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BACKGROUND: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. MATERIAL AND METHODS: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5-60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. RESULTS: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). CONCLUSIONS: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.

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Background: The objective was to report acute toxicity and quality of life in prostate cancer patients treated with definitive hypofractionated pelvic radiation therapy. Materials and methods: Patients were designated candidates for hypofractionated pelvic radiation therapy if biopsy or imaging studies evidenced unfavorable intermediate-risk, high-risk or node-positive disease. Patients were treated using a regimen of 44 Gy to the nodal areas and simultaneous integrated boost of 60 Gy to the prostate in 20 fractions with CBCT-based imaging and volumetric arc therapy (VMAT). Patient data was obtained retrospectively; acute gastrointestinal (GI) and genitourinary (GU) toxicity was classified per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and obtained from clinical records. Quality of life was surveyed via phone call using the European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ-PR25. Results: 78 patients were treated between May and December 2021. 83.33% of patients had high-risk disease, 16.67% had intermediate-risk disease, and 34.62% patients had node-positive disease. Median follow-up was 10.6 months. No patients presented acute grade >3 GI toxicity, and one patient presented grade 3 GU toxicity. 25.64% patients presented acute G2 GI toxicity and 17.95% patients presented acute G2 GU toxicity. 60.26% of patients responded to the EORTC-PR25 questionnaire. Mean scores for symptom scales were 11.26, 4.96 and 9.57 for Urinary Symptoms, Bowel Symptoms and Hormonal Treatment-Related Symptoms; mean scores for Sexual Activity and Functioning were 19.86 and 31.08, respectively. Conclusion: Definitive hypofractionated pelvic radiation therapy has an acceptable acute toxicity and QoL profile in this series of patients, although longer follow-up is needed to properly evaluate short and long-term toxicity. Further follow-up and patient recruitment is ongoing.

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Purpose: This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Results: Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. Conclusion: HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT40155531.

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BACKGROUND: This study aims to evaluate whether hypofractionated radiotherapy (HYPOFRT) is a cost-effective strategy than conventional fractionated radiotherapy (CFRT) for early-stage glottic cancer (ESGC) in the Brazilian public and private health systems. METHODS: Adopting the perspective of the Brazilian public and private health system as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 65-year-old men after with ESGC treated with either HYPOFRT or CFRT. Probabilities of controlled disease, local failure, distant metastasis, and death and utilities scores were extracted from randomized clinical trials. Costs were based on the public and private health system reimbursement values. RESULTS: In the base case scenario, for both the public and private health systems, HYPOFRT dominated CFRT, being more effective and less costly, with a negative ICER of R$264.32 per quality-adjusted life-year (QALY) (public health system) and a negative ICER of R$2870.69/ QALY (private health system). The ICER was most sensitive to the probability of local failure, controlled disease, and salvage treatment costs. For the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve indicates that there is a probability of 99.99% of HYPOFRT being cost-effective considering a willingness-to-pay threshold of R$2,000 ($905.39) per QALY (public sector) and willingness-to-pay threshold of R$16,000 ($7243.10) per QALY (private sector). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Considering a threshold of R$ 40,000 per QALY, HYPOFRT was cost-effective compared to CFRT for ESGC in the Brazilian public health system. The Net Monetary Benefit (NMB) is approximately 2,4 times (public health system) and 5,2 (private health system) higher for HYPOFRT than CFRT, which could open the opportunity of incorporating new technologies.

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INTRODUCTION: Patients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immune response. MATERIALS AND METHODS: We evaluated the efficacy and tolerance of ultra-hypofractionated immuno-radiotherapy (uhypo-IRT) in 17 patients with recurrent HNSCC and 1 with melanoma. Four of HNSCC patients also had oligometastatic disease. Using a dose/time/toxicity-based algorithm, 7, 7 and 4 patients received 1, 2 and 3 fractions of 8 Gy to the tumor, respectively. Nivolumab anti-PD-1 immunotherapy was administered concurrently with RT and continued for 24 cycles, or until disease progression or manifestation of immune-related adverse events (irAEs). RESULTS: Early and late RT toxicities were minimal. Three patients developed irAEs (16%). After the 12th cycle, 7/17 (41.2%) and 5/17 (29.4%) patients with HNSCC showed complete (CR) and partial response (PR), respectively. CR was also achieved in the melanoma patient. The objective response rates in HNSCC patients were 57%, 86% and 66%, after 1, 2 and 3 fractions, respectively (overall response rate 70.6%). Most responders experienced an increase in peripheral lymphocyte counts. The median time to progression was 10 months. The 3-year projected locoregional progression-free survival was 35%, while the 3-year disease-specific overall survival was 50%. CONCLUSIONS: Anti-PD1 uhypo-IRT is safe and effective in patients with recurrent HNSCC. The high objective response rates and the long survival without evidence of disease support further trials on uhypo-IRT.

