tbuckley/cabot-search huggingface dataset:
Study of circulating tumor DNA (ctDNA) of RAS-wild metastatic colorectal cancer (mCRC) as a tool for on-site mutation screening: A prospective study.
Authors: Takeshi Sawada, Keishi Nakamura, Naoki Takahashi, Eiji Kubota, Manabu Sugiyama, Shunsuke Nakano, Toshimitsu Ichijo, Rie Sakai, Daisuke Numai, Hiroyoshi Nakanishi, Satoko Inagaki, Shigenori Wakita, Ryosuke Ota, Kenkei Hasatani, Kunihiro Tsuji, Hisashi Doyama, Naoki Izawa, Akihiro Tsuyada
Journal: Journal of Clinical Oncology (2017)

e15077 Background: Clinical use of ctDNA has been become an important criterion for patient care. The transfer of this knowledge and technology from top clinical labs to local hospitals is still distant. With the goal of a robust, precise, simple and cost-effective genomic test, we designed a prospective study featuring high-sensitive mutation screening of ctDNA from RAS-wild mCRC with digital PCR (dPCR) technology. This approach allows detection of 85 hotspot mutations of KRAS, NRAS, BRAF and PIK3CA, which are present in approximately 60% of CRC, and is clinically important information for anti-EGFR treatment. Methods: 18 “ RAS-wildtype” mCRC patients, initially diagnosed with PCR-rSSO (RASKET) using CRC FFPE samples, were recruited. After extracting ctDNA from patient plasma, dPCR analysis was conducted with LBx Probes. Results: Mutations in KRAS, NRAS, BRAF and PIK3CA, were detected in 5 samples ( KRAS in 3 samples, NRAS in 1 sample, BRAF in 1 sample, and PIK3CA in 2 samples). In a patient undergoing treatment with panitumumab, two different KRAS clones were detected, indicating possible clonal evolution under drug pressure. Interestingly, we also encountered another patient who had never received anti-EGFR antibodies, but who tested RAS mutation-positive at a level below the detection sensitivity of PCR-rSSO. Conclusions: Our dPCR screening with ctDNA was able to identify mutations successfully in a previously-diagnosed “ RAS-wild” mCRC group. Based on these results, we designed the following test, which with &lt;0.1% mutation sensitivity, would be useful for 1) predicting the efficacy of anti-EGFR antibodies prior to treatment; 2) predicting early emergence of acquired resistance to EGFR blockade; and 3) monitoring disease progression during treatment. [Table: see text]
Quality of life and relationship with early lethality of elderly patients with cancer.
Authors: Jurema Telles O Lima, Anke Bergmann, Maria Julia Gonçalves Mello, Rousiane Cavalcanti, Coeli REGINA Ximenes, Luiz Claudio Santos Thuler
Journal: Journal of Clinical Oncology (2016)

e21529 Background: Health-related quality of life (QoL) is a major concern for older patients with cancer. Methods: Between 2015 and 2016, a prospective cohort study in 346 elderly incident cancer patients (≥ 60 years), at the time of enrollment, quality of life was assessed and collected socio-demographic and clinical variables. It was followed for a period of six months. As exposure was considered the quality of life at time of diagnosis through of questionnaire EORTC QLQ C30. It was considered outcome, early death occurred in the first six months after admission to the institution. Descriptive analysis the mean and standard deviation was performed for continuous variables, and absolute and relative frequencies for categorical variables. The Kaplan-Meier method was used to estimate the overall survival time and the respective confidence interval of 95%. Student's t test was use and its statistical significance was obtained by analysis of variance. It was then performs the univariate logistic regression (gross) and multiple (adjusted for clinical staging and age). Results: 346 elderly cancer patients , who had at the time of assessment of quality of life, mean age of 71.13 years (SD 7.41). The majority were males (50.9%), Prostate cancer were more frequent (29.4%). They were mostly patients with advanced stage (III and IV) at nutritional risk (52.6%). Patients were followed on average for 128 days (SD 54.37). During this period, there were 39 deaths (11.3%), with a mean of 165 days overall survival (95% CI 161.25 to 170.02). The mean of the quality of life domains measured by the EORTC-C30 according to the occurrence of early death, they were a significant diference beteween mean (P valor < 0.001) all domains,except the scales of symptoms, diarrhea and financial hardship. After adjusting for stage and age over all quality of life was observed reduction in risk of early death than 3%. Conclusions: For all function ranges and overall quality of life was observed worse scores of quality of life among those who had a early fatal outcome. The scales of symptoms, diarrhea and financial hardship were the ones that showed no statistically significant association with death. Inicial QOL can also be a good early predictor of mortality risk in cancer elderly patients.
Internet- and mobile-based lifestyle intervention for prostate cancer patients on androgen deprivation therapy: Prospective, multicenter, randomized trial.
Authors: Yong Hyun Park, Jong In Lee, Ji Youl Lee, In Yae Cheong, Ji Hye Hwang, Seong Il Seo, Kang Hyun Lee, Ji Sung Yoo, Seung Hyun Chung, Yoon-Seok Ko, Yong Ho Lee, Soo In Lee
Journal: Journal of Clinical Oncology (2018)

