bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of age and BMD to predict fracture risk in men on androgen deprivation therapy
Authors: Lin D. , Smith M. R. , Morton R. A. , Steiner M. S.
Published: August 2020

9517

Background: Androgen deprivation therapy (ADT) decreases bone mineral density by reducing estrogens to castrate levels and, as a result, increases fracture risk. We recently completed a two-year trial in 1382 men in which we examined the ability of toremifene to reduce fracture risk in men on ADT. Herein we describe analyses of the placebo group to assess the baseline characteristics associated with new fractures. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Entry criteria included age ≥ 50 years, continous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for their duration on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included bone mineral density, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: The modified intent to treat (MITT) population included subjects who took study medication and had an on-study radiograph. There were 467 subjects in the placebo MITT population. To identify factors associated with fracture risk in men on ADT we compared placebo subjects who suffered a fracture or during the first year on study suffered 7% or greater bone loss with those placebo subjects who did not. Baseline characteristics included: BMD (spine, hip, femoral neck), Age, history of fracture, ADT duration, bone turnover markers, and race. Logistic regression models of the probability of fracture/bone loss as a function of country showed that each of BMD at all sites, age, race, CTX, and history of previous fracture independently predicted fracture/7% bone loss. When all characteristics were analyzed in a multivariable model lower spine BMD (p=0.006) and older age (p=0.018) were significantly associated with incident fractures. Conclusions: In prostate cancer patients on ADT older age and lower baseline spine BMD were associated with a greater risk of fracture in untreated patients.

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A retrospective database analysis to assess the impact of zoledronic acid (ZOL) on skeletal-related events (SREs) in solid tumor cancer and multiple myeloma (MM) patients (pts)
Authors: Thayer S. , Cooke J. , Kaura S.
Published: August 2020

9518

Background: For cancer pts with malignant bone lesions (BM), SREs including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and radiotherapy and/or surgery to bone are associated with significant morbidity and mortality and reduced quality of life. ZOL is an IV bisphosphonate (BP) proven to reduce and delay incidence of SREs in several tumor types. This study was designed to assess the benefit of long-term ZOL use in a real-life setting. Methods: Claims-based analysis of commercial and Medicare data from a large US managed care plan and a 45 health-plan database was used to evaluate mortality rates, SRE rates, and time from BM to SREs in pts treated with ZOL, pamidronate (PAM), or no IV BP therapy. Pts older than 18 years with solid tumors (breast, prostate, lung, bladder, or renal cell cancers) or MM and BM diagnosed between Jan 2001 and Dec 2006 were included. Continuous enrollment in the health plan for 6 months before the index date and no prior evidence of BM or IV BP use were required. Pts were followed until they left the care plan, switched therapy, or completed the study period. SRE and mortality rates were assessed. Results: The study sample included 28,415 pts with a mean age of 62.5 ± 12.24 years; approx. 25% were treated with ZOL, 8% with PAM, and 67% with no IV BP. Incidences of first and subsequent SREs were higher in the no IV BP group (incidence rate ratio [IRR] = 2.27; 95% CI = 2.03, 2.53 and IRR = 1.3; 95% CI = 1.24, 1.37, respectively) vs the ZOL/PAM groups. Time to first SRE was delayed by approx. 153 days for ZOL vs no IV BP pts. Overall, pts who had greater persistency with ZOL had lower risks of first SRE compared with no IV BP, the greatest risk reduction being observed in the 12- to 18-month persistency cohort, which experienced > 5-fold risk reduction (IRR = 0.19; 95% CI = 0.11, 0.31). The same persistency cohort also had a 27% lower risk of developing a second SRE (IRR = 0.73; 95% CI = 0.62, 0.86) compared with no IV BP. Conclusions: This study showed that in cancer pts with BM, persistence with ZOL resulted in reduced risk of developing first and subsequent SREs. Pts with longer persistence with ZOL achieved better outcomes.

[Table: see text]
Scintigraphic evaluation of mandibular bone turnover inhibition by bisphosphonates in patients with solid tumors
Authors: Van den Wyngaert T. , Huizing M. T. , Fossion E. , Vermorken J. B.
Published: August 2020

9519

Background: Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of the jaw (ONJ), possibly by causing an excessive inhibition of local bone turnover. However, little in vivo evidence currently exists to support this theory. Methods: Whole-body scintigrams acquired after administration of 99mTc labeled medronate of 120 patients were studied. Patients with skeletal metastases from a solid tumor (n=40) were individually matched with cancer patients without BP exposure (n=40) and controls with neither a malignancy nor BP use (n=40). Controls were matched for age, gender, malignancy, steroid and hormonal therapy use, where appropriate. Patients with established ONJ or intense focal abnormalities in the studied regions were excluded. Mandibular bone turnover (MBT) was quantified relative to the femurs by defining regions-of-interest on the scintigrams with correction for background activity. The study had a power of 90% to detect a 10% reduction in MBT after BP use. Results were analyzed using a repeated-measures ANOVA with a two-sided significance level of p<0.05. Results: The patients with BP exposure (34 female, 6 male) had a median age of 62 years (range 25–80) and received a median number of 11 zoledronic acid administrations (range 1–48). Malignancies included: breast (n=30), prostate (n=4), colon (n=2) and bladder cancer (n=2); and neuroendocrine carcinoma (n=2). The mean MBT was significantly lower in BP using cancer patients (2.59) compared with matched controls from oncological patients without BP use 3.01 (difference 0.42; 95% CI 0.13 - 0.72; p=0.006), or patients without cancer or BP exposure 3.09 (difference 0.50; 95% CI 0.21 - 0.78; p=0.001). In contrast, there was no significant difference in MBT between non-BP users (difference 0.08; 95% CI -0.31 - 0.46; p=0.7). Likewise, no correlation between MBT and the number of BP administrations could be demonstrated (r2=0.01; p=0.4), suggesting a stochastic rather than a deterministic effect. Conclusions: This in vivo data suggests that BP cause a higher inhibition of bone turnover in the mandible relative to the femur, which strengthens the hypothesis that the inhibition of bone turnover may be important in the pathophysiology of ONJ.

