Postoperative complications, especially pulmonary complications, affect more than half the patients who undergo open esophagectomy for esophageal cancer. Whether hybrid minimally invasive ...esophagectomy results in lower morbidity than open esophagectomy is unclear.
We performed a multicenter, open-label, randomized, controlled trial involving patients 18 to 75 years of age with resectable cancer of the middle or lower third of the esophagus. Patients were randomly assigned to undergo transthoracic open esophagectomy (open procedure) or hybrid minimally invasive esophagectomy (hybrid procedure). Surgical quality assurance was implemented by the credentialing of surgeons, standardization of technique, and monitoring of performance. Hybrid surgery comprised a two-field abdominal-thoracic operation (also called an Ivor-Lewis procedure) with laparoscopic gastric mobilization and open right thoracotomy. The primary end point was intraoperative or postoperative complication of grade II or higher according to the Clavien-Dindo classification (indicating major complication leading to intervention) within 30 days. Analyses were done according to the intention-to-treat principle.
From October 2009 through April 2012, we randomly assigned 103 patients to the hybrid-procedure group and 104 to the open-procedure group. A total of 312 serious adverse events were recorded in 110 patients. A total of 37 patients (36%) in the hybrid-procedure group had a major intraoperative or postoperative complication, as compared with 67 (64%) in the open-procedure group (odds ratio, 0.31; 95% confidence interval CI, 0.18 to 0.55; P<0.001). A total of 18 of 102 patients (18%) in the hybrid-procedure group had a major pulmonary complication, as compared with 31 of 103 (30%) in the open-procedure group. At 3 years, overall survival was 67% (95% CI, 57 to 75) in the hybrid-procedure group, as compared with 55% (95% CI, 45 to 64) in the open-procedure group; disease-free survival was 57% (95% CI, 47 to 66) and 48% (95% CI, 38 to 57), respectively.
We found that hybrid minimally invasive esophagectomy resulted in a lower incidence of intraoperative and postoperative major complications, specifically pulmonary complications, than open esophagectomy, without compromising overall and disease-free survival over a period of 3 years. (Funded by the French National Cancer Institute; ClinicalTrials.gov number, NCT00937456 .).
No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.
We ...conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival.
The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval CI, 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.
Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).
Summary Traditionally, surgery is considered the best treatment for oesophageal cancer in terms of locoregional control and long-term survival. However, survival 5 years after surgery alone is about ...25%, and, therefore, a multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy, alone or in combination, could prove necessary. The role of each of these treatments in the management of oesophageal cancer is under intensive research to define optimum therapeutic strategies. In this report we provide an update on treatment strategies for resectable oesophageal cancers on the basis of recent published work. Results of the latest randomised trials allow us to propose the following guidelines: surgery is the standard treatment, to be used alone for stages I and IIa, or possibly with neoadjuvant chemotherapy or chemoradiotherapy for stage IIb disease. For locally advanced cancers (stage III), neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is appropriate for adenocarcinomas. Chemoradiotherapy alone should only be considered in patients with squamous-cell carcinomas who show a morphological response to chemoradiotherapy, and produces a similar overall survival to chemoradiotherapy followed by surgery, but with less post-treatment morbidity. Although the addition of surgery to chemotherapy or chemoradiotherapy could result in improved local control and survival, surgery should be done in experienced hospitals where operative mortality and morbidity are low. Moreover, surgery should be kept in mind as salvage treatment in patients with no morphological response or persistent tumour after definitive chemoradiotherapy.
Cancers of the esophagus and stomach have a major impact on patients’ nutritional status by virtue of these organs’ inherent digestive functions. Many patients with these cancers will require ...surgical intervention, which imposes further metabolic demands and compounds preexisting nutritional disorders. Patients with esophagogastric cancer are likely to have lost weight by the time the diagnosis is made. This fact alone is of clinical importance, because it is well known that patients who have lost weight will have higher operative mortality and morbidity rates than patients who maintain their weight. Initial assessment of patients with esophagogastric cancer should include a routine evaluation of nutritional status. This will allow the identification of patients who are at risk of complications, particularly in the postoperative setting. These patients should be targeted for specific nutritional support.
Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have ...investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate. Methods GRECCAR6 was a phase III, multicenter, randomized, open-label, parallel-group controlled trial. Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT (45 to 50 Gy with fluorouracil or capecitabine) were included. Patients were randomly included in the 7-week or the 11-week (11w) group. Primary end point was the pCR rate defined as a ypT0N0 specimen (NCT01648894). Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015. The majority of the tumors were cT3 (82%). After RCT, surgery was not performed in nine patients (3.4%) because of the occurrence of distant metastasis (n = 5) or other reasons. Two patients underwent local resection of the tumor scar. A total of 47 (18.6%) specimens were classified as ypT0 (four had invaded lymph nodes 8.5%). The primary end point (ypT0N0) was not different (7 weeks: 20 of 133, 15.0% v 11w: 23 of 132, 17.4%; P = .5983). Morbidity was significantly increased in the 11w group (44.5% v 32%; P = .0404) as a result of increased medical complications (32.8% v 19.2%; P = .0137). The 11w group had a worse quality of mesorectal resection (complete mesorectum I 78.7% v 90%; P = .0156). Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection. A longer waiting period may be associated with higher morbidity and more difficult surgical resection.