6518 Background: Androgen deprivation therapy (ADT) has several adverse effects including loss of libido, osteoporosis, and metabolic complications. We aimed to examine whether the Smart After-Care service (internet- and mobile-based lifestyle intervention) has an effect on clinical outcomes in patients with prostate cancer (PCa) on ADT. Methods: Two hundred patients with PCa on ADT were randomly assigned to the Smart After-Care or control group. The Smart After-Care group received a mobile application and wearable device, providing general health information, nutritional and medication care and exercise program (aerobic exercise at least 90 or 150 minutes every week for 12 weeks depending on patients' aerobic fitness and strengthening exercise at least 2 times a week for 12 weeks) while the control group was imparted brief education for the exercise program. Primary endpoint was an increase in patients' physical function as assessed using 2 minutes’ walk test. Secondary endpoints included improvement in muscle strength (30 seconds chair stand test, grip strength test), short physical performance battery, body composition, and health-related quality of life (EORTC-QLQ-C30, and PR 25). Results: In the aspect of physical performance, both groups showed significant improvement in 2 minutes’ walk test and 30 seconds chair stand test after 12 weeks of intervention, whereas a repeat measures ANOVA showed a significant improvement in 2 minutes’ walk test (P = 0.042) over time in the Smart After-Care group as compared to the control group. The Smart After-Care group had additional improvement in right hand grip strength (P = 0.038) and reduction in body fat percentage (P = 0.022) compared to the controls. Also, the Smart After-Care group showed significant improvement in social functioning (P = 0.016) as well as in appetite loss (P = 0.048). Both groups showed significant improvement in urinary symptom, whereas the Smart After-Care group showed significant improvement in sexual functioning (P = 0.032). Conclusions: The Smart After-Care service is an effective method in PCa patients on ADT in improving exercise capacity and general health related quality of life. Clinical trial information: NCT03264209.
Comparison of routine multidisciplinary lung cancer care (MDC) compared to enhanced MDC care (EMDC) at Geisinger Health: A prospective, cohort study.
Authors: Christian S. Adonizio, Himaja Konreu, Mark Wojtowicz, Jenna Carmichael, Al Woodward, Michael Hoffman, Deserae Clarke, Rebecca Stametz
Journal: Journal of Clinical Oncology (2018)

e18528 Background: Previous studies demonstrate improved patient outcomes in patients with advanced lung cancer by early integration of palliative medicine. The effect of the early introduction of this in earlier stage lung cancer presentation is unclear. Methods: We performed a prospective, cohort-controlled study comparing multidisciplinary lung cancer clinic (MDC) care to enhanced (EMDC) care with direct patient contact by palliative medicine physicians, clinical pharmacists, and nutritionists in addition to routine care (thoracic surgery, radiation and medical oncology, nurse navigator). The cohorts were patients at two Geisinger cancer centers, the intervention site: (GWV n = 81) and the control site (GMC n = 107) followed for 32 weeks. Results: Baseline demographics were not significantly different between groups (Table 1) Among outcomes, there were no statistically significant difference in ED visits (23 vs 22 p = 0.23), number of inpatient admissions per patient between the groups (42 vs 57 p = 0.88), number of admissions per patient, average length of stay (5.2 vs 4.7 days p = 0.47), number of outpatient visits between both the groups, and the number of unplanned admissions. We performed an analysis comparing staffing costs between the two clinics. Using standard hourly rates for 3 hours of a clinical pharmacist, 3 hours of palliative medicine, and 2 hours of nutritionist time per week, the EMDC accrued an additional $17,514 of staff costs without significant difference in outcomes. Conclusions: To our knowledge, this is first study evaluating the effect of early introduction of palliative care services in non-metastatic lung cancer. Further research needs to be done to personalize patient care in this population to determine the optimal deployment of clinical resources to provide high-value care. Table 1. Intervention (GWV) Control(GMC) Test of Diff Type of Test N % N % p-value Totals 81 107 Age (mean, std dev) 68.5 9.86 69.3 9.59 0.7815 ttest Sex Male 41 50.6 56 52.3 0.8831 Fisher's Exact Female 40 49.4 51 47.7 Charlson Score (Median, IQR) 5 3-7 3 3-6 0.0481 Wilcoxon
Association of weight change with telotristat ethyl in the treatment of carcinoid syndrome.
Authors: Martin O Weickert, Gregory Kaltsas, Dieter Hörsch, Pablo Lapuerta, Marianne Pavel, Juan W. Valle, Martyn E. Caplin, Emily K. Bergsland, Pamela L. Kunz, Lowell Brian Anthony, Enrique Grande, Kjell E. Oberg, Richard R. P. Warner, Catherine Lombard-Bohas, Staffan Welin, Rosanna Fleming, Ashwin Kittur, Karie Arnold, Qi Melissa Yang, Matthew H. Kulke
Journal: Journal of Clinical Oncology (2017)