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BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, recently, Radiotherapy (RT) protocols requiring fewer sessions (hypofractionated) have been used to shorten RT treatment and minimize patient exposure to medical centers, and decrease the risk of SARS-CoV-2 infection. METHODS: This longitudinal, prospective, observational study aimed to compare the quality of life (QoL) and the incidence of oral mucositis and candidiasis in 66 patients with head and neck cancer (HNC) who undergo a hypofractionated RT protocol (GHipo), total of 55 Gy for 4 weeks, or a conventional RT protocol (GConv), total of 66 - 70 Gy for 6 - 7 weeks. PURPOSE: To assess the incidence and severity of oral mucositis, the incidence of candidiasis, and QoL were evaluated using the World Health Organization scale, clinical evaluation, and the QLC-30 and H&N-35 questionnaires, respectively, at the beginning and the end of RT. RESULTS: The incidence of candidiasis did not show differences between the two groups. However, at the end of RT, mucositis had a higher incidence (p < 0.01) and severity (p < 0.05) in GHipo. QoL was not markedly different between the two groups. Although mucositis worsened in patients treated with hypofractionated RT, QoL did not worsen for patients on this regimen. CONCLUSIONS: Our results open perspectives for the potential use of RT protocols for HNC with fewer sessions in conditions that require faster, cheaper, and more practical treatments.

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Abstract The objective of this study was to compare the activation of gelatinases in dentin-enamel junction (DEJ) and underlying dentin of permanent teeth after experimental radiotherapy in conventional and hypofractionated modalities. Newly extracted third molars (n = 15) were divided into three experimental radiotherapy groups: control, conventional (CR), and hypofractionated (HR) (n = 5 per group). After in vitro exposure to ionizing radiation, following standardized protocols for each modality, a gelatinous substrate was incubated on the tooth slices (n = 10 per group). Activation of gelatinases was measured by in situ zymography, expressed in arbitrary fluorescence units (mm2) from three tooth regions: cervical, cuspal, and pit. Fluorescence intensity was compared among radiotherapy protocols and tooth regions in each protocol, considering a significance level of 5%. Considering all tooth regions, the fluorescence intensity of the CR group was higher than the HR and control groups, both in DEJ and underlying dentin (p <0.001). In addition, the fluorescence intensity was higher in underlying dentin when compared to DEJ in all groups (p <0.001). Considering each tooth region, a statistically significant difference between CR and HR was only observed in the pit region of underlying dentin (p <0.001). Significant and positive correlations between fluorescence intensities in DEJ and underlying dentin were also observed (p <0.001). Experimental radiotherapy influenced the activation of gelatinases, as well as exposure to the conventional protocol can trigger a higher activation of gelatinases when compared to hypofractionated, both in DEJ and underlying dentin.

Resumo O objetivo deste estudo foi comparar a ativação de gelatinases na junção dentina-esmalte (DEJ) e na dentina subjacente de dentes permanentes após a radioterapia experimental nas modalidades convencional e hipofracionada. Os terceiros molares recém-extraídos (n = 15) foram divididos em três grupos de radioterapia experimental: controle, convencional (CR) e hipofracionada (HR) (n = 5 por grupo). Após a exposição in vitro à radiação ionizante, seguindo protocolos padronizados para cada modalidade, um substrato gelatinoso foi incubado nas fatias de dente (n = 10 por grupo). A ativação das gelatinases foi medida por zimografia in situ, expressa em unidades arbitrárias de fluorescência (mm2) de três regiões do dente: cervical, cúspide e fossa. A intensidade da fluorescência foi comparada entre os protocolos de radioterapia e as regiões do dente em cada protocolo, considerando um nível de significância de 5%. Considerando todas as regiões do dente, a intensidade de fluorescência do grupo CR foi maior do que a dos grupos HR e controle, tanto no DEJ quanto na dentina subjacente (p <0,001). Além disso, a intensidade da fluorescência foi maior na dentina subjacente quando comparada à DEJ em todos os grupos (p <0,001). Considerando cada região do dente, uma diferença estatisticamente significativa entre CR e HR foi observada apenas na região da fossa da dentina subjacente (p <0,001). Também foram observadas correlações significativas e positivas entre as intensidades de fluorescência no DEJ e na dentina subjacente (p <0,001). A radioterapia experimental influenciou a ativação das gelatinases, assim como a exposição ao protocolo convencional pode desencadear uma maior ativação das gelatinases quando comparada ao hipofracionamento, tanto no DEJ quanto na dentina subjacente.

