bluuebunny/crossref_metadata_2025 huggingface dataset:
CheckMate 025 phase III trial: Outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC).
Authors: Motzer Robert J. , Sharma Padmanee , McDermott David F. , George Saby , Hammers Hans J. , Srinivas Sandhya , Tykodi Scott S. , Sosman Jeffrey Alan , Procopio Giuseppe , Plimack Elizabeth R. , Castellano Daniel E. , Gurney Howard , Donskov Frede , Bono Petri , Wagstaff John , Gauler Thomas Christoph , Ueda Takeshi , Zhao Huanyu , Waxman Ian M , Escudier Bernard
Published: February 2017

498

Background: Based on assessment by an independent Data Monitoring Committee, a phase III trial of NIVO (n=410) vs EVE (n=411) in previously treated patients with advanced or metastatic RCC (NCT01668784) was halted early as it met its endpoint; superior overall survival (OS) was seen with NIVO vs EVE. We present outcomes by key baseline factors, prior therapy, and subsequent anticancer therapy. Methods: Patients with 1 or 2 prior anti-angiogenic therapies and measurable disease (RECIST v1.1) were randomized 1:1 to NIVO 3 mg/kg IV every 2 weeks or EVE 10 mg orally once daily. Primary endpoint was OS. A key secondary endpoint was objective response rate (ORR). Results: The Table shows OS and ORR by key baseline factors. Median follow-up was 17-18 mo. 77% and 23% of patients received 1 or 2 prior anti-angiogenic therapies, respectively, for advanced RCC, mainly sunitinib (63%) or pazopanib (32%). In patients who had prior sunitinib, median OS was 23.6 mo for NIVO vs 19.8 mo for EVE; in those who had prior pazopanib, median OS was not estimable (NE) for NIVO vs 17.6 mo for EVE. For those who had prior IL-2 (10%), median OS was NE for NIVO vs 17.2 mo for EVE. Outcomes by subsequent anticancer therapy are planned. Conclusions: A consistent OS benefit with NIVO vs EVE was found across baseline factors (Karnofsky performance status [KPS], Heng risk group, number of prior therapies), and specific prior therapies (sunitinib, pazopanib, IL-2) in previously treated patients with advanced RCC. ORR benefit with NIVO was also seen across baseline factors. Clinical trial information: NCT01668784. [Table: see text]
Analysis of real-world treatment adherence in a cohort of 2,395 patients with metastatic renal cell carcinoma (mRCC).
Authors: Margolis Jay , Princic Nicole , Doan Justin , Lenhart Gregory , Motzer Robert J.
Published: February 2017

517

Background: Given recent European data highlighting the importance of real-world dose intensity(Cancer Med 2014; 3(6): 1517-26.), we sought to investigate real-world adherence in patients with mRCC from a US perspective. Methods: In this retrospective cohort study, patients with newly diagnosed mRCC were selected from the MarketScan Commercial and Medicare Supplemental administrative claims databases based on an index event from 1/1/2006 to 3/31/2014. First line (1L) therapy was defined as first prescription record post-index for any approved mRCC therapy; change in line of therapy was defined as a therapy switch. Adherence was measured using the medication possession ratio (MPR) during each and all lines. MPR was defined as total days of supply during the treatment period divided by total treatment period until the start of last treatment. Nonadherence was defined as an MPR <80%. Results: A total of 2,395 mRCC patients were identified as initiating 1L therapy. Across all treatments the mean MPR was 0.77 ± 0.20, which increased over time from 0.73 in 2006 to 0.81 in 2013. More than 50% of patients were nonadherent. During 1L, patients treated with sunitinib had significantly lower mean MPR compared with most other treatments (table). Adherence was higher during 2L (0.85 ± 0.18) vs 1L (0.80 ± 0.19). A larger proportion of patients who initiated therapy with temsirolimus were adherent compared with those who initiated with sunitinib (62% vs 38%). Additional analyses are being conducted to address adherence with alternative dosing schedules. Conclusions: Over half of treated mRCC patients were found to be nonadherent to therapy. Adherence was significantly better with IV administered temsirolimus relative to the reference oral therapy, sunitinib. Real-world analysis of treatment adherence provides information for clinicians in monitoring and optimizing targeted therapy. [Table: see text]
Cancer detection between peripheral zone and transitional zone targeted biopsies: Preliminary results from a prospective cohort of men undergoing MRI-US fusion biopsy.
Authors: Nahar Bruno , Soodana-Prakash Nachiketh , Pavan Nicola , Rai Samarpit , Munera Felipe , Castillo Rosa P , Balise Raymond R , Manoharan Murugesan , Kava Bruce , Satyanarayana Ramgopal , Gonzalgo Mark L. , Ritch Chad , Parekh Dipen , Punnen Sanoj
Published: February 2017

