tbuckley/cabot-search huggingface dataset:
UGT2B17 deletion polymorphism and exemestane-induced toxicity.
Authors: Elizabeth Packard, Cynthia Campbell-Baird, Kim Leitzel, Shaman Luo, Gang Chen, Junjia Zhu, Leah Cream, Philip Lazarus, Cristina I. Truica
Journal: Journal of Clinical Oncology (2018)

e12534 Background: Genetic polymorphisms in drug metabolizing enzymes can have significant impact on drug toxicity and/or efficacy. Exemestane (Exe), a steroidal aromatase inhibitor, is extensively metabolized by reduction to a major active metabolite, 17β-dihydro-EXE (17β-DHE), and by glucuronidation to inactive 17β-DHE-glucuronide (17β-DHE-gluc). UGT2B17 is the major enzyme responsible for glucuronidation of 17β-DHE. A polymorphic whole-gene deletion of the UGT2B17 gene has an allelic prevalence of 30% in Caucasians and leads to higher plasma levels of the active metabolite 17β-DHE. We hypothesized that UGT2B17 genotype could play a role in the variability of Exe-induced toxicity. Methods: Postmenopausal patients received 25 mg Exe daily for 30 days for treatment of early stage breast cancer or chemoprevention. Blood, urine collection and symptom assessment ( arthralgias, hot flashes) were obtained at baseline and after 30 days of treatment. Hot flashes and joint pain status at 1 month was correlated with UGT2B17 genotype. Presence of symptoms was dichotomized as any (mild/moderate/severe) vs none. Statistical analyses used Fisher’s exact test for categorical variables and nonparametric Wilcoxon Rank Sum test for quantitative variables. Results: 46% of the 130 Exe-treated patients were heterozygous for the UGT2B17 deletion (*1/*2 genotype) while 17% were UGT2B17 null (*2/*2 genotype), with a UGT2B17 deletion allelic frequency of 40%. Patients who were UGT2B17 null (*2*2) exhibited a 39-fold (p < 0.0001) and 29-fold (p < 0.0001) decrease in the levels of creatinine-adjusted urinary and plasma levels of 17β-DHE-gluc, respectively. Plasma levels of Exe–adjusted 17β-DHE were 28% higher (p = 0.004) in these patients. At 1 month post-Exe treatment, no association between UGT2B17 genotype and joint pain status or hot flashes was observed between patients with the UGT2B17 (*2/*2) genotype vs patients exhibiting the wild-type UGT2B17 (*1/*1) genotype (p = 0.062 for joint pains and p = 0.812 for hot flashes). We are currently exploring the role of genetic variants in other metabolic pathways that may be important in Exe metabolism. Conclusions: UGT2B17 genotype did not correlate with the severity of Exe-associated joint pains and hot flashes.
A novel bioscaffold with naturally-occurring extracellular matrix promotes hepatocyte survival and vessel patency in mouse models of heterologous transplantation
Authors: Wei Yang, Quanyu Chen, Renpei Xia, Yujun Zhang, Ling Shuai, Jiejuan Lai, Xiaolin You, Yan Jiang, Ping Bie, Leida Zhang, Hongyu Zhang, Lianhua Bai
Journal: Biomaterials (2018)
Survivorship care plans: Implementation in an academic medical center.
Authors: Hien Le, Matthew M Cadorette, William M Decaneas, Irving D. Kaplan, Mary Jane Houliahn, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2018)

