Meta-Analysis of STereotactic body radiothERapy in non-spine BONE metastaseS (MASTER-BONES).

PURPOSE: The efficacy and safety of stereotactic body radiation (SBRT) for patients with non-spine bone metastases (NSBM) remains in question. A systematic review and meta-analysis was performed to evaluate SBRT treatment outcomes in NSBM. METHODS AND MATERIALS: Eligible studies were retrieved from Medline, Embase, Scielo, the Cochrane Library, and annual meeting proceedings until July 6, 2023. We adhered to the PRISMA and MOOSE guideline recommendations. Quantitative synthesis was performed using a random effects model. RESULTS: Seven retrospective studies, with a total of 807 patients (1048 lesions) treated with stereotactic body radiation were included, with median follow-up ranging from 7.6-26.5 months. The most common stereotactic body radiation sites were pelvis (39.2%), ribs (25.8%), femur (16.7%), and humerus/shoulder region (8.7%). At 1-year, the LF and FR were 7% (95%CI 5.5-8.5%; I2=0, n= 75/1048), and 5.3% (95%CI 3-7.5%;I2=0, n= 65/1010). The 2-year cumulative LF incidence was 12.1% (95% CI: 10-15.5%). The OS and PFS at 1-year were 82% (95%CI 75-88%;I2=82%, n= 746/867), and 33.5%(95%CI 26-41%;I2=0%, n= 51/152), with a median of 20.2 months (95%CI: 10.9-49.1 months) and 8.3 months (95% CI: 6.3-10.3%) for OS and PFS, respectively. Meta-regression analysis revealed a significant relationship between planning target volume and fracture rate (p<0.05). Ribs 2.5% followed by the femur 1.9% (95%CI:0-6.1%) were the most common fracture sites. The occurrence of pain flare, fatigue and dermatitis were 7 %, 5.4 %, and 0.65 %, respectively. CONCLUSIONS: Stereotactic body radiation proves both safety and efficacy for non-spine bone metastases and serious complications (grade 3) are infrequent. Careful consideration of target volume is crucial due to its link with a higher fracture risk.

Moderately hypofractionated post-operative radiation therapy for breast cancer: preferences amongst radiation oncologists from countries in Latin America and the Caribbean.

Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer. Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions. Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules. Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.

Real-world evidence for oncological outcomes after radiotherapy or surgery for T1a-T1b glottic squamous cell carcinoma: A population-based cohort study.

BACKGROUND: Compare outcomes after surgery (S) or radiotherapy (RT) for T1a-T1b glottic squamous cell carcinoma (T1GSCC) in a population-based cohort study. METHODS: Patients diagnosed with T1GSCC from 1999 to 2020 were identified from a public database. Clinical, demographic, and social data were extracted. Treatment and patient groups and subgroups were compared with log-rank test, Cox proportional test, and propensity-score matched (PSM). RESULTS: Eight hundred and eighty-eight patients with T1GSCC were included in the study, with a median follow-up of 61 months. The 5- and 10-year overall survival (OS) S versus RT were 76% versus 71% and 60% versus 52% (p = 0.02), respectively. In the subgroup analysis, S was associated with better OS for T1b, male, and public service patients (p < 0.05). In the PSM cohort of S versus RT with 110 patients each, there was no significant difference in the OS, CSS, and LC. CONCLUSIONS: T1GSCC has favorable outcomes with S or RT.

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study.

