tbuckley/cabot-search huggingface dataset:
Refining TNM-8 M1 categories with anatomic subgroups for previously untreated de novo metastatic nasopharyngeal carcinoma.
Authors: Sik-Kwan Chan, Cheng Lin, Shao Hui Huang, Tin Ching Chau, Qiaojuan Guo, Brian O'Sullivan, Ka-On Lam, Sze Chun Chau, Ann SY Chan, Chi-Chung Tong, Varut Vardhanabhuti, Dora LW Kwong, Tsz Him So, Sherry CY Ng, To Wai Leung, Mai-Yee Luk, Anne WM Lee, Cheuk-Wai Choi, Jianji Pan, Victor Ho-Fun Lee
Journal: Journal of Clinical Oncology (2021)

6046 Background: The eighth edition TNM (TNM-8) classified de novo metastatic (metastatic disease at presentation) nasopharyngeal carcinoma (NPC) as M1 without further subdivision. However, survival heterogeneity exists and long-term survival has been observed in a subset of this population. We hypothesize that certain metastatic characteristics could further segregate survival for de novo M1 NPC. Methods: Patients with previously untreated de novo M1 NPC prospectively treated in two academic institutions (The University of Hong Kong [n = 69] and Provincial Clinical College of Fujian Medical University [n = 114] between 2007 and 2016 were recruited and re-staged based on TNM-8 in this study. They were randomized in 2:1 ratio to generate a training cohort (n = 120) and validation cohort (n = 63) respectively. Univariable and multivariable analyses (MVA) were performed for the training cohort to identify the anatomic prognostic factors of overall survival (OS). We then performed recursive partitioning analysis (RPA) which incorporated the anatomic prognostic factors identified in multivariable analyses and derived a new set of RPA stage groups (Anatomic-RPA groups) which predicted OS in the training cohort. The significance of Anatomic-RPA groups in the training cohort was then validated in the validation cohort. UVA and MVA were performed again on the validation cohorts to identify significant OS prognosticators. Results: The training and the validation cohorts had a median follow-up of 27.2 months and 30.2 months, respectively, with the 3-year OS of 51.6% and 51.1%, respectively. Univariable analysis (UVA) and multivariable analysis (MVA) revealed that co-existing liver and bone metastases was the only factor prognostic of OS. Anatomic-RPA groups based on the anatomic prognostic factors identified in UVA and MVA yielded good segregation (M1a: no co-existing liver and bone metastases and M1b: co-existing both liver and bone metastases; median OS 39.5 and 23.7 months respectively; P =.004). RPA for the validation set also confirmed good segregation with co-existing liver and bone metastases (M1a: no co-existing liver and bone metastases and M1b: co-existing liver and bone metastases), with median OS 47.7 and 16.0 months, respectively; P =.008). It was also the only prognostic factor in UVA and MVA in the validation cohort. Conclusions: Our Anatomic-RPA M1 stage groups with anatomical factors provided better subgroup segregation for de novo M1 NPC. The study results provide a robust justification to refine M1 categories in future editions of TNM staging classification.
Benefits of blood transfusions in palliative care patients with advanced cancer.
