tbuckley/cabot-search huggingface dataset:
Hematologic malignancy patients suffer higher mortality and morbidity from COVID-19 than solid tumor patients.
Authors: Maxwell Masters Krem, Snigdha Nutalapati, Hannah L. Latta, Chris Z. Thomas, Hanine El Haddad, Gabriel A. Vilchez, Gerhard Hildebrandt
Journal: Journal of Clinical Oncology (2021)

e19048 Background: Cancer patients experience morbidity and mortality from infections, including COVID-19. Results are in conflict as to whether hematologic malignancy (heme) patients or solid tumor (solid) patients are at particular risk. We compared COVID-19 infection outcomes in these cohorts at our institution. Methods: Retrospective chart review of COVID-19 patients diagnosed from February 2020 to January 2021 who had a heme or solid diagnosis. We used Chi square analyses and t-tests for statistical correlations. Results: We analyzed outcomes of 146 COVID-19 episodes. Median age was 64 (25-97), 49% were female, and 24% were minorities. 49 (34%) had heme malignancy. Age, race, BMI, Karnofsky, and Charlson index (CCI) were similar for heme and solid cohorts. All-cause mortality (37 vs 15%) and COVID-induced mortality (33 vs 10%) were higher in heme vs solid, Table 1. Need for hospitalization (73 vs 46%, p = 0.009) and ICU care (31 vs 14%, p = 0.02) were worse for heme. Mean length of stay was 14.6 days and did not statistically differ for both groups. Overall risk of thrombosis was 11%. Severity of hypoxemia correlated with mortality. Compared with patients not requiring oxygen, relative risk (RR) of mortality was 3.06 (p = 0.06) for nasal cannula, 3.82 (p = 0.03) for high-flow oxygen, and 11.9 (p = 0.0008) for ventilation. Heme patients trended towards increased need of high-flow oxygen or ventilation vs solid patients, RR = 1.65 (p = 0.06). Additional mortality predictors were chemo within 6 months of COVID-19, age &gt; 65, nursing home residency, CCI &gt; 5, ICU care, max CRP &gt; 100, ferritin &gt; 1000, abs lymph count &lt; 500, platelet count &lt; 100, and bacteremia or C. difficile coinfection (Table). Race, gender, Appalachian status, and BMI did not predict mortality. Among the above factors, recent chemo (p=0.0001) and bacteremia (p = 0.03) were more common in heme vs solid patients. A higher proportion of heme patients received treatment for COVID-19 (51 vs 32%, p = 0.03). The most frequent therapies across the whole group were steroids (n=43), remdesivir (n=29), and azithromycin (n = 17). Conclusions: COVID-19 poses elevated mortality and morbidity risk for hematologic malignancy vs other cancer patients despite similar pre-infection demographics. Not surprisingly, need for ICU care, age, recent chemotherapy, and comorbidities elevate mortality risk in both heme and solid patients. Elevated inflammatory markers and severe lymphopenia appear to identify those patients who have immune dysregulation and greatest mortality risk. Mortality predictors.[Table: see text]
Recurrence and disease-specific survival after 10-year disease-free interval in patients with primary retroperitoneal liposarcoma: Implications for long-term surveillance.
Authors: Mark Archer Eckardt, Danielle S. Graham, Brian E. Kadera, Kyle D. Klingbeil, Scott D. Nelson, Sarah M. Dry, Anusha Kalbasi, Arun S. Singh, Bartosz Chmielowski, Frederick R. Eilber, Joseph G. Crompton, Frederick C. Eilber
Journal: Journal of Clinical Oncology (2021)

