Yr Overall Survival Research Articles

Nipple sparing mastectomy in breast cancer patients and long-term survival outcomes: An analysis of the SEER database.

PurposeTo determine the prevalence of nipple-sparing mastectomy (NSM) and its long-term survival outcomes in breast cancer patients.MethodWe used the Surveillance, Epidemiology, and End Results database and identified 2,440 breast cancer patients who received NSM during 1998–2013. We used chi-square and binary logistic regression to identify factors associated with the use of radiotherapy after NSM. We used Kaplan-Meier analysis to estimate cancer-specific survival (CSS) and overall survival (OS). We used the log-rank test and Cox regression to identify factors associated with CSS and OS.ResultsThe median age of the population was 50 years. There were 725 (29.7%), 1064 (43.6%) and 651 (26.7%) patients who had Tis, T1 and T2-3 disease and 1943 (79.6%), 401 (16.4%) and 96 (3.9%) patients who had N0, N1 and N2-3 disease, respectively. The rates of RT use were 61.4%, 39.6% and 10.9% in patients with N2-3 disease, N1 or T3/N0 disease and Tis/T1-2N0 disease, respectively. Elderly age, African American race, and higher T-stage and N-stage were associated with receiving radiotherapy. For patients diagnosed between 1998–2010 (N = 763), the median follow-up was 69 months. The 5- and 10-yr CSS were 96.9% and 94.9%, respectively. The 5- and 10-yr OS were 94.1% and 88.0%, respectively. Ethnicity, T-stage and N-stage were factors independently associated with CSS, and age and T-stage were factors independently associated with OS.ConclusionsThe use of NSM has increased, and it is oncologically safe for breast cancer patients.

Abstract 3283: Adjuvant therapy associated with improved survival in gall bladder cancer: A single institution retrospective study

Abstract Introduction: The survival outcome of resected gallbladder carcinoma remains poor. We conducted a retrospective study to examine factors affecting patient outcomes in resectable gallbladder carcinoma. Methods: We retrospectively collected data on patients treated at our institution between January 2005 and June 2015 from the electronic medical record using a standardized data collection tool. The univariate Cox proportional hazard model was used for evaluating predictors of overall survival. Kaplan-Meier method was used to compare time-to-events among subgroups and the p values were calculated by the log-rank method. Overall survival (OS) was defined as the time between surgery and death, or censored at the last follow-up date. Progression-free survival (PFS) was defined as the time to recurrence or death. Results: Of 67 evaluable patients, 65.7% were female. While clinical staging determined 51% to be stage 2 or less, interval portal lymphadenectomy and hepatic resection upstaged 20% to stage 3 or 4. Adjuvant chemotherapy (CT) was given to 18% and adjuvant chemoradiation (CRT) to 15%. About 46% did not receive any post-operative treatment and data was not available in 21%. On multivariate analysis, albumin < 3.5g/dl, LN involvement and pathological (p)Stage >2 were independent predictors of OS and PFS. Median 5 yrs OS and PFS of pstage < 2 was 54% and 54% respectively. Median 5 yr OS and PFS of stage ≥3 was 10.9% and 5.8% respectively. Adjuvant therapy was administered commonly for stage 3 and 4 (20 patients) compared to stage 1 and 2 (2 patients). In stage ≥3, adjuvant therapy improved OS (17.5% vs 8.9% for surgery alone) and PFS (12% vs 0%). Adjuvant chemoradiation for stage 3/4 had better median OS advantage compared to chemotherapy alone (54 m vs 15m, p=0.0008). Conclusion: The use of adjuvant treatment may improve long-term disease control in patients with node positive tumors. A significant difference between CRT and CT was demonstrated in our series and needs further validation in a larger cohort. Overall survial (OS) and progression-free survival (PFS) among various subgroupsGroup (n)Median OS (months)5 year OSMedian PFS (months)5 year PFSstage 1&2 (21)NA54%NA54%stage 3&4 (46)13.410.9%9.45.8%Surgery + Adjuvant treatment (22)25.115.9%16.910.9%Surgery alone (31)26.134.4%21.331.8%Surgery + CRT (10)54.235%45.724%Surgery + CT (12)14.90%13.40%Stage 3 and 4- Surgery + Adjuvant treatment (20)27.317.5%22.512%Stage 3 and 4- Surgery alone (15)2.78.9%2.10% Citation Format: Lakshminarayanan Nandagopal, Martin J. Heslin, John R. Porterfield, Rojymon Jacob, Peng Li, James Posey, Ravikumar Paluri. Adjuvant therapy associated with improved survival in gall bladder cancer: A single institution retrospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3283. doi:10.1158/1538-7445.AM2017-3283

The impact of chronic hepatitis C virus infection on survival in oropharyngeal cancer patients.

