bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.