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Final results of a study comparing short-course and long-course radiotherapy (RT) for local control of metastatic spinal cord compression (MSCC)
Authors: Rades D. , Lange M. , Veninga T. , Stalpers L. J. , Bajrovic A. , Adamietz I. A. , Rudat V. , Schild S. E.
Published: August 2020

9522

Background: Many MSCC patients live long enough to develop a recurrence in the irradiated spinal area. This is the first prospective study comparing different RT schedules for local control (LC) of MSCC. Methods: 265 patients treated with RT alone (1/06–12/07) were included in this prospective non-randomized study. The primary goal was to compare short-course (1×8 Gy/5×4 Gy, N=131) and long-course RT (10×3 Gy/15×2.5 Gy/20×2 Gy, N=134) for 1-year LC. Secondary endpoints were motor function and 1-year survival (OS). Dutch patients received short-course, and German patients long-course RT. The analysis of LC (no MSCC recurrence in the irradiated spinal area) included the 224 patients with improvement or no change of motor deficits during RT. The difference in 1-year LC was previously reported to be 14% between short- and long-course RT. For a statistical power of 90 % (significance level 5%), ≥218 patients were required to detect this difference. Univariate analyses (UVA) for LC and OS were performed with Kaplan-Meier-method and log-rank test, multivariate analyses (MVA) with the Cox proportional hazards model. UVA and MVA for motor function were performed with the ordered-logit-model. Eleven additional factors were evaluated. Results: 1-year LC was 61% after short-course RT and 81% after long-course RT (P=0.005). On MVA, improved LC was only associated with long-course RT (P=0.018). Motor function improved in 37% after short- and 39% after long-course RT (P=0.95). Improved motor function was associated with better performance status (P=0.015), favorable tumor (P=0.034), and slower development of motor deficits (P<0.001). 1-year OS was 23% after short- and 30% after long-course RT (P=0.28). On MVA, improved OS was associated with better performance status (P<0.001), no visceral metastases (P<0.001), involvement of 1–3 vertebrae (P=0.040), ambulatory status (P=0.038), and bisphosphonates (P<0.001). Conclusions: Long-course RT was associated with better LC, similar functional outcome, and similar OS compared to short-course RT. Patients with a favorable OS prognosis should receive long-course RT, and those with a poor OS prognosis should receive short-course RT.

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Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies: Are clinicians responding appropriately?
Authors: Telli M. L. , Yoon G. , Kao D. , Matsuda K. , Witteles R. M.
Published: August 2020

9527

Background: Cancer survivors treated with anthracyclines and/or trastuzumab are at risk for cardiotoxicity. Left ventricular (LV) systolic dysfunction (symptomatic or asymptomatic) represents a Class I indication for therapy with beta-blockers and angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) according to American College of Cardiology/American Heart Association heart failure guidelines. We designed this study to examine treatment practices for patients with cancer therapy-associated LV dysfunction, and the real-world adoption of treatment guidelines. Methods: After IRB approval, we identified all patients who received anthracycline and/or trastuzumab cancer therapy at Stanford University from October 1, 2005 to October 31, 2007 using an institutional pharmacy database. Out of 6,530 total cycles of chemotherapy administered, we identified all unique patients who had at least one echocardiogram performed before and after the start of chemotherapy using an institutional echocardiography database. Details of the chemotherapy regimen, cardiac risk factors, cardiac imaging results, concomitant medications, and referrals/consultations were examined for these patients. Results: A total of 88 patients met inclusion criteria. Ninety-two percent were treated with anthracyclines, 25% with trastuzumab in combination with anthracyclines, and 8% with trastuzumab alone. Mean baseline ejection fraction (EF) was 60%, with 13% of patients having a baseline EF below normal. A total of 41% had LV dysfunction (EF less than 55%) during or after cancer therapy. Of these patients, 56% received beta-blocker therapy, 47% received ACE-I or ARB therapy, and 50% were referred for cardiology consultation. Of the patients with asymptomatic LV dysfunction (75% of the LV dysfunction cohort), 41% received beta-blocker therapy, 33% received ACE-I or ARB therapy, and 37% received cardiology consultation. Conclusions: In real-world clinical practice, many cancer survivors with cardiotoxicity are not adequately evaluated and treated from a cardiovascular standpoint. Multidisciplinary collaboration between oncologists and cardiologists is needed to improve the quality of care for these patients.

