Abstract
Background:
In locally advanced esophagogastric adenocarcinoma (EGA), perioperative chemotherapy is the standard of care and can result in complete/major pathological response. In this setting, real-world data on the impact of postoperative chemotherapy are scarce.
Objective:
The primary objective was to assess the impact of postoperative chemotherapy on overall survival (OS) in cases of complete/major pathological response and/or no serosal involvement. Secondary endpoints were disease-free survival (DFS) and the identification of predictive factors associated with OS.
Design:
A retrospective comparative multicentric study was conducted using the nationwide, prospectively collected FREGAT (FRench EsoGAstric Tumor) database.
Methods:
Patients with EGA treated with perioperative chemotherapy registered in the FREGAT database who had a complete/major pathological response and/or no serosal involvement (ypT0–2 or ypT3 Mandard TRG 2, ypN0, R0) were included.
Results:
Among 1870 patients with EGA treated with perioperative chemotherapy identified in the FREGAT database, 345 met the inclusion criteria, and 218 (63.2%) received postoperative chemotherapy. Postoperative chemotherapy was associated with OS improvement regardless of the regimen used (median OS: not achieved vs 65.7 months; p < 0.0001). Similarly, DFS was improved with postoperative chemotherapy (median DFS: not achieved vs 65.7 months; p < 0.0001). In multivariable analysis, age, primary tumor location, postoperative complications, and no postoperative chemotherapy were associated with poorer survival outcomes.
Conclusion:
Postoperative chemotherapy after resection of EGA with complete/major pathological response and/or tumors without serosal involvement remains the standard of care, improves survival outcomes, and should be recommended when the patient’s condition allows it.
Keywords: esophagogastric junction adenocarcinoma, FLOT, gastric adenocarcinoma, pathological response, perioperative chemotherapy
Introduction
Gastric cancer, which is the main histological subtype, is adenocarcinoma, 1 and is a leading cause of mortality and a public health problem worldwide. It is the sixth most common cancer and the third leading cause of cancer-related death worldwide, with 1.1 million new cases and 770,000 deaths in 2021.2–4 Europe accounted for an estimated 136,038 cases and 96,997 deaths in these global numbers.1,2 Esophagogastric junction and gastric adenocarcinomas (EGA) have a poor prognosis. At diagnosis, 60% of patients with EGA are not eligible for curative treatment owing to late presentation or comorbidities. 5 When resected, the recurrence rate of EGA remains high (20%–50%), and then overall survival (OS) rarely exceeds 12–15 months.6–8
Over the past two decades, several therapeutic strategies have been assessed in prospective trials9–13 to improve the rate of curative resection by down-staging the tumor, to reduce the risk of recurrence of resected EGA (eliminating micro metastases), rapidly improving tumor-related symptoms, and to determine the tumor’s sensitivity to chemotherapy. In 2006, the MAGIC trial 9 was the first and largest randomized study that demonstrate a significant improvement in OS for patients with resectable EGA, when treated with surgery and perioperative chemotherapy (epirubicin, cisplatin, fluorouracil/ECF regimen; 3 cycles before and 3 cycles after surgery; q3w), compared to those treated with surgical resection alone (hazard ratio (HR) = 0.75, 5-year survival rate of 36% vs 23%; p = 0.009). The standard of care in resectable EGA is still perioperative treatment: until recently, the FLOT regimen (fluorouracil, oxaliplatin, docetaxel; 4 cycles before and 4 cycles after surgery; q2w) was the recommended strategy, following the results of the phase III FLOT4 trial, 13 which demonstrated a significant improvement in OS (HR = 0.77, median OS: 50 vs 35 months) and in the complete pathological response rate (15% vs 6%; p = 0·02) compared to ECF/ECX (epirubicin, cisplatin, and fluorouracil/capecitabine) regimen. It has also recently been shown that the perioperative FLOT strategy is more effective than neoadjuvant chemoradiotherapy, which remains a therapeutic alternative.14,15 Nowadays, the perioperative FLOT regimen associated with durvalumab (anti-PD-L1; 1500 mg, every 4 weeks in preoperative setting (2 cycles) followed by 10 cycles in the postoperative setting) is considered the new standard of care for localized EGA3,16 following the publication of the recent phase III MATTERHORN trial results.16,17 Compared to the perioperative FLOT regimen alone, FLOT plus durvalumab significantly improved event-free survival (67.4% vs 58.5%; HR = 0.71; p < 0.001), OS (HR = 0.78; p = 0.021), and the complete pathological response rate (19% vs 7%, odds ratio 3.08; p < 0.00001).16–18
The significant improvement of pathological response in the surgical specimen since the introduction of the perioperative FLOT strategy raises the question of whether postoperative chemotherapy should be done in cases of a complete/major pathological response and/or tumor without serosal involvement. Some data suggest that continuing postoperative chemotherapy (same protocol as administered preoperatively) provides survival benefits,1,19 notably in cases where there is no complete pathological response on the resected tumor, as presented in the retrospective SPACE-FLOT study. 19 However, these data have not been stratified according to pathological response rate. Furthermore, data from the MAGIC trial showed that the presence of lymph node metastases on surgical specimen, rather than the pathological response to preoperative chemotherapy (Mandard tumor regression grade/TRG 3, 4, or 5 vs TRG 1 or 2), 20 was the only independent predictor of survival following chemotherapy and resection. 9
To address those uncertainties, the aim of this study was to assess the clinical impact of postoperative chemotherapy on survival outcomes in patients with locally advanced EGA with a complete/major pathological response and/or tumor without serosal involvement after preoperative chemotherapy.