Background: Stereotactic body radiotherapy (SBRT) has proven to provide high rates of tumor control for patients with early-stage non-small cell lung cancer (NSCLC). We are reporting a multicenter experience of long-term clinical outcomes and adverse effect profiles of patients with medically inoperable early-stage NSCLC treated with SBRT. Methods: A total of 145 early-stage NSCLC patients underwent SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Shandong Cancer Hospital and Institute, and Shanghai Pulmonary Hospital between October 2012 and March 2019. Four-dimensional computed tomography (4D-CT) simulation was used for all patients. All received a biologically effective dose (BED; α/ß=10) of 96-120 Gy with the prescribed isodose line covering >95% of the planning target volume (PTV). Survival was analyzed by the Kaplan-Meier method. Survival was estimated using the Kaplan-Meier method. Results: The median tumor diameter was 2.2 (range, 0.5-5.2) cm. The median follow-up was of 65.6 months. Thirty-five patients (24.1%) developed disease recurrence. The rates of local, regional, and distant disease recurrence were, respectively, 5.1%, 7.4%, and 13.2% at 3 years; and 9.6%, 9.8%, and 15.8% at 5 years. Progression-free survival (PFS) rates at 3 and 5 years were 69.2% and 60.5% respectively; the overall survival (OS) rates were 78.1% and 70.1%, respectively. Five patients (3.4%) experienced grade 3 treatment-related adverse events (AEs). No patient experienced grade 4 or 5 toxicity. Conclusions: From our retrospective analysis with long-term follow-up in Chinese population, SBRT achieved high rate of local control (LC) and low toxicity in patients with early-stage NSCLC. This study offered robust long-term outcome data of SBRT in the Chinese population, which was very rarely reported in China before.

System-Level Capacity of High-Dose Rate (HDR) Brachytherapy for Management of Cervical Cancer in an Upper-Middle Income Country: A Case Study From Brazil.

PURPOSE: Ensuring optimal access to radiation therapy (RT) facilities is challenging for many countries. External beam RT and brachytherapy (BCT) are required to treat advanced cervical cancer. In this analysis, we evaluated the system-level capacity of BCT in Brazil and its relationship with access to complete cervix cancer radiation treatment with both external beam RT and BCT. METHODS AND MATERIALS: We used official government reports to compile data on BCT and linear accelerator (LINAC) numbers, geographic distribution and coverage, cervical cancer annual incidence, and prevalence in Brazil. We also evaluated changes in national BCT capacity between 2001 and 2021. The 2020 relationship between cervical cancer cases for RT per BCT unit, LINAC per BCT unit, and the LINAC supply for each Brazilian state and region were evaluated. For comparison, the LINAC per BCT unit ratio in Brazil was compared with Europe using International Atomic Energy Agency data. RESULTS: Eighty-five percent (23/27) of Brazilian states have at least 1 BCT unit; nationally, there are 117 cervical cancer cases for RT per BCT unit. Compared with the benchmark of 200 cervical cancer cases per BCT device per year, there are enough BCT units to fill capacity in Brazil nationally and regionally. The ratio of total cervix cancer cases per BCT unit decreased substantially over time from 142 in 2013 to 117 in 2021 (P < .0001). Nationally, there are 252 LINAC units in the public system with a ratio of 1985 new cancer cases/LINAC. Brazilian regions have a LINAC shortage ranging from 15 to 141 units. There were 2.55 LINACs per BCT unit in Brazil, compared with 3.25 in Europe (P = .012). CONCLUSIONS: Over 20 years, BCT capacity in Brazil has increased to meet the cervical cancer demand. However, the LINAC shortage has persisted over the decades, affecting access to complete treatment and possibly the oncological outcomes. These data can help organize the patient treatment flow, avoid treatment delays, and improve survival.

Stereotactic body radiotherapy versus surgery for early-stage non-small cell lung cancer: an updated meta-analysis involving 29,511 patients included in comparative studies.

OBJECTIVE: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. RESULTS: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). CONCLUSIONS: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.

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.

Lessons from the Brazilian radiotherapy expansion plan: A project database study.

