tbuckley/cabot-search huggingface dataset:
Is adjuvant chemotherapy beneficial for stage II-III goblet cell tumors of the appendix?
Authors: Katerina Mary Zakka, Shayla Williamson, Renjian Jiang, Olatunji B. Alese, Walid Labib Shaib, Christina Wu, Madhusmita Behera, Bassel F. El-Rayes, Mehmet Akce
Journal: Journal of Clinical Oncology (2020)

796 Background: Goblet cell tumors (GCT) of the appendix are very rare tumors constituting 2.5%-5% of all primary appendiceal neoplasms. Role of adjuvant chemotherapy (AC) is not established for GCT. This study aims to evaluate the impact of AC in stage II-III appendiceal GCT. Methods: Patients with pathological stage II and III GCT who underwent surgical resection between 2006 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8243/3, 8245/3 and C18.1. Patients treated with neoadjuvant systemic and/or radiation therapy and adjuvant radiation were excluded. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received with Log-rank test. Results: A total of 1,046 patients were identified. 53.7% males and 89.0% Caucasian; median age 56 (range, 20-90) years. Distribution across pathological stages II-III was 83.6% (N = 874) and 16.4% (N = 172) consecutively. 8.3% (N = 73) of stage II and 50.6% (N = 87) of stage III patients received AC. In the total cohort, AC was not associated with better OS compared to no AC in univariate analysis (HR 1.84; 95% CI 1.26-2.67; p = 0.001) or multivariable analysis (HR 0.94; 95% CI 0.57-1.52; p = 0.790). For stage II patients, AC was not associated with better OS in univariate (HR 1.24; 95% CI 0.60-2.57; p = 0.562) or multivariable analyses (HR 1.67; 95% CI 0.76-3.64; p = 0.199). Similarly, in stage III patients, AC was not associated with better OS in univariate (HR 0.78; 95% CI 0.48-1.29; p = 0.340) or multivariable analyses (HR 0.55; 95% CI 0.28-1.04; p = 0.067). In the entire cohort 5-year OS for patients that received AC was 83.9% (80.3%, 86.9%) versus 70.7% (60.9%, 78.5%) (p = 0.001) with no AC. For stage II patients, 5-year OS was 77.3% with AC vs. 87.7% with no AC (p = 0.562). For stage III patients, 5-year OS was 64.8% with AC vs. 54.4% with no AC (p = 0.340). Conclusions: AC was not associated with improved 5-year OS in patients with pathological stage II and III GCT compared to no AC.
Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia
Authors: Shuangyou Liu, Biping Deng, Zhichao Yin, Jing Pan, Yuehui Lin, Zhuojun Ling, Tong Wu, Dong Chen, Alex H. Chang, Zhiyong Gao, Yanzhi Song, Yongqiang Zhao, Chunrong Tong
Journal: Blood Cancer Journal (2020)
Circulating ensembles of tumor-associated cells in gastrointestinal cancers.
Authors: Dadasaheb Akolkar, Darshana Patil, Raymond Page, Timothy Crook, Sewanti Limaye, Vineet Datta, Stefan Schuster, Pradip Fulmali, Pooja Fulmali, Navin Srivastava, Pradip Devhare, Sachin Apurwa, Shoeb Patel, Ajay Srinivasan, Rajan Datar
Journal: Journal of Clinical Oncology (2020)

