Jack A. Roth, MD, FACS

Surgical resection of isolated pulmonary metastases has been incorporated into the management of cancer for more than 70 years. However, many questions still remain concerning indications, technique, and efficacy for this approach.

Local-regional carcinoma of the esophagus is often diagnosed inadvanced stages because the diagnosis is established when symptomsare severe. The prognosis of patients with local-regional carcinoma ofthe esophagus continues to be grim. While preoperative chemoradiotherapyincreases the fraction of patients who achieve pathologiccomplete response, that percentage is approximately 25%. In an attemptto increase the number of patients with either no cancer in the surgicalspecimen or only microscopic cancer, we adopted a three-step strategy.The current study utilized up to two 6-week cycles of induction chemotherapywith irinotecan (CPT-11, Camptosar) and cisplatin as step 1.This was followed by concurrent radiotherapy and chemotherapy withcontinuous infusion fluorouracil (5-FU) and paclitaxel as step 2. Oncethe patients recovered from chemoradiotherapy, a preoperative evaluationwas performed and surgery was attempted. All patients signed aninformed consent prior to their participation on the study. A total of 43patients were enrolled. The baseline endoscopic ultrasonography revealedthat 36 patients had a T3 tumor, five patients had a T2 tumor, andtwo had a T1 tumor. Twenty-seven patients had node-positive cancer(N1). Thirty-nine (91%) of the 43 patients underwent surgery; all hadan R0 (curative) resection. A pathologic complete response was noted in12 of the 39 patients. In addition, 17 patients had only microscopic(< 10%) viable cancer in the specimen. Therefore, a significant pathologicresponse was seen in 29 (74%) of 39 taken to surgery or 29 (67%)of all 43 patients enrolled on the study. With a median follow up beyond25 months, 20 patients remain alive and 12 patients remain free ofcancer. Our preliminary data suggest that the proportion of patientswith significant pathologic response can be increased by using thethree-step strategy.

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date. [ ONCOLOGY 13(Suppl 5):148-154, 1999]

The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative extent of disease evaluation, and the role of the surgeon in

The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in

The appearance of metastases is generally thought to herald widespread dissemination of a primary cancer. At this point, surgery usually is either not indicated or palliative. Thus, it is somewhat surprising that surgical resection of metastases has become an accepted treatment modality in several clinical situations. This is due, in part, to the unique biology of several types of cancers and to well-defined clinical presentations that can be identified. Drs. Dresler and Goldberg succinctly review the indications for and results of resection of pulmonary metastases.