56

Background: Multiparametric MRI has emerged as a popular imaging modality to localize prostate cancer. Nevertheless, interpretation of MRI is subjective, with concerns for false positives, particularly in the transitional zone (TZ), where hyperplastic changes may be confused for suspicion of cancer. We analyzed a prospective cohort of men undergoing MRI-US fusion biopsy and compared cancer detection rate between lesions seen in the peripheral zone (PZ) and the TZ. Methods: 133 men with elevated PSA or positive DRE underwent MRI-US fusion biopsy with average of 2 cores taken per target for the detection of prostate cancer between October 2014 and July 2015. Each targeted lesion in the PZ and TZ was previously classified by radiologists according to the MRI PI-RADS score and grouped according to their level of suspicion as probably benign (1-2), indeterminate (3) or probably malignant (4-5). Histopathology from targeted cores were categorized as no cancer, non-significant cancer (Gleason 6) and significant cancer (Gleason ≥ 7). We compared the cancer detection rates between lesions in PZ and TZ lesions, based on PI-RADS score. Results: We identified 143 lesions in the PZ and 82 lesions in the TZ. Among lesions found in the TZ, 57.3% were reported as probably malignant, compared to 44.7% of lesions seen in the PZ. Cancer was diagnosed in 23% of the lesions in the PZ, compared to only in 9.7% in the TZ (p<0.01). With respect to significant cancer there was a trend towards higher detection of significant cancer in the PZ (13.29% vs. 6.10% p=0.12) compared to TZ. Furthermore, lesions in the PZ with a PI-RADS score > 4 were associated with a three-fold increase in the odds of detecting cancer compared to lesions with PI-RADS < 4 (OR 3.08; CI 95% 1.29 – 7.31, p<0.011), whereas in the TZ there was no increased risk of cancer with higher PI-RADS scores (OR 1.0 CI 95% 0.20 – 4.84, p<1.0). Conclusions: To our knowledge this is the first study to address a concern regarding an increased likelihood of false positives when reporting the presence and aggressiveness of cancer in the TZ versus the PZ. This may lead to unnecessary biopsies in men undergoing MRI of the prostate.
Differential overall survival (OS) results in RECORD-3 study based on three distinct mRCC molecular subgroups classified by BAP1 and/or PBRM1 mutations.
Authors: Hsieh James , Chen David , Wang Patricia , Chen Yingbei , Marker Mahtab , Patel Parul , Chevinsky Michael , Bhanot Umesh , Pinciroli Patrizia , Berger Michael F. , Cheng Emily , Lee William , Knox Jennifer J. , Voss Martin Henner , Voi Maurizio , Motzer Robert J.
Published: February 2017

561

Background: PBRM1 and BAP1, both of which encode chromatin modulating proteins, have recently been identified as frequently mutated tumor suppressor genes in RCC. However, their correlation with outcomes of targeted therapies is unknown. We explored correlations between overall survival (OS) and mutations in archival tumor samples from RECORD-3, a randomized phase 2 trial comparing first-line everolimus (EVE) then sunitinib (SUN) to first-line SUN then EVE at progression in 471 treatment-naïve mRCC patients (J Clin Oncol 2014; 32:2764). Methods: Somatic mutations in exons of 341 cancer related genes were identified by a next generation sequencing (NGS) assay (MSK IMPACT). Association between genotypes and OS was assessed by Cox PH models and log-rank tests. Results: DNA of 258 archival tumor and 181 matched germline samples was successfully analyzed (median coverage 530X). Three molecular subgroups Gr1 (BAP1 MT [mutant], PBRM1 WT [wild-type]/MT; 17.4%), Gr2 (PBRM1 MT, BAP1 WT; 38.4%), and Gr3 (PBRM1 WT, BAP1 WT; 44.2%) with different OS outcomes after sequential EVE-SUN or SUN-EVE were identified (Table). In the sequential EVE-SUN arm, median OS (months) was shortest with Gr1 (9.8; 95% CI, 7.8–20.0), longest with Gr2 (39.6; 95% CI, 31.7–not estimable), and intermediate with Gr3 (18.1; 13.7–30.0), whereas in the SUN-EVE arm there was no significant difference among groups. When comparing OS between treatment sequences within molecular groups, a trend suggested differences for EVE-SUN vs SUN-EVE in Gr1 (HR 1.5), Gr2 (0.8), and Gr3 (1.2), although comparisons were not statistically significant. Conclusions: Our results suggest that these genotypes may represent distinct RCC molecular subtypes with potentially different predictive/prognostic values on targeted therapies. Different treatment sequences may be considered depending on the genotypes. Clinical trial information: NCT00903175. [Table: see text]
Validation of the Decipher prostate cancer classifier for predicting 10-year postoperative metastasis from analysis of diagnostic needle biopsy specimens.
Authors: Magi-Galluzzi Cristina , Yousefi Kasra , Haddad Zaid , Palmer-Aronsten Beatrix , Lam Lucia L.C. , Buerki Christine , Li Jianbo , Kattan Michael W. , Stephenson Andrew J. , Davicioni Elai , Klein Eric A.
Published: February 2017

59

Background: Accurate riskstratification after diagnosis of prostate cancer (PCa) is key to optimal treatment decision-making. Decipher is an extensively validated genomic classifier of metastasis after radical prostatectomy (RP). Here, we evaluate its ability to predict metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens in a cohort of intermediate risk PCa patients treated with RP. Methods: Fifty-seven patients with available diagnostic biopsy specimens were identified from a previously reported post-RP validation study of Decipher in a cohort of 169 patients treated at Cleveland Clinic. The core with at least 1mm tumor of the highest Gleason grade was sampled and subjected to whole transcriptome analysis. Decipher was calculated based on a locked random forest model. Cox multivariable (MVA) proportional hazards model and survival c-index were used to evaluate the performance of Decipher. Results: 61% of patients had biopsy Gleason score 6 and 67% of patients had NCCN intermediate risk disease. With a median 8 years follow up, 8 patients metastasized and 3 of these patients died of PCa. Decipher had a c-index of 0.80 (95% confidence interval [CI], 0.58-0.95) compared to 0.58 (95% CI, 0.18-0.91) for biopsy Gleason score and 0.57 (0.57; 95% CI, 0.23-0.89) for preoperative PSA at 10 years post-RP for prediction of metastasis. A combined model consisting of Decipher, preoperative PSA, and Gleason score had a c-index of 0.84 (95% CI, 0.68-0.96). On MVA, Decipher was the only significant predictor of metastasis when adjusting for age, preoperative PSA and biopsy Gleason score (Decipher hazard ratio per 10% increase: 1.72; 95% CI, 1.04–2.83; P = 0.02). Conclusions: Decipher was able to predict metastatic outcome from diagnostic biopsy specimens in a cohort of primarily intermediate risk men treated with RP. This additional genomic information may help identify patients who may not be optimal candidates for active surveillance and better identify appropriate first line therapy for men with intermediate risk disease.
Detection of prostate cancer with the [68Ga]-labeled bombesin antagonist RM2 in patients undergoing radical prostatectomy.
Authors: Stephens Andrew , Loidl Wolfgang C. , Beheshti Mohsen , Jambor Ivan , Kemppainen Jukka , Bostrom Peter , Kahkonen Esa , Berndt Mathias , Mueller Andre , Minn Heikki , Langsteger Werner
Published: February 2017

