tbuckley/cabot-search huggingface dataset:
Bladder cancer in young adults: Disease and treatment characteristics of patients treated at tertiary cancer center.
Authors: Ramiz Ahmad Abu-Hijlih, Samer Salah, Akram Al-Ibraheem, Fawzi Abuhijla, Hashem Abu Serhan, Mohammed Shahait
Journal: Journal of Clinical Oncology (2021)

e16521 Background: The incidence of bladder cancer in the Middle East is increasing. The data on young population with urothelial carcinoma (UC) of urinary bladder in the region is scarce. We evaluated clinical and tumor characteristics, in addition to management details in patients younger than 45 years old. Methods: We reviewed of all patients presenting with UC of the urinary bladder from July 2006 to December 2019. Clinical characteristics including demographics, stage at presentation, and treatment outcomes were described. Results: Out of 1,272 new cases of bladder cancer, a total of 112 patients (8.8%) were ≤45 years old. Seven patients (6%) had non-urothelial histology and were excluded. The remaining 105 eligible patients with UC had a median age at presentation was 41 years (35-43). Ninety three patients (88.6%) were males. Tumor stage at presentation: non-muscle invasive disease (Ta-T1), locally advanced muscle invasive bladder cancer (MIBC) (T2-3), and metastatic disease were 14 cases (84.7%), 2.8%, and 12.5%, respectively. All patients with MIBC received neoadjuvant cisplatin-based chemotherapy. Radical cystectomy was performed in 8 cases (7.6%); 3 patients with MIBC and 5 with high volume non-MIBC. Neobladder reconstruction was done in 6 patients. A total of 13 patients with metastatic disease (93%) received palliative chemotherapy (Gemcitabine/Cisplatin), and one (7%) was candidate of best supportive care only. Conclusions: Bladder cancer is relatively rare in young population, though the incidence at our region is higher than other reports in the literature. Most of patients present with early disease. Early diagnosis and multidisciplinary approach are paramount for management of these patients.
In AML RAS pathway Mutations Confer Worse Outcome in IDH1 and IDH2 Mutated AML Patients Receiving Hematopoietic Stem Cell Transplantation
Authors: Stefanie Beinicke, Juliane Grimm, Madlen Jentzsch, Marius Bill, Janine Häntschel, Karoline Goldmann, Julia Schulz, Michael Cross, Georg-Nikolaus Franke, Vladan Vucinic, Wolfram Pönisch, Gerhard Behre, Dietger Niederwieser, Sebastian Schwind
Journal: Blood (2017)
Publisher Correction: The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics
Authors: Seppo Salminen, Maria Carmen Collado, Akihito Endo, Colin Hill, Sarah Lebeer, Eamonn M. M. Quigley, Mary Ellen Sanders, Raanan Shamir, Jonathan R. Swann, Hania Szajewska, Gabriel Vinderola
Journal: Nature Reviews Gastroenterology & Hepatology (2021)
Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial.
Authors: Catherine S. Magid Diefenbach, Pau Abrisqueta, Eva Gonzalez-Barca, Carlos Panizo, Jose Maria Arguinano Perez, Fiona Miall, Mariana Bastos-Oreiro, Armando Lopez-Guillermo, Lalita Banerjee, Andrew McMillan, Jamie Hirata, Lisa Musick, Sourish Saha, Brandon Croft, Erlene Kuizon Seymour
Journal: Journal of Clinical Oncology (2021)

