Seminars in surgical oncology最新文献

Among the patients with early stage (I/II) non-small cell lung cancer (NSCLC), there are those who, due to medical comorbidities, advanced age, or refusal, never undergo surgery. For them, exclusive radiation therapy (RT) has been the treatment of choice, achieving median survival times of 30 months and 5-year survival of up to 42%. Doses of > or =65 Gy with standard fractionation (or its radiobiological equivalent when altered fractionation is used) are necessary for long-lasting local control of the disease, with smaller tumors having a more favorable prognosis. The issue of elective nodal irradiation (ENI) remains controversial, since failure patterns identified local failure as the predominant pattern. None of the potential pretreatment patient- and tumor-related prognostic factors has been shown to clearly influence survival. Toxicity is generally mild to moderate, although high doses (e.g., 80 Gy) may carry a risk for an excessive rate of side effects. Conformal treatment and consideration of comorbidities such as altered lung function may be essential, since simultaneous supportive treatment of acute sequelae (mainly acute esophagitis) is necessary. RT is an effective treatment modality in technically operable, but medically inoperable patients with early stage NSCLC and offers a long-lasting cure.

Chemotherapy and radiotherapy are the keys of current management of SCLC. For many years, the diagnosis of small cell lung cancer has been considered a contraindication to surgery because radiotherapy was at least equivalent in terms of local control and the rate of resectability of SCLC patients was poor. The role of surgery has been defined by evidence accumulated in the last 30 years but conclusions are limited by the fact that the most important studies are dated and conducted when the main staging tool was exploratory thoracotomy. The rationale for surgery in the context of SCLC is based on 3 factors: 1) Several historical series on patients operated for limited SCLC reported some long term survivors, showing that permanent cure can be achieved. For this reason, it is now accepted that for the rare patients with very limited stage disease (T1-T2 tumors) surgical resection followed by platinum-based chemotherapy could be offered. 2) After chemotherapy and radiotherapy, the rate of local relapse is 20-30%. The assumption that surgery might be superior to radiotherapy in local control of limited SCLC has been suggested but not still proved. 3) Surgery can precisely assess pathological response to chemotherapy, identify carcinoids erroneously diagnosed as SCLC, treat the NSCLC component of tumors with a mixed histology. In the case of planned surgery, preoperative investigations should be completed by MRI of the brain, mediastinoscopy (to rule out subclinical N2/N3 patients) and probably PET scan. Even if some controversies exist, it is accepted that surgery can be proposed as the first treatment in patents with T1-T2 lesions without sign of lymph nodes involvement, followed by adjuvant chemotherapy. Surgery in stage II and III must be planned on a multidisciplinary basis, in the context of controlled clinical trials.

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.

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.

Advanced stage non-small lung cancers are currently considered unresectable. However numerous series on patients with locally advanced disease treated by surgery have been published. Surgery alone or induction treatments followed by surgery achieve long-term outcomes in an encouraging proportion of selected patients with T4 disease, despite the high rate of morbidity associated with technically demanding procedures.

Conventional radiation therapy has had limited success in curing inoperable lung cancer due to poor local control. There is evidence to suggest that higher doses of radiation will improve local control. In order to safely deliver higher doses of thoracic radiation, advanced treatment techniques are required. Different biologic indices have been utilized to determine whether dose escalation can be safely accomplished, and the results have been reported from many institutions. Tumor motion control aids in treatment since it allows radiation oncologists to more accurately target tumors and therefore to spare more normal tissue from the radiation field. The imaging information from 18-FDG-PET scans also improves target delineation. Advanced treatment delivery techniques, such as three-dimensional conformal radiation therapy, intensity modulated radiation therapy, and stereotactic radiosurgery are also being used to safely escalate the radiation dose. This article explores the current literature on these issues and other advanced radiation therapy techniques.

It is estimated that there will be 157,200 deaths from lung cancer in 2003. Current regimens of surgery, chemotherapy and radiation have not significantly changed overall 5-year survival rates for this disease. Thanks to intensive molecular studies over the last three decades, new targets for treatment have been identified, including replacement of tumor suppressor genes, prevention of angiogenesis and tumor growth, and regulation of programmed cell death. Promising advances have been made but obstacles still abound before effective use of these strategies at the patient bedside can occur. One area of concentration lies in developing more accurate and complete delivery of the therapeutic constructs. In the evolution of gene therapy approaches, from beginning theory to translational research, investigators in thoracic malignancies have played a leading role, utilizing a number of methods and delivery vehicles. The objective of this review is to discuss some of the major molecular targets available for manipulation in lung cancer, describe vectors and techniques currently used by thoracic researchers to deliver therapy, and provide the p53 model as an example of progression from bench research to clinical treatment.

Substantial improvements in treatment outcome for limited-disease small-cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high-dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival.

Many patients who receive a diagnosis of non-small cell lung cancer (NSCLC) have locally advanced disease at initial presentation. Historically, these patients were treated with primary thoracic radiation therapy and had poor long-term survival rates, secondary to both progression of local disease and development of distant metastases. With the goal of improving clinical outcomes, multiple concepts of combined-modality therapy for locally advanced NSCLC have been investigated. The rationale for using chemotherapy in the induction regimen is to eliminate subclinical metastatic disease while improving local control. The optimal treatment of locally advanced NSCLC continues to evolve, but combined-modality therapy has led to improved survival rates compared to treatment with radiation alone and has become the new standard of care. This report reviews the major trials that have investigated various combinations of surgery, radiation therapy, and chemotherapy in the treatment of locally advanced NSCLC.