Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non–small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer–specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68–0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63–0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

Background

Accurate initial staging is critical for appropriate management of small cell lung cancer (SCLC) because of stark differences in management and prognosis. Standard therapy for limited-stage SCLC (LS-SCLC) in patients with good performance status is 4 to 6 cycles of platinum-based chemotherapy with early concurrent thoracic radiotherapy (RT) with curative intent, followed by prophylactic cranial irradiation (PCI) in good responders.14 In contrast, extensive-stage SCLC (ES-SCLC) is treated with a backbone of 4 to 6 cycles of chemotherapy, potentially followed by thoracic RT and/or PCI for responders.48 Robust data exist on the impact of PET on stage migration and appropriate management911 in non–small cell lung cancer (NSCLC).1214 However, similar studies are rare regarding SCLC.1519 Although the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for SCLC recommend PET/CT in patients with suspected LS-SCLC based on staging accuracy and RT planning,4,15,17,18,20,21 investigation of the effect of PET on outcomes and stage migration is limited to a small single-institution study suggesting the association of PET staging with superior clinical outcomes in LS-SCLC.19 PET/CT is not currently recommended for ES-SCLC.

Because randomized studies to clarify the impact of PET on SCLC are likely not feasible, and large registries have the ability to evaluate both the longitudinal phenomenon of stage migration and its effect on outcomes (as in NSCLC), the authors assessed the Department of Veterans Affairs Central Cancer Registry (VACCR) and VA administrative databases for trends in the use of PET in staging SCLC and its impact on outcomes, primarily focusing on the cohort of patients with LS-SCLC receiving chemoradiotherapy (CRT), because treatment algorithms did not change during this period.

Patients and Methods

Data Source

The VACCR is a mandatory and quality-assured nationwide database of all veterans diagnosed with cancer in the Veterans Health Administration (VHA). It is linked to the VA electronic medical record (EMR) and administrative databases such as the VA Corporate Data Warehouse (CDW) and the National Death Index (NDI).2224 Baseline patient, disease, and treatment characteristics were obtained from the VACCR, and additional treatment details, comorbidities, and vital status were assessed using the CDW. The NDI was used to identify the cause of death. This study was approved by the Durham VA Institutional Review Board.

Study Design and Population

The initial study population consisted of all veterans in the VACCR diagnosed with SCLC between January 1, 2001, to December 31, 2010. To characterize the relationship with PET and other covariates, treatment outcomes were assessed in greater detail in the subcohort with LS-SCLC treated with concurrent CRT, including those who had received surgery. Patients with AJCC stage I–III disease were considered LS-SCLC, and those with stage IV disease were considered ES-SCLC. Concurrent CRT was defined as RT beginning within the window from 14 days before to 100 days after the start of chemotherapy. Patients were excluded from this subcohort if treatment started >180 days after diagnosis. A separate analysis was performed in all patients with ES-SCLC.

Measures, Outcomes, and Covariates

The primary outcomes of this study were PET use, overall survival (OS), and lung cancer–specific survival (LCSS). End points were assessed from the date of diagnosis. Survival data from the CDW were available through January 22, 2015. Because of available NDI data, LCSS was analyzable for patients diagnosed from 2001 through 2008 and censored after December 31, 2011. OS and LCSS were otherwise censored at the last encounter. The Charlson comorbidity index (CCI) was calculated using ICD-9 diagnoses in the year preceding diagnosis.

Radiation fractionation was determined based on Current Procedural Terminology (CPT) codes for treatment within 180 days of diagnosis and review of CDW free text data and individual patient records in the EMR. Fractionation was defined based on a requirement of 24 to 35 fractions if treated once daily and 28 to 30 fractions if treated twice daily. All other patients were classified as having incomplete RT or unknown fractionation. Early RT was defined by an RT start date before 9 weeks after the start of chemotherapy.25 Receipt of chemotherapy was determined based on the VACCR, and agents were identified with the VA Decision Support System Pharmacy file. Because patients may have received chemotherapy at outside facilities, they were classified as receiving platinum-based therapy, non–platinum-based therapy, or an unknown chemotherapy regimen. Patients documented as having received either agent in typical doublet therapy were classified as receiving platinum-based therapy. Patients documented in the VACCR as having undergone resection, surgery not otherwise specified, or tumor destruction were considered to have undergone surgery. Use of PET and brain MRI for staging was identified based on CPT codes claimed within and outside the VA and entered within 180 days before or after diagnosis but before treatment.