7512 Background: The combination of Pola-R-Len may enhance anti-tumor response in R/R DLBCL. We report the primary analysis of the R/R DLBCL cohort in a Phase 1b/2 study (GO29834; NCT02600897). Methods: Pts received induction with 6 x 28-Day (D) cycles (C) of: Pola 1.8mg/kg intravenous (IV; C1−6: D1); R 375mg/m 2 IV (C1−6: D1) and oral Len 10–20mg (dose escalation) or recommended Phase 2 dose (RP2D) daily on D1–21. Pts with a response at end of induction (EOI) received 6 months (mo) consolidation with R 375mg/m 2 (D1 every 2 mo) and Len 10mg (D1–21 monthly). Primary endpoints were safety/tolerability and positron emission tomography (PET)-complete response (CR) rate at EOI by independent review committee (IRC) by modified Lugano criteria. Results: At primary analysis (Sep 08, 2020), 57 pts were enrolled. Median age was 71 years (range 28–92); male (67%); Ann Arbor Stage III–IV (86%); International Prognostic Index 3–5 (60%); median 2 prior therapies; prior bone marrow transplant (11%); prior CAR-T therapy (5%); primary refractory (49%) and refractory to last therapy (65%). Grade 3–4 adverse events (AEs) were experienced by 75% of pts, most commonly, neutropenia (58%), thrombocytopenia (14%), infections (14%) and anemia (11%). AEs led to Len dose reduction in 25% and interruption in 63% of pts. One Grade 5 treatment-related AE (neutropenic sepsis) was reported. In total, 49 pts were treated at RP2D (Pola 1.8mg/kg + Len 20mg). IRC PET-CR rate at EOI was 29% (Table). A best overall response (BOR) assessed by investigator (INV) was seen in 36/49 (74%) pts with 17/49 (35%) pts achieving a CR; of these, 14/17 (82%) remain in remission at the cutoff date. Median duration of response (DOR) was 8.1 mo (95% confidence interval [CI]: 4.7–not evaluable [NE]). After a median follow-up of 9.7 mo, median progression-free survival (PFS) and overall survival (OS) were 6.3 mo (95% CI: 4.5–9.7) and 10.9 mo (95% CI: 7.4–NE), respectively. Conclusions: Our study of the novel triplet combination, Pola-R-Len, demonstrates a tolerable safety profile. This first efficacy report of Pola-R-Len shows promising activity in a difficult-to-treat R/R DLBCL population, particularly in pts achieving CR, a large proportion of whom remain in remission at the cutoff date. Further evaluation of Pola-R-Len and the impact of consolidation therapy is warranted to address the significant unmet need in this patient population. Clinical trial information: NCT02600897. [Table: see text]
Survival trends in chronic lymphocytic leukemia in the era of oral targeted therapies in the United States: SEER database analyses (1985 to 2017).
Authors: Neda Alrawashdh, Ali McBride, Daniel O. Persky, Joann Sweasy, Brian Erstad, Ivo Abraham
Journal: Journal of Clinical Oncology (2021)

7524 Background: The survival of chronic lymphocytic leukemia (CLL) patients has progressively improved after the approval of new targeted therapy for first-line treatment and relapsed disease. We performed a corresponding analysis from the U.S. population-based SEER database (1973–2017) to explore the trend of survival and the effect of advanced CLL treatment on overall survival in CLL patients. Methods: Data were extracted from SEER*Stat for all patients 15 years or older with a primary diagnosis of CLL with or without subsequent cancers. A period analysis was performed to estimate the 5- and 10-year relative survival rates for patients diagnosed (dx) during different calendar periods from 1985 to 2017, based on gender and age at time of diagnosis (15–44, 45–54, 55–64, 65–74, 75–84, 85 years or older). A mixture cure model was used to examine the proportion of long-term survivors per gender and age category among CLL patients diagnosed between 1985 and 2015. Cox proportional hazard modeling was used to calculate the hazard ratios (HRs) of death adjusted for gender and age at diagnosis for two cohorts: (a) diagnosed in 2000–2003 and followed to 2012; (b) 2004–2007 and followed to 2015. Results: For males, the 5-year age-adjusted relative survival rate improved progressively from 72.0% (dx 1985-1989) to 88.2% (dx 2010-2014); for females, from 76.8% (dx 1985-1989) to 90.8% (dx 2010-2014). The corresponding 10-year age-adjusted relative survival rates were 47.3% (dx 1985-1989) and 72.5% (dx 2005-2009) for males; and 58.2% (dx 1985-1989) and 78.7% (dx 2005-2009) for females. The table below shows the proportions of long-term survivors for the 1985–2017 cohort as estimated in the mixed cure model. The HRs (95%CI) of death for cohort (b) in comparison to cohort (a) were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.67), 0.68 (0.54–0.85); and 0.83 (0.68–1.02) for age categories of 45–54, 55–64, 65–74, 75–84, and 85 years or old. Conclusions: Survival is significantly improved by calendar period among patients diagnosed after 2004 and treated in the era of advanced therapies. Females and younger patients had a higher probability of long term survival. Future studies should consider such covariates as treatment type, disease stage and genetics.[Table: see text]
Outcomes of first, second, and third-generation anaplastic lymphoma kinase (ALK) inhibitors in non-small cell lung cancer brain metastases (NSCLCBM).
Authors: Vineeth Tatineni, Patrick Joseph O'Shea, Yasmeen Rauf, Xuefei Jia, Erin Sennett Murphy, Samuel T. Chao, John H. Suh, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2021)

