tbuckley/cabot-search huggingface dataset:
Molecular characteristics of <i>EGFR</i> exon 20 uncommon R776H mutation and response to osimertinib in NSCLC patients.
Authors: Gaili An, Li He, Xifang Wang, Yu Lei, Dejian Gu, Rongrong Chen, Xuefeng Xia, Jun Bai
Journal: Journal of Clinical Oncology (2021)

e21001 Background: EGFR R776H is an uncommon exon 20 mutation in non-small cell lung cancer (NSCLC) patients. This mutation was first reported in samples after first generation EGFR TKI treatment as an acquired resistant mutation to first generation of EGFR-TKI. We further analyzed the molecular characteristics of patients with EGFR R776H mutation and its correlation with EGFR TKI therapy. Methods: In this study, a total of 16131 NSCLC patients from multiple centers with NGS data were retrospectively analyzed to study the molecular characteristics and clinical outcomes of patients with EGFR R776H mutation. Results: 44 of the 16131 patients (0.27%) had EGFR R776H mutation, and 28 of them (63.6%) were treatment-naïve while performing the mutation test. TP53 was the most common concomitant mutation in both treatment-naïve (57.1%) and treated (81.3%) patients. EGFR R776H mutation was found to coexist with multiple types EGFR mutation. The common mutations were EGFR L858R (54%) and EGFR G719A/S (25%), but It almost never coexists with 19del (2%). The coexist of EGFR R776H mutation was similar in both treatment-naïve and treated patients. In 16 of treated patients, all had received first - or second-generation EGFR TKI treatment, and the median progression-free survival (PFS) was 9 months. Interestingly, four of them found the presence of not only EGFR R776H but also EGFR T790M. It may be that EGFR R776H and T790M appear together in drug resistance, or it may be that EGFR R776H and EGFR sensitive mutation are not in the same cell clone. Two patients with EGFR R776H received treatment of Osimertinib and achieved partial response. The PFS of two patients in Osimertinib were 11 and 10 months, respectively. Moreover, EGFR C797S mutation was detected in two patients after resistant to Osimertinib. Conclusions: Presence of EGFR R776H mutation was rare in NSCLC patients and our retrospective study provides clinical evidence that Osimertinib could be of benefit and may potentially be an effective treatment strategy to improve survival outcomes in patients with EGFR R776H.
An unusual presentation of prolonged delirium
Authors: Richard Burne, Russell Birkett, William Bennet, Abhi Shetty
Journal: BMJ (2021)

A woman in her 20s had a three week history of acute headaches, slurred speech, and unusual behaviour.

Neuropsychiatric symptoms were prominent, including confusion, confabulation, labile affect, persecutory beliefs, agitation, and aggression. No neurological deficits were present, her visual fields were normal, and she had no history of seizures.

Over the three weeks, her management had included: admission to neurology and discharge home; admission to psychiatry under the Mental Health Act and transfer back to neurology before discharge home again; readmission to psychiatry under the act.

Six months earlier she was investigated for hirsutism by her general practitioner: androgen levels were raised but pelvic ultrasonography did not show polycystic ovaries.

Moderate psychosocial stressors were present. She took no medication, had no psychiatric or substance misuse history, and had no relevant family history.

Routine delirium screen1—urinalysis, chest radiography, electrocardiogram, a computed tomography head scan, and blood tests (full blood count, …
Treatment patterns, overall survival, and healthcare utilization among Medicare beneficiaries with endometrial cancer in the United States.
Authors: Mugdha Gokhale, Jiemin Ma, Changxia Shao, Lei Chen, Robert Orlowski
Journal: Journal of Clinical Oncology (2021)