To test the hypothesis that signet ring cell (SRC) histology has a negative prognostic value in patients with gastric adenocarcinoma (ADC).
In western countries, gastric ADC with SRC often occurs ...after the disease has advanced. Consequently, the prognosis of SRC is generally regarded as poor, although survival studies comparing SRC and non-SRC have yielded inconsistent results.
: An intent to treat analysis was performed among 215 patients with gastric ADC scheduled for surgical resection from 1996 to 2007. Of these, 180 patients underwent the resection and 35 were not resected due to diffuse metastatic illness. From 59 resected patients with SRC (SRC group), control non-SRC resected patients matched by age, gender, American Society of Anaesthesiologists (ASA) classification, tumoral location, and pTNM stage were randomly selected by computer (non-SRC group: n = 100) during the same study period.
The overall median survival was 21 months, which was significantly higher in resected compared to non-resected patients (31 vs. 5 months, P < 0.001). In non-resected patients, SRC histological subtype was associated with higher rates of diffuse peritoneal carcinomatosis (90.1% vs. 62.5%, P = 0.053) and neoplastic ascitis (63.6% vs. 34.7%, P = 0.059) and poorer median survival (5 vs. 7 months, P = 0.062). For resected patients, the 2 groups (SRC and non-SRC) were comparable regarding matching variables, demographic variables, and postoperative course. The median survival was significantly lower for SRC patients (21 vs. 44 months, P = 0.004). SRC resected patients exhibited higher rates of localized peritoneal carcinomatosis (P = 0.013) and lymph node involvement (P < 0.001) at diagnosis, lower R0 resection rate (P = 0.019) and earlier tumor relapse (P = 0.009), which was generally in a peritoneal carcinomatosis form (P = 0.011). By multivariate analysis, we concluded that SRC histology was independently associated with a dismal prognosis after adjustment on confounding variables (hazard ratio = 1.5, 95% confidence interval 1.1-2.0, P = 0.004). The prognostic role of SRC was maintained after exclusion of patients with advanced stage at initial diagnosis such as localized peritoneal carcinomatosis or lymph node invasion.
This study is currently the best evidence showing that SRC is a major and independent predictor of poor prognosis due to specific characteristics such as more infiltrating tumors showing affinity for lymphatic tissue accompanied by a higher rate of peritoneal carcinomatosis. Our results suggest the need for a specific therapeutic strategy for such tumors.
Summary Gastric and oesophageal cancers are among the leading causes of cancer-related death worldwide. By contrast with the decreasing prevalence of gastric cancer, incidence and prevalence of ...oesophagogastric junction adenocarcinoma (OGJA) are rising rapidly in developed countries. We provide an update about treatment strategies for resectable OGJA. Here we review findings from the latest randomised trials and meta-analyses, and propose guidelines regarding endoscopic, surgical, and perioperative treatments. Through a team approach, members from all diagnostic and therapeutic disciplines, such as gastroenterologists, surgeons, oncologists, radiologists, and radiotherapists, can effectively administer a range of treatment modalities.
To investigate whether the number of lymph nodes metastasis (LNMs) and the ratio between metastatic and examined lymph nodes (LNs) are better prognostic factors when compared with traditional staging ...systems in patients with esophageal carcinoma.
The accuracy of the 6th UICC/TNM classification is suboptimal, especially when not taking into account neoadjuvant therapy and lymphadenectomy extent.
For 536 patients who underwent curative en bloc esophagectomy, in whom 51.5% (n = 276) received neoadjuvant chemoradiation, LNMs were classified according to the 6th UICC/TNM classification and systems based on the number (< or =4 and >4) or the ratio (< or =0.2 and >0.2) of LNMs. Survival of the respective stages, predictors of survival, and influence of both chemoradiation and number of examined LNs were studied.
After a median follow-up of 50 months, the 5-year survival rates were 47% for the entire population, significantly poorer for patients with >4 LNMs (8% vs. 53%, P < 0.001) or a ratio of LNMs >0.2 (22% vs. 54%, P < 0.001). After adjustment for confounding variables, a number of LNMs >4 and a ratio of LNMs >0.2 were the only predictors of poor prognosis. The prognostic role of both the number and the ratio of LNMs was maintained whether patients received neoadjuvant chemoradiation or not. Moreover, LN ratio is shown to be more accurate for inadequately staged patients (<15 examined LNs), whereas the number of LNMs is pertinent for adequately staged patients (> or =15 examined LNs).
Staging systems for esophageal cancer that use the number (< or =4 or >4) and the ratio (< or =0.2 or >0.2) of LNMs have greater prognostic importance than the current staging systems because of the good stratification of the groups and their clinical utility, taking into account neoadjuvant therapy and lymphadenectomy extent.
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