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Journal articles on the topic 'Radiation-induced lymphopenia'

Author: Grafiati

Published: 26 October 2024

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1

Wang, Xin, Peiliang Wang, Zongxing Zhao, Qingfeng Mao, Jinming Yu, and Minghuan Li. "A review of radiation-induced lymphopenia in patients with esophageal cancer: an immunological perspective for radiotherapy." Therapeutic Advances in Medical Oncology 12 (January 2020): 175883592092682. http://dx.doi.org/10.1177/1758835920926822.

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Radiotherapy is a frequently utilized therapeutic modality in the treatment of esophageal cancer (EC). Even though extensive studies are carried out in radiotherapy for EC, the design of the clinical target volume and the radiation dose is not satisfactorily uniform. Radiotherapy acts as a double-edged sword on the immune system; it has both an immunostimulatory effect and an immunosuppressive effect. Radiation-induced lymphopenia and its potential association with tumor control and survival outcomes remain to be understood. The advent of immunotherapy has renewed the focus on preserving a pool of functioning lymphocytes in the circulation. In this review, we summarize the potential impact mechanisms of radiotherapy on peripheral blood lymphocytes and the prognostic role of radiation-induced lymphopenia in patients with EC. We also propose the concept of organs-at-risk of lymphopenia and discuss potential strategies to mitigate its effects on patients with EC. From an immunological perspective, we put forward the hypothesis that optimizing radiation modalities, radiation target volume schemes, and radiation doses could help to reduce radiation-induced lymphopenia risks and maximize the immunomodulatory role of radiotherapy. An optimized radiotherapy plan may further enhance the feasibility and effectiveness of combining immunotherapy with radiotherapy for EC.

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2

Sashidharan, Srijith, Azadeh Abravan, Peter Sitch, Cy Howells, Ed Smith, and Shermaine Pan. "Radiation-induced lymphopenia with proton beam therapy (PBT)." Clinical Oncology 34 (September 2022): e2-e3. http://dx.doi.org/10.1016/j.clon.2022.08.009.

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3

Ballal, Suhas, Shruti Chandak, Karan Ram Lal Gupta, and Geetika M. Patel. "A systematic review of the management and implications of radiation-induced lymphopenia and the predictive rate of radiomic-based approaches in lung cancer." Multidisciplinary Reviews 6 (January 29, 2024): 2023ss008. http://dx.doi.org/10.31893/multirev.2023ss008.

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Radiation therapy remains a crucial treatment option for lung cancer, but radiation-induced lymphopenia can impact treatment results and patient well-being. Radiomics-based techniques have made it easier to predict therapy response and patient outcomes by extracting and analyzing quantitative imaging characteristics. This review examines radiation-induced lymphopenia management and its consequences while evaluating the predictive capabilities of radiomics-based approaches in the lung cancer context. A systematic review was undertaken using Scinapse, Scholar and PubMed, with 1247 papers chosen based on predefined criterion for inclusion and exclusion. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines declaration, 15 peer-reviewed studies published between 2019 and 2021 were included in the review after removing duplicates. The search technique retrieved 491 studies from PubMed, 540 from Scinapse and 250 from Google Scholar. In this quantitative statistic, we provided categorical data as the interquartile range (IQR) for constants and fractions. Then, we reviewed papers that examined techniques for managing radiation-induced lymphopenia and its implications for treatment results. These techniques were correlated with possible improvements in patient outcomes and a decrease in the degree of lymph node dysfunction. An examination of forest plots was carried out to assess the prediction efficiency of radiomics-based techniques in forecasting lung cancer patient survival and to summarize therapy regimens for radiation-induced lymphoma. The Radiomics Quality Score (RQS) was used as a quantitative tool to assess the consequences of radiation-induced lymphopenia. Patients having radiation-related lymph node dysfunction have an elevated risk of developing lung tambours and dying from it. Especially in people who have additional risk factors, minimizing the lung and heart dosage could reduce lymphopenia and perhaps enhance the course of therapy for these patients.

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Sengupta, Sadhak, Jaclyn Marrinan, Caroline Frishman, and Prakash Sampath. "Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy." Clinical and Developmental Immunology 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/831090.

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Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.

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Yu, Hao, Fang Chen, Li Yang, Jian-Yue Jin, and Feng-Ming Spring Kong. "Potential determinants of radiation-induced lymphocyte decrease and lymphopenia in breast cancer patients by machine learning approaches." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e12567-e12567. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e12567.

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e12567 Background: Radiation-induced lymphopenia accompanied with radiation therapy is associated with inferior clinical outcomes in a wide variety of solid malignancies. This study aimed to examine the potential determines of radiation-induced lymphocyte decrease and radiation-induced lymphopenia in breast cancer patients who underwent radiotherapy. Methods: Patients with breast cancer treated who underwent radiotherapy were enrolled in University of Hong Kong-Shenzhen Hospital (our cohort). Circulating lymphocyte levels were evaluated within 7 days prior to and end of radiation therapy. Feature groups including clinical data, tumor characteristics, radiotherapy dosimetrics, treatment regiments were also collected. We applied machine learning algorithms (Extreme Gradient Boosting, XGboost) to predict the ratio of lymphocyte level after radiotherapy to baseline lymphocyte level and the event of lymphopenia and compared with Lasso regression approaches. Next, we used Shapley additive explanation (SHAP) to explore the directional contribution of each feature for lymphocyte decrease and lymphopenia. For the purpose of model validation and proof-of-concept validation, an independent cohort of patients enrolled in prospective trial was eligible (IP cohort). Results: A total of 589 patients were enrolled in our cohort and 203 patients in IP cohort. XGboost models which trained in our cohort with performances of a mean RMSE: 0.157 and R2: 53.9% for the ratio of lymphocyte levels; a mean accuracy: 0.757 and ROC-AUC: 0.733 for the lymphopenia events, separately. These models can predict the ratio of lymphocyte levels with a mean RMSE: 0.175 and R2: 47%; predict the lymphopenia events with a mean accuracy: 0.739 and ROC-AUC: 0.737 in the totally independent IP cohort. The feature group of dosimetrics had the largest predictive power with RMSE: 0.192, R2: 29.8%, accuracy: 0.678 and ROC-AUC: 0.667; followed by the group of baseline blood cells with predictive power as RMSE: 0.207, R2: 18.9%, accuracy: 0.669 and ROC-AUC: 0.645. Next, by SHAP value analysis, we investigated that integral dose of the total body, V5 dose, mean lung dose and V20 dose of ipsilateral lung/bilateral lungs were in consequence important promote factors for lymphocyte decrease and for the event of lymphopenia, while the features of baseline monocyte, mean heart dose and tumor size played a role of protection at some extend. Conclusions: In this study, we constructed robust XGboost models for predicting the lymphocyte decrease and the event of lymphopenia in breast cancer patients who underwent radiation therapy. We also applied SHAP analysis for revealing the directional contribution of features. These results are important either for the understanding the contributions of dosimetrics on immune response or for the refine of radiation dosimetrics before treatment in future clinical usages.