11546 Background: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) following surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined as the long-term natural history of RP-LPS after treatment is poorly understood. We evaluate a cohort of RP-LPS patients—without evidence of disease 10 years following initial resection—to assess the long-term risk of recurrence and disease-specific survival (DSS). Methods: The prospectively maintained UCLA Sarcoma Database was used to identify RP-LPS patients who demonstrated 10-year progression-free survival (10yr-PFS) after initial diagnosis and treatment. Patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. Time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. Results: From 1972-2010, 76 patients with RP-LPS had at least 10 years of follow-up. Of these, 37 (49%) demonstrated 10yr-PFS. Median follow-up was 15 years (range 10-35 years). Among the 10yr-PFS patients, 43% (16/37) developed a recurrence &gt;10 years after the initial surgery, and 19% (7/37) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or peri-operative treatment with radiation or chemotherapy (Table). Conclusions: Patients with primary RP-LPS treated with surgical resection +/- multimodality therapy have a long-term risk of recurrence and disease-specific death that is unacknowledged by current surveillance imaging guidelines. Among the patients with a 10yr-PFS, 43% developed a recurrence and 19% died of disease. These findings suggest a need for lifelong surveillance imaging in patients with RP-LPS.[Table: see text]
Hypercalcemia as a predictor of adverse treatment outcomes in DLBCL during chemotherapy: A national inpatient database study.
Authors: Dennis Danso Kumi, Trilok Shrivastava, Maha A.T. Elsebaie, hisham laswi, Kriti Ahuja, Kunnal Batra
Journal: Journal of Clinical Oncology (2021)

e19571 Background: Hypercalcemia occurs in up to 7% of NHL and up to 18% in diffuse large B-cell lymphoma (DLBCL) representing about 60% of cases. Thus far, there are only a few studies that have established the poor prognosis between hypercalcemia and outcomes in DLBCL. We sought to outline specific acute complications that can during admission for chemotherapy in patients with hypercalcemia. Methods: This is a retrospective analysis of hospital admission using the National Inpatient Sample database (2018), including 15,636 adult patients with DLBCL admitted for chemotherapy. We obtained descriptive data, conducted chi-square test, and stratified logistic regression to look for possible chemotherapy related acute medical complications &amp; predictors of mortality in DLBCL with &amp; without hypercalcemia. Study limitations included lack of long term follow up, variations in chemotherapy and possible under-reporting of test subjects. Results: The mean age among DLBCL patients with &amp; without hypercalcemia were 65.41 and 58.52 years respectively and the mean length of stay were 6.56 and 4.98 days respectively. Patient’s race, type of insurance and Charlson’s comorbidity index were found to be significant predictors of mortality in patients with DLBCL admitted for chemotherapy. Among race, Hispanics &amp; Asian or Pacific islanders were found to be at higher risk for mortality, while patients who had private insurance were found to be associated with higher mortality risk (p&lt;0.01). Similarly, Native Americans (aOR 8.72, 1.93-39.34, p&lt;0.01) and patients with Charlson comorbidity index of 4 or more were at higher risk of mortality (aOR 4.34, 2.30-8.18, p&lt;0.01). In regard to acute medical complications, DLBCL patients with hypercalcemia were at higher risk for tumor lysis syndrome (TLS) (aOR 3.86, p&lt;0.01), acute kidney injury (AKI) (aOR 4.28, p&lt;0.01) and hyperuricemia (aOR 9.74, p&lt;0.01). There was no significant association of hypercalcemia in DLBCL with hyperkalemia, fluid overload, ICU admission, mortality, total cost, or length of stay. Conclusions: Hypercalcemia is associated with higher adverse outcomes during chemotherapy treatment in patients with DLBCL including TLS, hyperuricemia, and AKI during chemotherapy admission. This confirms to the overall accession of poor outcomes as published by other studies.[Table: see text]
Loss of 5'ALK leads to better response to crizotinib in sarcomas with ALK rearrangement.
Authors: Bin Li, Yongbin Hu, Qiongzhi He, Jingchen Lu, Gengwen Huang, Sheng Xiao
Journal: Journal of Clinical Oncology (2021)

