Background Although the signet ring cell histologic subtype (SRC) is an independent predictor of poor prognosis in advanced gastric adenocarcinomas (GA), its prognostic value in early GA remains ...highly controversial. The aim of the study was to evaluate the prognostic impact of SRC in mucosal and submucosal GAs. Methods Based on a multicenter cohort of 3,010 patients operated on for GA between January 1997 and January 2010, patients with pTis or pT1 tumors were extracted and analyzed comparatively between the SRC and non-SRC groups. The primary objective was to compare the 5-year survival rate between groups. Results Among 421 patients with a pTis or pT1 tumor, 104 (25%) were SRC and 317 (75%) were non-SRC. Demographic variables were comparable between groups, except median age, which was less in the SRC group (59.6 vs 68.8 years; P < .001). Submucosal involvement was more frequent in the SRC group (94% vs 85%; P = .043), whereas lymph node involvement and number of invaded nodes were comparable between the 2 groups. When comparing SRC and non-SRC, recurrence rates (6% vs 9%; P = .223) and sites of recurrence were similar. The 5-year overall survival benefit in SRC patients (85% vs 76%, respectively; P = .035), was not evident when considering exclusively disease-specific survival or in multivariable analysis. Conclusion Contrary to more advanced GA, SRC morphologic subtype is not a negative prognostic factor in early GA. Better survival identified in some reports may be related to the younger age in SRC patients.
Background
Surgical complications and particularly infections after digestive cancer surgery remain a major health and economic problem and its burden in France is not well documented.
Aims
The aim ...of this study was to analyse recent data regarding surgical complications in patients undergoing major digestive cancer surgery, and to estimate its burden for the French society.
Methods and Results
Using the 2018 French hospital discharge database and 2017 National CostStudy we studied hospital stays for surgical resection in patients withdigestive cancer. The population was divided into three groups based onpostoperative outcomes: no complications (NC), related infectious complications (RIC) and other complications. The main analysis compared the length and cost per stay between RIC and NC. Forty‐Four thousand one hundred and twenty‐three stays following a digestive cancer resection were identified. Lower gastro‐intestinal cancers were the most prevalent representing 74.8% of stays, the rate of malnutrition was 32.8% and 15.8% of patients presented RIC. Mean (SD) length of stay varied from 11,7 (9.0) days for NC to 25,5 days (19.5) for RIC (p < 0.01). The mean cost per patients' stay (SD) varied from €10 641 (€ 5897) for the NC to €18 720 (€7905) for RIC (p < .01).
Conclusion
The risk of RIC after digestive cancer resection remains high (>15%) and was associated with significantly longer length of stay and higher cost per stay. Although important prevention plans have been implemented in recent years, care strategies are still needed to alleviate the burden on patients and the healthcare system.
Background: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the ...clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. Methods: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. Results: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. Conclusions: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.
Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery ...based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. Methods: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. Results: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. Conclusion: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.
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.
•Adding Cetuximab to chemoradiotherapy in advanced esophageal cancer could improve pCR.•With a 5 weeks radiotherapy, we determined the optimal doses for 5FU, Cisplatin, Cetuximab based ...chemotherapy.•This regimen failed to reach a pCR > 20 %, and showed to be toxic.
Radiotherapy combined with fluorouracil (5FU) and cisplatin for locally advanced esophageal cancer is associated with a 20–25% pathologic complete response (pCR) rate. Cetuximab increases the efficacy of radiotherapy in patients with head and neck carcinomas. The aim of this phase I/II trial was to determine the optimal doses and the pCR rate with chemoradiotherapy (C-RT) plus cetuximab.
A 45-Gy radiotherapy regimen was delivered over 5 weeks. The phase I study determined the dose-limiting toxicity and the maximum tolerated dose of 5FU-cisplatin plus cetuximab. The phase II trial aimed to exhibit a pCR rate > 20 % (25 % expected), requiring 33 patients (6 from phase I part plus 27 in phase II part). pCR was defined as ypT0Nx.
The phase I study established the following recommended doses: weekly cetuximab (400 mg/m2 one week before, and 250 mg/m2 during radiotherapy); 5FU (500 mg/m2/day, d1-d4) plus cisplatin (40 mg/m2, d1) during week 1 and 5. In the phase II part, 32 patients received C-RT before surgery, 31 patients underwent surgery, and resection was achieved in 27 patients. A pCR was achieved in five patients (18.5 %) out of 27. After a median follow-up of 19 months, the median progression-free survival was 13.7 months, and the median overall survival was not reached.
Adding cetuximab to preoperative C-RT was toxic and did not achieve a pCR > 20 % as required. The recommended doses, determined during the phase I part, could explain these disappointing results due to a reduction in chemotherapy dose-intensity.
