Radiotherapy combined or not with chemotherapy in adult or pediatric patients with brainstem glioma: a population-based study.

Background: The purpose of this study was to assess the treatment outcomes and prognostic factors of brainstem glioma (BCG) patients treated by radiotherapy (RT) or chemoradiation (CHRT) in the last 20 years in a population cohort. Materials and methods: Patients diagnosed with BSG from 2000-2020 treated by RT or CHRT were identified from The Fundação Oncocentro de São Paulo database. Data on age, gender, practice setting, period of treatment, and treatment modality were extracted. The overall survival (OS) was estimated, and the subgroups were compared with the log-rank test. Cox proportional test was used in multivariate analysis. Results: A total of 253 patients with a median follow-up of 12 months were included. There were 197 pediatric and 56 adult patients. For the entire cohort, the 1 and 3-year OS was 46%, and 23%, with a median OS of 11 months. In the subgroup analysis, adults had a median survival of 33 months versus 10 months in pediatric patients (p = 0.002). No significant difference in OS between RT and CHRT was observed in pediatric or adult subgroups (p > 0.05). The use of CHRT has significantly increased over the years. In the multivariate analysis, adult patients were the only independent prognostic factor associated with a better OS (p < 0.001). Conclusions: BSG had poor survival with no significant improvement in the treatment outcomes over the last 20 years, despite the addition of chemotherapy. Adult patients were independently associated with better survival.

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.

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.

Exploration of exposure to artificial intelligence in undergraduate medical education: a Canadian cross-sectional mixed-methods study.

BACKGROUND: Emerging artificial intelligence (AI) technologies have diverse applications in medicine. As AI tools advance towards clinical implementation, skills in how to use and interpret AI in a healthcare setting could become integral for physicians. This study examines undergraduate medical students' perceptions of AI, educational opportunities about of AI in medicine, and the desired medium for AI curriculum delivery. METHODS: A 32 question survey for undergraduate medical students was distributed from May-October 2021 to students to all 17 Canadian medical schools. The survey assessed the currently available learning opportunities about AI, the perceived need for learning opportunities about AI, and barriers to educating about AI in medicine. Interviews were conducted with participants to provide narrative context to survey responses. Likert scale survey questions were scored from 1 (disagree) to 5 (agree). Interview transcripts were analyzed using qualitative thematic analysis. RESULTS: We received 486 responses from 17 of 17 medical schools (roughly 5% of Canadian undergraduate medical students). The mean age of respondents was 25.34, with 45% being in their first year of medical school, 27% in their 2nd year, 15% in their 3rd year, and 10% in their 4th year. Respondents agreed that AI applications in medicine would become common in the future (94% agree) and would improve medicine (84% agree Further, respondents agreed that they would need to use and understand AI during their medical careers (73% agree; 68% agree), and that AI should be formally taught in medical education (67% agree). In contrast, a significant number of participants indicated that they did not have any formal educational opportunities about AI (85% disagree) and that AI-related learning opportunities were inadequate (74% disagree). Interviews with 18 students were conducted. Emerging themes from the interviews were a lack of formal education opportunities and non-AI content taking priority in the curriculum. CONCLUSION: A lack of educational opportunities about AI in medicine were identified across Canada in the participating students. As AI tools are currently progressing towards clinical implementation and there is currently a lack of educational opportunities about AI in medicine, AI should be considered for inclusion in formal medical curriculum.

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.

Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer?

OBJECTIVES: To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. PATIENTS AND METHODS: A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. RESULTS: Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort. CONCLUSIONS: A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.

Radiation Oncology Fellowship: a Value-Based Assessment Among Graduates of a Mature Program.

