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N. Katakami



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    MO06 - NSCLC - Chemotherapy I (ID 108)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO06.02 - Monitoring EGFR T790M with plasma DNA in lung cancer patients treated with EGFR tyrosine kinase inhibitor in prospective observational study (ID 1399)

      16:20 - 16:25  |  Author(s): N. Katakami

      • Abstract
      • Presentation
      • Slides

      Background
      Detection of mutations with plasma DNA isolated from peripheral blood is an alternative method of biopsy. The gatekeeper T790M mutation of EGFR has been observed in half of patients who acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI). Considering that majority of lung cancer recurrence occurs as distant metastases, determination of T790M using a non-invasive mutation detection system with plasma DNA would be useful. We recently developed a novel non-invasive, fully-automated monitoring system, MBP-QP (mutation-biased PCR and quenching probe) method, to detect T790M using plasma DNA. The detection limit was two copies of control plasmid and 0.2 ng of genomic DNA, the T790M mutation was detected in plasma DNA from 53% of lung adenocarcinoma patients who acquired resistance in the previous retrospective study. Compared with the other methods such as PNA-LNA PCR clamp, the cycleave PCR technique, and digital PCR, the MBP-QP method is simple, sensitive, and reflective of clinical course. To determine the usefulness of the MBP-QP method for monitoring T790M during treatment of EGFR-TKI, a prospective clinical study has been performed.

      Methods
      This is a prospective, multicenter observational study involving lung adenocarcinoma patients carrying EGFR activating mutations such as L858R and exon 19 deletions treated with EGFR-TKI. Primary objective was to determine whether T790M was detected with plasma DNA at the time point of progressive disease (PD), and the secondary objective was correspondence of T790M with plasma and cancer specimens. The association between detection of T790M and effect of EGFR-TKI were also investigated as the exploratory objective. Plasma DNA was isolated from the patients before treatment of EGFR-TKI, every four months during treatment, at the time of occurrence of PD, and after two courses of post-chemotherapy.

      Results
      Ninety lung adenocarcinoma patients treated with EGFR-TKI were enrolled, in whom 51% of L858R and 49% of exon 19 deletions were determined in tumor specimens before treatment. Most of the patients, 92.1%, had adenocarcinoma. 62% (55/90) was stage IV, and 29% (26/90) had postoperative recurrent disease. 43% (38/90) of the patients were treated with EGFR-TKI as the first-line therapy, and the rest of them were previously treated including 17% of the patients experienced with EGFR-TKI. T790M was detected in 23% (21/90) among the entire patients. Forty patients showed PD two years after beginning of this trial, and T790M was detected in 13 patients among the patients who acquired resistance to EGFR-TKI; the frquency of T790M positive among the patients with PD was 32.5% (13/40). Although T790M was temporarily detected during treatment of EGFR-TKI in 8 patients who were still responded to EGFR-TKI, is disappeared after that.

      Conclusion
      T790M was detected in plasma DNA isolated from lung cancer patients whose diseases were progressed. Continuous detection of T790M in plasma DNA seemed to be related with occurrence of PD.

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    MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO21.03 - Variability of epidermal growth factor receptor (EGFR) mutations in serum during erlotinib therapy and its clinical implications: exploratory analysis of a phase II study of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations (ID 2719)

      10:40 - 10:45  |  Author(s): N. Katakami

      • Abstract
      • Presentation
      • Slides

      Background
      Erlotinib is a standard treatment for NSCLC patients harboring EGFR mutations. Many tumors acquire resistance mutations during erlotinib treatment; consequently, confirmation of EGFR mutation status is important to select appropriate subsequent therapy after progression. Obtaining tumor samples is not easy, therefore, serum samples are more applicable for this purpose. This analysis measured serum EGFR mutations before and after administration of erlotinib in a phase II study in Japanese chemotherapy-naïve patients with advanced NSCLC harboring EGFR mutations (JO22903).