Statistical Analysis

PET use and stage distribution during the study period were tabulated. OS and LCSS were assessed using the Kaplan-Meier method. Median OS and PET use were trended over time and assessed with time as a continuous variable with Cox regression.

For the LS-SCLC and ES-SCLC subcohorts, baseline patient characteristics were compared using the Pearson chi-square, Fisher exact, or Student t test as appropriate. Univariate and multivariate logistic regression were also used to assess the association between patient characteristics and PET use. OS and LCSS were assessed using the Kaplan-Meier method and log-rank test. Characteristics associated with clinical outcomes were assessed with the Cox proportional hazards method, including age, sex, year, race, tobacco use, AJCC stage, CCI, MRI brain staging, surgery, treatment fractionation, early or late RT, platinum-based chemotherapy, and PET staging. For LS-SCLC, the time between the most recent PET and the start of chemotherapy or RT was also considered. Multivariate models were constructed based on univariate analysis and clinical hypotheses. The proportional hazards assumption was evaluated based on the relationship between scaled Schoenfeld residuals and time.

The Kaplan-Meier method and log-rank test were also applied to propensity-matched cohorts based on predictors of PET staging from logistic regression. Cohorts were created with 1:1 nearest neighbor matching in each of the LS-SCLC and ES-SCLC subcohorts.26 Given the potential for bias between facilities’ expertise and resources, an additional propensity-matched analysis factoring in the treatment facility was performed.

Statistical analyses were performed with SAS 9.4 (SAS Institute Inc.) and R version 3.4.0 (R Foundation). Statistical tests were 2-sided, and P<.05 was considered statistically significant.

Results

Patient Characteristics

Among 10,135 patients in the VACCR diagnosed with SCLC from 2001 through 2010, 3,510 had LS-SCLC, 6,143 had ES-SCLC, and 482 had an unknown stage (see supplemental eFigure 1, available with this article at JNCCN.org). Median follow-up was 6.9 months; 9,865 of the 10,135 patients had died at last follow-up (97.3%). The mean age was 66.7 years. Most patients were male (98%), current smokers (59%), and had stage IV/ES-SCLC (61%). Diagnoses were distributed evenly through the study period (supplemental eTable 1).

In the decade analyzed, the authors observed an increase in median OS for all patients from 6.2 (95% CI, 5.6–7.0) to 7.9 months (95% CI, 7.3–8.4) (Figure 1A; hazard ratio [HR], 0.99 per year; 95% CI, 0.98–0.99; P<.0001). When analyzed by stage, median OS improved in both patients with LS-SCLC (from 10.9 [95% CI, 9.7–12.3] to 13.2 months [10.8–16.1]; HR, 0.98; 95% CI, 0.97–0.995; P=.004) and those with ES-SCLC (4.0 [3.2–4.7] to 6.1 months [5.5–6.9]; HR, 0.98; 95% CI, 0.97–0.99; P<.0001). These same trends were identified in LCSS, with an increase in the median LCSS of all patients (7.5 [6.9–8.23] to 8.6 months [8.03–9.33]; HR, 0.98; 95% CI, 0.97–0.99; P<.0001), those with LS-SCLC (12.1 [10.4–13.8] to 15.2 months [12.3–not reached]; HR, 0.96; 95% CI, 0.95–0.98; P<.0001), and those with ES-SCLC (5.0 [4.4–5.9] to 7.0 months [6.2–7.6]; HR, 0.98; 95% CI, 0.97–0.99; P<.0001) (Figure 1B).

Figure 1.
Figure 1.

Median OS and LCSS by stage over time. As PET use increased from 2001 to 2010, there was an increase in median OS rates in LS-SCLC (10.9–13.2 months; HR, 0.98; 95% CI, 0.97–0.995; P=.004) and ES-SCLC (4.0–6.1 months; HR, 0.98; 95% CI, 0.97–0.99; P<.0001). (A) Median OS for all patients also increased from 6.2 to 7.9 months during this period (HR, 0.99; 95% CI, 0.98–0.99; P<.0001). (B) Similar trends were seen in LCSS (12.1–15.2 months for LS-SCLC [HR, 0.96; 95% CI, 0.95–0.98; P<.0001], 5.0–7.0 months for ES-SCLC [HR, 0.98; 95% CI, 0.97–0.99; P<.0001], and 7.5–8.6 months overall [HR, 0.98; 95% CI, 0.97–0.99; P<.0001]).