No significant financial relationships to disclose.
Changes in body composition in women with breast cancer on aromatase inhibitors: A two-year trial
Authors: Van Londen G. J. , Perera S. , Vujevich K. , Rastogi P. , Lembersky B. , Brufsky A. , Vogel V. , Greenspan S.
Published: August 2020

9528

Background: Aromatase inhibitors (AIs), the preferred adjuvant therapy of postmenopausal breast cancer patients, induce severe hypo-estrogenemia which differentiates them from the Estrogen-Receptor-Agonists-Antagonists (ERAAs). Little is known about the effect of AIs on body composition. We sought to examine the impact of AIs on body composition, and whether any changes correlate with gonadal hormone levels. Methods: We analyzed a two year double-blind trial (Risedronate's Effect on Bone loss in Breast CAncer, REBBeCA). 81 chemotherapy-induced newly postmenopausal nonmetastatic breast cancer patients had been randomized to risedronate 35 mg once weekly or placebo and followed, some of whom were on or started AI during the trial. Measures included body composition by whole body DXA-scan and serum sex hormone levels. Combining the two treatment arms, we estimated and compared body composition changes in those on (AI) and not on AIs (no-AI) using a linear mixed model, and examined correlations with serum hormone levels. Results: By 24 months, 41 women were on an AI. Over 2 years, lean mass increased by 1159g (p=0.0003) in women on an AI and did not change (85g; p=0.7684) in the no-AI group (adjusted difference, AD=1047g; p=0.0004). Percent fat did not change (0.0; p=0.9344) in those on an AI and increased (1.2; p=0.0097) in the no-AI group (AD=1.6; p=0.0433). The change in estradiol was associated with changes in lean mass (correlation r=0.42, p=0.0020) and percent fat (r=-0.48, p=0.0003). Conclusions: The use of AIs is associated with a decrease in fat mass and an increase in lean mass. The changes in estradiol are associated with alterations in body composition. The mechanisms and implications of these changes need to be studied further.

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A randomized controlled trial evaluating a topical treatment for chemotherapy-induced neuropathy: NCCTG trial N06CA
Authors: Barton D. L. , Wos E. , Qin R. , Mattar B. , Green N. , Lanier K. , Bearden J. , Kugler J. , Rowland K. , Loprinzi C.
Published: August 2020

9531

Background: Chemotherapy induced peripheral neuropathy (CIPN) is a prevalent dose limiting toxicity for several important cancer treatment agents. CIPN can impair function and cause distress. There are no proven pharmacologic treatments for established CIPN currently. This double blind randomized placebo controlled trial evaluated a compounded topical gel for this problem. The novelty of this treatment is that it might incorporate several agents with different mechanisms of action to provide relief locally without negative systemic effects. Methods: Patients with CIPN (rated ≥4 out of 10) for at least one month, related to previous and/or concurrent exposure to neurotoxic agents, were randomized to baclofen 10 mg, amitriptyline HCL 40 mg and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) vs placebo (PLO) to determine its effect on numbness, tingling, pain, and motor function. Exclusion criteria included other causes and/or current treatment for peripheral neuropathy. The primary endpoint was the baseline adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. Results: Between February and May 2008, 208 patients were enrolled onto this trial. Four week data are shown in the table below, higher numbers being better. The percentage of patients that had improvements of at least 10, on a 100 point scale, in the motor subscale was statistically significantly higher in the BAK-PLO arm, p=.04. There were no unwanted toxicities associated with the BAK-PLO that were significantly different from placebo and no evidence of CNS or systemic toxicity. Conclusions: Topical treatment with BAK-PLO appears to moderately improve symptoms of CIPN. This topical gel was well tolerated without systemic side effects.

[Table: see text]

No significant financial relationships to disclose.
Predictors of aggressive end-of-life care among Hispanic and white advanced cancer patients
Authors: Trice E. D. , Nilsson M. E. , Paulk E. , DeSanto-Madeya S. , Wright A. A. , Balboni T. A. , Steiglitz H. , Maciejewski P. K. , Block S. D. , Prigerson H. G.
Published: August 2020

9538

Background: Some ethnic/racial minority cancer patients (e.g. African Americans) have been shown to receive more life-prolonging care at the end-of-life (EOL) than white patients. Nevertheless, few studies have investigated whether Hispanic cancer patients receive more aggressive care than white patients and limited information exists on the predictors of aggressive care among Hispanic patients. The present study examined rates and predictors of aggressive EOL care among Hispanic and white cancer patients. Methods: Subjects participated in a US multi-site, prospective study between September 2002 - August 2008. Data were derived from interviews, conducted in English or Spanish, of 292 self-reported Hispanic (N=58) or white (N=234) stage IV cancer patients and their caregivers. Patients were followed until death, a median of 118.5 days later. Caregiver post-mortem interviews documented patient care in the last week of life. “Aggressive EOL care” was operationalized as cardiopulmonary resuscitation and/or ventilation and death in an intensive care unit. Aggressive EOL care was regressed on the following baseline, patient-reported, independent variables: a preference for life-prolonging care, EOL treatment discussion, do-not-resuscitate (DNR) order, terminal illness acknowledgement, and religious coping. Logistic regression models were stratified by ethnic status and controlled for significant confounds (e.g. socioeconomic status). Results: Hispanic and white advanced cancer patients were equally likely to receive aggressive EOL care (5.2% and 3.4%, respectively; p=0.878). Although religious coping and treatment preferences predicted aggressive EOL care for white patients (adjusted odds ratio 7.76 [p=0.025] and 13.20 [p=0.008]), they were not predictive among Hispanic patients. Hispanic patients were less likely than white patients to have DNR orders (22.4% vs 50.4%; p=0.007). For both white and Hispanic cancer patients, no patient who reported an EOL discussion or DNR order at baseline received aggressive EOL care. Conclusions: Given that EOL discussions and DNR orders may prevent aggressive EOL care among Hispanic cancer patients, further efforts to engage Hispanic patients and their caregivers in these activities may reduce aggressive EOL care.

