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Treatment of resectable gastric cancer.

ABSTRACT: Stomach cancer is one of the most common cancers worldwide, despite its declining overall incidence. Although there are differences in incidence, etiology and pathological factors, most studies do not separately analyze cardia and noncardia gastric cancer. Surgery is the only potentially curative treatment for advanced, resectable gastric cancer, but locoregional relapse rate is high with a consequently poor prognosis. To improve survival, several preoperative and postoperative treatment strategies have been investigated. Whereas perioperative chemotherapy and postoperative chemoradiation (CRT) are considered standard therapy in the Western world, in Asia postoperative monochemotherapy with S-1 is often used. Several other therapeutic options, although generally not accepted as standard treatment, are postoperative combination chemotherapy, hyperthermic intraperitoneal chemotherapy and preoperative radiotherapy and CRT. Postoperative combination chemotherapy does show a statistically significant but clinically equivocal survival advantage in several meta-analyses. Hyperthermic intraperitoneal chemotherapy is mainly performed in Asia and is associated with a higher postoperative complication rate. Based on the currently available data, the use of postoperative radiotherapy alone and the use of intraoperative radiotherapy should not be advised in the treatment of resectable gastric cancer. Western randomized trials on gastric cancer are often hampered by slow or incomplete accrual. Reduction of toxicity for preoperative and especially postoperative treatment is essential for the ongoing improvement of gastric cancer care.

SUBMITTER: Dikken JL

PROVIDER: S-EPMC3263979 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Treatment of resectable gastric cancer.

Dikken Johan L JL van de Velde Cornelis J H CJ Coit Daniel G DG Shah Manish A MA Verheij Marcel M Cats Annemieke A

Therapeutic advances in gastroenterology 20120101 1

Stomach cancer is one of the most common cancers worldwide, despite its declining overall incidence. Although there are differences in incidence, etiology and pathological factors, most studies do not separately analyze cardia and noncardia gastric cancer. Surgery is the only potentially curative treatment for advanced, resectable gastric cancer, but locoregional relapse rate is high with a consequently poor prognosis. To improve survival, several preoperative and postoperative treatment strateg ...[more]

PMID: 22282708

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Project description:ImportanceTreatment of resectable gastric cancer (RGC) uses a multimodal approach, including surgical treatment and chemotherapy with or without radiation therapy, and the optimal treatment strategy and timing of each of these modalities is unknown.ObjectiveTo investigate the association of various neoadjuvant and adjuvant treatment modalities with pathologic complete response (pCR), surgical margin status (SMS), and overall survival (OS) in RGC.Design, setting, and participantsFor this comparative effectiveness study, the National Cancer Database was interrogated to identify patients with RGC diagnosed from 2004 to 2015. Patients with gastric adenocarcinoma that was cT2-T4b, any N, and M0 and who underwent definitive surgical treatment were included.Main outcomes and measuresThe association of 9 treatment groups (ie, neoadjuvant chemoradiation only [nCRT], neoadjuvant chemotherapy only, adjuvant chemotherapy only [aCT], adjuvant chemoradiation only [aCRT], neoadjuvant chemotherapy and adjuvant radiation, chemotherapy with timing unknown [CTTU], chemoradiation therapy with timing unknown, radiation therapy with timing unknown (RTTU), and no perioperative therapy [NT]) with 3 end points (ie, pCR, SMS, and OS) was analyzed. The analysis was done using logistic regression and Cox proportional hazards models with adjustment for baseline characteristics. Data were analyzed from September 2019 through February 2020.ResultsAmong 183 204 patients with RGC who were screened, 3064 patients were included in the analysis (median [IQR] age, 68 [57-77] years; 1764 [57.6%] men). There were 1584 tumors (51.7%) located in the antrum and 1539 stage 2 tumors (50.2%). On multivariable analyses among 1939 patients (owing to 137 patients with missing data for pCR and the exclusion of 988 patients with aCT and aCRT from pCR analysis), nCRT was associated with increased odds of pCR compared with NT, with the greatest odds ratio (OR) among all treatments (OR, 59.55; 95% CI, 10.63-333.56; P < .001). RTTU had the next highest OR (29.96; 95% CI, 2.92-307.53; P = .004). In multivariable analysis for OS among 3061 patients (owing to missing data for OS), CTTU was associated with decreased risk of death compared with NT (hazard ratio, [HR], 0.41; 95% CI, 0.35-0.48; P < .001), with the lowest HR, as was nCRT (HR, 0.48; 95% CI, 0.35-0.66; P < .001), with the next lowest HR. Median OS was greatest among patients treated with CTTU (53.9 months; 95% CI, 44.5-61.0 months), followed by nCRT (39.1 months; 95% CI, 26.9 months-not applicable) and aCT (36.1 months; 95% CI, 28.88-49.18 months), while 2-year OS rates were 65.6% (95% CI, 61.3%-69.5%) for CTTU, 63.6% (95% CI, 52.3%-73.0%) for nCRT, and 59.7% (95% CI, 54.2%-64.7%) for aCT.Conclusions and relevanceThis study found that nCRT was associated with the highest pCR rate, while CTTU (ie, neoadjuvant or adjuvant therapy) was associated with the greatest OS.

Project description:Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients.

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Treatment of resectable gastric cancer.

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Treatment of resectable gastric cancer.

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