tbuckley/cabot-search huggingface dataset:
P14.31 Between hospital variation in timings to multidisciplinary glioblastoma care in the Dutch Brain Tumor Registry
Authors: M E De Swart, V K Y Ho, F J Lagerwaard, D Brandsma, M P Broen, P French, A Gijtenbeek, M Geurts, M C J Hanse, B Idema, M Klein, J A F Koekkoek, S K Polman, C W Samuels, T Seute, A E J Sijben, M Smits, M J Vos, A M E Walenkamp, P Wesseling, M C M Kouwenhoven, P C De Witt Hamer
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Delay in cancer care may adversely affect emotional distress, treatment outcome and survival. Optimal timings in multidisciplinary glioblastoma care are a matter of debate and clear national guidelines only exist for time to neurosurgery. We evaluated the between-hospital variation in timings to neurosurgery and adjuvant radiotherapy and chemotherapy in newly diagnosed glioblastoma patients in the Netherlands. MATERIAL AND METHODS Data were obtained from the nation-wide Dutch Brain Tumor Registry between 2014 and 2018. All adult patients with glioblastoma were included, covering all 18 neurosurgical hospitals, 28 radiotherapy hospitals, and 33 oncology hospitals. Long time-to-surgery (TTS) was defined as &amp;gt;3 weeks from the date of first brain tumor diagnosis to surgery, long time-to-radiotherapy (TTR) as either &amp;gt;4 or &amp;gt;6 weeks after surgery, and long time-to-chemotherapy (TTC) as either &amp;gt;4 or &amp;gt;6 weeks after completion of radiotherapy. Between-hospital variation in standardized rate of long timings was analyzed in funnel plots after case-mix correction. RESULTS A total of 4203 patients were included. Median TTS was 20 days and 52.4% of patients underwent surgery within 3 weeks. Median TTR was 20 days and 24.6% of patients started radiotherapy within 4 weeks and 84.2% within 6 weeks after surgery. Median TTC was 28 days and 62.6% of patients received chemotherapy within 4 weeks and 91.8% within 6 weeks after radiotherapy. After case-mix correction, three (16.7%) neurosurgical hospitals had significantly more patients with longer than expected TTS. Three (10.7%) and one (3.6%) radiotherapy hospitals had significantly more patients with longer than expected TTR for &amp;gt;4 and &amp;gt;6 weeks, respectively. In seven (21.2%) chemotherapy hospitals, significantly less patients with TTC &amp;gt;4 weeks were observed than expected. In four (12.1%) chemotherapy hospitals, significantly more patients with TTC &amp;gt;4 weeks were observed than expected. CONCLUSION Between-hospital variation in timings to multidisciplinary treatment was observed in glioblastoma care in the Netherlands. A substantial percentage of patients experienced timings longer than anticipated.
P14.42 Neratinib for treatment of leptomeningeal metastases from HER2-positive breast cancer in extended access program: preliminary results
Authors: A Pellerino, R Palmiero, F Bruno, F Mo, E Muscolino, F Franchino, R Rudà, R Soffietti
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Leptomeningeal metastases (LM) occur in 5% of human epidermal growth factor receptor 2 (HER2) breast cancer (BC) with a poor overall survival (OS) of 3 months. Neratinib is an oral, irreversible tyrosine kinase pan-inhibitor that was approved by FDA for the treatment of HER2-enriched BC, who completed a prior adjuvant trastuzumab-based therapy. The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab. PATIENTS AND METHODS Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM according to LANO criteria; KPS ≥60 at the time of diagnosis of LM; coexistence of BM that have or not received WBRT or radiosurgery; systemic disease with a life expectancy of at least 3 months; concomitant drugs, including capecitabine, trastuzumab, TDM-1, pertuzumab, and hormone therapy were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. The primary endpoint was the OS after the diagnosis of LM. Secondary endpoints were progression-free survival (PFS) following the diagnosis of LM, neurological benefit, radiological response rate, and tolerability. RESULTS From January 2018 to April 2021, 9 patients with LM have been enrolled. Median age at the time of diagnosis of LM was 44 years (95%CI 36–59) with a median KPS of 80 (95%CI 60–90). Median time since LM onset from the diagnosis of primary BC was 42 months (95%CI 11–166), and patients underwent a median number of adjuvant treatments before LM of 3 (95%CI 2–5). Three patients developed LM alone, and other 6 had LM associated with multiple brain metastases. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3–13*). Median PFS was 3.5 months (95%CI 2–6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2–19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial response were achieved according to LANO and RANO criteria, respectively. A CSF clearance was observed in 1 patient only (11.1%) following two months of neratinib. Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib. CONCLUSION This is the first study that shows that neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.