Background: The Radiotherapy Expansion Plan for Brazil's Unified Health System (PER-SUS) was an innovative program designed by the Ministry of Health in 2012 to provide improvements to the challenging problem of access to radiotherapy in the country. This study sought to analyze the execution and implementation of installations proposed by PER-SUS, and their capacity to address the problems of radiotherapy access in Brazil. Methods: From the first release (February 2015) until October 2021, all PER-SUS monthly progress reports were retrospectively analyzed. The beneficiary institutions, project location, project status, project type, dates of the progress on the stages, and reasons for cancellations or possible justifications for changing the status were collected. Brazilian geographic data, health care demands, and cancer incidences were correlated. Finally, we performed an Ishikawa diagram and 5W3H methodology, aiming to better understand the findings and to yield possible ways to improve the access to radiotherapy. Findings: After ten years, the PER-SUS project delivered nearly 50% of the planned implementation of radiotherapy equipment. There was a 17% growth in the national number of linear accelerators (LINACS) with PER-SUS, against a 32% increase in cancer incidence in Brazil in the same period. The following points were identified: a high rate of beneficiary exclusions reflecting inappropriate selection or inadequate planning; delays in execution related to bureaucratic obstacles and underestimation of the requirements (logistics/people); early closing of the equipment factory as a result of lack of project prioritization by the Government. Interpretation: Only about 50% of PER-SUS are being carried out. However, delays and exclusions of beneficiaries were observed. The dimension of the need for radiotherapy care in Brazil is greater than considered, and might not be fully attended by PER-SUS. Geographic, epidemiological, logistical, and economic variables could be reevaluated to allow better strategic planning and improvement proposals. PER-SUS could be optimized for the next decade, by involving all stakeholders' participation, alignment, and engagement. In the future, the States and regions with a higher LINAC shortage should be prioritized to improve RT access across the country. Considering the data and the initial project deadline, PER-SUS did not achieve the pre-established goals specified by the Brazilian Government. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Stereotactic body radiotherapy versus surgery for early-stage non-small cell lung cancer: an updated meta-analysis involving 29,511 patients included in comparative studies / Radioterapia estereotáxica corporal vs. cirurgia para câncer de pulmão de células não pequenas em estágio inicial: meta-análise atualizada envolvendo 29.511 pacientes incluídos em estudos comparativos

ABSTRACT Objective: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. Results: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). Conclusions: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.

RESUMO Objetivo: Avaliar a eficácia da stereotactic body radiotherapy (SBRT, radioterapia estereotáxica corporal) vs. cirurgia para câncer de pulmão de células não pequenas em estágio inicial por meio de uma meta-análise de estudos comparativos. Métodos: Seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses e Meta-analysis of Observational Studies in Epidemiology, foram realizadas buscas no PubMed, MEDLINE, Embase e Cochrane Library por estudos elegíveis. A meta-análise comparou as razões de risco (RR) para sobrevida global (SG), sobrevida específica para câncer (SEC) e controle local (CL). As análises de subgrupo e metarregressão avaliaram a associação de extensão da ressecção cirúrgica, ano de publicação do estudo, estadiamento do tumor, correspondência de escore de propensão, porcentagem de quimioterapia e porcentagem de acometimento linfonodal com SEC e SG. Resultados: Trinta estudos envolvendo 29.511 pacientes foram incluídos (grupo cirurgia: 17.146 pacientes e grupo SBRT: 12.365 pacientes). Houve diferença significativa a favor da cirurgia vs. SBRT na SG em 3 anos (RR = 1,35; IC95%: 1,22-1,44; I2 = 66%) e na SEC em 3 anos (RR = 1,23; IC95%: 1,09-1,37; I2 = 17%), mas não no CL em 3 anos (RR = 0,97; IC95%: 0,93-1,08; I2 = 19%). Na análise de subgrupo para SG, nenhuma diferença significativa entre os grupos cirurgia e SBRT foi observada no subgrupo T1N0M0 (RR = 1,26; IC95%: 0,95-1,68; I2 = 0%). Na análise de subgrupo para SEC, nenhuma diferença significativa foi detectada entre o subgrupo ressecção sublobar e o grupo SBRT (RR = 1,21; IC95%: 0,96-1,53; I2 = 16%). Conclusões: A cirurgia geralmente resultou em melhor SG e SEC em 3 anos do que a SBRT; no entanto, viés de publicação e heterogeneidade podem ter influenciado esses achados. Já a SBRT produziu resultados de CL semelhantes aos da cirurgia, independentemente da extensão da ressecção cirúrgica. Esses achados podem ter implicações clínicas importantes para pacientes com comorbidades, idade avançada, baixa reserva pulmonar e outros fatores que possam contraindicar a cirurgia.

Cost-effectiveness analysis comparing intensity-modulated radiotherapy with conformational radiotherapy (3D-RT) for prostate cancer in the brazilian health system.

