tbuckley/cabot-search huggingface dataset:
Patient-specific meta-analysis of 3 validation studies of the 12-gene colon cancer recurrence score assay for recurrence risk assessment after surgery with or without 5FU and oxaliplatin.
Authors: Greg Yothers, Alan P. Venook, Takeharu Yamanaka, Yan Lin, Michael Crager, Calvin Y. Chao, Frederick L Baehner, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2021)

3599 Background: The 12-gene Oncotype DX Colon Recurrence Score assay is a clinically validated genomic assay that evaluates recurrence risks in stage II and stage III colon cancer patients independent of clinical-pathologic features. Improved colon cancer care has reduced recurrence rates since the late 1990’s. Methods: Pre-specified patient-specific meta-analysis methods were used to estimate 1-, 3- and 5-year recurrence risk combining the 12-gene colon recurrence score (RS) validation studies CALGB 9581, NSABP C-07 and SUNRISE. Cox models had effects for RS result, number of nodes examined (&lt;12 or ≥ 12), T-stage, MMR status, and stage (II, IIIAB or IIIC). Baseline cumulative hazard estimates used the latest two studies to reflect current medical practice. Estimates for surgery, surgery+5FU and surgery+5FU+oxaliplatin treatment were provided by integrating stage-specific 5FU hazard ratios from a meta-analysis of the QUASAR study (2007) and a pooled analysis of NSABP studies (Wilkinson 2010), and oxaliplatin treatment effect estimates from NSABP C-07. Recurrence risk with 5FU alone was not estimated for MMR-deficient patients due to expected lack of 5FU efficacy in these patients (Sargent 2010). Results: In the overall population of 2,179 patients, 55%, 32% and 13% were Stage II, IIIA/B and IIIC, 63% had ≥12 nodes examined, 90% were T3, and 88% were MMR proficient. Median RS result was 31 (IQR 23–39). RS result and each clinical-pathologic factor contributed independent prognostic information (meta-analysis Wald tests, all p&lt;.001). Risk estimates are generally lower than previous RS report risk estimates. For patients with pathological stage II, T3, MMR-proficient tumors with ≥12 nodes examined, approximately 40% are expected to have 5-year recurrence risk ≤10% with surgery alone based on the distribution of RS results. The table shows example 5-year recurrence risk estimates for specific RS results and clinical-pathologic characteristics. Conclusions: The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.[Table: see text]
A phase II trial of pembrolizumab and poly-ICLC in patients with metastatic mismatch repair-proficient colon cancer.
Authors: Nabin Raj Karki, Kulsum Bano, Sadek Ramses, Asha Nayak
Journal: Journal of Clinical Oncology (2021)

e15552 Background: Single agent programmed cell death protein 1 (PD1) inhibitor is ineffective against mismatch repair proficient (MMRp) colon cancer with response rates in single digits. Polyinosinic-Polycytidylic (Poly-ICLC) is a synthetic double stranded ribonucleic acid that generates inflammatory response increasing epitope recognition, develops tumor reactive T cells and induces interferon production which increases PD-L1 expression. In this trial, we test the effectiveness of combination of poly-ICLC and pembrolizumab in MMRp metastatic colon cancer. Methods: In this open label, single arm, single institution, phase 2 study, we enrolled 12 MMRp metastatic colon cancer patients from 1/25/2019 to 2/10/2021. Eligible patients had histologically confirmed MMRp metastatic colon cancer, ECOG 1-2 and progression on at least 2 lines of therapy. Treatment (Tx) consisted of Pembrolizumab (200 mg q3 weeks) and poly-ICLC (2 mg twice weekly, 3 days apart) for 1 year of treatment. Tx continued until progression, discontinuation or withdrawal. The primary endpoint was objective response rate by RECIST 1.1. Secondary endpoints included duration of response, adverse event profiling, progression free survival (PFS) and overall survival (OS). Intention-to-treat analyses (ITT) included all patient receiving at least one dose of the study agent. Results: 12 patients with median age 68.5 years (range 54-75) and 33% (4/12) male had been enrolled till 2/10/2021. Objective response rate was 8.3% (1 patient had partial response). The duration of response was 196 days. Among these 12 patients, median PFS was 63.5 days and median OS was 196 days. Treatment related adverse events of any grade were reported in 12/12 (100%) patients with the most common toxicities being nausea, vomiting, anorexia, dehydration and dizziness. 3/12 (25%) had serious (grade ≥ 3) toxicities and one patient died after experiencing leukocytosis, dehydration and hyperbilirubinemia attributed to the trial drugs. Conclusions: Poly-ICLC was not effective in combination with pembrolizumab for MMRp metastatic colon cancer in 3rd line setting and it did not seem to improve response rates to immunotherapy. Novel strategies for stimulating immunogenicity of cold tumors are needed. Clinical trial information: NCT02834052.
Effect of Right Atrial Isthmus Ablation on the Occurrence of Atrial Fibrillation
Authors: Ashish Nabar, Luz-Maria Rodriguez, Carl Timmermans, Adri van den Dool, Joep L. R. M. Smeets, Hein J. J. Wellens
Journal: Circulation (1999)

