tbuckley/cabot-search huggingface dataset:
Efficacy of a fully remote primary lecture series at an academic hematology and oncology fellowship program.
Authors: Sassine Ghanem, Janine Claudia Khadija Harewood, Jia-Llon Yee, Brian Campbell Jimenez, Jason Parker Gonsky
Journal: Journal of Clinical Oncology (2021)

11031 Background: 615 fellows began training in American combined hematology/oncology fellowship programs in July 2020. These new fellows face a steep learning curve. The coronavirus pandemic has significantly affected how we learn, with programs having to convert most collective learning to a completely virtual format. Research on the efficacy of introductory lecture series in academic hematology/oncology programs is limited especially regarding virtual formats. We introduced a virtual introductory lecture series with the goal of increasing the clinical confidence and knowledge base of first-year fellows. Methods: A once weekly remotely-delivered two-hour primer series was designed with lectures given by both third-year fellows and faculty from July-August 2020. Fellows were asked to complete pre &amp; post-test evaluations of each lecture. Evaluations included a combination of knowledge-based questions &amp; self-reported confidence assessment. Results: 14 fellows were assigned pre- and post-tests in the study. 1 fellow was excluded due to lack of participation. A total of 123 paired pre and post-tests were compared. Data analysis was performed with SPSS v 24.0 using the paired samples t-test. Pre and post-tests were graded on a scale of 0-100. The pre to post mean difference compares the mean test result of the post tests to that of the corresponding pretests. Questions were divided into 2 groups. The 1st group tested the fellow’s medical knowledge regarding the pathology while the 2nd group tested the comfort in the management, diagnosis and treatment. In the statistical analysis, these questions were defined as “Knowledge” and “Comfort” accordingly, the sum as “Complete”. A statistically significant improvement in post-test knowledge for fellows of all years was noted with a pre to post test mean difference of 12.52, P &lt;.0001. The difference was more pronounced among 1st year fellows with a pre to post test mean difference of 16.84, P &lt;.0001. A similar improvement was seen for the comfort in management questions. The post-test comfort pre to post test mean difference was 10.48, P &lt;.0001 for fellows of all years and 6.70, P &lt;.0001 for first year fellows. Conclusions: A remotely-delivered introductory lecture series for fellows in a hematology/oncology training program increases both clinical knowledge and clinical confidence in fellows of all years of training.[Table: see text]
A Response to Excessive Screening Questions
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2021)

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Molecular profiling of pancreatic neuroendocrine neoplasms (panNENs): A single-institution experience.
Authors: Ibrahim Azar, Omid Yazdanpanah, Shiva Swaroop Bongu, Mohammed Najeeb Al Hallak, W. Michael Korn, Anthony Frank Shields, Philip Agop Philip
Journal: Journal of Clinical Oncology (2021)

e16207 Background: PanNENs are rare with a heterogeneous pathophysiology and widely differing clinical course. Despite a recent update of the grading system, prognostication and prediction of response to therapy remain challenging. Somatostatin receptor aside, there are currently no predictive biomarkers or targeted agents for panNENs. Molecular profiling offers an opportunity to develop new drugs and personalize treatments. Methods: We compiled data from patients diagnosed with panNENs from Karmanos Cancer Institute between 2014 and 2020. Of the 35 patients with panNENs, 33 underwent Next Generation Sequencing (Caris Molecular Intelligence). Two tumor biopsies were insufficient for molecular analysis. Results: Of the 35 tumors analyzed, 11 were grade 1, 18 were G2, 2 were well-differentiated G3 and 4 were poorly differentiated pancreatic neuroendocrine carcinomas (panNEC). Median age at diagnosis was 61. 21 patients identified as White, 6 as Black and 8 as other. 21 were men. 28 patients were metastatic at diagnosis. The most frequently detected molecular alteration was MEN1 mutations (11 G1, 1 G1 and 1 G3). 3 G2 and 2 G3 tumors expressed PTEN mutations. All 3 p53 mutations were G3, 2 of them panNEC. An FGFR3 amplification was detected in a single G1 panNEN. Her2/Neu amplification was detected in a G2 tumor. Other frequent alterations were MGMT (4), TOP2A (4), ARID1A (3), TUBB3 (3) and TSC2 (3). 3 tumors were PD-L1 positive. All tumors were TMB non-high and MMR-proficient. Conclusions: Molecular profiling of panNEN can detect targetable alterations with currently validated commercial agents. panNENs are immunologically cold. Further genomic and epigenomic profiling studies can help understand the molecular underpinnings of pathophysiology and aid in the development of biology-driven targeted therapies.
Update and external validation of a multivariable prediction model for tube feeding dependency for at least four weeks during chemoradiotherapy for head and neck cancer.
Authors: Anna C. H. Willemsen, Annemieke Kok, Laura W.J. Baijens, J. P. De Boer, Remco de Bree, Lot Devriese, Chantal M.L. Driessen, Carla M.L.- Van Herpen, F. J.P. Hoebers, Johannes H.A.M. Kaanders, Rebecca T. Karsten, Sander Van Kuijk, Roy Iqbal Lalisang, Arash Navran, Susanne R. Pereboom, Annemie M.W.J. Schols, Chris H.J. Terhaard, Ann Hoeben
Journal: Journal of Clinical Oncology (2021)