OBJECTIVE: The intensity-modulated radiotherapy (IMRT) has been established as the standard external-beam radiation technique to treat prostate cancer in several countries. In Brazil, the public health system and the National Health Agency do not reimburse its utilization. This study compared the cost-effectiveness of IMRT and tridimensional radiotherapy (3D-RT) from a payer's perspective. METHODS: We built a Markov model to delineate the health states after treatment with IMRT and 3D-RT. The treatment-related toxicity data were extracted from the literature. The sensitivity analyses were performed over potential parameters. RESULTS: The incremental cost of IMRT was R$ 5,553.78. At a time horizon of 5 years, the quality-adjusted life expectancy after IMRT was higher than 3D-RT. The incremental cost-effectiveness ratio (ICER) of IMRT over 3D-RT was R$-296,74/quality-adjusted life year (QALY). Therefore, IMRT was the dominant strategy, which depended on the value of interventional procedures for severe toxicity and the difference between IMRT and 3D-RT reimbursement. The IMRT was still most likely to be cost-effective at a willingness-to-pay R$ 100,000/QALY, with a net monetary benefit (NMB) superior to 3D-RT after R$ 50,000.00, resulting in a difference of R$220.000,00 after 5 years. CONCLUSIONS: IMRT generated more values than 3D-RT for external-beam treatment. Given its potential to reduce late toxicity with hypofractionation, these data reinforce its incorporation to treat prostate cancer in the Brazilian health system from a payer's perspective.

Prophylactic corticosteroid to prevent pain flare in bone metastases treated by radiotherapy.

BACKGROUND: The aim of this study was to evaluate the effectiveness of prophylactic corticosteroids to prevent pain flare (PF) in bone metastases treated with radiotherapy performing a meta-analysis of randomized clinical trials (RCT). MATERIALS AND METHODS: RCTs were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-analysis was performed to assess if corticosteroids reduce the PF, pain progression, and the mean of days with PF compared with the placebo. A p-value < 0.05 was considered significant. RESULTS: Three RCTs with a total of 713 patients treated were included. The corticosteroids reduced the occurrence of early PF 20.5% (51/248) versus 32% (80/250) placebo, OR = 0.55 (95% CI: 0.36-0.82, p = 0.002). The mean days of PF were reduced to 1.6 days (95% CI: 1.3-1.9, p = 0.0001). Prophylactic corticosteroids had more patients with no PF and no pain progression, OR = 1.63 (95% CI: 1.14-2.32, p = 0.007). No significant corticosteroids effect was observed for pain progression (p = ns) and late PF occurrence (p = ns). CONCLUSION: Prophylactic corticosteroids reduced the incidence of early PF, the days with PF, resulting in a superior rate of patients with no PF and no pain progression, but with no significant benefit for reducing pain progression or late PF occurrence.

Radiotherapy for locally advanced head and neck cancer in elderly patients: results and prognostic factors a single cohort.

BACKGROUND: The objective of this study was to assess the treatment outcomes and prognostic factors of elderly patients with locally advanced head and neck cancer (LAHNC) undergoing radiotherapy (RT). MATERIALS AND METHODS: A retrospective cohort from a single institution, from 2000 to 2015, including patients older than 65 years old with LAHNC (stage III-IVa) treated by RT combined or not with chemotherapy (CRT). Univariate and multivariate analysis (MVA) were performed to identify prognostic factors associated with overall survival (OS), cancer-specific survival (CS), and locoregional control (LRC). A p-value < 0.05 was considered significant. RESULTS: 220 patients with LAHNC and > 65 years of age were identified. The median follow-up was 3.8 years, the 3/5 years estimated OS, CS, and LRC rate was 40%/30%, 49%/34%, 76%/45%, respectively. In the univariate analysis, clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.035), Karnofsky performance status (KPS, 60-70, p = 0.03) and tumor site (other than vs. hypopharynx, p = 0.0001) were associated with lower OS. Patients with clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.015), N stage (N0/1 vs. N2/3, p = 0.04), (KPS 60-70, p = 0.04) and tumor site (other than vs. hypopharynx, p = 0.0001) had worst CS. For the LRC, clinical stage (III vs. IVa/b, p = 0.02), tumor stage (T1/2 vs. T3/4, p = 0.02), treatment type (CRT vs. RT, p = 0.02), RT technique (IMRT vs. 2DRT/3DRT, p = 0.0001), and tumor site (other than vs. hypopharynx, p = 0.02) were significant. In the MVA, KPS maintained significant for OS and CS. For LRC, clinical stage (Iva/b, p = 0.007), tumor stage (T3/4, p = 0.047) and radiotherapy technique other than IMRT (p = 0.0001) were significant. CONCLUSION: The OS, CS, and LRC were associated with several prognostic factors. The clinical performance was the main marker of OS and CS. Chemoradiation should be offered to selected elderly patients using IMRT to improve LRC.

