bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of ROS1 translocations in triple-negative lung adenocarcinomas.
Authors: McLeer Florin Anne , Mescam-Mancini Lenaig , Moro-Sibilot Denis , Audigier-Valette Clarisse , Decroisette Chantal , Sabourin Jean-Christophe , Souquet Pierre Jean , Lantuejoul Sylvie
Published: March 2020

8099

Background: After ALK (anaplastic lymphoma kinase) rearrangements, ROS1 (c-ros oncogene 1, located at 6q22) translocations were recently shown to define a new molecular subgroup in non-small cell lung cancers (NSCLC). These translocations, activating a proto-oncogene with a tyrosine kinase domain, are also targeted by the MET and ALK crizotinib. ROS1 rearrangements are found in only 1.2-1.7% NSCLCs, but seemingly only in triple negative (EGFR and KRAS non-mutated and ALK non-rearranged) adenocarcinomas and preferentially in non- or light smokers. Methods: 60 triple negative non- or light-smoking patients with lung adenocarcinoma were screened for ROS1 rearrangements by fluorescent in situ hybridization (FISH). Two commercially available break-apart FISH probe kits containing a mixture of two probes hybridizing on each side of the ROS1 locus, one located in a centromeric (3’) position, and the other one in a telomeric (5’) position relative to the ROS1 gene were used. ROS1 fusions were therefore detected without any preconception on the fusion partner, as multiple fusion partners have been described. At least 100 nuclei were screened, and a tumor was considered positive if it contained more than 15% rearranged nuclei. Results: Forty-nine of the 60 tumors were interpretable. Four (8.2%) of theses 49 tumors were ROS1 rearranged by FISH. Only one of the positive cases showed a “classical” split rearrangement pattern (one fusion, one green and one red signal in more than 15% of nuclei), whereas the three other tumors showed a variant pattern, with a deletion of the telomeric probe, located in a 5’ position relative to the ROS1 gene locus, indicating the presence of a fusion partner upstream of the ROS1 gene. The four positive cases were all at an advanced stage (3 or 4), but did not display any common architectural feature. Conclusions: The prevalence of ROS1 positivity in our selected population was far superior (8.2%) to that of a non-selected NSCLC population, suggesting that this type of screening may be more effective (faster and more cost-worthy) to detect ROS1 positive tumors.
Prognostic value of ECOG performance status in lung cancer assessed by patients and physicians.
Authors: Johansen Jakob , Boisen Mogens Karsboel , Mellemgaard Anders , Holm Bente
Published: March 2020

8103

Background: Physician-reported Eastern Cooperative Oncology Group (ECOG) performance status (MD-PS) is a reliable prognostic factor of overall survival (OS) and has a major influence on treatment decisions. MD-PS is also used to quantify cancer patients' general well-being and activities of daily life. The extent and prognostic importance of disagreements between MD-PS and cancer patients' self-reported ECOG PS (Pt-PS) have not been adequately evaluated. Methods: Four hundred and sixty consecutive patients with lung cancer (LC) were referred to the Dept. of Oncology at Herlev University Hospital, Denmark, from February 1 2012 to January 31 2013. Three hundred and forty-seven (75%) of these patients were enrolled in a prospective, longitudinal, LC biomarker study, “LUCAS”. Patients assessed their own Pt-PS in a questionnaire at first visit. Treating physicians scored the MD-PS at first visit. Results: Fifty-four (16%) LUCAS patients had missing PS data (39 no Pt-PS; 14 no MD-PS; 1 neither). LUCAS patients were significantly younger than the total LC population (mean age, 68.1 vs. 71.1; t-test: p < 0.01). The MD-PS and Pt-PS were distributed differently in the LUCAS cohort: PS=0 (121 vs. 76), PS=1 (147 vs. 145), PS=2 (39 vs. 54), PS=3 (25 vs. 30), PS=4 (0 vs. 2) (X2 test: p < 0.01). In 170 (58%) cases the physician and patient were in concordance. In 24 (8%) cases the MD-PS scored the patient in poorer PS compared to the Pt-PS. In 99 (34%) cases the MD-PS scored the patient in better PS than the Pt-PS. In 11 (4%) cases the physician scored a PS value more than 1 different from the patient; all were towards a better PS. The median OS in the total cohort (460 patients) was 9.7 months. MD-PS and Pt-PS were both effective in predicting OS. For patients with MD-PS = 0, a poorer Pt-PS did not significantly predict worse outcome. However, for patients with MD-PS = 1, there was a trend (HR 1.98, p = 0.08; log rank test) towards worse outcome if Pt-PS was > 1. Conclusions: Oncologists and patients frequently disagree regarding PS. The physicians tend to note a better PS score than the patients. The differences between MD-PS and Pt-PS could influence the prognostic value. It may be beneficial in clinical practice to involve patients in PS assessments.
A phase I/II trial combining erlotinib with gamma secretase inhibitor RO4929097 in advanced non-small cell lung cancer (NSCLC).
Authors: Gold Kathryn A. , Byers Lauren Averett , Fan You Hong , Fujimoto Junya , Tse Warner H , Lee J. Jack , Gupta Sanjay , Wistuba Ignacio Ivan , Stewart David J. , Gibbons Don Lynn
Published: March 2020