we are forgetting
Authors: D.A. Frater
Journal: Annals of Internal Medicine (2021)

Ad LibitumSeptember 2021we are forgettingD.A. Frater, MDD.A. Frater, MDE. Barrow Medical Group Dallas, TexasSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-0742 Audio Reading - “we are forgetting” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “we are forgetting” by D.A. Frater, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail These are the wordswe are forgettingthe words that hauntedus before examsthat haunt us now in ourdigitized cells beautifulwords full of liltand resonance signifyingdisease sometimes even deathbeautiful like a petrelthat lights atop a mastand warns us beforethe squall descends thatno craft or optimism canescape its consequencewords that make you ownyour skill your presencein the life of anotheryour intent the goodnessof your will applied withoutcodes or qualifierswithout commerce lashedlike Ahab to his whaleaccounting for everythingand nothing worthwhileThese words are freefreed by all who learnedabout this gift of ... Author, Article, and Disclosure InformationAffiliations: E. Barrow Medical Group Dallas, TexasCurrent Author Address: D.A. Frater, MD, E. Barrow Medical Group, 8230 Walnut Hill Lane, Suite 620, Dallas, TX 75231; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “we are forgetting” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “we are forgetting” by D.A. Frater, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics September 2021Volume 174, Issue 9Page: 1348 ePublished: 21 September 2021 Issue Published: September 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
P14.23 Relation between neurological deficits and location of postsurgical ischemia in glioma resection
Authors: A T J van der Boog, S David, A M M Steennis, J W Dankbaar, T J Snijders, J J C Verhoeff, P A Robe
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Postoperative ischemia is a known complications of glioma resection and can lead to neurological deficits. New or worsened postoperative deficits are often transient, but some patients experience persisting effects after surgery. Neuroanatomical location of ischemia is suspected to play an important role in the development as well as persistence of neurological deficits. Therefore, the aim of this study was to investigate the spatial relation between postoperative ischemia and short-term and long-term neurological deficits. MATERIAL AND METHODS Postoperative ischemia was defined as new confluent areas of diffusion restriction on DWI in a retrospective database of 144 adult WHO grade II-IV supratentorial glioma patients, who received MRI within 3 days after resection in 2012–2014. New or worsened neurological deficits of any grade at discharge and after 3 months was assessed in relation to postoperative ischemia by an experienced neuro-oncologist. We manually delineated ischemic lesions and spatially normalized these to stereotaxic MNI space. Next, we performed voxel-based analysis (VBA) to identify locations of ischemia associated with new or worsened neurological deficits and corrected for multiple comparisons using family-wise error correction to eliminate false positive results. Delineations were labeled using the Harvard-Oxford cortical and subcortical atlases and a white matter atlas (XTRACT). RESULTS Any new or worsened neurological deficits were present in 44 (30.5%) cases at discharge and in 27 (20.9%) cases after 3 months, of which respectively 26 (18%) and 21 (16.3%) were related to ischemia. Volume of ischemia was significantly associated with deficits at discharge (P = 0.003) and after 3 months (P = 0.039). No areas of ischemia were associated with a lack of new or worsened deficits. A statistically significant cluster of 42.96cc was associated with deficits at discharge and encompassed the right frontal, insular and tempo-occipital regions. Voxels associated only with deficits at discharge included lateral occipital cortices and supramarginal gyri. A cluster of 17.68cc in the right frontal and insular lobes was significantly associated with deficits after 3 months. Overlapping areas included the right thalamus, caudate nucleus, putamen, globus pallidum, insular cortex, middle and inferior temporal gyri, corticospinal tract and superior thalamic radiation. CONCLUSION Transient and persisting new or worsened deficits after glioma resection were significantly associated with volume of postoperative ischemia. Ischemic lesions in right frontal and insular regions, including the basal nuclei, corticospinal tract and superior thalamic radiation were significantly associated with persisting neurological deficits after 3 months, while temporo-occipital lesions were associated with transient deficits only found at discharge.
