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Ritsuko Komaki
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MA 01 - SCLC: Research Perspectives (ID 650)
- Event: WCLC 2017
- Type: Mini Oral
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:John V Heymach, Eun Kyung Cho
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 503
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MA 01.10 - Outcome Based on Baseline Total Lymphocyte Count & Neutrophil-To-Lymphocyte Ratio in Extensive Stage Small-Cell Lung Cancer (ID 8570)
12:05 - 12:10 | Author(s): Ritsuko Komaki
- Abstract
- Presentation
Background:
The prognosis for patients with extensive stage small-cell lung cancer (ES-SCLC) is dismal. Immune suppression and systemic inflammation have been linked with outcomes for patients with a variety of malignancies, including lung cancer. The purpose of this study was to investigate the impact of baseline immune suppression and systemic inflammation as assessed with hematologic markers such as total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) on overall survival (OS) in patients with ES-SCLC.
Method:
We retrospectively investigated 253 consecutive patients with pathologically and radiographically proven ES-SCLC treated at a single tertiary cancer center from 1998 through 2015. Potential correlations between initial complete blood counts & differential and other clinicopathologic characteristics were sought. Hematologic markers such as pretreatment TLC, NLR, platelet count, and platelet-to-lymphocyte ratio and other clinical characteristics including age, sex, performance status, race, TNM stage (M1a vs. M1b), weight loss, smoking status, number of initial chemotherapy cycles (<4 vs. ≥4 cycles), thoracic radiation therapy (TRT) dose (<45 Gy vs. ≥45 Gy), and receipt of prophylactic cranial irradiation (PCI) were evaluated for correlation with OS. Median values for each hematologic marker were used as cutoffs. Factors identified as important by univariate analysis were selected as covariates to construct a multivariate Cox model for OS.
Result:
Pretreatment TLC was below the lower limit of normal (i.e., <1.0×10[3]/µL) in 58 patients (23%). Median OS was 11.0 months for the entire cohort. Median OS time was significantly worse in patients with lower pretreatment TLC (TLC ≤1.5×10[3]/µL: 9.8 months, 95% confidence interval [CI] 8.9‒10.7 vs. TLC >1.5×10[3]/µL: 11.6 months, 95% CI 9.3‒13.9) and higher pretreatment NLR (NLR >4.0: 9.3 months, 95% CI 8.8‒9.8 vs. NLR ≤4.0: 13.9 months, 95% CI 11.2‒16.6). Multivariate analysis identified lower pretreatment TLC (hazard ratio [HR] 0.735, 95% CI 0.561‒0.962, P=0.025) and elevated pretreatment NLR (HR 1.534, 95% CI 1.182‒1.991, P=0.001) as being independent predictors of inferior survival. Six other clinicopathologic factors (age >63 years, being male, performance status score ≥2, having <4 initial chemotherapy cycles, TRT <45 Gy, and no PCI) were also shown to be independent predictors of worse OS in multivariate analysis (P<0.05).
Conclusion:
Pretreatment TLC and NLR are useful prognostic markers for OS in patients with ES-SCLC. These findings have important implications for stratifying patients with ES-SCLC for various treatment approaches, possibly including immune modulation.
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.08 - Long Term Follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): a Randomized Phase II Study of 2 SBRT Schedules for Lung Cancer (ID 7390)
16:25 - 16:30 | Author(s): Ritsuko Komaki
- Abstract
- Presentation
Background:
NRG Oncology RTOG 0915/NCCTG N0927 was a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction (arm 1) versus 48 Gy in 4 fractions (arm 2) designed to select the better of the 2 regimens by comparing them at 1 year (yr): first by rates of pre-specified protocol-specified adverse events (psAEs), then by primary tumor control for each arm. 34 Gy emerged as the least toxic yet equally efficacious regimen. Herein, we update those results with long-term follow-up.
Method:
This phase II North American multicenter study of patients aged 18 yrs or older with medically inoperable non-small cell lung cancer with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors was designed to detect 1-yr psAEs rates >17% as primary endpoint. Primary tumor failure (PTF) (either infield or marginal failure) and local failure (either infield, marginal, or involved lobe failure) [with death without failure considered as a competing event]; overall survival (OS); disease-free survival (DFS) and progression-free survival (PFS) were secondary endpoints, but the study was not designed for statistical comparisons of these outcomes. The study opened in September 2009 and closed in March 2011. Updated data were analyzed through November 14, 2016.