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Jin, Jian-Yue, Todd Mereniuk, Anirudh Yalamanchali, Weili Wang, Mitchell Machtay, Feng-Ming (Spring)Kong, and Susannah Ellsworth. "A framework for modeling radiation induced lymphopenia in radiotherapy." Radiotherapy and Oncology 144 (March 2020): 105–13. http://dx.doi.org/10.1016/j.radonc.2019.11.014.

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7

Gupta, Priti, Min Wang, and Steven Lin. "Abstract 1118: Mitigating radiation-induced lymphopenia using interleukin-15: Preclinical rationale for clinical translation." Cancer Research 84, no. 6_Supplement (March 22, 2024): 1118. http://dx.doi.org/10.1158/1538-7445.am2024-1118.

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Abstract Background: Radiation therapy is a common treatment for cancer patients, with nearly 50% of them undergoing this procedure. While radiation is effective at targeting tumor cells, it also has the unintended consequence of killing lymphocytes, which are among the most sensitive cells to radiation within the erythroid, myeloid, and lymphoid lineages. This phenomenon is known as radiation-induced lymphopenia (RIL) and is considered a negative prognostic factor in various malignant solid tumors. It occurs severely in over 40% of solid tumor patients who receive radiotherapy. Some previous studies have shown promising results with IL15 therapy in increasing circulating lymphocytes in cancer patients. However, until now, no studies have investigated the impact of IL15 in the context of radiation-induced lymphopenia. Our study aims to investigate whether IL15 can boost lymphocyte numbers and decrease tumor burden following radiation treatment in a mouse model. Methods: To conduct our study, we subcutaneously injected TSA tumor cells into the flank region of mice. Once the tumors reached a palpable size, approximately 50mm3, we divided the mice into four groups: Control (Con), Irradiation (IR), Control with IL15 (Con+IL15), and Irradiation with IL15 (IR+IL15). The irradiated mouse groups received a radiation dose of 2 Gray in the thorax and 1 Gray in the spleen for five consecutive days, simulating the severe radiation-induced lymphopenia observed in cancer patients. After the radiation treatment, the IL15-treated groups received IL15 in combination with recombinant IL15 in a 1:6 ratio weekly. Throughout the experiment, we monitored the circulating lymphocytes and tumor growth. After two weeks following the last radiation dose, we euthanized the mice, collected blood, spleen, and tumor samples, and identified immune cells using flow cytometry. Results: The radiation treatment significantly increased tumor growth while decreasing the number of lymphocytes, including B cells, T cells, and NK cells, in the blood. IL15 administration led to an increase in the number of lymphocytes both in the blood and within the tumor compared to the irradiated group. We observed a trend toward reduced tumor growth in the group that received both IL15 and radiation (IR+IL15) compared to the group that received radiation alone (IR). Conclusion: IL15 effectively boosted the number of lymphocytes in both the bloodstream and tumors, resulting in slower tumor growth in the IL15-treated group compared to the irradiated group. This study is of significant importance as it demonstrates the potential of IL15 to counteract radiation-induced lymphopenia in mice with TSA tumors. Further testing of these findings is currently underway in MC38 tumor-bearing mice, a cell line known to be more radiation-sensitive. Citation Format: Priti Gupta, Min Wang, Steven Lin. Mitigating radiation-induced lymphopenia using interleukin-15: Preclinical rationale for clinical translation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1118.

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Zhao, Qianqian, Tingting Li, Shisuo Du, Jian He, and Zhaochong Zeng. "Shortened Radiation Time Promotes Recovery From Radiation-induced Lymphopenia in Early-Stage Non-small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy." Technology in Cancer Research & Treatment 21 (January 2022): 153303382211122. http://dx.doi.org/10.1177/15330338221112287.

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Background: To evaluate the potential impact of radiation time on radiation-induced lymphopenia (RIL) and subsequently recovery after stereotactic body radiation therapy (SBRT) and to examine the associations between radiation time and with patient outcomes in early-stage non-small cell lung cancer (NSCLC). Methods: Clinical and laboratory records of subjects consisted of 115 patients who had received SBRT for early-stage NSCLC. Clinical and laboratory records were retrospective reviewed to assess the changes in total lymphocyte counts (TLCs) following SBRT. Associations of TLCs kinetics with the clinical and treatment features, and outcomes were analyzed. Results: Most patients (100/115, 86.96%) experienced significantly decreased median TLCs following SBRT (1700 vs 1100 cells/µL; P < .001), and 52 patients (45.21%) met the criteria for lymphopenia. Six months after SBRT, 44 patients (38.26%) had recovered. A negative correlation between TLCs reduction and radiation time was observed ( r = −0.381, P < .001). According to the receiver-operating characteristic curve analysis, the optimal cut-off value for radiation time to was 3950 s to predict lymphocyte count recovery (LR) following RIL was 3950 s ( P < .001). Multivariate analyses demonstrated that radiation time was significantly associated with LR (odds ratio [OR], 0.113; 95% confidence interval [CI], 0.029-0.432; P = .001) but not TLCs reduction ( P = .575). LR within 6 months after SBRT was associated with improved progression-free survival in patients without non-lymphopenia ( P = .034), but had little effect in patients with lymphopenia ( P = .405). Conclusion: A longer radiation time was associated with a lower rate of LR within 6 months after SBRT in patients with early-stage NSCLC. Given the association of severe and persistent RIL with survival in NSCLC, further study of the effect of radiation time on immune status is warranted.