The Effect of Duration of Lenalidomide Maintenance and Outcomes of Different Salvage Regimens in Patients with Multiple Myeloma (MM)
Authors: Matthew Ho, Saurabh Zanwar, Prashant Kapoor, Morie Gertz, Martha Lacy, Angela Dispenzieri, Suzanne Hayman, David Dingli, Francis Baudi, Eli Muchtar, Nelson Leung, Taxiarchis Kourelis, Rahma Warsame, Amie Fonder, Lisa Hwa, Miriam Hobbs, Robert Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood Cancer Journal (2021)

Abstract The optimal duration of lenalidomide maintenance post-autologous stem cell transplant (ASCT) in Multiple Myeloma (MM), and choice of therapy at relapse post-maintenance, need further evaluation. This retrospective study assessed outcomes of patients with MM ( n = 213) seen at Mayo Clinic, Rochester between 1/1/2005–12/31/2016 who received lenalidomide maintenance post-ASCT. The median PFS was 4 (95% CI: 3.4, 4.5) years from diagnosis of MM; median OS was not reached (5-year OS: 77%). Excluding patients who stopped lenalidomide maintenance within 3 years due to progression on maintenance, ≥3 years of maintenance had a superior 5-year OS of 100% vs. 85% in &lt;3 years ( p = 0.011). Median PFS was 7.2 (95% CI: 6, 8.5) years in ≥3 years vs. 4.4 (95% CI: 4.3, 4.5) years in &lt;3 years (p &lt; 0.0001). Lenalidomide refractoriness at first relapse was associated with inferior PFS2 [8.1 (95% CI: 6.4, 9.9) months vs. 19.9 (95% CI: 9.7, 30.2; p = 0.002) months in nonrefractory patients]. At first relapse post-maintenance, median PFS2 was superior with daratumumab-based regimens [18.4 (95% CI: 10.9, 25.9) months] versus regimens without daratumumab [8.9 (95% CI: 5.5, 12.3) months; p = 0.006]. Daratumumab + immunomodulatory drugs had superior median PFS2 compared to daratumumab + bortezomib [NR vs 1 yr (95% CI: 0.5, 1.5); p = 0.004].
Association of treatment type with patient-reported quality of life in cancer distress screening.
Authors: Mohana Roy, Sarah Rosenthal, Manan P Shah, Ali Raza Khaki, Selen Bozkurt, Tina Seto, Douglas W. Blayney, Tina Hernandez-Boussard, Kavitha Ramchandran
Journal: Journal of Clinical Oncology (2021)

178 Background: Routine distress screening is recommended for all patients with cancer. In 2015, Stanford Cancer Center implemented such screening using a modified PROMIS-GH questionnaire. With the recent growth of oncology drugs, novel medications have been perceived as better tolerated than chemotherapy. We analyzed patient reported quality of life with global mental health (GMH) and global physical health (GPH) scores for different medication classes. Methods: Patients who completed a questionnaire at our center between 6/1/2015 and 12/31/2020 were included. Medications were classified as chemotherapy, targeted therapy, endocrine therapy, or immunotherapy using guidance from SEER.Rx ontology. Baseline (B) and treatment (Tx) questionnaires were completed before any treatment initiation of each medication type and within 3 months of each treatment, respectively. GPH and GMH scores were calculated using PROMIS T-scores stratified by medication type for B and Tx questionnaires. We analyzed for differences based on demographics and diagnoses. Clinically significant differences were defined as a 3-point difference in T-scores, which then prompted statistical comparison with t-tests to compare the B and Tx scores to each other and to the US population mean of 50. Results: We analyzed 28,180 questionnaires from 11,644 patients (59% women, median age 64; 23% stage I and II, 12% stage III, 23% stage IV, 51% missing). B and Tx mean GMH scores did not differ clinically compared to the US mean or to each other (baseline: 49.03 +/- 9.16, post: 48.5 +/- 9.1). However, both mean GPH scores were statistically and clinically lower (baseline: 44.2+/- 10.38, post: 42.4 +/- 10.1,) compared to the US mean (p &lt; 0.001). Changes in scores by treatment category are shown in the table below. There was a statistically significant difference in post-treatment GPH scores for chemo-immunotherapy patients when compared to both corresponding baseline scores (p &lt; 0.001) and post treatment chemotherapy alone scores (p &lt; 0.001). There was no clinically significant difference in scores when stratified by age, sex, primary language, insurance, disease stage or type. Conclusions: In this large retrospective study, we found that patients being treated for cancer did not report worse GMH scores compared to the US mean population, but do report lower GPH scores. While most scores varied little relative to other treatment types, those receiving chemo-immunotherapy had lower GPH scores when comparing baseline to treatment and to the US mean, warranting further investigation, given increasing use.[Table: see text]
