Recommendations for the treatment of vulvar cancer in settings with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods: The panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care. Results: Consensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations. Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.

Recommendations for the prevention, screening, diagnosis, staging, and management of cervical cancer in areas with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Nearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical cancer in limited resources countries. Methods: The expert panel, composed by invited specialists from 38 developing countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East, convened in Rio de Janeiro in September 2019, during the Global Meeting of the International Gynecological Cancer Society (IGCS). Panel members considered the published scientific evidence and their practical experience on the topics, as well as the perceived cost-effectiveness of, and access to, the available interventions. The focus of the recommendations was on geographic regions rather than entire countries because medical practice varies considerably in the countries represented. Resource limitation was qualified as limited access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or overall funding for provision of state-of-the-art care. Consensus was defined as at least 75% of the voting members selecting a particular answer of the multiple-choice questionnaire, whereas the majority vote was considered as 50% to 74.9%. Results: Consensus was reached for 25 of the 121 (20.7%) questions, whereas for 54 (44.6%) questions there was one option garnering between 50% to 74.9% of votes (majority votes). For the remaining questions, considerable heterogeneity in responses was observed. Discussion: The implementation of international guidelines is challenging in countries with resource limitations or unique health-care landscapes. The development of guidelines by the health care providers in those regions is more reflective of the reality on the ground and may improve medical practice and patient care. However, challenges remain toward achieving that goal at political, economic, social, and medical levels.

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil.

BACKGROUND: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. OBJECTIVE: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. METHODS: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. RESULTS: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. CONCLUSION: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

Consensus on Screening, Diagnosis, and Staging Tools for Prostate Cancer in Developing Countries: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Consensus on Treatment and Follow-Up for Biochemical Recurrence in Castration-Sensitive Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries.

PURPOSE: To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including "abstain" and/or "unqualified to answer," and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS: For most questions, a clear majority (> 50%) of clinicians agreed on a recommended treatment for imaging, treatment scenarios, and follow-up, although only a few topics reached a consensus > 75%. Limited resources did affect several areas of treatment, although in many cases, they reinforced more stringent criteria for treatment such as prostate-specific antigen values > 0.2 ng/mL and STAMPEDE inclusion criteria as a basis for recommending treatment. CONCLUSION: A majority of clinicians working in developing countries with limited resources use similar cutoff points and selection criteria to manage patients treated for biochemically recurrent castration-sensitive PCa.

Treatment of Localized and Locally Advanced, High-Risk Prostate Cancer: A Report From the First Prostate Cancer Consensus Conference for Developing Countries.

PURPOSE: To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS: A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.

Consensus on Prostate Cancer Treatment of Localized Disease With Very Low, Low, and Intermediate Risk: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS: A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Intensity-modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) for head and neck cancer: cost-effectiveness analysis.

BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

Analysis of the Abscopal Effect With Anti-PD1 Therapy in Patients With Metastatic Solid Tumors.

Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1. The abscopal effect was characterized as a response outside the irradiated field after radiotherapy plus anti-PD1. Sixteen patients were evaluated, including 12 metastatic melanoma, 2 metastatic NSCLC, and 2 metastatic renal cell carcinoma. The median time to disease progression on anti-PD1 was 3 months. The radiotherapy field included lung, lymph nodes, and bones, with a median total dose of 24 Gy (1-40 Gy), usually in 3 fractions (1-10 fractions). Three patients with melanoma developed an abscopal effect at a rate of 18.7% (25% among melanoma patients). Of note, one of them achieved a remarkable complete response lasting >6 months. Three patients with melanoma obtained a significant local response after radiotherapy, despite no response in distant metastases. Eleven patients presented disease progression after radiotherapy. No increased toxicity was observed. In conclusion, no patients with NSCLC or renal cancer showed abscopal effect, but 25% of patients with melanoma showed regression of nonirradiated lesions when anti-PD1 was continued after radiation to a tumor site that had progressed on anti-PD1 monotherapy.

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil / Abordando glioblastomas durante a pandemia pelo COVID-19: recomendações atuais e considerações no Brasil

