tbuckley/cabot-search huggingface dataset:
Opioid use in locally advanced or metastatic urothelial carcinoma patients and matched non-cancer controls.
Authors: Simrun Kaur Grewal, Zsolt Hepp, Yutong Liu, Rupali Fuldeore, Steve Sesterhenn, Nancy N. Chang, Matt D. Galsky
Journal: Journal of Clinical Oncology (2021)

e16517 Background: There are currently no published data on the patient experience with pain and pain medication use among the locally advanced or metastatic urothelial carcinoma (la/mUC) population. In this study, we quantified opioid use, as a proxy for pain, in patients with la/mUC and in matched non-cancer controls, using real-world data. Methods: We performed a retrospective claims analysis of adults diagnosed with UC who initiated ≥1 la/mUC therapy between 5/2016-6/2019 using the IBM MarketScan databases. Non-cancer controls were identified in 2 steps: 1) exact match on age/gender at index, 2) nearest neighbor propensity score matching (1:3 ratio) based on age, gender, region, insurance type, index year, enrollment time, and major comorbidities. Index was the date of first la/mUC therapy; index for controls was aligned to claims activity for matched patients with la/mUC. Baseline was the 6 months pre-index; follow-up was from index until disenrollment, death or study end (12/2019). Analyses examined the proportion of opioid users, number of opioid prescriptions, and daily morphine equivalent dose (MEQ). Results: A total of 1,293 patients with la/mUC and 3862 controls were included; mean (standard deviation [SD]) age at index was 64.1 (11.9) years for the la/mUC cohort and 64.8 (12.0) for controls, and most were male (60.2% and 61.3%, respectively). Mean (SD) follow-up was 15.1 (8.9) and 15.5 (8.6) months, respectively. A higher proportion of patients with la/mUC used opioids than controls during both baseline and follow-up (Table). Among opioid users, trends in opioid use were similar between the cohorts during baseline, with differences during follow-up (Table). At baseline, 63.6% (n=822) of patients with la/mUC had ≥1 opioid prescription which decreased during first-line (1L) treatment to 38.8% (n=502) and subsequently increased to 47.0% (n=159 of 338) during second-line (2L) treatment. The mean (SD) number of opioid prescriptions also increased during later therapy lines (1L: 0.92 [0.99], 2L: 1.37 [1.24]) along with increases in mean (SD) daily MEQ (1L: 69.8 [274], 2L: 133 [586]). Conclusions: This study underscores the impact of pain among patients with la/mUC, which is common at diagnosis, higher than matched controls, and worsens as the patient progresses. Improved disease control with more effective therapies may reduce pain in this population. [Table: see text]
IMMU-05. IMMUNOTHERAPY WITH RESIQUIMOD REPOLARIZES TUMOR-ASSOCIATED MYELOID CELLS AND IMPROVES EVENT-FREE SURVIVAL IN A TRANSGENIC MOUSE MODEL OF SONIC-HEDGEHOG (SHH) MEDULLOBLASTOMA
Authors: Christopher Park, Morrent Thang, Duhyeong Hwang, Chaemin Lim, Taylor Dismuke, Marina Sokolsky, Rajeev Vibhakar, Andrew Donson, Timothy Gershon
Journal: Neuro-Oncology (2021)

Abstract Resiquimod is a synthetic small molecule agonist of Toll-like receptors 7 and 8 (TLR-7/8) that modulates innate immune cells. We found TLR-7/8 are expressed in medulloblastoma exclusively by tumor-associated myeloid cells (TAMs). We tested whether systemically administered resiquimod modulated TAMs in a genetic Sonic hedgehog (SHH) medulloblastoma model, and whether this modulation would be therapeutically beneficial. We generated mice with medulloblastoma by crossing hGFAP-Cre and SmoM2 mouse lines. The resulting hGFAP-Cre/SmoM2 (G-Smo) mice developed medulloblastoma with 100% frequency and showed a median survival of 14.5 days (n=12). Treatment with 3 doses of resiquimod at postnatal days 10, 12 and 14 reduced tumor size and increased median survival to 37 days (n=10) (p=0.003508). Cellular studies showed that resiquimod altered TAM phenotype, rapidly inducing expression of the inflammatory marker VCAM1, and more slowly increasing TAM populations. Responses to the 3-dose regimen were ultimately limited by recurrence and all mice eventually died of tumor progression. Continued resiquimod therapy with every other day dosing was less effective than the 3-dose regimen, suggesting that TAM responses to resiquimod are dynamic and change with prolonged exposure. Our data show that innate immunity, mediated by TAMs and stimulated by TLR-7/8 agonist therapy, can produce a significant anti-tumor effect in medulloblastoma. The common expression of TLR-7/8 on TAMs in patient-derived medulloblastoma samples and in the mouse model suggests that resiquimod may produce similar anti-medulloblastoma effects in humans. Further studies are needed to define the mechanism of the anti-tumor effect in detail, to determine the optimal dose regimen, and to determine if resiquimod can combine effectively with additional adjuvant therapies to produce curative effects.
ATRT-02. THE DUAL MTORC1/2 INHIBITOR, TAK-228 COMBINES SYNERGISTICALLY WITH THE BH3 MIMETIC, OBATOCLAX TO IMPROVE SURVIVAL IN MICE BEARING ORTHOTOPIC XENOGRAFTS OF AT/RT
Authors: Tyler Findlay, Ashlyn Parkhurst, Sabrina Wang, Charles Eberhart, Eric Raabe, Jeffrey Rubens
Journal: Neuro-Oncology (2021)