      Methods
      We analysed serum samples from patients in the JO22903 study by Scorpion-ARMS to confirm the presence of EGFR mutations before and after erlotinib administration (190 days post treatment initiation and at disease progression). The mutation results were evaluated in relation to clinical characteristics and effects of erlotinib.

      Results
      Of the 103 patients registered in JO22903, 95 consented to the examination of EGFR mutations in serum samples prior to and following administration of erlotinib. Of these 95 patients, 26 were positive for EGFR mutations (16 were exon 19 deletions, nine were exon 21 L858R mutations, one was an exon 20 S768I mutation). In the 26 patients classed as EGFR mutation-positive in serum samples, the concordance rate between tumor samples and serum samples was 96.2% (matching 25 cases except the S768I mutation case). The EGFR mutation detection rate in serum samples prior to erlotinib administration was 35.6% for exon 19 deletions (16/45) and 18.0% for L858R mutations (9/50). In six cases where exon 20 T790M or minor mutations were detected alongside major mutations in tumor samples, the major mutations were detected in corresponding serum samples of four patients but the T790M mutations or minor mutations were not detected in any serum samples. In the 65 cases in which serum samples were taken 190 days after erlotinib administration, five were positive for EGFR mutations (exon 19 deletions in four, and L858R in one). Four of these cases were consistent with the mutation type of the tumor samples taken before erlotinib administration; one case changed from L858R to exon 19 deletion. Serum samples at disease progression were taken for 72 patients. Of these, 16 were positive for EGFR mutations (three were exon 19 deletions, five were exon 19 deletions + T790M, six were L858R and two were L858R + T790M). EGFR mutation type had changed after administration of erlotinib in three cases; these cases also had multiple metastases. Characteristics of EGFR mutation-positive cases in the pre-treatment serum samples were large tumor size, and metastases to other organs (bone, brain, liver). Patients with baseline serum EGFR mutations had median PFS of 9.7 months and those without baseline serum EGFR mutations had median PFS of 15.2 months. Further efficacy results will be presented.

      Conclusion
      The sensitivity of these analyses was not enough to draw firm conclusions; however, results show the possibility that serum EGFR mutations correlate with disease activity and emergence of resistance mutations. Further study is recommended to measure serum EGFR mutations throughout the treatment course, to ascertain whether this can predict the risk of disease progression.

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    MO25 - NSCLC - Combined Modality Therapy II (ID 112)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO25.02 - Thoracic Radiotherapy With or Without Concurrent Daily Low-Dose Carboplatin in Elderly Patients With Locally Advanced Non-small Cell Lung Cancer: Updated Results of the JCOG0301 and Pooled Analysis With the JCOG9812 Trial. (ID 734)

      10:35 - 10:40  |  Author(s): N. Katakami

      • Abstract
      • Presentation
      • Slides

      Background
      The Japan Clinical Oncology Group (JCOG) undertook 2 randomized phase III trials (JCOG9812 and JCOG0301) to assess whether daily low-dose carboplatin plus radiotherapy could improve survival in elderly patients with stage III non-small cell lung cancer (NSCLC) when compared to radiotherapy alone. Although JCOG9812 was prematurely terminated because of a high incidence of treatment-related deaths (TRDs) and instances of protocol violation, especially with regard to radiotherapy planning, the trial regimen was assumed promising. Therefore, JCOG0301 was conducted for the same subjects using the same protocol regimen with modified inclusion criteria regarding pulmonary function and radiotherapy quality control (RTQC) measures. We then carried out a preplanned pooled analysis of these 2 studies.

      Methods
      The eligibility criteria for both trials were age of ≥71 years and unresectable stage III NSCLC. Patients were randomized to receive radiotherapy alone (60 Gy, RT arm) or chemoradiotherapy (radiotherapy, 60 Gy plus concurrent carboplatin, 30 mg/m[2] per fraction up to the first 20 fractions, CRT arm). The primary endpoint for both studies was overall survival (OS). The pooled analysis included OS, progression-free survival (PFS), response rate, and toxicities.

