tbuckley/cabot-search huggingface dataset:
Survivors' perspectives on cancer: Results from a LIVESTRONG survey.
Authors: R. Rechis, E. B. Beckjord, S. Nutt, B. M. Hayes-Lattin
Journal: Journal of Clinical Oncology (2011)

9089 Background: There are nearly 12 million cancer survivors in the United States, making late effects caused by cancer and its treatment–for both those diagnosed with the disease and their loved ones–a public health priority. Methods: In 2010, the Lance Armstrong Foundation fielded its third LIVESTRONG Survey for People Affected by Cancer. The primary goals of the more than 300 question survey were to 1) assess the physical, emotional and practical needs of post-treatment cancer survivors (PTCS) and whether and from whom PCTS received care and 2) gauge the impact of cancer on survivors’ loved ones. Individuals were asked to participate in this survey through a number of means (including partnerships with national cancer organizations such as ASCO and NCI-designated cancer centers). Results: Between June 2010 and January 2011, 11,680 surveys were completed, including 3,798 from PTCS. Overall, the vast majority of PTCS experienced physical, emotional and/or practical concerns as a result of having cancer. The table highlights commonly reported concerns. As many as 58% PTCS did not receive the help they needed, because they had “learned to live with their concerns.” Survivors’ loved ones, reported that their overall outlook on life had been both positively and negatively impacted by cancer (51%), with an additional 18% reporting their outlook had been only positively impacted and 19% reporting their outlook had been only or mostly negatively impacted. Conclusions: Physical, emotional, and practical concerns are prevalent among PTCS, yet many do not receive care for these concerns. Their cancer journeys affect their loved ones in varied and complex ways. Data from this large-scale survey enables the voice of people affected by cancer to play a role in guiding programs and policies to meet the needs of this large and growing population. Commonly selected concerns. Concern resulting from cancer experience Percent experiencing concern I have worried about cancer coming back. 79% I have not had the energy to do the things that I’ve wanted to do. 56% I have been negatively impacted at my job. 53% I have felt blue or depressed. 53% I have had trouble remembering things. 50%
Quality-adjusted survival comparison between androgen deprivation with radiation therapy versus radiation therapy alone for locally advanced prostate cancer: Decision analysis from RTOG 85-31 trial.
Authors: Chang Wook Jeong, Soyeon Ahn, Minjung Lee, Ja Hyeon Ku, Cheol Kwak
Journal: Journal of Clinical Oncology (2016)

265 Background: Radiation Therapy Oncology Group (RTOG) trial 85-31 has shown that addition of androgen deprivation therapy to radiation therapy (RT+ADT) for patients with locally advanced prostate cancer benefits local control and progression-free survival compared to RT alone. However, the survival gain may be diluted with increased toxicity of hormone manipulation. There is a need to develop new decision analysis methods to incorporate survival time and quality of life (QoL) adjusting for various health states and persistent complications. Methods: We previously developed “quality-adjusted survival analysis using duration” (QASAD) and “quality-adjusted survival analysis using probability” (QASAP) to estimate quality-adjusted survival time. The QASAD uses the median duration in each state to weight the utilities, while the QASAP uses the proportional probability of being in each state for weighting. The survival and complication rates of RTOG 85-31 were reconstructed based on published Kaplan-Meier survival curves, and the utility values for states were obtained from the literature. Probabilistic sensitivity analysis was applied using Monte Carlo simulation with 1000 simulated samples. Results: QASAD and QASAP showed that the quality-adjusted life year (QALY) values in RT+ADT were generally higher than those in RT. In probabilistic sensitivity analysis, QASAD resulted in 4.93 (95% bootstrapped confidence interval [CI] = 4.12 to 5.71) for RT and 5.60 (95% CI = 4.30 to 6.48) for RT+ADT. QASAP resulted in 4.85 (95% CI = 4.16 to 5.39) for RT and 4.96 (95% CI = 3.73 to 5.78) for RT+ADT. Conclusions: The decision analyses showed that RT+ADT provided slightly better quality-adjusted survival outcome after treatment than RT alone. The QASAD and QASAP methods may help the decision of optimal treatment balancing between survival gain and unfavorable quality of life. [Table: see text]
Health plan, physician, and medical care ratings among end-of-life (EOL) cancer survivors.
Authors: Michael T. Halpern, Matthew Urato, Margot Schwartz, Erin E. Kent
Journal: Journal of Clinical Oncology (2015)

