Does Chemoradiotherapy Improve Outcomes for Surgically Resected Adenocarcinoma of the Stomach or Esophagus?

Background  

To use a population-based registry to evaluate the effect of chemotherapy or radiation on survival for patients undergoing curative-intent surgery for adenocarcinoma of the esophagus or stomach.     

Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience

Journal of Gastrointestinal Surgery - The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal...     

Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta-analyses and Systematic Review of Literature

Background

Standard therapy for loco-regionally advanced, resectable oesophageal carcinoma is trimodality therapy (TMT) consisting of neoadjuvant chemoradiotherapy and oesophagectomy. Evidence of survival advantage of TMT over organ-preserving definitive chemoradiotherapy (dCRT) is inconclusive. The aim of this study is to compare survival between TMT and dCRT.

Methods

A systematic review and meta-analyses were conducted. Randomised controlled trials and observational studies on resectable, curatively treated, oesophageal carcinoma patients above 18 years were included. Three online databases were searched for studies comparing TMT with dCRT. Primary outcomes were 1-, 2-, 3- and 5-year overall survival rates. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs and cohort studies. Quality of evidence was evaluated according to Grading of Recommendation Assessment, Development and Evaluation.

Results

Thirty-two studies described in 35 articles were included in this systematic review, and 33 were included in the meta-analyses. Two-, three- and five-year overall survival was significantly lower in dCRT compared to TMT, with relative risks (RRs) of 0.69 (95% CI 0.57–0.83), 0.76 (95% CI 0.63–0.92) and 0.57 (95% CI 0.47–0.71), respectively. When only analysing studies with equal patient groups at baseline, no significant differences for 2-, 3- and 5-year overall survival were found with RRs of 0.83 (95% CI 0.62–1.10), 0.81 (95% CI 0.57–1.14) and 0.63 (95% CI 0.36–1.12).

Conclusion

These meta-analyses do not show clear survival advantage for TMT over dCRT. Only a non-significant trend towards better survival was seen, assuming comparable patient groups at baseline. Non-operative management of oesophageal carcinoma patients might be part of a personalised and tailored treatment approach in future. However, to date hard evidence proving its non-inferiority compared to operative management is lacking.

     

Letter to the Editor: Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta-analyses and Systematic Review of Literature

World Journal of Surgery -     

Adenocarcinoma of the Esophagus in the Young

Introduction

Practitioners have noted a striking increase in the number of young patients under the age of 40 years old who develop esophageal adenocarcinoma. The aim of this study was to characterize the presentation, pathology and therapeutic outcome of these young patients.

Methods

The records of patients who presented to the Foregut Surgical Service at the University of Southern California with esophageal adenocarcinoma between 2000 and 2007 were retrospectively reviewed. The presentation, tumor stage and histology, therapy and outcome of the patients under the age of 40 were compared to those ≥40.

Results

Of the 374 patients reviewed, 20 (5 %) were under the age of 40. There were two patients in their second and 18 in their third decade of life. The youngest patient was 25 years old. A history of gastroesophageal reflux disease or Barrett’s esophagus was less common in patients <40 than in those ≥40; 15 and 5 % compared to 61 and 46 %. Similarly, patients <40 had a significantly longer time interval between the onset of symptoms and the diagnosis of their cancer than those ≥40; 4.5 vs. 2 months, p?=?0.04. They also had a higher prevalence of stage IV disease (30 vs. 6 %, p?=?0.0003), a shorter time to recurrence (9.5 vs.19 month, p?=?0.002), and a poorer median survival (17 vs. 43 month, p?=?0.04).

Conclusion

Esophageal adenocarcinoma in patients <40 years old commonly presents with an advanced stage of the disease and an associated poor survival. This is likely due to a low index of suspicion that dysphagia seen in younger patients is due to a malignancy.     

Retrospective Comparison of Robot-Assisted Minimally Invasive Versus Open Pancreaticoduodenectomy for Periampullary Neoplasms

Background

As with other open procedures now routinely performed using laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) may result in decreased pain, fewer wound complications, and accelerated recovery. However, when used for periampullary cancers, it is also important to assess if MIPD offers comparable oncologic outcomes.