8104

Background: All NSCLC patients treated with erlotinib (E) eventually develop resistance. Both the epithelial-mesenchymal transition (EMT) and cancer stem cells may contribute to resistance to E. The Notch pathway plays a key role in maintaining stem cell viability and in EMT. Gamma secretase inhibitors such as RO4929097 (R) inhibit Notch activity by preventing cleavage of Notch to its active form. In this CTEP-sponsored study, primary endpoint of phase I was to determine maximum tolerated dose (MTD) of the combination of E and R; primary endpoint of phase II was response rate. Methods: Eligible pts had incurable NSCLC, measurable disease, ECOG PS 0-1, and adequate laboratory parameters. There were no limits on prior therapy. All pts were required to have a tumor biopsy. Patients received E PO daily on a continuous schedule and R PO daily on days 1-3, 8-10, and 14-17 of a 21 day cycle. Dose cohorts (E/R both in mg) were as follows: 100 /20, 150/20, 150/30, 150/45. Imaging was performed every 6 weeks. Patients could remain on therapy until progression. Results: 21 pts were enrolled between 9/2010 and 3/2012. 5 were not eligible and did not receive treatment. For the 16 treated pts: median age was 61 yrs (40-75), 7 (44%) were male, 14 (88%) had adenocarcinoma. All pts had received prior chemotherapy (1-8 regimens); 7 (44%) had prior E. 3 pts had known EGFR mutations; 2 pts had KRAS mutations. Time on therapy ranged from 20 to 248 days. Median PFS was 42 days. Pts with prior progression on E had a median PFS of 64 days. 1 pt (6%) had a partial response, 4 (19%) had stable disease at 6 weeks. Median overall survival is 6.5 months (1.3 to 24.5+ months). Observed dose-limiting toxicity was hypophosphatemia in 1 pt in 150/45 cohort. Other toxicities included rash, neuropathic pain and nausea. MTD was determined to be 150/45. The study was halted early, after completion of the phase I cohort, as production of R was discontinued by the manufacturer. 12 pts (75%) have adequate tumor tissue for analyses. Biomarker studies are pending. Conclusions: Combination of R and E is safe and feasible in pts with NSCLC. Though development of R has been discontinued, other drugs targeting the Notch pathway are in development (NCI R21CA153017). Clinical trial information: NCT01193881.
Exploratory biomarker analyses from ECOG 4508: Three-arm randomized phase II study of carboplatin (C) and paclitaxel (P) in combination with cetuximab (CET), IMC-A12, or both for advanced non-small cell lung cancer (NSCLC) patients (pts).
Authors: Aggarwal Charu , Dahlberg Suzanne Eleanor , Hanna Nasser , Kolesar Jill , Hirsch Fred R. , Ramalingam Suresh S. , Schiller Joan H.
Published: March 2020

8106

Background: ECOG 4508 was a phase II study that randomized advanced NSCLC pts that were not candidates for bevacizumab to receive: C + P iv on day 1 every 3 wks with either CET iv weekly (arm A, n=39), IMC-A12 iv every 2 wks (arm B, n=42), or both (arm C, n=48). The study was closed prematurely due to safety concerns after 129 eligible pts were treated. The study failed to meet its primary objective (Hanna et al ASCO 2012). Methods: Tumor samples were analyzed by immunohistochemistry (IHC; EGFR, IGF-1R and IGF-2R expression), fluorescent in-situ hybridization (FISH; EGFR gene copy number) and DNA sequencing (EGFR, KRAS gene mutations). Time-to-event distributions were estimated using the Kaplan-Meier method, and differences were tested using the logrank test. Cox proportional hazards models were fitted to estimate hazard ratios. Results: Histology: 38% squamous cell, 39% adenocarcinoma, 2% BAC, 5% NOS and 6% other. OS was similar in EGFR FISH+ (Colorado classification system, n=30/70, 43%) vs EGFR FISH- pts (57%), (9.5 mos vs 8.6 mos, HR=0.62, p=0.08). For EGFR FISH+ pts, there was no difference in outcomes with CET (n=19, OS=9.7 mos, PFS=4.1 mos) vs no CET (n=11, OS=9.5 mos, PFS=5.5 mos). EGFR and KRAS mutations were detected in 6% (5/80) and 22% (6/27) of the pts respectively, but sample sizes were not large enough for robust testing. EGFR and IGFR IHC hybrid (H) scores were assessed on 98/102 available samples (Arm A=29, Arm B=34, Arm C=35). Median H scores (and range): IGF-1R: 190 (30-390), IGF-2R: 145 (20-350), EGFR membrane and cytoplasm: 190 (0-380) and EGFR membrane only: 160 (0-390). With IGF-1R and IGF-2R H score > 200, there was no association with OS (HR 1.3, p=0.26; HR 1.4, p=0.28) or PFS (HR=1.1, p=0.67; HR=1.2, p=0.56), adjusted for whether or not IMCA12 was received. Similarly, no associations with OS or PFS were seen with EGFR membrane H score > 200, adjusted for CET administration (OS HR=0.89, p=0.64; PFS HR 1.1, p=0.62). Conclusions: There was no correlation between EGFR FISH or H score and outcomes with CET. IGF-1R and IGF-2R expression was not predictive of favorable outcome with IMC-A12. Clinical trial information: NCI-2011-01976.
Pulsed dosing of erlotinib for central nervous system (CNS) progression in EGFR-mutant non-small cell lung cancer (NSCLC).
Authors: Jackman David Michael , Mach Stacy L. , Heng Jennifer C. , Rabin Michael S. , Barbie David Allen , Gandhi Leena , Marcoux J Paul , Costa Daniel Botelho
Published: March 2020

