tbuckley/cabot-search huggingface dataset:
Effects of cancer therapy on sexuality and quality of life (QoL) of patients with gynecologic malignancies (GM): Results from 55 pts.
Authors: Adak Pilger, Rolf Richter, Christina Fotopoulou, Carmen Rosa Beteta, Fakher Ismaeel, Jalid Sehouli
Journal: Journal of Clinical Oncology (2012)

e19597 Background: Sexuality is a crucial issue influenced by social norms, shame and moral taboos and is generally not discussed in the clinical day and research community. Aim of our study was to systematically evaluate the sexual function and quality of life of cancer pts after operative and systemic treatment in GM. Methods: We assessed in a prospective setting sexual function and quality of life aspects of patients with histological proven GM after completed treatment. Validated questionnaires about sexuality (Female Sexual Function Index 19 items), quality of life (SF-12) as well an additional semi-structured questionnaire consisting of 20 items were answered by all pts at the earliest 3 months after end of treatment during cancer care follow up visit. Results: Overall 55 pts with median age 61 (range, 22-74) were evaluated including 54% ovarian, 26% breast, 13% cervical cancer, 2% endometrial- and 6% vulvar cancer pts. Overall 32.7% (n=18) of the pts stated that they have sexual problems. Based on the FSFI (&lt;26.5) more pts (58.2%) presented sexual problems. The main reasons for an impaired sexuality were a subjective lost of attractiveness (45%; n=9); vaginal dryness (25%; n=5) followed by fear of injury (20%; n=4). 36.4% (n=20) described a change of sexuality after cancer therapy, 8 pts stated positive, 12 pts negative changes. 40% of the pts stated that they have not searched for information about sexual aspects during or after cancer therapy while 25% of the pts have asked their physicians. Patients who lived in a partnership had higher SF12 scores than singles but not different global QoL-scores. Multivariate analysis revealed ovarian, endometrial, and vulvar cancer but not age, disease stage and presence of partner to negatively affect sexual function . SF12 evaluation showed significantly higher psychological functionality with increasing age. Impaired sexuality was always associated with lower scores in SF12. Conclusions: There is a high need of sexual function assessment after cancer treatment of GM patients using validated questionnaires. Only few pts have access to information about sexuality. Strategies are warranted to improve the discussion about this relevant topic.
Should we screen extensively for cancer after unprovoked venous thrombosis?
Authors: Faizan Khan, Christian Vaillancourt, Marc Carrier
Journal: BMJ (2017)

#### What you need to know

How far to go in screening patients with an unprovoked venous thromboembolism (VTE) for an occult cancer is a clinical dilemma. Unprovoked VTE, either deep vein thrombosis or pulmonary embolism, can be the first manifestation of an undiagnosed cancer. Until recently, the literature suggested that up to 10% of such patients would be diagnosed with a cancer in the year after their diagnosis of VTE.1 However, the incidence of occult cancer in patients studied in two recent, high quality, randomised controlled trials was only about 4%.23 This drop in the proportion of people with occult cancer may require an adjustment in the clinical approach.

Fig 1⇓ outlines a conservative approach and a more detailed approach to investigating such patients. Extensive screening has become the standard of care, though it is based on limited data.



Fig 1  Occult cancer screening strategies in unprovoked venous thromboembolism (from NICE guidelines 20124)



However, high quality data from recently completed trials discussed below suggest that extensive screening strategies may not provide additional value over routine cancer screening in the frequency of cancer detection in these patients.

#### Search strategy and study selection

We searched PubMed (from inception to 31 December 2016) for randomised controlled trials and systematic reviews using the search terms “cancer screening,” “venous thromboembolism,” “unprovoked,” “meta-analysis,” and “randomized controlled trial.” We reviewed articles published in English between 2012 (publication of NICE guidelines) and 2016. We also searched the Cochrane Library and …
Feasibility trial of adjuvant chemotherapy with docetaxel (DOC) plus cisplatin (CDDP) followed by maintenance chemotherapy of S-1 in completely resected non-small cell lung cancer (NSCLC): Thoracic Oncology Research Group (TORG) 0809.
Authors: Seiji Niho, Kenji Suzuki, Hiroshi Sakai, Takayuki Kaburagi, Teruaki Koike, Koichi Minato, Terufumi Kato, Hiroaki Okamoto, Takashi Seto, Yukio Hosomi, Kimihiro Shimizu, Fumihiro Oshita, Masanori Tsuchida, Motohiro Yamashita, Osamu Kawashima, Kazuma Kishi, Hideo Kunitoh, Masahiro Takeuchi, Koshiro Watanabe, Norihiko Ikeda
Journal: Journal of Clinical Oncology (2012)