This trial was registered with EudraCT number 2006-004770-27.
Background
Whereas palliative chemotherapy offers a median survival of approximately 10 months in advanced gastric and junctional adenocarcinoma (AGJA), the survival impact of primary tumor resection ...is controversial. Our purpose was to identify which AGJA patients benefit from palliative resection.
Methods
In 3,202 AGJA patients scheduled for surgery in 21 French centers between 1997 and 2010, prognostic factors were identified in palliative group and the impact of each combination of these factors on survival was studied.
Results
Surgery was defined as palliative due to solid organ metastasis (5.6 %), localized (4.6 %) or diffuse (2.3 %) peritoneal carcinomatosis (PC), or incomplete tumoral resection (12.8 %). Median survival of AGJA patients resected with a palliative intent (
n
= 677) was longer than in nonresected patients (
n
= 532; 11.9 vs. 8.5 months,
P
< 0.001). Multivariable analyses identified ASA score III-IV (
P
< 0.001) as a predictor of postoperative mortality and solid organ metastasis (
P
= 0.009), localized PC (
P
= 0.004), diffuse PC (
P
= 0.046), and signet ring cell histology (SRC;
P
= 0.02) as predictors of survival. Only ASA I–II patients with incomplete resection without metastasis or PC, one site solid organ metastasis without PC, or localized PC without SRC had a survival benefit after palliative surgery with median survivals from 12.0 to 18.3 months. Nonresected ASA I–II patients with same risk factors had median survivals from 3.5 to 8.8 months (
P
< 0.05 for each).
Conclusions
In AGJA, patient and tumor-related factors should be used to select candidates for palliative surgery in association with chemotherapy.
Surgery remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Therefore, a predictive score for resectability on diagnosis is needed. A total of 814 patients were included ...between 2014 and 2017 from 15 centers included in the BACAP (the national Anatomo-Clinical Database on Pancreatic Adenocarcinoma) prospective cohort. Three groups were defined: resectable (Res), locally advanced (LA), and metastatic (Met). Variables were analyzed and a predictive score was devised. Of the 814 patients included, 703 could be evaluated: 164 Res, 266 LA, and 273 Met. The median ages of the patients were 69, 71, and 69, respectively. The median survival times were 21, 15, and nine months, respectively. Six criteria were significantly associated with a lower probability of resectability in multivariate analysis: venous/arterial thrombosis (
= 0.017), performance status 1 (
= 0.032) or ≥ 2 (
= 0.010), pain (
= 0.003), weight loss ≥ 8% (
= 0.019), topography of the tumor (body/tail) (
= 0.005), and maximal tumor size 20-33 mm (
< 0.013) or >33 mm (
< 0.001). The BACAP score was devised using these criteria (http://jdlp.fr/resectability/) with an accuracy of 81.17% and an area under the receive operating characteristic (ROC) curve of 0.82 (95% confidence interval (CI): 0.78; 0.86). The presence of pejorative criteria or a BACAP score < 50% indicates that further investigations and even neoadjuvant treatment might be warranted. Trial registration: NCT02818829.
While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to ...evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin.
Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively).
From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 95% CI: 16.4-39.4 and 40.3 months 95% CI: 27.5-NA, respectively.
Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).
Background
Perioperative oncologic treatments provide a survival benefit for junctional and gastric adenocarcinoma (JGA) and esophageal cancer (EC). Whether neoadjuvant therapy toxicity (NTT) ...correlates with increased perioperative risk remains unclear. We aimed to evaluate the impact of grade III/IV NTT on postoperative and oncologic outcomes in resected upper gastrointestinal malignancies.
Methods
A multicenter retrospective analysis was performed on consecutive patients who benefited from neoadjuvant chemo(radio)therapy followed by surgery between 1997 and 2010 for JGA (first cohort,
n
= 653) and for EC (second cohort,
n
= 640). Data between patients who experienced NTT were compared to those who did not.
Results
NTT was associated with higher postoperative mortality after resection of JGA (
P
= 0.001) and after esophagectomy (
P
< 0.001), more non-R0 resections (JGA
P
= 0.019, EC
P
= 0.024), a decreased administration of adjuvant treatment among the JGA cohort (
P
= 0.012), and higher surgical morbidity (JGA
P
= 0.005, EC
P
= 0.020). Median survival was reduced in patients who experienced NTT in both cohorts (JGA
P
= 0.018, EC
P
= 0.037). After adjustment on confounding variables, NTT was independently associated with postoperative mortality in both cohorts (
P
≤ 0.007).
Conclusions
NTT is a predictor of postoperative mortality, correlates with higher postoperative morbidity, and negatively affects oncologic outcomes for upper gastrointestinal carcinomas.
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