PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes.

Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a crucial role in the inhibition of melanoma progression through regulation of SRY-box transcription factors (SOX) gene family mRNA transcription. Overexpression of PITX1 in melanoma cell lines resulted in a reduction in cell proliferation and an increase in apoptosis. Additionally, analysis of protein levels revealed an antagonistic cross-regulation between SOX9 and SOX10. Interestingly, PITX1 binds to the SOX9 promoter region as a positive regulatory transcription factor; PITX1 mRNA expression levels were positively correlated with SOX9 expression, and negatively correlated with SOX10 expression in melanoma tissues. Furthermore, transcription of the long noncoding RNA (lncRNA), survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON), was decreased in PITX1-overexpressing cells. Taken together, the findings in this study indicate that PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the SOX signaling.

Integrative Molecular Characterization of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494.

Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations.

BACKGROUND: The aim of this study was to detect the epidermal growth factor receptor (EGFR)-activating mutations and other oncogene alterations in patients with non-small-cell lung cancers (NSCLC) who experienced a treatment failure in response to EGFR-tyrosine kinase inhibitors (TKIs) with a next generation sequencer. METHODS: Fifteen patients with advanced NSCLC previously treated with EGFR-TKIs were examined between August 2005 and October 2014. For each case, new biopsies were performed, followed by DNA sequencing on an Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel version 2. RESULTS: All 15 patients were diagnosed with NSCLC harboring EGFR-activating mutations (seven cases of exon 19 deletion, seven cases of L858R in exon 21, and one case of L861Q in exon 21). Of the 15 cases, acquired T790M resistance mutations were detected in 9 (60.0%) patients. In addition, other mutations were identified outside of EGFR, including 13 cases (86.7%) exhibiting TP53 P72R mutations, 5 cases (33.3%) of KDR Q472H, and 2 cases (13.3%) of KIT M541L. CONCLUSIONS: Here, we showed that next-generation sequencing (NGS) is able to detect EGFR T790M mutations in cases not readily diagnosed by other conventional methods. Significant differences in the degree of EGFR T790M and other EGFR-activating mutations may be indicative of the heterogeneity of disease phenotype evident within these patients. The co-existence of known oncogenic mutations within each of these patients may play a role in acquired EGFR-TKIs resistance, suggesting the need for alternative treatment strategies, with PCR-based NGS playing an important role in disease diagnosis.

EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer.

BACKGROUND: Efficacies of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) rechallenge have been demonstrated in EGFR-mutant non-small cell lung cancer (NSCLC). However, their efficacies were only moderate. Some preclinical studies suggested synergistic effects of bevacizumab to EGFR-TKI in TKI-resistant models. METHODS: We retrospectively evaluated clinical efficacy and safety of EGFR-TKI rechallenge with bevacizumab. Rebiopsy was performed on all studied cases to examine T790M-resistant mutation status. RESULTS: Between January 2010 and June 2014, a total of 24 EGFR-mutant NSCLC patients who had been previously treated with EGFR-TKIs (gefitinib, erlotinib, and/or afatinib) received EGFR-TKI rechallenge with bevacizumab. Twenty-two (92 %) patients underwent erlotinib and two (8 %) gefitinib as rechallenge EGFR-TKIs in combination with bevacizumab. Three patients achieved partial response, and 18 had stable disease, resulting in the response rate (RR) of 13 % and disease control rate (DCR) of 88 %, respectively. The median progression-free survival (PFS) was 4.1 [95 % confidence interval (CI) 2.3-4.9] months, and the median overall survival (OS) was 13.5 (95 % CI 9.7-27.4) months. The RR, DCR, median PFS, and median OS for T790M-positive versus T790M-negative were 0 versus 18 % (p = 0.530), 86 versus 88 % (p = 1.00), 3.3 versus 4.1 months (p = 0.048), and 15.1 versus 13.5 months (p = 0.996), respectively. Severe adverse events (≥grade 3): grade 3 of 1 (4 %) rash; grade 3 of 1 (4 %) paronychia; grade 3 of 1 (4 %) hypertension; and grade 3 of 1 (4 %) anemia, were observed. CONCLUSIONS: EGFR-TKI rechallenge with bevacizumab demonstrated higher DCR and modestly longer PFS than historical data on EGFR-TKI rechallenge alone. Its activity was notably higher in T790M-negative population.