8116

Background: Lung cancer is the most common cause of CNS metastases. Options for CNS progression are limited, particularly with leptomeningeal metastases (LM). High dose EGFR-TKIs have been used in this setting. This is a retrospective series of our experience with pulsed high dose erlotinib for these patients. Methods: Eligible pts with EGFR-mutant NSCLC were identified through our institutions’ databases and had received pulsed high dose erlotinib for CNS progression. Patients had received erlotinib 1000-1500 mg once weekly. The primary endpoint was CNS response; secondary endpoints included toxicity, systemic response, CNS progression-free survival, and overall survival. Results: Between 10/2010 – 10/2012, 10 eligible pts received pulsed dose erlotinib for CNS progression. The median age was 60 yrs; 8/10 were female, 7/10 were never-smokers, with a median of 2 pack-years. All pts had lung adenocarcinoma, and 9/10 had received prior EGFR-TKI. Median duration of prior TKI was 19 months. 6 received prior erlotinib, 1 received prior dacomitinib, and 2 received prior erlotinib followed by dacomitinib. The overall CNS response rate was 10% (1/10); 2 others achieved CNS stability. Median overall survival was 1.7 months (range 0.6 – 7.0). There was no clear correlation between outcomes and underlying EGFR genotype; type, duration, or dose of prior EGFR-TKI; or extent of CNS involvement. Conclusions: While there has been evidence of higher penetration of EGFR-TKI’s into cerebrospinal fluid with pulsed high doses of EGFR-TKI’s, the clinical efficacy of this strategy remains limited. [Table: see text]
Outcomes and toxicity for hypofractionated and single-fraction image-guided stereotactic radiosurgery for sarcoma metastatic to the spine.
Authors: Folkert Michael Ryan , Bilsky Mark , Tom Ashlyn K. , Alektiar Kaled M. , Laufer Ilya , Tap William D. , Yamada Yoshiya
Published: March 2020

9501

Background: Conventional radiation treatment (20-40 Gy total dose, 5-20 fractions, 2-5 Gy per fraction) for sarcoma metastatic to the spine provides subtherapeutic doses and results in poor local control (58-77% at 1 year). Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) may provide a more effective means of control and salvage for these lesions. Methods: Patients with pathologically-proven high-grade sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. Local control (LC) and overall survival (OS) were analyzed using Kaplan-Meier statistics; univariate/multivariate analyses were performed using Cox regression. Toxicities were assessed according to CTCAE v4.0 criteria. Results: From 5/2005 and 11/2012, 88 patients with 120 discrete metastases were treated with HF (3-6 fractions, median dose 28.5 Gy; n=52, 43.3%) or SF IG-SRS (median dose 24 Gy, n=68, 56.7%). Median followup was 12.3 months. LC at 12 months was 87.9% (95% CI 81.3-94.5%). OS at 12 months was 60.6% (95% CI 49.6-71.6%) with a median survival of 16.9 months. SF IG-SRS demonstrated superior LC to HF IG-SRS (P=.007) (Table). SF IG-SRS retained its significance in terms of improved LC on multivariate analysis, HR 0.304 (95% CI: 0.117-0.790); variables tested included prior radiation therapy, histology, IG-SRS fractionation, surgery, and chemotherapy. Treatment was well-tolerated with 1% acute Grade 3 toxicity and 4.5% chronic Grade 3 toxicity observed; there were no > Grade 3 toxicities. Conclusions: In the largest series of metastatic sarcoma to the spine to date, image-guided stereotactic radiosurgery provides excellent local control in the setting of an aggressive disease with low radiation sensitivity and poor prognosis. Single-fraction image-guided stereotactic radiosurgery demonstrates the highest rates of local control with minimal toxicity. [Table: see text]
Losing sleep over cancer: Relationships with negative affect, blood pressure, and disease-free interval among women with metastatic breast cancer.
Authors: Gerry Arianna Aldridge , Palesh Oxana , Rissling Michelle , Zeitzer Jamie M. , Dhabhar Firdaus S. , Jo Booil , Neri Eric , Nouriani Bita , Spiegel David
Published: March 2020

9504

Background: Few studies have examined how polysomnographic (PSG) measured sleep disturbance is associated with negative affect and markers of health status among women with metastatic breast cancer (MBC). Methods: 91 women with MBC (aged 57.9 ± 7.3 yrs) and Karnofsky ratings of at least 70 were recruited. We used latent profile analysis to identify distinct patterns of in-lab sleep disturbance. These profiles were used to predict affect (measured by PANAS), blood pressure, and disease progression (disease free months before metastases). Results: Two classes of women emerged and were distinguished as “severely disturbed sleepers” (n = 24) or “mildly disturbed sleepers” (n = 67). Severely disturbed sleepers had worse quality of sleep (e.g., sleep efficiency=54% vs. 69%) and spent significantly and less time in slow wave and REM sleep. One-way ANOVA revealed that severely disturbed sleepers reported significantly more negative affect (p < .05). Specifically, they reported greater negative affect in the afternoon (2-3pm) and evening (6:30-7pm) prior to lab-sleep, and the morning (9:30-10:30am) and afternoon (12:30pm and 2pm) following lab-sleep. In addition, severely disturbed sleepers had higher systolic blood pressure (M=140 vs. M=124, p = .001) measured the afternoon prior to lab-sleep. Strikingly, women with severely disturbed sleep had significantly shorter disease free intervals (49 months vs. 80 months, p < .05), and worse Karnofsky ratings (p < .05) indicating worse medical prognosis than mildly disturbed sleepers. Conclusions: Women with MBC and severely disturbed sleep experienced more negative affect prior to and following a poor night’s sleep. In addition, they exhibited hypertension and accelerated cancer progression relative to women with mild sleep disruption. These detrimental changes may be an indication of the effects of chronic sleep disruption. Understanding the role of daily negative affect in conjunction with physiological markers of disease progression may inform better treatment methods for women with MBC experiencing severe sleep disruption.
Association of pro-inflammatory biomarkers and post-chemotherapy cognitive changes in Asian breast cancer patients: A prospective cohort study.
Authors: Cheung Yin Ting , Ham Guo Maung Shwe , Kee Yuan Chuan , Chui Wai Keung , Ho Han Kiat , Fan Gilbert , Yong Wei Sean , Madhukumar Preetha , Ooi Wei Seong , Chay Wen Yee , Dent Rebecca Alexandra , Ang Soo Fan , Lo Soo Kien , Yap Yoon Sim , Ng Raymond C.H. , Chan Alexandre
Published: March 2020