      Results
      In JCOG9812, 46 patients (RT arm, n=23; CRT arm, n=23) were enrolled from November 1999 to August 2001. In JCOG0301, 200 patients (RT arm, n=100; CRT arm, n=100) were enrolled from September 2003 to May 2010, and in total, 246 patients were included in the pooled analysis. Patient characteristics for the RT (n=123) and CRT (n=123) arms were as follows: median age, 77 years (range, 71–93) and 77 years (range, 71–89); stage IIIA/IIIB, 65/58 patients and 63/60 patients; performance status (PS) 0/1/2, 44/74/5 patients and 50/69/4 patients; men/women, 103/20 patients and 96/27 patients, respectively. The median OS for the RT (n=121) and CRT (n=122) arms were 16.3 months (95% CI, 13.4–18.6) and 20.7 months (95% CI, 16.3–26.9), respectively (HR, 0.672; 95%CI, 0.502–0.898, stratified log-rank test one-sided p=0.0034). The pooled HR for PFS was 0.671 (95%CI, 0.514–0.875, stratified log-rank test one-sided p=0.0015). Response rates for the RT and CRT arms were 46.3% and 53.3%, respectively. The number of patients with grade 3/4 hematological toxicities was higher in the CRT arm than in the RT arm: leucopenia (62.2% vs 1.7%), neutropenia (54.6% vs none), and thrombocytopenia (30.3% vs 3.3%). The incidence of grade 3/4 pneumonitis decreased from 4.4% (JCOG9812; RT, 4.5% and CRT, 4.3%) to 2.1% (JCOG0301; RT, 3.1% and CRT, 1.0%), and that of late lung toxicity, from 14.0% (JCOG9812; RT, 10.0% and CRT, 17.4%) to 5.9% (JCOG0301; RT, 5.3% and CRT, 6.5%). The incidence of TRD also decreased from 8.9% (JCOG9812; RT, 1 patient and CRT, 3 patients) to 3.6% (JCOG0301; RT, 4 patients and CRT, 3 patients). As per subgroup analyses, ≤75 years, stage IIIA, male, PS 0, and smoking history were associated with statistically significant improvement in OS in the CRT arm.

      Conclusion
      This combination chemoradiotherapy for elderly patients with locally advanced NSCLC provides clinically significant benefits and RTQC measures are imperative to improve treatment outcome.

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    O15 - NSCLC - Chemotherapy II (ID 109)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O15.05 - Randomized Phase III Trial of S-1 plus Cisplatin versus Docetaxel plus Cisplatin for Advanced Non-Small-Cell Lung Cancer (TCOG0701): Subgroup Analysis. (ID 1895)

      11:15 - 11:25  |  Author(s): N. Katakami

      • Abstract
      • Presentation
      • Slides

      Background
      Docetaxel plus cisplatin (DP) is the only third-generation regimen that has demonstrated statistically significant improvements in overall survival and QOL by head-to-head comparison with a second-generation regimen (vindesine plus cisplatin) in patients with advanced non-small cell lung cancer (NSCLC). S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Molecularly targeted agents including bevacizumab (BEV) have shown activity and safety in non-squamous (non-Sq) NSCLC.

      Methods
      Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either oral S-1 80 mg/m[2]/day (40 mg/m[2] b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m[2] on day 8 every 5 weeks or docetaxel 60 mg/m[2 ]on day 1 plus cisplatin 80 mg/m[2] on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint was overall survival (OS). A non-inferiority study design was employed; the upper confidence interval (CI) limit of the hazard ratio (HR) was <1.322. Secondary endpoints included progression-free survival (PFS), response, safety, and QOL. Subgroup analysis by histology (non-Sq vs Sq) was conducted.

