Retrospective efficacy and safety analyses of erlotinib, pemetrexed, and docetaxel in EGFR-mutation-negative patients with previously treated advanced non-squamous non-small-cell lung cancer.

OBJECTIVE: Several guidelines recommend erlotinib, pemetrexed, or docetaxel for second-line chemotherapy in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The aim of this study was to retrospectively evaluate the efficacy of erlotinib, pemetrexed, and docetaxel in epidermal growth factor receptor (EGFR) mutation-negative patients with previously treated advanced non-squamous NSCLC. MATERIALS AND METHODS: We analyzed the efficacy of these agents in patients with previously treated advanced non-squamous NSCLC who had EGFR wild-type tumors, performance status (PS) of 0, 1, or 2 and received erlotinib, pemetrexed, or docetaxel between December 2007 and September 2011. Variability among patient backgrounds was evaluated using propensity scores to assess comparability. The efficacy of these agents was evaluated in patient subgroups with low variability. RESULTS: The propensity scores showed that the backgrounds of the groups that received second-line therapy with each agent had low variability and were adequate for comparison. Patients were divided into the PS0/1 and PS2 groups for analysis. The median progression-free survival (PFS) in patients treated with erlotinib was 2.8 months in the PS0/1 group, as compared with 1.0 month in the PS0/1/2 group and 0.90 months in the PS2 group. PFS in PS0/1 patients who received erlotinib was comparable to that in PS0/1 patients who received pemetrexed (2.5 months) or docetaxel (1.9 months). Overall survival (OS) in erlotinib-, pemetrexed-, and docetaxel-treated PS0/1 patients was 16.1, 7.4 and 10.0 months, respectively. The study had limited power to detect differences in PFS and OS because of the small sample size. CONCLUSIONS: Erlotinib appears to be a useful second-line option in PS0/1 patients with EGFR mutation-negative advanced non-squamous NSCLC given its mild adverse effects. The results should be carefully interpreted because of the small sample size, limited power, and retrospective nature of the study.

Porous diaphragm syndrome with repeated rapid accumulation of pleural effusion.

A 53-year-old woman was admitted with right massive transudative pleural effusion and acute renal failure. The amount of pleural fluid reduced in response to treatment with hydration and diuretics; however, the effusion recurred one month later. We suspected the presence of a right pleuroperitoneal communication allowing pleural fluid to accumulate from an origin of ascites triggered by renal failure. Chest computed tomography following pleural drainage revealed a small nodule in the right upper lobe of the lung. A diagnosis of T1aN0M0 lung adenocarcinoma was made based on the results of various examinations, including bronchoscopy. Video-assisted thoracoscopic surgery was performed, and the presence of a small hole communicating between the pleural and peritoneal cavities was confirmed in the right diaphragm during the surgery.

Novel chemoradiotherapy with concomitant boost thoracic radiation and concurrent cisplatin and vinorelbine for stage IIIA and IIIB non-small-cell lung cancer.

INTRODUCTION: Lung cancer is a leading cause of cancer death in the world. The results from concurrent chemoradiotherapy (CRT) are still disappointing, although long-term survival can be observed in certain populations of patients. Local control is a critical problem in CRT; dose escalation of thoracic radiation (TRT) in CRT has not been effective. PATIENTS AND METHODS: The authors developed a novel TRT scheme of accelerated hyperfractionation using concomitant boost TRT (ccbRT). Total doses of 64 Gy and 40 Gy were given to the gross tumor volume and elective clinical target volume, respectively, for 20 working days, combined with systemic chemotherapy with cisplatin (day 1) and vinorelbine (days 1, 8) with a 3-week interval (NP regimen). The purpose of this phase II study was to evaluate the efficacy and toxicity of this novel treatment. RESULTS: From July 2002 to July 2010, 56 patients were enrolled in this study. One patient was excluded from the analysis. All 55 patients completed ccbRT, and 52 patients (94.5%) underwent at least 2 cycles of NP. Grade 3 esophagitis and grade 3 radiation pneumonitis were observed in 18.2% and 3.6% of the patients. Complete response and partial response were achieved in 24.5% and 69.1% of the patients, resulting in a response rate of 93.6%. The median progression-free survival (PFS) and overall survival (OS) times were 16.7 months and 58.2 months. CONCLUSION: CRT using ccbRT with concurrent NP is safe and effective for locally advanced non-small-cell lung cancer, with good PFS and excellent OS.

Quantitative identification of mutant alleles derived from lung cancer in plasma cell-free DNA via anomaly detection using deep sequencing data.