No significant financial relationships to disclose.
National survey of oncology fellows on palliative care education
Authors: Buss M. K. , Lessen D. S. , Von Roenn J. , Sullivan A. M. , Arnold R. M. , Block S. D.
Published: August 2020

9541

Background: Palliative care (PC) is recognized as an integral part of the practice of oncology, yet many oncologists report inadequate training in critical PC domains, such as symptom management, psychosocial care and communication skills. We sought to assess the quantity and quality of PC education within oncology fellowships. Methods: Second year fellows enrolled in US oncology fellowships were invited to complete a 104 item survey that was modified from a national telephone survey of medical students and residents. Topics included: 1) quality and quantity of teaching and education, 2) observation and feedback, 3) knowledge, 4) attitudes and preparation. Items were designed to allow comparison between PC and non-PC topics. To reduce Type I errors from multiple testing, an alpha level of 0.01 was considered statistically significant. Results : Of 402 eligible fellows, 63.5% responded (n=254). Respondents were: 52% male, 62% White, 27% Asian and 64% US medical school graduates. One-quarter (26%) had completed a PC rotation and 68% reported exposure to palliative care during their fellowship. On a 5-point Likert Scale, fellows rated teaching on PC less highly than the overall quality of fellowship teaching (3.0 v 3.7; p<0.001). Fellows rated attending oncologists less favorably in performing PC skills compared to other oncology skills: managing pain in the terminally ill versus managing spinal cord compression (3.9 v. 4.5; p < 0.001); discussing the decision to stop chemotherapy versus discussing chemotherapy side effects (3.8 v. 4.2; p < 0.001). Fellows were less likely to be observed (81% v 93%; p =0.005) or receive feedback (80 v 93%; p= 0.02) on end-of-life (EOL) discussions than bone marrow biopsies. Many fellows reported not receiving explicit education on PC topics: managing depression at the EOL (68%), opioid rotation (67%), telling a patient she is dying (42%) and hospice referral (37%). Fellows who completed a PC rotation were more likely to report explicit teaching on opioid rotation (p =0.005) and hospice referral (p = 0.002). Conclusions: Our study reveals opportunities for improving the PC training of oncology fellows.

No significant financial relationships to disclose.
Predictors of prostate cancer-specific mortality in elderly men with intermediate-risk prostate cancer treated with radiation therapy
Authors: Nanda A. , Chen M. , Moran B. J. , Braccioforte M. H. , Dosoretz D. , Salenius S. , Katin M. , Ross R. , D'Amico A. V.
Published: August 2020

9543

Background: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for co-morbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy (EBRT). Methods: The study cohort comprised 1,978 men of median age 71 (interquartile range [IQR], 66–75) years with intermediate-risk prostate cancer (Gleason score 7 with PSA 20 ng/mL or less and tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether presence of cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category were associated with the risk of PCSM. Results: After a median follow up of 3.2 (IQR, 1.7 - 5.4) years, 15 men were observed to experience PCSM. The presence of CVD was significantly associated with a decreased risk of PCSM (AHR 0.20, 95% CI 0.04 - 0.99, P = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (AHR 1.14, 95% CI 1.02 - 1.27, P = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (P = 0.03) in men with PSA levels above as compared to the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (P = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL). Conclusions: Detection of intermediate-risk prostate cancer in elderly men without CVD at lower PSA levels is associated with a lower risk of PCSM; this risk reduction is not observed in men with known CVD.

[Table: see text]

No significant financial relationships to disclose.
Sexual dysfunction in women with breast cancer: Prevalence and severity
Authors: Goldfarb S. B. , Dickler M. , Sit L. , Fruscione M. , Barz T. , Atkinson T. , Hudis C. , Basch E.
Published: August 2020