Result:
Ninety four patients were accrued, with 86 eligible for analysis: 41 in arm 1 and 45 in arm 2, after 8 cases were excluded. Median follow-up time was 3.8 yrs for all patients, and 5.1 yrs for those alive at analysis. The grade 3 and higher treatment-related toxicity profile was unchanged since previous report, with specifically no new high grade chest wall or grade 5 events. Four of 48 Gy patients had subsequent grade 3 changes in spirometry since meeting the primary endpoint. Medians (in yrs) for 34 Gy and 48 Gy were: 4.1 vs. 4.0 for OS, and 2.6 vs. 2.8 for DFS, respectively. Five-yr outcomes as % (95% CI) for 34 Gy and 48 Gy were: PTF rate of 7.9 (2.0, 19.5) vs. 6.8 (1.7, 16.9); OS of 28.8 (15.4, 43.8) vs. 40.2 (24.9, 55.0); PFS of 19.1 (8.5, 33.0) vs. 31.8 (18.6, 45.9); and second primary rate of 15.5 (6.1, 28.9) vs. 13.3 (5.3, 25.1), respectively. Distant failure as the sole failure or a component of first failure was numerically higher in the 34 Gy arm (7 (46.7%)), but in the 48 Gy arm, rate of second primary development was higher (7 (43.8%)). Approximately 1/3 of patients’ causes of death was unknown, and another 1/3 was related to causes other than cancer or treatment.
Conclusion:
No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 yrs were similar by arm. Median survival times of 4 yrs for each arm suggest similar efficacy pending any larger studies appropriately powered to detect survival differences.
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OA 08 - Neuroendocrine Carcinoma: Translational (ID 667)
- Event: WCLC 2017
- Type: Oral
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:David S Ettinger, S. Zöchbauer-Müller
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 311 + 312
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OA 08.05 - Major Drivers of Chemotherapy and Radiation Utilization for Limited-Stage Small Cell Lung Cancer in the United States (ID 8475)
11:45 - 11:55 | Author(s): Ritsuko Komaki
- Abstract
- Presentation
Background:
Small cell lung cancer (SCLC) accounts for 15-30% of newly diagnosed lung cancers. Although chemotherapy and radiation play a vital role in the initial management of limited-stage SCLC, rates of combined modality utilization in the United States have not been comprehensively studied. As such, the National Cancer Database (NCDB) is a valuable resource to understand patterns of care for limited-stage SCLC, as it captures the majority of newly diagnosed thoracic malignancies in the United States.
Method:
All cases of IASLC defined limited-stage SCLC in the United States National Cancer Database (NCDB) were identified from 2004 to 2013. Rates of chemotherapy and radiation utilization were determined along with key factors associated with their use. Kaplan-Meier analysis and multivariable analysis were used to determine factors independently associated with overall survival.
Result:
From 2004 to 2013, there were 70,247 cases with analyzable data in the NCDB that met IASLC criteria for limited-stage SCLC. Of these cases, 40% did not receive radiation and 20% received neither chemotherapy nor radiation. For the irradiated group, the mean radiation dose was 52.8 Gy with a 16.2 Gy interquartile range. On multivariable analysis, being uninsured (OR 0.75, 95% CI 0.67-0.85, p < 0.001), Medicaid (OR 0.79, 95% CI 0.72-0.87, p < 0.001), and Medicare (OR 0.86, 95% CI 0.82-0.91, p < 0.001) were independently associated with a lower likelihood of radiation delivery in comparison to private/managed care insurance (after adjusting for age, tumor stage, and co-morbidity score). The irradiated group had significantly better median survival than the non-radiated group (33 vs. 17 months, p < 0.001). Radiation (HR 0.62, 95% CI 0.6-0.63, p < 0.001) and chemotherapy (HR 0.55, 95% CI 0.54-0.57, p < 0.001) delivery were both independently associated with better survival on multivariable analysis. Adjusted analysis showed that non-academic programs (HR > 1, p < 0.001) and non-private/managed care insurance (HR > 1, p < 0.001) was independently associated with a survival detriment.
Conclusion:
This is the most comprehensive study currently available describing the utilization of combined modality therapy in the initial management of limited-stage SCLC in the United States. A remarkable number of patients received neither radiation nor chemotherapy as part of their initial oncologic treatment. Insurance status was a key determinant of radiation and chemotherapy delivery even after adjusting for potentially confounding factors. Our findings highlight substantial barriers to quality care delivery and challenges in accrual seen for cooperative group clinical trials for limited-stage SCLC.
