bluuebunny/crossref_metadata_2025 huggingface dataset:
Population-based patterns of palliative systemic therapy use in elderly patients with metastatic colorectal cancer (mCRC).
Authors: Chan Matthew , Gresham Gillian , Cheung Winson Y.
Published: March 2020

9547

Background: Elderly cancer patients are consistently under-represented in clinical trials, which may lead to under-treatment. Our aims were to 1) determine the impact of advanced age on use of palliative systemic therapy in mCRC, 2) examine the reasons for treatment choices and 3) compare adverse events and treatment discontinuations in elderly vs young patients. Methods: All patients diagnosed with mCRC from 2006 to 2007 and referred to any 1 of 5 regional cancer centers in British Columbia, Canada were reviewed. Summary statistics were used to describe treatment patterns between elderly patients (EP; >/=70 years) and young patients (YP; <70 years). Cox regression models that adjusted for age and confounders were used to determine the effect of systemic therapy on overall survival (OS). Results: We identified 1,013 patients: median age was 67 years (range 23-93); 42% were elderly and 58% were young; 57% were men; and 66% had ECOG 0/1. Compared to YP, fewer EP were offered systemic therapy (46 vs 76%, p<0.001). Among those treated, EP were less likely than YP to be given combination chemotherapy (47 vs 81%, p<0.001) and bevacizumab (19 vs 47%, p<0.001). Most common reasons for no treatment were similar in EP and YP: patient choice (32% for both), poor ECOG (18% of EP and 16% of YP), and significant comorbidities (11% for both). Advanced age alone was also cited as a reason among EP (7%) for not receiving therapy. In the subset that was treated, risk of adverse events (24 vs 14%, p=0.24) and early treatment discontinuations (14 vs 13%, p=0.88) were comparable between EP and YP, respectively. Receipt of systemic therapy was associated with improved OS in both the elderly (HR for death 0.45, 95% CI 0.37-0.56, p<0.001) and the young (HR for death 0.43, 95% CI 0.35-0.53, p<0.001), regardless of age (p interaction of age and treatment >0.05). Conclusions: In this population-based cohort of mCRC, EP were more likely to receive no treatment, monotherapy rather than combination therapy, or a regimen without bevacizumab. In carefully selected EP, however, it appears that rate of adverse events, frequency of early treatment discontinuations, and magnitude of survival benefit from systemic therapy were comparable to YP.
Efficacy and safety data from elderly patients with pretreated advanced melanoma in the Italian cohort of ipilimumab expanded access programme (EAP).
Authors: Chiarion-Sileni Vanna , Pigozzo Jacopo , Ascierto Paolo Antonio , Maio Michele , Danielli Riccardo , Del Vecchio Michele , Ridolfi Laura , De Galitiis Federica , Testori Alessandro , Cocorocchio Emilia , Cognetti Francesco , Ferraresi Virginia , Bernengo Maria Grazia , Guida Michele , Antonuzzo Andrea , Mandala Mario , Parmiani Giorgio , Vanella Vito , Aglietta Massimo , Queirolo Paola
Published: March 2020

9548

Background: Ipilimumab was the first agent approved for the treatment of unresectable or metastatic melanoma that showed an overall survival benefit in randomised phase III trials. Here we evaluate the safety and efficacy of ipilimumab treatment outside of clinical trials in elderly (>70 years old) patients (pts) enrolled in the EAP in Italy. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Disease evaluation was performed at baseline and after completion of induction therapy using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, using Common Terminology Criteria for Adverse Events v.3.0. Results: Out of 855 Italian pts participating in the EAP from June 2010 to January 2012 across 55 centres, 193 (22.6%) were over 70 years old (median 75; 70-88). Of these, 132 pts (68.4%) received all 4 doses of ipilimumab, 24 (12.4%) 3 doses, 17 (8.8%) 2 doses and 20 pts (10.4%) received 1 dose. With a median follow-up of 7.6 months (range 1-26), the disease control rate among 188 pts evaluable for response was 38.3%, including 4 pts (2.1%) with a complete response, 24 (12.8%) with a partial response and 44 (23.4%) with stable disease. As of December 2012, median progression-free survival and overall survival were 3.7 months and 8.9 months respectively, with 1-year survival rate of 38%. In total, 96 pts (49.7%) reported an AE of any grade, which were considered treatment-related in 69 pts (35.7%), with a safety profile comparable to the general population. Grade 3/4 AEs were reported by 19 pts (9.8%) and drug-related in 11 pts (5.7%). AEs were generally reversible with treatment as per protocol-specific guidelines with a median time to resolution of 2.0 weeks. Conclusions: Based on the data from EAP, ipilimumab is a feasible treatment in the elderly population; efficacy and safety results were similar to those observed in the general population.
Identification of comprehensive geriatric assessment based risk factors for malnutrition in elderly Asian patients with cancer.
Authors: Tan Tira Jing Ying , Ong Whee Sze , Koo Khai-Nee , Tan Iain B. , Poon Donald , Kanesvaran Ravindran
Published: March 2020