Abbreviations: ES-SCLC, extensive-stage SCLC; HR, hazard ratio; LCSS, lung cancer–specific cancer; LS-SCLC, limited-stage SCLC; OS, overall survival; SCLC, small cell lung cancer.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Increasing PET Use and Staging

When analyzing both the LS and the ES cohorts, the authors hypothesized that staging changes during the decade in the study may be associated with the observed improvement in outcomes. More patients had pretreatment PET later in the decade, increasing from 1.1% in 2001 to 39.2% in 2010; this increase was greatest in patients with LS-SCLC (from 1.8% to 53.7%) (Figure 2A). The proportion of LS-SCLC decreased among staged patients, from 36.1% in 2001 to 34.3% in 2010, with a corresponding increase in ES-SCLC from 63.9% to 65.7%, respectively (Figure 2B). Overall during the study period, fewer patients had unknown stage (from 8.2% to 3.0%), which largely corresponded to an increase in ES-SCLC diagnoses (from 58.7% to 63.7%); LS-SCLC diagnoses remained static, from 33.1% to 33.2%.

Figure 2.
Figure 2.

PET use and stage over time. (A) Rates of PET staging increased from 1.1% in 2001 to 39.2% in 2010. This trend was seen across LS-SCLC and ES-SCLC. (B) As PET adoption increased, there was an increase in ES-SCLC (63.9%–65.7%) and a decrease in LS-SCLC (36.1%–34.3%) among staged patients.

Abbreviations: ES-SCLC, extensive-stage SCLC; LS-SCLC, limited-stage SCLC; SCLC, small cell lung cancer.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Limited-Stage SCLC

Among 1,536 patients with LS-SCLC treated with CRT, 397 were staged with PET. Patients staged with pretreatment PET were older, were more recently diagnosed, had a less advanced AJCC stage, were more likely to undergo surgery with CRT, had a higher CCI, had a higher rate of brain MRI for staging, and were more likely to be treated with twice-daily RT (supplemental eTable 2). Multivariate logistic regression identified age, diagnosis year, AJCC stage, and brain MRI for staging as independent factors associated with PET staging (Table 1).

Table 1.

Univariate and Multivariate Logistic Regression for Use of PET Staging in Patients With LS-SCLC Undergoing CRT

Table 1.

Median follow-up in the LS-SCLC cohort was 15.5 months; 1,387 of 1,536 patients (90.3%) died by the last follow-up, and median follow-up for surviving patients was 74.9 months. For LS-SCLC treated with CRT, median OS was 15.5 months (Figure 3A). With pretreatment PET, median and 3-year OS were significantly greater than without pretreatment PET (median, 19.8 vs 14.3 months; 3-year OS, 31% vs 20%; P<.0001; Figure 4A). This improvement in OS was evident after propensity matching (median, 19.8 vs 13.4 months; 3-year OS, 31% vs 19%; P<.0001; Figure 5A). Propensity matching with the inclusion of facility redemonstrated these results (median, 19.8 vs 14.3 months; 3-year OS, 31% vs 22%; P=.002). Cox proportional hazards demonstrated independently longer OS with PET staging (HR, 0.78; 95% CI, 0.68–0.90) in addition to younger age, female sex, less-advanced AJCC stage, lower CCI, complete RT/known RT fractionation, and platinum-based chemotherapy (Table 2). Neither the time between PET and start of treatment nor the fractionation schedule of RT (twice daily vs once daily) were significant in Cox proportional hazards analysis.

Figure 3.
Figure 3.

OS and LCSS for patients with limited-stage small cell lung cancer treated with chemoradiation. (A) Median OS was 15.5 months and (B) LCSS was 17.7 months.

Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Figure 4.
Figure 4.

OS and LCSS by PET staging in patients with limited-stage small cell lung cancer treated with chemoradiation. (A) OS was longer in patients who had PET staging (median, 19.8 months) than in those who did not. (B) LCSS was similarly longer in patients who had PET staging (median, 22.9 months) than in those who did not (16.7 months).

Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Figure 5.
Figure 5.

