tbuckley/cabot-search huggingface dataset:
The impact of an adolescent and young adult (AYA) consultation service on addressing patient needs at Princess Margaret Cancer Center.
Authors: Laura Mitchell, Seline Tam, Amirrtha Srikanthan, Natasha Puri, Justin Ming Zheng Ma, Derek Stephens, Carol Heck, David C. Hodgson, Abha A. Gupta
Journal: Journal of Clinical Oncology (2016)

e18164 Background: Few studies report impact of AYA oncology programs on addressing patient (pt) needs. At our center, the AYA program provides: 1) education on AYA issues to primary providers (PP) 2) development of AYA specific resources for pts and PP, and 3) pt consultations by an AYA clinical nurse specialist (AYA-C). This study assessed pt satisfaction with 1) PP after AYA education and 2) the AYA-C in addressing their needs. Methods: From May-Aug 2015, consecutive pts ≤ 39 years, on or off therapy, rated their satisfaction (10pt Likert; 1 = completely dissatisfied, 10 = completely satisfied) with information/resources relating to AYA domains provided by PP. Pts were then asked if the AYA-C provided more help than their PP (yes/no) for each domain. Between group (cancer diagnoses, age, gender) differences were compared using ANOVA. AYA-C impact was significant if > 50% of pts stated ‘Yes’ using 1-tail binomial test for 1 proportion = 50%. Results: Of 138 AYA pts approached, 1 declined. 34 (24.8%) were referred for an AYA-C. Median age of 137 pts was 31 years (range 18-39), 72 (53%) were female. Pts had the following diagnoses: leukemia (n = 31, 23%), lymphoma (46, 33%), breast (24, 18%), GI (10, 7%) and other (26, 19%). Satisfaction scores PP were highest for cancer information (8.1+2.3), social supports (SS, 7.5±2.4), hospital navigation (7.4±2.5), work/school (W/S, 7.3±2.8), fertility (7.2±2.9) and financial (7.2±3.1). Scores were slightly lower for physical appearance (PA, 7.0±2.6), exercise (6.7±2.8), sexuality (6.6±3.2), and diet (6.3±2.9). Age, gender had no impact on scores. GI pts were less likely to be satisfied in W/S (mean score 2.0, p = 0.002), diet (3.2, p = 0.018), exercise (2.6, p = 0.007), and cancer information (4.8, p = 0.004) compared to other sites. AYA-C was significantly helpful in the following areas: SS (85%, p = 0.0001), sexuality (76%, 0.013), PA (74%, 0.01), and fertility (73%, 0.008). Conclusions: Since implementation of AYA education to PP, pts are highly satisfied with information given to them by their PP. Additional AYA-C offers even more value in certain domains. Further work is required to ensure all AYA informational needs are being adequately met.
Expansion of oncomine cell-free research panels to enable copy number and gene fusion detection from liquid biopsy samples.
Authors: Jian Gu, Jeoffrey Schageman, Varun Bagai, Yanchun Li, Kristi Lea, Priyanka Kshatriya, Kelli Bramlett
Journal: Journal of Clinical Oncology (2018)

e24075 Background: With recent advances in next-generation sequencing technologies, it is now possible to detect somatic mutations with allele frequencies as low as 0.1% from circulating tumor DNA in blood samples. A natural extension to this achievement is adding the ability to simultaneously detect copy number variants and gene fusions. A panel such as this addresses a full repertoire of variant classes found to be linked with certain tumors and provides researchers additional tool sets to profile cancer samples dynamically. Methods: To achieve this, we have recently launched two new Oncomine cell-free assays to target all variant classes in lung and breast cancers. Control samples were used to test sensitivity and specificity of the assays. Results: In addition to maintaining the ability to detect somatic mutations at 0.1% limit of detection with > 80% sensitivity and > 98% specificity, we have reproducibly demonstrated detection of MET, ERBB2, FGFR1, and CCND1 gene amplifications at 1.4 fold difference with > 90% sensitivity and specificity. Input titration experiment demonstrated the robustness of CNV detection with as low as 1 ng cfDNA input. We also demonstrated the capability of detecting gene fusions simultaneously with DNA variants with no negative impact on sensitivity and specificity. Titration approach has demonstrated high sensitivity and specificity as fusion targets can be detected when as low as 10 copies are present in a sample. Conclusions: Overall, we have shown the ability to reproducibly and simultaneously detect copy number and gene fusion variants as well as somatic mutations at very low limits of detection in cell-free nucleic acid background derived from blood samples.
Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial
Authors: Shi Wu Wen, Ruth Rennicks White, Natalie Rybak, Laura M Gaudet, Stephen Robson, William Hague, Donnette Simms-Stewart, Guillermo Carroli, Graeme Smith, William D Fraser, George Wells, Sandra T Davidge, John Kingdom, Doug Coyle, Dean Fergusson, Daniel J Corsi, Josee Champagne, Elham Sabri, Tim Ramsay, Ben Willem J Mol, Martijn A Oudijk, Mark C Walker
Journal: BMJ (2018)