ABSTRACT Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

RESUMO Introdução: Pacientes com câncer, em geral, e particularmente pacientes com glioblastoma estão sob elevado risco de desenvolver síndrome respiratória aguda grave devido à infecção pelo SARS-CoV-2, e alcançar um equilíbrio entre risco de exposição à infecção e benefício clínico do tratamento seria o ideal. O comportamento agressivo desse grupo de tumores justifica a necessidade de equipe multidisciplinar para auxiliar nas decisões clínicas durante a pandemia vigente. O Brasil ocupa hoje o segundo lugar em número de casos e óbitos pela COVID-19, e as atuais disparidades no tratamento de pacientes neuro-oncológicos desafiarão as decisões clínicas e cirúrgicas dessa população, possivelmente afetando a sobrevida global. Objetivo: Guiar decisões clínicas e cirúrgicas relacionadas ao manejo de glioblastoma durante a pandemia pelo COVID-19 no Brasil por meio de pesquisa em literatura. Métodos: Busca sistemática no banco de dados eletrônico da PubMed por estudos ou consensos quanto à abordagem de glioblastoma durante a pandemia por COVID-19 até 18/07/2020. Resultado: Ao abordar o glioblastoma durante a pandemia pela COVID-19, parâmetros importantes que auxiliam no processo de tomada de decisão são idade, desempenho, perfil molecular tumoral e consentimento do paciente. Pacientes jovens devem seguir protocolo padrão após máxima ressecção cirúrgica, principalmente aqueles com metilação do promotor MGMT. Idosos e pacientes debilitados devem ser cuidadosamente avaliados, e monoterapia deve ser provavelmente considerada. Centros de saúde são orientados a utilizar-se da telemedicina e de meios para reduzir infecção local. Conclusão: A abordagem do glioblastoma durante a pandemia por COVID-19 será mundialmente desafiadora, mas particularmente no Brasil, onde ainda existe significativa inequidade no cuidado com a saúde.

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series.

PURPOSE: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. RESULTS: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.

Radiochemotherapy in the conservative treatment of anal canal carcinoma: retrospective analysis of results and radiation dose effectiveness.

PURPOSE: This retrospective analysis reports the results on patients with anal canal carcinoma treated by combined radiotherapy and chemotherapy. METHODS AND MATERIALS: Between March 1993 and December 2001, 43 patients with anal canal carcinoma were treated with radiochemotherapy at the Hospital do Cancer A.C. Camargo. Stage distribution was as follows: I, 3 (7%); II, 23 (53.5%); IIIA, 8 (18.6%); and IIIB, 9 (21%). The median age was 56 years (range, 36-77 years) with most patients being women (4:1). External radiotherapy (RT) was delivered at the whole pelvis followed by a boost at the primary tumor. The median dose of RT at the whole pelvis and at the primary tumor was 45 Gy and 55 Gy, respectively. Chemotherapy was carried out during the first and last 4 days of RT with continuous infusion of 5-fluorouracil (1000 mg/m(2)) and bolus mitomycin C (10 mg/m(2)). Median overall treatment time was 51 days (range, 30-129 days). Thirty-four patients (79%) did not receive elective RT at the inguinal region. Patient's age, tumor stage, overall treatment time, and RT dose at primary tumor were variables analyzed for survival and local control. RESULTS: Median follow-up time was 42 months (range, 4-116 months). Overall survival and colostomy-free survival at 5 years was 68% and 52%, respectively. Overall survival according to clinical stage was as follows: I, 100%; II, 82%; IIIA, 73%; and IIIB, 18% (p = 0.0049). Complete response was observed in 40 patients (93%). Local recurrence occurred in 9 (21%) patients, and of these, 6 were rescued by surgery. Local control with a preserved sphincter was observed in 34 patients (79%). According to the RT dose, local control was higher among patients who received more than 50 Gy at primary tumor (86.5% vs. 34%, p = 0.012). Inguinal failure was observed in 5 patients (15%) who did not receive inguinal elective RT. Distant metastasis was observed in 11 patients (25.6%). Temporary interruption of the treatment as a result of acute toxicity was necessary in 12 patients (28%). Four patients developed mild chronic complications. CONCLUSIONS: This analysis suggests that the treatment scheme employed was effective for anal sphincter preservation and local control; however, the incidence of distant metastases was relatively high. The clinical stage was the main prognostic factor for overall survival. Local control was higher in patients treated with doses of more than 50 Gy at primary tumor. The high incidence of inguinal failure implies the need for elective RT in this region.

Radiotherapy alone in the treatment of uterine cervix cancer with telecobalt and low-dose-rate brachytherapy: retrospective analysis of results and variables.

