tbuckley/cabot-search huggingface dataset:
Radiographic predictors of pathologic response to neoadjuvant chemotherapy with gemcitabine and cisplatin in patients with high-grade upper tract urothelial carcinoma.
Authors: Nathan Colin Wong, Soleen Ghafoor, Hebert Alberto Vargas, Dean F. Bajorin, Jonathan Coleman
Journal: Journal of Clinical Oncology (2020)

522 Background: Neoadjuvant chemotherapy (NAC) has established survival benefits prior to radical cystectomy for bladder cancer, yet its role in upper tract urothelial carcinoma (UTUC) prior to nephroureterectomy (NU) is less clear. We performed a phase II clinical trial of NAC with gemcitabine and cisplatin (GC) in patients with UTUC to evaluate pathologic response. We investigated if radiographic responses could predict pathologic response. Methods: Patients with high-risk localized UTUC (high grade on biopsy and/or radiographic evidence of cT2-4 disease with positive select cytology) were recruited to receive 4 cycles of GC prior to NU with the primary objective of the phase 2 study being pathologic response rate, defined as ≤pT1N0. All patients underwent CT imaging at before and after chemotherapy. All baseline imaging studies were categorized as: (i) no abnormality, (ii) focal mass or (iii) thickening without discrete mass. Post-chemotherapy imaging studies were categorized as: (i) stable disease, (ii) progression of disease, (iii) partial response or (iv) complete response. Radiographic responses were correlated with final pathologic staging. Results: 43 patients (pT0N0 = 9, ≤pT1N0 = 18 and &gt;pT1N0 = 16) had CT performed pre- and post-chemotherapy. All patients had a visible lesion seen (mass = 34 and thickening = 9). The median pre-chemotherapy mass size was 3.1cm (IQR 1.8, 4.1). Approximately 60.5% of patients (N = 26) had evidence of hydronephrosis prior to chemotherapy. Following chemotherapy, 10 patients had a complete response, 20 had a partial response and 13 had stable disease. No patients progressed radiographically while on chemotherapy. Patients who had a complete radiographic response were more likely to have a pathologic response (≤pT1N0 = 90%), compared to a partial response (90% vs 65%, P = 0.21) and stable disease (90% vs 38%, P = 0.01). Conclusions: Radiographic response following NAC for UTUC appears to be correlated with pathologic response at time of surgery. Radiographic response, in addition to other pre-operative predictors, may play a useful role in counselling and optimizing management of patients with UTUC.
The role of capecitabine as maintenance therapy in <i>de novo</i> metastatic nasopharyngeal carcinoma: A propensity score matching study
Authors: Xue‐Song Sun, Sai‐Lan Liu, Yu‐Jing Liang, Qiu‐Yan Chen, Xiao‐Yun Li, Lin‐Quan Tang, Hai‐Qiang Mai
Journal: Cancer Communications (2020)

Abstract Background Capecitabine was previously used as a second‐line or salvage therapy for metastatic nasopharyngeal carcinoma (NPC) and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers. This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein‐Barr virus (EBV) DNA levels before treatment. Methods We selected de novo metastatic NPC patients treated with locoregional radiotherapy (LRRT) for this retrospective study. The propensity score matching (PSM) was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3. Overall survival (OS) was the primary endpoint. The association between capecitabine maintenance therapy and survival was assessed using the log‐rank test and a Cox proportional hazard model. Results Among all patients eligible for this study, 64 received capecitabine maintenance therapy after LRRT. After PSM, 192 patients were identified in the non‐maintenance group. In the matched cohort, patients treated with capecitabine achieved a higher 3‐year OS rate compared with patients in the non‐maintenance group (68.5% vs. 61.8%, P = 0.037). Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor. In subgroup analysis, 3‐year OS rate was comparable between the maintenance and non‐maintenance groups in patients with high pretreatment EBV DNA levels (˃30,000 copies/mL) (54.8% vs. 45.8%, P = 0.835), whereas patients with low pretreatment EBV DNA levels (≤30,000 copies/mL) could benefit from capecitabine maintenance therapy in OS (90.0% vs. 68.1%, P = 0.003). Conclusion Capecitabine maintenance therapy may be superior to non‐maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA ≤ 30,000 copies/mL.
Real-world utilization of radium-223 (Ra-223) for the treatment of metastatic castration-resistant prostate cancer (mCRPC): A U.S. tertiary oncology center analysis.
Authors: Rana R. McKay, Rebecca Silver, Rachel Bhak, Caroline Korves, Mu Cheng, Sreevalsa Appukkuttan, Stacey J. Simmons, Mei Sheng Duh, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2020)

