Effect of BRM promoter variants on survival outcomes of stage III-IV non-small cell lung cancer (NSCLC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11057-11057 ◽  
Author(s):  
Sinead Cuffe ◽  
Lu Cheng ◽  
Abul Kalam Azad ◽  
Yonathan Brhane ◽  
Dangxiao Cheng ◽  
...  

11057 Background: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene in NSCLC. Loss of BRM expression occurs in 15% of NSCLC, and has been linked to adverse outcome. Recently, our group has shown that variants of two novel BRM promoter insertion polymorphisms (BRM-741, BRM-1321) lead to loss of BRM expression by recruiting histone deacetylases; individuals carrying homozygous variants for both polymorphisms have doubled NSCLC risk; pharmacological reversal of these epigenetic changes is a potentially viable therapeutic strategy. We thus evaluated the effect of BRM promoter variants on survival outcomes of advanced NSCLC patients, where initial clinical trials are likely to be focused. Methods: 564 stage III-IV NSCLC patients were genotyped for the BRM promoter variants using Taqman. Association of BRM variants and overall (OS) and progression-free survival (PFS) were assessed using Cox proportional hazard models adjusted for prognostic variables. Results: Among our patients, 73% were Caucasian, 52% male, median age 63yrs, 55% stage IV disease, and 67% adenocarcinoma. Median OS was 1.6yrs; median follow up, 3.6yrs. The frequency of homozygosity was BRM-741, 23%; BRM-1321, 21%; both, 12%. Homozygous variants of BRM-741 were strongly associated with worse OS (adjusted HR [aHR] 2.3 [p=2x10E-8]) and PFS (aHR 2.0 [p=2x10E-7]) compared to the wild types. Similar findings were observed for BRM-1321 homozygous variants (aHR for OS 1.8 [p=8x10E-5] and aHR for PFS 1.6 [p=2x10E-4]). Carrying homozygous variants of both BRM-741 and BRM-1321 was associated with substantially worse OS (aHR 2.3 [p=1x10E-5]) and PFS (aHR 2.2 [p=3x10E-6]), with similar associations seen among the stage III (aHR for OS 2.3 [p=6x10E-6]) and stage IV (aHR for OS 2.5 [p=5x10E-6]) patients. Conclusions: The same two homozygous BRM promoter variants that are associated with increased risk of NSCLC are also strongly associated with adverse OS and PFS in this cohort of stage III-IV NSCLC patients. Validation of results in a clinical trial dataset is underway, and will better elucidate the prognostic significance of these BRM promoter variants.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7126-7126 ◽  
Author(s):  
R. P. Abratt ◽  
H. Macha ◽  
S. Del Barco ◽  
D. Aubert ◽  
M. Mitrovic ◽  
...  

