Moderate hypofractionation for salvage radiotherapy (HYPO-SRT) in patients with biochemical recurrence after prostatectomy: A cohort study with meta-analysis.

OBJECTIVES: To assess the effectiveness and safety of HYPO-SRT in patients with biochemical recurrence after radical prostatectomy, we performed a cohort study followed by meta-analysis (MA). METHODS: A cohort study followed by a MA was designed to evaluate the biochemical relapse-free survival (bRFS) and toxicity rates with HYPO-SRT for patients with a biochemical recurrence after radical prostatectomy. Following the PRISMA and MOOSE guidelines, eligible studies were identified on electronic databases through February 2021. A meta-regression analysis was performed. A p-value <0.05 was considered significant. RESULTS: A cohort of 43 patients treated by HYPO-SRT was prospectively evaluated. With a median follow-up of 31 months, at 3 years, the bRFS was 93%. In the cohort study, the incidence of late grade 1, 2, and ≥3 GU and GI toxicities were 33% and 20%, 2% and 4%, and 0% and 0%, respectively. Combining our cohort with 5 studies, a total of 412 patients treated with HYPO-SRT were included in the MA. The 3-year bRFS was 73% (95% CI: 63-83%). The estimation of bRFS at 5 years was 61%. The rate of grade ≥2 late GU and GI toxicity was 6 % (95% CI: 1-12), and 3% (95% CI: 1-5), with no toxicities grade 3-5. In the meta-regression, % residual PSA, % positive margins, % ADT and % ≥ Gleason 8 had a significant association with bRFS (all P < 0.05). The late GU toxicity was associated with EQD2Gy1.5 ≥ 70 Gy (p = 0.01). CONCLUSION: HYPO-SRT produced satisfactory bRFS with reduced acute/ late GU and GI toxicity rates. The MA analysis supports future studies assessing HYPO SRT.

Neoadjuvant stereotactic ablative radiotherapy (SABR) for soft tissue sarcomas of the extremities.

BACKGROUND: Soft tissue sarcomas (STS) comprise a diverse group of mesenchymal malignancies that require multidisciplinary care. Although surgery remains the primary form of treatment for those with localized disease, radiation therapy (RT) is often incorporated either in the neo- or adjuvant setting. Given the development of modern RT techniques and alternative dosing schedules, stereotactic ablative radiotherapy (SABR) has emerged as a promising technique. However, the current role of SABR in the treatment of STS of the extremities remains uncertain. METHODS AND MATERIALS: This was a single-center, prospective, single-arm phase II trial. Patients with localized STS who were candidates for limb-preservation surgery were included. Experimental treatment consisted of SABR with 40 Gy in 5 fractions, administered on alternate days, followed by surgery after a minimum interval of 4 weeks. The primary outcome was the rate of wound complication. Secondary outcomes included 2-year local control (LC), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) rates (and other toxicities). RESULTS: Twenty-five patients were enrolled between October 2015 and November 2019 and completed the treatment protocol. The median rate of histopathologic regression was 65% (range 0-100) and 20.8% of tumors presented pathologic complete response (pCR). Wound complications were observed in 7/25 patients (28%). Three patients underwent disarticulation by vascular occlusion after plastic reconstruction and one patient was amputated by grade 3 limb dysfunction. After a median follow up of 20.7 months, the 2-year estimated risk of local recurrence, distant metastasis and cause-specific death were 0%, 44.7% and 10.6% respectively. CONCLUSIONS: Neoadjuvant SABR appears to improve the pCR for patients with eSTS, with acceptable rate of wound complications. Nevertheless, this benefit should be weighed against the risk of late of vascular toxicity with SABR regimen since, even in a short median follow-up, a higher rate of amputation than expected was observed. A larger sample size with longer follow-up is necessary to conclude the overall safety of this strategy.

Hypofractionated radiotherapy recommendations for localized prostate cancer in Brasil.

OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.

Hypofractionated Radiation Therapy to the Prostate Bed With Intensity-Modulated Radiation Therapy (IMRT): A Phase 2 Trial.