      Results
      From April 2007 through December 2008, 608 patients were randomly assigned to SP (n=303) or DP (n=305) at 66 sites in Japan. Patient demographics were well balanced between the two groups. Non-Sq and Sq patients in SP/DP arm was 251/247 and 50/48 respectively. Two interim analyses were preplanned. At the final analysis, a total of 480 deaths had occurred. The primary endpoint was met. OS in the SP arm was non-inferior to that in the DP arm (median survival, 16.1 vs. 17.1 months, respectively; HR=1.013; 96.4% confidence interval, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. The rates of febrile neutropenia (7.4% vs. 1.0%), grade 3/4 neutropenia (73.4% vs. 22.9%), grade 3/4 infection (14.5% vs. 5.3%), and grade 1/2 alopecia (59.3% vs. 12.3%) were significantly lower in the SP arm than in the DP arm. In terms of physical functioning and global functioning on the EORTC QLQ-C30 and lung cancer module (LC-13), QOL was better in the SP arm (repeated measures ANOVA: p<0.01). Subgroup analysis by histology revealed that the median OS of non-Sq and Sq patients in SP/DP group was 17.4/19.1 months and 12.3/11.7 months respectively, of which hazard ratio was 0.973 (95% CI, 0.797-1.187) and 1.239 (95% CI, 0.819-1.874). Interaction P value was 0.3004.

      Conclusion
      S-1 plus cisplatin is a standard first-line chemotherapeutic regimen for advanced NSCLC both non-Sq and Sq histology. Favorable toxicity profile of the SP regimen and encouraging outcome in patients with non-Sq prompted us to conduct a prospective study of SP plus BEV and maintenance S-1 BEV for non-SQ currently underway.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-019 - Differential efficacy of EGFR-TKI according to variants of exon 19 deletional mutation in non-small cell lung cancer (ID 1177)

      09:30 - 09:30  |  Author(s): N. Katakami

      • Abstract

      Background
      Deletional mutations in exon 19 (Del-19) and L858R point mutation in exon 21 are the most common mutations in the epidermal growth factor receptor (EGFR) gene. In Del-19, several variants actually exist, consisting of different amino acid positions or different sizes. Little evidence has been described whether the variation of Del-19 mutation affects EGFR-tyrosine kinase inhibitor (TKI) sensitivity.

      Methods
      Between December 2005 and March 2013, we screened 111 patients harboring Del-19 who had received EGFR-TKIs. Efficacies of EGFR-TKI such as response rate (RR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated among various patient characteristics (age, gender, ECOG performance status [PS], smoking status, clinical stage, histology, treatment line, types of TKI, initial site of deletion, and presence of insertion). We also performed a multivariate analysis with the proportional hazards model to exclude several confounds. A backward stepwise approach was adopted as our variable selection method for multivariate analyses.

      Results
      Among these 111 patients with exon 19 deletion mutations, 83 (75%) patients had a deletion from E746 (⊿E746 group), and a deletion from L747 (⊿L747 group) 28 (25%). PFS of ⊿E746 group (12.0 months, 95% confidence interval [CI] 9.27-15.63) was significantly longer than ⊿L747 group (10.0 months, 95% CI 6.43-14.27) (p = 0.0129). Insertion mutations were found in 20 patients (18%), and 91 patients (82%) were without insertions. PFS without insertions (12.0 months, 95% CI 9.27-15.17) was significantly longer than with insertions (10.0 months, 95% CI 3.97-12.67) (p = 0.0173). No relationships were found for RR in all patient characteristics. In univariate analysis, PS (0-1 vs 2-4, p = 0.0001), clinical stage (ⅢB/Ⅳ vs recurrence, p = 0.0408), treatment line (1st line vs after 2nd line, p = 0.0122), initial site of deletion, and presence of insertion were statistically significant factors for longer PFS. PS (p <0.0001), histology (Adeno vs Squamous, p = 0.0134) and treatment line (p = 0.0052) were statistically significant factors for longer OS. In multivariate analysis, PS (hazards ratio [HR] 0.580, 95% CI 0.43-0.80, p = 0.0009) and initial site of deletion (HR 0.696, 95% CI 0.55-0.89, p = 0.0047) remained as significant factors for longer PFS. PS (HR 0.525, 95% CI 0.35-0.78, p = 0.0016), gender (Female vs Male, HR 0.701, 95% CI 0.53-0.93, p = 0.0140) and histology (HR 0.479, 95% CI 0.30-0.83, p = 0.0120) were selected as significant factors for longer OS.

