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J.D. Cox



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    MINI 37 - SCLC Therapy (ID 165)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      MINI37.10 - Factors Associated with Severe Pneumonitis for Limited Stage Small Cell Lung Cancer (ID 1714)

      18:30 - 20:00  |  Author(s): J.D. Cox

      • Abstract
      • Presentation
      • Slides

      Background:
      Pneumonitis is a major side effect for the treatment of limited stage small cell lung cancer with concurrent chemotherapy and radiotherapy (CChRT). Prevention is more important than treatment when patients develop grade 3-5 severe pneumonitis (SP). We investigated factors causing SP among patients with limited stage small cell lung cancer (SCLC) treated by CChRT.

      Methods:
      This is a retrospective analysis of 559 patients with limited-stage SCLC treated at a single institution from 1986-2009 with definitive CChRT to a total dose of 45-70 Gray (Gy). Candidate variables included tumor size, year of diagnosis & treatment period (1986-1999 vs. 2000-2009), gender, age, Karnofsky’s Performance Status (KPS), ethnicity, radiation dose, cycles of induction chemotherapy, use of intensity-modulated-radiation-therapy (IMRT) and fractionation. CTCAE v2 before 2003 and CTAE v3 in 2003-2009 were used to evaluate SP Grade 3-5 which were similar. Chi-square test was used for between group comparisons for categorical variables and the median test was used for between group comparisons for continuous variables. Kaplan-Meier estimates were constructed for overall survival (OS), disease-free survival (DFS), local-recurrence-free survival (LRFS), distant metastasis-free survival (DMFS). Analysis was performed using Logistic regression analysis with SP as the primary endpoint.

      Results:
      Of the 559 patients included in this analysis, tumor size was available for 520 patients. Median follow-up was 21.2 months (range 1.2-240.8). Thirty-five (6.2%) patients developed SP (26 Grade-3, 8 Grade-4 & 1 Grade-5). 2D or 3DCRT was used before 2000 and IMRT was usually used for small cell lung cancer in 2000-2009. Univariate analysis (UVA)showed that SP was associated with treatment given in 2000-2009 ( OR 3.93, P<001) ,age ≥ 60 (OR 7.72, P=0.001) ,KPS < 90 (OR 2.22, P=0.02), IMRT (OR 2.3, P= 0.026) and twice daily fractionation( OR 2.38, P=0.03).Induction Chemotherapy reduced SP (OR 0.39, P= 0.023) compared to immediate CChRT. Tumor size (at cut points 3 cm & 5 cm) did not make significant difference regarding SP. Multivariate analysis (MVA) has shown that significantly higher SP was associated with treatment given in 2000-2009 (OR 3.42, P=0.006), age ≥ 60 (OR 7.77, P= 0.001), male (OR 2.12, P=0.047)and twice daily RT (OR 2.45, P=0.026) . OS was significantly reduced among SP group vs. Pneumonitis ≤ Grade 2 (MST 17.9 vs.25 months, P= 0.038) (5-year OS 16 % vs. 27%), respectively. SP were not significantly correlated with DFS, LRFS and DMFS.

      Conclusion:
      Significantly higher SP was seen among patients with limited stage small treated in 2000-2009, age ≥ 60, male and twice daily RT. OS was significantly reduced SP. UVA showed IMRT causing significantly higher SP. MVA did not show IMRT was a significant factor for SP. Tumor size did not show significant difference regarding SP.

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    P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      P2.07-014 - Does Prophylactic Cranial Irradiation Improve Overall Survival of Elderly Patients with Limited-Stage Small Cell Lung Cancer? (ID 2967)

      09:30 - 17:00  |  Author(s): J.D. Cox

      • Abstract
      • Slides

      Background:
      Prophylactic cranial irradiation (PCI) has led to improved overall survival (OS) for patients with small cell lung cancer (SCLC) that has responded completely to chemotherapy and thoracic radiotherapy. However, whether PCI is indicated for elderly patients remains unclear.

      Methods:
      We reviewed 658 patients with limited-stage SCLC treated in 1986-2009 at a single institution with definitive concurrent chemoradiation to a total radiation dose of 45-70 Gy. Variables investigated for possible association with OS included patient sex, age, ethnicity, Karnofsky performance status (KPS) score, year of diagnosis and treatment period (1986-1999 vs. 2000-2009), tumor size, radiation dose, cycles of induction chemotherapy, use of intensity-modulated-radiation-therapy (IMRT), and fractionation. Groups were compared with chi-square tests for categorical variables or medians tests for continuous variables. Kaplan-Meier estimates were constructed for overall survival (OS), disease-free survival (DFS), local-recurrence-free survival (LRFS), distant metastasis-free survival (DMFS).