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9

Ishida, Naoko, Yukinori Matsuo, Junki Fukuda, Aritoshi Ri, Saori Tatsuno, Takuya Uehara, Masahiro Inada, et al. "Radiation-Induced Lymphopenia and Its Impact on Survival in Patients with Brain Metastasis." Current Oncology 31, no. 8 (August 9, 2024): 4559–67. http://dx.doi.org/10.3390/curroncol31080340.

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Background: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear. Methods: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0–2, 2–4, and 4–8 weeks after RT completion. Persistent lymphopenia was defined as <800/μL at any time point. Results: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/μL (IQR: 923–1799). Follow-up TLC decreased significantly to 946/μL (626–1316), 992/μL (675–1291), and 1075/μL (762–1435) (p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/μL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group (p = 0.60). Conclusion: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients.

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Gomis Selles, E., Ó. Muñoz Muñoz, B. D. Delgado León, P. Cabrera Roldán, A. M. Burgueño Caballero, and J. L. López Guerra. "PO-1569 Radiation-induced lymphopenia in pediatric high-risk neuroblastoma." Radiotherapy and Oncology 182 (May 2023): S1273—S1274. http://dx.doi.org/10.1016/s0167-8140(23)66484-9.

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11

Al-Hamami, Sarah F. A., Samuel Kurucz, Vladimír Vondráček, Vladimír Pekar, and Jiří Kubeš. "607: Radiation-induced lymphopenia in proton therapy for prostate cancer." Radiotherapy and Oncology 194 (May 2024): S5160—S5162. http://dx.doi.org/10.1016/s0167-8140(24)01179-4.

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12

Alsamari, F., M. Aldehaim, A. Aldakheel, K. Shehzad, M. S. Anwar, G. Mohamed, M. Almahmoud, H. Ghebeh, and N. M. Alrajhi. "The Prognostic Significance of Radiation-Induced Lymphopenia in Nasopharyngeal Carcinoma." International Journal of Radiation Oncology*Biology*Physics 120, no. 2 (October 2024): e730. http://dx.doi.org/10.1016/j.ijrobp.2024.07.1605.

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13

Ellsworth, S., G. Rebesco, K. Fife, and S. Grossman. "Radiation-Induced Lymphopenia and Virologic Outcomes in HIV-Positive Patients Undergoing Radiation for Cancer." International Journal of Radiation Oncology*Biology*Physics 96, no. 2 (October 2016): E526—E527. http://dx.doi.org/10.1016/j.ijrobp.2016.06.1948.

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14

Ellsworth, S. G., T. Mereniuk, H. Zhang, S. Grossman, B. H. O'Neil, R. F. Hobbs, S. Shahda, R. Mohan, F. M. Kong, and J. Y. Jin. "Kinetics and Dosimetric Predictors of Acute Radiation-Induced Lymphopenia in Pancreatic Cancer." International Journal of Radiation Oncology*Biology*Physics 102, no. 3 (November 2018): e71. http://dx.doi.org/10.1016/j.ijrobp.2018.07.414.

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Ellsworth, Susannah G., Todd Mereniuk, Robert F. Hobbs, Hong Zhang, Joseph M. Herman, Stuart A. Grossman, Bert H. O'Neil, et al. "Kinetics and dosimetric predictors of acute radiation-induced lymphopenia in pancreatic cancer." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 300. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.300.

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300 Background: Radiation (RT) induced lymphopenia (RIL) is an adverse prognostic factor in pancreatic cancer (PC) and is likely due to the irradiation of lymphocytes in the RT field. The goal of this study was to identify dosimetric predictors for high rates of absolute lymphocyte count (ALC) loss during RT for PC. Methods: This was a retrospective study of 34 PC patients in an institutional database who had received concurrent 5-FU or gemcitabine-based chemoradiation (50-54 Gy) and had ≥ 3 ALCs measured during RT. Baseline ALC was normal (>1000 cells/uL) in 28/34 (82%) and grade 3-4 RIL occurred in 24/34 (71%). ALC was plotted against fraction # and a best-fit line for each patient was created to determine per-fraction loss in ALC (PFLAC). Linear regression was used to correlate PFLAC with dosimetric parameters including mean dose to gut, liver, kidney, spleen, and cisterna chyli, as well as estimated dose to immune cells (EDIC), which calculates dose to immune cells according to the % of body lymphocytes contained in each organ. Results: All patients exhibited exponential loss in ALC during RT. Mean PFLAC was 6.8% (range 1.7-13.4); fraction # was strongly correlated with ALC (mean R2 = 0.89). Patients with >/= grade 3 lymphopenia had a significantly higher PFLAC than those with grade 0 - 2 lymphopenia (mean daily loss 7.8% in Gr 3-4 vs. 4.8% in Gr 0-2, p = 0.001; independent sample T test). Field size was not correlated with PFLAC for high (> 1 Gy) or low (< 0.5 Gy) isodose volumes. Mean whole body (r = 0.59, p < 0.001), bowel (r = 0.39, p = 0.012), liver (r = 0.42, p = 0.007), and cisterna chyli (r = 0.583, p = 0.004) doses were moderately correlated with PFLAC; mean kidney (r = 0.22, p = 0.11) and spleen (r = 0.26, p = 0.06) doses were weakly correlated with PFLAC. EDIC was more strongly correlated with PFLAC than any individual organ mean dose (r = 0.69, p < 0.001). Conclusions: Patients undergoing RT for PC experience a predictable RIL characterized by an exponential loss of lymphocytes per day. PFLAC is a useful method of characterizing RIL and facilitates evaluation of dosimetric predictors of RIL. We identified dose to cisterna chyli as a significant contributor to RIL in PC; however, EDIC has a stronger correlation with RIL severity than any single organ dose.

