Добірка наукової літератури з теми "NTCP; second cancer; prostate radiotherapy"

Objective. To determine the most effective irradiation regimen (total dose and dose per fraction) for hypofractionated treatment for prostate carcinomas according the TCP/NTCP radiobiological criteria.Material and methods. Using the tomographic information of five patients with low-risk prostate adenocarcinoma as an example, the authors devised dosimetric radiation therapy plans using the volumetric modulated arc therapy (VMAT) procedure. They considered the range of total doses of 33.5 to 38 Gy administered in 4 and 5 fractions. Based on the equivalent uniform dose concept proposed by A. Niemierko and on the computed differential dose volume histograms, the investigators modeled local tumor control probability (TCP) values, by taking into account the uncertainties of main radiobiological parameters, and estimated normal tissue complication probabilities (NTCP) for the anterior rectal wall as the organ most at risk of irradiation. An effective dosimetric plan was selected according to the UTCP criterion and the probability of complication-free tumor control, i.e. TCP (1 – NTCP).Results. The results of modeling the UTCP criterion show that with a higher total dose, the TCP value increases and so does the NTCP value, therefore the optimal radiation therapy plans are to irradiate with a total dose of 34 Gy over 4 fractions or with a dose of 36–37 Gy over 5 fractions. The difference between the fractionation regimens is that the UTCP value is achieved with a higher TCP value over 4 fractions and with a lower load on the rectal wall over 5 fractions.Conclusion. The choice of a specific fractionation regimen should be determined from the calculated values of differential dose volume histograms for each patient, as well as from radiobiological criteria, such as TCP, NTCP and UTCP.

107 Background: Prostate dose-painting radiotherapy and hypo-fractionation both can improve biochemical contol in localised disease. We report toxicity and outcome for a cohort of high risk patients. Methods: We selected 28 patients with high-risk localised prostate cancer and 2 or 3 risk factors. Functional MRI’s were used to define boost volumes with a margin of 5 mm PTV. Neo-adjuvant hormone therapy was given for 3 months. Dose volume constraints, TCP and NTCP parameters were used for optimization of rotational IMRT treatment plans. We used fiducial markers, bowel and bladder preparation and daily IGRT. Results: Mean age was 66 years, mean PSA was 17.4 ng/ml (range 4.6-59.1), 20 patients had T3a and 10 had Gleason score ≥ 8. The mean dose to the prostate excluding the boost volume was 61.4 Gy (range 60.6-62.3) and the boost PTV 66.1 Gy (range 60.9-72.5). Mean NTCP for rectal bleeding was 4.7% (range 3.4-5.8), for faecal incontinence 3.5% (range 2.3-5) and mean TCP 75% (range 71-79) assuming a 71% biochemical control at 5 years for a standard plan. All patients completed radiotherapy, 16/28 patients had acute bladder toxicity grade 2 (RTOG score), but no grade 3 toxicity was observed. Worst acute bowel toxicity was grade 1 (4/28). Mean follow up was 15 months (range 8-25). For the 20 patients who had neo-adjuvant hormone therapy beyond 6months, the mean PSA was 0.33 ng/ml (range 0.2-0.8), 2 patients had relapsed at 12 month, 6 patients are still on hormone therapy. 4 patients had Grade 2 urinary late toxicities (CTCv4). Two patients developed grade 1 diarrhoea. Patient reported outcomes >6 month after completion of radiotherapy (EPIC QOL questionnaire) demonstrated similar scores to controls without prostate cancer for the bowel domains; reduction in the urinary domains was similar to other cohorts treated with external beam radiotherapy and hormone therapy. Conclusions: In this high risk group, dose escalation with hypo-fractionated dose painting radiotherapy achieved good biochemical control and urinary and bowel toxicity similar to standard dose radiotherapy during follow up.

