Association between neoadjuvant chemoradiation and survival for patients with locally advanced rectal cancer.

AIM: To examine the overall survival differences for the following neoadjuvant therapy modalities - no therapy, chemotherapy alone, radiation alone and chemoradiation - in a large cohort of patients with locally advanced rectal cancer. METHOD: Adults with clinical Stage II and III rectal adenocarcinoma were selected from the National Cancer Database and grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only or chemoradiation. Multivariable regression methods were used to compare adjusted differences in perioperative outcomes and overall survival. RESULTS: Among 32 978 patients included, 9714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1170 (3.5%) radiotherapy only and 21 204 (64.3%) chemoradiation. Compared with no therapy, chemotherapy or radiotherapy alone were not associated with any adjusted differences in surgical margin positivity, permanent colostomy rate or overall survival (all P > 0.05). With adjustment, neoadjuvant chemoradiation vs no therapy was associated with a lower likelihood of surgical margin positivity (OR 0.74, P < 0.001), decreased rate of permanent colostomy (OR 0.77, P < 0.001) and overall survival [hazard ratio (HR) 0.79, P < 0.001]. When compared with chemotherapy or radiotherapy alone, chemoradiation remained associated with improved overall survival (vs chemotherapy alone HR 0.83, P = 0.04; vs radiotherapy alone HR 0.83, P < 0.019). CONCLUSION: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter preservation, R0 resection and survival for patients with locally advanced rectal cancer. Despite this finding, one-third of patients in the United States with locally advanced rectal cancer fail to receive stage-appropriate chemoradiation.

Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy and morbidity of intraoperative radiation therapy (IORT) for advanced colorectal cancer. METHODS: All patients undergoing IORT for locally advanced rectal cancer from 2001-2009 were reviewed for cancer recurrence, survival, and procedure-related morbidity. Cumulative event rates were estimated using the method of Kaplan and Meier. RESULTS: Twenty-nine patients with locally advanced (n = 8) or recurrent (n = 21) rectal cancers were treated with IORT and resection. Surgical interventions included low anterior resection, abdominoperineal resection, pelvic exenteration, and a variety of non-anatomic resections of pelvic recurrences. R(0) resections were achieved in 16 patients, while R(1) resections were achieved in 10, and margins were grossly positive in 3 patients. IORT was delivered to all patients over a median area of 48 (42-72) cm(2) at a median dose of 12 (12-15) Gy. Local and overall recurrence rates were 24 % (locally advanced group) and 45 % (recurrent group). Median disease-free and overall survival were 25 and 40 months respectively at a median follow-up of 26 (18-42) months. The short-term (≤30 days) complication rate was 45 %. Eight patients developed local wound complications, 5 of which required operative intervention. Four patients developed intra-abdominal abscesses requiring drainage. Long-term (>30 days) complications were identified in 11 patients (38 %) and included long-term wound complications (n = 3), ureteral obstruction requiring stenting (n = 1), neurogenic bladder (n = 3), enteric fistulae (n = 2), small bowel obstruction (n = 1), and neuropathic pain (n = 1). CONCLUSIONS: Intraoperative brachytherapy is a viable IORT option during pelvic surgery for locally advanced or recurrent colorectal cancer but is associated with high postoperative morbidity. Whether intraoperative brachytherapy can improve local recurrence rates for locally advanced or recurrent colorectal cancer will require further prospective investigation.

Chemoradiotherapy in gastrointestinal malignancies.

Over the past 30 years, significant advances have been made in the integration of radiation therapy and chemotherapy in the treatment of patients with localised gastrointestinal malignancies. The therapeutic goal of chemoradiotherapy is to enhance local control resulting in improved survival and outcome of these patients. To define the optimal sequence, agents and efficacy of these modalities, an array of randomised studies have been conducted in malignancies of the oesophagus, stomach, pancreas, colon, rectum and anus. In oesophageal cancer, recent studies from Germany and France indicate that patients treated with 'definitive' chemoradiotherapy have similar survival to patients undergoing neoadjuvant chemoradiotherapy followed by surgery. For patients with locally advanced rectal cancer undergoing surgery, a phase III trial from Germany showed higher rates of local control with less acute and late morbidity for patients receiving neoadjuvant chemoradiotherapy vs adjuvant chemoradiotherapy. In contrast, the role of chemoradiotherapy in pancreatic cancer patients remains unclear and contentious. This overview highlights current results, controversies and potential future directions in the chemoradiotherapeutic treatment of selected gastrointestinal malignancies.

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Current perspectives on locally advanced pancreatic cancer.

This year, approximately 40% of the 28,300 patients diagnosed with pancreatic carcinoma in the United States will present with locally advanced disease. Radiotherapeutic approaches are often employed, as these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases. These treatments include external-beam irradiation with and without fluorouracil (5-FU)-based chemotherapy, intraoperative irradiation, and more recently, external-beam irradiation with new systemic agents, such as gemcitabine (Gemzar).