Citations

106 Background: Androgen deprivation therapy (ADT) is one of the main treatment options for locally advanced and metastatic prostate cancer. Neuroendocrine prostate cancer (NEPC) is inherently less sensitive or even resistant to ADT. NEPC can be observed de novo (e.g., small cell prostate cancer) but more commonly arises after exposure to ADT. We hypothesized that a gene expression signature of NEPC when measured in primary tumor specimens (RP) of prostatic adenocarcinoma may be useful for predicting patients with innate resistance to ADT. Methods: Expression profiles of 1023 PCa patients treated with RP were obtained from the Decipher GRID database. These were split into training (n=529) and validation (n=494) sets and stratified by the receipt of adjuvant ADT (n=243) or no adjuvant ADT (n=780). A literature review of ADT resistance and neuroendocrine genes identified 1,557 genes as candidates. This set was further filtered, using logistic regression to select a 52-gene ADT resistance signature (ARS). ARS was trained using a generalized linear model with lasso regularization. Survival c-index and Kaplan Meier was used to compare survival differences between treated and untreated patients with high and low ARS scores (defined by median split). Results: In validation cohorts, the ARS was predictive of metastasis in cohorts receiving adjuvant ADT (10-year metastasis free survival c-index of 0.69 (95% CI 0.59-0.78) as compared to 0.45 (95% CI 0.29-0.61) in patients not treated with ADT). Similarly in a separate cohort of untreated patients that received no ADT until after metastatic onset, ARS was not prognostic (c-index 0.53). Among ADT treated patients, those with low ARS scores had a 10 year MFS of 87%, versus 70% in those with high ARS scores (p<0.001). In the subset of men who received ADT after metastatic onset and who developed castrate-resistant prostate cancer (CRPC, n = 41), median time to treatment failure was 1 year in patients with high ARS compared to 2 years for those with low ARS scores (p=0.07). Conclusions: A 52-gene ADT resistance signature was developed which showed significant differences in metastasis-free survival among adjuvant hormone treated but not untreated patients.

103 Background: Beginning in 2014, the National Comprehensive Cancer Network (NCCN) recognized very high-risk (VHR) prostate cancer (cT3b-T4, or primary Gleason pattern 5, or more than 4 biopsy cores with Gleason score 8-10, or multiple HR features) as a classification distinct from high-risk (HR) disease. Using prospectively collected institutional data, we describe contemporary treatment patterns and short-term outcomes in the VHR population. Methods: Men who underwent radical prostatectomy (RP) between January 2010 and June 2015 were identified using the Johns Hopkins RP database, and trends in management were compared across the study period. Pathological and short-term clinical outcomes were assessed in men with VHR cancer. Non organ-confined disease (NOCD) was defined as ≥ pT3 disease or lymph node positivity, persistent postoperative PSA as ≥ 0.2 ng/mL, and biochemical recurrence (BCR) as a PSA ≥ 0.2 ng/mL following an initial undetectable postoperative PSA. Results: During the study period, 4,954 men underwent RP, of which 161 (3.2%) men had VHR cancer at diagnosis. The annual proportion of men who underwent RP with VHR cancer increased over the study period (chronologically 1.8%, 1.0%, 3.3%, 4.1%, 5.6%, and 5.2%; p<0.001). Sixteen percent of men with VHR disease were enrolled in pre-surgical clinical trials, with an increase from 0% of men in 2010 to 19.1% in 2015 (p=0.11). At RP, 39% of the VHR cohort had seminal vesicle invasion, 26% had lymph node involvement, and a total of 74% had NOCD. Following surgery, 33% of men had PSA persistence, and 40% experienced either PSA persistence or BCR during follow-up (median 13.4 months). Of 136 men with at least one follow-up assessment, 15 (11.0%) developed metastasis; 33% of the cohort was treated with radiation therapy, 42% with androgen deprivation, and 15% with docetaxel. Conclusions: The VHR population carries the greatest risk of clinical progression following local treatment. Over the past five years, we have observed increasing surgical treatment and clinical trial enrollment at our institution. Continued assessment of post-operative interventions and outcomes will help to facilitate counseling and establish point estimates from which to power clinical trials.

