tbuckley/cabot-search huggingface dataset:
Predictive value of lymphocyte immunophenotyping (LIP) in primary central nervous system lymphoma (PCNSL).
Authors: Axel Berthelot, Celine Boucard, Gregorio Petrirena, Chantal Campello, Olivier L. Chinot, Emeline Tabouret
Journal: Journal of Clinical Oncology (2021)

2063 Background: Immunity plays an important role in PCNSL development. PCNSL predictive factors need to be improved. Objective: to evaluate the characteristics and predictive value of blood LIP in PCNSL patients. Methods: we prospectively analyzed blood LIP in all newly PCNSL referred to our institution between December 2013 and January 2020. LIP analysis was performed before rituximab and chemotherapy administration. The clinical, radiological, histological, biological and treatment data were retrospectively collected. Results: fifty-three patients were included with a median age of 69.7 (range 21.7-87.5). Median KPS was 60 (range 30-100). All patients presented with cerebral involvement, 13 (25%) with cerebrospinal fluid extension and 8 (15%) with ocular extension. Thirty-four patients (62%) benefited of steroid treatment at the time of LIP. Patients characteristics did not differ depending on steroid intake. Forty-eight patients (95%) benefited of polychemotherapy with high-dose methotrexate as first line treatment. We observed three (6%) lymphoproliferative syndromes on the LIP and 33 patients (64%) presented with one or several lymphopenias: 21 (40%), 24 (46%) and 9 (17%) NK, T and B lymphopenias respectively. Only 11 patients (21%) had normal LIP. Median CD4/CD8 ratio was 2.11 (range 0.54-9.11). This ratio was normal, low or high in 27%, 28% and 44% of patients respectively. The presence of steroids did not impact LIP results, including CD4 (p = 0.475) or CD8 (p = 0.726) rates and CD4/CD8 ratio (p = 0.727). Complete or partial responses, stable and progressive disease (PD) were observed in 24 (50%), 10 (21%), 4 (8%), and 10 (21%) patients respectively. CD4/CD8 ratio tended to be different between refractory (PD patients) and non-refractory patients (p = 0.077). A ROC curve analysis was performed with an AUC of 0.684 allowing the selection of a CD4/CD8 ratio cutoff of 1.97 with a sensibility, specificity, positive predictive value, and negative predictive value to identify refractory patients of 90%, 55%, 35% and 95% respectively. Median progression-free survival (PFS) and overall survival (OS) were 14.7 (95%CI: 6.5-22.9) and 43.2 (95%CI: 21.6-64.9) months, respectively. In multivariate analyses, adjusted by KPS, a CD4/CD8 ratio &gt; 1.97 was associated with poor PFS (p = 0.043, HR = 3.32 [1.02-4.88]) and tended to be associated with worse OS (p = 0.064). Conclusions: LIP at baseline may predict refractory disease and exhibits a prognostic value in PCNSL patients.
Erectile Function Following Surgery for Benign Prostatic Obstruction: A Systematic Review and Network Meta-analysis of Randomised Controlled Trials
Authors: Alexander Light, Dost Jabarkhyl, Peter Gilling, Gincy George, Mieke Van Hemelrijck, Ben Challacombe, Sachin Malde, Rick Popert, Prokar Dasgupta, Oussama Elhage
Journal: European Urology (2021)
Type of 5-fluorouracil and risk of cardiovascular events in early-stage colon cancer.
Authors: Wen Kuan Huang, Lai-Chu See
Journal: Journal of Clinical Oncology (2021)

e15596 Background: Older patients with colorectal cancer are at increased risk of developing cardiovascular (CV) disease. 5-FU-based chemotherapy was found to increase CV morbidity; however, whether CV risks differ among different fluorouracil types, including infusional 5-FU, capecitabine, and tegafur-uracil (UFT), remains unclear. We aimed to assess the association between CV morbidities, including myocardial infarction and heart failure, and different 5-FU types in patients with colorectal cancer. Methods: We evaluated patients from Taiwan Cancer Registry linked with national health insurance research database with stage I to III colorectal cancer between January 1, 2004, and December 31, 2014. A multivariate Cox proportional model with age as the time scale was conducted for comparison. UFT alone was set as the control group. Results: In the cohort of 29176 patients (median [interquartile range] age, 65 [43-79] years), 2241 (7.6%) received UFT, 25181 (86.3%) received infusional 5-FU or capecitabine, 1754 (6%) received mixed. Overall, 290 patients were diagnosed with myocardial infarction (1.78 per 1000 person-years) during a median (interquartile range) follow-up of 5.5 years. Compared with those received UFT, those using infusional 5-FU or capecitabine showed no increased risk of myocardial infarction (weighted hazard ratio [HR], 0.84; 95% CI, 0.57-1.24). There were 376 patients diagnosed with heart failure, corresponding to 2.3 per 1000 person-years. The risks of heart failure between the UFT group and infusional 5-FU/capecitabine were similar (weighted HR, 0.9; 95% CI, 0.62-1.31). Conclusions: In this study, we did not observe any increased CV risk using infusional 5-FU or capecitabine compared with UFT alone use.
