Aspirin use and survival outcomes in patients (pts) with PIK3CA mutant colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3598-3598
Author(s):  
Ben Tran ◽  
Robert N Jorissen ◽  
Jayesh Desai ◽  
Fiona Day ◽  
Lara Rachel Lipton ◽  
...  

3598 Background: Aspirin has an established role in preventing CRC. Recent data suggests aspirin use may also benefit a subset of pts diagnosed with CRC. In one series, the authors identified PIK3CA mutations as a potential predictive biomarker for aspirin use, reporting that PIK3CA mutant CRC pts receiving aspirin had superior cancer specific survival (CSS) compared to those not receiving aspirin (HR 0.18, p<0.001), whereas in pts with wildtype PIK3CA, aspirin had no survival impact. Our study aims to confirm the survival benefit associated with aspirin use in pts with PIK3CA mutant CRC. Methods: A cohort of CRC pts with PIK3CA mutations (Sanger sequencing) was identified. Prospectively collected clinicopathological, treatment and outcome data was available. Aspirin use was confirmed by chart review. CSS and overall survival (OS) analyses were conducted using Cox proportional hazards in univariate and multivariate settings. Recurrence free survival (RFS) analyses were limited to early stage CRC pts (Stage A-C). Statistical differences in 5-year CSS (5YS) rates were calculated using Fisher’s exact test. Results: From a cohort of 1,019 CRC pts with known PIK3CA mutation status, 121 (12%) harbored PIK3CA mutations. Of these, 112 (92%) had aspirin usage data available: 27 (24%) pts used aspirin, 85 (76%) did not. In the aspirin group, there were 22 (81%) early stage and 5 (19%) metastatic CRC pts; in the no-aspirin group, there were 59 (69%) early stage and 26 (31%) metastatic CRC pts. In univariate analyses, aspirin use was not associated with superior CSS (HR 0.57, p=0.21), OS (HR 0.83, p=0.57), or RFS (HR 0.72, p=0.57). In multivariate analyses, aspirin use was not associated with improved OS (HR 1.07, p=0.86), CSS (HR 1.04, p=0.94) or RFS (HR 0.54, p=0.34). In 69 (62%) pts with mature follow-up, there was a trend towards superior 5YS for aspirin users (69% v 42%, p=0.09), but this may reflect imbalances in stage at diagnosis. Conclusions: Our study was unable to confirm the recently reported survival benefit associated with aspirin use in pts with PIK3CA mutant CRC. Given the small numbers of pts, a modest survival benefit associated with aspirin use cannot be excluded. Analyses in an expanded cohort of early stage pts are underway.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 618-618
Author(s):  
Chi Lin ◽  
Christopher K Brown ◽  
Charles Arthur Enke ◽  
Fausto R. Loberiza

618 Background: Gastrointestinal melanoma (GIM) is a rare disease. The objective of this study is to compare the overall survival (OS), cancer specific survival (CSS) and prognostic factors of GIM to those of skin melanoma (SKM) using the Surveillance, Epidemiology, and End Results (SEER) registry. Methods: Patients diagnosed with invasive GIM (406) and SKM (173,622) between 1973 and 2008 were identified from the SEER database. Factors analyzed included age (18-40/41-60/61-100), gender, race (White/nonwhite), marital status, stage (localized/regional/distant), year of diagnosis (1973-87/1988-97/1998-2008), and type of treatment (radiotherapy (RT)/surgery). OS and CSS were evaluated using the Kaplan-Meier method. Cox proportional hazards regression analysis examined what factors were prognostic of survival. Results: The median age was 69 and 57 for patients with GIM and SKM, respectively. The GIM group was older with more advanced-stage cancer than the SKM group. Surgery was performed on 85% and 95%, while RT was received by 18% and 2% of GIM and SKM patients, respectively. The GIM group had a median OS and CSS of 15 and 16 months, respectively, while the SKM group had a median OS of 283 months and did not reach a median CSS. Cox analysis showed that SKM had significantly lower risk of total and cancer-specific mortality compared to GIM (Hazard Ratio (HR) 0.40, p<0.0001) and (HR 0.34, p<0.0001). Factors associated with improved OS and CSS in SKM included: age ≤60, female gender, non-white race, early stage, being married, more recent diagnosis, undergoing surgery and not receiving RT. Factors associated with improved OS and CSS in GIM included: age ≤60, early stage, non-white race and undergoing surgery. Subgroup analysis on patients who underwent surgery showed that lymph node status was the only prognostic factor for GIM, while all of the previously identified prognostic factors except for race were associated with OS and CSS for SKM. Conclusions: Outcomes of patients with GIM are inferior to those with SKM. The melanomas in these two sites also have different prognostic factors. Future studies should explore the reasons behind these differences to improve treatment outcomes.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6028-6028 ◽  
Author(s):  
Barbara Burtness ◽  
Ju-Whei Lee ◽  
Donghua Yang ◽  
Fang Zhu ◽  
Joaquin J. Garcia ◽  
...  