9506

Background: Although existing evidence suggests that cytokines play an intermediary role in the development of post-chemotherapy cognitive changes, specific cytokines associated with this neurotoxic sequela of chemotherapy are still unknown. This study was designed to identify pro-inflammatory biomarkers that are associated with memory and attention impairment in Asian patients receiving chemotherapy. Methods: This is a prospective, cohort study conducted at the National Cancer Centre Singapore. Early-stage Asian breast cancer patients (Stage I to III), who received anthracycline and/or taxane-based chemotherapy were recruited. Computerized neuropsychological assessments (Headminder) were administered to evaluate patients’ memory and attention performances and a panel of pro-inflammatory plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α) was evaluated using multiplex immunoassay at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Memory and attention impairment were defined as a >2.5 reduction of the Zscore from baseline, as calculated by the reliable change index for repeated cognitive measurements. Results: Thirty-six patients were included (mean age 49.7±9.0 years; 80.6% Chinese). Comparing to T1, 50.0% and 36.1% of the patients suffered memory and attention impairment at T3, respectively. Comparing patients with intact memory to those who suffered impairment from T2 to T3, they had higher levels of circulating IL-1β [median (IQR): 0.44 (0.1-0.5) vs 0.56 (0.4-0.7) pg/ml, p=0.069], IL-4 [0.41 (0.0-0.8) vs 0.85 (0.2-1.5) pg/ml, p=0.067) and TNF-α [1.78 (1.3-2.2) vs 3.01 (1.3-3.5) pg/ml, p=0.069]. At T3, reduction of attention scores were associated with higher levels of IL-1β (rs= -0.37, p=0.023) and IL-6 (rs= -0.33, p=0.045). No significant associations were identified with IL-2, IL-8, IL-10, GM-CSF and IFN-γ. Conclusions: These findings suggest that an increase in the post-chemotherapy levels of TNF-α, IL-1β, IL-4 and IL-6 may have an association with the manifestations of memory and attention impairment in Asian breast cancer patients.
Do elderly patients benefit from enrollment in phase I clinical trials?
Authors: Tai Wai Meng David , Lim Cindy , Ahmad Aziah , Ong Whee Sze , Choo SuPin , Lim Wan-Teck , Tan Eng-Huat , Tan Daniel Shao-Weng
Published: March 2020

9509

Background: Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. We evaluated the clinical characteristics and outcomes of elderly pts enrolled in phase 1 clinical trials in our centre and evaluate the performance of Royal Marsden Hospital (RMH) prognostic score (albumin, LDH, no of met sites) in this pt population. Methods: 296 consecutive pts who were treated in 20 phase 1 trials from 2005-2012 in our unit were analysed. Clinical characteristics and outcomes between young pts (<65, n=202) and older pts (≥65, n=94) were compared. Results: The median age of the older pts was 69 (65-84), 71% were males. 51% of the pts received chemotherapy based treatment with or w/out biological agents. 61% of the pts had lung cancers and 32% had gastrointestinal cancers. 52% of pts had ≥2 co-morbidities. After median follow up of 7.5 mths (0.36-50.6 mths), the median progression free survival (PFS) and overall survival (OS) were 5.8 and 8.8 mths respectively. Although elderly pts had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 vs 9.9 mths), p=0.68) compared to younger pts. The prognostic factors for OS identified in multivariate analysis were prior lines of chemotherapy (0-2 vs ≥3), baseline sodium levels (≥135 vs <135mmol/L) and platelet levels (≤400 vs >400×10⁹). We developed a risk nomogram based on the factors identified prognostic of OS with concordance(c)-index of 0.65. RMH score (2-3 vs 0-1) predicted for OS with hazard ratio of 2.1, p=0.03 and c- index of 0.63. 26% of elderly pts experienced grade 3/4 toxicities in the first cycle of treatment. Common grade 3/4 toxicities were dermatological (25%), haematological (17%) and gastrointestinal (13%). Both age of pts (p=0.70) and dose levels (p=0.18) did not have any bearing on occurrence of grade 3/4 toxicities. Conclusions: Elderly pts (≥65) enrolled into phase 1 clinical trials had similar survival outcomes and toxicity profiles compared to younger pts. Risk scoring models to aid patient selection need further clarification in this population.
Baseline cognitive functions among elderly patients with localized breast cancer.
Authors: Joly Florence , Lange Marie , Heutte Natacha , Daireaux Aurélie , Rieux Chantal , Le Fel Johan , Rigal Olivier , Roy Vincent , Kurtz Jean-Emmanuel , Clarisse Benedicte , Giffard Benedicte , Eustache Francis , Noal Sabine
Published: March 2020

