tbuckley/cabot-search huggingface dataset:
The joint i3+3 (Ji3+3) design for phase I / II adoptive cell therapy clinical trials.
Authors: Yuan Ji
Journal: Journal of Clinical Oncology (2020)

e14083 Background: Adoptive cell therapy (ACT), such as chimeric antigen receptor (CAR) T-cell therapy, have demonstrated promising therapeutic effects. However, it has been shown by previous studies that dose-response of ACTs may be complex and non-monotonic. For example, a ten-fold increase in dose level may not necessarily lead to higher anti-cancer response. This creates a new challenge for dose-finding trials with ACTs since higher dose may not lead to higher probability of efficacy. Methods: We propose a novel statistical design called the joint i3+3 design (Ji3+3) which extends our previous work of the i3+3 design (ASCO 2019 abstract 268979) and addresses the dose-finding challenge for ACT trials. In particular, Ji3+3 is a rule-based method that can be easily understood, visualized, and implemented by clinicians. It uses a set of smart rules based on observed efficacy and toxicity outcomes, and conducts up-and-down dose escalation decisions based on dose-response intervals. The entire dose-finding algorithm and decision rules can be presented as a precalculated table, which can be examined, discussed, modified, and approved as part of trial design. Results: Motivated by a CAR T trial (NCT03971799) we demonstrate the superiority of the Ji3+3 design through extensive computer simulations. Compared with the 3+3 design and i3+3 design, we show that Ji3+3 has a much higher chance finding the BOD and allocates more patients to desirable doses. The impact of these results will be to help investigators and drug developers identify a dose that is efficacious and safe, thereby increasing the probability of success to market the ACT and improving patient care. Conclusions: The Ji3+3 design is a novel, simple, and effective method that can potentially significantly improve the dose finding for ACT clinical trials.
Mental distress among adolescent and young adult (AYA) and adult cancer survivors.
Authors: Eric Adjei Boakye, Katherine M. Polednik, Arun Sharma, Yamile Molina, Vy Pham, Teresa L. Deshields, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2020)

e19116 Background: Mental distress is associated with poor treatment adherence and adverse psychosocial outcomes, and cancer survivors, especially adolescent and young adults (AYA), may experience greater distress than older adults and the general population. We tested this hypothesis by examining the association between AYA vs. adult cancer survivors vs. the general population without a history of cancer, and mental distress. Methods: Using the 2014-2017 National Health Interview Surveys, 2,516 AYA cancer survivors (aged 15 – 39 years) were identified. We then used propensity score matching (matched on sociodemographics, comorbidities, smoking status and visit to mental health professional in past year) to create 2,516 older cancer survivors (aged ≥ 40 years); and 2,516 adults without cancer (general population) as the comparison groups. Mental distress (outcome of interest) was measured using the validated Kessler nonspecific mental/psychological distress (K6) scale. The 6-item K6 scale examines how frequently within the past 30 days an individual felt nervous, hopeless, restless or fidgety, worthless, sad, and that everything was an effort. Responses were summed to yield a score ranging between 0 and 24 and classified as none/low (0≤K6 &lt; 5), moderate (5≤K6 &lt; 13), and severe (K6≥13) mental distress. Two separate weighted multinomial logistic regression models estimated the odds of mental distress in study population (AYA vs. adult cancer survivors; and AYA vs. general population), adjusting for known covariates. Results: Mental distress was more prevalent among AYAs than adult cancer survivors (moderate: 24.0% vs 18.3%; and severe: 5.7% vs 4.2% [ P= .0002]); and the general population (moderate: 24.3% vs 16.7%; and severe: 6.1% vs 5.3% [ P&lt; .0001]). Similarly, prevalence was higher among adult cancer survivors than the general population (moderate: 16.8% vs 13.6%; and severe: 3.2% vs 2.7% [ P= .0002]). In the multivariable multinomial analyses, AYAs had greater odds of mental distress (aOR moderate = 1.44; 95% CI 1.09, 1.89; and aOR severe = 1.77; 95% CI 1.21, 2.58) vs. adult cancer survivors. AYAs also had greater odds of mental distress vs. the general population (aOR moderate = 1.39; 95% CI 1.08, 1.79), but no significant difference in severe distress. Conclusions: About 1-in-4 AYA cancer survivors report some mental distress, and distress is more prevalent among this younger age group than older adults with cancer and the general population. Psychosocial care may be especially needed in this younger population to mitigate adverse psychosocial outcomes.
Qualitative study on two-way referral system
Authors: Yue Sha, Xiao-ming Huang, Hui Wang, Xue-jun Zeng, He-ping Ji
Journal: BMJ (2013)