      Results:
      Among 658 patients, 507 patients were <70 years old (Group A) and 151 patients were ≥70 years old (Group B). Median survival time was significantly longer in the younger group (25.6 months vs. 20.3 months, P=0.007), but no differences were found in DFS, LRFS, or DMFS time by age. Of the 151 patients aged ≥70 years (54 of whom received PCI and 89 did not), those treated in 2000-2009 (vs. 1986-1999) had better brain MFS than those treated in 1986-1999 (P=0.048); those who received PCI had better brain MFS than those who did not (P=0.033). Multivariate analysis showed that among patients aged ≥70, receiving PCI, not receiving induction chemotherapy, and local-regional control were associated with fewer brain metastases (for PCI, subdistribution hazard ratio [SHR]=0.40, 95% confidence interval [CI] 0.17-0.95, P=0.037; for induction chemotherapy, SHR=0.43, 95% CI=0.19-0.96, P=0.039; and for local-regional failure, SHR=0.996, 95% CI=0.993-0.998, P=0.001). Among patients ≥70, receipt of PCI seemed to have been associated with better OS for those with small-volume disease (primary+nodal disease <5 cm, P=0.0545) but not for those with larger-volume disease (P=0.7387).

      Conclusion:
      Patients aged ≥70 years with small-volume limited-stage SCLC seemed to show a benefit in OS from the use of PCI, but those with larger-volume disease did not. Improved brain MFS was associated with use of PCI, no induction chemotherapy, and locoregional control.

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    P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P3.01-065 - PET Tumor Response by PERCIST Predicts Local-Regional Control in Locally Advanced NSCLC after Concurrent Chemoradiotherapy with Erlotinib (ID 1242)

      09:30 - 17:00  |  Author(s): J.D. Cox

      • Abstract
      • Slides

      Background:
      Assessing response of locally advanced non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy by computed tomography (CT) can be complicated by treatment-related pneumonitis or fibrosis. Hypothesizing that measurements of tumor response by [18]F-fluorodeoxyglucose standardized uptake values (SUVs) on positron emission tomography (PET) are more reliably associated with treatment outcomes than those by CT, we compared outcomes and responses according to PET SUV vs. CT among patients in a phase II study of erlotinib+chemoradiation for stage III NSCLC.

      Methods:
      Trial 2005-1023 enrolled 46 patients in 2007–2010; patients received 63 Gy in 35 fractions over 7 weeks with daily erlotinib and weekly paclitaxel-carboplatin. Tumor response was assessed on diagnostic CT scans with contrast or CT from PET-CT and scored according to RECIST 1.1. Tumor response was also assessed by PERCIST 1.0 (based on SUV) as follows: complete response (CR), disappearance of all measurable tumors; partial response (PR), ≥30% reduction in the sum of SUVs of target lesions; progressive disease (PD), ≥30% increase in the sum of SUVs of target lesions; and stable disease (SD), insufficient change in SUV to qualify for PR or PD. The longest diameter of measurable primary lesions and the short axis of measurable lymph nodes were measured. All non-target lesions were also measured. Two-sided Pearson’s chi-square tests were used to assess frequency associations. Overall survival (OS) and local-regional control (LRC) rates were assessed from treatment start by Kaplan-Meier analysis and log-rank tests; P≤0.05 indicated significance.

      Results:
      One patient did not have CT and PET after treatment. For the 45 evaluable patients, best response by PET-CT at 6 months after treatment was CR for 15 patients (33%), PR for 19 (42%), SD for 0, PD for 4 (9%), and not available due to did not have baseline or post treatment PET for 7 (16%). Best response by CT at 6 months was CR for 11 (24%), PR for 27 (60), SD for 3 (7%), and PD for 4 (9%) (P<0.001). The 3 patients with SD by CT all died within 7 months after treatment; the 4 patients with PD had new distant metastases. Four-year OS was associated with best overall response on both PET and CT at 6 months (P<0.05) and at 1 year (P<0.05). LRC was associated with best overall response on PET (P<0.01) and best primary tumor response on PET (P<0.05) at 6 and 12 months. Lymph node response was not associated with OS or LRC by PET or CT.

      Conclusion:
      The CR rate was higher with PET than with CT. Tumor response at 6 months by PET or CT predicted treatment outcomes after chemoradiotherapy for stage III NSCLC. The best overall and primary tumor response by PET within 6 months after treatment was more reliably associated with LRC than was response on CT because of difficulty to assess response due to pneumonitis/lung fibrosis.

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