e23554 Background: Crizotinib targets abnormal ALK activation, however, the clinical responses vary among patients with ALK rearrangement. A recent study showed that the NSCLC patients with 5'ALK loss have a favorable response to Crizotinib with doubled progression-free survival (PFS). We asked whether sarcoma patients with ALK rearrangement have a similar correlation between 5'ALK loss and clinical response to Crizotinib. Methods: The histopathologic diagnosis was made on H&amp;E staining and IHC, including anti-ALK(D5F3). DNA isolated from FFPE materials was subjected to an NGS assay targeting 295 genes including ALK rearrangement. Results: 4 cases were detailed in Table. Case#1 is an inflammatory myofibroblastic tumor with a PLEKHH2-ALK rearrangement, which was previously reported in an NSCLC but not in sarcomas. Case #2 is an undifferentiated sarcoma with 2 ALK fusions, RANBP2-ALK and TMEM217-ALK, both in-frame fusions containing intact tyrosine kinase domains. The TMEM217-ALK is a novel fusion. Case#3 is a leiomyosarcoma with MYH9-ALK fusion, which was often seen in ALK-positive large B-cell lymphoma but not in sarcoma. Case #4 is an undifferentiated sarcoma with EML4-ALK fusion. All 4 cases had positive ALK IHC, consistent with the expression of ALK fusion proteins. Case#1 and #2 had a loss of 5' ALK, while case #3 and #4 retained the 5' ALK. All cases received and responded to Crizotinib therapy, with the Karnofsky Performance Status (KPS) improved from 30-60 score pre-therapy to 90-100 score after 3 months of Crizotinib. While Case#3 and #4, both retained the 5' ALK, relapsed at 9.4 m and 6.1 m, case#1 and #2, both lost 5' ALK, remain progression-free at 15m and 27m, respectively. The side effect was manageable with a grade II hepatic toxicity in only one patient. Conclusions: We report here 4 sarcomas with ALK rearrangement, including a novel fusion TMEM217-ALK. Two of these cases had a 5' ALK loss in addition to the 3' ALK rearrangement, and both had much longer PFS on Crizotinib therapy. The underlying mechanism deserved further investigation. Four fibrosarcomas with ALK rearrangements and their response to Crizotinib therapy.[Table: see text]
Oncologists' perception of frailty.
Authors: Zuhair Alam, Brian Patrick Singeltary
Journal: Journal of Clinical Oncology (2021)

e24012 Background: Frailty is an under recognized yet clinically important consideration in treatment decision making for older adults with cancer. The Comprehensive Geriatric Assessment (CGA) is considered gold standard for recognition of frailty and is endorsed by the International Society of Geriatric Oncology. Additionally, multiple screening tools have been validated to reliably detect frailty. Nevertheless, studies suggest that formal screening for frailty is not prevalent in community oncology practices and that oncologists’ clinical judgement is not as sensitive in identifying frailty as CGA. This survey was designed to assess the perceptions of frailty amongst oncology providers, as well as the prevalence and method of frailty screening in these practices. Methods: After approval by an independent research ethics board, a secure online survey was circulated amongst community oncology providers within the TriHealth Cancer Institute, including MD’s, DO’s, and NP’s, via email. Survey was live from January 24 th to February 12 th . Data was analyzed using descriptive statistics. Results: There were 20 total respondents from medical, surgical, gynecologic, and radiation oncology, 70% MD/DO. 70% of total respondents reported having &gt; 50% of their patients over the age of 65. All respondents reported being familiar with the concept of frailty and the ECOG performance status, while only 45% had heard of CGA. 40% respondents reported that they screen for frailty and all used ECOG alone or along with Karnofsky, none used CGA or other validated screening tools. 60% respondents did not formally assess frailty, however all but one felt frailty assessment to be beneficial. Most commonly cited barriers to screening were time restraints and lack of availability of follow up services. Conclusions: Despite proven clinical benefit of CGA and various validated screening tools, few oncology providers screen for frailty. Furthermore, only 45% report having heard of CGA while none incorporate it in their practice. This shows that professional education amongst oncology providers is needed to promote the use of CGA or alternative frailty screening measures to improve outcomes in older adults with cancer. Additionally, strategies must be implemented that would mitigate time restraints and lack of access to follow up services so that these providers may be more inclined to conduct such frailty assessments. Limitations of this study include potential for reporting bias and indeterminate generalizability. Next steps include quality improvement initiative of implementing a frailty screening tool in these practices.
Tracking elimination of HIV transmission in men who have sex with men in England: a modelling study
Authors: Francesco Brizzi, Paul J Birrell, Peter Kirwan, Dana Ogaz, Alison E Brown, Valerie C Delpech, O Noel Gill, Daniela De Angelis
Journal: The Lancet HIV (2021)