6040 Background: Patients who receive chemoradiation or bioradiation (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates, which may interfere with oral intake, leading to (temporary) tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds four weeks. In this study we aimed to update and externally validate a prediction model to identify patients in need for TF for at least four weeks, meeting the international criteria for prophylactic gastrostomy insertion. Methods: This retrospective multicenter cohort study was performed in four tertiary referral head and neck cancer centers in the Netherlands. The prediction model was developed using data from the University Medical Center Utrecht and the Netherlands Cancer Institute. The model was externally validated in patients from the Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF, initiated during or within 30 days after completion of CRT/BRT, and administered for at least four weeks. Potential predictors were retrieved from patient medical records and radiotherapy dose-volume parameters were calculated. Results: The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed significant predictive value (p &lt; 0.05) for adjusted diet at start of CRT/BRT, percentage weight change prior to treatment initiation, WHO performance status, tumor-site, nodal stage, mean radiation dose to the contralateral parotid gland, and mean radiation dose to the oral cavity. The area under the receiver operating characteristics curve for the updated model was 0.73 and after external validation 0.64. Positive and negative predictive value at 90% cut off were 80.0% and 48.2% respectively. Conclusions: This externally validated prediction model to estimate TF-dependency for at least four weeks in LAHNSCC patients performs well. This model, which will be presented, can be used in clinical practice to guide personalized decision making on prophylactic gastrostomy insertion.
Clinicopathologic features of breast cancers diagnosed in females treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.
Authors: Stephanie M Wong, Lissa Ajjamada, Anna Weiss, Ipshita Prakash, Sonia Skamene, Jean-Francois Boileau, Michael N. Pollak, Mark Basik
Journal: Journal of Clinical Oncology (2021)

567 Background: Childhood and young adult survivors of Hodgkin Lymphoma are at an increased risk of developing breast cancer, although little data exist on the characteristics and biologic subtype of breast cancers that develop in this high-risk population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all histologically confirmed breast cancers diagnosed between 1990-2016 in women treated with prior radiation therapy for Hodgkin Lymphoma ≤ 30 years of age. Clinicopathologic features of subsequent breast cancers (BC-HL) were examined and compared to breast cancers diagnosed in women with no prior malignancy (BC-NPM). The association between prior chemotherapy use and biologic subtype of BC-HL was evaluated. Results: We identified 321 breast cancers diagnosed in 257 women with a history of radiation therapy for Hodgkin Lymphoma. The median age at Hodgkin Lymphoma diagnosis was 22 years (range, 12-30 years), and nearly all BC-HL (97.9%) were diagnosed 8 or more years after radiation therapy. Overall, 56 (21.8%) BC-HL patients developed bilateral breast cancer, of which 28 (50%) were synchronous. When compared to women with BC-NPM, women with BC-HL were significantly younger at time of diagnosis (median age, 43 years vs. 60 years, p&lt;0.001) and less likely to present with ductal carcinoma in situ (8.4% vs. 14.9%, p=0.001). Patients with invasive BC-HL were more likely to have high grade (43.8% vs. 32.9%, p&lt;0.001), estrogen receptor (ER) negative breast cancer (27.7% vs. 18.2%, p&lt;0.001), although pathologic tumor size, nodal status, and stage were not significantly different from those with BC-NPM. Compared to women with BC-NPM, the majority of operable BC-HL patients underwent surgical management with mastectomy (86.5% vs. 42.5%, p&lt;0.001). In subset analysis of 102 women for which HER2 status was available, BC-HL were HER2+ in 18.7% of patients. Distribution of biologic subtype between BC-HL and BC-NPM are shown in the table below. In BC-HL patients, prior chemotherapy exposure was not associated with substantial differences in the proportion of ER+HER2- breast cancers (65.8% vs. 63.5%, p=0.82). Conclusions: Breast cancers in women treated with radiation therapy for Hodgkin Lymphoma are characterized by earlier onset and more aggressive biologic features, although the majority remain estrogen sensitive and early stage at presentation. Further studies are warranted to evaluate the use of preventive strategies in this high-risk patient population.[Table: see text]
Health care cost impact associated with adverse events (AEs) among treatments in third-line+ (3L+) relapsed/refractory follicular lymphoma (R/R FL).
Authors: Sameh Gaballa, Moshe Y. Levy, Michael Keith, Alex Wong, David Proudman, Dave Nellesen, Khalid Mamlouk
Journal: Journal of Clinical Oncology (2021)