6028 Background: Abnormalities in EGFR signaling targets are associated with C resistance but no biomarker of C resistance has been identified in HNSCC. We hypothesized that cases with loss of PTEN protein expression (PTEN null) or PIK3CA mutation would display C resistance in HNSCC. Methods: E5397 was a phase III trial of CDDP plus P or CDDP plus C and enrolled 117 eligible and evaluable pts. PIK3CA and PTEN were analyzed for 52 and 67 consented pts, respectively. PTEN expression (PTEN Cell Signaling Technology, Cat. 9559) was determined by automated quantitative analysis (AQUA) on the PM-2000 (HistoRx, New Haven) using a cutpoint generated in 5 HNSCC tissue microarrays, each consisting of HNSCC as well as positive (small intestine, median AQUA score 2833.2) and negative controls (breast and colon carcinoma, median AQUA score 205.5). A cutpoint of 570 provides 100% specificity, 100% sensitivity, and identified 30% of the HNSCCs as PTEN null, consonant with the literature. The 3 most common PIK3CA mutations (E542K and E545K in exon 9 and H1047R in exon 20) were determined by BEAMing (Inostics, Heidelberg, Germany). Response, overall survival (OS) and progression-free survival (PFS) were compared between PTEN null or PIK3CA mutated pts and all others. Log rank and multivariable Cox proportional hazards modeling were used to calculate p values. Results: 23/67 (34%) tumors were PTEN null and 2/52 (4%) had PIK3CA mutations (E542K and E545K). Both tumors with PIK3CA mutation had PTEN expression. No statistically significant differences in response, OS or PFS were noted in this small sample. However, among PTEN expressing/PIK3CA WT pts, median PFS increased to 4.2 months (m) for C (N=22) from 2.9 m for P (N=26) (Wald p=0.07), compared with 4.6 m for C (N=12) and 3.5 m for P (n=13) among the PTEN null/PIK3CA mutated (Wald p=0.60). Conclusions: The PTEN loss or PIK3CA mutation signature warrants further investigation as a predictor of C resistance.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17520-e17520 ◽  
Author(s):  
Nnamdi Eze ◽  
Christine H. Chung ◽  
Veronique Neumeister ◽  
Teresa Sandoval-Schaefer ◽  
Ju-Whei Lee ◽  
...  

e17520 Background: No biomarker of C resistance has been identified in HNSCC. PTEN loss is present in approximately 30% of HNSCC. Biomarker analysis of the E5397 study suggested that addition of C to cisplatin in R/M HNSCC improves PFS in PTEN high/PIK3CA wild type patients but not those with PTEN loss or PIK3CA mutation. We hypothesized that PTEN testing may aid patient (pt.) selection for C therapy in HNSCC. Methods: MCC15780 was a phase II randomized trial of C plus sorafenib or C plus placebo in R/M HNSCC. 52/56 pts. in this study received C. PTEN analysis using AQUA as previously described was performed on tumor from 38 pts. Automated image capture was performed with HistoRx PM-2000 using the AQUAsition software. AQUA PTEN cut off determined as 1177 based on the first tertile.Fisher’s exact test used to compare low and high expression group. Event-time distributions estimated by Kaplan-Meier and compared using log-rank. Stratified Cox proportional hazards models used to estimate hazard ratios (HR) and test for significance for OS and PFS. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: 12/37 (32%) tumors were PTEN low. There was statistically significant improvement in PFS in PTEN high tumors compared to PTEN low tumors (HR (high/low) =0.33, 95% CI= (0.14, 0.75), p=0.008); and this remains significant after adjusting for age, sex, race, and ethnicity (HR (high/low) =0.27, 95% CI= (0.11, 0.67), p=0.004). Conclusions: PFS is significantly longer in PTEN high tumors compared to PTEN low tumors (HR=0.33, 95% CI= (0.14-0.75), p=0.008) in patients with R/M HNSCC treated with C. This finding remains significant after adjusting for age, sex, race, and ethnicity (HR=0.27, 95% CI= (0.11-0.67), p=0.004).This warrants PTEN analysis of specimens from larger cetuximab-based RCT. [Table: see text]


