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Seminars in Surgical Oncology

Wiley Online Library : Seminars in Surgical Oncology

Published: 2003-11-01T00:00:00-05:00


Foreword: Chemoradiation for GI cancers


Combined-modality therapy for gastric cancer


Gastric cancer has a poor prognosis. It is often diagnosed at an advanced stage, and potentially curative treatments often can not be exercised. Even when a curative surgical resection is possible, only a minority of patients survive beyond 5 years, and locoregional failures are frequent among patients undergoing curative resections. Recently, the use of postoperative adjuvant chemoradiotherapy has yielded some notable benefits. Earlier studies have shown survival benefits in patients undergoing chemoradiotherapy for locally advanced unresectable gastric cancer. The recently reported Intergroup 0116 trial compared surgery alone with surgery plus postoperative chemotherapy plus chemoradiotherapy. Superior overall and disease-free survival rates among patients given combined-modality postoperative therapy were observed. These results established a new standard of care for patients following resection of gastric carcinoma. Preoperative combined-modality chemoradiotherapy may improve resectability, and is under investigation at the University of Texas M. D. Anderson Cancer Center. The development of novel radioenhancers and the selection of therapy on the basis of molecular determinants of response may result in much-needed advances in this field. Semin. Surg. Oncol. 21:223–227, 2003. © 2003 Wiley-Liss, Inc.

Combined modality therapy in esophageal cancer: The Memorial experience


Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an aggressive disease, and poor survival is achieved with surgery or chemoradiation therapy alone. Ongoing trials are investigating the use of preoperative chemoradiation followed by surgical resection. Chemoradiation employing a combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is the most commonly used therapy. The significant gastrointestinal toxicity of traditional cisplatin/5-FU-based regimens has prompted the evaluation of new agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center has conducted chemoradiation trials with weekly paclitaxel/cisplatin and irinotecan/cisplatin, and the results suggest that this regimen has the potential to improve the therapeutic index without compromising efficacy. Randomized trials are now being conducted to evaluate the tolerance and efficacy of paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with radiotherapy in locally advanced esophageal cancer. The incorporation of these non-5-FU-based therapies with novel biologic agents is planned. Semin. Surg. Oncol. 21:228–232, 2003. © 2003 Wiley-Liss, Inc.

Gastrectomy, peritonectomy, and perioperative intraperitoneal chemotherapy: The evolution of treatment strategies for advanced gastric cancer


Gastric cancer disseminates by hematogenous, lymphatic, and transcoelomic routes. For maximal containment of the malignant process, perioperative intraperitoneal chemotherapy is necessary in two groups of patients in whom the primary cancer can be resected. Those patients who have been resected for cure and have a high likelihood of microscopic residual disease require intraperitoneal chemotherapy. This includes all T3 and T4 patients, and patients with N2 nodes present. A series of randomized and nonrandomized clinical studies have established the benefits of perioperative intraperitoneal chemotherapy in this group of patients. Patients with stage IV disease who are able to undergo a palliative resection require these treatments if peritoneal seeding is observed. Systemic chemotherapy is largely ineffective for peritoneal seeding, while intraperitoneal chemotherapy is most likely to produce a response with small volume, surgically debulked carcinomatosis. In addition, intraperitoneal chemotherapy can eliminate the future development of debilitating ascites. Sufficient data are available from the gastric cancer literature to support the use of these combined treatments on a routine basis if the primary cancer is resectable and gastrointestinal function can be reestablished. Semin. Surg. Oncol. 21:233–248, 2003. © 2003 Wiley-Liss, Inc.

Conformal chemoradiation for primary and metastatic liver malignancies


Historically, radiation therapy has played a minor role in the management of patients with unresectable primary hepatobiliary malignancies and liver metastases from colorectal cancer. This can be attributed chiefly to the low tolerance of the whole liver to radiation. Three-dimensional radiation planning techniques have allowed much higher doses of radiation to be delivered to focal liver tumors, while sparing the majority of the normal liver. When combined with fluorodeoxyuridine (FUdR), high-dose focal liver radiation is associated with excellent response rates, local control, and survival in patients with large unresectable tumors. There appears to be a radiation dose response for intrahepatic malignancies. Advancements in tumor imaging, radiation techniques that can safely deliver higher doses of radiation, novel tumor radiation sensitizers, and normal-tissue radioprotectors should substantially improve the outcome of patients with unresectable intrahepatic malignancies treated with chemoradiation. Semin. Surg. Oncol. 21:249–255, 2003. © 2003 Wiley-Liss, Inc.