e15692 Background: In the Phase 3 TELESTAR study, the oral tryptophan hydroxylase inhibitor telotristat ethyl (TE) significantly reduced bowel movement (BM) frequency compared with placebo (pbo) over a 12-week Double-blind Treatment (DBT) period in patients with carcinoid syndrome (CS). Weight loss has previously been associated with uncontrolled CS and may result in reduced survival, so it is important to examine weight changes in patients with neuroendocrine tumors (NETs). Methods: We conducted an analysis, prespecified in the statistical analysis plan, of the incidence of weight change of ≥3% at Week 12 in TELESTAR. Patients with metastatic NETs, CS, and ≥4 BMs per day were randomly assigned to receive pbo, TE 250 mg 3x/day (tid), or TE 500 mg tid for 12 weeks, in addition to somatostatin analog therapy. Results: There were 45 patients in each group. Mean baseline age was 63.5 years, with 5.8 BMs/day and mean body mass index 24.87 kg/m 2 . Weight gain ≥3% at Week 12 was observed in 2/39 (5.1%), 7/41 (17.1%), and 13/40 (32.5%) patients on pbo, TE 250 tid, and TE 500 mg tid, respectively. The Cochrane–Armitage test for trend in weight gain incidence across groups yielded p = 0.0017. Among the 20 patients with a ≥3% weight gain on TE, 10 patients experienced a reduction of at least 30% in BM frequency at Week 12 (maximum reduction 75%). Weight loss ≥3% at Week 12 was observed in 5 (12.8%), 4 (9.8%), and 6 (15.0%) patients on pbo, TE 250 tid, and TE 500 mg tid. Adverse events of vomiting, decreased appetite, cachexia, and performance status decreased were reported during the DBT period among those with weight loss but not those with weight gain. Conclusions: The incidence of weight gain was dose-related on TE and was greater than that on pbo. It was possibly related to a reduction in diarrhea severity, and it may be a relevant aspect of TE efficacy among patients with functioning metastatic NETs. Clinical trial information: NCT01677910.
The reasons and timing of the oral transmucosal fentanyl administration in Japan.
Authors: Shinya Kajiura, Tatsuhiko Kashii, Akiyoshi Takaki, Shingo Chikaoka, Naomi Hayashi, Takako Matsushita, Ayaka Kadota, Sakie Fukai, Rumi Nakaya, Natsumi Tachida, Keiko Yamamoto, Kazunori Nakajima, Hideyo Horikawa, Yoshinori Takemura, Tomoko Shima, Astushi Furuichi, Takayuki Ando, Toshiro Miwa, Nozomu Murakami
Journal: Journal of Clinical Oncology (2017)