Patient-specific IMRT QA verification using machine learning and gamma radiomics.

Gamma function is the standard methodology for comparing dose distributions. It is calculated in dedicated software, and its results verification is not performed. Thus we developed an automatic tool for patient-specific QA results verification through high accuracy machine learning (ML) models based on the radiomics characteristics extraction from gamma images. We used 158 patient-specific QA tests and extracted 105 radiomics features from each gamma image. Three random forest models were developed (ML I, ML II, and ML III). ML I and ML II verified the gamma image approval using criteria of 2%/2mm/15% threshold and 3%/3mm/15% threshold, respectively. ML III verified if the gamma analyzes software recommended protocol was followed to detect if the TPS grid modification step was done. The models were based on the most important features selected using the mean decreased impurity, and their performances were evaluated. ML I included 25 features. Its accuracy was 0.85 using the test set and 0.84 using dataset B. ML II included 10 features, and its accuracy with the test set was 0.98; the same value was achieved using the never seen data (dataset B). The First-order 10th percentile feature was identified as a feature strongly related to the approved classification. ML III selected 23 features with an accuracy of 0.99 for test set and 0.98 for dataset B. An automatic workflow example for gamma analyses QA results verification could be proposed combining the models to detect grid inconsistencies on software evaluation, followed by the test approval classification.

Evaluation of survival of patients with locally advanced head and neck cancer treated in a single center / Avaliação da sobrevida de pacientes com câncer de cabeça e pescoço localmente avançado tratados em um único centro

Abstract Introduction: Even with improved treatment outcomes with multimodality approaches, the question of what is the best initial treatment for locally advanced head and neck cancer still remains unanswered. Objective: To review the overall survival of a large cohort of head and neck cancer, patients with locally advanced head and neck cancer treated in a single institution. Material and methods: We studied a cohort of patients with locally advanced head and neck cancer treated in our institution in the last fifteen years. To gather a large sample of patients with adequate follow-up time, a cross-check between ours and Fundação Oncocentro de São Paulo databases were done. We included patients with head and neck cancer, clinical or pathological staging III or IV, treated with surgery followed by radiotherapy or surgery plus chemoradiation or radiotherapy alone or chemoradiation alone. Results: 796 patients with locally advanced head and neck cancer were included, 88% male, 44% age >60 years and 76% stage IV. The tumor location was the oral cavity (34%), oropharynx (27%), hypopharynx (17%) and larynx (17%). The treatment groups were chemoradiation alone (39.7%), surgery plus chemoradiation (26.3%), surgery followed by radiotherapy (18.5%) and radiotherapy alone (15.5%). Comparing the clinical variables between the treatment groups significant differences in age and clinical stage were observed. With a median follow up of 7.5 years (1-16 years), for the entire cohort, the overall survival at 5 and 10 years was 34.8% and 28%. The overall survival at 5 and 10 years was 16.7% and 12.2% for radiotherapy alone, 38.8% and 26.3% for surgery followed by radiotherapy, 28% and 16.6% for chemoradiation alone, and 37.3% and 23.2% for surgery plus chemoradiation. The staging IV (p = 0.03) and radiotherapy alone (p = 0.05), had a worst survival in multivariate analysis. Surgical groups vs. chemoradiation alone had no significant difference for overall survival. Conclusion: The present study is the largest cohort of locally advanced head and neck cancer of Brazilian patients to evaluate treatment outcomes. Although there were significant clinical differences between surgical and radiotherapy groups, surgery or chemoradiation alone as the initial treatment resulted in no significant difference in survival.