Chitosan hydrogel/3D-printed poly(ε‐caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment
Authors: Pinxue Li, Liwei Fu, Zhiyao Liao, Yu Peng, Chao Ning, Cangjian Gao, Daxu Zhang, Xiang Sui, Yunfeng Lin, Shuyun Liu, Chunxiang Hao, Quanyi Guo
Journal: Biomaterials (2021)

Articular cartilage (AC) injury repair has always been a difficult problem for clinicians and researchers. Recently, a promising therapy based on mesenchymal stem cells (MSCs) has been developed for the regeneration of cartilage defects. As endogenous articular stem cells, synovial MSCs (SMSCs) possess strong chondrogenic differentiation ability and articular specificity. In this study, a cartilage regenerative system was developed based on a chitosan (CS) hydrogel/3D-printed poly(ε‐caprolactone) (PCL) hybrid containing SMSCs and recruiting tetrahedral framework nucleic acid (TFNA) injected into the articular cavity. TFNA, which is a promising DNA nanomaterial for improving the regenerative microenvironment, could be taken up into SMSCs and promoted the proliferation and chondrogenic differentiation of SMSCs. CS, as a cationic polysaccharide, can bind to DNA through electrostatic action and recruit free TFNA after articular cavity injection in vivo. The 3D-printed PCL scaffold provided basic mechanical support, and TFNA provided a good microenvironment for the proliferation and chondrogenic differentiation of the delivered SMSCs and promoted cartilage regeneration, thus greatly improving the repair of cartilage defects. In conclusion, this study confirmed that a CS hydrogel/3D-printed PCL hybrid scaffold containing SMSCs could be a promising strategy for cartilage regeneration based on chitosan-directed TFNA recruitment and TFNA-enhanced cell proliferation and chondrogenesis.
Association of TGFBR2 mutations with shorter survival in non-small cell lung cancer treated with immune checkpoint inhibitors.
Authors: Linxin Zheng, Mengmei Yang, Mengli Huang, Weifeng Li
Journal: Journal of Clinical Oncology (2021)

e21166 Background: Transforming growth factor beta receptor 2 (TGFBR2) is a transmembrane receptor that plays an important role in both cellular functions and immune reaction, including cell proliferation, cell differentiation and extracellular matrix production. It forms a heterodimeric complex with TGF-beta receptor type-1 and binds TGF-beta. The association between TGFBR2 gene mutations and efficiency of immune checkpoint inhibitors (ICIs) has not been investigated in non-small cell lung cancer (NSCLC). Methods: Two published cohorts of NSCLC patients treat with ICIs were used to explore the immunotherapeutic predictive role of TGFBR2 gene mutations, including a discovery cohort (Gandara et al., Nature Genetics, 2018) and a validation cohort(Samstein et al. Nature Genetics, 2019). The Cancer Genome Altas (TCGA) Pan -Lung Cancer dataset was used for prognostic analysis. Results: TGFBR2 mutations were identified in 1.6% (7/429) and 2.3% (8/344) patients with NSCLC in the discovery and validation cohort, respectively. In the discovery cohort, patients with TGFBR2 mutations had shorter progression-free survival (PFS, median, 1.3 months vs 2.7 months; HR = 2.83; 95% CI, 1.33–6; p = 0.0046) and dramatically shorter overall survival (OS, median, 2.4 months vs 11.1 months; HR = 3.46; 95% CI, 1.63–7.35; p = 0.00058) than those with wild-type TGFBR2. Consistent with this, TGFBR2 mutations were significantly correlated with shorter OS (3 months vs 10 months; HR = 3.46; 95% CI, 1.63–7.35; p = 0.00058) in the validation cohort. In addition, no significant difference was found in OS between TGFBR2-mutant and TGFBR2-wild-type NSCLC patients with standard treatment in TCGA cohort (p = 0.821). Conclusions: TGFBR2 gene mutations are associated with shorter survival in NSCLC patients treated with ICIs, suggesting that TGFBR2 mutations be used as a potential biomarker of predicting the efficiency of immunotherapy and guiding NSCLC systemic treatment.