e18698 Background: Endometrial cancer (EC) is the most common gynecologic cancer in the US, yet real-world disease burden is poorly understood. To address this, we conducted a retrospective study exploring patient (pt) characteristics, treatment patterns, overall survival (OS), and healthcare resource utilization (HCRU) among elderly US pts with EC. Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data, we identified beneficiaries aged ≥65 y with newly diagnosed EC between Jan 1, 2007–Dec 31, 2013. Pts were followed from the EC diagnosis date to the earliest of death, loss to follow-up, or Dec 31, 2014. Descriptive analyses were conducted for pt characteristics assessed in the 6-mo baseline period and for treatment patterns and HCRU assessed during follow-up. Median OS was estimated from the start of each line of systemic therapy using the Kaplan-Meier method. Lines of therapy started when pts received a new systemic therapy regimen and ended when pts switched to another regimen, after a 90-d treatment gap, or at end of follow-up. For pts with surgery, systemic therapy starting &gt;120 d after surgery or after discontinuation of adjuvant therapy was defined as first-line (1L) therapy. Adjuvant therapy was defined as any systemic therapy starting ≤120 d after surgery for EC and ending after a 90-d treatment gap following the last prescription. Results: There were 12,710 eligible pts with EC during 2007–2013 in the SEER-Medicare database; median age at diagnosis was 73 y. At initial diagnosis, 9395 (73.9%) pts had stage I/II EC, 2042 (16.1%) had stage III, and 1273 (10.0%) had stage IV. 778 pts did not receive surgery/radiation, 1230 pts received surgery/radiation plus adjuvant therapy, 9729 pts received surgery/radiation only, and 973 (7.7%) pts received 1L systemic therapy. Of these 973 pts, 370 (38.0%) received second-line (2L) and 157 (16.1%) received third-line (3L) treatment. Pts receiving 1L therapy had a mean of 5.6 outpatient physician office visits per month, 22.1% had ≥1 hospitalization, and 38.5% had ≥1 emergency room visit during follow-up. Carboplatin-based regimens were the most frequently used 1L therapies (56.8%), typically combined with paclitaxel (43.5%). Median OS was generally short, particularly for those diagnosed with stage III/IV EC (Table). Conclusions: Medicare beneficiaries receiving systemic chemotherapy for EC generally had high HCRU and poor survival, particularly among pts diagnosed at later stages. This highlights the underlying disease burden and unmet need for more effective treatments in these pts.[Table: see text]
Efficacy of temozolomide in pretreated patients with metastatic sarcoma.
Authors: Nail Paksoy, Izzet Dogan, Meltem Ekenel, Mert Basaran
Journal: Journal of Clinical Oncology (2021)

e23550 Background: Sarcoma is a rare heterogeneous group malignancy and most commonly arises from soft tissue. The primary treatment modality is surgery. However, in metastatic disease, treatment options are limited. Cytotoxic chemotherapy is preferred for palliative treatment. This study aimed to assess the efficacy of temozolomide in heavily pretreated soft tissue sarcoma. Methods: We evaluated the patients with a metastatic various types of soft tissue sarcoma retrospectively. The patients with gastrointestinal stromal tumors and bone sarcomas were excluded from the study. We recorded the clinical, pathological, and treatment data of the patients. SPSS 25v was used for statistical analysis. Survival analysis was performed with the Kaplan-Meier method. Results: Sixteen patients were included in this study. The median age was 48 (range, 21-73) years. Six (37.5%) patients were de-novo metastatic. Tumor localizations were intra-abdominal (43.8%), extremity (31.2%), intrathoracic (12.5%), and head-and-neck (12.5%). The most common metastatic sites were lung (75%), bone (31.8%), liver (18.8%), respectively. For metastatic disease, the patients received at least two different chemotherapy regimens (75%), pazopanib (50%) and palliative radiotherapy (31.3%). Metastasectomy was also performed on five (31.3%) patients. Median progression-free survival was 3.5 (95% CI, 2.6-4.3) months. Partial response was observed in one (6.3%) patients, stable disease in four (25 %) patients. Eleven (68.8%) patients had progressive disease. Grade 1-2 adverse events were observed in nine (56.3%) patients, grade 3-4 in one (6.3%) patients. Conclusions: We showed that temozolomide was well-tolerated but had a limited efficacy for the treatment of patients with metastatic sarcoma. Treatment options for metastatic sarcomas are limited. Temozolomide may be considered a treatment option in patients with heavily pretreated soft tissue sarcoma.
Surgical outcomes and rate of pathological response in resectable/borderline resectable pancreatic cancer patients undergoing neoadjuvant gemcitabine/nab-paclitaxel versus FOLFIRINOX: A retrospective institutional analysis.
Authors: Abraham Attah Attah, Saleha Rizwan, Khaled Alhamad, Micheal Turk, Palash Asawa, Karthik Shankar, Lynna Alnimer, Srividya Srinivasamaharaj, Yazan Samhouri, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2021)

