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W. Curran
Moderator of
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OA09 - Locally Advanced NSCLC: Innovative Treatment Strategies (ID 384)
- Event: WCLC 2016
- Type: Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 8
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OA09.01 - The Number or the Position is the Main Prognostic Factor for N2 NSCLC? A Validation of New IASLC N Staging Proposal (ID 5186)
11:00 - 12:30 | Author(s): S. Ricciardi, P. Bertoglio, M. Lucchi, V. Aprile, C.C. Zirafa, A. Mussi
- Abstract
- Presentation
Background:
The eighth edition of lung TNM does not change any N descriptors, but it suggests some potential changes that might be used in the next edition. In fact, N2 would be divided into three groups: pN2a1 (skip lymph-node involvement), pN2a2 (single mediastinal station with hilar involvement) and pN2b (multiple mediastinal involvement). The aim of this study was to verify the value of this classification proposal analyzing our recent surgical experience.
Methods:
We retrospectively selected all patients treated with lobectomy, bilobectomy or pneumonectomy for T1/T2 N2 NSCLC (VII TNM edition) in the period between 2006 and 2010. We excluded all patients who underwent any kind of extended resection and who had another active tumor at the time of operation. A systematic lymph-node dissection was always carried out according to the IASLC guidelines. All patients were then restaged according to the new IASLC proposal. Overall Survival (OS), Disease Free Interval (DFI) and most important variables were analyzed.
Results:
Among 248 surgically treated pN2 patients, 108 entered our inclusion criteria. Pathology report showed a majority of T2 tumors (67,6%) and in almost half of cases an adenocarcinoma (50,9%); a mean number of 16,4 (DS 7,8) lymph-nodes were resected (5,8 (DS 2,9) from the hilum and 10,6 (DS 5,9) from the mediastinum). After restaging all cases with the new IASLC proposal we observed: 30 (27,8%) pN2a1; 57 (52,8%) pN2a2 and 21 (19,4%) pN2b. With a median follow up of 93 months, the median overall survival of the entire cohort was 27 months. pN2a1 had a significant better overall survival compared with the other two groups (p=0,020); conversely no statistically significant difference was found in OS between pN2a2 and pN2b. 1, 3 and 5-year survival for pN2a1, pN2a2 and pN2b were 90%, 81% and 71%; 53%, 37% and 24%; 45%, 26% and 19% respectively. Concurrently DFI was significantly better for pN2a1 (p=0,025). At univariate survival analysis age>65 years, more than 4 positive lymph nodes and postoperative complications were statistically significant variables. At the multivariate analysis only age and the number of positive lymphnodes were independent prognostic factors of a worse survival.
Conclusion:
Our experience partially validate the new proposal of IASLC of N2 staging. Patients with skip lymph-node metastasis (pN2a1) have a statistically significant better prognosis. Concurrently we observed and confirmed the important prognostic value of the number of the involved lymph-node, which should be considered as well in the next editions of the lung cancer staging system.
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OA09.02 - Should Surgery Be Part of the Multimodality Treatment for Stage IIIB Non-Small Cell Lung Cancer (ID 5221)
11:00 - 12:30 | Author(s): S. Collaud, B. Provost, D. Fabre, S. Mussot, B. Besse, O. Mercier, E. Fadel
- Abstract
- Presentation
Background:
Stage IIIB non-small cell lung cancer (NSCLC) is a heterogeneous patient group, including T4N2 and T1-4N3 NSCLC. Traditionally, treatment for stage IIIB consists in definitive chemoradiation. Surgical treatment for stage IIIB NSCLC is used anecdotally in highly selected patients. Here, we studied patient outcome who underwent surgical resection as part of multimodality treatment for stage IIIB NSCLC.
