bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase Ib study of pembrolizumab in combination with bevacizumab for the treatment of metastatic renal cell carcinoma: Big Ten Cancer Research Consortium BTCRC-GU14-003.
Authors: Dudek Arkadiusz Z. , Sica R. Alejandro , Sidani Amer , Jha Gautam Gopalji , Xie Hui , Alva Ajjai Shivaram , Stein Mark N. , Singer Eric A.
Published: February 2017

559

Background: Renal cell carcinoma (RCC) tumor vasculature is abnormal and does not provide nutritive blood flow, which results in regions of hypoxia. This hypoxia contributes to the immune tolerance of tumor cells by impeding the homing of cytotoxic T cells into tumor parenchyma. In addition, tumor angiogenesis enhances activity of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that suppress innate anti-cancer immunity. It has been demonstrated in preclinical models that antiangiogenic therapy decreased the number of MDSCs and changed polarization of TAMs from an immunosuppressive (M2-like) to an immunostimulatory (M1-like) phenotype. We hypothesized that therapy with bevacizumab will normalize the tumor vasculature, promote M1-like phenotype of TAMs, and thus potentiate the immunotherapeutic activity of pembrolizumab. As a prerequisite to testing this hypothesis, the objective of this study was to establish the safe dose of bevacizumab when used in combination with pembrolizumab. Methods: Our subject population included males and females (age > 18 y) with metastatic clear cell RCC after failure of at least one systemic therapy. In this Phase Ib dose escalation study, pembrolizumab (200 mg fixed dose every 3 weeks) was given in combination with bevacizumab (either at 10 mg/kg or 15 mg/kg every 3 weeks). The primary endpoint was to establish the maximum safe dose. Results: 12 subjects have been enrolled: 10 males (ages 33-68 y, mean: 52.7, median: 54.5) and 2 females (ages 61 and 62 y). To date 3 patients have received 1 cycle; 2 patients have received 2, 3, and 4 cycles each; and there are single patients who have received 5, 6, and 7 cycles each. No dose-limiting toxicity or serious adverse events related to the study drug have been reported. There were no grade 3 or 4 drug-related toxicities noted, and the most common grade 1 and 2 toxicities were diarrhea, fatigue, fever, hypertension, nausea, rash, and rigors. Conclusions: The 200 mg fixed dose of pembrolizumab and 15 mg/kg dose of bevacizumab, both given every 3 weeks, was determined to be safe and recommended for a multicenter Phase 2 study that is ongoing. Clinical trial information: NCT02348008.
The role of metastasectomy in patients with renal cell carcinoma with sarcomatoid dedifferentiation: A matched controlled analysis.
Authors: Thomas Arun Z. , Adibi Mehrad , Slack Rebecca , Borregales Leonardo Daniel , Merrill Megan M. , Tamboli Pheroze , Sircar Kanishka , Jonasch Eric , Tannir Nizar M. , Matin Surena F. , Wood Christopher G. , Karam Jose A.
Published: February 2017

565

Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive tumor generally associated with a poor clinical course. Management of metastatic sRCC remains a therapeutic challenge with no standard treatment strategies. Our objective was to evaluate whether metastasectomy has any survival benefit in patients with synchronous or asynchronous metastatic sRCC treated with radical nephrectomy (RN). Methods: From an institutional database of 273 patients with sRCC treated with nephrectomy, we matched 80 patients with synchronous and asynchronous metastasis for age, ECOG performance status, histology and nodal status. Matched pairs were then retained only if patients who did not undergo metastasectomy were comparably alive at the time of metastasectomy in matched surgical patients to reduce the bias in survival outcomes. Overall survival (OS) from nephrectomy was studied using univariable and multivariable proportional hazards regression. Results: Median OS was 8.3 months (95%CI 6.5-10.5 months) and 18.5 months (95%CI 11.5-42.9 months) for patients with synchronous and asynchronous metastases, respectively. OS for patients undergoing metastasectomy for synchronous metastasis was comparable to non-surgical patients (8.4 and 8.0 months, respectively, p=0.35). Similarly, within the asynchronous cohort, median OS was 36.2 months (95%CI 7.6-Not Reached) in the metastasectomy group and 13.7 months (95%CI 8.8-41.6) in the non-metastasectomy group (p=0.29). On multivariable analysis, positive lymph node (LN) at nephrectomy was associated with increased risk of death in both synchronous and asynchronous patients groups; (HR=2.1 [95%CI 1.1-4.0] p=0.03) and (HR=3.3 [95%CI 1.2-9.2] p=0.02), respectively. Conclusions: Metastasectomy in patients with synchronous or asynchronous metastases after nephrectomy does not appear to confer significant survival benefit in patients with sRCC, particularly in patients with pathological LN positive disease at nephrectomy.
PD-1 expression and its impact on survival in localized clear cell renal cell carcinoma.
Authors: Sekar Rishi Robert , DiMarco Michelle A. , Patil Dattatraya , Osunkoya Adeboye O. , Pollack Brian P. , Sica Gabriel , Master Viraj A.
Published: February 2017

