Value of precision medicine in advanced NSCLC: Real-world outcomes associated with the use of companion diagnostics.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Ani John ◽  
Roma Shah ◽  
William Bruce Wong ◽  
Charles Schneider ◽  
Hamid H. Gari ◽  
...  

e20015 Background: Five-year survival rates as low as 2.8% have been reported in patients with non-small cell lung cancer (NSCLC), highlighting the need for individualized diagnosis and treatment. Companion diagnostic testing (CDx) identifies patients with molecular targets likely to respond better to particular therapies; however, not all cancer patients receive CDx in the real-world setting. This study evaluated the clinical value of CDx in the real world with respect to overall survival among patients with non-squamous advanced (Stage IIIB/IV) NSCLC (aNSCLC). Methods: Patients were from the Flatiron Health electronic health-derived database, treated with systemic therapy, and diagnosed with aNSCLC between January 1, 2011 and May 31, 2018; those who received CDx with their first line of treatment were compared with those who did not. Logistic regression using components of the modified Lung Cancer Prognostic Index (LCPI; age, sex, stage, actionable mutation(s), smoking, respiratory comorbidity; Alexander et al. Br J Cancer. 2017) and other factors were used to predict characteristics associated with receiving CDx. Overall survival was evaluated using Kaplan-Meier analysis. Unadjusted and adjusted Cox proportional hazards regression models were used to evaluate the association between CDx and overall survival. Results: A total of 17,143 patients with aNSCLC (CDx, n = 14,389; no CDx, n = 2754) and a mean (SD) age at diagnosis of 67.2 (10.0) years (CDx, 67.1 [10.1]; no CDx, 67.5 [9.2]) were included. There were more nonsmokers in the CDx group (17.4%) than the no CDx group (5.5%). Patients who were female, diagnosed after 2014, receiving multiple lines of therapy or had advanced stage at diagnosis were more likely to receive CDx. Patients receiving CDx had decreased mortality risk (unadjusted HR [95% CI] = 0.54 [0.52-0.57]) and lived longer than those not receiving CDx (median survival = 14 vs 7 months). The significant reduction in mortality associated with CDx remained after adjusting for factors included in the modified LCPI (adjusted HR [95% CI] = 0.78 [0.75-0.82]) as well as a model without actionable mutations (adjusted HR [95% CI] = 0.70 [0.66-0.73]). Conclusions: Among patients with non-squamous aNSCLC, use of CDx was associated with reduced risk of mortality compared with no CDx.

Author(s):  
Claudius E. Degro ◽  
Richard Strozynski ◽  
Florian N. Loch ◽  
Christian Schineis ◽  
Fiona Speichinger ◽  
...  

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 519-519 ◽  
Author(s):  
M. N. Ibrahim ◽  
Z. Abdullah ◽  
L. Healy ◽  
C. Murphy ◽  
I. Y. Yousif ◽  
...  

519 Background: Carcinoma in situ (CIS) of the breast is a precancerous lesion with the potential to progress to invasive cancer. In 2003, CIS accounted for 19% of all newly diagnosed invasive and non-invasive breast lesions combined in the United States. Current treatment options are mastectomy ± tamoxifen, and breast-conserving surgery with radiotherapy ± tamoxifen. As there are no randomized comparisons of these 2 treatments, data from the Surveillance Epidemiology and End Results (SEER) database was used to compare their survival rates. Methods: 88,285 patients were identified with CIS from 1988 - 2003. Of these, 27,728 patients were treated with a total mastectomy, and 25,240 patients received breast-conserving surgery with radiotherapy. Kaplan-Meier survival analyses and Cox proportional hazards regression were used to compare overall survival and disease specific survival at 5 and 10 years. Results: Kaplan-Meier analyses demonstrated 5 year overall survival rates for total mastectomy vs. breast conserving surgery with radiotherapy of 95.46% vs. 97.59% respectively (Log-rank P < 0.0001). The 5 year rates for disease specific survival were 99.16% vs. 99.72% respectively (Log-rank P < 0.0001). At 10 years the overall survival rates had fallen to 91.96% vs. 96.09% respectively (Log-rank P < 0.0001). The 10 year disease specific survival rates were 98.61% vs. 99.50% respectively (Log-rank P < 0.0001). Cox proportional hazards regression demonstrated a relative risk of 0.847 (95% confidence interval (CI) 0.790 - 0.907) and 1.110 (95% CI 0.931 - 1.324) for 5 year overall survival and disease specific survival respectively, when total mastectomy was compared with breast conserving surgery and radiotherapy. At 10 years, the relative risks were 0.865 (95% CI 0.820 - 0.913) and 1.035 (95% CI 0.900 - 1.190) for overall survival and disease specific survival respectively. Conclusions: Overall, when looking at disease-specific survival rates by multi-variate analysis, there does not appear to be a significant difference between total mastectomy and breast-conserving surgery with radiotherapy in the treatment of CIS. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14106-e14106
Author(s):  
Susan H Foltz Boklage ◽  
Charles Kreilick ◽  
Carl V Asche ◽  
Sally Haislip ◽  
James W. Gilmore ◽  
...  