7012 Background: Maintenance chemotherapy could prolong overall and/or progression-free survival in advanced NSCLC. S-1 is an oral anticancer agent comprised of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate. The TORG 0809 study was conducted to evaluate the feasibility and efficacy of maintenance chemotherapy of S-1 following DOC+CDDP in patients (pts) with curatively resected stage II and IIIA NSCLC. Methods: Pts received 3 cycles of DOC (60mg/m 2 d1) plus CDDP (80mg/m 2 d1), q3-4w, and subsequently S-1 at 40mg/m 2 twice a day for 14 consecutive days, q3w, for more than 6 months (max 1 year). The primary endpoint was determination of feasibility, which was defined as the proportion of pts who had completed maintenance for 8 cycles of S-1 or more. If the lower confidence interval (CI) of this proportion was 50% or more, the feasibility of the treatment was considered confirmed. The sample size was set to be 125. Results: Between Jun 2009 and Nov 2010, 131 pts were enrolled, of whom 129 pts were eligible and assessable. The median age was 63 (23-74 years); PS 0: 107, 1: 22; p-stage IIA: 19, IIB: 30, IIIA: 80; adenocarcinoma: 99, non-adenocarcinoma: 30. Of 129 pts, 109 pts (84.5%) completed 3 cycles of DOC+CDDP. 106 pts initiated the maintenance S-1 and 66 pts (51.2%, 95% CI: 42.5-59.8) completed 8 cycles or more S-1 treatment; this percentage was less than our previously defined criterion for treatment feasibility, since 32 pts terminated maintenance S-1 at 3 cycles or less. Grade 3/4 toxicities during the maintenance S-1 included anemia (7.3%), neutropenia (3.7%), anorexia (3.7%), dyspnea (1.8%), infection with neutropenia of grade 0 to 2 (1.8%). Febrile neutropenia was not observed. One pt developed interstitial pneumonia and sepsis, resulting in treatment-related death. Recurrence-free survival data will be presented. Conclusions: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule of maintenance S-1, such as a 2-week rest period rather than 1-week, might improve treatment compliance.
Integrated genomics and avatar mouse models for personalized cancer treatment.
Authors: Elena Garralda, Keren Paz, Pedro P. López-Casas, Siân Jones, Amanda Katz, Lisa M. Kann, Fernando López-Ríos, Francesca Sarno, Fatima Al-Shahrour, David Vasquez, Elizabeth Bruckheimer, Samuel V. Angiuoli, Luis A. Diaz, Alfonso Valencia, Victor E. Velculescu, David Sidransky, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2013)

2511 Background: Every cancer has its unique set of molecular changes and the knowledge of such alterations is enabling an individualized approach to cancer treatment. The great intellectual challenge lies in linking confirmed mutations to protein function. Methods: Using massive parallel sequencing we performed whole exome sequencing analysis of 30 patients (pts) with advanced solid tumors to identify putatively actionable tumor-specific genomic alterations. We used 2 in silico methods (Polyphen and SIFT) to estimate the functional significance of a given confirmed mutation. Avatar models generated by direct engraftment of tumor samples from the patients into immunocompromised mice were used as an in vivo platform to test proposed treatment strategies. Results: Successful exome sequencing analyses has been obtained for 28 pts. Tumor specific mutations (Muts) and copy number variations were identified ranging from 5 to 952 and 0 to 956 respectively. All samples profiled contained relevant genomic alterations. Some of the most relevant actionable alterations were: CHEK1, FGFR2, IGF1R, MET, BRCA1, XPC, NOTCH, CREB3LB, GNA11, SMAD4, NF1, PTPRC, PI3KA, DDR2 and EGFR. An Avatar model was generated for 15 patients. In occasions actionable alterations such as muts in NF1, PTPRC, PI3KA and DDR2 failed to provide any benefit when a targeted drug was tested in the Avatar and accordingly treatment of the pts with these drugs was not effective. So far 13 pts have received a personalized treatment: two, as expected based on the avatar model, did not response; 5 resulted in durable partial remissions. Eight pts are currently on treatment with at least disease stabilization. Bench testing of candidate treatments in Avatar models correlated with clinical response and helped to select empirical treatments in patients with no actionable mutations. Conclusions: The use of full genomic analysis for cancer care is promising but presents important challenges that will need to be solved for broad clinical application. Avatar models are a powerful investigational platform for therapeutic decision making and help to guide cancer treatment in the clinic. While limitations still exist, this strategy should be tested in prospective randomized clinical trials.
Tumor location and neurocognitive impairment in adult survivors of pediatric brain tumors: A report from the St. Jude Lifetime Cohort (SJLIFE).
Authors: Tara M. Brinkman, Wei Liu, Gregory T. Armstrong, Amar J. Gajjar, Thomas E. Merchant, Cara I. Kimberg, Larry E. Kun, Deo Kumar Srivastava, James G. Gurney, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2012)

