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Background Combination carboplatin and S-1 is active in the treatment of non-small cell lung cancer (NSCLC). However, data on this combination for elderly patients with NSCLC are insufficient. Methods Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >75 y, and adequate hematological, hepatic, and renal functions. Carboplatin was administered on day 1 and S-1 was administered orally, twice a day, between days 1 and 14, repeated every 3 weeks. In phase I, the primary end-point was determination of the recommended dose. Starting doses of carboplatin and S-1 were area under the curve (AUC) of 4 and 80 mg/m2/day, respectively. In the extension study, the effects and tolerability of this combination therapy of recommended dose were confirmed. Results A total of 10 patients were entered into phase I and 14 patients were entered into the extension study. The recommended doses for this drug combination are AUC 5 for carboplatin and 80 mg/m2/day every 3 weeks for S-1. With carboplatin and S-1 combination therapy at the recommended dose, the response rate was 30.0% (95% confidence interval (CI): 12-54%) and the disease control rate was 90.0% (95%CI: 68-99%). Thrombocytopenia and neutropenia were major adverse events. Conclusions The recommended doses for this combination therapy are carboplatin AUC 5 and S-1 80 mg/m2/day every 3 weeks, and this combination is effective with tolerable toxicities for advanced NSCLC patients >75 y old. Legal entity responsible for the study University Hospital Medical Information Network. Funding Tokyo Clinical Oncology Group. Disclosure All authors have declared no conflicts of interest.

Introduction: Bronchial-associated lymphoid tissue (BALT) lymphoma is a primary pulmonary B-cell lymphoma. It has an indolent course, with a survival rate of 80% to 95% for 5 years from diagnosis, but progression-free survival is relatively short. There is no consensus on the standard initial treatment for BALT lymphoma. The purpose of this study is to assess the optimal treatment for this rare disease. Patients: We retrospectively studied a total of 8 cases with biopsy-proven BALT lymphoma from August 2003 to March 2013 in 3 institutions. The original study was carried out by Shizuoka Cancer Center. This study includes Shizuoka Cancer Center, Nishigunma National Hospital and Hiroshima University Hospital. Methods: There were 4 men and 4 women, median age 59 years (range, 32–74 years); Five were asymptomatic at diagnosis. In the remaining 3 cases, non-specific pulmonary complaints such as sputum and dyspnea were observed. Five patients had only unilateral lung disease, 3 had bilateral locations and 2 had bone marrow involvement. All patients treated primarily with rituximab mono-therapy, intravenous rituximab 375 mg/m2 per day was added for 4 to 8 cycles. Five achieved complete remission (CR) and 1 had partial response (PR), while the remaining 2 had stable disease (SD). One SD patient, who had dyspnea, received chemotherapy with mitoxantrone plus cladribine and rituximab obtained PR. The remaining non-CR patients had no symptoms, so we decided to observe then with no therapy. All 8 patients were alive during the median follow-up period of 58 months (range, 2-124 months). Results: BALT lymphoma has an indolent nature with favorable prognosis. Intensive chemotherapy may not be necessary. Rituximab mono-therapy may be enough treatment to control symptoms. We will continue to follow these 8 cases and will report on any new additional cases.

Background: Whether local treatment would be equally effective in non-small cell lung cancer patients with postoperative mediastinal lymph nodes recurrence (group A) and primary stage III disease (group B) remains unclear. Methods: Between 2002 and 2009, in a total of 190 non-small cell lung cancer patients with mediastinal lymph nodes metastases treated by radiotherapy alone or chemoradiotherapy, the baseline patient characteristics, responses to radiotherapy alone or chemoradiotherapy and survival were compared between group A (n = 33) and group B (n = 157). Results: Male was the predominant gender, accounting for 60.6% of patients in group A and 78.9% of patients in group B (P = 0.04). Performance status (PS) 0 was the predominant PS, accounting for 78.7% of patients in group A and 57.3% of patients in group B (P = 0.02). The response rates in group A and group B were 66.6 and 72.3%, respectively (P = 0.64). PFS was not significant in group A and group B (median, 15.0 versus 11.0 months; hazard ratio, 0.78; 95% CI, 0.51–1.20; P = 0.26). Meanwhile, OS was superior in group A than in group B (median, 67.0 versus 39.0 months; hazard ratio, 0.56; 95% CI, 0.29–0.97; P = 0.03). Among postoperative patients, PFS (median, 12.5 versus 19.0 months; hazard ratio, 1.50; 95% CI, 0.64–3.49; P = 0.34) and OS (median, 67.0 versus 60.0 months; hazard ratio, 1.22; 95% CI, 0.36–4.14; P = 0.74) were no significance in radiotherapy alone group and chemoradiotherapy group, respectively. Conclusions: Postoperative mediastinal lymph nodes recurrent non-small cell lung cancer showed distinctive features: OS was superior in patients with postoperative mediastinal lymph nodes recurrence than in those with primary stage III disease, although the two groups showed comparable responses and PFS.