Patients and methods
Patients
A retrospective comparative multicentric study was conducted using the nationwide, prospectively collected FREGAT (FRench EsoGAstric Tumor) database. FREGAT is a national, multicenter, prospective cohort study of adult patients treated for esophageal or gastric cancer (NCT02526095). 21 This study is reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. 22
For this study, all patients with locally advanced EGA at diagnosis treated with perioperative chemotherapy (regardless of the regimen used) registered in the FREGAT database and with documented complete/major pathological response and/or tumor without serosal involvement (i.e., ypT0-2, ypN0, R0 or ypT3 Mandard TRG 2, ypN0, R0) after preoperative chemotherapy (at least 6 weeks of preoperative chemotherapy) diagnosed between January 2015 and January 2024 were included. These pathological criteria were chosen because they are associated with a lower risk of recurrence, especially for ypT3 tumors, which are heterogeneous. A Mandard TRG 1–2 pathological response is also associated with better survival outcomes, notably for ypT3 tumors.23–27 Patients registered in the database but without follow-up data were not included.
Data collection
Data were extracted from the FREGAT database. Patients’ and tumors’ characteristics, epidemiological, preoperative, and postoperative treatments, pathological data, follow-up, and survival data were collected, as well as the date of the last follow-up and the date/cause of death.
Objectives
The main objective was to assess the real-world impact of postoperative chemotherapy on OS of patients who were resected for locally advanced EGA and who had a complete/major pathological response and/or tumor without serosal involvement after preoperative chemotherapy.
The secondary endpoint was first to assess disease-free survival (DFS). Other secondary endpoints were exploratory and aimed to identify predictive factors associated with OS in the study population. OS and DFS were also compared according to time to resumption of chemotherapy (⩽8 vs >8 weeks after surgical resection)28–30 in patients who received postoperative chemotherapy.
Statistical analyses
Continuous variables were described as medians with their 25–75 interquartile (Q1, Q3) and compared with Student or Wilcoxon tests. Categorical variables were described as frequencies and percentages and compared using the Chi-square test or Fisher’s exact test, as most appropriate.
OS was defined as the time elapsed between EGA surgical resection and death from any cause. Patients were censored at their last known follow-up before the database lock.
DFS was defined as the time elapsed between EGA surgical resection and disease recurrence (defined as radiological recurrence on tomodensitometry following RECIST 1.1 criteria) or death.
Median OS and DFS were estimated by the Kaplan–Meier method and compared by the log-rank test. Survival analyses were performed on the overall study population and by treatment type (before FLOT era vs after FLOT era).
As part of a prespecified sensitivity analysis, OS was assessed using a Cox proportional hazards model adjusted for the stratification factors: sex, age at EGA diagnosis, tumor location (esophagogastric junction/lower esophagus vs gastric), cT, chemotherapy regimen (triplet chemotherapy with taxane vs others), postoperative complications (according to Dindo-Clavien classification (grade 1 vs >1)), and postoperative chemotherapy. The factors associated with OS were identified with a Cox model. Variables with a p-value <0.2 in the univariable model were eligible for the multivariable model. A stepwise selection procedure was applied. The significance threshold was set at 5%. Analyses were performed using SAS 9.4 (SAS Inst., Cary, NC, USA).
Results
Description of the study population
In the FREGAT database, 1870 patients with EGA and perioperative chemotherapy were identified. After excluding patients who were treated with preoperative or postoperative concomitant chemoradiotherapy (n = 141), who presented with metastatic disease at diagnosis (n = 100), who showed no complete/major pathological response (n = 1191), and cases with missing follow-up data (n = 93), 345 patients met the inclusion criteria and were finally included in the study (Figure 1). Among them, 218 (63.2%) received adjuvant chemotherapy, and 127 (36.8%) did not. In the whole cohort, 277 (80.3%) were male, and the median age at EGA diagnosis was 66.0 years old (Q1–Q3: 57–72). Most of the tumors were located at the esophagogastric junction (45.3%), one-third (34.5%) were gastric, and 20.2% were located in the lower third of the esophagus. Half of the tumors were classified as cN+ at radiological baseline evaluation. Regarding the chemotherapy protocols administered, 195 patients (56.5%) were treated with perioperative triplet chemotherapy including a taxane according to the FLOT (docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, leucovorin 200 mg/m2 on day 1, and 5-FU 2600 mg/m2 as 24-h infusion on day 1, q2w, 4 cycles pre- and postoperative) or DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2 (day 1) plus fluorouracil 750 mg/m2 days 1–5, q3w, 3 cycles preoperative and postoperative) regimens.