Methods:
All patients from a single institution who underwent surgery for stage IIIB between 2000 and 2015 were included. Surgical candidates were selected on a case-by-case basis during multidisciplinary tumorboard conference. In general, N2-N3 diseases are not considered an absolute contraindication to surgery if lymph node involvement is limited to a non-bulky single site, the tumor is deemed completely resectable without major morbidity and the patient will tolerate multimodality treatment. Mediastinal staging comprised cervical mediastinoscopy, positron emission tomography coupled with CT from 2005 and endobronchial ultrasound guided fine-needle aspiration from 2011. Charts were retrospectively reviewed and data analyzed. Survival was calculated from the date of surgery until last follow-up. Univariate and multivariate analysis were performed to identify prognostic factors.
Results:
From 2000 to 2015, 5416 patients underwent lung resection for NSCLC in our center. Sixty patients (1%) underwent surgery for stage IIIB NSCLC. Forty-three were males (72%). Median age was 58 years (from 22 to 79). Thirty-two patients had T4N2 NSCLC involving the carina (n=16, 50%), superior vena cava (n=4, 12%), carina and superior vena cava (n=5, 16%), left atrium (n=5, 16%), pulmonary artery (n=1, 3%) and spine (n=1, 3%). Twenty-eight patients had N3-disease, involving supraclavicular (n=14, 50%) or contralateral mediastinal lymph nodes (n=14, 50%). Pneumonectomy was performed in 27 patients (45%). Twenty-nine patients (48%) had induction therapy, consisting in chemotherapy alone for all patients. Adjuvant therapy was administered to 52 patients (87%) and consisted mostly of chemoradiation (n=35, 67%). Complete resection (R0) was performed in 55 patients (92%). Post-operative mortality was 3% (n=2). Three- and 5-year overall survivals were 51% and 39%, respectively. Median survival was 40 months. Median follow-up was 17 months. Results of the multivariate analysis identified incomplete resection (p=0.008) and absence of adjuvant treatment (p=0.032) as prognostic factors for poor survival.
Conclusion:
An excellent 5-year survival of 39% was achieved in highly selected patients with stage IIIB NSCLC and treated with multimodality including surgery. Patients with stage IIIB NSCLC should therefore be discussed in a multidisciplinary setting, including thoracic surgeons.
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- Abstract
- Presentation
Background:
Adjuvant chemotherapy is the standard of care for completely resected stage II-IIIa non-small cell lung cancer (NSCLC). A few trials suggest that neoadjuvant chemotherapy is a promising strategy for resectable NSCLC. Indirect comparison meta-analysis of adjuvant versus neoadjuvant therapy showed no difference in survival. This study was conducted to determine the difference of disease-free survival(DFS) between adjuvant chemotherapy and neoadjuvant chemotherapy among patients with resectable NSCLC.
Methods:
Patients with clinical stage IB-IIIA NSCLC were eligible. Patients were randomly assigned to 3 cycles adjuvant DC (Docetaxel: 75mg/m2, Carboplatin:AUC=5 on day 1, every 3wk) after completely resection (lobectomy or pneomonectomy with mediastinal lymphnode dissection, or 3 cycles neoadjuvant DC at the same schedule followed by surgery 3-6 wk after chemotherapy. The primary end point was 3 years DFS; secondary end points were 3ys and 5ys Overall Survival(OS) and Safety. Planned sample size is 410. The trail was early closed because slowly accrued.
Results:
Between March 2006 and May 2011,198 patients from 8 Institute were randomized to neoadjuvant arm (97 cases) or adjuvant arm (101 cases). The median age was 58, male accounted for 80.3%, Adenocarcinoma 48.5%, stage Ib, II a, II b and IIIa were 32.5%, 12.2%, 28.4% and 26.9% respectively. Two arms were balanced. 100% cases received neoadjuvant chemotherapy and 87.4% finished the planned adjuvant chemotherapy. No unexpected toxicities were seen and 41.2% of patients experienced grade 3-4 neutropenia. In neoadjuvant arm, the ORR was 34% and 12.4% patients developed PD. No difference in postoperative complication was found between two arms. Survival analysis show in Table 1.Figure 1
Conclusion:
Adjuvant or neo-adjuvant chemotherapy with docetaxel plus carboplatin in resectable clinical stage IB-IIIA NSCLC are feasible and safe. The final results showed no difference in 3ys DFS and OS between two arms. Long term survival in Adjuvant arm show the tendency of superior to neoadjuvant arm.