80

Background: Gastrin-releasing-peptide receptor (GRPr) is overexpressed in prostate carcinoma (PCa) and offer new means to detect prostate cancer. The bombesin derivative RM2 (DOTA-4-amino-1-carboxymethylpiperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) is a GRPr antagonist with high binding affinity (Kd 3 nM). A first-in-man study was performed to assess tumor targeting potential of [68Ga]RM2 in patients with local PCa using PET/CT. Based on promising results a Phase I/II study in local PCa was initiated. Methods: In the initial study eleven men with biopsy-proven PCa scheduled for radical prostatectomy were enrolled. The patients (pt) received an i.v. dose of 140 MBq of [68Ga]RM2 followed by dynamic imaging for at least 60 min p.i. The PET assessment included visual evaluation of [68Ga]RM2 intra-prostatic and nodal uptake as well as quantification. An ongoing Phase I/II study is designed to enroll 30+50 biopsy-positive PCa patients. The initial 30 pt have been enrolled, stratified into high, intermediate and low risk of prostate Ca recurrence as defined by NCCN criteria. Results: High uptake of [68Ga]RM2 is seen in pancreas and the urinary system with low background in the rest of the body. Despite of high bladder activity focal or multifocal intraprostatic uptake was detectable. In the first study 10 of 11 pt had positive scans. Subsector analysis of PET positivity vs. pathology yielded a sensitivity, specificity and accuracy of 89, 81, and 83%, respectively. SUVmax was measured in 14 lesions from 9 pts, classified in two groups according to postoperative Gleason score (GS). The higher GS group showed a trend toward higher SUV-values, 10.0 ± 6.7 vs. 6.2 ± 2.5 (t-test: t = -1.21, p-value = 0.28). Both of which were elevated compared to normal tissue 1.2 ± 0.8 The ongoing study is designed with a power of 95% to discriminate between the two GS groups with statistical significance (p = 0.05). Conclusions: [68Ga]RM2 is a promising new tracer with a high detection rate for PCa. Preliminary data indicates higher uptake in more aggressive cancers. The current study is assessing the diagnostic accuracy and impact of presurgical risk assessment on tumor detection in newly diagnosed PCa patients. Clinical trial information: NCT02483884.
Genetic ancestry and odds of prostate cancer diagnosis in African American and European American men.
Authors: Nyame Yaw A. , Murphy Adam , Batai Ken , Shah Ebony , Ruden Maria , Hollowell Courtney M.P. , Kajdacsy-Balla Andre , Catalona William , Kittles Rick
Published: February 2017

86

Background: Although ethnic differences in disease incidence among African American (AA) men may reflect differences in screening behaviors and behavioral and socioeconomic factors, genetic ancestry may be a factor. This study will investigate the association between West African and Native American genetic ancestry and PCa diagnosis. Methods: We enrolled 40-79 year-old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for the genotyping of 105 ancestry informative markers. West African (WAA), European (EA), and Native American (NAA) genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Univariate analysis was performed by Wilcoxon rank-sum test for continuous variables. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the odds of having high-risk PCa relative to controls, adjusting for age, body mass index (BMI), alcohol-use, and family history of PCa. Results: 857 men were enrolled; 34.5 % were diagnosed with PCa, 50.9 % were controls and 14.6 % were men with negative prostate biopsies. AAs comprised 27% of the sample. The median was 63 years (IQR 57 – 68). Among AA men, the median genetic WAA proportion was 0.78 (IQR 0.69 – 0.83) and NAA was 0.04 (IQR 0.02 – 0.09). There was no significant difference in genetic WAA among AA men with and without PCa diagnosis (p = 0.54); however, genetic NAA was significantly lower among PCa cases (median 0.034 vs 0.057,p = 0.03) compared to controls. Among EA men, the media NAA was 0.067 (IQR (0.03 – 0.10). Similarly among EA men, genetic NAA was significantly lower among cancer cases (0.04 vs. 0.08, p < 0.001). On logistic regression, WAA ≥ 88% was associated with increased odds of PCa in AA men (OR 2.6 95% CI 1.1 – 6.7). In both AAs (OR 0.5, 95% CI 0.2 – 1.1) and EAs (OR 0.3, 95 % 0.2 – 0.6), men in the highest genetic NAA quintile had a decreased risk of PCa on logistic regression compared to men in the lowest quintile. Conclusions: Our study reveals that NAA is protective against PCa diagnosis among all men. Additionally, AA men with a high degree of WAA demonstrate an increased risk of PCa. Future work will focus on determining the association of known prostate cancer risk SNPs such as the 8q24 regions and genetic ancestry.
Early salvage versus adjuvant post-prostatectomy radiation therapy: Long-term results of a large institutional experience.
Authors: Buscariollo Daniela , Drumm Michael , Claymann Rebecca , Rodin Danielle , Galland-Girodet Sigolene , Feldman Adam S. , Dahl Douglas M. , McGovern Francis J. , Olumi Aria F. , Eidelman Alec , Niemierko Andrzej , Shipley William U. , Zietman Anthony L. , Efstathiou Jason A.
Published: February 2017

