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.

Scoping review protocol on the impact of antimicrobial resistance on cancer management and outcomes.

INTRODUCTION: Antimicrobial resistance (AMR) is a growing global public health concern and is becoming a significant challenge in the management of patients with cancer. Due to the immunosuppressive nature of cancer treatment, infection is a common complication and the necessary high usage of antibiotics increases the risk of AMR. Failure to adequately prevent and treat infection in patients with cancer as a result of AMR can increase the morbidity and mortality of the disease. The objective of this scoping review is to understand the relationship between AMR and cancer in order to develop effective antimicrobial stewardship in this patient population and minimise the detrimental effects of AMR on cancer outcomes. METHODS AND ANALYSIS: This scoping review will follow the Arksey and O'Malley methodology framework. An exploratory review of the literature on antibiotic resistance in cancer care will help to define the research questions (stage 1). A broad range of electronic databases (MEDLINE ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Embase) and search terms will be used to retrieve relevant articles published between 2000 and 2021 (stage 2). Studies will be systematically selected based on the eligibility criteria by two independent reviewers (stage 3). The titles and abstracts will be appraised to determine whether articles meet the eligibility criteria. This will be followed by screening of the full texts and only relevant publications will be retrieved. Data will then be extracted, collated and charted (stage 4); and the summary of aggregated results will be presented (stage 5). ETHICS AND DISSEMINATION: As this scoping review will collect and synthesise data from publicly available sources, no ethics review is required. When data collection and summarisation is completed, results will be disseminated through peer-reviewed publication and the key findings of the review will be presented at relevant conferences.

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.

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.

Diagnostic and prognostic implications of a three-antibody molecular subtyping algorithm for non-muscle invasive bladder cancer.

Intrinsic molecular subtypes may explain marked variation between bladder cancer patients in prognosis and response to therapy. Complex testing algorithms and little attention to more prevalent, early-stage (non-muscle invasive) bladder cancers (NMIBCs) have hindered implementation of subtyping in clinical practice. Here, using a three-antibody immunohistochemistry (IHC) algorithm, we identify the diagnostic and prognostic associations of well-validated proteomic features of basal and luminal subtypes in NMIBC. By IHC, we divided 481 NMIBCs into basal (GATA3- /KRT5+ ) and luminal (GATA3+ /KRT5 variable) subtypes. We further divided the luminal subtype into URO (p16 low), URO-KRT5+ (KRT5+ ), and genomically unstable (GU) (p16 high) subtypes. Expression thresholds were confirmed using unsupervised hierarchical clustering. Subtypes were correlated with pathology and outcomes. All NMIBC cases clustered into the basal/squamous (basal) or one of the three luminal (URO, URO-KRT5+ , and GU) subtypes. Although uncommon in this NMIBC cohort, basal tumors (3%, n = 16) had dramatically higher grade (100%, n = 16, odds ratio [OR] = 13, relative risk = 3.25) and stage, and rapid progression to muscle invasion (median progression-free survival = 35.4 months, p = 0.0001). URO, the most common subtype (46%, n = 220), showed rapid recurrence (median recurrence-free survival [RFS] = 11.5 months, p = 0.039) compared to its GU counterpart (29%, n = 137, median RFS = 16.9 months), even in patients who received intravesical immunotherapy (p = 0.049). URO-KRT5+ tumors (22%, n = 108) were typically low grade (66%, n = 71, OR = 3.7) and recurred slowly (median RFS = 38.7 months). Therefore, a simple immunohistochemical algorithm can identify clinically relevant molecular subtypes of NMIBC. In routine clinical practice, this three-antibody algorithm may help clarify diagnostic dilemmas and optimize surveillance and treatment strategies for patients.

Practical considerations for prostate hypofractionation in the developing world.

External beam radiotherapy is an effective curative treatment option for localized prostate cancer, the most common cancer in men worldwide. However, conventionally fractionated courses of curative external beam radiotherapy are usually 8-9 weeks long, resulting in a substantial burden to patients and the health-care system. This problem is exacerbated in low-income and middle-income countries where health-care resources might be scarce and patient funds limited. Trials have shown a clinical equipoise between hypofractionated schedules of radiotherapy and conventionally fractionated treatments, with the advantage of drastically shortening treatment durations with the use of hypofractionation. The hypofractionated schedules are supported by modern consensus guidelines for implementation in clinical practice. Furthermore, several economic evaluations have shown improved cost effectiveness of hypofractionated therapy compared with conventional schedules. However, these techniques demand complex infrastructure and advanced personnel training. Thus, a number of practical considerations must be borne in mind when implementing hypofractionation in low-income and middle-income countries, but the potential gain in the treatment of this patient population is substantial.