To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35.Randomised, phase III, double blinded international, multicentre clinical trial.70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK).2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses.Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation.The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets).Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes.Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition.Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.
Quality of life by smoking status in patients with metastatic or advanced NSCLC from Phase 2 clinical trial of veliparib with carboplatin and paclitaxel.
Authors: Patrick Bonnet, Martin Cloutier, Mark D. McKee, Marjolaine Gauthier-Loiselle, Jane Qian, Fan Mu, Qin Q. Qin, Annie Guerin, Eric Qiong Wu, Vincent L. Giranda
Journal: Journal of Clinical Oncology (2016)

e20549 Background: A Phase 2 clinical trial of veliparib + carboplatin (C) and paclitaxel (P) in patients (pts) with previously untreated metastatic/advanced NSCLC showed that veliparib may improve survival compared to placebo and that smoking history was a strong predictor of efficacy for veliparib+CP. This study compares quality of life (QoL) by smoking status in pts receiving veliparib+CP vs placebo+CP. Methods: This study is a secondary analysis of a Phase 2 clinical trial (NCT01560104) where pts were randomized 2:1 to veliparib+CP (120mg BID) or placebo+CP for up to 6 treatment cycles (study period). Pts with ≥ 1 QoL measurement at baseline (pre-treatment initiation) and during ≥ 1 cycle were selected and stratified by smoking status in the year preceding the trial (smokers [S] vs non-smokers [NS]). Proportions of pts with a QoL improvement (QoL+)/deterioration (QoL-) from baseline achieving minimal important difference ( ≥ 10 points on a 100-point scale) across the study period were compared by treatment and smoking status using generalized estimating equation models adjusted for baseline QoL score, gender, and ECOG, for each of the 22 EORTC QLQ-C15-PAL/LC13 questionnaire items. Results: Among 143 pts (657 pt-cycles), mean age was 62 years, 67% were male, and 59% were S. In S, veliparib+CP pts had better or non-different QoL compared to placebo+CP pts; a higher proportion of veliparib+CP pts had QoL+ for dyspnea (odds ratio [OR] = 3.63) and a lower proportion of pts had QoL- for physical functioning (OR = 0.46), appetite loss (OR = 0.37), and dysphagia (OR = 0.12), all p < .05. In veliparib+CP pts, S had better or non-different QoL compared to NS (emotional functioning: both QoL+ and QoL- OR = 2.80 and 0.38, respectively; pain in chest: QoL+ OR = 3.86; coughing: QoL- OR = 0.48; all p < .05). The magnitude of the difference in QoL for S vs NS was larger or non-different in veliparib+CP pts compared to placebo+CP pts (dyspnea: QoL+ OR = 8.48; appetite loss: QoL+ OR = 11.54, QoL- OR = 0.27; dysphagia: QoL- OR = 0.05; all p < .05). Conclusions: Smokers receiving veliparib+CP had better or non-different QoL compared to both non-smokers receiving veliparib+CP and to smokers receiving placebo+CP. Clinical trial information: NCT01560104.
AUCtox: A new method to evaluate the safety of anticancer drugs.
Authors: Vincent Launay-Vacher, Carole Helissey, Brigitte Laguerre, Dominique Spaeth, Thomas Lloret, Jerome Stevens, Paolo Bossi, Florian Scotte
Journal: Journal of Clinical Oncology (2018)