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.

Validation of an Ion Torrent Sequencing Platform for the Detection of Gene Mutations in Biopsy Specimens from Patients with Non-Small-Cell Lung Cancer.

BACKGROUND: Treatment for patients with advanced non-small cell lung cancer (NSCLC) is often determined by the presence of biomarkers that predict the response to agents targeting specific molecular pathways. Demands for multiplex analysis of the genes involved in the pathogenesis of NSCLC are increasing. METHODS: We validated the Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel and compared the results with those obtained using the gold standard methods, conventional PCR and Sanger sequencing. The cycleave PCR method was used to verify the results. RESULTS AND CONCLUSION: The Ion Torrent PGM resulted in a similar level of accuracy in identifying multiple genetic mutations in parallel, compared with conventional PCR and Sanger sequencing; however, the Ion Torrent PGM was superior to the other sequencing methods in terms of increased ease of use, even when taking into account the small amount of DNA that was obtained from formalin-fixed paraffin embedded (FFPE) biopsy specimens.

A new strategy for metachronous primary lung cancer: stereotactic body radiation therapy with concurrent chemotherapy.

BACKGROUND/AIM: Patients with malignant lung cancer often develop a solitary pulmonary nodule after treatment of the initial cancer. In those cases, it is difficult to distinguish primary lung cancer (PLC) from lung metastasis. Therefore, both local therapy for a single lung lesions and systemic therapy for micrometastases are needed. This retrospective study aimed to evaluate the safety and tolerability of concurrent stereotactic body radiation therapy (SBRT) and chemotherapy in patients with metachronous PLC. PATIENTS AND METHODS: We reviewed the records of 10 patients with metachronous PLC treated with SBRT and concurrent chemotherapy with curative intent from 2007 to 2013. The delivered radiation dose was 48 Gy in four fractions. RESULTS: All patients received SBRT with concurrent chemotherapy on schedule. Complete response rate was 90%. Safety profile of this treatment was compatible with that of traditional chemoradiotherapy. CONCLUSION: Our study showed good feasibility and safety for SBRT with concurrent chemoradiotherapy.

A phase II study of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group performance status 2 patients with EGFR wild-type or unknown advanced non-squamous non-small cell lung cancer (HANSHIN Oncology Group 002).

PURPOSE: The aim of our study was to investigate the efficacy and safety of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 patients with epidermal growth factor receptor (EGFR) wild-type or unknown advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: Pemetrexed was administered at 500 mg/m(2) triweekly until progression with supplementations in chemo-naïve ECOG PS 2 patients with EGFR wild-type or unknown advanced non-squamous NSCLC. RESULTS: Between September 2009 and April 2013, twenty-eight patients were enrolled. Median age was 75 (range 59-89). Nineteen (68 %) of 28 were ever smoker, and 18 (64 %) had pulmonary emphysema. Sixteen (57 %) had comorbidities such as hypertension, heart disease, and/or diabetes. In 26 eligible patients, the overall response rate, disease control rate, median PFS, and median overall survival were 11.5, 53.8 %, 3.0 [95 % confidence interval (CI) 1.9-5.7] months and 9.5 (95 % CI 3.3-12.5) months, respectively. Median administered course number was 3 (range 1-14). Median duration of PS maintenance ≤2 was 4.9 (95 % CI 1.3-9.7) months. Common (≥10 %) grade 3/4 toxicities included 7 (27 %) neutropenia, 7 (27 %) leukopenia, 4 (15 %) fatigue, and 3 (12 %) thrombocytopenia. Febrile neutropenia and interstitial lung disease were not observed. There were no treatment-related deaths. CONCLUSION: Pemetrexed monotherapy demonstrated moderate efficacy and good safety in chemo-naïve PS 2 patients with EGFR wild-type or unknown non-squamous NSCLC. It can be a therapeutic option in "frail" PS 2 non-squamous NSCLC patients without the indication of combination regimens, if the patient is EGFR wild-type.

