Real-World Evidence on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study.

INTRODUCTION/BACKGROUND: This study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. MATERIALS/METHODS: This retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: We analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). CONCLUSIONS: The benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.

Integration of Postoperative Radiation Therapy with Cyclin-Dependent Kinase (CDK) Inhibitors.

PURPOSE OF REVIEW: Sequential use of radiation therapy before cyclin-dependent kinase (CDK) inhibitors in women with early breast cancer seems reasonable and with a low toxicity rate. This study aimed to evaluate the possible interaction between RT and CDK inhibitors in the adjuvant setting for patients with positive hormone receptors and HER-2 negative, investigating toxicity and the treatment sequencing. RECENT FINDINGS: CDK inhibitors have been studied in patients with localized breast cancer and can improve invasive disease-free survival outcomes. Regarding the time of RT, all trials used CDK inhibitors after the RT. Interruptions in the CDK inhibitors were performed in 27.1% in Pallas, 17.5% in Penelope-B, and 16.6% in Monarch-E trials due to adverse events. Data from the Natalee trial are still not reported. The main adverse event grade III was neutropenia, with good resolution of the symptoms over time. CDK inhibitors applied sequentially and after RT postoperative showed a low profile of acute toxicity and suitable oncological outcomes.

Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator.

Purpose: To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. Methods and Materials: The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). Results: A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n = 131); luminal B, 19.1% (n = 40); HER2 enriched 13.4% (n = 28); and triple negative, 4.8% (n = 10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Conclusions: Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Vestibulocochlear Delineation for Vestibular Schwannoma Treated With Radiation Therapy.

Purpose: To develop a specialist-based consensus of cochlear contouring to be used in patients undergoing stereotactic radiosurgery (SRS) treatment for vestibular schwannoma. Methods and Materials: Representative computed tomography (CT) and magnetic resonance imaging (MRI) were used for cochlear contouring. The semicircles, cochlea, vestibule, and internal acoustic meatus were delineated by 7 radiation oncology department physicians and reviewed by neuroradiologists. A total of 12 cases accrued from a single academic institution were studied for a similarity analysis by the Dice coefficient. Results: The suggested guideline is an easily reproductive tool that allows radiation oncologists to accurately contour the vestibulocochlear system to avoid toxicity due to inadequate dosimetry of organs at risk. This could be a useful tool even for non-vestibular schwannoma radiation therapy. The Dice coefficient suggests reproducible results as long as the following contouring recommendations are observed. Conclusions: The template for vestibulocochlear delineation may be useful for an adequate organs at risk definition. Future studies are required to find specific constraints for each segment of the vestibulocochlear system, and to mitigate interobserver variations.

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series.

Background: Patients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions. Materials and methods: This study is a retrospective analysis of SRS for brain metastasis using VMAT. The primary endpoints were local disease-free survival (LDFS) and overall survival (OS). The secondary outcomes were intracranial disease-free survival (IDFS) and meningeal disease-free survival (MDFS). Results: The average number of treated lesions was 5.79 (range: 2-20) per treatment in a total of 113 patients. The mean prescribed dose was 18 Gy (range: 12-24 Gy). The median LDFS was 46 months. The LDFS in 6, 12, and 24 months was for 86%, 79%, and 63%, respectively. Moreover, brain progression occurred in 50 patients. The median overall survival was 47 months. The OS in 75%, 69%, and 61% patients was 6, 12, and 24 months, respectively. IDFS was 6 and 24 months in 35% and 14% patients, respectively. The mean MDFS was 62 months; it was 6 and 24 months for 87% and 83% of patients. Acute severe toxicity was relatively rare. During follow-up, the rates of radionecrosis and neurocognitive impairment were low (10%). Conclusion: The use of VMAT-SRS for multiple BM was feasible, effective, and associated with low treatment-related toxicity rates. Thus, treatment with VMAT is a safe technique to plan to achieve local control without toxicity.

Lessons from the Brazilian radiotherapy expansion plan: A project database study.

