e16535 Background: Prior studies suggest a survival benefit of adjuvant abdomino-pelvic XRT for the treatment of low stage, non-serous EOC. However, the long-term risk of a SCa from XRT is unknown. We examined the relationship between XRT use and the risk of SCas in a population-based cohort of EOC pt. Methods: We determined the rates of SCa in a previously described cohort of stage I-III (microscopic residual only) EOCs, diagnosed between 1984-2008 and treated with adjuvant chemotherapy +/-XRT(45 Gray to abdomen and pelvis) at any of 5 regional Cancer Centers in British Columbia. SCas were any non-skin cancer(ca) diagnosed > / = 12mo after the primary EOC. The site of SCa relative to the XRT field was determined by a radiation oncologist(in-field/field border/out-of-field)(CH). Cox regression accounting for age, stage and histotype comparing XRT vs. no XRT was used to determine the hazard for developing SCa as the event of interest. Competing risk analysis was carried out looking at either SCa or death due to XRT. Results: 703 pts were included in the analysis: median age 56 years (yrs)(range 25-89), 38% stage I, 44% stage II and 18% stage III, 37% high grade serous ca (HGSC), 25% endometrioid ca, 22% clear cell ca, 10% mucinous ca and 6% unknown. 351(49.9%) pt received XRT, while 352(50.1%) did not. XRT was associated with a longer median survival (14.1 vs 8.3 yrs,p < 0.0001). Median time to SCa was 8.4 yrs overall. The rate of SCa was 15%(53 pt) with and 10%(34 pt) without XRT, p = 0.04. Among pt who had XRT, 45% of SCas were in-field, 36% out-of-field, 11% along the field border and the remaining unknown. There was no difference in time to SCA between in-field/border vs. out-of-field SCa(p = 0.292). Cox regression analysis revealed no significant difference in the risk of SCa according to XRT use(HR 1.21,95%CI,0.77-1.90,p = 0.40). There was no increased risk of SCa on the basis of EOC histotype. Competing risk analysis did not demonstrate a significant increase in cumulative incidence of SCa due to XRT, p = 0.26. Conclusions: In this population-based cohort of low stage EOCs, XRT was not associated with a higher risk of SCAs. This study is limited by the small sample size and relatively short median follow up.
To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence.Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population.In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37).In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.
e14568 Background: HER2 positive gastric (GC) and GEJ adenocarcinoma has been associated with a worse survival outcome. This study examines the survival rate of patients with metastatic HER2 positive GC and GEJ adenocarcinomas in the province of BC. Methods: Formalin fixed embedded tissue from patients (pts) with resected gastric or GEJ adenocarcinoma from 2004-2011 were identified retrospectively through the BC Cancer Agency registry and prospectively for pts with a new diagnosis of advanced disease. Biopsies and resection samples were analyzed via previously validated methods. IHC scores of 3 were considered positive (+), 2 were equivocal and 0 or 1 were negative (-). A 10% cut-off was used to determine positive samples. Equivocal staining was considered positive via FISH or SISH with a ratio of > 2.2 considered amplified. Patient characteristics were abstracted to an anonymized database. Kaplan-Meier curves were calculated to evaluate overall survival from time of diagnosis or relapse to death for pts with HER2 + or - disease. Results: 179 of 304 pts were identified with metastatic or relapsed gastric or GEJ adenocarcinoma without Traztumumab treatment. 21 (12%) pts were HER2 + either by IHC, FISH or SISH. Refer to the table for characteristics of both groups. Median survival was not significantly different among HER2 + and - pts (4.0 mo vs. 7.3 mo, p=0.089). Conclusions: The rate of HER2 positivity is similar to that seen in trial data. HER2 positivity trends to a worse prognosis but was not significant in this study. [Table: see text]
Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors.Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses.261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS.In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.
