Postoperative radiation therapy for lung cancer: where do we stand?

Lung cancer is the leading cause of cancer mortality in the United States. Local recurrence after surgery for operable disease has long been recognized as a hindrance to long-term survival. Postoperative radiation therapy was logically explored as a means to improve local control and survival. Multiple randomized trials were conducted, many showing improved local control, but none demonstrated a statistically significant survival benefit. In fact, a meta-analysis showed a rather large survival detriment, presumably from treatment-related complications. Radiation therapy has evolved over the years, and more modern treatment planning and delivery has the potential to treat sites deemed at high risk of recurrence while limiting the dose to critical intrathoracic structures, which should decrease the risk of treatment-related complications. Recent studies have supported this supposition. Similarly, since cancer is often a systemic disease, local control will become a more pressing issue as systemic micrometastatic disease is eradicated with effective chemotherapy. Unfortunately, randomized trials testing the effectiveness of modern postoperative radiation therapy in the chemotherapy era have not been performed. Clinicians must therefore counsel patients regarding the risk of disease recurrence after surgery, the potential but unproven benefit of postoperative radiation therapy, and the possibility of treatment-related complications.     

EGFR inhibitors: what have we learned from the treatment of lung cancer?

Tyrosine kinase inhibitors directed against the epidermal growth factor receptor (EGFR) are the first molecular-targeted agents to be approved in the US and other countries for the treatment of advanced non-small-cell lung cancer after failure of chemotherapy. Some patient characteristics, such as never-smoking, female gender, East Asian origin, adenocarcinoma histology, and bronchioloalveolar subtype, are associated with a greater benefit from treatment with EGFR inhibitors. Recently, studies have identified gene mutations targeting the kinase domain of the EGFR that are related to the response to inhibitors. Most EGFR mutations predict a higher benefit from treatment compared with wild-type receptors and are correlated with clinical features related to better outcome; some EGFR mutations, however, confer drug resistance. The analysis of material usually available from lung cancer patients, using techniques such as direct sequencing to determine EGFR mutational status, can be technically challenging. In this regard, high EGFR copy number and EGFR protein detected by immunohistochemistry can also be used to select those patients who would benefit from treatment. Prospective validation of biological and clinical markers of sensitivity needs to be performed.     

Fluorescent bronchoscopy: contribution for lung cancer screening?

The majority of early lesions, even when centrally located, is missed by conventional white-light (WL) bronchoscopy. Fluorescent bronchoscopy is a promising tool in localising early malignant changes in the central airways, because it is significantly more sensitive than WL bronchoscopy. Originally, drug-induced fluorescence has been used, but today autofluorescence bronchoscopy is more common in relation to its simplicity and advantages. Different systems are available which yield comparable results. However, there are no studies comparing all systems. The disadvantage is the low specificity of the method. Fluorescent bronchoscopy will be more effective if carried out in high-risk patients and/or embedded in a program of preprocedural evaluation of sputum and together with a CT examination of the thorax. But a reduction of mortality as a result of such efforts has not been shown until the present time.     

Particle therapy in lung cancer: Where do we stand?

BACKGROUND: From a theoretical point of view, charged particles should lead to superior results compared to photons. In this review, we searched for clinical evidence that protons or C-ions are really beneficial to patients with lung cancer. METHODS: A systematic literature review based on an earlier published comprehensive review was performed and updated until November 1st 2007. RESULTS: Ten fully published series, all dealing with non-small cell lung cancer (NSCLC), mainly stage I, were identified. No phase III trials were found. On proton therapy, 2-5 year local tumor control rates varied between 87% and 57%. The 2 year/5 year overall survival and 2 year/5 year cause specific survival varied between 31-74%/23% and 58-86%/46%, respectively. Late side effects were observed in about 10% of the patients. For C-ion therapy, the local tumor control rate was 77%, while 95% when using a hypofractionated radiation schedule. The 5 year overall survival and cause specific survival rates were 42% and 60%, respectively. Slightly better results were reported when using hypofractionation, 50% and 76%, respectively. The reported late side effects for C-ions were 4%. CONCLUSION: The results with charged particles, at least for stage I disease, seem to be promising. A gain can be expected in reduction of late side effects, especially after treatment with C-ions. Available data demonstrate that particle therapy in general is a safe and feasible treatment modality. Although current results are promising, more evidence is required before particle therapy can become internationally the standard treatment for (subsets of) lung cancer patients.     

Immunotherapy for cervical cancer: Can it do another lung cancer?

Cervical cancer, although preventable, is still the second most common cancer among women worldwide. In developing countries like India, where screening for cervical cancer is virtually absent, most women seek treatment only at advanced stages of the disease. Although standard treatment is curative in more than 90% of women during the early stages, for stage IIIb and above this rate drops to 50% or less. Hence, novel therapeutic adjuvants are required to improve survival at advanced stages. Lung cancer has shown the way forward with the use of Immunotherapeutic interventions as standard line of treatment in advanced stages. In this review, we provide an overview of mechanisms of immune evasion, strategies that can be employed to boost the immune system in order to improve the overall survival of the patients and summarize briefly the clinical trials that have been completed or that are underway to bring therapeutic vaccines for cervical cancer to the clinics.     

Adjuvant chemotherapy for lung cancer: cisplatin doublets only?

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite adequate resection, more than half of patients die of recurrent disease, usually at distant sites. Adjuvant systemic chemotherapy is mainly used to eradicate micrometastatic disease. Since the seminal 1995 meta-analysis from earlier studies showed a trend toward improved survival with the use of cisplatin-based adjuvant chemotherapy, several randomized prospective adjuvant trials have addressed this question and eventually established the role for platinum-based adjuvant chemotherapy in patients with stage II or IIIA non-small cell lung cancer who have undergone complete resection. The role of adjuvant chemotherapy in patients with stage I disease remains controversial. Although no clinical or molecular predictors of recurrent disease after surgical resection are reliable, encouraging preliminary data on gene expression studies suggest that identifying, and perhaps treating, only patients at high risk for relapse might be possible in the near future. Furthermore, molecular predictors of resistance may guide the selection of chemotherapy in this setting.