568

Background: Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have been shown to have activity in advanced renal cell carcinoma (RCC), prompting research into PD-1 as a potential biomarker. In this study, we evaluate tumor PD-1 expression and its prognostic value in patients with localized clear cell RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC (T1-T3) with >4 years of follow-up were queried from our nephrectomy database. Tissue blocks with tumor and adjacent benign renal parenchyma were selected for analysis. Immunohistochemical staining for PD-1 was performed on tumor specimens using anti-PD-1 clone NAT105 (Abcam). Focusing on immune cells, PD-1 positivity was defined as >1% expression and graded in 10% increments. The relationship between PD-1 positivity, FNG, and TNM stage was evaluated using Pearson’s chi-square test. The impact of PD-1 positivity on overall and recurrence-free survival was evaluated using the Kaplan-Meir method. Results: Fifty-three patients were included in the study. The distribution of PD-1 expression in 10% increments can be seen in Table. No statistically significant correlation was found between PD-1 positivity, TNM stage and FNG (chi-square test; p=0.15, p=0.62, respectively). No statistically significant differences in overall or recurrence-free survival were found between positive and negative PD-1 expression groups (log-rank; p=0.32, p=0.43, respectively). Conclusions: Our data show that primary tumor PD-1 expression varies widely in patients with clear cell RCC and that PD-1 positivity does not correlate with commonly reported histopathological features such as TNM stage and FNG. Further, PD-1 positivity does not have a significant impact on overall and recurrence-free survival. These findings contrast with previous studies of PD-1 expression in RCC, suggesting that further research into the role of PD-1 in tumor progression as well as methods of case/tissue block selection and PD-1 quantification is needed. [Table: see text]
Pilot study of dovitinib in patients with VHL disease.
Authors: Pilie Patrick Glen , Matin Surena F. , Woodson Ashley Henriksen , Marcott Valerie D. , Bird Shelly , Slack Rebecca , Fuller Greg , McCutcheon Ian E. , Jonasch Eric
Published: February 2017

587

Background: Von Hippel-Lindau (VHL) is an autosomal dominant inherited disease occurring in 1 in 35,000 births. Individuals with germline mutations in the VHL gene may phenotypically express a variety of lesions including hemangioblastomas (HBs), pancreatic cysts, renal cysts, and renal cell carcinomas (RCC). Previous studies have shown differentially increased FGFR3 levels in HBs compared to RCC. In this pilot trial, we investigated the safety and efficacy profile of TKI 258 (dovitinib), a tyrosine kinase inhibitor of VEGF and FGF receptors, in VHL related lesions, focusing on HBs. Methods: A MDACC IRB-approved protocol planned to enroll 25 subjects who had genetically confirmed VHL disease or clinical diagnosis of VHL, and measurable HBs with no immediate risk of needing intervention. Dovitinib 500mg/day was given in a 4 week cycle on 5 day on/2 day off schedule. In the absence of adverse events (AE), treatment lasted 6 cycles or until disease progression. Evaluation of response to treatment was done every 8 weeks including imaging, laboratory, and clinical evaluation. The trial design used a continuous Bayesian stopping rule based on toxicities that resulted in discontinuation of dovitinib and another for lack of efficacy. Signed informed consent completed on all patients enrolled. Results: Trial stopped after six patients enrolled due to toxicity stopping rule. Patients’ ages ranged 18-61 with 5/6 being male. With regards to safety, 6/6 subjects had at least one AE with the most common AEs being rash, diarrhea, and fatigue including a grade 3 AE (severe rash) in one patient. 1/6 was stopped due to noncompliance, 1/6 stopped due to progression, 3/6 stopped due to side effects despite dose reduction, and 1/6 completed full six cycles at full dose. Best response in 6/6 subjects was stable disease (SD) in HBs. Conclusions: This pilot study of dovitinib in patients with VHL disease with measureable HBs did not show a favorable safety or efficacy profile for this dose and schedule. Half of the patients discontinued the drug due to AEs before study completion, and the best achieved response was SD. Further investigation into alternative scheduling and other FGFR inhibitors in the treatment of HBs is warranted given the strong pre-clinical data. Clinical trial information: NCT01266070.
The relationship between preoperative c-reactive protein and Fuhrman nuclear grade in stage T1 renal cell carcinoma.
Authors: Sekar Rishi Robert , Patil Dattatraya , Pearl Jeff , Baum Yoram , Alemozaffar Mehrdad , Filson Christopher Paul , Ogan Kenneth , Master Viraj A.
Published: February 2017

593

Background: In an era of active surveillance for small renal masses (SRMs), non-invasive predictors of tumor aggressiveness may be helpful in identifying high-risk patients for surgical intervention. In this study, we evaluate the predictive value of preoperative C-reactive protein (CRP) on Furhman Nuclear Grade (FNG) in patients with stage T1 renal cell carcinoma (RCC). Methods: Patients who underwent nephrectomy for stage T1 RCC with documented preoperative CRP within 15 days of surgery were included in the study. Surgical pathology reports were used to determine TNM stage and FNG. Receiver operating characteristic (ROC) analysis, sensitivity-specificity analysis, and Youden index were used to determine the optimal threshold of preoperative CRP in predicting FNG 4 disease versus FNG 1-3 disease. Logistic regression analysis was then performed to assess the significance and independence of preoperative CRP in predicting FNG 4 disease. Results: 351 patients were included in the study. On ROC analysis, area under the curve (AUC) was 0.7576. The optimal threshold of preoperative CRP was determined to be 4.8 mg/dL. On univariate and multivariate analysis, CRP ≥ 4.8 mg/dL was found to be a significant and independent predictor of FNG 4 disease (log-rank, p=0.014, p=0.006, respectively). Conclusions: Our data show that preoperative CRP ≥ 4.8 mg/dL is a significant and independent predictor of FNG 4 disease in patients with stage T1 RCC. These findings suggest that a standardized and cost-effective preoperative laboratory value can provide crucial prognostic information in patients undergoing active surveillance for SRMs, allowing for improved patient selection for definitive surgical therapy. [Table: see text]
Long-term response to sunitinib treatment in metastatic renal cell carcinoma (mRCC).
Authors: Tannir Nizar M. , Figlin Robert A. , Gore Martin Eric , Michaelson Dror , Motzer Robert J. , Porta Camillo , Rini Brian I. , Hoang Caroline J. , Lin Xun , Escudier Bernard
Published: February 2017