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Mohanty, S., A. Singh, U. Velu, K. Sharan, N. P. Jayashree, and S. Lewis Salins. "130P Radiation induced lymphopenia (RAILs on time saves nine): In carcinoma esophagus." Annals of Oncology 33 (November 2022): S1482—S1483. http://dx.doi.org/10.1016/j.annonc.2022.10.166.

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Kuncman, Ł., K. Stawiski, M. Bilski, J. Nowak-Potemska, M. Bilewicz, and J. Fijuth. "Radiation Induced Lymphopenia Depends on Lymph Node Irradiation in Prostate Cancer Radiotherapy." International Journal of Radiation Oncology*Biology*Physics 120, no. 2 (October 2024): e549-e550. http://dx.doi.org/10.1016/j.ijrobp.2024.07.1216.

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Balmanoukian, Ani Sarkis, Xiaobu Ye, Joseph M. Herman, Dan Laheru, and Stuart A. Grossman. "Effect of treatment-related lymphopenia on survival in newly diagnosed patients with resected adenocarcinoma of the pancreas." Journal of Clinical Oncology 30, no. 4_suppl (February 1, 2012): 270. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.270.

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270 Background: Severe treatment-related lymphopenia is associated with shorter survival in patients with high grade gliomas. This study was performed to determine if patients with resected pancreatic adenocarcinoma treated with post-operative radiation and chemotherapy develop significant lymphopenia and if this affects overall survival. Methods: Patients selected for this retrospective analysis underwent pancreatic cancer resection between 1997 and 2008, and received post-operative radiation with gemcitabine or 5-FU based chemotherapy at Johns Hopkins Hospital. Serial lymphocyte counts were recorded and survival was analyzed as a function of lymphopenia and known prognostic factors. Results: Fifty-three adults met the eligibility criteria. Their median age was 64, median tumor size was 3 centimeters, 83% underwent a pancreaticoduodenectomy, 47% had positive margins, and 92% had positive nodes. Total lymphocyte counts were normal in 91% of patients prior to receiving radiation and concomitant chemotherapy with 5FU(59%) or gemcitabine (41%). Total lymphocyte counts fell to <500 cells/mm3 in 45% of patients two months after initiating therapy with a median reduction of 63% from the baseline (p<0.0001). The median survival of patients with lymphocyte counts <500 cells/mm3 at 2 months was 14 months versus 20 months in patients with more lymphocytes (p=0.0485). Univariate analysis revealed no significant association between pre-treatment patient characteristics and survival. Multivariate analysis revealed a significant association between survival and lymphocyte count (<500 vs ≥ 500 cells/mm3) at 2 months (HR 2.2, p = 0.014). Conclusions: Adjuvant radiation and chemotherapy induced lymphopenia is frequent, severe, and an independent predictor for survival in patients with resected pancreatic adenocarcinoma.

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McLaughlin, Mark F., Morshed Alam, Lynnette Smith, Jeffrey Ryckman, Chi Lin, and Michael J. Baine. "Stereotactic body radiation therapy mitigates radiation induced lymphopenia in early stage non-small cell lung cancer." PLOS ONE 15, no. 11 (November 30, 2020): e0241505. http://dx.doi.org/10.1371/journal.pone.0241505.

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Introduction Radiation-induced lymphopenia (RIL) occurs during treatment with conventional radiation in multiple organ sites. Development of RIL portends poor prognosis. Stereotactic body radiation therapy (SBRT) spares RIL in pancreatic cancer, but has not been examined in other sites commonly treated with SBRT. This work examines if SBRT similarly spares RIL in patients with non-small cell lung cancer (NSCLC). Materials and methods Retrospective analysis was done at a single institution on 40 distinct cases of SBRT for early stage NSCLC from 2006–2017. Incidentally collected lymphocyte counts collected within 6 months of SBRT treatment were analyzed to determine if RIL occurred. The presence of RIL was correlated with location of initial failure and survival endpoints. Kaplan-Meier curves were constructed with significance defined at the level p < 0.05. Results RIL was observed in 35% of the analyzed patients. Patterns of failure and survival data were comparable to prior SBRT literature. There was no observed association in two year local, nodal, or distant failure, progression free survival, or overall survival based on the presence of RIL. Discussion SBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents further analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.

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Kim, Daniel W., Grace Lee, Theodore S. Hong, Guichao Li, Eric Roeland, Florence Keane, Christine Elissa Eyler, et al. "Prognostic impact of chemoradiation-related lymphopenia in patients with gastric and gastroesophageal cancer." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 249. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.249.

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249 Background: Limited data exists on how chemoradiation (CRT)-induced lymphopenia affects survival outcomes in patients with gastric and gastroesophageal junction (GEJ) cancer. We evaluated the association between severe lymphopenia and its association with survival in gastric and GEJ cancer patients treated with CRT. We hypothesized that severe lymphopenia would be a poor prognostic factor. Methods: We performed a retrospective analysis of 154 patients with stage 1-3 gastric or GEJ cancer who underwent CRT at our institution. Patients underwent photon-based radiation therapy (RT) with a median dose of 50.4 Gy (IQR 45.0-50.4 Gy) over 28 fractions and concurrent chemotherapy (CTX) with carboplatin/paclitaxel, 5-fluorouracil based regimen, or capecitabine. 49% received CTX prior to RT. 84% underwent surgical resection, 57% pre-CRT and 26% post-CRT. Absolute lymphocyte count (ALC) at baseline and at 2 months since initiating RT were analyzed. Severe lymphopenia, defined as Grade 3 or worse lymphopenia (ALC < 0.5 k/μl), was analyzed for any association with overall survival (OS). Results: Median time of follow up was 48 months. Median age was 65. 77% were male and 86% were Caucasian. ECOG PS was 0 or 1 in 90% and 2 in 10%. Tumor location was stomach in 38% and GEJ in 62%. Timing of CRT was preoperative among 68% and postoperative among 32%. The median ALC at baseline for the entire cohort was 1.6 k/ul (range 0.3-7.0 k/ul). At 2 months post-CRT, 49 (32%) patients had severe lymphopenia. Patients with severe lymphopenia post-CRT had a slightly lower baseline TLC compared to patients without severe lymphopenia (median TLC 1.4 k/ul vs. 1.6 k/ul; p = 0.005). There were no differences in disease and treatment characteristics between the two groups. On the multivariable Cox model, severe lymphopenia post-CRT was significantly associated with increased risk of death (HR = 3.99 [95% CI 1.55-10.28], p = 0.004). ECOG PS 2 (HR = 34.97 [95% CI 2.08-587.73], p = 0.014) and postoperative CRT (HR = 5.55 [95% CI 1.29-23.86], p = 0.021) also predicted worse OS. The 4-year OS among patients with severe lymphopenia was 41% vs. 61% among patients with vs. without severe lymphopenia (log-rank test p = 0.041). Conclusions: Severe lymphopenia significantly correlated with poorer OS in patients with gastric or GEJ cancer treated with CRT. CRT-induced lymphopenia may be an important prognostic factor for survival in this patient population. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia.