Methods

Technical and perioperative outcomes were compared between patients with a preoperative diagnosis of periampullary neoplasm offered MIPD or open pancreaticoduodenectomy (OPD) from November 2009 to July 2011.

Results

Fifty-six consecutive MIPD and OPD (28 each) procedures were analyzed. Comparing MIPD to OPD, significant differences included longer median procedure time (431 vs 410 min, p?=?.04) and fewer median lymph nodes harvested (15 vs 20, p?=?.04). R0 resection rate tended to be lower (63 vs 88 %, p?=?.07) as well as surgical site infections (18 vs 43 %, p?=?.08). Clinically significant pancreatic fistula rate was the same between groups (21 %). Other outcomes such as narcotic pain medication use, length of stay, and 30-day readmission rates were also similar.

Conclusions

MIPD is feasible with comparable technical success and outcomes to OPD. However, there is a learning curve to the procedure and further experience and prospective study will be required to better establish the oncologic efficacy of MIPD to open resection.     

Current Status of Neoadjuvant Therapy for Adenocarcinoma of the Distal Esophagus

Prospective studies dealing with preoperative therapy in adenocarcinoma of the esophagus alone are rare. The interpretation of the preferential phase II trials and a few phase III trials is complicated, as most studies include adenocarcinoma of the esophagus (i.e., Barretts carcinoma), adenocarcinoma of the esophagogastric junction (including cardia carcinoma and subcardia carcinoma), or squamous cell carcinoma. Preoperative chemotherapy, generally well tolerated, cannot decrease the incidence of local failure beyond the level achieved with surgery alone, but it might delay systemic relapse. Preoperative radiotherapy can enhance local control, but it fails to improve overall survival. Neoadjuvant chemoradiation was demonstrated in only one randomized trail to have a survival benefit, but survival in the surgery-alone group was unusually low. Generally, survival was ameliorated in patients responding to neoadjuvant treatment. However, preoperative chemoradiation was often accompanied by a remarkable increase in postoperative morbidity and mortality. Nonresponding patients have, in this respect, a worse prognosis than responders after resection. The prediction of responding patients to neoadjuvant therapy as well as the early identification of patients who will not respond is of utmost clinical importance. Today, there is no absolute evidence that neoadjuvant treatment for patients with potentially resectable Barretts cancer prolongs survival. In patients with locally advanced, presumably not completely resectable adenocarcinoma of the esophagus, preoperative treatment appears to increase the chance for a curative resection and enhance survival in responding patients. Neoadjuvant treatment of adenocarcinoma of the esophagus, as a consequence, is currently not the standard treatment and should be performed only within controlled clinical trials.     

Lymph Node Retrieval after Preoperative Chemoradiotherapy for Rectal Cancer

Background

Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients.

Methods

An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained.

Results

On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P?P?=?0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not.

Conclusions

Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.     

Oncological Feasibility of Laparoscopic Distal Pancreatectomy for Adenocarcinoma: A Single-Institution Comparative Study

Background

Laparoscopic distal pancreatectomy (LDP) is performed increasingly for pancreatic pathology in the body and tail of the pancreas. However, only few reports have compared its oncological efficacy with open distal pancreatectomy (ODP). We compared these two techniques in patients with pancreatic ductal adenocarcinoma.

Methods

From a prospectively maintained database, all patients who underwent either LDP or ODP for adenocarcinoma in the body and tail of the pancreas between January 2008 and December 2011 were compared. Data were analysed using SPSS^® v19 utilising standard tests. A p value <0.05 was considered significant.

Results

Of 101 patients who underwent distal pancreatectomy, 22 had histologically confirmed adenocarcinoma (LDP n = 8, ODP n = 14). Both groups were well matched for age and the size of tumour (22 vs. 32 mm, p = 0.22). Intraoperative blood loss was 306 ml compared with 650 ml for ODP (p = 0.152). A longer operative time was noted for LDP (376 vs. 274 min, p < 0.05). Total length of stay was shorter for LDP compared with ODP (8 vs. 12 days, p = 0.05). The number of postoperative pancreatic fistulas were similar (LDP n = 2 vs. ODP n = 3, p = 0.5). Complete resection (R0) was achieved in 88 % of LDP (n = 7) compared with 86 % of ODP (n = 12). The median number of lymph nodes harvested was 16 for LDP versus 14 for ODP. Overall 3-year survival also was similar: LDP = 82 %, ODP = 74 % (p = 0.89).