e18836 Background: Tazemetostat, a first-in-class oral, selective methyltransferase inhibitor of enhancer of zeste homolog 2 (EZH2) activity, was approved by the US Food and Drug Administration for treatment of patients with R/R FL after demonstrating single-agent antitumor activity in patients with wild-type or mutant EZH2. Phosphoinositide 3-kinase inhibitors (PI3Kis; idelalisib, duvelisib, and copanlisib) are also indicated for 3L+ R/R FL, but these drugs are associated with serious toxicities, such as neutropenia, infection, and immune-mediated toxicities. A matching-adjusted indirect comparison (MAIC) of tazemetostat with these 3 PI3Kis was previously presented in 3L+ R/R FL, showing that tazemetostat is associated with more favorable safety, and similar efficacy compared to each of the PI3Kis. The objective of this study was to estimate the difference in AE-related health care costs for each treatment. Methods: AE-related costs were sourced from a study of costs in patients hospitalized with AEs, using oncology-specific data when available. Matching-adjusted AE incidence was multiplied by costs related to each AE. Grade ≥3 AEs with incidence ≥5% for any of the evaluated treatments were included. Cost differences were estimated per treatment episode, based on duration of exposure in the tazemetostat clinical trial (9.3 months for tazemetostat, &lt;7 months for the 3 comparators). Incidence rates were then converted to a monthly basis using an exponential curve. Results: The PI3Kis are estimated to incur $13,534 to $18,737 higher AE-related management costs per episode compared with tazemetostat. Adjusting for duration of exposure, each of the PI3Kis is project to cost $2,563 to $3,820 more per month than tazemetostat in AE-related costs. These estimates indicate that the AE-related cost impact of PI3Kis compared with tazemetostat is 3.4- to 6.1-fold higher on a per-episode basis, and 5.0- to 10.4-fold higher on a monthly basis. Conclusions: Quantifying the AE cost impact of tazemetostat based on AE incidence rates estimated by MAIC analysis adjusts for population differences and allows for more direct cost savings comparisons when accounting for duration of exposure to different treatments. Patients with 3L+ R/R FL who are treated with tazemetostat are estimated to incur substantially lower AE-related costs compared with PI3Kis (idelalisib, duvelisib, and copanlisib). [Table: see text]
Facility contextual effects influence the use of adjuvant immunotherapy in stage III melanoma.
Authors: Laura D. Leonard, Robert J. Torphy, Laurel Beaty, Thiago B. de Araujo, Kathryn Colborn, Felix Ho, Arthur Albuqueque, Karl D. Lewis, Rene Gonzalez, Theresa Michelle Medina, Martin McCarter, Camille L. Stewart, Ana Gleisner
Journal: Journal of Clinical Oncology (2021)

e18758 Background: There are now numerous effective adjuvant immunotherapy options for surgically resected stage III melanoma including novel checkpoint inhibitors and targeted therapies. Current guidelines recommend that the decision to treat stage III melanoma with adjuvant immunotherapy should be individualized and based upon disease burden, patient goals and anticipated therapy tolerance. We sought to assess the contribution of patient, tumor and facility factors on the implementation of immunotherapy in patients with surgically resected stage III melanoma. Methods: Using the National Cancer Database (NCDB), patients from 2012-2017 that underwent excision and were found to have a positive sentinel node were identified. A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and facility variables on the probability of immunotherapy. Reference Effect Measures (REM) were used to estimate the variation in immunotherapy use due to unmeasured facility factors (contextual effects) after adjusting for measured patient, tumor, and facility variables. Results: From 2012 to 2017, the percent of patients with stage III melanoma treated with adjuvant immunotherapy increased from 23.7% to 38.5% (p &lt; 0.05). Overall, younger patients and patients with private insurance were more likely to receive immunotherapy. Tumor factors associated with increased use of adjuvant immunotherapy included increasing depth, mitotic rate ³1, ulceration, lymphovascular invasion (LVI), and undergoing a completion lymph node dissection (CLND). Additionally, treatment at a facility with a surgical volume &lt;190 cases/year was associated with increased immunotherapy use. However, the width of the 90% REM range for unmeasured facility effects exceeded that of the measured facility, tumor, time, and patient demographics suggesting that contextual effects had a higher contribution to the variation in immunotherapy use. Conclusions: Our analysis suggests that uninsured patients and patients with government insurance (Medicaid and Medicare) are not receiving immunotherapy at the same frequency as privately insured patients with the same tumor characteristics treated at the same facility. Lastly, compared to known patient, tumor and facility factors, institutional contextual effects were the major drivers of the implementation of immunotherapy.[Table: see text]
The efficacy and safety of EGFR-TKI combined with chemotherapy in NSCLC patients with EGFR co-mutation with other oncogenic alterations.
Authors: Wenhua Zhao, Wei Jiang, Hongtu Qiu, Aiping Zeng, Xiangqun Song, Shaozhang Zhou, Ruiling Ning, Cuiyun Su, Huilin Wang, Jianbo He, Yun Zhao, Liping Tan, Qitao Yu
Journal: Journal of Clinical Oncology (2021)