598

Background: A subset of patients (pts) with mRCC treated with sunitinib achieves a long-term response. This study aimed to characterize the duration of treatment and clinical outcomes of pts with mRCC who were long-term responders (LTRs), defined as pts who had progression-free survival (PFS) > 2 years, while on sunitinib therapy. Methods: A retrospective analysis of data from 5714 pts with mRCC treated with sunitinib in 8 phase II or III clinical trials and pts treated in the expanded access program (EAP). Data on treatment duration and response to treatment were compared between LTRs and pts who had PFS ≤ 2 years (others). Results: A total of 529 (9.3%) pts achieved a long-term response, 5162 (90.3%) achieved other response, and data were missing for 23 (0.4%) pts. Overall, 309 (5.4%) pts achieved PFS between >2 and ≤3 years, 125 (2.2%) pts achieved PFS between >3 and ≤4 years, 62 (1.1%) pts achieved PFS between >4 and ≤5 years, and 33 (0.6%) pts achieved PFS between >5 and ≤6 years. The median (range) duration of sunitinib treatment was 36.7 (23.4–71.7) months for LTRs versus 6.5 (0–69.8) months for others. Response rates comparing LTRs versus others are presented in Table. Conclusions: With over 500 pts with mRCC achieving PFS >2 years and 33 achieving PFS >5 years, this analysis of sunitinib LTRs is the largest published to date. Additional analyses are being conducted to describe the clinical characteristics of these LTRs and identify risk factors that may predict long-term response. [Table: see text]
Initial compared to deferred cytoreductive nephrectomy for metastatic kidney cancer and its association with improved survival in the targeted therapy era.
Authors: Macleod Liam Connor , Tykodi Scott S. , Holt Sarah , Gore John L.
Published: February 2017

607

Background: Since 2005 seven new agents were approved for metastatic renal cell carcinoma (mRCC), demarcating a transition from the cytokine to the targeted therapy era. Trials demonstrated a survival benefit for upfront cytoreductive nephrectomy (CN) pre-2005. However, upfront versus delayed CN relative to targeted therapy has not been reported in the trial arena. We hypothesized that upfront CN confers a survival benefit in the targeted therapy era. We analyze survival in a population based cohort exposed to targeted therapies with upfront CN compared to deferred CN. Methods: Patients from SEER registries (2005-2011) with mRCC were categorized into: 1.) CN followed by targeted therapy or 2). initial targeted therapy. Additional exclusions were age < 66, due to chance of uncaptured non-Medicare care, competing non-renal stage IV cancer and non-clear cell histology. Targeted therapy was identified from Medicare Part D files (bevacizumab, sunitinib, sorafenib, axitinib, pazopanib, temsirolmus, everolimus) and duration of use. Clinical data, including co-morbidities, were obtained from Medicare inpatient and outpatient files, and cancer data from Medicare-linked SEER files. Unadjusted and multivariable Cox proportional hazards regression determined association between survival in the two groups. Propensity matching with bootstrapping was performed to control for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases screened, 491 met the inclusion criteria. Median survival in the initial CN group (N = 194) was 20 months (IQR 12-32) compared to 14 months (IQR 6-27) in the initial targeted therapy group (N = 297, p < 0.01). On multivariable analysis upfront CN was associated with improved survival (HR 0.57 95% CI 0.44, 0.74). On propensity matched analysis the survival advantage (average treatment effect on the treated, ATT) for upfront CN was 7.4 months (95% CI 3.86, 11.21). Conclusions: This study population closely resembles the treatment groups in ongoing randomized trials on the surgical management of mRCC in the targeted therapy era and demonstrates a survival advantage for upfront CN.
Trends of metastasectomy for metastatic renal cell carcinoma and their impact on overall survival.
Authors: Meyer Christian P , Sun Maxine , de Velasco Guillermo , Trinh Quoc-Dien , Choueiri Toni K.
Published: February 2017

