Efficacy and safety of hypofractionated radiotherapy versus conventional fractionated radiotherapy in diffuse intrinsic pontine glioma: A systematic review and meta-analysis.

Background: Diffuse intrinsic pontine glioma (DIPG) stands as the predominant type of brainstem glioma. It is characterized by a notably brief median survival period, with the majority of patients experiencing disease progression within six months following radiation therapy. This systematic review and meta-analysis aims to assess the efficacy and safety of hypofractionated radiotherapy (HFRT) compared to conventionally fractionated radiotherapy (CFRT) in DIPG treatment. Materials and methods: A systematic literature search was conducted in four databases, and relevant studies comparing HFRT and CFRT in DIPG were included. Data were extracted and analyzed for overall survival (OS), progression-free survival (PFS), and treatment-related toxicities. Statistical analysis was performed using random-effects models with heterogeneity assessment. Results: Five studies met the inclusion criteria, comprising 518 patients. No significant difference in one-year OS was observed between HFRT and CFRT (29% vs. 22%, p = 0.94). The median OS was similar in both treatment groups (9.7 vs. 9.3 months, p = 0.324). Similarly, no significant difference in one-year PFS was found between HFRT and CFRT (19.8% vs. 16.6%, p = 0.82), with comparable median PFS (9.3 vs. 9.4 months, p = 0.20). In meta-regression analysis, there was no association of chemotherapy (p > 0.05) or radiation biologically effective dose (BED) (p > 0.05) regarding OS or PFS outcomes. There were no significant differences in treatment-related toxicities. Conclusions: HFRT yields one-year OS and PFS rates similar to CFRT in DIPG, with no significant differences in treatment-related toxicities. Chemotherapy and BED did not affect OS or PFS.

Challenges in building radiotherapy capacity: A longitudinal study evaluating eight years of the Brazilian radiotherapy expansion plan.

BACKGROUND: In 2012, the Brazilian government launched a radiotherapy (RT) expansion plan (PER-SUS) to install 100 linear accelerators. This study assesses the development of this program after eight years. METHODS: Official reports from the Ministry of Health (MoH) were reviewed. RT centres projects status, timeframes, and cost data (all converted to US dollars) were extracted. The time analysis was divided into seven phases, and for cost evaluation, there were five stages. The initial predicted project time (IPPT) and costs (estimated by the MoH) for each phase were compared between the 18 operational RT centres (able to treat patients) and 30 non-operational RT centres using t-tests, ANOVA, and the Mann-Whitney U. A p-value < 0.05 indicates statistical significance. RESULTS: A significant delay was observed when comparing the IPPT with the overall time to conclude each 48 RT centres project (p < 0.001), with considerable delays in the first five phases (p < 0.001 for all). Moreover, the median time to conclude the first 18 operational RT centres (77.4 months) was shorter compared with the 30 non-operational RT centres (94.0 months), p < 0.001. The total cost of 48 RT services was USD 82,84 millions (mi) with a significant difference in the per project median total cost between 18 operational RT centres, USD1,34 mi and 30 non-operational RT centres USD2,11 mi, p < 0.001. All phases had a higher cost when comparing 30 non-operational RT centres to 18 operational RT centres, p < 0.001. The median total cost for expanding existing RT centres was USD1,30 mi versus USD2,18 mi for new RT services, p < 0.0001. CONCLUSION: After eight years, the PER-SUS programs showed a substantial delay in most projects and their phases, with increased costs over time. POLICY SUMMARY: Our findings indicate a need to act to increase the success of this plan. This study may provide a benchmark for other developing countries trying to expand RT capacity.

Assessing the efficacy of palliative radiation treatment schemes for locally advanced squamous cell carcinoma of the head and neck: a meta-analysis.