e17556 Background: An association between Hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported; however, the clinical significance of this epidemiological finding remains unknown. We therefore analyzed the oncologic outcomes of HCV-infected patients (pts) with OPCs. Methods: In this retrospective cohort study, all pts with OPCs seen at MD Anderson (1/2004-12/2015) were reviewed. HCV infection was defined as detectable HCV RNA in serum. Risk of 5-year (yr) overall survival (OS) and progression-free survival (PFS) was compared between HCV-infected (HCV+) and uninfected (HCV-) pts. OPCs that were positive for p16 by immunohistochemistry were considered HPV-related. Antiviral therapy (AVT) included either interferon (IFN)-based or IFN-free regimens. Multivariate cox proportional hazards model was used to identify independent predictors of mortality. Results: We studied 161 pts. Most of the pts were white (141; 88%), male (132; 82%) and had tumor stage 3 or 4 (147; 92%). The OPC involved tonsils (83; 52%), base of tongue (67; 42%) or soft palate (11; 7%). The median follow-up time after OPC diagnosis was 3 yrs (range: 1-13 yrs). HCV+ (n = 25) and HCV- pts (n = 136) were comparable in regards to smoking and alcohol status. In univariate analysis, HCV+ pts had more OPC progression after 1stline cancer treatment (48% vs 20.6% in HCV-, P = .0009) and were more likely to relapse (26% vs 5% in HCV-, P = .02). In multivariate analysis, HCV was associated with increased all-cause mortality [hazard ratio (HR): 2.15, 95% confidence intervals (CI): 1.08-6.85; P = .02] and risk of OPC progression [HR: 5.42, 95% CI: 2.64-11.14; P = .0008] independent of age and cirrhosis status. In HPV+ OPCs (n = 86), HCV + and HCV- pts did not have significant difference in mortality [HR: 2.03, 95% CI: 0.82-4.98; P = .12]. AVT was administered after OPC diagnosis in 8 of the 25 HCV+ pts (32%), with 6 of them receiving IFN-free AVT. HCV+ pts that received AVT had better 5 yr OS (median of 5.2 vs 2.3 yrs, P = .005) and PFS (median of 3.1 vs 0.7 yrs, P = .007) than the ones who did not. Conclusions: HCV seems to affect the oncologic outcomes of pts with OPCs and treating this infection might be beneficial. HCV screening and treatment should be considered in such pts.

Type, intensity, and duration of chemotherapy (CHT) and their correlation with prognosis of localized soft tissue Ewing tumors (STET): Experience of the Cooperative Weichteilsarkomstudiengruppe (CWS).

10527 Background: The optimal type and intensity of CHT in the treatment of STET is still a matter of debate. The CWS group has treated STET similar to rhabdomyosarcoma. We have analyzed the prognosis of STET in relation to the CHT regimens used in three consecutive CWS studies CWS-91, -96 and CWS- 2002P. Methods: 243 pts with localized STET were included. Their median age was 12 (range 0.1-29) yrs. In the CWS-91 pts with primary tumor resection (IRSG I and II) were treated with VACA (vincristine (VCR), actinomycin D (Act D), cyclophosphamide (CYC), doxorubicin (DOX), for 10 or 20 weeks. All other CWS-91 pts (high risk group, HRG) received EVAIA (ifosfamide (IFO) instead of CYC plus VP16) for 37 weeks. In the CWS-96 and CWS-2002P all STET pts were allocated to the HRG. In CWS-96 therapy was randomized: VAIA (IFO, DOX, Act D, VCR) vs. CEVAIE (Epi-DOX instead of DOX, plus carboplatin and VP16), for 25 weeks. In CWS-2002P VAIA (25 weeks) plus maintenance CHT with CYC and vinblastine (VBL) for 26 weeks were used. The cumulative doses varied: IFO 24-72 g/m², CYC 4.8-7.35 g/m², DOX 120-360 mg/m², Act D 3-9 mg/m², VP16 1.8-5.4 g/m². Irradiation was stratified depending on results of the primary or secondary resection and response. Results: 5 yr event free (EFS) and overall survival (OS) were 64% and 73%. The median observation time of survivors was 9 yrs. 5yr EFS and OS by study were: CWS-91 64 % and 72 %, CWS-96 57% and 70 %, CWS-2002P 78 % and 86 % respectively (n.s.). 5 yr EFS and OS for VACA arm were 79% and 90%. 5 yr EFS and OS by CHT for HRG were: EVAIA 57% and 65%, VAIA 64% and 80%, CEVAIE 45% and 54%, VAIA with CYC/VBL 84% and 87%, respectively (p = 0 .003). 5yr EFS and OS for irradiated (n = 181) vs. not irradiated (n = 48) patients were 63 % and 72% vs. 63% and 79%, respectively. Conclusions: The outcomes between CHT arms differed significantly: CEVAIA correlated with the worst outcome while VAIA with CYC/VBL showed the best results. A small group of low risk patients have an excellent prognosis with substantially reduced CHT. Ewing tumors are biologically heterogeneous and more diversification in therapy stratification is warranted to avoid overtreatment.

Adjuvant chemotherapy and outcome in patients (pts) with nodal (N-) and resection margin negative (R0) pancreatic adenocarcinoma (PC): A systematic review and meta-analysis.