620

Background: The treatment of metastatic renal cell carcinoma (mRCC) has profoundly changed over the last decade. There is little comprehensive evidence evaluating the role of metastasectomy (MSx) in in this context. We assessed trends and predictors of MSx and their impact on overall survival in a large national cohort. Methods: The National Cancer Data Base from 1998-2012 was queried to identify 25,455 mRCC patients with 5,315 undergoing MSx. Covariates included the application of targeted chemotherapy (CTX) and immunotherapy (ITX). Baseline descriptive and multivariable logistic regression analyzes for prediction of MSx were conducted. Trends for chemo- (CTX) and immunotherapy (ITX) as well as MSx were assessed using the annual percent change linear regression technique (EAPC). Kaplan-Meier curves and adjusted Cox-proportional hazard models assessed the impact of MSx on overall survival. Results: Compared to controls, MSx patients were significantly younger (p<0.001), had a lower CCI (p=0.03), more often private insurance (p=0.04) and a higher income (p<0.001). They were more often treated at an academic center (p<0.001), but less often received ITX/CTX (both p<0.001). The rates of MSx increased significantly over the years (9.9-24.5%, EAPC 4.52, p<0.001) while CTX (EAPC 3.08, p<0.001) increased and ITX decreased (EAPC -12.9, p<0.001). Diagnosis after 2006 (OR 1.21, 95%CI 1.02-1.23) and private insurance (OR 1.43, 95% CI 1.14-1.79) were positive predictors of MSx, whereas increasing age (OR0.98, 95%CI 0.98-0.99), black race (OR 0.73, 95%CI 0.63-0.84), ITX (OR 0.8, 95%CI 0.68-0.94) and CTX (OR 0.75, 95% 0.69-0.82) were negatively associated with MSx. The combined treatment with MSx conferred a survival benefit compared to no MSx (HR 0.75, 95%CI 0.72-0.78) and CTX alone (HR 0.82, 95%CI 0.74-0.90). Conclusions: The addition of MSx to CTX conferred a survival benefit in our study despite lower usage of MSx after CTX. This suggests a potential underutilization, which might be a consequence of underlying health care access disparities as implied by lower odds of receiving MSx in blacks and higher odds in privately insured patients.
Differential side effects profile in mCRPC patients treated with abiraterone or enzalutamide: A meta-analysis of randomized controlled trials.
Authors: Moreira Raphael Brandao , Debiasi Marcio , Maluf Fernando C. , Bellmunt Joaquim , Fay Andre Poisl , Choueiri Toni K. , Schutz Fabio Augusto Barros
Published: February 2017

73

Background: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the risk of adverse events associated with both drugs. Methods: We performed a literature search on MEDLINE for studies reported from January 1966 to July 31, 2015. Abstracts presented at ASCO meetings from 2004 to 2015 were selected manually. Phase III RCT were included in analysis. We assessed the risk of adverse events reported in RCT by performing two meta-analysis: abiraterone-prednisone vs. placebo-prednisone (2,283 pts) and enzalutamide vs. placebo (2,914 pts). Summary of incidence, relative-risks (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: Overall, enzalutamide was not associated with all-grade (RR 1.06 - 95% CI 0.67-1.65) or grade ≥3 (RR 0.81 - 95% CI 0.28-2.33) cardiovascular events, but was associated with increased risk of all-grade fatigue (RR 1.29 - 95% CI 1.15-1.44). On the other hand, abiraterone was associated with increased risk of all-grade (RR 1.28 - 95% CI 1.06-1.55) and grade ≥3 (RR 1.76 - 95% CI 1.12-2.75) cardiovascular events, but was not associated with all-grade (RR 0.85 - 95% CI 0.58-1.23) or grade ≥3 (RR 1.07 - 95% CI 0.97-1.19) fatigue. No evidence of publication bias was observed. Conclusions: In this meta-analysis, abiraterone was associated with an increased risk of cardiovascular events, while enzalutamide was associated with an increased risk of fatigue.
Increased cholesterol synthesis via squalene monooxygenase to predict lethal prostate cancer.
Authors: Stopsack Konrad Hermann , Gerke Travis , Cerhan James Robert , Mucci Lorelei A. , Rider Jennifer R.
Published: February 2017

77

Background: Prostate cancer cells rely on cholesterol for proliferation and androgen production. We recently demonstrated that increased expression of the second key enzyme of cholesterol synthesis, squalene monooxygenase (SQLE), is associated with higher prostate cancer-specific mortality (PCSM). We here validate findings in two additional prospective studies and investigate putative mechanisms. Methods: We analyzed the prospective prostatectomy cohorts within the Health Professionals Follow-up Study (HPFS) and the Physicians’ Health Study (PHS) as well as initially expectantly managed patients in the Swedish Watchful Waiting Study (SWWS). 258 lethal cancer cases and 469 patients who survived > 8 years without metastases were included. SQLE mRNA was measured in tumor specimens at diagnosis of all patients and in benign prostate tissue of 197 patients. Markers of tumor angiogenesis were assessed via immunohistochemistry in 169 HPFS patients. We estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. Results: Higher SQLE expression was confirmed to be predictive of higher PCSM in the validation prostatectomy cohort PHS. Combining the two prostatectomy cohorts, men with high SQLE expression ( > 1 standard deviation above the mean) were 6.7 times (95% CI, 2.9 to 15.8; p < 0.001) more likely to die from their cancer compared to men with the mean level of SQLE expression. A 10% higher ratio of SQLE mRNA expression in tumor vs. benign prostate tissue of the same patient was predictive of 42% higher PCSM (95% CI, 15% to 74%). Higher SQLE expression was strongly associated with increased angiogenesis markers (all p ≤ 0.001). This increased risk associated with high SQLE expression was not modified by statin use (p ≥ 0.52). In initially untreated patients in SWWS, a more modest association of tumor SQLE expression with PCSM was observed (p = 0.047). Conclusions: SQLE, the second rate-limiting enzyme of cholesterol synthesis, is associated with prostate cancer progression. Its expression at cancer diagnosis is predictive of lethal disease both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.
Predicting return of erectile function following external beam radiotherapy or brachytherapy for prostate cancer using EPIC-CP.
Authors: Mihalcik Stephen A. , Chipman Jonathan , Sanda Martin G. , Kaplan Irving D. , Crociani Catrina , Chang Peter ,   PROST-QA Consortium
Published: February 2017