Outcomes in AML patients receiving HMA + venetoclax combination with prior HMA exposure.
Authors: Bakos Keegan Jonathan, Dena Blanding, Christopher Andrew Rangel, Sarah Pasyar, Elizabeth Goodwin Hill, James Davis, Irl Brian Greenwell, Praneeth Baratam, Brian T. Hess
Journal: Journal of Clinical Oncology (2021)

e19011 Background: Venetoclax (Ven) is a BCL-2 inhibitor approved in combination with hypomethylating agents (HMAs) in newly diagnosed AML patients who are not candidates for intensive induction based on impressive response rates (CR+CRi of 66.4%) and median overall survival (14.7 months) compared to HMA therapy alone (DiNardo CD, NEJM, 2020). Ven was also used in combination with 10 days of a HMA (Decitabine) in a phase II study. In the subgroup of patients with relapsed AML, some of which previously received HMA, the ORR, CR+CRi, and median OS were 62%, 42%, and 7.8 months respectively. (DiNardo CD, Lancet, 2020). To our knowledge there are no studies specifically looking at patients with AML receiving HMA + Ven with previous exposure to a HMA agent. Methods: We conducted a single center retrospective study of AML patients who received HMA + Ven therapy after previously receiving a HMA agent. Baseline demographic, clinical, laboratory, pathology, and outcomes data were collected by retrospective chart review. Response criteria was determined by 2017 ELN recommendations. Kaplan Meier was constructed to summarize time to event data. Results: A total of 17 patients were identified that met these criteria. 7 patients (41%) had progressed on prior HMA treatment, 11 patients (65%) received prior intensive chemotherapy, and 5 patients (29%) received previous Allogenic SCT prior to HMA+Ven therapy. 10 patients (59%) had either a TP53 mutation or 17p deletion and 11 patients (65%) had complex cytogenetics (≥ 3 cytogenetic abnormalities). Other patient characteristics are included in table below. For the entire cohort, the ORR (CR, CRi, PR) was 41% and the CR/CRi rate was 6%; The ORR in the following subgroups for previous HMA failure, TP53 mutation/17p deletion, and complex cytogenetics were 14%, 30%, and 36% respectively. The median Progression free survival and overall survival for the entire cohort was 2 months (1-4 months 95% CI) and 3 months (1-5 months, 95% CI) respectively. 15 patients (88%) were deceased and all deaths were attributed to AML (12/15) or infection (3/15). None of the patients went on to receive an Allogenic SCT. Conclusions: Although a limited sample size which includes many patients with a TP53/17p aberration, complex cytogenetics, Allogenic SCT relapse, and/or heavily pre-treated AML, this data describes poor outcomes in patients receiving HMA+Ven after previous HMA exposure. Patients with previous HMA failure in particular had a poor response rate. None of the patients received 10 day decitabine and it is unclear if this had any effect on the results. It would be beneficial to supplement this data with experience from multiple centers. Patient Characteristics (N = 17).[Table: see text]
Clinical utility of FDG PET-CT in stage 1 and advanced testicular seminoma.