      Conclusion
      Our data indicated better efficacy of EGFR-TKI in ⊿E746 group than ⊿L747 group. Deletional locations may affect the sensitivity to EGFR-TKI.

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    P2.21 - Poster Session 2 - Diagnosis and Staging (ID 170)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.21-007 - Computed tomography-guided needle aspiration and biopsy of pulmonary lesions: a single-center experience on 750 biopsies in Japan (ID 3288)

      09:30 - 09:30  |  Author(s): N. Katakami

      • Abstract

      Background
      Computed tomography (CT)-guided fine needle aspiration (FNA) and biopsy is a well-established diagnostic method for pulmonary lesion.The aim of our study was to update the diagnostic outcomes and the safety profile of CT-guided lung biopsies.

      Methods
      We retrospectively analyzed the results of the CT -guided FNA and biopsies for 750 pulmonary lesions in 696 patients, and investigated the diagnostic yield, and complication rates.The independent risk factors for the diagnostic failure (ie, nondiagnostic, false-positive, and false-negative results) and the complications (severe pneumothorax) were determined using multivariate logistic regression analysis.

      Results
      The study included 417 male patients and 279 female patients, with a mean age of 71 years.The mean lesion size was 2.0 cm in maximal diameter.The biopsy results were nondiagnostic in 1.4% of the lesions (11 of 750 cases).The diagnostic accuracy was 92.6% (685/739cases).The sensitivity and specificity for the diagnosis of malignancy was 91.7% (534 of 582 cases) and 99.3% (156 of 157 cases), respectively.The significant independent risk factor for diagnostic failure was Lesions measuring < 2.0 cm (OR, 3.94; p <0.0001).Pneumothorax was the most common complication, and occurred in 36% (272 cases), pneumothorax requiring temporal drainage or chest tube insertion in 7.3% (55 cases), and tension pneumothorax, in 0.2% (2 cases).There were 27 cases (3.6%) with pulmonary hemorrhage, 63 cases (8.4%) with hemoptysis, 2 cases (0.2%) with air embolism , 5 cases (0.6%) with hypertension requiring antihypertensive treatment , 1 case (0.1%) with posterior reversible encephalopathy syndrome（PRES）, and 8 cases (1.0%) with others, including pain, shock, subcutaneous emphysema, subcutaneous hematoma, epilepsy, and bradycardia or tachycardia spell.From a total of 13 patients with severe complications, 12 patients recovered without sequela, however 1 patient recovered but developed paraplegia due to spinal cord infarction; there were no fatalities.The significant independent risk factors for pneumothorax requiring drainage were the depth from pleura < 3.0 cm (OR, 3.60; p <0.001), lesions in the middle lobe (OR, 2.25; p 0.0284),　and COPD patients(OR, 4.38; p <0.001).

      Conclusion
      CT-guided lung FNA and biopsy have a high diagnostic yield, but factors such as the acquisition of lesions measuring <2.0 cm significantly increased the rate of diagnostic failure.The complication rates were acceptable and comparable to previously published figures.The rate of pneumothorax requiring drainage was correlated with the depth from pleura < 3.0 cm, lesions in the middle lobe, and COPD patients.

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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-001 - Feasibility of stereotactic body radiation therapy with concurrent chemotherapy for patients over 75 years old with Stage I non-small-cell lung cancer. (ID 241)

      09:30 - 09:30  |  Author(s): N. Katakami

      • Abstract

      Background
      Stereotactic body radiation therapy (SBRT) is now the standard treatment for elderly patients with inoperable Stage I non-small-cell lung cancer (NSCLC). However SBRT with concurrent chemotherapy may be feasible and effective to selected elderly patients with NSCLC. This retrospective study was aimed to evaluate the safety and tolerability of concurrent SBRT and chemotherapy in patients aged 75 years or older.