4114 Background: Adjuvant chemotherapy following PC resection improves overall survival (OS). It is uncertain whether benefit is influenced by nodal and resection status or other factors. Methods: A systematic review of electronic databases identified published phase 2/3 studies investigating use of adjuvant chemotherapy in pts with resected PC. Efficacy (disease-free survival [DFS], OS, 5 yr OS) was explored using meta-analysis. Subgroup analysis explored effects based on nodal/resection status. Meta-regression also explored influence of age, gender, performance status [PS] and proportion of pts with head of pancreas (HOP) tumors on benefit of adjuvant chemotherapy. Results: Ten studies comprising 3644 pts were included. Two prospective phase 2 studies; 8 phase 3 trials. Median age was 63 yrs (range 24-84), 46% male. In 2268 pts with PS reported; 42% were PS 0, 51% PS 1. Tumor location was reported in 719 pts; 82% had HOP tumors. Of 3524 pts with available data; 33% N- and 67% R0. Overall, in studies of experimental vs control, adjuvant therapy significantly improved DFS (HR 0.67, CI 0.48-0.93, P = 0.02), OS (HR 0.77, 95% CI 0.68-0.87, P < 0.001) and odds of death risk at 5 yrs (OR 0.53, 95% CI 0.41-0.70, P < 0.001). In studies comparing chemotherapy to surgery only, adjuvant therapy also significantly improved DFS (HR 0.57, 95% CI 0.49-0.76, P < 0.001) and OS (HR 0.74, 95% CI 0.64-0.87, P < 0.001). There was a numerical but non-significant greater effect of adjuvant therapy in N- vs N+ pts (HR 0.58 vs 0.71, P for difference = 0.29). There was no difference in effect between pts with R0 or R1 disease (HR 0.70 vs 0.69, P for difference = 0.95). There was greater OS benefit from adjuvant therapy in pts with PS 0 (P = 0.04) and significantly less benefit on 5 yr OS in pts with HOP tumors (P = 0.04). Conclusions: The relative benefit of adjuvant chemotherapy seems similar in N-/N+ and in R0/R1 pts. This will translate into greater absolute benefit in the N+ and R1 pts due to their greater absolute risk of recurrence/death. Adjuvant chemotherapy is recommended for all pts with resected PC, where clinically appropriate, and greater benefit was seen in pts with PS 0 and body/tail tumors.

A single institutional experience of 261 patients with large granular lymphocytic leukemia (LGLL).

7555 Background: LGLL is a rare clonal lymphoproliferative disorder of post-thymic T-cell or natural killer (NK)-cell lineage associated with cytopenias, splenomegaly, autoimmune disorders, and recurrent mucocutaneous infections. Treatment is dictated by the presence of these manifestations and consists of immunosuppressive therapy. Methods: This is a retrospective analysis of clinical and laboratory features, treatment modalities, and outcomes of LGLL patients evaluated at Moffitt Cancer Center between 1995 and 2016. Continuous and categorical variables were tested via Kruskal-Wallis ANOVA and Fisher’s Exact Test. Kaplan-Meier curves were used for overall survival (OS). P-values were two-sided with significance set at < 0.05. Results: We identified 261 patients with LGLL (91.6% T, 8.4% NK). Median age was 66 years [21-90] and M:F ratio 1.2:1. Median follow up was 3.07 years [0-21.88]. 42.9% presented with anemia, 37.1% neutropenia, 30.7% thrombocytopenia, 29.1% bicytopenia and 6.9% pancytopenia. Transfusion dependence was noted in 20.3%, splenomegaly in 27.2% and bone marrow (BM) involvement in 69.3%. 24.9% had autoimmune diseases and 9.2% autoimmune cytopenias. 45.6% were observed while the remainder required at least 1 line of therapy. 5-yr and 10-yr OS were 75.0% and 63.1% respectively. There was no statistically significant difference in OS, complete response or duration of response based on first line agent (methotrexate, cyclophosphamide, cyclosporine A). However, there was a statistically significant improved partial response with methotrexate versus other therapies (p=0.01). A marginally significant association between severe anemia/transfusion dependence and poor overall response rate (p=0.075) to any therapy was noted. There was no statistically significant difference in OS based on absolute LGL count. Mean number of therapies was 1.08 (range 0-6) and was higher in those with LGL count <0.5 k/μL (p=0.0078), BM involvement (p<0.0001), and splenomegaly (p<0.0001). Conclusions: In this large retrospective study, we described the frequency of LGLL-associated manifestations and their impact on the course of LGLL. We confirmed that there is no difference in OS among first line therapies.

Prognostic implications of lymph node metastasis in advanced ovarian cancer: Analysis of National Cancer Database.

5567 Background: During debulking surgery (Surg) for advanced ovarian cancer (OvCa), lymph node (LN) sampling are not routinely performed. Hence, prognostic implications of LN involvement following debulking surg and chemotherapy (ChemoRx) were analyzed from National Cancer Database (NCDB). Methods: Only Stage III and Stage IV patients (pts) from 2004 –2014 NCDB pts undergoing Debulking surg. and ChemoRx were included. Group A included pts with debulking surg without bowel resection; Group B with major bowel resection and Group C with bowel and bladder resection. Pts were further subdivided according to the use of 1) NeoAdjuvant (NeoAdj) 2) Adjuvant (Adj) and 3) Neo Adj and Adj ChemoRx. Survival analysis was done based on -ve or +ve LN status. using Pearson Chi Square testing. Results: Out of 10,737 Stage III and 3,102 Stage IV pts, there were 6828 Group A, 6413 Group B and 598 Group C pts. Five year overall survival (OS) for all pts in Stage III with LN-ve vs LN +ve was 59.9% vs 53.9% and Stage IV was 48.7% vs 41.2%. In Group A, B, and C, the 5 yr OS was better in LN – ve than LN +ve pts (Table1). The OS for both LN –ve and LN +ve groups were better in Adjuvant chemoRx in all 3 groups. OS was slightly better in Stage III vs Stage IV pts. Conclusions: Even though LN dissection are not routinely done during debulking surg, overall pts with LN metastasis do worse than LN –ve pts irrespective of the timing of ChemoRx. Hence, LN sampling during debulking surg should be strongly considered as it may provide important prognostic information. [Table: see text]

Long-term outcomes after irradiation (RT) for pediatric low-grade glioma.