Objective
To evaluate the current situation of two-way referral system by qualitative study.


Methods
The qualitative study was carried out in Department of General Internal Medicine of Peking Union Hospital and 4 clinics under Beijing Gaobeidian Community Health Center from June to December 2009. In-depth interview was conducted on 6 patients, who were referring from community health center to tertiary hospital and 16 general practitioners in the community. The method of thematic framework was used for data analysis.


Results
Only 1 of the 6 patients, who made the appointment, completed the two-way referral. From the view of the patients, the interrupt of the two-way referral was due to long-time waiting, inconvenient transportation to the hospital, availability of specialists, unsmooth process of referral and unsatisfied doctors. However, the community health service staff thought that difficulties of the two-way referral originated from the system, doctors, patients, and doctor-patient relationship. Sometimes patients distrusted doctors both in hospital and in community; communications between doctors or between doctors and patients were less efficient; patients had multiple choice for their primary care and they may go to any hospital freely bypass community-based referral system; patients had excessive expectation for medicine and doctors; some patients paid less attention to their own health, and so on. For improvement of the two-way referral system, the community health service staff proposed concrete measures in terms of relevant policy, the hospital, community health service, the doctors and patients; they emphasized the importance of upgrading their own communication ability and professional skills for primary care.


Conclusions
Many factors may influence successful implement of two-way referral, so it is necessary to improve the relevant policy and procedures and to upgrade medical staff in community.


Key words: 
Community health services; Patients transfer; Qualitative research
Maternal caffeine consumption during pregnancy and the risk of low birth weight
Authors: Hongli Qin
Journal: BMJ (2017)

Low birth weight is associated with newborn mortality and adult chronic diseases. Some studies found that maternal caffeine consumption during pregnancy was closely related with low birth weight. Resent research evidence indicates that caffeine may induce low birth weight by blocking adenosine receptors, inhibiting phosphodiesterase(PDE) and enhancing angiotensin Ⅱ(AT2) receptor gene expression to lower the placenta blood flow. We recommend that women should reduce caffeine intake during pregnancy.


Key words: 
Infant, low birth weight; Caffeine; Pregnancy
Enhancing the effectiveness of chemotherapy prescribing: A validation study of ChemoPalRx.
Authors: Serene Tareen, Sharvina Ziyeh, Leland Duer Powell, Kin Wai (Tony) Hung
Journal: Journal of Clinical Oncology (2020)