9552

Background: Elderly patients with cancer are at increased risk for poor nutrition. Malnutrition is associated with increased morbidity and mortality. There is limited information on the clinical risk factors for malnutrition in elderly Asian cancer patients. We aim to identify comprehensive geriatrics assessment (CGA) based clinical factors in elderly Asian cancer patients associated with an increase in malnutrition risk. Methods: CGA data was collected from 249 Asian patients aged 70 years or older who attended the outpatient oncology clinics at the National Cancer Centre Singapore. Nutritional status, one of the seven domains of CGA, was assessed based on the DETERMINE nutritional risk index. Univariate and multivariate logistic regression analyses were applied to assess the association between patient clinical factors together with domains within the CGA and moderate to high nutritional risk. Goodness of fit was assessed using Hosmer-Lemeshow test and discrimination ability assessed based on the area under the receiver operating characteristics curve (AUC). Internal validation was performed using simulated datasets via bootstrapping. Results: Among the 249 patients, 184 (74%) had moderate to high nutritional risk. Multivariate logistic regression analysis identified stage 3–4 disease (Odds Ratio [OR] 2.54; 95% CI, 1.14-5.69), ECOG performance status of 2-4 (OR 3.04; 95% CI, 1.57–5.88), presence of depression as measured by geriatric depression scale (OR 5.99; 95% CI, 1.99-18.02) and haemoglobin levels <12 g/dL (OR 3; 95% CI 1.54-5.84) as significant independent factors associated with moderate to high nutritional risk. The model achieved good calibration (Hosmer-Lemeshow test’s p = 0.17) and discrimination (AUC = 0.80). It retained good calibration and discrimination (bias-corrected AUC = 0.79) under internal validation. Conclusions: Having advanced stage of cancer, poor performance status, depression and anaemia were found to be independent predictors of moderate to high nutritional risk. Early identification of patients with these risk factors will allow for nutritional interventions which may improve treatment tolerance, quality of life and survival outcomes.
Best supportive care (BSC) in published clinical trials.
Authors: Abernethy Amy Pickar , Nipp Ryan David , Currow David , Cherny Nathan , Strasser Florian , Zafar Yousuf
Published: March 2020

9560

Background: BSC as a control arm in clinical trials is poorly defined. A systematic review was conducted to evaluate clinical trial concordance with published, consensus-based framework for BSC delivery in trials. Methods: A consensus-based Delphi panel previously identified 4 key domains of BSC delivery in trials: multidisciplinary care; supportive care documentation; symptom assessment at least as often as the intervention arm; and guideline-based symptom management. A systematic review of trials including BSC control arms assessed BSC concordance to the consensus-based domains. Databases were searched from 2002-2012 using search strings: “cancer”; “best supportive care”; “randomized” or “random allocation”; and “supportive” or “palliative.” Exclusion criteria were: no BSC arm, non-human trial, not randomized, not English, not advanced cancer, or not including anticancer therapy. Data were independently extracted by 2 reviewers and scored by 4 reviewers for conformance with consensus-based BSC framework. Results: 373 articles were retrieved, 17 retained after applying exclusion criteria. Overall, trials conformed to <18% of the consensus-based BSC standards. 35% of articles offered a detailed description of BSC. 65% reported baseline and regular symptom assessment, and 47% reported using validated symptom assessment measures. 35% reported symptom assessment at identical intervals in both experimental and BSC arms. None listed an evidence-based guideline for symptom management. None of the multicenter trials reported standardization of BSC across sites. No studies reported educating patients on symptom management or goals of anti-cancer therapy. No studies reported offering access to palliative care specialists, social workers, financial or spiritual counseling. Conclusions: Reporting of BSC in trials is incomplete, resulting in uncertain internal and external validity. Such poorly defined interventions and variation between sites is unacceptable for other aspects of a clinical trial. Unless it is truly best supportive care, such studies may risk systematically over-estimating the clinical effect of the comparator arms. Standardization of a BSC delivery framework is needed to improve trial design and data generalization.
Long-term use of fentanyl pectin nasal spray in patients with breakthrough pain in cancer.
Authors: Taylor Donald , Radbruch Lukas , Revnic Julia , Torres Luis M. , Ellershaw John E , Perelman Michael Sidney
Published: March 2020

9563

Background: Given that patients with cancer are living longer, there is a need to ensure that treatments used for palliative care are well tolerated and effective during long-term use. The objective of this study was to investigate the use of fentanyl pectin nasal spray (FPNS) for the treatment of breakthrough pain in cancer (BTPc) in patients taking regular opioid therapy. Methods: A total of 401 adult patients, taking at least 60 mg/day oral morphine or equivalent, with an average of 1 to 4 episodes of BTPc per day, who were either newly enrolled or had completed a randomized controlled trial with FPNS, entered into an open-label assessment study (NCT00458510). Of these, 171 patients, continued into an extension period. Up to 4 episodes of BTPc per day were treated with FPNS at titrated doses between 100 µg and 800 µg. Patients returned to the clinic at 4-week intervals for assessment and reporting of any adverse events (AEs). Results: There were 163 patients with documented FPNS use. The mean duration of use was 325 days; 46 patients used FPNS for more than 1 year, while the maximum duration was 3 years and 8 months. In total, 2% of patients withdrew from the study due to lack of efficacy. Seventy-four percent of patients did not change their FPNS dose. The most common AEs, aside from disease progression, were: insomnia, 9.9%; nausea, 9.4%; vomiting, 9.4%; and peripheral edema, 9.4%. The overall incidence of treatment-related AEs was 11.1%, the most common being constipation (4.1%), with no apparent dose relationship. Ten patients (5.8%) experienced treatment-related nasal AEs, which, with the exception of 1 severe event, were all mild or moderate. Conclusions: FPNS appeared to provide a sustained benefit and was well tolerated during the long-term treatment of BTPc. Clinical trial information: NCT00458510.
Attitudes regarding privacy of genomic information in personalized cancer therapy.
Authors: Rogith Deevakar , Yusuf Rafeek Adeyemi , Hovick Shelly Renee Anstey , Peterson Susan K. , Burton-Chase Allison Michelle , Li Yisheng , Meric-Bernstam Funda , Bernstam Elmer Victor
Published: March 2020

