Frontiers of Radiation Therapy and Oncology最新文献

Stage III includes a large variety of clinical situations from chest wall invasion together with intralobar lymph node metastasis to any size of a lung cancer in combination with mediastinal lymph node involvement (N2/N3). Furthermore, the prognosis of patients with lymph node metastasis depends largely on the extent of the disease, which may range from micro-metastasis occasionally found during surgery to bulky and/or multilevel involvement of the mediastinum or extracapsular infiltration. Not surprising the optimal treatment including the role of surgery for stage IIIA (N2) and stage IIIB (T4/N3) non-small cell lung cancer is discussed controversially. Adequate analysis of the clinical stage is key to select the best treatment. In general, patients benefit from surgery, when a radical resection can be achieved with a low morbidity and mortality. A multidisciplinary approach is indicated in most patients, which present with stage III disease at diagnosis. Preferentially patients should be treated in study protocols whenever they are available. Radical surgery including chest wall resection may result in a 5-year survival rate of up to 50% in T3N1 disease. Adjuvant chemotherapy is recommended and radiotherapy is reserved for cases with unclear resection margins. Clinical trials of preoperatively proven N2 patients could show a better outcome when downstaging is achieved after neoadjuvant chemo- or chemoradiotherapy prior to surgery. Patients who may need a pneumonectomy should be selected with caution since some centers experience a high perioperative mortality rate. If unforeseen N2 disease is found during surgery, an adjuvant therapy is recommended. Patients with T4 tumors (infiltration of great vessels, trachea, esophagus, vertebral bodies, etc.) show an increasing 5-year survival from 15 to 35% after radical resection with acceptable perioperative mortality if treated in experienced centers. In stage III non-small cell lung cancer, surgery should be performed within a multimodality approach. Surgery should be recommended when resection is radical including systematic lymph node dissection and mortality and morbidity are low.

Background: Mediastinal lymphadenectomy is usually performed at thoracotomy together with lung resection. It is a prerequisite for accurate nodal staging and has an impact on survival.

Methods: VAMLA (video-assisted mediastinoscopic lymphadenectomy) dissection is guided by anatomical landmarks. It includes en bloc resection of the right and central compartments, and dissection and lymphadenectomy of the left-sided compartment.

Results: VAMLA harvested significantly more mediastinal lymph nodes than open lymphadenectomy (p < 0.001). Mean duration was 54 min, the complication rate 4.6%, sensitivity 93.8%, specificity 100%, and the false-negative rate 0.9%. 16 of 24 cT4 tumors were correctly predicted to be resectable by MUS (mediastinoscopic ultrasound). For minimally invasive oncological lung resections, combined VATS + VAMLA harvested significantly more lymph nodes than VATS alone without impact on operation time and complication rate (p < 0.05).

Conclusion: VAMLA is a well-tolerated minimally invasive method for accurate mediastinal staging and radical mediastinal dissection. VAMLA can be carried out independently from tumor resection. We suggest its application together with neoadjuvant strategies, trials, VATS lobectomy, and radiation therapy for curatively intended involved field radiation. Additional MUS is helpful to detect resectable cT4 cases, and offer them curative treatment.

The role of systematic mediastinal lymph node dissection in the staging and treatment of non-small cell lung cancer (NSCLC) is the subject of ongoing debate. Surgical practice varies from simple visual inspection of the unopened mediastinum to radical, systematic lymphadenectomy of all accessible lymph node levels. As the evaluation of mediastinal lymph nodes is a precondition for accurate intraoperative staging of NSCLC we advocate for complete interlobar, hilar and mediastinal lymphadenectomy as compartment dissections in patients with NSCLC. The therapeutic effect of extensive mediastinal lymphadenectomy, however, remains controversial. In this review we discuss the role of mediastinal lymph node dissection in the management of NSCLC.

Study on the use of complementary and alternative medicine (CAM) in lung cancer patients has been widely neglected. Therefore, we initiated a study on the use of CAM in lung cancer patients in addition to radiation treatment. Overall, 120 patients from 3 institutions were interviewed by a standardized questionnaire. Besides the tumor parameters and the use of CAM, the reason for the use, patient information of the medication, the information sources and the subjective condition of the patient. Altogether, 54% of the patients reported using CAM (66% of female patients, 52% of male patients). The most frequently used CAM measures were vitamin combinations (17%), mistletoe (15%), and selenium (12%). A total of 52% reported the wish to support the tumor treatment as a reason for using CAM and 27% had a 'better feeling' using CAM. 50% of CAM was bought by the patients themselves and 50% were prescribed by their family physicians. The use of CAM is frequent in lung cancer patients. Our results suggest that it is very important to obtain information on the CAM use of patients and, particularly in controlled clinical trials, to prospectively document it.

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy.