2034 Background: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastases. ALK, which codes for tyrosine kinase receptors, is rearranged in 4-7% of NSCLC. First-generation ALK inhibitors have restricted efficacy due to poor blood-brain barrier (BBB) penetration and ALK-resistant tumor mutations. Second-generation ALK inhibitors have shown better BBB penetration, while third-generation ALK inhibitors were efficacious even against ALK-resistant mutations. In this retrospective study, we investigated the overall survival (OS) and progression-free survival (PFS) in NSCLCBM patients treated with first, second, and third-generation ALK inhibitors. Methods: NSCLCBM patients between 2010 and 2019 were evaluated. We analyzed data regarding molecular marker status, systemic therapies, and date of progression. OS was defined as the start date of systemic therapy to the date of last follow-up or death. The Cox proportional model was used to estimate OS and PFS. Results: A total of 90 patients had ALK gene rearrangement. 16 ALK positive patients received first-generation ALK inhibitor (crizotinib), with a median age of 59.2 years, 50% of the cohort being female and 83.3% being white. Another 17 patients received second-generation (alectinib, ceritinib, brigatinib) and third-generation ALK inhibitors (lorlatinib), with a combined median age of 52.2 years and a cohort of 52.6% females and 72.2% white patients. The 5-year OS rate was 49% (95% confidence interval (CI) = 24%, 71%) for first-generation ALK inhibitors and 76% (95% CI = 40%, 92%) for second and third-generation ALK inhibitors (p-value (p) = 0.019). The median PFS (mPFS) for patients who received first-generation ALK inhibitors was 45.3 months and for those who received second or third-generation ALK inhibitors was 180.1 months. The respective 5-year PFS rate was 43% (95% CI = 19%, 65%) and 72% (95% CI = 42%, 89%). Conclusions: Newer generations of targeted therapies in NSCLCBM have improved BBB penetration and effectiveness against resistant mutations. We determined that there was a significant 5-year OS benefit in patients who received second and third-generation ALK inhibitors compared to first-generation ALK inhibitors, and a respective trend towards significant PFS benefit in newer-generation ALK inhibitors when compared to first-generation. These results are encouraging, but the effect on intracranial lesion size and response rates should be examined in the future.[Table: see text]
Genome-wide cfDNA fragmentation in patients with cancer and other diseases.
Authors: Jacob Carey, Sian Jones, Alessandro Leal, Bryan Chesnick, Denise Butler, Michael Rongione, Robert B. Scharpf, Julia S. Johansen, Victor E. Velculescu, Nicholas C Dracopoli
Journal: Journal of Clinical Oncology (2021)

3136 Background: Genome-wide cfDNA fragmentation patterns have previously been demonstrated to distinguish with high sensitivity and specificity between plasma samples from individuals with and without cancer. Methods: To further evaluate cfDNA fragmentation as a blood-based screening test for cancer, we have evaluated these genomic features in patients with and without cancer who have been diagnosed with other common comorbidities. For this study, we have used low coverage (1-2x) whole genome sequencing to analyze plasma samples from 412 patients referred to an advanced diagnostic center due to unexplained signs and symptoms associated with cancer. Results: Seventy-seven of these patients were ultimately diagnosed with one of sixteen different solid cancers, 68 with cardiovascular disease, 48 with diabetes, as well as other comorbidities. We used the DELFI approach (DNA evaluation of fragments for early interception) to measure the cfDNA fragmentation in plasma from all 412 patients included in the study using a cross-validated machine learning model. Patients with cancer could be distinguished from non-cancer individuals with high sensitivity and specificity (AUC = 0.92), including for common cancers such as colorectal and lung cancer. Conclusions: These data support the hypothesis that abnormal cfDNA fragmentation is a consequence of unregulated mitoses in cancer cells and can be distinguished from fragmentation patterns of individuals with co-morbidities.
Impact of COVID19 pandemic on treatment outcome of locally-advanced head and neck squamous cell carcinoma (LA-HNSCC): IMPACCT study.
Authors: Pau Guillen Sentis, Carmen Castillo Manzano, Beatriz Quirós, Francisca Morey Cortes, Sara Tous, Maria Plana, Jesús Brenes Castro, Alicia Lozano, Isabel Linares, M. Esther Vilajosana Altamis, Victoria Gomez Garcia, Maria Labori Trias, Montse Goma, Antonio Mari Roig, Oriol Bermejo, Jordi Tornero Salto, Miren Taberna, Laia Alemany, Ricard Mesia, Marc Oliva Bernal
Journal: Journal of Clinical Oncology (2021)