153 Background: The volume of rectum receiving high-dose (i.e. > or = 60 Gy) is consistently associated with the risk of Grade > or = 2 rectal toxicity or rectal bleeding based on common terminology criteria for adverse events (CTCAE). Our goal was to compare intensity-modulated photon radiotherapy (IMRT) with proton radiotherapy in regard to the rectal dose using the normal tissue complication probability (NTCP). Methods: Between July 2014 and September 2015 the first 10 consecutive low or intermediate risk prostate cancer patients were treated with proton therapy at our institution. All 10 patients were planned with three-dimensional conformal proton therapy (3D-CPT) using two parallel opposed fields as well as comparison IMRT plans. A rectal balloon filled with water was used in all patients treated. Prescribed dose to the prostate was 79.2 Gy or cobalt Gy equivalent (CBE) for protons. Dose-volume histograms were compared. The Lyman-Kutcher-Burman model (n = 0.09, m = 0.13, and TD50 = 76.9 Gy) was used to generate NTCP estimates for both IMRT and proton plans. Results: At least 95% of the planning target volume received the prescription dose for both proton and IMRT plans. Dose constraints placed on the rectum included volume receiving 65 Gy (V65) less than 17% and V40 less than 35%. The mean dose to the rectum was 24.5 Gy (range, 19.5-30.1 Gy) and 31.7 Gy (range, 23.7-39.4 Gy) for the proton and IMRT plans, respectively. The V65 constraint was unachievable in 3 of the proton plans and 3 of the IMRT plans. The mean V70 and V75 for proton plans was 8.4% and 5.4% compared to 7.5% and 4.8% for the IMRT plans. The mean NTCP for proton treatment plans was 7.72% (range, 2.7-11.7%) and 7.92% (range, 1.7-15.3%) for IMRT (P = 0.45). After median follow-up of 6 months, no grade 2 or higher toxicity has been reported. Conclusions: Utilizing NTCP estimations, proton therapy and IMRT have similar predicted rates of rectal toxicity. Currently, a Phase III randomized clinical trial is underway comparing proton therapy and IMRT with regards to rectal toxicity and quality of life.

135 Background: ED remains a common toxicity of prostate RT despite technological advances. Penile bulb (PB) dose has been proposed as a predictor of ED post RT. The main objective of this study was to develop NTCP models for ED. Methods: 162 men treated within the CHHiP IGRT substudy (CRUK/06/16) had baseline clinical data, PB dosimetric data & evaluation of ED using EPIC-26 at least 3 years post RT. Planning CT and reference dose distributions were imported into analysis software (VODCA, MSS GmbH) and PB retrospectively contoured by one clinician. The defined endpoint (severe ED) was a standardised average value of 0-33 for EPIC-26 sexual domain. Predictive models of ED were generated using PB dose in EQD2 (α/β ratio = 3Gy) & clinical data (age, diabetes, hypertension, NCCN risk group, baseline PSA, hormone therapy, IGRT, margin size, PB volume). Multivariate logistic regression method using resampling methods was applied to select model order and parameters. Models were fitted using logistic regression of the form Probability = eA(x)/1+eA(x), where A(x) = constant + sum of (variables * associated regression coefficients). Model performance was evaluated through area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow (HL) goodness-of-fit test. Results: 101/162 (62%) men had severe ED with statistically significant difference in PB max and mean dose between those patients with or without severe ED (max: 61.8Gy vs 43Gy & mean: 27.4Gy vs 14Gy respectively; p = 0.001). In the univariate analyses, age, diabetes, risk group, PB mean and max doses were significantly associated with EPIC calculated severe ED. The optimal NTCP model (AUC 0.78; CI 0.71-0.86: p for HL = 0.75) for EPIC calculated severe ED included age, PB mean dose and diabetes where A(x) = -10.13+(0.14*age)+(0.03*PB mean dose)+(2.88 if diabetic). A comparable model using clinician completed outcomes will be reported. Conclusions: This study provides the first known clinical prediction model for ED including PB dose, with good model performance. The determined predictors for the NTCP model of severe ED in this cohort were PB mean dose, age & diabetes. External validation of this model is desirable. Clinical trial information: 97182923.