High-dose erlotinib for refractory leptomeningeal metastases after failure of standard-dose EGFR-TKIs.

BACKGROUND: After initial response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM). To achieve longer survival, control of CNS metastases is important, but therapeutic options are limited for LM after failure of standard-dose EGFR-TKIs. METHODS: We retrospectively evaluated the efficacy and safety of high-dose erlotinib in EGFR-mutant non-small cell lung cancer (NSCLC) patients with refractory LM after failure of standard-dose EGFR-TKIs. Survivals from diagnosis of LM to death were compared in patients with or without high-dose erlotinib. RESULTS: Between January 2007 and April 2013, we identified 35 patients with EGFR-mutant NSCLC, complicated with LM, and 12 underwent high-dose erlotinib, while the other 23 received only standard-dose EGFR-TKIs. In patients receiving high-dose erlotinib, magnetic resonance imaging response was confirmed in 3 (30 %) of 10 evaluable patients. Median time to CNS progression was 2.3 months (95 % confidence interval [CI] 1.8-5.5 months). Performance status and neurological symptoms improved in 4 (33 %) of 12 and 6 (50 %) of 12 patients, respectively. No severe adverse events (≥grade 3) associated with high-dose erlotinib were observed. Median survival time from diagnosis of LM in patients with high-dose erlotinib was 6.2 months (95 % CI 2.5-8.5 months), and in those without 5.9 months (95 % CI 1.3-7.8 months) (p = 0.94). CONCLUSION: High-dose erlotinib suggested its efficacy and safety in some patients with refractory LM. It represents a potential therapeutic option against LM after failure of standard-dose EGFR-TKIs, especially to palliate LM-related neurological symptoms.

Response to bevacizumab combination chemotherapy of malignant pleural effusions associated with non-squamous non-small-cell lung cancer.

Malignant pleural effusion (MPE) is a common complication of lung cancer with devastating consequences. Since vascular endothelial growth factor (VEGF) has been implicated in MPE, we hypothesized that bevacizumab, an anti-VEGF antibody, may be effective against MPE in patients with non-small-cell lung cancer (NSCLC). We analysed the records of 21 patients treated for NSCLC-associated MPE between February, 2010 and August, 2013 who consequently underwent bevacizumab combination chemotherapy at the Institute of Biomedical Research and Innovation Hospital. The results were retrospectively analysed using case records and radiographic imaging records. Three patients exhibited complete response of the pleural effusion to bevacizumab treatment, 8 patients achieved a partial response (PR) and 6 patients showed no response. When efficacy was assessed by the response of the measurable primary or metastatic lesions to the treatment, 5 patients achieved a PR, 13 patients had stable disease and 3 patients exhibited progressive disease. The response rate (RR) of the pleural effusion to the antibody treatment was 71.4% and the overall RR of measurable lesions was 23.8%. The median time-to-response for pleural effusion was 132 days. In conclusion, this study demonstrated a high R R to bevacizumab combination therapy for the MPE associated with non-squamous NSCLC. Therefore, bevacizumab therapy may be considered a therapeutic option for patients with non-squamous NSCLC who develop MPE.

Multiple primary malignancies in patients with non-small cell lung cancer.

