tbuckley/cabot-search huggingface dataset:
Identfying barriers to providing tobacco cessation support for cancer patients.
Authors: James Roger Marshall, Shiva Dibaj, Alan Hutson, Kenneth Michael Cummings, Carolyn M. Dresler, Graham Walter Warren
Journal: Journal of Clinical Oncology (2014)

1578 Background: The 2014 Surgeon General’s Report concluded that smoking caused increased mortality in cancer patients, but data demonstrate that most physicians do not regularly provide tobacco cessation support. The purpose of this study was to identify predictors of providing tobacco cessation support through a large physician provider survey administered through the International Association for the Study of Lung Cancer (IASLC). Methods: An online survey was developed and administered to IASLC members asking about tobacco assessment and cessation practices. Barriers to providing cessation support were also asked. Responses were analyzed to identify demographic, perception, and practice related correlates of decreased cessation support. Results: A total of 1,507 respondents replied to the survey representing a 40.5% response rate. Respondents from the United States (US) , in an academic practice, and devoting more time to patient care were associated with higher rates of asking about tobacco use. However, only practice in the US predicted for higher rates of providing cessation assistance. Respondents reporting clinicians need more education on cessation and respondents stating they had sufficient education was predictive of regularly providing cessation support. Believing that tobacco cessation does not affect cancer treatment outcome predicted for lower rates of assisting with cessation support. Reimbursement concerns and belief that patients were not receptive to cessation support did not affect physicians regularly providing cessation support. However, lack of resources, lack of training and experience with cessation, and lack of time were all predictive of decreased tobacco cessation support by respondents. Conclusions: Lack of time, training, and resources were the primary determinants of providing tobacco cessation support for cancer patients. Efforts are needed to address these issues to improve tobacco cessation support in the standard clinical care of cancer patients.
Targeting VEGFRi resistance through HIF-1á suppression: Phase II clinical trial evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent platinum resistant ovarian cancer.
Authors: Carolyn N. Krasner, Michael J. Birrer, Suzanne T. Berlin, Mary K. Buss, Scott Eliasof, Edward Graeme Garmey, Meliessa Hennessey, Neil S. Horowitz, Panagiotis Konstantinopoulos, Ursula A Matulonis
Journal: Journal of Clinical Oncology (2015)

TPS5614 Background: Ovarian cancer (Ov.Ca.) is the leading cause of death among gyn malignancies. Limited treatment options exist for women whose tumors have become platinum resistant. Hypoxia Inducible Factor-1α (HIF-1α) is a master regulator of key cancer cell survival pathways and facilitates resistance to anti-angiogenic therapies. CRLX101, a novel nanoparticle-drug conjugate that differentially delivers camptothecin into cancer cells, durably suppresses HIF-1α and the combination of CRLX101 with anti-angiogenic drugs incl. bevacizumab (Avastin, Genentech/Roche)(BEV) achieves notable drug-drug synergy in pre-clinical models. Phase 2 monotherapy results achieved with CRLX101 and presented at ASCO 2014 exceeded expectations in this setting and established the basis for this follow-on study. Methods: This phase 2 open label, two-stage clinical trial evaluates the combination of CRLX101 plus BEV in pts. with epithelial ovarian, tubal or primary peritoneal cancer progressing through prior platinum-containing chemotherapy. Eligible pts. must have platinum-resistant measurable disease and may have received 1 or 2 prior regimens of chemotherapy that includes no prior topo-1 inhibitors or BEV. Pts. receive CRLX101 15 mg/m2 IV plus BEV 10 mg/kg IV on days 1 and 15 of their 28-day cycles. All pts. undergo CT-based tumor evaluations every 2 cycles. The primary endpoint is progression free survival (PFS) at 6 months (PFS6) and secondary objectives include response rate and assessment of toxicity. A 2-stage design is being employed with the study terminated if ≤ 2/18 stage 1 pts. achieve the PFS6 endpoint. As this gate has now been met, a 2nd stage will enroll 25 additional pts. and the treatment will be considered worthy of further investigation if ≥ 8/43 total pts. achieve PFS6. Enrollment is ongoing and to-date the drug appears well tolerated with no drug-related SAEs, treatment discontinuations, or deaths observed. Clinical trial information: NCT01652079.
Comparison of fludarabine (F), cyclophosphamide (C), and rituximab (R) versus FCR plus bevacizumab (B) in relapse chronic lymphocytic leukemia (CLL).
Authors: Hun Ju Lee, William G. Wierda, Alessandra Ferrajoli, Jan Andreas Burger, Long Trinh, Susan Lerner, Michael J. Keating, Susan Mary O'Brien
Journal: Journal of Clinical Oncology (2012)