Abstract mTOR activation drives tumorigenicity by regulating transcription factor expression and downstream growth and survival pathways. We have previously shown that mTORC1 and mTORC2 are highly activated in AT/RT and the dual mTORC1/2 inhibitor, TAK-228 (Sapanisertib) improves survival in mice bearing orthotopic xenografts of AT/RT. To design a rational combination therapy that enhances TAK-228’s efficacy and durability, we performed RNASeq 4 hours after TAK-228 treatment of AT/RT cell models. Pathway analysis revealed disruption of the NRF2-mediated stress response. NRF2 is a cap’n’collar leucine zipper transcription factor that regulates expression of genes involved in redox homeostasis, energy metabolism, cell proliferation, and survival. Analysis of publicly available RNASeq data on 32 human tumors identified elevated expression of NRF2 in AT/RT (median expression 40.78, normal brain 18.81). Short-hairpin knockdown of NRF2 decreased the expression of NRF2 as well as the anti-apoptotic proteins MCL-1, BCL-xL, and BCL-2 (western blot), and intracellular concentrations of reduced glutathione (p&amp;lt;0.005, t-test). TAK-228 similarly decreased expression of NRF2, MCL-1, and glutathione (p&amp;lt;0.005, t-test) demonstrating that TAK-228 compromises AT/RT defenses against oxidative stress and cell death. The brain-penetrant BH3 mimetic, Obatoclax increases oxidative stress and induces apoptosis in AT/RT (MUSE oxidative stress, cPARP western blot, t-test p&amp;lt;0.05). These complementary mechanisms of action synergize to slow AT/RT cell growth (MUSE Cell viability assay, ANOVA p&amp;lt;0.05) and induce high rates of cell death (MUSE ANNEXIN V assay, ANOVA p&amp;lt;0.05, Western blot for cPARP, Compusyn Synergy analysis CI&amp;lt;1.0). Once-weekly treatments of TAK-228 combined with Obatoclax in orthotopic mouse models of AT/RT is well tolerated, slows tumor growth (bioluminescence imaging, ANOVA p&amp;lt;0.05) and significantly extends median survival from 35 to 55 days (Log-rank p&amp;lt;0.05). These findings support a new clinical trial aimed at improving AT/RT survival.
Impact of clostridiodes difficile infection on acute graft-versus-host disease in allogenic transplant patients.
Authors: Prasanth Lingamaneni, Vatsala Katiyar, Rohit Kumar, Maha A.T. Elsebaie, Hashim Mann, Pierre Rodriguez, Maryam Zia
Journal: Journal of Clinical Oncology (2021)

