bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic changes in circulating tumor cell levels as a prognostic marker in stage IV non-small cell lung cancer.
Authors: Carlsson Anders , Bazhenova Lyudmila , Kolatkar Anand , Luttgen Madelyn , Bethel Kelly , Nieva Jorge J. , Kuhn Peter 
Published: March 2020

8109 Background: We have previously reported the performance of our immuno-enrichment free HighEDefinition CTC (HDECTC) assay in the enumeration and characterization of circulating tumor cells (CTCs) in lung cancer patients. In the HD-CTC assay, nucleated cells are fluorescently labeled and imaged using automated microscopy. CTCs are defined as morphologically distinct, cytokeratin positive, CD45 negative cells. Here, we investigate further how CTCs numbers and physical properties relate to prognosis in NSCLC patients. Methods: The HD-CTC assay was applied for CTC enumeration in 362 blood samples collected longitudinally from 81 Stage IV NSCLC patients. Blood was collected at time 0, 3 weeks, and every 3 months thereafter. The collection protocol was restarted at disease progression, resulting in a sample number ranging between one and 12 samples per patient. Results: Eighty-one patients were enrolled, with 41 patients in 1st line therapy, 11 in 2nd, 17 in 3rd, 7 in 4th, 3 in 5th and 2 in 6th line therapy. Average age was 63, range 33 to 90; male to female ratio was 1:1.19. Eighty-six percent of patients had CTCs in at least one blood sample; CTC counts ranged from 0 to 885 CTCs/ml with a mean of 23.5 CTCs/ml across all samples. While no correlation was found between the absolute CTC concentration and survival, it was observed that for the 26 patients that had samples collected both at the start and during firstEline chemotherapy, an increase in CTC level between the two time points was significantly associated with longer survival (p < 0.001). Conclusions: As detected with our assay, it is the change in CTC level upon entering 1st line chemotherapy and not the absolute CTC concentration that carries prognostic information. This observation highlights not only the importance of CTCs as prognostic biomarkers, but also that of access to serially collected specimens. The latter is here made possible only by the fact that the HDECTC assay samples tumor cells from peripheral blood.
DDR2 mutations in lung cancer in adenocarcinoma and squamous cell carcinoma and association with MET activation.
Authors: Windham Justin P , Wang Yongbao , Hilferty Rebecca A , Sanidad Marc A , Jones Daniel 
Published: March 2020

8115 Background: The discoidin domain receptor tyrosine kinase 2 (DDR2) gene is mutated in a small subset of squamous cell carcinomas (SQCAs) of the lung. Targeting of DDR2 with the inhibitor dasatinib inhibits DDR2-mutated cell line growth and is being investigated in clinical trials for treatment of DDR2-mutated lung tumors. We investigated the frequency and type of DDR2 mutations and their association with other targetable growth factor pathway alterations in non-small cell lung carcinoma (NSCLC). Methods: DNA was extracted from macro-dissected FFPE sections of 105 advanced stage lung carcinomas. Next-generation sequencing was performed using a 36-amplicon panel including the coding regions of DDR2 and exons 11 and 15 of BRAF. DDR2 mutations were confirmed by bidirectional Sanger sequencing. Lung tumors were classified using a standard immunohistochemistry panel. MET pathway activation was assessed with immunohistochemistry using an activation-specific phospho-antibody (pMET, Try1234/1235). MET amplification and ALK rearrangement were assessed using FISH. Mutational analysis for EGFR (exon 18-21), PIK3CA (exons 9 and 20), and KRAS(exons 1-2) was performed using PCR-based DNA sequencing. Results: Heterozygous DDR2 point mutations were identified in 7/105 (6.7%) NSCLCs, including 3/29 (10.3%) SQCAs and 4/69 (5.8%) ACAs, but not in neuroendocrine/large cell carcinomas (0/7). DDR2 mutations were scattered throughout the gene, with 4 present in the discoidin domain and 3 in the kinase domain. MET pathway activation, seen in 25% of DDR2-unmutated cases, was found in 3/6 (50%) DDR2-mutated cases, including 1 SQCA with high-level MET gene amplification. DDR2 mutations were mutually exclusive with BRAF or EGFR mutation or ALK rearrangement, with 1 KRAS-mutated case. Conclusions: DDR2 mutations occur in lung carcinomas with a range of histologic features and in association with MET activation. Dual targeting of the MET and DDR2 kinases in such cases may warrant further investigation.
Magnetic resonance guided focused ultrasound surgery for palliation of painful bone metastasis: Results of a multicenter phase III trial.
Authors: Hurwitz Mark , Meyer Joshua E. , Iozeffi Dimitri , Ghanouni Pejman , Gianfelice David , Fennessy Fiona M. , Kuten Abraham , LeBlang Suzanne , Roberts Anne C. , Choi Junsung , Napoli Alessandro , Turkevich Vladimir , Tempany Clare M. , Inbar Yael , Pfeffer Raphael M. , Larner James Mitchell , Kanaev Sergy 
Published: March 2020