e21077 Background: Previous studies indicated primary resistance to EGFR-TKIs might occur in EGFR co-mutation with other oncogenic alterations. However, the optimal therapeutic regimen for advanced NSCLC with EGFR co-mutation was still unknown. This respective observation study aimed to assess the efficacy and safety of the combination therapy with EGFR-TKI and chemotherapy in this sub-population. Methods: In this retrospectively study, from March 2017 to November 2019 advanced NSCLC patients with EGFR mutation detected using next-generation sequencing targeting 59 genes were screened for eligibility. We included patients of EGFR co-mutation with other oncogenic alterations receiving EGFR-TKI monotherapy or TKI plus chemotherapy as first-line therapy. The primary outcome was objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Disease control rate (DCR) and safety profile were considered to be the secondary endpoints. Results: Total 48 patients were enrolled. Among patients with concomitant mutation, the combination of chemotherapy with TKI was found to prolong mPFS (12.5 vs 7.3 months; HR, 0.38; 95%CI: 0.17-0.81; P = 0.012) compared with TKI monotherapy, with a trend of longer mOS (27.0 vs 22.4 months; HR, 0.40; 95%CI: 0.15-1.05; P = 0.062) and higher ORR (68.4% vs 44.8%, P = 0.113). The DCR were 100% in combination group and 93.1% in monotherapy group (P = 0.99). A proportion of 13.8% patients reported grade≥3 treatment-related adverse events in monotherapy group and 36.8% in combination group. Conclusions: EGFR co-mutation with other oncogenic alterations associated with poor treatment outcome with EGFR-TKI monotherapy. The combination of EGFR-TKI and chemotherapy was effective in this sub-population and side-effects were tolerable. The outcomes of this study should be confirmed by prospective clinical trials in future.
Outcomes of curative intent treatment in advanced gynecological cancer with recurrent, distant lymph node, or visceral organ metastasis: Retrospective study from a single community center.
Authors: Sujatha Narayanamoorthy, Yunhong Wu, David Berlach, Yiqing Xu
Journal: Journal of Clinical Oncology (2021)

e17566 Background: Uterine, cervical and ovarian cancers with isolated recurrences in the pelvic, para-aortic or distant lymph nodes, such as axillary, supraclavicular lymph node, or visceral organs, are uncommon conditions. The standard care is palliative systemic chemotherapy. We hypothesized that combined modality treatment (CMT) incorporating surgery or radiation for curative intent may increase local disease control and delay or mitigate further distant metastasis, thereby increase overall survival (OS). Methods: We retrospectively reviewed characteristics and outcomes of patients who had localized recurrence of gynecological malignancies and who were treated with an aggressive approach of salvage chemotherapy + radiation +/- surgery or radiofrequency ablation. Results: We identified 23 patients, including 6 cervical, 14 uterine and 3 ovarian cancer patients who were treated from 2005 to 2021. The mean age was 68. About 47.8% patients had advanced stages of disease at diagnosis (stage 3+4). Serous carcinoma (n = 7, 30.4%) was the most common uterine cancer pathology. All patients received curative intent therapy at initial diagnosis. The first recurrence sites are shown in the table, and the visceral organs involvement were liver, gluteal muscle, etc. The recurrence was within previous radiation field in 9 patients (39.1%) and outside radiation field in 12 (52.1%). 16 patients had local radiation + chemo, 6 had systemic chemo only and 1 had radiation only (see table below). Only 13 patients had a second recurrence, including 5 from the previous systemic treatment only group. Seven had local recurrence only and all received local therapy. Six patients eventually developed wide spread disease, and 2 died. After a median follow up of 56 months (range 22 to 186 months), 17 patients were alive (4 lost for follow up), and 15 had no evidence of disease (NED). The median time to first recurrence was 14.5 m [Interquartile range (IQR), Q1, Q3 to be 7, 19]. The PFS for those patients who had only 1 recurrence was 41.5 m (IQR 21, 63). The PFS for those who had the second recurrence until the next progression was 15 months (IQR 9, 37). The overall survival in all patients was 56 m (IQR 39, 71). Conclusions: A curative intent, salvage CMT protocol for advanced GYN cancer patients who develop isolated local or distant recurrence may have a therapeutic advantage. It renders a longer PFS and OS than those from systemic therapy alone reported in the historical data.[Table: see text]