Background: The objective to assess the outcomes from different palliative radiotherapy (RT) schedules in incurable head and neck cancer (HNC), to evaluate if there is a relationship between RT dose, technique, and fractionation with tumor response in contrast to the occurrence of adverse effects. Materials and methods: Eligible studies were identified on Medline, Embase, the Cochrane Library, and annual meetings proceedings through June 2020. Following PRISMA and MOOSE guidelines, a cumulative meta-analysis of studies for overall response rate (ORR), overall survival (OS), progression-free survival (PFS), pain/dysphagia relief, and toxicity was performed. A meta-regression analysis was done to assess if there is a connection between RT dose, schedule, and technique with ORR. Results: Twenty-eight studies with 1,986 patients treated with palliative RT due to incurable HNC were included. The median OS was 6.5 months [95% confidence interval (CI): 5.6-7.4], and PFS was 3.6 months (95% CI: 2.7-4.3). The ORR, pain and dysphagia relief rates were 72% (95% CI: 0.6-0.8), 83% (95% CI: 52-100%), and 75% (95% CI: 52-100%), respectively. Conventional radiotherapy (2D-RT) or conformational radiotherapy (3D-RT) use were significantly associated with a higher acute toxicity rate (grade ≥ 3) than intensity-modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). On meta-regression analyses, the total biological effective doses (BED) of RT (p = 0.001), BED > 60 Gy10 (p = 0.001), short course (p = 0.01) and SBRT (p = 0.02) were associated with a superior ORR. Conclusions: Palliative RT achieves tumor response and symptom relief in incurable HNC patients. Short course RT of BED > 60 Gy using IMRT could improve its therapeutic ratio. SBRT should be considered when available.

Tumor, Patient, and Social Determinants of Health Affecting Survival in Patients With Anal Cancer Treated By Chemoradiation.

PURPOSE: Anal cancer (AC) is a rare disease with scarce evidence from developing countries. We performed a population-based cohort study to investigate the relationship between tumor, patient, and social determinants of health with treatment outcomes of AC treated by chemoradiation (CRT). METHODS AND MATERIALS: Patients who received a diagnosis of AC from 1999 to 2020 were identified from the Fundação Oncocentro de São Paulo database. Only patients with AC stage I-III treated by CRT were included. Age, sex, tumor category (T), nodal category (N), education level, practice setting, time to radiation therapy, histology, and treatment local data were extracted. With the Cox proportional hazard model, the hazard ratio and 95% confidence interval were used to test the relationship between tumor, patient, and social factors with overall survival (OS) and cancer-specific survival (CSS). RESULTS: With 1462 patients assessed, the median follow-up was 72 months, and the OS and CSS at 5/10 years were 61%/46% and 67%/60%, respectively. In the univariate analysis, T category, N category, sex, practice setting, and education level were associated with OS and CSS (P < .05). In the multivariate analysis, female sex, T1/2 category, N0 category, and private service were independently associated with OS (P < .05). For CSS, female sex, T1/2 category, private service, and N0 category remained significant (P < .05). CONCLUSIONS: CRT produced satisfactory rates of OS and CSS in patients with AC, with tumor, patient, and social determinants of health influencing the outcomes. These data could help mitigate the effects of social distortions on the survival of AC.

Radiotherapy activity in the COVID 19 pandemic: Brazil's operational national-level study.