e19161 Background: ChemoPalRx is a free iOS mobile application developed for chemotherapy referencing and prescribing. Providers can readily download and use ChemoPalRx to generate and print chemotherapy formatted prescriptions. In the absence of a computerized chemotherapy order entry system, institutions may adopt ChemoPalRx for chemotherapy prescribing in place of traditional methods such as handwritten prescriptions. However, effectiveness of ChemoPalRx in the real-world practices has not been established. Methods: With our aim to determine the effectiveness of ChemoPalRx, we conducted a cross sectional study at an academic institution. Our study primary predictor was the method of generating a chemotherapy order, dichotomized as “handwritten” or “ChemoPalRx”. Primary outcome was corrected order, dichotomized as “corrected” or “satisfactory” order. Corrections were defined as any correction made to an order (e.g. illegible handwriting, modifications in drug dosing, missing chemotherapy or patient’s information). Covariates included fellowship training year (first, second, or third) and complexity of order (“simple” = 2 drugs or less; “complex” = 3 drugs or more). Correction rate (CR) was defined as the proportion of corrected orders. Chi Square test was used for statistical analysis. Results: From October 2019 to December 2019, 288 chemotherapy orders were examined, of which, 226 were handwritten (78.5%) and 62 were ChemoPalRx (21.5%). Of the 226 handwritten orders, 184 (81%) were satisfactory, 42 (19%) were corrected. Of the 62 ChemoPalRx orders, 57 (92%) were satisfactory, 5 (8%) were corrected. CR was significantly reduced by ChemoPalRx compared to handwritten (p = 0.034). Subgroup analysis found that first-year fellows tend to make more corrections on complex orders (CR: 19%) compared to second- and third-year fellows (CR: 6%) (p = 0.19), while second- and third- year fellows made more corrections on simple orders (CR: 22%) compared to first-year fellows (CR: 9%) (p = 0.013). Conclusions: ChemoPalRx significantly enhanced prescription accuracy compared to handwritten chemotherapy orders. Implementation of ChemoPalRx in real-world practices is validly feasible and effective. While ChemoPalRx may support less experienced providers on more complex orders, it may help to catch overlooked simple details for the experienced providers. In the evolving digital era in oncology, ChemoPalRx may be a promising alternative to handwritten prescriptions that can be readily available at one’s fingertips.
新しいプラチナ誘導体テトラクロロ(d,l-トランス)1,2-ジアミノシクロヘキサンプラチナ(IV)(テトラプラチン)の治療効果および薬理学的研究 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Rahman A, Roh J K, Wolpert-Defilippes M K, Goldin A, Venditti J M, Woolley P
Journal: Cancer Research (1988)
An innovative, internet-based assessment of financial toxicity (FT), psychological distress, and quality of life (QOL) in ovarian cancer survivors (OCS).
Authors: Fay J. Hlubocky, Jeffery Peppercorn, Karen Young, Sandra Cord, Kristen Wroblewski, Seiko Diane Yamada, David Cella, Nita Karnik Lee, Christopher Daugherty
Journal: Journal of Clinical Oncology (2020)

e24168 Background: FT is recognized as a significant predictor of stress for OCS on treatment yet little is known about its impact during long-time survivorship. Using an innovative, internet-based design, we assessed the prevalence of FT, psychological distress, and QOL among OCS. Methods: OCS members from the National Ovarian Cancer Coalition (NOCC) completed this web-based assessment using the following measures: COmprehensive Score for Financial Toxicity (COST); Hospital Anxiety/Depression Scale (HADSA/D); and the Functional Assessment of Cancer Therapy-Ovarian (FACIT-O/QOL). Clinical/socio-demographic data were collected. COST-FT severity was categorized into low FT/high FT and the correlation (r) between COST scores and self-reported QOL and distress was conducted. Results: A total of 146/300 (49% ) NOCC subjects were approached for study participation and completed the FT, distress, QOL web-based assessment. Demographics include: median age 59y (range 32-83y); 92.5% Caucasian, 64.4% married/domestic partnership; 59.6% Stage III-IV cancer-diagnosis; median disease duration 6y (range &lt; 1-34y); 50% employed full/part-time; 54.8% college/post-graduate education; and 71.9% completed treatment. Median COST score for the total population was 27 (range: 1–44). The median score in the low FT tertile was 16 (range: 1-22), while the high FT median score was 31 (range: 23-44). High FT respondents rated their HADS-anxiety (8.3 ± 4.9 v. 6.2 ± 3.5, p = 0.002); HADS-depression (5.3 ± 4.2 v. 3.1 ± 3.0, p = 0.004); and overall FACT-O/QOL (99.8 ± 23.6 v. 118.7 ± 19.5; p = 0.001) as significantly worse compared to low FT respondents. Significant moderate correlations between COST and FACT-O/QOL (r = -0.52; p &lt; 0.001), HADS-anxiety (r = 0.4, p &lt; 0.001), and HADS-depression (r = 0.44, p &lt; 0.001) were identified. Older age was associated with less FT (r = -0.30, p &lt; 0.001). Conclusions: Innovative methods of FT evaluation, e.g. using advocacy groups (NOCC) and internet-based assessment, is feasible, and may offer new ways to follow the distress of long term survivor cohorts. Our study data reveal that FT impacts OCS QOL and distress.
Pooled safety analysis of single-agent lurbinectedin versus topotecan (Results from a randomized phase III trial CORAIL and a phase II basket trial).
Authors: Alexandra Leary, Stephanie Gaillard, Ignace Vergote, Jose Trigo, Carmen Maria Kahatt, Antonio Nieto, Cristian Marcelo Fernandez, Martin Cullell-Young, Ali Hassan Zeaiter, Vivek Subbiah
Journal: Journal of Clinical Oncology (2020)