6598 Background: There is significant data to show that vascular endothelial growth factor (VEGF) is important in the development and progression of CLL. Bevacizumab (B) is an anti-VEGF monoclonal antibody associated with improvement in progression free survival (PFS) when combined with chemotherapy in pts with solid malignancies. FCR is the most active chemoimmunotherapy in treatment of CLL. We report data on a phase II trial combining FCR-B and comparing the results to those seen in a trial with FCR for pts with relapsed CLL (Badoux et al. Blood, March 2011). Methods: FCR consisted of F: 25 mg/m 2 and C: 250 mg/m 2 on D2-4; R: 375 mg/m 2 on D1 (for the first course) and 500 mg/m 2 for courses 2-6, every 4 weeks for 6 courses. FCR-B consisted as above for FCR and (B) 10 mg/kg was given on D3 of each cycle. Indications for treatment and response assessment were according to 1996 NCI-WG guidelines for both groups. Results: Baseline characteristics, complete remission (CR), overall response rate (ORR), PFS and OS of relapsed CLL pts are shown (Table). Conclusions: In relapsed pts with CLL, FCR-B showed a trend toward improved PFS compared to FCR. [Table: see text]
Second Attempt to Discontinue TKI in CML Patients Who Have Sustained CMR for over 2 Years Is Rarely Successful Even with the Use of Second Generation TKIs
Authors: Eri Matsuki, Masatoshi Sakurai, Daiki Karigane, Hidenori Kasahara, Taku Kikuchi, Takayuki Shimizu, Kenji Yokoyama, Takehiko Mori, Shinichiro Okamoto
Journal: Blood (2016)
Biologic pathways, candidate genes, and molecular markers associated with quality-of-life domains.
Authors: Jeff A. Sloan, Melissa Thong, Meike Bertels, Andrea Barsevick, Juan Ordonana, Shelley Wang, Pal Klepstad, Ailko Zwinderman, Eddy Weirenga, Jasvinder A Singh, Gen Shinozaki, Mirjam Sprangers
Journal: Journal of Clinical Oncology (2014)

1561 Background: There is now compelling evidence of a genetic foundation for patient-reported quality of life (QOL) domains. This work reports the results of a systematic review of thebiological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods: We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. We conducted a computerized literature search on PubMed for the years November 2007- November 2012 to build on our previous work (Sprangers, QOLR, 2009). A gene or molecular marker was included if there is at least one publication (either empirical, meta-analysis or review) reporting a significant association with a QOL domain. Results: More than 200 articles were identified and reviewed. Multiple major biological pathways are involved in each QOL domain, summarized into a series of seven tables describing each biological pathway and candidate gene. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. In total, more than 50 candidate genes were identified as having previously published evidence of at least a preliminary relationship with patient-reported QOL-related domains. Conclusions: We have produced a set of candidate genes and biological pathways for researchers to use when embarking on studies relating candidate genes and/or molecular markers to QOL.
Surgery for Cancer: A Trigger for Metastases
Authors: Samer Tohme, Richard L Simmons, Allan Tsung
Journal: Cancer Research (2017)