9531 Background: Follow-up guidelines identify supratentorial tumor location as a risk factor for poor neurocognitive outcomes during childhood; yet few studies have systematically compared long-term cognitive outcomes between adult survivors of childhood infratentorial and supratentorial brain tumors. Methods: Neurocognitive functions were evaluated in 130 adult survivors of pediatric brain tumors (58 supratentorial and 72 infratentorial, mean [SD] current age = 27.4 years [5.2], age at diagnosis = 8.6 years [4.6], and time since diagnosis = 18.8 years [4.8]) participating in the SJLIFE long-term follow-up protocol. Age-adjusted standard scores for measures of intelligence, attention, memory, processing speed, and executive functioning were calculated, with clinical impairment defined as scores &lt;10th percentile. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models to examine associations between neurocognitive functions and tumor location. Results: As a group, survivors performed below average across multiple neurocognitive domains, including full scale IQ (mean=88.1; SD=18.2), with 34% demonstrating impaired IQ. Survivors of infratentorial tumors were more likely to be impaired on measures of focused attention (OR=2.19, 95% CI=1.03-4.65) and fine motor dexterity (OR=2.62, 95% CI=1.21-5.66) compared to survivors of supratentorial tumors. After adjusting for sex, age at diagnosis, shunt placement and cranial radiation (yes/no), infratentorial tumor location was only associated with reduced performance on a task of visual abstract reasoning (OR=3.76, 95% CI=1.40-10.1). Cranial radiation therapy was independently associated with impaired short-term memory (OR=15.6, 95% CI=1.64-147.8) and processing speed (OR=3.86, 95% CI=1.15-13.0). Conclusions: Tumor location was not associated with neurocognitive impairment after adjusting for treatment exposures. To further delineate potential differences associated with tumor location, future studies will examine factors including radiation dose/volume, extent of surgical resection, and medical complications.
Genomic profiling of large-cell neuroendocrine carcinoma of the lung.
Authors: Tomohiro Miyoshi, Shigeki Umemura, Yuki Matsumura, Sachiyo Mimaki, Satoshi Tada, Genichiro Ishii, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Kanji Nagai, Koichi Goto, Masahiro Tsuboi, Katsuya Tsuchihara
Journal: Journal of Clinical Oncology (2015)