6061 Background: Treatment (ttm) of cancer patients (pts) was compromised during the first wave of COVID19 pandemic due to collapse of healthcare systems. Standard of care (SOC) for LA-HNSCC pts had to be adapted as operating rooms were temporarily unavailable, and to reduce risk of COVID19 exposure. The IMPACCT study evaluated the outcome of LA-HNSCC pts treated at the Catalan Institute of Oncology during the first semester of 2020 and compared it to a control cohort previously treated in the same institution. Methods: Retrospective single institution analysis of two consecutively-treated cohorts of newly-diagnosed HNSCC pts: from January to June of 2020 (CT20) and same period of 2018 and 2019 (CT18-19). Pt demographics and disease characteristics were obtained from our in-site prospective database. Ttm modifications from SOC as per COVID19-contingency protocol in CT20 for LA-HNSCC were collected. Chi-squared was used to compare variables and ttm response between cohorts. One-year recurrence-free survival (1yRFS) and overall survival (1yOS) of LA-HNSCC pts were estimated by Kaplan-Meier method and compared by Log-rank test. Results: A total of 306 pts were included: CT20=99; CT18-19=207. Baseline characteristics were balanced between cohorts (Table1). In pts treated with conservative ttm (non-surgical approach), persistence disease was higher in CT20 vs CT18-19 (26 vs. 10% p=0.02). Median follow-up of CT20 and CT18-19 was 6.8 months (IQR 5.1-7.9) and 12.3 (6.7-18.4), respectively. A trend towards lower 1yRFS and 1yOS was observed in CT20 vs CT18-19 (72 vs 83% p=0.06; 80 vs 84% p=0.07), respectively. Within CT20, 37 pts (37%) had one or more ttm modifications: switch from surgery to conservative ttm (n=13); altered radiotherapy fractionation (n=14); reduced cisplatin cumulative dose to 200mg/m2 (n=19); no adjuvant ttm (n=1). Pts who received modified ttm had no differences in 1yRFS vs those who did not (80 vs 66% p=0.31), but higher 1yOS was observed (97 vs 67% p&lt;0.01). When stratified by stage, 1yOS difference remained significant in stage III/IVA (100 vs 61% p&lt;0.01) but not in I/II (100 vs 77% p=0.28) or IVB (67 vs 50% p=0.54). Conclusions: COVID19 pandemic had a negative impact on ttm outcomes and survival in LA-HNSCC pts when compared to our historical cohort. Ttm modifications based on COVID19-contingency protocol did not compromise ttm efficacy in terms of RFS and was associated with better OS in Stage III/IVA.[Table: see text]
Impact of cancer- and patient-level factors on provider risk in the Oncology Care Model.
Authors: Basit Iqbal Chaudhry, Andrew Yue, Shuchita Kaila, Kay Sadik, Lisa Tran, Nora Connor
Journal: Journal of Clinical Oncology (2021)

e18852 Background: Transferring financial risk from payers to providers to align incentives is central to value-based payment (VBP) reform, including Medicare’s Oncology Care Model (OCM). We simulated the impact of selected cancer- and patient-level factors on providers’ risk in OCM for multiple myeloma (MM), due to its clinical complexity. We hypothesize that risk exposure is sensitive to factors extrinsic to the OCM methodology, including clinical phenotype, disease state and progression rate. Methods: Simulation was used to address omitted variable bias in payer data. We developed 9 key clinical MM scenarios to examine provider risk, based on conceptual frameworks that included patient- and cancer-level factors. The model was parameterized using the Medicare limited data set, research literature and domain knowledge. Twenty factors were varied for each model, e.g. age, autologous stem cell transplant (ASCT). Results: Simulations results showed MM risk for providers depended highly on cancer and patient level factors (see table). For example, high-risk patients were on average $21.5K over target while undergoing ASCT (despite risk adjustment for ASCT) and $18-28K under target for follow on maintenance (maint.) episodes. Conclusions: Provider exposure to risk in OCM is highly sensitive to factors at the cancer and patient level. The distribution of clinical phenotypes, state of disease, and rate of disease progression can significantly impact risk exposure for providers in OCM. New methodologies that model risk in more clinically granular ways are needed to improve VBP in oncology. [Table: see text]
Serial single-cell genomics reveals convergent subclonal evolution of resistance as patients with early-stage breast cancer progress on endocrine plus CDK4/6 therapy
Authors: Jason I. Griffiths, Jinfeng Chen, Patrick A. Cosgrove, Anne O’Dea, Priyanka Sharma, Cynthia Ma, Meghna Trivedi, Kevin Kalinsky, Kari B. Wisinski, Ruth O’Regan, Issam Makhoul, Laura M. Spring, Aditya Bardia, Frederick R. Adler, Adam L. Cohen, Jeffrey T. Chang, Qamar J. Khan, Andrea H. Bild
Journal: Nature Cancer (2021)
Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block
Authors: Ole J. Sletten, John M. Aalen, Hava Izci, Jürgen Duchenne, Espen W. Remme, Camilla K. Larsen, Einar Hopp, Elena Galli, Per A. Sirnes, Erik Kongsgard, Erwan Donal, Jens U. Voigt, Otto A. Smiseth, Helge Skulstad
Journal: JACC. Cardiovascular imaging (2021)