9576

Background: Cancer therapy is increasingly personalized to the molecular characteristics of a particular patient and his/her tumor. Patients and providers express interest in personalized therapy yet concerns regarding the privacy of genomic data have been raised, particularly in the context of research. We evaluated patients’ attitudes regarding privacy of genomic data. Methods: Newly registered female breast cancer patients at MD Anderson Cancer Center were invited to participate. Of 308 consecutive patients approached, 100 completed a survey assessing attitudes regarding association of personal identifying information with genomic data, risks for potential insurance and employment discrimination based on genomic information, and willingness to share genomic data (32% response rate). Results: Most patients (83%) indicated that genomic data should be protected. However, only 13% endorsed concern regarding genomic data privacy, measured using a composite scale (α= 0.92). Patients expressed more concern about insurance discrimination than employment discrimination (43% vs. 28%, p<0.001), and these two variables were highly correlated (χ2=32.7, p<0.001). Patients expressed greater trust in research institutions like MD Anderson to protect the security of their molecular data compared with government agencies or drug companies (80% vs. 63% vs. 56%; p < 0.001). Most did not endorse concern regarding association of their genomic data with their name and identities (51%), billing and insurance (56%), or clinical data (73%). Patients were more willing to share de-identified data than identified data with researchers other than their treating physicians (p<0.001). 36% of patients were willing to share identified data with any MD Anderson researcher and 14% with any cancer researcher. Conclusions: Patients generally expressed low levels of concern regarding privacy of genomic data. Cancer patients may recognize the clinical and research value of genomic testing and a significant proportion are willing to share their genomic data with researchers.
Correlations of patient-reported measures (PRM) for health, quality of life (QOL), functional status, and social supports with survival in early-stage colon cancer.
Authors: Chen Annie , Hsu Tina , Kennecke Hagen F. , Lai Anky , Chen Leo , Speers Caroline , Woods Ryan , Cheung Winson Y.
Published: March 2020

9577

Background: PRM can enhance our understanding of patients’ needs and facilitate cancer treatment decision making. Few studies have explored the relationships between brief PRM and outcomes in early stage colon cancer. Our aims were 1) to determine the effects of prospectively collected PRM on cancer-specific (CSS) and overall survival (OS) and 2) to examine if this association is modified in the elderly. Methods: Patients diagnosed with stage 1 to 3 colon cancer in 2008, evaluated at 1 of 5 regional cancer centers in British Columbia, and provided baseline PRM were included. PRM consisting of a series of short, self-administered scales that described patient-reported health, QOL, functional status and social supports were collected at baseline and correlated with CSS and OS using regression models that controlled for known prognostic factors such as tumor and nodal stage. We subsequently assessed for effect modification by age, stratifying the cohort into younger (YP; <70 years) and elderly patients (EP; >/=70 years). Results: In total, 223 patients were included: 94 (42%) were EP, 111 (49%) were women, and 152 (68%) were white. Compared to YP, EP were more frequently widowed (27 vs 9%, p=0.0005) and reported having children (92 vs 81%, p=0.03), but they were less likely to receive chemotherapy (57 vs 90%, p<0.0001). There were no significant differences in PRM based on age, with the majority indicating they had regular contact with family and friends (92%) and many describing good overall health, QOL, and functional status (48, 61, and 69%, respectively). However, a significant proportion wished for more emotional support (54%). In regression models, self-reported poor functional status was associated with worse OS (HR 2.69, 95%CI 1.09-6.65), but not CSS (HR 1.74, 95%CI 0.61-4.94). This did not differ significantly between YP and EP (p interaction >0.05). No other PRM correlated with OS or CSS (all p>0.05). Conclusions: For early stage colon cancer, self-reported functional status was independently associated with OS. Additional PRM failed to enhance prognostication, suggesting that more comprehensive tools may be required to improve patient assessments.
Role of religiosity in medical decision making among patients with colorectal cancer.
Authors: Surati Mosmi , Davis Rachel , Hawley Sarah T. , Abrahamse Paul , Ward Kevin C. , Kato Ikuko , Morris Arden M.
Published: March 2020

