tbuckley/cabot-search huggingface dataset:
Phase 2, randomized, 3-arm study of abiraterone acetate and prednisone (AAP), AAP plus degarelix (AAP+D), and degarelix (D) alone for patients (pts) with biochemically-recurrent prostate cancer (PC) following radical prostatectomy (RP).
Authors: Karen A. Autio, Emmanuel S. Antonarakis, Tina M. Mayer, Ulka N. Vaishampayan, Daniel H. Shevrin, Michael Roger Harrison, Scott T. Tagawa, Matthew I. Milowsky, Julie Nicole Graff, Tomasz M. Beer, Arjun Vasant Balar, Mark Stein, Elisabeth I. Heath, Andrew J. Armstrong, Channing Judith Paller, Luke T. Nordquist, Erica Simone Dayan, Kin Tse, Glenn Heller, Howard I. Scher
Journal: Journal of Clinical Oncology (2018)

5016 Background: Androgen deprivation therapy (ADT) with GnRH analogs does not entirely suppress androgen signaling. AAP + ADT decreases blood and intratumoral testosterone (T) levels by ≥1 log, and in pre-RP trials resulted in greater pathologic responses relative to ADT alone. Trial designs that can rapidly assess therapies (txs) are critical given the long natural history of PC and resources required for phase 3 trials. Using a novel endpoint (endpt) (undetectable PSA [PSA0] with T recovery [rec]), we hypothesized that AAP+D given in the rising PSA state post-RP, a low volume but potentially lethal setting, could eliminate all disease, a prerequisite to cure. Methods: Post RP ± salvage radiotherapy pts with a rising PSA ≥1.0 ng/ml, doubling time ≤9 months (mo), no metastases (met) on CT/bone scan, and T ≥150 ng/dl were eligible [NCT01751451]. Prior ADT ≤8 mo was allowed. Pts were randomized (1:1:1) to AA 1000 mg + P 5 mg QD (Grp 1), AAP + monthly D (Grp 2), or monthly D (Grp 3) for 8 mo, followed by cessation of txs. The primary (10) endpt was PSA0 with T > 150 at 18 mo and secondary, PSA0 at 8 mo. Results: 120 pts were treated; 113 were evaluable for the 10 endpt; 7 had PSA0 at 18mo without T rec. No difference was seen in PSA0 at 8 mo with AAP vs AAP+D (p > 0.99), or AAP vs D (p = 0.11) (Table). Overall, 11.5% of pts achieved the 10 endpt with no difference between groups (Grp 1 vs Grp 3; Grp 2 vs Grp 3 [p = 0.43; p = 0.75]). T rec was shortest in Grp 1 relative to Grp 3 (p < 0.001). Clinical trial information: NCT01751451. Conclusions: Although no difference between tx grps was identified by the 10 endpt (PSA0 + T rec), these results set a benchmark for future trials that 10-15% of pts can achieve this outcome. Given the survival benefit of AAP + ADT in non-castrate met PC, a longer duration of androgen suppression may yield greater benefit. In addition to novel systemic txs, use of PET directed imaging to identify and target micro-mets with focal txs may enhance the likelihood of eliminating disease in this setting. Cohort PSA0 at 8mo Median time to T rec (wks) PSA0 + T > 150 at 18mo Grp 1: AAP 31/37 (84%) 36 2/37 (5%) Grp 2: AAP+D 32/37 (86%) 57 6/37 (16%) Grp 3: D 26/39 (67%) 54 5/39 (13%)
Characteristics and outcomes of head and neck cancer in solid organ transplant recipients.
Authors: Samer Alsidawi, Katharine Andress Rowe Price, Ashish V. Chintakuntlawar, Joaquin J. Garcia, Gustavo Figueiredo Marcondes Westin, Scott H. Okuno
Journal: Journal of Clinical Oncology (2017)