OBJECTIVE: Information regarding multiple primary malignancies is important, as it has the potential to clarify etiological factors and may indicate the need to refine patient follow-up to include screening for associated malignancies. Upper aerodigestive tract cancer often develops in patients with smoking-related lung cancer; however, little is known about the frequencies or types of other primary malignancies in patients with non-small cell lung cancer (NSCLC) without a history of smoking. METHODS: We retrospectively evaluated the records of patients examined and/or treated for NSCLC at the Institute of Biomedical Research and Innovation between January 2007 and June 2012. Patients In total, 938 patients, including 599 men (never-smoker/ever-smoker: 35/564) and 339 women (never-smoker/ever-smoker: 236/103), were analyzed. RESULTS: Among the 209 patients (22.3%) with multiple primary malignancies, 151 had a history of smoking and 58 were never-smokers. The most common cancers were gastric (43 cases), colorectal (33 cases), and prostate (29 cases) cancer. Smoking-related cancer was more common in current smokers and ex-smokers for both men and women. Among women with NSCLC, never-smokers were more likely to have thyroid cancer than those with a history of smoking (5.1% vs. 0%, p=0.021). CONCLUSION: In this study, several differences in malignancies were observed between never-smokers and patients with a history of smoking. Thyroid cancer and NSCLC co-existed in some women without a history of smoking, implicating predisposing factors other than tobacco smoke in the onset of these cancers.

Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases.

AIM: The aim of the present study was to investigate the prognostic impact of central nervous system metastases (CNS) after acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in EGFR-mutant non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We defined CNS-collapse as death due to uncontrolled and progressive CNS metastases. Post-progression survival (PPS) after initial TKI failure and T790M status were retrospectively compared in 92 patients with or without CNS collapse. RESULTS: The median PPS in 32 patients with CNS-collapse (16.7 months) was significantly shorter than that of 60 without (26.8 months) (p=0.0002). T790M was detected in four (12%) out of the 32 CNS-collapse patients and in 26 (43%) out of 60 without (p=0.0026). Median PPS in 39 patients with leptomeningeal metastases (LM) (11.4 months) was significantly shorter versus 53 without (26.8 months) (p=0.0006). The median PPS was 25.1 months in 40 patients with brain metastases and 11.2 months in 52 without (p=0.0387). T790M was detected in 4/5 resected brain tumors (80%) and in 1/26 cerebrospinal fluid (CSF) samples (4%) (p=0.0008). CONCLUSION: CNS-collapse represented poorer prognosis, which was associated with T790M-negative status and LM. Controlling CNS metastases, especially LM, is important to achieve longer survival.

CT-guided fine-needle aspiration and core needle biopsies of pulmonary lesions: a single-center experience with 750 biopsies in Japan.

OBJECTIVE: CT-guided lung biopsy is a well-established diagnostic method for pulmonary lesions. The aim of our study was to evaluate the diagnostic outcomes and safety profile of conventional CT-guided lung biopsies. MATERIALS AND METHODS: We retrospectively analyzed the results of CT-guided lung biopsies for 750 patients to determine the diagnostic accuracy, complication rates, and independent risk factors for diagnostic failure and severe pneumothorax. RESULTS: Diagnostic accuracy was 92.9%. Independent risk factors for diagnostic failure were malignant lesions (odds ratio [OR], 4.20; 95% CI, 1.66-14.1; p = 0.001), lesions in the lower lobe (OR, 2.01; 95% CI, 1.17-3.47; p = 0.011), lesions 2.0 cm or smaller (OR, 2.87; 95% CI, 1.59-5.48; p < 0.001), and the presence of pneumothorax during the procedure (OR, 2.18; 95% CI, 1.27-3.78; p = 0.004). Pneumothorax requiring drainage occurred in 7% of patients. Independent risk factors for pneumothorax requiring drainage were age of 73 years or older (OR, 2.19; 95% CI, 1.21-4.05; p = 0.009), the presence of emphysema (OR, 4.29; 95% CI, 2.05-8.82; p < 0.001), benign lesions (OR, 2.33; 95% CI, 1.20-4.40; p = 0.012), supine positioning of the patient (OR, 2.61; 95% CI, 1.44-4.84; p = 0.001), and length from the pleura to the lesion of 1.5 cm or greater (OR, 3.08; 95% CI, 1.63-6.17; p < 0.001). CONCLUSION: CT-guided lung biopsy has a high diagnostic accuracy. Complication rates were acceptable and comparable to those of previous studies.

