bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer versus non-cancer caregivers: An analysis of communication needs from the 2015 Caregivers in the U.S. study.
Authors: Kent Erin E. , Longacre Margaret , Weber-Raley Lisa , Whiting C. Grace , Hunt Gail
Published: February 2017

4

Background: Informal caregiving for cancer patients can be both demanding and burdensome – physically, emotionally, and financially – for many caregivers. Cancer caregivers play a large role in advocating for and administering care for their recipients. The current study aimed to explore if cancer caregivers differ from non-cancer caregivers with regard to communicating with healthcare providers, and need for information about end-of-life care. Methods: Data were used from the 2015 Caregiving in the U.S. (CGUS) dataset, a nationally-representative online probability-based panel study of unpaid adult caregivers. The analysis compared cancer and non-cancer caregivers to determine similarities and differences in characteristics and experiences, with a focus on unmet needs in communication with healthcare providers and end-of-life decision-making. Statistical significance was determined at the p < 0.05 level. Results: Approximately 7% (2.8 million) of caregiver participants in the CGUS study indicate cancer as the primary reason for providing care. Cancer caregivers report higher burden than non-cancer caregivers (62% vs. 38%) and significantly more hours per week caregiving (32.9 vs. 23.9 hours per week). Significantly more cancer caregivers indicate interacting with key providers, agencies, and professionals on behalf of their care recipients: 82% report communicating with healthcare professionals (vs. 62%), 76% monitor/adjust care (vs. 66%), and 62% report advocating for care recipient (vs. 49%). Finally, almost twice the number of cancer caregivers than non-cancer caregivers (40% vs. 21%) report needing more help/information with making end-of-life decisions. Conclusions: These findings indicate the burdensome and demanding role of cancer caregiving. These caregivers play a substantial role in directing, monitoring, and advocating for survivor care. Yet, many need more information about end-of-life care. This suggests a gap in preparation despite the roles provided, and suggest a need to explore strategies to engage patient-provider-caregiver communication about care, particularly end of life care.
Effect of discharge to subacute rehabilitation (SAR) on hospitalized patients with progressive gastrointestinal (GI) cancer.
Authors: Epstein Andrew S. , Desai Anjali V. , Saltz Leonard
Published: February 2017

41

Background: SAR may be an alternative when hospice is declined. However, the outcomes of discharges to SAR in cancer patients with progressive (chemotherapy-refractory) disease are not known. We examined the characteristics and outcomes of patients with debility from progressive metastatic GI cancer who were discharged to SAR after an admission to our center. Methods: An institutional electronic database was queried to identify patients of the GI medical oncology service of Memorial Sloan Kettering Cancer Center who had been discharged to a SAR facility. Patient exclusion criteria were: incomplete follow-up, non-metastatic cancer, low grade neuroendocrine tumors, patients receiving first-line chemotherapy or with newly diagnosed cancer awaiting planned chemotherapy, patients off treatment with a remote history of metastatic cancer, and a primary admitting diagnosis representing an acute complication of cancer treatment. Results: From 2008-2014, 22 patients meeting criteria were identified. Median overall survival from the time of discharge to SAR was 0.8 months (range 0.2-5.2 months). Of the 22 patients, 7 (32%) died at the SAR. Twelve (55%) and 19 (86%) died within 1 and 3 months of discharge to SAR, respectively. For 7 patients (32%), documentation indicated that hospice, instead of SAR, had been recommended by clinicians but declined by family. Nine patients (41%) ultimately were transitioned to hospice within 3 months of discharge to SAR. Eight (36%) were readmitted to hospital within 1 month of discharge to SAR. Two (9%) were able to follow up with their medical oncologist for an outpatient appointment after discharge to SAR. None of the 22 patients received further chemotherapy after discharge to SAR. Conclusions: SAR is not a productive alternative to hospice in hospice-eligible patients with GI malignancies.In patients with metastatic GI cancers whose diseases had progressed beyond first-line therapy and who were hospitalized for reasons other than acute reversible toxicity, discharges to SAR were not associated with either prolonged survival or resumption of chemotherapy. These data can help inform decisions and establish goals of care in advanced GI cancer patients.
Usage of Oregon’s Death With Dignity Act (DWDA).
Authors: Blanke Charles David , LeBlanc Michael Leo , Hershman Dawn L. , Ellis Lee M. , Meyskens Frank L.
Published: February 2017

