Association of histologic grade and subtypes of gastric cancer (GC) with chemoradiation response.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 97-97
Author(s):  
Nikolaos Charalampakis ◽  
Graciela M. Nogueras-Gonzalez ◽  
Xuemei Wang ◽  
Elena Elimova ◽  
Hironori Shiozaki ◽  
...  

97 Background: Patients with localized gastric cancer (LGC), when treated with preoperative therapy, tend to have heterogeneous and unpredictable outcomes. Currently, no clinical variables or biomarkers can predict response. Methods: We analyzed 107 LGC patients who were treated with chemoradiation followed by surgery (trimodality therapy; TMT). Tumors were grouped into poorly (G3) or moderately (G2) differentiated and signet ring cell (SRC) or non-SRC histology. Association was made with pathologic complete response (pathCR) or < pathCR. Descriptive statistics and survival analyses were utilized. Results: The majority of the patients were male (60%), had clinical stage III cancer (51%), and received chemotherapy before chemoradiation (94%). All had adenocarcinoma and most had G3 (78%) and SRC histology (58%). PathCR was noted in 18% of patients with G3 and 33% of patients with G2 (p=0.125). Overall survival (OS) was significantly shorter for G3 patients compared to G2 patients (p=0.045). Patients with SRC histology had a lower rate of pathCR than those with non-SRC (8% vs 40%, p<0.001). Patients with SRC histology had a trend towards shorter OS (p=0.063). Surgical pathologic stage was independently associated with OS and recurrence-free survival (RFS) (p<0.001). Conclusions: Our data suggest that histologic grade/ subtypes are associated with response to preoperative chemoradiation. Independent validation and addition of biomarkers could allow individualization of therapy of LGC patients. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI). Dr. Nikolaos Charalampakis has been awarded a scholarship from the Hellenic Society of Medical Oncology.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 321-321
Author(s):  
Michael K. Turgeon ◽  
Adriana C. Gamboa ◽  
Manali Rupji ◽  
Rachel M. Lee ◽  
Jeffrey M. Switchenko ◽  
...  

321 Background: Upfront surgery is standard of care for stage I gastric cancer. Despite this, many clinicians administer preoperative therapy for clinical stage I disease with signet ring cell histology, given its aggressive biology. We aimed to assess the validity of this practice. Methods: The National Cancer Database (2004-2015) was reviewed for pts with non-metastatic signet ring cell gastric cancer who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical stage and pathologic stage. Primary outcome was overall survival (OS). Results: Of 3000 pts, median age was 61 (IQR: 51-70). 34% were clinical stage I (n = 1018) of which 53% received surgery alone (n = 542), 5% perioperative chemotherapy (n = 47), 12% neoadjuvant therapy (n = 125), and 30% adjuvant therapy (n = 304). Median follow-up was 26 mos. For clinical stage I disease, surgery alone was associated with improved median OS (108 mos) when compared to perioperative chemotherapy (80 mos), neoadjuvant therapy (41 mos), or adjuvant therapy (73 mos, all p < 0.001). For pathologic stage I, surgery alone had equivalent survival to perioperative and adjuvant therapy (5-yr OS: 81 vs 82 vs 79%, p = 0.22). Concordance between clinical and pathologic stage I was 56%, specifically, 41% of clinical stage I pts were upstaged to pathologic stage II (44%) and stage III (56%). Adjuvant therapy for these pts was associated with improved median OS compared to pretreatment (perioperative chemotherapy / neoadjuvant therapy) for those upstaged to pathologic stage II (122 vs 37mos, p < 0.001) or stage III (40 vs 18mos, p < 0.001) disease. Conclusions: Our stage-stratified study demonstrates improved survival with upfront surgery for clinical stage I signet ring cell gastric cancer. Despite 41% of clinical stage I pts being upstaged to stage II or III on final pathology, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared to those treated preoperatively. Surgery alone also affords similar survival for pathologic stage I disease compared to multimodal therapy. This study challenges the intrinsic bias to over-treat stage I signet ring cell gastric cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7561-7561 ◽  
Author(s):  
L. M. Krug ◽  
H. Pass ◽  
V. W. Rusch ◽  
H. L. Kindler ◽  
D. Sugarbaker ◽  
...  