e17529 Background: The immune system plays a major role in anti-tumor surveillance in healthy individuals. Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients (pts) with post-transplant HNSCC are unknown. Methods: After Institutional Review Board approval, we retrospectively identified pts who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and good follow up were included. Cutaneous cancers were excluded. Median overall survival (mOS) and progression free survival (mPFS) were analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. Results: 33 pts met study inclusion criteria. The median time to HNSCC after transplant was 5.9 years. The primary site was the oral cavity in 15 pts, the oropharynx in 10, the larynx in 3, the hypopharynx in 2, the parotid in 2 and unknown in 1 pt. 58% of pts presented with locally advanced disease, 39% with localized disease and one pt with metastatic disease. 87% underwent upfront surgical resection. Of those, 66% received adjuvant therapy (38% radiation alone and 28% chemoradiation). 6% of pts had definitive chemoradiation. After a median follow up of 10.5 years, the 5-year OS rate was 45% and 37% for localized and locally advanced disease respectively. 75% of pts with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year OS rate of 67%). The mPFS for the cohort was 22.8 months (95% CI; 11.6-50.1) with a median time to relapse of 15.2 months. The pattern of relapse was local in 69% of pts, distant in 25% and local plus distant in 6%. In a multivariate analysis, age &gt; 60 years was a negative predictor of survival (HR 2.7; 95% CI, 1.1 to 6.5; P = 0.03). Conclusions: This retrospective study evaluated the clinical course and outcomes of pts with non-cutaneous HNSCC after solid organ transplant. Pts had inferior survival compared to historical controls. older pts had poor prognosis. The risk of local and distant recurrence was high. HPV-positive oropharyngeal tumors continue to have better outcomes in this population.
Incidence and risks of pneumonia in patients with multiple myeloma treated with daratumumab: A systematic review and meta-analysis of randomized controlled trials.
Authors: Aung Tun, Katy Ticona, Kyaw Zin Thein, Poras Patel, Vadim Zarubin, Elizabeth Guevara
Journal: Journal of Clinical Oncology (2018)

e20021 Background: The addition of human anti CD38 IgGκ monoclonal antibody Daratumumab (DARA) to standard multiple myeloma (MM) regimen significantly improves response rates, progression-free survival and the risk of death with notable safety concerns. We performed a systematic review & meta-analysis of RCTs to determine the risk of pneumonia in MM patients receiving DARA. Methods: We conducted a literature search using MEDLINE, EMBASE and SCOPUS databases using the terms “multiple myeloma AND daratumumab”, “MM AND daratumumab”, “plasma cell disorder AND daratumumab” through January 2018. The primary meta-analytic approach was a fixed effects model using the Mantel-Haenszel method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Pooled rates of pneumonia were estimated as follows: we multiplied the median follow-up duration by the sample size. Crude study-specific pneumonia rates were then calculated by dividing the number of pneumonia cases by the total number of person-months follow-up. Results: 1744 patients were eligible. The study arm used bortezomib (V), mephalan (M), prednisone (P) plus DARA; V, dexamethasone (D) plus DARA; and lenalidomide (R), D plus DARA. The control arm used VMP, VD, and RD. The incidence of pneumonia was 122 (14%) in DARA group vs 82 (9.4%) in control group, with grade 3 & 4 pneumonia rates of 81 (9.3%) vs 60 (6.9%). Pooled RR for pneumonia was 1.48 (95% CI: 1.14 - 1.93, P = 0.002) and the absolute RD was 0.05 (95% CI: 0.02 - 0.08, P = 0.004) while the pooled RR for grade 3 or 4 pneumonia was 1.35 (95% CI: 0.98 – 1.86, P = 0.07) and the absolute RD was 0.02 (95% CI: -0.00 – 0.05, P = 0.07). Over median follow up of 24 months, the RR for pneumonia was 1.35 (95% CI: 1.15 – 1.58, P < 0.0003) and RD was 0.07 (95% CI: 0.03 – 0.11, P < 0.0002). The pooled rate of pneumonia among DARA group was 41 per person years Vs 30 per person years in control arm. Conclusions: Addition of DARA to standard MM regimen contributes a higher risk of pneumonia, without significant increase in the risk of grade 3 or 4 events. More data are required to determine the actual relation and definitive incidence of pneumonia.
Patterns of comorbidity, treatment, resource utilization, and referral in malignant pleural mesothelioma patients in the US.
Authors: Marjorie Glass Zauderer, Anne S. Tsao, Dean A Fennell, William Bruce Wong, Thirupathi Pattipaka, Michael T Bretscher, Michael Peake
Journal: Journal of Clinical Oncology (2017)