7126 Background: NVB i.v. day 1 (25 mg/ m2) & NVBo day 8 (60 mg/ m2) and CBDCA AUC 5 have been previously studied in chemonaive NSCLC patients (pts) (O’Brien et al, Ann Oncol 2004; 15: 921). We investigated the efficacy and safety of NVBo weekly with CBDCA AUC 5 q3w for 4 cycles(Cy) followed by maintenance therapy with single agent NVBo in non progressive pts. Methods: Inoperable NSCLC stage IIIB, stage IV or delayed relapse of any stage becoming unresectable, KPS ≥ 80%, treated with combination therapy every 3 weeks for 4 Cy: NVBo 60 mg/m2 on days 1, 8 and 15 (Cy1), 80 mg/m2 (Cy2–4) in absence of neutropenia NCI CTC V2 G3/4; CBDCA AUC 5 day 1, administered over 1 hour. Maintenance therapy if pts did not have a PD: NVBo 60 mg/m2 for the first three weekly administrations, followed by NVBo at 80 mg/m2/week until PD. Results: from December 2003 to January 2005 57/56 pts have been registered/treated: median age 61 yrs (37–71); median KPS 90%; male 71.4%; Squamous cell 30%, Adenocarcinoma 50%; Stage III/IV 32.1/62.5% ; median dose intensity NVBo (% RDI) : combination, 50.1 mg/m2/w (67.3%), maintenance 56.2 mg/m2/w (70.2%); pts with NVBo dose escalation from 60 to 80 mg/m2 during combination : 36/52 (69.2%). Tolerance (% of pts with G3/4 NCI CTC V2) : Neutropenia 23.2/44.6; Platelets 16.1/1.8; Hb 19.6/3.6; Nausea 7.1/0; Vomiting 7.1/0; Diarrhea 5.4/0. No G3/4 toxicity was reported for Infection, Bilirubin, Creatinine, Stomatitis, and motor/sensory Neuropathy. Febrile Neutropenia was reported in 5 patients (8.9%). Efficacy: (RECIST) Percent Overall Response rates (n =56 pts) PR 17.9, SD 53.6, PD 23.2, NE 5.4; Progression-Free Survival 4.3 (95% CI [3.1–5.1]) months; Overall Survival 9.7 (95% CI [7.7–11.9]) months. Conclusions: NVBo on a weekly schedule and CBDCA AUC5 in combination therapy for 4 Cy followed by NVBo in maintenance therapy is an effective and safe treatment regimen for advanced NSCLC. The avoidance of further CBDCA administrations after 4 Cy and the use of NVBo as a maintenance therapy until PD has promise as an alternative to the 6 Cy option and calls for further comparative studies. [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5582-5582
Author(s):  
Jochen H. Lorch ◽  
Glenn Hanna ◽  
Wei Dai ◽  
Vijaya Thotakura ◽  
Vidya Nair ◽  
...  

5582 Background: HPV status is a major prognostic marker for survival in patients with OPC. We examined overall survival (OS) and progression free survival (PFS) in patients with OPC and known HPV status treated at Dana-Farber Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280 patients with OPC and known HPV status were identified retrospectively and clinical information was recorded. Results: 174 patients were treated with CRT (124 HPV positive, 50 HPV negative) and 106 patients were treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients, OS and PFS were significantly better for patients who were HPV positive compared to those who were HPV negative. 3 year OS was 89.1% for HPV positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients (95%CI, 59.9-83%, HR 0.37, p=0.0007). Among HPV positive patients treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI 81.7-95.9) while 13 deaths were recorded among 50 HPV negative patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p=0.011). PFS at 3 years was also significantly better for HPV positive versus HPV negative patients(81.7% vs 58.8%, HR 0.42, p=0.006). In the group treated with ST, outcomes were similar despite a higher rate of stage IV versus stage III disease compared to the group treated with CRT (100% stage IV in ST versus 77% stage IV and 23% stage III disease in CRT group). Three year OS was 89.7% for HPV positive and 68.2% in the HPV negative group (8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p=0.015). PFS was borderline better for HPV positive patients (81% vs 61.7%, HR 0.48, p= 0.058). Conclusions: We present the DFCI experience treating OPC with ST and CRT for patients with known HPV status over one decade.OS and PFS were superior for HPV positive versus HPV negative patients. Outcomes were virtually identical for patients treated with CRT versus ST despite a higher rate of stage IV disease in the ST group. Outcomes for the HPV negative patients in particular were superior compared to the published literature.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19026-e19026
Author(s):  
Joseph J. Maly ◽  
Lai Wei ◽  
Jessica Hemminger ◽  
Beth Christian ◽  
Kami J. Maddocks ◽  
...  