9510

Background: Cognitive deficits (CD) were reported among patients receiving chemotherapy (CT) for cancer, but could also be observed before treatment. Elderly patients were poorly studied although they are more prone to present age-related CD and CD onset or enhancement during CT. This study assessed baseline cognitive functions among elderly localized breast cancer (LBC) patients before adjuvant treatment therapy. Methods: Episodic memory, working memory, executive functions and information processing speed were assessed with neuropsychological tests. Validated questionnaires were used to assess subjective CD, anxiety, depression and fatigue before adjuvant treatment. Geriatric assessment was also realized. Objective CD were defined as a score less than 1.5 standard deviation (SD) of normative data on >2 tests, or less than two SDs on >1 test. Significant subjective CD (evaluated by the FACT-Cog) were defined when the 4 subscales below the first tercile distribution. Results: Results concern 123 elderly LBC (71±4 years): planned treatment included CT and radiotherapy (RT) for 61 patients and RT only for 62 patients. Characteristics are as follows: mastectomy (28%), stage (I: 60%, II: 27%, III: 13%), positive hormonal receptor (88%) and positive Her2 (17%). Before any adjuvant treatment, objective CD were observed in 40% of patients (46% in CT group, episodic memory mainly impaired and 37% in RT group, executive functions and information processing speed mainly impaired). No relation was observed between cancer stage, geriatric frailty and objective CD. Twenty nine percents of patients presented fatigue, 6% anxiety and 10% depression. These variables were not related to objective CD but they were related to subjective CD. Conclusions: More than 40% of elderly LBC patients presented objective CD before any adjuvant therapy that is higher than observed among younger patients. It is important to take account in the decision making of adjuvant treatment in elderly patients. Clinical trial information: NCT01333735.
Intensity of palliative care and its impact on the aggressiveness of end-of-life care in patients with advanced pancreatic cancer.
Authors: Jang Raymond Woo-Jun , Krzyzanowska Monika K. , Zimmermann Camilla , Taback Nathan , Alibhai Shabbir M.H.
Published: March 2020

9518

Background: Quality indicators have been developed to avoid overly aggressive care in patients with advanced cancer. Specialized palliative care (PC) may reduce overly aggressive care in patients with advanced pancreatic cancer. Our objective was to examine the impact of the intensity of specialized PC (defined as a physician consultation focusing on PC needs, lasting at least 40 minutes) on (a) use of chemotherapy within 14 days of death; (b) more than one emergency department (ED) visit; (c) more than one hospitalization; and (d) at least one intensive care unit (ICU) admission, all within 30 days of death. Methods: A retrospective population-based cohort study using linked administrative databases in Ontario, Canada was conducted with patients diagnosed with advanced pancreatic cancer from Jan 1 2005 to Dec 31 2010. Multivariable logistic regression analyses were performed with the above quality indicators as the outcomes of interest and the intensity of PC visits as the exposure, adjusting for other variables (age, sex, comorbidity, rurality, and health region). Intensity of PC was defined in both absolute numbers (ie 0, 1, 2, 3+ visits) and rate of visits per month. Results: Of 6076 patients with advanced pancreatic cancer, 5381 had died at last followup. 2816 (52%) received a PC consultation, 218 (4%) received chemotherapy near death, 234 (4%) patients went to the ICU near death, 993 (18%) had multiple ED visits near death, and 447 (8%) had multiple hospitalizations near death. 2565 (48%) had 0 PC visits, 513 (10%) had 1, 555 (10%) had 2, and 1748 (32%) had 3 or more. In multivariable analyses, having had one PC consultation was associated with a lower odds of ICU admission near death (odds ratio (OR) 0.25; 95% CI 0.13-0.46), multiple ED visits near death (OR 0.44; 95% CI 0.33-0.58), and multiple hospitalizations near death (OR 0.47; 95% CI 0.33-0.69). Two PC visits were associated with a lower OR for chemotherapy near death (OR 0.26; 95% CI 0.14-0.51). Using the monthly PC visit rate, a higher rate was associated with less aggressive care for each outcome. Conclusions: In patients with advanced pancreatic cancer, more intensive PC involvement is associated with less frequent overly aggressive care.
Prospective study of vaginal dilator use adherence and efficacy following pelvic and intravaginal radiotherapy.
Authors: Law Ethel , Kelvin Joanne Frankel , Thom Bridgette , Riedel Elyn , Tom Ashlyn , Goodman Karyn A.
Published: March 2020

9524

Background: Vaginal stenosis (VS) as a late effect of pelvic radiotherapy (RT) and intravaginal brachytherapy (IVB) can impair long-term quality of life. The best care guideline for post-treatment 3x/week vaginal dilator (VD) use is based on limited research. This prospective study aimed to determine adherence and efficacy of VD use as measured by ability to return to pre-RT VD size at 12 months (mos). Methods: From 2009-2011, women with rectal (n=28), anal (n=35), endometrial (n= 45) and cervical (n=1) cancers were followed for one-year post-radiation therapy (RT). Clinicians provided structured teaching to use dilators 3x/week, regardless of frequency of sexual intercourse. For 12 mos, patients self-reported dilator size and vaginal symptoms in monthly diaries. At pre-RT, 1, 6 and 12 mos post-RT, clinicians graded VS using CTCAE v3. Adherence was measured as the percentage of times patients used the dilator out of the number of times they were instructed (3x/week X 52 weeks=156). Fisher’s exact and Kruskal-Wallis tests were used to assess differences among groups. Results: Among 109 participants, aged 28-81 years (median = 58), mean adherence with VD use over a 12 mos period was 42% (sd 34%, 95% Cl:36%- 49%). Adherence was highest in the first quarter (58%), but fell to 25% by the fourth quarter. Disease type, treatment sequence and chemotherapy were predictors of adherence (all p<0.05). Rectal cancer patients were less likely to adhere to dilator use than anal and endometrial patients. 82% of all patients returned to pre-RT size at 12 mos; of the 49% who reported a decrease in dilator size from pre-RT to 1 month post-RT, 71% were able to return to pre-RT size at 12 mos. Anal cancer patients were most likely to report a decrease in VD size at 1 mo post-RT (77%), but 68% of these patients were able to return to baseline at 12 mos. Disease type and greater adherence to VD use at 6 months were associated with returning to pre-RT size at 12mos (both p <0.05). Conclusions: Based on this prospective study, VD use is an effective strategy in minimizing VS, but adherence at 12 mos was poor. Future studies are needed to evaluate methods of improving adherence with VD use and to determine the optimal frequency and duration of VD use.
Perceived versus measured functional vaginal capacity in cancer patients with sexual function concerns.
Authors: Kennedy Vanessa , Abramsohn Emily , Asiedu Lisa , Makelarski Jennifer , Wroblewski Kristen , Matthews Amber , Yamada Seiko Diane , Lindau Stacy Tessler
Published: March 2020