Figure 1.
Flow chart of the study population.
EGA, esophagogastric junction and gastric adenocarcinoma.
Considering the two distinct groups of patients (no postoperative chemotherapy vs postoperative chemotherapy), some significant differences were noticed (Table 1). There was an overrepresentation of women in the subgroup receiving postoperative chemotherapy (22.9% vs 14.2%; p = 0.0485). In that same group, patients were also older at EGA diagnosis (35.8% aged ⩽60 years old vs 25.2%; p = 0.0046), had gastric tumors more often (39.9% vs 25.2%, p = 0.0056), and were more exposed to the FLOT regimen (63.3% vs 44.9%, p = 0.0068). In the no postoperative chemotherapy group, patients did not receive postoperative chemotherapy for two main reasons: postoperative complications (33%) and the oncologist’s or patient’s choice (16%). Indeed, during the postoperative period, patients in that group were more likely to present an altered general condition (ECOG PS >1, 45.4% vs 21.0%; p < 0.0001) and had more postoperative complications (p < 0.0001).
Table 1.
Patients’ and tumors’ characteristics at the esophagogastric junction or gastric adenocarcinoma diagnosis.
| Patients’ and tumors’ characteristics | Postoperative chemotherapy arm (n = 218) | No postoperative chemotherapy arm (n = 127) | p Value |
|---|---|---|---|
| Sex | 0.0485 | ||
| Male, n (%) | 168 (77.1) | 109 (85.8) | |
| Female, n (%) | 50 (22.9) | 18 (14.2) | |
| Age (years) at EGA diagnosis, median (Q1, Q3) | 68.0 (59.75–74) | 66.0 (57–71) | 0.0419 |
| Tobacco consumption, n (%) | 129 (59.2) | 88 (69.3) | 0.0606 |
| Alcohol consumption, n (%) | 59 (27.1) | 40 (31.5) | 0.3801 |
| Primary tumor location | 0.0056 | ||
| Esophagus/esogastric junction, n (%) | 131 (60.1) | 95 (74.8) | |
| Stomach, n (%) | 87 (39.9) | 32 (25.2) | |
| Tumor clinical staging (N) at diagnosis | 0.0848 | ||
| cN0, n (%) | 91 (42.7) | 66 (52.4) | |
| cN+, n (%) | 122 (57.3) | 60 (47.6) | |
| Tumoral pathological subtype | 0.0796 | ||
| Adenocarcinoma, n (%) | 209 (95.9) | 123 (96.9) | |
| Signet ring cells, n (%) | 9 (4.1) | 2 (1.6) | |
| Chemotherapy regimens | 0.009 | ||
| Triplet with taxane (FLOT or DCF), n (%) | 138 (63.3) | 57 (44.9) | |
| Platinum salt and fluoropyrimidine, n (%) | 67 (30.7) | 60 (47.2) | |
| ECF/ECX, n (%) | 10 (4.6) | 7 (5.5) | |
| Other, n (%) | 3 (1.4) | 3 (2.4) | |
DCF, docetaxel, cisplatin, and fluorouracil; ECF/ECX, epirubicin, cisplatin, and fluorouracil/capecitabine; EGA, esophagogastric junction and gastric adenocarcinoma; FLOT, 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel; Q1, first quartile; Q3, third quartile.
Patients, chemotherapy regimens, and tumors’ main characteristics are described in Table 1.
Survival data
In the whole cohort, the median follow-up was 45.1 months from the date of EGA surgery and death.
There was a significant difference in survival outcomes in patients resected for EGA in complete/major pathological response and/or tumor without serosal involvement (i.e., ypT0-2, ypN0, R0 or ypT3 Mandard TRG 2, ypN0, R0) after preoperative chemotherapy, according to the postoperative therapeutic strategy (no postoperative chemotherapy vs postoperative chemotherapy). In the no postoperative chemotherapy group, median OS was not achieved versus 65.7 months when treated with postoperative chemotherapy (p < 0.0001, Figure 2). After adjusting for factors that differed between groups, the difference in survival remained statistically significant (p = 0.0011). Adjuvant chemotherapy was independently associated with improved OS. Similarly, the median DFS rate was not achieved versus 65.7 months with postoperative chemotherapy (p < 0.0001, Figure 3). Those findings were confirmed by a sensitivity analysis that excluded patients with ypT3N0 Mandard 2 (median OS not achieved with postoperative chemotherapy vs 80.6 months; p < 0.0001, Supplemental Material 1(A) and median DFS not achieved with postoperative chemotherapy vs 65.7 months, Supplemental Material 1(B)). These findings were also observed when adjusting for factors that differed between groups and regardless of the chemotherapy regimen administered (triplet chemotherapy including a taxane (i.e., FLOT or DCF) vs other regimens, Supplemental Material 2(A) and (B)).
Figure 2.