9500 Background: Pain due to bone metastases is a common cause of cancer-related morbidity. Magnetic resonance guided focused ultrasound surgery (MRgFUS) is a non-invasive approach to thermal tissue ablation. This multi-center phase III trial assessed efficacy of MRgFUS compared with sham treatment to alleviate pain due to bone metastases. Methods: Subjects with a painful bone metastasis amenable to MRgFUS treatment for whom radiation therapy was ineffective or contraindicated were randomized 3:1 to MRgFUS or sham treatment in a single blind design. Un-blinding of sham subjects who did not experience significant pain relief within 2 weeks was permitted with crossover allowed to salvage MRgFUS treatment. Pain response and impact on quality of life (QOL) were assessed using the numerical rating scale (NRS) and Brief Pain Inventory-Quality of Life (BPI-QOL). Safety was also assessed. Results: 142 randomized subjects were included in an intent-to-treat analysis. 67% (95%CI: 57.5-76.0%) of 107 subjects in the MRgFUS arm experienced clinically significant pain relief, equating with an anchor descriptor of “much improved” or better at 3 months compared to 20% of 35 sham arm subjects (p<0.0001). Median baseline and 3 month NRS scores were 7.0 and 2.0 for the MRgFUS arm vs. 7.0 and 6.0 for the sham arm. A clinically significant improvement at 3 months in BPI-QOL score for MRgFUS but not sham treatment was noted [average change: 2.4 vs. 0.2 respectively, (p<0.0001)]. MRgFUS treatment was well tolerated. Conclusions: MRgFUS, as demonstrated by this phase III trial, results in excellent rates of pain relief and improvement in QOL for patients with oncologic related bone pain who are not candidates for radiation therapy. Given these excellent results coupled with a favorable side effect profile, MRgFUS should be considered a primary choice for this patient population. Clinical trial information: NCT00656305.
A randomized trial of single versus multiple fractions (Fx) for re-irradiation (RE-RT) of painful bone metastases (PBM): NCIC CTG SC.20.
Authors: Chow Edward , van der Linden Yvette , Roos Daniel , Hartsell William F. , Hoskin Peter , Wu Jackson S.Y. , Brundage Michael , Nabid Abdenour , Wilson Carolyn F. , Meyer Ralph M. , Chen Bingshu E , Wong Rebecca 
Published: March 2020

9502 Background: The optimal RE-RT dose and fractionation schedule for PBM is uncertain. Methods: Patients (pts) with PBM after previous radiation (RT) to the same site were stratified by previous Fx schedule and pain response and randomized to 8 Gy in 1 Fx or 20 Gy in 5 Fx (8 Fx if previous RT was to spine/whole pelvis in multiple Fx). The primary endpoint was overall response rate (RR) at 2 months using the International Consensus schema (Chow 2002) which combines Brief Pain Inventory worst pain score and opioid analgesic use. We tested if 8Gy was non-inferior (NI), analyzed by intention to treat (ITT) and a per-protocol (PP) sensitivity analysis excluding those who were ineligible, inevaluable or received non-allocated therapy. Sample size was calculated using an expected RR of 70% with 20Gy and a NI margin of 10% (i.e. upper boundary of 1-sided 95% CI for the RR difference). Pts reported adverse events (AEs) by questionnaire on Day 14. Quality of life (QoL) was assessed using the EORTC QLQ C30. Results: Between 01/2004 and 06/2012, we enrolled 850 pts from 9 countries. Most common cancers were prostate (27%), breast (26%) and lung (22%). Before the 2 month assessment, 98 (11%) pts died. By ITT, the 2-month RR was available in 66% (557/850) and was 119/425 (28%) with 8Gy and 136/425 (32%) with 20Gy (P=0.2); the upper boundary of the 95% CI for RR difference = 9.2% and is less than the pre-specified NI margin. By PP analysis, 2-month RR was available in 521 and was 117/258 (45.3%) with 8Gy and 135/263 (51.3%) with 20Gy (P=0.17); the upper boundary of the 95% CI for RR difference = 13.2%, which exceeds 10% non-inferiority boundary. Day 14 AEs differing by treatment were: lack of appetite (P=0.01), vomiting (P= 0.001), diarrhea (P=0.02) and skin reddening (P=0.002); all were worse with 20Gy. There were 30 vs 20 pathological fractures and 7 vs 2 spinal cord compressions with 8Gy and 20Gy, respectively (P=NS). No difference in QoL existed between arms. Conclusions: In pts with PBM receiving RE-RT, the 2-month RR obtained with 8Gy is non-inferior to 20 Gy when assessed by ITT but findings were not robust to a PP sensitivity analysis. When choosing between options tested, trade-offs exist between pain response and acute toxicity. Clinical trial information: NCT00080912.
The course of depression, inflammation in the serum and tumor microenvironment, and survival in the context of advanced cancer.
Authors: Steel Jennifer Lynne , Kim Kevin H , Gamblin T. Clark , Fraser Danyelle , Biala Michelle , Savkova Alexandra , Butterfield Lisa , Geller David A. , Marsh J. Wallis , Tsung Allan 
Published: March 2020

