tbuckley/cabot-search huggingface dataset:
Efficacy of niraparib maintenance therapy in Chinese women with platinum-sensitive recurrent ovarian cancer with and without secondary cytoreductive surgery: Results from the NORA trial.
Authors: Lingying Wu, Xiaohua Wu, Jianqing Zhu, Rutie Yin, Jiaxin Yang, Jihong Liu, Jing Wang, Ziling Liu, Yunong Gao, Danbo Wang, Ge Lou, Hongying Yang, Qi Zhou, Beihua Kong, Yi Huang, Lipai Chen, Guiling Li, Ruifang An, Tao Tan, Juan Dong
Journal: Journal of Clinical Oncology (2021)

5534 Background: NORA is the first, phase III, randomized controlled trial (RCT) that demonstrated individualized starting dose regimen of niraparib, which significantly improved PFS in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC). This sub-group analysis evaluated the efficacy of niraparib maintenance therapy with and without secondary cytoreductive surgery (SCS) in PSROC. Methods: The NORA phase III RCT included adult (≥18 years) Chinese women with PSROC who were randomized in a 2:1 ratio to receive oral niraparib (n = 177) or matched placebo (n = 88). This retrospective subgroup analysis was based on the progression-free survival (PFS) of niraparib maintenance therapy in these two groups of patients with PSROC, patients with SCS, and patients without SCS. The PFS was assessed by blinded independent central review. The Kaplan-Meier (KM) estimator and log-rank test were performed to calculate the median PFS time. Results: Of the 265 evaluable patients, 69 (26.0%) patients received the SCS (niraparib, n = 48; placebo, n = 21), and 196 (74.0%) patients were without SCS (niraparib, n = 129; placebo, n = 67). Among patients with and without SCS, baseline characteristics for BRCA mutation were 26.1% vs 41.8%, complete response to last platinum-based chemotherapy were 68.1% vs 43.9%, time (6-12 months) to progression after penultimate therapy were 23.2% vs 34.7%, respectively. Treatment with niraparib led to a significant reduction of risk to disease progression compared with placebo in patients with SCS (Hazard ratio [95% CI]: 0.32 [0.13–0.78]; P = 0.0102) and without SCS (0.34 [0.23–0.50]; P&lt; 0.001). Moreover, in the subgroups of patients who received SCS, niraparib maintenance therapy had a significantly longer PFS compared with placebo (Median [95% CI]: not reached [18.33 – not estimable] vs 5.75 months [3.68 – not estimable]; P = 0.0102). This trend was also similar in the subgroup of patients who did not receive SCS (Median [95% CI]: 10.28 months [7.49 – 18.37] vs 4.90 months [3.71 – 5.52]; P &lt; 0.0001). Conclusions: The results from this retrospective sub-group analysis revealed that niraparib maintenance therapy provided significant clinical efficacy in patients with PSROC, irrespective of SCS. Clinical trial information: NCT03705156.
Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.
Authors: Ines Pires Da Silva, Judith M. Versluis, Tasnia Ahmed, Douglas Buckner Johnson, Jennifer Soon, Clara Allayous, Camille Lea Gerard, Joanna Mangana, Oliver Klein, Lisa Zimmer, Caroline Robert, Maria Grazia Vitale, Hui-Ling Yeoh, Olivier Michielin, Celeste Lebbe, Shahneen Kaur Sandhu, Christian U. Blank, Matteo S. Carlino, Alexander M. Menzies, Georgina V. Long
Journal: Journal of Clinical Oncology (2021)

9533 Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) &lt; 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head &amp; neck primary melanomas and lung metastases were more likely to have PD &lt; 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]
EPCT-03. SERIAL PLASMA AND CSF CELL-FREE TUMOR DNA (CF-TDNA) TRACKING IN DIFFUSE MIDLINE GLIOMA PATIENTS UNDERGOING TREATMENT WITH ONC201
Authors: Evan Cantor, Kyle Wierzbicki, Rohinton S Tarapore, Chase Thomas, Rodrigo Cartaxo, Viveka Nand Yadav, Ramya Ravindran, Amy K Bruzek, Jack Wadden, Clarissa May Babilla, Abed Rhaman Kawakibi, Sunjong Ji, Johanna Ramos, Alyssa Paul, Ian Wolfe, Marcia Leonard, Partricia Robertson, Andrea Franson, Rajen Mody, Hugh Garton, Yazmin Odia, Cassie Kline, Nicholas A Vitanza, Soumen Khatua, Sabine Mueller, Joshua E Allen, Sharon Gardner, Carl Koschmann
Journal: Neuro-Oncology (2021)