e19026 Background: PET scan is frequently utilized in FL. Reduced EFS has been observed in DLBCL pts with SL treated with RCHOP (Held, JCO 31:4115, 2013). Methods: We performed a retrospective single center study to assess outcomes of FL pts with PET avid SL between January 2005 and November 2015. 131 pts with newly diagnosed FL and PET performed within 1 month of diagnosis were included. Results: 32 of these pts had SL (median 4, range 1-11) on initial PET. Median age was 57 (range 43-79), 15 (47%) were female, 30 (94%) had stage IV disease, LDH was elevated in 6 (19%), 6 (19%) had bulky disease > 6 cm, and FLIPI-1 score was low in 5, intermediate in 11, and high 16 pts. 27 pts had grade (gr) 1-2 FL, 2 had gr 3a, and 3 had gr 3 (not classified). All but 1 patient received rituximab (R)-containing therapy (9 received BR, 7 received RCHOP, 5 RCVP, 9 other). 8 pts received maintenance R, and none received radiation. There were no statistically significant differences in median age, tumor gr, LDH, or use of anthracycline containing therapy (28% in SL group vs 16% in non-SL group, p = 0.13) in pts with SL compared to those without SL (n = 99). Pts with SL had higher incidence of bone marrow involvement (27% vs 9%, p = 0.013). With a median follow-up of 35 months, SL pts had 44% rate of transformation to DLBCL compared 12% in non-SL pts (p = 0.004). Median PFS was 45.8 months in SL pts not-reached in non-SL pts (p = 0.003). Median OS was 105.9 months in SL pts and not reached in non-SL pts (p = 0.08). In the multi-variate analysis, SL (p = 0.037), male gender (p = 0.048), higher FLIPI-1 score (p = 0.009), and absence of anthracycline containing therapy (p = 0.005) were significantly associated with decreased PFS using backward selection. Conclusions: The presence of PET identified SL in previously untreated FL is associated with an increased risk of transformation and reduced PFS in this single center retrospective analysis. Larger studies of uniformly treated pts are needed to validate these data. The identification of high-risk PET avid SL in FL pts in future prospective therapeutic trials could be used to select pts for specific induction regimens, maintenance rituximab, or consolidative radiation.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2710-2710 ◽  
Author(s):  
David G Crockett ◽  
Anamarija M. Perry ◽  
James O. Armitage ◽  
Dennis D Weisenburger ◽  
Martin Bast ◽  
...  

Abstract Abstract 2710 Introduction Recent refinement in B-cell lymphoma classification by the WHO in 2008 has defined an entity that exists in the gray zone between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Varying in morphology, immunohistochemical, or genetic features, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (Intermediate DLBCL/BL) has been reported to have a poor clinical outcome. We aim to describe the clinical factors affecting outcomes and compare therapy response in a representative population. Methods A retrospective search of the Nebraska Lymphoma Study Group Registry from 1983–2009 meeting the diagnostic criteria for Intermediate DLBCL/BL yielded clinical data at presentation, follow-up, and treatment information. Treatments were grouped as CHOP-like +/− Rituximab (R) vs. intensive regimens (e.g. CODOX-M +/− R, R-EPOCH). Diagnostic slides were re-reviewed to verify the diagnosis. Probabilities of progression-free survival (PFS) and overall survival (OS) were approximated using Kaplan-Meier method. Cox proportional regression analysis was used to evaluate the clinical variables associated with risk of treatment-failure and death. Results Our cohort of 63 patients had a median age of 69 (19–93), male sex in 49%, a Karnofsky performance status of at least 80 at time of diagnosis in 73%, an elevated serum lactate dehydrogenase (LDH) in 62%, and stage IV disease in 46%. International Prognostic Index (IPI) scores were low in 38%, low-intermediate in 27%, high-intermediate in 24% and high in 11%. The probability of PFS at 5 and 10 years was 25% (95% CI 15–37%) and 10% (95% CI 4–21%) respectively, with a median time to treatment-failure of only 5.7 months. The 5 and 10 year probability of OS was 32% (95% CI 21–44%) and 20% (95% CI 10–32%) respectively, with a median survival of 10.4 months. Univariate regression analysis showed the following factors to be associated with an increased risk for treatment-failure: Ann Arbor stage IV disease (HR 2.49, 95% CI 1.33–4.68); elevated LDH (HR 1.85, 95% CI 1.02–3.37) and having at least 2 extra-nodal sites (HR 2.12, 95% CI 1.12–4.04). The following factors were associated with an increased risk of death: elevated LDH (HR 2.03, 95% CI 1.08–3.81), stage IV disease (HR 1.88, 95% CI 1.00–3.45), and having at least 2 extra-nodal sites (HR 2.26, 95% CI 1.15–4.40). The IPI scores of low-intermediate, high-intermediate, and high risk were associated with treatment-failure (HR 2.01, 95% CI 1.00–4.11; 4.62, 95% CI 2.11–10.14; 6.11, 95% CI 2.31–16.17) respectively, and death (HR 2.57, 95% CI 1.23–5.37; 3.13, 95% CI 1.41–6.94; 8.30, 95% CI 3.07–22.43) respectively. The median OS of patients who received CHOP/CHOP-like regimens +/− R was 8.7 months, whereas those who received a more intensive regimen +/− R was 45 months (p=0.38). The median PFS was 5.4 months for CHOP/CHOP-like regimens +/− R and 52.3 months for a more intensive regimen (p=0.08) (Fig.1).Figure 1.Progression free survival intensive versus CHOP/CHOP-like regimens +/− Rituximab, p=0.08Figure 1. Progression free survival intensive versus CHOP/CHOP-like regimens +/− Rituximab, p=0.08 Summary Our analysis confirmed poor clinical outcome with stage IV disease, elevated serum LDH, at least 2 extra-nodal sites at presentation, or worse IPI score. There was a better outcome with intensive chemotherapy regimens. This study underscores the importance of early identification and proper treatment choice. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Feng Bao ◽  
Li-rong Wu ◽  
Zhi-gang Deng ◽  
Chun-hua Xiang ◽  
Guo-qiang Li ◽  
...  