PURPOSE: During the COVID-19 pandemic, patients with cancer are at increased risk of not having timely diagnosis and access to cancer treatment. The present study evaluated the COVID-19 pandemic impact on radiotherapy activity in Brazil. METHODS: A national-level study was performed to evaluate the RT utilization for prostate, breast, head & neck (HN), Gynecology (GYN), Gastrointestinal (GI), lung cancers, and bone/brain metastases. The data on the RT executed was extracted from the Brazilian Ministry of Health database. The NON-COVID period was considered the control group, and the comparison groups were COVID-2020 (without vaccine) and COVID-2021 (with vaccine). RESULTS: We collected the data of 238,355 procedures executed on three periods. Significant difference in the RT utilization between NON-COVID and COVID-2020 were observed for prostate cancer, bone and brain metastases (-12.3 %, p = 0.02, +24 %, p = 0.02 and +14 %, p = 0.04, respectively). Comparing 2 equivalents months from NON-COVID-2019 (ref), COVID-2020, and COVID-2021, a significant increase was identified for bone and brain metastases (2020 +21 %, and 2021 +32 %), and (2020 +20 %, and 2021 +14 %). A stable drop occurred for prostate cancer (2020 -11 % and 2021 -10 %), and a variation was observed for breast (2020 +8 %, and 2021 -1 %) and lung cancer (2020 +10 %, and 2021 -3 %). For other cancers, non-significant changes were observed when comparing 2020 and 2021. CONCLUSION: The RT activity was heterogeneously affected with a substantial increase for bone and brain metastases and a meaningful decline for prostate cancer. POLICY SUMMARY: With a significant increase in the use of palliative radiotherapy for bone and brain metastases and a meaningful reduction in curative radiotherapy for prostate cancer, we hope these findings can help governments, RT services, medical communities, and other stakeholders develop strategies to mitigate the impact of the present and future pandemics. Finally, despite the changes imposed by the COVID pandemic, it is imperative to enhance screening, increase cancer diagnosis at an early stage, and improve access to all cancer treatments, including radiotherapy.

Impact of COVID-19 on the curative treatment of prostate cancer: a national cross-sectional study.

Background: COVID-19 pandemic affected access to cancer treatment worldwide. However, there is a lack of data about the impact in developing countries. The objective was to evaluate COVID-19 impact on curative prostate cancer (Pca) treatment in Brazil. Materials and methods: With data extracted from the Brazilian Ministry of Health database, the Non-COVID and COVID periods were analyzed to compare the absolute number of radical prostatectomy (RP) and radiotherapy (RT) executed in the country and regions. Results: With data from 50,169 Pca patients (Non-COVID = 28,106 cases and COVID = 22,063) treated with RP or RT in Brazil, a significant decline in patients receiving RT or RP (-6.043 cases; p = 0.0001) was detected. Both treatment procedures (RT or PR) were reduced in all five Brazilian regions comparing the Non-COVID and COVID periods. Overall, there was a reduction on RP and RT procedures in 92% (24/25) and 76% (19/25) of the evaluated states, respectively. Comparing the variation of RT and RP per state between COVID and Non-COVID period, there is a significant difference (-18.6% vs. -29%, p = 0.03) with a higher negative impact on the RP group. The RT and RP variation had no significant relationship with the incidence of COVID cases in the states. Limitations include the non-evaluation of treatment combinations, the impact of hypofractionated radiotherapy, and other factors influencing the treatment choice. Conclusions: During the COVID-19 pandemic, the curative treatment with RP and RT of Pca was abruptly limited and affected. However, the number of RP was more impacted than RT during the COVID period.

Meta-analysis of Elective Pelvic Nodal Irradiation Using Moderate Hypofractionation for High-Risk Prostate Cancer.

PURPOSE: Despite several advances in planning and delivery of radiation therapy (RT) for prostate cancer, the role of elective pelvic nodal irradiation (EPNI) remains controversial for high-risk disease. We performed a meta-analysis to evaluate the outcomes of patients treated with moderate hypofractionated RT (MHF-RT) with EPNI using modern RT techniques. METHODS AND MATERIALS: Eligible studies were identified on MEDLINE, Embase, the Cochrane Library, and proceedings of annual meetings through October 2021. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. A metaregression analysis was performed to assess a possible correlation between selected variables and outcomes. A P value <.05 was considered significant. RESULTS: Eighteen studies with a total of 1745 patients (median follow-up, 61 months) treated with EPNI using MHF-RT were included. The biochemical relapse-free survival at 5, 7, and 10 years was 90% (95% confidence interval [CI], 88%-94%), 83% (95% CI, 78%-91%), and 78% (95% CI, 68%-88%). The 5-year prostate cancer-specific survival, disease-free survival, distant metastases-free survival, and overall survival were 98% (95% CI, 97%-99%), 88.7% (95% CI, 85%-93%), 91.2% (95% CI, 88%-92%), and 93% (95% CI, 90%-96%), respectively. The rates of local, pelvic, and distant recurrence were 0.38% (95% CI, 0%-2%), 0.13% (95% CI, 0%-1.5%), and 7.35% (95% CI, 2%-12%), respectively. The rate of late grade ≥2 gastrointestinal and genitourinary toxic effects were 6.7% (95% CI, 4%-9%) and 11.3% (95% CI, 7.6%-15%), with heterogeneity, but with rare cases of grade 3 to 5 toxic effects. CONCLUSIONS: EPNI with concomitant MHF-RT provides satisfactory biochemical relapse-free survival in long-term follow-up, with low rates of genitourinary and gastrointestinal severe toxic effects and minimal pelvic and local failure.