Resumo Introdução: Mesmo com a melhora dos desfechos de tratamento com abordagens multimodais, a dúvida sobre qual seria o melhor tratamento inicial para o câncer de cabeça e pescoço localmente avançado ainda permanece sem resposta. Objetivo: Mostrar a sobrevida global de uma grande coorte de pacientes com câncer de cabeça e pescoço localmente avançado tratados em uma única instituição. Material e método: Projetamos uma coorte de pacientes com câncer de cabeça e pescoço localmente avançado tratados em nossa instituição nos últimos 15 anos. Para reunir uma grande amostra de pacientes com tempo de seguimento adequado, foi realizada uma verificação cruzada entre nosso banco de dados e o banco de dados da fundação oncocentro de São Paulo. Foram incluídos os pacientes com câncer de cabeça e pescoço, estadiamento clínico ou histopatológico III ou IV, tratados com cirurgia seguida de radioterapia ou quimiorradioterapia ou radioterapia isolada ou quimiorradioterapia isolada. Resultados: Foram incluídos 796 pacientes com câncer de cabeça e pescoço localmente avançado, sendo 88% do sexo masculino, 44% com idade > 60 anos e 76% no estágio IV. O tumor estava localizado na cavidade oral (34%), orofaringe (27%), hipofaringe (17%) e laringe (17%). Os grupos de tratamento foram quimiorradioterapia (39,7%), cirurgia seguida de radioterapia ou quimiorradioterapia (26,3%), cirurgia seguida de radioterapia (18,5%) e radioterapia isolada (15,5%). Comparando as variáveis clínicas entre os grupos de tratamento, foram observadas diferenças significativas de idade e estágio clínico. Com uma mediana de tempo de seguimento de 7,5 anos (1-16 anos) para toda a coorte, a sobrevida global em 5 e 10 anos foi de 34,8% e 28%. A sobrevida global em 5 e 10 anos foi de 16,7% e 12,2% para radioterapia isolada, 38,8% e 26,3% para cirurgia seguida de radioterapia, 28% e 16,6% para quimiorradioterapia e 37,3% e 23,2% para cirurgia seguida de radioterapia ou quimiorradioterapia. O estágio IV (p = 0,03) e a radioterapia isolada (p = 0,05) apresentaram pior sobrevida na análise multivariada. Grupos cirúrgicos versus quimiorradioterapia não apresentaram diferença significante para a sobrevida global. Conclusão: O presente estudo é a maior coorte de câncer de cabeça e pescoço localmente avançado de pacientes brasileiros para avaliação dos desfechos do tratamento. Embora houvesse diferenças clínicas significativas entre os grupos cirúrgico e radioterápico, a cirurgia ou a quimiorradioterapia, como tratamento inicial, não apresentaram diferenças significantes em relação à sobrevida.

HDR brachytherapy as monotherapy for prostate cancer: A systematic review with meta-analysis.

PURPOSE: The effectiveness and safety of high dose brachytherapy as monotherapy (HDR-BRT-M) in prostate cancer is limited to retrospective studies. We performed a meta-analysis to summarize existing data and identify trends in biochemical recurrence-free survival (bRFS) and toxicity after HDR-BRT-M in patients with prostate cancer. METHODS AND MATERIALS: Retrospective, prospective, or randomized clinical trials were identified on electronical databases through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-regression analysis was performed to assess if there is a relationship between moderator variables and bRFS. A p-value < 0.05 was considered significant. RESULTS: Fourteen studies with a total of 3534 patients treated were included. The cumulative size of the bRFS at 5 years was 0.92 (95% confidence interval (CI) 0.48-0.61). The five-year bRFS for low, intermediate, and high risk was 97.5% (95% CI 96-98%), 93.5% (95% CI 91-96%), and 91% (95% CI 88-93%), respectively. The total biological effective dose (BED) (p = 0.02), the BED per fraction (p = 0.001), androgen deprivation therapy usage (p = 0.04), and the number of fractions of HDR-BRT-M (p = 0.024) were significantly associated with bRFS rate. The rate of late Grade 2/3 or > genitourinary and gastrointestinal toxicity was 22.4% (95% CI 9-35,2%)/1.4% (95% CI 0.8-2.1%) and 2.7% (95% CI 0-6.8%) and 0.2% (95% CI 0.1%-0.4%), respectively. CONCLUSIONS: HDR-BRT-M is safe with excellent rates of bRFS for all risk groups. The total BED, the BED per fraction, and number of fractions were the key factors associated with the biochemical control. These data can be useful to choose the size and number of BRT fractionation.