Background: The effects of first-line chemotherapy on overall survival(OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer(NSCLC) harboring EGFR mutation. We retrospectively examined whether progression-free survival(PFS), post-progression survival(PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapy with gefitinib in advanced NSCLC harboring EGFR mutation in our institute. Patients and methods: Between January 2006 and June 2012, 35 patients with advanced NSCLC treated with gefitinib as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Male/female = 11/24; Median age was 67 years(range: 45 to 88); adenocarcinoma/others = 35/0; stageIIIB/IV = 3/32; ECOG PS0/1/ ≥ 2 = 15/17/3; EGFR mutation ex19del/ex21L858R/others = 20/15/0; Number of regimens after progression 0/1/2/3/4/5/ ≥ 6 = 11/6/6/3/5/1/3. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS(r = 0.85, P Conclusions: Analysis of individual-level date suggested that PPS could be used as a surrogate for OS in patients with advanced NSCLC with EGFR mutation.Our findings suggest that subsequent treatment after disease progression following first-line chemotherapy with gefitinib for the patients with advanced NSCLC harboring EGFR mutation may greatly influence OS.

Aim: Recently,genomic profiling of lung cancer has been elucidated. However, the characteristics of concurrent genetic alterations remain unclear because of its low frequency. We conducted the Shizuoka Lung Cancer Mutation Study to analyze genetic alterations in patients with thoracic malignancies. Methods: A tumor genotyping panel was designed to assess 23 hotspot sites of genetic alterations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), and gene copy number gain in 5 genes (EGFR, MET, PIK3CA, FGFR1 and FGFR2), and ALK, ROS1, and RET fusions using pyroseqencing plus capillay electrophoresis, quantitative polymerase chain reaction (PCR), and reverse transcription PCR, respectively. Results: Out of 674 lung cancer patients enrolled in our study between July 2011 and March 2013, a total of 50 (7.4%) patients were identified as carrying multiple genetic alterations (44 double, 6 triple mutations). Patient characteristics were as follows: median age (range) 70 (37-93) years; female 32%; never-smorker 24%; histology adenocarcinoma/ squamous cell carcinoma/ small cell carcinoma/ other 70/ 22/ 6/ 2 %. Of the 44 double genetic alterations, 6 patients carried EGFR+PIK3CA mutations; 5 EGFR double mutations (3 exon19del+L858R, 1 exon19del+T790M, 1 L858R+T790M, and 1 G719X+L861Q); 4 EGFR+KRAS mutations; 4 EGFR mutations+EGFR copy number gain; and 1 EGFR+BRAF mutations. Two patients carried EGFR mutations (exon19del or L858R)+ T790M and 3 patients carried EGFR mutations (exon19del or L858R)+MET gene copy number gain in pre-EGFR-TKI treatment setting. Fourteen patients with concurret EGFR(exon19del or L858R)+other mutations received EGFR-TKI treatment. As compared with single EGFR(exon19del or L858R) mutations group of our cohort, patients with concurrent EGFR(exon19del or L858R)+other mutations tend to have shorter survival, however there was no statistically significant difference (MST, 35.3 versus 18.5 months, respectively; p=0.08). Conclusions: Concurrent genetic alterations were detected in 7.4% of patients with lung cancer in Japanese cohorts. EGFR mutations were not mutually exclusive with KRAS and BRAF mutations. T790M and MET gene copy number gain were detected in the patients before EGFR-TKI treatment. Disclosure: All authors have declared no conflicts of interest.