10549 Background: Treatment for pediatric low-grade glioma (LGG) is variable, depending on age and tumor location. Systemic therapy (ST) is often used to delay RT, but ST does not result in durable local control. The goal of this study was to evaluate event-free survival (EFS) and toxicities for pediatric LGG treated with RT over a 30-year period. Methods: All patients age ≤21 with intracranial pediatric LGG (WHO grade I-II) treated with RT at a single institution since May 1986 were included in this retrospective review. Patients with metastatic disease (M+) received craniospinal irradiation (CSI); otherwise, RT was conformal. EFS and overall survival (OS) were measured from the first day of RT. Events included death, progression, or secondary high-grade glioma. Results: 221 patients were eligible. Median follow-up was 11.3 yrs (range, 0.1-30.5). Median RT dose was 54 Gy. 10-yr EFS and OS were 67.9% (95% CI 60.4-74.3) and 91.1% (95% CI 85.8-94.5) for non-metastatic patients, respectively. For 12 M+ patients treated with CSI, 10-yr EFS and OS were 58.9% (95% CI 23.4-82.5) and 70.0% (32.9-89.2), respectively. 28.6% developed pseudoprogression (PP) with median time to onset and resolution of 6.1 months (IQR 3.6-14.6) and 6.4 months (IQR 3.5-11.7), respectively. Patients with PP had improved 10-yr EFS (83.4% vs. 61.0%, HR 0.40, p = .006). Patients with grade II tumors and who received pre-RT ST had lower EFS (Table). Sex, NF-1, tumor location, extent of surgery and CSI were not independently associated with EFS. 10-yr cumulative incidence of grade ≥2 vasculopathy was 7.5% (95% CI 4.9-11.4). There were 12 cases of secondary high-grade glioma, with a 20-yr cumulative incidence of 5.5% (95% CI 2.6-11.4). Conclusions: Irradiation provides long-term control of pediatric LGG in a majority of patients. Receipt of pre-RT systemic therapy was associated with reduced EFS; this association requires further investigation. [Table: see text]

Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.

e12590 Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) > 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.

Developing and validating a multivariable predictive biomarker for treatment selection for oropharyngeal squamous cell carcinoma: The PREDICTR-OPC study.

6004 Background: To date there are no validated predictive tests to inform treatment selection for patients with oropharyngeal cancer (OPC). Currently treatment is decided on disease resectability, clinician preference and patient choice. Methods: Objective To develop a predictive test to select treatment for advanced OPC. Participants Training cohort: 543 cases from 10 cancer centres. External validation cohort: 442 cases from 3 centres. Design Multivariable logistic regression of 8 clinical parameters and 10 biomarkers to develop biomarker-only and composite clinical/biomarker predictive models; subsequently validated on a separate cohort. Biomarkers scored by ≥2 ‘blinded’ pathologists. Outcomes Primary: overall survival (OS). Results: 724 males, 261 females; Median follow-up =8.8 (6.86-10.47) years. More validation cases received surgery (53.5% vs 37.9%, p=0.001) and fewer received chemo/radiotherapy (42%vs67.5%; p=0.001) compared to training cohort. The biomarker-only model performed better than the clinical/biomarker one. The final OS model - comprising p16, high risk HPV DNA ISH, survivin and tumour infiltrating lymphocyte score (TILS)- was not only prognostic for OS, but importantly was predictive for surgery+/-adjuvant RT over CRT (3yr OS 63%, vs 42.5% respectively) in the High Risk group. Treatments were equally effective in the Low Risk group. The RFS model (p16, PLK1, survivin, TILS) was prognostic, but not predictive for treatment. Validation testing confirmed good calibration and concordance (C-index =0.73; 0.68-0.79). The OS model remained prognostic and predictive for surgical treatment in High Risk group (HR=0.51; 95%CI= 0.3-0.85, p=0.01). Conclusions: To our knowledge, this is the first-ever validated model for treatment selection in HNC. Clinicians can now recommend the treatment most likely to be effective on the basis of an easily-applied, relatively inexpensive panel of 4 biomarkers. [Table: see text]

Claudin-4 Expression is Associated With Survival in Ovarian Cancer But Not With Chemotherapy Response.

The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ test. A dataset of >1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1-2.5), P=0.020 and HR=1.6 (1.0-2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0-2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1-1.5), P<0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7-2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.

MP34-05 THE PROGNOSTIC SIGNIFICANCE OF TNM STAGING IN BLADDER CANCER AFTER NEOADJUVANT CHEMOTHERAPY CAN BE ENHANCED WITH TUMOR REGRESSION GRADING