99

Background: Randomized trials and consensus statements support consideration of adjuvant radiation therapy (ART) after radical prostatectomy (RP) for adverse pathologic features (pT3, positive margins), although its use remains low. Whether early salvage radiation therapy (ESRT) is as effective as ART remains unknown. The objective of this study was to compare outcomes after ART and ESRT. Methods: We performed a retrospective institutional analysis of 719 consecutive patients receiving post-RP RT from 1992 to 2013. ESRT was defined as RT for biochemical failure (BF) with post-RP PSA ≤ 0.5 ng/ml. All included ART and ESRT patients had adverse surgical pathologic features. Outcomes examined were freedom from BF (FFBF; rising PSA ≥ 0.2 ng/ml with subsequent confirmation), freedom from subsequent androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS). ART and ESRT were compared using multivariable analyses (MVA) with propensity score (PS) matching for pre-RP PSA, age at RT, Gleason score, pT-stage, and margin status. Results: 537 patients received salvage RT, of whom 195 received ESRT; 181 patients received ART. Median follow-up from RP was 7.0 and 8.1 years in the ART and ESRT cohorts, respectively. Median time to BF after RT was 4.4 and 4.7 years in the ART and ESRT cohorts, respectively. On MVA, ART was associated with improved 10-year FFBF (74 vs 60%, HR 0.36 [95% CI: 0.23-0.58], P < 0.0001) and 10-yr FFADT (91 vs 83%, HR 0.37 [95% CI: 0.18-0.76], P = 0.007). There were no significant differences in FFDM (96 vs 92%, HR 0.58 [95% CI: 0.19-1.7], P = 0.3), and OS (98 vs 95%, HR 1.24 [95% CI: 0.4-3.89], P = 0.7). After PS matching, ART (n = 169) remained significantly associated with improved FFBF (p < 0.0001) and FFADT (p = 0.01), compared to ESRT (n = 176). Conclusions: Post-prostatectomy RT confers excellent long-term prostate cancer control, a finding supported by the long follow-up in this series. ART is associated with improved FFBF and FFADT compared to ESRT, although there were no statistically significant differences in FFDM and OS. Optimal timing of postoperative RT further awaits the results of ongoing randomized trials.
Rehabilitation strategies following oesophageal cancer: The ReStOre trial—A feasibility study.
Authors: Guinan Emer M. , Doyle Suzanne , O'Neill Linda , O'Sullivan Jacintha , Reynolds Prof John V , Hussey Juliette M.
Published: February 2017

176

Background: Esophageal cancer is an examplar model of complex cancer care with defined quality of life (QOL) consequences. While prognosis for this aggressive disease is poor, survival is slowly improving leading to the emergence of a unique group of cancer survivors with complex rehabilitation needs. The ReStOre trial will implement a multi-disciplinary programme to improve functional performance and QOL for esophageal cancer survivors. This pilot work examines the feasibility of the proposed intervention. Methods: This study was a single-arm feasibility study. Patients who had completed curative treatment for esophageal cancer including esophagectomy and who had node-negative post-surgical pathology received a letter of invitation to participate. The programme consisted of 12 weeks supervised and home-based exercise, dietetic counselling and education sessions from the multi-disciplinary team. Feasibility outcomes included recruitment rates, adherence, adverse events and retention. Other outcomes, including cardiopulmonary fitness (maximal cardiopulmonary exercise test and six minute walk test (6MWT)), QOL (EORTC questionnaire) and body composition (bioimpedence analysis), were assessed pre- and post-intervention. Results: Twelve participants (mean (standard deviation (SD) age 61.4 (7.29) years, 8 male) consented to participate, representing a recruitment rate of 55%. Mean class attendance was 82% and mean adherence to the home exercise programme was 118%. No adverse events occurred and all participants completed programme. Aerobic fitness improved by 3.71(2.7) ml/kg/min (19.0 ml/kg/min pre-intervention, 22.7 ml/kg/min post-intervention, p < 0.001). 6MWT distance improved by 56.3 (35.3)m (p < 0.001). Global and functional QOL scores increased while symptom scores decreased. Body composition remained stable. Conclusions: The ReStOre trial demonstrated high feasibility and acceptability in this complex cohort. Improvements in functional performance and QOL were evident without compromise to body composition. While current results are limited due to the selected population and single-arm design they will guide the design of the forthcoming larger randomised controlled trial.
Emotional concerns in cancer survivors not treated with chemotherapy.
Authors: Nikoomanesh Tina , Goldfarb Melanie
Published: February 2017

233

Background: Emotional concerns can impact quality of life in all cancer (CA) survivors, regardless of receipt of chemotherapy. Methods: Surgically treated CA survivors that were not treated with chemotherapy were identified in the 2010 LiveStrong Survey. Only patients that responded to all 9 categories of emotional concern questions were included (energy/fatigue, depression and mood, identity and grief/guilt, faith and spirituality, fear of recurrence, social anxiety, shame, concern for family, insecurity). A total emotional concern score was calculated (0-9) and independent t-tests or ANOVA identified factors that impacted the total score. After stratification by CA type, linear regression determined which factors, if any, were important predictors of having more emotional concerns. Results: Of 649 CA survivors, most were white (91.0%), insured (97.8%), employed/student (79.3%), married/domestic partner (76.2%), and had survived at least 5 years (69.8%); many were > 40 years old (62.8%). The median number of reported emotional concerns was 4 (mean 4.3, SD 2.0) with 3.1% of patients reporting no concerns. Patients with brain or head/neck CAs had the highest scores (5.3, SD 1.5-1.7), whereas those with other endocrine tumors or melanoma had the lowest scores (3.9, SD 2.0-2.1), (p = 0.001). Additionally, age < 40 at diagnosis, female gender, being employed, uninsured, having less education, and having received radiation (RT), hormone (HT), or other additional therapy all increased the emotional concern score (p < 0.05); race/ethnicity, marital status, and income did not impact the score. After stratification by CA type, only the following increased emotional concerns: receipt of HT for breast CA (B = 0.30), being employed (B = 0.82) or retired (B = 0.41) for thyroid CA, female gender (B = 0.51) or receiving RT (B = 0.38) for bone/soft tissue CA, age < 40 (B = 0.37) and receipt of other/HT (B = 0.31) for melanoma, and female gender for (B = 0.76) for other endocrine tumors. Conclusions: Significant emotional concerns are reported by surgically treated cancer survivors not treated with chemotherapy. These concerns are most influenced by cancer type and treatment, but not race/ethnicity, marital status, or income.
Incidental renal tumors in cancer survivors: Minimally invasive management by image-guided thermal ablation.
Authors: Abdelsalam Mohamed E. , Sabir Sharjeel H , Kusin Samuel B. , Matin Surena F. , Wood Christopher G. , Karam Jose A. , Ahrar Kamran
Published: February 2017