PURPOSE: This retrospective analysis aims to report results and variables from patients with cervix cancer treated by radiation therapy alone with telecobalt and low-dose-rate brachytherapy (LDRB). METHODS AND MATERIALS: Between September 1989 and September 1995, 190 patients with histologic diagnosis of cervix carcinoma were treated with telecobalt for external beam radiotherapy (EBR), followed by one or two insertions of LDRB. Stage distribution according to patients was the following: IB, 12; IIA, 4; IIB, 105; and IIIB, 69. Median dose of EBR at whole pelvis was 40 Gy, and median parametrial doses for Stages II and III patients were 50 Gy and 60 Gy, respectively. Median doses of LDRB at point A for patients treated with one and two insertions were 38 Gy and 50 Gy, respectively. RESULTS: Median follow-up time was 70 months (range: 8-127 months). Overall survival, disease-free survival, and 5-year local control of patients at Stages I, II, and III were 83%, 78%, and 46%; 83%, 82%, and 49%; and 92%, 87%, and 58%, respectively. Overall incidence of late complications in the rectum, small bowel, and urinary tract was 15.3% (19/190), 4.2% (8/190), and 6.8% (13/190), respectively. The actuarial 5-year rectal, small bowel, and urinary incidence of late complications was 16.1%, 4.6%, and 7.6%, respectively. Clinical stage was the only significant variable for overall 5-year survival (p = 0.001), for disease-free survival (p = 0.001), and for local control (p = 0.001). Stage II patients more than 50 years old had better disease-free survival and local control at 5 years (p = 0.004). None of the analyzed variables influenced the actuarial 5-year incidence of late complications. CONCLUSIONS: Results of this series suggest that the use of telecobalt equipment for EBR with doses up to 50 Gy at whole pelvis, prior to brachytherapy, is an acceptable technique for radiation therapy alone in the treatment of cervix cancer, especially in developing countries, including Brazil, where telecobalt machines still prevail.

Results of high dose rate afterloading brachytherapy boost to conventional external beam radiation therapy for initial and locally advanced prostate cancer.

PURPOSE: To evaluate the impact on biochemical control (bNED), acute and late gastro-intestinal (GI) and urological (GU) morbidity of initial and locally advanced prostate cancer treated with fractionated transrectal ultrasound-guided (TRUS) high dose rate after loading brachytherapy (HDR-B) as a boost to conventional external beam radiation therapy (EBRT). PATIENTS AND METHODS: From March 1997 to February 2000 a total of 119 patients with any of the following characteristics were eligible for study entry: biopsy proven adenocarcinoma Gleason scored (GS), initial prostatic specific antigen (PSA) level dosage 1992 AJCC clinical stage T3a or less, and prostatic volume <60 cc. All patients had prior to HDR-B a course of EBRT 6 MV photons to a median dose of 45 Gy, in 1.8 Gy fractions, to the prostate and seminal vesicles only. HDR-B treatment planning and dosimetric calculations were generated with the Nucletron Planning System. Patients were grouped into two groups, according to their risk for biochemical failure: low-risk group without (LR) or with neoadjuvant total androgen deprivation (AD) prior to EBRT (LR+AD) and high-risk group without (HR) or with neoadjuvant AD (HR+AD), for bNED and dose-escalation protocol. LR encompassed patients who presented GS<6, T1 or T2a and or initial PSA<10 ng/ml, who were treated with 16 Gy (4 Gy fractions, b.i.d.) HDR-B. The remaining patients were grouped into HR or HR+AD and received 20 Gy (5 Gy fractions, b.i.d.) HDR-B. The planning was optimized using the standard geometric optimization. Biological effective doses (BED) for tumor control and late responding tissue were calculated using a alpha/beta ratio of 1.5 and 3 Gy, respectively. They were matched with bNED, acute and late gastrointestinal (GI) and urological (GU) morbidity, according to the RTOG/EORTC scoring criteria. RESULTS: Median age of patients was 68 years (range 47-83), with a median follow-up of 41 months (range 18-48). The crude and actuarial biochemical controls (bNED) in 48 months for all patients were 69.5 and 75.3%, respectively. When grouped into LR, LR+AD, HR and HR+AD the actuarial bNED were 78.2, 76, 76 and 72.3% (P=0.89), respectively. Acute GU and GI morbidity G1-2 were seen in 18.5% (20/108) and 10.2% (11/108) of patients with spontaneous regression. Late GI and GU morbidity G1-2 were seen in 12% (13/108) and 4.6 (5/108) of patients, with no need of intervention. No acute or late G3-4 GU or GI morbidity was seen. CONCLUSIONS: There are many advantages in HDR-B, but the most important ones are the capability of on-line dosimetry, quality control and the procedure being very conformal. There is a low incidence of GU and GI acute and late morbidity with acceptable bNED when treating initial and locally advanced prostate cancer with HDR-B as a boost to EBRT, but we still need to wait for results of phase III open trials that analyze HDR-B and conformal therapy.

Ototoxicity evaluation in medulloblastoma patients treated with involved field boost using intensity-modulated radiation therapy (IMRT): a retrospective review.