The chief aim in developing radiation treatment plans is to maximise tumour cell kill while minimising the killing of normal cells. The acceptance by a radiation oncologist of a radiation therapy treatment plan devised by the radiation therapist, at present is largely based on the oncologists' previous clinical experience with reference to established patterns of treatment and their clinical interpretation of the dose volume histogram. Some versions of radiotherapy planning computer software now incorporate a function that permits biologically based predictions about the probability of tumour control (TCP) and/or normal tissue complications (NTCP). The biological models used for these probabilities are founded upon statistical and mathematical principles as well as radiobiology concepts. TCP and NTCP potentially offer the capability of being able to better optimise treatments for an individual patient's tumour and normal anatomy. There have been few attempts in the past to correlate NTCPs to actual treatment complications, and the reported complications have generally not shown any significant correlation. Thus determining whether either or both NTCPs and TCPs could be correlated with the observed clinical outcomes of prostate radiotherapy is the central topic of this thesis. In this research, TCPs and NTCPs were prospectively calculated for prostate cancer patients receiving radiation therapy, and subsequently assessed against the clinical results of the delivered treatments. This research was conducted using two different types of NTCP models, which were correlated against observed treatment-induced complications in the rectum and bladder. The two NTCP models were also compared to determine their relative efficacy in predicting the recorded toxicities. As part of this research the refinement of some of the published bladder parameters required for NTCP calculations was undertaken to provide a better fit between predicted and observed complication rates for the bladder wall which was used in this research. TCPs were also calculated for each patient using the best available estimate of the radiosensitivity of the prostate gland from recent research. The TCP/NTCP data was analysed to determine if any correlations existed between the calculated probabilities and the observed clinical data. The results of the analyses showed that a correlation between the NTCP and a limited number of toxicities did occur. Additionally the NTCP predictions were compared to existing parameters and methods for radiotherapy plan evaluation - most notably DVHs. It is shown that NTCPs can provide superior discriminatory power when utilised for prospective plan evaluation. While the TCP could not be correlated with clinical outcomes due to insufficient follow-up data, it is shown that there was a correlation between the TCP and the treatment technique used.

Ce travail de thèse est centré sur l'établissement de modèles prédictifs de toxicité radio-induite et sur l’étude de leur intérêt en cas de radiothérapie par modulation d’intensité. Six modèles NTCP ont été implémentés et leur paramètres identifiés pour la prédiction des toxicités rectale et vésicale tardives dans le cancer de la prostate. Leur capacité prédictive a été démontrée pour les deux organes. Par ailleurs, le modèle LKB a été utilisé pour la prédiction de l’œsophagite aiguë en cas de radiothérapie du cancer bronchique non à petites cellules. Ensuite, le bénéfice tiré de l’incorporation du paramètre de dose équivalent uniforme (EUD) pour la planification inverse de la radiothérapie par modulation d’intensité (IMRT) a été évalué. L’évaluation de cette approche a montré une baisse significative de la dose dans les parois vésicale et rectale. L’incorporation de plusieurs modèles biologiques dans le processus d’optimisation de l’IMRT a aussi été réalisée. Des fonctions objectif ont été établies pour les différents facteurs biologiques comme le NTCP, l’EUD et le TCP. Les résultats dosimétriques obtenus montrent la supériorité de l’optimisation basée sur des facteurs biologiques sur celle reposant uniquement sur des facteurs physiques. Enfin, les modèles NTCP classiques ont été améliorés en intégrant un paramètre radiobiologique supplémentaire, le rapport α/β. Ce rapport α/β a été identifié pour différents types de toxicité. Avec ce nouveau paramètre, les modèles NTCP peuvent finalement être étendus à des patients traités suivant différents fractionnements, les traitements hypofractionnés étant de plus en plus utilisés