80 Background: High-quality EOL care is critical for patients and families. However, little is known about factors influencing patient satisfaction with their healthcare near EOL. This study’s objective is to assess the role of characteristics of individuals with cancer near EOL on their ratings for medical care, health plans, and physicians. Methods: Retrospective analyses of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare Survey linked to NCI’s Surveillance, Epidemiology, and End Results (SEER) Program. CAHPS collected Medicare beneficiaries’ ratings for overall care, physicians, health plans, and 5 composite scores of aspects of care; SEER provided data on cancer diagnosis and characteristics. The study included 5,102 Medicare beneficiaries diagnosed with cancer in SEER regions 1997-2011 who completed CAHPS following diagnosis and within one year before death. Logistic regression was used to examine associations of EOL patient characteristics with their ratings. Results: Self-reported very good or excellent (vs. poor) general health significantly (p &lt; 0.05) predicted greater likelihood of higher ratings for all measures (ORs ranged 1.5 to 2.2). Very good/excellent mental health also predicted increased likelihood of higher ratings for all except one category (ORs 1.8 to 2.7). Other patient factors were significantly associated with a subset of ratings. For example, Hispanics (vs. Whites) were more likely to provide higher ratings for health plans (OR 1.5) and specialist physicians (OR 1.7) but lower ratings for getting needed care (OR 0.62). Fee-for-service (vs. Medicare Advantage) beneficiaries were more likely to provide higher ratings for health plans, getting needed care, and getting care quickly (ORs 1.4, 1.3, 1.6). Patient age, cancer site, and time since diagnosis had few or no significant associations with any measure. Conclusions: Among cancer patients near EOL, better self-reported general and mental health consistently predicted higher ratings. Fee-for-service Medicare patients provided higher ratings for several important categories. These results may help guide future research on interventions to improve the EOL experience among Medicare beneficiaries.
A phase II study of personalized selection of peptide vaccines combined with conventional chemo- or endocrine therapy for refractory breast cancer.
Authors: U. Toh, H. Otsuka, N. Iwakuma, K. Shirouzu, E. Ogo, H. Yamana, K. Itoh, M. Tanaka, T. Fujii
Journal: Journal of Clinical Oncology (2010)

TPS173 Background: Immunotherapy using selected personalized peptide vaccines (PPV) has been reported to be effective for boosting anticancer immunity in many patients (pts) even in an advanced status. This study evaluate the anti-tumor immunologic effect and safety of PPV for pts with refractory breast cancer. Methods: Patient eligibility criteria: all patients had histologically confirmed measurable metastatic breast cancer and their HLA A molecules should be each of HLA-A2, A3, A11, A24, A26, A31 or A33. The following criteria were also required: age > 20 years, life expectancy of at least 3 months, ECOG performance status of 0 or 1, adequate vital organ function (WBC > 2,500/μ L; platelets > 80,000/μ L; serum creatinine < 1.5 mg/dL or creatinine clearance > 50 mL/min; AST and ALT < 2 times the upper limit of the institution's normal range; and total bilirubin < 2.5 mg/dL. All subjects provided written informed consent and the clinical protocol was approved by each institutional review board before patient enrollment. Treatment schedule:Pre- vaccination plasma was measured for their IgG levels reactive to each of the previously reported 31 candidate peptides followed by administration subcutaneously of the four peptides at maximum showing higher levels of IgG in order with schedule of every 1-2 week for a total of 6-24 doses. The concurrent conventional chemotherapy or endocrine therapy was available for the combination of PPV. Study design: This is an open-label, multicenter, single-arm, phase II study. The primary endpoint was anti-tumor immunologic effect and safety, and the secondary endpoints were clinical responses. The planned sample size was 60-80. Immune and clinical response assessment : Levels of IgG reactive to each of the 31 peptides in the pre- and post-treatment plasma at every 6 times of vaccination were measured using LUMNEX system. Clinical response was evaluated by RECIST criteria. Correlation between overall survival and the increased IgG levels was also investigated. No significant financial relationships to disclose.
A novel methodology for the identification of drugable enzymes as targets in cancer via meta analysis of gene expression microarrays
Authors: M. Bhandari, D. Rhodes, A. Chinnaiyan
Journal: Journal of Clinical Oncology (2005)