Background —The goal of this study was to test the hypothesis that the occurrence of atrial fibrillation (AF), in at least some patients with coexisting type I atrial flutter (AFL), is based on macro-reentry around the tricuspid valve orifice, including the right atrial (RA) isthmus, by evaluation of AF recurrences after successful ablation of AFL. Methods and Results —Eighty-two consecutive patients with type I AFL, with or without concomitant AF, underwent radiofrequency ablation (RFA) of the RA isthmus by an anatomical approach. The results were analyzed in 4 groups of patients: group 1 (only AFL; 29 patients), group 2 (AFL &gt;AF; 22 patients), group 3 (AF &gt;AFL; 15 patients), and group 4 (developing AFL while receiving class IC antiarrhythmic drug therapy for AF, the “class IC atrial flutter”; 16 patients). In all groups, RFA of type I AFL was performed with a high (≥93%) procedural success rate. In group 1, only 2 patients (8%) had AF after (18±14 months) AFL ablation. These figures were 38% (20±14 months) and 86% (13±8 months) in groups 2 and 3, respectively. Group 4 patients (4±2 months) had a 73% freedom of AF recurrences with continuation of the class IC agent. Conclusions —The low incidence of new AF during long-term follow-up after RFA of type I AFL makes it unlikely that radiofrequency lesions promote the development of AF. The impact of isthmus ablation on AF recurrences differs according to the clinically predominant atrial arrhythmia and suggests a possible role of the RA isthmus in the occurrence of AF in some patients. Ablation of class IC atrial flutter in patients with therapy-resistant AF is a novel approach to management of this patient subset. Careful classification of AF patients plays a role in the selection of the site of ablation therapy.
Secondary hemophagocytic lymphohistiocytosis (HLH): Five years’ experience at the UTHealth McGovern Medical School at Houston, Texas.
Authors: Frances Natalia Cervoni-Curet, Adan Rios, Binoy Yohannan, Hongyu Miao
Journal: Journal of Clinical Oncology (2021)

e19578 Background: Secondary HLH in adults is associated to infections, malignancies, and autoimmune disorders. HLH in children has been the basis for the management and treatment of HLH in adults. Despite their clinical similarities there are fundamental differences. Children’s HLH is caused by gene mutations in granule-mediated cytotoxicity while secondary HLH does not have known apparent genetic causes. This may affect the clinical outcomes based in how we approach the diagnosis and management of secondary HLH in adults. Methods: We reviewed 49 cases of secondary HLH at our institution over a five-year period. Patients median age was 47 years, with 31 males, 18 females. Fifteen were Caucasian, 10 Asians, 8 African American and 15 Hispanics. One was not specified. Results: Fever, hyperferritenemia and cytopenia correlated with 100% elevation of sCD25R, the most important biomarker of HLH. Patients with these three criteria were urgently treated with dexamethasone-etoposide (HLH-94 protocol) or dexamethasone alone (autoimmune related) while completing identification of other criteria described in the pediatric population together with treatment of the secondary cause. Conclusions: Secondary HLH is not rare. Etoposide and dexamethasone (preferred dose:40 mg total/day initially) are the most important current therapeutic approaches. Secondary HLH must be treated urgently and independently of the secondary cause. Treatment should not be delayed awaiting results of sCD25R, NK-cell activity and presence of hemophagocytosis in the bone marrow (often absent). Further work needs to be done to elucidate the physiopathology of secondary HLH.[Table: see text]
Health disparities experienced by Black Americans with multiple myeloma in the United States: A population-based study.
Authors: Samer Al Hadidi, Deepa Dongarwar, Hamisu Salihu, Rammurti T. Kamble, Premal D. Lulla, LaQuisa Hill, George Carrum, Carlos Almeida Ramos, Helen E. Heslop, Saad Zafar Usmani
Journal: Journal of Clinical Oncology (2021)