808 Background: CEA and CA19-9 are non-specific markers for Gastrointestinal (GI) cancers. Molecular analysis of fecal blood is of limited utility in colorectal cancers. A non-invasive pan-GI-cancer blood-based test with high specificity and sensitivity is an unmet medical need. Considering that unprovoked thromboembolism is a significant risk in multiple cancers, we hypothesized that circulating thrombotic emboli in peripheral blood could comprise cancer cells and would serve as a reliable biomarker for detection of GI cancers. Methods: We obtained 15ml of blood from 7481 individuals, including 181 cases of Esophageal cancer, 125 cases of Gastric cancer, 448 cases of colorectal cancer and from 6727 asymptomatic individuals with age related elevated risk who underwent evaluation of serum CA19-9 and AFP. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation and further processes for negative enrichment and harvesting of circulating tumor cell clusters which were characterized by immunostaining. Circulating Ensembles of Tumor Associated Cells (C-ETACs) were defined as clusters of 3 or more cells which were positive for EpCAM and CK, irrespective of CD45 status. Results: C-ETACs were detected in 86.7% of esophageal cancers, 94.4% of gastric cancers and 91.3% of colorectal cancers respectively irrespective of extent (stage / metastatic status) of disease and prior treatments. Overall sensitivity among 754 cancer patients was 90.7%. Among the asymptomatic individuals, C-ETACs were detected in 31 / 366 (8.5%) individuals with elevated CEA and 10 / 152 (6.2%) individuals with elevated CA19-9. C-ETACs were detected in 160 / 5333 (2.9%) of the asymptomatic individuals who had no abnormal findings in any of the said markers. Conclusions: C-ETACs were ubiquitously detected in cancers of Oesophagus, Stomach and Colorectum regardless of stage and treatment status, and pose significant latent risk of thromboembolism and metastasis/recurrence. The relative undetectability of C-ETACs in the asymptomatic cohort indicates causative connection with malignancies and are suitable for screening for these cancers.
Characteristics of gastrointestinal stromal tumors incidentally discovered during abdominal surgery.
Authors: Meera Garg, Kyle Joseph Hitscherich, Joseph J. Bennett
Journal: Journal of Clinical Oncology (2020)

835 Background: Gastrointestinal Stromal Tumors (GISTs) are rare sarcomas with 5000 new cases each year. Despite their low incidence, surgeons should be familiar with this pathology since GISTs can be encountered incidentally during abdominal surgery. Methods: A retrospective series was conducted by querying pathology and operative reports from a community cancer center between 2005 and 2019 for all GIST diagnoses. Patients identified to have incidental GISTs discovered intra-operatively while undergoing surgery for another diagnosis were the focus of this study. Patient and tumor characteristics were evaluated. Results: A total of 195 patients had a diagnosis of a resected GIST during our study period. Of these 195, 48 patients were incidentally discovered to have a GIST excised during another index operation. The average age of these patients was 62 years old, 27 were female and 21 male. The primary location of these incidental GISTs in descending frequency was stomach (62.5%, n = 30), small bowel (31.3%, n = 15), colon (4.2%, n = 2) and esophagus (2.1%, n = 1). The average GIST size for the cohort was 1.7cm, with stomach, small bowel, colon and esophagus measured at 1.8cm, 1.7cm, 0.65cm and 0.30cm, respectively. Mitotic rate was &lt; 5 mitosis/50 HPF in 96% of patients. Incidental GISTs were identified during the following surgery: colon (n = 14), bariatric (n = 13), non-bariatric gastric (n = 10), hernia (n = 4), pancreatic (n = 3), esophageal (n = 2) and other (n = 2). Most incidental GISTs were discovered during elective surgery (81.3%, n = 39) compared to emergency surgery (18.8%, n = 9), and for benign disease (n = 33) compared to malignant (n = 15). Conclusions: Approximately one quarter of all GISTs resected at our community cancer center in 15 years were discovered incidentally, and during a wide variety of abdominal surgeries for both benign and malignant disease. Almost all these GISTs were &lt; 2cm, benign, and should be cured with the incidental resection. Abdominal surgeons should be aware of unexpectedly finding small GISTs and should not be apprehensive about resecting since they have indolent characteristics. Larger lesions should trigger expert surgical oncology consultation.
Palliative Programs for Persons With Parkinsonism—The Next Frontier
Authors: Bastiaan R. Bloem, Sirwan K. L. Darweesh, Marjan J. Meinders
Journal: JAMA Neurology (2020)

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Pharmacokinetics/pharmacodynamics (PK/PD) of ivosidenib in patients with mutant <i>IDH1</i> advanced cholangiocarcinoma from the phase III ClarIDHy study.
Authors: Bin Fan, Ghassan K. Abou-Alfa, Andrew X. Zhu, Shuchi Sumant Pandya, Hongxia Jia, Feng Yin, Liewen Jiang, Camelia Gliser, Hua Yang
Journal: Journal of Clinical Oncology (2020)