8554 Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer, which may be challenging to diagnose. The standard of care for MPM is cisplatin plus pemetrexed. In the recent phase III MAPS trial, addition of bevacizumab provided a significant survival benefit. There is limited data on real-world MPM treatment patterns to provide context to trial results. Consequently, the present study was conducted to evaluate treatment and referral patterns, co-morbidities and resource use in patients with MPM in the U.S. Methods: Patients ≥18 years old with a diagnosis of MPM between Jan 2004 and September 2015 were identified from the MarketScan claims database. Patients were required to have data for 12 months prior, and at least 3 months post, the diagnosis index date. Patients with other (non-MPM) cancers, malignant mesothelioma of non-pleural origin and those enrolled in clinical trials were excluded from the analysis. Treatment and resource utilization were identified by their corresponding HCPCS and DRG codes. Referral patterns were estimated starting from the first lung-related visit during the year preceding MPM diagnosis. Results: In the cohort of 1,869 patients, the median age was 71 years (range 61–79) and 65% were male. 4.1% of patients underwent radical surgery and of the remaining 96%, 15.6% had first-line chemotherapy, 33.2% had first-line chemotherapy plus radiotherapy, 11.7% received radiotherapy, and 39.5% received no chemotherapy or radiotherapy. The most common diagnosis on the first lung-related visit was pleural effusion (16.5%), followed by chest pain (10.7%), shortness of breath (9.6%) and cough (8.5%). The median time from first lung-related visit to MPM diagnosis was 77 days (mean 134 days, IQR 23–258). Conclusions: This real-world analysis showed that only a small proportion of MPM patients (~4%) received radical surgery and a large number of patients did not receive any treatment at all, indicating a large unmet need for effective treatments in this disease area. Additionally, the pathway to MPM diagnosis may be challenging in this population with a poor prognosis, often involving multiple healthcare contacts over an extended period of time.
Association of Depression With Risk of Incident Systemic Lupus Erythematosus in Women Assessed Across 2 Decades
Authors: Andrea L. Roberts, Laura D. Kubzansky, Susan Malspeis, Candace H. Feldman, Karen H. Costenbader
Journal: JAMA Psychiatry (2018)

It has long been hypothesized that depression may increase the risk of developing autoimmune disease; however, rigorous empirical evidence is sparse.To evaluate whether an association exists between depression and risk of incident systemic lupus erythematosus (SLE), a paradigmatic, systemic autoimmune disease.This 20-year prospective, longitudinal cohort study evaluated data collected from 2 cohorts of women participating in the Nurses' Health Study (1996-2012) and the Nurses' Health Study II (1993-2013). Data analyses were conducted from August 2017 to May 2018.Incident SLE with 4 or more American College of Rheumatology criteria was ascertained by self-report and confirmed by medical record review. Depression was assessed repeatedly throughout follow-up according to whether women reported having received a clinician's diagnosis of depression, regular antidepressant use, or a score of less than 60 on the 5-item Mental Health Inventory (MHI-5). Whether longitudinally assessed health risk factors (eg, cigarette smoking, body mass index, oral contraceptive use, menopause or postmenopausal hormone use, alcohol use, exercise, or diet) accounted for increased SLE risk among women with vs without depression was examined. Cox proportional hazards regression models were used to estimate risk of SLE. In addition, the association of depression lagged by 4 years, and depression status at baseline with incident SLE throughout follow-up was assessed.Data from 194 483 women (28-93 years of age; 93% white) were included. During 20 years of follow-up, 145 cases of SLE occurred. Compared with women with no depression, women with a history of depression had a subsequent increased risk of SLE (HR, 2.67; 95% CI, 1.91-3.75; P < .001). Adjustment for body mass index, cigarette smoking, and oral contraception and postmenopausal hormone use slightly attenuated associations (adjusted HR, 2.45; 95% CI, 1.74-3.45; P < .001). The SLE risk was elevated with each of the 3 following depression indicators modeled separately: clinician's diagnosis of depression (HR, 2.19; 95% CI, 1.29-3.71), antidepressant use (HR, 2.80; 95% CI, 1.94-4.05), and MHI-5 scores indicating depressed mood (HR, 1.70; 95% CI, 1.18-2.44). Associations remained strong when depression status was lagged by 4 years with respect to the outcome (HR, 1.99; 95% CI, 1.32-3.00) and when depression status at baseline was used as the exposure (HR, 2.28; 95% CI, 1.54-3.37).This study contributes to increasing evidence that depression may be associated with increased risk of SLE and suggests that the association is not fully explained by measured health factors or behaviors.
More is not better. a time-dependent analysis of mortality in association with multiple treatments in the management of metastatic colorectal cancer.
Authors: Young soo Rho, Sabin Dragos Filimon, Ivan Barrera, Laurent Azoulay, James McLean, Tomas Kavan, Aline Mamo, Gerald Batist, Petr Kavan
Journal: Journal of Clinical Oncology (2016)