2009 ◽  
Vol 27 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Ivo A. Olivotto ◽  
Mary L. Lesperance ◽  
Pauline T. Truong ◽  
Alan Nichol ◽  
Tanya Berrang ◽  
...  

PurposeTo determine the interval from breast-conserving surgery (BCS) to radiation therapy (RT) that affects local control or survival.Patients and MethodsThe 10-year Kaplan-Meier (KM) local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and breast cancer–specific survival (BCSS) were computed for 6,428 women who had T1 to 2, N0 to 1, M0 breast cancer that was diagnosed in British Columbia between 1989 and 2003, and who were treated with BCS and RT without chemotherapy. Intervals from BCS to RT were grouped by weeks as follows: ≤ 4 (n = 83), greater than 4 to 8 (n = 2,288; reference group); greater than 8 to 12 (n = 2,606); greater than 12 to 16 (n = 961); greater than 16 to 20 (n = 358); and greater than 20 weeks (n = 132). Cox proportional hazards models and matching were used to control for confounding variables.ResultsThe median follow-up time was 7.5 years. The 10-year KM outcomes were as follows: LRFS, 95.4%; DRFS, 90.5%; and BCSS, 92.5%. Compared with the greater than 4 to 8 weeks group, hazard ratios (HR) were not significantly different for any outcome among patients who were treated up to 20 weeks after BCS. However, LRFS (hazard ratio [HR], 2.00; P = .15), DRFS (HR, 1.86; P = .02) and BCSS (HR, 2.15; P = .009) were inferior for women with BCS-to-RT intervals greater than 20 weeks compared with those greater than 4 to 8 weeks. The matched analysis yielded similar results.ConclusionOutcomes were statistically similar for BCS-to-RT intervals up to 20 weeks, but they were inferior for intervals beyond 20 weeks. Time can be reasonably allowed for the breast to heal and for patients to consider treatment options, but RT should start within 20 weeks of BCS.


2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.


2001 ◽  
Vol 19 (6) ◽  
pp. 1671-1675 ◽  
Author(s):  
Shari Gelber ◽  
Alan S. Coates ◽  
Aron Goldhirsch ◽  
Monica Castiglione-Gertsch ◽  
Gianluigi Marini ◽  
...  

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (± SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% ± 3% and 86% ± 4%, respectively. For the matched comparison group survival was 85% ± 3% at 5 years and 74% ± 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P = .04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.


2007 ◽  
Vol 25 (11) ◽  
pp. 1316-1322 ◽  
Author(s):  
Pierre I. Karakiewicz ◽  
Alberto Briganti ◽  
Felix K.-H. Chun ◽  
Quoc-Dien Trinh ◽  
Paul Perrotte ◽  
...  

Purpose We tested the hypothesis that the prediction of renal cancer–specific survival can be improved if traditional predictor variables are used within a prognostic nomogram. Patients and Methods Two cohorts of patients treated with either radical or partial nephrectomy for renal cortical tumors were used: one (n = 2,530) for nomogram development and for internal validation (200 bootstrap resamples), and a second (n = 1,422) for external validation. Cox proportional hazards regression analyses modeled the 2002 TNM stages, tumor size, Fuhrman grade, histologic subtype, local symptoms, age, and sex. The accuracy of the nomogram was compared with an established staging scheme. Results Cancer-specific mortality was observed in 598 (23.6%) patients, whereas 200 (7.9%) died as a result of other causes. Follow-up ranged from 0.1 to 286 months (median, 38.8 months). External validation of the nomogram at 1, 2, 5, and 10 years after nephrectomy revealed predictive accuracy of 87.8%, 89.2%, 86.7%, and 88.8%, respectively. Conversely, the alternative staging scheme predicting at 2 and 5 years was less accurate, as evidenced by 86.1% (P = .006) and 83.9% (P = .02) estimates. Conclusion The new nomogram is more contemporary, provides predictions that reach further in time and, compared with its alternative, which predicts at 2 and 5 years, generates 3.1% and 2.8% more accurate predictions, respectively.