9602 Background: Many studies have used expression microarrays to identify cancer signatures for diagnostic and prognostic purposes. We hypothesized that identifying enzymes with known therapeutic inhibitors, which are highly over-expressed in cancer as compared to benign tissue, may uncover drugable targets shared by multiple cancers and those specific to a cancer type. To test the methodology, we analyzed arrays from untreated prostate and non-small cell lung cancer (NSCLC) patients for their variation in tumor biology and large patient samples. Methods: Utilizing ONCOMINE (www.oncomine.com), we meta-analyzed eight prostate & six lung cancer arrays published in literature. Prior well characterized drug targets such as DNA topoisomerase 1 & 2 were excluded. Differential expression analysis was done utilizing t-statistics and corrected for multiple comparisons using adjusted Qvalues (Q = p* n/I; where n = total number of genes and I=sorted rank of p value). Results: We identified 10 significant enzymes (Q ≤ 1.0e-2): 4 shared, 3 unique to prostate and 4 to NSCLC. Shared targets include two epigenetic enzymes, histone deacetylase1 (HDAC1) and poly (ADP-ribose)polymerase1 (PARP1), guanine monophosphate synthetase (GMPS), an enzyme in nucleoside catabolism involved in DNA synthesis and cellular metabolism, and cyclin-dependent kinase 4 (CDK4), a cell-cycle regulatory protein. Targets unique to prostate cancer are endothelin converting enzyme1 (ECE1) which forms endothelin-1 from its precursor, and two critical enzymes in fatty acid systhesis pathways implicated in prostate cancer pathogenesis: fatty acid synthase (FASN) and acetyl-Coenzyme A carboxylase alpha (ACACA). NSCLC enzymes are a protein that regulates p53 function, NADPH dehydrogenase (NQO1), macrophage migration inhibitory factor (MIF), minichromosome maintenance deficient 6 (MCM6) which is a DNA helicase and casein kinase 2 (CSNK2A1), a putative target of the active anti-oxidant of red wine, resveratrol. Conclusions: Meta-analysis of expression microarrays is a novel methodology which can quickly uncover targets over expressed in multiple cancers and help identify potential therapeutic inhibitors. No significant financial relationships to disclose.
Liquid biopsy leads to a paradigm shift in cancer treatment.
Authors: Koichi Suzuki, Yuji Takayama, Kosuke Ichida, Taro Fukui, Nao Kakizawa, Yuta Muto, Fumiaki Watanabe, Fumi Hasegawa, Shingo Tsujinaka, Yuji Kaneda, Yasuyuki Miyakura, Hiroshi Noda, Hirokazu Kiyozaki, Fumio Konishi, Toshiki Rikiyama
Journal: Journal of Clinical Oncology (2016)

602 Background: Liquid biopsy represents an ideal non-invasive tool allowing multiple testing over time, monitoring real time changes occurring within the tumor and evaluation of therapeutic response. Here we show monitoring of KRAS mutation in detection of circulating tumor DNA (ctDNA) during treatments for metastatic colorectal cancer patients (pts). Methods: 238 plasma samples were collected from 57 pts who underwent chemotherapy. KRAS mutant ctDNA (MctDNA) was determined by digital PCR as a tool of Liquid biopsy, detecting rare mutant clones in blood. Results: KRAS assessment in tumor tissues showed 19 pts with mutation (M) and 38 without mutation (W). Among 19 pts with M, 12 pts displayed MctDNA at the initial assessment and 7 pts showed no MctDNA. Then, one (M*) of 7 pts exhibited MctDNA during treatments. While 38 pts with W showed no MctDNA before chemotherapy except one pt (M**), 4 pts exhibited MctDNA after treatments with different regimens. MctDNA was detectable in the blood of these 4 pts prior to radiographic detection of disease progression. Regardless of KRAS status in tumor tissues, poor response was seen in pts with MctDNA. Conclusions: Liquid biopsy provides us a circulating biomarker for monitoring treatment response and choice of optimal regimens. [Table: see text]
Chemoradiotherapy for cancer of the cervix
Authors: J. F. Gonzalez Guerrero, J. P. Alarcon Caballero, J. L. Martinez Rodriguez, R. G. Najera Hernandez, R. Lopez Rod, D. Fierro Fuentes, J. L. Gonzalez Perez, D. Hernandez Barajas, J. L. Gonzalez Vela
Journal: Journal of Clinical Oncology (2005)