539 Background: Mutations in isocitrate dehydrogenase 1 (m IDH1) occur in up to 20% of intrahepatic cholangiocarcinomas (CC), leading to accumulation of 2-hydroxyglutarate (2-HG) and epigenetic dysregulation, promoting oncogenesis. Ivosidenib (IVO; AG-120), a first in-class, oral, targeted inhibitor of the mIDH1 enzyme, showed improved progression-free survival and a positive trend in overall survival versus placebo (PBO) in ClarIDHy, a global, phase 3, multicenter, double-blind study (Abou-Alfa et al. ESMO 2019 LBA10_PR; NCT02989857). Methods: Patients (pts) with unresectable or metastatic m IDH1 CC were randomized 2:1 to IVO (500 mg once daily in continuous 28-day cycles) or matched PBO, stratified by number of prior systemic therapies (1 or 2). Crossover from PBO to IVO was permitted at radiographic progressive disease. Blood samples for PK/PD analyses, a secondary endpoint, were collected predose, 0.5, 2, and 4 h postdose on day (D) 1 of cycles (C) 1–2, predose and 2 h postdose on D15 of C1–2, and predose on D1 from C3 onwards. Plasma IVO and 2-HG were measured using validated or qualified LC-MS/MS methods. Results: As of 31Jan2019, 185 pts were randomized to IVO (n = 124) or PBO (n = 61); 35 pts crossed over to IVO. PK/PD analysis was available from 156 pts receiving IVO. IVO was absorbed rapidly following single and multiple oral doses; exposure, as measured by C max and AUC, was higher at C2D1 than after a single dose, with low accumulation. Plasma IVO reached steady state within C1 of daily dosing. In pts receiving IVO, baseline mean plasma 2-HG concentration was reduced from 1108 ng/mL to 97.7 ng/mL at C2D1, close to levels in healthy subjects (72.6±21.8 ng/mL). 2-HG inhibition was robust and persistent up to Cycle 19. An average 2-HG inhibition of 75.0% (up to 97.3%) was observed at steady-state after multiple IVO administrations. No plasma 2-HG decreases were seen with PBO. Analyses of plasma 2-HG levels and association with clinical outcomes will be presented. Conclusions: In pts with advanced m IDH1 CC, oral IVO 500 mg once-daily demonstrated good exposure, and maintained the inhibition of 2-HG to levels observed in healthy subjects, whereas 2-HG remained elevated with PBO. Clinical trial information: NCT02989857.
Real-world experience of regorafenib in patients with hepatocellular carcinoma: A multicenter United Kingdom study.
Authors: Paul J. Ross, Yuk Ting Ma, Daniel H. Palmer, Mark Peter Lythgoe, Sophie Merrick, Adel Samson, Ankit Rohit Rao, Bristi Basu, Debi Prasad, Tony Dhillon, David Lau, Suzanne Darby, James Orr, Jane Margetts, Richard Hubner, Shobhit Baijal, Rohini Sharma, Olusola Olusesan Faluyi, Lennard Lee, Kiruthikah Thillai
Journal: Journal of Clinical Oncology (2020)

499 Background: Regorafenib was the first treatment to demonstrate a survival benefit in patients with HCC after progression on sorafenib. The RESORCE trial found that regorafenib improved overall survival with acceptable toxicity, in patients with disease progression on sorafenib who tolerated ≥400mg sorafenib daily and had Child-Pugh A liver function. Methods: We performed a multicentre, retrospective, observational study of patients with HCC receiving regorafenib in the UK, following its availability in April 2018. Results: Data on a total of 104 patients were included from April 2018–August 2019, and 80.8% were male. Age was collected in 85 patients, with a median of 68 years (range 22–86). 23.5% had NAFLD, 21.2% had ALD, 12.9% had HBV, and 3.5% had HCV. Prior management included sorafenib (100%), TACE (30.8%), resection (12.9%). Duration of sorafenib treatment was evaluable in 99/104 patients, and reported a median of 8.7 months (range 1.8–76.6). Duration of regorafenib treatment was evaluable in 92/104 patients, and reported a median of 3.9 months (range 0.0–15.7). Following treatment with regorafenib, 6 patients (5.8%) achieved partial response, 37 (35.6%) achieved stable disease and 45 (43.3%) had progressive disease as the best response. 15 (14.4%) were not assessed and 1 (1.1%) had mixed response. Survival data is immature with 62/101 (61.4%) patients alive at the time of census with median survival currently 6.5 months. Fatigue was the most frequent AE, with 69/88 patients (85.2%) for all grades. 12/88 patients (14.8%) had Grade 3 fatigue. Other significant AEs include hand-foot syndrome (6/85 patients [7.3%] had Grade 3) and diarrhoea (4/83 patients [4.9%] had Grade 3). Conclusions: The population in our real-world experience of regorafenib for HCC had a similar duration of prior sorafenib to those in the RESORCE trial. However, there was different balance of aetiologies with a lower proportion of patients with HBV and HCV. The rate of partial response is similar to the RESORCE trial with fewer patients achieving stable disease. The incidence of fatigue was higher, but the incidence of hand-foot syndrome and diarrhoea were lower. Further expansion and follow-up of this population is warranted.
Impact of surveillance among patients with resected pancreatic cancer following adjuvant chemotherapy.
Authors: Selina Wong, Lovedeep Gondara, Daniel John Renouf, Howard John Lim, Sharlene Gill
Journal: Journal of Clinical Oncology (2020)