7519 Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung shares many clinical characteristics with small-cell lung cancer (SCLC). However, little is known about the molecular biology of LCNEC. We analyzed lung LCNECs for biologically relevant genomic alterations using a next-generation sequencing-based genomic profiling assay. Methods: Genomic DNAs extracted from surgically resected or biopsy samples were subjected to a 1.499 Mb custom target capturing panel including all exons of 244 cancer-related genes. Seventy eight LCNEC samples including 10 LCNECs combined with other non-small cell lung cancers (NSCLCs) were applied to the target sequencing. In the 10 combined LCNECs, both morphologic components of LCNEC and other NSCLCs (adenocarcinoma: 5, squamous cell carcinoma: 5) were analyzed separately. Frequencies of detected driver gene alterations were compared with those in previous reports regarding SCLC. Results: The demographics of the 78 patients were as follows: median age 70 years (range: 22-84); male 67 (86%); history of smoking 76 (97%); pathological stage I/II/III = 38/14/13 for 65 resected cases and clinical stage II/III/IV = 1/4/8 for 13 biopsy cases. We identified high prevalence of inactivating mutations in TP53 (74%) and RB1 (29%), and mutations of histone modifiers, CREBBP (10%) and EP300 (4%), were detected as with the previous reports on SCLC. Genetic mutations in the PI3K/AKT/mTOR pathway were detected in 30 (40%) of the tumors: PIK3CA 3%, PTEN 6%, AKT2 1%, AKT3 1%, TSC1 5%, TSC2 3%, RPTOR 4%, RICTOR 10% and mTOR 5%. Other known activating mutations were also detected in KIT (1%), KRAS (4%) and HRAS(1%). In the combined cases, the concordance rate of types of genetic alterations between the two components was 87% (range: 50-97). Conclusions: The genomic profile of LCNEC was similar to that of SCLC. Genetic alterations of the individual components in combined LCNEC were closely concordant with each other despite their distinct histologic morphologies.
Impact of body mass index (BMI) on plerixafor efficacy during hematopoietic progenitor cell (HPC) mobilization.
Authors: Rebecca M. Gonzalez, Alexandra Shillingburg, Michael David Newton, Sijin Wen, Sonia Leadmon, Abraham Sebastian Kanate, Michael Craig, Mehdi Hamadani, Aaron Cumpston
Journal: Journal of Clinical Oncology (2014)

7047 Background: Plerixafor in combination with G-CSF is commonly used to mobilize HPC for autologous transplantation. The effect of BMI on plerixafor mobilization efficacy is controversial, with conflicting results from previous studies. Methods: One hundred and fourteen patients received G-CSF (10mcg/kg TBW) daily, with plerixafor (0.24mg/kg TBW) added on the evening of day 4 of G-CSF, to mobilize and collect HPCs from 12/2009-12/2013. The first 83 patients before 11/2012 received upfront plerixafor/GCSF mobilization, and the remaining patients received a “just in time” approach, with plerixafor added if peripheral CD34 count was <10/µL by day 4 of G-CSF. Patients receiving plerixafor were divided into obese (BMI ≥30) and non-obese (BMI <30) groups, and were compared to evaluate the effect of BMI on plerixafor HPC mobilization outcomes. Results: Patient demographics are listed in Table 1. A median of 2 plerixafor doses were given in both the obese (range 1-4) and non-obese (range 1-5) patients. The median peak peripheral CD34+ count was 38/µL (range 2-389.2) in obese versus 39.5/µL (range 3-350) in non-obese patients (P=0.25). Median CD34+ collection Day 1 was 2.2 (obese) versus 2.3 x 106 cells/kg TBW (non-obese). Total CD34+ cell yield after a median of 2 apheresis sessions was 4.3 x 106 cells/kg TBW in each group (P=0.51). Successful collection of ≥ 2 and 5 x 106 CD34+ cells/kg TBW occurred in 90% and 40% of obese compared to 87% and 43% of non-obese patients, respectively (P = 0.77, 0.71). Conclusions: Obesity is not a negative predictive factor for plerixafor HPC mobilization. All collection parameters were similar between both groups. Demographics Non-Obese (N=54) Obese (N=60) P-Value Median age,yrs (range) 59.5 (22-75) 61.5 (23-75) 0.64 Male Gender 52% 52% 0.85 Myeloma Lymphoma 52% 48% 53% 47% 0.85 BM Involvement 50% 40% 0.45 Prior Radiation 17% 25% 0.26 Lines of Prior Therapy, mean/median (range) 1.8/2 (1-5) 1.5/2 (1-3) 0.24 Lenalidomide Therapy · # of cycles, mean/median (range) 22% 20% 1.0 4.1/4 (1-6) 4/4.8 (2-8) 0.65 KPS, median (range) 80 (60-100) 80 (70-90) 0.27 HCT-CI score, median (range) 2 (0-7) 2 (0-9) 0.88 Pre-Transplant Status · CR · PR · <PR (N=52) 48% 52% 0% (N=57) 61% 37% 2% 0.15
Impact of zoledronic acid (ZA) versus pamidronate (P) on overall survival (OS) in multiple myeloma (MM).
Authors: Kristen Marie Sanfilippo, Suhong Luo, Brian Gage, Ravi Vij, Kenneth Robert Carson
Journal: Journal of Clinical Oncology (2013)