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.

60 Background: A significant number of patients with advanced cancer die in the hospital. Examination of patterns of care and palliative care (PC) involvement may identify opportunities for process of care improvements for this vulnerable population. Methods: Patients were identified using the institutional mortality review system registry (Mayo Clinic hospitals from July, 2013-June, 2014). Within this group, patients with a diagnosis of terminal malignancy were identified by chart review and ICD-9 codes. Patient demographics, clinical characteristics, and use of PC resources were characterized in the last 60 days of life. Results: There were 159 of 924 decedents identified whose primary cause of death was advanced malignancy (Table). Ninety-two patients (57%) had PC consultation during the index admission preceding death, while 31 (19%) patients had seen PC as an outpatient or inpatient prior to index admission. Lack of inpatient PC consultation at index admission was associated with hematologic malignancy (p < 0.001), full code status at death (p 0.009), shorter median time between change of code status to DNR and death (13 vs 67 hrs, p < 0.001), death in the ICU (58% vs 31%, p < 0.001), and presence of code blue (22% vs 5%, p-value = 0.003). Patients who received a PC consultation were less likely to have chemotherapy within 14 days of death (15% vs 37%, p-value = 0.001), and had a median composite aggressive end of life score (6 factor composite score based on utilization in last 30 days of life, higher score indicating more aggressive care) of 3 vs 4 (p 0.002). Conclusions: Inpatient PC consultation for cancer patients who die in the hospital is associated with less aggressive cancer care at end of life. The single-institution patient population and small sample size are the limitations of our study. [Table: see text]

29 Background: Good communication is crucial to good patient care. Gynecologic oncology providers often face challenging communication scenarios, including giving serious news and discussing goals of care. Communication skills training (CST) has been shown to improve skill acquisition among providers of multiple specialties, but it has not been described in providers from gynecologic oncology or any surgical oncology specialty. Methods: We conducted a two-day CST workshop, based on the VitalTalk© model, with four faculty members (2 gynecologic oncologists and 2 palliative care physicians) and 10 gynecologic oncology provider participants (5 fellows and 5 advanced practice providers). Using didactics, demonstrations and practice sessions with simulated patients we focused on giving serious news and discussing goals of care. Pre and immediate post-workshop surveys evaluated acceptability of the workshop, perceived impact of preparedness to address challenging communication scenarios and anticipated impact on clinical practice. We compared pre and post-workshop prevalence of score of 4 or 5 out of 5 on a Likert scale for preparedness to handle 14 challenging communication scenarios. Results: Participants reported statistically significant increase in preparedness to handle 13 out of 14 challenging communication scenarios. Among those 13 topics, magnitude of improvement in proportion of participants rating preparedness 4 or 5 out of 5 ranged from 40-100% (all p < 0.05). All participants would recommend the course to others and all strongly agreed that this training should be required of all gynecologic oncology clinicians. Conclusions: Participants felt strongly that the workshop provided high quality education relevant to their practice. As a result of the workshop, participants reported statistically significantly increased preparedness to handle challenging communication scenarios. CST is feasible and has high perceived effectiveness for clinicians in the primarily surgical oncologic specialty of gynecologic oncology.