e21665 Background: The oral transmucosal fentanyl disintegrating tablet, Abstral, is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid onset analgesia, and which may be effective for breakthrough cancer pain. It can be administered for the patients who cannot take the oral medicine. It has been marketed since 2014 in Japan. Methods: We selected patients who were administered Abstral for breakthrough cancer pain between 2014 and 2016 at Toyama University Hospital in Japan. We retrospectively investigated administration reasons based on medical record of those patients. Results: There were 111 patients who were administered Abstral. Primary lesions of lung/Gastrointestin/others were 43/52/16, respectively. ECOG PS 0-2/3-4 were 27/84, respectively. The median age was 66 y.o. (range 35-91 y.o.). Regularly using opioid were fentanyl patch prescribed for all patients. Median dose of fentanyl patch was 25mcg/hr (range 12.5-250mcg/hr). 90 patients (81%) had difficulties in the administration of oral medicine, which was the main reason of Abstral administration. Four patients (4%) were to reduce constipation and vomiting as side effects of oxycodone. Seven patients (6%) were to start a fentanyl patch. Three patients (3%) were assessed poor effect for short-acting opioid. Only seven patients (6%) were expected of rapid onset of analgesia effect. Abstral was administered in 27 patients (24%) during aggressive treatment such as chemotherapy administration and in 84 patients (76%) after aggressive treatment. Conclusions: The oral transmucosal fentanyl was administered for the patients who cannot take the oral medicine in Japan while it is expected to be administered to those who want to relieve breakthrough pain fast. Affirming a common understanding of the efficacy of the oral transmucosal fentanyl and breakthrough cancer pain is necessary in Japan.
Phase Ib study of gemcitabine, nab-paclitaxel, and ficlatuzumab in patients with advanced pancreatic cancer.
Authors: Kimberly Perez, Colin D. Weekes, James M. Cleary, Thomas Adam Abrams, Lawrence Scott Blaszkowsky, Peter C. Enzinger, Marios Giannakis, Lipika Goyal, Jeffrey A. Meyerhardt, Douglas Adam Rubinson, Matthew B. Yurgelun, Danielle Stonely, Srivatsan Raghavan, Basil Bakir, Koushik Das, Jason Pitarresi, Andrew Aguirre, Michael N. Needle, Anil Rustgi, Brian M. Wolpin
Journal: Journal of Clinical Oncology (2020)

693 Background: Paired-related homeodomain transcription factor 1 (Prrx1) isoforms are involved in pancreatic development, pancreatitis, and carcinogenesis. Hepatocyte growth factor (HGF) is a transcriptional target of Prrx1b. Ficlatuzumab is a recombinant humanized HGF antibody, that neutralizes HGF/c-Met binding and HGF-induced c-Met phosphorylation. In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of Prrx1b-HGF signaling using ficlatuzumab and gemcitabine reduced primary tumor volume and eliminated metastatic disease. Methods: Patients (pts) with previously-untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3+3 design and two dose cohorts of ficlatuzumab (10mg/kg and 20mg/kg) administered intravenously every other week with gemcitabine (G; 1000mg/m 2 ) and nab-paclitaxel (A; 125mg/m 2 ) given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose (MTD) of the combination. Results: 24 pts (sex, 12M:12F; median age, 69 years [range, 51-82 years]) were enrolled. No dose-limiting toxicities were identified in the phase 1b (N = 6 pts) and ficlatuzumab at 20mg/kg with GA was advanced to the expansion phase (N = 18 pts). By RECISTv1.1 in the full study population, 7 (29%) pts had partial response, 15 (63%) had stable disease, and 2 (8%) could not be evaluated. Median progression-free survival was 8 months (range, 3-16 months), 4 pts are still on study treatment. The primary toxicities attributed to ficlatuzumab included hypoalbuminemia (grade 3, 21%; any grade, 91%) and edema (grade 3, 8%; any grade, 91%). Nine (38%) of the 24 pts discontinued study treatment due to these toxicities prior to disease progression. Conclusions: The combination of ficlatuzumab with gemcitabine and nab-paclitaxel is associated with durable treatment responses but also significant hypoalbuminemia and edema that may impair treatment tolerability. Serial blood samples were collected for circulating HGF measurements, and mandatory pretreatment biopsies were collected for tumor c-MET pathway activation and 3D organoid culture drug sensitivity testing. Clinical trial information: NCT03316599.
Re: Valeria Panebianco, Yoshifumi Narumi, Ersan Altun, et al. Multiparametric Magnetic Resonance Imaging for Bladder Cancer: Development of VI-RADS (Vesical Imaging-Reporting And Data System). Eur Urol 74, 2018, 294–306
Authors: Jeremy Y.C. Teoh, Thomas R.W. Herrmann, Marek Babjuk
Journal: European Urology (2018)
Hospitalizations and emergency department (ED) visits pre- and post-approval of immuno-oncology agents (IO) in advanced non-small cell lung cancer (aNSCLC).
Authors: Janna Radtchenko, Beata Korytowsky, Esmond Nwokeji, Ken Tuell, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2018)

