tbuckley/cabot-search huggingface dataset:
Phase II study of neoadjuvant weekly paclitaxel and carboplatin with lapatinib in HER2+ breast cancer.
Authors: Andrea Li Ann Wong, Sing Huang Tan, I Peng Thomas Soh, Chee Seng Tan, Yi Wan Lim, Angela Pang, Jingshan Ho, Samuel Guan Wei Ow, Raghav Sundar, Mei-Yan Pang, Ching-Wan Chan, Shaik Ahmad Buhari, Mikael Hartman, Philip Iau, Anthony Tang, Nan-Soon Wong, Yoon Sim Yap, Bee-Luan Khoo, Jean Paul Thiery, Soo-Chin Lee
Journal: Journal of Clinical Oncology (2014)

619^ Background: The optimal neoadjuvant regimen in HER2+ breast cancer is undefined. We evaluated the efficacy and tolerability of weekly paclitaxel/carboplatin with lapatinib. Methods: HER2+ stage I-III breast cancer patients received 4 cycles of 3 weekly PCL [IV paclitaxel (P) 80mg/m2 (days 1, 8, 15), carboplatin (C) AUC 2 (days 1, 8), oral lapatinib (L) (750mg daily)] followed by surgery. Lapatinib dose reductions were not allowed. Patients with pCR (ypT0N0) received 2 cycles of adjuvant PCL; those without received 4 cycles of doxorubicin/cyclophosphamide. All received 1 year of adjuvant trastuzumab and at investigators’ discretion, concurrent lapatinib 1000mg/day for 52 weeks (neoadjuvant + adjuvant). Primary endpoint was pCR; secondary endpoints were clinical CR/PR, toxicities and DFS. Results: 36 patients were recruited (Chinese/Malay/Others: 52.8/36.1/11.1%). Median age at diagnosis was 51 (29-78) years. 69.4%, 63.9%, 80.6% and 61.1% had cT3/4, cN+, grade 3 and hormone receptor positive tumors. 63.9% achieved CR/PR after 2 cycles. At surgery, 33.3% were ypN0, and 11.1% achieved pCR, which was limited to patients with cN0 tumors (n=8; 50% pCR). At 21 month median follow-up, 2 year DFS was 83.3%. G3/4 non-hematologic toxicities occurred in 19.4%, mainly from non-neutropenic infections (11.1%) and gastrointestinal toxicities (8.3%). None developed cardiac dysfunction. Patients with G3/4 non-hematologic toxicities had lower mean relative dose intensity of all 3 drugs (P: 0.61 + 0.33 vs 0.91 + 0.16, p=0.002; C: 0.65 + 0.30 vs 0.95 + 0.14, p=0.001; L: 0.62 + 0.34 vs 0.97 + 0.10, p<0.01) and lower clinical CR/PR rates (40% vs 90.3%, p=0.024) than those without. Dose interruptions (P: 37.1%, C: 34.4%, L: 11.4%) and reductions (P: 16.7%. C: 19.5%) were common. Serial samples from 5 patients without pCR showed general progressive decline in circulating tumor cells with treatment but remained measurable before surgery. Conclusions: While the low pCR rate was contributed by advanced tumors, PCL dose intensity was difficult to maintain and its efficacy/toxicity ratio not favorable in unselected patients. Tumor immunohistochemistry and pharmacogenetic studies are ongoing to select patients most likely to benefit. Clinical trial information: NCT01309607.
Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes
Authors: Mary T. Korytkowski, Daniel E. Forman
Journal: Diabetes Care (2017)