Abstract Diffuse midline glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n=24) underwent serial lumbar puncture (baseline, 2, 6 months) for cell-free tumor DNA (cf-tDNA) analysis at time of MRI. Additionally, patients on all arms of the trial at the University of Michigan underwent serial plasma collection. CSF collection was feasible in this cohort, with no procedural complications. We collected 96 plasma samples and 53 CSF samples from 29 patients, including those with H3F3A (H3.3) (n=13), HIST13HB (H3.1) (n= 4), and unknown H3 status/not biopsied (n=12) [range of 0–8 CSF samples and 0–10 plasma samples]. We performed digital droplet polymerase chain reaction (ddPCR) analysis and/or amplicon-based electronic sequencing (Oxford Nanopore) of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Preliminary analysis of samples demonstrates a correlation between changes in tumor size and H3K27M cf-tDNA VAF, when removing samples with concurrent bevacizumab. In multiple cases, early reduction in CSF cf-tDNA predicts long-term clinical response (&amp;gt;1 year) to ONC201, and does not increase in cases of later-defined pseudo-progression (radiation necrosis). For example, a now 9-year old patient with thalamic H3K27M-mutant DMG underwent treatment with ONC201 after initial radiation and developed increase in tumor size at 4 months post-radiation (124% baseline) of unclear etiology at the time. Meanwhile, her ddPCR declined from baseline 6.76% VAF to &amp;lt;1%, which has persisted, with now near complete response (15% tumor reduction) at 30 months on treatment from diagnosis. In summary, we present the feasibility and utility of serial CSF/plasma monitoring of a promising experimental therapy for DMG.
Adaptive adversarial neural networks for the analysis of lossy and domain-shifted datasets of medical images
Authors: Manoj Kumar Kanakasabapathy, Prudhvi Thirumalaraju, Hemanth Kandula, Fenil Doshi, Anjali Devi Sivakumar, Deeksha Kartik, Raghav Gupta, Rohan Pooniwala, John A. Branda, Athe M. Tsibris, Daniel R. Kuritzkes, John C. Petrozza, Charles L. Bormann, Hadi Shafiee
Journal: Nature Biomedical Engineering (2021)
Erratum: Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes (Nature Genetics (2005) 37 (110-111))
Authors: D J Smyth, Howson Jmm., C E Lowe, N M Walker, A C Lam, S Nutland, J Hutchings, E Tuomilehto-Wolf, J Tuomilehto, C Guja, C Ionescu-Tîrgovişte, D E Undlien, K S Rønningen, D Savage, D B Dunger, Twells Rcj., W L McArdle, D P Strachan, J A Todd
Journal: Nature Genetics (2005)
Descriptive cross-sectional analysis of lung cancer screening in inner city resident run clinic.
Authors: Meghana Singh, Radhika Kulkarni, Nerea Lopetegui-Lia, James J. Vredenburgh
Journal: Journal of Clinical Oncology (2021)

e18668 Background: Lung cancer is one of the leading causes of cancer-related morbidity and mortality. The 5-year survival rate is 19% but goes up to 57% if diagnosed at early stage. The recommendation for lung cancer screening is low-dose computed tomography (LDCT) for adults of age 55 to 80 years who have a 30 pack-year smoking history and are currently smoking or have quit in the past 15 years. Unfortunately, less than 5% of eligible patients undergo LDCT. Methods: A retrospective chart review was done for patients with any smoking history, who had internal medicine residents as their primary care provider. The data collected included baseline characteristics and the rates of LDCT scan being ordered and completed. Results: 706 medical charts were reviewed. 178 patients (25.2%) qualified for LDCT screening. The average age of patients included was 64.41 years and average BMI was 28.8 kg/m 2 . 48.3% were female and 51.6% were male. 54% were current smokers and 46% were former smokers. The ethnic/racial distribution was as follows: 19% African American, 36.5% Hispanic,16.2% Caucasian and 27.5% belonging to other groups. The primary insurance was as follows: 48.8% Medicaid, 19.6% Medicare, 25.8% private insurance and 5% were uninsured. 95 patients (53.3%) had a LDCT scan ordered and 73/95 (76.8%) completed the LDCT scan. The rate of compliance among patients based on their race/ethnicity and primary insurance is detailed in the table. Only 30% of the patients initially screened had a follow up LDCT ordered in one year. Conclusions: Low screening rate LDCT may be due to new residents not prioritizing preventative care. Patients at this clinic belong to a lower socioeconomic class with limited resources. There may be barriers to completion of the ordered test, like poor health literacy, scheduling issues, transportation, fear of being diagnosed with cancer and poor understanding of preventative health. Residents need to be educated about the importance of lung cancer screening as early detection translates into better outcomes and lower mortality. Patients need to be informed of the benefit of screening to improve compliance rate. Assessing the barriers these patients face to completing the screening test should also be carefully evaluated to better identify areas of improvement.[Table: see text]
The experience of pain among cancer patients at the University of the Philippines: Philippine General Hospital Cancer Institute—A cross-sectional study.
Authors: Harold Nathan C. Tan, Rogelio Nona Velasco, Lance Isidore Garcenila Catedral, Michael Ducusin San Juan, Corazon Ngelangel, Emiliano Calvo
Journal: Journal of Clinical Oncology (2021)

