tbuckley/cabot-search huggingface dataset:
Impact of systemic therapy on the outcomes of patients with metastatic breast cancer to brain: MD Anderson Cancer Center (MDACC) experience 1999-2012.
Authors: Diogo Bugano Diniz Gomes, Rita Elias Deeba, Dima Suki, Vicente Valero, Stacy L. Moulder, Banu Arun, Kimberly Higginbotham Koenig, Eric A Strom, Limin Hsu, Raymond Sawaya, Debu Tripathy, Nuhad K. Ibrahim
Journal: Journal of Clinical Oncology (2015)

1046 Background: Management of metastatic breast cancer to the brain (MBC-B) is mainly surgery and/or radiation. The efficacy of systemic therapy remains controversial. Methods: Out of 1514 consecutive patients (pts) with MBC-B treated at MDACC October 1999-December 2012, 882 had complete data and were included in this retrospective study. We used a Cox multivariate model to identify the effect of any systemic therapy on time-to-progression in the brain (TTP-B) and overall survival (OS). Results: Disease subtypes: ER+/HER2- (26%) ER+/HER2+ (17%); ER-/HER2+ (20%); ER-/HER2- (33%), missing (4%). Number of brain metastasis (BM): 1 (24%), > 1 (67%), concurrent LMD (8%), missing (1%). Local treatment: metastasectomy (S) (5%), stereotactic radio-surgery (SRS) (14%), whole-brain radiation (WBRT) (58%), combination S/SRS with WBRT (12%); no treatment (11%). Subsequent systemic therapy was given to 679 pts (77%). Median OS was 9.7 months (m) (4.0-21.9). Systemic therapy prolonged OS (HR 0.44 CI 0.36-0.52 p < 0.001) for all subgroups: HER2+ (17.8 vs 3.3m); ER+/HER2- (10.7 vs 2.3m); ER-/HER2- (8.4 vs 2.4m). Other factors associated with OS: ER+, HER2+, age < 60, ECOG 0-1, single BM, controlled extra-cranial disease, local therapy to the brain, less than 3 lines of therapy prior to diagnosis of BM. Disease progression in the brain was documented in 359 pts (40.7%). Median TTP-B was 6.8m (3.7-12.1). Systemic therapy prolonged TTP-B (7 vs 4.5m; HR 0.58 CI 0.40-0.84 p = 0.005). Other factors associated with TTP-B: ER+, HER2+, single BM, and local therapy to the brain. In pts receiving anti-HER2 based therapy at diagnosis of BM, continuation of anti-HER2 agents prolonged TTP-B (HR 0.41 CI 0.23-0.72, p < 0.001) and OS (HR 0.41 CI 0.28-0.59, p < 0.001). Lapatinib-based was not superior to trastuzumab-based therapy and capecitabine was not superior to other cytotoxic agents. Pts who were on systemic therapy at diagnosis of BM and had controlled extra-cranial disease did not benefit from switching to non-cross-resistant agents. Conclusions: In patients with breast cancer metastatic to the brain, systemic chemotherapy was associated with better control in the brain and longer survival.
Disparities in access to dental care appointments among head and neck cancer patients.
Authors: Samuel Swisher-McClure, Shayna Cohen, Justin E. Bekelman, Jiaqi Li, Alexander Lin, Nandita Mitra, Karin Rhodes
Journal: Journal of Clinical Oncology (2015)

e17019 Background: Pre-radiation dental care is a critical component of head and neck cancer (HNC) treatment, but is not always covered by health insurance. Even if covered, the extent to which dental practices accept public insurance (Medicare and Medicaid) for cancer patients requiring pre-radiation dental care is not known. Methods: We conducted an audit study of a random sample of 148 dental practices in a large Mid-Atlantic metropolitan area to determine the association of payment status with dental appointment access for HNC patients requiring pre-radiation dental care. A research assistant identified herself as a radiation oncology scheduling assistant, requesting the soonest available appointment for a HNC patient requiring pre-radiation dental care. Each practice was contacted twice, 3 weeks apart, using the same scripted vignette but different payment status. Payment status for the paired calls was randomized to cash vs. Medicare or cash vs. Medicaid. We compared the proportion of calls that resulted in a successfully scheduled appointment by payment status using Mcnemar’s test, and time to an appointment by payment status using student’s t-test. Results: Of the 148 practices, 34 (22.9%) did not meet inclusion criteria based on scope of practice, and 33 (22.2%) could not be reached by phone. We completed paired calls to 81 (54.7%) practices (43 cash vs. Medicare, 38 cash vs. Medicaid). All 81 practices reported routinely providing care for HNC patients. Overall, appointments were offered in 13.9 % of Medicare calls, compared to 100% of cash calls (p < 0.001), and 28.9% of Medicaid calls, compared to 100% of cash calls (p < 0.001). When appointments were offered, there was no significant association of payment status with mean time to appointment (Cash vs. Medicare: 4.3 vs. 5.5 days, p = 0.65; Cash vs. Medicaid: 4.2 vs 3.1 days, p = 0.25). Conclusions: HNC patients with public insurance are likely to experience significant difficulty accessing the dental care required before starting radiation treatment, despite having insurance policies covering these services. Policy interventions should evaluate incentives that would encourage dental care providers to accept public insurance.
Antioxidant micronutrients and renal cell carcinoma: Results from the Women’s Health Initiative.
Authors: Won Jin Ho, Michael S. Simon, Vedat O. Yildiz, James Shikany, Ikuko Kato, Jennifer Beebe-Dimmer, Jeremy Paul Cetnar, Cathryn Bock
Journal: Journal of Clinical Oncology (2014)