Background: The Radiotherapy Expansion Plan for Brazil's Unified Health System (PER-SUS) was an innovative program designed by the Ministry of Health in 2012 to provide improvements to the challenging problem of access to radiotherapy in the country. This study sought to analyze the execution and implementation of installations proposed by PER-SUS, and their capacity to address the problems of radiotherapy access in Brazil. Methods: From the first release (February 2015) until October 2021, all PER-SUS monthly progress reports were retrospectively analyzed. The beneficiary institutions, project location, project status, project type, dates of the progress on the stages, and reasons for cancellations or possible justifications for changing the status were collected. Brazilian geographic data, health care demands, and cancer incidences were correlated. Finally, we performed an Ishikawa diagram and 5W3H methodology, aiming to better understand the findings and to yield possible ways to improve the access to radiotherapy. Findings: After ten years, the PER-SUS project delivered nearly 50% of the planned implementation of radiotherapy equipment. There was a 17% growth in the national number of linear accelerators (LINACS) with PER-SUS, against a 32% increase in cancer incidence in Brazil in the same period. The following points were identified: a high rate of beneficiary exclusions reflecting inappropriate selection or inadequate planning; delays in execution related to bureaucratic obstacles and underestimation of the requirements (logistics/people); early closing of the equipment factory as a result of lack of project prioritization by the Government. Interpretation: Only about 50% of PER-SUS are being carried out. However, delays and exclusions of beneficiaries were observed. The dimension of the need for radiotherapy care in Brazil is greater than considered, and might not be fully attended by PER-SUS. Geographic, epidemiological, logistical, and economic variables could be reevaluated to allow better strategic planning and improvement proposals. PER-SUS could be optimized for the next decade, by involving all stakeholders' participation, alignment, and engagement. In the future, the States and regions with a higher LINAC shortage should be prioritized to improve RT access across the country. Considering the data and the initial project deadline, PER-SUS did not achieve the pre-established goals specified by the Brazilian Government. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Social determinants of health and survival on Brazilian patients with glioblastoma: a retrospective analysis of a large populational database.

Background: The majority of patients diagnosed with glioblastoma develop recurrent disease resulting in poor prognoses. The current study aimed to determine the survival rates of patients diagnosed with glioblastoma in Brazil accounting for the influence of age, treatment modalities, public and private practices, and educational level using a population-based national database. Methods: Patients diagnosed with glioblastoma from 1999-2020 were identified from The Fundação Oncocentro de São Paulo database to create a retrospective cohort. Patients were described according to age, education level treatment modalities and medical practice. In a Cox proportional hazards model, controlled for confounding factors for overall survival, the hazard ratio and 95% CI of overall survival in adults was evaluated. Findings: A total of 4,511 patients were included. The median lengths of survival for patients treated in the public and private settings were 8 and 17 months (p<0.001), respectively. Young patients had longer median overall survival (OS: 18 to 40 years, 41 to 60 years, 61 to 65 years, 66 to 70 years and over than 70 years was 22 months, 10 months, 6 months, 5 months, 4 months, respectively (p<0.001). In general, combined treatments were associated with higher median survival compared to monotherapy. The higher educational level, the higher median survival was observed (4 months for illiterate versus 14 months for university degree). In the multivariable analyses, the significant independent predictors for overall survival were practice setting, educational level, age and treatment modalities. Interpretation: Public practice, older patients, less intensive treatment, and lower educational level were associated with worse survival outcomes in Brazilian glioblastoma patients.

Surgical resection, intraoperative radiotherapy and immediate plastic reconstruction: A good option for the treatment of distal extremity soft tissue sarcomas.

AIM: To show three patients with soft tissue sarcomas of distal extremities conservatively treated after tumor-board discussion, involving margin-free surgery, exclusive intraoperative radiotherapy, and immediate reconstruction. BACKGROUND: Current guidelines show clear and robust recommendations regarding the composition of the treatment of sarcomas of extremities. However, little evidence exists regarding the application of these treatments depending on the location of the primary neoplasia. Tumors that affect the distal extremities present different challenges and make multidisciplinary discussions desirable. METHODS/RESULTS: We reported 3 patients who were approached with a conservative intention, after tumor board recomendation. The goals from the treatment performed were aesthetic and functional preservation, while enruring locoregional control. We had wound healing complications in 2 of the cases, requiring additional reconstruction measures. Patients are followed up for 24, 20 and 10 months; local control is 100%, and functional preservation is 100%. CONCLUSIONS: Despite being a small series, it was sufficient to illustrate successful multidisciplinary planning, generating a therapeutic result with improved quality of life for patients who had an initial indication for extremity amputation.