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Antunac, Katarina, Petar Suton, and Sara Bilić-Knežević. "Prognostic significance of radiation induced lymphopenia in patients with high risk prostate cancer." Libri Oncologici Croatian Journal of Oncology 46, no. 2-3 (January 29, 2019): 55–59. http://dx.doi.org/10.20471/lo.2018.46.02-03.09.

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Pan, S., P. Sitch, S. Gaito, A. McPartlin, S. Sashidaran, E. Smith, G. Whitfield, and A. Abravan. "PD-0076 Predictive factors of severe radiation-induced lymphopenia in proton-treated patients." Radiotherapy and Oncology 170 (May 2022): S51—S53. http://dx.doi.org/10.1016/s0167-8140(22)02746-3.

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Mohanty, Sheel, Priyanka Augustine, Umesh Velu, Anshul Singh, Anusha Reddy, Shirley Salins, and Krishna Sharan. "CLO22-069: Radiation Induced Lymphopenia (RAILs on Time Saves Nine!) In Carcinoma Esophagus!" Journal of the National Comprehensive Cancer Network 20, no. 3.5 (March 31, 2022): CLO22–069. http://dx.doi.org/10.6004/jnccn.2021.7233.

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Campos, C. Terrones, B. Ledergerber, I. Vogelius, M. Helleberg, L. Specht, and J. Lundgren. "OC-0278 Radiation-induced lymphopenia: Fractionation effect and association with infections and mortality." Radiotherapy and Oncology 133 (April 2019): S137—S138. http://dx.doi.org/10.1016/s0167-8140(19)30698-x.

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Ellsworth, S. G., H. Zhang, T. Mereniuk, N. Agrawal, R. C. Zellars, F. M. Kong, and J. Y. Jin. "Factors Affecting Kinetics of Acute Radiation-Induced Lymphopenia in Patients with Gastrointestinal Cancer." International Journal of Radiation Oncology*Biology*Physics 102, no. 3 (November 2018): e162-e163. http://dx.doi.org/10.1016/j.ijrobp.2018.07.623.

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MIRESTEAN, Camil Ciprian, Roxana Irina IANCU, and Dragos Teodor IANCU. "Immunotherapy and radiotherapy – a future partnership Focus on radiation induced lymphopenia (RIL) implications." Bratislava Medical Journal 124, no. 01 (2022): 70–73. http://dx.doi.org/10.4149/bll_2023_011.

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Kanehira, Takahiro, Hiroshi Taguchi, Jun Sakakibara-Konishi, Norio Katoh, Yusuke Uchinami, Keiji Kobashi, Takayuki Hashimoto, and Hidefumi Aoyama. "1081: Comparing predictors of radiation-induced lymphopenia in various timeframes in NSCLC radiotherapy." Radiotherapy and Oncology 194 (May 2024): S5012—S5015. http://dx.doi.org/10.1016/s0167-8140(24)01550-0.

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Chan, Landon L., Vanessa T. Y. Yeung, Frankie Mo, Darren M. C. Poon, Macy Tong, Florence S. T. Mok, Winnie M. T. Soo, et al. "336: Radiation-induced lymphopenia predicts poor survival in HCC patients treated with radiotherapy." Radiotherapy and Oncology 194 (May 2024): S2133—S2137. http://dx.doi.org/10.1016/s0167-8140(24)00989-7.

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Monti, Serena, Giuseppe Palma, Radhe Mohan, Ting Xu, Zhongxing Liao, and Laura Cella. "950: Prediction of radiation induced lymphopenia during chemoradiation therapy for lung cancer patients." Radiotherapy and Oncology 194 (May 2024): S5006—S5008. http://dx.doi.org/10.1016/s0167-8140(24)01449-x.

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Sun, G., S. Wang, Y. Song, J. Jin, Y. Liu, H. Ren, H. Fang, et al. "Radiation-Induced Lymphopenia is Associated with Radiation Fractionation and Predicts Poorer Prognosis in Patients with Breast Cancer." International Journal of Radiation Oncology*Biology*Physics 105, no. 1 (September 2019): E46. http://dx.doi.org/10.1016/j.ijrobp.2019.06.2369.

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Chen, Fang, Hao Yu, Hong Zhang, Yaqing Nong, Qian Wang, Haiman Jing, Ying Han, et al. "Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy." Annals of Translational Medicine 9, no. 16 (August 2021): 1288. http://dx.doi.org/10.21037/atm-21-2150.

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Pike, Luke R. G., and Jonathan D. Schoenfeld. "Radiation-induced lymphopenia may negatively affect outcomes in patients receiving PD-1 directed immunotherapy." Therapeutic Radiology and Oncology 3 (December 2019): 37. http://dx.doi.org/10.21037/tro.2019.10.01.

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Spina, C. S., B. Wothuis, C. Elliston, F. Baez, and T. J. C. Wang. "Chemoradiation-Induced Lymphopenia in Glioblastoma Patients and the Influence of Total Radiation Exposure Time." International Journal of Radiation Oncology*Biology*Physics 99, no. 2 (October 2017): E110—E111. http://dx.doi.org/10.1016/j.ijrobp.2017.06.858.

