tbuckley/cabot-search huggingface dataset:
KEYNOTE-799: Phase 2 trial of pembrolizumab plus platinum chemotherapy and radiotherapy for unresectable, locally advanced, stage 3 NSCLC.
Authors: Salma K. Jabbour, Ki Hyeong Lee, Nicolaj Frost, Valeriy Vladimirovich Breder, Dariusz M. Kowalski, Issam Abdelkarim Alawin, Evgeny Levchenko, Noemi Reguart, Alex Martinez-Marti, Baerin Houghton, Jean-Baptiste Paoli, Sufia Safina, Keunchil Park, Takefumi Komiya, Amy Sanford, Vishal Boolell, Hong Liu, Ayman Samkari, Steven M. Keller, Martin Reck
Journal: Journal of Clinical Oncology (2021)

8512 Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5% in cohort B (nonsquamous, n = 61), and grade ≥3 pneumonitis in 8.0% and 7.9% of pts, respectively. Here, we present results for all pts enrolled in KEYNOTE-799. Methods: This nonrandomized, multisite, open-label phase 2 trial enrolled pts aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA‒C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received 1 cycle of carboplatin AUC 6 and paclitaxel 200 mg/m 2 and pembro 200 mg. After 3 wks, pts received carboplatin AUC 2 and paclitaxel 45 mg/m 2 QW for 6 wks and 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin 75 mg/m 2 , pemetrexed 500 mg/m 2 , and pembro 200 mg Q3W, and TRT in cycles 2 and 3. All pts received an additional 14 cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Efficacy and safety were assessed in all pts as-treated. Results: Of 216 pts enrolled in KEYNOTE-799 (cohort A, n = 112; cohort B, n = 104), 112 in cohort A and 102 in cohort B received treatment. As of October 28, 2020, the median (range) time from first dose to database cutoff was 18.5 (13.6–23.8) mo in cohort A and 13.7 (2.9–23.5) mo in cohort B. ORR (95% CI) was 70.5% (61.2%‒78.8%) in cohort A and 70.6% (60.7%‒79.2%) in cohort B. Median DOR was not reached in either cohort (Table). ORR was similar regardless of PD-L1 status ([TPS &lt;1% and TPS ≥1%]; Cohort A, 66.7% and 75.8%; Cohort B, 71.4% and 72.5%) and tumor histology (Cohort A, squamous, 71.2% and nonsquamous, 69.2%). Grade ≥3 pneumonitis occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3‒5 treatment-related AEs occurred in 72 pts (64.3%) in cohort A and 51 (50.0%) in cohort B. Conclusions: Pembro plus cCRT continues to demonstrate promising antitumor activity, regardless of PD-L1 TPS and tumor histology, and manageable safety in pts with previously untreated, locally advanced, stage III NSCLC with longer follow-up. Clinical trial information: NCT03631784. [Table: see text]
Late morbidity and mortality among survivors of neuroblastoma treated with contemporary therapy: A report from the Childhood Cancer Survivor Study.
Authors: Danielle Novetsky Friedman, Pamela J. Goodman, Wendy M. Leisenring, Lisa Diller, Susan Lerner Cohn, Emily S. Tonorezos, Rebecca M. Howell, Susan A. Smith, Suzanne L. Wolden, Joseph Philip Neglia, Kirsten K. Ness, Todd M. Gibson, Paul C. Nathan, Leslie L. Robison, Kevin C. Oeffinger, Gregory T. Armstrong, Charles A. Sklar, Tara O. Henderson
Journal: Journal of Clinical Oncology (2021)