87

Background: EPIC-CP (Expanded Prostate Cancer Index Composite for Clinical Practice) is a one page, 16-item questionnaire designed and validated to measure patient-reported health related quality of life in prostate cancer (PC) patients at the point of care in the clinical setting. We previously developed and externally validated models predictive of intact sexual function (i.e. achieving an erection firm enough for intercourse) at two years following external beam radiation (EBRT) or brachytherapy (BT) using EPIC-26, the parent tool from which EPIC-CP was derived. We aimed to enable the use of these models in clinical practice by recalibrating them for use with EPIC-CP. Methods: Using a previously described multicenter longitudinal cohort (PROST-QA), we identified 217 men treated with EBRT and 230 with BT with complete sexual domain and model covariate information. We used the established covariates predictive of functional erections in the EPIC-26-based models (baseline sexual score, neoadjuvant hormonal therapy, and baseline PSA for EBRT, and baseline sexual score, age, race, and BMI for BT) to recalibrate the multivariable logistic regression models for use with EPIC-CP. We examined Pearson residuals to determine goodness of fit and compared the individual predictions based on the revised models with those generated by the EPIC-26-based models. Results: The recalibrated EPIC-CP-based models demonstrated excellent discrimination (AUC 0.81 for EBRT, AUC 0.87 for BT). Odds ratio estimates for the EPIC-CP models changed by no more than 0.2 from their EPIC-26 counterparts, and remained statistically significant. EPIC-CP and EPIC-26-based predictions had good concordance: the mean ± SD difference in predicted probability between EPIC-26 and EPIC-CP models was 0.0 ± 0.08 in each treatment group. Predicted probabilities were within 15.4% and 15.8% for 95% of the subjects treated with EBRT and BT, respectively. Conclusions: EPIC-CP-based nomograms predicting erectile function two years after EBRT or BT are in good agreement with established EPIC-26-based tools and offer an easily applied and accurate prediction regarding a common and impactful side effect of PC treatment.
Partner’s survivorship care needs: Multivariable analysis in head and neck cancer patients.
Authors: Giuliani Meredith Elana , McQuestion Maurene , Sampson Lorna , Le Lisa W , Jones Jennifer M. , Cheng Terry , Waldron John N. , Ringash Jolie
Published: February 2017

120

Background: The purpose of this study was to determine the number and predictors of head and neck cancer (HNC) survivors’ partners unmet needs and how they correspond to the unmet needs of the survivor. Methods: This study accrued consenting partners from among 158 patients with HNC who had completed a onetime survey including demographic information and the Cancer Survivors’ Unmet Needs Measure (CaSUN) between January 2013 and May 2014. Patients’ caregivers were invited to complete the Cancer Survivors’ Partners Unmet Needs Survey (CaSPUN). The mean (± standard deviation) number and proportion of unmet needs on the CaSPUN was calculated. Multivariable analyses (MVA) were performed to determine factors associated with greater unmet needs using linear regression. Kappa co-efficient was calculated to examine the agreement between the unmet needs of patients and their partners on 22 corresponding items. Results: The CaSPUN survey was completed by 44 partners of head and neck cancer survivors. At least one unmet need was reported by 29 partners and 4 had a very high number of needs between 31 and 35. The most common unmet needs were “I need help to manage my concerns about the cancer coming back” (41%), “I need more accessible hospital parking” (34%), “ I need help to cope with others not acknowledging the impact of having a partner experience cancer has had on my own life” (30%), “ I need help dealing with changes that cancer has caused in my partner” (27%) and “I need to know all my partners doctors talk to each other to coordinate my partner’s care” (27%). Of the 5 most common items, 3 were in the Relationships domain. On MVA increasing number of unmet needs in patients was significantly associated with increased unmet needs in their partners (p < 0.01). Of the 22 paired items there was fair agreement in 12 items, moderate agreement in 8 items and good agreement in 2 items between patients and partners. Conclusions: A significant proportion of partners of cancer patients experience unmet needs which may differ from those of the patient themselves. Survivorship program should consider independent needs assessment and program development for partners.
Financial and work related impact of cancer in young adult (YA) survivors.
Authors: Baker Kevin Scott , Ambrose Kelly , Arvey Sarah R. , Casillas Jacqueline N. , Ganz Patricia A. , Jacobs Linda A. , McCabe Mary S. , Overholser Linda , Partridge Ann H. , Rajotte Emily Jo , Risendal Betsy C , Rosenstein Donald , Syrjala Karen
Published: February 2017