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Recent Approaches to Targeting Canonical NFκB Signaling in the Early Inflammatory Response to Renal IRI
Authors: Shelby Reid, James W. Scholey
Journal: Journal of the American Society of Nephrology (2021)

Ischemia reperfusion injury (IRI) is the most common cause of in-hospital AKI and is associated with increased morbidity and mortality. IRI is associated with an early phase of inflammation primarily regulated by the canonical NF
Prevalence and variety of HPV types in dependence on gender and age.
Authors: Tatiana A. Zykova, Vera P. Nikitina, Oksana E. Zhenilo, Ekaterina V. Verenikina, Viktoria A. Ivanova, Anna P. Menshenina, Alexey N. Shevchenko, Irina A. Khomutenko, Elena V. Filatova, Elena A. Shevyakova, Lilia A. Velikorodnaya
Journal: Journal of Clinical Oncology (2021)

e17575 Background: Analysis of the typical structure of age, sex and territorial patterns of HPV spread is of interest, since it allows assessing the potential impact of modern immunoprophylaxis. The purpose of the study was to analyze the prevalence and variety of HPV types in dependence on gender and age. Methods: The study included 424 patients (334 women and 90 men) under 45 years of age (228 women and 46 men) and over 46 years old (106 and 44, respectively). Vaginal and cervical swabs were examined in women and urethral swabs in men. DNA extraction was performed by Real-time PCR. Results: HPV DNAs were found in 150(35.4%) patients, including 115(34.4%) women and 35(38.9%) men (p &gt; 0.05). HPV was less frequently detected in older women, and more frequently in older men. Thus, HPV DNAs were found in 85(37.3%) women &lt; 45 years and in 30(28.3%, p = 0.068) women &gt;46 years; in men – 14(30.9%) and 21(47.7%, p = 0.071), respectively. Some HPV types were more frequent in younger patients, compared to older ones: in 26(26.3%) and in 5(9.8%), p = 0.068) of HPV-positive patients, respectively. The most common HPV types were 16(46.7%), 52(16.0%), 56(12.7%), 31(10.7%); HPV16 dominated both in females - 50(50.4%) and males - 12(34.6%). After HPV16, most frequent types in women were: 31-12(11.3%) and 52-13(11.3%), 18-12(10.4%) and 56-119(, 6%); in men - 52-11(31.4%), 56-8(22.9%), 45-4(11.4%) and 18-3(8.6%) types. The total share of two HPV types with the greatest oncogenic potential (types 16 and 18) was 85(56.7%) of all HPV-positive patients, and in women it was higher than in men: 70(60.9) vs. 15(42.9%, p = 0.046), respectively. Conclusions: Simultaneous infection with several HPV types was statistically significantly more often detected in younger patients compared with the older age group among men. HPV16 was the most common type both in men and women; however, the rates of other HPV types differed. Cumulative frequency of types 16 and 18 was statistically significantly higher in women, compared to men.
In-depth proteomics analysis of sentinel lymph nodes from individuals with endometrial cancer
Authors: Soulaimane Aboulouard, Maxence Wisztorski, Marie Duhamel, Philippe Saudemont, Tristan Cardon, Fabrice Narducci, Anne-Sophie Lemaire, Firas Kobeissy, Eric Leblanc, Isabelle Fournier, Michel Salzet
Journal: Cell Reports Medicine (2021)

Endometrial cancer (EC) is one of the most common gynecological cancers worldwide. Sentinel lymph node (SLN) status could be a major prognostic factor in evaluation of EC, but several prospective studies need to be performed. Here we report an in-depth proteomics analysis showing significant variations in the SLN protein landscape in EC. We show that SLNs are correlated to each tumor grade, which strengthens evidence of SLN involvement in EC. A few proteins are overexpressed specifically at each EC tumor grade and in the corresponding SLN. These proteins, which are significantly variable in both locations, should be considered potential markers of overall survival. Five major proteins for EC and SLN (PRSS3, PTX3, ASS1, ALDH2, and ANXA1) were identified in large-scale proteomics and validated by immunohistochemistry. This study improves stratification and diagnosis of individuals with EC as a result of proteomics profiling of SLNs.