9579

Background: Physician-based medical decision making (DM) has declined in favor of more patient-centered approaches. Most studies indicate that patients want to be involved; however, the level of desired involvement varies between patients wanting to make their own decisions and those preferring to leave decisions to physicians. Little is known of the factors associated with DM preferences. Given data demonstrating the influence of religion among cancer patients, we explored religiosity and decision making preferences in colorectal cancer (CRC) patients. Methods: We surveyed a population-based cohort of Stage III CRC patients from the Detroit and Georgia SEER registries. Patients were queried about desired level of involvement in DM, trust in physicians, religiosity, receipt of adjuvant chemotherapy, and demographics. Religiosity was assessed using the Holland System of Belief Inventory. Physician trust was assessed using the Wake Forest Physician Trust scale. Responses were collected along a Likert scale and results were dichotomized. Surveys were analyzed using univariate and bivariate methods. Results: Thus far, 430 CRC patients have responded (56% response rate). The median participant age is 61 years, 45% are female, and 19% are black. 54% indicated a preference for shared DM, 35% prefer “doctors to make [their] decisions”, and 11% prefer to “make [their] own decisions”. The distribution did not differ by age, gender, race, income, or level of education. Higher religiosity was associated with higher trust in the surgeon (p=0.007) but not the oncologist (p=0.3). Patients with higher religiosity scores and higher physician trust were more likely to prefer that their doctors make the decisions (p= 0.023, p<0.001). Preference for physician DM was associated with higher receipt of adjuvant chemotherapy (p=0.002). Conclusions: Patients who were more religious preferred to leave medical DM to physicians. Those who relied on physician DM were more likely to receive chemotherapy. This association may be mediated through higher trust. Understanding the influence of religiosity may be a tool to help providers get their patients appropriate cancer care.
Risk and predictors of suicide in colorectal cancer patients: A SEER analysis.
Authors: Samawi Haider , Shaheen Abdel Aziz , Tang Patricia , Heng Daniel Yick Chin , Cheung Winson Y. , Vickers Michael M.
Published: March 2020

9596

Background: Colorectal cancer (CRC) patients have a higher risk of suicide as compared with the general population. Due to differences in the sites/morbidity of recurrences as well as ostomy rates, we sought to evaluate the distribution and predictors of suicide among patients with colon and rectal cancer. Methods: A retrospective analysis was undertaken using the Surveillance, Epidemiology, and End Results (SEER) database from 1973-2009. Patients included were >18yrs and had confirmed adenocarcinoma of the colon or rectum. Results: Included in this analysis were 187,996 rectal cancer and 443,368 colon cancer patients. Colon cancer patients were older (median age 71 vs. 67 yrs, p <0.001) and included more females (51 vs. 43%, p <0.001) as compared to rectal cancer patients. Suicide rates were similar (611 [0.14%] vs. 337 [0.18%], p <0.001), as was the median time to suicide for colon vs. rectal cancer patients respectively (37 vs.32 months, p = 0.13). On univariate analysis, having rectal cancer was a predictor of suicide (HR 1.26; 95% CI: 1.10-1.43). However after adjustment for age, sex, race, marital, primary site surgery, stage and one primary, rectal cancer was not a predictor of suicide (HR 1.05; CI: 0.83- 1.33). In the combined CRC cohort, independent predictors of suicide included age >70 (HR 1.55; CI: 1.23-1.94), male gender (HR 7.56; CI: 5.34-10.70), being single (HR 1.56; CI: 1.14- 2.13), distant metastases at diagnosis (HR 1.58; CI: 1.13- 2.21), and white race (HR 3.21; CI: 1.75- 5.88). Also, lack of resection of primary tumor was associated with increased risk of suicide (HR 2.83; CI: 1.97- 4.05). Among colon cancer cohort, older age, male gender, and white race as well as lack of primary resection were independent predictors of suicide. Similarly, the aforementioned predictors as well as metastatic disease on presentation were the independent predictors of suicide in the rectal cohort. Conclusions: The suicide risk in CRC patients is low (< 0.2%) and no difference was found based on location of primary tumor. Gender, age, distant spread of disease, intact primary tumour and race are the main predictors of suicide among colorectal patients. Future studies and interventions are needed to target these high risk groups.
Racial and ethnic variation in employment and financial experiences of breast cancer survivors.
Authors: Jagsi Reshma , Pottow John A.E. , Griffith Kent A. , Hamilton Ann S. , Graff John , Katz Steven J. , Hawley Sarah T.
Published: March 2020

9601

Background: Concerns exist regarding the employment and financial experiences of cancer survivors and whether they differ by race/ethnicity. Methods: In a longitudinal survey of women reported to the Los Angeles and Detroit SEER registries for nonmetastatic breast cancer, we compared experiences of 4-year survivors by race/ethnicity. Results: Overall, 31% of 1,536 respondents (68% response rate) felt their financial status was worse since diagnosis (63% attributed this to breast cancer). This varied by race/ethnicity: 41% of Spanish-speaking Latinas (SSL), 33% English-speaking Latinas (ESL), 23% blacks (B), and 29% whites (W), p<0.001. The median respondent had spent ≤$2000 on breast cancer medical expenses; 16% had spent >$5000. 12% had medical debt 4 yrs post-diagnosis: 17% of ESL, 14% B, 10% SSL, and 9% W (p=0.01). Minority respondents were more likely to report foregoing medical care due to cost and other privations due to their medical expenses (Table). Overall, 14% felt their employment status was worse since diagnosis, and 61% of these attributed this to breast cancer. 755 worked for pay some time after diagnosis, of whom 56% said it was at least somewhat important to work to keep health insurance (55% of SSL, 65% ESL, 65% B, 50% W, p=0.03); 24% would look for a new job if assured of comparable benefits (45% of SSL, 29% ESL, 22% B, 17% W, p<0.001); 7% had increased work hours to cover cancer-related expenses; 27% had decreased work hours due to cancer-related health issues; and 7% believed they had been denied job opportunities because of cancer. Conclusions: In this population-based sample of breast cancer survivors, job lock was common, and many women perceived being worse off with respect to finances and employment as a result of their breast cancer. Medical debt and privation varied significantly by race/ethnicity. [Table: see text]
Pain sensitivity and aromatase inhibitor (AI)-associated arthralgias (AIAA).
Authors: Henry Norah Lynn , Harte Steven , Conlon Anna S.C. , Griffith Kent A. , Ramirez Gabriela , Hayden Jill , Smerage Jeffrey B. , Schott Anne F. , Hayes Daniel F. , Williams David A. , Clauw Daniel A
Published: March 2020