9528

Background: Actual and perceived loss of vaginal capacity can be a source of distress among female cancer survivors. The objective of this study was to assess perceived (PC) versus measured (MC) functional vaginal capacity in patients presenting with sexual function concerns. Methods: This was a cross-sectional registry-based study of women seen at the Program in Integrative Sexual Medicine for Women and Girls with Cancer (PRISM) Clinic. During the visit, patients were presented with graduated vaginal dilators and asked to select the largest dilator they perceived could be inserted without pain (PC) and the dilator representing their desired functional capacity (DC) (for patients with a male partner, this was the size closest to the partner’s erect penis). Two models of dilators were offered. Dilators were numbered 1-24 in order of increasing volume. If the patient could accommodate the dilator chosen as PC without pain, she was examined with dilators of gradually increasing size until the patient reported discomfort. The largest dilator tolerated without pain was MC. Differences between PC and MC, and between DC and MC were calculated. The association between penetrative sexual activity in the prior 4 weeks and accuracy of PC was assessed using the Mann-Whitney U test. Results: Mean patient age was 46 years (range 21-80, N=69). Most patients had breast (60%) or a gynecologic cancer (23%). Nearly half reported two or more sexual concerns; painful intercourse (81%), vaginal complaints (21%), and loss of libido (19%) were most common. Mean PC was 16.9 (SD 5.2, range 3-24), mean MC was 20.8 (SD 3.4, range 10-24), and mean DC was 21.8 (SD 3.4, range 6-24). PC equaled MC in 22%. PC was less than MC in 75% and less than DC in 81% of patients. Of patients with PC less than DC, 41% had MC equal to or larger than DC. PC was closer to MC in patients reporting penetrative sexual activity in the prior 4 weeks (p=0.03). Conclusions: In this single-site study, many cancer survivors seeking care for sexual concerns underestimate their functional vaginal capacity. Further study is needed to determine whether correcting patient perception of capacity lessens distress and improves function.
Prevalence and predictors of suicidal ideation in long-term prostate cancer survivors.
Authors: Recklitis Christopher J , Zhou Eric , Zwemer Eric , Hu Jim C. , Kantoff Philip W.
Published: March 2020

9529

Background: Prostate cancer (PC) is associated with an increased risk of suicide, even a decade after diagnosis. Prior research has relied largely on registry data collected at diagnosis, so little is known about the role of post-treatment functioning on the development of suicidal ideation (SI) in long-term prostate cancer survivors (PCS). To address this, our study examined the prevalence of SI, and the association with cancer therapy and post-treatment physical and emotional health in a cohort of long-term PCS. Methods: 695 PCS (5-10 years post-diagnosis) completed a mailed survey on physical and psychological functioning, including the SF-12, EPIC-26, a d epression rating scale and 8 items about SI in the prior year. Results: 12% endorsed having SI and 2% reported serious SI, plans or urges. Serious SI was more common in PCS compared to age and gender-adjusted normative data. SI was not associated with demographic variables (age, ethnicity, marital status, education, income). SI was not associated with prostate cancer stage, treatments or progression. In univariate analyses, SI was significantly associated with prostate-specific symptoms, poor physical and emotional function, a higher frequency of significant pain, and clinically significant depression (p<.01). In an adjusted logistic model, depression and frequent pain remained associated with SI. Of note, 61% of PCS with SI denied a prior depression diagnosis, and 47% denied elevated current depressive symptoms. The majority of PCS with SI (97%) had a recent physician visit, and reported significant interest in receiving mental health information. Conclusions: A significant proportion of PCS report recent SI, which is associated with physical and psychological dysfunction, but not PC treatments. Depression and frequent pain, rather than PC-specific symptoms, are most important in the development of SI. While depression is strongly associated with SI, many PCS with SI have no prior or current depression, underscoring the need to evaluate SI independently. PCS with SI reported receiving regular medical care and interest in information about mental health. This emphasizes the critical role that physicians can play in identifying PCS at high risk for suicide.
Long-term symptom burden and orodental health of oropharyngeal cancer (OPC) survivors following treatment with chemoradiotherapy (CRT) or sequential therapy (ST).
Authors: Limaye Sewanti Atul , Haddad Robert I. , Partridge Ann , O'Neill Anne M. , Radossi Andrea , Shreenivas Aditya V. , Lorente David , Hanna Glenn J. , Sonis Stephen T. , Shulman Lawrence N. , Posner Marshall R. , Lorch Jochen H.
Published: March 2020