e21006 Background: The management of NSCLC has changed since IO and new targeted therapies (TT) gained front-line and salvage indications. This study assessed frequency of hospitalizations, ED visits, and length of stay (LOS) among patients (pts) starting systemic therapy (ST) pre- and post-approval of IO for aNSCLC (pre-/post-IO periods). Methods: A retrospective cohort study of continuously enrolled adult pts with lung cancer initiating first-line (1L) ST within 6 months (mo) of diagnosis identified from the MORE2 Registry® claims dataset. Baseline characteristics and healthcare resource utilization (HRU) were assessed for pts in mutually exclusive cohorts receiving ST from Mar 2013–Mar 2014 (pre-IO) vs Mar 2015–Dec 2016 (post-IO). Six and 12-mo sensitivity analyses were performed. Results: Of 5741 treated aNSCLC pts, 2997 (52%) were treated in post-IO period. By cohort (pre- vs post-), mean age was 64.5 vs 66.1 years, Charlson Comorbidity Index: 2.2 vs 2.4, tx lines per pt: 1.9 vs 1.4, follow-up: 16.9 vs 8.9 mo, received 2L: 52% vs 30%, received 3L+: 20% vs 8%. Adjusted analyses (table, follow-up: 11.4 vs 11.3 mo, p=0.650) showed significantly lower frequency of hospitalizations and ED visits in post-IO period. In 2L+ pts (pre- vs post-), 56% vs 39% were hospitalized, and 71% vs 56% had ED visits (p<0.001). Subgroup analyses showed similar trends but did not reach significance. Conclusions: Hospitalizations and ED visits have been significant contributors to HRU and cost in aNSCLC management. Analysis of real-world data shows decreasing trends in HRU in the post-IO era. Future research should examine how IO and TT may reduce the burden of care in aNSCLC. A: Pre-IO (N=2744) B: Post-IO (N=2997) A: Adjusted* (N=1550) B: Adjusted* (N=1550) Hospitalized: n (%), p 1188 (43) 1124 (38) 0.003 689 (45) 576 (37) <0.001 ED visits: n (%), p 1629 (59) 1638 (55) <0.001 914 (59) 854 (55) <0.029 # Hospitalizations: mean (SD), p 2.5 (2.1) 2.0 (1.5) <0.001 2.3 (1.6) 2.0 (1.7) 0.007 LOS: mean (SD), days, p 1.9 (4.3) 2.2 (9.5) 0.189 1.8 (3.3) 1.8 (3.6) 0.592 # ED visits: mean (SD), p 3.7 (4.4) 2.7 (2.5) <0.001 3.3 (3.0) 2.9 (2.6) 0.002 *Matched for differences in demographic and clinical characteristics
Effectiveness of a Therapeutic<i>Tai Ji Quan</i>Intervention vs a Multimodal Exercise Intervention to Prevent Falls Among Older Adults at High Risk of Falling
Authors: Fuzhong Li, Peter Harmer, Kathleen Fitzgerald, Elizabeth Eckstrom, Laura Akers, Li-Shan Chou, Dawna Pidgeon, Jan Voit, Kerri Winters-Stone
Journal: JAMA Internal Medicine (2018)

Falls in older adults are a serious public health problem associated with irreversible health consequences and responsible for a substantial economic burden on health care systems. However, identifying optimal choices from among evidence-based fall prevention interventions is challenging as few comparative data for effectiveness are available.To determine the effectiveness of a therapeutically tailored tai ji quan intervention, Tai Ji Quan: Moving for Better Balance (TJQMBB), developed on the classic concept of tai ji (also known as tai chi), and a multimodal exercise (MME) program relative to stretching exercise in reducing falls among older adults at high risk of falling.A single-blind, 3-arm, parallel design, randomized clinical trial (February 20, 2015, to January 30, 2018), in 7 urban and suburban cities in Oregon. From 1147 community-dwelling adults 70 years or older screened for eligibility, 670 who had fallen in the preceding year or had impaired mobility consented and were enrolled. All analyses used intention-to-treat assignment.One of 3 exercise interventions: two 60-minute classes weekly for 24 weeks of TJQMBB, entailing modified forms and therapeutic movement exercises; MME, integrating balance, aerobics, strength, and flexibility activities; or stretching exercises.The primary measure at 6 months was incidence of falls.Among 670 participants randomized, mean (SD) age was 77.7 (5.6) years, 436 (65%) were women, 617 (92.1%) were white, 31 (4.6%) were African American. During the trial, there were 152 falls (85 individuals) in the TJQMBB group, 218 (112 individuals) in the MME group, and 363 (127 individuals) in the stretching exercise group. At 6 months, the incidence rate ratio (IRR) was significantly lower in the TJQMBB (IRR, 0.42; 95% CI, 0.31-0.56; P < .001) and MME groups (IRR, 0.60; 95% CI, 0.45-0.80; P = .001) compared with the stretching group. Falls were reduced by 31% for the TJQMBB group compared with the MME group (IRR, 0.69; 95% CI, 0.52-0.94; P = .01).Among community-dwelling older adults at high risk for falls, a therapeutically tailored tai ji quan balance training intervention was more effective than conventional exercise approaches for reducing the incidence of falls.ClinicalTrials.gov identifier: NCT02287740.