1515 Background: Renal cell carcinoma (RCC) is the 8thleading cancer in women, commonly diagnosed at more advanced stage. Oxidative stress has been considered to play an important role in the pathogenesis of RCC. Various dietary micronutrients have antioxidant properties, including carotenoids, vitamin C, and vitamin E, and thus diets rich in these nutrients have been evaluated in relation to renal cancer prevention. The aim of this study is to explore the relationship between antioxidant micronutrient and RCC risk in the Women’s Health Initiative (WHI). Methods: A total of 91,913 postmenopausal women enrolled between 1993 and 1998 and followed through July 2013 were included in the analysis. Dietary micronutrient intake was estimated from the baseline WHI food frequency questionnaire, and data on supplement use was collected via interview-based inventory procedure. RCC cases were ascertained from medical records and centrally adjudicated. Risk for RCC associated with α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene, vitamin C, and vitamin E was analyzed using Cox proportional hazards analysis, adjusted for confounders. Results: There were 383 RCC cases identified in the WHI during follow-up. Lycopene intake was inversely associated with RCC risk (p = 0.001); compared to the quartile of lowest lycopene intake, the quartile with highest lycopene intake was associated with a 45% lower risk of RCC (HR 0.55; 95% CI, 0.38 to 0.80). There were no significant associations with RCC for any of the other micronutrients. No substantial correlation was found among micronutrients to suggest multicollinearity. Conclusions: These results suggest that further investigation into the relationship between dietary lycopene intake and RCC risk is warranted.
Clinical characteristics of colorectal cancer as a second primary malignancy.
Authors: Larysa Jessica Sanchez, Narjust Duma, Natalie Cedeno, Daniel Bodek, Daniel Pievsky, Sarah Lee, Kalpesh Patel, James Wang, Andrew Jennis, Martin Gutierrez
Journal: Journal of Clinical Oncology (2015)

e14691 Background: Advances in cancer screening and treatment in the past 20 years have improved cancer specific survival rates, raising questions regarding second primary malignancies and the pathologic characteristics of those tumors. The aim of this study was to investigate the characteristics of colorectal (CRC) as a second primary malignancy. Methods: We reviewed the records of 1602 patients (pts) diagnosed with CRC between 2005 and 2013 in our institution. Demographics, tumor characteristics, and survival were studied. Kaplan Meier was used for survival analysis. Results: Of 1602 pts, 109 pts (6.8%) were identified with CRC as a second primary malignancy. Median (M) age at diagnosis was 71 years (40-91). There were more males than females (62% vs 38%, p < 0.0001). 86 (79%) were Caucasian. 59% of pts were current or former smokers and 13% had a history of alcohol abuse. Most common sites for primary malignancies were skin (32%), breast (19%), lymphoma (16%), prostate (14%) and thyroid (12%). Only 12 pts (11%) had prior radiation therapy. The M interval time to diagnosis of CRC was 83.7 months (8-621). At diagnosis, 67% of pts were stage III/IV compared to 33% stage I/II (p < 0.001). Pts were more likely to have poorly differentiated tumors than all other histologic grades combined (67% vs. 33%, p < 0.0001). There was no difference in M overall survival between the two groups: 55 months (95% CI: 52-60) for pts with CRC as a second malignancy and 60 months (95% CI: 50-69) for pts with CRC as primary malignancy, p < 0.07. Age < 65 years (OR: 0.90, 95%CI: 0.51-0.98 p < 0.01) and non-adenocarcinoma histology (OR: 1.21, 95%CI: 1.05-1.52 p < 0.003) were independent predictors of survival in pts with CRC as a second malignancy by multivariate analysis. There were no statistically significant differences in overall survival between each subtype of primary malignancy. Conclusions: We observed that CRC as a second primary malignancy was more common in males, to present at an advanced stage and to have poorly differentiated tumors. Age < 65 years and non-adenocarcinoma histology were independent predictors of survival. Our study seems to be one of the first to investigate these characteristics and survival in pts with CRC presenting as a second primary malignancy.
Clinical activity of irofulven in hormone refractory prostate cancer
Authors: E. Cvitkovic, C. Kahatt, N. Senzer, B. Tombal, S. Culine, E. Raymond, J. Alexandre, G. Weems, J. MacDonald
Journal: Journal of Clinical Oncology (2004)