This thesis is focused on the predictive models of irradiation induced toxicities in intensity modulated radiotherapy. Six different NTCP models were implemented and their parameters were identified at predicting late rectal and bladder toxicities in prostate cancer. Their predictive skills have been demonstrated on both organs. Second, LKB model was used to predict the irradiation induced acute esophagitis after nun-small-cell lung cancer. Then, the benefit of using EUD in prostate cancer IMRT inverse planning was evaluated. The evaluation of the proposed approach proved that the use of EUD significantly decreased both the dose in the bladder and rectum walls. Then, the incorporation of different biological models in IMRT optimization process has been realized. Objective functions were established for different biological factors like NTCP, EUD and TCP. Obtained results show the superiority of the optimization based on biological factors over the optimization relying only on physical factors. Finally, classical NTCP models were corrected to deal with another radiobiological parameter, the α/β ratio. With this additional factor, NTCP models can be extended to predict toxicity for patients with different dose fractionation, these kinds of treatments being more and more clinically used

Orientador: Marco Antônio Rodrigues Fernandes
Resumo: O sucesso da radioterapia está intimamente ligado à razão terapêutica que representa o quociente entre a quantidade de tecido tumoral irradiado e o volume de tecido sadio atingido. A Probabilidade de Complicação em Tecidos Normais (NTCP) e a Probabilidade de Controle do Tumor (TCP) são parâmetros fornecidos por Sistemas de Planejamentos de Tratamentos (TPS) computadorizados, usados na rotina da radioterapia que auxiliam na interpretação da qualidade do tratamento. Neste trabalho são analisados os planejamentos de radioterapia de 03 pacientes portadores de câncer de próstata. Os planejamentos dos tratamentos foram realizados no TPS XiO, simulando as técnicas de radioterapia por intensidade modulada de feixe (IMRT) e radioterapia tridimensional conformada (3D-CRT). A dose de radiação preconizada para o volume de tratamento planejado (PTV) foi de 7.600 cGy, as simulações foram realizadas para um arranjo de 6 campos de radiação com feixes de raios X de megavoltagem e energia de 10 MV. Os volumes prostáticos variaram entre 107 cm3 e 143 cm3. A dose de cobertura D98% do PTV variou de 6.940 cGy a 7.570 cGy com IMRT e de 6.410 cGy a 7.250 cGy com 3D-CRT. Os valores obtidos para o TCP ficaram entre 73,5% a 81,1% com IMRT e entre 70,6% a 75,9% com 3D-CRT. Considerando os valores de NTCP para o reto e a bexiga, os maiores valores encontrados foram 6,9% para o reto e 6,1% para a bexiga, ambos planejados com a técnica de 3D-CRT. Para os casos analisados, os resultados mostram que a técnic... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The success of radiotherapy is closely related to the therapeutic ratio which represents the ratio of the amount of irradiated tumor tissue to the volume of healthy tissue achieved. Normal Tissue Complication Probability (NTCP) and Tumor Control Probability (TCP) are parameters provided by computerized treatment planning systems (TPS), used in radiotherapy routine and also allow the interpretation of treatment quality. The aim of this work is analyze the planning of 03 cases of patients submitted to prostate cancer radiotherapy. The treatment plans were performed in TPS XiO, simulating the techniques of beam intensity modulated radiotherapy (IMRT) and tree-dimensional conformal radiation therapy (3D-CRT). The recommended radiation dose for the planned treatment volume (PTV) was 7600 cGy, the simulations were performed for an arrangement of 6 radiation fields with megavoltage X-ray beams and 10 MV energy. Prostatic volumes ranged from 107cm3 to 143cm3 . The D98% PTV coverage dose ranged from 6,940 cGy to 7,570 cGy with IMRT and from 6,410 cGy to 7,250 cGy with 3D-CRT. The values obtained for TCP were between 73.5% to 81.1% with IMRT and between 70.6% to 75.9% with 3D-CRT. Considering the NTCP values for the rectum and bladder, the highest values found were 6.9% for the rectum and 6.1% for the bladder, both planned using the 3D-CRT technique. For the analyzed cases, the results show that the IMRT technique presents better NTCP and TCP values than the 3D-CRT technique. These par... (Complete abstract click electronic access below)
Mestre

