Management of stage III non–small cell lung cancer

Optimal management of patients with locally advanced non–small cell lung cancer remains challenging in the context of this heterogeneous disease. Despite aggressive therapeutic approaches, survival benefits are still unsatisfactory for what might be viewed as a localized malignancy. A combined modality approach offers patients superior outcomes, especially because technological advances and refined surgical procedures now provide better results with fewer complications. Nevertheless, several features of therapy remain controversial and lack formal prospective data. Traditional cytotoxic chemoradiation therapy may have reached a plateau and future perspectives opting to integrate molecularly targeted agents and immunotherapy might be the way to improve outcomes in this disease subset.     

Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non–small cell lung cancer

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non–small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post–marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD.     

Prognostic factors in patients with stage IV non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths among both men and women over the world. In 2002, lung can- cer accounted for more deaths than breast cancer, prostate cancer, and colon cancer combined[1]. Non-small cell lung cancer (NSCLC) represents 75%–85% of all lung cancers. Lung cancer is hard to discovered until it’s at an advanced stage and the outlook for recovery is poor. Approximately two-thirds of NSCLC patients have advanced-stage at di- agnosis. Stage IV NSCLC denotes …     

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non–small cell lung cancer

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non–small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia–like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia–like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia–like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.     

Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes

Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,     

Conformal radiotherapy of stage III non–small cell lung cancer: a class solution involving non–coplanar intensity-modulated beams

Purpose: We developed a semiautomatic class solution to irradiate centrally located Stage III non–small cell lung cancer (NSCLC), involving a beam intensity modulation technique and optimization using a biophysical cost function.Methods and Materials: Treatment for 10 patients with Stage III NSCLC was planned, using a conventional three- or four-beam three-dimensional (3D) technique and two techniques involving, respectively, seven (BIM1) and five (BIM2) noncoplanar beam incidences with intensity modulation. Two planning target volumes were defined: PTV1 included macroscopic tumor volume and PTV2 included macroscopic and microscopic disease. Beams were divided into beam parts (segments) and their outlines were defined during virtual simulation. Optimization using a biophysical cost function determined beam weights, segment weights, and wedge angles. Biological end points included tumor control probability of both target volumes (TCP1 and TCP2) and normal tissue complication probability (NTCP) of heart, lung, and spinal cord. The resulting uncomplicated local control probability (UCLP) was calculated. Physical end points included dose at PTV1 expressed as a dose minimum and dose maximum. Target-dose inhomogeneity was constrained in all plans.Results: Concerning tumor evaluation, TCP1 was 74% (range 54–89%) for the 3D plan, 78.0% (range 62–94%) for BIM1, and 86.0% (range 59–93%) for BIM2. TCP1 1 TCP2 was, respectively, 67.0% (range 39–81%), 73.0% (range 56–94%), and 81.0% (range 54–93%). Minimum doses to PTV1 were 85, 80, and 88 Gy with the three respective techniques, while dose maxima were 89, 101, and 100 Gy. NTCPs of lung were 45.0% (range 11–75%) for 3D, 19.5% (range 8–59%) for BIM1, and 24.5% (range 3–61%) for BIM2. NTCPs of heart and spinal cord were comparable for all techniques. ULCPs were 37.0% (range 9–73%), 52.5% (range 22–86%), and 60.0% (range 20–85%), respectively. Applying physical limits to ensure clinical safety, minimum doses at PTV1 were recalculated. These were 72, 71, and 74 Gy for 3D, BIM1, and BIM2, respectively.Conclusion: The BIM2 plan is a candidate class solution for dose escalation studies in centrally located Stage III NSCLC.     

Second–line chemotherapy for non—small–cell lung cancer

Most of the experience with second-line chemotherapy for non-small-cell lung cancer (NSCLC) comes from small phase II trials, which have shown disappointing or inconsistent results. The notable exception has been docetaxel, which has been extensively studied as a second-line therapy for NSCLC. On the basis of consistent phase II activity, two large randomized phase III trials were conducted for patients with advanced NSCLC that had progressed either on or after first-line platinum-based therapy. In one trial, docetaxel, at either 100 or 75 mg/m2, was compared with a regimen of either vinorelbine or ifosfamide. In the second trial, docetaxel 75 to 100 mg/m2 was compared with best supportive care. Both trials showed significant improvement in survival, time to progression, and quality of life in the patients receiving docetaxel versus the control therapy. Based on these two large trials, it appears that the use of second-line therapy with single-agent docetaxel at a dose of 75 mg/m2 every 3 weeks is a reasonable practice in patients who maintain a good performance status.     

Prognostic factors in patients with stage Ⅳ non-small cell lung cancer

Objective： To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer （NSCLC） with distant metastasis and establish a reliable model of clinical prognostic index. Methods： From January 1990 to April 2005, 313 primary NSCLC patients with metastasis, who had been treated in Shanghai Chest Hospital, were reviewed. Survival time was estimated according to the Kaplan-Meier method. Cox proportional hazard regression model was used for multivariate analysis. Results：Among the 313 cases of non-small cell lung cancer （NSCLC） at stage Ⅳ, there were 218 and 95 patients with metastasis to single and different organs, respectively. The overall median survival time for all 313 cases of NSCLC patients was 10.8 （9.00, 12.30） months and the overall 1-, 2-, 3-, 4- and 5-year survival rate was 45%, 18%, 12%, 4% and 0%. There were 63, 174, 127, 36, 18, 11 and 5 patients with metastasis to brain （20.13%）, bone （55.59%）, lung （40.58%）, liver （11.50%）, adrenal gland （5.75%）, subcutaneous （3.51%） and others, respectively. The survival time was shortest in subcutaneous metastasis （4.6 months）, and liver 7.0 months, brain 8.0 months, adrenal gland 8.6 months, bone 10.6 months, lung 11.8 months. Kaplan-Meier estimation showed that patients anatomic typing, KPS, numbers of organ with metastasis, appetite, liver, adrenal gland and subcutaneous metastasis, body weight loss, smoking, index of smoking, chemotherapy, cycles of chemotherapy were the predictors of survival. Multivariate analysis showed survival statistically significant correlation with anatomic typing, KPS, appetite, liver and subcutaneous metastasis, body weight loss, cycles of chemotherapy. The relative risk （RR） was 1.51, 1.97, 1.55, 1.67, 2.56, and 2.56 respectively. Conclusion： Survival time decreases distinctly in patients who had distant metastasis to more than two different organs （P〈0.01）. Bone is the commonest organ for distant metastasis in lung cancer. The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis. Independent prognostic factors in patient with stage Ⅳ non-small cell lung cancer were liver and subcutaneous metastasis, anatomic typing, KPS, appetite, body weight loss, cycles of chemotherapy.     

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non–small cell lung cancer patients with brain metastases

High expression of fibrinogen and platelets are often observed in non-small cell lung cancer （NSCLC） patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age 〉 65 years （P = 0.011）, smoking status （P = 0.009）, intracranial symptoms （P = 0.022）, clinical T category （P = 0.010）, clinical N category （P = 0.003）, increased partial thromboplastin time （P 〈 0,001）, and platelet count （P 〈 0.001）. Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration （median, 17.3 months versus 11.1 months; P 〈 0.001）. A similar result was observed for platelet counts （median, 16.3 months versus 11.4 months; P = 0.004）. Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases （R2 = 1.698, P 〈 0.001 and R2 = 1.699, P 〈 0.001, respectively）. Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.