PURPOSE: Postoperative radiation therapy (RT) is a common therapy used for patients with prostate cancer. Although clinical trials have established the safety and efficacy of hypofractionation as a primary therapy, there are limited data in a postoperative setting. We conducted a prospective trial to evaluate the safety and feasibility of postoperative hypofractionated RT to the prostate bed. METHODS AND MATERIALS: In this phase 2 trial, patients submitted to radical prostatectomy were treated with hypofractionated RT to the prostate bed (adjuvant or salvage). The prescribed dose was 51 Gy in 15 fractions (3.4 Gy per fraction), using intensity modulated and image guided radiation therapy techniques. The primary endpoint was the rate of acute genitourinary (GU) grade ≥2 toxicity. Secondary endpoints included acute gastrointestinal (GI) and late GU/GI toxicities, biochemical failure-free survival (BFFS), metastasis-free survival, cancer-specific survival, overall survival, and health-related quality of life. RESULTS: Of 64 enrolled patients, 61 received radiation therapy (57 salvage and 4 adjuvant radiation therapy). After a median follow-up of 16 months, 11.5% of patients experienced acute grade ≥2 GU symptoms and 13.1% experienced acute grade ≥2 GI symptoms. The late grade ≥2 GU toxicity rate was 8.2%, and 1 patient (1.6%) developed both acute and late grade 3 GU toxicity. The late grade ≥2 GI toxicity rate was 11.5%, and no grade 3 GI adverse events were reported. The short follow-up limits our ability to perform a robust oncologic endpoint assessment; however, the 2-year BFFS, use of subsequent salvage therapy, and the development of metastasis were 95.1%, 0%, and 0%, respectively. CONCLUSIONS: Hypofractionated RT to the prostate bed in 15 treatments was safe, with an acceptable GU and GI toxicity profile. Further study in large, randomized trials is warranted.

Second brazilian consensus on the treatment of advanced prostate cancer: a SBOC-SBU-SBRT panel review

ABSTRACT Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The first Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Second brazilian consensus on the treatment of advanced prostate cancer - a SBOC-SBU-SBRT panel review.

Prostate cancer is the second most common cancer and the fi fth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The fi rst Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Prostate brachytherapy with iodine-125 seeds: analysis of a single institutional cohort

ABSTRACT Objectives: Brachytherapy (BT) with iodine-125 seeds placement is a consolidated treatment for prostate cancer. The objective of this study was to assess the clinical outcomes in patients with prostate cancer who underwent low-dose-rate (LDR) -BT alone in a single Brazilian institution. Materials and Methods: Patients treated with iodine-125 BT were retrospectively assessed after at least 5 years of follow-up. Patients who received combination therapy (External beam radiation therapy-EBRT and BT) and salvage BT were not included. Results: 406 men were included in the study (65.5% low-risk, 30% intermediate-risk, and 4.5% high-risk patients). After a median follow-up of 87.5 months, 61 (15.0%) patients developed biochemical recurrence. The actuarial biochemical failure-free survival (BFFS) at 5 and 10 years were 90.6% and 82.2%, respectively. A PSA nadir ≥ 1 ng / mL was associated with a higher risk of biochemical failure (HR = 5.81; 95% CI: 3.39 to 9.94; p ≤ 0.001). The actuarial metastasis-free survival (MFS) at 5 and 10 years were 98.3% and 94%, respectively. The actuarial overall survival (OS) at 5 and 10 years were 96.2% and 85.1%, respectively. Acute and late grade 2 and 3 gastrointestinal toxicities were observed in 5.6%, 0.5%, 4.6% and 0.5% of cases, respectively. For genitourinary the observed acute and late grade 2 and 3 toxicities rates were 57.3%, 3.6%, 28% and 3.1%, respectively. No grade 4 and 5 were observed. Conclusions: BT was effective as a definitive treatment modality for prostate cancer, and its endpoints and toxicities were comparable to those of the main series in the literature.

Prostate brachytherapy with iodine-125 seeds: analysis of a single institutional cohort.

OBJECTIVES: Brachytherapy (BT) with iodine-125 seeds placement is a consolidated treatment for prostate cancer. The objective of this study was to assess the clinical outcomes in patients with prostate cancer who underwent low-dose-rate (LDR) -BT alone in a single Brazilian institution. MATERIALS AND METHODS: Patients treated with iodine-125 BT were retrospectively assessed after at least 5 years of follow-up. Patients who received combination therapy (External beam radiation therapy-EBRT and BT) and salvage BT were not included. RESULTS: 406 men were included in the study (65.5% low-risk, 30% intermediate-risk, and 4.5% high-risk patients). After a median follow-up of 87.5 months, 61 (15.0%) patients developed biochemical recurrence. The actuarial biochemical failure-free survival (BFFS) at 5 and 10 years were 90.6% and 82.2%, respectively. A PSA nadir ≥ 1 ng / mL was associated with a higher risk of biochemical failure (HR = 5.81; 95% CI: 3.39 to 9.94; p ≤ 0.001). The actuarial metastasis-free survival (MFS) at 5 and 10 years were 98.3% and 94%, respectively. The actuarial overall survival (OS) at 5 and 10 years were 96.2% and 85.1%, respectively. Acute and late grade 2 and 3 gastrointestinal toxicities were observed in 5.6%, 0.5%, 4.6% and 0.5% of cases, respectively. For genitourinary the observed acute and late grade 2 and 3 toxicities rates were 57.3%, 3.6%, 28% and 3.1%, respectively. No grade 4 and 5 were observed. CONCLUSIONS: BT was effective as a definitive treatment modality for prostate cancer, and its endpoints and toxicities were comparable to those of the main series in the literature.

