Nodal downstaging in gastric cancer in relation to survival when ypN0 is achieved.

93 Background: The AJCC 8th edition introduced ypStage for patients with gastric cancer due to the increasing use of preoperative therapy. ypN0 patients have better survival than ypN+ patients; however, whether patients who had clinically positive nodal disease before preoperative therapy (cN+ ypN0) have similar survival to those who had “natural N0” (cN0 ypN0) disease is unknown. Methods: We reviewed an institutional database to identify patients with gastric adenocarcinoma who underwent potentially curative R0 resection after preoperative chemo- or chemoradiation therapy. Patients were categorized into 3 groups based on nodal status: natural N0 (cN0 ypN0), downstaged N0 (cN+ ypN0), and ypN+. Univariable and multivariable Cox regressions were performed to determine associations with overall survival (OS). Results: We identified 316 patients who met study criteria, including 74 (23%) patients with GEJ tumors; 56% were white and 62% were male. Preoperative chemoradiation therapy was given to 239 (76%). Ninety-four (30%) had natural N0, 93 (29%) had downstaged N0, and 129 (41%) had ypN+ disease. Of all patients, 136 (43%) patients died during a median follow-up of 3.1 y. Median OS was 7.7 y, and 5-year OS was 60.3%. OS did not differ in patients with natural N0 disease (5-y OS, 72%) and those with downstaged N0 disease (5-y OS, 69%) ( p = 0.776), even though the downstaged N0 group had more advanced baseline cT disease than did the natural N0 group ( p < 0.001). On multivariable analysis adjusting for other factors, including ypT category, OS did not differ between natural N0 and downstaged N0 patients (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.54-1.48; p = 0.666), but it was shorter in ypN+ patients (HR, 1.82; 95% CI, 1.15-2.87; p = 0.010). Sensitivity analyses also showed equivalent OS in the natural N0 and downstaged N0 groups within the ypT0-2 group ( p = 0.936) and the ypT3-4 group ( p = 0.608). Conclusions: In patients with gastric cancer who underwent preoperative therapy, we found similar OS in patients with natural N0 and those with downstaged N0 disease. As ypN+ patients had poor OS, achieving ypN0 status is an important hallmark demonstrating the effectiveness of preoperative therapy.

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Tumor regression grade in gastric cancer after preoperative therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.168 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 168-168

Author(s):

Naruhiko Ikoma ◽

Jeannelyn Estrella ◽

Prajnan Das ◽

Bruce D. Minsky ◽

Keith F. Fournier ◽

...

Keyword(s):

Gastric Cancer ◽

Treatment Response ◽

Tumor Regression ◽

Multivariable Analysis ◽

Chemoradiation Therapy ◽

Preoperative Therapy ◽

Tumor Regression Grade ◽

R1 Resection ◽

Viable Cells ◽

Regression Grade

168 Background: The AJCC 8th edition updated ypStage TNM grouping for patients with gastric cancer due to the increasing use of preoperative therapy. We previously reported that nodal status after preoperative therapy (ypN) was most predictive for overall survival (OS). We intended to investigate if tumor regression grade (TRG) of the primary tumor scored by pathologists is helpful to predict survival of gastric cancer patients treated with preoperative therapy. Methods: We reviewed an institutional database to identify patients with clinically non-metastatic gastric adenocarcinoma who underwent gastrectomy after preoperative chemo- or chemoradiation therapy. Pathology reports were reviewed, and TRG was classified into following categories: 0 (complete response), 1 (few clusters of viable tumor cells, £1-2%), 2 (significant response, viable cells £ 50%), 3 (minor or no treatment response, viable cells > 50%). Associations between TRG and clinicopathological factors were examined. Univariable and multivariable Cox regressions were performed to determine associations with OS. Results: We identified 356 patients who met study criteria, including 80 (23%) patients with GEJ tumors; 56% were white and 60% were male. Preoperative chemoradiation therapy was given to 268 (75%). Fifty-six (16%) had TRG 0, 57 (16%) had TRG 1, 128 (36%) had TRG 2, and 115 (32%) had TRG 3. There were no associations between TRG and pretreatment factors. TRG 2 or 3 was associated with advanced ypT and ypN categories (both p < 0.001), ypM1 (p = 0.004), and R1 resection (0.052). Of all patients, median OS was 6.6 y, and 5-year OS was 54.1%. TRG 3 was associated with worse OS than other groups ( p = 0.015), while there was no significant OS difference among TRG 0-2 groups ( p = 0.803) in univariate analyses. On multivariable analysis, TRG was not associated with OS after adjustment for ypN status. Conclusions: In patients with gastric cancer who underwent preoperative therapy, TRG 3 was associated with advanced ypStage and R1 resection. Patients with TRG 3 had worse OS, due to associated advanced ypStage, particularly ypN+ status. Further studies are warranted to identify better definitions of treatment response and to identify the optimal modality for obtaining ypN0 status.