223 Background: Guidelines for optimal sequencing of approved mCRPC therapies do not exist. This study evaluated treatment patterns and overall survival (OS) among patients (pts) with mCRPC treated with Ra-223 in an academic clinical setting. Methods: A retrospective chart review study was conducted at Dana-Farber Cancer Institute of bone metastases-predominant mCRPC pts treated with Ra-223. Treatment patterns from 2013-2018 were evaluated including Ra-223 initiation pre- vs. post-chemotherapy (chemo). OS was examined using Kaplan-Meier medians and 95% confidence intervals (CIs). Results: 220 pts were treated with Ra-223 (64 pre-chemo, 83 post-chemo, 73 no chemo). Median Ra-223 injections per pt was 6.0 and 5.0 in the pre- vs. post-chemo cohorts, respectively (p&lt;0.001). Mean chemo cycles received was 9.0 (pre-chemo) and 9.2 (post-chemo); on average, Ra-223 was given in the 3rd and 5th mCRPC line of therapy (pre- and post-chemo, p&lt;0.001). 41.8% of pts were treated with Ra-223 in combination (combo) with another mCRPC therapy, commonly abiraterone acetate (37.0%) or enzalutamide (44.4%). The majority received combo therapy for the duration of Ra-223 treatment. 17.6% started another agent after Ra-223 initiation; 17.6% initiated Ra-223 while on an established therapy. Median OS from Ra-223 initiation was 12.4 months (95% CI 10.2, 13.9). Median OS from first mCRPC treatment was slightly longer for pts with Ra-223 pre- vs. post-chemo (by 2 months) and for pts with Ra-223 combo vs. monotherapy (by 3 months). Conclusions: Ra-223 improves OS in mCRPC, and longest OS was seen in those with Ra-223 pre-chemo. Retrospective analysis of 5 years of Ra-223 treatment data from an academic center demonstrates that pts treated pre-chemo on average obtained 1 additional cycle of Ra-223, subsequent chemo administration was not limited and OS measured from first mCRPC therapy was not significantly different.[Table: see text]
Association of serum iron and response to immune checkpoint inhibitors (ICIs) in metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Nityam Rathi, David D. Stenehjem, Neeraj Agarwal, Andrew W Hahn, Deepika Sirohi, Prayushi Sharma, Mei Yee Koh, Benjamin Louis Maughan
Journal: Journal of Clinical Oncology (2020)

723 Background: ICIs have improved survival in mRCC patients (pts), yet response rates (RR) to these treatments are variable. Biomarkers predictive of response to ICIs may improve outcomes for mccRCC pts. Genes that promote tumor-specific iron accumulation such as hepcidin (HAMP) or transferrin (TF) are significantly correlated with decreased overall survival in clear cell RCC (TCGA-KIRC). Iron deficiency in cancer patients is positively correlated with tumor stage and inversely proportional to treatment response (PMID: 23567147). Here, we investigate whether serum iron profile may be associated with response to ICIs in mccRCC pts. Methods: Clinical data was obtained from an mRCC registry at the Huntsman Cancer Institute, University of Utah. Analyses were limited to mccRCC pts who had serum iron studies within 6 months before initiating an ICI and had been assessed for RR. ICIs included nivolumab + ipilimumab, atezolizumab, or nivolumab alone. Responses were defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by RECIST criteria. Clinical benefit (CB) was defined as CR + PR + SD. Descriptive statistics were used to assess associations between iron stores and response to ICIs and IMDC criteria. Results: 36 pts met all aforementioned eligibility criteria (29 were of IMDC intermediate risk, 7 were of IMDC poor risk). 5 pts received a first-line ICI, and the remaining 31 pts received ICIs as salvage therapy. Pts with CB had a significantly higher median serum iron level compared to those with no CB (59 vs 38.5 ug/dL; p=0.024). Furthermore, pts with normal transferrin saturation (TSAT %) were more likely to derive CB from ICIs (p=0.048). No association was found between serum ferritin (a marker of inflammation and tissue iron) and response to ICIs. Conclusions: In this hypothesis-generating study, increased serum iron, and TSAT levels within the normal range are associated with an increased likelihood of response to ICIs in pts with mccRCC. Once validated, these results may establish serum iron profile as a predictive marker of response to ICIs, in addition to providing the rationale for ruling out iron deficiency before starting ICIs.
Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Claudia C. Dobler, Allison S. Morrow, Bradley Beuschel, Magdoleen H. Farah, Abdul M. Majzoub, Michael E. Wilson, Bashar Hasan, Mohamed O. Seisa, Lubna Daraz, Larry J. Prokop, M. Hassan Murad, Zhen Wang
Journal: Annals of Internal Medicine (2020)

Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations.To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD.English-language searches of several bibliographic sources from database inception to 2 January 2019.68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, "usual care," or other pharmacologic interventions.Two reviewers independently extracted data and rated study quality and strength of evidence (SOE).Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function.Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs.Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD.Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609).
Comparison of the Pharmacokinetics and Pharmacodynamics of Epinephrine After Intranasal (IN), Intramuscular (IM) and Subcutaneous (SC) Administration in Three Landmark Studies
Authors: Richard Lockey, F. Estelle Simons, Michael Kaliner, Phillip Lieberman, Sarina Tanimoto, Richard Lowenthal
Journal: Journal of Allergy and Clinical Immunology (2020)
Clinical importance of urinary sodium excretion in acute heart failure
Authors: Kevin Damman, Jozine M. Ter Maaten, Jenifer E. Coster, Jan A. Krikken, Vincent M. van Deursen, Hidde K. Krijnen, Mischa Hofman, Wybe Nieuwland, Dirk J. van Veldhuisen, Adriaan A. Voors, Peter van der Meer
Journal: European Journal of Heart Failure (2020)

Abstract Aims Urinary sodium assessment has recently been proposed as a target for loop diuretic therapy in acute heart failure (AHF). We aimed to investigate the time course, clinical correlates and prognostic importance of urinary sodium excretion in AHF. Methods and results In a prospective cohort of 175 consecutive patients with an admission for AHF we evaluated urinary sodium excretion 6 h after initiation of loop diuretic therapy. Clinical outcome was all‐cause mortality or heart failure rehospitalization. Mean age was 71 ± 14 years, and 44% were female. Median urinary sodium excretion was 130 (67–229) mmol at 6 h, 347 (211–526) mmol at 24 h, and decreased from day 2 to day 4. Lower urinary sodium excretion was independently associated with male gender, younger age, renal dysfunction and pre‐admission loop diuretic use. There was a strong association between urinary sodium excretion at 6 h and 24 h urine volume (beta = 0.702, P &lt; 0.001). Urinary sodium excretion after 6 h was a strong predictor of all‐cause mortality after a median follow‐up of 257 days (hazard ratio 3.81, 95% confidence interval 1.92–7.57; P &lt; 0.001 for the lowest vs. the highest tertile of urinary sodium excretion) independent of established risk factors and urinary volume. Urinary sodium excretion was not associated with heart failure rehospitalization. Conclusion In a modern, unselected, contemporary AHF population, low urinary sodium excretion during the first 6 h after initiation of loop diuretic therapy is associated with lower urine output in the first day and independently associated with all‐cause mortality.
The deleterious association between proton pump inhibitors and prostate cancer specific death.
Authors: Hanan Goldberg, Faizan Moshin, Refik Saskin, Girish S. Kulkarni, Alejandro Berlin, Miran Kenk, Christopher J.D. Wallis, Thenappan Chandrasekar, Zachary William Abraham Klaassen, Olli Saarela, Linda Penn, Shabbir M.H. Alibhai, Neil Eric Fleshner
Journal: Journal of Clinical Oncology (2020)