2020 ◽  
Vol 7 (2) ◽  
pp. MMT43
Author(s):  
Alexandra Ikeguchi ◽  
Michael Machiorlatti ◽  
Sara K Vesely

Background: Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. Materials & methods: We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan–Meier method and Cox proportional hazards models. Results: All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Conclusion: Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.


2016 ◽  
Vol 10 (9-10) ◽  
pp. 321 ◽  
Author(s):  
R. Christopher Doiron ◽  
Melanie Jaeger ◽  
Christopher M. Booth ◽  
Xuejiao Wei ◽  
D. Robert Siemens

Introduction: Thoracic epidural analgesia (TEA) is commonly used to manage postoperative pain and facilitate early mobilization after major intra-abdominal surgery. Evidence also suggests that regional anesthesia/analgesia may be associated with improved survival after cancer surgery. Here, we describe factors associated with TEA at the time of radical cystectomy (RC) for bladder cancer and its association with both short- and long-term outcomes in routine clinical practice.Methods: All patients undergoing RC in the province of Ontario between 2004 and 2008 were identified using the Ontario Cancer Registry (OCR). Modified Poisson regression was used to describe factors associated with epidural use, while a Cox proportional hazards model describes associations between survival and TEA use.Results: Over the five-year study period, 1628 patients were identified as receiving RC, 54% (n=887) of whom received TEA. Greater anesthesiologist volume (lowest volume providers relative risk [RR] 0.85, 95% confidence interval [CI] 0.75‒0.96) and male sex (female sex RR 0.89, 95% CI 0.79‒0.99) were independently associated with greater use of TEA. TEA use was not associated with improved short-term outcomes. In multivariable analysis, TEA was not associated with cancer-specific survival (hazard ratio [HR] 1.02, 95% CI 0.87‒1.19; p=0.804) or overall survival (HR 0.91, 95% CI 0.80‒1.03; p=0.136).Conclusions: In routine clinical practice, 54% of RC patients received TEA and its use was associated with anesthesiologist provider volume. After controlling for patient, disease and provider variables, we were unable to demonstrate any effect on either short- or long-term outcomes at the time of RC.


2013 ◽  
Vol 7 (5-6) ◽  
pp. 299 ◽  
Author(s):  
Julie M. DeGroot ◽  
Michael D. Brundage ◽  
Miu Lam ◽  
Susan L. Rohland ◽  
Jeremy Heaton ◽  
...  

Objective: We compared the cause-specific survival of patientswho received radiotherapy to those who received surgery for cureof their prostate cancer using a number of design and analytic stepsto mitigate confounding by indication.Methods: This was a case-cohort study of 2213 patients in theOntario Cancer Registry diagnosed between 1990 and 1998 whowere either treatment candidates or received curative radiotherapyor surgery. Cases included patients who died of prostate cancerwithin 10 years. The study population was restricted to those whowere candidates for either treatment (radiotherapy or surgery)based on disease severity (low and intermediate risk using theGenitourinary Radiation Oncologists of Canada risk groups). Themedian follow-up was 51 months. Cause-specific survival wasanalyzed using Cox-proportional hazards regression with casecohortvariance adjustment.Results from intent-to-treat analyseswere compared to results by treatment received.Results: Adjusted hazard ratios for risk of prostate cancer death forradiotherapy compared to surgery for the entire study populationwere 1.62 (95%CI 1.00-2.61) and 2.02 (1.19-3.43) analyzing byintent-to-treat and treatment received, respectively. Intent-to-treathazard ratios for the low- and intermediate-risk groups were 0.87(0.28-2.76) and 1.57 (0.95-2.61), respectively.Conclusion: Overall results were driven by the finding in the intermediate-risk group, which indicated that radiotherapy was not aseffective as surgery in this group. Confirmation was needed withspecial attention paid to risk stratification and the impact of morecontemporary delivery of these treatment options.


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