Surgery is a crucial intervention and provides a chance of cure for patients with cancer. The perioperative period is characterized by an increased risk for accelerated growth of micrometastatic disease and increased formation of new metastatic foci. The true impact for cancer patients remains unclear. This review summarizes the often fragmentary clinical and experimental evidence supporting the role of surgery and inflammation as potential triggers for disease recurrence. Surgery induces increased shedding of cancer cells into the circulation, suppresses antitumor immunity allowing circulating cells to survive, upregulates adhesion molecules in target organs, recruits immune cells capable of entrapping tumor cells, and induces changes in the target tissue and in the cancer cells themselves to enhance migration and invasion to establish at the target site. Surgical trauma induces local and systemic inflammatory responses that can also contribute to the accelerated growth of residual and micrometastatic disease. Furthermore, we address the role of perioperative factors, including anesthesia, transfusions, hypothermia, and postoperative complications, as probable deleterious factors contributing to early recurrence. Through the admittedly limited understanding of these processes, we will attempt to provide suggestions for potential new therapeutic approaches to target the protumorigenic perioperative window and ultimately improve long-term oncological outcomes. Cancer Res; 77(7); 1548-52. ©2017 AACR.
Late recurrence in survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: K. Wasilewski-Masker, W. Leisenring, L. R. Meacham, S. Hammond, A. T. Meadows, L. L. Robison, A. C. Mertens
Journal: Journal of Clinical Oncology (2007)

9534 Background: An increasing percentage of childhood cancer patients are surviving their disease, but limited research suggests that late recurrences may impact overall survival. The goal of this study is to estimate late recurrence rates for the most common pediatric cancers and to determine additional risk factors for late recurrence. Methods: CCSS is a retrospective cohort study of five-year survivors of childhood cancer diagnosed before 21 years of age, between 1970 and 1986 at one of 26 consortium centers. Late recurrence was defined as first recurrence occurring &gt; five years post-diagnosis. Recurrences were determined by self-report questionnaire or by confirmation through medical record, death certificate or pathologic review. Probability of late recurrence was calculated using cumulative incidence. Adjusted hazard ratios (HR) were obtained using Cox proportional hazards regression. Results: In 12,948 survivors with no recurrence = five years from diagnosis, 670 (5.2%) subjects had a first recurrence &gt; five years after their primary diagnosis. Late recurrences ranged from 5 to 28.9 years from diagnosis (median 7.9 years). Cumulative incidence varied by diagnosis ( table ). In multivariate analysis, significant risk factors for increased late recurrence included a primary diagnosis of Ewing's sarcoma or CNS tumors (HR of 2.3 and 2.7 respectively vs. leukemia survivors), age = 10 years at diagnosis (HR 1.4 vs. age &lt; 10 years), chemotherapy exposure (HR 1.5 vs. none), and radiation exposure (HR 1.4 vs. none) (p &lt; 0.001 for all). At the time of last follow-up, 51.6% of subjects with a late recurrence had died versus 6.4% of those with no history of recurrence. Conclusions: Late recurrences occur in survivors of childhood cancers with a significant risk of mortality. This emphasizes the importance of long-term survivor follow-up into adulthood, particularly for adolescents and patients with Ewing's sarcoma and CNS tumors. [Table: see text] No significant financial relationships to disclose.
Outcomes of 3-weekly doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) in a randomized trial (RCT) compared to a case-control matched British Columbia (BC) breast cancer population.
Authors: Sheridan Marie Wilson, Yvonne Zheng, Judy-Anne W. Chapman, Margot J. Burnell, Caroline Speers, Emily Baxter, Scott Tyldesley, Lois E. Shepherd, Karen A. Gelmon, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2014)