5183 Background: Cancer of the cervix continues to be the most frequent neoplastic disease in Mexico. Most cases are detected in Stage II and III. Radiotherapy is the mainstay of treatment but results are unsatisfactory. Previous reports of combined modality therapy with fluorouracil and cisplatin have shown improved outcomes. The objective of this report is to confirm these results in our patients. Methods: We reviewed the charts of 55 pts. with cancer of the cervix, from 2000 to 2004. Most were squamous (86%), 5 adenocarcinoma, 1 adenosquamous, and 1 small cell. Clinical staging was stage II 63%, stage III 25%, IB 10%, stage IV 2%. The age was 19 to 94 yr. cisplatin was the most frequent chemotherapeutic used (85%) at a dose range of 20 to 40 mg. per sq. meter BSA, per week during radiotherapy. 15% of pts received fluorouracil 1 gr. M2 96hr, d cisplatin 100mg. M2 day 2. Radiotherapy was 50 Gy. external beam and brachiterapy using Fletcher procedure (two applications) for a total (average) of 74 Gy to Point A. Results: 7pts. abandoned treatment, 4 due to economic difficulty, and 3 to toxicity, adinamic ileus (1), neutropenia (1), nephrotoxicity (1). 48pts. completed therapy, 83.3% achieved complete response. (physical exam and negative pap smear.) 16.7% had persistent disease. Median survival has not been reached, currently there have been 18 pts who completed one yr of follow up and 2 have recurred with distant metastases (liver and retroperitoneum). Four pts have died from progressive disease, three of them after achieving complete response. Conclusions: Combined modality therapy is feasable in this group of pts, well tolerated, with a high response rate. Longer follow up is neccesary to report the overall survival of this group of pt. No significant financial relationships to disclose.
Longitudinal segmentation of age-related white matter hyperintensities
Authors: Carole H. Sudre, M. Jorge Cardoso, Sebastien Ourselin
Journal: Medical Image Analysis (2017)

Although white matter hyperintensities evolve in the course of ageing, few solutions exist to consider the lesion segmentation problem longitudinally. Based on an existing automatic lesion segmentation algorithm, a longitudinal extension is proposed. For evaluation purposes, a longitudinal lesion simulator is created allowing for the comparison between the longitudinal and the cross-sectional version in various situations of lesion load progression. Finally, applied to clinical data, the proposed framework demonstrates an increased robustness compared to available cross-sectional methods and findings are aligned with previously reported clinical patterns.
Meta-analysis: Risk of congestive heart failure (CHF) in selected targeted agents.
Authors: Carmelita P. Escalante, Linda S. Elting, Josiah Halm, Ali Zalpour, Paolo Bossi, SWamique Yusuf, Norman Brito-Dellan, Sunil Sahai, Satish Bhadriraju, Tanya Rouleau, Yuchia Chang
Journal: Journal of Clinical Oncology (2015)

64 Background: Congestive heart failure (CHF) is among the most serious cardiovascular side effects of targeted agents (TA) impacting the clinical outcomes (including survival) of cancer patients on this therapy. Although clinical trials have reported this toxicity, often sample sizes are small and systemic evaluations are lacking. The objective of this study is to estimate risk and severity of CHF due to selected TAs. Methods: We identified 110 English language studies of 26 TA’s approved by the Food and Drug Administration as of November 2013 via MEDLINE. Of those, 8 studies including nearly 8000 patients provided TA-related data on the incidence and severity of CHF. Using meta-analytic methods, we calculated the relative risks of CHF, adjusting for sample size using the inverse variance technique. For each TA, we also determined the number needed to harm. Results: See table. Conclusions: In 5 studies including more than 7,000 patients, trastuzumab showed significantly greater risk of CHF. For every 9 patients treated with trastuzumab, there was 1 additional case of CHF compared to control regimens. A careful patient selection before therapy and early detection of CHF by judicious monitoring of patients on this therapy may prevent serious complications and allow maintenance of cancer treatment. [Table: see text]
Alectinib for Patients with ALK Rearrangement–Positive Non–Small Cell Lung Cancer and a Poor Performance Status (Lung Oncology Group in Kyushu 1401)
Authors: Eiji Iwama, Yasushi Goto, Haruyasu Murakami, Taishi Harada, Shinsuke Tsumura, Hiroyuki Sakashita, Yoshiaki Mori, Noriaki Nakagaki, Yuka Fujita, Masahiro Seike, Akihiro Bessho, Manabu Ono, Akihito Okazaki, Hiroaki Akamatsu, Ryotaro Morinaga, Shinichiro Ushijima, Takayuki Shimose, Shoji Tokunaga, Akinobu Hamada, Nobuyuki Yamamoto, Yoichi Nakanishi, Kenji Sugio, Isamu Okamoto
Journal: Journal of Thoracic Oncology (2017)
Comparison of strategies for identifying colorectal cancer patients with Lynch syndrome: A comparative-effectiveness analysis.
Authors: S. DaCosta Byfield
Journal: Journal of Clinical Oncology (2010)