64 Background: There are more than 14 million cancer survivors in the US. The Commission on Cancer requires survivorship care plans (SCPs) for patients with Stages I-III cancer. We developed a centralized process to create and monitor SCPs at an academic medical center. Methods: Tumor registry (TR) and clinical decision support teams built an SCP report to identify patients with stage I-III malignancies diagnosed within the past year (18 months for breast cancer patients on hormonal therapy) with a future appointment with medical, radiation or surgical oncology. The TR runs this report to identify patients nine-months post-diagnosis and then e-mails providers a draft SCP two days prior to the appointment. The provider edits this SCP and creates a note linked to the problem list item “Cancer Survivorship,” which is captured as a field in the SCP report. The SCP is mailed to the PCP and handed to the patient. If the SCP is not completed, the TR will send a reminder to the clinician. Results: From September to October 2017, 77 potential cases were reviewed by the TR and 25 (32%) were excluded because of active treatment (9), treatment with palliative intent (5), recurrence (8), and treatment by an outside provider (1). Of the 53 SCP’s e-mailed to providers, 12 were completed and 11 were excluded for active treatment (3), treatment with palliative intent (1), recurrence (3), missed/cancelled appointment (2), SCP sent to provider not providing treatment (1) and inability to discuss SCP with patient (1). An additional five had SCPs completed but were not in the electronic medical record. The overall completion rate of SCPs on eligible patients was 17/42 (40%). SCPs were completed in melanoma, breast, stomach, colon, and prostate cancers by medical, surgical, and radiation oncologists. Conclusions: At an academic medical center, we centrally implemented SCPs across a variety of disease types by a variety of providers. SCPs were completed without the need for additional visits, providers or workspace. Screening patients for eligibility before sending SCPs was vital as many were ineligible. Resources including 20% of a tumor registrar’s time, disease-group level buy-in and leadership support were vital.
An open-label, dose-escalation phase I study to evaluate RC48-ADC, a novel antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer.
Authors: Jiayu Wang, Binghe Xu, Wenxiang Wang, Jianmin Fang
Journal: Journal of Clinical Oncology (2018)

1030 Background: There is still urgent medical needs for new therapeutics in the patients with metastatic breast cancer (MBC) and other solid tumors with HER2 overexpression. RC48-ADC is an antibody-drug conjugate drug with a novel humanized anti-HER2 antibody conjugated to monomethyl auristatin E (MMAE) through a cleavable linker. Preclinical data in various animal models, including breast cancer, gastric cancer and ovarian cancer, suggested excellent antitumor efficacy. Methods: It was an open-label, single-center, phase I study. Eligible pts (18-65 years) were confirmed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) as HER2-positive (IHC 2+/FISH+ or IHC 3+) MBC. A 3+3 dose-escalation was conducted with a 28-day window to evaluate dose limiting toxicity (DLT). DLT was mainly defined as Grade 4 neutropenia effectively managed with symptomatic treatment, Grade 3 neutropenia accompanied by infection and Grade 3 non-hematological toxicity. Tumor response was accessed per RECIST 1.1 every 6 weeks. Results: As of 29 Jan, 2018, 23 female pts with MBC were treated in 5 dose escalation cohorts (dose levels 0.5, 1.0, 1.5, 2.0, 2.5 mg/kg) once every two weeks (Q2W). Median age was 57 (32-65), and the course of disease was more than 3 years in 15 pts (65.2%). 16 pts (69.7%) were previously treated with trastuzumab. Median prior lines of therapy in metastatic setting was 3 (1-6). 14 pts (60.9%) had≥3 visceral metastatic sites of disease. MTD was not reached at doses up to 2.0 mg/kg Q2W. The most common treatment-related AEs (TRAEs) were leucopenia (43.5% Grade 1-2; 4.3% Grade 3), AST elevation (43.5% Grade 1-2; 4.3% Grade 3), followed by neutropenia (30.4%, Grade 1-2, 13% Grade 3-4), which could be readily managed. 20 pts were evaluable for response. Of 14 pts at doses≥1.5mg/kg , 8 (57.1%) achieved PR and 4 (28.6%) SD. For 11 trastuzumab-pretreated pts, ORR was 72.7%. Conclusions: RC48-ADC administrated with Q2W has demonstrated good tolerability and promising antitumor activity in HER2-positive pts with MBC. The MTD has not been determined and 2.5 mg/kg Q2W dose escalation is ongoing. Clinical trial information: NCT02881138. Clinical trial information: NCT02881138.
Barriers of EQ5D-5L implementation into routine clinical practice: A multisite evaluation.
Authors: Justine Baek, Tiffany Tse, M Catherine Brown, Amy Skitch, Judy Chen, Mindy Liang, Hiten Naik, Lawson Eng, Doris Howell, Wei Xu, David Shultz, Christine B. Brezden, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

