Curative Intent For Gastric Cancer Research Articles

OGC P30 Prophylactic HIPEC and Intro-Operative Radiotherapy (IORT) in the Management of Gastric Cancer: An international retrospective case-control study

Abstract Background The combination of surgery and peri-operative chemotherapy is a well-established cornerstone of treatment with curative intent for gastric cancer in the UK. However, this approach has not necessarily been adopted globally. Hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiation therapy (IORT) may improve survival amongst patients with advanced gastric cancer, however the evidence base for its use is limited and its efficacy remains unclear. The present study investigated the effectiveness of prophylactic HIPEC and IORT compared to peri-operative chemotherapy and gastrectomy in patients with gastric cancer. Methods A retrospective study including patients with gastric adenocarcinoma (stages 1-3) between 2014 and 2020 was undertaken. All patients received peri-operative chemotherapy and radical gastrectomy in an academic surgical centre in the Kingdom of Saudi Arabia or a regional tertiary oesophago-gastric centre in the North-West of England. Two groups were formed – one (study group – KSA; HIPEC-IORT) which also received combined prophylactic HIPEC and IORT and one which did not (control – UK; CS). Three parameters were utilized as control variables (age, gender, tumour stage and location). 2:1 matching between the control and study group (86 vs 43 patients) was performed. Results Mean age was 60 (SD = 14.5; 81.5% male). R0 rates were 74.5% in the HIPEC-IORT group vs 82.5% in the CS group. LVI and PNI rates were higher in the HIPEC-IORT group (55.8% vs 32.6%)(55.8% vs 32.6%) as were rates of diffuse-type morphology (39.5% vs 17.5%). Pathological stage distribution in the study group was different (37.2% II and 62.8% III) vs (31.4% I, 34.9% II, 33.7% III). Cox regression analysis which controlled for age, gender, and cancer stage, found no difference in survival between HIPEC-IORT and CS groups (p=0.219). Conclusions The findings of the present study suggest that the combination of prophylactic HIPEC and IORT following radical gastrectomy cancer does not significantly improve survival. Further exploration which compares the short-term outcomes of both approaches is required. These results should be interpreted with caution as the groups showed morphologically different tumour-types. A larger prospective study which controls for more variables may be warranted.

Surgical and oncological outcomes of D1 versus D2 gastrectomy among elderly patients treated for gastric cancer.

Gastrectomy with D2 lymphadenectomy is considered standard treatment in gastric cancer (GC). Among Western patients, morbidity and mortality seem to increase in D2 relative to D1 lymphadenectomy. As elderly patients with co-morbidities are more prone to possible complications, it is unclear whether they benefit from D2 lymphadenectomy. This study aims to compare the short- and long-term results of D1 and D2 lymphadenectomy in elderly patients undergoing gastrectomy for GC. All elderly (⩾75 years) patients undergoing gastrectomy with curative intent for GC during 2000-2015 were included and grouped according to the level of lymph node dissection into the D1 or D2 group. Short-term surgical outcome included the Comprehensive Complication Index (CCI) and 30-day mortality. Long-term outcomes comprised overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Cox regression was used in multivariable analyses. In total, 99 elderly patients were included in the study (51 in D1 group, 48 in D2 group). The median follow-up was 32.5 months. Patients in the D1 group were older and had a higher American Society of Anesthesiologist (ASA) score. Both groups had similar burden of postoperative complications (CCI 20.9 versus 22.6, p = 0.26, respectively) and 90-day mortality (2% for both groups). The OS, DSS, and DFS were similar between groups. Multivariable analysis adjusted for potential confounders detected no difference in the survival between the D1 and D2 groups. Gastrectomy with D2 lymphadenectomy can be performed with low postoperative morbidity and mortality suggesting its use also in the elderly. Long-term outcomes seem similar but need further studies.

Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer.

A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.

ERAS pathway for gastric cancer surgery: adherence, outcomes and prognostic factors for compliance in a Western centre.

Adherence to an ERAS program guarantees an evidence-based approach for patient care, but the compliance to ERAS in patients undergoing surgery for gastric cancer in Western countries has not been clearly investigated. Our Institution has implemented an ERAS pathway (EP) for gastric surgery, composed of 24 items, since December 2016. We retrospectively analyzed the data of all consecutive patients undergoing surgery with curative intent for gastric cancer between January 2017 and December 2019 at our Institution, and were eligible for our EP. The primary endpoint was patients' compliance to the EP. Secondary endpoints were patients' adherence to each ERAS item and detection of variables associated with compliance failure. Seventy-three patients were included. Among these, 75.3% completed the EP, with a median number of items accomplished per patient of 21. Items with critical adherence were restrictive intraoperative fluid infusion (37%), avoidance of abdominal drain (14%), first clear liquid intake (67%), first solid food intake (48%). At univariate analysis age > 75 years, ASA > 2 and total gastrectomy were associated with failure to complete the EP. At multivariate analysis, ASA Score > 2 was the only preoperative factor associated with EP failure. Application of an ERAS program for malignant gastric surgery seems to be feasible with an acceptable completion rate in a tertiary referral Western centre. Preoperative factors, such as old age, advanced stage at diagnosis and neoadjuvant chemotherapy should not be considered as exclusion criteria for ERAS.

Modification of the TNM Staging System for Stage II/III Gastric Cancer Based on a Prognostic Single Patient Classifier Algorithm.