44

Background: In 1997, OR enacted a voter initiative allowing terminally ill residents to self-administer physician-prescribed medication to end their lives. Statute requires prescriptions written for lethal medications be reported; the state also collects demographic and intended use data. We wished to to evaluate and report participation trends. Methods: OR's Public Health Division gathers compliance forms from prescribing/consulting physicians, pharmacists, and psychiatrists, prescribing physician follow-up forms, and death certificates. Data from 1998-early 2016 were reviewed, collated, and interpreted. Results: 1,545 prescriptions were written; 991 pts died from legally-prescribed lethal medication. The % of prescription recipients dying from drug use per yr ranged from 48-82, with no significant trend (logistic regression 2-sided p = .90) The prescribing rate increased 12%/yr on average through 2013, with a 28% increase in 2014 and 40% in 2015, not explainable by growth in population. Characteristics of 991 pts dying from drug: Most recipients had cancer (77%); 8% had ALS, 4.5% lung disease, 2.6% heart disease, and 0.9% HIV. 5.3% were sent for psychiatric evaluation. M/F (%) 51.4/48.6; median age (years) 71 (range 25-102); race white/black/asian/hispanic (%) 97/0.1/1.3/1; hospice Y/N (%) 90.5/9/5. 94% died at home. Estimated median time between intake and coma (min): 5 (range 1-38); to death (min): 25 (range 1-6240). 3.3% had known complications. Reasons for DWD (%): ADL not enjoyable 90; loss of autonomy 92, dignity 79, or bodily functions 48; inadequate pain control 25; financial 3. Conclusions: The number of prescriptions written for ORDWDA medications increased annually since enactment. The % of recipients self-administering drugs has varied. Very few pts are referred for psychiatric consultation prior to DWD. Most pts dying from lethal medications have cancer, and the overwhelming majority expire at home. Medications used are effective and rapidly acting. Little evidence exists disadvantaged pts are disproportionally using DWD. Pts use DWD for reasons related to QOL, autonomy, and dignity, and relatively rarely because of inadequate pain palliation. Future studies should evaluate why many pts prescribed lethal drugs choose not to take them.
A quality improvement approach to oncologist referrals for hospice care.
Authors: Von Gunten Charles F.
Published: February 2017

45

Background: Cancer patients frequently experience short lengths of service in home hospice care. Methods: The Oncology Clinical Guidance Council, composed of medical, surgical, gynecological and radiation oncologists sets standards of care for the OhioHealth system serving central Ohio. The Council was polled for consensus on how long a cancer patient should be enrolled in hospice care. Then, median length of stay of patients referred by 18 medical oncologists from their offices to OhioHealth hospice for calendar year 2014 were obtained. A letter from the Chairs of the Oncology Clinical Guidancee Council was sent to each medical oncologist noting the council's opinion about optimal length of stay, the length of stay reported by the National Hospice and Palliative Care Organization (NHPCO), and the median length of stay of all patients referred by OhioHealth oncologists. A chart graphing the median length of stay by oncologist, indicating the name of the oncologist to which the letter was directed, was mailed to each oncologist. One year later, for calendar year 2015, the measurement of median length of stay by oncologist was repeated. Results: 64% of the Oncology Clinical Guidance Council members polled think the median length-of-service for hospice care for cancer patients should be 90 days (3 months) and 20% think it should be 45 days (6 weeks). The NHPCO national median is 43 days. At baseline, the median length of stay for 176 cancer patients referred in calendar 2014 was 19.7 days. The median length of stay for 133 patients referred in the first 10 months of 2015 was 39.6 days. Conclusions: A simple quality improvement approach to improving hospice length of service by oncologists yielded a doubling to reach the national median in one year.
Perception of curability in an international cohort of advanced cancer patients receiving palliative care.
Authors: Yennu Sriram , Shamieh Omar M. , Rodrigues Luis Fernando , Tricou Columbe , Filbet Marilène , Naing Kyaw , Ramaswamy Akhileswaran , Bautista Mary Joycylyn S. , Perez-Cruz Pedro Emilio , Fakrooden Sarah , Muckaden Mary Ann , Bunge Sofia , Sewram Vikash , Noguera Tejedor Antonio , Hui David , Park Minjeong , Liu Diane D , Bruera Eduardo
Published: February 2017

5

Background: There is limited data on the illness understanding and perception of cure among advanced cancer patients (ACP) receiving palliative care around the world. The aim of the study was to determine the frequency and factors associated with perception of curability in countries in North and South Americas , Europe, Asia and Africa. Methods: Secondary analysis of a study to determine the decisional control preferences in different countries. ACP receiving palliative care were surveyed to assess the patients’ Understanding of Illness using a Understanding Of Illness questionnaire. Descriptive statistics and Logistic regression analysis were performed. Results: A total 1390 ACPs were evaluated. The median age was 58, 55% were female, 59% were married, 47% were catholic, 36.2% were educated college or higher degree. 681/1390 (49%) reported that their cancer is curable, 60% felt perceived that the goals of therapy was “to get rid of their cancer,” 79% perceived that the goals of the therapy was to “make them feel better.” 62 % perceived they were relatively healthy. Logistic regression analysis (Table 1) shows that better Karnosfsky performance status (OR 1.009, P = 0.04), higher education (OR 0.52, P = 0.0001), ACP's belonging to Brazil, France and S. Africa were less likely and ACPs from Philippines, Jordan were more likely to have a perception of curability. Age, gender, marital status, religion and passive decision control preferences were not significantly associated with perception of curability. Conclusions: The perception of curability in ACP's is 49% and significantly differs by education, performance status, and country of origin. Integration of Palliative Care can be more complex in these patients. Further studies are needed to develop strategies to reduce this misperception so as to have early integration of palliative care. [Table: see text]
Utilizing electronic technologies to measure patient-reported outcomes (PRO) assessment completion time.
Authors: Brito-Dellan Norman , Lam Tony , Richardson Marsha N. , Manzullo Ellen F. , Kallen Michael , Yang DerShung , Haas Niina Mari , Escalante Carmelita P.
Published: February 2017