Overall survival curves in patients with locally advanced esophagogastric junction and gastric adenocarcinoma treated with postoperative chemotherapy versus no postoperative chemotherapy.
Figure 3.
Disease-free survival curves in patients with locally advanced esophagogastric junction and gastric adenocarcinoma treated with postoperative chemotherapy versus no postoperative chemotherapy.
Prognosis data
In univariate analysis, age (>60 vs ⩽60 years old), primary tumor location, tobacco consumption, ypT stage, chemotherapy regimen, administration of postoperative chemotherapy, and postoperative complications were associated with OS. In multivariate analysis, age, primary tumor location, postoperative complications, and the administration of postoperative chemotherapy were the four identified prognosis factors associated with poorer survival outcomes (age >60 vs ⩽60 years old: HR = 1.9; p = 0.0235; esophageal/cardia primary tumors location: HR = 2.3; p = 0.0065; postoperative complications: HR = 1.9; p = 0.0076; no postoperative chemotherapy vs postoperative chemotherapy: HR = 2.1; p = 0.0020). Details are provided in Table 2.
Table 2.
Clinical, biological, and pathological factors associated with the overall survival rate.
| Clinical/biological/pathological factors | All patients (n = 345) | Death (n, %) | HR (95% CI) | Univariate regression | HR (95% CI) | Multivariate analysis |
|---|---|---|---|---|---|---|
| Sex | 0.1417 | |||||
| Male | 277 | 68 (24.5) | ||||
| Female | 68 | 10 (14.7) | ||||
| Age at EGA diagnosis | 0.0069 | 0.0235 | ||||
| ⩽60 years | 110 | 15 (13.6) | ||||
| >60 years old | 235 | 63 (26.8) | 2.2 (1.2–3.8) | 1.9 (1.1–3.4) | ||
| Tobacco consumption | 0.1964 | |||||
| No | 128 | 25 (19.5) | ||||
| Yes | 217 | 53 (24.4) | 1.4 (0.8–2.2) | |||
| Preoperative ASA score | 0.3431 | |||||
| 1 | 43 | 9 (20.9) | ||||
| 2 | 193 | 40 (20.7) | 1.0 (0.5–2.1) | |||
| 3 | 93 | 24 (25.8) | 1.3 (0.6–2.8) | |||
| 4 | 4 | 2 (50.0) | 3.1 (0.7–14.4) | |||
| Primary tumor location | 0.0010 | 0.0065 | ||||
| Stomach | 119 | 15 (12.6) | ||||
| Esophagus and junction | 226 | 63 (27.9) | 2.6 (1.5–4.7) | 2.3 (1.3–4.0) | ||
| Postoperative tumoral stage (ypT) | 0.0571 | |||||
| ypT0 | 106 | 15 (14.2) | ||||
| ypTis | 4 | 2 (50.0%) | 3.7 (0.8–16.1) | |||
| ypT1a | 52 | 10 (19.2) | 1.4 (0.6–3.1) | |||
| ypT1b | 78 | 19 (24.4) | 1.9 (0.9–3.7) | |||
| ypT2 | 82 | 22 (26.8) | 1.8 (0.9–3.5) | |||
| ypT3 | 23 | 10 (43.5) | 3.4 (1.5–7.5) | |||
| Chemotherapy regimens | 0.4269 | |||||
| Triplet with taxane (FLOT or DCF), n (%) | 195 | 37 (19.0) | ||||
| Others, n (%) | 150 | 41 (27.3) | 1.2 (0.8–1.9) | |||
| Postoperative chemotherapy | <0.0001 | 0.0020 | ||||
| Yes | 218 | 33 (15.1) | ||||
| No | 127 | 45 (35.4) | 2.7 (1.7–4.3) | 2.1 (1.3–3.3) | ||
| Postoperative complications | <0.0001 | 0.0076 | ||||
| No, n (%) | 222 | 36 (16.2) | ||||
| Yes, n (%) | 123 | 42 (34.1) | 2.4 (1.6–3.8) | 1.9 (1.2–3.0) | ||
ASA, American Society of Anaesthesiologists; CI, confidence interval; DCF, docetaxel, cisplatin, and fluorouracil; EGA, esophagogastric junction and gastric adenocarcinoma; FLOT, 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel; HR, hazard ratio.
Among patients who received postoperative chemotherapy, those who started treatment more than 8 weeks after surgery had a worse median DFS (median DFS not reached; p = 0.00082, Supplemental Material 3(A)), and median OS (median OS not reached; p = 0.0294, Supplemental Material 3(B)).