10044 Background: Survival rates for neuroblastoma vary widely based on risk group. Therapies have evolved over the past four decades to de-intensify treatment for individuals with low/intermediate risk disease and intensify therapy for those with high risk disease. Risk stratification is predicted to result in differential outcomes in late morbidity and mortality; the magnitude of these differences has not been well studied. Methods: We evaluated late mortality, subsequent malignant neoplasms (SMN) and chronic health conditions (CHC) graded according to CTCAE v4.03 among 491 5-year CCSS survivors of neuroblastoma diagnosed 1987-1999 at ≥1 year of age. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n=182]; intermediate [n=70]; high [n=239]). Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) of SMN were calculated using rates from NCHS and SEER, respectively. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC compared to 1,029 CCSS siblings. Results: Among survivors (48% male; median age 22 years, range 7-42; median follow-up 19 years, range 5-29), 80.4% with low risk disease were treated with surgery alone, while 77.8% with high risk disease received surgery, radiation, chemotherapy ± transplant. The 15-year cumulative incidence of all-cause mortality was 9.2% (CI: 7.1-11.4), with a recurrence-related mortality of 7.3% (CI: 5.3-9.3) and SMN-related mortality of 0.3% (CI: 0-0.7). All-cause mortality was significantly higher in all risk groups: (low, SMR=5.8 [CI: 2.6-13.0]; intermediate, SMR=5.7 [CI: 1.4-23.5]; high, SMR=38.6 [CI: 27.9-53.5]). The risk of SMN was elevated among high risk survivors (SIR=25.1, CI: 16.7-37.6), but did not differ from the US population for survivors of low or intermediate risk disease. Table describes the HR of CHCs (grades 1-5 and 3-5) in survivors, by risk group, as compared with siblings, as well as categories of CHCs for which survivors were at increased risk. Conclusions: Long-term survivors of neuroblastoma have a high risk of late morbidity and mortality; risk is particularly pronounced among survivors of high risk disease. Vigilant lifelong medical surveillance will be required for this relatively young population as they age.[Table: see text]
Functional precision medicine in colorectal cancer based on patient-derived tumoroids and in-vitro sensitivity drug testing.
Authors: Lars Henrik Jensen, Anders Kristian Moeller Jakobsen, Birgitte Mayland Havelund, Cecilie Abildgaard, Chris Vagn-Hansen, Claus Dam, Jan Lindebjerg, Luisa M Canto, Silvia Regina Rogatto, Soeren Rafael Rafaelsen, Torben Hansen
Journal: Journal of Clinical Oncology (2021)

e15567 Background: Precision oncology based on in-vitro, functional assays has potential advantages compared to the much more common molecular approach, but the clinical benefit is unknown. We here report the results from the largest prospective interventional clinical trial testing the clinical outcome in colorectal cancer patients treated with drugs showing cytotoxic effect in matched patient-derived tumoroids. Methods: This single-center, phase II trial included patients with metastatic colorectal cancer previously exposed to all standard therapies. Specimens from one to three 18-16 G core needle biopsies were manually dissected, enzymatically treated, cultivated, and incubated to form 3D spherical microtumors, i.e. tumoroids. In the assay for in-vitro sensitivity testing, the tumoroids were challenged with single drugs and combinations thereof to determine patient-specific responses. Using tumoroid screening technology (IndiTreat, 2cureX, Copenhagen, Denmark), results were generated by comparing the sensitivity of the individual patient’s tumoroids with a reference panel from other patients. The testing included standard cytostatics and drugs with proven effect in previous early-phase clinical trials, a total of 15 drugs. The primary endpoint was the fraction of patients with progression-free survival (PFS) at two months. Based on placebo arms in randomized last-line trials, a minimal relevant difference of 20% (20% to 40%) was stated. Using Simon's two-stage design, a sample size of 45 patients was calculated with at least 14 PFS at two months (significance 5%, power 90%). Results: Ninety patients were enrolled from 9/2017 to 9/2020. Biopsies from 82 patients were obtained and sent for tumoroid formation of which 44 (54%, 95% CI 42-65) were successful and at least one treatment was suggested. Thirty-four patients initiated treatment according to the response obtained in the drug assays within a median of 51 days from inclusion (IQR 39-63). The primary endpoint, PFS at two months, was met in 17 of 34 patients (50%, 95%CI 32-68). There were no radiological responses. Median PFS was 81 days (95% CI 51-112) and median OS was 189 days (95% CI 103-277). Conclusions: Precision oncology using a functional approach with patient-derived tumoroids and in-vitro drug sensitivity testing seems feasible. The approach is limited by the fraction of patients with successful tumoroid development. The primary endpoint was met, as half of the patients were without progression at two months. Further clinical studies are justified. Clinical trial information: NCT03251612.
KEYNOTE-555 Cohort B: Efficacy, safety, and PK of pembrolizumab (pembro) 400 mg every 6 weeks (Q6W) as 1L therapy for advanced melanoma.
Authors: Conrad R. Jacobs, Bernardo Leon Rapoport, Sze Wai Chan, Paul Ruff, Ana Maria Arance, Karmele Mujika, James Robert Anderson, Mallika Lala, Lokesh Jain, Omobolaji Oyekunle Akala, Elliot Chartash, Graham Lawrence Cohen
Journal: Journal of Clinical Oncology (2021)