Clinicopathological factors affecting progression-free survival of patients with previously treated advanced non-small cell lung cancer after S-1 therapy with or without bevacizumab.

OBJECTIVES: The aim of the present study was to analyze factors that affect progression-free survival (PFS) of patients with previously treated advanced non-small cell lung cancer (NSCLC) after S-1 therapy, in particular epidermal growth factor receptor (EGFR) mutation status. PATIENTS AND METHODS: Between October 2009 and June 2013, 56 patients with advanced NSCLC were analyzed for EGFR somatic mutations and treated with S-1 with or without bevacizumab. Risk factors associated with PFS were evaluated using a Cox proportional hazards regression model with a step-down procedure. Proportional hazards assumptions were checked and satisfied and only variables with statistical significance in univariate analysis were included in multivariate analysis. RESULTS: The median PFS of patients with EGFR mutations who received S-1 therapy was significantly longer than that of patients with wild-type EGFR. The median PFS of patients with good performance status (PS) was significantly longer than that of patients with poor PS. In multivariate analysis, wild-type EGFR and poor PS were significant and independent negative factors that affect PFS after S-1 therapy. CONCLUSION: EGFR mutation and good PS were positive predictive factors for PFS after S-1 therapy, suggesting that S-1 therapy is efficacious for patients with EGFR-activating mutations even in a multi-line setting.

[Comparison of garenoxacin and levofloxacin for the prophylaxis of febrile neutropenia].

Placebo-controlled randomized trials have demonstrated that prophylactic levofloxacin (LVFX) significantly reduced the incidence of febrile neutropenia (FN) in patients receiving chemotherapy for advanced solid tumors. Garenoxacin (GRNX) has been reported to be more effective than LVFX against gram-positive bacteria especially Streptococcus pneumoniae. Against this background we conducted a study to compare the efficacy and safety of GRNX with that of LVFX for the prophylaxis of FN. We retrospectively analyzed 127 patients at high risk for FN who were administered GRNX or LVFX for the prophylaxis of FN that occurred during chemotherapy for advanced solid tumors. Our primary outcome of interest was the incidence of febrile episodes. Secondary outcomes included evidence of bacterial infection and infection focus when febrile episodes were observed; adverse drug reactions and mortality were also evaluated. Febrile episodes were observed in 2 patients administered GRNX and 7 patients administered LVFX (p=0.044). Definitive pathogenic bacteria and infection focus could not be identified in any patient with febrile episodes and all cases of fever resolved simultaneously with the recovery from neutropenia. We observed 4 cases of rashes and 3 cases of liver dysfunction in the GRNX group and 2 cases of rashes and 2 cases of liver dysfunctions were observed in the LVFX group(not statistically significant in both the groups). No severe adverse effects or deaths were associated with either of these drugs. These results suggest that GRNX is useful for the prophylaxis of FN.

Community-acquired pneumonia caused by carbapenem-resistant Streptococcus pneumoniae: re-examining its prevention and treatment.

A 73-year-old man with no significant past medical history or any history of health care visits was hospitalized for pneumonia. Sputum culture revealed multidrug-resistant Streptococcus pneumoniae, even to carbapenems. The patient was later treated successfully with levofloxacin. Throat cultures from his two grandchildren revealed S. pneumoniae with the same susceptibility pattern. Analysis for resistant genes revealed gPRSP (pbp1a + pbp2x + pbp2b gene variants) in both the patient and his grandchildren, none of whom had received pneumococcal vaccines of any kind. This case illustrates the importance of the emergence of carbapenem-resistant S. pneumoniae. Non-rational use of carbapenems for community-acquired infections may be counterproductive. This case also highlights the importance of pneumococcal vaccinations in children and the elderly.

Prognostic value of bronchoalveolar lavage in patients with non-HIV pneumocystis pneumonia.