Self-reported Conflicts of Interest and Trial Sponsorship of Clinical Trials in Prostate Cancer Involving Radiotherapy.

OBJECTIVES: To examine the association between trial sponsorship and conflicts of interest (COI) with clinical trial conclusions for prostate cancer trials related to radiotherapy. MATERIALS AND METHODS: The MEDLINE database was searched for all prostate cancer clinical trials published between 2004 and 2013 and identified 1396 studies. Two investigators independently identified trials published in the English language of ≥30 patients, and extracted relevant data. Clinical trials were classified according to trial characteristics, sponsorship source and type, COI, and study conclusion, and analyzed by univariable and multivariable logistic regression. RESULTS: Of 240 eligible trials, 160 (67.5%) evaluated drugs without radiotherapy, 60 (25%) involved radiotherapy, and 18 (7.5%) involved procedures without radiotherapy. Of the 60 radiotherapy trials eligible for analysis, positive sponsorship and potential COI were present in 58.3% and 20% of trials, respectively. Study conclusions were positive, negative, or neutral in 78.3%, 5%, and 16.7% of trials, respectively. No association was found between positive conclusions and either industry support of potential COI. Positive conclusions were reported in 86.7% and 83.3% of trials with sponsorship and COI, respectively, as compared with 75.6% and 77.1% of those without sponsorship (P=0.37) and COI (P=0.64). Sponsorship was significantly associated with radiotherapy trials combined with drugs (odds ratio 5.5, P=0.01) and higher-risk disease (odds ratio 4.71, P=0.01). CONCLUSIONS: The presence of sponsorship was associated with radiotherapy trials involving drugs or studying higher-risk prostate cancer. However, there were no identified associations between study conclusion and sponsorship type or COI.

Incidental irradiation of internal mammary lymph nodes in breast cancer: conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy.

OBJECTIVE: To evaluate incidental irradiation of the internal mammary lymph nodes (IMLNs) through opposed tangential fields with conventional two-dimensional (2D) or three-dimensional (3D) radiotherapy techniques and to compare the results between the two techniques. MATERIALS AND METHODS: This was a retrospective study of 80 breast cancer patients in whom radiotherapy of the IMLNs was not indicated: 40 underwent 2D radiotherapy with computed tomography for dosimetric control, and 40 underwent 3D radiotherapy. The total prescribed dose was 50.0 Gy or 50.4 Gy (2.0 or 1.8 Gy/day, respectively). We reviewed all plans and defined the IMLNs following the Radiation Therapy Oncology Group recommendations. For the IMLNs, we analyzed the proportion of the volume that received 45 Gy, the proportion of the volume that received 25 Gy, the dose to 95% of the volume, the dose to 50% of the volume, the mean dose, the minimum dose (Dmin), and the maximum dose (Dmax). RESULTS: Left-sided treatments predominated in the 3D cohort. There were no differences between the 2D and 3D cohorts regarding tumor stage, type of surgery (mastectomy, breast-conserving surgery, or mastectomy with immediate reconstruction), or mean delineated IMLN volume (6.8 vs. 5.9 mL; p = 0.411). Except for the Dmin, all dosimetric parameters presented higher mean values in the 3D cohort (p < 0.05). The median Dmax in the 3D cohort was 50.34 Gy. However, the mean dose to the IMLNs was 7.93 Gy in the 2D cohort, compared with 20.64 Gy in the 3D cohort. CONCLUSION: Neither technique delivered enough doses to the IMLNs to achieve subclinical disease control. However, all of the dosimetric parameters were significantly higher for the 3D technique.

