Maximum standardized uptake value of primary tumor (SUVmax_PT) and horizontal range between two most distant PET-positive lymph nodes predict patient outcome in inoperable stage III NSCLC patients after chemoradiotherapy.

BACKGROUND: 18F-FDG-positron emission tomography (PET)/computed tomography (CT) is a standard for initial staging in patients with locally advanced stage III non-small cell lung cancer (NSCLC). We evaluated a PET/CT staging score to characterize disease extension and patient outcome in this disease. METHODS: Ninety-nine consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), who underwent 18F-FDG-PET/CT before the start of chemoradiotherapy (CRT) were analyzed. Maximum standardized uptake value of primary tumor (SUVmax_PT) and range between two most distant PET-positive (SUV ≥2.5) lymph nodes in two directions were analyzed for their correlation with patient outcome. The vertical distance was defined as A- and the horizontal as a B-line. RESULTS: According to the results of univariate analysis, score included the SUVmax_PT and horizontal B-line, patients were divided into three risk subgroups: low, intermediate and high-risk subgroups. Subgroups were defined as SUVmax_PT <8 and B-line <3.7 cm, SUVmax_PT >8 or B-line >3.7 cm and SUVmax_PT >8 plus B-line >3.7 cm, respectively. Twenty-eight (28%), 45 (46%) and 26 (26%) patients were assigned to the low, intermediate and high-risk subgroup, respectively. Median event-free survival (EFS) in low, intermediate and high-risk subgroups was 16 (95% CI: 7-25), 13 (95% CI: 12-15) and 10 (95% CI: 7-13) months (P=0.002, log-rank test). Median OS in the low, intermediate and high-risk subgroups was 40 (95% CI: 11-69), 23 (95% CI: 15-31) and 14 (95% CI: 13-14) months (P=0.0001, log-rank test). In the multivariate analysis, SUV, B-line and PET/CT score were significantly associated with EFS [harard ratio (HR) 2.12 (95% CI: 1.27-3.55) and intermediate risk HR 2.01 (95% CI: 1.13-3.59), P=0.003] and OS [high-risk HR 2.79 (95% CI: 1.16-4.55) and intermediate risk HR 2.30 (95% CI: 1.58-4.94), P=0.001]. CONCLUSIONS: A PET/CT score was developed for inoperable stage III NSCLC patients treated with CRT and was an independent predictor of patient outcome in the single-center cohort.

Pattern-of-failure and salvage treatment analysis after chemoradiotherapy for inoperable stage III non-small cell lung cancer.

BACKGROUND: Loco-regional and distant failure are common in inoperable stage III non small-cell lung cancer (NSCLC) after chemoradiotherapy (CRT). However, there is limited real-world data on failure pattern, patient prognosis and salvage options. METHODS: We analysed 99 consecutive patients with inoperable stage III NSCLC treated with CRT between 2011 and 2016. Follow up CT scans from date of the first-site failure were matched with the delivered radiation treatment plans. Intra-thoracic loco-regional relapse was defined as in-field (IFR) vs. out-of-field recurrence (OFR) [in- vs. outside 50Gy isodose line in the involved lung], respectively. Extracranial distant (DMs) and brain metastases (BMs) as first site of recurrence were also evaluated. Using the Kaplan-Meier method, impact of salvage surgery (sS), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on patient survival was assessed. RESULTS: Median follow-up was 60.0 months. Median PFS from the end of CRT for the entire cohort was 7.5 (95% CI: 6.0-9.0 months) months. Twenty-six (26%) and 25 (25%) patients developed IFR and OFR. Median time to diagnosis of IFR and OFR was 7.2 and 6.2 months. In the entire cohort, onset of IFR and OFR did not influence patient outcome. However, in 73 (74%) patients who survived longer than 12 months after initial diagnosis, IFR was a significant negative prognostic factor with a median survival of 19.3 vs 40.0 months (p < 0.001). No patients with IFR underwent sS and/or sRT. 18 (70%) and 5 (19%) patients with IFR underwent sCT and sIO. Three (12%) patients with OFR underwent sS and are still alive with 3-year survival rate of 100%. 5 (20%) patients with OFR underwent sRT with a median survival of 71.2 vs 19.1 months (p = 0.014). Four (16%) patients with OFR received sIO with a numerical survival benefit (64.6 vs. 26.4 months, p = 0.222). DMs and BMs were detected in 27 (27%) and 16 (16%) patients after median time of 5.8 and 5.13 months. Both had no impact on patient outcome in the entire cohort. However, patients with more than three BMs showed significantly poor OS (9.3 vs 26.0 months; p = 0.012). CONCLUSIONS: After completion of CRT, IFR was a negative prognostic factor in those patients, who survived longer than 12 months after initial diagnosis. Patients with OFR benefit significantly from salvage local treatment. Patients with more than three BMs as first site of failure had a significantly inferior outcome.

External Validation of a Survival Score for Limited-Stage Small Cell Lung Cancer Patients Treated with Chemoradiotherapy.