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34

Damen, Pim J. J., Max Peters, Brian Hobbs, Yiqing Chen, Uwe Titt, Remi Nout, Radhe Mohan, Steven H. Lin, and Peter S. N. van Rossum. "923: Defining the optimal radiation-induced lymphopenia metric to discern survival in esophageal cancer." Radiotherapy and Oncology 194 (May 2024): S2176—S2178. http://dx.doi.org/10.1016/s0167-8140(24)01428-2.

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35

Bendavid, Jerome, Roger Sun, Pierre Blanchard, Eric Deutsch, Philippe Gorphe, Yungan Tao, France Nguyen, Ines Chaffai, Camelia Billard Sandu, and Caroline Even. "Radiation induced lymphopenia in unilateral versus bilateral radiochemotherapy in treatment of head and neck cancer: A retrospective case-control study." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e18065-e18065. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e18065.

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e18065 Background: Grade 3+ radiation-induced lymphopenia is a frequent biological complication of external beam radiotherapy (RT) in the management of head and neck cancers, likely due to the large irradiated cervical volume. This complication has been shown to be a significant prognostic factor for mortality. The aim of this study is to evaluate the difference in lymphopenia and prognosis between unilateral and bilateral prophylactic lymph node irradiation in head and neck cancers. Methods: This is a retrospective, single center case – control study in patients who received unilateral or bilateral radio chemotherapy for head and neck cancers between 2014 and 2020. Cases (unilateral neck irradiation) were matched to controls (bilateral neck irradiation) according to initial TNM, histology, tumor location, postoperative status. The comparison of the evolution of the lymphocyte count during treatment was evaluated by univariate analysis, as well as the evaluation of the overall survival (OS) and the progression free survival (PFS) between these two groups. Another univariate analysis is used to compare OS and PFS in these two groups between patients who developed Grade 3 or higher lymphopenia during treatment and those who did not. Results: In this retrospective study, 94 patients were analyzed (n = 47 in the RT unilateral group and n = 47 in the RT bilateral group). All patients received concomitant systemic therapy. Median age was 59,3 years in the unilateral group (vs 59 years in the control group). Radiotherapy was given postoperatively in 66% vs 53.2% of patients. Squamous cell carcinoma was the most frequent histological subtype with 93,6% in each RT group. All patients were treated in Intensity modulated radiation therapy (IMRT). Median follow up was 38 months in the case group and 37,6 months in the control group. Biological data from the start of radiotherapy to day 100 posttreatment was available for 90 patients (45 in each group). A linear regression model as a function of time and lymphocyte count estimated a -0.011 G/l decrease in lymphocyte count each day and a higher lymphocyte count with unilateral neck irradiation of 0.16 G/l. This was consistent with a mixed model considering the patient as a random effect. In univariate analysis, the lymphocyte nadir was significantly higher in the unilateral group 0.30 [0.15- 0,42] vs 0.37 [0,26-0.48] p = 0,029, with no significant difference in OS and PFS between these two groups. In each of the two groups, there was no significant difference in OS and PFS according to the presence or absence of grade 3 or higher lymphopenia during the treatment. Conclusions: This study, although retrospective, showed a slight benefit on radiation-induced lymphopenia in the context of unilateral radiotherapy without negative impact on OS and PFS.

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Chen, F., H. Yu, Y. Nong, H. Jing, Y. Han, J. Wu, M. Zhou, et al. "Risk Factors for Radiation Induced Lymphopenia in Patients With Breast Cancer: Does Radiotherapy Technique Matter?" International Journal of Radiation Oncology*Biology*Physics 111, no. 3 (November 2021): e204-e205. http://dx.doi.org/10.1016/j.ijrobp.2021.07.727.

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Monti, Serena, Ting Xu, Zhongxing Liao, Radhe Mohan, Laura Cella, and Giuseppe Palma. "On the interplay between dosiomics and genomics in radiation-induced lymphopenia of lung cancer patients." Radiotherapy and Oncology 167 (February 2022): 219–25. http://dx.doi.org/10.1016/j.radonc.2021.12.038.

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Monti, S., L. Cella, T. Xu, R. Mohan, Z. Liao, and G. Palma. "OC-0637 Thoracic dose patterns associated with radiation induced lymphopenia in patients treated for NSCLC." Radiotherapy and Oncology 161 (August 2021): S502—S503. http://dx.doi.org/10.1016/s0167-8140(21)06993-0.

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Zhao, X., H. Fang, H. Jing, N. Zhang, J. Zhang, J. Jin, Q. Z. Zhong, et al. "Radiation-Induced Lymphopenia in Patients with Breast Cancer after Mastectomy: Results from Chinese POTENTIAL Trial." International Journal of Radiation Oncology*Biology*Physics 114, no. 3 (November 2022): e39. http://dx.doi.org/10.1016/j.ijrobp.2022.07.760.

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Ishida, Naoko, Yukinori Matsuo, Aritoshi Ri, Saori Tatsuno, Masahiro Inada, Tomohiro Matsuura, Hiroshi Doi, Kiyoshi Nakamatsu, and Makoto Hosono. "744: Radiation-induced lymphopenia and its impact on survival in patients treated with brain radiotherapy." Radiotherapy and Oncology 194 (May 2024): S782—S784. http://dx.doi.org/10.1016/s0167-8140(24)01287-8.

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41

Sampson, J. H., K. D. Aldape, M. R. Gilbert, S. J. Hassenbusch, R. Sawaya, B. Schmittling, G. E. Archer, et al. "Temozolomide as a vaccine adjuvant in GBM." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 2020. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.2020.