69

Background: Patient-reported outcomes (PROs) contribute to the assessment and treatment of cancer-related fatigue (CRF). Paper-based symptom assessments are cumbersome and time-consuming. Electronic assessments are an efficient alternative. This study describes CRF Clinic patients at a major cancer Institution, the time they required to complete self-reported CRF symptom assessments via a tablet computer (iPad), and the factors influencing PRO assessment completion time. Methods: From 1/1/2011 to 8/21/2012, 190 newly-referred CRF Clinic patients utilized an iPad to complete standardized CRF symptom assessments for: fatigue, pain, depression, anxiety, stress, sleepiness, and apathy. A web-based assessment module (BrightOutcome) was employed, which recorded assessment start and completion times. Non-Parametric test statistics were utilized for analysis. Results: Of the initial 190 patients, 3 were excluded due to non-cancer diagnoses and 1 was excluded due to an erroneous completion time of 8,903 minutes. Sample size is 186 patients; mean age was 55.49 years (range: 31-89); 69.4% (n = 119) were female. Patient mean fatigue score (Brief Fatigue Inventory) was 6.4. Mean assessment completion time was 16.73 minutes (range: 4-47). Assessments took longer to complete for patients ≥ 65 years (mean: 21.53 minutes; range: 9-43), males (mean of 18.3 vs. 16 minutes for females), patients with severe fatigue (7-10) (mean 18.31 minutes; range: 4-47), greatest apathy (38-72) (mean: 19.5 minutes; range 8-47), those with active cancer (mean: 18.02 minutes vs. 15.15 minutes in cancer survivors), and those with 2 or more comorbidities (mean: 18.41 minutes vs. 15.86 minutes in those with less than 2 comorbidities). Pain severity and interference, anxiety, depression, stress, and sleepiness did not statistically significantly impact assessment completion time. Conclusions: Patients who are older, male, fatigued, apathetic, with active cancer or with 2 or more comorbidities may require longer in-clinic time to complete standard symptom assessments. Further studies exploring these and other patient characteristics potentially impacting the integration of new technologies into patient care and research are warranted.
A consolidated screening tool for supportive oncology needs and distress.
Authors: Scheu Amy , Wiebe Lauren Allison , Lo Shelly S. , Deamant Catherine , Roggenkamp Betty , Patel Urjeet , Khosla Pam , Robinson Patricia A. , Penedo Frank J. , Gerhart James , Lillis Teresa , Dale William , Gordon Ana , Kothari Rajul , Berardi Rosa , Trosman Julia Rachel , Weldon Christine B.
Published: February 2017

72

Background: The IOM 2013 Report recommends that supportive oncology care start at cancer diagnosis; the Commission on Cancer (CoC) standard 3.2 requires distress screening and indicated action. Screening tools are not standardized across institutions and often address only a portion of patients’ supportive oncology needs. Methods: A collaborative of 100+ clinicians, funded by The Coleman Foundation, developed a patient-centric consolidated screening tool based on validated instruments (NCCN Distress Problem List, PHQ-4, PROMIS) and IOM and CoC. The screening tool was piloted at 6 practice improvement cancer centers in the Chicago area (3 academic, 2 safety-net, 1 public). Patients, providers assessing each patient’s screening results (assessors), and providers receiving referrals (referral providers) were surveyed after each use of the screening tool. Descriptive statistics were used to assess effectiveness of the tool. Results: Responders included 29 patients, 81 assessors and 26 referral providers (SW, chaplain, subspecialist). The majority of patients (22/29, 75%) completed the screening in < 10 minutes without assistance and will complete at every visit. Most assessors (59/77, 76%) spent < 5 minutes reviewing screening results. The majority of patients, assessors, and referral providers reported that the screening tool asked the “right questions”. Assessors reporting partial relevance of some screening questions for 34% (26/77) of patients, uncovered ≥ 1 relevant needs for 96% (25/26) of those patients (p = 0.002). Conclusions: Use of a consolidated supportive oncology screening tool across multiple institutions is feasible, discovered unmet patient needs, and was beneficial for assessors and providers. As the tool is adopted by collaborating institutions, variations in supportive oncology screening may decline, thus improving access to supportive oncology care with implications for national dissemination. [Table: see text]
Strategy of using herbal extract preparations for stage IV cancer in palliative care: An enhanced and maintenance therapy.
Authors: Rong Pu , Lingyan Zhang , Xiaoxia Zhou , Weihua Yin , Xiulian Zhang , Hong Liu , Xiaopeng Duan , Cui Yu , Xiaolu Luo , Qingfeng Zhong , Fen Zhao , Xianyong Li
Published: February 2017