11 Background: As numbers of cancer survivors increase, health-related quality of life and healthcare service utilization warrant closer attention, which requires routine valuations such as health utility scores (e.g. EQ5D-5L). EQ5D-5L implementation into routine clinical practice requires systematic evaluation to assess project scalability with goals of eventual roll-out across all 15 Ontario cancer centres in all disease sites. Methods: We used the Canadian Institutes of Health Research’s Knowledge-to-Action (KTA) framework as a guide to assess implementation of EQ5D-5L in two outpatient cancer populations; St. Michael’s Hospital’s general breast cancer clinic (GBR) and Princess Margaret Cancer Centre’s multidisciplinary brain metastases clinic (MBM), chosen to represent two very different organizational structures and patient populations. KTA steps from landscape assessment and engagement of stakeholders through to pilot implementation using paper surveys are reported. Results: After assessing 270 patients (GBR = 137; MBM = 117) across 57 days, implementation issues at the two sites were noted. GBR clinic’s larger and more general patient base was associated with a lower average socioeconomic status than MBM clinic, which targets a specialized patient population. More barriers to implementation at GBR were systemic and organizational in nature, whereas barriers at MBM were associated with patient management, where patients’ functional disabilities or neglect to return completed questionnaires hindered data collection. For both sites, successful EQ5D-5L implementation was contingent on senior management support and engagement of multiple stakeholders throughout the implementation process, leading to site-specific suggestions. Conclusions: Differing implementation strategies at both sites is reflective of target sites’ distinctive systemic and organizational characteristics and findings can be used to inform the translation of EQ5D-5L to other sites. We present recommendations to aid scalability and implementation efforts, including future transition to electronic routine assessments.
Response by Vallejo-Vaz et al to Letters Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up”
Authors: Antonio J. Vallejo-Vaz, Chris J. Packard, Kausik K. Ray
Journal: Circulation (2018)
Come back: Identifying targets to engage young adult survivors who have been lost to follow-up.
Authors: Lynda M. Beaupin, Anne Boldt, Katharine Amato
Journal: Journal of Clinical Oncology (2018)

29 Background: Despite national survivorship guidelines, follow-up care after treatment has ended is generally lacking for AYA survivors. Our previous pilot study involving 27 AYA in a focus group found that the major barriers to follow-up included loss of health insurance, poor communication with their oncologist, and on-going adjustment challenges. The current study aimed to determine the proportion of young adult survivors who no longer continued with follow-up care at our institution and examine which factors contributed to the lack of follow-up. Our objectives were: 1. Evaluate how many AYAs who completed treatment may be lost to follow up over time; 2. Determine which AYAs are most at risk of being lost to follow-up. Methods: Data Analysis: 1. AYA Survivorship Dataset – Tumor Registry used to include the following: Current age, age at diagnosis (captured those 18 and 39 years of age), gender, date of diagnosis, date of most recent visit, disease type and histology. 2. Compare follow-up appointments and insurance status between two sets of survivors: Cohort A - 852 patients diagnosed between 2010-2014; Cohort B - 783 patients diagnosed between 2005-2009. Results: 2367 AYAs were diagnosed between 2000-2015; 37% did not have a follow-up visit since 2015 and no significant variation across disease types Regardless of insurance coverage, 33% of Cohort A and 48% of Cohort B survivors were not seen in 2016. Follow-up status was not related to disease type or insurance status. Conclusions: Many AYAs do not continue with survivorship care. Health insurance status did not predict follow-up adherence, nor did disease type. The longer survivors are from the end of their treatment, the less likely they are to have follow-up care at a cancer center. Further research is needed to determine other implicating factors, such as age at diagnosis and type and intensity of cancer treatment received. [Table: see text]
Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma
Authors: J. Lewin, L. Sayers, D. Kee, I. Walpole, A. Sanelli, L. te Marvelde, A. Herschtal, J. Spillane, D. Gyorki, D. Speakman, V. Estall, S. Donahoe, M. Pohl, K. Pope, M. Chua, S. Sandhu, G.A. McArthur, C.J. McCormack, M. Henderson, R.J. Hicks, M. Shackleton
Journal: Annals of Oncology (2018)