The detection of rare mutants using next generation sequencing has considerable potential for diagnostic applications. Detecting circulating tumor DNA is the foremost application of this approach. The major obstacle to its use is the high read error rate of next-generation sequencers. Rather than increasing the accuracy of final sequences, we detected rare mutations using a semiconductor sequencer and a set of anomaly detection criteria based on a statistical model of the read error rate at each error position. Statistical models were deduced from sequence data from normal samples. We detected epidermal growth factor receptor (EGFR) mutations in the plasma DNA of lung cancer patients. Single-pass deep sequencing (>100,000 reads) was able to detect one activating mutant allele in 10,000 normal alleles. We confirmed the method using 22 prospective and 155 retrospective samples, mostly consisting of DNA purified from plasma. A temporal analysis suggested potential applications for disease management and for therapeutic decision making to select epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).

A retrospective study of the novel combination of paclitaxel and S1 for pretreated advanced non-small cell lung cancer.

BACKGROUND: Recently, multiple-line chemotherapy has become popular for non-small cell lung cancer (NSCLC). The survival time of patients is influenced by patient characteristics and subsequent treatments. METHODS: The usefulness of paclitaxel plus S1 (PTX+S1) was evaluated in 46 pretreated NSCLC patients. Time from the start of individual regimens till the start of the next one (TNR) was calculated for regimens administered to the study population including PTX+S1 and analyzed by the shared frailty Cox model. RESULTS: The response rate and the median progression-free survival time of PTX+S1 were 32.6% and 253 days, respectively. Substantial difference in TNR was observed in epidermal growth factor receptor mutation status and in line and type of regimens, but not in stage, age, sex, performance status and histology, by univariate analysis. Multivariate analysis revealed that PTX+S1 was only one factor to prolong TNR. CONCLUSION: Because of long progression-free survival and long TNR, further evaluation of PTX+S1 is necessary.

Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas.

PURPOSE: Examination of somatic epidermal growth factor receptor (EGFR) mutations is now a diagnostic routine for treatment of cancer using EGFR tyrosine kinase inhibitors (EGFR-TKI). Circulating tumor DNA is a promising target for noninvasive diagnostics. We evaluated its utility by quantitatively detecting activating and resistant mutations, which were measured with BEAMing (beads, emulsion, amplification, and magnetics). EXPERIMENTAL DESIGN: Twenty-three patients with lung cancer with progressive disease after EGFR-TKI treatment and 21 patients who had never been treated with EGFR-TKIs were studied. Their primary tumors were confirmed to have activating mutations. In the plasma DNA of each patient, the activating mutation found in the corresponding primary tumor and the T790M resistance mutation were quantified by BEAMing. RESULTS: In 32 of 44 patients, activating mutations were detected in the plasma DNA [72.7%; 95% confidence interval (CI), 58.0%-83.6%]. The T790M mutation was detected in 10 of 23 patients in the first group (43.5%; 95% CI, 25.6%-53.4%). The ratio of T790M to activating mutations ranged from 13.3% to 94.0%. The peak of the distribution of the mutation allele fraction in the plasma DNA was in the 0.1% to 1% range. CONCLUSIONS: The major advantage of BEAMing is its ability to calculate the fraction of T790M-positive alleles from the alleles with activating mutations. This feature enables the detection of increases and decreases in the number of T790M mutations in cancer cells, regardless of normal cell DNA contamination, which may be useful for monitoring disease progression. Circulating tumor DNA could potentially be used as an alternative method for EGFR mutation detection.

Small-cell lung carcinoma with long-term survival: A case report.

Small-cell lung carcinoma is the most aggressive among lung cancer subtypes, has a poor prognosis and is highly associated with smoking. We present a case of small­cell lung carcinoma in a patient who had never smoked and has survived for 14 years without achieving a complete remission since the first relapse. His long-term survival may be ascribed to the slow growth of the cancer cells, limited metastasis and favorable responses to the treatments he has received. During these 14 years, only two lymph node metastases and a single metastasis to the brain developed. His small-cell lung carcinoma has been well controlled each time by the various treatments he has received, including chemotherapy, radiotherapy and surgery. Pathologically, the tumor was a typical small-cell lung carcinoma with extensive necrosis. Results showed the mitotic rate and the cell proliferation markers to be greater than those in the intermediate-grade atypical carcinoid, but relatively low. Thus, we conclude that this case belongs to an overlap between intermediate- and high-grade neuroendocrine tumors.

Endotracheal bronchogenic cyst.

A 68-year-old woman was admitted with symptoms of dry cough and stridor. Computed tomography of the chest revealed a cystic, polypoid lesion protruding inside the trachea, extending to the subcarina. The patient underwent a resection of the cyst, which was found to penetrate the wall of the trachea. Most commonly, bronchogenic cysts appear in the medial one third of the lungs or in the mediastinum. This is a rare case of a mediastinal bronchogenic cyst protruding into the trachea.