      Methods
      We reviewed the records of 11 NSCLC patients who were 75 years or older when treated with SBRT and concurrent chemotherapy with curative intent from 2009 to 2012. Five patients had T1 tumor, the others had T2 tumors. The median age was 81 years with a range of 76 to 88 years. Eight (72%) patients had chronic obstructive pulmonary disease. The median number of Eastern Cooperative Oncology Group (ECOG) performance status of the cases in the beginning of treatment was 1 with a range from 0 to 2. The median delivered radiation dose was 48 Gy in 4 fractions. Concurrent chemotherapy regimen was carboplatin plus paclitaxel, carboplatin plus docetaxel, paclitaxel alone, pemetrexed alone, and S1 alone.

      Results
      All patients received SBRT on schedule. Out of 11 patients, concurrent chemotherapy was successfully accomplished as originally planned in 8 (72%) patients. Initial effect of SBRT plus chemotherapy could be evaluated in all cases. Complete local remission was achieved in 10 patients. One patient alone had local recurrence. Distant metastases observed in 4 patients. In 2 patients, chemotherapy was intermitted due to grade 3 neutrophil count decreased and anemia (Common Terminology Criteria for Adverse Events version 4.0). In another, chemotherapy was broken off because of Grade 2 radiation pneumonitis. During the treatment, no other adverse event was shown. No treatment-related death was observed.

      Grade 2 Grade 3
      Neutrophil count decreased 6 (55%) 1 (9%)
      Anemia 1 (9%) 2 (10%)
      Radiation pneumonitis 1 (9%) 0

      Conclusion
      SBRT plus concurrent chemotherapy might be feasible in selected patients aged 75 years or older with Stage I NSCLC.

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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-007 - Update data of biomarker analysis of WJOG4107 (A randomized phase II trial of adjuvant chemotherapy with S-1 versus CDDP+S-1 for resected stage II-IIIA non-small cell lung cancer (NSCLC)) (ID 1504)

      09:30 - 09:30  |  Author(s): N. Katakami

      • Abstract

      Background
      We conducted a randomized phase II trial for patients with resected stage II-IIIA NSCLC comparing postoperative oral S-1 (80 mg/m2/day for consecutive 2 weeks q3w for 1 year) (S) (N=100) or cisplatin (CDDP) (60 mg/m2 day1) plus oral S-1, (80 mg/m2/day for 2 weeks) q3w for 4 cycles (PS)(N=100). We reported that disease free survival rate at 2 years (DFS@2) (95% confidence interval: CI), a primary endpoint, was 66 (55-74) % for S and 58 (48-67)% for PS. Here, we report the preliminary results of preplanned biomarker analysis, a co-primary endpoint, to identify molecules whose expression is significantly associated with patient outcome.

      Methods
      　cDNA extracted from macro-dissected formalin-fixed paraffin-embedded specimens were available for 197/200 patients. Thirty-one genes including those whose expressions have been potentially associated with　CDDP (e.g. ERCC1, XRCC1, BRCA1, GSTpi, HMG1, TBP) or fluorouracil (FU) sensitivity (TS, DHFR, DPD, UMPS, UPP1) were measured by QGE analysis (MassArray, Sequenom, CA). Additional analysis are being performed to assess ERCC1 isoform expression with an isoform-specific TaqMan probe (Applied Biosystems, CA). The expression of each gene was dichotomized according to its median value.

      Results
      Molecules such as ERCC1 and GSTpi whose expression have been previously associated with CDDP sensitivity did not emerge as predictive markers (P=0.7908, 0.6406, respectively). We quantitated ERCC1 by isotype (202 and 204 cannot be distinguished). There was a trend in patients with high 201 or 202/204, CDDP/S-1 was worse than S-1.

      Conclusion
      Quantitation of ERCC1 by isotype may define a patient subset that would benefit from postoperative platinum therapy.