e24078 Background: Pain is one of the most common and dreaded sequelae of cancer, occurring in approximately 55% of patients. The experience of pain takes a toll on the patients’ quality of life. However, many patients do not receive adequate pain management. This study aimed to determine the prevalence of pain, its severity, and the adequacy of pain management among cancer patients in the Philippines. Methods: A cross-sectional study was conducted at a representative cancer center in the Philippines, enrolling 351 cancer patients. Pain severity was assessed using the Brief Pain Inventory-Short Form (BPI-SF) Filipino. The BPI evaluates pain severity and its impact on daily functioning (pain interference). To ascertain the adequacy of pain control, the pain management index (PMI) was calculated by subtracting the subtracting the severity of pain reported by the patient from the type of analgesic treatment received. Logistic regression analysis was conducted to evaluate the factors associated with worst pain and adequacy of pain management. Data were analyzed using Stata version 16.0, with statistical significance set at p &lt; 0.05. Results: Three hundred three cancer patients (86.3%) experienced pain. Approximately 3 out of 5 patients (n = 208) did not receive adequate pain control, and one-third of patients experienced severe pain (n = 121). Patients who reported severe pain interference (n = 110) had three times greater odds to experience severe pain (OR 3.2, 95% CI 1.82-5.61, p &lt; 0.001). Those patients who had regular follow up were 65% less likely to experience severe pain (OR 0.35, 95% CI 0.16 – 0.78, p = 0.01). Patients who used pain medications (n = 196) were 14 times more likely to experience adequate pain management (OR 14.19, 95% CI 6.53 – 30.83, p &lt; 0.001). Patients who were referred to pain service (n = 25) were seven times more likely to report adequate pain control (OR 6.62, 95% CI 2.50 – 17.56, p &lt; 0.001). Conversely, those patients who reported a severe rating on total pain interference were 75% less likely to experience adequate pain management (OR 0.25, 95% CI 0.17 – 0.35, p &lt; 0.001). Conclusions: Unexpectedly, there was a high prevalence of pain among cancer patients at a representative cancer center in the Philippines. Pain exerts a heavy toll on patients, affecting daily functioning. The undertreatment of pain discovered in this study (59% of cancer patients) is alarming. Timely pain evaluation can help identify the presence of pain and the need for appropriate use of analgesics. The assessment and management of pain is a critical component of cancer care that should not be neglected.
Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced squamous non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).
Authors: Aung Tun, Wai Lin Thein, James Gasperino, Aymen Elfiky, Elizabeth Guevara
Journal: Journal of Clinical Oncology (2019)

121 Background: Squamous Non-small cell lung cancer (NSCLC) accounts for ~30% of lung cancers, and long-term survival remains poor for advanced disease. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Three phase 3 RCTs (Keynote – 407, IMpower – 131, and Govindan et al) including 1991 patients with advanced squamous NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, or atezolizumab, while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.71 (95% CI: 0.56-0.9; P = 0.005), the pooled HR for OS was 0.84 (95% CI: 0.68-1.04; P = 0.11), and the pooled RR for ORR was 1.19 (95 CI: 0.9-1.56; P = 0.22). The pooled RRs for all-grade AEs and high-grade AEs were 1.17 (95% CI: 0.99-1.39; P = 0.07) and 1.36 (95% CI: 1.19-1.56; P = 0.0001), respectively. Conclusions: The combined chemo-immunotherapy improves PFS without significant improvement in OS &amp; ORR compared to standard chemotherapy for the first-line treatment of advanced squamous NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.
Clinical presentation of multiple myeloma by race/ethnicity and Asian subgroup in an integrated healthcare system.
Authors: Adnan Ahmed Khan, Raleigh Ayoolu Fatoki, Diane M. Carpenter, Joan C. Lo, David M. Baer
Journal: Journal of Clinical Oncology (2021)