e18512 Background: Multiple Myeloma (MM) is the most common hematologic malignancy in Black Americans. Incidence and death rates for MM in Black Americans are more than double those in Whites. Our study aimed to evaluate trends of all cause in-hospital mortality among Black Americans with MM and to investigate characteristics of MM-related hospitalizations. Methods: We conducted a retrospective cross-sectional study of hospitalizations in adult patients with MM during 2008-2017 using the National Inpatient Sample (NIS), the largest all-payer inpatient care database in the US. We used joinpoint regression to assess temporal trends in the national incidence of in-hospital death. We conducted adjusted survey logistic regression to generate adjusted odds ratios to measure the likelihood of in-hospital death among MM related hospitalizations. Results: Admissions related to MM constituted 0.32% of all hospitalizations in the study period (913,967 out of 285,876,821). The prevalence of MM related hospitalizations was higher in Black Americans when compared with Whites (476.0 vs 305.6 per 100,000 hospitalizations, p &lt;0.01). In-hospital mortality with MM was higher in older patients, males, those belonging to lowest zip code quartile, and who self-paid for their treatment. Average Annual Percent Change (AAPC) showed a statistically significant decline of in-hospital mortality among all MM patients except Black Americans who had the highest inpatient mortality in 2016 and 2017. Black Americans received less autologous stem cell transplantation (ASCT) (2.8% vs. 3.8%, p &lt;0.01), more blood product transfusions (23.0% vs. 21.1%, p &lt;0.01), less palliative care consultation (4.0% vs. 4.6%, p &lt;0.01), less chemotherapy (10.8% vs. 11.2%, p &lt;0.01), and more intensive care utilization (5.3% vs. 4.3%, p &lt;0.01), when compared with Whites. Adjusted association between race/ethnicity and various outcomes confirmed observed differences [Table]. Conclusions: Black Americans with MM had the slowest improvement and highest inpatient mortality in recent years. Data suggests higher disease burden, more frequent hospitalizations, delay in accessing care and lower utilization of supportive care measures compared with White MM patients. Data highlight disparities in MM care for Black Americans necessitating a clarion call for urgent changes in health care systems.[Table: see text]
Outcomes of CNS involvement in blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Authors: Irl Brian Greenwell, James Davis, Hong Li, Deborah Soong, Justin Taylor, Andrew A. Lane, David Rizzieri
Journal: Journal of Clinical Oncology (2021)

e19043 Background: BPDCN is rare cancer commonly involving the skin and marrow. Tagraxofusp (Tag), a CD123 targeted therapy, was the first FDA approved drug for BPDCN in 2018. CNS involvement occurs in 10-60% of patients and CNS staging and prophylactic (ppx) practices are variable. The pivotal trial of Tag in BPDCN did not require CNS staging and excluded those patients with known CNS involvement. Here, we describe one of the largest cohorts of BPDCN patients with known CNS involvement, including patients treated with Tag. Methods: We collected data from 4 centers on patients with CNS involvement defined by LP or imaging with high clinical suspicion. Survival was estimated via the Kaplan-Meier method with other analyses being descriptive. Results: CNS involvement was identified in 11 patients. Median age was 74 (range 51–83) and 10 were male. 5 patients had CNS staging at initial diagnosis. At time of CNS involvement, 6/11 patients had neuro symptoms. Prior to diagnosis of CNS involvement, 5 received Tag and none received CNS ppx. Of 9 patients treated for their known CNS involvement (table), one received CNS directed systemic therapy, with all others being treated with intrathecal (IT) chemotherapy. All patients treated with 3 or more doses of IT chemotherapy cleared their CSF, and survived at least 6 months from the diagnosis of CNS involvement, including two patients (#5 and 8) with large burden CNS disease and neuro symptoms. Median survival from time of diagnosis of BPDCN was 13.8 months (2.7-35.5) and from time of diagnosis of CNS involvement was 6.0 months (0.1-25.7). Conclusions: Asymptomatic CNS involvement by BPDCN is common; routine staging and ppx should be considered at diagnosis. Tagraxofusp did not appear to prevent the development of CNS disease. IT therapy effectively cleared and controlled CNS involvement in a majority of patients. IT therapy may be sufficient to control CNS disease and IT prophylaxis should be considered, including in patients on CD123 targeting therapies. Our results provide new insights into BPDCN with CNS involvement and include patients treated with recently developed novel systemic therapies.[Table: see text]
Shave biopsy of pediatric melanocytic tumors compromises staging and therapy planning.
Authors: Jessica Daley, John M. Kirkwood, Brittani Seynnaeve
Journal: Journal of Clinical Oncology (2021)