253 Background: cPMP is chronic pain in the front thorax, axilla, and/or upper half of the arm beginning after mastectomy or lumpectomy persisting > 3 months after treatment and presents with pain, allodynia and disability. cPMP occurs in half of all patients with breast cancer and is severe in 13% (Gartner R JAMA 2009). Epidural bupivacaine, memantine, gabapentin or venlafaxine may help prevent cPMP, but there are no established proven treatments. (Shen J, Up to Date 2016) Scrambler therapy (ST) is an FDA-cleared treatment for neuropathic pain supported by multiple trials in over 800 patients with cancer pain, chemotherapy induced neuropathic pain, back pain, and post herpetic neuropathy (PHN). (Majithia N JSSC 2016) Methods: We treated 2 women with cPMP with standard ST, with repeated treatment if the pain returned. ST was done with ECG pads above and below the pain for 45 minutes daily, until pain resolved, and repeated if/when pain recurred. Results: Case 1: A 60 year-old woman had bilateral mastectomy 2 years prior with cPMP like “a barbed wire bra”. Before treatment, her pain was 8, which decreased to 0-2 after 5 treatments. Her pain returned 4 months later and was successfully retreated. She resumed a more normal life and was able to taper and eventually stop her opioids. Case 2: A 56 year-old woman had deep aching cPMP for a year following chemo, Mastectomy, and RT. Her pain was 10, decreased to 0-1/10. Her pain returned 1 month later; 3 treatments reduced her pain from 4/10 to 0/10 and improved her quality of life, which lasted for several months until cancer recurrence. Conclusions: Scrambler therapy successfully treated cPMP in 2 patients with improved pain and quality of life, and enabled one patient to stop her opioids in line with new CDC guidelines. Scrambler therapy appears to hold promise, as it does in chemotherapy-induced neuropathy, failed back syndrome, PHN, low back pain and other conditions; prospective trials are indicated to further evaluate this treatment modality. [Table: see text]

250 Background: Testicular germ cell tumor survivors (TGCTSs) contend with treatment side effects for decades after cure, and many have metabolic syndrome (MTS), a modifiable cardiometabolic risk factor. Because reliably predicting MTS could prompt interventionreducing risk, we analyzed clinical data and body composition in computed tomography (CT) scans to identify associations. Methods: In a retrospective review of 196 TGCTSs treated at a single institution from 1970 to 2007, we collected patient (pt) demographics, clinical data, body fat composition measures, and evidence from CT scans from baseline through posttreatment. NIH Image J was used to analyze cross-sectional CT images and measured subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle. Visceral fat-to-muscle ratio (VMR), visceral-to-subcutaneous fat ratio (VSR), and change in VMR and VSR from baseline to 3 to 5 years posttreatment (ΔVMR and ΔVSR) were calculated. We also gathered posttreatment glucose, blood pressure, lipid data, and body weight and height measured at time of scans. The 2001 U.S. National Cholesterol Education Program Adult Treatment Panel III guideline defined MTS. Univariate and multivariate logistic regression analyses identified associations. Results: Of the 167 pts included in the final analysis, 37.7% had MTS, 76.6% were white, and 68.9% had chemotherapy. Pts with MTS had significantly higher VMRs (p = .007) and VSRs (p = .021) than those without. Pts receiving chemotherapy and radiotherapy were significantly more likely to have MTS (p = .044 and p = .037). A multinomial logistic regression model including year of diagnosis, age, race, tumor histology, treatment, VSR, and VMR identified the association of high VMR and VSR with MTS; ΔVMR and ΔVSR were not statistically significant predictors. Conclusions: Body composition analyses identified VMR and VSR as significant predictors of MTS.

232 Background: Screening for distress in cancer patients (pts) is recommended by several national guidelines. High distress scores are associated with increased depression. We established universal depression screening and investigated its impact on cancer patient management. Methods: Patient Health Questionnaire (PHQ9) was administered to newly diagnosed cancer patients prior to receiving their first non-oral antineoplastic agent. Patient demographics, disease characteristics, chronic medication load, antidepressant use, treatment interruptions, weight change, referral and adherence to psychiatry were recorded. Pts with high (> 9) and low (< 4) PHQ9 scores were compared using Chi-square and Wilcoxon rank-sum tests. Results: Screening was performed in 1,190 consecutive pts over an 18 month period at Mayo Clinic. Responses were received from 1055 (89%) pts, of which 144 had high score (PHQ-H). These were compared with 99 randomly selected low score (PHQ-L) pts. The 243 pts (median age 65; range 18-92 years) in the final analysis included: 53.5% females, 90% Caucasians, 74% married and 77% living with others. Diagnosis was solid organ cancer in 81% and metastatic disease in 54% patients, and 13% were on antidepressants for preexisting depression. PHQ-H were more likely to be on antidepressants than PHQ-L (19% vs. 3%; p = 0.0002), be referred to psychiatry (69% vs. 12%; p < 0.0001), attend psychiatry appointment (45% vs. 12%; p < 0.0001) and require behavioral therapy (50% vs 8%; p = 0.0065). PHQ-H did not have a significantly increased antidepressant use, treatment interruptions (p = 0.5) or weight change (p = 0.4). Race, gender, chronic medication load, marital status, living situation, metastatic disease and type of cancer were not significantly different between PHQ-H and PHQ-L. Conclusions: We implemented a universal depression screening and management plan for cancer pts and noted that previously being on antidepressants was associated with higher patient distress. Higher score led to more frequent behavioral therapy, possibly preventing non-compliance or need for increased psychotropic medications. Our model identifies cancer pts with depression and implements an effective management plan for their care.