9558

Background: Sexual dysfunction (SD) is reported after chemotherapy and endocrine therapies, and causes a substantial burden on women with breast cancer. However, the prevalence and severity of SD in this population is not well defined. Improved understanding of SD may allow for enhanced treatment and interventions in patients with breast cancer undergoing active treatment, and in survivors of this disease. Methods: We developed a survey that includes a previously validated questionnaire, the female sexual function index (FSFI), and disease-specific items to characterize SD and its causes based on literature review and expert consultations. Anonymous administration of the surveys was conducted in outpatient clinic waiting areas of the M64/Breast Center Memorial Sloan-Kettering Cancer Center (MSKCC), under an IRB waiver of consent. Results: During November-December 2008, 100 women with breast cancer of any stage were each queried once. The mean age was 52 (range 26–75). 68% reported current or past hormonal treatment, and 63% reported current or past chemotherapy (84% adjuvant; 16% for metastatic disease). SD attributed to breast cancer or its treatment, defined as an FSFI score <26, was reported by 75% of respondents. Among these women, severe symptoms were noted by 38/75 (51%), and moderate by 37/75 (49%). 87/95 (92%) patients considered their sexual symptoms to be bothersome, with 59/95 (62%) noting moderate or severe levels of bother (score >=5/10). Patients attributed their SD to chemotherapy in 52/63 (83%) of cases; to hormonal therapy in 56/68 (82%) of cases; and to surgery in 68/92 (74%) of cases. Other contributors to SD were felt to include anxiety by 83% of respondents, and change in relationship with a partner by 46%. Conclusions: SD is prevalent in women treated for breast cancer and should be discussed with patients as a potential adverse effect of therapy. Assessment of sexual symptoms throughout treatment and beyond may facilitate the use of potential interventions such as lubricants, dilators, treatment modification, topical estrogens, and counseling. A longitudinal prospective trial is planned to further characterize the etiologies of these symptoms.

No significant financial relationships to disclose.
Predictors of recurrent thrombosis and anticoagulant-related bleeding in patients with cancer
Authors: Lee A. , Parpia S. , Julian J. , Rickles F. , Prins M. , Levine M.
Published: August 2020

9565

Background: Anticoagulant therapy is treatment of choice for cancer-associated thrombosis. However, the risk of symptomatic recurrent thrombosis (RT) is approximately 9% on low molecular weight heparin (LMWH) and 17% on vitamin K antagonist (VKA) therapy, while the risk of anticoagulant-related major bleeding is about 5%. Given such complications are associated with morbidity and increased resource utilization, prognostic factors that identify patients at high risk for RT or bleeding would be useful for individualizing therapy. We performed a post-hoc analysis of the CLOT study (N Eng J Med 2003;349,146–53) for predictors of RT and bleeding in patients with proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) who were randomized to receive either dalteparin LMWH or VKA for 6 months. Methods: Cox proportional hazards modeling analyses were performed using prospectively collected data from the CLOT study database. Potential baseline factors associated with RT and bleeding examined in the models were identified a priori based on published literature. Factors for RT were: dalteparin, age, gender, ECOG status, smoking status, presence of metastases, tumor site, history of DVT or PE, recent surgery, cancer treatment and body mass index. Factors for bleeding were: dalteparin, age, gender, ECOG, tumor type, major surgery, cancer treatment, platelet count, body mass index, creatinine, and concurrent use of antiplatelet agents. Results: Data from 673 cancer patients were available for the analysis. There were 80 patients with RT, 31 with major bleeds and 77 with minor bleeds. Three statistically significant predictors for RT were identified (with their hazard ratio and corresponding 95% CI): dalteparin (0.52; 0.32–0.82), every 10 year increase in age (0.77; 0.66–0.90) and presence of metastases (2.59; 1.20–6.60). Of the tumour sites investigated, lung (3.51; 1.62–7.62) and unknown primaries (3.63; 1.36–1.90) were predictive of RT. None of the factors examined in the models were found to be predictive of bleeding. Conclusions: Baseline factors may identify cancer patients with a higher risk of RT despite anticoagulant therapy. The risk of anticoagulant-related bleeding is not predictable at treatment onset.

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Effect of chemotherapy on the risk of erlotinib-induced skin rash in cancer patients: A meta-analysis
Authors: Jia Y. , Lacouture M. E. , Su X. , Wu S.
Published: August 2020

9573

Background: Erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is effective in the treatment of non-small cell lung cancer (NSCLC) as a single agent and pancreatic cancer when combined with chemotherapy. Its application in other types of cancer is also undergoing extensive clinical assessment. Skin rash is a major side effect of erlotinib. This study aims to gain a better understanding of skin toxicity with erlotinib through a systematic review and meta-analysis of randomized controlled clinical trials. Methods: Relevant studies were identified from Medline (1966 to October 2008), Web of Science, and abstracts presented at the American Society of Clinical Oncology Conferences between January, 2004 and October, 2008. Eligible studies included prospective randomized controlled clinical trials in which cancer patients were treated with erlotinib at 150 mg daily as single agent or in combination with other agents. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 3,562 patients with a variety of solid tumors from 12 randomized controlled clinical trials were included for analysis. The overall incidence of all-grade skin rash associated with erlotinib was 68.7% (95% CI: 63.0–73.8%) with 8.9% (95% CI: 7.7–10.3%) being high-grade (grade 3 or above). There was a significantly increased risk of skin toxicity with erlotinib in comparison with controls (all-grade: RR 3.1, 95% CI: 2.2–4.3, p < 0.001; high-grade: RR 10.1, 95% CI: 5.5–18.5, p < 0.001). Interestingly, chemotherapy may decrease the risk of skin rash associated with erlotinib. RR of all-grade skin rash was 4.7 (95% CI: 3.6–6.2) for single-agent erlotinib and 2.3 (95% CI: 2.0–2.7) for erlotinib in combination with chemotherapy; RR of high-grade skin rash was 17.3 (95% CI: 3.3–90.5) for single-agent erlotinib and 9.3 (95% CI: 4.8–17.8) for erlotinib in combination. Conclusions: Erlotinib was associated with significantly increased risk of skin toxicity among cancer patients. Its combination with chemotherapy may decrease the risk of skin rashes.