e19027 Background: Clostridiodes difficile infection (CDI) is reported to occur up to 9-fold higher in allogenic hematopoietic stem cell transplant (HSCT) recipients compared to the general population of hospitalized patients. This is attributed to disruption of gut microbiome by antibiotics, myeloablative regimens, neutropenia, prolonged hospitalization, and immunosuppressive regimens administered to prevent acute graft-versus-host disease (aGVHD). CDI by disruption of the intestinal microbiome may trigger gastrointestinal aGVHD. Previous studies from HSCT centers have reported conflicting data on the relationship between CDI and subsequent development of aGVHD. Methods: The Nationwide Readmissions Database was queried for admissions of adult allogenic HSCT patients between 2016 and 2018. Those with and without CDI during index admission were compared. Multivariable logistic regression was used to evaluate the primary outcome of risk of aGVHD in the index admission or within 100 days post-engraftment. Results: A total of 13518 allogenic HSCT patients were included in the study. Mean age was 52.4 years. 57.2% of patients were female. The most common underlying diagnoses were acute myeloid leukemia (38%), myelodysplastic syndrome (17%) and acute lymphoblastic leukemia (14%). 11.1% of the index admissions were complicated by CDI. Rates of aGVHD during the index admission or 100 days post-engraftment were similar between CDI and non-CDI groups: 13.8% vs. 12.1%, p=0.19 during index admission and 29.2% vs. 26.1%, p=0.09 during 100 days post-engraftment. Nonetheless, patients with CDI had longer length of hospital stay (34.6 vs 29.8 days, p&lt;0.0001), higher hospitalization costs ($608K vs $506K USD) and greater rate of inpatient mortality (7.3% vs 4.6%, p&lt;0.001). In the multivariate regression analysis, CDI during index admission was not associated with risk of development of aGVHD (Adjusted Odds Ratio 1.14, 95% Confidence Interval 0.87-1.48, p=0.34). Age and unrelated donor HSCT were predictive of risk of aGVHD. Conclusions: CDI during index admission was not predictive of aGVHD during the first 100 days post-allogenic HSCT. HSCT patients are frequency colonized with C.difficile. Diarrhea secondary to CDI may resemble gastrointestinal aGVHD. Therefore, overdiagnosis of CDI in this population is a concern. Antimicrobial stewardship and use of clinical decision support tools have been advocated recently to decrease testing of HSCT patients with C.difficile colonization. Multivariable analysis of risk factors of aGVHD.[Table: see text]
A cohort study on the molecular mechanism of distinct therapeutic effects and prognosis in Chinese colorectal cancer patients who underwent neoadjuvant or surgical therapies.
Authors: Ye Xu, Tianhao Mu
Journal: Journal of Clinical Oncology (2021)

e15544 Background: Colorectal cancer is one of the most common and lethal types of cancer in the world. However, the molecular mechanism of colorectal cancer and predicting biomarkers for prognosis are still not fully understood. Methods: Here, we investigated a cohort study to explore the genetic alteration of Chinese colorectal cancer patients. Primary tumors and metastatic tumors were collected and performed with whole exome sequencing. Distinct therapeutic effects of patients were recorded and analyzed. Overall survival of patients was also collected. Results: 57 patients with colorectal cancer (CRC) were enrolled in this study. The mutation landscape of primary tumors showed that the TOP 10 most frequently mutated genes were APC, TP53, KRAS, FRG1, SOX9, PIK3CA, MUC12, SMAD4, MUC4, and DNAH9. The main genetic mutation type was missense. Both primary tumors and metastatic tumors shared the feature of mutated TP53, APC, and KRAS. However, the primary tumors harbored higher mutated FMN2, PLXNB2, DSCAM, SSPO, and PCDHA13, while the metastatic tumors harbored RYR2, RAB15, WNK1, MUC16, and HERC2. Moreover, APC mutation showed a better overall survival (p = 0.029). Co-mutation of APC and FRG1 also presented a better overall survival than one-mutation or none-mutation types (p = 0.029). In contrast, ARID3A mutation (p &lt; 0.001), NUDT6 mutation (p &lt; 0.0099), ZNF717 mutation (p = 7e-04). Curative surgery showed better overall survival than palliative surgery (p = 0.042). However, EBV infection showed no significant relation to overall survival (p = 0.89). In addition, patients harboring FRG1 or CEL mutation were more sensitive to chemotherapy (p = 0.01 and p = 0.02 respectively), while TMB was not significantly related to the effects of chemotherapy. Interestingly, somatic mutations, including NEURL4, DLGAP5, EML1, MBD3L1, SETBP1, TMC4, YTHDC1, PLXNB2, ARHGAP8, and CHD2 were found to be significantly related to patients with family histories (p &lt; 0.05). Conclusions: In this study, we investigated the mutation landscape of primary tumors and metastatic tumors of Chinese colorectal cancer patients. Moreover, the associations between prognosis and different factors, including genetic mutations, surgery strategies, TMB, EBV, and family histories were explored, which may help shed light on better clinical treatment for colorectal cancer in the future.
Bone Marrow Involvement in Primary Mediastinal B-Cell Large-Cell Lymphoma
Authors: Ekaterina Alexsandrovna Fastova, Aminat U. Magomedova, Alla M. Kovrigina, Yana K. Mangasarova, Sergey K. Kravchenko, Valeriy G. Savchenko, Andrey I. Vorobiev
Journal: Blood (2017)
A potential survival impact of blood immune cells in patients with locoregionally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy.
Authors: Li Yang, Zhiyuan Xu, Victor Ho-Fun Lee, Anne W. M. Lee
Journal: Journal of Clinical Oncology (2021)