Discussion
In locally advanced EGA, perioperative chemotherapy has become a commonly used treatment strategy in Western countries over the past two decades. However, there have been some changes over time regarding the preferred perioperative chemotherapy regimen. 1 Since 2019 and the publication of the results of the FLOT4 phase III trial, the FLOT triplet regimen is the standard of care in this setting, provided that the patient is in good general health (i.e., ECOG PS 0–1) and the tumor does not have a deficiency in the mismatch repair system (dMMR)/microsatellite instability (MSI). To our knowledge, we reported here one of the most important retrospective multicenter studies assessing the impact of postoperative chemotherapy on survival outcomes in patients with locally advanced EGA who presented a complete/major pathological response and/or a tumor without serosal involvement after preoperative chemotherapy. In that specific context, and especially since the perioperative “FLOT era,” the use of postoperative chemotherapy is perceived to be limited in the real-world setting. Based on the multicenter and prospective FREGAT cohort, we showed that postoperative chemotherapy was significantly associated with an improvement in OS and DFS for resected EGA that were in complete/major pathological response and/or without serosal involvement (i.e., ypT0-2, ypN0, R0 or ypT3 Mandard TRG 2, ypN0, R0) after preoperative chemotherapy. These results were observed regardless of the chemotherapy regimens administered, especially a triplet regimen using a taxane (FLOT or DCF), considering that three-drug regimens such as the parent DCF would be associated with comparable efficacy profiles in the perioperative setting.13,31,32 A landmark analysis at 200 days confirmed that the survival benefit of postoperative chemotherapy was mainly early (0–200 days: HR = 15.7), whereas the late period showed attenuated and non-significant differences (>200 days: HR = 1.53). Such results emphasize the importance of maintaining chemotherapy after surgery, if the patient’s condition allows it, which is the current standard of care. 1
Recently, two retrospective studies19,33 also assessed the value of postoperative chemotherapy in real-world settings. In the first one, 33 147 patients resected for locally advanced EGA after preoperative FLOT were studied: tumors were mainly ypT3-4 (65.9%), ypN+ (56.4%), and R1/2 (20%). Authors demonstrated that survival rates of patients with marked tumor regression (TRG 1) were not improved by adjuvant chemotherapy. In the international cohort SPACE-FLOT study, 19 DFS (HR = 0.73; 95% CI: 0.58–0.92) and OS (HR = 0.63; 95% CI: 0.50–0.79) were significantly higher with postoperative FLOT in cases of partial pathological response in the resected tumor. However, no significant differences in DFS or OS were observed in cases of minimal or complete pathological response. In our cohort, patients achieving a complete/major pathological response after preoperative chemotherapy also exhibited favorable survival outcomes despite omission of postoperative chemotherapy, suggesting that the main therapeutic benefit may be derived from the preoperative phase. The latter study showed that it was difficult to deliver the postoperative component of perioperative chemotherapy, with a substantial proportion of patients unable to complete postoperative treatment.
Although our results are significant, our study presents some limitations. The most significant of these is that the new standard of care for localized EGA is now the combination of the FLOT triplet with durvalumab since the recent phase III MATTERHORN results demonstrated a significant improvement in both recurrence-free 16 and OS 17 compared to the FLOT triplet alone (considered as the new standard of care; however, this regimen is not yet included in the routine clinical practice, pending from authorities approval in some countries). Therefore, our results need to be validated in the context of the MATTERHORN regimen. Moreover, other biases are due to the retrospective setting and the disparities observed in the two groups of patients. Cause-specific mortality could not be reliably assessed, and competing causes of death may have contributed to OS outcomes. A significantly higher rate of postoperative complications was observed in patients who did not receive postoperative chemotherapy. This constitutes a notable selection bias, especially since it is a factor associated with poorer survival. 34
In addition, some analyses could not be performed due to insufficient data and statistical power, which were affected by small sample sizes in certain patient subgroups (e.g., signet ring cells adenocarcinoma were rare in our study, mainly excluded due to a pathological response considered “poor” according to our inclusion criteria). Similarly, molecular biology data (e.g., dMMR/MSI status, HER2, or Claudin 18.2 immunohistochemistry results) could not be studied, as most of them were unavailable. Our observations should therefore be treated with caution. In addition, it was not possible to conduct radiological/pathological reviews. Consequently, potential inconsistencies in TRG assessment between centers are possible, which could have implications for the interpretation of results. Furthermore, it was not possible to make a centralized decision about the time to disease recurrence, which may also have introduced bias. Consequently, only the ATTENUATION phase III trial, which will begin enrollment in 2026, will be able to answer all these questions. This trial will prospectively assess the impact of postoperative chemotherapy with FLOT in cases of a complete/major pathological response (i.e., ypT0- 2, ypN0, R0 or ypT3 Mandard TRG 2, ypN0, R0) on surgical specimens following preoperative chemotherapy. Although the ATTENUATION study will use the perioperative FLOT regimen, it may provide additional information on the therapeutic strategy to adopt in cases involving a very good pathological response and/or a tumor without serosal involvement following preoperative chemotherapy. MATTERHORN applied a uniform treatment intensification strategy to all patients, regardless of their pathological response to preoperative chemotherapy. As a consequence, this approach does not address the marked heterogeneity in tumor biology and treatment sensitivity observed after neoadjuvant therapy. While MATTERHORN 16 supports treatment escalation for patients at higher risk, it also highlights the unmet need for response-adapted strategies. The ATTENUATION study specifically addresses this gap by evaluating whether postoperative surveillance may be a safe and clinically meaningful alternative in patients with a good pathological response to preoperative chemotherapy, potentially avoiding overtreatment and unnecessary toxicity. A better understanding of the molecular biology of EGAs, along with the identification of new therapeutic targets, will help to personalize perioperative treatment for EGAs in the near future.