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2017MP34-05 THE PROGNOSTIC SIGNIFICANCE OF TNM STAGING IN BLADDER CANCER AFTER NEOADJUVANT CHEMOTHERAPY CAN BE ENHANCED WITH TUMOR REGRESSION GRADING Roland Seiler, Htoo Zarni Oo, Tilman Todenhöfer, Ladan Fazli, Mads Daugaard, and Peter Black Roland SeilerRoland Seiler More articles by this author , Htoo Zarni OoHtoo Zarni Oo More articles by this author , Tilman TodenhöferTilman Todenhöfer More articles by this author , Ladan FazliLadan Fazli More articles by this author , Mads DaugaardMads Daugaard More articles by this author , and Peter BlackPeter Black More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1022AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Classification of response to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is based primarily on TNM stage at cystectomy. We recently described post-NAC tumor regression grades (TRG) as an alternative method of risk stratification. Here we aim to validate our findings in an independent cohort and to integrate TRG with TNM staging. METHODS Fifty-five patients with MIBC received at least 3 cycles of cisplatin-based NAC and underwent cystectomy. As previously described (Fleischmann et al. Am J Surg Pathol 2014) TRG was assessed in cystectomy specimens by two independent investigators blinded to patient outcomes. TRG 1 represents absence of residual cancer, TRG 2 is characterized by predominant fibrosis containing scattered residual cancer cells, and TRG 3 shows residual cancer with minor component of fibrosis or absence of regressive changes. Major response to NAC was defined as absence of muscle invasive disease and lymph node involvement (<pT2 and pN0). The remaining patients were grouped in partial-responders (=pT2 or pN+ and TRG2) and non-responders (=pT2 or pN+ and TRG3), respectively. TNM stages with and without integration of TRG were correlated with overall survival (OS). RESULTS The 22/55 (40%) patients with major response to NAC had a significantly longer OS compared to the remaining patients (90% vs. 50% 5yr OS, p=0.005). TRG was successfully determined in all cases and concordance between both observers was high (91%). Of the 33/55 (60%) patients without major response, 13/55 (24%) and 20/55 (36%) were partial- and non-responders after combining TRG with the TNM stages. Kaplan-Meier estimates yielded an additional stratification of the cohort in 3 separated prognostic categories. Five-year OS of major-, partial- and non-responders was 90%, 65% and 40%, respectively. Multivariate survival analysis showed that the prognostic stratification of the cohort could be improved by integrating the TRG with the TNM stages (p<0.001). CONCLUSIONS Measurement of TRG after NAC is simple and reproducible. We successfully validated our prior discovery in an independent cohort. Moreover, integrating TRG with the current TNM classification significantly improved prognostic stratification. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e428 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Roland Seiler More articles by this author Htoo Zarni Oo More articles by this author Tilman Todenhöfer More articles by this author Ladan Fazli More articles by this author Mads Daugaard More articles by this author Peter Black More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP76-09 PREDICTORS OF METASTASIS AT TIME OF DIAGNOSIS AND OVERALL SURVIVAL IN METASTATIC TESTICULAR CANCER

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making IV1 Apr 2017MP76-09 PREDICTORS OF METASTASIS AT TIME OF DIAGNOSIS AND OVERALL SURVIVAL IN METASTATIC TESTICULAR CANCER Marshall Shaw, Andrew Bachman, Alexander Parker, Brian Cross, Kelly Stratton, Michael Cookson, and Sanjay Patel Marshall ShawMarshall Shaw More articles by this author , Andrew BachmanAndrew Bachman More articles by this author , Alexander ParkerAlexander Parker More articles by this author , Brian CrossBrian Cross More articles by this author , Kelly StrattonKelly Stratton More articles by this author , Michael CooksonMichael Cookson More articles by this author , and Sanjay PatelSanjay Patel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2137AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Few large series in the literature examine predictors of metastatic disease at time of testicular cancer diagnosis. We performed an analysis of the National Cancer Database (NCDB) to examine predictors of metastatic disease at the time of diagnosis and overall survival (OS) based on site of metastatic disease. METHODS Utilizing the NCDB, 44,354 patients were identified with data available for metastatic disease at time of diagnosis and tumor histology. Metastases were stratified as either absent, lymph node only, lung, brain, liver or bone metastases. Demographic characteristics, socioeconomic indicators and tumor histology were compared using the chi-squared test. Univariate survival analysis was performed using the Kaplan Meier method. Multivariate survival analysis was performed using cox proportional hazard model. RESULTS Mean age of diagnosis was 35 and mean follow-up was 53 months. On univariate analysis decreased age at diagnosis (p<0.001), non-white race (p=0.002), uninsured status (p=<0.001), <$38,000 annual income (p=<0.001), distance from treating hospital (p<0.001), and pure choriocarcinoma histology (166/202, 82%, p<0.001) were associated with metastases at time of diagnosis. 3,504 (7.9%) patients had metastatic disease at diagnosis. Kaplan Meier survival analysis showed significant differences in OS between metastatic sites at presentation, with 5 yr OS of 87% for lymph node only metastases compared to 48% OS in those with brain metastases (p<0.001). On multivariate analysis while controlling for age, race, insurance status, income, comorbidities, histology, receipt of chemotherapy, and primary tumor size, metastases to any site were associated with worsened survival compared to no metastases (referent): metastasis to lymph nodes (3.4, 95% CI: 2.70-4.50, p<0.001), lung (4.48, 95% CI: 3.69-5.43, p<0.001), liver (10.32, 95% CI: 6.78-15.7), bone (12.99, 95% CI: 7.93-21.29) and brain (14.4, 95% CI: 9.53-21.89). Private insurance status (0.48, 95% CI: 0.40-0.56, p<0.001) and income >$63,000 (0.72, 95% CI: 0.60-0.87, p=0.001) were favorable predictors of OS. CONCLUSIONS There are significant differences in OS dependent on site of metastases at time of testicular cancer diagnosis. Several sociodemographic factors likely contribute to likelihood of metastases at presentation as well. Further prospective studies are warranted to better characterize the impact of sociodemographic factors on metastases at presentation and to improve access to care in high-risk populations. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1016 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Marshall Shaw More articles by this author Andrew Bachman More articles by this author Alexander Parker More articles by this author Brian Cross More articles by this author Kelly Stratton More articles by this author Michael Cookson More articles by this author Sanjay Patel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