15

Background: YA survivors face challenges unique from those of survivors of childhood cancer or of older adults. The potential impact of cancer or its treatment upon employment and finances for YA survivors is unknown. Methods: Eligibility included diagnosis of malignancy between ages 18-39, 1-5 years from diagnosis and > 1 year from therapy completion. Participants (see Table) were randomly selected from tumor registries of 7 academic institutions; 875 (41% of attempted contacts) enrolled and completed online patient reported outcomes survey related to the effects of cancer/treatment on employment, finances, and cancer-related distress. Results: Overall 84% were employed sometime between cancer diagnosis and study enrollment. Of those, 76% took paid time off (40% < 2 mo, 29% 2-5 mo, 31% > 6 mo). Unpaid time off was required by 39% (37% < 2 mo, 25% 2-5 mo, 38% > 6 mo). Other impairments included inability to carry out physical (59%) or mental (55%) tasks required for their job, being less productive (67%), and not pursuing an advancement/promotion (21%). Financial impacts were substantial: 61% worried about medical bills, 31% went into debt related to their cancer/treatment. Of those incurring debt, most (53%) reported this amount to be < $10,000, 29% $10,000-$24,999, and 18% > $25,000; 13 (4.8%) filed for bankruptcy. Chi squares comparing those receiving extensive treatment vs. surgery only indicated greater likelihood of financial debt (10.6, P=.001) and residual distress (13.9, P < .001) if treated with more than surgery. Conclusions: Most YA survivors experience a significant negative impact on employment and finances related to their cancer and treatment, which occurs at a critical time in their careers and at a life phase inherently more financially unstable. Longitudinal follow-up is required to better quantify the long-term burden on work and finances from cancer diagnosed in young adulthood. [Table: see text]
Adolescent and young adult (AYA) survivors of childhood cancers: A challenge in after completion of therapy (ACT) clinic in resource-constrained country.
Authors: Kurkure Purna Arun , Panda Saroj Prasad , Prasad Maya , Goswami Savita
Published: February 2017

19

Background: To assess the evaluation of late effects in childhood cancer survivors who have transitioned to AYA age group on longitudinal follow up in After Completion of Therapy (ACT) clinic at Tata Memorial Hospital, Mumbai. Methods: ACT clinic database was analyzed for childhood cancer survivors who have attained age 15-30 yrs at last follow up in the clinic for demographics, grade of late effects &pattern of follow up. Results: Of 1720 childhood cancer Survivors ( > , 2 yrs off therapy & disease free) registered in ACT clinic from Feb 91-Feb15, 976(56.7%) are in AYA group, M.F = 707/269 (2.6:1), Hematolymphoid : Solid tumours = 543/433 (1.3:1), Mumbai based: Non Mumbai = 306/670 (1:2.2).Median age at diagnosis 8 yrs, current median age 20 yrs, median duration of ACT clinic follow up is 6 yrs. At registration 448 (47%) had no late effects. 230(24%) had grade I, 81(8.4%) grade II 195 (20%) had grade III. Only 9(1%) had grade IV late effects which increased to 53 (6%) at last follow up due to recurrence & second neoplasia. Only 29(3%) were at low risk of developing potential late effects. 466(48.5%) were in intermediate risk & 48.5% (466) fell in high risk category requiring at least annual follow up. 72% of survivors registered in ACT clinic from 1991-2001 had stopped follow up as compared to 36% registered in subsequent decade (p < 0.01). Conclusions: AYA survivors of childhood cancers form major (56.7%) group in Long Term Follow up clinic. The increasing incidence of life threatening late effects on longitudinal follow up combined with statistically significant increasing trend of stopping follow up over period of time since ACT registration is alarming & calls for innovative approaches for maintaining good follow up through survivor centric approaches such as use of IT based communication technologies & formation of childhood cancer survivors support groups like Ugam.
Caregiver work modifications: A hidden cost of cancer care.
Authors: Blackmon Emma , Bell Janice , Whitney Robin L. , Reed Sarah C. , Kim Katherine , Joseph Jill
Published: February 2017

190

Background: Recent national reports highlight the dramatically rising costs of cancer care and its impact on financial hardship among survivors. Comparatively little attention, however, has been paid to the contributions of family and friends in unpaid caregiving roles—specifically, the impact of caregiving on caregivers jobs and work life. Methods: Using data collected in the 2012 LIVESTRONG Survey of People Affected by Cancer, we examined the prevalence of cancer survivors reporting that they had a friend or family member providing care to them during or after cancer treatment. Then, among those reporting they had a caregiver employed at that time, we used logistic regression to examine caregiver work modifications (i.e., paid time, unpaid time off, changing hours or duties, or making a change in employment status. All models controlled for survivor age at diagnosis, sex, race/ethnicity, income, education and employment status as potential predictors. Results: Of the respondents (n = 6310), 88% reported a family member or friend provided care as follows (in non-mutually exclusive categories): spouses (64%), friends (47%), parents (40%), siblings (31%), children (28%) or other family member (14%). Among survivors with employed caregivers (n = 4,984), 41% reported that their caregiver made a work modification; of these 57% took paid time off, 41% took unpaid time off, 4% switched from full time to part time and 3% took early retirement. Caregivers were more likely to make work modifications for survivors with low (versus high) income or education and for unemployed (versus employed) survivors. The age of the survivor was also a significant factor, with caregivers making more work modifications for younger survivors (ages 18-64) compared to older survivors (age > 65)—with ORs of caregiver work modfications increasing from 1.70 to 6.92 in a dose response by survivor age. Conclusions: Family and friends provide care to a majority of individuals with cancer and many make substantial modifications to their work—contributions which are not routinely counted in estimates of the cost of cancer care. Interventions may be warranted to support caregivers, particular those of survivors with lower income, less education and those of younger age.
Influence of clinical and psychological variables on coping strategies and quality of life of cancer patients: NEOCOPING study.
Authors: Rodriguez Rubi David , Calderon Caterina , Beato Carmen , Garcia Teresa , Ramchandani Avinash , Castelo Beatriz , Soriano Carmen , de la Morena Pilar , Sanchez Mar Munoz , Fernandez Sanchez Ana , Mangas Montserrat , Martinez de Castro Eva , Carrion Galindo Rafael , Donnay Olga , Cumplido Buron Jose David , San Gil Raquel Hernández , Carmona Bayonas Alberto , Jiménez-Fonseca Paula , Ayala Francisco , Jara-Sanchez Carlos ,   Grupo de Cuidados Continuos de la Sociedad Española de Oncología Médica (SEOM)
Published: February 2017