Postoperative adjuvant therapy for pancreatic cancer


The majority of patients diagnosed with pancreatic cancer present at an advanced stage, and only a small percentage are considered technically resectable at diagnosis. The overall prognosis for the majority is dismal, with a median survival in untreated cases of only 24 weeks. Even in resected patients the overall 5-year survival rate is generally only 5% to 10%; however, some reports indicate higher 5-year survival rates in patients treated with surgery who are pathologically staged with no lymph node involvement. Even when macroscopically complete resection is achieved, local recurrence (LR) rates are unacceptably high (30% to 70%), which is usually attributed to the difficulty of obtaining microscopically free surgical margins. Microscopic clearance is difficult to achieve because these tumors frequently extend into the peripancreatic tissues (e.g., retropancreatic fat), abut or invade the adjacent large vessels (the portal vein and superior mesenteric artery), and have a propensity to invade the lymphovascular and perineural space. Other common sites of failure after attempted curative resection include metastasis to the liver and the peritoneal cavity. Patients who present with pancreatic cancer, and for whom curative surgery is deemed possible, are thus potential candidates for adjuvant therapy because of the high local failure rate following resection alone. The radiotherapy dose that can be achieved in the postoperative setting for pancreatic cancer is limited because of the proximity of critical structures (e.g., the kidney, liver, small intestines, stomach, and spinal cord). Newer techniques such as conformal radiotherapy and intensity-modulated radiotherapy have the advantage of being able (theoretically) to precisely localize the dose to the target volume while reducing the dose to critical structures. These techniques may potentially enable the tumorcidal dose to be increased; however, they are only now becoming widespread. Systemic radiation-sensitizing chemotherapy is also a promising approach to take advantage of additive or synergistic effects with radiation locally, and for the sterilization of systemic disease. This concept of concomitant chemotherapy with radiotherapy, or chemoradiotherapy, has proved effective in a number of sites, including the anal canal, rectum, lung, and pancreas. The recent trials reviewed here varied considerably in terms of the total dose and technique used, and the choice of radiation sensitizing treatment. Semin. Surg. Oncol. 21:256–260, 2003. © 2003 Wiley-Liss, Inc.

Preoperative chemoradiation for locally advanced rectal adenocarcinoma–the University of Florida experience


To evaluate the efficacy of preoperative radiotherapy alone or combine with chemotherapy. Between 1975 to 1997, 318 patients with locally advanced rectal adenocarcinomas were treated with preoperative radiation therapy. Between 1991 and 1997, approximately 60% of patients received fluorouracil (5-FU)-based adjuvant chemotherapy. Patients treated since 1991 had improved downstaging compared with those treated prior to 1991. Patients treated between 1991 and 1997 were also more likely to undergo a sphincter preserving surgical procedure. Preoperative chemoradiation probably results in improved downstaging and survival compared with preoperative irradiation alone. Semin. Surg. Oncol. 21:261–264, 2003. © 2003 Wiley-Liss, Inc.

Preoperative chemoradiation for locally advanced rectal cancer: rationale, technique, and results of treatment


Over the past decade, 392 patients with stage II and III rectal cancer have been managed with preoperative chemoradiation and surgery at the M. D. Anderson Cancer Center (MDACC). Aggressive surgical techniques such as total mesorectal excision, proctectomy with coloanal anastamosis, and multivisceral excisions have been used. Initial pelvic chemoradiation is also used in patients who present with metastases. Preoperative chemoradiation followed by surgery has resulted in excellent sphincter preservation (SP) and pelvic control with minimal acute, perioperative, and late morbidity. SP has been achieved in greater numbers of patients over the past 3 years due to the increased use of coloanal anastamosis in very low tumors. There has been no increase in pelvic failure or perioperative morbidity with this practice. Patients with clinical T4 disease have significantly worse pelvic control. An assessment of the impact of CB on pelvic control and survival requires further follow-up. Poor differentiation and poor response to preoperative therapy predict a worse overall survival. Durable symptom control without colostomy has been achieved using initial chemoradiation in patients who present with metastases. Aggressive bowel management and skin care can minimize hospitalization and treatment interruption due to acute toxicity. Multidisciplinary therapy using preoperative chemoradiation and aggressive surgery has resulted in excellent SP and pelvic control. However, more effective systemic therapies are needed, especially for patients who do not respond well to preoperative chemoradiation. Semin. Surg. Oncol. 21:265–270, 2003. © 2003 Wiley-Liss, Inc.