Impact of prior radiation on survival in metastatic lung cancer ECOG-ACRIN trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
Saad A. Khan ◽  
Maneka Puligandla ◽  
Suzanne Eleanor Dahlberg ◽  
Gregory A. Masters ◽  
Corey J. Langer ◽  
...  

9051 Background: Up to 50% of advanced NSCLC patients receive radiation therapy at some point in their course. We sought to determine whether patients with prior radiation demonstrate altered outcomes on subsequent metastatic clinical trials. Methods: We reviewed 8 ECOG-ACRIN advanced non-small cell lung cancer studies conducted between 1993 and 2011 in which information was collected about receipt of prior radiation. Whether radiotherapy was given with curative or palliative intent, or to specific sites was not recorded. Median follow-up among all trials was 66 months. We used the log-rank, Wilcoxon and Fisher’s exact tests to compare patients, and Cox Model and Kaplan-Meier method to calculate survival. Results: 574/3041 (18.9%) patients had received prior radiation. These patients were more likely to be male (64% vs 58%), have squamous histology (20% vs 14%) and have had prior surgery (48% vs 33%) compared to those with no prior radiation. At registration, prior radiation patients were more likely to have an ECOG PS of 1 (66% vs 58%), while they were less likely to have a PS of 0 (24% vs 36%) or have a pleural effusion (23% vs 37%). Patients who received radiation were more likely to have been registered on to studies between 1993-1999 than 2000-2011 (69% vs 31%) (all p < 0.001). Median Overall Survival (OS) for patients with prior radiation was 7.6 months (range 7-8.3) vs 9.5 (9.1-9.8) for those without (p < 0.001). Median Progression Free Survival (PFS) for those with prior radiation was 3.5 months (3-3.9) vs 4.2 (4.1-4.4) for those without (p < 0.001). In multivariable analysis controlling for stage IIIB/IV, sex, PS, histology, and prior surgery, the impact of prior radiation on overall survival remained significant (p = 0.042, HR (95% CI) = 1.11 (1.00, 1.22)). Conclusions: Almost one-fifth of lung cancer patients on systemic therapy trials for advanced disease previously received radiation. They are more likely to be male, have squamous histology, have an ECOG PS of 1 and have had prior surgery. Prior radiation is significantly associated with inferior OS and PFS. For advanced NSCLC clinical trials, documentation of whether curative intent/palliative intent radiation was given and stratification by prior radiation exposure should be considered.

2018 ◽  
Vol 25 (4) ◽  
Author(s):  
K. Al-Baimani ◽  
H. Jonker ◽  
T. Zhang ◽  
G.D. Goss ◽  
S.A. Laurie ◽  
...  

Background Advanced non-small-cell lung cancer (nsclc) represents a major health issue globally. Systemic treatment decisions are informed by clinical trials, which, over years, have improved the survival of patients with advanced nsclc. The applicability of clinical trial results to the broad lung cancer population is unclear because strict eligibility criteria in trials generally select for optimal patients.Methods We performed a retrospective chart review of all consecutive patients with advanced nsclc seen in outpatient consultation at our academic institution between September 2009 and September 2012, collecting data about patient demographics and cancer characteristics, treatment, and survival from hospital and pharmacy records. Two sets of arbitrary trial eligibility criteria were applied to the cohort. Scenario A stipulated Eastern Cooperative Oncology Group performance status (ecog ps) 0–1, no brain metastasis, creatinine less than 120 μmol/L, and no second malignancy. Less-strict scenario B stipulated ecog ps 0–2 and creatinine less than 120 μmol/L. We then used the two scenarios to analyze treatment and survival of patients by trial eligibility status.Results The 528 included patients had a median age of 67 years, with 55% being men and 58% having adenocarcinoma. Of those 528 patients, 291 received at least 1 line of palliative systemic therapy. Using the scenario A eligibility criteria, 73% were trial-ineligible. However, 46% of “ineligible” patients actually received therapy and experienced survival similar to that of the “eligible” treated patients (10.2 months vs. 11.6 months, p = 0.10). Using the scenario B criteria, only 35% were ineligible, but again, the survival of treated patients was similar in the ineligible and eligible groups (10.1 months vs. 10.9 months, p = 0.57).Conclusions Current trial eligibility criteria are often strict and limit the enrolment of patients in clinical trials. Our results suggest that, depending on the chosen drug, its toxicities and tolerability, eligibility criteria could be carefully reviewed and relaxed.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18018-e18018
Author(s):  
Dai Chu Nguyen Luu ◽  
Rizvan Mamet ◽  
Carrie C. Zornosa ◽  
Joyce C. Niland ◽  
Thomas A. D'Amico ◽  
...  