No significant financial relationships to disclose.
Correlates of hospice use in elders with cancer
Authors: Owusu C. , Koroukian S. , Madigan E.
Published: August 2020

9579

Background: Use of hospice has remained relatively low. We aim to identify correlates of hospice in elders with cancer, hypothesizing that the presence of functional limitations and geriatric syndromes are associated with hospice use, independently of age and comorbidities. Methods: The study population included Ohio residents age 65 years or older, diagnosed with breast (n=774), prostate (n=271), or colorectal cancer (n=1,011) during the period 07/1999–12/2001, receiving care through the Medicare fee-for-service system, and first receiving home health care (HHC) in the 30 days before or after cancer diagnosis. This strategy was aimed at obtaining clinical data at baseline, as documented in the HHC Outcome Assessment Information Set (OASIS). Our data source consisted of records from the Ohio Cancer Incidence Surveillance System (OCISS) linked with Medicare data, and the OASIS. In addition to descriptive analyses, multivariable logistic regression analysis was conducted to evaluate the association between hospice use, comorbidity, functional limitations, and geriatric syndromes, after adjusting for patient and tumor attributes. Results: Respectively across the anatomic cancer sites, hospice was used by 9.8%, 22.5%, and 25.1%, of patients. Hospice use increased significantly with age, and was higher among men than women. No differences in hospice use were observed by race, Medicaid status, or the presence of comorbidities. Conversely, hospice use was significantly higher (p < 0.001) among patients with functional limitations (24.0% vs. 16.5% in all others), and those with geriatric syndromes (23.8% vs. 15.3% in all others). Results from the multivariable logistic regression analysis indicated that comorbidities and functional limitations were not associated with hospice use, whereas patients with geriatric syndromes were 1.5 times as likely as those without geriatric syndromes to use hospice (adjusted odds ratio (AOR): 1.5, 95% confidence interval (1.2–1.9). Conclusions: The findings highlight the importance of clinical data that extend beyond comorbidities, when analyzing hospice use. Given marked differences in the disease trajectory across the anatomical cancer sites, future studies should analyze these associations separately in breast, prostate, and colorectal cancer patients.

No significant financial relationships to disclose.
Vitamin D deficiency, incidence, and response to oral supplementation among various gastrointestinal malignancies
Authors: Gilmore C. , James J. , Zubal B. , Thomas D. , Tan B.
Published: August 2020

9586

Background: Vitamin (vit) D dficiency is prevalent amongst patients (pts) with colorectal and pancreatic cancers. Data for other GI malignancies are limited and the impact of short-course vit D supplementation is unclear. Methods: An IRB-approved retrospective review of 202 pts with GI cancers from 12/2007 to 9/2008 was done to evaluate the incidence of vitamin D deficiency defined as serum 25-OH vit D levels of ≤ 30 ng/ml (severe=<10 ng/ml; moderate=10–20 ng/ml; mild=21–30 ng/ml) and incidence of ‘low-normal' (31–50 ng/ml) and normal (>50 ng/ml) vit D levels. Oral supplementation with vit D at 50,000 ‘u' weekly x 8–12 weeks were done and serum levels were redrawn at 2–3 months for pts with low normal and deficient vit D, respectively. Results: 87.6% of all 202 pts is vit D deficient (61% severe to moderate). (see Table ). 92 pts were re-evaluated after 2–3 months of oral vit D supplementation. Among this cohort, the incidence of pts with vitamin deficiency decreased from 91.3% to 57.6% after first re- evaluation. Severe/moderate deficiency rates also decreased from 71.7% to 13%. There were no significant difference in response between males/females, age < or ≥ 65, caucasian or non-caucasian or tumor type. Conclusions: Vitamin D levels should routinely be evaluated for patients with GI maligancies. Oral supplementation decreases the rate 'any' vit D deficiency from 91% to 57%, and of 'severe to moderate' deficiency from 72% to 13%. Prospective studies on the impact of vit D deficiency and supplementation on various clinical outcomes among patients with GI cancers would improve supportive care management of these patients.