9530

Background: OPC treatment is associated with significant long-term toxicity. Very little is known about the long-term symptom burden and orodental health in OPC survivors >2 yrs from treatment. Methods: Survivors treated for OPC with CRT/ST (involving definitive RT) at Dana Farber Cancer Institute between 2002-2011 and >2 yrs from treatment completion, were identified by chart review and asked to complete the Vanderbilt Head and Neck Symptom Survey version 2 (VHNSS v2), National Health And Nutrition Examination Survey for Oral Health Questionnaire, health care availability survey. Results: 200 survivors were contacted, 127 responded (RR: 64%). Median age at diagnosis was 54 yrs; 85% males; 85% stage IVA/B, 13% stage III; 56% CRT, 43% ST. HPV status: 47% (+), 10% (-), 43% unknown. Median time from treatment completion: 50 mths (24-135 mths). Residual moderate to severe toxicities reported in VHNSS v2: 71% dry mouth; 59% difficulty chewing/swallowing food; 53% feeling of food becoming stuck in the throat; 53% prolonged time to eat; 31% thick mucus, 6% had difficulty sleeping secondary to this; 16% trouble speaking, 27% trouble hearing;30% limitation of neck/shoulder movement; altered taste/smell - 45%/23%; sensitivity to spicy food and dryness-57%/62%; 30% decreased desire to eat, 11% had moderate weight loss. Orodental health assessment: 13% thermal sensitivity, 21% teeth cracking and chipping, 20% loose teeth, 33% had treatment for gum disease, 42% had lost bone around teeth. 98% survivors had health insurance; only 66% had dental insurance. No statistically significant difference was noted with respect to symptoms between CRT or ST. ST did not affect long-term toxicity compared to CRT alone. Conclusions: OPC is known to correlate with HPV positivity, early age at diagnosis and high rates of long-term survival after appropriate therapy. Our study documents that the OPC survivors have substantial residual long-term head and neck and orodental symptoms directly related to the treatment that significantly impacts their quality of life. A substantial number of patients lack dental health coverage, which likely further impacts symptom burden and QOL.
From Bayesian modeling to genomic mapping: Biologic validity of predictive single nucleotide polymorphism networks for chemotherapy-related side effects.
Authors: Sonis Stephen T. , Schwartzberg Lee Steven , Weidner Susan M , Alterovitz Gil
Published: March 2020

9535

Background: Using proprietary Bayesian network (BN) algorithms, we discovered interacting single nucleotide polymorphism (SNP)-BNs predicting patient-risk for 6 chemotherapy (CT)-induced side effects (SEs): oral mucositis (OM), diarrhea (D), CT-induced nausea and vomiting (CINV), fatigue, cognitive dysfunction (CD) and peripheral neuropathy (PN). To assess biologic validity, SNP-BNs mapped each SE to its gene loci, exploring biologic pathways for those genes. Roles of genes and pathways found in similar phenotypic diseases (e.g., Inflammatory Bowel Disease [IBD] for D, Alzheimer disease [AD] for CD, chronic fatigue syndrome [CFS] for F) were explored. Methods: Via an FDA-cleared DNA extraction kit, saliva was collected from 78 women with breast cancer (dose-dense AC+T) and 57 patients with colon cancer (FOLFOX +/- bevacizumab). We assessed 2.5M SNPs/patient (Illumina OmniQuad bead chip assays). SEs were measured via a validated tool (Patient Care Monitor). Analyzed SNP arrays and SEs discovered SNP-BNs. Final SNP-BNs per SE included gene name, symbol, and loci. Pathways and networks were analyzed for gene function and related genes, querying 6 databases (NLM, NextBio, Weizmann Institute, SPRING, Gene Ontology, AmiGO). Results: Mucosal injury-implicated networks and genes were identified, including oxidative stress, NF-κB, pro-inflammatory cytokines IL-1, IL-6, and TNF, MMPs and fibronectin breakdown (SPOCK3). D networks and genes overlapped with IBD (ERG, IER2, CASK). SNP-BNs for CINV overlapped in both CT regimens with genes for neurotransmitters (serotonin, dopamine, substance P) and nerve impulse transmission. B3GAT1, involved with opioid-induced CINV, was identified. F networks involving genes and pathways for cytokines and skeletal muscle overlapped to CFS. CD networks involve genes in AD. PN networks mapped genes involving myelination, demyelination, inflammation, and toxic neuropathy. Conclusions: SNP-BNs predicting CT-induced SEs mapped to genes associated with known biology of each SE, sharing central traits with other diseases, and are targets for drug discovery in cancer-related SEs and unmet needs, including AD.
Opportunities for improved end-of-life (EOL) care for adult patients with advanced cancer: Results of a longitudinal assessment of care provided by Quality Oncology Practice Initiative (QOPI) participants.
Authors: Dougherty David W. , Kadlubek Pamela , Pham Trang , Earle Craig , Malin Jennifer , Breathwaite Larry , Jacobson Joseph O.
Published: March 2020

