ORCID Profile
0000-0002-1462-8275
Current Organisations
Azienda Ospedaliera di Padova
,
Università degli Studi di Padova Scuola di Medicina e Chirurgia
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Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-05-2021
DOI: 10.1200/JCO.2021.39.15_SUPPL.4067
Abstract: 4067 Background: Defining the optimal neoadjuvant treatment for resectable locally advanced esophageal carcinoma remains an open question. The debate is fuelled by the fact that most of the available randomized clinical trials (RCT) accrued two histological subtypes (adenocarcinoma (AC) and squamous cell carcinoma (SCC)) and two anatomical locations (TE and GEJ). The aim of this in idual patient data (IPD) meta-analysis was to investigate the effect of preoperative chemotherapy on survival with a specific focus on histological subtypes and anatomical locations. Methods: Were eligible published or unpublished RCT closed to accrual before December 2015 and comparing neoadjuvant chemotherapy (CS) to primary surgery (S), identified by electronic database, conference proceedings and clinical trial register. All analyses were conducted on IPD obtained from trial Investigators. The Primary endpoint was overall survival (OS), Secondary endpoints were disease-free survival (DFS) with a 6-months landmark time, local/distant relapse/death without relapse as competing events. Two subgroup analyses were pre-planned one on the histological subtype and another on the anatomical location. A stratified logrank test was used for OS and DFS, and a stratified fine and gray model for competing events. HR, and risk ratios (RR) were combined using a random effect model. Results: IPD were obtained from 12 RCT (2601 patients) out of 16 identified (2863 patients) When compared to S, CS was associated with a significantly increased OS, (HR = 0.85[0.78-0.92], p 0.0001), with a 5-year absolute OS benefit of 5.7%. However, the subgroup analysis by histological subtype showed an OS benefit from CS higher for AC (HR = 0.80[0.72-0.91], p 0.01), when compared to SCC (HR = 0.90[0.80-1.01], p = 0.06), but with p for interaction = 0.2. In the subgroup analysis by anatomical location CS benefit was seen across both anatomical location with a trend in favor of GEJ (TE: HR = 0.89[0.81-0.98], p = 0.02 GEJ: HR = 0.71[0.57-0.88]), p 0.01, p for interaction = 0.057). CS also improved DFS (HR = 0.81[0.74-0.88], p 0.0001), with the same trend for the subgroup analyses, with apparent significant benefit for AC HR = 0.80[0.72-0.91] when compared to SCC HR = 0.90[0.80-1.01], (p for interaction 0.045) and a similar benefit for both location (TE: HR = 0.89[0.81-0.98] p 0.01, GEJ: HR = 0.71[0.57-0.88], p = 0.095, P for interaction 0.11). Local (HR = 0.76[0.63-0.92], p = 0.0045) and distant (HR = 0.87[0.76-0.99], p = 0.04) relapses were also significantly lower in the CS arm, with no significant variation according to histological subtypes or tumor location. Conclusions: Neoadjuvant chemotherapy significantly improves OS when added to upfront surgery and was equally effective in AC and SCC. A slightly more pronounced effect was observed for overall survival in the GEJ location vs. the TE.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.EJCA.2021.08.014
Abstract: Which neoadjuvant treatment for locally advanced thoracic oesophagus (TE) or gastro-oesophageal junction carcinoma is best remains an open question. Randomised controlled trials variously accrued patients with adenocarcinoma and squamous cell carcinoma, making strong conclusions hard to obtain. The primary objective of this in idual participant data meta-analysis was to investigate the effect of neoadjuvant chemotherapy on overall survival (OS). Eligible trials should have closed to accrual before 2016 and compared neoadjuvant chemotherapy and surgery (CS) to surgery alone. All relevant published and unpublished trials were identified via searches of electronic databases, conference proceedings and clinical trial registers. The main end-point was OS. Investigators were contacted to obtain the in idual patient data, which was recorded, harmonised and checked. A random-effects Cox model, stratified by trial, was used for meta-analysis and subgroup analyses were preplanned. 16 trials were identified as eligible. In idual patient data were obtained from 12 trial and 2478 patients. CS was associated with an improved OS versus surgery, hazard ratio (HR) = 0.83 [0.72-0.96], p < 0.0001, translating to an absolute benefit of 5.7% at 5-years from 16.8% to 22.5%. Treatment effects did not vary substantially between adenocarcinoma (HR = 0.73 [0.62-0.87]) and squamous cell carcinoma (HR = 0.91 [0.76-1.08], interaction p = 0.26). A somewhat more pronounced effect was observed in gastro-oesophageal junction (HR = 0.68 [0.50-0.93]) versus TE (HR = 0.87 [0.75-1.00], interaction p = 0.07). CS was also associated with a greater disease-free survival (HR = 0.74 [0.64-0.85], p < 0.001). Neoadjuvant chemotherapy conferred a better OS than surgery alone and should be considered in all anatomical location and histological subtypes.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-2023
DOI: 10.1200/JCO.22.02279
Abstract: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an in idual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors ( P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women ( P = .003, .012, respectively). Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-08-2021
DOI: 10.1126/SCITRANSLMED.AAY9592
Abstract: Neuromuscular junction remodeling and deterioration due to impaired BMP signaling are associated with cancer-induced muscle wasting.
Publisher: Oxford University Press (OUP)
Date: 23-02-2022
DOI: 10.1093/BJS/ZNAC016
Abstract: Textbook outcome has been proposed as a tool for the assessment of oncological surgical care. However, an international assessment in patients undergoing oesophagectomy for oesophageal cancer has not been reported. This study aimed to assess textbook outcome in an international setting. Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018 to December 2018. Textbook outcome was defined as the percentage of patients who underwent a complete tumour resection with at least 15 lymph nodes in the resected specimen and an uneventful postoperative course, without hospital readmission. A multivariable binary logistic regression model was used to identify factors independently associated with textbook outcome, and results are presented as odds ratio (OR) and 95 per cent confidence intervals (95 per cent c.i.). Of 2159 patients with oesophageal cancer, 39.7 per cent achieved a textbook outcome. The outcome parameter ‘no major postoperative complication’ had the greatest negative impact on a textbook outcome for patients with oesophageal cancer, compared to other textbook outcome parameters. Multivariable analysis identified male gender and increasing Charlson comorbidity index with a significantly lower likelihood of textbook outcome. Presence of 24-hour on-call rota for oesophageal surgeons (OR 2.05, 95 per cent c.i. 1.30 to 3.22 P = 0.002) and radiology (OR 1.54, 95 per cent c.i. 1.05 to 2.24 P = 0.027), total minimally invasive oesophagectomies (OR 1.63, 95 per cent c.i. 1.27 to 2.08 P & 0.001), and chest anastomosis above azygous (OR 2.17, 95 per cent c.i. 1.58 to 2.98 P & 0.001) were independently associated with a significantly increased likelihood of textbook outcome. Textbook outcome is achieved in less than 40 per cent of patients having oesophagectomy for cancer. Improvements in centralization, hospital resources, access to minimal access surgery, and adoption of newer techniques for improving lymph node yield could improve textbook outcome.
Location: Italy
No related grants have been discovered for Michele Valmasoni.