Seminars in surgical oncology最新文献

Locally advanced non-small cell lung carcinoma (NSCLC) presents enormous challenges to clinicians and researchers. Because of the absence of metastatic disease, it is a potentially curable condition, greatly differentiating it from stage IV NSCLC. The median and actuarial survival rates are poor, though clearly improved in the past decade, and clearly better than several other types of locally advanced malignancies (e.g., pancreatic cancer, glioblastoma). As demonstrated in Table I, the combination of chemotherapy and radiotherapy has earned the designation of "standard of care" for most good-performance-status patients with locally advanced NSCLC. It is likely that improvements in radiotherapy have also contributed to the enhanced survival and local control rates in this disease. With concurrent chemoradiotherapy, the majority of patients can receive a substantial local response (Fig. 1). Many achieve durable local control, only to succumb to eventual distant metastatic failure. There remains much room for improvement, and there are several avenues for clinical and translational research that offer promise. These include new systemic chemotherapy options (and newer ways of combining these drugs with radiotherapy), improvements in radiotherapy fractionation and dose intensity, methods of protection from chemoradiotherapy toxicity, specific therapies to prevent brain metastatic failure, and the integration of biologically targeted molecules into chemoradiation programs. This article summarizes the advances in the treatment of locally advanced NSCLC over the past several decades and explores some of the many remaining controversies and areas for future investigation.

Lung cancer accounts for 28.2% of all cancer-related deaths in the United States. Most patients present with advanced-stage disease, with only 15% having disease confined to the lung. Surgical resection is the optimal treatment for Stage I and II non-small cell lung cancer. Pre-resection staging includes various radiographic modalities, including PET scan and mediastinoscopy. Survival and local recurrence statistics favor full anatomic lobar resection over sublobar resection, although cases must be judged individually. Lobectomy via thoracoscopic approach appears to have equivalent outcome as lobectomy via thoracotomy. Characteristics of the counseling physician and the hospital volume at which the surgery is performed can also influence outcome. After surgical resection, stage IA patients have about 70% 5-year survival, but this falls below 50% for stage IIB patients. Methods that identify early-stage lung cancer patients at greatest risk for recurrence are needed to identify patients who may benefit from additional therapies.

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.

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.

A Breast Task Force comprised of nationally known experts in the field of breast cancer treatment was charged with recommending additions and changes for the 6th edition of the TNM Classification that were based on published evidence and/or were consistent with widespread clinical consensus. Additions made to the staging system were designed to facilitate the uniform collection of clinically relevant information about new techniques for the detection of metastatic cells. These additions include quantitative criteria to distinguish micrometastases from isolated tumor cells, and specific identifiers to record the use of sentinel lymph node biopsy, immunohistochemical (IHC) staining, and molecular biology techniques. Revisions of the previous staging system are related to the number of affected axillary lymph nodes and to the classification of level III axillary lymph nodes and lymph nodes outside of the axilla.

The majority of patients with non-small cell lung cancer have locally advanced and metastatic disease at diagnosis. Combination platinum-based chemotherapy is the standard treatment for patients with advanced disease who have a performance status of 0-1. Chemotherapy is superior to supportive care alone in terms of survival, palliation of symptoms, and in many studies, improving quality of life. Newer third generation therapies such as paclitaxel, docetaxel, vinorelbine, and gemcitabine have been proven effective as single agents with minimal toxicity, compared with supportive care alone. In combination with platinum, these agents produce higher response rates than older platinum-based regimens, are associated with additional survival benefits, and are generally more convenient and less toxic for patients. Newer nonplatinum doublets appear equivalent to newer platinum-regimens and have expanded the options available for patients. Targeted agents are promising and may soon offer patients more effective and less toxic therapies. Progress in treatment in the advanced setting has led to advances in the care of locally advanced disease. Combination chemoradiotherapy is a standard treatment for locally advanced disease, and studies with newer agents are in progress.

Extensive-stage small-cell lung cancer (ES-SCLC) continues to be a difficult management issue. While response rates to therapy are relatively high, durable responses are rare, and long-term survival rates are dismal. Although many attempts have been made to develop new therapies, cisplatin-based combination chemotherapy remains the mainstay in the management of these patients. In this review we highlight recent developments in the treatment and management of this malignancy, and discuss future prospects in treatment.