Conclusion
In this real-world study from the prospective FREGAT cohort, we observed that postoperative chemotherapy following resection of EGA in cases of major pathological response after preoperative chemotherapy resulted in significant improvements in OS and DFS. Therefore, in accordance with international guidelines and pending the results of the prospective French trial ATTENUATION, postoperative chemotherapy remains the standard of care for patients fit for adjuvant chemotherapy, whatever the response to the neoadjuvant chemotherapy.
Supplemental Material
Supplemental material, sj-docx-1-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Supplemental material, sj-docx-2-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Supplemental material, sj-docx-3-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Supplemental material, sj-docx-4-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Acknowledgments
None.
Footnotes
ORCID iD: Marie Muller 
https://orcid.org/0000-0001-6412-932X
Supplemental material: Supplemental material for this article is available online.
Contributor Information
Laure Corazzin, Department of Hepato-gastroenterology and Digestive Oncology, Nancy University Hospital, University of Lorraine, Nancy, France.
Elodie Jeanbert, DRCI, MPI Department, Methodology, Data Management and Statistics Unit, Nancy University Hospital, Nancy, France.
Olivier Glehen, Surgical Department, Centre Hospitalo-Universitaire Lyon Sud, Pierre Bénite, France.
Caroline Gronnier, Eso-Gastric Surgery Unit, Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, Pessac, France.
Laurent Sulpice, Department of Hepatobiliary and Digestive Surgery Hospital Rennes, Rennes, France.
Jean-Marc Gornet, Department of Gastroenterology, Saint-Louis Hospital, APHP, Paris, France.
Brice Paquette, Surgical Department, University Hospital Centre Besançon, Besançon, France.
Jean-Marc Regimbeau, Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France.
Cécile Brigand, Department of General and Digestive Surgery, University Hospital of Hautepierre, Strasbourg, France.
Xavier-Benoît D’Journo, Department of Thoracic Surgery, North Hospital, Aix-Marseille University, Marseille, France.
Pierre-Yves Brichon, Department of Thoracic Surgery, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France.
Johan Gagnaire, Department of Digestive and Hepatobiliary Surgery–Liver Transplantation, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.
Thibault Voron, Digestive and Oncological Surgery Department, Saint-Antoine Hospital, AP-HP, Paris, France.
Muriel Mathonnet, Department of Digestive, General and Endocrine Surgery, University Hospital of Limoges, Limoges, France.
Christophe Penna, Department of Surgical Oncology, Bicêtre Hospital, APHP, Paris, France.
Nicolas Regenet, Department of Digestive Surgery, Nantes University Hospital, Nantes, France.
Côme Lepage, Fédération Francophone de Cancérologie Digestive, University of Burgundy and Franche Comté, Dijon, France.
Nicolas Carrere, Department of Digestive Surgery, Toulouse Rangueil University Hospital, Toulouse, France.
Ugo Marchese, Department of Hepato-Pancreatic-Biliary and Endocrine Surgery, Hospital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Leonor Benhaim, Department of Digestive Surgery, Gustave Roussy Institute, Villejuif, France.
Jean-Michel Fabre, Department of Oncologic and Minimally Invasive Digestive Surgery, Hospital Saint Eloi, University Hospital of Montpellier, Montpellier, France.
Frédéric Di Fiore, Department of Hepato-Gastroenterology and Digestive Oncology, CHU Rouen, Rouen, France.
Frédéric Borie, Digestive Surgery Department, Carémeau Hospital, University of Montpellier–Nîmes, Place du Professeur Debré, Nîmes, France.
Pierre Emmanuel Bonnot, Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France.
Olivier Bouché, Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France.
David Tougeron, Department of Hepatology and Gastroenterology, Poitiers University Hospital, Poitiers, France.
Antoine Adenis, Medical Oncology Department, Montpellier Cancer Institute, Montpellier University, Montpellier, France.
Guillaume Piessen, Department of Digestive and Oncological Surgery, CHU Lille, Lille, France.
Marie Muller, CHRU de Nancy, Allée du Morvan, Service d’Hépato-gastroentérologie, Vandœuvre-lès-Nancy 54500, France; Department of Hepato-gastroenterology and Digestive Oncology, Nancy University Hospital, University of Lorraine, Nancy, France.
Declarations
Ethics approval and consent to participate: In accordance with the Declaration of Helsinki and French regulations on clinical trials, authorizations were obtained for all French participating centers from the following: Ethics Committee, French Health Products Safety Agency, Advisory Committee on Processing Information Associated with Health Research, and French Data Protection Authority. Patients were enrolled in the cohort before receiving any treatment, and informed consent was obtained prior to enrollment.