258

Background: To investigate presentation, management and outcome of renal tumors in patients with prior or current history of cancer. Methods: A retrospective review of a database for patients undergoing ablation of renal tumors between January 2012 and June 2014 was performed. For each patient , the following was recorded: Prior or current history of cancer (other than renal cell carcinoma), histology of primary tumor, status of primary cancer (remission or under therapy), size of the renal tumor, thermal ablation technology , complications of ablation, development of metastases from renal tumor, deceased or alive , cause of death and the length of follow up. Results: Ninety five renal ablation procedures were performed in 91 patients between January 2012 and June 2014. Of this subset, 37 patients (27 male and 10 females) with average age 63 years (Age range 53-85 Years) had prior or current history of malignancy (6 patients had more than one primary cancer) other than renal tumor including Prostate(6), colorectal (4), Breast (4) lymphoma (3) and others (20). All renal tumors were discovered incidentally, none of the patients had symptoms related to renal tumors. Twenty four patients were in remission and 13 patients were undergoing therapy for their primary malignancy at the time of ablation. Ablation was performed using radiofrequency (n = 30) or cryoablation (n = 9) for 39 renal lesions with average size of 2.4cm (Range 1.1 to 4 cm). After average of 20 months (range 5-35 months) of observation 34 patients (92%) were still alive. Three patients died of their primary cancer. None of the patients developed complication from the procedure, 1 patient had recurrence after 6 month; for which renal ablation was performed. None of the patients developed metastatic disease from or died of renal cell carcinoma. Conclusions: Staging workup and surveillance imaging studies in cancer patients can lead to incidental detection of primary renal tumors. Minimally invasive therapy with image guided radiofrequency ablation or cryotherapy is feasible, safe and effective. Image guided ablation has no discernable impact on the course of therapy for the primary tumor. Furthermore, it has minimal to no morbidity for patients in remission.
A randomized controlled study for the long term follow-up of breast cancer survivors: A primary care physician (PCP) coordinated care delivery model.
Authors: Wang Yong Alison , Chen Shih-Ping , Horng Chen-Fang , Hsieh Ling-Ling , Hsu Kai-Hsin , Chu Chen-Shin , Tsai Shu-Yi , Chan Yu-Hui , Shih Shih-Ming , Cheng Chun-Chiu
Published: February 2017

36

Background: Generalist involvement in cancer survivorship care is becoming a global trend, however, significant barriers exist. As a major cancer center in Taiwan, KF-SYSCC is implementing an academic institution-based comprehensive survivorship program, a PCP-coordinated care delivery model. Our goal is to promote health, manage chronic diseases, attend to psychosocial needs, and optimize health care resources without compromising cancer-related clinical outcome or patient satisfaction. Methods: We designed a randomized study with staggered transition of stage 0-3 breast cancer patients from oncologist care to the PCP-coordinated program at one or two years after cancer surgery. The outcomes for comparing the two care models include late effects of breast cancer treatment, anxiety and depression, health-related quality of life, recurrence-related clinical outcome, preventive care, chronic disease management, patient satisfaction, and health services utilization. Questionnaires were given every 6 months from 6 to 30 months after surgery. Results: Within six months, 270 eligible individuals were approached with an enrollment rate of 58% (target sample 1,200). The barriers for non-enrollment include: having established relationship with oncologist, transfer time too soon, lack of trust for non-oncologist, unwilling to change care provider, treatment not yet completed. The 113 non-participants did not differ from the 157 participants in age or cancer characteristics. Between the 1-year and 2-year transfer groups, there were no significant differences in demographics, tumor characteristics and treatment modalities. The initial BCPT and SF-36 questionnaires showed poorer performance in the areas of hot flashes, pain, cognition, weight, role physical, energy, and health perception, as compared with areas of bladder, vaginal, arm problems, physical and social functioning, mental health, and role emotional. Conclusions: We have started a randomized study to evaluate a generalist care model to survivorship care. Baseline patient characteristics were defined. Several barriers to the transition of the new care delivery model were identified.
Impact of sarcopenia on short- and long-term outcomes in patients with gastric cancer.
Authors: Hirata Fumiko , Kawamura Taiichi , Nishiwaki Noriyuki , Fujiya Keiichi , Omori Hayato , Takagi Wataru , Tatsubayashi Taichi , Honda Shinsaku , Hikage Makoto , Makuuchi Rie , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kinugasa Yusuke , Sugiura Teiichi , Uesaka Katsuhiko , Terashima Masanori
Published: February 2017