[Table: see text]

No significant financial relationships to disclose.
Relationship of sensory symptoms and motor function in patients with chemotherapy-induced peripheral neuropathy (CIPN) utilizing the EORTC QLQ CIPN20: NCCTG study N06CA
Authors: Wolf S. L. , Qin R. , Barton D. L. , Sloan J. A. , Liu H. , Aaronson N. K. , Satele D. V. , Green N. B. , Mattar B. I. , Loprinzi C. L.
Published: August 2020

9587

Background: CIPN is characterized by adjectives not covered directly by most common measures of pain and functional limitations. Possible descriptors include numbness, tingling and shooting/burning pain. A prospective neuropathy treatment trial provided data to explore the relationship between self-reported aspects of this symptom. Methods: Baseline EORTC QLQ CIPN20 data and NCI CTCAE V3.0 (CTC)neuropathy grade (I-IV) were provided for all patients on trial. Spearman correlation coefficients and Kappa's coefficients of agreement were calculated between individual items and subscales of the CIPN20 as well as the CTC neuropathy scale. Simple regression models were applied to examine the association between the sensory symptoms and motor function in the fingers/hands (F/H). 200 patients provided 80% power to detect a correlation coefficient of 0.20 with a 5% Type I error. Results: A majority of patients reported “quite a bit” to “very much” numbness (57%) or tingling (62%) in F/H compared to “a little” or “not at all” (numbness (43%), tingling (38%)) by the CIPN20. In contrast, only 13% of the participants had grade III/IV neuropathy determined by the CTC scale. Fewer patients reported the higher two levels of CIPN20-measured shooting/burning pain in F/H (20% “quite a bit” to “very much”). Numbness and tingling were highly correlated (kappa=0.56), while neither were in high agreement with shooting/burning pain (kappa= 0.05 (tingling) and 0.14 (numbness)). The CIPN20 sensory and motor subscales were significantly associated with each other (p<.0001) but were not or only weakly associated with the CTC. Specifically, tingling, numbness, and shooting/burning pain were not associated with the CTC (R=0.16, 0.18 and 0 .11, respectively). Using the CIPN20, all three sensations; numbness, tingling and shooting or burning pain were strongly associated with motor function. Conclusions: The most common moderate to severe CIPN symptoms were numbness and tingling with shooting/burning pain being less common. Shooting/ burning pain appears to be a separate symptom experience from numbness and tingling. The CTC neuropathy grading scale appears to be less sensitive than the CIPN20 in picking up sensory symptoms.

No significant financial relationships to disclose.
Symptom burden in cancer survivors: A report from the American Cancer Society's studies of cancer survivors
Authors: Shi Q. , Smith T. , Mendoza T. , Kaw C. , Cleeland C. S.
Published: August 2020

9598

Background: Cancer survivors may have persistent symptoms as a result of the cancer or the late effects of cancer treatment, although few studies have assessed symptom burden after completion of cancer therapy. We described symptom burden and risk factors for high symptom burden in a population-based sample of cancer survivors. Methods: Cancer survivors were drawn from 11 state cancer registries and surveyed by telephone or mail approximately 1 year after diagnosis; 3697 respondents completed the Modified Rotterdam Symptom Checklist (RSCL-M) and Profile of Mood States-37 (POMS-37). Factor analyses were used to generate composite scores from RSCL-M and POMS-37.Two-step cluster analyses using these composite scores were performed to identify cancer survivors with high symptoms. Results: Six composite scores (pain, nausea/vomiting, fatigue, poor bowel and bladder control, weight loss, and unspecified symptoms) were generated for physical symptoms (RSCL-M). Five composite scores (anxious/depressed, miserable, energetic, exhausted, and annoyed) were generated for mental symptoms (POMS-37). Cluster analyses revealed that 20% of survivors reported both high physical and high mental symptoms. Multivariate logistic regression revealed risk factors associated with high physical and high mental symptoms: younger than 55, household income lower than $40,000, high school or lower education level, unemployed when diagnosed with cancer, lack of health insurance, distant cancer, one or more comorbid conditions, diagnosis of lung cancer, and previous chemotherapy. Conclusions: One of five cancer survivors in this survey belonged to a group with high physical and mental symptoms, which were associated with certain risk factors. These findings will help clinicians and researchers identify subgroups of survivors most likely to report high symptoms and therefore most in need of symptom management. The high symptoms reported by survivors without insurance may have policy implications.

No significant financial relationships to disclose.
Smoking and quality of life among elderly survivors of non-smoking related cancers in a prospective cohort study
Authors: Jang S. , Prizment A. , Lazovich D.
Published: August 2020

9600

Background: Although the effect of smoking on quality of life (QOL) has been examined among survivors of lung or head and neck cancers, little is known about how smoking affects QOL among elderly survivors of non-smoking related cancers. Methods: The Iowa Women's Health Study (IWHS), a prospective cohort study initiated in 1986, collected self-reported QOL using the SF-36 in 2004. Cancer diagnosis and treatment among cohort participants were obtained from Iowa's cancer registry. Behavioral and health characteristics, including smoking status, were collected from periodic follow-up questionnaires between 1986 and 2004. We included 1,920 women, aged 55 to 69 years at baseline, who developed breast, colorectal, or endometrial cancers and responded to the 2004 questionnaire. We compared age-adjusted and multivariate-adjusted mean scores for eight SF-36 scales between nonsmokers (no reported smoking in 1986 or 2004), quitters (reported smoking in 1986 but not 2004), and persistent smokers (reported smoking in 1986 and 2004). Results: Among 1,920 cancer survivors, 1,720 (89.6%) were nonsmokers, 141 (7.3%) were quitters, and 59 (3.1%) were persistent smokers. After age adjustment, quitters had lower scores for vitality, physical functioning, mental health, social functioning, and general health scales compared to nonsmokers. Persistent smokers scored worse on the physical functioning, mental health, role emotional, and social functioning scales compared to nonsmokers. Except for mental health, these differences in QOL scores were attenuated after further adjustment for physical activity. Accounting for other factors, including baseline general health perception and education, cancer type, surgery, radiation therapy, chemotherapy, and length of survival, or occurrence of hypertension, diabetes, heart disease, stroke or fracture by 2004 did not change the differences observed between survivors who had ever reported smoking versus nonsmokers. Conclusions: Quitters and persistent smokers tended to fare worse than nonsmokers on many QOL scales. In most instances, these differences were explained by lower levels of physical activity which may have been a consequence of smoking.