e18018 Background: Clinical trials have failed to demonstrate that age is a significant prognostic indicator among patients treated for non-small cell lung cancer (NSCLC). Clinical trials do not necessarily represent real-world experience, however. We sought to analyze the impact of age on survival in patients in the National Comprehensive Cancer Network (NCCN) NSCLC Outcomes Database. Methods: We performed a retrospective analysis of 6,834 NSCLC patients from the NCCN NSCLC Database representing 8 NCCN institutions. Of this population, 4,943 patients were eligible for our analysis. Exclusion criteria included the following: alive patients with < 180 days of follow-up, patients with incomplete staging, and patients with a prior cancer diagnosis. The study population was separated into five age quintiles with equal number of patients in each group. Variables included institution, smoking status, gender, race, Charlson comorbidity score, ECOG performance status (PS), histology, stage, and receipt of resection, drug and radiation therapy. Multivariable Cox model was performed for the effect of age on survival after adjusting for the above variables. Model assumptions were evaluated via graphs and residual tests. Results: Across the five quintiles (< 54, 54-60, 61-66, 67-72 and ≥ 73) there was a trend towards lower stage and higher Charlson score with increasing quintile. In addition, there was an increased proportion of patients with squamous cancer in the older age group. In the adjusted Cox model, there was a statistically significant longer survival in each of four younger quintiles compared to the reference group of ≥ 73 years of age (p=0.01). The adjusted hazard ratio of death for patients < 54 was .82 (95% CI = .72 to .94), for patients 54-60 was .86 (95% CI = .76 to .97), for patients 61-66 was .84 (95% CI = .74 to .95), and for patients 67-72 was .84 (95% CI = .74 to .95). There were no statistically significant pairwise interactions among age, smoking status and stage. Conclusions: Even after adjusting for institution, comorbidity scores, smoking status, race, gender, ECOG PS, histology, stage and treatment, NSCLC patients who were ≥ 73 years of age had a worse survival when compared to younger age groups.


2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 260-260
Author(s):  
Doran Ksienski ◽  
Elaine Wai ◽  
Nicole Croteau ◽  
Mary Lesperance

260 Background: In advanced NSCLC, clinical trials have shown significant benefits to pembrolizumab (P) and nivolumab (N). At BC Cancer, clinicians utilize protocol based algorithms to manage immune related adverse events (irAE). The incidence of irAE and efficacy of PD-1 Ab in everyday practice might differ from clinical trials. Methods: Advanced NSCLC patients (pts) treated with N or P between 11/2015 to 10/2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Gr, CTCAE v4.0) of irAE, were abstracted. Kaplan-Meier curves of median overall survival (OS) from initiation of PD-1 Ab were generated. Multivariable analysis (MVA) with 6-week landmark analysis was performed with Cox proportional hazard regression models. Results: Characteristics of cohort (230 N- and 41 P- treated): median age 64y (range 39-82), non-squamous histology 75%, ECOG PS > 1 at start of PD-1 Ab 31%, brain metastases (mets) 13%, liver mets 12%, and median Charlson Comorbidity Index (CCI) score 6. One hundred sixteen pts experienced 169 separate irAE: Gr1(74), Gr2 (68), Gr3(13), Gr4(10), Gr 5(4). Pneumonitis (14.6% vs. 4.8%, p = 0.041) and arthralgias (12.2% vs. 3.5%, p = 0.044) were more common in P than N. Steroids were administered to 25.2% of N pts and 19.5% of P pts (p = 0.557). Median follow-up from initiation of PD-1 Ab was 8.1months (range 0.1-33.9); median OS (95% CI) for N was 9.2 months (7.75-12.4) and for P was 13.5 months (10.6-not reached). 6-week landmark MVA for whole cohort revealed that male sex (p = 0.051), CCI≥3 (p < 0.001), ECOG PS > 1 (p < 0.001), liver mets (p = 0.017) and development of irAE > Gr2 versus no irAE (p = 0.036) were associated with decreased OS. Age, smoking status, histology, brain mets, EGFR status, irAE Gr 1/2 versus no irAE, and type of PD-1 Ab were not significant. Conclusions: Severe irAE were rare; pneumonitis and arthralgias were more common in P- than N- treated patients. The association with CCI, ECOG PS, and liver mets with decreased OS are consistent with literature. Association of severe irAE with shorter OS might reflect the need for improved physician education in irAE treatment algorithms.


2021 ◽  
Vol 9 (4) ◽  
pp. e002421
Author(s):  
Alessio Cortellini ◽  
Massimo Di Maio ◽  
Olga Nigro ◽  
Alessandro Leonetti ◽  
Diego L Cortinovis ◽  
...  