9537

Background: End of life care of patients with advanced cancer has received recent attention because of evidence of widespread variation in utilization of aggressive therapies and interventions and possible suboptimal use of palliative care and hospice services. QOPI, the ASCO sponsored quality assessment program, has been available to all United States physician members since January 2006 and has assessed EOL care since its inception. The current analysis explores whether the increased national focus on EOL and increased availability of palliative care and hospice services has resulted in improvements in EOL care as reported by QOPI participants. Methods: Data was aggregated across all EOL care quality measures for 9 sequential semi-annual QOPI collection periods from 2008 through 2012. Trends were analyzed among rates of eligible patients related to hospice enrollment and timing of enrollment, palliative care referrals, discussions about hospice and palliative care, and chemotherapy administration at the end of life. The Cochran-Armitage trend test was performed to determine the significance of trends and differences in measure performance over time. Results: From Fall 2008 to Fall 2012, the rate of hospice enrollment for appropriate patients improved by 7.4% [51.8% to 59.2%; p<0.0001] and the rate of hospice enrollment or palliative care referral improved by 5.6% [63.3% to 68.9%; p<0.0001]. Modest improvements were seen in the rates of hospice enrollment more than 3 and 7 days before death [2.8%, 2.6%], discussion of hospice or palliative care with patients not referred for these services within the last 2 months of life [2.7% increase; 19% to 21.7%], and chemotherapy administration within the last 2 weeks of life [2.4% improvement from 13.7% to 11.3%]. Conclusions: Despite modest increases in the rate of hospice enrollment and palliative care referrals over time, EOL care for adult patients with cancer associated with QOPI practices remains suboptimal. Opportunities exist to increase more meaningful participation in hospice and palliative care and to reduce exposure to chemotherapy near death.
End-of-life experience of patients with rare cancers and their caregivers.
Authors: Loggers Elizabeth Trice , Prigerson Holly Gwen
Published: March 2020

9540

Background: Cancers are defined as rare if fewer than 35,000 cases are diagnosed per year. Rare cancers represented 23% of incident cancer cases and 33% of cancer deaths in 2008. However, little is known about the end-of-life (EOL) experience of patients with rare cancers or their caregivers. Methods: From September 2002 to August 2008, 618 advanced cancer patients (195 with rare and 423 with common stage IV cancers following failure of first line chemotherapy) and their caregivers participated in a U.S. multi-site, prospective, interview-based cohort study (Coping with Cancer). Patients were interviewed about EOL preferences, planning, and care at study entry. Interviews with caregivers at baseline assessed caregiver mental and physical health, while post-mortem surveys assessed EOL patient care. Descriptive statistics (t-test, chi-square) were used to characterize the study sample; logistic regression tested the association between cancer type and care received, controlling for confounders. Results: Rare cancer participants were more likely to be younger (57.7 vs 60.7 years, p=.01), Hispanic (19% vs 9%, p=.002) and have fewer co-morbidities (Charlson comorbidity index, mean 5.9 vs 6.5, p=.004), than their common-cancer counterparts. Rare cancers patients were four times more likely to be receiving both radiation and chemotherapy at study entry than common cancer patients (10.3% versus 3.3%, OR 4.31, p=0.003), but equally as likely to acknowledge their illness was terminal, have EOL discussions, and participate in advance care planning as common cancer patients. Caregivers of patients with rare cancers were more likely than common cancer caregivers to report declining health during the prior year of care-giving (22.1% versus 15.7%, p=0.05) and marginally more likely to prefer the patient choose treatment focusing on extending life rather than pain relief (22.3% vs 16.5%, p=0.08). Conclusions: Patients with advanced-stage, rare cancers may be treated more aggressively following failure of first line chemotherapy than individuals with common cancers. Future research should investigate patterns and quality of care for terminally ill patients with rare cancers and caregiver burden.
Health behaviors (HB) and geriatric assessment (GA) in older women with breast cancer (BC).
Authors: Jolly Trevor Augustus , Deal Allison Mary , Alston Shani Malia , Gordon Brittaney-Belle Elizabeth , Dixon Samara Ann , Williams Grant Richard , Muss Hyman Bernard
Published: March 2020

9543

Background: Physical inactivity (PI), alcohol (A) and tobacco (T) abuse are associated with poor health outcomes in older adults, however, little is known about the prevalence of these HB and their associations with GA domains in older cancer patients (pts). This study explores the relationship between HB and GA in older BC pts. Methods: Between 03/2010-01/2013, 111 pts ≥65 yrs completed a predominantly self-administered GA (Hurria et al. Cancer 2005) comprising measures of comorbidity, polypharmacy, cognitive, functional, psychosocial and nutritional status as well as a nine-item HB questionnaire based on the 2006/7 National Health Interview Survey ( www.cdc.gov/nchs/nhis.htm ) assessing PI, A and T use. Fisher’s Exact and Wilcoxon Rank sum test were used to evaluate associations with GA measures. Results: Median age was 72 (range 65-94). Most pts were white (89%), married (61%), retired (86%) and at least high school graduates (96%). 51% never smoked while 45% were former and 4% current smokers. Former/current smokers were more likely than never smokers to have slower gait speeds (Timed “up and go” >14 second; 32 vs 14%; p=.04) and took more daily prescription medications (mean 5 vs. 4; p=.04). 52% of pts consumed at least one alcoholic drink per week (median 3.5). Modest alcohol consumption was associated with less activity of daily living (ADL) impairment (p=.03), lower mean BMI (29 vs. 26 kg/m2 p=.03) and greater non-prescription medication use (p=.04). 48% never performed vigorous activity and these pts were more likely than those exercising to have one or more functionally impairing comorbidities (p=.03); mainly arthritis. PI correlated with more impairment in both ADL (p<.0001) and instrumental ADL (p=.004). HB were not associated with demographic factors, treatment phase, weight loss, falls, sensory impairment, social activity, anxiety or depression in this dataset. Conclusions: PI, T and A use were common in this cohort of older BC pts and were associated with significant impairments in several GA domains. These findings reinforce the need for interventions to improve HB in older BC pts. Support: Breast Cancer Research Foundation, New York, NY and Lineberger Comprehensive Cancer Center, Chapel Hill, NC.