OBJETIVO: Avaliar a irradiação incidental dos linfonodos da cadeia mamária interna (LCMIs) com campos tangenciais opostos por meio de radioterapia bidimensional (2D) convencional ou tridimensional (3D) e comparar as duas técnicas quanto aos resultados obtidos. MATERIAIS E MÉTODOS: Trata-se de um estudo retrospectivo com 80 pacientes com câncer de mama sem indicação de radioterapia dos LCMIs: 40 foram submetidos a radioterapia 2D com tomografia computadorizada para controle dosimétrico e 40 foram submetidos a radioterapia 3D. A dose total prescrita foi 50,0 Gy ou 50,4 Gy (2,0 ou 1,8 Gy/dia, respectivamente). Os planos de tratamento foram analisados e os LCMIs foram definidos conforme as recomendações do Radiation Therapy Oncology Group. No tocante aos LCMIs, foram analisadas a proporção do volume que recebeu 45 Gy, a proporção do volume que recebeu 25 Gy, a dose para 95% do volume, a dose para 50% do volume, a dose média, a dose mínima (Dmín) e a dose máxima (Dmáx). RESULTADOS: Tratamentos do lado esquerdo predominaram na coorte 3D. Não houve diferenças entre as coortes 2D e 3D quanto ao estágio do tumor, ao tipo de cirurgia (mastectomia, cirurgia conservadora ou mastectomia com reconstrução imediata) ou à média do volume delineado dos LCMIs (6,8 vs. 5,9 mL; p = 0,411). À exceção da Dmín, todos os parâmetros dosimétricos apresentaram médias maiores na coorte 3D (p < 0,05). A mediana da Dmáx na coorte 3D foi 50,34 Gy. No entanto, a dose média nos LCMIs foi 7,93 Gy na coorte 2D e 20,64 Gy na coorte 3D. CONCLUSÃO: Nenhuma das duas técnicas emitiu doses suficientes aos LCMIs para que se alcançasse o controle subclínico da doença. No entanto, todos os parâmetros dosimétricos foram significativamente maiores com a técnica 3D.

Incidental irradiation of internal mammary lymph nodes in breast cancer: conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy / Irradiação incidental da cadeia mamária interna no câncer de mama: comparação entre a técnica convencional (bidimensional) e a técnica tridimensional

Abstract Objective: To evaluate incidental irradiation of the internal mammary lymph nodes (IMLNs) through opposed tangential fields with conventional two-dimensional (2D) or three-dimensional (3D) radiotherapy techniques and to compare the results between the two techniques. Materials and Methods: This was a retrospective study of 80 breast cancer patients in whom radiotherapy of the IMLNs was not indicated: 40 underwent 2D radiotherapy with computed tomography for dosimetric control, and 40 underwent 3D radiotherapy. The total prescribed dose was 50.0 Gy or 50.4 Gy (2.0 or 1.8 Gy/day, respectively). We reviewed all plans and defined the IMLNs following the Radiation Therapy Oncology Group recommendations. For the IMLNs, we analyzed the proportion of the volume that received 45 Gy, the proportion of the volume that received 25 Gy, the dose to 95% of the volume, the dose to 50% of the volume, the mean dose, the minimum dose (Dmin), and the maximum dose (Dmax). Results: Left-sided treatments predominated in the 3D cohort. There were no differences between the 2D and 3D cohorts regarding tumor stage, type of surgery (mastectomy, breast-conserving surgery, or mastectomy with immediate reconstruction), or mean delineated IMLN volume (6.8 vs. 5.9 mL; p = 0.411). Except for the Dmin, all dosimetric parameters presented higher mean values in the 3D cohort (p < 0.05). The median Dmax in the 3D cohort was 50.34 Gy. However, the mean dose to the IMLNs was 7.93 Gy in the 2D cohort, compared with 20.64 Gy in the 3D cohort. Conclusion: Neither technique delivered enough doses to the IMLNs to achieve subclinical disease control. However, all of the dosimetric parameters were significantly higher for the 3D technique.