e21576 Background: Melanoma is the dominant skin cancer of pediatric patients, and accounts for 1-3% of pediatric malignancies. The prognosis for both adults and children with melanoma correlates with stage at diagnosis, and initial Breslow depth is a critical determinant. Kaplan-Meier melanoma-specific survival curves show survival rates ranging from 98% (T1a) to 75% (T4b) at 10 years for adult patients with stage I and II disease at diagnosis. Pediatric patients are known to present with thicker primary melanomas as compared to their adult counterparts. The preferred biopsy method of the American Academy is Dermatology for melanoma is excisional, however partial shave biopsy is most frequently performed in children, given its simplicity, efficiency, and often low clinical suspicion for cutaneous malignancy. Despite the ease of this biopsy technique, shave biopsy has a high rate of base transection, reducing accuracy of microstaging, which is crucial for therapy planning. Methods: Retrospective chart review evaluation of the potential effects of biopsy method on staging, surgical recommendations, and treatment approach for pediatric patients with melanocytic tumors. Results: Data was available for 91 pediatric patients with a spectrum of melanocytic tumors ranging from atypical with unknown malignant potential, to melanoma. Patient characteristics including gender, age at biopsy, biopsy method, status of biopsy margins, recommendations for re-excision, sentinel lymph node biopsy, and treatment plan were collected and analyzed. There were 48 females and 43 males with age range 1—22 years (mean 10 years). Sixty-eight of 91 (75%) tumors had a positive margin (deep, peripheral, or both) on diagnostic biopsy, 52/68 (76.5%) were obtained using shave method. Evaluating the deep margin specifically, 50/91 (55%) tumors had a positive deep margin, 46/50 (92%) of which were obtained using shave method. No tumor evaluated by punch had a positive deep margin (0/18). Of all shave biopsies, 77% had positive deep margin as opposed to only 13% using alternative biopsy methods. In 10/91 (11%) patients, surgical recommendations were changed based on inaccurate microstaging and positive deep biopsy margins, 9/10 (90%) of these patients had undergone shave biopsy. Most (8/10) patients had melanoma, the remaining 2/10 had highly atypical spitzoid tumors in which melanoma could not be ruled out. Conclusions: Pediatric patients with melanocytic tumors most commonly underwent shave biopsy as the initial diagnostic biopsy method. This method of biopsy was associated with higher incidence of positive margins at diagnosis and more aggressive definitive surgical management. These findings suggest that more routine use of excisional biopsy in pediatric patients with lesions being evaluated for malignancy could decrease the incidence of inaccurate microstaging and reduce the need for more aggressive definitive surgical management.
AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib (palbo) in postmenopausal women with ER+/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).
Authors: Sarat Chandarlapaty, Hannah M. Linden, Patrick Neven, Katarina Petrakova, Aditya Bardia, Peter Kabos, Sofia A. D. S. Braga, Valentina Boni, Alice Gosselin, Sylvaine Cartot-Cotton, Séverine Doroumian, Marina Celanovic, Patrick Cohen, Gautier Paux, Mario Campone
Journal: Journal of Clinical Oncology (2021)