e16508 Background: Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of inherited colorectal cancer (CRC). Identifying HNPCC is important for management of patients and their mutation-positive relatives. Germline testing (GT) can definitively identify HNPCC but is costly. Various strategies have been proposed to better select who should undergo GT but, the optimal strategy is unclear. This study evaluates the comparative effectiveness of strategies for identifying CRC patients with HNPCC. Methods: A decision-analytic model was used to evaluate 31 strategies for detecting patients with HNPCC, including use of cancer history assessment tools (Amsterdam Criteria [AC], Revised Bethesda Guidelines [RBG], or PREMM diagnostic model) with or without molecular evaluation (immunohistochemistry [IHC], microsatellite instability [MSI] testing and BRAF testing] of CRC tumors prior to GT. For an estimated 150,000 patients newly diagnosed with CRC in a year (3% of whom are expected to have HNPCC), the model estimated the number of HNPCC patients each strategy would detect and associated costs. Results: Universal GT identified all HNPCC patients and cost $386 million. The next most costly strategy at $167 million, universal IHC and MSI testing then GT, detected > 97% HNPCC. Strategies employing RBG then MSI and/or IHC detected > 85% of HNPCC patients, with costs from $58-$166 million. Strategies relying on AC for further testing were the least costly ($17-$22 million) but detected < 50% of HNPCC patients. Regardless of the strategy, inclusion of BRAF testing (detects sporadic CRC) reduced costs by 0.5%-26.7%. Considering cost-effectiveness, strategies using RBG or the PREMM model followed by molecular evaluation then GT, were more effective and less costly than strategies of universal molecular testing. Conclusions: Costs and effectiveness of strategies for identifying HNPCC patients vary greatly and some may be prohibitively expensive. However, programs that employ the PREMM model or the RBG followed by molecular testing may be optimal. If cancer history assessment is difficult, “Universal IHC” may be the next most cost-effective option. No significant financial relationships to disclose.
Effect of generation 2.5 antisense inhibitor of androgen receptor on MDV3100-resistant prostate cancer cell growth in vitro and in vivo.
Authors: Yoshiaki Yamamoto, Eliana Beraldi, Yohann Loriot, Tianyuan Zhou, Youngsoo Kim, Brett P. Monia, A. Robert MacLeod, Ladan Fazli, Amina Zoubeidi, Martin Edwin Gleave
Journal: Journal of Clinical Oncology (2013)

94 Background: MDV3100 is a potent androgen receptor (AR) antagonist with activity in castration resistant prostate cancer (CRPC); however, progression to MDV3100-resistant (MDV-R) CRPC frequently occurs with rising serum PSA levels, implicating AR full length or variants in disease progression. We studied the activity of Generation 2.5 antisense oligonucleotide (ASO) targeting the AR full length (AR fl ) and splice variants in MDV-R CRPC models. Methods: and Results: ThreeASOs targeting exon 1, intron 1, or exon 8 were designed to suppress AR fl and known AR splice variants. We generated by selection MDV-R LNCaP-derived sub-lines that uniformly expressed high levels of both AR fl and AR-V7 compared to CRPC LNCaP cell lines. MDV-3100 induced time- and dose-dependent increases in AR fl and AR-V7 protein levels; AR fl levels were ~20-fold higher than AR-V7. All 3 AR-ASO decreased AR fl and PSA expression. Exon 1 ASO decreased expression of both AR fl and AR-V7 in MDV-R-LNCaP cells; in contrast, exon 8 ASO decreased AR fl without reducing AR-V7 levels. Exon 1 ASO also most potently suppressed AR fl and splice variants in M12 cells stably overexpressing AR splice variants AR-V7 and AR-V567es. Despite these differential effects on AR fl and splice variant knockdown, the AR ASO similarly inhibited cell growth and induced apoptosis and G1 cell cycle arrest in LNCaP-derived CRPC and MDV-R cell lines. In 22RV-1 cells (which express endogenous AR fl and AR-V7), exon 1 ASO more potently suppressed AR fl and AR-V7 levels, AR transcriptional activity and AR-regulated gene expression compared to exon 8 ASO, but inhibition of cell growth did not differ significantly. Exon 1 ASO was evaluated in vivo in MDV-R49F CRPC LNCaP xenografts; mean tumor volume and serum PSA levels decreased significantly by 40% and 50%, respectively, compared to controls. Conclusions: While MDV-3100 induces both AR fl and AR-V7 levels, the biologic consequences appear cell line dependent and mainly driven by AR fl . AR-ASO knockdown of AR fl and its splice variants suppresses MDV-R LNCaP tumor growth, providing pre-clinical proof of principle to support clinical evaluation in post-AR pathway inhibitor CRPC.