e16247 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors, predicted to become the second leading cause of cancer related death in some regions of the world. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Only about 20% of the cases are diagnosed early enough to undergo surgical resection leading to complete remission. While chemotherapy has an established role in the setting of metastatic disease, utilizing it in the neo-adjuvant setting has been adopted by most institutes for resectable/ borderline resectable cases. Ongoing trials are exploring the use of different regimens in the neo-adjuvant setting. The aim of our study was to identify patients with resectable/borderline resectable PDAC undergoing neoadjuvant chemotherapy and differences in surgical outcome based on the regimen received i.e gemcitabine/ nab-Paclitaxel vs FOLFIRINOX. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 121 patients who received and completed treatment in our institution, 30 underwent neoadjuvant chemotherapy treatment followed by surgical intervention. 21 (70%) patients were found to be borderline resectable, 8 (27%) patients were resectable and 1 patient had locally advanced PDAC. 16 (53%) patients received FOLFIRINOX compared to 13 (43%) patients received gem/nab-paclitaxel. Among patients who received neoadjuvant FOLFIRINOX, 5 out of 16 (31%) patients had moderate to significant treatment response at the time of surgery compared to 7 out of 13 (54%) patients who received gemcitabine/nab-paclitaxel. Conclusions: Our study revealed no significant difference (p=0.21) between the patients who received neoadjuvant gemcitabine/nab-paclitaxel vs FOLFIRINOX in terms of treatment response assessed pathologically at the time surgical resection. We recognize the limitations of our study in terms of it being a retrospective analysis with a small sample size and therefore further prospective and randomized controlled trials are needed to determine the most suitable and effective regimen in the neoadjuvant setting for resectable/borderline resectable PDAC patients. Response to treatment among different chemotherapy groups.[Table: see text]
IMMU-09. MODULATING THE MYELOID POPULATION IN DIPG MODELS WITH ONCOLYTIC VIRUS AND COMPLEMENT INHIBITORS SHOWS THERAPEUTIC EFFICACY
Authors: Montserrat Puigdelloses, Virginia Laspidea, Dolores Hambardzumyan, Zhihong Chen, Sumit Gupta, Candelaria Gomez-Manzano, Sara Labiano, Oren J Becher, Trent Woodruff, Ruben Pío, Daniel Ajona, Jaime Gállego Pérez-Larraya, Marta M Alonso
Journal: Neuro-Oncology (2021)

Abstract Diffuse intrinsic pontine glioma (DIPG) is the leading cause of brain tumor-related death in children. It is characterised for having a non-inflammatory microenvironment and be immunologically inert. Therefore, strategies aiming to break the microenvironment status-quo in this disease could provide therapeutic benefit. The complement system promotes tumor progression due to the continuous production of anaphylatoxins leading to the infiltration of myeloid cells, which express high levels of complement receptors (C3aR and C5aR1). We have in silico data showing the high expression of C5aR1 in DIPGs. Thus, we wanted to assess first whether complement C5aR1 could constitute an actionable target, and second whether combining C5aR1 inhibitors with oncolytic virus could result in a superior antitumor immune response than either agent alone in DIPG. In this study, we used two different peptide inhibitors of C5aR1, PMX53 and PMX205 combined with the virus Delta-24-ACT (an oncolytic virus armed with 4-1BBL). We performed in vivo studies to evaluate the efficacy of this combination in immunocompetent DIPG models. Our data showed that the combination Delta-24-ACT/PMX53 significantly extended the median survival of the animals when compared with either agent alone, and led to long-term survivors that generated immune memory. The combination treatment modulated the tumor microenvironment promoting an increase in lymphocytes, mainly CD8+ cells presenting an active phenotype, and a reduction in C5aR1 expression in the myeloid compartment. We are currently evaluating in vivo whether PMX205, which has an improved ability to cross the blood brain barrier, leads to better therapeutic response. In summary, the combination of Delta-24-ACT with a C5aR1 inhibitor showed the capacity to shake the DIPG tumor microenvironment and unleashed an antitumor immune response. These data underscore the possibilities to combine oncolytic virus with targets of the tumor microenvironment to improve their therapeutic benefit in DIPGs.
The impact of atrial fibrillation on hospitalization outcomes for patients with chronic lymphocytic leukemia: A large database analysis.
Authors: Mohammad Ammad Ud Din, Samarthkumar Thakkar, Harsh P. Patel, Syed Ather Hussain, Aneeqa Zafar, Hania Liaqat, Zunairah Shah, Sarju Ganatra, Muhammad Umair Mushtaq, Faiz Anwer
Journal: Journal of Clinical Oncology (2021)