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PC 02 - Is Radiotherapy Necessary for Extensive SCLC? (Thoracic Radiation/PCI) (ID 582)
- Event: WCLC 2017
- Type: Pros & Cons
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:J.B. Sørensen, Young-Taek Oh
- Coordinates: 10/17/2017, 11:00 - 12:30, F203 + F204 (Annex Hall)
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PC 02.01 - Thoracic Radiation - YES (ID 7827)
11:00 - 11:20 | Presenting Author(s): Ritsuko Komaki
- Abstract
- Presentation
Abstract:
Small cell lung cancer (SCLC) accounts for 15%–20% of all lung cancers, and the overwhelming majority (>95%) are associated with tobacco exposure. The incidence of all types of lung cancer, including SCLC, has been declining in the United States with the onset of tobacco smoking cessation programs, although this trend took nearly 20 years to become evident among men. Overall survival (OS) rates for patients with lung cancer have also increased by about 5% since the advent of low-dose spiral computed tomography (CT) scanning to detect early lung cancer. The prognosis for patients with SCLC continues to be poor but has improved with the advent of smoking cessation campaigns, more effective chemotherapy agents and radiation planning and delivery techniques, and the use of prophylactic cranial irradiation (PCI) for those who experience a complete response to therapy. Consolidation with chest radiotherapy has improved OS among patients with extensive-stage SCLC who achieved a complete response to chemotherapy. SCLC often presents as bulky symptomatic masses, and mediastinal involvement is common with or without pleural effusion and extrathoracic disease. Extrathoracic spread (i.e., extensive-stage disease) is also quite common, being present in 80%-85% of cases at diagnosis. Brain metastases are present in approximately 20% of patients at diagnosis; roughly half of these metastases are symptomatic and the other half are detected by imaging. Predictors of poor prognosis include poor performance status, older age, and being male. The pathologic subtypes of the disease (small cell carcinoma and combined small cell carcinoma) all carry a similarly poor prognosis. Current guidelines of the U.S. National Comprehensive Cancer Network recommend the use of positron emission tomography (PET), CT scanning, or fused PET/CT scanning of the chest, liver, adrenals, bone, and other areas of concern in the diagnosis and staging of SCLC (NCCN guideline-SCLC 2017) . Thoracic radiotherapy has also become important for improving OS among patients with SCLC who achieved a complete response to chemotherapy. In one prospectively randomized study of 498 patients with extensive-stage SCLC (WHO performance status score 0-2) who achieved complete response to chemotherapy, patients who received consolidation thoracic radiotherapy (30 Gy in 10 fractions) had significantly better 2-year OS rates than did those who did not receive thoracic radiotherapy (13% vs. 3%, P=0.004). Thoracic radiotherapy further improved thoracic-only failure rates (19.8% vs. 46% without, P=0.001) (Slotman B et al, Lancet Oncol 2015;385:36-42). However, many patients with extensive-stage SCLC do not respond to the standard etoposide/cisplatin chemotherapy (Figure 1). Those patients may need to receive molecular-targeted therapies or immunotherapy with the consolidating thoracic radiotherapy. Several histologic and immunohistochemical markers have been evaluated for diagnosing or monitoring treatment response in SCLC, including transcription thyroid factor-1 (positive in >85% of SCLC cases); cytokeratin 7; deletions in chromosome 3; Leu-7; chromogranin A; synaptophysin; myc amplification; and p53 mutations (present in ~75% of cases). Deletions in tumor-suppressor genes are also relatively common and include fragile histidine triad (FHIT) (80%); RAS effector homologue (RASSF1) (>90%); TP53 (>75%); retinoblastoma-1 (RB1) (>90%); and retinoic acid receptor-beta (72%). However, to date no biomarkers have been validated for use in diagnosing SCLC. Moreover, mutations that are often present in non-small cell lung cancer (such as epidermal growth factor receptor [EGFR] mutations and anaplastic lymphoma kinase [ALK]) are rare in SCLC. Several clinicopathologic features have been linked with worse prognosis, including poor performance status, significant weight loss, high lactate dehydrogenase levels, large numbers of metastatic sites, and the presence of paraneoplastic syndromes. Because SCLC has the among the highest rates of somatic driver mutations, and because more than 95% of patients with SCLC are former or current smokers, immunotherapy seems a reasonable approach, as high mutation burdens correlate with good response to chemoradiotherapy and sensitivity to immunomodulators (Peifer M et al., Nat Genet 2012;44(10):1104-10). At MD Anderson Cancer Center, an ongoing phase I/II study of patients with extensive-stage SCLC has been proposed to the NRG as a prospective randomized study (PI J Welsh) (Figure 2). Use of thoracic radiotherapy to consolidate a site at which SCLC is quite likely to recur is reasonable, given that recurrence considerably reduces quality of their life as well as OS. In summary, in most cases SCLC presents as extensive-stage disease, for which outcomes are very poor. Consolidation with thoracic radiotherapy for patients who achieve a complete response to chemotherapy can improve 2-year OS rates. However, less toxic and more effective systemic treatment is also required to derive the greatest benefit from consolidation thoracic radiotherapy. Figure 1(Figure 1) Figure 2(Figure 2)
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