9615

Background: AIAA affect up to half of AI-treated women with early stage breast cancer, and can lead to treatment discontinuation in 20-30%. The etiology is thought to be related to estrogen deprivation although the mechanism is unknown. In premenopausal women, lower estrogen levels have been associated with increased pain. Impaired descending pain inhibitory pathways, which may be a risk factor for developing chronic pain, have also been associated with lower estrogen levels. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AIAA. Methods: Fifty postmenopausal women with early stage breast cancer initiating AI therapy were enrolled to the study. Subjects underwent experimental pressure pain testing and conditioned pain modulation (CPM) assessment and completed symptom questionnaires prior to AI initiation and after 3 months. Positive CPM values (>0) signify impaired descending pain inhibition. Serum estradiol concentrations were determined using an ultrasensitive assay. T-tests, Fisher’s exact test, and linear regression models were used to assess associations among baseline (BL) experimental pain measures, patient-reported pain, and clinical factors. P values <0.05 were considered statistically significant. Results: All subjects had decreased serum estradiol concentrations with AI therapy. No statistically significant change in pressure pain threshold or CPM with AI therapy was detected. In addition, no association between change in patient-reported pain with AI therapy and change in pain threshold or CPM was identified. Patients demonstrated impaired CPM at baseline (mean 8.0, SD 14.9), and this impairment was greater in patients previously treated with chemotherapy 14.4 vs 2.0, p=0.006), with non-significant trends towards this being more pronounced in those with more severe pain. Conclusions: AI therapy did not impact pressure pain threshold or CPM, suggesting that AIAA is not likely due to pain amplification from estrogen depletion. Studies examining chemotherapy-induced changes in pain processing are needed to better understand how these alterations might contribute to the pain that these patients often develop.
Randomized double-blind placebo-controlled trial of celecoxib for radiation-induced oral mucositis.
Authors: Lalla Rajesh V. , Choquette Linda E. , Curley Kathleen F. , Dowsett Robert J. , Feinn Richard S. , Hegde Upendra P. , Pilbeam Carol C. , Salner Andrew L. , Sonis Stephen T. , Peterson Douglas E.
Published: March 2020

9620

Background: Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck (H&N) cancer. OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Due to the role of inflammatory pathways in the pathogenesis of OM, this study investigated the effect of inhibition of cyclooxygenase-2 (COX-2) on severity and morbidity of OM. Methods: In this randomized double-blind placebo-controlled trial,40 H&N cancer patients were randomized to daily use of 200 mg celecoxib or matched placebo, for the duration of RT. Eligibility criteria included planned RT dose of ≥ 5000 cGy to 2+ areas of the mouth and no contraindication for celecoxib use. The planned sample size of 20 per arm provided 80% power to detect a 1 point difference in mean Oral Mucositis Assessment Scale (OMAS) score (range 0-5) at 5000 cGy RT (primary endpoint), applying a two-tailed, two-sample t-test at the 5% level of significance. Clinical OM, normalcy of diet, pain scores and analgesic use were assessed 2-3 times a week by blinded investigators during the 6-7 week period of RT, using validated scales. Results: Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over the course of RT. Intent-to-treat analyses demonstrated no significant difference in mean (SD) OMAS scores at 5000 cGy [celecoxib 1.32 (0.71), placebo 1.27 (0.86), p = 0.83, two sample t-test]. There was also no difference between the celecoxib and placebo arms respectively, in mean OMAS scores over the period of RT (SD) [0.98(0.77) & 0.97 (0.86), p = 0.84], mean worst pain scores [3.38 (3.07) & 3.31 (3.32), p = 0.83], mean normalcy of diet scores [5.43 (3.86) & 5.11(3.94), p = 0.65], or mean daily opioid medication use in IV morphine equivalents [19.08 (16.57) & 20.48 (19.07), p = 0.48], all by linear mixed model fixed effects regression analysis. There were no SAEs attributed to celecoxib use. Conclusions: Daily use of a selective COX-2 inhibitor, during the period of RT for H&N cancer, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. Clinical trial information: NCT00698204.
A genetic variant of 5-hydroxytryptamine receptor 3C (HTR3C): A novel link to chemotherapy-induced side effects.
Authors: Rubinek Tami , Pud Dorit , Har-Zahav Gil , Symon Zvi , Laitman Yael , Wolf Ido
Published: March 2020