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OA09.04 - Discussant for OA09.01, OA09.02, OA09.03 (ID 6949)
11:00 - 12:30 | Author(s): M. Tsuboi
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
Tumor hypoxia is an adverse prognostic factor in many cancers. Hypoxia tracer [18]F-FAZA provides a non-invasive method of hypoxia imaging. This study aims to evaluate the feasibility and potential benefits of using FAZA-PET scans to assess NSCLC tumor hypoxia.
Methods:
The initial 17 patients of an ongoing study with stage II–III NSCLC have been analyzed prospectively by imaging with FAZA-PET before initiation of a radical course of radiotherapy. The hypoxic volume (HV) was defined as all voxels within the tumor with standard uptake value (SUV) more than 1.2 times the aorta SUVmean. The Tmax/Bmean ratio (T/B) was defined as maximum tumor SUV divided by aorta SUVmean. The hypoxic fraction (HF) was determined by dividing the HV by the entire gross tumor volume. Spearman correlation and Fisher’s test were used to explore potential correlations among several variables.
Results:
Median primary and nodal FAZA SUVmax were 1.7 (range: 1.0-3.8) and 1.7 (range: 1.0–3.3). Median primary and nodal T/B ratios were 1.4 (range: 1.0–2.5) and 1.3 (range: 1.0–2.2). Median primary and nodal HF were 3.9% (range: 0.0-38.2%) and 0.6% (range: 0.0-50.7%). The median time from diagnostic FDG PET to study FAZA PET scans was 28 days (range: 1–63). Median primary and nodal FDG SUVmax were 13.5 (range: 5.1–32.2) and 8.3 (range: 2.3–15.7). Larger primary tumor volume is correlated with higher FAZA-T/B (p=0.01) and higher HF (p=0.01). Primary tumors with higher T/B also had higher HF (p<0.0001). The same correlations also apply to nodal disease. Nodal FAZA SUVmax is correlated with primary FAZA SUVmax (p<0.0001). When comparing FAZA-PET with FDG-PET, nodal FDG SUVmax is correlated with nodal FAZA T/B (p=0.01) and nodal FAZA HF (p=0.01), which was not observed for primary disease. For each patient, the nodal station with the highest FAZA SUVmax correlates with the highest FDG SUVmax (p=0.02).
Conclusion:
Imaging intra-lesional hypoxia in NSCLC primary and nodal tumors is feasible and can be achieved with FAZA-PET. Larger tumor volume is correlated with higher T/B and HF in both primary and nodal masses. In the nodal volume only, higher FDG activity is correlated with higher FAZA T/B and higher HF. Ongoing trial accrual and follow-up of our patient cohort will provide more information with regards to the imaging and clinical value of FAZA-PET. This study may eventually lead to using FAZA-PET as a guiding tool to escalate dose to the hypoxic region of the tumor.
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OA09.06 - Metformin Use during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (Abstract under Embargo until December 6, 7:00 CET) (ID 3753)
11:00 - 12:30 | Author(s): K. Wink, J. Belderbos, E. Dieleman, M.M.G. Rossi, C. Rasch, R. Damhuis, R. Houben, E.G.C. Troost
- Abstract
- Presentation
Background:
An increasing body of (pre)clinical evidence has suggested that metformin has an anticancer effect. The aim of this study was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome.
Methods:
A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS)
Results:
No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p = 0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p = 0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p = 0.02 and 0.03).
Conclusion:
Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial.