2534 Background: The evaluation of anticancer drugs safety currently relies on the NCI-CTCAE classification. Most often in clinical trials, attention is focused on severe adverse events (AE) i.e. grade 3 or more. However, AE of lower grades can have a significant deleterious impact, especially when recurrent or permanent. We aimed at defining a new method to better describe the impact of treatment on quality of life (QoL). Methods: The oncology patient monitoring program OptiSoins prospectively records treatment, number of cycles, and toxicities (NCI-CTCAE). Patients with castration-resistant metastatic prostate cancer treated with either docetaxel (DOC) or cabazitaxel (CABA) were identified in the database. For each patient, toxicities and their grade reported in medical records were plotted against time under treatment, to calculate the area under the curve of toxicities (AUCtox) that takes into account both the intensity and duration of toxicities, and the number of events. AUCtox was calculated for any toxicity reported at least once. The association with QoL, evaluated by EQ-5D-3L was determined. Results: In total, 146 patients were evaluable [DOC 85 (58%), CABA 61 (42%)]. Median age was 70.5 years (Q1-Q3: 64.7; 76.0). Median follow-up was 4.0 months. Patients underwent a median number of 6 cycles, with a median number of 15.0 evaluations (monitoring calls). At least one grade ≥3 AE was reported by 45.2% of patients, most frequently fatigue (20.6%) and pain (12.3%). A negative impact on global health status, assessed by the VAS of EQ-5D-3L, was identified for 3 AEs based on grade alone vs. 8 when considering AUCtox. Conclusions: Current evaluation of toxicity, based on grade alone, underestimates the impact of anticancer drugs on QoL. Our method, using AUCtox, can better detect this impact, allowing a more patient-oriented evaluation of drug safety. Adverse events significantly associated with a negative impact on VAS, univariate analysis (p≤0.05). Type of AE AUCtox ≥Grade 3 Alopecia + - Anorexia + + Dyspnea + + Fatigue/Asthenia + + Tearing/Watering eye + - Nausea + - Peripheral sensory neuropathy + - Nail loss/Onycholysis + -
Outcome of patients with advanced endometrial and cervical cancer treated in a phase 1 unit.
Authors: Rowan Miller, Michael-John Devlin, Nicholas Fraser Brown, Tami Grunewald, Mary McCormack, Michelle Lockley, Jonathan A. Ledermann, Tim Meyer, Martin David Forster, Rebecca Sophie Kristeleit
Journal: Journal of Clinical Oncology (2017)

5597 Background: Patients (pts) with advanced endometrial (EC), cervical and vulval (CVC) cancer have limited therapeutic options and poor prognosis. Early phase trials may be a suitable option for pts with good performance status aided by molecular selection. We sought to determine the outcome of EC and CVC pts treated in a phase 1 unit. Methods: Medical records of pts with EC and CVC treated within an early phase trial between 2010 and 2016 were reviewed. Data comprised pt and tumor characteristics, prior therapy, trial therapy and outcome. Results: 38 pts, median age 59 years (21-74) with EC (19) or CVC (19) were identified. Median prior therapies for advanced disease: 1 (1-3). Histological subtypes: endometrioid (4), high grade serous (HGS 7), carcinosarcoma (CS 4), clear cell (1), and adenosquamous (3) for pts with EC; adenocarcinoma (5), squamous (11), clear cell (2) and neuroendocrine (1) for CVC pts. 20 pts (53%) had Next Generation Sequencing (NGS) using a targeted panel with actionable mutations identified in 10 (KRAS (4), PIK3CA (6) and EGFR (1)). Pts were allocated in order of priority to a trial (1) on the basis of NGS (‘genomic’ 8%), (2) within a ‘tumor specific’ expansion cohort (45%) or (3) a ‘generic’ study (47%). The overall response rate (ORR) was 21% with 34% stable disease (SD) and median progression free survival (PFS) and overall survival (OS) of 11 and 42 weeks respectively, with 10 pts still on study. Within the EC cohort ORR was 21% with 32% SD and PFS and OS of 9 and 38 weeks respectively. For the CVC cohort ORR was 21% with 37% SD and PFS and OS of 12 and 42 weeks respectively. Outcomes were better for the pts in the genomic and tumour specific groups. Both PFS and OS were longer with median PFS of 42, 32 and 8 weeks and OS of 91, not reached and 37 weeks for genomic, tumor specific and generic trials respectively. Conclusions: Early phase trials represent a good option for pts with advanced EC and CVC with meaningful clinical benefit observed even in this small cohort. Encouraging RR and PFS were observed in these pts with limited standard treatment options. This includes pts with difficult to treat histological subtypes such as HGS and CS EC and clear cell and adenocarcinoma CVC. NGS is feasible in real time and increasing use may benefit pts further.
Effectiveness and safety of systematic and selective lymphadenectomies in Chinese patients with non-small cell lung cancer who received sublobar resection.
Authors: Min Zhu, Heng Zhao, Lunxu Liu, Jian Hu, Yang Liu, Xiaofei Li, Lin Xu, Deruo Liu, Yin Li, Xianghui Zhu, Haiying Yang, Xiangning Fu
Journal: Journal of Clinical Oncology (2018)