9541 Background: In KEYNOTE-555, a model-based approach suggested expected drug exposure with pembro 400 mg Q6W is similar to that observed with approved doses of pembro 200 mg or 2 mg/kg Q3W. The pembro Q6W dose is now approved. We present interim efficacy, safety and PK of 1L pembro 400 mg Q6W for patients (pts) with advanced melanoma in KEYNOTE-555 Cohort B (NCT03665597). Methods: Eligible pts had unresectable stage III or IV melanoma, ECOG PS ≤1, and no prior systemic therapy for advanced disease.Pts received pembro 400 mg Q6W for up to 18 cycles (≈2 years).The primary efficacy endpoint was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included PFS by BICR per RECIST v1.1 and safety. PK profile and exposure were evaluated for cycle 1 and steady state (cycle 4). Results: Between May 2019 and Jan 2020, 101 pts were enrolled and received ≥1 dose of pembro. Baseline characteristics were generally similar to pt cohorts of historical pembro studies in advanced melanoma. As of the data cutoff date of August 6, 2020, all pts had ≥6 mo of follow-up and 40.6% of pts had discontinued study treatment. Median (range) duration of treatment and doses administered were 8.2 mo (1 day–13.9 mo) and 6 (1–11) doses, respectively. Observed exposure with pembro 400 mg Q6W had lower variability than model predictions and was within PK parameters from clinical experience with other pembro regimens (Table). ORR was 50.5% (95% CI 40.4–60.6). 12.9% of pts had CR and 37.6% had PR. Median PFS was 13.8 mo (95% CI 3.0–not reached). Estimated PFS rates were 56.5% at 6 mo and 54.3% at 12 mo. Treatment-related AEs of any grade occurred in 79.2% of pts (grade 3–4: 6.9% of pts; no deaths due to a treatment-related AE). The most common immune-mediated AEs were hyperthyroidism (6.9%) and hypothyroidism (6.9%). Conclusions: 1L treatment with pembro 400 mg Q6W yielded a clinically meaningful ORR in pts with advanced melanoma. PK, efficacy and safety results from KEYNOTE-555 Cohort B support prior findings from the model-based assessment and indicate that the benefit-risk profile for the more practical pembro 400 mg Q6W regimen is consistent with that of 200 mg or 2 mg/kg Q3W regimens. Clinical trial information: NCT03665597. [Table: see text]
Use of the geriatric assessment in clinical practice in Mexico: A survey of cancer providers.
Authors: Haydee Cristina Verduzco-Aguirre, Laura Margarita Bolano Guerra, Hector Martínez-Said, Gregorio Quintero Beulo, Eva Culakova, Supriya Gupta Mohile, Enrique Soto Perez De Celis
Journal: Journal of Clinical Oncology (2021)

e24013 Background: Despite the growing burden of cancer in older adults in Mexico, it is unknown how many cancer care providers in Mexico use information obtained through a geriatric assessment (GA) and/or geriatric oncology principles in their everyday clinical practice. Methods: We administered a cross-sectional survey to oncology providers in Mexico via the Mexican Society of Oncology mailing list (n = 1240). The survey included questions on demographics, awareness about geriatric oncology principles, and the use of the GA and other geriatric clinical tools. The primary outcome was to estimate the proportion of providers using GA tools through the question: “For your patients ≥65 years, do you perform a multidimensional geriatric assessment using validated tools?”. We hypothesized that ≤10% of respondents would give a positive answer. We used descriptive statistics and X2 tests to compare groups of respondents. Results: We obtained 196 answers (response rate 15.8%). 121 (62%) respondents were male; median age 42. 98 (50%) were surgical oncologists, 59 (30%) medical oncologists, and 38 (19%) radiation oncologists. Median time in practice was 8 years, with 39% practicing in Mexico City. A third had their practice at a public institution, 26% at a private institution, and 38% in both. The proportion of patients aged 65-79 and ≥80 seen on an average clinic day by the respondents was 30% and 10%, respectively. 121 (62%) reported having a geriatrician available at their practice site. 37 respondents (19%) reported using validated GA tools to evaluate older adults with cancer in their practice. The proportion of respondents who evaluated each GA domain is shown in Table 1. Male respondents (p=0.03), medical oncologists (p&lt;0.01), and those with a less busy practice (≤10 patients/day) (p=0.01) were more likely to use validated tools to perform a GA. Regarding barriers for implementing GA, 37% reported lack of time, 49% lack of qualified personnel, 44% lack of knowledge of geriatric tools, 6% patient unwillingness to undergo a GA, and 8% prohibitive cost. Only 17 (9%) thought that information obtained through a GA would not lead to practice changes. Conclusions: According to our survey, the proportion of Mexican oncology providers using validated tools to perform a GA is 19%, which is higher than expected. Some GA domains, such as comorbidity and functional status, were commonly assessed, while others, such as fall history, were seldom evaluated. Common barriers for GA implementation were lack of qualified personnel and of knowledge about geriatric tools. We plan to further explore these barriers and potential facilitators through focused interviews in order to guide future interventions.[Table: see text]
Waiting list for hospital treatment tops “grim milestone” of five million
Authors: Matthew Limb
Journal: BMJ (2021)