1037 Background: NCIC CTG MA.21 was a North American RCT of 3 adjuvant chemotherapies (adjCT), of which one was 3-weekly AC/T. We compared Relapse Free Survival (RFS) for this standardised adjCT given in MA.21 to that in a general population from a BC database, using a matched case-control design. Methods: Matching was based on age +/- 3 years (y) and MA.21 stratification factors: number of positive nodes [NP], surgery type, and estrogen receptor (ER). Patients (pts) who received > 1 cycle of AC/T were included. RFS was defined as time from randomisation (per protocol, AC/T started within 5 days) to recurrence for MA.21, and from first AC/T to recurrence for BC. A sensitivity analysis using HER2 negative (HER2-) pts was done, as testing and trastuzumab (TZ) use changed over time. RFS was estimated with Cox survivor plots, adjusting for factors significant in multivariate Cox step-wise forward regression. Results: 473 of 671 BC pts were matched to 473 of 696 MA.21 pts. Median follow up was 8 y and median time from surgery to AC/T was 48 days for both. After matching 52% were ER +; 37% node negative (NN); 62% of MA.21 and 56% of BC cases were HER2-. 76% of NN BC cases were grade 3; grade was unavailable for MA.21. Unadjusted 5 y RFS was 85% (95% confidence interval [CI] 81, 88) for BC and 82% (CI 78, 85) for MA.21. For HER2- only, 5y RFS was 85% (CI 80, 89) for BC and 79% (74, 83) for MA.21 pts. The Table shows multivariable analysis (ER and age were not significant). The HR in HER2- only cases was 0.68 (CI 0.47, 0.98, p = 0.04) for BC vs MA.21 pts. Conclusions: BC pts had superior adjusted RFS compared with matched pts who received AC/T in a RCT. We were unable to compare adherence to ET and ethnic distribution, which may explain some of the disparity. Also, BC has long had a low threshold for offering radiation for NP. It is reassuring that RCTs do not appear to overestimate adjCT RFS benefits in the general breast cancer population. Variable Hazard ratio (Hz) 95% CI P BC vs MA.21 0.65 0.48, 0.89 0.008 Endocrine therapy (ET) 0.44 0.33, 0.60 <0.001 NP (NN as reference) 1-3 NP 1.24 0.86, 1.78 0.252 4-10 NP 2.46 1.65, 3.66 <0.001 >10 NP 7.26 4.33, 12.19 <0.001 TZ use 0.53 0.28, 0.991 0.047
Patterns of trastuzumab (T) use in three Canadian provinces
Authors: K. A. Gelmon, T. Whelan, J. Latreille, I. Olivotto, C. Sawka, K. Pritchard, S. Bondy, R. Cosby, R. Roberts, M. Levine
Journal: Journal of Clinical Oncology (2004)

633 Background: New therapies for breast cancer are not always readily and appropriately adopted in clinical practice. The objective of this study was to examine patterns of T use in three Canadian provinces: Ontario (ON), Quebec (QC) and British Columbia (BC). While all 3 provinces have publicly funded health care systems, the care delivery models are different. ON has a centralized cancer system with the use of evidence based guidelines and the requirement for completion of new drug eligibility forms. BC has a more centralized system with less restrictive guidelines and implementation requirements. QC has none of these factors. In 1999 the federal regulatory agency approved T for use as a single agent or combined with chemotherapy in HER 2 positive metastatic breast cancer (MBC). ON and BC guidelines recommended T for use in combination with paclitaxel (P) or vinorelbine (V) (the latter in BC only) after anthracycline failure or as a single agent after taxane failure. Methods: Case specific data were collected on all patients treated with T for 3 years from 1999–2002. Patients on a T clinical trial were excluded. Information was collected from provincial cancer registries and patient charts. Patients were evaluated for consistency with federal agency recommendations and provincial guidelines. Results: T was used in 398 women in ON; 322 in QC; and 205 in BC representing respectively 6.6%; 7.4% and 10.7% of the estimated number of women who died of MBC in those provinces during the study period. Patients in ON and BC were more likely to be treated consistent with federal agency recommendations and provincial guidelines (Table). Response rates were higher in BC which was associated with earlier use in patients with fewer sites of MBC and less prior treatment. Conclusions: The presence of a centralized cancer system led to better adherence to federal agency recommendations. Less restrictive guidelines may facilitate earlier use of T. No significant financial relationships to disclose.
Quality of life in patients with malignant brain tumors.
Authors: Ali K. Choucair, Lisa B.E. Shields
Journal: Journal of Clinical Oncology (2012)