Recommendations for radiotherapy during the novel coronavirus pandemic

SUMMARY

Frameless Image-Guided Radiosurgery for Multiple Brain Metastasis Using VMAT: A Review and an Institutional Experience.

We undertook a structured review of stereotactic radiosurgery (SRS) using linear particle accelerator (linac) equipment, focusing on volumetric modulated arc therapy (VMAT) technology, and frameless image-guided radiotherapy (IGRT), for the treatment of brain metastases. We analyzed the role of linac SRS and its clinical applications, exploring stereotactic localization. Historically, there was a shift from fixed frames to frameless approaches, moving toward less invasive treatments. Thus, we reviewed the concepts of VMAT for multiple-target applications, comparing its dosimetric and technical features to those of other available techniques. We evaluated relevant technical issues and discussed the planning parameters that have gained worldwide acceptance to date. Thus, we reviewed the current literature on the clinical aspects of SRS, especially its main indications and how the advantages of VMAT may achieve clinical benefits in such scenarios. Finally, we reported our institutional results on IGRT-VMAT for SRS treatments for patients with multiple brain metastases.

Cosmesis in patients with breast neoplasia submitted to the hypofractionated radiotherapy with of intensity-modulated beam.

OBJECTIVE: To assess the cosmetic satisfaction of patients diagnosed with breast cancer submitted to the hypofractionated radiotherapy with IMRT (hIMRT) technique and its correlation with dosimetric data of the radiotherapy planning. METHODS: The retrospective cohort study that assessed women with a diagnosis of malignant breast neoplasia submitted to the conservative treatment or radical mastectomy and treated with hIMRT. In the period between August 2007 to December 2014, in a philanthropic / private institution, 170 records were selected. The cosmetic assessment was carried out by means of the Harvard/RTOG/NSABP scale with one-year minimum range after treatment. The collected dosimetric data were: breast / chest wall volume, volume that received 95% (V95%) and 107% (V107%) of the prescribed dose. RESULTS: The volume of the treated breasts ranged from 169 to 2.103 ml (median = 702; IQR: 535 to 914 ml). Median V95% was 86.7% (54.6-96.6%; IQR: 80.0% to 90.6%); eight (5.7%) patients had V95% higher than 95%. Median V107% was 0% (0%-16.3%; IQR: 0.0% to 0.3% and 13); 9.3% patients had V107% higher than 2%. One hundred and thirty-three (78.2%) patients responded to the cosmetic assessment: 99 (74.4%) considered the cosmetic results excellent. Significant associations between cosmetic assessment and breast volume (p=0.875), V95% (p=0.294) e V107% (p=0.301) were not found. CONCLUSION: The cosmetic results showed favorable when using hIMRT, and the lack of correlation with usual the dosimetric data illustrates the capacity of hIMRT to minimize the heterogeneity of the dose in this endpoint, even in voluminous breasts.

Cosmesis in patients with breast neoplasia submitted to the hypofractionated radiotherapy with of intensity-modulated beam