9630

Background: Symptom clusters are defined as three or more concurrent symptoms that are related to each other. Clusters may stem from common physiological mechanisms and may better represent adverse effects to chemotherapy compared to individual symptoms. We aimed to identify association between the experience of symptom clusters and specific genetic alterations. Methods: Study population consisted of 108 breast cancer patients who received over two cycles of adjuvant doxorubicin and cyclophosphamide (AC) treatment at the oncology institute of the Sheba Medical Center. Participants completed the Memorial Symptom Assessment Scale, the Lee Fatigue Scale and the Center for Epidemiological Studies Depression Scale. Hierarchical cluster analysis was used to identify patients' subgroups based on their symptom experience. For the genetic analyses, DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) of candidate genes were tested using restriction endonuclease assays. Results: Two distinct subgroups were identified based on severity of fatigue, depression, nausea, and change in food tastes: "all high" (n=79) and "all low" (n=29) level of all symptoms. As patients did not have active cancer, symptoms were attributed solely to chemotherapy. A genetic variant of HTR3C (rs6766410) results in a substitution of asparagine to lysine (N163K) may be associated with nausea and vomiting. We tested the association between this variant and symptom score. 51 of 75 (68%) patients with high symptom score harbored the variant allele, compared to 13 of 28 (46%) of those with low symptom score (p=0.038). Conclusions: Analysis of genetic background of clusters, rather than for individual symptoms, represents a novel approach for the study of chemotherapy-induced side effects. This approach enabled the identification of HTR3C variant as a possible mediator of side effects following treatment with AC. Discovering the genetic basis of symptom clusters may lead to the development of novel diagnostic and therapeutic modalities able to improve symptom management. This may translate to improved outcome among chemotherapy-treated cancer patients.
Treatment of depressive symptoms in breast cancer patients undergoing adjuvant therapy.
Authors: Navari Rudolph M.
Published: March 2020

9631

Background: Studies have shown a high prevalence of depression in patients with cancer. Women with breast cancer may have a high risk of depression particularly in a post-menopausal or estrogen deficient state and may develop a high level of depressive symptoms at the time of initial diagnosis. Newly diagnosed early stage breast cancer patients were screened for depressive symptoms prior to the initiation of adjuvant therapy. The oral antidepressant fluoxetine was studied to determine if its use affected depressive symptoms, completion of adjuvant treatment, quality of life, and survival. Methods: Patients with newly diagnosed early stage breast cancer were screened for depressive symptoms prior to the initiation of adjuvant therapy. Patients with depressive symptoms were randomized in a double blind fashion to daily oral fluoxetine (20 mg) or placebo. Patients were then followed for 6 months and evaluated for quality of life, completion of adjuvant treatment, and depressive symptoms. Patients with stage I disease at the time of initial diagnosis were subsequently assessed for disease recurrence and survival at five years. Results: Two hundred three of 357 screened patients with newly diagnosed early stage breast cancer were found to have depressive symptoms prior to the initiation of adjuvant therapy. One hundred ninety-three patients were randomized to fluoxetine or placebo. The use of fluoxetine for 6 months resulted in a significantly (p<0.01) higher number of patients with an improvement in quality of life, a higher completion of adjuvant treatment (chemotherapy, hormonal therapy, chemotherapy plus hormonal therapy) and a reduction in depressive symptoms compared to patients who received placebo. At five years, there was a significant (p<0.01) improvement in survival for patients with Stage I disease who received fluoxetine, possibly related to a higher completion of adjuvant treatment. Conclusions: An antidepressant should be considered for early stage breast cancer patients with depressive symptoms who are receiving adjuvant treatment.
Incidence of osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases from solid tumors or multiple myeloma: Results from three phase III trials.
Authors: Lipton Allan , Saad Fred , Van Poznak Catherine H. , Brown Janet Elizabeth , Stopeck Alison , Fizazi Karim , Henry David H. , Shore Neal D. , Diel Ingo J. , Tonkin Katia Sonia , De Boer Richard H. , Wang Huei , Braun Ada H.
Published: March 2020

9640

Background: In patients with metastatic bone disease (MBD), the use of antiresorptive therapies such as denosumab or zoledronic acid (ZA) reduces the risk of skeletal-related events but is associated with a small risk of osteonecrosis of the jaw (ONJ). Two phase 3 clinical trials of denosumab vs ZA in patients with MBD showed overall cumulative ONJ incidences to be 3.8% to 4.7% at approximately 5 years of treatment with denosumab across blinded and open-label extension phases. ONJ associated with ZA was only assessed in the blinded treatment phases, as patients switched to denosumab once superior efficacy was demonstrated. Here we report incidence rates of ONJ by first vs subsequent years of exposure for the blinded treatment phase of all three phase III clinical trials. Methods: Patients (n = 5,677) with bone metastases from solid tumors or multiple myeloma received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the double-blinded treatment phase of each trial. Patients who received ≥ 1 active dose during the blinded treatment phase were included in this analysis for up to 44.5 months of denosumab exposure and 41.3 months of ZA exposure. Oral assessments were conducted at baseline and every 6 months thereafter by the investigator or other qualified examiner. Potential ONJ events were independently adjudicated by a blinded committee of experts. Results: The median (Q1, Q3) time to onset of ONJ was similar in both treatment groups (15.6 [9.5, 20.0] months for denosumab, 15.8 [11.0, 23.6] months for ZA). Cumulative incidence rates of ONJ during the blinded treatment phases for all three trials by patient-years of follow-up are shown below (Table). Conclusions: The incidence of ONJ increased with longer duration of antiresorptive exposure. There were no significant differences between treatment groups in ONJ incidence at year 1 or beyond. Clinical trial information: NCT00321464; NCT00330759; NCT00321620. [Table: see text]
The efficacy of subclinical lymphedema detection in high-risk breast cancer survivors.
Authors: Soran Atilla , DeGore Lori , McGuire Kandace P. , Bonaventura Marguerite , McAuliffe Priscilla F. , Diego Emilia , Ahrendt Gretchen M. , Johnson Ronald
Published: March 2020