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Background: NEOCOPING study analyzes the influence of clinicopathological, personal and social variables on coping strategies and quality of life (QoL) in patients with resected tumors at the time of starting adjuvant chemotherapy. Methods: NEOCOPING is a prospective, multicenter, observational study that involves 19 centers and 34 researchers. Applied main questionnaires were: Mini-Mental Adjustment to Cancer (MAC), EORTC QLQ-C30, Brief Symptom Inventory (BSI-18), Shared Decision Making Questionnaire (SDM-Q) patient and doctor, and Multidimensional Scale of Perceived Social Support (MSPSS). Results: Table summarizes the characteristics of the first 71 patients enrolled. The most used coping strategies were fighting spirit (X=75.8, SD=25.9) and avoidance (X=64.6, SD=25); most patients were found to have good QoL (X=76.5, SD=16.6). Most did not have psychiatric symptoms, and were pleased with family and social support perceived. Patients were very satisfied with the information received (X=83, SD=19.9), and shared opinions with the doctor (X=90, SD=22.9). QoL was significantly negatively correlated with depression (r=-.688, r=.0001), anxiety (r=.-655, p=.0001), somatization (r=-.638, p=.0001) and hopelessness (r =-.287, p =.033). Depression and somatization predicted 54.8% of the QoL of this sample (F=23,636, p=.0001). Conclusions: Even though patients have a good QoL, adaptative coping strategies and no noticeable psychopathological symptoms at baseline, these symptoms may influence the well-being perception and modulate personal adaptations to the diagnosis and treatment of cancer at a curable stage. [Table: see text]
Psychosocial well-being assessment in women with breast cancer.
Authors: Gnanajothy Rosana , Correll Jennifer Aileen , Peterson Lindsay Leuthen
Published: February 2017

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Background: A breast cancer (BC) diagnosis can affect psychosocial wellbeing. The goal of the current study is to identify the severity of and specific risk factors for depression, anxiety, and quality of life impairment in a sample of BC patients. Early identification of at risk individuals can expedite appropriate referrals and interventions. Methods: Data from 53 female BC patients referred to a Behavioral Medicine service at a large academic medical center in 2013-2015 by medical providers who identified distress at routine clinic visits were analyzed. Patients completed the Center for Epidemiology Studies Depression Scale, State Trait Anxiety Inventory, McGill Pain Questionnaire, and the Short Form 12 Quality of Life Inventory as part of their initial assessment following referral. Demographic factors, disease and treatment related factors were analyzed for correlation with psychosocial wellbeing. Results: Mean age was 52. The majority of the population were Caucasian (79%), and 53% were married. All stages of disease were represented. Significant depression, anxiety and psychological quality of life impairment were seen in 53%, 50%, and 39% of patients respectively. There was a trend towards a significant difference in higher anxiety scores in patients who were not on chemotherapy (M=44.2, SD 5.4) compared to those on chemotherapy at the time of assessment (M=38.54, SD 9.3; t (51) = -1.94 p=0.077). A positive correlation was seen between depression and pain scores (r 0.294, p=0.038). Depression and psychological quality of life scores were negatively correlated (r -0.632 p<0.001), as were pain and physical quality of life scores (r -.343, p 0.024). There was no correlation between higher rates of depression or anxiety with type of surgical intervention or stage of disease. Conclusions: Significant depression, anxiety and quality of life impairment were seen in a large percentage of BC patients referred to Behavioral Medicine for perceived distress, regardless of type of surgery and disease stage. Higher rates of anxiety were seen in patients referred while not on chemotherapy compared to patients who were on chemotherapy at the time of referral. Early referral is the key to proper identification and treatment of high risk individuals.
Functional consequence of cognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL): The role of cancer symptoms as mediators.
Authors: Huang I-Chan , Brinkman Tara M. , Cheung Yin Ting , Pui Ching-Hon , Hudson Melissa M. , Krull Kevin R.
Published: February 2017