To manage the HIV epidemic among men who have sex with men (MSM) in England, treatment as prevention strategies based on test and treat were strengthened between 2011 and 2015, and supplemented from 2015 by scale-up of pre-exposure prophylaxis (PrEP). We examined the effect of these interventions on HIV incidence and investigated whether internationally agreed targets for HIV control and elimination of HIV transmission by 2030 might be within reach among MSM in England.We used a novel, age-stratified, CD4-staged Bayesian back-calculation model to estimate HIV incidence and undiagnosed infections among adult MSM (age ≥15 years) during the 10-year period between 2009 and 2018. The model used data on HIV and AIDS diagnoses routinely collected via the national HIV and AIDS Reporting System in England, and knowledge on the progression of HIV through CD4-defined disease stages. Estimated incidence trends were extrapolated, assuming a constant MSM population from 2018 onwards, to quantify the likelihood of achieving elimination of HIV transmission, defined as less than one newly aquired infection per 10 000 MSM per year, by 2030.The peak in HIV incidence in MSM in England was estimated with 80% certainty to have occurred in 2012 or 2013, at least 1 year before the observed peak in new diagnoses in 2014. Results indicated a steep decrease in the annual number of new infections among MSM, from 2770 (95% credible interval 2490-3040) in 2013 to 1740 (1500-2010) in 2015, followed by a steadier decrease from 2016, down to 854 (441-1540) infections in 2018. A decline in new infections was consistently estimated in all age groups, and was particularly marked in MSM aged 25-34 years, and slowest in those aged 45 years or older. Similar trends were estimated in the number of undiagnosed infections, with the greatest decrease after 2013 in the 25-34 years age group. Under extrapolation assumptions, we calculated a 40% probability of achieving the defined target elimination threshold by 2030.The sharp decrease in HIV incidence, estimated to have begun before the scale up of PrEP, indicates the success of strengthening treatment as prevention measures among MSM in England. To achieve the 2030 elimination threshold, targeted policies might be required to reach those aged 45 years or older, in whom incidence is decreasing at the slowest rate.UK Medical Research Council, UK National Institute of Health Research Health Protection Unit in Behavioural Science and Evaluation, and Public Health England.
A phase 2 trial of talimogene laherparepvec (TVEC) in combination with neoadjuvant chemotherapy for the treatment of nonmetastatic triple-negative breast cancer.
Authors: Hatem Hussein Soliman, Hyo S. Han, Deanna Hogue, Blaise Mooney, Ricardo L Costa, Marie Catherine Lee, Bethany Niell, Angela Williams, Alec Chau, Shannon Falcon, Nazanin Khakpour, Aixa Soyano, Avan J. Armaghani, Robert J Weinfurtner, Susan Hoover, John Kiluk, Marilin Rosa, Brooke Fridley, Hung T. Khong, Brian J. Czerniecki
Journal: Journal of Clinical Oncology (2021)