Older adults with diabetes are at higher risk for atherosclerotic cardiovascular disease (ASCVD) than younger adults with diabetes and older adults without diabetes. The rationale to implement ASCVD risk–lowering therapies in older adults with diabetes is compelling. Recommendations for lifestyle modification, lipid-lowering therapy, blood pressure management, blood glucose control, and aspirin therapy are often based on studies that show their efficacy in younger populations. However, the risks associated with each of these interventions increase with age, and favorable risk-to-benefit ratios demonstrated in younger adults with diabetes are less certain in older populations. The variability in health status among older adults is pertinent. Those with robust health are more likely to tolerate and derive benefit from many therapies when compared with those who have more complex health including frailty. Age- and/or frailty-stratified data to help clarify these relationships are sparse. In this Perspective, current recommendations for modifying ASCVD risk are described with a review of the pertinent literature that guides their application in older adults. A pragmatic approach to the treatment of ASCVD risk factors in older adults with diabetes is presented.
Association Between High-Sensitivity Cardiac Troponin Levels and Myocardial Ischemia During Mental Stress and Conventional Stress
Authors: Muhammad Hammadah, Ibhar Al Mheid, Kobina Wilmot, Ronnie Ramadan, Ayman Alkhoder, Malik Obideen, Naser Abdelhadi, Shuyang Fang, Ijeoma Ibeanu, Pratik Pimple, Heval Mohamed Kelli, Amit J. Shah, Brad Pearce, Yan Sun, Ernest V. Garcia, Michael Kutner, Qi Long, Laura Ward, J. Douglas Bremner, Fabio Esteves, Paolo Raggi, David Sheps, Viola Vaccarino, Arshed A. Quyyumi
Journal: JACC. Cardiovascular imaging (2017)
Using scenarios to explain survival time: Attitudes of people with a cancer experience.
Authors: Martin R. Stockler, Belinda E. Kiely, Georgia J. McCaughan, Sophie Christodoulou, Philip James Beale, Judith Trotman, Peter Grimison, Martin HN Tattersall
Journal: Journal of Clinical Oncology (2012)

9126 Background: Most people with advanced cancer want some information on their life expectancy. We sought the attitudes of people with a cancer experience to using three scenarios for survival (best-case, worst-case, and typical) to explain life expectancy to people with advanced cancer. Methods: Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with incurable cancer - providing either three scenarios for survival or just the median survival time. Associations between respondent attitudes and their demographic and tumour characteristics were explored. Results: Characteristics of the505 respondents from outpatient clinics (n=251) and BCNA (n=254) were: median age 58 years; female 74%; completed high school education 80%; breast primary 64%; self-report of cancer spread to other body parts 23% and; a median of 4 years since diagnosis of cancer. More respondents agreed that explaining three scenarios (vs. just the median survival time) would: make sense (93% vs. 75%), be helpful (93% vs. 69%), convey hope (68% vs. 44%), reassure (60% vs. 40%) and help family members (91% vs. 71%); all p-values &lt;0.001. Fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24% v 36%); p&lt;0.001. The proportions of respondents agreeing that each of the 3 scenarios should be presented were: best-case 89%, worst-case 82%, and typical 92%. Most respondents (85%) agreed it would be helpful to receive a printed summary of the scenarios for survival. For information about their own prognosis, 88% preferred all three scenarios and 5% a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95% v 90%, p=0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31% v 13%, p&lt;0.001). Conclusions: Most respondents judged presentation of best-case, worst-case and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.
Palliative inpatient chemotherapy: Clinical benefit or harm?
Authors: Maria Ali, M. Christine Cripps, Katelyn Balchin, Jennifer Spencer, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2012)

e19527 Background: Palliative chemotherapy (CT) is given with the goals of palliating cancer symptoms and prolonging life. Patients with a poor performance status (PS) generally derive less benefit from CT and may experience greater toxicity. Advanced cancer patients admitted to hospital generally have a poor PS, and yet palliative CT is often administered to hospitalized patients. The evidence to support palliative CT in hospitalized patients is scarce. We hypothesize that palliative in-patient CT does not result in meaningful clinical benefit. Methods: With ethics approval, a retrospective chart review was undertaken to report outcomes from in-patient CT at the Ottawa Hospital Cancer Centre between April 2008- January 2010. From hospital pharmacy records, all advanced solid tumor patients receiving in-patient palliative CT were identified. Patients receiving radical, curative, neo- or adjuvant therapy, or those admitted for an inpatient regimen, were excluded. The primary endpoints were overall survival following CT, place of discharge from hospital, and whether further CT was received. Results: We report 199 in-patients (23% breast cancer, 22% small cell lung cancer, 16% NSCLC, 39% other) who received CT (median 1 cycle, range 1-5) during the study period. The median age was 61 (range 19-88); 59% were female. The main reasons for hospital admission were dyspnea (31%) or pain (29%). At baseline 25% were anemic, 36% had leucocytosis and 70% were hypoalbuminemic (&lt;30g/l). 67% were receiving 1 st line CT. The median overall survival was 4.5 months (95% CI: 3.2 - 5.8). Longest survival was seen in SCLC patients (7.3m). 77% of patients were discharged home, but 17% died during the admission. 72% of patients received further systemic therapy. Factors significantly associated with shorter survival were hypoalbuminemia (HR 1.52, 95% CI 1.06- 2.18, p=0.02), and therapy in 2 nd line or beyond (HR 2.10, [1.37-3.23], p&lt;0.001). Receiving treatment beyond 1 st line, and baseline leucocytosis, were both significantly associated with patients being less likely to be discharged home or receive further CT. Conclusions: While in-patient palliative CT is associated with short survival, many patients remain well enough to be discharged home and receive further therapy.
Cabozantinib for the treatment of patients with metastatic variant histology renal cell carcinoma (vhRCC): A retrospective study.
Authors: Matthew T. Campbell, Mehmet Asim Bilen, Cihan Duran, Emre Altinmakas, Zita Dubauskas Lim, Eric Jonasch, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2017)