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- Abstract
- Presentation
Background:
RTOG 0617 recommended 60Gy as the standard dose for unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) Is the conclusion true? The phase I/II trial to determine the feasibility and effects of individual isotoxic radiation dose escalation in unresectable stage Ⅲ NSCLC treated with CCRT based on bilateral lung V20 and advanced technologies was studied.
Methods:
Consecutive patients with unresectable stage III NSCLC were entered in cohorts of eight from March 2006 to May 2009. Patients were assigned to receive concurrent administration of late course accelerated hyperfrationation (LCAHF) intensity modulated radiotherapy (IMRT) and chemotherapy. Isotoxic dose escalation was based on V20 and advanced technologies including PET-CT, single-photon emission computed tomography (SPECT) and LCAHF IMRT. PET-CT was used to delineate the gross tumor volume. SPECT lung perfusion was applied to define different functional lung regions, which was used to optimize the IMRT plans. Patients with a V20 of 27% as a base level were enrolled into the first cohort. From the second cohort, the V20 further increased to 30%, 33%, 35%, 37%, and so on. The criteria for cessation of dose escalation was defined as more than 25% of patients in the cohort experienced dose limiting toxicity (DLT). To test the power of escalation dose, patients with total radiation dose over 66Gy would be assigned to the higher dose group (HD), while the other patients would be assigned to the standard dose one (SD).
Results:
Forty patients were enrolled. The maximum tolerated value of V20 was 37% in this study. Nineteen patients entered SD group, while twenty-one in HD. The overall response rate was as high as 80%. Follow-up for all patients ranged from 1 to 112 months with survival patients from 101 to 112 months. The median overall and progression free survivals were 25.0 and 13.0 months, respectively. 1-, 3-, 5- and 8-year overall survival (OS) rates were 72.5%, 22.5%, 17.5%, and 10.0%, respectively. Patients with stage Ⅲa achieved a longer median OS than those of stage Ⅲb (31 vs. 21 months, P=0.029). Especially, patients received HD radiotherapy got a significant better OS and local recurrence free survival than those in SD (27, 23 vs. 16, 19 months, P = 0.053, 0.037) without increasing severe toxicity.
Conclusion:
The protocol is feasible and effective. In the future, the radiation dose escalation for unresectable stage Ⅲ NSCLC treated with CCRT should be focused on toxicity control and advanced technology application.
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OA09.08 - Discussant for OA09.05, OA09.06, OA09.07 (ID 6955)
11:00 - 12:30 | Author(s): P. Van Houtte
- Abstract
- Presentation
Abstract not provided
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Author of
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MA06 - Locally Advanced NSCLC: Risk Groups, Biological Factors and Treatment Choices (ID 379)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:P. Van Houtte, M. Zemanová
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 2
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MA06.10 - A Pooled Analysis Comparing the Outcomes of Elderly to Younger Patients on NCTN Trials of Concurrent CCRT for Stage 3 NSCLC (ID 4219)
16:00 - 17:30 | Author(s): W. Curran
- Abstract
- Presentation
Background:
Concurrent chemoradiotherapy (CCRT) is the standard treatment (TRT) for stage 3 NSCLC. Elderly patients (pts) are common, may have increased toxicity,& poorer results from CCRT
Methods:
Individual patient data (IPD) from NCTN phase 2/3 trials of CCRT for stage 3 NSCLC from 1990-2012 was collected. We compared the overall survival (OS), progression-free survival (PFS), & adverse events (AE’s) for pts age ≥70 years (yrs) (elderly) vs. <70 yrs (younger). Unadjusted & adjusted Hazard Ratios (HRs) for survival time & their confidence intervals (CIs) were estimated by single-predictor & multivariable Cox models. Unadjusted & adjusted Odds Ratio (OR) for AE’s & their CIs were obtained from single-predictor & multivariable logistic regression models
Results:
IPD from 16 trials were analyzed; 2,768 pts were younger & 832 were elderly. Median OS & PFS for elderly & younger pts are in the table. In the unadjusted & multivariable models elderly pts had worse OS (HR=1.23; 95%CI =1.13-1.35, and 1.20; 95%CI=1.10-1.32, respectively). In the unadjusted & multivariable models, elderly & younger pts had a similar PFS (HR=1.02; 95% CI=0.94-1.11 and 1.01, 95% CI=0.92-1.10, respectively). Elderly pts had a higher rate of grade ≥3 AE’s in the unadjusted & multivariable models (OR=1.25; 95% CI=1.00-1.57 and 1.30; 95%CI=1.03-1.62, respectively). A lower percentage of elderly pts compared to younger completed TRT (47% and 57%, respectively; P<0.0001) & higher percentage stopped due to AE’s (20% and 13%; P<0.0001). Grade ≥ 3 AE’s (occurring at a rate ≥ 2.5%) with a higher rate in the elderly: neutropenia, dyspnea, fatigue, anorexia, vomiting, dehydration, hypoxia, hypotension, & pneumonitis (P<0.05).