3527 Background: AC is frequently considered inpatients (pts) with "high risk" stage II CC, defined by the presence of >/=1 poor prognostic features, such as obstruction or perforation, T4 stage, <12 lymph nodes retrieved, positive margins, and lymphovascular or perineural invasion. However, survival benefits associated with AC use in high risk pts remain largely unproven. Our aims were to 1) examine patterns of AC use in stage II CC and 2) explore the relationship between AC use and survival in high vs low risk pts. Methods: All pts diagnosed with stage II CC in British Columbia from 1999 to 2008 and evaluated at any 1 of 5 regional centers were reviewed. Kaplan-Meier and Cox regression methods were used to correlate a) high vs low risk status and b) receipt of AC with relapse-free (RFS), disease specific (DSS) and overall survival (OS). Results: We identified 1,697 stage II CC pts: 1,236 (73%) high risk and 461 (27%) low risk among whom 363 (29%) and 61 (13%) received AC, respectively. Individuals with high risk features who received AC were younger (median 62 vs 72 years, p<0.001) and had better performance status (ECOG 0/1 47% vs 34%%, p=0.02). In the high risk group, AC was associated with improved 5-year OS, but not with RFS or DSS (Table). After adjusting for confounders, an OS advantage from AC persisted for high risk pts (HR 0.67, 95CI 0.52-0.86, p=0.002), but no significant RFS or DSS benefits were seen (HR 0.76, 95CI 0.58-0.99, p=0.05 and HR 0.75, 95CI 0.55-1.02, p=0.11, respectively). Subgroup analyses showed that individuals with T4 lesions had improved RFS (HR 0.63, 95CI 0.42-0.95, p=0.03), DSS (HR 0.59, 95CI 0.37-0.93, p=0.02), and OS (HR 0.50, 95CI 0.33-0.77, p=0.002). Conclusions: In this population-based cohort of stage II CC, AC was associated with an OS advantage in high risk pts, likely due to pt selection. RFS and DSS benefits were mainly seen in T4 lesions, suggesting a limited role for AC in pts deemed high risk based on clinical and pathological factors. Risk stratification based on molecular testing should be further explored. [Table: see text]
398 Background: High-risk stage II CC is defined as those presenting with T4 stage, obstruction or perforation, <12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. Our prior findings suggest that improved outcomes from AC are limited to specific high-risk features, such as T4 disease (Kumar et al, ASCO 2012). It is unclear if this benefit is seen across all ages. Our aim was to compare patterns of AC use and outcomes in YP and EP with high-risk stage II CC. Methods: All patients diagnosed with high-risk stage II CC from 1999 to 2008 and evaluated at any 1 of 5 regional cancer centers in British Columbia were categorized into YP (age <70 years) or EP (age >/=70 years). Kaplan-Meier methods and Cox regression were used to correlate receipt of AC with overall survival (OS), disease specific (DSS), and relapse-free survival (RFS), stratified by age group. Results: A total of 1,236 patients were identified: 636 (51%) YP and 600 (49%) EP among whom 363 (57%) and 85 (14%) received AC, respectively. Individuals who received AC in either age group had better performance status than those who did not (ECOG 0/1 47% vs. 34%, p=0.02). After adjusting for known prognostic factors, a significant advantage in OS, but not DSS or RFS, from AC was observed for both YP and EP (Table). The impact of AC on these outcomes was similar across age groups (p interaction of age and treatment = 0.46, 0.64, and 0.69 for OS, DSS, and RFS, respectively). In the entire cohort, individuals with T4 lesions had significantly improved OS (HR 0.50, 95%CI 0.33-0.77, p=0.002), DSS (HR 0.59, 95%CI 0.37-0.93, p=0.03), and RFS (HR 0.63, 95%CI 0.42-0.95, p=0.03). The effect of AC in the T4 subgroup was also similar for both YP and EP in terms of OS, DSS and RFS (p interaction of age and treatment = 0.41, 0.71, and 0.77, respectively). Conclusions: In this population-based cohort of high-risk stage II CC, improvements in outcomes from AC were seen mainly in those with T4 disease, regardless of age. [Table: see text]
