Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Organ-sparing techniques and dose-volume constrains used in breast cancer radiation therapy - Results from European and Latin American surveys.

Background: Advances in local and systemic therapies have improved the outcomes of patients with breast cancer (BC), leading to a possible increased risk for postoperative radiation therapy (RT) late adverse events. The most adequate technologies and dose constraints for organs at risk (OAR) in BC RT have yet to be defined. Methods: An online survey was distributed to radiation oncologists (ROs) practicing in Europe and Latin America including the Caribbean (LAC) through personal contacts, RO and BC professional groups' networks. Demographic data and clinical practice information were collected. Results:  The study included 585 responses from ROs practicing in 57 different countries. The most frequently contoured OAR by European and LAC participants were the whole heart (96.6 % and 97.7 %), the ipsilateral (84.3 % and 90.8 %), and contralateral lung (71.3 % and 77.4 %), whole lung (69.8 % and 72.9 %), and the contralateral breast (66.4 % and. 83.2 %). ESTRO guidelines were preferred in Europe (33.3 %) and the RTOG contouring guideline was the most popular in LAC (62.2 %), while some participants used both recommendations (13.2 % and 19.2 %). IMRT (68.6 % and 59.1 %) and VMAT (65.6 % and 60.2 %) were the preferred modalities used in heart sparing strategies, followed by deep inspiration breath-hold (DIBH) (54.8 % and 37.4 %) and partial breast irradiation (PBI) (41.6 % and 24.6 %). Only a small percentage of all ROs reported the dose-volume constraints for OAR used in routine clinical practice. A mean heart dose (Heart-Dmean) between 4 and 5 Gy was the most frequently reported parameter (17.2 % and 39.3 %). Conclusion:  The delineation approaches and sparing techniques for OAR in BC RT vary between ROs worldwide. The low response rate to the dose constraints subset of queries reflects the uncertainty surrounding this topic and supports the need for detailed consensus recommendations in the clinical practice.

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 on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study.

INTRODUCTION/BACKGROUND: This study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. MATERIALS/METHODS: This retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: We analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). CONCLUSIONS: The benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.

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.

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.

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.