e15030 Background: More than ever, patients with metastatic colorectal cancer (mCRC) are exposed to multiple sequential chemotherapeutic and biological treatment lines (CLs) / agents (CAs). Yet recent insights regarding tumor heterogeneity and global evolution under the selection pressure of cytotoxic chemotherapy raises some questions of continuous exposure to multiple agents. Methods: We assembled a cohort of 277 patients diagnosed with mCRC between 2002-2015. Time-dependent Cox proportional hazards models were used to estimate hazards ratios (HRs) with 95% confidence intervals (CIs) of overall mortality associated with the number of CLs / CAs received. These exposures were treated as time-varying variables, allowing patients to contribute person-time in each CLs / CAs received. CLs were defined in accordance to previous studies to reflect daily clinical practice. All models were adjusted for relevant potential confounders. Results: A total of 146 patients died during 708 person-years of follow-up, yielding a crude incidence rate of 20.6% (95% CI: 17.4-24.3) per year. Compared with the use of one CL, the use of subsequent CLs was associated with an increased risk of death (second, HR: 1.79, 95% CI: 01.13-2.82; third, HR: 2.97, 95% CI: 1.75-5.06; fourth, HR: 4.35, 95% CI: 2.18-8.67). Similarly, compared with receiving 1-2 agents, the use of additional agents was associated with a gradual increased risk of death (3-6, HR: 1.26, 95% CI: 0.65-2.45; ≥ 7, HR: 2.61: 95% CI: 1.25-5.43). These findings trended in the opposite direction when the exposures were treated as time-fixed variables. Conclusions: Each additional CL and ≥ 7 CAs were associated with increased risk of death, unlike previously reported. Our findings, in particular the methodology, can be seen as supportive of recent evidence of inutility of systemic therapy in the final months of life. It is also possible that with multiple CLs/CAs, heterogeneous cell populations will have selective pressures resulting progressively a poly-resistant phenotype. Further research is needed to assess contributory roles of innate tumor biology and toxicity on the observed increased mortality.
Recombinant human adenovirus p53 injection (rAd-p53) is a challenge for anaplastic thyroid cancer treatment.
Authors: Wenshuang Wu, Zhimian Huang, Jingqiang Zhu
Journal: Journal of Clinical Oncology (2016)

e17561 Background: to evaluate the activity and mechanism of rAd-p53 combined with chemotherapeutics in treatment of ATC in vitro and in vivoand clinical therapies. Methods: p53-mutant ATC cells (C643 cells) were received with vehicle, paclitaxel, cisplatin, rAd-p53, paclitaxel combined with cisplatin, and rAd-p53 combined with paclitaxel and cisplatin to evaluate the in vitro anti-tumor activity and mechanism. The in vivo anti-tumor activity of rAd-p53 combined with paclitaxel and cisplatin was evaluated with a C643 xenograft model. Intratumoral rAd-p53 was administered at a dose of 1×1010 VP/cm2 per 3 days for 8 times and intraperitoneal injection of Paclitaxel and cisplatin was administered at a dose of 5 mg/kg per 5 days for 4 times. The ATC patients received a pre-operative rAd-p53 therapy combined with chemotherapeutic treatment. rAd-p53 was injected intra-tumoral with 2-4×1012rAd-p53 viral particles (VP) per 3 days for 10 times. A cycle of chemotherapy including paclitaxel and cisplatin were also finished. Results: Both of MTT assay and C643 xenograft modelshowed rAd-P53 combined with paclitaxel and cisplatin significantly inhibited the growth of C643 tumors. And rAd-P53 displayed an enhanced sensitivity to chemotherapeutics. The in vitroexperiments demonstrated that rAd-P53 combined with paclitaxel and cisplatin did not only induce C643 cells apoptosis with DNA damage pathway but also inhibit cell metastasis via Raf-MEK-Erk pathway. 2 ATC patients who received rAd-p53 intratumoral injection and chemotherapy had a continued response (CR) and without evidence of distant metastasis after the combined treatment, then received surgery. All cases were followed up and the survival time for ATC patients was between 9-35 months. Conclusions: rAd-P53 combined with paclitaxel and cisplatin showed an enhanced sensitivity to chemotherapeutics to inhibit the tumor growth of C643 cells both in in vitro and in vivo. ATC patients receiving a pre-operative rAd-p53 therapy combined with chemotherapeutic treatment had a radical surgery and long-term survival. These results hinted that rAd-P53 combined with chemotherapeutics had a potential utility for the clinical treatment for ATC.
Effect of national policy changes on hospice utilization and the invasiveness of end-of-life care in cancer patients.
Authors: Yu Yun Shao, Han-Chung Emily Hsiue, Chih-Hung Hsu, Ho-Min Chen, Mei-Shu Lai, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2016)