478 Background: Cabozantinib (C) prolongs overall survival (OS) and progression-free survival (PFS) in patients with metastatic clear-cell renal cell carcinoma (ccRCC) that progressed on first-line VEGFR-TKI. No standard of care systemic therapy exists for the management of patients with metastatic vhRCC. Methods: This is a retrospective, IRB approved study of patients with vhRCC who received C at MD Anderson Cancer Center from January 2014 till June 2016. Information collected from the medical records included the baseline characteristics, toxicity, dose reductions, and OS. A blinded radiologist assessed the radiographic response using RECIST v1.1. Descriptive statistics, the Kaplan Meier method and the log rank test were applied using Microsoft Excel and GraphPad Prism version 6 software. Results: Median PFS was 8.1 months (mos) (95% CI: 5.8-17.8), and median OS was 22.7 mos (95% CI:11-NR), median follow up 13.3 months (95% CI: 9.6-17) . There were no significant differences detected between patients with papillary versus non-papillary histologies with respect to PFS or OS. At last follow-up, 7 patients remain on treatment with median time on therapy for all patients of 17.7 months. There were 2 confirmed PRs (both P) for a 12% ORR, 2 unconfirmed PRs (1 chr, 1 sarc), 10 of 17 (59%) with stable disease, and 5 of 19 with progressive disease (26%), for a disease control rate of 14 of 19 (74%). Of 15 patients who started C at 60 mg/d, 10 (67%) required dose reduction due to toxicity. Multiple patients required treatment breaks but none discontinued therapy due to toxicity. Conclusions: In this retrospective study, cabozantinib produced a clinically meaningful benefit in patients with metastatic vhRCC, the majority of whom had PD on prior VEGFR-TKIs. Prospective trials of cabozantinib in vhRCC are warranted.[Table: see text]
Clinicopathologic predictors of distant metastasis in head and neck cancer
Authors: F. C. Holsinger, W. Dong, N. Bekele, R. S. Weber, M. S. Kies, B. S. Glisson
Journal: Journal of Clinical Oncology (2009)

6086 Background: Despite advances in achieving improved locoregional control for patients with head and neck cancer (HNC), overall survival has not improved in the last 30 years. Several studies have implicated distant metastasis as a potential cause, hindering progress in the treatment of HNC. However, little is known about which patients fail systemically. We therefore sought to identify clinico-pathological factors that are associated with distant metastasis as the only cite of failure. Methods: We retrospectively studied 389 patients with head neck squamous cell carcinomas with distant metastases as the primary site of failure excluding all patients with locoregional recurrence and those receiving chemotherapy at primary presentation. The median follow up period was 5.3 years. An estimate of the risk of DM and DM free survival by prognostic factors was calculated using multivariate analysis and Cox proportional modeling. Results: Overall, 11% (43/389) of the patients developed DM. With univariate analysis, site of the tumor arising within the laryngopharynx, T stage (T3–4), N stage&gt;2, and metastasis to level IV were significantly associated with DM. However, using Cox proportional hazards regression modeling, two clinicopathologic variables, N classification &gt;N2b and diminishing degree of histologic differenention, were found to be most significantly associated with the development of systemic, distant metastasis. For patients staged as N2b or N2c, there was a relative risk (RR) of 6.13 (95% CI: 2.61 - 14.38; p &lt; 0.0001) for developing DM. For patients staged as N3, the RR was 8.23 (95% CI: 2.39 - 28.38; p &lt; 0.001). For patients with poorly differently HNSCC, RR was 11.01 (95% CI: 1.42 - 85.15; p = 0.022) Conclusions: Recognizing patients at primary presentation with tumors with the highest risk for the development of DM might le us to selectively treat them aggressively with systemic therapy to eradicate the tumor, thus improving overall survival rates. No significant financial relationships to disclose.
Phase I Study of Combination Chemotherapy Plus Ixazomib in Adults with Relapsed or Refractory Acute Lymphoblastic Leukemia/Lymphoma (ALL)
Authors: Ehab Atallah, Laura C Michaelis, Karen B. Carlson, Anita D'Souza, Timothy S. Fenske, Marcelo C. Pasquini, Mehdi Hamadani, Arielle Baim, Jessica Guhl, Hari Parameswaran
Journal: Blood (2016)
Multicenter, randomized trial comparing a combined gemcitabine and cisplatin 3-week regimen with a 4-week regimen in non-small cell lung cancer (NSCLC) patients
Authors: M. Liao, Y. Zhu, L. Li, H. Wan, S. Yu, B. J. Hall, L. Wang
Journal: Journal of Clinical Oncology (2006)