Authors: Joana Catarina Lima Marinho, Sara Marote, Maria Cândida Silva, Jose Ferraz Gonçalves
Journal: Journal of Clinical Oncology (2021)

e24090 Background: Anemia is highly prevalent in patients with advanced cancer and adversely affects quality of life. There is limited data on the frequency, clinical utility and effectiveness of red blood cell transfusions (RBC), and no randomized controlled trials or clinical practice guidelines on this subject are available. The aim of this study was to evaluate clinician practices on RBC transfusion in an oncologic palliative care unit (PCU), its impact on patients’ symptoms, overall survival and to identify predictive factors for survival. Methods: Retrospective cohort study of all advanced cancer patients who had received RBC transfusions over a 3-year period, after admission to the PCU for symptomatic control, as inpatients or outpatients. All had histologically confirmed malignant tumors and were not under anti-cancer treatments. Patients’demographics, clinical and laboratory features, symptoms and mortality were reviewed. Survival analysis was estimated using the Kaplan-Meier method and Cox's regression was used for multivariate analysis. Results: We identified 179 patients with a median age of 68 years [30-93], 60% were male, with a mean Charlson comorbidity index of 8.9 (SD ±2.3). The majority had gastrointestinal (42%) and genitourinary (35%) malignancies. A total of 435 RBC units, during 301 transfusion episodes were recorded. The majority (58%) were performed as inpatients. A combination of symptoms with low haemoglobin (Hb) levels was the main reason for transfusion (80%). Asthenia/fatigue was the most frequent symptom (68%). Prior to transfusion, the majority (73%) had an ECOG-performance status (ECOG-PS) greater than 2. The mean pretransfusion Hb was 6.9 g/dL and 48% patients had an Hb above 7 g/dL. Symptomatic benefit post-transfusion was achieved in 36% of patients. A statistically significant association between ECOG-PS and symptomatic benefit was found (p = 0.005). Median overall survival post-transfusion was 41 days (IC95% 30.6-51.4). On multivariate analysis, Hb level pre-transfusion, ECOG-PS and symptomatic benefit with transfusions were significantly associated with survival. Conclusions: Transfusion practices are more liberal in palliative care, increasing iatrogenic risk, while consuming a valuable and limited resource. However, transfusion does provide symptom relief, and should be offered to advanced cancer patients with a higher level of functioning. Post-transfusion symptomatic benefit, and pre-transfusion ECOG-PS and hemoglobin levels seem to be independent predictors of survival. Further high-quality trials are needed to develop validated measures of objective functional changes to evaluate the clinical impact of transfusions and to identify patients most likely to be positively impacted by transfusion.
Factors Associated With Inpatient Endoscopy Delay and its Impact on Hospital Length-of-Stay and 30-Day Readmission
Authors: Chelsea C. Jacobs, Johnny F. Jaber, Michael Ladna, Sandeep Ponniah, Ishaan Madhok, Nicole Ruiz, Haley Podeschi, Francesca Gesiotto, Walid Khan, Nabeel Moon, April Mathews, Vikas Patel, Brett Styskel, Tony S. Brar, Peter V. Draganov, Dennis Yang
Journal: Clinical Gastroenterology and Hepatology (2021)
Laboratory trends, hyperinflammation, and clinical outcomes for patients with a systemic rheumatic disease admitted to hospital for COVID-19: a retrospective, comparative cohort study
Authors: Tiffany Y-T Hsu, Kristin M D'Silva, Naomi J Patel, Jiaqi Wang, Alisa A Mueller, Xiaoqing Fu, Lauren Prisco, Lily Martin, Kathleen M M Vanni, Alessandra Zaccardelli, Claire Cook, Hyon K Choi, Yuqing Zhang, Ellen M Gravallese, Zachary S Wallace, Jeffrey A Sparks
Journal: The Lancet Rheumatology (2021)
Clinical trial representativeness and treatment intensity in a real-world sample of women with early-stage breast cancer.
Authors: Nicole E. Caston, Courtney Williams, Jeffrey Franks, Monica S. Aswani, Andres Azuero, Risha Gidwani, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2021)

6584 Background: Early stage breast cancer (EBC) treatment is used in women of all ages, races, and health states. However, as clinical trials often do not represent real-world populations, the extent to which evidence-based treatments are prescribed to populations not well represented in these trials is not known. This study evaluated treatment intensity for patients traditionally well represented, underrepresented, and unrepresented in clinical trials. Methods: This retrospective cohort study used the nationwide de-identified electronic health record derived Flatiron Health database for patients diagnosed with EBC between 2011-2020. We categorized treatments as either high- (AC-TH [doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel, trastuzumab]; ACT [paclitaxel or docetaxel, doxorubicin, cyclophosphamide]; TCH [paclitaxel or docetaxel, carboplatin, trastuzumab]; TCHP [paclitaxel or docetaxel, carboplatin, trastuzumab, pertuzumab]) or low-intensity (AC [doxorubicin, cyclophosphamide]; TC [paclitaxel or docetaxel, cyclophosphamide]; TH [paclitaxel or docetaxel, trastuzumab]). Unrepresented patients often have one or more comorbidities and/or prior cancer; underrepresented patients are typically Black, Indigenous, people of color, or of age extremes ( &lt; 45, 70+); well represented patients are White and between the ages of 45-69. Odds ratios (OR), predicted proportions, and 95% confidence intervals (CI) from a two-level (patients nested in practice) hierarchical logistic regression model evaluated associations between receipt of high-intensity chemotherapy and patient characteristics of clinical trial representation (age, race/ethnicity, presence of comorbidity). Results: Our study included 970 patients with EBC with 13%, 45%, and 41% characterized as unrepresented, underrepresented, and well represented in clinical trials, respectively. In the adjusted model, those aged ≥ 70 vs 45-69 had lower odds of receiving a high-intensity treatment (OR 0.40, 95% CI 0.26-0.60), while those aged &lt; 45 vs 45-69 had higher odds of receiving high-intensity treatment (OR 1.82, 95% CI 1.10-3.01). The predicted proportion of patients receiving a high-intensity treatment was 87% (95% CI: 80%-92%) for patients aged &lt; 45, 79% (95% CI: 74%-84%) for patients aged 45-69, and 60% (95% CI: 50%-70%) for patients aged ≥ 70. Neither race/ethnicity nor comorbidity status were associated with odds of receiving high-intensity chemotherapy. Conclusions: Over half of the EBC population is not well represented in clinical trials. Age was associated with differential treatment intensity, despite a lack of evidence that these differences are appropriate. Widening clinical trial eligibility criteria is one way to better understand survival outcomes, identify potential toxicities, and ultimately make evidence-based treatment decisions using a more diverse sample.
EMBR-25. GENOME-WIDE GENETIC AND EPIGENETIC ASSESSMENT OF GROUP 4 MEDULLOBLASTOMA FOR IMPROVED, BIOMARKER DRIVEN, PROGNOSTICATION AND RISK-STRATIFICATION
Authors: Jack Goddard, Jemma Castle, Emily Southworth, Stephen Crosier, Idoia Martin-Guerrero, Miguel Garcia-Ariza, Aurora Navajas, Franck Bourdeaut, Christelle Dufour, Tobias Goschzik, Torsten Pietsch, Dan Williamson, Simon Bailey, Ed Schwalbe, Steven Clifford, Debbie Hicks
Journal: Neuro-Oncology (2021)

Abstract Introduction Medulloblastoma (MB) is the most common malignant brain tumour in children. The most frequent molecular subgroup, Group 4 (MBGrp4) accounts for ~35/40% of cases, however it has the least understood underlying biology. Clinical outcomes are heterogeneous in MBGrp4 and are not accounted for by established clinico-pathological risk factors. There is now a requirement for a comprehensive study of MBGrp4, considering established clinico-pathological features and novel molecular biomarkers to enhance risk-stratification and identify novel therapeutic targets. Methods A clinically-annotated, retrospective MBGrp4 discovery cohort (n = 420) was generated from UK CCLG institutions, collaborating European centres and SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials. Contemporary, multi-omics profiling was performed. Focal and arm level copy number aberrations (CNAs) were determined from molecular inversion probe (MIP) or DNA methylation array which additionally provided next generation non-WNT/non-SHH (Grp3/Grp4) subtype classifications. Targeted next-generation DNA sequencing was performed to overlay the mutational landscape. Survival modelling was carried out with patients &amp;gt;3 years old who received craniospinal irradiation. Results MBGrp4 subtypes were assigned to 88% of tumours with available data. Subtype VIII was strongly associated with i17q (p&amp;lt;0.0001). The favourable-risk cytogenetic signature (2 or 3 of; chromosome 7 gain, chromosome 8 loss and/or chromosome 11 loss) associated with both subtypes VI and VII (p&amp;lt;0.0001). MYCN amplifications were strongly associated with subtype V (p&amp;lt;0.0001) in addition to 16q loss (p&amp;lt;0.0001). The high-risk CNA group was enriched for mutations in genes involved in chromatin remodelling (p&amp;lt;0.0001). Risk factors were identified from multivariate survival modelling. Subtype and CNA groups contributed to improved risk-stratification models that outperformed current clinical schemes. Conclusion Comprehensive genetic and epigenetic profiling in this large retrospective cohort has improved our understanding of the molecular and clinical heterogeneity within MBGrp4. Incorporation of molecular biomarkers improved risk-stratification for MBGrp4.