The University of Toronto - Department of Radiation Oncology (UTDRO) has had a well-established Fellowship Program for over 20 years. An assessment of its graduates was conducted to evaluate training experience and perceived impact on professional development. Graduates of the UTDRO Fellowship Program between 1991 and 2015 were the focus of our review. Current employment status was collected using online tools. A study-specific web-based questionnaire was distributed to 263/293 graduates for whom active e-mails were identified; questions focused on training experience, and impact on career progression and academic productivity. As a surrogate measure for the impact of UTDRO Fellowship training, a comparison of current employment and scholarly activities of individuals who obtained their Fellow of the Royal College of Physicians of Canada (FRCPC) designation in Radiation Oncology between 2000 and 2012, with (n = 57) or without (n = 230) UTDRO Fellowship training, was conducted. Almost all UTDRO Fellowship graduates were employed as staff radiation oncologists (291/293), and most of those employed were associated with additional academic (130/293), research (53/293), or leadership (68/293) appointments. Thirty-eight percent (101/263) of alumni responded to the online survey. The top two reasons for completing the Fellowship were to gain specific clinical expertise and exposure to research opportunities. Respondents were very satisfied with their training experience, and the vast majority (99%) would recommend the program to others. Most (96%) felt that completing the Fellowship was beneficial to their career development. University of Toronto, Department of Radiation Oncology Fellowship alumni were more likely to hold university, research, and leadership appointments, and author significantly more publications than those with FRCPC designation without fellowship training from UTDRO. The UTDRO Fellowship Program has been successful since its inception, with the majority of graduates reporting positive training experiences, benefits to scholarly output, and professional development for their post-fellowship careers. Key features that would optimize the fellowship experience and its long-term impact on trainees were also identified.

Stereotactic ablative radiation therapy for spinal metastases: experience at a single Brazilian institution.

BACKGROUND: This study aims to assess the clinical outcomes of patients with spine metastases who underwent stereotactic ablative radiation therapy (SABR) as part of their treatment. SABR has arisen as a contemporary treatment option for spinal metastasis patients with good prognoses. MATERIALS AND METHODS: Between November 2010 and September 2018, Spinal SABR was performed in patients with metastatic disease in different settings: radical (SABR only), postoperative (after decompression and/or fixation surgery), and reirradiation. Local control (LC), pain control, overall survival (OS) and toxicities were reported. RESULTS: Eighty-five patients (corresponding to 96 treatments) with spine metastases were included. The median age was 59 years (range, 23-91). In most SA BR (82.3%, n = 79) was performed as the first local spine treatment, while in 12 settings (12.5%), fixation and/or decompression surgery was performed prior to SABR. Two-year overall survival rate was 74.1%, and median survival was 19 months. The LC rate at 2 years was 72.3%. With regard to pain control, among 67 patients presenting with pain before SA BR, 83.3% had a complete response, 12.1% had a partial response, and 4.6% had progression. Vertebral compression fractures occurred in 10 patients (11.7%), of which 5 cases occurred in the reirradiation setting. Radiculopathy and myelopathy were not observed. No grade III or IV toxicities were seen. CONCLUSION: This is the first study presenting a Brazilian experience with spinal SA BR, and the results confirm its feasibility and safety. SABR was shown to produce good local and pain control rates with low rates of adverse events.

Core elements of national cancer control plans: a tool to support plan development and review.

When developed and implemented effectively, national cancer control plans (NCCPs) improve cancer outcomes at the population level. However, many countries do not have a high-quality, operational NCCP, contributing to disparate cancer outcomes globally. Until now, a standard reference of NCCP core elements has not been available to guide development and evaluation across diverse countries and contexts. In this Policy Review, we describe the methods, process, and outcome of an initiative to develop an itemised and evidence-based comprehensive checklist of core elements for NCCP formulation. The final list provides a ready-to-use guide to support NCCP development and to facilitate internal and external critical appraisal of existing NCCPs for countries of all income levels and settings. Governments, policy makers, and stakeholders can utilise this checklist, while considering their own unique contexts and priorities, from the drafting through to the implementation of NCCPs.

International Multicenter Validation of an Intermediate Risk Subclassification of Prostate Cancer Managed with Radical Treatment without Hormone Therapy.