10008 Background: In 2011, two significant policy changes to foster hospice service for terminal cancer patients became effective in Taiwan. The single-payer National Health Insurance (NHI) of Taiwan started to reimburse full hospice service, and National hospital accreditation included hospice utilization in the evaluation. We aimed to assess their influence on hospice utilization and end-of-life (EOL) care of patients with cancer. Methods: We reviewed the NHI research database (NHIRD) and National Death Registry to include all patients who aged ≥ 18 years and died of cancer from Jan 1 2008 to Dec 31 2013. Data regarding utilization and costs of medical service were retrieved from NHIRD. Data regarding cancer diagnosis were retrieved from the database of National Cancer Registry. We compared the hospice utilization and invasive EOL care in the last month of life before (year 2008 to 2010) and after (year 2011 to 2013) the policy changes were implemented. Results: A total of 249,394 cancer patients were included. Comparing before and after the policy changes in 2011, hospice utilization increased from 20.8% to 36.2%, intensive care unit (ICU) admission decreased from 17.7% to 15.7%, invasive mechanical ventilation (IMV) decreased from 16.7% to 13.0%, and cardiopulmonary resuscitation (CPR) from 8.3% to 6.6%. Before and after the policy changes, 0.65% and 0.61% of total NHI expenditure was spent in the last month of life of cancer patients, respectively. In multivariate analysis adjusting for age, gender, marital status, socioeconomic status, cancer origin, cancer survival time, comorbidities, hospital characteristics, and hospice availability, hospice utilization significantly increased after the policy changes (adjusted odds ratio [AOR], 2.36, p < 0.001), accompanied by a decrease in ICU admission, IMV, and CPR (AORs, 0.86, 0.93, 0.80, respectively, all p < 0.001). Patients who received hospice service were significantly less likely to have ICU admissions, IMV, and CPR (AORs, 0.20, 0.12, 0.10, respectively, all p < 0.001). Conclusions: Policy changes fostering hospice care significantly increased hospice utilization and decreased invasiveness of EOL care in terminal cancer patients.
Comprehensive study of risk factors for chemotherapy-induced nausea and vomiting in cancer patients receiving cisplatin-based chemotherapy: A TRIPLE pharmacogenomics study.
Authors: Hideaki Ayuhara, Daiki Tsuji, Mari Yokoi, Kenichi Suzuki, Yohei Kawasaki, Masahiko Nakao, Yuki Kogure, Kazuhiko Shibata, Toshinobu Hayashi, Keita Hirai, Kazuyuki Inoue, Toshihiro Hama, Koji Takeda, Makoto Nishio, Kunihiko Itoh
Journal: Journal of Clinical Oncology (2017)

10091 Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most unpleasant adverse effects of chemotherapy. Resistance to prophylactic antiemetic treatment is problematic, with 30%–50% of patients experiencing unsatisfactory control. Younger age and female sex are well-known risk factors for CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response. Methods: This study included a subset of patients previously enrolled in a randomised controlled trial. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study’s efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR 0-24 ) and delayed (CR 24-120 ) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables. Results: In this genetic polymorphism association study, 156 patients with solid cancer were evaluated. Multivariate logistic regression analysis revealed that ERCC1 8092AA (odd ratio [OR]: 11.251; 95% confidence interval [CI]: 1.741–72.712, P = 0.011) and female sex (OR = 3.630; 95% CI = 1.138–11.578, P = 0.029) were significant predictors of CR 0-24 . No significant association of CR 24-120 with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis. Conclusions: ERCC1 polymorphism might be influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy. Clinical trial information: 000009335.