e20012 Background: Several US studies have evaluated ethnic differences in patients with multiple myeloma (MM), but few have focused on populations other than non-Hispanic Whites and Blacks. We examined ethnic differences in a contemporary cohort of MM patients and their presenting laboratory findings in a large, insured, community-based population, including findings across Asian American subgroups. Methods: Using the Kaiser Permanente Northern California (KPNC) Cancer Registry, we identified all new cases of MM from 2010-2018 and obtained data on age, sex, race/ethnicity, Asian subgroup, and presenting hemoglobin, calcium, and estimated renal function (eGFR derived from serum creatinine) from health plan databases. Moderate to severe anemia was defined by hemoglobin &lt;10 g/dL, hypercalcemia by calcium &gt;11 mg/dL, and chronic kidney disease (CKD) by eGFR: stage 3 (eGFR 30-59) and stages 4-5 (eGFR &lt;30). MM incidence was estimated using membership denominators. Results: There were 2224 new MM cases (mean age 68y, 60% male) in 2010-2018, with an annual MM incidence of 7.9-9.8/100,000. Table 1 compares presentation by race/ethnicity. Non-Whites (45%) were more likely to present at age &lt;65 than non-Hispanic Whites (30%, p&lt;0.01). Black (43%) and Asian (39%) adults were more likely to present with hemoglobin &lt;10 g/dL than non-Hispanic Whites (27%, p&lt;0.01); Black adults were more likely to present with hemoglobin &lt;10 g/dL than Hispanic adults (31%, p=0.02). Among the primary Asian subgroups, proportions with hemoglobin &lt;10 g/dL were 38% (East Asian), 43% (Filipino), and 45% (South Asian). Blacks were more likely to present with CKD stage 4-5 (19.5%) than other races/ethnicities (p=0.04); differences between White vs non-White or Asian vs non-Asian were not significant. In Asians, 12.7% (South Asian) and 19.0% (Filipino, East Asian) presented with CKD 4-5. Asians were least likely to present with hypercalcemia (6.7%, p=0.03), and this was similar for Asian subgroups. Conclusions: We observed ethnic differences in MM presentation in a large integrated healthcare system. Blacks were more likely to have CKD stage 4-5 and hemoglobin &lt;10 g/dL than non-Hispanic Whites. Asians were more likely to have CKD stage 4-5 than non-Hispanic Whites but least likely to have hypercalcemia. This is one of the first studies to identify Asian subgroups and examine variation across East Asians, Filipinos, and South Asians. Analyses examining ethnic differences in survival among MM patients are in progress.[Table: see text]
Global trends of COVID-19 research in cancer: A scientometric study.
Authors: Noha Sharafeldin, Hai Quang Pham, Long Hoang Nguyen, Giang Thu Vu, Trang Huyen, Tham Thi Nguyen, Bach Xuan Tran
Journal: Journal of Clinical Oncology (2021)

e13549 Background: The scientific literature experienced an unprecedented growth in archived pre-prints and peer-reviewed COVID-19 related publications with regional variations making the task of synthesizing the information burdensome. This study aims to characterize global patterns and domains of COVID-19 research in cancer. Methods: We used the NIH COVID-19 portfolio and Web of Science (WOS) curated databases to extract abstracts using standard search terms for COVID-19 and cancer between Nov 1 2019 and Dec 31 2020. A total of 21,325 publications matched the study search criteria (NIH: 18,029 records; WOS: 3512 records; 204 records overlapped). We performed a descriptive analysis to calculate country citations and intercountry collaboration networks. The Jaccard similarity index was utilized to identify the most frequently co-occurring terms. Latent Dirichlet Allocation (LDA) was used for classifying publications into corresponding research topics. Results: The most productive period was May 2020 with 3,181 published articles, mean citation rate per paper was highest in Jan 2020 (1,620.5) followed by Feb 2020 (236.7), highest mean use rate in the last 12 months was March 2020. Top productive countries are classified as High and Upper Middle-income countries, 17% of research contributed by USA, 12% by China PR, and 11.4% by Italy. Linkage between top 30 productive countries show USA, Italy, and England with the highest inter-country co-ordination. Analysis of keywords co-occurring at least 5 times resulted in 12 major clusters including: 1) cancer treatment and mortality; 2) inflammation and immunology; 3) chronic diseases and co-morbidities; and 4) mental health and social psychology. Ranked topics with the highest volume of publications include 1) effect of COVID-19 on treatment outcomes; 2) individual risk factors of COVID-19 severity and mortality, and 3) novel treatment options relevant to cancer patients [Table]. Growth of articles peaked between Mar and Apr 2020 with a steady decline across all topics in Sept 2020. Conclusions: Global cancer –related research productivity peaked following the declaration of the pandemic and first wave in Mar- Apr 2020. Systematic synthesis of a large volume of COVID-19 literature revealed the global research landscape highlighting focus on the study of outcomes in cancer patients.[Table: see text]