9507 Background: The aims of the present study were to study the course of depression in patients diagnosed with cancer and the link with biomarkers of inflammation in the serum or tumor microenvironment and survival. Methods: A total of 474 patients diagnosed with advanced cancer were administered the Center for Epidemiological Studies-Depression (CES-D) scale every 2-months and blood samples were drawn to assess biomarkers of inflammation in the serum and tumor microenvironment. The course of depression was estimated using a semi-parametric trajectory analyses and cross-lagged panel analyses were performed to assess the link between depression and biomarkers of inflammation. Cox regression analysis was use to test the link between depression and survival while adjusting for demographic and disease specific factors. Results: A three-class solution was chosen based on Bayesian information criterion and theory. The first class, “not depressed,” with a mean CES-D score of 6.7 at baseline contained 32% of patients and no significant change in depression scores across time. The second class, “mildly depressed” (53% of sample) had a significant increase in the mean CES-D from 14.5 at baseline to 18.0 at 12 months and 20.0 at 16 months [B = .35, z = 3.12, p = .002]. The third class, “severely depressed,” with a mean of 31.5 at baseline (15% of patients) and no significant change win depression over 24 months. Depression predicted serum levels of Tumor Necrosis Factor (TNF)-alpha and Interleukin-1alpha at subsequent time points and was associated with High Mobility Group Box 1 in the tumor microenvironment. Trajectory group assignment significantly predicted survival after demographic and disease specific factors were adjusted (p=0.04). The non-depressed trajectory group had a median survival of 13 months (95%CI=8.9-17.1), the mildly depressed group median survival was 10 months (95% CI 7.1-12.9) and the severely depressed group median survival was 6 months (95% CI=7.6-12.4). Conclusions: These findings may facilitate the targeting of psychosocial and biological interventions to reduce depression symptoms, improve quality of life, and potentially slow disease progression.
The role of age on dose-limiting toxicities (DLTs) in phase I dose-escalation trials.
Authors: Schwandt Anita , Harris Pamela Jo , Hunsberger Sally , Deleporte Amélie , Smith Gary L , Vulih Diana , Anderson Barry Douglas , Ivy S. Percy 
Published: March 2020

9517 Background: Elderly oncology patients are not enrolled on phase I trials in proportion to the prevalence of cancer in the age-matched population. They are excluded from these trials based on the perception that these patients will have an increased number of and more severe toxicities, per dose level, than younger patients. We hypothesize that if other patient characteristics are accounted for, then age will not be an independent predictor of dose limiting toxicities (DLTs). Methods: We retrospectively reviewed data from 162 single- agent dose-escalation phase I clinical trials performed at the Cancer Therapy Evaluation Program/National Cancer Institute. Several baseline patient characteristics, including age, were collected. Patient dose levels were described as %MTD and an analysis of age, dose and DLTs was performed. Results: Data was obtained from 5,401 patients who were divided into five age groups, with 556 pts < 40 years old, 2,438 between 40-59, 1,481 between 60-69, 836 between 70-79 and 90 pts > 79. Proportion of DLT occurring in each age group and %MTD are described in the Table. Conclusions: This analysis of DLTs occurring in nearly 1000 patients over 70 years of age on phase I dose-escalation trials is the largest reported. A logistic regression model will be performed to determine if age, by itself, predicts for DLTs and what concurrent patient characteristics contribute to their occurrence. [Table: see text]
Prognostic information (PI), psychological well-being, and quality of life for advanced cancer patients (ACP) in phase I trials and their spousal caregivers (SC).
Authors: Hlubocky Fay J. , Cella David , Sher Tamara , Yap Bonnie , Ratain Mark J. , Daugherty Christopher 
Published: March 2020