4766 Background: Irofulven, a novel DNA binding antitumor agent, is a semisynthetic derivative of the natural product illudin S. It inhibits DNA synthesis, induces S-phase arrest, has activity independent of common resistance mechanisms such as multidrug resistance and apoptosis inhibiting proteins, and causes a potent induction of apoptosis in cancer cells. Strong antitumor activity alone and synergistic activity in combination with mitoxantrone or docetaxel has been demonstrated against androgen-independent prostate cancer in both in vitro and in vivo preclinical models. Furthermore, irofulven monotherapy and combination therapy regimens have demonstrated antitumor activity in patients (pts) with a variety of solid tumors with a safety profile characterized primarily by mild to moderate thrombocytopenia. Throughout phase I and II monotherapy and combination therapy studies, consistent evidence of activity in HRPC has been reported. Methods: An update of HRPC data, including ongoing and recently completed studies, is presented to establish a basis for further development work. Results: A summary of results is shown in the table. Conclusion: Additional HRPC patients will be enrolled in ongoing IROF phase I combination studies with oxaliplatin, capecitabine, docetaxel and gemcitabine. Phase II evaluation of IROF combination regimens in taxane-pretreated HRPC patients is planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cvitkovic & Associes Consultants; MGI Pharma, Inc. MGI Pharma, Inc. MGI Pharma, Inc. MGI Pharma, Inc. MGI Pharma, Inc.
Review: Different bisphosphonates are equally effective and safe for preventing fragility fractures
Authors: KoKo Aung, Thwe Htay
Journal: Annals of Internal Medicine (2017)

Source Citation Davis S, Martyn-St James M, Sanderson J, et al. A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures. Health Technol Assess. 2016;20:1-406. 27801641
A pooled safety and efficacy analysis examining the effect of performance status (PS) on outcomes in nine first-line treatment (rx) trials (cts) of 6,286 patients (pts) with metastatic colorectal cancer (MCRC)
Authors: R. M. Goldberg, C. H. Köhne, M. T. Seymour, A. de Gramont, R. Porschen, L. Saltz, P. Rougier, C. Tournigand, A. Grothey, D. J. Sargent
Journal: Journal of Clinical Oncology (2007)

4011 Background: While pt PS is a known prognostic factor in MCRC, most phase III CTs enroll &lt; 10% PS2 pts. This pooled analysis compares safety and efficacy in PS 0–1 versus (v) PS 2 MCRC pts on first-line CTs testing both single agents and combination rx. Methods: This retrospective analysis included 6,286 MCRC pts (509 PS 2) from 9 CTs (control arms: 5 5FU/LV, 2 FOLFOX, 1 FUFOX, 1IFL). Five CTs specifically compared mono to combination rx (3,814 pts; 335 PS 2). The primary endpoint was progression-free survival (PFS). Other endpoints included grade 3+ adverse events, 60-day all cause mortality, overall survival (OS), and response rate (RR). Efficacy endpoints were explored in both the full set of 9 CTs &amp; the subset of 5 CTs that compared mono to combination rx. Results: Severe (grade 3+) nausea (7.0% v 13.0%; P &lt; .0001), vomiting (6.4% v 10.5%; P = .0002), and stomatitis (2.0% v 4.2%; P = .0332) were significantly higher in PS 2 pts. PS 2 was not associated with incidence of severe diarrhea or neutropenia. 60-day all cause mortality was significantly higher in PS 2 pts (2.8% v 12.0% in PS 0–1 v PS 2 respectively, P &lt;.0001). PS 2 was a prognostic factor for PFS (HR=1.52, P &lt; .0001, median 7.6 v 4.9 months (mos) in PS 0–1 v 2), OS (HR=2.18, P &lt; .0001, median 17.3 v 8.5 mos in PS 0–1 v 2), &amp; RR (OR=0.60, P &lt; .0001, 43.5% v 32.0% in PS 0–1 v 2). The relative benefit of experimental (exp) v control rx did not differ in PS 0–1 v PS 2 pts for RR, PFS, or OS (see table ). This was true both when assessing all 9 CTs and the subset of 5 mono v combination rx CTs. Conclusions: In CTs, pts with PS 2 derive similar advantages with regard to efficacy from superior Rx as do pts with PS 0–1, but with higher risk of some gastrointestinal toxicities. Twelve percent of PS 2 pts die within 60 days of rx start. Median OS is &lt; 9 months. While current Rx does provide benefit, new approaches are required to approach 1 year median survival for PS 2 pts. [Table: see text] No significant financial relationships to disclose.
Perspectives of patients and healthcare professionals on mHealth for asthma self-management
Authors: Andrew J. Simpson, Persijn J. Honkoop, Erika Kennington, Jiska B. Snoeck-Stroband, Ian Smith, Jessica East, Courtney Coleman, Ann Caress, Kian Fan Chung, Jacob K. Sont, Omar Usmani, Stephen J. Fowler
Journal: European Respiratory Journal (2017)