e14106 Background: Improvements in survival for advanced-stage colorectal cancer (CRC) patients who receive chemotherapy have been reported. We compared survival rates for patients with 3+ vs. <3 lines of therapy using electronic medical records of a local oncology practice in Georgia, USA. Methods: The Georgia Cancer Specialist (GCS) EMR Database (1/1/2005–07/ 31/2010) was used. The database contains data on patient demographics, cancer diagnostic information, chemotherapy and non-chemotherapy drugs administered written prescriptions, chemotherapy/radiation protocols, chemotherapy protocol changes, office visit information, and hospitalizations. Patients newly diagnosed with CRC between 01/01/05 and 06/31/10 treated with systemic therapy for CRC were identified. Patients were followed from initial CRC diagnosis to death, loss to follow-up, or end of study. Patients were categorized by number of lines of therapy received (1, 2, 3+) and original stage at diagnosis (III b/c, IV, unknown). Survival following initial line of therapy was evaluated using Cox proportional hazards models controlling forstage at diagnosis, type of 1st line treatment, and other patient characteristics. Results: The study included 704 patients with a median age of 63 years (age range 26-85 years) at diagnosis and 49% (n=345) female. 45% (n=317) and 42% (n=296) had stage IV and III b/c CRC at diagnosis, respectively. 53% (n=373) received only 1st line treatment, 27% (n=190) received 1st and 2nd line treatment and 20% (n=141) received 3rd line and beyond. The median follow up was 431 days and death was reported in 27%(n=190) of subjects. The multivariate Cox proportional hazard analysis indicated that there was no statistical difference in survival between patients who received 2nd line of therapy vs. 3 plus lines of therapy (HR=1.42; p<0.067). Conclusions: A non-statistical significant association between 2nd and more than 3 total lines of therapy in survival was found in subjects diagnosed with stage III B/C and IV. However the trend towards survival was present, indicating that some patients could benefit from the addition of 3rd line but it would require additional studies to confirm this.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17553-e17553
Author(s):  
Dimitrios Matthaios ◽  
Panagiotis Hountis ◽  
Grigorios Trypsianis ◽  
Athanasios Zissimopoulos ◽  
Demosthenes Bouros ◽  
...  

e17553 Background: Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study we assessed the expression of γ-Η2ΑΧ in a cohort of 96 patients with non-small cell lung carcinoma and evaluated its role as a prognostic indicator in resectable NCSLC patients. Methods: 96 parafin-embedded specimens of non-small lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph nodes dissection. γ-Η2ΑΧ expression was assessed by standard immunohistochemistry.Multivariate Cox proportional hazards regression analysis, using a backward selection approach, were performed to explore the independent effect of variables on survival. All tests were two tailed and statistical significance was considered for p values <0.05. Results: Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2-57 months, median 24 months). Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% CI = 28.5 to 35.8 months; median 30.0 months); one, two and three-year survival rates were 86.5 ± 3.5%, 57.3 ± 5.1% and 37.1 ± 5.4% respectively. Low γ-H2AX expression was associated with a significant better survival as compared with those having high γ-H2AX expression (23.2 months for high γ-Η2ΑΧ expressin vs 35.3 months for low γ-H2AX expression, p=0.009; HR=1.95, 95% CI=1.15-3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained independent prognostic factors of worse overall survival (HR=2.15, 95% CI=1.22-3.79, p=0.026). Conclusions: Our study is the first study to demonstrate that overexpression of γ-Η2ΑΧ is an independent prognostic indicator of worse overall survival in patients with non-small lung cancer. Further studies are needed to confirm our results.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20646-e20646
Author(s):  
Hosam Hakim ◽  
Ahmed Abdalla ◽  
Tarik H. Hadid