3635 Background: Lurbinectedin (L), an inhibitor of active transcription, has shown activity in second-line (2L) small cell lung cancer (SCLC) (ASCO 2019). Topotecan (T) is the only approved drug in 2L SCLC and is also used in platinum resistant ovarian cancer (PROC). Methods: This pooled safety analysis includes data from 554 patients (pts) treated with L at 3.2 mg/m 2 Day 1 q3wk 1-h (no primary prophylaxis with G-CSF required): 335 with selected solid tumors (9 indications, including 105 pts with SCLC) from a phase II Basket study and 219 with PROC in the phase III CORAIL study. An indirect exploratory comparison (pooled data from CORAIL + Basket) and a direct comparison (data from CORAIL) of L vs. T are presented. Results: Most common adverse events with L were grade 1/2 fatigue, nausea and vomiting. Treatment-related (L/T): dose reductions: 22.9/48.3%, delays: 25.8/52.9%, grade ≥3 serious adverse events (SAEs): 15.0/32.2%, discontinuations: 3.2/5.7%, deaths: 1.3/1.5%, G-CSF use: 23.8/70.1%, and transfusions: 15.9/52.9%. Conclusions: Lurbinectedin has a predictable and manageable safety profile. A significant safety advantage was observed when lurbinectedin was compared with topotecan in the CORAIL trial in terms of hematological toxicities. With the limitations of indirect comparisons, in the pooled safety analysis, fewer lurbinectedin-treated pts had severe hematological toxicities, SAEs, dose adjustments, treatment discontinuations and use of supportive treatments than topotecan-treated pts. Clinical trial information: NCT02421588 and NCT02454972 . [Table: see text]
Secondary myelodysplastic syndrome identified via next-generation sequencing in non-small cell lung cancer patients.
Authors: Yongzhi Feng, Feng Tao, Libin Jiang, Dan Ni, Jun Zhang, Linxin Wu, Lin Shi, Genhua Yu
Journal: Journal of Clinical Oncology (2020)