Sequential or concomitant chemotherapy with hypofractionated radiotherapy for locally advanced non-small cell lung cancer: a meta-analysis of randomized trials.

BACKGROUND: For patients with locally advanced non-small cell lung cancer (NSCLC), the standard treatment is concurrent or sequential chemotherapy with radiotherapy. Most treatment schedules use radiotherapy with conventional fractionation; however, the application of hypofractionated radiotherapy (HYPO-RT) regimens is rising. A meta-analysis was performed to assess the efficacy and safety of chemotherapy combined with HYPO-RT and indirectly compare with the outcomes from previous studies employing concomitant conventional radiotherapy (CONV-RT). METHODS: Randomized controlled trials (RCTs) were identified on the electronic database sources through June 2020. Following the PRISMA guidelines, a meta-analysis was performed to assess if there were significant differences in the overall mortality (OM), local failure (LF), and disease progression (DP), comparing HYPO-RT-C vs. sequential chemotherapy followed HYPO-RT (HYPO-RT-S). To establish an indirect comparison with the current standard treatment, we calculate the risk ratio (RR) of the OM from RCTs using conventional chemoradiation, concurrent (CONV-RT-C), and sequential (CONV-RT-S), and compared with HYPO-RT. A P value <0.05 was considered significant. RESULTS: Two RCTs with a total of 288 patients were included. The RR for the OM, DP and LF at 3 year comparing HYPO-RT-C vs. HYPO-RT-S were 1.09 (95% CI: 0.96-1.28, P=0.17), 1.06 (95% CI: 0.82-1.23, P=0.610), and 1.06 (95% CI: 0.86-1.29, P=0.490), respectively. The late grade 3 pneumonitis and esophagitis had no significant difference between HYPO-RT groups. In the indirect comparison of RCTs using CONV-RT, the RR for the OM at 3 years was 1.03 (95% CI: 0.96-1.10, P=0.36) with no significant difference for the HYPO-RT arms 1.09 (95% CI: 0.96-1.28, P=0.17). DISCUSSION: HYPO-RT given with chemotherapy provides satisfactory OM, LF, and DP in locally advanced NSCLC with similar rates to the CONV-RT. These findings support HYPO-RT inclusion in future clinical trials as an experimental arm in addition to the incorporation of new strategies, such as immunotherapy.

Evaluation of survival of patients with locally advanced head and neck cancer treated in a single center.

INTRODUCTION: Even with improved treatment outcomes with multimodality approaches, the question of what is the best initial treatment for locally advanced head and neck cancer still remains unanswered. OBJECTIVE: To review the overall survival of a large cohort of head and neck cancer, patients with locally advanced head and neck cancer treated in a single institution. MATERIAL AND METHODS: We studied a cohort of patients with locally advanced head and neck cancer treated in our institution in the last fifteen years. To gather a large sample of patients with adequate follow-up time, a cross-check between ours and Fundação Oncocentro de São Paulo databases were done. We included patients with head and neck cancer, clinical or pathological staging III or IV, treated with surgery followed by radiotherapy or surgery plus chemoradiation or radiotherapy alone or chemoradiation alone. RESULTS: 796 patients with locally advanced head and neck cancer were included, 88% male, 44% age >60 years and 76% stage IV. The tumor location was the oral cavity (34%), oropharynx (27%), hypopharynx (17%) and larynx (17%). The treatment groups were chemoradiation alone (39.7%), surgery plus chemoradiation (26.3%), surgery followed by radiotherapy (18.5%) and radiotherapy alone (15.5%). Comparing the clinical variables between the treatment groups significant differences in age and clinical stage were observed. With a median follow up of 7.5 years (1-16 years), for the entire cohort, the overall survival at 5 and 10 years was 34.8% and 28%. The overall survival at 5 and 10 years was 16.7% and 12.2% for radiotherapy alone, 38.8% and 26.3% for surgery followed by radiotherapy, 28% and 16.6% for chemoradiation alone, and 37.3% and 23.2% for surgery plus chemoradiation. The staging IV (p = 0.03) and radiotherapy alone (p = 0.05), had a worst survival in multivariate analysis. Surgical groups vs. chemoradiation alone had no significant difference for overall survival. CONCLUSION: The present study is the largest cohort of locally advanced head and neck cancer of Brazilian patients to evaluate treatment outcomes. Although there were significant clinical differences between surgical and radiotherapy groups, surgery or chemoradiation alone as the initial treatment resulted in no significant difference in survival.

