A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

Impact of cranial stereotactic radiotherapy associated with immunotherapy with nivolumab and ipilimumab on overall survival in patients with melanoma brain metastases: a real-world evidence.

PURPOSE: To evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting. METHODS/PATIENTS: The study was performed by using TriNetX, a global health network dataset of electronic medical records from patients in 49 healthcare organizations. We queried for patients with specific terms between January 2016 and December 2020 and run a propensity score matching (PSM) analysis. OS was estimated by Kaplan-Meier and log-rank test was applied. RESULTS: After initial query and PSM, 114 patients were selected in each cohort. Median OS was 327 days in CNI and not reached in the CNI + SRT cohort, with OS probability of 54.4 and 40.9%, respectively (log-rank P = .0057). CNI + SRT was associated with significantly decreased mortality (HR, 0.57; 95% CI 0.377-0.853; proportionality P = .0034). CONCLUSIONS: This real-world analysis showed that CNI + SRT led to an improvement in OS compared to CNI.

Organ Preservation in cT2N0 Rectal Cancer After Neoadjuvant Chemoradiation Therapy: The Impact of Radiation Therapy Dose-escalation and Consolidation Chemotherapy.

OBJECTIVE: To demonstrate the difference in organ-preservation rates and avoidance of definitive surgery among cT2N0 rectal cancer patients undergoing 2 different chemoradiation (CRT) regimens. BACKGROUND: Patients with cT2N0 rectal cancer are more likely to develop complete response to neoadjuvant CRT. Organ preservation has been considered an alternative treatment strategy for selected patients. Radiation dose-escalation and consolidation chemotherapy have been associated with increased rates of response and may improve chances of organ preservation among these patients. METHODS: Patients with distal and nonmetastatic cT2N0 rectal cancer managed by neoadjuvant CRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5-FU-based chemotherapy) were compared with those undergoing extended CRT (54 Gy and 6 cycles of 5-FU-based chemotherapy). Patients were assessed for tumor response at 8 to 10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy ("Watch and Wait"). Patients were referred to salvage surgery in the event of local recurrence during follow-up. RESULTS: Thirty-five patients underwent standard and 46 patients extended CRT. Patients undergoing extended CRT were more likely to undergo organ preservation and avoid definitive surgical resection at 5years (67% vs 30%; P = 0.001). After development of a cCR, surgery-free survival is similar between extended and standard CRT groups at 5 years (78% vs 56%; P = 0.12). CONCLUSIONS: Dose-escalation and consolidation chemotherapy leads to increased long-term organ-preservation rates among cT2N0 rectal cancer. After achievement of a cCR, the risk for local recurrence and need for salvage surgery is similar, irrespective of the CRT regimen.

Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. METHODS: Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. RESULTS: 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). CONCLUSIONS: Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival.

Radioterapia fipofracionada em câncer de pulmäo avançado / Hypofractiionated radiotherapy in advanced lung cancer

Os doentes portadores de tumores avançados de pulmäo apresentam prognóstico reservaado e, muitas vezes, acabam sendo submetidos a tratamentos prolongados, nem sempre eficazes. Apresenta-se um estudo realizado com 51 doentes, no qual foi utilizada radioterapia hipofracionada, de acordo com dois esquemas distintos, baseados no performance status e condiçäo sócio-econômica de cada doente: a) tratamento contínuo: 30 Gy em dez fraçöes de 5 Gy, cinco vezes por semana (37 casos); b) tratamento semanal: 30 Gy em 6 fraçöes de Gy uma vez/semana (14 casos). Alívio de sintomas, bem como o impacto na sobrevida, foram avaliados. Em ambos os grupos observa-se melhora dos sintomas em torno de 70 por cento das ocorrências, com sobrevida mediana de 3 meses. Conclui-se que o hipofracionamento é eficaz como tratamento paliativo para os tumores de pulmäo, devendo ser considerado como opçäo em casos avançados, em doentes com expectativa de vida muito curta e que mereçam alguma intervençäo

Suporte nutricional, radicais livres e antioxidantes.(Editorial) / Nutritional support, free radicals and antioxidants.(Editorial)

Antioxidants and free radical scavengers are molecules endowed with the ability of neutralizing reactive oxygen species that may accumulate in the organism during various pathologic processes...

Irradiaçäo de hemicorpo; experiência de seis casos / Half-body irradiation; experience of six cases

Entre 1983 e 1989 foram tratados 6 pacientes com doença neoplásica disseminada, rebelde aos tratamentos convencionais, com intuito paliativo, antiálgico: 3 casos de câncer de mama, 2 de câncer de próstata e um de sarcoma de Ewing, num total de 8 irradiaçöes. Os tratamentos foram iniciados pelo hemicorpo com sintomatologia mais acentuada, sendo realizada dose única de 800 cGy na metade inferior e 600 cGy na metade superior. Obtivemos alívio da dor em 24 a 48 horas após o tratamento em todos os pacientes. A tolerância hematológica foi boa e os óbitos desses pacientes näo foram relacionados a complicaçöes da radioterapia

Molde plástico de contençäo em radioterapia experimental / A restricting plastic mold for experimental radiotherapy

A imobilizaçäo do paciente durante a irradiaçäo fracionada desempenha um papel fundamental no sucesso do programa radioterápico pré-estabelecido. Essa imobilizaçäo permite aumentar a acuracidade da irradiaçäo pela reproduçäo diária da posiçäo do paciente nas várias sessöes porgramadas, além de diminuir os efeitos colaterais decorrentes da lesäo de tecidos normais adjacentes à área irradiada. Dentro desse contexto, os autores desenvolveram um molde plástico de contençäo para pequenos animais de laboratório, visando a sua imobilizaçäo e permitindo a irradiaçäo seletiva do abdome ou pelve em doses fracionadas. Esse molde apresenta ainda a vantagem de dispensar a administraçäo de altas doses anestésicas aos animais durante o tratamento

Pneumonite actínica no câncer de mama / Actinic pneumonitis in breast neoplasms

Foram revistos os prontuários e as radiografias de tórax de 49 pacientes portadores de câncer de mama, atendidos entre 1980 e 1985 e que foram submetidos à radioterapia. Em 22 (44,9%) dos pacientes estudados foi detectado quadro radiológico de pneumonite actínica, porém apenas dois (9%) apresentaram sintomatologia respiratória leve ou moderada. Apesar de relativamente freqüente, a baixa repercussäo clínica do quadro radiológico da pneumonite por radiaçäo nos permite continuar com a indicaçäo desta terapêutica, mantendo a técnica atualmente utilizada. Os dados referentes à radioterapia säo importantes também para o diagnóstico diferencial com outras patologias que apresentam imagem radiológica semelhante

Radioterapia no seminoma / Radiotherapy in seminomas

Analisam-se os resultados obtidos no tratamento radioterápico de 82 pacientes portadores de seminoma puro do testículo. Os resultados säo considerados satisfatórios para os estádios I, II A e II B, e tecem-se outras consideraçöes terapêuticas para os estádios II C e III