Optimizing Clinical Implementation of Hypofractionation: Comprehensive Evidence Synthesis and Practical Guidelines for Low- and Middle-Income Settings.

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care.

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.

Unraveling the multifaceted resilience of arsenic resistant bacterium Deinococcus indicus.

Arsenic (As) is a toxic heavy metal widely found in the environment that severely undermines the integrity of water resources. Bioremediation of toxic compounds is an appellative sustainable technology with a balanced cost-effective setup. To pave the way for the potential use of Deinococcus indicus, an arsenic resistant bacterium, as a platform for arsenic bioremediation, an extensive characterization of its resistance to cellular insults is paramount. A comparative analysis of D. indicus cells grown in two rich nutrient media conditions (M53 and TGY) revealed distinct resistance patterns when cells are subjected to stress via UV-C and methyl viologen (MV). Cells grown in M53 demonstrated higher resistance to both UV-C and MV. Moreover, cells grow to higher density upon exposure to 25 mM As(V) in M53 in comparison with TGY. This analysis is pivotal for the culture of microbial species in batch culture bioreactors for bioremediation purposes. We also demonstrate for the first time the presence of polyphosphate granules in D. indicus which are also found in a few Deinococcus species. To extend our analysis, we also characterized DiArsC2 (arsenate reductase) involved in arsenic detoxification and structurally determined different states, revealing the structural evidence for a catalytic cysteine triple redox system. These results contribute for our understanding into the D. indicus resistance mechanism against stress conditions.

Insights into the role of three Endonuclease III enzymes for oxidative stress resistance in the extremely radiation resistant bacterium Deinococcus radiodurans.

The extremely radiation and desiccation resistant bacterium Deinococcus radiodurans possesses three genes encoding Endonuclease III-like enzymes (DrEndoIII1, DrEndoIII2, DrEndoIII3). In vitro enzymatic activity measurements revealed that DrEndoIII2 is the main Endonuclease III in this organism, while DrEndoIII1 and 3 possess unusual and, so far, no detectable EndoIII activity, respectively. In order to understand the role of these enzymes at a cellular level, DrEndoIII knockout mutants were constructed and subjected to various oxidative stress related conditions. The results showed that the mutants are as resistant to ionizing and UV-C radiation as well as H2O2 exposure as the wild type. However, upon exposure to oxidative stress induced by methyl viologen, the knockout strains were more resistant than the wild type. The difference in resistance may be attributed to the observed upregulation of the EndoIII homologs gene expression upon addition of methyl viologen. In conclusion, our data suggest that all three EndoIII homologs are crucial for cell survival in stress conditions, since the knockout of one of the genes tend to be compensated for by overexpression of the genes encoding the other two.

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.

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.

Once daily (OD) versus twice-daily (BID) chemoradiation for limited stage small cell lung cancer (LS-SCLC): A meta-analysis of randomized clinical trials.

OBJECTIVES: Assess Once daily (OD) chemoradiation effectiveness for LS-SCLC compared with twice daily (BID) chemoradiation. METHODS AND MATERIALS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, eligible randomized clinical trials (RCT) comparing OD and BID were identified on electronic databases. A meta-analysis was performed to compare overall survival (OS), progression-free survival (PFS), and toxicity. A metaregression analysis was conducted to explore the influence of fractionation, biological effective dose (BED), the proportion of patients treated with prophylactic cranial irradiation (PCI), elective nodal irradiation (ENI), and the start of radiotherapy (week 1 or week 4). RESULTS: Five RCTs with a total of 1941 patients (OD vs. BID) were included. The relative risk (RR) for OS and PFS was 0.97 (CI95% 0.8-1.1, p = 0.731) and 0.90 (CI95% 0.7-1.1, p = 0.20) at 3-years. In the metaregression analysis, hypofractionated radiotherapy schedules were associated with an improvement in overall survival (p = 0.03). The start of radiotherapy (W1 or W4), BED, and ENI had no significant effect on OS and PFS. The complete response rate partial response and overall response rate for BID vs OD were 40% vs. 33% (p = 0.97), 50% vs. 57% (p = 0.94), and 89% vs. 93% (p = 0.99). The rate of completed planned RT 96% vs. 94% (p = 0.66), and the % of ≥4 chemotherapy cycles received 74% vs. 74% (p = 0.99), did not differ between OD and BID. The local and distant failure rates were not significantly different between OD and BID 40% vs. 33% (p = 0.88) and 36% vs. 36% (p = 0.99). No difference in grade 2 or grade 3 pneumonitis and esophagitis was observed among the groups (p = NS). CONCLUSION: For LS-SCLC, OD conventional chemoradiation results in similar outcomes to BID chemoradiation. In contrast, hypofractionated radiotherapy was associated with a better OS and PFS than BID. Additional randomized phase III trials exploring hypofractionation with systemic therapy are warranted to validate our findings.

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis.