Patterns of recurrence and outcomes of glioblastoma multiforme treated with chemoradiation and adjuvant temozolomide.

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Palliative radiotherapy for gastric cancer: Is there a dose relationship between bleeding response and radiotherapy?

The aim of this study was to evaluate whether there is a relationship between bleeding response and radiotherapy dose to palliate patients with local recurrence or progression of gastric cancer (GC). To this end, we conducted a systematic review and meta-analysis of observational studies that evaluated the bleeding response in patients with GC with local recurrence or progression. A meta-regression analysis between biological effective dose (BED) and bleeding response was performed, as was subgroup analysis to evaluate the outcome by BED level and radiotherapy (RT) technique. A p-value <0.05 was considered significant. Ten non-comparative retrospective studies and one prospective study were included. In general, RT was effective at controlling tumor bleeding, and the bleeding response rate was 0.77 (95% confidence interval (CI), 0.73-0.81). Meta-regression analysis demonstrated a linear correlation between BED Gy 10 and bleeding response (p=0<0001). Studies using conformational RT had a significant bleeding response rate compared to those using 2D (0.79; 95%CI, 0.74-0.84 vs 0.65; 95%CI, 0.56-0.75; p=0.021). In terms of the BED level, a significant difference in BR was identified on comparing BED Gy10 ≥40 (0.79; 95%CI, 0.7-0.8), BED Gy10 30-39 (0.79, 95%CI, 0.71-0.86), and BED Gy10 <30 (0.64; 95%CI, 0.5-0.7; p=0.0001). The mean survival time was 3.31 months (95%CI, 2.73-3.9) months, and the responders had a significantly longer survival (longer by 2.5 months) compared to the non-responders (95%CI, 1.7-3.3; p<0.0001). Palliative RT is effective at controlling bleeding due to local recurrence/progression from GC. Our findings reveal a relationship between BR and BED. BED <30 Gy 10 should not be recommended, and 3DRT should be indicated instead in order to improve the result.

Significant impact on the oncologic outcomes with intensity modulated radiotherapy and conformational radiotherapy over conventional radiotherapy in cervix cancer patients treated with radiotherapy.

OBJECTIVE: We designed a retrospective cohort of women with cervix cancer treated by radiation therapy with an extended follow-up to evaluate if the incorporation of modern radiation techniques was a prognostic factor. MATERIAL AND METHODS: We studied a cohort of patients with cervix cancer FIGO stage I-IVa treated in the last fifteen years. Patients were treated with radiotherapy alone (RT) or chemoradiation alone (CRT) using conventional radiotherapy (2DRT), conformational radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) followed by high dose rate brachytherapy. Univariate and multivariate analysis was conducted to identify significant prognostic factors (p < 0.05). RESULTS: 228 patients with cervix cancer were included. The treatment groups were CRT (64.8%), and RT (34.2%), with 31.6% submitted to 2DRT and 68.4% to IMRT/3DRT. The median follow-up was 6.3 years, the OS in 5 years according to the treatment groups was 48% for CRT, and 27.8% for RT (p < 0.001). The early-stage I-IIa (p = 0.001), CRT, and IMRT/3DRT were significant factors for better overall survival (OS) in the multivariate analysis. For the cancer-specific survival (CSS), chemoradiation, age <60 years, and IMRT/3DRT were significant. Treatment with IMRT/3DRT was the only prognostic factor associated with event-free survival (EFS). CONCLUSION: In a long-term follow-up, chemoradiation, early-clinical stage, and age <60 years were significant factors associated with better OS and CSS at 5 and 8 years. The incorporation of new radiation techniques, such as IMRT/3DRT, over time has a significant impact on all endpoints (EFS, OS, and CSS) of this cohort. These outcomes are useful to decide about the radiation technique to achieve satisfactory oncological results outside a clinical trial.