No significant financial relationships to disclose.
Mood state and melanoma outcome in the Multicenter Selective Lymphadenectomy Trial
Authors: Garreau J. R. , Faries M. , Ye X. , Morton D.
Published: August 2020

9603

Background: Emotional state has been linked to cancer survival, but its influence on the outcome of early melanoma is unclear. The Multicenter Selective Lymphadenectomy Trial (MSLT-I) randomized patients with clinically localized cutaneous melanoma to wide local excision (WEX) plus observation or to WEX plus sentinel lymph node biopsy (SNB). Clinical endpoints included disease-specific and disease-free survival. A substudy of this phase III trial evaluated the impact of mood state on survival, and the impact of recurrence on mood state. Methods: Patients were asked to complete a 65-question form within 6 months of enrollment (baseline) and every 12 months thereafter. This questionnaire measured 6 identifiable mood states (vigor-activity, tension-anxiety, depression, anger-hostility, fatigue-inertia, confusion-bewilderment) of the Profile of Mood States (POMS), a validated mood scale for assessing responses to therapy. Self-reported data from the questionnaires were linked to demographic and clinical variables. Results: Of 2,001 patients accrued to MSLT-I, 1,620 completed the questionnaire at baseline. The baseline distribution of POMS variables was similar in the two treatment arms (data not shown). Patients with more vigor at baseline had a significantly longer disease-free and overall survival ( Table ), even after adjusting for age, tumor thickness, site, and ulceration status (p <0.001). Among 136 patients who completed a questionnaire within 6 months after recurrence, comparison of baseline and post-recurrence responses revealed significant changes in mood state: tension, fatigue and confusion increased, whereas vigor decreased (p = 0.0004, 0.0171, 0.0089, and 0.0028, respectively). Conclusions: Vigor, a measure of energy and optimism, is directly correlated with disease-free and overall survival in early melanoma. The negative impact of recurrence on mood state suggests that SNB as a tool for preventing recurrence might also improve mood state and psychological well-being. Supported by NIH CA29605. [Table: see text]

No significant financial relationships to disclose.
Single-day regimen of palonosetron (PALO) and dexamethasone (DEX) for the prevention of emesis associated with moderately emetogenic chemotherapy (MEC): Subgroup analysis from a randomized phase III trial
Authors: Celio L. , Bajetta E. , Denaro A. , Bichisao E. , Frustaci S. , Ardizzoia A. , Piazza E. , Fabi A. , Capobianco A. , Isa L.
Published: August 2020

9620

Background: We have recently shown non-inferiority in preventing acute and delayed nausea and vomiting associated with MEC between the PALO plus 1-day DEX and PALO plus 3-day DEX regimens. Planned analysis stratified by type of chemotherapy (anthracycline + cyclophosphamide [AC] group or patients receiving at least one moderately emetogenic agent according to modified Hesketh classification) has been performed. Methods: A total of 332 chemo-naïve patients with solid tumors were randomized to receive a single IV dose of PALO 0.25 mg plus DEX 8 mg IV on day 1 of chemotherapy (arm A; n=166) or the same regimen followed by DEX 8 mg orally on days 2 and 3 (arm B; n=166). Endpoints included complete response rates (CR: no emetic episodes [EE], no rescue antiemetics; primary endpoint) and proportion of patients with no EE throughout the 5 days after the first cycle of chemotherapy. Subgroups were analyzed by two-sided chi-square test. Results: Per-protocol population included 324 patients (65% women; median age 57.5 years); 35% received AC regimens, and 65% other MEC regimens. There were no significant differences between arms in CR rates according to the type of chemotherapy: 1) CR rates on AC regimens (arm A, 55.8% versus arm B, 60.7%; p=0.599); and 2) CR rates on other MEC regimens (arm A, 68.5% versus arm B, 72%; p=0.576). No significant differences between arms were also observed in the rates of patients with no EE: 1) emesis-free patients on AC regimens (arm A, 78.8% versus arm B, 73.8%; p=0.528); 2) emesis-free patients on other MEC regimens (arm A, 83.8% versus arm B, 90%; p=0.184); 3) nausea-free patients on AC regimens (arm A, 38.5% versus arm B, 44.3%; p=0.533); and 4) nausea-free patients on other MEC regimens (arm A, 58.6% versus arm B, 64%; p=0.418). Conclusions: The single-day regimen of PALO and DEX can provide effective protection against acute and delayed emesis from AC- and MEC-based regimens while avoiding to unnecessarily prolong treatment with DEX.

No significant financial relationships to disclose.