89

Background: Palliative care is focused and seems as rationally anti-cancer way that have low systemic toxicity and acceptable effectiveness for stage IV cancer, especially herbal extracted medicines, which can regulate tumor microenviroment and body immune system. Our previous lab studies have indicated that TGF-beta, EGF, VEGF, IL-10 cytokines expression and mico-vessel density can be downgraded in tumor microenviroment by herbal extract preparation from Ginseng, Herba Agrimonia, Hairyvein and Arginine etc. Methods: 13 patients with unresectable pancreatic cancer, 31 patients with liver cancer, and 168 patients with stage IV lung cancer were studied. Herbal extract preparation, which was approved by the China Food and Drug Administration; hyperthermia; and psychological rehabilitation were initiated as alternative therapies. Survival time, quality of life and toxicity were evaluated during treatment. Results: The average ECOG score decreased from 3 to 2, and appetite and sleep improved in all three groups. According to CTCAE criteria, no severe hematology and digestion side-effect above grade 2 were observed. In pancreatic cancer group, the median and the average survival time were 5.1 and 6.5 months. The longest survival time was 16.7 months and patient still alive. The 3-, 6-, and 10-month survival rates were 92.3%, 46.2% and 30.8%, respectively. In liver cancer group, the average and median survival time were 12.48 and 5.03 months, respectively; the longest survival time was 84.17 months. The 3-, 6-, and 12-month survival time rates were 77.42%, 38.71%, and 29.03%, respectively. In lung cancer group, 31.58% patients suffered from pleural effusion. The 6 month, 1-, 2- and 5-year survival time rates were 33.93%, 19.05%, 14.29% and 4.17%, respectively. Furthermore, once the survival time was beyond 6 months, the average and median survival time reached 29.98 and 14.80 months; and the 1-, 2- and 5-year survival time rates were up to 56.14%, 42.11% and 12.28%, respectively. Conclusions: Herbal extract preparations, which are a part of palliative care, show acceptable effectiveness and toxicity. Thus, it may prove to be a considerable strategy and optional maintenance therapy for stage IV patients.
The effect of reflexology on quality of life in Iranian patients with breast cancer.
Authors: Pedramrazi Shadan
Published: February 2017

90

Background: Breast cancer is one the most prevalent cancers among Iranian women. One of the complementary therapies is reflexology. The extant paper has been provided with the objective of determining the effect of reflexology on quality of life of patients with breast cancer undergoing chemotherapy in the breast disease center. Methods: This study is a randomized clinical trial which has been applied to 60 patients suffering from breast cancer under chemotherapy in breast diseases center, in 2012. The patients were selected randomly in three test, control and placebo groups. In test group, reflexology was implemented for 3 weeks and each session lasted half an hour. In placebo group, only relaxation techniques were implemented for 3 weeks, each session lasted 20-30 minutes. Control group received the routine therapies of breast cancer center. Results: Data were collected by standard questionnaires of EORTIC QLQ-C30.V.3 and EORTIC QLQ-BR23.V.3. The questionnaires were filled before intervention and two weeks after applying study. There was no significant difference in demographic characteristics or quality of life score of three groups, before intervention. Total score of quality of life was higher in interventional group compared to placebo group before and two weeks after intervention (p < 0.001) Results also indicated a significant difference in total score of quality of life between three test, placebo, and control groups after intervention (p < 0.001). A considerable improvement was noticed in the different aspects of quality of life in the test group compared to two other placebo and control groups. Conclusions: Reduction of pain, anxiety, nausea, and other symptoms related to cancer in patients suffering from cancer are assumed as the important cases of nursing cares focus, and precise nursing may diminish these symptoms considerably. Using reflexology in patients suffering from breast cancer may improve the quality of life as an effective method, and can be recommended for use in patients with breast cancer if it is supervised by health system personnel.
Evaluating the prognostic effect of a pain classification system in patients with advanced cancer.
Authors: Arthur Joseph Anthony , Tanco Kimberson Cochien , Haider Ali , Maligi Courtney , Park Minjeong , Liu Diane D , Bruera Eduardo
Published: February 2017

95

Background: The Edmonton Classification System for Cancer Pain (ECS-CP) has been shown to predict pain management complexity based on five features: pain mechanism, incident pain, psychological distress, addictive behavior, and cognitive function. The main objective of our study was to explore the association between increasing sum of negative ECS-CP features and achievement of good pain control at first follow up visit at an outpatient palliative care clinic. Methods: Initial and follow up clinical information of 409 eligible supportive care outpatients such as patient demographics, ECS–CP assessment, morphine equivalent daily dose (MEDD), opioid rotation, Edmonton Symptom Assessment Score (ESAS), and personalized pain goal (PPG) were retrospectively reviewed and analyzed. Results: Between the initial consultation and the first follow up visit, the median MEDD requirement increased from 30mg/day to 45mg/day (p < 0.0001) and median pain intensity improved from 6 to 4 (p < 0.0001). Increasing sum of negative ECS–CP features was associated with higher MEDD at consultation, with an increase from 30mg/day with no negative features to 40mg/day with ≥2 negative features (p = 0.046). There was no significant association between increasing sum of negative ECS-CP features and achievement of pain control at follow up visit (0.991, 95% CI: 0.747 – 1.304, p = 0.948). Conclusions: Increasing sum of negative ECS-CP features was associated with higher MEDD at referral but was not predictive of pain control at the follow up visit when pain was managed by a palliative medicine specialist. Further research is needed to further explore these observations.
Impact of age on sexual preservation after prostate brachytherapy: A prospective evaluation in men without erectile dysfunction.
Authors: Brahmi Tristan , Lapierre Ariane , Samlali Hamza , Selmaji Imad Eddine , Udrescu Corina , Ruffion Alain , Chapet Olivier
Published: February 2017