e19531 Background: Chemotherapy and radiotherapy used in cancer treatment are associated with increased risk of secondary myelodysplastic syndrome (MDS). MDS is characterized with specific chromosomal abnormalities and genomic alterations in JAK2, KRAS, CBL, DNMT3A, TET2, IDH1/2, EVI1, RUNX1, GATA2, EZH2, ASXL1, SF3B1, U2AF1, SRSF2 and ZRSR2. Since next generation sequencing (NGS) techniques have been widely used for the detection of actionable genomic variation in solid tumor patients, analysis of NGS data for chromosomal abnormalities and gene mutations may be supplementary for diagnosis of secondary MDS. Methods: We retrospectively analyzed targeted NGS data of paired tumor and blood samples from patients with non-small cell lung cancer (NSCLC) for chromosomal abnormalities and gene mutations. Sequence panel covered whole exons of 381 genes associated with cancers. Sequence data were processed using a customized analysis pipeline designed to accurately detect multiple classes of genomic alterations in routine clinical specimens. All testing was done in a CLIA-certified, CAP-accredited laboratory. Clinical information of cases with chromosomal abnormalities was reviewed, including treatment for previous cancer, blood and bone marrow tests. Results: We found 4 cases carrying MDS associated chromosome abnormalities among 3523 NSCLC patients with the prevalence of0.1%. They were old (from 66 to 71 years old), and were more likely to be male (3 males and 1 females). All of 4 cases included common abnormalities associated with MDS like 5q-, 7q-, -7, +21. 3 cases had complex (≥3) abnormalities and 1 case had double abnormalities. Point mutations were identified in blood samples of 3 cases. Mutations in TP53 occurred in 3 cases, mutations in ASXL1, DNMT3A, FLT3 and CBL occurred in one case respectively. Among the 4 cases, 2 cases were confirmed as MDS by blood and bone marrow tests. Conclusions: We identified 4 MDS associated chromosomal abnormalities from 3523 NSCLC patients through analyzing NGS data. NGS techniques could serve as supplementary for diagnosis of secondary MDS. [Table: see text]
Preprocurement <i>In Situ</i> Donor Lung Tissue Gene Expression Classifies Primary Graft Dysfunction Risk
Authors: Edward Cantu, Mengying Yan, Yoshikazu Suzuki, Taylor Buckley, Vito Galati, Neha Majeti, Christian A. Bermudez, Joshua M. Diamond, Jason D. Christie, Rui Feng
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Results of a phase II trial of intense androgen deprivation therapy prior to radical prostatectomy (RP) in men with high-risk localized prostate cancer (PC).
Authors: Rana R. McKay, Wanling Xie, Fiona M. Fennessy, Zhenwei Zhang, Rosina Lis, Dana E. Rathkopf, Vincent Paul Laudone, Glenn Bubley, David Johnson Einstein, Peter Chang, Andrew Wagner, Mark A. Preston, Kerry L. Kilbridge, Steven Lee Chang, Atish Dipankar Choudhury, Mark Pomerantz, Quoc-Dien Trinh, Adam S. Kibel, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2020)

5503 Background: Patients with high-risk localized PC have an increased risk of recurrence and death despite treatment. Abiraterone acetate (AA), a potent CYP17 inhibitor, and apalutamide, a next generation anti-androgen, have each demonstrated improved overall survival in metastatic PC. In this multicenter randomized phase II trial we investigate the impact of intense androgen deprivation on RP pathologic response (NCT02903368). Methods: Eligible patients had a Gleason score ≥4+3=7, PSA &gt;20 ng/mL or T3 disease (by prostate MRI) and lymph node &lt;20 mm. During Part 1 of the study, patients were randomized 1:1 to AA + prednisone + apalutamide + leuprolide (APAL) or AA + prednisone + leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by RP. All RPs underwent central pathology review. The primary endpoint was the rate of a pathologic complete response (pCR) or minimum residual disease (MRD, tumor ≤5 mm). Secondary endpoints include PSA response, surgical staging at RP, positive margin rate, and safety. Results: 118 patients were enrolled at four sites. Median age was 61 (range 46-72) years. The majority of patients had NCCN high-risk disease [n=111, 94%; T3 n=73 (62%), Gleason 8-10 n=84 (71%), PSA &gt;20 ng/mL n=28 (24%)]. 114 (97%) patients completed 6 therapy cycles followed by RP. Median PSA nadir was &lt;0.01 versus 0.02 ng/mL and time to nadir was 4.2 versus 4.6 months in the APAL and APL arms, respectively. RP outcomes are displayed in Table. The combined pCR or MRD rate was 21.8% in the APAL arm and 20.3% in the APL arm (p=0.85). 13 (11%) patients (8 in APAL; 5 in APL) experienced grade 3 treatment-related adverse events (TrAEs). The most common grade 3 TrAEs were hypertension (5%), elevated ALT (3%) and elevated AST (3%). No grade 4 or 5 TrAE was reported. Conclusions: Intense neoadjuvant hormone therapy followed by RP in men with high-risk PC resulted in favorable pathologic responses (&lt;5 mm residual tumor) in 21% of patients. Pathologic responses were similar between the treatment arms. Follow-up is necessary to evaluate the significance of a pathologic response on recurrence rates. Part 2 of this trial will investigate the impact of an additional 12 months of APAL post-RP on biochemical recurrence. A phase 3 trial investigating neoadjuvant apalutamide + leuprolide prior to RP is ongoing. Clinical trial information: NCT02903368 . [Table: see text]
Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.
Authors: Lynda M McSorley, Fathiya Al Rahbi, Mehala Tharmabala, Denis Evoy, James G. Geraghty, Ruth Prichard, Jane Rothwell, Damian McCartan, Enda McDermott, Maccon M. Keane, John Kennedy, Seamus O'Reilly, Steve Millen, John Crown, Lillian Mary Smyth, Catherine Margaret Kelly, Cecily Quinn, Janice Maria Walshe
Journal: Journal of Clinical Oncology (2020)