Concurrent chemoradiotherapy is presently the standard treatment for stage III inoperable non-small cell lung cancer. Within this treatment framework, conventionally fractionated radiotherapy to a total dose of 60-66 Gy has proven effective. The chemotherapy should be performed using a cisplatin-based regimen or, if contraindicated, carboplatin. The base drug can be combined with another cytostatic, such as etoposide, vinorelbine, paclitaxel or gemcitabine. There is no evidence from randomized clinical trials suggesting that addition of induction chemotherapy or adjuvant chemotherapy to the concurrent chemotherapy regimen improves the prognosis of these patients. Therefore, induction or adjuvant chemotherapy should not be used outside the framework of clinical trials. Age over 70 years and concomitant diseases are not contraindications for concurrent radiochemotherapy per se, but an increased rate of side effects can be expected in such elderly patients or patients with comorbidities. Consequently, these patients require intensive supportive care. Presumably, advanced age is not an adverse prognostic factor per se, but reduced heart and lung function are. Conclusive evidence confirming this assumption is lacking.

Hyperfractionation and hypofractionation combined with acceleration have been investigated in stage I-III NSCLC patients. In stage I tumors, hypofractionated radiation schedules given with highly conformal stereotactic body radiotherapy (SBRT) techniques have been proven safe and effective with local control rates > 85% and meanwhile have been accepted as the standard treatment in stage I patients who are medically unfit for surgery or who refuse resection. When comparing the dose-effect relationship derived from local control data of various clinical studies using conventional fractionation (CF) with that obtained from SBRT trials using doses per fraction from 7.5 to 30 Gy based on the linear quadratic model without parameters considering repopulation or hypoxia, the alpha/beta ratio for biological equivalent doses with the different fractionation schedules was found to be 8.2 (7.0-9.4) Gy for stage I NSCLC. From this, it can be concluded that using an alpha/beta value of 10 Gy for tumors is conservative, underestimating the BED of SBRT schedules relative to CF schedules with regard to tumor control. If repopulation is the dominant resistance-promoting factor for CF schedules and hypoxia for hypofractionated SBRT schedules, and the true alpha/beta value of tumors is assumed to be 10 Gy, then the observed alpha/beta value of 8.2 Gy can imply that the effect of repopulation during CF is higher than the effect of hypoxia during SBRT. Patients with locally advanced NSCLC in whom contraindications preclude the use of concurrent chemotherapy with CF radiotherapy may be treated outside clinical trials with CHART. Combinations of hyperfractionated-accelerated RT schedules with concurrent platinum-based chemotherapy have been proven safe and effective in stage III NSCLC patients.

Patients with advanced NSCLC receive palliative chemotherapy with platinum-based doublets. Cisplatin-based doublets are preferred in patients with good performance status, whereas carboplatin-based protocols are preferred in patients with impaired organ functions (kidney, heart). Customized chemotherapy appears promising but still remains experimental. Improvements of the outcome of first-line chemotherapy have been achieved by the addition of cetuximab in patients with EGFR-positive NSCLC and of bevacizumab in selected patients with non-squamous cell NSCLC. The optimal combination of chemotherapy with targeted therapies remains a challenge. Maintenance therapy and early second-line chemotherapy might improve outcome but are not yet considered as standard treatments. Patients progressing after first-line chemotherapy are treated with docetaxel, pemetrexed or erlotinib. Finally, the efficacy of new anticancer treatments should be assessed by several clinical endpoints with overall survival remaining the most important endpoint in patients with advanced NSCLC.

The prognosis of lung cancer patients mostly depends on the stage at which the disease is diagnosed. Contrast-enhanced CT (ceCT) and MRI play a significant role in initial staging, but often the morphological information is insufficient when compared to the metabolic or molecular information obtained by positron emission tomography (PET). [18]F-fluorine deoxyglucose (FDG) is based upon the increased demand of ATP leading to increased consumption of glucose in the tumor tissues. FDG-PET/CT has been proven to be of immense value in the initial diagnosis, evaluation of therapy reponse, detection of recurrent tumor, radiation therapy planning and in the multidisciplinary management of patients with non-small cell lung cancer as well as in patients with small cell lung cancer. The aim of this article is to present a concise summary of the present status of FDG-PET/CT.

Endobronchial ultrasound (EBUS) has emerged as a new diagnostic tool that allows the bronchoscopist to see beyond the airway. The radial probe EBUS was first introduced to evaluate the airway structure, which has been shown to be useful for identifying the extent of tumor invasion in the central airway. The newest development is the convex EBUS-TBNA scope with a curvilinear electronic transducer on the tip of a flexible videoscope. Linear EBUS allows a real-time EBUS-guided TBNA. Although the main indication for EBUS-TBNA is lymph node staging, it can also be used for diagnosis of intrapulmonary tumors, of unknown hilar and/or mediastinal lymphadenopathy, and of mediastinal tumors. To date, there are no reports of complications related to EBUS-guided TBNA. It is a novel approach that has a good diagnostic yield with excellent potential in assisting safe and accurate diagnostic interventional bronchoscopy. The aim of this review is to highlight the current status of the EBUS-TBNA technique and to discuss the future direction of EBUS.