Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

BACKGROUND: Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. METHODS/DESIGN: PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. DISCUSSION: This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. TRIAL REGISTRATION: NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014)

Gastric Cancer Surgery

Le cancer de l’estomac est l’une des principales causes de mortalité par cancer dans le monde. Même si des progrès dans les traitements non chirurgicaux ont été réalisés, avec l’avènement de la chimiothérapie périopératoire, la chirurgie reste au centre de la prise en charge de ces tumeurs, représentant la seule option curative à l’heure actuelle, si une résection complète dite « R0 » peut être obtenue. Des recommandations ont ainsi été émises par la Société Française de Chirurgie Digestive (SFCD) et l’Association de Chirurgie Hépato-Biliaire et Transplantation (ACHBT), recommandations labellisées par l’Institut National du Cancer (INCa). Le but de cet article est de discuter de l’étendue de la résection digestive et du curage ganglionnaire ainsi que de la technique de reconstruction digestive à effectuer, et de préciser la place de la chimiohyperthermie intrapéritonéale et de la chirurgie palliative dans la prise en charge des adénocarcinomes gastriques

Evaluation of pathological complete response as a surrogate endpoint for overall survival in resectable oesophageal cancer:integrated analysis of individual patient data from phase III trials

Background Overall survival (OS) is the standard endpoint for oncological treatment efficacy, but requires long follow-up. The aim of this study was to evaluate pCR as a surrogate for OS in oesophageal cancer. Methods An integrated analysis of individual patient data (IPD) from phase III trials comparing perioperative therapies for resectable oesophageal and gastro-oesophageal junction cancer was conducted. Individual-level surrogacy between pCR and OS was assessed using Kendall's rank correlation coefficient (τ). A τ of 0.8 was considered a threshold for a good surrogate. As no method estimating τ between an ordinal endpoint and OS has been reported, a new method was proposed using the inverse-probability-of-censoring weighted estimator adjusted for tied data. Results Of 22 eligible trials, 10 provided IPD for 1641 patients, including 624 who received neoadjuvant chemotherapy (NAC; 45 (7.2%) achieved pCR) and 1017 who received neoadjuvant chemoradiotherapy (NACRT; 299 (29.4%) achieved pCR). In the NAC subgroup, patients with pCR had an HR for OS of 0.12 (95% c.i. 0.05 to 0.33), the C-index was 0.54 (95% c.i. 0.52 to 0.56), and τ was 0.256. In the NACRT subgroup, the HR was 0.57 (95% c.i. 0.47 to 0.70), the C-index was 0.56 (95% c.i. 0.54 to 0.58), and τ was 0.174. Hypothetical data suggested that achieving strong surrogacy (τ of 0.8) required an HR of 0.09 (95% c.i. 0.07 to 0.11). Conclusion Although pCR was correlated with OS, no evidence of individual-level surrogacy with OS was demonstrated, making it inappropriate to consider pCR as a surrogate endpoint for OS in resectable oesophageal cancer.</p

Surgical Outcomes After Neoadjuvant Chemoradiation Followed by Curative Surgery in Patients With Esophageal Cancer: An Intergroup Phase lll Trial of the Swiss Group for Clinical Cancer Research (SAKK 75/08).

OBJECTIVE To assess the impact of surgical technique in regard to morbidity and mortality after neoadjuvant treatment for esophageal cancer. BACKGROUND The SAKK trial 75/08 was a multicenter phase III trial (NCT01107639) comparing induction chemotherapy followed by chemoradiation and surgery in patients with locally advanced esophageal cancer. METHODS Patients in the control arm received induction chemotherapy with cisplatin and docetaxel, followed by concomitant chemoradiation therapy with cisplatin, docetaxel, and 45Gy. In the experimental arm, the same regimen was used with addition of cetuximab. After completion of neoadjuvant treatment, patients underwent esophagectomy. The experimental arm received adjuvant cetuximab. Surgical outcomes and complications were prospectively recorded and analyzed. RESULTS Total of 259 patients underwent esophagectomy. Overall complication rate was 56% and reoperation rate was 15% with no difference in complication rates for transthoracic versus transhiatal resections (56% vs 54%, P = 0.77), nor for video assisted thoracic surgeries (VATS) versus open transthoracic resections (67% vs 55%, P = 0.32). There was a trend to higher overall complication rates in squamous cell carcinoma versus adenocarcinoma (65% vs 51%, P = 0.035), and a significant difference in ARDS in squamous cell carcinoma with 14% versus 2% in adenocarcinoma (P = 0.0002). For patients with involved lymph nodes, a lymph node ratio of ≥0.1 was an independent predictor of PFS (HR 2.5, P = 0.01) and OS (HR 2.2, P = 0.03). CONCLUSIONS This trial showed no difference in surgical complication rates between transthoracic and transhiatal resections. For patients with involved lymph nodes, lymph node ratio was an independent predictor of progression free survival and overall survival

Limited Resection Versus Pancreaticoduodenectomy for Duodenal Gastrointestinal Stromal Tumors? Enucleation Interferes in the Debate: A European Multicenter Retrospective Cohort Study

Background The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate. Objectives The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN). Methods In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated. Results Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p &lt; 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors &lt; 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences. Conclusions For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed

Outcomes of a new slowly resorbable biosynthetic mesh (Phasix (TM)) in potentially contaminated incisional hernias : a prospective, multi-center, single-arm trial

Background: Resorbable biomaterials have been developed to reduce the amount of foreign material remaining in the body after hernia repair over the long-term. However, on the short-term, these resorbable materials should render acceptable results with regard to complications, infections, and reoperations to be considered for repair. Additionally, the rate of resorption should not be any faster than collagen deposition and maturation; leading to early hernia recurrence. Therefore, the objective of this study was to collect data on the short-term performance of a new resorbable biosynthetic mesh (Phasix (TM)) in patients requiring Ventral Hernia Working Group (VHWG) Grade 3 midline incisional hernia repair. Materials and methods: A prospective, multi-center, single-arm trial was conducted at surgical departments in 15 hospitals across Europe. Patients aged >= 18, scheduled to undergo elective Ventral Hernia Working Group Grade 3 hernia repair of a hernia larger than 10 cm(2) were included. Hernia repair was performed with Phasix (TM) Mesh in sublay position when achievable. The primary outcome was the rate of surgical site occurrence (SSO), including infections, that required intervention until 3 months after repair. Results: In total, 84 patients were treated with Phasix (TM) Mesh. Twenty-two patients (26.2%) developed 32 surgical site occurrences. These included 11 surgical site infections, 9 wound dehiscences, 7 seromas, 2 hematomas, 2 skin necroses, and 1 fistula. No significant differences in surgical site occurrence development were found between groups repaired with or without component separation technique, and between clean-contaminated or contaminated wound sites. At three months, there were no hernia recurrences. Conclusion: Phasix (TM) Mesh demonstrated acceptable postoperative surgical site occurrence rates in patients with a Ventral Hernia Working Group Grade 3 hernia. Longer follow-up is needed to evaluate the recurrence rate and the effects on quality of life. This study is ongoing through 24 months of follow-up

Western European Variation in the Organization of Esophageal Cancer Surgical Care

Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5-4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe

Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the “All or None” method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the “ideal” and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.</p

Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the “All or None” method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the “ideal” and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.</p

Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial

<p>Abstract</p> <p>Background</p> <p>Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma.</p> <p>Methods/Design</p> <p>The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A.</p> <p>Discussion</p> <p>Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00937456">NCT00937456</a> (ClinicalTrials.gov)</p