17062 Background: This multicenter, randomized Phase II study (B9E-GH-JHSE) was aimed to compare the efficacy and safety of a gemcitabine-cisplatin combination over a 3-week schedule versus a 4-week schedule as first line treatment for Chinese patients with advanced NSCLC. Methods: Patients (pts) with pathologically or histologically confirmed stage IIIB/IV NSCLC not amenable to curative surgery, and presenting at least one measurable lesion were eligible for this study. Pts were randomized to receive cisplatin (cis) 75 mg/m 2 on Day 1 plus either gemcitabine (gem) 1250 mg/m 2 on Day 1 and 8 of a 21-day cycle (3-week arm) or gem 1000 mg/m 2 on Day 1, 8, and 15 of a 28-day cycle (4-week arm). Patients received up to 6 cycles of treatment during this study. The primary endpoint was WHO objective response rate (ORR) and secondary endpoints included time to progression (TTP), CTC toxicity, and overall survival. Results: Of the 100 pts who were randomized to treatment, there were 51 pts in the 3-week arm: 14 females; mean age 59±8 yrs; 37% stage IIIB, 63% stage IV. In the 4-week arm, there were 49 pts: 24 females; mean age 56 ± 13 yrs; 33% stage IIIB, 67% stage IV. In the 3-week arm the overall response rate (complete response or partial response) was 24%, compared to 27% in the 4-week arm (Odds ratio: 1.17, 95% CI 0.47– 2.9, p = .819). There were no statistically significant differences between the two treatment arms in median overall survival time (3-week: 12.1 mths, 4-week: 13.8 mths; Hazard ratio (HR): 1.19, 95% CI 0.68–2.1, p = .54) and TTP (3-week: 4.9 mths, 4-week: 6.9 mths; HR: 1.33, 95% CI 0.85–2.1, p = .21). The difference in grade 3/4 hematological toxicities did not reach statistical significance (3-week: 37%, 4-week: 57%, p = .07), while grade 3/4 non-hematological toxicities were statistically significantly reduced in the 3-week arm (33% vs. 63%, p = .005). Grade 3/4 study drug related neutropenia (3-week: 27%, 4-week: 51%, p = .02) and thrombocytopenia (3-week: 8%, 4-week: 31%, p = .005) were reduced in the 3-week arm. Conclusions: While all efficacy endpoints were numerically superior in the 4-week arm, the difference was not statistically significant. However, grade 3/4 toxicities were reduced in the 3-week arm. [Table: see text]
Pharmacological targeting of plasmin prevents lethality in a murine model of macrophage activation syndrome
Authors: Hiroshi Shimazu, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Douaa Dhahri, Salita Eiamboonsert, Yasunori Ota, Haruo Onoda, Yuko Tsuda, Yoshio Okada, Hiromitsu Nakauchi, Beate Heissig, Koichi Hattori
Journal: Blood (2017)
Second cancer risk after diagnostic and monitoring radiation exposure with computed tomography in patients with hepatocellular carcinoma.
Authors: Joong-Won Park, Moran Ki, Hwa Young Choi, Hyunsoon Cho, Ju Hee Lee, Young Hwan Koh
Journal: Journal of Clinical Oncology (2017)