The role of human endogenous retroviruses in gliomas: from etiological perspectives and therapeutic implications
Authors: Ashish H Shah, Mark Gilbert, Michael E Ivan, Ricardo J Komotar, John Heiss, Avindra Nath
Journal: Neuro-Oncology (2021)

Accounting for approximately 8% of the human genome, human endogenous retroviruses (HERVs) have been implicated in a variety of cancers including gliomas. In normal cells, tight epigenetic regulation of HERVs prevent aberrant expression; however, in cancer cells, HERVs expression remains pervasive, suggesting a role of HERVs in oncogenic transformation. HERVs may contribute to oncogenesis in several ways including insertional mutagenesis, chromosomal rearrangements, proto-oncogene formation, and maintenance of stemness. On the other hand, recent data has suggested that reversing epigenetic silencing of HERVs may induce robust anti-tumor immune responses, suggesting HERVs' potential therapeutic utility in gliomas. By reversing epigenetic modifications that silence HERVs, DNA methyltransferase, and histone deacetylase inhibitors may stimulate a viral-mimicry cascade via HERV-derived dsRNA formation that induces interferon-mediated apoptosis. Leveraging this anti-tumor autoimmune response may be a unique avenue to target certain subsets of epigenetically-dysregulated gliomas. Nevertheless, the role of HERVs in gliomas as either arbitrators of oncogenesis or forerunners of the innate anti-tumor immune response remains unclear. Here, we review the role of HERVs in gliomas, their potential dichotomous function in propagating oncogenesis and stimulating the anti-tumor immune response, and identify future directions for research.
Scalp-sparing radiation with concurrent temozolomide and tumor treating fields (SPARE) for patients with newly diagnosed glioblastoma.
Authors: Ryan C Miller, Andrew Jehyun Song, Ayesha Ali, Voichita C Bar-Ad, Nina Leyson Martinez, Jon Glass, Iyad Alnahhas, David W. Andrews, Kevin Judy, James J Evans, Christopher Farrell, Maria Werner-Wasik, Inna Chervoneva, Michele Ly, Joshua David Palmer, Haisong Liu, Wenyin Shi
Journal: Journal of Clinical Oncology (2021)

2056 Background: Standard of care for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our clinical trial evaluating safety and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. Methods: This is a single arm pilot study. Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of TTFields concurrent with chemoradiation in patients with newly diagnosed glioblastoma. Results: A total of 30 patients were enrolled in the trial. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). Median follow-up was 8.9 months (range 1.6 to 21.4 months). Twenty (66.7%) patients had unmethylated MGMT promotor status and ten (33.3%) patients had methylated promoter status. Median time from surgery to radiation was 34 days (26 to 49 days). Scalp dose constraints were achieved for all patients, with the mean dose having a median value of 8.3 Gy (range 4.3 to 14.8 Gy), the D20cc median was 26.1 Gy (range 17.7 to 42.8 Gy), and the D30cc median was 23.5 Gy (range 14.8 to 35.4 Gy). Skin adverse events (AEs; erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). Nineteen patients (63.3%) had progression, with a median PFS of 7.6 months (range 1.6 to 12.7 months). Overall survival was not reached. Conclusions: Concurrent TTFields (200 kHz) with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation. Clinical trial information: NCT03477110.
Comprehensive Genomic Profiling Identifies Genomic Alterations That Define Philadelphia-like B-Acute Lymphoblastic Leukemia
Authors: Eric A Severson, Sugganth Daniel, Julia A Elvin, James Suh, Michelle Nahas, Vincent A Miller, Philip J Stephens, Jeffrey S Ross, Shakti Ramkissoon, Jo-Anne Vergilio
Journal: Blood (2017)
Comprehensive geriatric assessment and management for Canadian elders with Cancer: The 5C study.