PURPOSE: The NCCN Guidelines® recently endorsed a subclassification of intermediate risk prostate cancer into favorable and unfavorable subgroups. However, this subclassification was developed in a treatment heterogeneous cohort. Thus, to our knowledge the natural history of androgen deprivation treatment naïve favorable and unfavorable intermediate risk prostate cancer cases remains unknown. MATERIALS AND METHODS: Groups at 3 academic centers pooled data on patients with intermediate risk prostate cancer treated with radical monotherapy (dose escalated external beam radiotherapy, brachytherapy or radical prostatectomy) without combined androgen deprivation treatment. We used the cumulative incidence with competing risk analysis to estimate biochemical recurrence, distant metastasis and prostate cancer specific mortality. RESULTS: A total of 2,550 men at intermediate risk were included in study, of whom 1,063 and 1,487 were at favorable and unfavorable risk, respectively. Of the men 1,149 underwent radical prostatectomy, 1,143 underwent dose escalated external beam radiotherapy and 258 underwent brachytherapy. Median followup after the different treatments ranged from 60.4 to 107.4 months. The 10-year cumulative incidence of distant metastasis in the favorable vs unfavorable risk groups was 0.2% (95% CI 0.2-0.2) vs 11.6% (95% CI 7.7-15.5) for radical prostatectomy (p <0.001), 2.8% (95% CI 0.8-4.8) vs 13.5% (95% CI 9.6-17.4) for dose escalated external beam radiotherapy (p <0.001) and 3.5% (95% CI 0-7.4) vs 10.2% (95% CI 4.3-16.1) for brachytherapy (p = 0.063). The 10-year rate of prostate cancer specific mortality in the favorable vs unfavorable risk groups was 0% (95% CI 0-0) vs 3.7% (95% CI 1.7-5.7) for radical prostatectomy (p = 0.016), 0.5% (95% CI 0.5-0.5) vs 5.6% (95% CI 3.6-7.6) for dose escalated external beam radiotherapy (p = 0.015) and 0% (95% CI 0-0) vs 2.5% (95% CI 0.5-4.5) for brachytherapy (p = 0.028). CONCLUSIONS: This multicenter international effort independently validates the prognostic value of the intermediate risk prostate cancer subclassification in androgen deprivation treatment naïve cases across all radical treatment modalities. It is unlikely that treatment intensification would meaningfully improve oncologic outcomes in men at favorable intermediate risk.

Accelerated partial breast irradiation: Current status with a focus on clinical practice.

Accelerated partial breast irradiation (APBI), a radiation technique in which only the tumor bed is treated, has now become an acceptable radiation modality for selected early-stage breast cancer patients. Compared to conventional whole breast irradiation (WBI), APBI has some benefits with regard to the reduced total irradiated breast volume and the shorter treatment time. The role of APBI, which can be delivered using diverse techniques, has been evaluated in several prospective randomized phase III trials. These clinical trials demonstrate diverging outcomes relating to local recurrence, while establishing comparable effect in terms of survival between APBI with WBI. The aim of this study was to review the current status of APBI with a focus on clinical practice.

Funding source, conflict of interest and positive conclusions in neuro-oncology clinical trials.

We aimed to test any association between authors' conclusions and self-reported COI or funding sources in central nervous system (CNS) studies. A review was performed for CNS malignancy clinical trials published in the last 5 years. Two investigators independently classified study conclusions according to authors' endorsement of the experimental therapy. Statistical models were used to test for associations between positive conclusions and trials characteristics. From February 2010 to February 2015, 1256 articles were retrieved; 319 were considered eligible trials. Positive conclusions were reported in 56.8% of trials with industry-only, 55.6% with academia-only, 44.1% with academia and industry, 77.8% with none, and 76.4% with not described funding source (p = 0.011). Positive conclusions were reported in 60.4% of trials with unrelated COI, 60% with related COI, and 60% with no COI reported (p = 0.997). Factors that were significantly associated with the presence of positive conclusion included trials design (phase 1) [OR 11.64 (95 CI 4.66-29.09), p < 0.001], geographic location (outside North America or Europe) [OR 1.96 (95 CI 1.05-3.79), P = 0.025], primary outcomes (non-overall or progression free survival) [OR 3.74 (95 CI 2.27-6.18), p < 0.001], and failure to disclose funding source [OR 2.45 (95 CI 1.22-5.22), p = 0.011]. In a multivariable regression model, all these factors remained significantly associated with trial's positive conclusion. Funding source and self-reported COI did not appear to influence the CNS trials conclusion. Funding source information and COI disclosure were under-reported in 14.1 and 17.2% of the CNS trials. Continued efforts are needed to increase rates of both COI and funding source reporting.