19

Background: Depletion of skeletal muscle in aged people (sarcopenia) regarded as a poor prognostic factor in various cancers. The aim of this study was to assess the impact of preoperative sarcopenia on postoperative short- and long-term outcomes in patients with gastric cancer underwent curative resection. Methods: A total of 881 patients who underwent R0 resection for gastric cancer aged 65 or older between June 2003 and March 2011 were included in this study. Muscle mass was assessed by measuring percentage of arm muscle area (%AMA). Preoperative sarcopenia was defined as aged 65 or older, %AMA <80%, and decline in grip strength ( <25kg in men, <20kg in women), according to algorithm suggested by European Working Group on Sarcopenia in Older People (EWGSOP) with slight modification. Relationship between sarcopenia and short- and long-term outcomes were evaluated using uni- and multi-variate analysis. Results: Of 881 patients, sarcopenia was diagnosed in 62 patients (7.0%). Incidence of sarcopenia was significantly higher in patients with aged (75 or older), female, low BMI (18.5 or less) and poor PS (2). There was no significant difference of operation time or blood loss between sarcopenic and non-sarcopenic patients. Postoperative complications (Clavien–Dindo classification grade III or higher) was observed in 124 patients (14.1%). Multivariate analysis revealed that T stage and intraoperative blood loss were significant independent risk factors for postoperative complications. The incidence of postoperative complication was similar regardless of the sarcopenia status. The 5-year survival rate was tended to be worse in the sarcopenic patients (67.7%) than in the non-sarcopenic patients (78.4%) (p = 0.058). Multivariate analysis demonstrated that age (75 or older), male, total gastrectomy, D2 lymph node dissection, and sarcopenia were selected as independent prognostic factors for gastric cancer. Conclusions: Preoperative sarcopenia determined by %AMA seems not to be a risk for postoperative morbidity. However, sarcopenia appears to be a significant prognostic factor in patients with gastric cancer underwent curative resection.
Stromal characterization of small bowel adenocarcinomas.
Authors: Pedersen Katrina , Smyrk Thomas C. , McWilliams Robert R.
Published: February 2017

288

Background: Programmed-death 1 (PD-1) receptor and its corresponding ligand, PD-L1, have been found to be clinically relevant in maintaining immune tolerance to malignant cells in an increasing number of tumor types. We have previously shown that nearly half of 48 randomly selected, resected small bowel adenocarcinomas at any stage exhibit positive PD-L1 expression. Furthermore, a larger quantity of tumor infiltrating lymphocytes (TILs) within the tumor stroma or microsatellite instability (MSI-H) have been associated with improved likelihood of response to PD-1 and PD-L1 inhibitors. We have descriptively characterized the stromal components of small bowel adenocarcinomas to determine if similar tumor/stromal features to drug-responsive tumors can be seen. Methods: 30 tumors were immunohistochemically stained for CD8 (T-lymphocytes), CD68 (macrophages), and e-cadherin. They were morphologically screened for MSI-H status with light microscopy. PD-L1 staining was previously performed and reported. Results: Of the 30 tumors, there was no correlation between the density of macrophages and T-lymphocytes, nor was there a correlation with the burden of immune cells with e-cadherin expression. 14/30 (47%) tumors had 3+/4+ expression of CD8+ lymphocytes. 7/14 (50%) of these tumors were morphologically MSI-H. No tumors with low CD8+ cells (1+/2+) were MSI-H. PD-L1 expression colocalized exclusively with macrophages and not with lymphocytes. Conclusions: There appears to be no association between the proportions of immune cells and basement membrane integrity. MSI-H tumors are more likely to have a greater quantity of CD8+ lymphocytes in the stroma; however, PD-L1 stromal expression appears to colocalize with macrophages. Further pathologic characterization is needed in patients treated with PD-1 and other immune checkpoint inhibitors to determine the clinical significance of these observations.
Comparative effectiveness of combination TACE/ablation vs. monotherapy in hepatocellular carcinoma.
Authors: Winer Arthur , Rosen Yohei , Lu Frederick , Berman Russell S. , Melis Marcovalerio , Miller George , Pachter H. Leon , Newman Elliot , Hatzaras Ioannis
Published: February 2017

350

Background: Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death worldwide. Loco-regional treatment modalities for HCC include Trans-Arterial Chemoembolization (TACE) and Radiofrequency/Microwave Ablation (RFA/MWA). Studies have shown that dual therapy with both TACE and ablation is beneficial, though data is limited. We retrospectively studied all HCC patients treated with either TACE, ablation, or dual therapy at a tertiary referral public hospital to determine differences in survival. Methods: Following IRB approval, all patients diagnosed with HCC (1998-2013) at our institution were retrospectively analyzed for date of diagnosis, treatment-type, length of follow-up, and survival. Patients were excluded if they did not undergo TACE or RFA/MWA, or underwent other treatments, such as surgery. The primary outcome was all-cause mortality 5 years after diagnosis. Kaplan Meier curves were created and statistics with Log-rank testing and hazard ratios (HR) were performed. Results: Of 509 patients diagnosed with HCC, 109 (21.4%) met inclusion criteria. 60 were treated with TACE alone, 30 with ablation alone, and 19 were treated with both, either concomitantly or in sequence. Median follow-up and overall median survival was 15.5, 19, and 52 months for TACE, ablation, and dual therapy, respectively. Survival at 5 years was 11.9%, 13.3% and 42.1% for TACE, ablation, and combination groups respectively. Kaplan Meier analysis revealed a significant increase in survival in the combination therapy group vs. RFA or TACE alone at 5 years (p = 0.0006). However, there was no significant difference in survival when comparing TACE vs. RFA/MWA at 5 years (HR = 1.18, p = 0.48). Conclusions: Our study suggests a greater survival benefit for patients treated with TACE and RFA/MWA versus either modality alone.
A phase Ib/IIa study of combination therapy with gemcitabine and Atu027 in patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Schultheis Beate , Strumberg Dirk , Kuhlmann Jan , Wolf Martin , Link Karin , Seufferlein Thomas , Kaufmann Joerg , Gebhardt Frank , Bruyniks Nico , Pelzer Uwe
Published: February 2017

