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Y. Kamiyama



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    O20 - Staging and Advanced Disease (ID 102)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O20.07 - Local therapy for limited distant metastasis in patients with completely resected NSCLC (ID 1262)

      16:15 - 17:45  |  Author(s): Y. Kamiyama

      • Abstract
      • Presentation
      • Slides

      Background
      In general, distant metastasis is regarded as an incurable systemic disease. Therefore, local therapies including metastasectomy or radiotherapy are rarely applied, and the treatment goals are disease control using chemotherapy or palliation. There are, however, several reports in which local therapy can contribute to long-term survival in patients with metastatic disease, especially for brain metastasis or adrenal metastasis in patients with NSCLC.

      Methods
      Between 1986 and 2009, among 1548 patients who underwent surgical resection for NSCLC in our institution, we identified 405 patients who experienced recurrence after R0 resection, without history of other malignancy, and detailed recurrence information available. We investigated the recurrent mode, number of metastatic focus and organ, treatment for metastasis, and prognosis.

      Results
      Among 405 patients, 245 patients had distant metastasis without local recurrence, 115 had local recurrence, and 45 had both local and distant metastasis. We focused on the 245 patients with distant metastasis without local recurrence, including 215 patients who had only single organ metastasis and 93 patients who had only solitary metastasis. The treatments for distant metastasis and the 5-year survival rates were shown in the Table 1. The number of organ involved and metastatic focus were significantly associated with prolonged survival. Local therapy were mainly applied for limited metastases, and associated with higher survival rates. The number of patients and the 5-year survival rates according to the metastatic organ in patients with solitary metastasis are shown in Table 2. Other metastatic organ included soft tissue in 3 patients, kidney in 3, and trachea, intestine, and abdominal lymph node in 1.Finally, 6 patients survived more than 5 years with disease-free status; these included 2 brains, 2 lungs, 1 bone, and 1 subcutaneous metastasis.

      Table 1
      Multiple organ Single organ Multiple Single
      Treatment Number of pts 5y OS (%) Number of pts 5y OS (%) Number of pts 5y OS (%) Number of pts 5y OS (%)
      BSC 8 0 48 6.4 43 7.1 5 0
      Chemo Tx 3 0 32 16.3 30 17.7 2 0
      Radio Tx 19 5.7 101 11.8 43 0 58 21.4
      Surgery 0 - 34 38.0 6 66.7 28 33.4
      Total 30 3.5 215 15.2 122 8.9 93 23.3
      Table 2
      Organ Number of pts 5y OS (%)
      Brain 36 19.2
      Bone 24 16.7
      Lung 18 32.4
      Adrenal gland 6 0
      Other 9 55.6

      Conclusion
      Prolonged survival can be achieved using local therapy in patients with limited distant metastasis irrespective of metastatic organ.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-030 - A Phase II study of Pemetrexed/Carboplatin for Previously Untreated Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: Analysis of the correlation between the Anti-Tumor Efficacy/Toxicity and SNPs of MTHFR. (ID 1822)

      09:30 - 16:30  |  Author(s): Y. Kamiyama

      • Abstract

      Background
      Previous studies investigating a combination of Pemetrexed (P)/Carboplatin (C) showed promising efficacy in the treatment of non-squamous (Sq) non-small cell lung cancer (NSCLC). However, there is no sufficient data of biomarkers. In the present study, we determined the efficacy and toxicity of 6 cycles of P/C for previously untreated patients with advanced non-Sq NSCLC. In addition, we investigated the correlation between the anti-tumor efficacy/toxicity and single nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate reductase (MTHFR).

      Methods
      Eligibility criteria were no prior chemotherapy, StageIIIB without any indications for radiotherapy or IV, non-Sq NSCLC patients, performance status (PS) 0-1, age <76 yrs, and adequate hematological, hepatic, and renal function. Patients received 6 cycles of P (500mg/m[2])/C (AUC6) on day 1, repeated every 3 weeks. Primary end-point was the assessment of tumor response rate measured by RECIST criteria. The SNPs of the MTHFR gene were analyzed from the genomic DNA extracted from the peripheral blood cells drawn prior to the chemotherapy.

      Results
      Thirty-nine patients (pts) were enrolled and all pts evaluable for toxicity and response. Male/Female: 30/9; PS 0/1: 11/28; median age 62(45-75); Path: adeno 37(95%), NSCLC unclassified 2(5%); EGFR mutation: positive 2(5%), negative 35(90%), unknown 2(5%). Evaluations of responses were 1CR, 17PR, 16SD, 5PD (response rate 46.2%). The median progression free survival time (PFS) was 6.8 months, and the median survival time (MST) was 18.1 months. Grade 3/4 toxicities in the first cycle included: leukopenia(3/1), anemia(1/1), thrombocytopenia(4/2), neutropenia(2/1), and AST/ALT elevation(2/0). SNPs of the MTHFR at codon 677 were examined in 28 pts. MTHFR genotypes were as follows: C677C; 8 cases, C677T; 14 cases and T677T; 6 cases. Response rates and disease control rates of MTHFR codon677 genotypes were as follows: C677C (50%/75%), C677T (36%/79%) and T677T (50%/100%). Median PFS and MST of MTHFR codon677 genotypes were as follows: C677C; 4.8/7.6 months, C677T; 6.4/20.6 months and T677T; 6.9/18.5 months. Although there were no significant differences of PFS and overall survival between MTHFR genotypes, those of C677C subjects were shorter as compared to the others.

      Conclusion
      In patients with previously untreated advanced non-Sq NSCLC, P/C appears to be well tolerated and demonstrates encouraging activity. PFS and overall survival of the MTHFR C677C subjects were shorter than those of the C677T or T677T subjects, while the disease control rate of the T677T subjects was higher than that of the C677C or C677T subjects.