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2020 Background: Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide (TMZ) is an effective chemotherapeutic for patients with glioblastoma multiforme (GBM), but it induces significant lymphopenia. Methods: In a Phase II trial, patients with newly-diagnosed, completely resected GBM are vaccinated with an EGFRvIII-specific peptide q2 weeks X 3 after radiation (XRT)(∼60Gy) and TMZ (75mg/m2/d) and then monthly with 5 day TMZ cycles (200mg/m2/d). Results: TMZ induces transient, Grade 3 lymphopenia (< 500 cells/uL) in 70% of patients after the first TMZ cycle with nadirs occurring 14–21 days after treatment (n=10). Regulatory T cell (TReg) (CD4+CD25++CD45RO+FOXP3+) levels increased from 5.2+1.5% (3.3 - 7.5) to 11.8+2.6% (6.9 - 13.8)(P=0.0004; paired t-test) with TMZ and XRT and averaged 12.2+4.0% (6.4 - 18.1) after the second TMZ cycle (P=0.007) (n=6). Despite these findings, in patients assayed, both humoral and cellular EGFRvIII-specific immune responses appear to be enhanced with TMZ. Median survival and TTP after vaccination is 26.2 weeks with no patients progressing (n=8). Conclusions: Despite conventional dogma, we demonstrated that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. TMZ-induced lymphopenia may prove to be synergistic with a peptide vaccine. No significant financial relationships to disclose.

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Sun, Joseph C., Joshua N. Beilke, Natalie A. Bezman, and Lewis L. Lanier. "Homeostatic proliferation generates long-lived natural killer cells that respond against viral infection." Journal of Experimental Medicine 208, no. 2 (January 24, 2011): 357–68. http://dx.doi.org/10.1084/jem.20100479.

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Cells of the immune system undergo homeostatic proliferation during times of lymphopenia induced by certain viral infections or caused by chemotherapy and radiation treatment. Natural killer (NK) cells are no exception and can rapidly expand in number when placed into an environment devoid of these cells. We explored the lifespan and function of mouse NK cells that have undergone homeostatic proliferation in various settings of immunodeficiency. Adoptive transfer of mature NK cells into lymphopenic mice resulted in the generation of a long-lived population of NK cells. These homeostasis-driven NK cells reside in both lymphoid and nonlymphoid organs for >6 mo and, similar to memory T cells, self-renew and slowly turn over at steady state. Furthermore, homeostatically expanded NK cells retained their functionality many months after initial transfer and responded robustly to viral infection. These findings highlight the ability of mature NK cells to self-renew and possibly persist in the host for months or years and might be of clinical importance during NK cell adoptive immunotherapy for the treatment of certain cancers.

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Ghosh, Subhajit, Ran Yan, Sukrutha Thotala, Arijita Jash, Anita Mahadevan, Tong Hu, Byung Ha Lee, et al. "EXTH-14. A NOVEL LONG-ACTING INTERLEUKIN-7 AGONIST, NT-I7, INCREASES CYTOTOXIC CD8 CELLS AND ENHANCES SURVIVAL IN MOUSE GLIOMA MODELS." Neuro-Oncology 22, Supplement_2 (November 2020): ii89. http://dx.doi.org/10.1093/neuonc/noaa215.368.

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Abstract BACKGROUND Patients with glioblastoma (GBM) are treated with radiation (RT) and temozolomide (TMZ). These treatments can cause prolonged severe lymphopenia, which is associated with shorter survival. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 would protect T cells from treatment-induced lymphopenia and improve survival. METHODS C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-17 (10 mg/kg on the final day of RT completion). We followed for survival and profiled CD3, CD8, CD4, FOXP3 in peripheral blood over time. In parallel, we assessed cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. RESULTS Median survival in mice treated with NT-I7 combined with RT was significantly better than RT alone (GL261: 40d vs 34d, p< 0.0021; CT2A: 90d vs 40d, p< 0.0499) or NT-I7 alone (GL261: 40d vs 24d, p< 0.008; CT2A: 90d vs 32d, p< 0.0154). NT-17 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261 (40d vs 47d) and CT2A (90d vs 90d). NT-I7 treatment significantly increased the amount of CD8+ cells in the peripheral blood and tumor. NT- I7 rescued CD8+ T cells from RT induced lymphopenia in peripheral blood, spleen, and lymph nodes. NT-I7 alone or NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood and tumor while reducing the FOXP3+ T-reg cells in the tumor microenvironment. CONCLUSIONS NT-I7 protects T-cells from RT induced lymphopenia, improves cytotoxic CD8+ T lymphocytes systemically and in the tumor, and improves survival. Presently, a phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

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Venkatesulu, Bhanu Prasad, Supriya Mallick, Steven H. Lin, and Sunil Krishnan. "A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors." Critical Reviews in Oncology/Hematology 123 (March 2018): 42–51. http://dx.doi.org/10.1016/j.critrevonc.2018.01.003.

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van Rossum, P. S. N., B. Stam, C. Juan-Cruz, M. M. G. Rossi, J. Belderbos, and J. J. Sonke. "Severe Radiation-Induced Lymphopenia during Concurrent Chemoradiotherapy for Lung Cancer: External Validation of Two Prediction Models." International Journal of Radiation Oncology*Biology*Physics 114, no. 3 (November 2022): e394. http://dx.doi.org/10.1016/j.ijrobp.2022.07.1553.

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46

van Rossum, P., P. Damen, T. Xu, B. Hobbs, R. Mohan, Z. Mohan, and S. Lin. "PD-0152 Radiation-induced lymphopenia risk model predicts durvalumab benefit in non-small cell lung cancer." Radiotherapy and Oncology 182 (May 2023): S113—S114. http://dx.doi.org/10.1016/s0167-8140(23)08796-0.

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47

Appel, S., J. Bar, Y. R. Lawrence, D. Urban, Z. Symon, J. Goldstein, and S. Felder. "PD-0153 Radiation induced lymphopenia, its effect on pathologic regression and prognosis in LA lung cancer." Radiotherapy and Oncology 182 (May 2023): S114—S115. http://dx.doi.org/10.1016/s0167-8140(23)08797-2.

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Chuong, Michael D., Roberto Herrera, Nicolas Carvallo, Muni Rubens, Rupesh Kotecha, Matthew D. Hall, Kathryn E. Mittauer, Nema Bassiri-Gharb, Alonso N. Gutierrez, and Adeel Kaiser. "Abstract A004: Lymphopenia and spleen dose for inoperable pancreatic cancer patients receiving ablative 5-fraction radiation therapy." Cancer Research 84, no. 2_Supplement (January 16, 2024): A004. http://dx.doi.org/10.1158/1538-7445.panca2023-a004.