PURPOSE: In order to personalize multimodal treatment regimens in limited-stage small cell lung cancer (LS-SCLC), a survival score for these patients was proposed. The aim of this study is to validate the score in an independent external patient cohort. METHODS: We collected data of 78 patients treated with chemoradiotherapy for LS-SCLC between 2004 and 2015. The survival score was calculated by independent prognostic factors: gender, Karnofsky performance status, tumor substage, and hemoglobin level before treatment. Scoring points were derived from 2-year survival rates divided by 10 and the values for each prognostic factor were tallied. Three risk subgroups were defined (high, intermediate, low risk: 9-13, 14-18, 19-26 points). The 2-year survival rate of each subgroup from the original study was compared to its corresponding subgroup from the validation cohort. RESULTS: Median survival time in the entire validation cohort was 17 months (range: 1-123 months). The 2-year survival rates were 0% in the 9-13, 35% in the 14-18, and 43% in the 19-26 points group, respectively (p = 0.018). The difference in 2-year survival between the 9-13 points and the 14-18 points group was significant in the validation cohort (p = 0.007) as well after stratification of concurrent chemoradiotherapy (p < 0.001), whereas the difference between the 14 and 18 points and the 19-26 points group was not significant (p = 0.602, p = 0.770). CONCLUSION: The score was reproducible to estimate the 2-year survival rate of patients with LS-SCLC, especially in the high- and intermediate-risk subgroups. In order to improve the differentiation between patients with an intermediate and favorable survival prognosis, the scoring system needs further development.

Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND/AIM: mmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT). PATIENTS AND METHOD: We retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0-40% vs. 41-100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated. RESULTS: Median OS was 14 months (range: 3-167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression < 1% on tumor cells was associated with improved OS, PFS and local control in patients treated with concurrent CRT. Univariate analysis showed a trend towards improved OS and local control in patients with low CD8+ TIL density. Evaluation of Tumor Immunity in the MicroEnvironment (TIME) appears to be an independent prognostic factor for local control, PFS and OS. The longest and shortest OS were achieved in patients with type I (PD-L1neg/CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57 ± 37 vs. 10 ± 5 months, p = 0.05), respectively. CONCLUSION: Assessment of PD-L1 expression on tumor cells in combination with CD8+ TIL density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT.

Survival score to characterize prognosis in inoperable stage III NSCLC after chemoradiotherapy.

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) represents a heterogeneous disease regarding principal patient- and tumor characteristics. A simple score may aid in personalizing multimodal therapy. METHODS: The data of 99 consecutive patients with performance status ECOG 0-1 treated until the end of 2016 with multimodal approach for inoperable NSCLC (UICC 7th edition stage IIIA/B) were evaluated. Patient- and tumor-related factors were examined for their impact on overall survival. Factors showing a negative association with prognosis were then included in the score. Three subgroups with low, intermediate and high-risk score were defined. The results were then validated in the prospective cohort, which includes 45 patients. RESULTS: Most Patients were treated with concurrent (78%) or sequential (11%) chemoradiotherapy. 53% received induction chemotherapy. Median survival for the entire cohort was 20.8 (range: 15.3-26.3) months. Age (P=0.020), gender (P=0.007), pack years (P=0.015), tumor-associated atelectasis (P=0.004) and histology (P=0.004) had a significant impact on overall survival and were scored with one point each. Twelve, 59 and 28 patients were defined to have a low (0-1 points), intermediate (2-3 points) and high-risk (4-5 points) score. Median survival, 1-, 2- and 3-year survival rates were not reached, 100%, 83% and 67% in the low, 22.9 months, 80%, 47% and 24% intermediate and 13.7 months, 57%, 25% and 18% high-risk patients, respectively (P<0.001). Median survival was not reached in prospective cohort; analysis has revealed a trend for the 1-year survival rates with 100% for the low, 93% intermediate and 69% high-risk patients (P=0.100). CONCLUSIONS: The score demonstrated remarkable survival differences in inoperable stage III NSCLC patients with good performance status receiving multimodal therapy.

Performance Status and Its Changes Predict Outcome for Patients With Inoperable Stage III NSCLC Undergoing Multimodal Treatment.

BACKGROUND/AIM: Patient performance scores are used widely in clinical practice to assess a patient's general condition. The aim of this study was to evaluate the prognostic role of Eastern Cooperative Oncology Group performance score (ECOG PS) before, after and its changes during chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Records of 99 patients with stage III NSCLC were evaluated. ECOG PS before, during and after chemoradiotherapy was analyzed for prognostic impact on overall (OS) and event-free (EFS) survival. RESULTS: Median OS considering the entire cohort was 20.8 months (range=15.3-26.2 months). Median OS, and 1- and 2-year survival rates were 26.4 months, 85% and 53% in patients with ECOG PS 0 versus 18.9 months, 69% and 37% in patients with ECOG PS 1 (p=0.1, log-rank test), respectively. After the first follow-up, 35% of patients presented worsening ECOG PS, while in 65% it was stable or improved. Median EFS according to ECOG PS 0, 1, 2 and 3 was 9.6, 9.0, 7.9 and 3.5 months, respectively, at the first follow-up (p=0.018, log-rank test). Deterioration of ECOG PS after chemoradiotherapy resulted in reduced OS in the subgroups with initial ECOG PS 0 and 1 (p=0.005 and p=0.001, log-rank test). CONCLUSION: ECOG PS and its changes have a strong impact on patient outcome. Deterioration of performance status was a strong negative prognostic factor for EFS and OS.