e18027 Background: To exam the changes of blood immune cells during concurrent chemoradiotherapy (CCRT) and explore their effects on survival in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Study population included stage III-IVA (TNM-8 th edition) locoregionally advanced nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy followed by CCRT from January 2015 to October 2019. Patients received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles or 40mg/m 2 weekly for a total of 6 weeks concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. All had complete blood counts with differentials at baseline and before each chemotherapy. The primary endpoint was progression-free survival (PFS). “Immune cells” of our interest included lymphocytes, neutrophils and platelets. Results: A total of 139 patients were eligible and recruited. The median follow-up was 34 months (range 4-72). All immune cells decreased significantly during CCRT; the rate of grade 3/4 lymphopenia, neutropenia and thrombocytopenia during CCRT were 96.4%, 25.2% and 9.4%, respectively. The median (interquartile range, IQR) time to nadir from the start of CCRT were 40 (32-44), 26 (20-42) and 30 (15-39) days for lymphocytes, neutrophils and platelets, respectively. The median PFS was not reached and estimated 2-year PFS was 90.2%. Patients with lymphocyte nadir ≤ 0.2×10 9 /L had better PFS compared with those with lymphocyte nadir &gt; 0.2×10 9 /L（2-yr PFS 95.5% vs. 87.5%, P=0.048). Patients with platelet nadir &lt; 100×10 9 /L had better PFS compared with those with platelet nadir ≥ 100×10 9 /L(2-yr PFS 96.9% vs. 84.2%, P=0.011). Neutrophil nadir was not associated with PFS in univariate analysis. Multivariate analysis including prognostic variables in univariate analysis showed that platelet nadir (&lt; 100 × 10 9 /L vs ≥ 100 × 10 9 /L, hazard ratio [HR] 0.279, 95% confidence interval [CI] 0.091-0.857, P=0.026), stage (III vs IVA, HR 0.321, 95% CI 0.115-0.901, P=0.031) and cumulative concurrent cisplatin dose (&lt; 180mg/m 2 vs ≥ 180mg/m 2 , HR 3.422, 95% CI 1.366-8.577, P=0.009) were prognostic of PFS by adjusting lymphocyte nadir and baseline hemoglobin. Conclusions: Blood immune cells decreased during CCRT and thrombocytopenia was prognostic of PFS in patients with LANPC. Longer follow-up is warranted to identify prognostic factors of overall survival.
Association and prevalence of venous thromboembolism in cancer patients with COVID-19: A single healthcare system experience.
Authors: Aneesha Ananthula, Dat Tran, Katharine Thomas, Katie Lauren McLemore McQueen Amaker, Anh Nguyen, Soham Mahato, Brandon T Thrash, Andrew G Chapple, Suki Subbiah
Journal: Journal of Clinical Oncology (2021)

2627 Background: There are increasing reports of thromboembolic complications in patients with COVID-19 infection. According to a meta-analysis of 28,173 patients, the prevalence of venous thromboembolism (VTE) in hospitalized COVID-19 patients ranges from 7.9% to 22.7% based on the severity of COVID-19. Cancer and anti-cancer therapies are known risk factors for thrombosis. Another study based on registry data reported the overall prevalence of VTE in hospitalized COVID-19 patients with cancer to be 14.5%. Our study aimed to assess the prevalence of VTE in cancer patients diagnosed with COVID-19 as well as the association between VTE and cancer in the setting of COVID-19 infection in a large predominantly urban healthcare system. Methods: We utilized a cohort data query tool in the electronic medical record at University Medical Center in New Orleans, Louisiana to identify patients &gt;17 years of age with a hospital or clinic visit in the LCMC Health system between March 1, 2020 and December 31, 2020 which were considered the base population for the study. Cancer patients were identified via the cancer registry tool. Patients with COVID-19 were identified using the abnormal COVID-19 PCR test result search field. An encounter diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) was used to identify patients with VTE. Odds ratios, p-values, and corresponding confidence intervals (CI) were calculated using 2x2 contingency tables. Results: In our database, we identified 3,807 patients with a diagnosis of COVID-19 and 9,560 with a cancer diagnosis. 158,812 patients had neither COVID-19 nor cancer. There were statistically significant greater odds of developing VTE in all subgroups compared: COVID-19 alone vs neither (OR 2.43), cancer alone vs neither (OR 3.8), and COVID-19 and cancer vs neither (OR 10.65). Conclusions: COVID-19 and cancer are both risk factors for VTE. Based on our study, appears that cancer has the greater effect on VTE compared with COVID-19 infection. Also, there is possibly a synergistic effect between COVID-19 and cancer, which further increases the likelihood of VTE. This study is a preliminary analysis. Further investigation is warranted in the form of either variable adjusted analysis of the same data, individual chart review, or a prospective study.[Table: see text]
Cost-effectiveness analysis of gastric cancer management using perioperative chemotherapy versus adjuvant chemoradiation therapy.
Authors: Vishnu Prasath, Patrick L. Quinn, Joseph B. Oliver, Omar Mahmoud, Mohammed Jaloudi, Vikas Akkaraju, Simran Arjani, Sushil Ahlawat, Ravi Chokshi
Journal: Journal of Clinical Oncology (2021)