The probabilities of developing radiation-induced normal tissue complications and second primary cancers were evaluated using dose-volume histograms as well as dose measurements covering a range of radiotherapy techniques including External Beam Radiotherapy (EBRT) and Brachytherapy (BT) for prostate cancer. There are two major parts in this thesis. In the first part, the Dose-Volume Histograms (DVHs) of the Organs-At-Risk (OARs) such as rectum, bladder, urethra, and femoral heads were retrieved from the radiation treatment plans of 4-field standard fractionated (2 Gy/fraction) Three-Dimensional Conformal Radiotherapy (3D-CRT) to total dose of 64 Gy, 4-field hypofractionated (2.75 Gy/fraction) 3D-CRT to total dose of 55 Gy, 5-field 3D-CRT to total dose of 70 Gy, 4-field 3D-CRT to total dose of 70 and 74 Gy, Low-Dose-Rate Brachytherapy (LDR-BT) with I-125, High-Dose-Rate Brachytherapy (HDR-BT) with Ir-192, and combined-modality treatment (3D-CRT & HDR-BT) techniques. The DVHs of these normal organs/tissues were converted to Biologically Effective Dose based DVHs (BEffDVHs) and Equivalent Dose based DVHs (DeqVHs) respectively in order to account for differences in radiation treatment modality and fractionation schedule. For assessment of the Normal Tissue Complication Probability (NTCP), the Lyman and Relative Seriality NTCP models were applied to the differential DeqVHs of the OARs. For the assessment of risk of radiation-induced Second Primary Cancer (SPC), the Competitive Risk model was used. In total, 223 DVHs from 101 patients were analysed in this thesis. In the second part, a radiation dosimetry technique was developed and used in measuring the doses delivered to distant organs/tissues (e.g. lungs and thyroid) as a result of prostate irradiation. In this case, simulation of prostate cancer radiotherapy was performed with the anthropomorphic Rando phantom using 4-field 3D-CRT technique to the total dose of 80 Gy with the 18 MV X-ray beam from Varian iX linear accelerator (linac). Radiation doses at different locations in the Rando phantom resulting from scattered and leakage photon and neutron radiations were measured using enriched 6Li and 7Li LiF:Mg,Cu,P glass-rod thermoluminescence dosimeters (TLDs). Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75-Gy fraction and 5 times/week to total dose of 55 Gy) NTCP of rectum, bladder and urethra were less than those for standard fractionated 3D-CRT using 4-field technique (32 fractions of 2-Gy fraction and 5 times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6% respectively) following the dose-escalated 4-field 3D-CRT (2 Gy per fraction to total dose of 74 Gy) were the highest amongst the analysed treatment techniques. The average NTCP for rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques except in the case of urethra due to much smaller volumes irradiated to higher doses. Amongst normal tissues analysed, femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower equivalent doses compared to other tissues. The average estimated radiation-induced SPC risk was no greater than 0.6% for all treatment plans corresponding to various treatment techniques but was lower for either LDR or HDR brachytherapy alone compared with any EBRT technique. For LDR and HDR brachytherapy alone, the risk of SPC for rectum was approximately 2.0 x 10-4% and 8.3 x 10-5% respectively compared with 0.2% for EBRT using 5-field 3D-CRT to total dose 74 Gy. Treatment plans which deliver equivalent doses of around 3 – 5 Gy to normal tissues were associated with higher risks of development of cancers. Results from TLDs measurements in the Rando phantom indicated that photon doses were highest close to the irradiation volume and the photon dose equivalent ratio (dose equivalent per unit of target dose) decreases proportionally with the distance from the isocentre (e.g. 6.5 mSv/Gy for small intestine to 0.2 mSv/Gy for thyroid). In contrast, the dose equivalent ratio of neutrons in the Rando phantom was observed to be constant at approximately 5.7 mSv/Gy for up to 50 centimeters from the edge of the treatment field (from pancreas to oesophagus). The total dose equivalent (photon and neutron) for each organ/tissue approximated for the 4-field standard fractionated 3D-CRT technique to total dose of 80 Gy using 18 MV X-ray beam from Varian iX linac ranged between 323.0 mSv (for thyroid) and 1203.7 mSv (for colon). Based on the competitive risk model and on the assumptions that the dose