OBJECTIVES: Stereotactic ablative radiotherapy (SABR) has been reported to be an effective treatment for oligometastatic disease from different primary cancer sites. Here we assess the effectiveness and safety of SABR for oligometastatic breast cancer patients by performing a meta-analysis. METHODS: Following PRISMA and MOOSE guidelines, a systematic review and meta-analysis was performed. Eligible studies were identified on Medline, Embase, Cochrane Library, and annual meetings proceedings from 1990 to June 2021. A meta-regression analysis was performed to assess if there was a correlation between moderator variables and outcomes, and a p-value <0.05 was considered significant. RESULTS: Ten studies met criteria for inclusion, comprising 467 patients and 653 treated metastases. The 1- and 2-year local control rates were 97% (95% CI 95-99%), and 90% (95% CI 84-94%), respectively. Overall survival (OS) was 93% (95% CI 89-96%) at 1 year, 81% (95% CI 72-88%) at 2 years. The rate of any grade 2 or 3 toxicity was 4.1 % (95% CI 0.1-5%), and 0.7% (0-1%), respectively. In the meta-regression analysis, only prospective design (p = 0.001) and bone-only metastases (p = 0.01) were significantly associated with better OS. In the subgroup analysis, the OS at 2y were significantly different comparing HER2+, HR+/HER2(-) and triple negative breast cancer 100%, 86% and 32%, p = 0.001. For local control outcomes, hormone receptor status (p = 0.01) was significantly associated on meta-regression analysis. CONCLUSION: SABR for oligometastatic breast cancer is safe and associated with high rates of local control. Longer follow-up of existing data and ongoing prospective trials will help further define the role of this management strategy.

Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis.

OBJECTIVES: To provide an overview of the achievements and future research with stereotactic body radiotherapy (SBRT) in prostate cancer. METHODS: SBRT publications for prostate cancer were retrieved from the Web of Science and Dimension database. Bibliometric analyses were performed using VOSviewer and Prism graph. Analysis of variance test was used to compare the publication, citation, and the mean citation between specialty journals. Network maps were produced to identify authors' and countries' collaboration clusters. RESULTS: Between 2006 and 2020, 574 publications fulfilling the inclusion criteria were identified, and a significant growth trend in publication (P<0.0001) and citation (P=0.001) number was recognized over the period. The United States was the most productive country with 253 (44.2%) articles. The RED Journal had the highest number of publications (14%) and citations (19%). Urology journals published (P=0.01) and cited significantly less than radiation oncology journals (P=0.01). All open access and non-open access number of publications increased over time, with a significant difference between non-open access and open access journals (P<0.0001). Two author clusters were identified, in the United States with the collaboration of Canadian and British authors, and in Italy with the participation of European authors. CONCLUSION: The number of publications and citations on SBRT for prostate cancer has grown linearly in the last decades. The United States is the leading country in this research field, and the use of SBRT in oligometastatic disease, reirradiation, and salvage seems to be hot topics in this research field.

Advances in radiotherapy in bone metastases in the context of new target therapies and ablative alternatives: A critical review.

In patients with bone metastases (BM), radiotherapy (RT) is used to alleviate symptoms, reduce the risk of fracture, and improve quality of life (QoL). However, with the emergence of concepts like oligometastases, minimal invasive surgery, ablative therapies such as stereotactic ablative RT (SABR), radiosurgery (SRS), thermal ablation, and new systemic anticancer therapies, there have been a paradigm shift in the multidisciplinary approach to BM with the aim of preserving mobility and function survival. Despite guidelines on using single-dose RT in uncomplicated BM, its use remains relatively low. In uncomplicated BM, single-fraction RT produces similar overall and complete response rates to RT with multiple fractions, although it is associated with a higher retreatment rate of 20% versus 8%. Complicated BM can be characterised as the presence of impending or existing pathologic fracture, a major soft tissue component, existing spinal cord or cauda equina compression and neuropathic pain. The rate of complicated BM is around 35%. Unfortunately, there is a lack of prospective trials on RT in complicated BM and the best dose/fractionation regimen is not yet established. There are contradictory outcomes in studies reporting BM pain control rates and time to pain reduction when comparing SABR with Conventional RT. While some studies showed that SABR produces a faster reduction in pain and higher pain control rates than conventional RT, other studies did not show differences. Moreover, the local control rate for BM treated with SABR is higher than 80% in most studies, and the rate of grade 3 or 4 toxicity is very low. The use of SABR may be preferred in three circumstances: reirradiation, oligometastatic disease, and radioresistant tumours. Local ablative therapies like SABR can delay change or use of systemic therapy, preserve patients' Qol, and improve disease-free survival, progression-free survival and overall survival. Moreover, despite the potential benefit of SABR in oligometastatic disease, there is a need to establish the optial indication, RT dose fractionation, prognostic factors and optimal timing in combination with systemic therapies for SABR. This review evaluates the role of RT in BM considering these recent treatment advances. We consider the definition of complicated BM, use of single and multiple fractions RT for both complicated and uncomplicated BM, reirradiation, new treatment paradigms including local ablative treatments, oligometastatic disease, systemic therapy, physical activity and rehabilitation.

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.