The number of people waiting for hospital treatment in England has topped five million for the first time, raising fresh alarm over impacts on patients.

Doctors’ and trusts’ leaders warned of unrelenting pressures on NHS staff and services while health officials said there were “encouraging” signs of a “rebound” in delivery of routine operations.

The latest monthly performance data on NHS referral to treatment show that the waiting list rose by 171 720 in April to 5 122 017.1 Some 385 490 patients were waiting over a year for treatment—50 000 fewer than in March. At the end of April 2021, 64.6% of patients waiting to start treatment were waiting up to 18 …
FRI0567-PC Using adaptive choice based conjoint (ACBC) analysis to study patients’ preferences regarding pharmaceutical treatment for osteoarthritis (OA).
Authors: B. Al-Omari, M. Frisher, P. Croft, J. Sim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adaptive Choice Based Conjoint (ACBC) is a technique for eliciting and quantifying people's preferences. This is the first application of ACBC in rheumatology research. The advantage of this method is that it adapts to patients' responses to different medication scenarios. This research is concerned with the extent to which the benefits of medication are traded-off against serious adverse effects such as kidney impairment and stroke. <h3>Objectives</h3> To determine the relative importance of 8 medication attributes, using the Adaptive Choice Based Conjoint. <h3>Methods</h3> 11 participants were recruited from the Research User Group (RUG) at the Arthritis Research UK Primary Care Centre, Keele University, UK, to evaluate a newly developed ACBC questionnaire. Participants were over 50 years of age and suffering from OA in at least one of their joints. Participants completed an ACBC questionnaire involving 8 attributes: medication availability, frequency, route of administration, expected benefit, risk of addiction, risk of stomach side effects, risk of kidney and liver side effects, and risk of heart attacks and strokes. The relative importance of the 8 attributes, which sum to 100%, was calculated using Hierarchical Bayes (HB) estimation. <h3>Results</h3> Rather than medication benefits being the top priority, the greatest impact on patients' preference regarding medication was the risk of kidney and liver side effects (22%), followed by the risk of heart attacks and strokes (17%), then the risk of stomach side effects (16%). The route of administration, frequency, and expected benefit were the least important factors influencing patients' preference (7%). <h3>Conclusions</h3> ACBC reveals information about patients' preferences and the precise trade-offs that patients are willing to make. For example, OA patients are willing to trade off the benefits of medication for low risks of adverse effects. The benefits that patients expect from the medication are not very important when traded-off against serious medication adverse effects such as kidney and liver side effects. This shows the importance of making patients aware of OA medication side effects within the context of other treatment options. <h3>Acknowledgements</h3> We are extremely grateful to Carol Rhodes and Adele Higginbottom (Patient and Public Involvement Co-ordinator and assistant at the Arthritis Research UK Primary Care Centre) for their effort to facilitate the RUG involvement. Special thanks to the Research User Group at the Arthritis Research UK Primary Care Centre, Keele University, UK, as this research work would not have been possible without their participation. <h3>Disclosure of Interest</h3> None Declared
Mortality risk for patients undergoing cancer treatment who acquire SARS-CoV-2: ASCO registry.
Authors: Kathryn Finch Mileham, Suanna Steeby Bruinooge, Charu Aggarwal, Alicia L. Patrick, Christiana Davis, Daniel Mesenhowski, Alexander I. Spira, Eric J. Clayton, David Michael Waterhouse, Sue Moore, Abdul-Rahman Jazieh, Ronald C. Chen, Melinda Kaltenbaugh, Jen Hanley Williams, Richard L. Schilsky, Liz Garrett-Mayer
Journal: Journal of Clinical Oncology (2021)