e16795 Background: Pancreatic adenocarcinoma carries a poor prognosis and high risk of recurrence even after surgery and adjuvant chemotherapy (AC). Guidelines recommend against routine surveillance imaging due to lack of evidence supporting a survival benefit. With current first-line chemotherapy options, it is unclear whether surveillance scans allow for early detection of asymptomatic disease and therefore an opportunity to offer fit patients chemotherapy. We describe the patterns of surveillance in patients followed at a Canadian provincial cancer agency and determine whether routine imaging after AC is associated with receipt of palliative chemotherapy (PC). Methods: A retrospective review was completed to identify patients treated at British Columbia (BC) Cancer centres between January 1, 2010 and December 31, 2016 who had undergone curative intent resection and received at least one cycle of AC. Baseline characteristics, number of scans done after completing AC to recurrence, and PC were collected. Logistic regression analysis was performed. Results: A total of 151 patients followed at BC Cancer were identified. Patients who recurred within 28 days after AC were excluded, leaving 142 patients, of which 115 patients had recurrence (81%). We defined 2 cohorts based on number of scans done between completion of AC and recurrence: those with 0-1 scans were “symptomatic” recurrences (22 patients, median age 68y, 64% female, and 91% node-positive) and those with &gt; 1 scan were “surveillance” recurrences (93 patients, median age 64y, 43% female, and 81% node-positive). Patients who underwent surveillance scans were more likely to receive PC at time of recurrence, though statistical significance was not reached (OR 2.11, 95% CI 0.75-6.58, p = 0.17). Conclusions: Despite guidelines, the majority of patients treated in BC underwent surveillance imaging. Within the limits of our sample size, we demonstrated a trend towards increased likelihood of receiving PC in patients who receive surveillance scans following AC. With efficacious PC options available, studies to determine whether receipt of PC in asymptomatic recurrences detected on imaging translates into improved survival and/or quality of life are warranted.
Lentivirus-mediated RNA interference of EZH2 inhibits proliferation, invasion, and decreases aneuploidy in breast cancer cells
Authors: Maria Gonzalez, Tracey Filzen, Sophia Merajver, Celina Kleer
Journal: Cancer Research (2008)

5802  Background: Enhancer of zeste homolog 2 (EZH2) has been shown to be overexpressed in breast carcinomas with high propensity to metastasize. EZH2 is an oncogene essential to promote proliferation and capable to trigger neoplastic conversion in the breast. Invasive carcinomas with high EZH2 are often hormone receptor negative and have a worse prognosis than tumors with low EZH2. We hypothesized that inhibition of EZH2 may decrease the tumorigenicity especially of triple negative breast cancer cells.  Methods: EZH2 protein was detected by immunohistochemistry on 10 triple negative hereditary invasive breast carcinomas from women carrying BRCA1 mutations. Lentivirus-mediated RNA interference targeting EZH2 was performed on MDA-MB-231, CAL51, and SUM149 breast cancer cells. Western blots, invasion, proliferation, and FACS analyses were performed.  Results: EZH2 protein was highly expressed in all triple negative BRCA1-associated invasive carcinomas. Inhibition of EZH2 in a triple negative cancer cell increases BRCA1 protein level in the nucleus. shRNA knock-down of EZH2 in breast cancer cells including the triple negative CAL51 cells, reduced invasion and proliferation (p
Palliative and End-of-Life Care for Patients With Hematologic Malignancies
Authors: Areej El-Jawahri, Ashley M. Nelson, Tamryn F. Gray, Stephanie J. Lee, Thomas W. LeBlanc
Journal: Journal of Clinical Oncology (2020)