Hospital admissions and place of death prior and during COVID-19: Real-world data from a Brazilian cancer center.
Authors: Karla Lúcia Lucia Nascimento, Errol James Philip, Luana Sacchi, Juliana Pereira, Jose Nazario, Joao Nunes Matos Neto, Cristiane Decat Bergerot, David Lee, Paulo Gustavo Bergerot
Journal: Journal of Clinical Oncology (2021)

313 Background: Treatment decisions for patients with cancer have changed during the COVID-19 pandemic due to the increased risk of infection among this population. In recognition of the impact of COVID-19 in Brazil, this study sought to explore the potential consequences of this disruption to oncology care by comparing the prevalence and place of death one year prior to the pandemic (January 2019 to February 2020) and during the pandemic (March 2020 to March 2021). Methods: Consecutive patients with cancer receiving treatment at a single institution located in the capital of Brazil were included in this analysis. Patients’ characteristics were collected via chart review: age, sex, histology, COVID-19, hospital admission and place of death. Chi-square analysis was used to determine differences among this sample of patients (pre-COVID-19 and during COVID-19). Results: We reviewed data from 3,833 patients (53% of patients during the pandemic). Patients’ characteristics were well balanced between both groups of patients. The proportion of patients with breast and prostate cancers increased (P &lt; 0.01). Rates of hospital admission were similar between both timepoint, with reasons for hospital admission also similar: surgery (22% vs 19%, respectively) and pulmonary dysfunction (14% vs 19%, respectively); 9% were diagnosed with COVID-19 during the pandemic. Similarly, no differences were found among rates of deaths between samples (7%); 42% of patients pre-COVID were receiving supportive care, while 40% were during pandemic. The proportion of patients dying at home was the same among both groups (12%). A slight increase was observed for those dying in the ICU (45% vs 46%, respectively) or hospital (35% vs 36%, respectively). Pre-COVID-19, no patient has died in the emergency room, and during pandemic, 3% has died). Conclusions: A similar proportion of hospital admission and place of death were found between patients prior and during the COVID-19 pandemic. Most patients died in institutional settings. Future studies are needed to better understand patient’s wishes and preferences and to develop strategies to improve communication surrounding death and dying.
Polymyxin B‐Triggered Assembly of Peptide Hydrogels for Localized and Sustained Release of Combined Antimicrobial Therapy
Authors: Yejiao Shi, David W. Wareham, Yichen Yuan, Xinru Deng, Alvaro Mata, Helena S. Azevedo
Journal: Advanced Healthcare Materials (2021)

Abstract Repurposing old antibiotics into more effective and safer formulations is an emergent approach to tackle the growing threat of antimicrobial resistance. Herein, a peptide hydrogel is reported for the localized and sustained release of polymyxin B (PMB), a decade‐old antibiotic with increasing clinical utility for treating multidrug‐resistant Gram‐negative bacterial infections. The hydrogel is assembled by additing PMB solution into a rationally designed peptide amphiphile (PA) solution and its mechanical properties can be adjusted through the addition of counterions, envisioning its application in diverse infection scenarios. Sustained release of PMB from the hydrogel over a 5‐day period and prolonged antimicrobial activities against Gram‐negative bacteria are observed. The localized release of active PMB from the hydrogel is shown to be effective in vivo for treating Pseudomonas aeruginosa infection in the Galleria mellonella burn wound infection model, dramatically reducing the mortality from 93% to 13%. Complementary antimicrobial activity against Gram‐positive Staphylococcus aureus and enhanced antimicrobial effect against the Gram‐negative Acinetobacter baumannii are observed when an additional antibiotic fusidic acid is incorporated into the hydrogen network. These results demonstrate the potential of the PMB‐triggered PA hydrogel as a versatile platform for the localized and sustained delivery of combined antimicrobial therapies.