The relationship of study and authorship characteristics on trial sponsorship and self-reported conflicts of interest among neuro-oncology clinical trials.

PROPOSE: To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT). METHODS: MEDLINE search was performed for original CT on "Central Nervous System Neoplasms"[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics. RESULTS: From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant. CONCLUSIONS: The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.

Management and Outcomes in the Oldest-Old Population with Glioblastoma.

OBJECTIVES: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. METHODS: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. CONCLUSIONS: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.

An integrated multidisciplinary algorithm for the management of spinal metastases: an International Spine Oncology Consortium report.

Spinal metastases are becoming increasingly common because patients with metastatic disease are living longer. The close proximity of the spinal cord to the vertebral column limits many conventional therapeutic options that can otherwise be used to treat cancer. In response to this problem, an innovative multidisciplinary approach has been developed for the management of spinal metastases, leveraging the capabilities of image-guided stereotactic radiosurgery, separation surgery, vertebroplasty, and minimally invasive local ablative approaches. In this Review, we discuss the variables that should be considered during the management of these patients and review the role of each discipline and their respective management options to provide optimal care. This work is synthesised into a practical algorithm to aid clinicians in the management of patients with spinal metastasis.

Meta-analysis of 5-day preoperative radiotherapy for soft tissue sarcoma (5D-PREORTS).

BACKGROUND AND PURPOSE: Although the role of conventionally fractionated radiotherapy (RT) in combination with surgery in the limb-sparing treatment of soft tissue sarcoma (STS) patients is well established, the effectiveness and safety of 5-day preoperative radiotherapy (RT) remain controversial. We performed a meta-analysis to evaluate the treatment outcomes of 5-day preoperative RT using ≥ 5 Gy per fraction with contemporary radiotherapy techniques. MATERIALS AND METHODS: Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through March 2022 were used to identify eligible studies. Following the PRISMA and MOOSE guidelines, a meta-regression analysis was performed to assess possible correlations between variables and outcomes. A p-value < 0.05 was considered significant. RESULTS: Nine prospective studies with 786 patients (median follow-up 35 months, 20-60 months) treated with preoperative RT delivered a median total of 30 Gy (25-40 Gy) in 5 fractions. The local control (LC), R0 margins, overall survival (OS), and distant relapse (DR) rates were 92.3% (95% CI: 87---97%), 84.5% (95% CI: 78---90%), 78% (95% CI: 70---86%), and 36% (95% CI: 70---86%). The meta-regression analysis identified a significant relationship between biological equivalent dose (BED) and larger tumor size for LC and R0 margins (p < 0.05). The subgroup analysis reveals that patients receiving BED ≥ 90 (equivalent to 30 Gy in 5 fractions) had a higher LC control rate than BED < 90 (p < 0.0001). The complete pathologic response and amputation rates were 19% (95% CI: 13-26%) and 8.3% (95% CI: 0.5-15%). Amputation rates were higher in studies using the lowest and highest doses and were related to salvage surgery after recurrence and complications, respectively. The rate of wound complication and fibrosis grade 2 or worse was 30% (95% CI 23-38%) and 6.4% (95% CI 1.9-11%). CONCLUSION: A 5-day course of preoperative RT results in high LC and favorable R0 margins, with acceptable complication rates in most studies. Better local control and R0 margins were associated with regimens using higher BED, i.e., doses equal to or higher than 30 Gy when using 5 fractions.

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.