Hematologic malignancies are a heterogeneous group of diseases with unique illness trajectories, treatment paradigms, and potential for curability, which affect patients' palliative and end-of-life care needs. Patients with hematologic malignancies endure immense physical and psychological symptoms because of both their illness and often intensive treatments that result in significant toxicities and adverse effects. Compared with patients with solid tumors, those with hematologic malignancies also experience high rates of hospitalizations, intensive care unit admissions, and in-hospital deaths and low rates of referral to hospice as well as shorter hospice length of stay. In addition, patients with hematologic malignancies harbor substantial misperceptions about treatment risks and benefits and frequently overestimate their prognosis. Even survivors of hematologic malignancies struggle with late effects, post-treatment complications, and post-traumatic stress symptoms that can significantly diminish their quality of life. Despite these substantial unmet needs, specialty palliative care services are infrequently consulted for the care of patients with hematologic malignancies. Several illness-specific, cultural, and system-based barriers to palliative care integration and optimal end-of-life care exist in this population. However, recent evidence has demonstrated the feasibility, acceptability, and efficacy of integrating palliative care to improve the quality of life and care of patients with hematologic malignancies and their caregivers. More research is needed to develop and test population-specific palliative and supportive care interventions to ensure generalizability and to define a sustainable clinical delivery model. Future work also should focus on identifying moderators and mediators of the effect of integrated palliative care models on patient-reported outcomes and on developing less resource-intensive integrated care models to address the diverse needs of this population.
Re: Aurélie De Bruycker, Elise De Bleser, Karel Decaestecker, et al. Nodal Oligorecurrent Prostate Cancer: Anatomic Pattern of Possible Treatment Failure in Relation to Elective Surgical and Radiotherapy Treatment Templates. Eur Urol 2019;75:826–33
Authors: Francesco Montorsi, Nicola Fossati, Giorgio Gandaglia, Alberto Briganti
Journal: European Urology (2020)
A phase II trial of [fam-] trastuzumab deruxtecan (T-DXd, DS-8201a) in subjects with HER2-positive, unresectable, or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Charles S. Fuchs, Javad Shahidi, Lijoy Mathew, Amy Qin, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2020)

TPS460 Background: Despite attempts, no HER2-directed therapies have been approved for gastric or GEJ cancer after disease progression on trastuzumab. [Fam-] trastuzumab deruxtecan (T-DXd, DS-8201a) is a novel HER2-targeted antibody-drug conjugate composed of a humanized monoclonal antibody specifically targeting HER2, a cleavable tetrapeptide-based linker (drug-to-antibody ratio of ≈8), and a potent topoisomerase I inhibitor payload. In a phase 1 study, T-DXd (5.4 or 6.4 mg/kg) showed promising antitumor activity in a variety of tumor types, including a confirmed objective response rate (ORR) of 43% among subjects with extensively pretreated HER2-positive gastric cancer (Shitara et al. Lancet Oncol. 2019;20(6):827-836). Here we describe the phase 2 trial evaluating the efficacy and safety of T-DXd in subjects with HER2-positive gastric/GEJ cancer previously treated with trastuzumab (NCT04014075). Methods: This is a single-arm, open-label, multicenter, phase 2 study in subjects with centrally confirmed, HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization positive), unresectable or metastatic gastric/GEJ cancer that progressed on or after first-line therapy with a trastuzumab-containing regimen. HER2 status will be confirmed by a fresh biopsy before enrollment. Subjects are excluded if they received anticancer therapy after a first-line trastuzumab-containing regimen. The study began in August 2019 and will recruit ≈ 72 subjects from 25 to 30 sites in North America and Europe. T-DXd at 6.4 mg/kg will be administered intravenously once every 3 weeks until disease progression. The primary efficacy endpoint is confirmed ORR by independent central review (ICR) using RECIST v1.1 criteria. Secondary endpoints include duration of response and progression-free survival by ICR and investigator assessment, ORR by investigator assessment, and overall survival. Additional endpoints include safety, disease control rate, and pharmacokinetic analyses. Health-related quality of life will also be measured. Clinical trial information: NCT04014075.