Mobile healthcare (mHealth) has the potential to revolutionise the self-management of long-term medical conditions such as asthma. A user-centred design is integral if mHealth is to be embraced by patients and healthcare professionals.The aim of this study was to determine the perspectives of individuals with asthma and healthcare professionals on the use of mHealth for asthma self-management.We used a sequential exploratory mixed methods design; focus groups informed the development of questionnaires, which were disseminated to individuals with asthma and healthcare professionals.Focus group participants (18 asthma patients and five healthcare professionals) identified 12 potential uses of mHealth. Questionnaire results showed that individuals with asthma (n=186) most frequently requested an mHealth system to monitor asthma over time (72%) and to collect data to present to healthcare teams (70%). In contrast, healthcare professionals (n=63) most frequently selected a system alerting patients to deteriorating asthma control (86%) and advising them when to seek medical attention (87%). Individuals with asthma were less likely than healthcare professionals (p<0.001) to believe that assessing medication adherence and inhaler technique could improve asthma control.Our data provide strong support for mHealth for asthma self-management, but highlight fundamental differences between the perspectives of patients and healthcare professionals.
Prospective evaluation of the G8 and dementia screening scores (DSS) for frailty in elderly patients (pts) with lung cancer.
Authors: Yoko Agemi, Kazuhito Miyazaki, Yuki Misumi, Akira Sato, Mari Ishii, Yukiko Nakamura, Tsuneo Shimokawa, Hiroaki Okamoto
Journal: Journal of Clinical Oncology (2015)

e20526 Background: Although comprehensive geriatric assessment (CGA) has been widely used to determine the medical, psychological and functional capabilities of older pts, it is time-consuming method. The G8 is a quick and easy-to-use screening tool and has high sensitivity for predicting abnormalities on the full CGA. However, because G8 has only one question to evaluate dementia, the addition of DSS to G8 might be helpful for the geriatric evaluation. Methods: Pts older than 70 years with lung cancer who were candidate for medical treatment such as chemotherapy (CT), radiotherapy (RT) or chemoradiotherapy (CRT) were eligible in this study. All pts were prospectively evaluated using the G8 score (cutoff ≤ 14) and DSS (cutoff ≤ 12) consisting of three questions (Urakami 2003) before any cancer treatments. The relationships between these scores and patient characteristics, severe adverse events (SAE), chemotherapy relative dose intensity (RDI), cessation of treatment (COT), and overall survival (OS) were analyzed. Results: Between Sep 2011 and Aug 2014, 101 pts were enrolled. Median age was 79 (range: 70-95), M/F: 81/20, Ad/Sq/NOS/SCLC: 45/30/7/19, c- I/II/III/IV/recurrent: 5/6/25/47/18, ECOG PS 0/1/2/3:8/50/32/11, RT/CT/CRT/BSC: 16/68/8/9. The number of pts with impaired G8 and DSS was 83 (82%) and 35 (35%), respectively. The G8 score was significantly correlated with PS. The frequency of impaired DSS in SCLC pts was significantly higher than that in NSCLC and the frequency of impaired DSS in BSC pts was significantly higher than that in non-BSC pts, suggesting that the DSS influenced decision making of treatment. Although both G8 score and DSS were not significantly associated with SAE and COT, impaired G8 tended to be correlated with RDI < 0.65. In a multivariate analysis for 76 pts receiving CT or CRT, independent prognostic factors for OS were impaired G8 (HR:3.75, p = 0.007) and poor PS (HR:2.37, p = 0.02). Conclusions: This is the first report on the prognostic relevance of G8 in elderly pts with lung cancer. The addition of DSS to G8 might be useful for managing elderly pts and further researches are warranted.
Cancer gene profile of metastatic breast cancer.
Authors: Funda Meric-Bernstam, Garrett Frampton, Jaime Ferrer-Lozano, Roman Yelensky, Gary A. Palmer, Maureen T. Cronin, Philip J Stephens, Katherine Stemke Hale, Juan Barrera, Octavio Burgues, Ana Lluch, Gordon B. Mills, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2012)