7561 Background: The optimal management for fit patients with early stage MPM remains controversial. One approach involves neoadjuvant chemotherapy followed by EPP and hemithoracic RT and prior trials using gemcitabine and cisplatin have been reported (Weder JCO 2004, Flores JTO 2006). We administered PC, followed by EPP and RT to further assess feasibility and survival of trimodality therapy in a larger, multicenter study. Methods: Eligibility criteria: Stage T1–3 N0–2, no prior surgical resection, adequate organ function (including predicted post-op FEV1 >35%) and PS 0–1. Pts received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 with vitamin supplementation for 4 cycles. Pts without disease progression underwent EPP followed by RT (54 Gy). The primary endpoint was pathologic complete response (pCR) rate. Enrollment was completed in March, 2006. Results: 77 patients were enrolled and 72 are evaluable. Median age 63.5 (range 34–78), M:F = 51:21, Clinical stage I:II:III:IV = 5:31:33:1, epithelial:nonepithelial = 58:15, ECOG PS 0:1:2 = 28:42:2. 83% of patients completed all four cycles of PC. Grade 3/4 events related to chemotherapy included: neutropenia (4%), febrile neutropenia (3%), nausea (1%), vomiting (3%), pneumonia (6%), pulmonary embolism (1%), and chest pain (3%). Of 73 pts assessed for radiologic response, 3 CRs, 21 PRs, 36 SDs, 3 PDs, and 10 were unevaluable; (RR= 33% [95% CI, 0.22, 0.45]). Of 54 pts who underwent surgery, EPP completion rate was 87% (47/54); that is 47/77 (61%) by ITT. Pathologic stage I:II:III:IV:NE = 4:12:24:3:11. One pCR was confirmed. 35/39 completed RT. Preliminary TTP =13.1 mo (95% CI=9.6, 15.9; 48% censored) and median survival=16.6 mo (95% CI=13.9, 19.3; 55% censored;1-yr survival = 68%). Conclusions: This multicenter trial testing trimodality therapy in MPM showed that it is feasible with a high rate of chemotherapy delivery. One pCR was observed. Preliminary survival is below that reported by single institutions for patients undergoing EPP but with a high censorship rate at this early time point. Further analyses are necessary to identify a cohort of patients most likely to benefit. This study was sponsored by Eli Lilly & Company. No significant financial relationships to disclose.


Author(s):  
Maitham A. Moslim ◽  
Michael J. Minarich ◽  
Mengying Deng ◽  
Elizabeth Handorf ◽  
Stephanie H. Greco ◽  
...  

2021 ◽  
pp. 165-172
Author(s):  
Héctor Hugo Buerba-Vieregge ◽  
Ricardo Fernández-Ferreira ◽  
Pamela Denisse Soberanis-Piña ◽  
Ildefonso Roberto De la Peña-López ◽  
Lilian Mónica Navarro-García ◽  
...  

Breast metastasis from gastric signet ring cell carcinoma is extremely rare in clinical practice. The estimated incidence is 0.5–1.3%. There are few cases reported in the literature (approx. less than 60) of breast metastasis from gastric signet ring cell carcinoma, and due to the rare association between gastric cancer and its extension to the breast, it is difficult to establish the diagnosis. Clinical history, histological findings, and immunohistochemical markers are helpful in distinguishing primary breast cancer from breast metastasis of gastric cancer. The treatment for breast metastasis from gastric carcinoma remains controversial. The prognosis of breast metastasis from gastric carcinoma is generally poor. We report a case of breast metastasis of gastric signet ring cell carcinoma in a 38-year-old woman. She started chemotherapy with ramucirumab, paclitaxel, and irinotecan. Three months later, a combined 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography showed a complete response. This is the first reported case of breast metastasis from gastric signet ring cell carcinoma with a complete response.


2020 ◽  
Vol 28 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Michael K. Turgeon ◽  
Adriana C. Gamboa ◽  
Manali Rupji ◽  
Rachel M. Lee ◽  
Jeffrey M. Switchenko ◽  
...  

2005 ◽  
Vol 23 (33) ◽  
pp. 8331-8339 ◽  
Author(s):  
Roman Rouzier ◽  
Lajos Pusztai ◽  
Suzette Delaloge ◽  
Ana M. Gonzalez-Angulo ◽  
Fabrice Andre ◽  
...  

