribution differences, we used Kaplan–Meier plots and Log-rank tests. Results: Sequencing did not reveal VHL mutations or other known driver mutations commonly seen in ccRCC or pRCC and no recurrent mutations were identified. The median follow up period for cpRCC was 27 months, for ccRCC 59 months and for pRCC 63 months. cpRCC frequently co-occured with ccRCC or other RCC subtypes (17/44 cases). Female patients developed cpRCC significantly more frequently than ccRCC or pRCC (47.7% P<0.001) and Kruskal-Wallis test revealed differences in tumor size between the 3 groups (cpRCC median size 2.5 cm, P<0.001). Recurrence, metastatic development and death from kidney cancer was observed in ccRCC (3.7%, 2.3% and 0.8%) and in pRCC (4.5%, 1.8% and 2%), but not in the cpRCC cohort. Conclusions: cpRCC is genomically distinct from ccRCC and pRCC and lacks driver mutations commonly associated with aggressive disease. The tumors tend to present smaller than other RCC subtypes, commonly co-occur with other RCCs and disproportionately affect women. Extended follow-up of larger cohorts is necessary to confirm the true indolent nature of cpRCC.
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Grenader, Tal, Eli Rosenbaum, Sofia Zilber, Naama Bogot, and Linda Shavit. "Spontaneous Regression of Metastatic Papillary Renal Cell Cancer After Cessation of Treatment With Sorafenib." Clinical Genitourinary Cancer 11, no. 2 (June 2013): 201–3. http://dx.doi.org/10.1016/j.clgc.2012.11.005.
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Prager, Gerald, and Marina Poettler. "CD98hc expression to predict prognosis in renal cell cancer." Journal of Clinical Oncology 30, no. 30_suppl (October 20, 2012): 26. http://dx.doi.org/10.1200/jco.2012.30.30_suppl.26.
Full textAbstract:
26 Background: CD98, a transmembrane protein, has a heteromeric structure, consisting of a heavy subunit (CD98hc) and a light subunit, extracellular linked together via disulfid bounds. A genetic knockout of CD98hc is embryonic lethal and overexpression of CD98hc in somatic cells led to malignant transformation. CD98hc is highly expressed in low differentiated papillary, clear cell and chromophobe RCC, but not in benign tumors. Notably, CD98hc expression directly correlated with grade of differentiation. Methods: To evaluate a potential functional role of CD98hc in renal cancer cell metastatic behavior, we generated a stable low CD98hc clear cell RCC cell line (Caki2) via lentiviral shRNA infection and compared tumor cell behavior with a high expressing mock transfected control. Results: We found that tumor cell behavior such as proliferation (52 ± 3% less 3[H] thymidin – incorporation in low CD98hc/Caki2 cells), cell survival upon anoikis (46% late and 45% early apoptosis in low CD98hc/Caki2 cells compared to high/CD98hc/Caki2 cells with 18% late apoptosis and 64% early apoptosis) and invasion/transmigration (520 ± 67 cells / field after 24h in low CD98hc/ Caki2 cells and 1257 ± 346 cells / field in high CD98hc/Caki2 cells analyzed in a modified boyden chamber) were considerably impaired whenever CD98hc expression was downregulated. To examine the mechanism by which CD98hc affected metastatic tumor cell behavior, we introduced two mutations in a reconstitution (silent mutation). A truncation mutant interfered with integrin interaction and a two point mutations (Cys109Ser and Cys330Ser) mutant affected amino acid transporter activity. Whenever integrin/CD98hc interaction was impaired tumor cell behavior including cell proliferation, cell survival, invasio/transmigration, and cell spreading as well as signal transduction pathways including FAK, c-src, MEK/ERK pathways were significantly compromised resembling the low CD98hc phenotype. Conclusions: For these data we conclude that metastatic tumor cell behavior such as cell survival, invasion and proliferation are dependent on CD98hc expression in renal cancer cells.