578 Background: TVEC is a modified oncolytic herpes simplex 1 (HSV1) virus currently FDA approved for the treatment of unresectable cutaneous and nodal melanoma. TVEC is designed to preferentially lyse tumor cells over normal tissue to release tumor associated antigens, produces GM-CSF to activate dendritic cells, and stimulates T cells to infiltrate the tumor (TILs). TILs in breast cancer are associated with better response to neoadjuvant chemotherapy (NAC), so we hypothesized that intratumoral TVEC may enhance response to NAC. We report results of a phase 2 trial combining NAC with TVEC in stage 2-3 TNBC. Methods: Stage II-III TNBC pts (N = 37) were to be enrolled into a single arm, optimal Simon 2 stage phase 2 trial with TVEC (10^6 PFU 1 st dose then 10^8 PFU x 4 doses) weeks 1,4,6,8,10 + weekly paclitaxel (80mg/m2) IV x 12, followed by dose dense AC (doxorubicin/cyclophosphamide 60/600 mg/m2) IV q2weeks x 4 alone given preoperatively. Primary endpoint was residual cancer burden 0 rate (RCB0). Trial meets primary endpoint with ≥15 RCB0 responses out of 37 evaluable pts, assuming p1 = 45% vs. p0 = 30% with one sided type I error rate at 0.10 and power at 70%. Results: Forty pts were enrolled at Moffitt (5/2018 – 4/2020) and evaluable for safety with 3 pts non-evaluable for efficacy due to incomplete treatment. Study demographics: median age 49 (27-66), 67.5% White, 10% Black, 15% Hispanic, clinical stage II 83% and III 17%, node + 42%. The RCB0 rate = 16/37 (43%, 95% CI 27-61%) and additional 9 pts with RCB-1 (RCB0/1 rate 68%, 95% CI 50-82%). Toxicities did not differ significantly from expected NAC toxicities except for increased brief G1-2 fevers, chills, injection site pains. Four pts had G2-3 thromboembolic events (10%) slightly greater than expected 6% rate on NAC. Conclusions: Addition of TVEC to NAC increased RCB0 rates with manageable toxicities and warrants additional investigation in TNBC. Immune correlates and updated survival data will be presented at the meeting. Clinical trial information: NCT02779855.
Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, attenuates nonalcoholic fatty liver disease in mice
Authors: Ying Hong, Lili Sheng, Jing Zhong, Xin Tao, Weize Zhu, Junli Ma, Juan Yan, Aihua Zhao, Xiaojiao Zheng, Gaosong Wu, Bingbing Li, Bangxing Han, Kan Ding, Ningning Zheng, Wei Jia, Houkai Li
Journal: Gut Microbes (2021)

The emerging evidence supports the use of prebiotics like herb-derived polysaccharides for treating nonalcoholic fatty liver disease (NAFLD) by modulating gut microbiome. The present study was initiated on the microbiota-dependent anti-NAFLD effect of Astragalus polysaccharides (APS) extracted from Astragalus mongholicus Bunge in high-fat diet (HFD)-fed mice. However, the exact mechanisms underlying the beneficial effects of APS on NAFLD formation remain poorly understood.Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS. Then, targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids (SCFAs) and bacteria that were specifically enriched by APS. Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium. Finally, the anti-NAFLD efficacy of identified bacterium was tested in HFD-fed mice.Our results first demonstrated the anti-NAFLD effect of APS in HFD-fed mice and the contribution of gut microbiota. Moreover, our results indicated that SCFAs, predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment. Metagenomics revealed that D. vulgaris from Desulfovibrio genus was not only enriched by APS, but also a potent generator of acetic acid, which showed significant anti-NAFLD effects in HFD-fed mice. In addition, D. vulgaris modulated the hepatic gene expression pattern of lipids metabolism, particularly suppressed hepatic fatty acid synthase (FASN) and CD36 protein expression.Our results demonstrate that APS enriched D. vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid, and modulation on hepatic lipids metabolism in mice. Further studies are warranted to explore the long-term impacts of D. vulgaris on host metabolism and the underlying mechanism.
CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC).
Authors: Qiang Xue, Baogui Wang, Xiaona Wang, Xuewei Ding, Yong Liu, Xuejun Wang, Ning Liu, Hongjie Zhan, Bin Ke, Bin Li, Mingzhi Cai, Jingyu Deng, Liangliang Wu, Wenbai Huang, Hongmin Liu, Yan Sun, Han Liang
Journal: Journal of Clinical Oncology (2021)

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 &amp; PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8 th ) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m 2 , iv, d1; w/ peritoneal spread: 180 mg/m 2 , iv, d1 and 80 mg/m 2 , ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]