Purpose To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis–free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram. Patients and Methods Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model. Results The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of ≥ 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02). Conclusion Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.


2021 ◽  
Vol 20 ◽  
pp. 153303382110195
Author(s):  
Sang-Ho Jeong ◽  
Miyeong Park ◽  
Sun Yi Park ◽  
Jiho Park ◽  
Tae-Han Kim ◽  
...  

Introduction: There have been few studies about gene differences between patients with diffuse-type gastric cancer and those with intestinal-type gastric cancer. The aim of this study was to compare the transcriptomes of signet ring cell gastric cancer (worst prognosis in diffuse-type) and well-differentiated gastric cancer (best prognosis in intestinal-type); NUDC was identified, and its prognostic role was studied. Materials and Methods: We performed next-generation sequencing with 5 well-differentiated gastric cancers and 3 of signet ring cell gastric cancer surgical samples. We performed gene enrichment and functional annotation analysis using the Database for Annotation, Visualization and Integrated Discovery bioinformatics resources. Immunohistochemistry was used to validate NUDC expression. Results: Overall, 900 genes showed significantly higher expression, 644 genes showed lower expression in signet ring cell gastric cancer than in well-differentiated gastric cancers, and there was a large difference in adhesion, vascular development, and cell-to-cell junction components between the 2 subtypes. We performed variant analysis and found 52 variants and 30 cancer driver genes, including NUDC. We analyzed NUDC expression in gastric cancer tissue and its relationship with prognosis. Cox proportional hazard analysis identified T stage, N stage, and NUDC expression as independent risk factors for survival ( P < 0.05). The overall survival of the NUDC-positive group was significantly higher (53.2 ± 0.92 months) than that of the NUDC-negative group (44.6 ± 3.7 months) ( P = 0.001) in Kaplan-Meier survival analysis. Conclusion: We found 30 cancer driver gene candidates and found that the NUDC-positive group showed significantly better survival than the NUDC-negative group via variant analysis.


2021 ◽  
Author(s):  
Donglang Jiang ◽  
Xing Chen ◽  
Zhiwen You ◽  
Hao Wang ◽  
Xiaoyun Zhang ◽  
...  

Abstract Introduction Early and precise diagnosis and staging of gastric cancer are important for its treatment and management. However, the low sensitivity of 18F-fluorodeoxyglucose (18F-FDG) for gastric cancer diagnosis limits its application. Currently, the tracer 68Ga-FAPI, which targets fibroblast activation protein (FAP), is widely used to diagnose various cancers. However, the diagnostic value of 68Ga-FAPI in gastric cancer is still unclear. In this study, we aimed to investigate the potential advantage of 68Ga-FAPI-04 over 18F-FDG in the evaluation of gastric cancer.Methods: Thirty-eight patients with gastric cancer (31 with adenocarcinoma and 7 with signet ring cell carcinoma) were recruited for this study. All of the participants underwent 68Ga-FAPI-04 and 18F-FDG imaging by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance (MR). The results were interpreted by two experienced nuclear medicine physicians, and the maximum standardized uptake value (SUVmax) was calculated.Results: For the detection of primary gastric cancer, the sensitivities of 68Ga-FAPI-04 PET and 18F-FDG PET were 100% (38/38) and 81.6% (31/38), respectively. Four cases of adenocarcinoma and three cases of signet ring cell carcinoma were missed by 18F-FDG PET. The SUVmax of 68Ga-FAPI-04 in tumors greater than 4 cm (11.0 ± 4.5) was higher than tumors less than 4 cm (4.5 ± 3.2) (P = 0.0015). The SUVmax of 68Ga-FAPI-04 was higher in T2-4 tumors (9.7 ± 4.4) than in T1 tumors (3.1 ± 1.5) (P = 0.0002). For the detection of metastatic lesions, the sensitivities of 68Ga-FAPI-04 PET and 18F-FDG PET in 10 patients with regional lymph node metastasis and distant metastasis were 6/10 and 5/10, respectively.Conclusion: Compared to 18F-FDG PET, 68Ga-FAPI-04 PET had superior potential in detecting primary gastric cancers and metastatic lymph nodes, 68Ga-FAPI-04 PET also had a better performance on small gastric cancer detection. 68Ga-FAPI-04 PET could provide better performance for gastric cancer diagnosis and staging.


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