As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance.From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes.One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median).Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.
Lifestyle and outcomes after gastrointestinal cancer: A prospective cohort study (LOGIC).
Authors: Marissa Barbara Savoie, Katherine Van Loon, Angela Laffan, Andrea Grace Bocobo, Li Zhang, Alan T Paciorek, Chloe Evelyn Atreya, Mekhail Anwar, Tami Rowen, James F Smith, Dianne Shumay, Stacey A. Kenfield, June M. Chan, Alan P. Venook, Erin Van Blarigan
Journal: Journal of Clinical Oncology (2018)

180 Background: The number of individuals living after a diagnosis of gastrointestinal (GI) cancer is increasing. Emerging data suggest modifiable lifestyle factors impact survival after colorectal cancer (CRC), however very little is known about survivorship in other GI cancers. Given the common thread of multimodality therapy among many GI cancer survivors, there is a paucity of data on sexual function, fertility, anxiety/depression, changes in comorbidities, and quality of life after cancer treatment. Additionally, existing cohort studies of GI survivors are primarily European, and further data are needed from survivor populations in the US . Methods: Patients of the University of California, San Francisco GI Oncology Survivorship Clinic who are designated disease-free are recruited by mail or in clinic. We send secure online questionnaires to participants every six months for five years and annually thereafter. At varying intervals, questionnaires solicit sociodemographics, diet, physical activity, fertility, medical and smoking history, fear of cancer recurrence, sexual health, quality of life, psychological well-being, and sleep quality. Pathoclinical disease characteristics, treatment, and recurrence status are abstracted from the medical record at baseline and updated annually. Results: Between February and August 2017, 111 patients were enrolled; 68% of participants completed ≥1 and 57% completed all baseline questionnaires. Most patients had a history of colon cancer (52%, n = 58) or rectal cancer (31%, n = 34). Other diseases include: anal cancer (12%, n = 13), gastrointestinal stromal tumor (3%, n = 3), and other GI cancers (3%, n = 3). Fifty-eight percent of patients were female, 76% identified as white and median age at diagnosis was 55 (range 20-81). Median time from initial GI cancer diagnosis to study entry was 27 months. Following the initial recruitment wave of established patients, the average rate of enrollment is ~3 patients/week. Conclusions: Results from this ongoing cohort study will improve our understanding of modifiable risk factors for GI cancer recurrence and key survivorship issues related to psychological well-being, sexual function, fertility management, and quality of life.
High Altitude Medicine and Pathology
Journal: Thorax (1990)

1 2 2 1 of Population Censuses and Surveys, we calculate that in the last 10 years the ratio of the number of deaths from tuberculosis per 100 notifications in the 15-29 age group is 0 75.In other words, one death apparently results from 140 notified cases.On the basis of the figures of Drs Springett and Sutherland for the increased numbers of notifications which are likely to result from discontinuing BCG, the table above shows an estimate of the number of "preventable" deaths in the 15-29 age group which may result in the next 30 years.The possible increase in mortality is obviously another important factor which should be borne in mind when we are considering discontinuation of routine BCG vaccination.
Pooled analysis of two randomized phase III trials (PlanB/SuccessC) comparing six cycles of docetaxel and cyclophosphamide to sequential anthracycline taxane chemotherapy in patients with intermediate and high risk HER2-negative early breast cancer (n=5,923).
Authors: Wolfgang Janni, Ulrike Nitz, Brigitte Kathrin Rack, Oleg Gluz, Andreas Schneeweiss, Ronald E. Kates, Tanja N. Fehm, Hans Heinrich Kreipe, Sherko Kummel, Rachel Wuerstlein, Andreas D. Hartkopf, Michael Clemens, Toralf Reimer, Thomas W. P. Friedl, Lothar Haeberle, Peter A. Fasching, Nadia Harbeck
Journal: Journal of Clinical Oncology (2018)