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Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.7136 ◽

2012 ◽

Vol 30 (19) ◽

pp. 2327-2333 ◽

Cited By ~ 444

Author(s):

Stephen R. Smalley ◽

Jacqueline K. Benedetti ◽

Daniel G. Haller ◽

Scott A. Hundahl ◽

Norman C. Estes ◽

...

Keyword(s):

Gastric Cancer ◽

Substantial Reduction ◽

Phase Iii ◽

R0 Resection ◽

Second Malignancies ◽

Adjuvant Radiochemotherapy ◽

Phase Iii Trial ◽

Failure Patterns ◽

Postoperative Radiochemotherapy

Purpose Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. Patients and Methods In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. Results Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. Conclusion Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.

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Predictors of Survival in Patients with Resectable Gastric Cancer Treated with Preoperative Chemoradiation Therapy and Gastrectomy

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2015.04.004 ◽

2015 ◽

Vol 221 (1) ◽

pp. 83-90 ◽

Cited By ~ 23

Author(s):

Brian Badgwell ◽

Mariela Blum ◽

Jeannelyn Estrella ◽

Yi-Ju Chiang ◽

Prajnan Das ◽

...

Keyword(s):

Gastric Cancer ◽

Preoperative Chemoradiation ◽

Chemoradiation Therapy ◽

Preoperative Chemoradiation Therapy ◽

Resectable Gastric Cancer

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Preoperative Chemoradiation Therapy Does Not Increase Risk of Anastomotic Leak in Patients With Gastric Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2017.07.018 ◽

2017 ◽

Vol 99 (3) ◽

pp. 660-666 ◽

Cited By ~ 11

Author(s):

Naruhiko Ikoma ◽

Prajnan Das ◽

Mariela Blum ◽

Jeannelyn S. Estrella ◽

Catherine E. Devine ◽

...

Keyword(s):

Gastric Cancer ◽

Anastomotic Leak ◽

Preoperative Chemoradiation ◽

Chemoradiation Therapy ◽

Preoperative Chemoradiation Therapy ◽

Increase Risk

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Long-term outocomes of preoperative chemoradiation therapy with gemcitabine and accelerated hyperfractionated radiation for respectable pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14004 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14004-14004

Author(s):

S. Nakamori ◽

S. Nakahira ◽

A. Miyamoto ◽

S. Marubashi ◽

H. Nagano ◽

...

Keyword(s):

Pancreatic Cancer ◽

Local Recurrence ◽

Preoperative Chemoradiation ◽

Chemoradiation Therapy ◽

Control Group ◽

R0 Resection ◽

Survival Times ◽

Resectable Pancreatic Cancer ◽

Preoperative Chemoradiation Therapy

14004 Background: Gemcitabine (GEM) is recognized as an effective chemotherapeutic agent for non-curative pancreatic cancer and has an activity for radiosensitizer. Although preoperative chemoradiation therapy (preCRT) with GEM is one of the promising adjuvant therapies for potentially curative pancreatic cancer, the clinical significance of the treatment remains to obscure. Methods: Potentially resectable pancreatic cancer patients were recruited in this study from September 2001 through August 2004. Patients were randomly divided into preCRT group and a control group. Patients in preCRT group received GEM (400 mg/m2 or 800 mg/m2 on day 1 and 7) and concomitant accelerated hyperfractionated irradiation (1.5 Gy ×2/day, 5 days/weeks, total dose 30Gy or 36 Gy). After 3–4 weeks’ rest of the preCRT, patients were re-evaluated for resectability. Patients who underwent R0 resection did not received any postoperative adjuvant treatment until recurrence. Results: There were 23 patients in preCRT group and were 19 patients in control group. After re-evaluation, 4 patients (17%) were considered as unresectable due to the progressed disease. 19 patients (83%) in preCRT group and 19 patients (100%) in control group underwent laparotomy. Sixteen patients (70%) in preCRT group and 17 patients (89%) in control group underwent R0 resection. Median survival times were 17.6 months in preCRT group and 16.7 months in control group, respectively (p=0.65). Among patients underwent R0 resection, one and three-years survival rate were 81.2% and 27.1% in preCRT group, while these were 70.6% and 15.4% in the control group (p=0.26). Local recurrence was observed in 4 (25%) of 16 patients who underwent R0 resection in preCRT group and in 7 (41%) of 17 patients who underwent R0 resection in control group, while recurrence at distant organs (liver, lung, peritoneum, bone) were observed in 8 patients (50%) of preCRT group and 8 patients (47%) in control group. Conclusions: Although the preoperative chemoradiation therapy with GEM and accelerated hyperfractionated radiation for potentially curative pancreatic cancer is likely to be promising against local recurrence after R0 resection, survival benefit of the therapy was unsatisfactory. No significant financial relationships to disclose.