Consent for publication: Not applicable.
Author contributions: Laure Corazzin: Data curation; Investigation; Writing – original draft; Writing – review & editing.
Elodie Jeanbert: Conceptualization; Formal analysis; Investigation; Methodology; Writing – original draft; Writing – review & editing.
Olivier Glehen: Data curation; Investigation; Writing – review & editing.
Caroline Gronnier: Investigation; Writing – review & editing.
Laurent Sulpice: Investigation; Writing – review & editing.
Jean-Marc Gornet: Investigation; Writing – review & editing.
Brice Paquette: Investigation; Writing – review & editing.
Jean-Marc Regimbeau: Investigation; Writing – review & editing.
Cécile Brigand: Investigation; Writing – review & editing.
Xavier-Benoît D’Journo: Investigation; Writing – review & editing.
Pierre-Yves Brichon: Investigation; Writing – review & editing.
Johan Gagnaire: Investigation; Writing – review & editing.
Thibault Voron: Investigation; Writing – review & editing.
Muriel Mathonnet: Investigation; Writing – review & editing.
Christophe Penna: Investigation; Writing – review & editing.
Nicolas Regenet: Investigation; Writing – review & editing.
Côme Lepage: Investigation; Writing – review & editing.
Nicolas Carrere: Investigation; Writing – review & editing.
Ugo Marchese: Investigation; Writing – review & editing.
Leonor Benhaim: Investigation; Writing – review & editing.
Jean-Michel Fabre: Investigation; Writing – review & editing.
Frédéric Di Fiore: Investigation; Writing – review & editing.
Frédéric Borie: Investigation; Writing – review & editing.
Pierre Emmanuel Bonnot: Investigation; Writing – review & editing.
Olivier Bouché: Investigation; Writing – review & editing.
David Tougeron: Investigation; Writing – review & editing.
Antoine Adenis: Investigation; Writing – review & editing.
Guillaume Piessen: Investigation; Resources; Software; Writing – review & editing.
Marie Muller: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Visualization; Writing – original draft; Writing – review & editing.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
D.T. reports consultancy, advisory fees, honoraria from Servier, Pierre Fabre, Merck Serono, MSD, BMS, AZ, Roche, Sanofi; research funding from Sandoz, AstraZenenca, Servier, MSD; travel grants from Pierre Fabre, MSD, Servier, Roche. M.Mu. reports consultancy, advisory fees, honoraria from Pierre Fabre, Merck Serono, MSD, Takeda; travel grants from Pierre Fabre, Servier. O.B. reports consultancy, advisory fees, honoraria from Servier, Amgen, Pierre Fabre, Merck Serono, MSD, Takeda, Deciphera; travel grants from Pierre Fabre, Servier, MSD.
Availability of data and materials: Data are available upon reasonable request.
References
- 1. Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 2022; 33(10): 1005–1020. [DOI] [PubMed] [Google Scholar]
- 2. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: an overview. Int J Cancer 2021; 149(4): 778–789. [DOI] [PubMed] [Google Scholar]
- 3. Sundar R, Nakayama I, Markar SR, et al. Gastric cancer. Lancet 2025; 405(10494): 2087–2102. [DOI] [PubMed] [Google Scholar]
- 4. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74(3): 229–263. [DOI] [PubMed] [Google Scholar]
- 5. Allum W, Lordick F, Alsina M, et al. ECCO essential requirements for quality cancer care: oesophageal and gastric cancer. Crit Rev Oncol Hematol 2018; 122: 179–193. [DOI] [PubMed] [Google Scholar]
- 6. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 2021; 398(10294): 27–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023; 29(8): 2133–2141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Zaanan A, Bouché O, De La Fouchardière C, et al. TFOX versus FOLFOX in first-line treatment of patients with advanced HER2-negative gastric or gastro-oesophageal junction adenocarcinoma (PRODIGE 51-FFCD-GASTFOX): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2025; 26(6): 732–744. [DOI] [PubMed] [Google Scholar]
- 9. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355(1): 11–20. [DOI] [PubMed] [Google Scholar]
- 10. Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011; 29(13): 1715–1721. [DOI] [PubMed] [Google Scholar]
- 11. Van Hagen P, Hulshof MCCM, Van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366(22): 2074–2084. [DOI] [PubMed] [Google Scholar]
- 12. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001; 345(10): 725–730. [DOI] [PubMed] [Google Scholar]
- 13. Al-Batran SE, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019; 393(10184): 1948–1957. [DOI] [PubMed] [Google Scholar]
- 14. Hoeppner J, Brunner T, Schmoor C, et al. Perioperative chemotherapy or preoperative chemoradiotherapy in esophageal cancer. N Engl J Med 2025; 392(4): 323–335. [DOI] [PubMed] [Google Scholar]
- 15. Eyck BM, Van Lanschot JJB, Hulshof MCCM, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS trial. J Clin Oncol 2021; 39(18): 1995–2004. [DOI] [PubMed] [Google Scholar]
- 16. Janjigian YY, Al-Batran S-E, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med 2025; 393(3): 217–230. [DOI] [PubMed] [Google Scholar]