9643

Background: Lymphedema (LE) is associated with profound functional, psychosocial and medical consequences. Early intervention may decrease morbidity from LE. Bioimpedance spectroscopy (BIS) allows subclinical diagnosis by detecting subtle differences in extracellular fluid volume between the limbs. In our lymphedema program, we prospectively monitor BIS in patients (pts) undergoing axillary lymph node dissection (ALND). The aim of this study is to investigate whether early diagnosis of LE after ALND using BIS can allow early intervention. Methods: BIS in the “Pre-Operative Group,” measurements using L-Dex U400 were obtained pre-operatively (n=123) and at 3-6 month intervals thereafter. In the “Follow-up Group" pts who had ALND previously (n=89) had baseline measurements and monitoring at the same intervals. Age, BMI, dominant hand use, side of ALND, type of breast surgery, receipt of radiation therapy, and number of LN removed were recorded. L-Dex values > 10 units or increase > 10 units above the initial measurement was treated with LE education, an over-the-counter compression sleeve, less intensive physical therapy sessions and daily exercise. Results: The mean age was 58 (27-90). The mean BMI was 28.5 (17.1-65.7)kg/m2. ALND was on the side of the dominant hand in 56% of pts (n=119). The mean number of LNs removed was 16 (5-49). The majority of pts underwent mastectomy (59%; n=126), 73% (n=55) received RT, and 80% (n=191) received neo- or adjuvant chemotherapy. 87 pts (41%) were followed for more than 1 year from initial measurement. Since the monitoring began, 18% (n=22) in the Preoperative Group and 23% (n=20) in the Follow-up group were diagnosed with subclinical LE and received early intervention. 41 pts (97.6%) remain stable with no worsening of LE 1 yr after diagnosis. One pt advanced to stage 2 LE but declined further monitoring at 6 mo. Conclusions: Subclinical detection of LE with BIS and timely intervention reduced the incidence of late-stage LE among women undergoing ALND to <3% compared with historical incidence of >25%. Periodic monitoring of women at high risk for LE can minimize costly and intensive LE treatment such as custom made sleeves, pump and surgery while anticipating elimination of more advanced LE.
Hepatotoxicity with chemotherapy in patients infected with hepatitis B virus.
Authors: Szpakowski Jean-Luc , Tucker Lue-Yen , Pauly Mary Pat , Nanfro John , Hwang David , Baer David M.
Published: March 2020

9645

Background: Patients with chronic hepatitis B virus infection (HBV) are at risk for hepatotoxicity (HT) from viral reactivation during chemotherapy courses (TC). This can be minimized with antiviral prophylaxis (AV). Screening for HBV before TC remains controversial. Methods: A retrospective observational data only study was conducted at a Northern California integrated health care delivery system examining patients undergoing TC between 2000 and 2010. Patients were categorized as HBV positive (HBV+) if they had a positive HBsAg, HBeAg, or HBV DNA any time before and 1 year post TC. Grade 3 and 4 HT was determined using the National Cancer Institute Common Toxicity Criteria, with adaptation for those who had baseline abnormal liver function tests. We excluded patients with HIV, co-infection with both HBV and hepatitis C, and HBsAb of unclear provenance. Two control groups (CTRL1 and CTRL2) were established that had tested negative for HBV and HCV 1996 through 1 year after the last TC: CTRL1 tested negative for both before TC initiation (index TC); CTRL2 tested negative for one pre and the other post index TC or both at any time after index TC. AV prophylaxis (AVP+) was defined as anti-HBV medication given before HT; the remainder were AVP-, including those given AV after HT. Electronic medical record review was conducted on all HBV+ patients. Results: We identified 9,279 patients who received 15,960 TC; 57.8% were female with a mean age of 57.8 (±14.4) at TC initiation. 464 TC were given to 289 HBV+ patients; 22.8% had HT, with 7 deaths from HT, all AVP-. The rate of HT in the controls was 9.9% in CTRL1 (34/343), 12.6% in CTRL 2 (1907/15,153). Conclusions: These findings support the recommendation that all patients planning to receive TC should be screened for HBV. Those found positive should receive AV prophylaxis during therapy. [Table: see text]
Chemotherapy-induced peripheral neuropathy in multiple myeloma patients undergoing maintenance therapy.
Authors: Shi Qiuling , Wang Xin Shelley , Reuben James M. , Cohen Evan N. , Williams Loretta A. , Mendoza Tito R. , Sailors Mary L , Ilagan Venus M , Cleeland Charles S.
Published: March 2020