221 Background: To our knowledge, no study has examined adherence to antiemetic guidelines with soon-to-be-approved or newly approved chemotherapy agents. In 2015, the Food and Drug Administration approved 18 cancer drugs, underscoring the timeliness of this topic. Here, we hypothesize that patients prescribed new drugs are at risk for poor guideline adherence, and we report on antiemetic prescribing practices and outcomes with TAS-102, a recently approved drug for metastatic colorectal cancer. Methods: This study focused on all patients prescribed TAS-102 in 2015 at the Mayo Clinic in Rochester, MN for compassionate use or routine care within 3 months of FDA approval. First-cycle antiemetic prophylaxis was examined for adherence to National Comprehensive Cancer Network Guidelines, version 1.2015, for chemotherapy of low emetogenic potential based on TAS-102 phase 3 data. Results: Among 44 patients, 28 (64%) had nausea and vomiting with prior chemotherapy. With the first cycle of TAS-102, 25 (57%) were prescribed antiemetics in a guideline-adherent manner; 15 (34%) in a non-guideline-adherent/more aggressive manner; and 4 (9%) in a non-guideline-adherent/less aggressive manner. In guideline-adherent patients, rates of nausea and vomiting were 52% and 24%, respectively, with one patient requiring an unscheduled clinic visit and another an emergency department visit and hospital admission - all for nausea and vomiting. In non-guideline-adherent/more aggressive patients (who received more prophylaxis than called for), these rates were 33% and 27%, respectively, with one patient requiring a clinic visit and emergency department visit and another an emergency department visit. In non-guideline-adherent/less aggressive patients, no nausea or vomiting was reported. Conclusions: Poor adherence to antiemetic guidelines occurred often. However, because adherence was not associated with better control of nausea and vomiting, clinical judgment should complement guidelines in patients about to receive new cancer drugs, particularly with drugs of low emetogenic potential and also in patients with a history of chemotherapy-induced nausea and vomiting.

220 Background: Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Preliminary animal data suggest that minocycline may be effective for the prevention of chemotherapy-induced neurotoxicity. The purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and P-APS. Methods: Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks. They were randomized to receive minocycline 200mg on day 1 followed by 100mg twice daily or a placebo, with the same dosing schedule. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy, and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment. The primary goal was to obtain pilot data regarding the possible effect of minocycline on the prevention of paclitaxel-induced CIPN and P-APS, to determine if conducting a larger phase III placebo-controlled trial was indicated. Scores obtained from patient questionnaires were converted to a 0-100 scale, where higher scores = better quality of life. Results: Forty-seven patients were randomized, 45 of which were evaluable, with a mean age of 55. There were no remarkable differences noted between the two groups for the overall sensory score of the EORTC-CIPN 20 or its individual sub-questions, which evaluated tingling, numbness, or shooting burning pain in hands and feet. However, there was a significant difference in the daily average AUC pain score attributed to P-APS, favoring minocycline (median 96.0 vs 84.3; p = 0.02). Correspondingly, patients receiving minocycline used less opioid pain medications for control of P-APS (0% vs 23%, P = 0.05). Not only were no increased toxicities reported with minocycline, but there was an apparent improvement in fatigue (median AUC 76.7 vs 59.0; P = 0.02). Conclusions: Based on the results of this pilot study, minocycline did not appear to be beneficial for the prevention of CIPN, but did look promising for reducing P-APS. Further study of this effect may be warranted. Clinical trial information: NCT02297412.