e20646 Background: There have been numerous advances in the management of metastatic lung cancer, including targeted therapy against certain mutations in cancer cells and later developing immune therapy with check point inhibitors.From the pre-immune therapy era, a simple blood test allowing the calculation of the neutrophil-to-lymphocyte ratio (NLR) was established as a strong prognostic marker associated with worse overall survival (OS) in several tumor types including non-small cell lung cancer (NSCLC). Methods: We have retrospectively reviewed electronic medical records for patients with Metastatic NSCLC whom received at least one dose of Checkpoint Inhibitors from January 2014 till January 2019 in Van Eslander Cancer Center.The analysis was done using SPSS v. 25.0 and a p-value of 0.05 or less was considered to indicate statistical significance. A univariant analysis was done using Student’s t-test, the Mann-Whitney U test and the chi-squared test. Survival analysis was conducted using Kaplan Meier methodology as well as Cox proportional hazards models. Results: There were 80 patients with metastatic NSCLC received at least one dose of a checkpoint inhibitor. Median age was 63.9 ± 9.3; Males were 45%; Whites were 62.5%. 67.5% of patient had adenocarcinoma and 24% had squamous cell carcinoma. Twenty patients had brain metastasis (25%) and nineteen patients had liver metastasis (24.6%). Eleven patients (13.8%) had PDL-1 greater than 50% and 11 patients (13.8%) had PDL-1 between 1%-50% and 22 patients (27.5%) had negative PD-L1 status. 18.8% received immunotherapy as a first-line treatment and 65% got immunotherapy on their second line and 16.3% had immunotherapy as the third line of treatment or more. Sixty-one patients (76.2%) received Nivolumab and nineteen patients (23.8%) received pembrolizumab. Mean duration of immunotherapy was 13.7 months ± 20.7. Mean NLR was 6.1 ± 5. Patient with NLR > 5:1 had statistically significant higher progression-free survival (PFS) 27.5 months compared to 12 months P = 0.02. Also, Patients with baseline NLR > 5:1 had a trend toward higher median overall survival (OS) but was not statistically significant 41 months compared to 12 months P = 0.08. Conclusions: Our data showed similar finding to Bagley et al and other retrospective analysis from multiple institutes showing that NLR could be a good predictor of response to checkpoint inhibitors And a cutoff of NLR higher than 5.1 was associated with statistically significant better PFS and a trend towards a better OS.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomoyuki Hida ◽  
Akinori Hata ◽  
Junwei Lu ◽  
Vladimir I. Valtchinov ◽  
Takuya Hino ◽  
...  

Abstract Background Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort. Methods Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables. Results ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 – not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment. Conclusions ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6086-6086
Author(s):  
F. C. Holsinger ◽  
W. Dong ◽  
N. Bekele ◽  
R. S. Weber ◽  
M. S. Kies ◽  
...  

6086 Background: Despite advances in achieving improved locoregional control for patients with head and neck cancer (HNC), overall survival has not improved in the last 30 years. Several studies have implicated distant metastasis as a potential cause, hindering progress in the treatment of HNC. However, little is known about which patients fail systemically. We therefore sought to identify clinico-pathological factors that are associated with distant metastasis as the only cite of failure. Methods: We retrospectively studied 389 patients with head neck squamous cell carcinomas with distant metastases as the primary site of failure excluding all patients with locoregional recurrence and those receiving chemotherapy at primary presentation. The median follow up period was 5.3 years. An estimate of the risk of DM and DM free survival by prognostic factors was calculated using multivariate analysis and Cox proportional modeling. Results: Overall, 11% (43/389) of the patients developed DM. With univariate analysis, site of the tumor arising within the laryngopharynx, T stage (T3–4), N stage>2, and metastasis to level IV were significantly associated with DM. However, using Cox proportional hazards regression modeling, two clinicopathologic variables, N classification >N2b and diminishing degree of histologic differenention, were found to be most significantly associated with the development of systemic, distant metastasis. For patients staged as N2b or N2c, there was a relative risk (RR) of 6.13 (95% CI: 2.61 - 14.38; p < 0.0001) for developing DM. For patients staged as N3, the RR was 8.23 (95% CI: 2.39 - 28.38; p < 0.001). For patients with poorly differently HNSCC, RR was 11.01 (95% CI: 1.42 - 85.15; p = 0.022) Conclusions: Recognizing patients at primary presentation with tumors with the highest risk for the development of DM might le us to selectively treat them aggressively with systemic therapy to eradicate the tumor, thus improving overall survival rates. No significant financial relationships to disclose.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1160
Author(s):  
Sandra Pietrzak ◽  
Janusz Wójcik ◽  
Piotr Baszuk ◽  
Wojciech Marciniak ◽  
Małgorzata Wojtyś ◽  
...  