Aim: Although epidermal growth factor receptor (EGFR) mutation analysis has been important to decide treatment of advanced non-small cell lung cancer patients (NSCLC), this analysis requires a tumor tissue, which may not be available in certain situations. About 50% of resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC patients is reported to be attributed to the T790M mutation in exon 20. Although there are some reports to detect EGFR gene mutation using cell-free DNA (cf DNA) from plasma including digital PCR, there is no methods established in clinical studies. We conducted a prospective study to evaluate plasma EGFR gene mutations for advanced NSCLC patients using RNase H-dependent PCR method and Blocking oligo dependent PCR, which can method with high sensitivity and low price, in Shizuoka Cancer Center. Methods: Patients included were as follows: advanced or recurrent NSCLC patients; harboring EGFR mutations (exon 19 deletion or L858R in exon 21) in tumor tissues confirmed by Scorpion ARMS method; pre-treatment or post-progression treatment with EGFR-TKI; written informed consent.Cf DNAs were extracted from plasma by QIAamp Circulating Nucleic Acid Kit (QIAGEN®). L858R and T790M were analyzed by the rhPCR and Luminex Technology®. The Blocking oligo dependent PCR and Luminex Techology® were used for detecting exon 19 deletion. Results: Forty-nine patients, including 22 pre-treatment and 27 post-progression of EGFR-TKI were enrolled in this study. Thirty four patients had exon 19 deletion and 15 had L858R in exon21. In those with exon 19 deletion and L858R in exon 21, the sensitivities of detection of EGFR mutation were 59% (20/34) and 67% (10/15), respectively. 37 % of patients with post-progression of EGFR-TKI showed T790M in exon 20 from their plasma samples, and none of those with pre-treatment did. T790M mutation was detected in 2 re-biopsy tissue samples, and T790M was also detected in their plasma samples. Conclusions: These results suggested that the RNase H-dependent PCR and Blocking oligo dependent PCR methods may be acceptable to evaluatehave a potential as an alternative method to detect EGFR mutations of cf using DNA from plasma. In future, these methods should be validated for large population in multi-institutional studies.Larger study should be conducted to validate these results. Disclosure: Y. Fukuda, K. Yamasaki and R. Umehara: Employee of G and G science. All other authors have declared no conflicts of interest.

Background and aim Several studies suggest that cisplatin-based adjuvant chemotherapy improves survival in patients with completely resected non-small-cell lung cancer in stage II and III; thus, this chemotherapy is recognized as a global standard regimen. However, the efficacy and safety of first-line platinum-based chemotherapy in patients with post-operative recurrence after platinum-based adjuvant chemotherapy has not yet been fully assessed. The aim of this study is to assess these clinical outcomes of platinum-based chemotherapy in patients with post-operative recurrence. Subjects and methods Clinical records of patients with post-operative recurrence who received platinum-based chemotherapy as first line after platinum-based adjuvant chemotherapy at Juntendo University Hospital and Shizuoka Cancer Center between April 2008 and December 2011 were reviewed, and the clinical efficacy and the toxicity were retrospectively evaluated. Result A total of 11 patients were included in this study. The median age was 61 years (range, 36–71 years). Five patients were female. Eight patients were PS 0, the others were PS 1. Adjuvant chemotherapy regimens were CDDP + VNR in five patients, CBDCA + GEM in four patients, CBDCA + PTX in one patient and CDDP + TS-1 in one patient. 72.7 % of patients received at least three cycles of adjuvant chemotherapy. The median recurrence-free survival was 495 days (range, 98–1358 days). First-line chemotherapy regimens were CDDP + PEM in six patients (including one patient with a combination of VEGF-TKI), CBDCA + PTX + Bev in three patients, CDDP + VNR in one patient and CDDP + DTX in one patient. 63.6% patients received at least three cycles of first-line chemotherapy. The overall response rates and the disease control rates were 27.3 and 72.7% (CR/PR/SD/PD/NE: 0/3/5/0/3), respectively. The median overall survival was 841 days (range, 210–1918). Two patients (16.7%) were dropped out. The receiving dose was reduced because of toxicity in four patients (36.4%). Conclusion The first-line platinum-based chemotherapy was effective, but highly toxic in patients with post-operative recurrence after platinum-based adjuvant chemotherapy.