9646

Background: After 3-months autologous stem cell transplant (AuSCT), a percentage of multiple myeloma (MM) patients during maintenance therapy continue to experience a complex of symptoms related to peripheral neuropathy. This longitudinal study examined these self-reported neuropathy symptoms and identified circulating inflammatory markers associated with high neuropathy-related symptoms. Methods: MM patients (N=51) rated symptom severity on 0-10 scale via the M. D. Anderson symptom Inventory (MDASI) weekly from 3 to 9 months post AuSCT during maintenance therapy. Patient also rated pain on hand or foot in routine clinic visit. A panel of pro- and anti-inflammatory cytokines, receptors, chemokines was evaluated on serum samples by Luminex. Mixed effect analysis was used to describe the changes on cytokines and symptom outcomes across time. Trajectory analysis identified patients that persistently reported higher or lower symptom severity overtime. Results: During the study period, there was no significant reduction on pain in general or on hand/foot, or change in neuropathic symptoms such as numbness/tingling and muscle weakness. Among a third (33%) of patients who was consistently in high pain (mean 5.5), MIP-1a (p=.001) and MCP-1 (p=.032) showed significant decrease. Approximately 40 % had persistently high numbness/tingling (mean 5.2) across the observation period. Compared to low symptom group patients, this high numbness group had significantly higher IL-6 (p=.019) and TNF-alpha (p=.006). High muscle weakness (mean 3.1) was for 69% of the sample. This group had significantly higher CRP (p=.005) and TNF-alpha (p=.001). Conclusions: This is the first longitudinal study that tracked persistent neuropathy-related symptoms for MM patients post AuSCT. Approximately one third reported painful neuropathy, either from induction therapy or ongoing maintenance therapy. High levels of these neuropathy symptoms were associated with higher levels of specific pro-inflammatory markers. This study provided rationale for examining the effectiveness of anti-inflammation as mechanism driven intervention on peripheral neuropathy in this cohort of MM patients.
HER2/neu status in primary breast cancer and in metastatic site as detected using FNA.
Authors: Giotta Francesco , Asselti Maria Consilia , Petroni Stella , Popescu Onsina , Rubini Vincenza , Latorre Agnese , Lorusso Vito , Gadaleta Cosimo , Simone Giovanni
Published: March 2020

e11502

Background: As for hormonal receptor (ER, PgR), also human epidermal growth factor receptor-2 (HER-2) expression in breast cancer primitive tumor (PT) could be different from that of metastatic site (MS). These differences arise some questions about clinically useful information given and accuracy of methods to detect biological features. Fine Needle Aspiration (FNA) of metastatic sites could be an available tool to characterize biologic pattern of lesions, using immunocytochemical and/or molecular assay. The aim of the study is to compare prognostic and predictive factors obtained from PT and corresponding MS. Methods: Thirty-eight consecutive metastatic breast cancer patients underwent FNA on metastatic sites in order to re-evaluate receptor status, proliferative activity and HER-2/Neu amplification. In MS the material was achieved using FNA with a 21-23 G needle and obtaining monolayer and the corresponding cito-inclusion. MS were localized in liver (21), lung (8) and distant lymph-nodes (9). ERs, PgRs and Ki-67 were detected in both PT and MS, in 38 cases by immunochemistry, whereas HER-2/Neu amplification was detected on citoinclusion in 35 evaluable cases by FISH. Results: ERs, PgRs and Ki-67 were detected in both PT and in MS, in 36, 34, 25 out of 38 cases respectively, showing a significant loss of hormonal receptors and a decreased proliferative activity in MS versus PT (t-test p: 0.0195, <0.0001 and 0.0120 respectively). Regarding to HER-2/Neu amplification, 28 out of 35 evaluable cases were not amplified while 6 were amplified both in PT and in MS (Pearson Test: r=0.9 p: <0.0001). Another case, HER/Neu amplified in TP, after therapy with trastuzumab resulted not amplified in MS. Conclusions: According to other authors, our data demonstrated that the lost of HER/Neu amplification in MS is a possible event and that FNA samples of MS are available for HER/Neu detection.
Breast cancer in the elderly.
Authors: Erdem Dilek , Yilmaz Bahiddin , Cilingir Fatih Mehmet , Kocasarac Selim , Teker Fatih , Gonullu Guzin , Yucel Idris
Published: March 2020

e11506

Background: Breast cancer is one of the age-related tumors that accompany with population ageing and approximately 50 % of this disease occur in 65 years of age or older and also more than 30 % occur after age of 70. This study aims to examine characteristics of patients with breast cancer 65 years or older. Methods: The study was carried out on a series of 177 breast cancer patient followed up at our outpatient clinic who are 65 years or older chosen among 848 breast cancer patients during the period 1995-2012. Physical examination, annual chest x-ray, mammography, abdominal ultrasonography and bone scan were the tools to assess the disease status. SPSS 16 was used. Results: The mean age was 70.8 years old (range 65-85 years). There was only one patient whose age is older than 85 years. 85 % of histopathology was infiltratif ductal carcinoma. 83 % of patients underwent mastectomy while 92 % was performed axillary dissection. 56 % had node positivity and 54 % had 2 cm or bigger tumor. ER/PR status was both negative in 54 women (30 %) and both positive in 82 of them. Also cerbB2 was negative in most of the patients (70 %). At the diagnosis, 20 patients (11.3 %) had metastatic disease and 157 were without metastases. Totally 44 patients (32 %) had metastatic disease and most of them (29 patients) had bone disease. Only 52 did not have endocrine therapy with 48 % had tamoxifen as a part of hormonal therapy. Most of them received radiotherapy (54 %). DFS was within 7-182 months with a median of 54 months. PFS was between 2-60 months and patients had a median OS about 61 months. 30 patients died because several causes owing to ageing causes. Conclusions: Breast cancer is the most significant cancer of women and the screening modalities with adjuvant postoperative therapies have increased survival. Acute and chronic medical conditions, nutritional status, poly-pharmacy, level of activity, disease-spesific symptoms and patient decision all need to be taken into consideration. Both in early and advanced stages of the disease, quality of life and related aspects have critical importance in elderly women who have more limited life-expectancy. It is also essential that women with breast cancer 65 years and older be included in trials and that they be recommended the best therapies available.