105

Background: Sexual preservation is an important issue in the treatment of localized prostate cancer. In this study, we evaluate the long-term incidence of erectile dysfunction (ED) after prostate brachytherapy (PBT), in men without ED. Methods: Between 2006 and 2012, prospective data of patients treated with brachytherapy for a low or intermediate-risk prostate cancer (d’Amico classification), were collected. Erectile function (EF) was assessed with IIEF5 score (5-Item Version of the International Index of Erectile Dysfunction) at six weeks and then every year during the follow-up. No ED was defined by an IIEF5 score ≥ 22/25 and a mild ED by a score between 17 and 21. Results: Up to this point, 70 patients, with an initial IIEF5 ≥22, were analyzed with a mean follow-up of 46.5 months. At 6 weeks and 1, 2, 3 and 4 years after brachytherapy, mean IIEF5 scores in all 70 patients were 24.6, 21.3, 19.7, 19.1 and 17.3, respectively. In ≤ 65 years old group, the scores were 24.7, 20.9, 21.3, 21.1, 19.7 and 20, respectively. In > 65 years old group, the scores were 24.6, 21.8, 21.3, 18.1, 18.2 and 14.9, respectively. The evaluation of ED according to age groups is represented in the table. Conclusions: At 4 years of follow-up after brachytherapy, patients 65 years old and younger have an EF preservation rate >80% with 50% of them having no ED. For patients older than 65 years, the rate of EF preservation decreased at 50% after 4 years of follow up with only few of them having no ED. This difference between the 2 groups of age is probably more related to an age effect than a brachytherapy toxicity. At the time of the meeting, more data and results will be available. [Table: see text]
Development and validation of an ADT resistance signature to predict adjuvant hormone treatment failure.
Authors: Karnes Jeffrey , Ashab Hussam Al-Deen , Trock Bruce J. , Ross Ashley , Tsai Harrison , Tosoian Jeffrey J. , Erho Nicholas , Choeurng Voleak , Yousefi Kasra , Haddad Zaid , Abdollah Firas , Klein Eric A. , Nguyen Paul L. , Feng Felix Yi-Chung , Dicker Adam , Den Robert Benjamin , Davicioni Elai , Jenkins Robert B. , Lotan Tamara L. , Schaeffer Edward M.
Published: February 2017

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.
Comparative study of late rectal toxicity in veterans undergoing low-dose rate prostate brachytherapy treated with or without supplemental external beam radiotherapy.
Authors: Serrano Nicholas A , Moghanaki Drew , Asher David , Karlin Jeremy , Schutzer Matthew , Chang Michael G. , Hagan Michael Philip
Published: February 2017

112

Background: Supplemental external beam radiation therapy (sEBRT) is often prescribed in men undergoing low dose rate (LDR) brachytherapy for prostate cancer. A population of patients was analyzed to assess the effect of sEBRT on late rectal toxicity. It was hypothesized that sEBRT+LDR would be associated with a higher risk of late rectal toxicity, compared to LDR brachytherapy alone. Methods: This retrospective cohort study examined LDR brachytherapy patients, treated with or without sEBRT, with a minimum of 5 years follow-up. All were treated at a credentialed Veterans Affairs medical center that enrolled many of these patients on RTOG 0234. Longitudinal assessments were evaluated using the Computerized Patient Record System, and toxicities were coded using the CTCAE v4.0. The Kaplan-Meier method was used for analysis. Results: Median follow-up was 7.5 years for 245 consecutive patients from 2004 and 2007. sEBRT was administered to 33.5%. Follow-up beyond 5 years was available for 89%. Overall rates of grade ≥ 2 and ≥ 3 rectal toxicities were 6.9% and 2.9%, respectively. The risk of grade ≥ 2 rectal toxicity was 2.8-fold higher for patients receiving sEBRT (1.1 - 7.2, 95% CI, p = 0.02). The risk of grade ≥ 3 rectal toxicity was 11.9-fold higher for patients who received sEBRT (1.5 - 97.4, 95% CI, p = 0.003). Six out of 7 patients with a grade ≥ 3 rectal toxicity received sEBRT, including one who required an abdominoperineal resection due to radiation proctopathy. The median post-LDR D90, V150, V200, and R100 values were 103.3%, 59.4%, 30.1%, and 0.5 cc. The minimum R100 associated with a grade ≥ 2 toxicity was 0.2 cc, and the minimum R100 for a grade ≥ 3 toxicity was 0.4 cc. Grade ≥ 2 rectal toxicity was seen in 3% vs 13% of patients who had post-implant dosimetry of R100 < 1 cc vs R100≥ 1 cc, respectively. Conclusions: In a cohort of LDR brachytherapy patients with high rates of follow-up, sEBRT+LDR was associated with significantly higher risk of grade ≥ 2 and ≥ 3 late rectal toxicity. This analysis supports previous findings and maintains concern about the supplemental use of EBRT with LDR brachytherapy while its benefit for tumor control has yet to be prospectively validated.
Prostate brachytherapy as salvage for local failure after external beam radiation.
Authors: Baumann Brian Christopher , Baumann John Charles , Christodouleas John Paul , Soffen Edward M
Published: February 2017