540 Background: Treatment of hormone receptor positive (HR+) ESBC is evolving. The use of chemotherapy (CT) is declining with use of the 21-gene RS assay. This validated tool predicts the likelihood of adjuvant CT benefit in HR+ ESBC. Results from the TAILOR-x study suggest up to 70% of HR+ node negative ESBC patients (pts) may avoid CT with RS ≤25. Our objectives were to assess the clinical and economic impact of RS testing on treatment decisions using real-world data. Methods: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ node negative ESBC pts who had RS testing in Ireland. A survey of Irish breast medical oncologists provided the assumption for the decision impact analysis that grade (G) 1 pts would not receive CT pre RS testing and G2/3 pts would receive CT. Using TAILOR-x results, pts were classified low risk (RS ≤ 25) and high risk (RS &gt; 25). Data was collected via electronic patient records. Descriptive statistics were used. Cost data was obtained via the National Healthcare Pricing Regulatory Authority. The economic analysis was adjusted for changing treatment and assay costs over the study period. Results: 963pts were identified. Mean age 56 years. Mean tumour size 1.87cm. 114 (11.8%), 636(66%), 211(22%), 2(0.2%) pts had G1, G2, G3 and unknown G respectively (resp). 797pts (82.8%) had low RS, 159 (16.5%) had high RS, and 7pts(0.7%) unknown RS. 251pts(26%) were aged &lt; 51 at diagnosis. Of these, 45(17.9%), 145(57.8%), 58(23%), 3(1.2) had G1, G2, G3 and unknown G resp. 208pts(82.9%) had RS ≤ 25, 39pts(15.5%) had RS &gt; 25 and 4pts(1.6%) unknown RS. In the RS ≤ 25 group, 111pts(44%) had RS 0-15, 59(23.5%) had RS16-20, and 38(15.1%) had RS21-25. Post RS testing 595pts(61.8%) had a change in CT decision; 586 changed to hormone therapy (HT) alone, and 9 from HT to CT. In total, 227pts(23.5%) received CT, and 3pts(0.3%) declined. Of pts treated with CT; 9(4%) had RS 0-15, 89(39.2%) had RS16-25, 129(56.8%) had RS &gt; 25. The most common CT regimen was docetaxel and cyclophosphamide(TC), administered to 121pts(53%). RS assay use achieved a 69% change in treatment decision among G2/3 pts and a net 61% reduction in CT use. This resulted in savings of over €4 million in treatment costs. Deducting the assay cost, net savings of over one million euro was achieved. Conclusions: Ireland was the first public healthcare system to approve reimbursement for RS testing. Over the 8 year period of the study, a net 61% reduction in CT use in Irish pts with HR+ ESBC was achieved with conservative net savings of over €1,000,000.