3628 Background: Clinical trial data does not support the routine use of adjuvant chemotherapy (ACT) following neoadjuvant chemoradiation (nCRT) and surgery (Sx) in rectal cancer (Ca). Few studies have included oxaliplatin-based ACT or assessed the benefit in specific pathologic stage (Pstage) subgroups. Methods: Data from patients (pts) with locally advanced rectal Ca who received nCRT and had curative intent Sx from 2005 to 2012 were collected from Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and Dr. H. Bliss Murphy Cancer Centre. The effect of ACT on Time Free of Recurrence (TFR – death without recurrence censored), Disease Free Survival (DFS) and Overall Survival (OS) was assessed using cox proportional hazards model, controlling for age, sex, performance status (PS), circumferential resection margin (CRM), location of tumor, RT dose, Clinical stage (Cstage), Pstage. Results: 1172 pts were included, with a mean age of 61.6 (± 0.33) and a mean follow-up time of 3.8 years (± 0.05). 303 (25.9%) pts received oxaliplatin-based ACT, while 328 (28%) did not receive any ACT and these pts were more likely to be older (65.8 v 65 yrs, p<0.0001), have worse PS (p=0.009), receive lower doses of RT (p=0.0003) and have earlier Cstage (p=0.004) on univariate analysis compared with ACT pts. Univariate analyses for Pstage 0-II were non-significant (NS) for effect of ACT on TFR and DFS. See Table for all pts and Pstage III outcomes controlling for covariates above. Assessment of ACT in high risk v low risk stage II (as in colon Ca) was NS for TFR (p=0.47), DFS (p=0.7) and OS (p=0.7) adjusting for age, PS and CRM. Conclusions: ACT improved clinical outcomes in our retrospective database, however the benefits may be limited to those with Pstage III. Studies are needed to clarify if factors used to stratify stage II colon Ca into high vs. low risk may be applied to estimate recurrence risk in Pstage II rectal Ca. Population TFR (95% CIs) p-value DFS (95% CIs) p-value OS (95% CIs) p-value All pts ACT v no ACT 0.84 (0.59 – 1.18) 0.31 0.63 (0.47 –0.85) 0.002 0.52 (0.36 – 0.75) 0.0004 Pstage III ACT v no ACT 0.6 (0.39 – 0.93) 0.02 0.53 (0.35 – 0.8) 0.002 0.48 (0.29 – 0.79) 0.004
3569 Background: High-risk stage II CC is defined as those presenting with T4 stage, obstruction or perforation, <12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. Our prior findings suggest that improved outcomes from AC are limited to specific high risk features, such as T4 disease (Kumar et al, ASCO 2012). It is unclear if this benefit is seen across all ages. Our aim was to compare patterns of AC use and outcomes in YP and EP with high risk stage II CC. Methods: All patients diagnosed with high risk stage II CC from 1999 to 2008 and evaluated at any 1 of 5 regional cancer centers in British Columbia were categorized into YP (age <70 years) or EP (age >/=70 years). Kaplan-Meier methods and Cox regression were used to correlate receipt of AC with overall survival (OS), disease specific (DSS) and relapse free survival (RFS), stratified by age group. Results: A total of 1,236 patients were identified: 636 (51%) YP and 600 (49%) EP among whom 363 (57%) and 85 (14%) received AC, respectively. Individuals who received AC in either age group had better performance status than those who did not (ECOG 0/1 47% vs. 34%, p=0.02). After adjusting for known prognostic factors, a significant advantage in OS, but not DSS or RFS, from AC was observed for both YP and EP (Table). The impact of AC on these outcomes was similar across age groups (p interaction of age and treatment = 0.46, 0.64 and 0.69 for OS, DSS and RFS, respectively). In the entire cohort, individuals with T4 lesions had significantly improved OS (HR 0.50, 95%CI 0.33-0.77, p=0.002), DSS (HR 0.59, 95%CI 0.37-0.93, p=0.03), and RFS (HR 0.63, 95%CI 0.42-0.95, p=0.03). The effect of AC in the T4 subgroup was also similar for both YP and EP in terms of OS, DSS and RFS (p interaction of age and treatment = 0.41, 0.71 and 0.77, respectively). Conclusions: In this population-based cohort of high risk stage II CC, improvements in outcomes from AC were seen mainly in those with T4 disease, regardless of age. [Table: see text]