Propensity-matched OS and LCSS by PET staging in patients with limited-stage small cell lung cancer treated with chemoradiation. (A). OS remained longer in patients who had PET staging (median, 19.8 months) than in matched patients who did not (13.8 months). (B) LCSS was similarly longer in patients who had PET staging (median, 22.9 months) than in matched patients who did not (15.7 months).

Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Table 2.

Univariate and Multivariate Analysis of OS in Patients With LS-SCLC Undergoing CRT

Table 2.

LCSS similarly increased with pretreatment PET. This was 17.7 months for all patients (Figure 3B) and 22.9 months with PET compared with 16.7 months without (P<.0001) (Figure 4B). Propensity matching confirmed increased LCSS (median, 22.9 vs 15.0 months; 3-year LCSS, 40% vs 26%; P<.0001) (Figure 5B). Including the facility in propensity matching corroborated these results (median, 22.9 vs 16.7 months; 3-year LCSS, 40% vs 29%; P=.0003). PET staging (HR, 0.74; 95% CI, 0.63–0.87), younger age, less-advanced AJCC stage, complete RT/known RT fractionation, and platinum-based chemotherapy were associated with longer LCSS (Table 3).

Table 3.

Univariate and Multivariate Analysis of LCSS in Patients With LS-SCLC Undergoing CRT

Table 3.

Extensive-Stage SCLC

Among 6,143 patients with ES-SCLC, 793 (13%) were staged by PET and 5,350 (87%) were not. Chemotherapy was given to 4,195 patients (68%). Those with PET tended to be younger, were more recently diagnosed, had greater comorbidity, were more likely to have brain MRI for staging, and received chemotherapy (supplemental eTable 3). Using multivariate logistic regression, year of diagnosis, CCI, staging brain MRI, and receipt of chemotherapy were associated with use of PET staging (Table 4).

Table 4.

Univariate and Multivariate Logistic Regression for PET Staging in Patients With ES-SCLC

Table 4.

Median follow-up in patients with ES-SCLC was 4.7 months. Those staged with PET had longer median OS of 7.83 versus 4.23 months (P<.0001; Figure 6A). This difference remained with propensity matching (7.83 vs 5.80 months; P<.0001; Figure 7A) even with the facility included as a factor (7.83 vs 5.20 months; P<.0001). A Cox proportional hazards analysis showed that in addition to PET staging (HR, 0.69; 95% CI, 0.64–0.75; P<.001), younger age, black race, lower comorbidity, staging brain MRI, and chemotherapy were associated with OS (Table 5).

Figure 6.
Figure 6.

OS and LCSS by PET staging in patients with extensive-stage small cell lung cancer. (A) OS was longer in patients who had PET staging (median, 7.8 months) than in those who did not (4.2 months). (B) LCSS was similarly longer in patients who had PET staging (median, 8.6 months) than in those who did not (5.3 months).

Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Figure 7.
Figure 7.

Propensity-matched OS and LCSS by PET staging in patients with extensive-stage small cell lung cancer treated with chemoradiation. (A) OS remained longer in patients who had PET staging (median, 7.8 months) than in matched patients who did not (5.8 months). (B) LCSS was similarly longer in patients who had PET staging (median, 8.6 months) than in matched patients who did not (6.5 months).

Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 17, 2; 10.6004/jnccn.2018.7090

Table 5.

Univariate and Multivariate Analysis of OS in Patients With ES-SCLC

Table 5.

PET staging was also associated with LCSS, with those staged by PET having median LCSS of 8.57 months compared with 5.30 months for those who were not (P<.001; Figure 6B). Propensity matching confirmed these findings (8.57 vs 6.47 months; P<.0003; Figure 7B) even with inclusion of facility as a factor (8.57 vs 5.87 months; P=.0003). PET staging (HR, 0.70; 95% CI, 0.64–0.76; P<.001), younger age, black race, lower comorbidity, staging brain MRI, and chemotherapy were associated with LCSS (Table 6).

Table 6.

Univariate and Multivariate Analysis of LCSS in Patients With ES-SCLC

Table 6.

Discussion

In this analysis of patients with SCLC treated in the largest integrated healthcare system in the United States, survival improved from 2000 to 2010 in patients with LS-SCLC and ES-SCLC. The authors found increasing use of pretreatment PET staging associated with an increase in ES-SCLC diagnoses, likely resulting in stage migration and stage-appropriate therapy with improved OS and LCSS. This was present in an era when treatment of LS-SCLC did not change (concurrent CRT with platinum-based chemotherapy).