Authors: Martine Puts, Naser Alqurini, Fay Strohschein, Johanne Monette, Doreen Wan-Chow-Wah, Rama Koneru, Ewa Szumacher, Rajin Mehta, Caroline Joy Mariano, Anson Li, Tina Hsu, Sarah Brennenstuhl, Bianca Mclean, Aria Wills, Eitan Amir, Monika K. Krzyzanowska, Christine Elser, Eric Pitters, Henriette Breunis, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2021)

12011 Background: Comprehensive Geriatric Assessment (CGA) is recommended by ASCO for older adults with cancer undergoing chemotherapy to identify issues that can interfere with treatment delivery and optimize functional status and quality of life. However, few randomized controlled trials have been completed so far. Our objective is to evaluate the effectiveness of CGA on improving quality of life for older adults receiving cancer treatment. Methods: Eligible patients were aged 70+, diagnosed with a solid tumour, lymphoma or myeloma, referred for first/second line chemotherapy, speaking English/French, and with an Eastern Collaborative Oncology Group Performance Status 0–2. The CGA was done by a nurse and geriatrician followed by monthly phone calls by the study nurse for 6 months. Patients were randomly assigned (1:1) to receive either the intervention (CGA plus follow-up by geriatric trained team in addition to usual oncology care) or usual care alone. All participants received a monthly healthy aging booklet for attention control. Randomization was stratified by center and treatment intent (curative/adjuvant versus palliative). Our primary outcome was health-related quality of life (HRQOL) assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health scale (items 29 and 30). Secondary outcomes include functional status (Instrumental Activities of Daily Living). Outcome data collection was completed monthly for the first 6 months, then at 9 and 12 months. For the primary outcome we used a pattern mixture model using an intent-to-treat approach (at 0, 3, and 6 months). The last data collection took place March 8 2021. Results: From May 2017 to March 2020, 351 participants from 8 hospitals across Canada were enrolled. All patients were seen on or after day 1 of treatment for the intervention per patient request. Patient characteristics at baseline were similar in both arms. The average age was 75.7 (SD = 4.8), 60.4% was male and 54.3% had treatment with palliative intent. Change in HRQOL scores did not differ by arm (p =.80). Neither group exceeded the MCID of 10 points. There was also no difference in IADL between the groups (p = 0.82). Conclusion: CGA was not effective in improving quality of life for older adults receiving cancer treatment in this study. CGA may need to be performed prior to treatment initiation to achieve benefits. Clinical trial information: NCT03154671.
Protein expression of programmed cell death ligand 1 and ligand 2 and their prognostic values in extensive-stage small cell lung cancer.
Authors: Ke (Kirsten) Zu, Jeanette Bæhr Georgsen, Peter Meldgaard, Anne Deitz, Mark Ayers, Maria Catherine Pietanza, Torben Steiniche
Journal: Journal of Clinical Oncology (2021)

e20593 Background: The receptor-ligand interaction between programmed cell death protein-1 (PD-1) and its ligands (PD-L1 and PD-L2) plays a critical role in tumor immune evasion and has become a therapeutic target in a number of cancer types, including extensive stage small cell lung cancer (ES-SCLC). While there are some published data on PD-L1 expression in ES-SCLC, the results vary with different laboratory assays or thresholds of positivity employed. Data on PD-L2 expression is very limited in ES-SCLC. The prognostic values of these biomarkers are not well understood. The current study aims to address this data gap. Methods: A retrospective cohort study of patients with ES-SCLC receiving usual care in the clinical setting in Denmark was conducted. Formalin-fixed paraffin embedded (FFPE) tumor tissue samples and data on patient characteristics and clinical outcomes were obtained for the patient population. Protein expression of PD-L1 and PD-L2 was determined by immunohistochemistry (IHC), and a combined positive score (CPS, the percentage of tumor cells and mononuclear inflammatory cells expressing the biomarker at any intensity out of the total number of tumor cells) of ≥1 was used to define biomarker positivity. Kaplan-Meier plots and Cox proportional hazard models were employed to assess the relationship between PD-L1 and PD-L2 protein expression and overall survival (OS). Results: Among the 80 patients with ES-SCLC included in this study, 25 and 29 were positive for PD-L1 and PD-L2, respectively (Table). A total of 68 patients had concordant expression status of PD-L1 and PD-L2 (21 as double positive and 47 as double negative). There was a significant association between PD-L1 positivity and longer OS, which persisted after adjustment for age and stage at SCLC diagnosis, performance score, prior exposure to chemotherapy, and lactate dehydrogenase levels (Table). Similar results were observed for PD-L2 (Table), and the data did not suggest any additional prognostic value of PD-L2 expression independent of PD-L1 expression. Conclusions: PD-L1 and PD-L2 positivity was both observed, and highly correlated with each other, in approximately one third of the ES-SCLC tumor samples tested. Patients with PD-L1 or PD-L2 positive tumors have significantly longer OS than those with negative tumors in this study, independent of other known prognostic factors.[Table: see text]