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.ConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.


Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 198
Author(s):  
Ji Yeon Park ◽  
Byunghyuk Yu ◽  
Ki Bum Park ◽  
Oh Kyoung Kwon ◽  
Seung Soo Lee ◽  
...  

Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.


2012 ◽  
Vol 30 (36) ◽  
pp. 4501-4507 ◽  
Author(s):  
Andrea Ardizzoni ◽  
Marcello Tiseo ◽  
Luca Boni ◽  
Andrew D. Vincent ◽  
Rodolfo Passalacqua ◽  
...  

Purpose To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with advanced NSCLC, in progression during or after first-line platinum-based chemotherapy, were randomly assigned to receive pemetrexed (arm A) or pemetrexed plus carboplatin (arm B). Primary end point was progression-free survival (PFS). A preplanned pooled analysis of the results of this study with those of the NVALT7 study was carried out to assess the impact of carboplatin added to pemetrexed in terms of overall survival (OS). Results From July 2007 to October 2009, 239 patients (arm A, n = 120; arm B, n = 119) were enrolled. Median PFS was 3.6 months for arm A versus 3.5 months for arm B (hazard ratio [HR], 1.05; 95% CI, 0.81 to 1.36; P = .706). No statistically significant differences in response rate, OS, or toxicity were observed. A total of 479 patients were included in the pooled analysis. OS was not improved by the addition of carboplatin to pemetrexed (HR, 90; 95% CI, 0.74 to 1.10; P = .316; P heterogeneity = .495). In the subgroup analyses, the addition of carboplatin to pemetrexed in patients with squamous tumors led to a statistically significant improvement in OS from 5.4 to 9 months (adjusted HR, 0.58; 95% CI, 0.37 to 0.91; P interaction test = .039). Conclusion Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.


Chemotherapy ◽  
2017 ◽  
Vol 62 (4) ◽  
pp. 205-213 ◽  
Author(s):  
Mie Kotake ◽  
Yosuke Miura ◽  
Hisao Imai ◽  
Keita Mori ◽  
Reiko Sakurai ◽  
...  

Background: In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Methods: Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Results: Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Conclusions: In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS.


2015 ◽  
Vol 46 (6) ◽  
pp. 1762-1772 ◽  
Author(s):  
Dermot S. O'Callaghan ◽  
Elton Rexhepaj ◽  
Kathy Gately ◽  
Linda Coate ◽  
David Delaney ◽  
...  

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3+, CD8+ and forkhead box P3 (Foxp3)+ T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8+ TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3+ TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8+ islet (HR 0.48, p<0.001) and Foxp3+ stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3+ and CD8+ stromal counts and high Foxp3+ islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8+ TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3+ TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16534-e16534
Author(s):  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Matteo Santoni ◽  
Andrea Marchetti ◽  
Matteo Rosellini ◽  
...  

e16534 Background: Immune checkpoint inhibitors (ICIs) have recently revolutionized the treatment landscape of metastatic urothelial carcinoma (mUC). Nonetheless, little is known regarding the impact of clinicopathological features in this setting. We performed a meta-analysis aiming to evaluate the predictive value of ECOG-PS, age, gender, liver metastases, and histology in randomized controlled trials (RCTs) comparing ICI-based combinations versus chemotherapy in mUC patients. Methods: We retrieved all the relevant RCTs through PubMed/Med, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs comparing ICI-based combinations versus chemotherapy alone in mUC patients. The primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). All statistical analyses were performed using R studio software. Results: Overall, 1032 mUC patients were included in the analysis. Compared with chemotherapy, ICI-based combinations significantly decreased the risk of death in several clinicopathological subgroups, including no liver metastases (HR, 0.84; 95% CI, 0.74-0.95) and ECOG-PS 0 patients (HR, 0.84; 95% CI, 0.72-0.97). Similarly, ICI-based combinations were associated with prolonged OS in mUC patients who were < 65 years old (HR, 0.82; 95% CI, 0.72-0.95), as well as in male (HR, 0.90; 95% CI, 0.82-0.99) and female patients (HR, 0.81; 95% CI, 0.68-0.97). Conversely, a non-statistically significant benefit was observed for chemotherapy alone in mUC patients with liver metastases (HR, 1.06; 95% CI, 0.86-1.31). Conclusions: According to our results, the magnitude of benefit of ICI-based combinations over chemotherapy in mUC was consistent across a number of clinicopathological subgroups, while a proportion of patients could respond to chemotherapy alone.Despite several limitations affect our analysis, we believe these results could guide in everyday treatment decision-making, also assisting in the design and interpretation of future clinical trials on ICIs in mUC.


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