To our knowledge, stage migration has not previously been described with PET use in SCLC. More broadly termed as the Will Rogers phenomenon,26 stage migration occurs when improved detection of metastatic disease moves patients from a lower to a higher stage group, resulting in improved outcomes in both groups. Although the use and impact of PET staging in NSCLC911 and consequent stage migration1214 are robustly explained, data regarding the association of PET in staging SCLC and survival remain limited.19 Over the decade of this study, rates of PET increased from 1.1% to 39.2%, associated with improved survival. In addition, PET staging was independently associated with OS and LCSS in patients with LS-SCLC treated with standard-of-care CRT and in those with ES-SCLC. Therefore, our data suggest that PET staging may identify patients with otherwise undetectable metastatic disease, selecting the patients most likely to benefit from appropriate treatment of LS-SCLC. This is consistent with prior studies reporting more accurate detection of metastatic disease with PET4,15,17,18,20,21 and a small single-institution cohort finding improved disease control and survival with PET staging in LS-SCLC.19 Moreover, in LS-SCLC, PET/CT has been noted to be integral to RT planning, which may be a contributor to the improved clinical outcomes observed.18 In our analysis, the authors were able to confirm these findings and demonstrate their impact in a population-wide analysis with propensity matching.

Patients undergoing PET for ES-SCLC may also have had otherwise undetectable metastatic disease and thus a lower burden of systemic disease, resulting in improved outcomes. Some studies suggest that metastatic burden in SCLC may be correlated with outcomes.2830 However, RTOG 0937 (ClinicalTrials.gov Identifier: NCT01055197) was unable to detect a benefit to consolidative extracranial CRT to thoracic and limited metastatic disease in patients with ES-SCLC with a response to chemotherapy.31

This study may be limited by complex relationships between PET use, staging, and selection bias. PET use may be based on results of pre-PET imaging studies and comorbidities, subsequently impacting staging and treatment decisions. Although our study is an analysis of the veteran population diagnosed and treated in the VHA, prior studies have suggested that VHA cancer outcomes parallel those in clinical trials and in other care settings.22,23 The representation of SCLC among lung cancers in the VHA cohort during this time (13%) and the proportion of LS-SCLC (36%) are consistent with prior reports.32 In addition, 5-year survival in this nontrial population (20% with PET) compares favorably to previously reported trials of LS-SCLC.33,34 However, our analyses are limited by available data. Local recurrence was not an available endpoint. Similarly, the authors could not accurately identify the use of PCI; however, the data supporting its routine use for LS-SCLC precede our study period.2 As with other retrospective series, potential confounders not recorded or ascertainable may impact outcomes, even with propensity matching for variables associated with treatment selection. For instance, despite propensity matching with the inclusion of the treatment facility, one can argue that the patients who receive FDG PET scans had better access to more state-of-the-art care. Despite these limitations, best efforts were made to minimize and characterize the impact of confounders, the available data were mandatorily collected, and the quality was assured.

In addition, the thoracic RT schedule (once vs twice daily) did not impact outcomes for LS-SCLC. These data corroborate the recent CONVERT study, that was unable to detect a survival benefit with once- versus twice-daily RT.35 Note that 5-year follow-up was necessary to detect the survival improvement in the intergroup study of 45 Gy twice-daily thoracic RT compared with 45 Gy once-daily thoracic RT; median follow-up on that study was approximately 8 years with a minimal follow-up of 5 years, comparable to our 6-year follow-up.33 By comparison, the CONVERT results had a median follow-up of 45 months. Moreover, the comparison between fractionation schedules in the CONVERT study may have been impacted by better-than-expected outcomes in both arms.35 Among ongoing studies, CALGB 30610 (ClinicalTrials.gov identifier: NCT00632853) is comparing 45 Gy twice daily with a higher 70-Gy dose once daily.

Finally, the authors saw an improvement in OS in ES-SCLC during the studied decade, with increasing survival in patients with pretreatment PET. However, analyses in this cohort were confounded by changing treatment paradigms including the incorporation of PCI and thoracic RT for responders to systemic therapy that the authors could not account for with available data.5,7,8,36 However, based on matching, including year of diagnosis, it is likely that stage migration had a significant effect on the changing survival in patients with ES-SCLC.