e16079 Background: The most commonly used treatment options for gastric cancer include complete resection with adequate margins with either perioperative chemotherapy (PCT) or adjuvant chemoradiotherapy (CRT). While both treatment strategies have shown superiority over surgical resection alone, it is not clear which treatment strategy is more optimal. Methods: Our decision tree model was built to analyze the survival and costs associated with the two major management methods: perioperative chemotherapy and adjuvant chemoradiation therapy. Costs were obtained from Medicare reimbursement rates using a third-party payer perspective. Our model’s effectiveness was represented using quality-adjusted life years (QALYs). Our analysis tested the robustness of our conclusions by utilizing one-way, two-way, and probabilistic sensitivity analyses. Results: PCT was the preferred treatment strategy for diagnosed gastric cancer over CRT, with a cost of $54,326.10 and 4.08 QALYs. CRT was the costliest economic strategy with a cost of $77,987.52 and 4.28 QALYs and an ICER of 115,907.48. We set a threshold of $100,000 per QALYs gained which CRT surpassed making PCT the preferred treatment modality. Over 100,000 simulations, 51.4% of simulations favored PCT. CRT became favored when CRT non-curative procedure rates rose 3% higher than PCT non-curative procedure rates and when PCT complication rates rose 15% higher than CRT complication rates. Conclusions: In our simulated patients with diagnosed gastric cancer, the most cost-effective treatment strategy was PCT. We see cost-effectiveness alternating to favor CRT with changes in non-curative procedure rates and adjuvant therapy complication rates.[Table: see text]
Impact and predictors of readmission in hypercalcemia of malignancy: Findings of a nationwide analysis.
Authors: Binav Baral, Miguel Salazar, Victor Prado, Estefania Gauto, Shristi Upadhyay, Trilok Shrivastava, Navika Chhabra, Fred R. Rosen
Journal: Journal of Clinical Oncology (2021)

e18809 Background: Hypercalcemia of malignancy (HCM) is common in cancer. It is a sign of advanced malignancy and associated with poor outcomes. Although a well-known phenomenon, treatment options are limited and recurrence leading to readmissions is common, increasing morbidity and mortality. We attempt to explore the mortality, healthcare resource utilization, 30-day readmission rate and independent predictors of readmission for HCM. Methods: We queried the 2017 National Readmission Database (NRD) of adults readmitted within 30 days after index admission for HCM with a concomitant diagnosis of solid tumors. T test was used for continuous variables and chi square test was used for categorical variables. Multivariate regression was used to identify predictors for unplanned readmissions. Results: A total of 14,323 patients with solid tumors were admitted with HCM. The 30-day readmission rate was 24.9%. Common causes for readmission were sepsis, respiratory failure, hypercalcemia, distant metastases and AKI. At 30 days, readmitted patients were less likely to be discharged compared to patients admitted initially due to hypercalcemia (27.4 vs 30.8%; P&lt;0.01). Readmitted patients had a higher in-hospital mortality at 30 days (1.5 vs. 0.1%; P&lt;0.01), more incidence of chemotherapy induced pancytopenia (3.8 vs 2.5%; P&lt;0.01), mechanical ventilation (5.8 vs 4.7%; P=0.05) and venous thromboembolism (8.3 vs 5.9%; P&lt;0.01). Total economic burden of readmission was $251 million in total charges and $62.6 million in total costs. Adjusting for age and comorbidities, independent predictors of readmission were anemia of chronic disease, iron deficiency anemia and obesity. Conversely, predictors for lower odds of readmission were disposition to skilled facility and discharge with home health care services (Table). Conclusions: Nationally, HCM has a high rate of readmissions with increased morbidity and mortality making it a consequential healthcare burden. Among causes of readmission, potentially targetable include AKI and sepsis while among readmission predictors, iron deficiency anemia and anemia of chronic disease warrant further attention. Similarly, negative predictors highlight the importance of proper disposition planning and supportive care in malignancy.[Table: see text]