OBJECTIVE: Non-HIV patients with pneumocystis pneumonia (PCP) have a poor prognosis. We aimed to evaluate the prognostic factors for in-hospital mortality in terms of the clinical findings, including the results of bronchoalveolar lavage fluid (BALF)-analyses, in non-HIV PCP patients. METHODS: We retrospectively reviewed non-HIV PCP patients diagnosed using bronchoalveolar lavage between April 2006 and July 2012. For patients with a poor respiratory status, noninvasive positive pressure ventilation (NPPV) was used during the bronchoalveolar lavage (BAL) procedure. Data regarding demographics, laboratory findings and the prognosis were evaluated. RESULTS: A total of 29 non-HIV PCP patients were analyzed. NPPV was carried out safely and successfully in 12 patients during the BAL procedure. Twelve patients (41%) died. The multivariate logistic regression analysis identified only BALF neutrophilia to be a significant prognostic factor determining in-hospital mortality. The log-rank test showed that the patients with BALF neutrophilia (≥ 31%) had a significantly lower survival rate than the other patients (p=0.001). CONCLUSION: Only BALF neutrophilia was found to be a significant predictor of survival in patients with non-HIV PCP. Our data also emphasize the significance of performing BAL in such patients, as it provides both diagnostic and prognostic information.

Weekly administration of paclitaxel and carboplatin with concurrent thoracic radiation in previously untreated elderly patients with locally advanced non-small-cell lung cancer: A case series of 20 patients.

Elderly patients with stage III non-small-cell lung cancer (NSCLC) are frequently underrepresented in clinical trials that evaluate chemoradiotherapy, due to their poor functional status, coexisting illnesses and limited life expectancy. The Japan Clinical Oncology Group 0301 trial (JCOG0301) was the first study to demonstrate that thoracic radiation therapy (TRT) with daily low-dose carboplatin may improve the outcome of elderly patients with stage III NSCLC. However, the efficacy and safety profiles of chemoradiotherapy, including platinum doublets, have not been clearly determined in this patient population. We retrospectively assessed the efficacy and toxicity of weekly paclitaxel in combination with carboplatin and concurrent TRT in patients aged ≥75 years with previously untreated locally advanced NSCLC. Between February, 2004 and July, 2013, we collected the data of 20 patients treated with weekly paclitaxel and carboplatin for 6 weeks and concurrent TRT. The objective response rate was 90%, the disease control rate was 95%, the median progression-free survival was 8.63 months [95% confidence interval (CI): 5.7-16.7] and the median overall survival (OS) was 16.1 months (95% CI: 10.7-41.6). There were no grade 4 hematological or non-hematological toxicities and no reported treatment-related deaths. Therefore, platinum doublet therapy in combination with TRT did not provide a clinically significant survival benefit in our population of elderly patients with locally advanced NSCLC. However, the present study demonstrated the good feasibility and safety of this regimen. Further prospective clinical trials are required to evaluate the efficacy and safety of platinum doublet with TRT in elderly patients.

Bevacizumab plus weekly paclitaxel with or without carboplatin for previously-treated non-squamous non-small cell lung cancer.

AIM: The aim of this retrospective study was to evaluate bevacizumab combined with weekly paclitaxel with and without carboplatin in pre-treated patients with non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between November 2009 and October 2011, 43 pre-treated patients with non-squamous NSCLC received bevacizumab (15 mg/kg, day 1) plus weekly paclitaxel (60-80 mg/m(2), days 1, 8, 15) with carboplatin (area under the curve=4-5, day 1) (n=36), or bevacizumab plus weekly paclitaxel (n=7) alone every four weeks. RESULTS: The response rate and disease control rates were 48.8% (21/43) and 86.0% (37/43), respectively. Median progression-free survival was 5.7 months, and overall survival was 14.5 months. Grade 3/4 neutropenia was observed in 37.2% of patients and peripheral neurotoxicity in 0%. No bevacizumab-related death was observed. CONCLUSION: Even for heavily pre-treated patients, bevacizumab plus weekly paclitaxel with or without carboplatin was effective and tolerable in non-squamous NSCLC.