- 17. Tabernero J, Al-Batran SE, Wainberg ZAA, et al. LBA81 Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: a randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ann Oncol 2025; 36: S1738–S1739. [Google Scholar]
- 18. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. LBA73 Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): interim results of the global, phase III MATTERHORN study. Ann Oncol 2023; 34: S1315–S1316. [Google Scholar]
- 19. SPACE-FLOT Investigators; Liu DS, Lee MM, Hall K, et al. Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT): international cohort study. Br J Surg 2025; 112(4): znaf056. [DOI] [PubMed] [Google Scholar]
- 20. Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994; 73(11): 2680–2686. [DOI] [PubMed] [Google Scholar]
- 21. FREGAT Working Group; Mariette C, Renaud F, Piessen G, et al. The FREGAT biobank: a clinico-biological database dedicated to esophageal and gastric cancers. BMC Cancer 2018; 18(1): 139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370(9596): 1453–1457. [DOI] [PubMed] [Google Scholar]
- 23. Abboretti F, Mantziari S, Didisheim L, et al. Prognostic value of tumor regression grade (TRG) after oncological gastrectomy for gastric cancer. Langenbecks Arch Surg 2024; 409(1): 199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Chen M, Yu S, Chen C, et al. Development and evaluation of the Newstage system: integrating tumor regression grade and lymph node status for improved prognostication in neoadjuvant treatment of gastric cancer. World J Surg Oncol 2024; 22(1): 16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Weng CM, Zhong Q, Sun YQ, et al. A novel ypN-TRG staging system for gastric cancer patients after neoadjuvant therapy based on the metro-ticket paradigm: a multicenter and large sample retrospective analysis. Gastric Cancer 2025; 28(3): 465–477. [DOI] [PubMed] [Google Scholar]
- 26. Saliba G, Detlefsen S, Carneiro F, et al. Tumor regression grading after neoadjuvant treatment of esophageal and gastroesophageal junction adenocarcinoma: results of an international Delphi consensus survey. Hum Pathol 2021; 108: 60–67. [DOI] [PubMed] [Google Scholar]
- 27. Ikoma N, Estrella JS, Blum Murphy M, et al. Tumor regression grade in gastric cancer after preoperative therapy. J Gastrointest Surg 2021; 25(6): 1380–1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Zheng HL, Zhang LK, Zheng HH, et al. Timing of postoperative chemotherapy and prognosis in neoadjuvant-treated gastric cancer patients: a multicenter real-world cohort study. Ann Med 2025; 57(1): 2500690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Hejna M, Wöhrer S, Schmidinger M, et al. Postoperative chemotherapy for gastric cancer. Oncologist 2006; 11(2): 136–145. [DOI] [PubMed] [Google Scholar]
- 30. Glatz T, Verst R, Kuvendjiska J, et al. Pattern of recurrence and patient survival after perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin and docetaxel (FLOT) for locally advanced esophagogastric adenocarcinoma in patients treated outside clinical trials. J Clin Med 2020; 9(8): 2654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Uçar G, Sekmek S, Karahan İ, et al. The comparison of FLOT and DCF regimens as perioperative treatment for gastric cancer. Oncology 2025; 103(2): 128–133. [DOI] [PubMed] [Google Scholar]
- 32. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol 2006; 24(31): 4991–4997. [DOI] [PubMed] [Google Scholar]
- 33. Heckl SM, Behrens HM, Ebert U, et al. Impact of adjuvant therapy on outcomes of cancer of the stomach and gastroesophageal junction in the real-world. Gastric Cancer 2025; 28(5): 982–992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Sauvanet A, Mariette C, Thomas P, et al. Mortality and morbidity after resection for adenocarcinoma of the gastroesophageal junction: predictive factors. J Am Coll Surg 2005; 201(2): 253–262. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplemental material, sj-docx-1-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Supplemental material, sj-docx-2-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Supplemental material, sj-docx-3-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology
Supplemental material, sj-docx-4-tam-10.1177_17588359261435406 for Impact of postoperative chemotherapy in patients resected for esophagogastric adenocarcinoma with major pathological response after preoperative chemotherapy: a study from the FREGAT database by Laure Corazzin, Elodie Jeanbert, Olivier Glehen, Caroline Gronnier, Laurent Sulpice, Jean-Marc Gornet, Brice Paquette, Jean-Marc Regimbeau, Cécile Brigand, Xavier-Benoît D’Journo, Pierre-Yves Brichon, Johan Gagnaire, Thibault Voron, Muriel Mathonnet, Christophe Penna, Nicolas Regenet, Côme Lepage, Nicolas Carrere, Ugo Marchese, Leonor Benhaim, Jean-Michel Fabre, Frédéric Di Fiore, Frédéric Borie, Pierre Emmanuel Bonnot, Olivier Bouché, David Tougeron, Antoine Adenis, Guillaume Piessen and Marie Muller in Therapeutic Advances in Medical Oncology