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Background: Although cognitive impairment of childhood cancer survivors affects daily functional status, the mechanisms are less understood. This study aimed to examine the role of cancer symptoms on the association of cognitive impairment with functional status in childhood ALL survivors treated on a chemotherapy only protocol. Methods: 213 survivors (mean age = 14.8 years) were assessed at > 5 years post-diagnosis. Testing included measures of executive function (Delis-Kaplan Executive Function System; Wechsler Intelligence Scale for Children-IV [WISC-IV]), processing speed (WISC-IV; Grooved Pegboard), visual-spatial processing (Wechsler Abbreviated Scale of Intelligence), memory span (WISC-IV), and attention (Conners CPT-II). Symptoms (e.g., pain, worry, cognitive, communication) and daily functional status (physical, emotional, social, school) were reported by parents using the PedsQL. Association of cognitive impairment with symptoms and functional status was tested using regression analyses. The extent to which cognitive impairment influences functional status through symptoms was tested using mediation analyses. Results: Cognitive impairment ( > 1SD below age-adjusted norm) was identified in 18-41% of the survivors. Impaired executive function, processing speed, and memory span were associated with high cancer symptoms (all p’s < 0.05), typically driven by perceived cognitive and communication problems. Impaired executive function, processing speed, visual-spatial processing, and memory span were associated with poor functional status (all p’s < 0.05). In each cognitive domain, impairment was related to poor school function (all p’s < 0.05). Impact of cognitive function (except attention) on overall functional status was mediated by overall cancer symptoms (all p’s < 0.05). Conclusions: Although the frequency of impairment in survivors treated with chemotherapy was less than that seen with cranial irradiation, cognitive impairment is related to elevated cancer symptoms and decreased functional status. Mediation analyses suggest that cognitive function works through cancer symptoms to impact functional status.
Health-related quality of life in underserved patients with hematologic malignancies.
Authors: Mushtaq Muhammad Umair Umair , Mangla Ankit , Hamad Hussein , Khurana Sharad , Catchatourian Rosalind
Published: February 2017

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Background: Patients diagnosed with hematologic malignancies have poor general health and the issues faced by vulnerable population segments further aggravate the situation. We aimed to explore the health-related quality of life (HRQoL) among underserved patients with hematologic malignancies. Methods: A cross-sectional study, including 95 patients diagnosed with hematologic malignancy, was conducted at Cook County Hospital, Chicago from Dec. 2014 to July 2015. European Organization for Research and Treatment of Cancer questionnaire was used to ascertain HRQoL. A standardized score (scale 0-100) was calculated for all variables and mean scores (MS) are reported. Higher score for HRQoL and functional scales and lower score on symptom scales indicated good health. Bivariate analysis, using t-test and ANOVA, was conducted to explore predictors of HRQoL. Results: The study included 48% Hispanics, 27% Afro-Americans, 14% Asians and 7% Caucasians. Median age was 53.8 years and 55% were males. Demographic analysis showed- 47% were fluent in english, 40% had insurance, 56% were US citizens, 14% were employed, 33% were high school graduates and 79% had good social support. Primary diagnosis were non-Hodgkin lymphoma (29.5%), AML (26%), ALL (17%), CML (9.5%), Hodgkin lymphoma (9.5%), CLL (4%) and multiple myeloma (4%). Median time since diagnosis was 2 years where 35% patients were in remission, 16% had relapsed disease and 58% were on chemotherapy. Overall HRQoL was poor (MS 62). Functional impairment was noted (MS 69) in all aspects including physical (MS 72), role (MS 66), emotional (MS 70), cognitive (MS 74) and social functioning (MS 65). Financial difficulties (MS 54), insomnia (MS 35), pain (MS 32), dyspnea (MS 24), poor appetite (MS 24), constipation (MS 23), fatigue (MS 17) and diarrhea (MS 14) were reported (symptom scale MS 29). Age, gender, socio-demographics, cancer type and treatment status did not significantly affect HRQoL, functional and symptom scores. Information regarding the disease was poor (MS 41). Conclusions: Poor HRQoL amongst underserved patients was observed which should be addressed. Our findings warrant large-scale studies to explore resources amongst the urban underserved blood cancer patients.
Associations between morning–evening chronotype, fatigue, and QOL in breast cancer survivors.
Authors: Palesh Oxana , Packer M. Melissa , George Holly , Koopman Cheryl , Innominato Pasquale F.
Published: February 2017

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Background: Emerging evidence suggests that circadian disruption is associated with cancer and cancer treatments. Chronotype is defined as a behaviorally manifested preference for a certain timing of sleep and activity. Previous studies have revealed that living out of sync from one’s innate chronotype can have detrimental effects on one’s health. Although there has been research examining the associations between chronotype and health, not much is known about the relationship between chronotype, fatigue, and QOL in cancer survivors. Methods: 68 Breast cancer survivors completed questionnaires to assess their chronotype (Horne-Ostberg), to rate their fatigue (MDASI), and to evaluate their QOL (FACIT). The Horne-Ostberg questionnaire yields a range of values indicating survivors’ preference for early or late activity. The study sample was divided by terciles according to survivors’ “morningness” or “eveningness” preferences (i.e., chronotypes). Results: Morning chronotype was associated with significantly less severe tiredness and drowsiness as well as significantly better physical well-being and fatigue subscale scores as compared to evening chronotype. Tiredness median (M) scores were highest for evening chronotype (M=5.5), moderate for mid-range chronotype (M=4.5), and lowest for morning chronotype (M=3.0), a significant difference (p=0.046). Drowsiness scores were highest for evening chronotype (median=6.0), moderate for mid-range chronotype (M=4.0), and lowest for morning chronotype (M=3.0), p=0.046. The median score for physical well-being was significantly lower for evening compared to morning chronotypes (22.5 vs. 25.0, p=0.038) and morning types reported significantly better health in respect to fatigue compared to evening types (40.5 vs. 35.5, p=0.045). Conclusions: Survivors with early chronotype (early to bed, early to rise) reported less fatigue, drowsiness, and better overall physical well-being. While chronotype is believed to be genetically driven, certain behavioral, pharmacological, and bright light modifications can be used to help patients shift their circadian rhythm towards earlier morning type and may experience improvements in physical well-being.