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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 11 th , 2021., (© 2023. The Author(s).)

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., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Purpose: To investigate ion recombination correction and polarity effects in four ion chamber models in flattening-filter-free (FFF) beams to (1) evaluate their suitability for reference dosimetry; (2) assess the accuracy of the two-voltage technique (TVA) against the Bruggmoser formalism; and (3) examine the influence of the accelerator type on the recombination correction., Methods: Jaffé plots were created for a variety of microchambers, small-volume and Farmer-type chambers to obtain k S , the recombination correction factor, using two different types of accelerators. These values were plotted against dose-per-pulse and Jaffé plots for opposite polarities were created to determine which chambers meet the AAPM TG-51 addendum recombination and polarity specifications., Results: Nearly all small-volume chambers exhibited reference-class behavior with respect to ion recombination and polarity effects. The microchambers exhibited anomalous recombination and polarity effects, precluding their use for reference dosimetry in FFF beams. For the reference-class chambers, agreement between TVA-determined k S values and Jaffé and Bruggmoser formalisms-determined k S values was within 0.1%. No significant differences were found between the k S values obtained with the two different accelerators used in this work., Conclusions: This study stresses the need to characterize ion recombination correction and polarity effects for small-volume chambers and microchambers on an individual chamber basis and with the more rigorous criteria of the AAPM TG-51 addendum. Furthermore, the study demonstrated the suitability of the TVA method for chambers that exhibit reference-class behavior in FFF beams. Finally, this work has shown that the recombination correction does not depend on the type of accelerator but on its dose-per-pulse., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

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.

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., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)