OS04.3 Extent of resection and overall survival in risk adjusted and exact matched analyses of 22,928 glioblastoma (all molecular subtypes) patients

Abstract Maximal tumor resection, chemo- and radiotherapy are the standard of care for glioblastoma (GBM), of which robust assessment by clinical trial methodology has been limited by GBM’s severely abridged survival and relatively rare prevalence. The United States National Cancer Database was queried for GBM patients newly-diagnosed from 2004–2014. Overall survival (OS) was assessed by Cox proportional hazards, stratified by extent of resection, and risk adjusted for age, sex, race, Charlson’s comorbidity index, insurance, facility location, facility annual case volume, chemotherapy, radiotherapy, tumor location, tumor laterality, and tumor size; and estimated by Kaplan-Meier methods. Subgroup analyses included MGMT methylation or Karnofsky Performance Score, in the risk adjustment. Coarsened exact matching was used to simulate allocation in an interventional trial. 82,960 adult GBM (all molecular subtypes) patients remained after exclusion, 22,928 with complete data for extent of resection and risk adjustment variables, 83% (n=19,007) of which reached endpoint for OS. Median OS for gross total resection (GTR) was 15.5 mos. (95%CI: 15.2–15.9), compared to 11.7 mos. for subtotal resection (STR; 95%CI: 11.3–12.0; HR 1.29, p<0.001) and 5.9 mos. for those who did not undergo resection (NR; 95%CI: 5.7–6.2; HR 1.56, p<0.001). Estimated 2yr OS rates were GTR 30.7% (95%CI: 29.7–31.8), STR 22.1% (95%CI: 21.1–23.0), and NR 14.8% (95%CI: 14.1–15.5). Notably, in the risk-adjustment adjuvant chemotherapy (HR 0.63, 95%CI: 0.60–0.66), radiotherapy (HR 0.71, 95%CI: 0.68–0.75), unilateral tumor (HR 0.66 vs. bilateral, 95%CI: 0.58–0.76), and supratentorial tumors (HR 0.77 vs. infratentorial, 95%CI: 0.71–0.86) were associated with significantly (p<0.001) improved OS. Additionally, coarsened exact matched (5,867 GTR: 5,867 STR) cohorts demonstrated similar outcomes, (GTR HR vs. STR: 0.74, 95%CI: 0.71–0.78). Median OS for patients with these favorable characteristics was 24.2 mos. vs. 1.5 mos. for those with unfavorable characteristics. In subgroup analyses, GTR significance remained after including MGMT (n=2,776) status in the risk-adjustment (HR vs. STR: 0.74) and MGMT methylation was associated with improved OS (HR 0.66, 95%CI: 0.60–0.72). Compared to STR, GTR was associated with reduced rates of 30- and 90-day mortality (OR 0.71 and 0.64, respectively). In the largest prospectively collected dataset of its kind, GTR for GBM was associated with significantly improved OS compared to STR or NR, in risk adjusted and exact matched analyses. Adjuvant chemotherapy, radiotherapy, unilaterality, supratentorial location, and MGMT methylation in the risk adjusted analysis were also associated with significantly improved OS.

A multi-institutional study of immunosuppressed and immunocompetent patients with cutaneous squamous cell carcinoma of the head and neck treated with definitive surgery and radiotherapy: Outcomes after disease recurrence.

63 Background: Our multi-institutional group previously demonstrated that immunosuppressed (IS) patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) treated with surgery and adjuvant radiotherapy had inferior survival compared to immunocompetent (IC) patients. This study further examines those patients who experienced disease recurrence and compares the impact of immune status on overall survival after recurrence. Methods: Pts who received surgical resection and postoperative RT for primary or recurrent, stage I-IV (non-metastatic) cSCC-HN between 1995-2015 at Cleveland Clinic, Washington University St. Louis, and University of California San Francisco were included in this IRB approved study. Pts were categorized as IS if they were diagnosed with chronic hematologic malignancy, HIV/AIDS, or were treated with immunosuppressive therapy for organ transplantation ≥ 6 months prior to diagnosis. Pts with recurrence included those who experienced local, regional, or distant failure after completion of definitive surgery and radiation. Overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan Meier method. Results: In the initial study of 205 pts, 138 (67.3%) were immunocompetent (IC) and 67 (32.7%) were IS, and were followed for a median of 25 months. PFS was significantly lower in IS pts compared to IC at 2 years (38.7% vs. 71.6%; p = 0.002), while 2yr OS demonstrated a similar but non-significant trend (60.9% vs. 78.1%; p = 0.135). A total of 72 patients (35%) recurred, including 31 with distant failure. 1yr post-recurrence OS was 42% with a median survival of 8.4 months. Median survival did not significantly differ between the IS and IC groups (8.0 vs. 12.9 months; p = 0.9). Conclusions: Pts with cSCC-HN who experience disease recurrence after definitive treatment with surgery and radiation have poor survival, irrespective of immune status. Clinical trials testing immunotherapies are needed for both IC and IS patients with this understudied disease.

Meta-analysis of disease free survival (DFS) as a surrogate for overall survival (OS) in localized renal cell carcinoma (RCC).