SUMMARY OBJECTIVE: To assess the cosmetic satisfaction of patients diagnosed with breast cancer submitted to the hypofractionated radiotherapy with IMRT (hIMRT) technique and its correlation with dosimetric data of the radiotherapy planning. MATERIALS AND METHODS: The retrospective cohort study that assessed women with a diagnosis of malignant breast neoplasia submitted to the conservative treatment or radical mastectomy and treated with hIMRT. In the period between August 2007 to December 2014, in a philanthropic / private institution, 170 records were selected. The cosmetic assessment was carried out by means of the Harvard/RTOG/NSABP scale with one-year minimum range after treatment. The collected dosimetric data were: breast / chest wall volume, volume that received 95% (V95%) and 107% (V107%) of the prescribed dose. RESULTS: The volume of the treated breasts ranged from 169 to 2.103 ml (median = 702; IQR: 535 to 914 ml). Median V95% was 86.7% (54.6-96.6%; IQR: 80.0% to 90.6%); eight (5.7%) patients had V95% higher than 95%. Median V107% was 0% (0%-16.3%; IQR: 0.0% to 0.3% and 13); 9.3% patients had V107% higher than 2%. One hundred and thirty-three (78.2%) patients responded to the cosmetic assessment: 99 (74.4%) considered the cosmetic results excellent. Significant associations between cosmetic assessment and breast volume (p=0.875), V95% (p=0.294) e V107% (p=0.301) were not found. CONCLUSION: The cosmetic results showed favorable when using hIMRT, and the lack of correlation with usual the dosimetric data illustrates the capacity of hIMRT to minimize the heterogeneity of the dose in this endpoint, even in voluminous breasts.

RESUMO OBJETIVO: Avaliar a satisfação cosmética de pacientes diagnosticadas com câncer de mama submetidas à radioterapia hipofracionada com técnica IMRT (hIMRT) e sua correlação com dados dosimétricos do planejamento radioterápico. MATERIAIS E MÉTODOS: Estudo de coorte retrospectivo que avaliou mulheres com diagnóstico de neoplasia maligna de mama submetidas a tratamento conservador ou mastectomia radical e tratadas com hIMRT. No período de agosto de 2007 a dezembro de 2014, em uma instituição filantrópica/particular, foram selecionados 170 prontuários. A avaliação cosmética foi feita por meio da escala de Harvard/RTOG/NSABP com um intervalo mínimo de um ano após o tratamento. Dados dosimétricos coletados foram: volume da mama/plastrão, volume que recebeu 95% (V95%) e 107% (V107%) da dose prescrita. RESULTADOS: O volume das mamas tratadas variou de 169 a 2.103 ml (mediana = 702; IQR: 535 a 914 ml). O V95% mediano foi 86,7% (54,6-96,6%; IQR: 80,0% a 90,6%); oito (5,7%) pacientes tiveram o V95% superior a 95%. O V107% mediano foi 0% (0%-16,3%; IQR: 0,0% a 0,3% e 13); 9,3% pacientes tiveram o V107% superior a 2%. Cento e trinta e três (78,2%) pacientes responderam à avaliação cosmética: 99 (74,4%) consideraram o resultado cosmético excelente. Não foram encontradas associações significativas entre a avaliação cosmética e o volume da mama (p=0,875), V95% (p=0,294) e V107% (p=0,301). CONCLUSÕES: Os resultados cosméticos mostraram-se favoráveis com o uso de hIMRT, e a ausência de correlação com os dados dosimétricos usuais ilustra a capacidade do hIMRT em minimizar a heterogeneidade da dose neste desfecho, mesmo em mamas volumosas.

Analysis of Skin Flap Thickness and Residual Breast Tissue After Mastectomy.