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Conditional survival nomogram after an R0 resection for gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.11 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 11-11

Author(s):

J. L. Dikken ◽

C. J. Van De Velde ◽

M. Verheij ◽

R. Baser ◽

M. Gonen ◽

...

Keyword(s):

Gastric Cancer ◽

Weight Loss ◽

Predictive Accuracy ◽

Performance Status ◽

R0 Resection ◽

Conditional Survival ◽

Disease Free Interval ◽

The Us ◽

One Year

11 Background: The risk of dying of cancer is highest in the first two years after a curative resection for gastric cancer. Therefore, the prognosis of patients who did not recur in the first two years is improved because they survived this critical period, a phenomenon called conditional survival. The US-derived gastric cancer nomogram predicts disease-specific survival (DSS) based on pathological variables. However, a disease-free interval after surgery, which improves the prognosis, is not captured by the nomogram. Therefore, it has only been used directly after surgery and not in the follow-up setting. The purposes of this study were to develop a conditional survival nomogram for 1, 2 and 3-year survivors (step 1) and to test if the introduction of follow-up variables would improve predictive accuracy of the nomogram in the follow-up setting (step 2). Methods: In a combined US-Dutch population of 1642 patients who underwent an R0 resection for gastric cancer and for whom the old nomogram variables were available, a conditional survival nomogram based on the original variables was developed for one (N=1147), two (N=879) and three (N=721) year survivors (step 1). To improve predictive accuracy in the follow-up setting, weight loss, performance status (PS), hemoglobin (HGB), and albumin (ALB) at one year after resection were retrospectively collected and added to the baseline variables in a new nomogram (step 2). Results: The conditional survival nomograms for 1, 2 and 3-year survivors (step 1) showed a high predictive accuracy in the calibration plots. Surviving one, two and three years shows a median improvement of 5-year DSS of 4%, 9% and 14% respectively. The introduction of weight loss, PS, HGB, and ALB at one year after surgery (step 2) did not improve this nomogram, but availability of these variables was limited. Conclusions: A strongly predictive conditional survival nomogram was developed, giving an improved prognosis for 1, 2 and 3-year survivors of gastric cancer. Introduction of variables available at one year after resection did not further improve this nomogram. This might be caused by the limited availability of follow-up data, as well as the strong predictive accuracy of the original variables. No significant financial relationships to disclose.

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The prognostic value of neutrophil–lymphocyte ratio is superior to derived neutrophil–lymphocyte ratio in advanced gastric cancer treated with preoperative chemotherapy and sequential R0 resection: a 5-year follow-up

OncoTargets and Therapy ◽

10.2147/ott.s135641 ◽

2017 ◽

Vol Volume 10 ◽

pp. 2655-2664 ◽

Cited By ~ 10

Author(s):

Hailong Jin ◽

Jianyi Sun ◽

Kankai Zhu ◽

Xiaosun Liu ◽

Qing Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Preoperative Chemotherapy ◽

Prognostic Value ◽

R0 Resection ◽

Lymphocyte Ratio

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Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group’s analysis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02442-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Luigina Graziosi ◽

Elisabetta Marino ◽

Maria Bencivenga ◽

Alessia D’Ignazio ◽

Leonardo Solaini ◽

...

Keyword(s):

Gastric Cancer ◽

Peritoneal Carcinomatosis ◽

Stage Iv ◽

R0 Resection ◽

Extended Lymphadenectomy ◽

Multicentric Study ◽

Factors Affecting ◽

Aggressive Surgical Approach ◽

Retrospective Nature

Abstract Background The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery. Methods It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences. Results Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment. Conclusion The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with “radical oncological intent”, that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.

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n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies

10.2337/figshare.13724110.v1 ◽

2021 ◽

Author(s):

Frank Qian ◽

Andres V Ardisson Korat ◽

Fumiaki Imamura ◽

Matti Marklund ◽

Nathan Tintle ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acid ◽

Prospective Studies ◽

Multivariable Analysis ◽

Sensitivity Analyses ◽

Omega 3 ◽

Individual Participant ◽

Fatty Acid Biomarkers

Objective Prospective associations between omega-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize prospective associations between biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), and T2D risk through an individual participant-level pooled analysis. Research Design and Methods Our analysis incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a pre-specified protocol and cohort-specific associations were pooled using inverse variance-weighted meta-analysis. Results A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per inter-quintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89) and 0.81 (0.75, 0.88), respectively (all P<0.001). ALA was not associated with T2D, 0.97 (0.92, 1.02) per inter-quintile range. Associations were robust across pre-specified subgroups as well as in sensitivity analyses. Conclusions <a></a><a>Higher circulating biomarkers of seafood-derived omega-3 fatty acids, including EPA, DPA, DHA, and their sum were associated with lower risk of T2D in a global consortium of prospective studies. </a>The biomarker of plant-derived ALA was not significantly associated with T2D risk.

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