1058 Background: AMEERA-1 (NCT03284957) investigates amcenestrant, an oral SERD, as monotherapy and combined with targeted therapies in ER+/HER2– mBC. Here we report data from dose escalation (Part C) and dose expansion (Part D) of amcenestrant + palbo. Methods: Patients (pts) were postmenopausal women with ER+/HER2– mBC and ≥ 6 mos prior advanced endocrine therapy (ET) or adjuvant (adj) ET resistance (relapse on adj ET started ≥ 24 mos ago or &lt; 12 mos after completing adj ET). Prior chemotherapy (≤ 1) for advanced disease was allowed; targeted therapies were not except ≤ 1 CDK4/6i in Part C. Part C assessed dose-limiting toxicities (DLTs) and aimed to establish the recommended phase 2 dose (RP2D) for amcenestrant (200 or 400 mg once daily [QD], in 28-day cycles) in combination with palbo (125 mg QD for 21 days on/ 7 days off). Safety (treatment-emergent adverse events [TEAEs] and lab abnormalities per CTCAE v4.03) and pharmacokinetics (PK) were evaluated. Antitumor activity at the RP2D for amcenestrant + palbo was evaluated in a subset of Part C pts and Part D, according to RECIST v1.1, determined locally by investigators. Results: Feb 8, 2021 data cutoff. In Part C (n = 15; 200 mg: 9; 400 mg: 6), no DLTs occurred and amcenestrant 200 mg QD was selected as the RP2D with palbo, based on PK and safety data. In the pooled safety population at the RP2D (n = 39; Part C: 9; Part D: 30), median (range) age was 59 y (33–86) with ECOG PS 0 (74.4%) or 1 (25.6%) and 2 (1–6) organs involved. Immediate prior therapy was neo/adj (41.0%, all ET resistant) or advanced (59.0%, range 1–4 lines). Median (range) exposure was 32 wks (1–66) with 59.0% pts on ongoing therapy. No amcenestrant dose reductions occurred; 25.6% had ≥ 1 palbo dose reduction. Most common non-hematological TEAEs related to amcenestrant were Grade 1–2 nausea and fatigue (17.9% each), asthenia and hot flush (10.3% each); to palbo were fatigue (30.8%), nausea (25.6%), asthenia and dysgeusia (10.3% each). Two pts discontinued due to AEs. The majority (94.9%) had neutrophil count decrease (53.8% Grade ≥ 3). Preliminary antitumor activity after at least 6 cycles of therapy (unless early treatment discontinuation) is reported in the table below. Conclusions: In pts with ER+/HER2– mBC, safety at the RP2D of amcenestrant + palbo was favorable, with no safety signals of bradycardia or eye disorders. Preliminary antitumor activity was observed (ORR: 31.4% and CBR: 74.3%). Clinical trial information: NCT03284957 .[Table: see text]
Dietary intervention influence on physical activity in the Women’s Health Initiative randomized Dietary Modification trial.
Authors: Kathy Pan, Aaron K. Aragaki, Yvonne Michael, Cynthia A. Thomson, Aladdin H. Shadyab, Linda Snetselaar, Jean Wactawski-Wende, David O. Garcia, Nazmus Saquib, Rowan T. Chlebowski
Journal: Journal of Clinical Oncology (2021)

10511 Background: In the Women’s Health Initiative (WHI) Dietary Modification (DM) randomized trial, after 8.5 years dietary intervention and 19.5 years cumulative (median) follow-up, dietary intervention participation was associated with a statistically significantly 22% lower breast cancer mortality (P = 0.02). In observational studies, physical activity has been associated with lower breast cancer risk with emerging results now indicating, compared to inactivity, any increase in physical activity has health benefits. Currently, longitudinal data on whether an intervention targeting dietary change influences other health-related behaviors as a gateway effect is limited. To evaluate whether randomization to a dietary intervention was associated with self-directed change in physical activity. Methods: In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer and baseline normal mammogram were randomized at 40 US clinical centers to a dietary intervention (19,541) or a comparison group. Dietary goals were to reduce fat intake to 20% of energy and increase intake of vegetable, fruit, and grains addressed in 18 group sessions in year 1 then quarterly. Neither randomization group received specific or ongoing instructions to increase physical activity, but physical activity was referenced in written materials given to the intervention groups in 7 of the 56 sessions. Episodes per week of moderate or vigorous recreational physical activity (MVPA) were collected at baseline and serially through 15.9 years follow-up by self-report questionnaire. Marginal longitudinal logistic regression models were used to assess physically inactive (MVPA = 0) or physically active (MVPA &gt; 0) participants by randomization group. Marginal Poisson regression models estimated mean weekly MVPA by randomization group. Results: 45.6% of participants reported 0 MVPA at baseline which largely persisted throughout follow-up. During cumulative follow-up, relative to the comparison group, dietary intervention group participation was associated with 7% lower physical inactivity rate (odds ratio [OR] 0.93 95% confidence interval [CI] 0.91, 0.95, P &lt; 0.001) and a 4% higher mean MVPA (ratio of means [RM] 1.04 95% CI 1.02, 1.06, P &lt; 0.001). The association between dietary intervention participation with higher physical activity level was stronger with increasing BMI (P-interaction 0.01) and for women with waist circumference ≥ 88 cm (P-interaction 0.02). Conclusions: In conclusion, in a randomized trial setting, a low-fat dietary pattern intervention was associated with a significantly lower physical inactivity rate and significantly higher moderate and vigorous physical activity level which could be associated with health benefits. Clinical trial information: NCT00000611 .