9520 Background: The impact of the physician’s (MD) disclosure of PI on the psychological well-being and quality of life (QoL) of clinical trial subjects with terminal disease on Phase I trials has not been formally evaluated. Methods: A prospective cohort of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) utilizing various measures including: state-trait anxiety (STAI-S/T), depression (CES-D), quality of life/QoL (FACIT-Pal), and global health (SF-36). Semi-structured interviews of ACPs also evaluated MD-Pt communication re prognosis and worry about ACP death. Results: 100 subjects (50 Phase I ACPs and 50 SC) were separately interviewed at T1 and T2. For the population as a whole: median age 62 (28-78y); 51% male; 100% married; 88% Ca; 68% > HS educ; 56% GI dx; 54% income <$65,000 yr. At T1, 45% of ACPs acknowledged having a discussion re life expectancy with MD; 35% stated the MD gave a prognostic timeframe; and 41% reported worry re death. For SC at T1, 62% recalled a prognosis discussion with the MD; 50% stated MD gave a timeframe; 53% reported PI disclosure was initiated by the MD; 66% reported worry re ACP death. At T2, rates remained consistent for both ACP and SC with the exception of increased reported worry re ACP death at 55% and 70% respectively. At T2, ACP who denied a prognosis was given by the MD had higher STAI-S (35 ± 10 v 29 ± 9, p=0.03) and CES-D scores (16 ± 12 v 7 ± 4, p=0.01); and lower FACT-Pal scores (128 ± 18 v 153 ± 24, p=0.01). SC with acknowledgement of a prognostic timeframe given by the MD had higher STAI-S anxiety (39 ± 16 v 35 ± 14, p=0.04) at T2. Regression analyses revealed that ACP with acknowledgement of a prognostic timeframe given by the MD had poorer FACIT-Pal QoL over time. Also, SC with acknowledgement of a prognostic timeframe at T2 was negatively associated with SF-36 scores. ACP and SC qualitative responses re PI disclosure revealed salient themes: hope for a positive outcome or prolonged survival; stabilization of disease; emotional distress; ambivalence/fear; acceptance. Conclusions: Physician disclosure of a prognostic timeframe is negatively associated with QoL among clinical trial subjects and SC in phase I trials.
Actigraphy measured sleep disruption as a predictor of survival in advanced breast cancer.
Authors: Palesh Oxana , Gerry Arianna Aldridge , Zeitzer Jamie M. , Koopman Cheryl , Jo Booil , Neri Eric , Nouriani Bita , Spiegel David 
Published: March 2020

9532 Background: Sleep disruption, prevalent in cancer patients and survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Previous studies in cancer patients and survivors have pointed out the association between poor sleep and faster disease progression. However, until now these studies have been limited by their retrospective or correlational design, providing little resolution of the question of whether sleep disruption accelerates disease progression or whether disease progression dysregulates sleep, or whether a third factor might underlie the association between sleep dysregulation and disease progression. This study aimed to clarify this relationship by using a longitudinal research design to examine whether sleep disruption assessed at baseline predicts survival in women with metastatic breast cancer. Methods: We examined sleep quality and duration in 97 women diagnosed with metastatic breast cancer (mean age=54.6, SD=9.8) via wrist-worn actigraphy for 3 days and sleep diaries. Sleep quality was operationalized as poor sleep efficiency (the ratio of total asleep time to total time in bed * 100%). Results: As hypothesized, poor sleep efficiency was found to predict shorter survival (Hazard Ratio (HR), 0.96, 95% CI, 0.93 to 0.98, p<0.001) over 6 years. This relationship remained significant (HR, 0.94, CI, 0.91 to 0.97, p<.001) even after controlling for other known prognostic factors (age, ER status, cancer treatment, metastatic spread, cortisol levels, and depression). Conclusions: Our findings show that sleep dysregulation is a clear and significant independent prognostic factor for disease progression in metastatic breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral therapy or medication can improve survival in metastatic breast cancer. Funded by P01AG018784, R01CA118867, K07CA132916.
The role of social exposure to smoking on smoking cessation in adult cancer survivors.
Authors: Eng Lawson , Pringle Dan , Qiu Xin , Shen Xiaowei , Niu Chongya , Mahler Mary , Halytskyy Oleksandr , Charow Rebecca , Lam Christine , Shani Ravi M. , Villeneuve Jodie , Tiessen Kyoko , Brown M Catherine , Alibhai Shabbir M.H. , Jones Jennifer M. , Howell Doris , Goldstein David P. , Xu Wei , Selby Peter , Liu Geoffrey 
Published: March 2020