Prioritising locations for radiotherapy equipment in Brazil: a cross-sectional, population-based study and development of a LINAC shortage index.

BACKGROUND: Similarly to several other upper-middle-income countries, there is a major shortfall in radiotherapy services for the treatment of cancer in Brazil. In this study, we developed the linear accelerator (LINAC) shortage index to assess the LINAC shortage and support the prioritisation of new LINAC distribution in Brazil. METHODS: This cross-sectional, population-based study used data from the National Cancer Institute 2020 Cancer estimates, the Ministry of Health 2019 radiotherapy census, the Minister of Health radiotherapy expansion programme progress reports, and the Fundação Oncocentro de São Paulo public database of the Cancer Hospital Registry of the State of São Paulo to calculate the LINAC shortage index. Data collected were number of new cancer cases in Brazil, number of LINACs per region and state, number of cancer cases treated with radiotherapy, patient state of residence, and radiotherapy treatment centre and location. National, regional, and state-level data were collected for analysis. LINAC numbers, cancer incidence, geographical distribution, and radiotherapy needs were estimated. A LINAC shortage index was calculated as a relative measure of LINAC demand compared with supply based on number of new cancer cases, number of patients requiring radiotherapy, and the number of LINCAS in the region or state. We then built a prioritisation framework using the LINAC shortage index, cancer incidence, and geographical factors. Finally, using patient-level public cancer registry data from the Fundação Oncocentro de São Paulo and Google maps, we estimated the geospatial distance travelled by patients with cancer from their state of residence to radiotherapy treatment in São Paulo from 2005-14. Non-parametric statistics were used for analysis. FINDINGS: Data were collected between Feb 2 and Dec 31, 2021. In 2020, there were 625 370 new cancer cases in Brazil and 252 LINAC machines. The number of LINACs was inadequate in all Brazilian regions, with a national LINAC shortage index of 221 (ie, 121% less than the required radiotherapy capacity). The LINAC shortage index was higher in the midwest (326), north (313), and northeast (237) regions, than the southeast (210) and south (192) regions. Four states (Tocantins, Acre, Amapá, and Roraima) in the north region were ranked first on the prioritisation rank due to no availability of LINACs. There was an association between LINAC shortage index and the number of patients who travelled to receive radiotherapy (p<0·0001). Patients living in the midwest (793 km), north (2835 km), and northeast (2415 km) regions travelled significantly longer average distances to receive radiotherapy treatment in São Paulo than patients living in the southeast or south regions (p=0·032). The reduced number of LINACs in these regions was associated with longer distance travelled (p=0·032). INTERPRETATION: There is substantial discordance between distribution of cancer cases and LINAC availability in Brazil. We developed a tool using the LINACs shortage index to help prioritise the development of radiotherapy infrastructure across Brazil; this approach might also be useful in other health systems. FUNDING: None.

Response evaluation after stereotactic ablative radiotherapy for localised non-small-cell lung cancer: an equipoise of available resource and accuracy.

There is growing evidence supporting the use of stereotactic ablative radiotherapy (SABR) on the treatment of localised stage non-small-cell lung cancer (NSCLC). Distinctive imaging challenges are posed post-SABR treatment. Thus, it is imperative to provide guidance on assessing treatment response, especially for new adopters. This commentary is about filling a gap in response evaluation after SABR for localised NSCLC.