PURPOSE: Residual breast tissue (RBT) after mastectomy represents an unknown risk for local recurrence or development of a new cancer and affects decisions regarding adjuvant radiation therapy. This study used breast magnetic resonance imaging to evaluate the frequency of RBT and provide average thickness skin flap measurements in patients with total mastectomy, skin-sparing mastectomy, and nipple-sparing mastectomy (NSM) followed by breast reconstruction. METHODS AND MATERIALS: We carried out a retrospective analysis of 7432 consecutive postoperative breast magnetic resonance imaging examinations performed between August 2008 and July 2013, selecting 367 women (mean ± standard deviation age, 46.7 ± 8.7 years) who had undergone therapeutic or prophylactic mastectomy with reconstruction, for a total of 501 cases. The variables analyzed included fibroglandular tissue presence, skin flap thickness at 11 pre-established points, age, weight, height, body mass index, laterality, surgical indication, surgery type, reconstruction type, adjuvant therapy, and cancer treatment history. Statistical analyses were descriptive and comparative and included logistic regression models (P < .05). RESULTS: At 9 of the 11 points of measure, the median thickness of the flap exceeded 5.5 mm. Excluding the areolar region, RBT was identified in 29.9% of the cases: 21.3% of the therapeutic mastectomy cases and 51% of the NSM cases. The variables independently associated with the presence of RBT were flap thickness (P < .001), patient height (P < .03), mastectomy indication (P < .001), mastectomy type (P < .012 for skin-sparing mastectomy and P < .001 for NSM and total mastectomy), and breast reconstruction with flap (P < .019). CONCLUSIONS: All forms of mastectomy leave RBT. Our study has demonstrated that the RBT amount can be variable and quite prevalent. Because of the low quality of the evidence to ensure the oncological safety of sparing mastectomies, we suggest that knowledge of the extent of the remaining breast tissue is important for guiding additional surveillance and therapeutic interventions, including radiation therapy.

Tumor Reduction with Pazopanib in a Patient with Recurrent Lumbar Chordoma.

INTRODUCTION: Chordomas are rare malignancies of bone origin that occur in the axial skeleton, typically the skull base and lumbar/sacral regions. Although often classified as low-grade neoplasms, its locally infiltrative behavior may result in significant morbidity and mortality. Optimal surgical resection may be curative, but up to 50% of the cases relapse within 5 years, and currently there are no systemic treatments approved in this setting. A large proportion of these tumors express stem-cell factor receptor (c-KIT) and platelet-derived growth factor receptors (PDGFRs), providing a rationale for the use of tyrosine-kinase inhibitors (TKIs). CASE REPORT: A 27-year-old male presented with recurrent chordoma of the lumbar spine 4 years after initial diagnosis. Salvage therapies in the interval included repeat resections and radiation therapy. He ultimately developed multifocal recurrence not amenable to complete excision or reirradiation. A comprehensive genomic profiling assay was performed and revealed nondrugable alterations. Decision was made to proceed with systemic treatment with pazopanib 800 mg/day, resulting in tumor reduction (-23.1% reduction in size) and prolonged disease control. CONCLUSION: For this patient with a multiple recurrent chordoma and limited treatment options, pazopanib resulted in sustained clinical benefit following initial tumor reduction.

Self-reported Conflicts of Interest and Trial Sponsorship of Clinical Trials in Prostate Cancer Involving Radiotherapy.

OBJECTIVES: To examine the association between trial sponsorship and conflicts of interest (COI) with clinical trial conclusions for prostate cancer trials related to radiotherapy. MATERIALS AND METHODS: The MEDLINE database was searched for all prostate cancer clinical trials published between 2004 and 2013 and identified 1396 studies. Two investigators independently identified trials published in the English language of ≥30 patients, and extracted relevant data. Clinical trials were classified according to trial characteristics, sponsorship source and type, COI, and study conclusion, and analyzed by univariable and multivariable logistic regression. RESULTS: Of 240 eligible trials, 160 (67.5%) evaluated drugs without radiotherapy, 60 (25%) involved radiotherapy, and 18 (7.5%) involved procedures without radiotherapy. Of the 60 radiotherapy trials eligible for analysis, positive sponsorship and potential COI were present in 58.3% and 20% of trials, respectively. Study conclusions were positive, negative, or neutral in 78.3%, 5%, and 16.7% of trials, respectively. No association was found between positive conclusions and either industry support of potential COI. Positive conclusions were reported in 86.7% and 83.3% of trials with sponsorship and COI, respectively, as compared with 75.6% and 77.1% of those without sponsorship (P=0.37) and COI (P=0.64). Sponsorship was significantly associated with radiotherapy trials combined with drugs (odds ratio 5.5, P=0.01) and higher-risk disease (odds ratio 4.71, P=0.01). CONCLUSIONS: The presence of sponsorship was associated with radiotherapy trials involving drugs or studying higher-risk prostate cancer. However, there were no identified associations between study conclusion and sponsorship type or COI.