Authors: Ciara Conduit, Michael S Hofman, Jeremy Howard Lewin, Guy C. Toner, Ben Tran
Journal: Journal of Clinical Oncology (2021)

5027 Background: Testicular seminoma is highly curable; however, treatments can cause long-term morbidity in survivors. Following chemotherapy for advanced seminoma, positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose together with computerised tomography (PET-CT) can identify patients with residual masses who do not need additional treatment. Its role in detecting recurrence during active surveillance, particularly in patients with small indeterminate masses, is unknown. We assessed the clinical utility of PET-CT in testicular seminoma undergoing active surveillance for stage 1 disease and following curative-intent treatment for advanced disease. Methods: An institutional database was interrogated to identify patients with testicular seminoma who underwent PET-CT between 2000-2020. Demographic, clinicopathological, PET-CT findings and outcome data were retrieved. The positive predictive value (PPV) of PET-CT for correctly identifying disease recurrence was calculated, with disease recurrence (true positive) defined as progressive radiological change, response to treatment or histological confirmation. Negative predictive value (NPV) was calculated for correctly identifying non-recurrence (true negative) at 24-months post PET-CT. Results: We identified 193 PET-CT in 181 stage 1 patients. Of these, 18 (10%) PET-CT were positive, with all correctly diagnosing recurrence, PPV 100%. Of the 138 negative PET-CT with at least 24 months follow up, 5 recurrences developed, NPV 96%. In the subset of PET-CT conducted for suspicion of recurrence in stage 1 patients (n = 71: abnormal imaging n = 65, elevated markers n = 4, other clinical suspicion n = 2), 16 (23%) PET-CT were positive, with all correctly diagnosing recurrence, PPV 100%. In this subset, the NPV is 93% at 24 months (3 recurrences in 44 negative PET-CT). We also identified 154 PET-CT in 77 post-treatment, advanced stage patients. Of these, 69 (45%) PET-CT were positive, with 51 correctly diagnosing recurrence, PPV 74%. Of the 66 negative PET-CT with at least 24 months follow up, 5 recurrences developed, NPV 92%. In the subset of PET-CT performed for suspicion of recurrence following treatment for advanced disease (n = 61: abnormal imaging n = 49, elevated markers n = 5, other clinical suspicion n = 7), 41 (67%) PET-CT were positive, with 36 correctly diagnosing recurrence, PPV 88%. In this subset, the NPV is 94% at 24 months (1 recurrence in 17 negative PET-CT). Conclusions: At our centre, PET-CT has a very high PPV for recurrence, particularly in stage 1 disease, and a very high NPV for non-recurrence in all disease settings. In the subset of PET-CT performed for suspicion of recurrence, PPV is &gt; 88% and NPV is &gt; 93%. The role of PET-CT should be considered in patients with suspicion of recurrence where it may prevent over-treatment in up to 70% patients in stage 1 or 30% in advanced disease.
Augmenting machine learning algorithms to predict mortality using patient-reported outcomes in oncology.
Authors: Ravi Bharat Parikh, Jill Schnall, Manqing Liu, Peter Edward Gabriel, Corey Chivers, Michael Draugelis, Will Ferrell, Caryn Lerman, Justin E. Bekelman, Jinbo Chen
Journal: Journal of Clinical Oncology (2021)

1510 Background: Machine learning (ML) algorithms based on electronic health record (EHR) data have been shown to accurately predict mortality risk among patients with cancer, with areas under the curve (AUC) generally greater than 0.80. While patient-reported outcomes (PROs) may also predict mortality among patients with cancer, it is unclear whether routinely-collected PROs improve the predictive performance of EHR-based ML algorithms. Methods: This cohort study included 8600 patients with cancer who had an outpatient encounter at one of 18 medical oncology practices in a large academic health system between July 1 st , 2019 and January 1 st , 2020. 4692 (54.9%) patients completed assessments of symptoms, performance status, and quality of life from the PRO version of the Common Terminology Criteria for Adverse Events and the Patient-Reported Outcomes Measurement Information System Global v.1.2 scales. We hypothesized that ML models predicting 180-day all-cause mortality based on EHR + PRO data would improve AUC compared to ML models based on EHR data alone. We assessed univariate and adjusted associations between each PRO and 180-day mortality. To train the EHR-only model, we fit a Least Absolute Shrinkage and Selection Operator (LASSO) regression using 192 EHR demographic, comorbidity, and laboratory variables. To train the EHR + PRO model, we used a two-phase approach to fit a model using EHR data for all patients and PRO data for those who completed assessments. To test our hypothesis, we compared the bootstrapped AUC, area under the precision-recall curve (AUPRC), and sensitivity at a 20% risk threshold for both models. Results: 464 (5.4%) patients died within 180 days of the encounter. Decreased quality of life, functional status, and appetite were associated with greater 180-day mortality (Table). Compared to the EHR-only model, the EHR + PRO model significantly improved AUC (0.86 [95% CI 0.85-0.86] vs. 0.80 [95% CI 0.80-0.81]), AUPRC (0.40 [95% CI 0.37-0.42] vs. 0.30 [95% CI 0.28-0.32]), and sensitivity (0.45 [95% CI 0.42-0.48] vs. 0.33 [95% CI 0.30-0.35]). Conclusions: Routinely collected PROs augment EHR-based ML mortality risk algorithms. ML algorithms based on EHR and PRO data may facilitate earlier supportive care for patients with cancer. Association of PROs with 180-day mortality.[Table: see text]
奇異性低流量低圧較差重症大動脈狭窄症に関する求心性左室肥大:Japanese Multicenter Aortic Stenosis Study,Retrospective Registry(JUST-R)の成績
Authors: Yamashita Eiji, Takeuchi Masaaki, Seo Yoshihiro, Izumo Masaki, Ishizu Tomoko, Sato Kimi, Suzuki Kengo, Akashi Yoshihiro, Aonuma Kazutaka, Otsuji Yutaka, Oshima Shigeru
Journal: Circulation (2014)
Polymorphisms rs4673 and rs28714259 as predictors of anthracycline-mediated cardiotoxicity in patients with breast cancer.