125

Background: Local failure (LF) after external beam radiation (EBRT) for prostate cancer is a serious problem. Most patients receive non-curative androgen deprivation therapy (ADT), but there is a subset with LF who are still potentially curable. There is limited evidence to suggest that prostate brachytherapy (BT) is an effective, potentially curative salvage therapy with acceptable toxicity. We hypothesize that salvage BT following EBRT can achieve high rates of biochemical control with acceptable toxicity. Methods: We analyzed 39 consecutive patients treated from 1998-2013 with salvage BT at 2 centers. All patients had pathologically confirmed LF following previous EBRT without distant mets & a disease-free interval of ≥ 18-24 mo. Salvage BT to the whole prostate was delivered to 29 patients using low-dose rate I-125 or Pd-103 seed implants (median dose 100 Gy with Pd-103) while 10 received HDR BT (median 30 Gy in 6 fractions). Cases were planned as if de novo but to a lower dose. 33 (85%) received neoadjuvant and/or adjuvant ADT as part of their salvage therapy. Biochemical failure (BF) was defined using the Phoenix criteria. Risk factor analysis was conducted to identify characteristics that predict BF after salvage BT. Results: For the 39 patients, median PSA at diagnosis was 8.4, and 21 (54%) had high-risk disease. Median EBRT dose was 70 Gy with 11 patients (28%) receiving ADT. Median PSA nadir following EBRT was 0.8 (range 0 – 2.6). Median time to recurrence was 53 mo (range 18 – 150), and median pre-salvage PSA was 4.8. Median follow-up after salvage BT was 60.1 mo (range 7 – 150). Biochemical failure-free survival, DMFS and OS at 5 & 7 yrs were 76% & 67%; 91% & 85% and 92% & 84%, respectively. On univariate analysis, PSA nadir after EBRT & pre-salvage PSA were significant predictors of BF (p< 0.01 for both). On multivariate analysis, only pre-salvage PSA was a significant independent predictor of BF (p< 0.01). Freedom from late grade 3 GU toxicity at 3 yrs was 83%. There were no late Grade 3 GI toxicities. Conclusions: This is the largest series reporting on salvage prostate brachytherapy plus ADT for local-only failures after EBRT & suggests that salvage BT with ADT offers selected patients prolonged disease-free survival with acceptable toxicity.
Metastasis free survival following salvage radiotherapy versus hormonal therapy alone in patients with biochemical recurrence after radical prostatectomy.
Authors: Kim Jae-Sung , Song Changhoon , Hong Sung Kyu , Byun Seok-Soo , Lee Sang Eun
Published: February 2017

130

Background: To describe metastasis-free survival (MFS) in patients with biochemical recurrence following radical prostatectomy (RP), and to define clinical prognostic factors for metastasis. Methods: From our institutional database, 1,408 patients underwent primary RP between 2005 and 2011. Of these, 267 patients who had biochemical recurrence (two consecutive PSA ≥ 0.2 ng/mL) and had post-biochemical recurrence follow-up greater than 12 months were used as the study cohort. As an initial management for biochemical recurrence, salvage radiotherapy (SRT) combined with or without androgen deprivation therapy (ADT) was administered to 186 patients, while 33 patients received salvage ADT alone. Remaining 48 patients had been observed without any treatments. We estimated MFS using the Kaplan–Meier method, and investigated factors influencing the risk of metastasis using Cox proportional hazards regression. Results: Median follow-up after RP was 6.0 years, and after biochemical recurrence was 4.2 years. At last follow-up, 28 of 267 patients (10.5%) had developed metastasis, while 5-year MFS rate was 88.6%. No one developed metastasis in patients under observation. SRT resulted in an improved 5-year MFS rate (89.3% vs. 76.7%; p =0.022) compared with salvage ADT alone. This inferiority of salvage ADT alone compared with salvage SRT was marginally significant in the multivariate analysis (hazard ratio [HR] 2.24; 95% confidence interval [CI] 0.93–5.36; p = 0.071). Gleason score ≥8 (HR 4.10; 95% CI 1.77–9.51; p = 0.001) and seminal vesicle invasion (HR 2.37; 95% CI 1.06–5.30; p = 0.036) were significantly associated with MFS in the multivariate analysis. Conclusions: In patients undergoing prostatectomy, MFS after biochemical recurrence is variable and is most strongly influenced by Gleason score and seminal vesicle invasion. These parameters serve to stratify patients into different risk groups with respect to metastatic progression. Salvage ADT alone should be used with caution with select patients.
Nature of intrafractional and interfractional prostate motion during stereotactic radiation.
Authors: Perumal Karthikeyan , Potharaju Mahadev
Published: February 2017