238 Background: Contrast-enhanced dynamic computed tomography (CT) is preferred for initial diagnosis and post-treatment monitoring of hepatocellular carcinoma (HCC). The risk of a second cancer with diagnostic and monitoring CT radiation exposure in HCC patients is unclear. Methods: We analyzed cumulative radiation dose (CRD) for diagnostic and monitoring CT with/without transarterial chemoembolization (TACE) in patients with HCC alone (HA group) and HCC patients with a second cancer (SC group), using the big dataset of the National Health Insurance of South Korea. We performed survival analysis, with death treated as a competing risk. Results: A total of 20,073 patients with HCC were enrolled. With a median follow-up of 5.7 years, the SC group comprised 2,005 patients, resulting in a standardized incidence ratio of 1.5 (95% confidence interval [CI], 1.4-1.6) in men and 1.7 (95% CI, 1.6-1.9) in women, as compared with the general population. Use of CT/positron emission tomography (PET) was significantly higher in the SC group (p&lt;0.001). However, the CRD of CT/PET was not significantly different between the SC group and the alive HA group (median effective dose [ED], 93 mSv for the SC group and alive HA group, respectively, p=0.510). After including TACE (n= 9,004 [44.9%], median frequency 2), total CRD was not significantly different between the SC group and the alive HA group. CRD &gt;300 mSv significantly increased the risk of second malignant neoplasms in the subgroup with &gt;7 years of follow-up (YFU) (hazard ratio [HR] 2.01, 95% CI 1.38-2.92, p&lt;0.001). Second cancers in digestive organs and respiratory-intrathoracic organs were significantly increased by CRD in the subgroup with &gt;300 mSv and over 7 YFU (HR 2.41, 95% CI 1.26-4.62; HR 5.69, 95% CI 1.62-20.04, respectively, p&lt;0.01). TACE did not affect the increased risk of second cancers in digestive and respiratory organs in the subgroup &gt;300 mSv and over 7 YFU. Conclusions: The risk of second cancers increased in HCC patients who survived over 7 years with CRD &gt;300 mSv. Consideration of alternative monitoring tests and guidelines for reducing radiation exposure is crucial for long-term HCC survivors.
Psychosocial outcomes among bereaved and non-bereaved parents of children with cancer.
Authors: Abby R. Rosenberg, Miranda Bradford, Michele Shaffer, Joanne Wolfe, Kevin Scott Baker
Journal: Journal of Clinical Oncology (2013)

9526 Background: Psychosocial outcomes among parents of children with cancer are not well characterized and may affect the well-being of cancer-survivors and other children in the home. In order to examine adverse psychosocial outcomes among bereaved (BR) and non-bereaved (NBR) parents, we conducted a cross-sectional, survey-based study. Methods: Enrolled parents completed the “Resilience in Pediatric Cancer Assessment” (RPCA) at least 6 months after their child completed therapy or died from cancer. The RPCA is comprised of validated instruments to assess resilience, emotional distress, social function, health-related quality of life, and financial hardship. Descriptive statistics were used to characterize groups. Differences between groups were assessed with t or Fisher’s exact tests. Differences between the combined sample and population norms were assessed with one-sample t or binomial tests. Results: 120 (78%) of invited parents completed the RPCA (24 BR; 96 NBR). Compared to the general population, parents had lower levels of self-perceived resilience and higher levels of psychological distress. They were more likely to meet criteria for serious, debilitating psychological distress, or Post-Traumatic Stress Disorder (PTSD). All parents (100%) endorsed at least some PTSD symptoms. Parents also reported less marital satisfaction and family cohesion, and more sleep disturbance and binge drinking than population norms. Conversely, enrolled parents reported higher levels of social support and family adaptability, and were less likely to smoke cigarettes (all p&lt;0.05). Compared to parents of survivors, BR parents were less likely to report appreciation for life, an ability to cope, or deal with stress. They had higher levels of psychological distress, more sleep difficulties, and greater financial hardship (all p&lt;0.05). There were no differences between BR and NBR parents with respect to marital satisfaction, family function, or perceived general health. Conclusions: Parents of children with cancer are at high risk for poor psychosocial outcomes. Compared to parents of survivors, bereaved parents are at additional risk. Interventions aimed at improving resilience and other psychosocial outcomes are needed.