e19508 Background: With the increased use of novel agents like Bruton tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukemia (CLL), the incidence of atrial fibrillation (AF) is on the rise in these patients. However, the excess burden added by AF to the morbidity and mortality of CLL patients is unclear. Methods: Using the appropriate ICD-9 and ICD-10 codes, the National Inpatient Sample (NIS) database was accessed to gather data of hospitalized CLL patients with AF from 2008 to 2019. Propensity-score matching (PSM) and logistic regression model were performed to control for baseline patient factors like age, sex, income, and the relevant co-morbidities to match 7265 CLL patient admissions with AF and 7265 CLL patient admissions without AF. The primary outcome was all-cause mortality (ACM), while secondary outcomes included stroke, acute heart failure (AHF), and total cost of hospital stay. Results: The mean age of the cohorts was 82 years. Females made up 44% of both groups. The AF group had similar prevalence of systemic hypertension (62.38% vs 62.10%; p= 0.73), diabetes mellitus (5.09% vs 5.43%; p= 0.35), congestive heart failure (5.57% vs 5.36%; p= 0.58), valvular heart disease (1.17% vs 1.44%; p= 0.14), and pulmonary hypertension (0.21% vs 0.14%; p= 0.31) compared to the group without AF. PSM revealed CLL patients with AF had a higher rate of ACM (6.06% vs 4.47%; p= &lt;0.0001), AHF (7.50% vs 3.85%; p= &lt;0.001), and stroke (3.09% vs 1.65%; p= &lt;0.0001). Admission in the AF group also had a higher median total cost of hospital stay ($9097 vs $7646). A logistic regression model was done to adjust for confounders which revealed similar results for the AF group with increased adjusted odd’s ratio (aOR) of ACM (aOR:1.39, 95% confidence interval (CI): 1.19-1.61; p= &lt;0.001), AHF (aOR: 2.16, 95% CI: 1.85-2.52; p= &lt;0.001), and stroke (aOR:1.94, 95% CI: 1.54-2.44; P= &lt;0.001) (Table). Conclusions: Our data suggest that hospitalized CLL patients with AF are at a significantly increased risk of all-cause mortality, AHF, and stroke. Several limitations like the inability to establish the temporal relationship between CLL and AF and the lack of data regarding medications of individual patients are important to keep in mind while interpreting the results.[Table: see text]
Porphyria Cutanea Tarda Associated with Hepatitis C
Authors: Tejesh S. Patel, Evgeniya Teterina Mohammed
Journal: New England Journal of Medicine (2021)

A 65-year-old man with hepatitis C virus infection presented with lesions on his hands and forearms. A 24-hour urine sample showed an elevated level of uroporphyrins, and a diagnosis of porphyria cutanea tarda was made.
Treatment response among patients with multiple myeloma initiating daratumumab across different lines of therapy: A real-world chart review study.
Authors: Shebli Atrash, Philippe Thompson-Leduc, Ming-Hui Tai, Shuchita Kaila, Kathleen Gray, Isabelle Ghelerter, Marie-Hélène Lafeuille, Patrick Lefebvre, Adriana C. Rossi
Journal: Journal of Clinical Oncology (2021)