6509 Background: The ASCO Registry was created to analyze the impact of COVID-19 (COVID) on treatment (Tx) and outcomes of patients (pts) with cancer. Methods: The Registry includes pts with 1) a confirmed COVID diagnosis (Dx) and 2) clinically evident cancer receiving Tx/supportive care or resected cancer on adjuvant Tx &lt;12 mos since surgery. Practices report data on cancer Dx and Tx at COVID Dx, COVID symptoms, comorbidities, cancer/COVID Tx, and survival. Kaplan-Meier estimation provided 30- and 90-day mortality rate estimates for pts with COVID Dx before or since 6/1/20 within pt subgroups with 95% confidence intervals (CI). Data submission cutoff for all practices was 10/24/20, except one that was 11/16/20. Results: This analysis reports on 453 pts with COVID Dx 3/5/20 to 10/22/20 who were on anticancer drug Tx for regional (9%) or metastatic (53%) solid tumors or hematologic cancers (38%) at COVID Dx. 38 practices entered data: health system-owned 51% of pts, privately-owned 25%, academic 24%. 53% of pts have ≥30 days follow-up or died ≤30 days from COVID Dx. Median age is 64 years; 53% of pts are female; 28% of pts are asymptomatic at COVID Dx. Multiple myeloma was most frequent cancer (17%). All-cause mortality rates (30 and 90 days) increased with pts’ age at COVID Dx [Table]. No mortality difference was seen based on sex, race, or comorbidities (hypertension, diabetes, pulmonary disease). Pts with COVID Dx before June 1 had worse survival than pts diagnosed on/after June 1. Pts with B-cell malignancies had higher mortality rates than pts with solid tumors. Conclusions: Severity of COVID illness and mortality were greater for patients with COVID Dx pre-June 1 than on/after June 1. Differences on/after June 1 may be attributed to improvements in COVID management, higher COVID testing rates, and more asymptomatic pts diagnosed. Variations in COVID-19 pt populations over time due to these changes should be considered when analyzing and interpreting pandemic data. Cancer pts with advanced age and B-cell cancers are at greatest risk of death but mortality rates for all groups (except those admitted to ICU) improved after 6/1/2020.[Table: see text]
A young man with shortness of breath
Authors: Michael Blank, Oliver Collas, Hassan Hirji
Journal: BMJ (2021)

A man in his 30s presented to the emergency department with a three week history of chest pain (worse on inspiration), cough, shortness of breath, and discomfort in his left groin. He had been admitted six weeks earlier with deep vein thrombosis of the right femoral vein and cellulitis in the left foot (with a fully sensitive Staphylococcus aureus bacteraemia); he was treated with antibiotics until discharge but was non-compliant with anticoagulation on discharge. He reported weight loss of 5 kg over the past two months. He was an injecting drug user of heroin, most recently using both his groins as injection sites—although he said he previously used most of his other veins—and had been a smoker of 150 g of tobacco (roll-up) a week for 14 years.

On examination, he was alert, had a temperature of 38°C, oxygen saturations 99% on room air, respiratory rate 36 beats/min, pulse rate 91 beats/min, and blood pressure 98/64 mm Hg. He had no palpable lymphadenopathy and no added heart sounds. He had reduced air entry and dull percussion on the left side of his chest. He …
Safety and Efficacy Trial of Escalation of Plerixafor for Mobilization of CD34+ Hematopoietic Progenitor Cells (HPCs) for Globin Gene Transfer in Patients with Sickle Cell Disease
Authors: Farid Boulad, Tsiporah B. Shore, Koen Van Besien, Danielle Guarneri, June Greenberg, Caterina Minniti, Sylvie wiener Fedus, Fabiana Perna, Xiuyan Wang, Isabelle Riviere, Michel Sadelain, Patricia Shi
Journal: Blood (2017)