Conclusions

From an oncological perspective, LDP is a viable procedure and its results are comparable to ODP for ductal adenocarcinomas arising in the body and tail of the pancreas.     

Oncologic Outcomes After Radical Surgery Following Preoperative Chemoradiotherapy for Locally Advanced Lower Rectal Cancer: Abdominoperineal Resection Versus Sphincter-Preserving Procedure

Background  Over the past several years, preoperative chemoradiotherapy (CRT) has contributed remarkably to make more sphincter-preserving procedure (SPP) possible for lower rectal cancer. The aim of this study was to compare the outcomes between abdominoperineal resection (APR) and SPP after preoperative CRT in patients with locally advanced lower rectal cancer. Methods  A retrospective investigation was conducted with a total of 122 patients who underwent radical surgery combined with preoperative CRT for locally advanced lower rectal cancer. Of these, 50 patients underwent APR and 72 received SPP. Surgery was performed 6–8 weeks after completion of preoperative CRT. Oncologic outcomes were compared between the two groups, and the clinicopathologic factors affecting the treatment outcomes were evaluated. Results  Circumferential resection margin (CRM) involvement (P = 0.037) and postoperative complication rate (P = 0.032) were significantly different between APR and SPP. Patients who underwent APR had a higher 5-year local recurrence (22.0% vs. 11.5%, P = 0.028) and lower 5-year cancer-specific survival (52.9% vs. 71.1%, P = 0.03) rate than those who underwent SPP. Pathologic N stage was the most critical predictor for local recurrence and survival. Conclusions  Our study shows that APR following preoperative CRT exhibited more adverse oncologic outcomes compared with SPP. This result may be due to higher rates of CRM involvement in APR even with preoperative CRT. We suggest that sharp perineal dissection and wider cylindrical excision at the level of the anorectal junction are required to avoid CRM involvement and improve oncologic outcomes in patients who undergo APR following preoperative CRT.     

Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer

Background Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. Methods Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.Results The estimated overall survival (median±SE) in the entire group of patients undergoing resection was 23±4.2 months, with an estimated 3-year survival of 37%±6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.Conclusions Histological response to neoadjuvant CRT—as measured by residual tumor load—may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.     

A Pilot Study of Preoperative Chemoradiotherapy for Resectable Gastric Cancer

Background: The goals of this study were to assess the feasibility and toxicity of a regimen of preoperative chemoradiotherapy, surgery, and intraoperative radiotherapy in the treatment of patients with potentially resectable gastric cancer. A secondary objective was to assess pathologic response to chemoradiotherapy in the treated tumors.Methods: Twenty-four patients were entered in the protocol. Treatment regimen consisted of 45 Gy of external beam radiotherapy with concurrent 5-FU given as a continuous infusion at a dose of 300 mg/m². Patients were restaged 4–6 weeks after chemoradiotherapy and then underwent surgical resection and intraoperative radiotherapy to a dose of 10 Gy.Results: Twenty-three patients (96%) completed chemoradiotherapy in accordance with the study protocol. Nineteen (83%) of 23 patients who completed chemoradiotherapy underwent surgical resection with D2 lymphadenectomy. Four patients (17%) had progressive disease and were not resected. The morbidity and mortality rates were 32% and 5%, respectively. Of the resected patients, two (11%) had complete pathologic responses while 12 (63%) had pathologic evidence of significant treatment effect.Conclusions: Preoperative chemoradiotherapy for gastric cancer can be delivered safely and is well tolerated. The rate of surgical complications is consistent with that of other recently reported prospective trials of gastrectomy alone. Preoperative chemoradiotherapy resulted in significant pathologic responses in the majority of treated tumors, and complete pathologic responses were achieved in some patients.     

Neoadjuvant Chemoradiotherapy for Adenocarcinoma of the Pancreas: Treatment Variables and Survival Duration

Background:For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors, and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head.Methods:Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence.Results:The overall median survival from the time of tissue diagnosis was 21 months (range 19–26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect.Conclusion:This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.Presented at the 53rd Annual Cancer Symposium of the Society of Surgical Oncology, New Orleans, Louisiana, March 18, 2000