e18737 Background: Daratumumab (DARA), a CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma (MM) among previously-treated patients since 2015, and among newly-diagnosed patients since 2018. This study aimed to describe real-world treatment response among patients initiating DARA across different lines of therapy since 2018. Methods: A retrospective chart review of adult patients with MM initiating DARA (monotherapy or as part of a combination regimen) between 1/2018 and 5/2020 was conducted at two clinical sites in the US (Levine Cancer Institute &amp; Weill Cornell Medical College). De-identified patient-level data were abstracted in an electronic case report form. Treatment patterns, overall response rate (ORR) and proportion of patients with very good partial response (VGPR) or better were reported using descriptive statistics and stratified by line of therapy (first line [1L], second line [2L] or third line or later [3L+]). Results: A total of 202 patient charts were extracted. Patients were, on average, 65.3 years old at MM diagnosis and 68.1 years old at DARA initiation; 109 (54.0%) were male; 104 (51.5%) were White and 65 (32.2%) were Black or African American; 64 (31.7%) received a stem cell transplant (SCT) prior to the line of DARA initiation. Twenty-one (10.4%), 53 (26.2%) and 128 (63.4%) patients initiated DARA in 1L, 2L and 3L + , respectively. Median follow-up time was 6.2 months for 1L patients and 13.8 months for 2L+ patients. The most common 1L regimen was DARA with bortezomib, lenalidomide ± dexamethasone (DVRd; n=10, 47.6%) followed by DARA with lenalidomide ± dexamethasone (DRd; n=8, 38.1%). The most common 2L regimen was DRd (n=15, 28.3%) followed by DARA with pomalidomide ± dexamethasone (DPd, n=13, 24.5%) and DARA with bortezomib ± dexamethasone (DVd, n=13, 24.5%). The most common regimen in 3L+ was DPd (n=62, 48.4%). Among patients initiating DARA in 1L, 2L or 3L+ the ORR was 100.0%, 81.6% and 76.0%, and the proportion of patients achieving VGPR or better was 73.3%, 65.8% and 51.0%, respectively (Table 1). Median time to treatment response ranged between 2.6 and 2.8 months post-initiation. Conclusions: In this study, patients initiated on DARA had high ORR and rates of VGPR or better, including an ORR of 100% among 1L DARA users. These findings suggest that DARA-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1L. [Table: see text]
広島市民病院における経皮的中隔心筋焼灼術(PTSMA)の臨床成績
Authors: 青景聡之, 井上一郎, 河越卓司, 石原正治, 嶋谷祐二, 栗栖智, 中間泰晴, 大河啓介, 丸橋達也, 香川英介, 臺和興
Journal: Circulation (2007)
Cost-effectiveness of concomitant and adjuvant temozolomide for glioblastoma patients with unmethylated O<sup>6</sup>-methylguanine-DNA methyltransferase promoter regions in the United States.
Authors: Manav Dev Midha, Mark Edward Votruba
Journal: Journal of Clinical Oncology (2021)

2058 Background: Promoter region methylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) gene has emerged as a predictive factor for longer overall (OS) and progression-free (PFS) survival response to concomitant and adjuvant temozolomide (TMZ) chemotherapy in glioblastoma. Recently, several investigators have suggested the small survival benefit of TMZ for unmethylated patients is insufficient to warrant the increased risk of adverse events and that these patients should instead be enrolled in clinical trials. This study informs the debate by estimating the incremental costs and benefits associated with TMZ use in methylated and unmethylated patients based on available published evidence. Methods: Published OS and PFS Kaplan-Meier curves were digitized, parameterized, and extrapolated to ten years. Partitioned Survival Analysis trees were constructed in TreeAge Pro 2020. Costs of TMZ, RT, and inpatient hospitalization were included, among others. It was assumed that all patients receive surgery prior to beginning radiation, and that RT and TMZ (six adjuvant cycles) dosing was standard. Published utilities associated with the progression-free and post-progression health states, subject to each treatment, were used. A 3% annual discount rate and a willingness-to-pay of $150,000/quality-adjusted life year (QALY) were assumed. Probabilistic sensitivity analysis (PSA) was conducted. Results: In methylated patients, RT + TMZ versus RT is associated with $67,622 in additional costs and 10.91 additional quality-adjusted life months (QALMs). In unmethylated patients, RT + TMZ versus RT is associated with $9,203 in additional costs and 2.24 additional QALMs. The implied incremental cost effectiveness ratios (ICERs) support TMZ use in both populations and suggest it is more favorable for unmethylated patients ($74,378/QALY and $49,302/QALY for methylated and unmethylated patients, respectively). However, the incremental net monetary benefit (INMB) associated with TMZ use is substantially smaller for unmethylated patients ($18,797 versus $68,753) due to the smaller survival gains for this population. PSA results indicate that TMZ is more likely to be cost-effective for methylated (89.3%) than unmethylated (77.4%) patients. Conclusions: Post-radiation clinical trial enrollment should be considered instead of TMZ for unmethylated glioblastoma patients. While the estimated ICER justifies the use of TMZ for unmethylated patients – in fact, does so more strongly than for methylated patients – the relatively small incremental health benefit is plausibly outweighed by the opportunity cost of not enrolling these patients in clinical trials that offer the possibility of more substantive gains to current and future glioblastoma patients.
Constance Mary Hunter
Authors: Frances Hunter
Journal: BMJ (2021)

Constance Mary Hunter (nee Wilton) was raised in Heywood, Lancashire, and studied medicine at Leeds University. She became a GP in Chapeltown, Leeds, in 1961 and spent most of her working life there.

Constance was committed to the principles of the NHS. She was an active member of a number of medical professionals led organisations formed to defend …