Authors: Dmitry Yu. Gvaldin, Natalya N. Timoshkina, Ekaterina P. Omelchuk, Larisa N. Vashchenko, Anastasia S. Ratieva, Ludmila A. Ryadinskaya, Natalia M. Tikhanovskaya, Natalia A. Abramova, Irina L. Popova, Kristina A. Novoselova, Valeriya S Myagkova, Aza A. Agieva, Maria A. Teplyakova, Faina V. Alieva, Marina M. Sergeeva, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2021)

12005 Background: Numerous pharmacogenetic studies have led to the identification of genetic polymorphisms associated not only with the development of cardiovascular disease, but also increase the risk of complications due to the use of anthracycline drugs, widely used in the treatment of cancer. The purpose of this study was to study the frequency of rs4673 and rs28714259 and possible associations with the risk of cardiovascular changes in patients with breast cancer during anthracycline therapy (anthracycline-mediated cardiotoxicity — AMC). Methods: The study included 256 Caucasian patients (median age - 55 years) with a diagnosis of breast cancer without diagnosed cardiovascular changes, who were treated with anthracyclines at the National Medical Research Center of Oncology in 2019-2020. For genotyping of rs4673 and rs28714259, DNA was extracted from blood using DNA-sorb-B (AmpliSens, Russia) and HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphisms was confirmed by Sanger sequencing on a Genetic Analyzer 3500 (ABI, USA). Results: During the follow-up period 21 (8.2%) patients were diagnosed with signs of subacute (changes developed within several weeks after the last course of therapy) or early chronic AMC (changes developed within a year after completion of anthracycline therapy). In the group of patients without AOC the allelic frequency of rs4673 (c.214T &gt; C CYBA) was 0.38, the frequency of genotypes C/C – 0.4, C/T – 0.43, and T/T – 0.17. In the same group, the frequency of the A allele rs28714259 was 0.07, the frequency of the G/G genotypes – 0.87, G/A – 0.13, and A/A – 0. The prevalence of genotypes T/T rs4673 and allele G rs28714259 in a cohort of Russian patients differed from the European population (p = 0.014 and p = 0.05, respectively). The risk of cardiovascular changes on the background of anthracycline therapy increased in the presence of the rs4673 polymorphic allele by 6.49 times, in the case of the G/A and A/A rs28714259 genotypes - by 3.27 times. The results of the ROC-analysis suggested high quality of the tests based on the dominant models rs4673 and rs28714259 (AUC was 71.9% and 76.3% correspondingly). Conclusions: In this study the prognostic efficiency of the genetic markers rs4673 and rs28714259 was shown for the prompt detection of the risks of AMC development in the management of cancer patients. However, population characteristics should be taken into consideration for risk assessment.
BEGONIA: Phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first-line metastatic triple-negative breast cancer (mTNBC): Addition of arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062).