385

Background: Atu027 is a liposomally formulated short interfering RNA with anti-metastatic activity, which silences expression of protein kinase N3 (PKN3) in the vascular endothelium. PKN3 acts as a Rho effector downstream of PI3K. This trial was designed to assess safety, pharmacokinetics and efficacy of Atu027 in combination with gemcitabine in advanced pancreatic carcinoma (APC). Methods: 23 patients (pts) with APC stage 3 or 4 were enrolled and randomly assigned to different Atu027 dosing schedules (arm 1: 0.253mg/kg once weekly, n = 11; arm 2: 0.253mg/kg twice-weekly, n = 12) but identical gemcitabine regimen. Response was evaluated according to RECIST 1.1. Quality of life was assessed with EORTC questionnaire QLQ-C30. Results: Combination therapy with Atu027 and gemcitabine was given up to 7.8 months until progression. Grade 3 adverse events (AEs) were reported by 9/11 pts (82%) in arm 1 and 11/12 pts (92%) in arm 2. Grade 4 AEs were reported by two pts in each arm. Interestingly, there was a difference in median progression free survival (mPFS) between the two treatment arms. Arm 1 showed an mPFS of 1.8 [95%CI: 0.4-5.5] months vs. 5.3 [95%CI: 1.5-6.0] months in arm 2, p= 0.399. In a post-hoc analysis of metastatic disease only, the difference in mPFS between the two arms reached statistical significance (1.6 [95%CI:0.4-2.1] vs 2.9 [95%CI:1.0-7.3] months, n = 9 vs 10, p= 0.025). Disease control during treatment was achieved in 4/11 (36%) pts in arm 1 and in 7/12 (58%) pts in arm 2. New lesions occurred in all (6/6) pts in arm 1 who had at least one RECIST re-evaluation but only 5/10 pts (50%) in arm 2. In quality of life analysis, pts in the once-weekly arm showed a stable global health status while pts in the twice-weekly arm reported an improvement (0-100 score change from baseline: -2.3 vs +21.6 after one cycle, N = 7 vs 7). Conclusions: Combination of Atu027 with gemcitabine for the treatment of APC is safe and was well tolerated. Despite the small patient number, there is a clear signal that twice-weekly Atu027 dosing might be superior to the once-weekly regimen. These results suggest efficacy of Atu027 and warrant further investigation with Atu027 added to standard of care in APC. Clinical trial information: NCT01808638.
Phase Ib study of cancer stem cell (CSC) pathway inhibitor BBI-608 administered in combination with FOLFIRI with and without bevacizumab (Bev) in patients (pts) with advanced colorectal cancer (CRC).
Authors: Hubbard Joleen Marie , O'Neil Bert H. , Jonker Derek J. , Halfdanarson Thorvardur Ragnar , Starodub Alexander , Grothey Axel , Borodyansky Laura , Li Chiang
Published: February 2017

569

Background: BBI-608 is an oral first-in-class cancer stemness inhibitor that blocks STAT3-mediated transcription of cancer stemness genes. Potent anti-CSC activity was observed in vitro and in vivo,in mono and combination therapy. In phase I studies, BBI-608 was generally well tolerated with encouraging signs of anti-tumor activity. Methods: A phase Ib open label, multi-center study in pts with advanced CRC was undertaken to confirm the RP2D of BBI-608 in combination with FOLFIRI with or without BEV. BBI-608 was administered at 240 mg BID in combination with FOLFIRI (5-FU 400 mg/m2 bolus with 2400 mg/m2, irinotecan 180 mg/m2, and leucovorin 400 mg/m2infusion) with or without BEV 5 mg/kg, administered bi-weekly until progression of disease, unacceptable toxicity, or other discontinuation criterion was met. Results: 18 heavily pretreated pts with an average of > 3 prior lines of therapy of which 10 pts (56%) previously progressed on FOLFIRI were enrolled. Of the 17 pts evaluable for response, 8 pts received FOLFIRI and 9 pts received FOLFIRI with BEV in combination with BBI-608. Most common adverse events included grade 1 and 2 diarrhea, abdominal pain, nausea, vomiting and anorexia. No dose limiting toxicity or new adverse events were seen, and the safety profile was similar to that of each regimen as monotherapy. Grade 3 events related to protocol therapy included diarrhea occurring in 3 pts, fatigue in 2 pts and dehydration in 1 pt. All events resolved after dose reduction and/or start of anti-diarrheal medications. No significant pharmacokinetic interactions were observed. Disease control (PR+SD) was observed in 16 of 17 evaluable pts (94%) with 2 PR (per RECIST 1.1 criteria: 44% and 33% regression) and 14 SD (of which 13 (93%) had tumor regression < 25%). In the evaluable pts, median progression free survival was 5.54 months. Of 17 pts, 7 (41%) had prolonged SD of > 6 months. Conclusions: This phase Ib study confirmed that BBI-608 at 240 mg bid can be safely combined with FOLFIRI with and without BEV, and shows encouraging anti-tumor activity in heavily pretreated CRC pts, even in pts with prior progression on FOLFIRI-based therapy. Clinical trial information: NCT02024607.
Prognostic impact of primary tumor site location in metastatic colorectal cancer (mCRC).
Authors: Matos Ignacio , Ortiz Carolina , Elez Elena , Argiles Guillem , Grasselli Julieta , Macarulla Teresa , Capdevila Jaume , Alsina Maria , Sauri Tamara , Hierro Cinta , Verdaguer Helena , Sanz-Garcia Enrique , Martinez Ana Maria , Espin Eloy , Dopazo Cristina , Landolfi Stefania , Nuciforo Paolo , Vivancos Ana , Dienstmann Rodrigo , Tabernero Josep
Published: February 2017