e17546 Background: Nitrogen-containing bisphosphonates (BPs) have been shown to improve OS compared to non-nitrogen containing BPs in MM (Morgan et al. Lancet 2010). Treatment guidelines recommend use of ZA or P (both nitrogen-containing) in MM patients with bone disease. No study has compared the effect of these two drugs on OS. We compared the impact of ZA versus P on OS in United States Veterans with MM. Methods: We retrospectively identified patients diagnosed with MM from 10/2002-2/2009 within the Veterans Heath Administration Central Cancer Registry who received ZA (n=482) or P (n=757) by linking registry data to pharmacy records. Cox multivariable analysis was used to estimate the association between choice of BP and OS while controlling for potential confounders: body mass index (BMI), age, race, Charlson comorbidity index, year, treatment, hemoglobin (Hgb), creatinine (Cr), and albumin. Results: The median OS in patients receiving ZA was 34.5 months, compared to 26.4 months in the P group. After adjusting for confounders, ZA reduced the risk of death by 24% compared to P (hazard ratio [HR] 0.76; 95% confidence interval [CI]: 0.66-0.88) at 5 years (Table). A sensitivity analysis that compared ZA only (n=482) versus all patients who received P, regardless if they later received ZA (n=1117) continued to show decreased mortality (HR 0.82; 95% CI: 0.71-0.94) after controlling for the same potential confounders. Conclusions: In this, the largest study to evaluate the association between ZA versus P on OS in MM, we found decreased mortality associated with ZA. Given the similar toxicity profiles, this study supports preferential use of ZA over P and may serve as evidence for re-evaluation of current guidelines for BP use in MM. [Table: see text]
Understanding the physical attractiveness literature: Qualitative reviews versus meta-analysis
Authors: Alan Feingold
Journal: Behavioral and Brain Sciences (2017)

Abstract The target article is a qualitative review of selected findings in the physical attractiveness literature. This commentary explains why the meta-analytic approach, frequently used by other attractiveness reviewers, is preferable for drawing unbiased conclusions about the effects of attractiveness. The article's main contribution is affording a foundation for subsequent meta-analysis of the studies discussed in a subjective fashion.
Cancer-related infertility education in a public rural institution: Patient needs and provider attitudes.
Authors: Hannah E Spencer, Gina R. Petroni, Jeanne Marie Erickson, Shahleen Z. Ahmed, Linda R. Duska
Journal: Journal of Clinical Oncology (2014)

e20605 Background: The National Cancer Institute estimates 50% of the 70,000 15-to-39-year olds diagnosed with cancer in the U.S. each year receive counseling on cancer-related infertility. The need for infertility and fertility preservation education in a population of cancer patients at the University of Virginia (UVA) is likely but unknown. Also unknown are attitudes and practices of our oncologists and midlevel providers with respect to counseling patients on infertility and fertility preservation. Before developing infertility counseling services at UVA, it is imperative to measure patient interest and provider attitudes and practices. Methods: A multidisciplinary team with interest in cancer patients and infertility was formed with physicians, nurses, researchers, and a statistician. Surveys were reviewed from 1990-2014 with PubMed, Ovid MEDLINE, and Google Scholar using keywords such as fertility preservation, cancer, attitude, and barriers. The team developed 2 surveys to evaluate patients and providers using published literature and unique questions targeting our population. The order of survey questions was designed to investigate participant knowledge of fertility topics. Surveys avoid prompts for personal identifiers, and wording that may cause discomfort. Results: From January 2012 to June 2013, 367 women ages 18-45 and 833 men ages 18-60 were newly diagnosed with cancer at UVA. UVA’s Institutional Review Board (IRB) authorized the surveys as IRB exempt. Nurses from all oncology clinics were engaged to assure patient survey distribution and collection. Providers receive electronic surveys. For ease, surveys can be completed in less than 5 minutes. Each survey evaluates 5 domains (Table). Conclusions: Preliminary results will be ready for the May 2014 meeting. Findings will inform provider practices related to infertility education for patients. A supplemental survey will assess our current institutional oncology nursing practices related to this critical survivorship topic. Patient measures Provider measures Demographics Demographics Interest Practice behaviors Education received Education barriers Satisfaction Attitude Knowledge assessment Future referral