The effects of heavy metals on cancer risk have been widely studied in recent decades, but there is limited data on the effects of these elements on cancer survival. In this research, we examined whether blood concentrations of the heavy metals arsenic, cadmium, mercury and lead were associated with the overall survival of lung cancer patients. The study group consisted of 336 patients with lung cancer who were prospectively observed. Blood concentrations of heavy metals were measured to study the relationship between their levels and overall survival using Cox proportional hazards analysis. The hazard ratio of death from all causes was 0.99 (p = 0.94) for arsenic, 1.37 (p = 0.15) for cadmium, 1.55 (p = 0.04) for mercury, and 1.18 (p = 0.47) for lead in patients from the lowest concentration quartile, compared with those in the highest quartile. Among the patients with stage IA disease, this relationship was statistically significant (HR = 7.36; p < 0.01) for cadmium levels in the highest quartile (>1.97–7.77 µg/L) compared to quartile I (0.23–0.57 µg/L, reference). This study revealed that low blood cadmium levels <1.47 µg/L are probably associated with improved overall survival in treated patients with stage IA disease.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 419-419 ◽  
Author(s):  
Ademi E. Santiago-Walker ◽  
Fei Chen ◽  
Yohann Loriot ◽  
Arlene O. Siefker-Radtke ◽  
Libo Sun ◽  
...  

419 Background: FGFR alterations have been shown to be associated with immunologically “cold” UC tumors with low immune marker expression and T cell infiltrate, a poorly receptive environment for immune checkpoint inhibitors. Using a real world matched clinical and genomic dataset of pts with advanced UC, we explored their predictive value in pts receiving anti-PD-(L)1 therapy. Methods: The Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) contained full clinical and treatment information and molecular data on a cohort of pts with confirmed advanced UC. The populations of interest are FGFR+ and FGFR- patients determined by the presence or absence of a prespecified panel of FGFR2/3 mutations and fusions. Overall survival (OS), measured from the start of anti-PD-(L)1 therapy, was analyzed using Kaplan-Meier estimation and Cox proportional hazards models adjusted for left truncation (delayed entry model). Results: 118 pts ( FGFR+ n = 26, FGFR- n = 92) treated with anti-PD-(L)1 therapy for advanced UC were assessed for OS. Median OS for FGFR+ pts who received any line of anti-PD-(L)1 therapy (n = 26) was 3.1 mo vs 6.1 mo for FGFR- pts (n = 92) (hazard ratio [HR] 1.33, 95% CI 0.78-2.26, p = 0.30). For first-line anti-PD-(L)1 therapy, median OS in FGFR+ pts (n = 12) was 4.7 mo vs 11.3 mo for FGFR- pts (n = 28) (HR 1.94, 95% CI: 0.78-4.82, p = 0.15); median OS in second-line were 3.1 mo (n = 12) vs 6.1 mo (n = 47), respectively (HR 1.17, 95% CI 0.53-2.59, p = 0.70). Per multivariate analysis, FGFR+ status appears to be associated with poorer OS in pts treated with any line of anti-PD-(L)1 therapy (HR 1.25, 95% CI 0.71-2.21, p = 0.43). Conclusions: These real-world data suggest that FGFR+ pts following anti-PD-(L)1 therapy for advanced UC may be associated with a trend in poorer overall survival outcome compared with FGFR- pts. These findings are in alignment with treatment history data from BLC2001 (Siefker-Radtke A, et al. ASCO-GU 2018), which showed low response rates to prior anti-PD-(L)1 therapies among FGFR+ pts.


Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew J. Jacobs ◽  
Ryan Michels ◽  
Joanna Stein ◽  
Adam S. Levin

Several patient demographic factors, including marital status, have been demonstrated to have prognostic significance for survival in extremity soft tissue sarcoma (ESTS). A study population of 12,546 adult patients diagnosed with ESTS from 1991 to 2010 was identified from the SEER database, a large population-based registry, in order to determine whether overall survival had changed over this recent 20-year period. The study population was divided into three groups by year of diagnosis: 1991–1996, 1997–2003, and 2004–2010. We used the Kaplan-Meier method and Cox proportional hazards regression to assess survival differences between different demographic groups and prognostic clinical characteristics. Over the course of time, the 5-year overall survival rates have increased from 28% in the earliest time period to 62% in the latest(P<0.0001). On multivariate analysis, the mortality rate progressively declined from the 1991–1996 group (HR: 3.02, CI: 2.78–3.29) to the 1997–2003 group (HR: 2.21, CI: 2.06–2.37), with the 2004–2010 group having the best overall survival, despite increases in the proportion of patients with tumors greater than 5 cm in size(P<0.0001), and those presenting with metastasis(P<0.0001).


Sign in / Sign up

Export Citation Format

Share Document