1015 Background: There is great interest in using genomic information to guide therapy selection in cancer patients. The aim of this study was to determine the spectrum of genomic alterations identified in MBC patients, and evaluate the concordance of alterations between primary and recurrent tumors. Methods: We performed comprehensive profiling on formalin-fixed paraffin embedded samples from 42 patients with MBC using a targeted next generation sequencing (NGS) assay in a CLIA laboratory (Foundation Medicine). Genomic libraries were captured for 3,230 exons in 182 cancer related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to an average depth of 390X with 99% of bases covered &gt;100X. In total 30 primary and 37 recurrent tumors were profiled, including 3 separate recurrences in 1 patient and matched primary-recurrences in 22 patients. Point mutations, indels, copy number alterations and rearrangements were assessed. Alterations that are targetable with established or investigational therapeutics were considered “actionable”. Results: At least 1 genomic alteration was identified in all but 2 breast samples (both primary tumors). Point mutations were identified in several cancer-related genes including PIK3CA, TP53, PTEN, CDH1, ARID1A, AKT1, NF1, FBXW7 and FGFR3. Amplification was observed in HER2; 11 of 12 HER2 IHC positive samples were found to have HER2 gains by NGS; in addition, a HER2 gain was identified by NGS in a HER2- (1+ IHC) sample. Amplification of PIK3CA, IGF1R, FGFR2, AKT2, MDM2, and MCL1 plus a CDKN2A homozygous deletion were also identified. While the majority of known driver alterations (85%) were concordant in the matched pairs of primary and recurrent tumors, in 11 of 22 sets there was at least 1 discordant driver alteration, and these included both gains and losses of potential therapeutic targets. Overall 32 of 42 patients (76%) had an actionable genomic alteration. Conclusions: Genomic profiling of breast cancer samples reveals genomic alterations in most metastatic breast cancer patients. Over three quarters of patients have actionable findings, suggesting that genomic profiling may assist in individualized pathway-directed therapy.
Dermatologic toxicities of 3,517 solid tumor patients on phase I clinical trials of the National Institutes of Health Cancer Therapy Evaluation Program (CTEP).
Authors: Alexander E. Drilon, Anne Eaton, Katja Schindler, Mrinal M. Gounder, Gary L. Smith, Diana Vulih, Pamela Jo Harris, David R. Spriggs, Percy Ivy, Alexia Iasonos, Mario E. Lacouture, David Michael Hyman
Journal: Journal of Clinical Oncology (2015)

2546 Background: Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability, and the maximum tolerated and recommended phase II doses of therapy on phase I trials. We present the largest dedicated analysis of dermatologic AEs on phase I trials to date. Methods: Data from a prospectively maintained database of solid tumor patients (pts) enrolled onto CTEP-sponsored phase I trials from 2000 to 2010 was analyzed. Cumulative incidence, site, type, and timing of drug-related dermatologic AEs were described and compared between pts who received molecularly targeted agents (MTAs), cytotoxic therapy, or a combination of both. Results: 3,517 solid tumor pts and 6,165 unique drug-related dermatologic AEs were analyzed: 1,545 pts on MTA only trials, 671 on cytotoxic only trials, and 1,392 on combination MTA and cytotoxic trials. Percent grade 1, 2, 3, and 4 dermatologic drug-related AEs were 75.5%, 22.6%, 1.9% and < 0.1%, respectively. Most common drug-related dermatologic AEs were alopecia (23%) and maculopapular rash (21%). Of 1,270 pts with drug-related dermatologic AEs, timing of worst drug-related toxicity was: 743 pts (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). While cumulative incidence of ≥ grade 3 drug-related dermatologic AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. Cumulative incidence of drug-related dermatologic AEs was highest in pts with MTA only therapy, and significantly differed by dose level (p < 0.001). In pts who received MTA only therapy, drug-related dermatologic toxicity was most common for combination kinase inhibitor-containing therapy (p < 0.001). Conclusions: A substantial proportion of drug-related dermatologic AEs occurs after the traditional DLT monitoring period. Future phase I trial designs should account for delayed toxicities to avoid defining intolerable doses of study therapy.