578

Background: CRC site is associated with differences in key molecular features that may impact survival in the metastatic (met) setting. We assessed the magnitude of outcome differences in a non-clinical trial scenario and explored how rectum cancer (RC) compares with right- and left-sided (RS and LS) colon tumors. Methods: Retrospective analysis of clinicopathological and molecular data from all mCRC patients (pts) treated at VHIO from January 2010 to June 2015. Targeted mutation (mut) profiling of driver oncogenes was performed by mass spectrometry (MassARRAY, Sequenom) or with next generation sequencing (Amplicon MiSeq, Illumina). Survival after relapse (SAR) was defined as time from diagnosis of met disease to death. Tumor site was categorized as RS (cecum, ascending, hepatic flexure, and transverse), LS (splenic flexure, descending, and sigmoid) or RC. We performed Cox proportional hazards models and adjusted for covariates including number and location of met sites, surgical resection of met lesions, and KRAS, BRAF and PIK3CA mut. Results: From 686 pts analyzed, primary site was RS/LS/RC in 29.4%/43.4%/27.2%, respectively. Pts with LS tumors were less likely to have ≥ 2 met sites (32%/20%/29%; p = 0.01). Lung metastases were more common in RC pts (20%/15%/36%; p < 0.001), peritoneal metastasis in pts with RS tumors (28%/14%/5%, p < 0.001). Surgical resection of any met disease was performed less frequently in pts with RS tumors (28%/46%/41%; p < 0.001). KRAS mut (59%/45%/44%), BRAF V600E mut (9%/5%/3%) and PIK3CAmut (25%/14%/11%) were more prevalent in RS tumors. In the overall population with survival data (n = 606, 424 events), SAR was significantly lower in pts with RS tumors (31/46/46 months; RS vs. LS HR = 1.54 [1.2-2.0], p < 0.001; rectum vs. left HR = 1.0 [0.7-1.3], p = 0.83). For comparison, worse SAR was also seen in the subset of pts (n = 337; 276 events) not eligible for surgical resection of met disease (26/31/35 months; right vs. left HR = 1.60 [1.2-2.2], p = 0.004; rectum vs. left HR = 0.9 [0.6-1.2], p = 0.42). Conclusions: The worse SAR of pts diagnosed with right-sided CRC tumors cannot be explained only by their distinctive met pattern or mutation profile of common oncogenes. Left-sided and rectum tumors have similar outcomes.
The usefulness of clinical pathways (CP) in managing quality and cost in oncology networks.
Authors: Ellis Peter G. , O'Neil Bert H. , Earle Martin F. , McCutcheon Stephanie , Benson Hans
Published: February 2017

715

Background: UPMC CancerCenter (UPMC) and Indiana University Health (IUH) utilize Via Pathways (VP) for their CP initiative. VP are developed and maintained by disease committees that evaluate therapies on merit of efficacy, then toxicity, and finally cost (if efficacy and toxicity are comparable) to provide a recommendation for specific patient presentations. Recent data from key studies regarding the use of panitumumab (PAN) or cetuximab (CET) in the setting of metastatic colo-rectal cancer by the colo-rectal committee led to the determination that both treatments were equally effective with no significant difference in toxicity (Price et al., 2014; Peeters et al., 2014). A subsequent cost comparison utilizing CMS average sales prices demonstrated an approximate 14% monthly cost advantage for PAN. A substitution of PAN for CET across all metastatic lines of therapy in the pathway was initiated as of August 2014. This analysis was undertaken to understand the impact of this change. Methods: We reviewed the UPMC and IUH data within the VP database to compare new treatment starts of CET and PAN before and after this change was put in place. Results: There was rapid change in the selection behavior between the two drugs as demonstrated in the table. Conclusions: The results in this simple example of substituting equivalent drugs based on cost exemplify the power of CP to rapidly change prescribing habits across two large cancer networks. CP serve as an invaluable tool to allow oncology practices to quickly respond to the changing treatment norms of oncology care. [Table: see text]
Treatment for RAS wild-type (wt) metastatic colorectal cancer (mCRC): Continuation of anti-EGFR therapy while switching chemotherapy regimen.
Authors: Vladimirova Liubov Yu , Abramova Natalya A , Kit Oleg Ivanovich
Published: February 2017

744

Background: The purpose of the study was to assess the effeciency and safety of continuing of EGFR-inhibition while switching the chemotherapy (CT) from FOLFOX+Cetuximab (C) as the 1st-line to FOLFIRI+С as the 2nd-line treatment for pts with RAS wt mCRC. Methods: Pts with RAS wt mCRC were enrolled to the pilot study according to inclusion criteria: ECOG≤2, normal bone marrow, liver and kidney functions, no brain metastases, measurable metastatic lesions. The therapy included: the 1st-line with FOLFOX-6+C until progression, then FOLFIRI+C as the 2nd-line therapy. The treatment continued until progression or unacceptable toxicity. Response rate (RR), PFS after the 1st and the 2ndlines of treatment as well as toxicity were evaluated. Results: 20 pts (11 men, 9 women), 38-58 years old, mean age 48.3±1.3 years, were recruited. All pts had multiple visceral metastases: to the liver –30.0%(6), lungs and pleura – 20.0%(4), liver and lungs – 50.0%(10), including the bone metastases – 15.0%(3). The RR was 85.0 %(17), including PR - 4(20.0%) and SD - 13(65.5%). Median PFS after the 1st-line therapy was 12.3±2.6 months, median PFS after the 2nd-line therapy - 6.5±2.8 months. Median OS was not reached yet. Adverse events included: neutropenia Gd2 – 30.0%(6), Gd3 – 20.0%(4), anemia Gd2 – 10.0%(2), stomatitis Gd2-3 – 20.0%(4), diarrhea Gd2 - 55.0%(11), thrombophlebitis – 10.0%(2). C-associated dermatologic toxicity: acneiform rash Gd2-3 – 85.0%(17), skin itching Gd2 - 30.0%(6), panaritium Gd1-2 -30.0%(6), blepharitis Gd1-2 – 10.0%(2), hypertrichosis – 20.0%(4). Conclusions: Continuing EGFR-inhibition with C while switching CT regimens beyond progression provided significant tumor control and was not accompanied by unacceptable toxicity. This strategy deserves futher evaluation in randomized studies in EGFR-dependent mCRC pts.