This analysis of a large cohort of veterans demonstrates the effect of PET staging on survival and the phenomenon of stage migration in SCLC. These findings emphasize the importance of PET in accurate staging in SCLC and support its routine use.

Author contributions: Study concept and design: All authors. Data collection and assembly: Hong, Boyer, Spiegel, Williams, Kelley. Data analysis and interpretation: All authors. Manuscript preparation: All authors. Final approval of manuscript: All authors.

Disclosures: Dr. Tong has disclosed that she is a consultant for Medtronic. Dr. Kelley has disclosed that he receives grants from Bristol-Meyers Squibb, Bavarian Nordic, and Novartis and serves as a consultant for AstraZeneca. The remaining authors have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

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Correspondence: Joseph K. Salama, MD, Department of Radiation Oncology, Duke University, 201 Trent Drive, Box 3085, Durham, NC 27710. Email: joseph.salama@duke.edu
  • View in gallery

    Median OS and LCSS by stage over time. As PET use increased from 2001 to 2010, there was an increase in median OS rates in LS-SCLC (10.9–13.2 months; HR, 0.98; 95% CI, 0.97–0.995; P=.004) and ES-SCLC (4.0–6.1 months; HR, 0.98; 95% CI, 0.97–0.99; P<.0001). (A) Median OS for all patients also increased from 6.2 to 7.9 months during this period (HR, 0.99; 95% CI, 0.98–0.99; P<.0001). (B) Similar trends were seen in LCSS (12.1–15.2 months for LS-SCLC [HR, 0.96; 95% CI, 0.95–0.98; P<.0001], 5.0–7.0 months for ES-SCLC [HR, 0.98; 95% CI, 0.97–0.99; P<.0001], and 7.5–8.6 months overall [HR, 0.98; 95% CI, 0.97–0.99; P<.0001]).

    Abbreviations: ES-SCLC, extensive-stage SCLC; HR, hazard ratio; LCSS, lung cancer–specific cancer; LS-SCLC, limited-stage SCLC; OS, overall survival; SCLC, small cell lung cancer.

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    PET use and stage over time. (A) Rates of PET staging increased from 1.1% in 2001 to 39.2% in 2010. This trend was seen across LS-SCLC and ES-SCLC. (B) As PET adoption increased, there was an increase in ES-SCLC (63.9%–65.7%) and a decrease in LS-SCLC (36.1%–34.3%) among staged patients.

    Abbreviations: ES-SCLC, extensive-stage SCLC; LS-SCLC, limited-stage SCLC; SCLC, small cell lung cancer.

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    OS and LCSS for patients with limited-stage small cell lung cancer treated with chemoradiation. (A) Median OS was 15.5 months and (B) LCSS was 17.7 months.

    Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

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    OS and LCSS by PET staging in patients with limited-stage small cell lung cancer treated with chemoradiation. (A) OS was longer in patients who had PET staging (median, 19.8 months) than in those who did not. (B) LCSS was similarly longer in patients who had PET staging (median, 22.9 months) than in those who did not (16.7 months).

    Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

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    Propensity-matched OS and LCSS by PET staging in patients with limited-stage small cell lung cancer treated with chemoradiation. (A). OS remained longer in patients who had PET staging (median, 19.8 months) than in matched patients who did not (13.8 months). (B) LCSS was similarly longer in patients who had PET staging (median, 22.9 months) than in matched patients who did not (15.7 months).

    Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

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    OS and LCSS by PET staging in patients with extensive-stage small cell lung cancer. (A) OS was longer in patients who had PET staging (median, 7.8 months) than in those who did not (4.2 months). (B) LCSS was similarly longer in patients who had PET staging (median, 8.6 months) than in those who did not (5.3 months).

    Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

  • View in gallery

    Propensity-matched OS and LCSS by PET staging in patients with extensive-stage small cell lung cancer treated with chemoradiation. (A) OS remained longer in patients who had PET staging (median, 7.8 months) than in matched patients who did not (5.8 months). (B) LCSS was similarly longer in patients who had PET staging (median, 8.6 months) than in matched patients who did not (6.5 months).

    Abbreviations: LCSS, lung cancer–specific survival; OS, overall survival.

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