9536 Background: We previously described a strong inverse relationship between social smoking exposures (at home, spousal and with peers) and smoking cessation in lung cancer, with adjusted odds ratios (aOR) of 3-8 (Eng et al, ASCO 2012, abst 9032). In the current analysis, we evaluated whether these associations hold true in adult cancers in general, particularly cancers not traditionally known to have smoking as a risk factor. Methods: 616 cancer survivors across multiple cancer sites were surveyed on their smoking, alcohol, and physical activity habits before and at various times after cancer diagnosis. Social smoking exposures were documented. Multivariate logistic regression models evaluated the association of each variable with change in each habit after diagnosis adjusted for significant socio-demographic and clinico-pathological covariates. Results: Median follow-up after diagnosis was 26 months. 15% had breast cancers; 15% gastrointestinal; 20% genitourinary-gynecological; 24% haematological; 36% other. Among current smokers at diagnosis, 56% quit after diagnosis; no ex- or never-smoker restarted. Patients without secondary home smoking exposure were significantly more likely to quit smoking than those with home exposures (aOR=9.5, 95% CI [2.4-37.8]). Similar results were seen in patients with non-smoking spouses versus smoking spouses (aOR=3.7 [1.0-13.4]), and with lack of peer smoke exposure (aOR=3.7 [1.3-10.7]). 63% patients who quit did so in the 1 year period surrounding the diagnosis date (6-months pre or post diagnosis). In comparison, first and second-hand smoking exposures did not affect other modifiable behaviours such as alcohol or physical activity. Patient awareness of quality of life and survival benefits of smoking cessation and receiving smoking cessation counselling were not associated with improved smoking cessation. Conclusions: Secondary smoking exposures are associated with lack of smoking cessation in adult cancer survivors, even in cancers not traditionally linked to smoking. Being diagnosed with cancer may be an important `teachable moment` to help patients quit, but results are strongly influenced by the surrounding social exposure to smoking. PS and GL contributed equally.
Factors related to end-of-life (EOL) chemotherapy in solid tumor (ST) patients.
Authors: Rodriguez Maria Alma , DeJesus Yvette A , Cheng Lee , Buzdar Aman , Burke Thomas W. 
Published: March 2020

9538 Background: Oncologists will be required to report quality measures for cancer care, including use of chemotherapy in the last two-weeks of life. In this study, we evaluated how use of chemotherapy in ST patients (pts) within 14 days of EOL may be influenced by clinical factors. Methods: Adult pts (≥18 years) treated for ST at our institution, deceased December 01, 2010 through May 31, 2012, were retrospectively studied. Data on demographics, chemotherapy (excluded: hormones) within 14 days EOL, comorbidities, and cancer diagnoses were from tumor registry and administrative databases. Logistic regression analysis was performed for association of EOL chemotherapy with age, gender, ethnicity, comorbidities , cancer types, and metastatic status. Results: 5,607 pts met study criteria: median age 64 years; 48% female; 76% metastatic disease. EOL chemotherapy frequency was 3.9% overall, 4.6% in metastatic disease versus 1.7% in non-metastatic disease (p<0.01). In 23 patients with non-metastatic disease who received chemotherapy, the diagnoses were: brain/other nerve system (34.8%, 8/23) and lung/bronchus (21.7%, 5/23).The top 10 frequencies in chemotherapy use by tumour sites were: melanoma (6.7%), female breast (5.5%), lung & bronchus (4.9%), pancreas (4.2%), brain/other never system (3.9%), head & neck (3.8%), female genital system, excluding ovary (3.4%), ovary (3.2%), liver/intrahepatic bile duct (3.0%), colon & rectum (2.6%). By regression analysis, the factor statistically significantly associated with receiving chemotherapy was metastatic disease (odds ratio [OR], 3.29; 95% CI,1.96-5.54), while factors associated with significantly less treatment were age ≥ 65 (OR, 0.66; 95% CI, 0.49-0.90); and any co-morbid conditions (≥1 versus 0) (OR, 0.58; 95% CI, 0.38-0.89). Conclusions: A small portion of ST patients who died received EOL chemotherapy (3.9%). However, metastatic disease and diagnosis category influenced treatment. Melanoma and breast cancer patients had higher frequency of EOL treatment. Older age and comorbidities were associated with less treatment. Variation in EOL treatment of ST patients is thus influenced by several clinical factors, but did not seem influenced by gender or ethnicity factors.