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Abstract Background: Treatment-induced lymphopenia in pancreatic ductal adenocarcinoma (PDAC) patients after radiation therapy (RT) may negatively impact overall survival (OS). While non-ablative RT (NA-RT) is routine for borderline resectable (BRPC) and locally advanced (LAPC) PDAC, ablative RT (A-RT) has garnered increasing interest based on data suggesting improved clinical outcomes including OS. Absolute lymphocyte count (ALC) changes after A-RT and the potential association with spleen dose in this setting have not been previously described. Methods: We performed a single-institution retrospective analysis of BRPC, LAPC, and medically inoperable PDAC patients to evaluate ALC values 1 month before vs. 1-3 months after A-RT and evaluate their association with patient outcomes. All patients were treated with 5-fraction A-RT on a 0.35 T MR-Linac using step-and-shoot IMRT with ~15-20 fields; the spleen was not considered an organ-at-risk during treatment planning. Lymphopenia was assessed using CTCAE version 5.0. Results: 101 patients were evaluated with median age 71 years (range 35-94 years), median maximum tumor size of 3.6 cm (range, 1.3-6.8 cm), and frequently tumor in the pancreas head (84.2%). Most had LAPC (61.4%) followed by BRPC (28.7%). Induction chemotherapy (ICT) was routine (89.1%), most commonly FOLFIRINOX (61.4%) with a median ICT duration of 5.2 months (range, 0.2-14.0 months). Median prescribed dose was 50 Gy (range, 40-50 Gy). The median mean spleen dose was 2.75 Gy (range, 0.38-16.79 Gy). The median spleen V5Gy, V10Gy, V15Gy, and V20Gy were 12.8% (range, 0 - 77.5%), 1.9% (range, 0 - 66.2%), 0% (range, 0 - 54.5%), and 0% (range, 0 - 39.2%), respectively. [KEM1] The median ALC at a median 25.5 days before A-RT was 1.39 no./mL (range, 0.24 - 3.00 no./mL), and this decreased to 0.85 no./mL (range, 0.20-2.45 no./mL) a median 6 weeks after A-RT[MH2]. Grade 2 lymphopenia (G2L) prior to vs. after A-RT was 6.9% vs. 27.7% (p<0.001). Grade 3 lymphopenia (G3L) prior to vs. after A-RT was 1.0% vs. 13.9% (p<0.001). No grade 4+ lymphopenia was observed. Significant factors on multivariable analysis (MVA) for G2L were age (OR: 1.05, 95% CI 1.01-1.09, p=0.019), male vs. female (OR: 0.30, 95% CI:0.11-0.82, p=0.019), and T1-3 vs. T4 (OR: 0.27, 95% CI: 0.10-0.71, p=0.007); ICT duration, target volume dose/volume, and spleen dose were not significant on univariate analysis (UVA). No factors were significant on UVA for G3L, but a trend was observed for T1-3 vs. T4 (OR[MH3] : 3.5, 95% CI: 0.91-13.42, p=0.067) and spleen V5Gy (OR: 1.44, 95% CI: 0.85-3.26, p=0.065). Discussion: To our knowledge, this is the first study to evaluate spleen dose and ALC changes after A-RT for PDAC. We observed a similar incidence of grade 2+ lymphopenia compared to prior 5-fraction NA-RT studies. There was a trend towards significance of higher spleen V5Gy being associated with a higher probability of G3L. We are currently evaluating whether grade 2+ lymphopenia is associated with long-term clinical outcomes after A-RT for inoperable PDAC. Citation Format: Michael D. Chuong, Roberto Herrera, Nicolas Carvallo, Muni Rubens, Rupesh Kotecha, Matthew D. Hall, Kathryn E. Mittauer, Nema Bassiri-Gharb, Alonso N. Gutierrez, Adeel Kaiser. Lymphopenia and spleen dose for inoperable pancreatic cancer patients receiving ablative 5-fraction radiation therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A004.

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Dai, Dongjun, Qiaoying Tian, Genhua Yu, Yongjie Shui, Hao Jiang, and Qichun Wei. "Severe Radiation-Induced Lymphopenia Affects the Outcomes of Esophageal Cancer: A Comprehensive Systematic Review and Meta-Analysis." Cancers 14, no. 12 (June 20, 2022): 3024. http://dx.doi.org/10.3390/cancers14123024.

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The aim of the current study was to evaluate the influence of severe radiation-induced lymphopenia (RIL) on the outcomes of esophageal cancer (EC). A systematic review and meta-analysis was performed through the PRISMA guideline. Seventeen studies were included in the current systematic review, with eight included in the meta-analyses. Meta-analyses found that severe RIL was associated with lower pathologic complete response (pCR) rate (odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.30–0.66, I2 = 0%), inferior overall survival (OS) (hazard ratio (HR) = 1.50, 95% CI = 1.29–1.75, I2 = 6%), and worse progression-free survival (PFS) (HR = 1.70, 95% CI = 1.39–2.07, I2 = 0%) of EC patients. The lymphocyte nadir was found during 4–6 weeks after the start of radiotherapy. The leading dosimetric factors associated with severe RIL included larger PTV, higher dose to heart and body, and higher effective dose to the immune cells (EDIC). Clinical risk factors for RIL mainly comprised lower baseline ALC, higher tumor length and clinical stage, and distal EC. In conclusion, severe RIL might be associated with a lower pCR rate and worse OS and PFS of EC patients. Minimizing the dosimetric risk factors, especially in patients with clinical risk factors, might benefit their outcomes.

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Damen, P., T. Kroese, R. van Hillegersberg, E. Schuit, M. Peters, J. Verhoeff, S. Lin, and P. van Rossum. "PO-1515 Meta-analysis on the influence of radiation-induced lymphopenia on overall survival in solid tumors." Radiotherapy and Oncology 161 (August 2021): S1241—S1242. http://dx.doi.org/10.1016/s0167-8140(21)07966-4.

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