Abstract Background: The prognosis of middle-aged patients with CRC treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for patients with CRC and 45-65 years of age.Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was done to handle the selection bias based on age, gender, body mass index (BMI), tumor location, AJCC stage, and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and progression-free survival (PFS).Results: After PSM, 217 patients were included in each group. There were no differences in OS and PFS between the two groups (all P>0.05). There was less blood loss for LR (P<0.001), but the other complications were similar between the two groups. The multivariate analysis showed that high histological grade (hazard ratio [HR]=2.262, 95%CI: 1.334-3.836, P=0.002), stage III (HR=1.744, 95%CI: 2.360-25.406, P=0.001), stage IV (HR=47.905, 95%CI: 14.430-159.033, P<0.001), and adjuvant therapy (HR=0.547, 95%CI: 0.358-0.838, P=0.006) were independently associated with OS. High preoperative CEA (HR=1.585, 95%CI: 1.049-2.394, P=0.029), high histological grade (HR=2.128, 95%CI: 1.272-3.558, P=0.004), stage III (HR=5.562, 95%CI: 1.980-15.624, P=0.001), and stage IV (HR=26.338, 95%CI: 9.090-76.315, P<0.001), were independently associated with OS. LR was not associated with OS and PFS.Conclusions: In middle-aged patients with CRC, OR and LR have similar survival outcomes and complications.


2013 ◽  
Vol 31 (9) ◽  
pp. 1196-1201 ◽  
Author(s):  
Peter F. Ehrlich ◽  
James R. Anderson ◽  
Michael L. Ritchey ◽  
Jeffrey S. Dome ◽  
Daniel M. Green ◽  
...  

Purpose Stage III designation in NWTS-5 (National Wilms Tumor Study–5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria. Patients and Methods Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis. Results There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05). Conclusion LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.


2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.