e20534 Background: Even though anatomical lobectomy with dissection of systematic mediastinal lymph nodes has been the standard treatment for the patients with non-small cell lung cancer (NSCLC), the optimal modes of lymphadenectomies in the patients with sublobar resection are still controversial. The purposes of the study are to evaluate effectiveness and safety of lymphadenectomies and explore the clinical characteristics and survivals in the patients with sublobar resection. Methods: The NSCLC patients ( > = 18 years) with sublobar resection and systematic/selective lymphadenectomies from 2014 to 2017 were evaluated based on the LinkDoc database. Systematic lymphadenectomies was defined as ≥ 5 lymph node stations resected and selective lymphadenectomies as < 5. The overall survivals (OS) were measured by the Kaplan-Meier method and the Log-Rank test. Propensity score matching (PSM) method was implemented to reduce selection bias. Results: A total of 3902 NSCLC subjects were recruited including 35.7% (64.3%) of patients with systematic (selective) lymphadenectomy. Of all, 28.8% of patients were performed with segment resection, 67.6% with wedge resection, and 3.6% with mixed resections. In the total population, no difference in OS rates was observed between the groups with systematic and selective lymphadenectomies regardless of PSM. Further subgroup analysis showed that the OS of the patients with systematic lymphadenectomy was superior to that with selective lymphadenectomy in the group of patients with adenocarcinoma (HR of systematics vs selective lymphadenectomies = 0.49, p < 0.05) and in the group of tumor size ≥1& < 3cm (HR of systematic vs selective lymphadenectomies = 0.33, p < 0.05). No significant difference was observed in the subpopulations categorized by age and N staging. Conclusions: As the additional evidence-based data, this real-world study presented clinical evidences on the indications of systematic/selective lymphadenectomies and clinical characteristics of the Chinese NSCLC patients with sublobar resection and lymphadenectomies. Clinical trial information: NCT03427567.
Abstract IA17: PARP inhibitor resistance in prostate cancer
Authors: Alan D. D’Andrea
Journal: Cancer Research (2018)