equivalents were uniformly distributed in the volumes of these organs/tissues, the estimated risks of SPC range from 1.5% (in thyroid) up to 4.5% (in colon). Different radiation treatment techniques for prostate cancer are associated with different probabilities of developing radiation-induced normal tissue complications and second primary cancers. In the case of brachytherapy for prostate cancer, due to its specific dose-volume characteristics in addition to not having the leakage or neutron radiation associated with external beam radiotherapy, this treatment modality is associated with a reduced risk of NTCP and SPC compared with EBRT techniques for both organs situated close to and organs situated at a distance from the treatment field. In this current work, the radiation dosimetry technique based on the 6LiF:Mg,Cu,P and 7LiF:Mg,Cu,P glass-rod TLDs was developed to determine the radiation doses received by organs/tissues positioned away from the irradiation field due to scattered and leakage photons and neutrons. This radiation measurement technique enables the evaluation of the prostate radiation treatment plan to include the assessment of organs/tissues of interest in both high and low dose regions. It was demonstrated in this thesis that the relative seriality (NTCP) and the competitive risk (SPC) are useful models which can be used for the purpose of relative comparison and evaluation of prostate radiation treatment plans even though they may need to be further verified and fine tuned against clinical data.
Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 2010

Radiation-induced cancer first occurred in a radiology technologist over a hundred years This chapter discusses radiation-induced cancer and covers molecular mechanisms of radiation carcinogenesis, cancer mortality and cancer incidence in relation to the Japanese A-bomb survivor lifespan study, Chernobyl, patients treated with radiotherapy for non-cancer diseases, Radon exposure, and second cancers after cancer therapy (including prostate, breast, Hodgkin lymphoma, and paediatric malignancies). Patients infrequently now receive radiotherapy alone. Studies in patients treated as children with chemotherapy plus radiotherapy demonstrate that both treatment modalities increase the risk of secondary malignancy in cured patients. Therefore, the risk of cancer induced by the combination of chemotherapy, radiotherapy, and novel molecular agents need to be closely watched in future.

Bladder cancer—the seventh commonest cancer in the United Kingdom and the fourth most common in men. Nonmuscle-invasive disease is usually treated by transurethral resection with postoperative intravesical chemotherapy with mitomycin or bacillus Calmette–Guérin. Local muscle-invasive disease in patients who are fit enough is usually treated with radical cystoprostatectomy and cisplatin-based chemotherapy. Metastatic disease is typically treated with cisplatin-based chemotherapy. Renal cell cancer—approximately 3% of the total cancer burden. For operable patients with no distant disease, the treatment of choice is nephron-sparing (if possible) or radical nephrectomy. Metastatic renal cancer can behave in a very variable manner. Palliative nephrectomy may be required for bleeding or pain. First-line systemic treatment is with antiangiogenic tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor signalling. Prostate cancer—second most common cause of male cancer deaths in the Western world. Most cases are asymptomatic at presentation, being detected following measurement of serum prostate-specific antigen (PSA) or after digital rectal examination, although screening by measurement of PSA remains a contentious issue. Clinically localized prostate cancer is treated with active monitoring, radiotherapy, or minimally invasive surgery. Locally advanced disease is likely to progress and requires intervention, usually in the form of androgen deprivation therapy and radiotherapy. First-line treatment for metastatic prostate cancer is androgen deprivation therapy; second-line treatment may be with newer antiandrogens in combination with steroids and cytotoxics. Testicular cancer—affects predominantly young adult men in whom they are the most common malignant tumours. For most patients, initial management consists of an inguinal orchidectomy, with or without immediate adjuvant therapy. Standard treatment of metastatic germ cell tumours is with a combination of bleomycin, etoposide, and cisplatin.