152

Background: To characterize the intra-fraction and inter-fraction prostate motion as tracked by the X-ray images of the implanted gold fiducials during stereotactic radiotherapy with CyberKnife. The published data have analysed the linear and angular prostate motion intrafraction and interfraction prostate motion among patients. We sought to quantify the same within each patient. Methods: Twenty Five patients with localized prostate cancer treated with CyberKnife radiosurgery between January 2013 and August 2015 were studied retrospectively. A data set constitutes the deviations derived from X-ray images obtained between two consecutive couch motions. Results: Included in the analysis were 3926 data sets. A total of 210 non-coplanar fields were used per fraction. The mean total treatment time for all fields per fraction was 36.13 minutes. The detected and corrected movements over all were in a range of ± 10.1 mm in linear direction (Right: mean 1.1±0.4 mm; Left: mean 1.0±0.6 mm; Superior: mean 0.7±0.3 mm; Inferior: mean 1.6±0.6 mm; Anterior: mean 1.6±0.7 mm; Posterior: mean 0.5±0.3 mm with maximum (max) movement range of Right max 9.9±6.4 mm, Left max 7.1±3.4 mm, Superior max 8.6±5.4 mm, Inferior max 10.1±8.5 mm, Anterior max 9.2±6.5 mm, Posterior max 8.4±2.9 mm) and angular movements were in a range of ± 6.7 deg in all directions (Right Angle: mean 0.6±0.3 deg; Left Angle: mean 0.6±0.3 deg; Head Up(H-U): mean 1.3±0.6 deg; Head Down(H-D): mean 1.4±0.6 deg; Counter-Clockwise movement (CCW): mean 0.7±0.3 deg; Clockwise movement (CW): mean 0.5±0.3 deg with max rotation range of Right angle max 2.4±2 deg, Left angle max 2.7±2 deg, H-U max 10.2±3.5 deg, H-D max 6.7±4.8 deg, CCW 4±2.9 deg, CW max 2.8±2.4 deg). There was an unpredictable change in prostate motion inter-fraction in each patient. But, a unique observation is that a predictable pattern exists for prostate motion intra-fraction within a patient. Change in the linear or angular prostate motion intra-fraction in any direction is not erratic. Conclusions: The linear and rotational prostate motion intra-fraction in any direction has a predictable pattern and any change is gradual and not erratic. The motion shows secular trend during the course of treatment.
Initial acute toxicity report of post-prostatectomy proton therapy for prostate cancer patients undergoing adjuvant or salvage radiotherapy.
Authors: Deville Curtiland , Both Stefan , Gabriel Peter Edward , Tochner Zelig , Vapiwala Neha
Published: February 2017

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Background: Purpose is to report acute genitourinary (GU) and gastrointestinal (GI) toxicities associated with post-prostatectomy proton beam radiotherapy (PBT). Methods: The first 50 patients undergoing post-prostatectomy PBT on a prospective, IRB-approved, institutional protocol for image-guided radiotherapy were assessed. Patients received a median dose of 70.2 Gy relative biological effectiveness (RBE) in 1.8 GyRBE daily fractions using traditional, laterally-opposed beams to the prostate bed only, as defined by RTOG consensus guidelines, passive scattering or pencil beam scanning technique, and 100 cc water-filled endorectal balloon, from 10/2011 to 7/2015. One patient received concurrent androgen deprivation. Acute toxicity was scored by CTCAE v4.0. Results: The Table summarizes the clinical characteristics. Median age was 62 years and median months from surgery were 23. Passive scattering was used for 16% of cases and pencil beam scanning for 84%. A GyRBE dose of 70.2 was used for 88% of cases, 66.6 for one case, and 75.6 for the remaining 10% with gross local recurrence. All patients completed treatment and there were no acute grade 3 or greater GU or GI toxicities. Regarding GU, most reported grade 1 (78%) toxicity, 18% grade 2, and 4% none (grade 0). Regarding GI, most patients (54%) reported no toxicity (grade 0), 36% grade 1, and 10% grade 2. Conclusions: Our results report for the first time to our knowledge, the clinical feasibility and favorable GU and GI toxicity profile of post-prostatectomy PBT. Future studies with larger patient numbers are planned to further validate our preliminary findings. [Table: see text]
Genomic profiling of metastatic prostate cancer through analysis of circulating tumor DNA (ctDNA).
Authors: Gourdin Theodore Stewart , Lilly Michael B.
Published: February 2017

174

Background: We have performed genomic analysis of circulating tumor DNA (ctDNA) to identify actionable anomalies in 55 patients with metastatic prostate cancer. Methods: A publically-accessible assay (Guardant Health) was used to analyze 68 known cancer genes for anomalies (missense mutations, amplifications) by a digital PCR technique. The racial profile included Caucasian (27), African-American (27), Asian (1) patients. Most subjects (82%) had CRPC and had been treated with multiple forms of androgen deprivation and chemotherapy. Results: Genomic anomalies were found in 52/55 subjects. 127 missense mutations and 78 amplifications were identified in 35 genes. Missense mutations in each gene were overwhelmingly single (98/127). African-American patients each had an average of 3.9 genomic anomalies, whereas Caucasian patients each had an average of 2.7 anomalies (p = NS). Anomalies most commonly involved TP53 (43.2%), AR (43.4%), MYC (21.8%), BRAF (21.8%), and DNA repair genes (BRCA1, BRCA2, or ATM; 16.4%). Taxane-based chemotherapy was given to 24/55 subjects with mCRPC. These 24 patients were grouped by TP53 status (WT, n = 13; MUT, n = 11) and progression-free survival (PFS) was determined by PCWG2 criteria (PSA or imaging). Data for PFS vs time were presented as Kaplan-Meier plots and compared by the log rank test. Median PFS during taxane chemotherapy was approximately twice as long for subjects with MUT TP53, compared with that of subjects with WT TP53 (p = 0.013; HR = 2.5 [1.1-6.0]). Conclusions: 1. Genomic analysis on ctDNA from patients with metastatic prostate cancer is feasible and identifies anomalies in most patients. 2. Within the limits of the assay, ctDNA analysis provides similar findings to those identified by analysis of FFPE tissue (Robinson et al., Cell, 2015). 3. ctDNA analysis can identify missense mutations that are associated with an improved PFS from taxane-based chemotherapy. ctDNA analysis may help clinicians to judge the potential benefits of chemotherapy in subjects with mCRPC.
Phase Ib trial of cabazitaxel and tasquinimod in men with heavily pretreated metastatic castration resistant prostate cancer (mCRPC): The CATCH trial.
Authors: Armstrong Andrew J. , Healy Patrick , Szmulewitz Russell Zelig , Winters Carolyn , Harrison Michael Roger , Martinez Elia , Mundy Kelly , Halabi Susan , George Daniel J.
Published: February 2017