459 Background: OS is a critical endpoint for adjuvant RCC trials testing the benefit of early systemic therapy to increase cure rates, but requires long duration and significant patient resources. We explored the potential use of DFS as a surrogate for OS when assessing the efficacy of adjuvant therapy in localized RCC. Methods: We performed a systematic literature review following the PRISMA statement. Inclusion criteria required randomized controlled trials (RCT) for adjuvant systemic therapy in localized RCC, which reported on both DFS and OS. DFS was defined from randomization or nephrectomy (R/N) to the first evidence of clinical recurrence (loco-regional or distant) or death from any cause. OS was defined from R/N to death from any cause. We extracted data on hazard ratio (HR) and 5-year event free rate from Kaplan Meier estimates. We performed a meta-analysis and correlated these estimates for OS and DFS, weighted by number of DFS events. R-square &gt;0.7 would indicate a strong correlation and potential surrogacy. Results: Of the more than 315 studies screened, 10 studies investigating various forms of cytokine and vaccine immunotherapy and angiogenesis inhibitors (e.g., sunitinib, sorafenib, thalidomide) between 1987 and 2016 were eligible for the analyses. The total enrolled patients were 5,497, with median follow-up ranging 3 to 10 years. Conclusions: Across trials of adjuvant systemic therapy for localized RCC, we observed a moderate correlation between 5 yr DFS and OS rate and between treatment effects (HRs) on these endpoints. Future meta-analyses of more mature trials in the era of modern adjuvant targeted therapy are needed to evaluate the surrogacy of intermediate endpoints. Further granularity may be achieved using individual patient data to assess different and earlier time points for surrogacy than are commonly reported. [Table: see text]

Impact of use of phosphodiesterase type 5 inhibitors (PDE5-I) after radical prostatectomy (RP) on biochemical recurrence-free (BCRF) and overall survival (OS): A retrospective study from the Northwestern University SPORE in prostate cancer.

27 Background: The correlation between PDE5-I use to improve erectile function post RP and BCRF and OS on prostate cancer (PCa) patients (pts) has yielded conflicting results among prior retrospective cohort studies (Michl, 2015). Recent data suggests that these drugs may have an impact on immunity that may explain possible benefits. This study’s purpose was to determine whether PDE5-I use affects BCRF and OS for pts treated with RP for PCa. Methods: This is an IRB approved retrospective cohort study analyzing a subset of pts consented to the SPORE in PCa at Northwestern University’s Lurie Cancer Center. Inclusion criteria included men diagnosed with PCa and treated with RP with curative intent between 2003-2015. Study population (n = 2,410) showed 834 (34.6%) received a PDE5-I post-RP, while 1,576 (65.4%) did not. Pts were grouped based on PDE5-I use and no PDE5-I use after RP. A PDE5-I user must have filled at least 2 prescriptions or completed at least 2 inpatient administrations of a PDE5-I. Continuous variables were summarized by descriptive statistics and differences between groups were assessed via the Wilcoxon rank sum test. Categorical variables were reported by frequencies and percentages and compared via Fisher’s exact test. OS and BCRF survival were summarized for 10-yr rates using Kaplan-Meier estimates. The difference in BCRF and OS between groups was evaluated via log-rank test. Results: Mean age at RP was 60, and 90.95 % were Caucasian. Except for pairwise comparisons for significance of Gleason 3+3 vs. 3+4 histology with higher prevalence of 3+4 in the PDE5-I group (p = 0.0004) and a higher percent of clinical stage T2b-c than T2a in the no PDE5-I group (p = 0.01), no differences were noted in demographics. The 10-yr BCRF survival among PDE5-I users was 92.53% compared to 79.63% among non-users after RP (p &lt; 0.0001). The 10-yr OS rate among PDE5-I users was 97.22% compared to 92.69% among non-users (p = 0.008). Conclusions: This retrospective analysis suggests that PDE5-I use improves biochemical recurrence free survival and overall survival in pts treated with RP for PCa.

Survival Outcomes in Octogenarian and Nonagenarian Patients Treated with First-line Androgen Deprivation Therapy for Organ-confined Prostate Cancer

BackgroundThe use of primary androgen deprivation therapy (PADT) is common in elderly men with early-stage prostate cancer (PCa), despite the absence of guideline recommendations. ObjectiveTo examine survival patterns of octo- and nonagenarian men with organ-confined PCa exposed to PADT, to assess whether their life expectancy warrants androgen deprivation therapy use. Design, setting, and participantsIn the Surveillance, Epidemiology, and End Results-Medicare-linked database, we identified 14 785 octo- and nonagenarian organ-confined PCa patients treated with PADT between 1991 and 2009. Outcome measurements and statistical analysisThe smoothed cumulative incidence method was used to examine 10-yr overall mortality, cancer-specific mortality (CSM), and other-cause mortality (OCM) rates. Multivariable Cox regression analyses focused on the combined effect of age and Charlson comorbidity index (CCI) after adjusting for different confounders. Results and limitationsOf all the deaths observed during the study period, 80% were due to non-cancer causes and 20% were due to PCa. The 10-yr overall survival (OS) rate in the overall population was 15.4%. The 10-yr OS rates ranged from 19.9% in patients aged 80–84 yr to 3.1% in those aged ≥90 yr. Similarly, the 10-yr OS rates ranged from 18.7% in patients with CCI=0 to 11.5% in those with CCI≥2. The 10-yr OCM rate in the overall population was 68.2%. The 10-yr OCM rates ranged from 64.6% in patients aged 80–84 yr to 77.2% in patients aged ≥90 yr. Similarly, the 10-yr OCM rates ranged from 62.1% in patients with CCI=0 to 75.2% in those with CCI≥2. The 10-yr CSM rate in the overall population was 16.4%. The 10-yr CSM rates ranged from 15.5% in patients aged 80–84 yr to 19.7% in those aged ≥90 yr, and from 19.2% in patients with CCI=0 to 13.3% in those with CCI≥2. ConclusionsOf the elderly patients with organ-confined PCa exposed to PADT, only 15% survive at 10-yr follow-up. Mortality related to non-cancer causes is the leading cause of death in the same follow-up period. These figures question the rationale for PADT in elderly men with organ-confined PCa. Patient summaryIn this study, we looked at the survival patterns of octo- and nonagenarians treated with primary androgen deprivation therapy for organ-confined prostate cancer. We found that a small proportion of patients who received primary androgen deprivation therapy remain alive at 10-yr follow-up, and the leading cause of death was not attributable to prostate cancer.