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Background and Objectives: Conventional long-course radiotherapy (LCRT) and a new paradigm of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) are used in locally advanced rectal cancer (RC). There are few economic assessment reports available on TNT that focus on cost analysis in a country with limited funding for healthcare systems. The objective of this study was to perform a cost analysis comparing SCRT-TNT versus LCRT. Materials and Methods: In 2020-2021, a prospective registry was created to document RC patients who received neoadjuvant therapy and the costs of cancer treatments, transportation and the time patients and family members spent in the hospital. This registry outlined the direct and indirect costs of LCRT versus SCRT-TNT. Results: LCRT and SCRT-TNT regimens have direct costs that range from S/.5,993.30 to S/.27,928.36 and from S/.3,409.81 to S/.18,159.42, respectively. FOLFOX regimens are the most expensive. Administering radiotherapy in 28 3D sessions and 5 sessions of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) sessions costs S/.2,603.88, S/.1,277.19 and S/.1,027.77, respectively. The indirect cost of FOLFOX regimens is twice that of the similar modality that combines irradiation and Oxaliplatin IV and Capecitabine VO (CAPOX). SCRT-TNT regimens with CAPOX reduce costs by at least 50%, while SCRT-TNT regimens with FOLFOX reduce costs by 32%. Conclusion: Despite using IMRT/VMAT, SCRT-TNT is a less expensive approach for patients with RC when compared to LCRT. The costs to patients using SCRT-TNT are much lower, but it is also a better option because it saves hospital resources.

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INTRODUCTION: Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. MATERIALS AND METHODS: Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. RESULTS: Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. CONCLUSION: Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.

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Background: Results from numerous clinical trials have led to a consensus that moderately hypofractionated radiation therapy is the ideal postoperative irradiation treatment plan in patients with breast cancer (BC). However, there are specific situations such as chest wall (with or without breast reconstruction) and regional node irradiation that still face obstacles in its widespread use. There is a lack of evidence supporting the use of moderately hypofractionated irradiation from the Latin American context. This study aims to describe the profile and clinical outcomes of patients treated with moderate hypofractionation for both early-stage (Stage I and II) and locally advanced BC (Stage III) regardless of the type of surgery in a Brazilian Oncology Center. Methods: All patients with non-metastatic BC who were treated with moderately hypofractionated schedules of 40Gy in 15 fractions or 42.4Gy in 16 fractions between 2010 to 2019 at Hospital Sírio-Libanês, Brazil were retrospectively analyzed. The rates of local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distance recurrence-free survival (DRFS) and overall survival (OS) were estimated. Acute and late toxicity profiles were accessed for the entire cohort. Findings: A total of 670 patients were included. The median age was 57 years and the median follow-up time was 31 months. Most of the patients had stage I and II breast cancer, and 81.6% underwent breast-conserving surgery. Of the 123 women who underwent mastectomy treatment, 29% (n = 37) had immediate reconstruction with implants and 28% (n = 35) with autologous tissue. Seventy-one per cent of the patients presented luminal subtype tumour and 84.3% received adjuvant hormonal therapy. Chemotherapy was administered to almost half of the patients and all 80 patients with Her-2 positive disease received trastuzumab-based systemic therapy. One-third of patients received regional node irradiation; boost was performed in 41.1% of treatments. The 5-year LRFS, RRFS, DRFS and OS was 95.6%, 97.6%,92.2% and 95.9%, respectively. Acute and late side effects profile were mild and only 2.9% of patients developed grade 3 dermatitis. Among patients with breast implants, 11.4% had capsular contracture. Interpretation: In this Brazilian institution experience, moderately hypofractionated irradiation to the breast, chest wall (with or without breast reconstruction), and regional lymph nodes was safe and with an acceptable toxicity profile. Funding: None.