522 Background: Recent studies draw different conclusions concerning whether omission of anthracyclines (A) in adjuvant chemotherapy for HER2-negative early breast cancer (EBC) may reduce toxicity without compromising efficacy. Methods: The prospectively randomized PlanB and Success C trials compared 6 cycles of docetaxel (D) and cyclophosphamide (C) with either 4 cycles of epirubicin (E) and C, followed by 4 cycles of D (EC-D, PlanB) or 3 cycles of 5-FU, E and C, followed by 3 cycles of D (FEC-D, SuccessC). Disease-free survival (DFS) was analyzed using univariable and multivariable Cox models adjusted for hormone receptor status (HRS) and histologic grade (G), age, menopausal status, type of surgery, pT, pN, and histologic type. Results: Overall, 5923 patients with follow-up data were available for this pooled analysis, with 2979 and 2944 patients randomized to A-free and A-containing chemotherapy, respectively. After 62 months median follow-up, DFS of patients receiving A-free vs A-containing chemotherapy was quite similar in univariable analysis (hazard ratio, HR = 1.04; 95% confidence interval, CI: 0.88 – 1.22, p = 0.64) and in multivariable analysis (HR = 1.00, 95% CI: 0.85 – 1.19, p = 0.96). Defining biological subtypes “luminal A-like” as HRS positive, G1/2, “luminal B-like” as HRS positive, G3, and TN (triple negative), no significant differences were seen in DFS between A-free and A-containing chemotherapy in luminal A-like (HR = 1.06, 95% CI 0.81 – 1.39, p = 0.66), luminal B-like (HR = 1.07, 95% CI 0.78 – 1.48, p = 0.68), or TN tumors (HR = 0.99, 95% CI 0.76 – 1.30, p = 0.95). However, in high-risk patients with four or more affected lymph nodes (pN2-3), A-containing chemotherapy was associated with significantly better DFS (HR = 0.69, 95%-CI 0.48- 0.98, p = 0.04). Conclusions: Our results suggest that 6 cycles of DC provide sufficient efficacy compared to an anthracycline-containing regimen in most patients with HER2-negative EBC. However, subgroup analyses indicate that high-risk patients might benefit from anthracycline-containing chemotherapy.
Availability of therapeutic sexual aids for cancer survivors: A survey of major cancer centers.
Authors: Sharon Bober, Alexis L Michaud, Christopher J. Recklitis
Journal: Journal of Clinical Oncology (2018)

134 Background: Treatment-related sexual dysfunction is a distressing problem for many cancer survivors. Cancer treatment guidelines recommend therapeutic aids for sexual health rehabilitation (e.g., vaginal dilators, moisturizers, vacuum erection device). However, survivors often don't know how or where to access sexual aids or may be uncomfortable procuring them. 25 NCI-designated Cancer Centers/NCCN-member institutions were surveyed about availability of sexual aids and resources for survivors. Methods: Using phone and internet, potential sources of aids/resources at each center (e.g, custom boutiques, specialty retail shops) were identified. Relevant retail staff at each center were approached by phone and using a structured script, study staff queried about the availability of aids/resources. Separate calls were made regarding aids for men and women. Additional inquiry included access to aids elsewhere at the cancer center and recommendations for accessing resources if none were available. Results: Of the 25 cancer centers contacted, 23 responded about men and 22 responded about women. Two centers never responded to multiple attempts. Of the centers contacted, 87% reported having no sexual aids for men and 72% had no aids for women. One center carried a vacuum device and two had penile support rings. Six centers had some aids for women, most commonly reported were personal lubricants, moisturizers and dilators. One center stood out, having several types of aids for men and women. Additional recommendations were limited to suggesting a local pharmacy or doing an internet search. Conclusions: In contrast to other widely available cancer care products, e.g., wigs and prosthetics, availability of sexual aids and resources at major cancer centers is very low. The stark absence of sexual aids underscores the cultural taboos around cancer-related sexual dysfunction. Efforts to improve availability of sexual aids for survivors would likely promote sexual health rehabilitation and validate this under addressed aspect of cancer survivorship.