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Background: Cabazitaxel resistance develops within a few months of treatment initiation in most men with mCRPC in post-docetaxel, and thus combination therapy with other active agents may improve outcomes. Tasquinimod is an oral immunomodulatory agent with anti-angiogenic and anti-tumor in preclinical models of PC and clinical activity in phase II and III trials. Methods: We conducted a phase I dose escalation trial of cabazitaxel plus tasquinimod in men with mCRPC. Cabazitaxel was dosed at 25 mg/m2 every 3 weeks with low dose prednisone and PEG-filgrastim support, and tasquinimod dose levels included 0.25, 0.5, and 1.0 mg, using a 3 week within-patient dose escalation for dose levels 2 and 3, starting all patients at 0.25 mg once daily. The primary objective was to define the recommended phase II dose (RP2D) based on safety and dose limiting toxicity. Preliminary efficacy (PSA decline, PFS) and pharmacokinetic interactions were key secondary objectives. Results: We enrolled 25 men with mCRPC who had failed docetaxel across 3 dose levels. Median PSA at entry was 220 ng/dl. The RP2D was 0.5 mg tasquinimod based on excess DLTs (2 of 3 men) observed at dose level 3 (1.0 mg) including grade 3 sensory neuropathy and grade 3 atrial fibrillation). Dose level 2 was expanded to 14 men, where 3 DLTs were observed: grade 3 fatigue, grade 4 febrile neutropenia, and grade 3 liver function test abnormalities. The proportion of men with a > 30% PSA decline was 63% (95% CI: 41%, 81%). The median composite PFS was 8.5 months (95% CI 4.2-16.4 months) based on 12 PFS events. The median number of cycles of cabazitaxel was 6 (range 1-13), with 6 men receiving > 10 cycles. Best overall RECIST responses (CR+PR) were observed in 3 men (12%), stable disease in 12 (48%). No unexpected adverse events were observed and no pharmacokinetic interactions were observed. Conclusions: The RP2D was cabazitaxel 25 mg/m2 with prednisone and PEG-filgrastim every 3 weeks with tasquinimod 0.25 mg once daily for 3 weeks followed by 0.5 mg. Preliminary evidence of efficacy over cabazitaxel alone is based on observed PSA response and PFS data, and a substantial number of men were progression free beyond 10 cycles with good tolerability. Clinical trial information: NCT01513733.
Combined Akt and MEK pathway blockade in pre-clinical models of enzalutamide-resistant prostate cancer.
Authors: Toren Paul , Kim Soojin , Fazli Ladan , Davies Barry , Gleave Martin , Zoubeidi Amina
Published: February 2017

192

Background: Despite recent advances with newer androgen receptor(AR) pathway inhibitors, treatment resistance in castrate resistant prostate cancer continues to remain a clinical problem. Co-targeting approaches are of significant interest to slow the progression of disease and delay the onset of resistance. With both Akt and MEK pathways becoming activated as prostate cancer develops resistance to AR-targeted therapy, this study explores co-targeting these pathways in AR positive prostate cancer models. Methods: Using in vitro models of prostate cancer progression from androgen dependent to castrate resistant and ENZ-resistant disease, we evaluated the effect of Akt and/or MEK inhibition with AZD5363 and PD0325901, respectively, on cell proliferation, apoptosis and downstream signalling pathways. For in vivo models, we tested the combination of Akt and MEK inhibition castrated mice bearing MR49F and 22RV1 cells which are resistant to ENZ. Results: Inhibition of Akt reduced S6 phosphorylation, inhibited growth and induced apoptosis in LNCaP-derived cells; the addition of a MEK inhibitor increased apoptosis and cell cycle arrest, but did not further decrease cell proliferation. In contrast, PTEN wild-type 22RV1 cells demonstrated a greater sensitivity to MEK inhibition, but were generally insensitive to Akt inhibition. In vivo, combination of Akt and MEK inhibition resulted in more consistent tumour growth inhibition of MR49F xenografts and longer disease specific survival than Akt inhibitor monotherapy, with induction of pERK staining being evident in some AZD5363 monotherapy treated tumours. Conversely, 22RV1 xenografts had greater resistance to Akt inhibition and greater sensitivity to MEK inhibition. Conclusions: Our data suggest that combination of Akt and MEK inhibition may improve prostate cancer control in ENZ-resistant prostate cancer. Further, with the major effect in both MR49F and 22RV1 xenografts attributable to one inhibitor, our results also suggest the importance of characterizing the dominant oncogenic pathway in each patient’s tumour in order to select optimal therapy.