BACKGROUND: Ototoxicity is a known side effect of combined radiation therapy and cisplatin chemotherapy for the treatment of medulloblastoma. The delivery of an involved field boost by intensity modulated radiation therapy (IMRT) may reduce the dose to the inner ear when compared with conventional radiotherapy. The dose of cisplatin may also affect the risk of ototoxicity. A retrospective study was performed to evaluate the impact of involved field boost using IMRT and cisplatin dose on the rate of ototoxicity. METHODS: Data from 41 medulloblastoma patients treated with IMRT were collected. Overall and disease-free survival rates were calculated by Kaplan-Meier method Hearing function was graded according to toxicity criteria of Pediatric Oncology Group (POG). Doses to inner ear and total cisplatin dose were correlated with hearing function by univariate and multivariate data analysis. RESULTS: After a mean follow-up of 44 months (range: 14 to 72 months), 37 patients remained alive, with two recurrences, both in spine with CSF involvement, resulting in a disease free-survival and overall survival of 85.2% and 90.2%, respectively.Seven patients (17%) experienced POG Grade 3 or 4 toxicity. Cisplatin dose was a significant factor for hearing loss in univariate analysis (p < 0.03). In multivariate analysis, median dose to inner ear was significantly associated with hearing loss (p < 0.01). POG grade 3 and 4 toxicity were uncommon with median doses to the inner ear bellow 42 Gy (p < 0.05) and total cisplatin dose of less than 375 mg/m2 (p < 0.01). CONCLUSIONS: IMRT leads to a low rate of severe ototoxicity. Median radiation dose to auditory apparatus should be kept below 42 Gy. Cisplatin doses should not exceed 375 mg/m2.

Intensity-modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) for head and neck cancer: cost-effectiveness analysis

SUMMARY BACKGROUND: A cost-effectiveness analysis of IMRT compared to 3D-CRT for head and neck cancer patients (HNCPs) was conducted in the Brazilian Public Health System. METHODS: A Markov model was used to simulate radiation therapy-induced dysphagia and xerostomia in HNCPs. Data from the PARSPORT trial and the quality-of-life study were used as parameters. The incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained were calculated. RESULTS: At 2 years, IMRT was associated with an incremental benefit of 0.16 QALYs gained per person, resulting in an ICER of BRL 31,579 per QALY gained. IMRT was considered cost-effective when using the guideline proposed by the World Health Organization (WHO) of three times the national gross domestic product (GDP) per capita (BRL 72,195). Regarding life expectancy (15 years), the incremental benefit of IMRT was 1.16 QALYs gained per person, with an ICER of BRL 4,341. IMRT was also cost-effective using the WHO definition, which states that the maximum cost is equal to the GDP per capita (BRL 24,065). CONCLUSIONS: IMRT was considered cost-effective from the perspective of the Brazilian public health system.

RESUMO INTRODUÇÃO: Foi realizada uma análise de custo-efetividade da radioterapia com intensidade modulada de feixe (IMRT) comparada com a radioterapia conformada para pacientes com câncer de cabeça e pescoço (CCP) no contexto do Sistema Único de Saúde (SUS). MÉTODOS: Foi elaborado um modelo de Markov para comparar os custos médicos diretos e os desfechos de saúde relacionados à qualidade de vida do paciente pós-intervenção radioterápica sofrendo de xerostomia e disfagia. Com essa finalidade, foram usados os dados do estudo PARSPORT e parâmetros de qualidade de vida. Os resultados comparativos das estratégias alternativas de tratamento foram medidos pela razão de custo-efetividade incremental (RCEI). O desfecho analisado foi o de anos de vida ajustados à qualidade (QALY). RESULTADOS: Em um horizonte de tempo de dois anos, a IMRT foi associada com um benefício incremental de ganho de 0,16 QALYs por indivíduo, resultando em um RCEI de R$ 31.579 por QALY ganhado. A IMRT foi custo-efetivo, adotando-se o limite máximo de disposição a pagar, proposto pela OMS, de três vezes o PIB per capita nacional, equivalente a R$ 72.195. No horizonte de tempo de 15 anos, o benefício incremental de ganho foi de 1,16 QALYs por indivíduo, com um RCEI de R$ 4.341. A IMRT foi custo-efetivo, adotando-se o limite de disposição a pagar, proposto pela OMS, de uma vez o PIB per capita nacional, equivalente a R$ 24.065. CONCLUSÃO: A IMRT foi considerada um tratamento custo-efetivo na perspectiva do SUS.

Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity.

BACKGROUND: This retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors. METHODS: From January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria. RESULTS: Absence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99). CONCLUSIONS: This comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups.

Intensity-modulated and 3D-conformal radiotherapy for whole-ventricular irradiation as compared with conventional whole-brain irradiation in the management of localized central nervous system germ cell tumors.

PURPOSE: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). METHODS AND MATERIALS: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a "boost" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. RESULTS: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. CONCLUSIONS: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.