PurposeThe modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility.Materials and MethodsWe previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical.ResultsAmong the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P<0.001) and 2.54 (95% CI, 1.84–3.50; P<0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P<0.001).ConclusionsThe pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

Actual 5-Year Nutritional Outcomes of Patients with Gastric Cancer.

PurposeIn this study, we aimed to evaluate the rarely reported long-term nutritional results of patients with gastric cancer after curative gastrectomy.Materials and MethodsWe retrospectively reviewed the prospectively collected medical records of 658 patients who underwent radical gastrectomy with curative intent for gastric cancer from January 2008 to December 2009 and had no recurrences. All patients were followed for 5 years. Nutritional statuses were assessed using measurements of body weight, serum hemoglobin, total lymphocyte count (TLC), protein, albumin, cholesterol, and nutritional risk index (NRI).ResultsPatients who underwent total gastrectomy had lower body weights, hemoglobin, protein, albumin, and cholesterol levels. TLC and NRI valued after the first postoperative year (P<0.05), and lower hemoglobin and NRI valued during the fifth postoperative year than patients who underwent distal gastrectomy (P<0.05). Patients who received adjuvant chemotherapy after gastrectomy had lower hemoglobin, protein, albumin, and cholesterol levels. TLC and NRI valued during the first postoperative year, than those who underwent gastrectomy only (P<0.05). Regarding post-distal gastrectomy reconstruction, those who underwent Roux-en-Y had lower cholesterol levels than did those who underwent Billroth-I and Billroth-II reconstruction at the first and fifth years after gastrectomy, respectively (P<0.05).ConclusionsPatients undergoing total or distal gastrectomy with Roux-en-Y anastomosis or adjuvant chemotherapy after surgery should be monitored carefully for malnutrition during the first postoperative year, and patients undergoing total gastrectomy should be monitored for malnutrition and anemia for 5 years.

Surgical management of gastric cancer: Single center experience from a developing country

Background:Geographical distributional of gastric cancer (GC), differences in stage at the time of presentation and varying surgical expertise have resulted in different management strategies around the world. The aim of this study is to determine postoperative morbidity/mortality and overall survival in patients with GC treated at a cancer hospital in Pakistan.Patients and Methods:A retrospective review of patients who underwent surgical resection with curative intent for GC from June 2006 to July 2012 was performed. Primary end point was overall survival after a minimum follow-up of 15 months. For categorical data, frequencies were calculated, and means were measured for continuous variables. Chi-square test was used to compare categorical data and Kaplan–Meir survival analysis was performed to estimate 5 years survival outcome using SPSS.Results:Majority of the patients were males with median age of 51 years. Perioperative chemotherapy was offered to 75 patients while upfront surgery was performed in 23 patients. In perioperative chemotherapy group 51 patients and 22 in the upfront surgery group ended up having curative resection. The 5 years survival (n = 98) was found to be of 37%. The 5 years survival of patients in perioperative chemotherapy group (n = 75) was 44% while those who had a curative resection (n = 73) had survival of 46%.Conclusion:Gastric adenocarcinoma is an aggressive disease. Perioperative chemotherapy works well in Pakistani population as the results at our institution are comparable with international data.

Peri-operative blood transfusion in gastric cancer surgery: prognostic or confounding factor?

Background and PurposeThe relationship between peri-operative blood transfusions (PBTs) and poor prognosis in gastric cancer (GC) patients is still debated. The aim of this study is to examine the real prognostic impact of PBTs in comparison to well-known prognostic factors. MethodsWe retrospectively analyzed a series of 224 patients who underwent surgery with curative intent for GC from January 1995 to December 2011. Among 224 patients, 46 (20%) required PBTs. ResultsThe overall 5-year survival was 77% in non-transfused patients and 65% in patients who received PBTs (p = 0.03). PBTs did not further stratify any recognized prognostic category (such as pT or pN according to the 7th edition of the TNM staging system). Multivariate analysis including all known prognostic variables (both cancer- and non-cancer-related) did not select PBTs as an independent prognostic factor. Only preoperative hemoglobin and albumin level, pT and operative time were significantly associated with the requirement for PBTs. ConclusionsThe study showed a worse prognosis for transfused patients, but PBTs seem a confounding factor more than a prognostic indicator, as they are obviously affected by other variables.

Enforcing centralization for gastric cancer in Denmark

Background Population-based data on the early postoperative outcome after surgery for gastric cancer are very sparse. We examined the development in the quality of surgery and early postoperative outcomes in Denmark following centralization of gastric cancer surgery and implementation of national clinical guidelines. Methods All patients in Denmark who underwent resection with curative intent for gastric cancer between 1st July 2003 and 31st December 2008 in one of five university hospitals were registered in a national database. Data on surgical quality and mortality were obtained from the database and compared with the results from the period before centralization (1999–2003). Results A total of 416 patients underwent resection in the study period. The risk of anastomotic leakages for the whole period was 5.0% (95%CI; 3.2–7.7) compared to 6.1% (95%CI; 4.3–8.6) before centralization, whereas the 30-days hospital mortality was 2.4% (95%CI; 1.2–4.4) compared to 8.2% (95%CI; 6.0–10.4) before centralization. In addition, the percentage of patients with at least 15 lymph nodes removed increased during the study period from 19 in 2003 to 76 in 2008. Conclusions Centralization of gastric cancer surgery in Denmark and implementation of national clinical guidelines monitored by a national database was associated with improvements in surgical quality and substantially lower in-hospital mortality.