a: Log-rank test for survival times, chi-square test for AE’s, and Fisher’s exact test for deaths. The P-values from these tests are unadjusted. b: Data available on 2,091 patientsAge ≥ 70yrs Age < 70 yrs P-value[a] Median OS (months) 17.0 20.7 < 0.01 Median PFS (months) 8.7 9.1 0.68 All toxicities grade ≥3 86% 84% 0.04 Hematologic AE’s grade ≥3 65% 61% 0.04 Non-hematologic AE’s ≥3 68% 62% <0.01 Grade 5 AE’s 9.0% 4.4% <0.01 TRT related deaths[b] 3.2% 2.0% 0.12
Conclusion:
Elderly pts in CCRT trials had worse OS, similar PFS, & a higher rate of severe AE's.
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P1.01 - Poster Session with Presenters Present (ID 453)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.01-035 - Trends, Patterns of Treatment and Outcomes in Non-Small Cell Lung Cancer (NSCLC) as a Second Primary: A National Cancer Data Base (NCDB) Analysis (ID 6185)
14:30 - 15:45 | Author(s): W. Curran
- Abstract
Background:
The prevalence of NSCLC as a second primary tumor has been increasing over the past decades, though very little data are available in the literature. We analyzed the NCDB, an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society, to study the outcomes and patterns of treatment of patients (pts) diagnosed with NSCLC as a second or subsequent primary (SP).
Methods:
The NCDB was queried from 2004 to 2012 for NSCLC pts. Pts diagnosed with NSCLC as SP were compared with pts with de novo (DN) NSCLC as defined by sequence number in the database. Univariate (UV) and multivariable analyses (MV) with overall survival (OS) were conducted by Cox proportional hazards model. Kaplan-Meier plots were produced to compare the survival curves by subgroups along with log-rank p-values.
Results:
A total of 207,518 pts in SP and 697,709 pts in DN groups were included in the analysis, which accounted for 22% and 74% of all NSCLC pts respectively. Pt characteristics (SP/DN %): median age 72/68, male 53/53, white 89/84, stage IV 28/41, treated at academic centers 33/32, government insured 72/57, mean tumor size (cm) 3.5/4.4. An increasing trend in incidence of SP was observed (19.5% in 2004 to 24% in 2012) vs. a decreasing trend in DN (75.6% in 2004 to 73% in 2012). About 12% in SP and 15% in DN received chemotherapy as part of their treatment. Surgery was performed in 39% of SP group vs. 28% in DN. Radiation was given to 43% of the pts in DN vs. 36% in SP. On UV and MV analysis, SP was associated with better survival than DN (HRs 0.84 and 0.93 respectively; p<0.001). The SP group had higher 5-year OS (23% vs. 19.6%, p<0.001) and a higher median survival (17 vs. 11.5 months) compared to DN. On stratifying by stage, DN had inferior survival in stage IV pts (HR 1.12, p<0.001) compared to SP but better survival in stage I and II pts (HRs 0.86 and 0.93, p<0.001). No difference in OS was seen in stage III pts (HR 1.01, p= 0.4).