2058 Background: A positive quality of life (QOL) serves as an important outcome priority in patients with malignant brain tumors whose survival is limited by tumor resistance to treatment. The FDA and ASCO have designated QOL as an outcome secondary in importance to survival. We conducted a prospective longitudinal collection of QOL measures (EORTC QLQ-C30, EORTC QLQ-BN20, and Hospital Anxiety and Depression Scale [HADS]) coupled with clinical standards of care (brain MRI and clinical history and physical examinations) in patients with newly diagnosed primary brain tumors (PBT). We also examined the QOL measures over time as related to tumor progression. Methods: Under an IRB-approved protocol, we reviewed the validated QOL measures and standard clinical measures from patients who were newly diagnosed with PBT. The patients were followed every 3 months over 2 years. No proxies were allowed. A total of 52 patients were enrolled in the study. Survey responses were compared between two tumor groups of patients: patients with tumor recurrence and/or died and patients without a recurrence (n=26 each group). A total of 17 patients succumbed to a tumor-related death. Statistical analysis utilizing non-parametric t-tests and Wilcoxon sign tests assessed QOL responses. Results: Significant group differences were noted in the questions of the QOL measures surveys with more negative responses in the recurrence group. The questions with significant group differences on the EORTC QLQ-C30 ranged from symptoms of dyspnea (p&lt;.05) and difficulty sleeping (p&lt;.05) as well as a poor QOL (p&lt;.005) and pain interfering with daily activities (p&lt;.05). Significant group differences of questions on the EORTC QLQ-BN20 included weakness of the legs (p&lt;.05), coordination difficulties (p&lt;.005), and unsteady gait (p&lt;.05). Significant group differences of questions on the HADS reflected a patient who is "slowed down" (p&lt;.01) and "frightened" (p&lt;.05). Conclusions: Our analysis of questions answered by patients with newly diagnosed PBT may shed light on the impact of cancer and its treatment and potential recurrence on a patient's QOL. Further research is warranted to incorporate QOL measurements into improvement of patient care and their use in clinical trials and as a prognostic indicator.
Outcome of pelvic exenteration for recurrent endometrial and cervical cancers.
Authors: Christelle Abboud, Charlotte Ngo, Paul Meria, Virginie Fourchotte, Pascale Mariani, Bernard Baranger, Peter Petrow, Xavier Sastre, Paul H. Cottu, Anne Delarochefordiere, Severine Alran
Journal: Journal of Clinical Oncology (2012)

e15524 Background: Pelvic exenteration has been used as a potentially curative operation in recurrent pelvic malignancies. However, treatment-related morbidity is over 50% in radiated pelves. We evaluated the outcome and the morbidity of pelvic exenteration in women with recurrent cervical and endometrial cancer. Methods: We studied retrospectively all the patients who underwent a pelvic exenteration for recurrent cervical or endometrial cancer in our institution, from January 1999 to November 2011. All medical data were collected. Survival rates were calculated according to Kaplan-Meier method and compared using the log-rank test. Results: twenty-five patients were identified, 17 (68%) had cervical cancer and 8 (32%) endometrial cancer. All patients received a radiation therapy during their initial treatment. All patients had a central pelvic recurrence, in a median time of 30 months [4-384]. 15 patients (60%) had an urinary diversion with incontinent ileoconduit (Bricker). 22 patients (88%) had a complete tumor resection. Severe early complications needing a re-laparotomy occurred in 9 patients (36%) (insufficiencies of intestinal anastomosis, insufficiencies of the ureteral anastomosis and pelvic abscesses). One patient (4%) had a recto-vaginal fistula. Late complications included 1 (4%) vaginal fistula, 1 (4%) intestinal fistula), 2 (8%) intestinal occlusion and 1 (4%) ureteral stenosis. Disease Free and Overall survival rates are better in cervical than in endometrial cancer (median DFS in months 17 [2-145] vs 9.5 [3-21], p= 0.064, median OS in months 20 [2-145] vs 13 [4-42], p=0.019) (table 1). Conclusions: Morbidity of pelvic exenteration remains high. Endometrial cancer is associated with a poorer prognosis. In those patients, the benefit of exenteration should be discussed compared to best supportive care for palliative treatment. [Table: see text]