Evaluating associations of diabetes, insulin use, and BMI with efficacy in patients with resected pancreatic cancer: An ancillary analysis of NRG Oncology/RTOG 9704.

369 Background: Diabetes mellitus (DM) has been linked to poor prognosis in pancreatic cancer in numerous retrospective datasets, potentially due to higher levels of insulin and insulin-like growth factor increasing cellular proliferation. Additionally, the hyperglycemic state as well as obesity may lead to a pro-inflammatory state that may enhance tumor progression and metastases. In this analysis, the prognostic significances of diabetes, insulin use, and BMI are evaluated in a prospective, randomized trial of resectable pancreatic ductal adenocarcinoma. Methods: As previously reported, RTOG 9704 pts with resected pancreatic cancer were randomized to 5-fluorouracil (5-FU) or gemcitabine (Gem), given pre and post radiation (RT). Pts in both arms received RT to 50.4 Gy with 5-FU. DM and insulin use were collected on the RTOG 9704 CRFs. BMI was dichotomized as normal/underweight vs. overweight/obese. Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier method and variable levels were compared using log-rank test. Cox models were used for multivariable analyses. Results: 538 pts were enrolled from 1998-2002. 238 pts were eligible with analyzable diabetes and insulin use data, in addition to surgical pathology, and CA19-9 data. 32% and 35% of pts in the 5-FU and Gem arms, respectively, had DM. Of which, 24% and 19% used insulin in the 5-FU and Gem arms, respectively. 55% were overweight/obese. The 4 yr OS was 25% (95% CI: 18, 32) in pts with no diabetes, vs. 18% (10, 27) with DM (HR = 1.3 [0.9, 1.7]; p = 0.11). The 4-yr DFS was 14% (9, 20) in pts with no diabetes, vs. 9% (4, 16) with diabetes (HR = 1.2 [0.9, 1.5]; p = 0.31). Neither insulin use nor BMI was univariately associated with OS or DFS. On multivariate analysis, including nodal status, CA19-9, and other variables, DM, insulin use, and BMI were not associated with OS or DFS. Conclusions: DM, insulin use, and BMI were not associated with OS in pts with resected pancreatic cancer treated with adjuvant chemotherapy and chemoradiation. Node involvement and CA19-9 remain the most significant predictors of OS. Supported by NCI grants U10CA180868, U10CA180822, UG1CA189867 and Eli Lilly Clinical trial information: NCT00003216.

Renal Cell Carcinoma with Isolated Lymph Node Involvement: Long-term Natural History and Predictors of Oncologic Outcomes Following Surgical Resection

BackgroundRenal cell carcinoma (RCC) with isolated lymph node (LN) involvement has historically been associated with poor prognosis. However, a subset of patients may experience long-term survival. ObjectiveTo examine the natural history of RCC with isolated LN involvement following surgical resection with long-term follow-up, and to evaluate clinicopathologic features associated with disease progression and survival. Design, setting, and participantsA total of 138 patients with isolated pN1M0 RCC underwent partial or radical nephrectomy and LN dissection from 1980 to 2010. InterventionPartial or radical nephrectomy with LN dissection. Outcome measurements and statistical analysisMetastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between clinicopathologic features and oncologic outcomes were evaluated using Cox regression models. Results and limitationsMedian follow-up among survivors was 8.5 yr. The 5-yr and 10-yr MFS, CSS, and OS rates were 16% and 15%, 26% and 21%, and 25% and 15%, respectively. The median time to development of metastases was only 4.2 mo. On multivariable analysis, symptoms at presentation (hazard ratio [HR] 2.40; p=0.03), inferior vena cava tumor thrombus (HR 1.99; p=0.003), clear cell (HR 2.21; p=0.01) and collecting duct/not otherwise specified (HR 4.28; p<0.001) histologic subtypes, pT4 stage (HR 2.64; p=0.005), and coagulative tumor necrosis (HR 2.51; p<0.001) were independently associated with development of metastases. MFS rates at 1 yr after surgery were 71%, 63%, 33%, and 7% for patients with one, two, three, and four to five adverse features, respectively. Limitations include surgical selection bias. ConclusionsAlthough isolated pN1 disease portends a poor prognosis, a small subset of patients experience durable long-term survival after surgical resection of isolated lymphatic metastases. Adverse prognostic features may enhance patient risk stratification and facilitate multimodal management approaches. Patient summaryAlthough isolated lymph node metastases portend a poor prognosis, a small subset of patients experience long-term survival following surgical resection.