Authors: Peter Schmid, Ana Tablante Nunes, Hannah Dry, Rachel Dougherty, Vatsala Karwe, Urban J. Scheuring
Journal: Journal of Clinical Oncology (2021)

TPS1105 Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The combination of immune checkpoint inhibitors with chemotherapy shows promise, but only a subset of pts with mTNBC derive benefit, highlighting the need for new combinations. BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of D, an anti–PD-L1 monoclonal antibody, with or without P, in combination with novel oncology therapies as first-line treatment for mTNBC (NCT03742102). Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (TROP2) IgG1 monoclonal antibody, a stable tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. Dato-DXd displayed encouraging clinical activity with a manageable safety profile in heavily pretreated pts with metastatic NSCLC in the phase 1 TROPION-PanTumor01 (NCT03401385) study. TROP2 is highly expressed on breast and other epithelial tumors, and a TROP2 ADC showed activity in heavily pretreated pts with mTNBC (Bardia, NEJM 2019). Methods: Eligible female pts are aged ≥18 years with untreated unresectable, locally advanced or mTNBC, ≥12 months since prior taxane therapy, ECOG PS 0/1, adequate organ function, and ≥1 nonirradiated measurable lesion. For Arm 7, pts are excluded if they have clinically significant corneal disease, history of interstitial lung disease/pneumonitis, underlying pulmonary disorder, or prior treatment with an ADC containing a topoisomerase I inhibitor. Arm 7 will evaluate D (1120 mg) + Dato-DXd (6 mg/kg) given intravenously every 3 weeks until disease progression or unacceptable toxicity. Part 1 of each arm includes a total of 30 pts with a safety run-in (n=6) to observe dose-limiting toxicities, identify the recommended phase 2 dose (RP2D), and detect an efficacy signal for part 1 expansion. The primary endpoint of part 1 is safety and tolerability. Secondary endpoints include investigator-assessed objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Once the RP2D has been established for part 1, a futility analysis will be performed with an option to expand the cohort to an additional 27 pts if expansion criteria are met. The primary endpoint for part 1 is ORR. Tumors will be assessed every 6 weeks per RECIST v1.1. Kaplan-Meier analysis will be used for PFS and OS. PD-L1 and TROP2 expression will be assessed by immunohistochemistry. Enrollment is ongoing. Clinical trial information: NCT03742102 .
Clinicians’ perspectives on strategies to improve cross-institutional collaboration and coordination of pancreatic cancer care for rural patients.
Authors: Matthew DePuccio, Natasha A Kurien, Angela Sarna, Ann Scheck McAlearney, Aslam Ejaz
Journal: Journal of Clinical Oncology (2021)

e13532 Background: Rural pancreatic cancer patients often lack access to high-volume pancreatic cancer specialists. This lack of access can result in fragmented cancer care—when patients receive care at multiple institutions—and necessitates that specialists engage in cross-institutional collaboration. In the context of fragmented pancreatic cancer care, the strategies specialists use to facilitate collaboration across institutions are poorly understood. Methods: We conducted semi-structured interviews with cancer specialists (medical, surgical, and radiation oncologists) from a high-volume pancreas cancer center (n = 9) and rural community cancer centers (n = 11) to examine specialists’ coordination practices related to treating and co-managing pancreatic cancer patients across their respective institutions. Using qualitative methods, two of the co-authors independently coded the interview transcripts to identify themes related to cross-institutional coordination practices, noting improvement opportunities and facilitative strategies. Results: Cancer specialists described multiple practices to coordinate cross-institutional care including one-on-one phone calls and using a shared electronic medical record or secure email to exchange clinical notes. In recognizing the limitations of these practices, specialists acknowledged the need to develop and implement communication systems that could facilitate real-time discussions and information sharing between high-volume and rural specialists to coordinate diagnostic and treatment plans. Cross-institutional virtual tumor boards were viewed as a potentially useful approach to foster shared clinical decision-making and treatment plan development across institutions, but specialists perceived that logistical, institutional, and technological challenges could limit the use of this approach. Regardless, specialists indicated that cross-institutional virtual tumor boards could help disseminate treatment recommendations as well as identify barriers to care for mutually-shared rural cancer patients. Specialists also indicated that a dedicated patient navigator could help facilitate cross-institutional coordination by bridging communication between specialists while also assisting cancer patients with issues related to housing, transportation, scheduling, and treatment finances. Conclusions: It is important for cancer specialists treating rural cancer patients to have strategies that support efficient communication and decision-making. Cross-institutional virtual tumor boards and dedicated patient navigators are two such strategies that may help facilitate collaboration between high-volume and rural cancer specialists. Future research should examine the impact of these strategies on patients receiving cancer care at multiple institutions.
The Genomic Landscape of MYD88 Wild-Type WaldenströM's Macroglobulinemia Ischaracterized By Somatic Mutations in TBL1XR1, the CBM Complex, and NFKB2
Authors: Zachary Hunter, Nickolas Tsakmaklis, Maria Demos, Amanda Kofides, Lian Xu, Gloria Chan, Jiaji Chen, Manit Munshi, Xia Liu, Joshua Gustine, Christopher Patterson, Toni Dubeau, Patricia Severns, Jorge J. Castillo, Guang Yang, Steven P Treon
Journal: Blood (2017)