2018 ◽  
Vol 103 (9) ◽  
pp. 3566-3573 ◽  
Author(s):  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Subhashini Yaturu ◽  
Electron Kebebew

Abstract Context Adrenocortical carcinoma (ACC) is rare; knowledge about prognostic factors and survival outcomes is limited. Objective To describe predictors of survival and overall survival (OS) outcomes. Design and Patients Retrospective analysis of data from the National Cancer Database (NCDB) from 2004 to 2015 on 3185 patients with pathologically confirmed ACC. Main Outcome Measures Baseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC. Results Median age at ACC diagnosis was 55 (range: 18 to 90) years; did not differ significantly by sex or stage of the disease at diagnosis. On multivariate analysis, increasing age, higher Charlson-Deyo comorbidity index score, high tumor grade, and no surgical therapy (all P &lt; 0.0001); and stage IV disease (P = 0.002) and lymphadenectomy during surgery (P = 0.02) were associated with poor prognosis. Patients with stage I-III disease treated with surgical resection had significantly better median OS (63 vs 8 months; P &lt; 0.001). In stage IV disease, better median OS occurred in patients treated with surgery (19 vs 6 months; P &lt; 0.001), and postsurgical radiation (29 vs 10 months; P &lt; 0.001) or chemotherapy (22 vs 13 months; P = 0.004). Conclusion OS varied with increasing age, higher comorbidity index, grade, and stage of ACC at presentation. There was improved survival with surgical resection of primary tumor, irrespective of disease stage; postsurgical chemotherapy or radiation was of benefit only in stage IV disease.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Julian Taugner ◽  
Monika Karin ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Julian Guggenberger ◽  
...  

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p < 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18719-e18719
Author(s):  
Natalie R. Dickson ◽  
Karen Beauchamp ◽  
Toni S. Perry ◽  
Ashley Roush ◽  
Deborah Goldschmidt ◽  
...  

e18719 Background: Clinical pathways have been introduced as tools to optimize cancer care delivery, but evidence of their value in the real world is limited. This retrospective study was performed to assess treatment patterns and clinical outcomes in patients with non-small cell lung cancer (NSCLC) before and after pathway implementation at Tennessee Oncology (TO). Methods: Chart data were abstracted for patients (≥18 years) diagnosed with Stage I-IV NSCLC who initiated first-line (1L) systemic treatment at a TO clinic and had follow-up for ³6 months or until death. Patients were divided into two cohorts: pre-pathways (treatment initiation 2014–2015) and post-pathways (treatment initiation 2016–2018). Patient characteristics, treatment patterns, and outcomes were described and compared across cohorts. An exploratory study endpoint was the evaluation of outcomes based on disease stage at diagnosis. Results: Among 501 patients (251 pre-pathways and 250 post-pathways), most had advanced or metastatic NSCLC at diagnosis (Stage III: 40%; Stage IV: 42%). Chemotherapy comprised almost all 1L systemic therapy used pre-pathways (Stage I/II: 100%; Stage III: 96%; Stage IV: 83%). Post-pathways, chemotherapy remained the most common 1L therapy in patients with Stage I/II (89%) and Stage III (72%) disease, but among patients with Stage IV disease, use of chemotherapy decreased (47%) and immuno-oncology (IO) therapy alone or in combination became common (45%). Median duration of 1L therapy was longer post-pathways in patients with Stage III (2.1 months vs 1.4 months pre-pathways; P < 0.01) and Stage IV disease (3.3 months vs 2.3 months pre-pathways; P < 0.01) but did not differ among Stage I/II patients. Median progression-free survival was significantly longer post-pathways in patients with Stage IV disease (7.0 months vs 4.2 months pre-pathways; P < 0.05), but not in other disease-stage subgroups. Median overall survival increased non-significantly post-pathways for all disease stage subgroups (Stage I/II: 26 months vs 20 months pre-pathways; Stage III: 26 months vs 20 months; Stage IV: 10 months vs 9 months). For each disease stage, rates of severe adverse events were similar between cohorts. Conclusions: While outcomes for patients diagnosed with Stage III/IV NSCLC were generally improved following the implementation of clinical pathways, this change coincided with a dramatic shift in available treatment options. Improvements post-pathways were mainly observed in patients diagnosed with advanced disease. Thus, differences in outcomes between pre-pathways and post-pathways cohorts in our study are more likely attributable to other evolving practices in cancer care, particularly the availability of newer, more effective treatments such as IO therapy as part of standard practice, than implementation of the clinical pathways.


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