Resumo Objetivo: Avaliar a irradiação incidental dos linfonodos da cadeia mamária interna (LCMIs) com campos tangenciais opostos por meio de radioterapia bidimensional (2D) convencional ou tridimensional (3D) e comparar as duas técnicas quanto aos resultados obtidos. Materiais e Métodos: Trata-se de um estudo retrospectivo com 80 pacientes com câncer de mama sem indicação de radioterapia dos LCMIs: 40 foram submetidos a radioterapia 2D com tomografia computadorizada para controle dosimétrico e 40 foram submetidos a radioterapia 3D. A dose total prescrita foi 50,0 Gy ou 50,4 Gy (2,0 ou 1,8 Gy/dia, respectivamente). Os planos de tratamento foram analisados e os LCMIs foram definidos conforme as recomendações do Radiation Therapy Oncology Group. No tocante aos LCMIs, foram analisadas a proporção do volume que recebeu 45 Gy, a proporção do volume que recebeu 25 Gy, a dose para 95% do volume, a dose para 50% do volume, a dose média, a dose mínima (Dmín) e a dose máxima (Dmáx). Resultados: Tratamentos do lado esquerdo predominaram na coorte 3D. Não houve diferenças entre as coortes 2D e 3D quanto ao estágio do tumor, ao tipo de cirurgia (mastectomia, cirurgia conservadora ou mastectomia com reconstrução imediata) ou à média do volume delineado dos LCMIs (6,8 vs. 5,9 mL; p = 0,411). À exceção da Dmín, todos os parâmetros dosimétricos apresentaram médias maiores na coorte 3D (p < 0,05). A mediana da Dmáx na coorte 3D foi 50,34 Gy. No entanto, a dose média nos LCMIs foi 7,93 Gy na coorte 2D e 20,64 Gy na coorte 3D. Conclusão: Nenhuma das duas técnicas emitiu doses suficientes aos LCMIs para que se alcançasse o controle subclínico da doença. No entanto, todos os parâmetros dosimétricos foram significativamente maiores com a técnica 3D.

Change in the risk stratification of prostate cancer after Slide Review by a uropathologist: the experience of a reference center for the treatment of prostate cancer.

INTRODUCTION: Brachytherapy is an option for treating low-risk prostate cancer (PC). Biochemical control of low-risk disease can reach 95 %. The practice advocated is that a review of prostate biopsies should be mandatory before choosing the best treatment for patients with PC. Our objective was to evaluate the change in PC risk after review of a prostate biopsy by an experienced uropathologist at a reference hospital. MATERIALS AND METHODS: Between December 2003 and August 2012, 182 men were referred to our institution for brachytherapy to treat PC. Their slides were reviewed by the same uropathologist. RESULTS AND DISCUSSION: Classification risk disagreement occurred in 71 (39 %) cases, including one in which no tumor was observed. The main cause of risk change was related to the Gleason score (GS), with 57 (81.4 %) cases upgraded to GS 7 or 8. Tumor volume was also compared, although only the number of fragments was reported in most original reports. The concordance of the number of cores affected by tumor was 43.9 %, and in 49 % of the cases, the number was decreased by the uropathologist. Perineural invasion (PNI) was reported in one quarter of original reports, and the agrement was 58 %. CONCLUSION: Slide review by an uropathologist remains essential at reference radiotherapy centers for the treatment of PC. The change in PC risk evaluation is mainly due to the GS, but tumor volume and PNI, which are important for the characterization of tumor aggressiveness, are also misinterpreted and could drive a change in the therapy choice.

Change in the risk stratification of prostate cancer after Slide Review by a uropathologist: the experience of a reference center for the treatment of prostate cancer

Introduction Brachytherapy is an option for treating low-risk prostate cancer (PC). Biochemical control of low-risk disease can reach 95%. The practice advocated is that a review of prostate biopsies should be mandatory before choosing the best treatment for patients with PC. Our objective was to evaluate the change in PC risk after review of a prostate biopsy by an experienced uropathologist at a reference hospital. Materials and Methods Between December 2003 and August 2012, 182 men were referred to our institution for brachytherapy to treat PC. Their slides were reviewed by the same uropathologist. Results and Discussion Classification risk disagreement occurred in 71 (39%) cases, including one in which no tumor was observed. The main cause of risk change was related to the Gleason score (GS), with 57 (81.4%) cases upgraded to GS 7 or 8. Tumor volume was also compared, although only the number of fragments was reported in most original reports. The concordance of the number of cores affected by tumor was 43.9%, and in 49% of the cases, the number was decreased by the uropathologist. Perineural invasion (PNI) was reported in one quarter of original reports, and the agreement was 58%. Conclusion Slide review by an uropathologist remains essential at reference radiotherapy centers for the treatment of PC. The change in PC risk evaluation is mainly due to the GS, but tumor volume and PNI, which are important for the characterization of tumor aggressiveness, are also misinterpreted and could drive a change in the therapy choice. .