Conclusion:
The incidence of second primary has increased over the past decade. Second primary NSCLC is diagnosed at an earlier stage, smaller tumor size, and is associated with a better survival, compared to de novo NSCLC.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-015 - Guideline Concordant Care is Associated with Better Survival for Patients with Stage III Non-Small Cell Lung Cancer (ID 5103)
14:30 - 15:45 | Author(s): W. Curran
- Abstract
Background:
Current evidence-based guideline-concordant care (GCC) is administration of platinum-based chemotherapy during thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (NSCLC) patients with good performance status. This study evaluates factors associated with lack of GCC.
Methods:
Patients (pts) with unresected stage IIIA/IIIB NSCLC diagnosed from 2005 – 2013 and Charlson-Deyo Score 0 were identified from the National Cancer Data Base (NCDB). Primary outcomes measured were receipt of GCC, defined by administration of chemotherapy with TRT commencing within 2 weeks of each other and minimum TRT dose of 60 Gy, and overall survival (OS). Multivariable logistic regression (MLR) modeling was performed to identify variables associated with non-GCC. Cox proportional hazard modeling was utilized to examine OS.
Results:
Patient characteristics (n=37,809) included: mean age 67.8 years; 55% male; 13% African American; 3.4% Hispanic, 3.6% ‘other’ race/ethnicity; 66% government-insured; mean tumor size 5.0 cm; 38% adenocarcinoma; 32% squamous cell carcinoma (SCC); 30% large cell/other histology. In total, 28% of pts received GCC. On MLR analysis, Hispanic pts were more likely to receive non-GCC (OR=1.34, p <0.001) compared to non-Hispanic pts. Uninsured pts were more likely to receive non-GCC (OR=1.57, p<0.001) compared to privately-insured pts. Patients treated in the western, southern, or northeastern U.S. were more likely to receive non-GCC (OR= 1.43, 1.45, 1.21, all p values <0.001) compared to pts treated in the Midwest. Adenocarcinoma and large-cell/other histological types were more likely to receive non-GCC (OR= 1.71, 1.39, both p<0.001) compared to SCC. For every one-year increase in age or 50-mile increase in distance to treatment facility, patients had a 4% or 3% increased odds of not receiving GCC (OR=1.04, 1.03; p<0.001, p = 0.003, respectively). On hazard modeling, those receiving non-GCC had higher death rates compared to those receiving GCC (HR=1.42, p<0.001). Survival rates were lower for Hispanics receiving non-GCC versus GCC (HR=1.24, p=0.034). Other groups with lower OS for non-GCC versus GCC included: the uninsured (HR=1.61, p<0.001), treatment in the western, southern, or northeastern US (HRs= 1.56, 1.40, 1.33, respectively, p<0.001), adenocarcinomas and large cell/other histologies (both HR=1.40, p<0.001).
Conclusion:
Socioeconomic factors, including Hispanic ethnicity, lack of insurance, geographic location, and distance from treatment facility are associated with receipt of non-GCC. Patient and disease specific factors including increasing age and adenocarcinoma histology are also associated with non-GCC. Future interventions could target these groups to improve provision of GCC.
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SC03 - Advances in Radiation Oncology (ID 327)
- Event: WCLC 2016
- Type: Science Session
- Track: Radiotherapy
- Presentations: 1
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SC03.04 - Molecular Predictive Biomarkers for Radiotherapy Outcome in Lung Cancer (ID 6611)
11:00 - 12:30 | Author(s): W. Curran
- Abstract
- Presentation
Abstract not provided
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