Abstract Large-scale genomic studies have demonstrated that approximately 15% of metastatic castration-resistant prostate cancer (mCRPC) harbors genetic and epigenetic alterations in homologous recombination repair (HRR) pathway genes. The most commonly altered HRR genes are BRCA2, BRCA1, and ATM, followed by other Fanconi anemia genes including FANCN/PALB2 and FANCA. Loss of HRR causes genomic instability, hyperdependence on alternative DNA repair mechanisms, and enhanced sensitivity to platinum analogues and PARP inhibitors (PARPi). The synthetic lethal interaction with PARPi is being exploited therapeutically in diverse clinical contexts and most notably in BRCA2-deficient mCRPC where the PARPi olaparib has demonstrated improvements in progression-free survival. PARPi resistance has already emerged as a vexing clinical problem for the treatment of BRCA1/2-deficient tumors. The most prevalent mechanism of PARPi resistance is secondary events that cancel the original HRR alteration and restore HRR proficiency. These somatic reversions of mutant BRCA2 alleles can be monitored by sequencing of ctDNA. However, PARPi resistance may also develop without restoration of HRR proficiency via disruption of multiple proteins, such as PTIP or CHD4, that leads to replication fork (RF) stabilization. Importantly, this latter mechanism—namely, the restoration of RF stability—appears to be a highly prevalent mechanism of PARP inhibitor resistance in vitro and in vivo, particularly in tumor cells with an underlying BRCA2 deficiency. Due to their underlying deficiency in BRCA2 and inability to generate RAD51 nucleofilaments, these tumor cells are unable to restore HRR mechanisms. Instead, these cells acquire may PARPi resistance by limiting the nucleolytic degradation of their stalled replication forks. We have recently made the surprising observation that BRCA2-deficient ovarian and breast cancer cells can become resistant to PARPi by downregulating the expression of the polycomb repressive complex PRC2, a methyltransferase complex containing EZH2, SUZ12, EED, and RbAp48. Importantly, downregulation of PRC2 results in the reduced recruitment of the nuclease MUS81 to the RF, thereby providing a novel mechanism of RF protection and PARPi resistance. Whether or not the downregulation of the PRC2/MUS81 pathway is also a mechanism of PARPi resistance in mCRPC remains to be determined. A molecular understanding of PARPi resistance mechanisms may allow the generation of a new class of drugs, or a repurposing of existing drugs, which may reverse this resistance and extend the use of PARPi to more tumor types. Citation Format: Alan D. D’Andrea. PARP inhibitor resistance in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA17.
Doctors’ personal reflections should not include case details, says new guidance
Authors: Clare Dyer
Journal: BMJ (2018)

Doctors recording their personal reflections on lessons learnt from their practice and clinical outcomes should anonymise patient information and should focus on learning for the future rather than the details of cases, new guidance suggests.1

The joint guidance for doctors and medical students comes from the Academy of Medical Royal Colleges, the Conference of Postgraduate Medical Deans (COPMeD), the General Medical Council (GMC), and the Medical Schools Council.

It follows a furore over the case of Hadiza Bawa-Garba, the trainee paediatrician found guilty of gross negligence manslaughter after the death of Jack Adcock, 6, from septic shock. Her reflections were appended to a statement …
Current treatment trajectory for castration-resistant prostate cancer in the community setting.
Authors: Kjel Andrew Johnson, Jeff Scott, Jennifer Webster
Journal: Journal of Clinical Oncology (2018)

e17050 Background: In the past decade, new drugs for the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been approved by the FDA, adding options to treating with docetaxel. Treatment trajectory, including first line therapy use, number of lines of therapy (LOT), and sequencing of therapies, is unknown, as is the proportion of mCRPC patients that receive drugs considered non-standard of care. This is largely due to the limited ability to map medical chemotherapy claims to oral chemotherapy claims. This study evaluated the treatment trajectories for men diagnosed with prostate cancer and who failed androgen deprivation therapy (ADT). Methods: We evaluated 85,554 Medicare Oncology Care Model patients treated in the community care setting. Men diagnosed with prostate cancer by ICD-10 diagnosis code c61, who had received ADT with a LHRHa in the prior 3 months and who received a mCRPC approved drug following ADT between July 1, 2016 and December 31, 2016 were included in the study. Patients were excluded if they had any prior history of cancer. Patients who failed ADT and were subsequently treated first-line with abiraterone, cabazitaxel, docetaxel, enzalutamide, or sipuleucel-T were considered standard of care. Results: 1,031 patients met the inclusion criteria and were treated with 111 different treatment trajectories. First line therapy was considered standard of care in 92.4% of patients; abiraterone was used first line in 32.8% of patients, enzalutamide in 31.8%, docetaxel in 19.4%, cabazitaxel in 4.7% and sipuleucel-T in 3.7%. Only one LOT was used in 49.5% of patients, 26.7% received two LOT, 5.4% received three LOT and 0.6% received 4 to 6 LOT. Conclusions: The majority of mCRPC patients following ADT are treated with standard of care first LOT drug with half receiving only one therapy. Further research is required to understand why the wide variability in sequencing occurs.