309 Background: Proton pump inhibitors (PPIs) are a commonly prescribed class of medications. Although in-vitro and in-vivo data have shown PPIs to have anti-tumor effects, more recent studies suggest an increased cancer risk in several solid organs. Pantoprazole, a commonly prescribed PPI, has been shown to harbor a protective effect in human prostate cancer (PCa) cells. We aimed to investigate the effect of pantoprazole and other PPIs on PCa-specific death and additional PCa outcomes. Methods: In this retrospective, population-based cohort study, data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all men aged 66 and above with a history of a single negative prostate biopsy between 1994 and 2016. We used multivariable Cox regression models with time-dependent covariates, to assess the effect of PPIs on PCa diagnosis, androgen deprivation therapy (ADT) use, and PCa-specific death. All models included other medications with a putative effect on PCa. All models were adjusted for age, rurality, comorbidity, and year of patient study inclusion. Results: Overall, 21,512 men were included, with a mean follow-up time of 8.06 years (SD 5.44 years). A total of 10,999 patients (51.1%) used a PPI. A total of 5,187 patients (24.1%) were diagnosed with PCa, 2,043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. Pantoprazole was associated with a 3.0% (95% CI 0.3%-6,0%) increased rate of being treated with ADT for every six months of cumulative use, while any use of all other PPIs was associated with a 39.0% (95% CI 18.0%-64.0%) increased PCa-specific mortality. No significant association was found with PCa diagnosis. Conclusions: Upon validation of the potentially negative association of PPIs with PCa outcomes, the expansive use of PPIs may need to be reassessed, especially in PCa patients.
Real-life study on the efficacy of tiotropium bromide in pediatric severe asthma
Authors: Juliana Murata, Jessica Drobrzenski, Caroline Ferreira, Nathalia Vital, Renata Dias, Dirceu Sole, Nelson Rosario, Antonio Pastorino, Herberto Chong Neto, Gustavo Wandalsen
Journal: Journal of Allergy and Clinical Immunology (2020)
Magnetic targeted delivery of the SPIONs-labeled mesenchymal stem cells derived from human Wharton's jelly in Alzheimer's rat models
Authors: Farshid Qiyami Hour, Amir Johari Moghadam, Ali Shakeri-Zadeh, Mehrdad Bakhtiyari, Ronak Shabani, Mehdi Mehdizadeh
Journal: Journal of Controlled Release (2020)
Clinical fracture associated with androgen deprivation therapy: A retrospective study of early phase clinical trial cohorts.
Authors: Zin Myint, Charles Kunos
Journal: Journal of Clinical Oncology (2020)

234 Background: Androgen deprivation therapy (ADT) is the mainstay treatment in both locally advanced and metastatic prostate cancer. Unfortunately, ADT is associated with rapid loss of bone mineral density (a surrogate for fracture risk) within the first 12 months of initial therapy. Methods: A retrospective review of early phase NCI clinical trials from 2006 to 2013 was conducted to assess the risk of fracture for prostate cancer patients treated with ADT. Results: Seven clinical trials of prostate cancer patients who received ADT between 2006 and 2013 were identified. A total of 464 patients were enrolled in the trials. Patient median age was 64 years, the majority were white (90%), and had good performance status. The median baseline prostate specific antigen level was 29.3 ng/ml and the majority of patients had a Gleason score pattern of &gt;7 (71%). Disease was characterized as involving bone only in 43% of patients and multiple sites (bone, node and/or visceral) in 35%. Of 381 patients for which data were available, 36% received prior hormonal therapy, 37% underwent surgical castration, and 16% received radiation therapy. The most common grade 1-2 adverse events reported in the 7 trials were fatigue (36%), followed by hot flashes (27%), anemia (17%) and hyperglycemia (15%). The most common grade &gt;3 adverse events reported were hypertension and hyperglycemia (3% each). Of the total 464 patients, 7 (0.4%) reported having a fracture (5 were baseline and 2 developed while on treatment). Conclusions: Our study reconfirms the association between clinical fracture and ADT exposure; however, the incidence of fracture rate was less than 1%, which was lower than the published population-based cohorts. The difference could be attributed to short-term ADT exposure, and short-duration of follow up. Clinicians should educate patients about risk of fracture with ADT and offer bone health agent earlier in patients at high risk for fracture and also with underlying co-morbidities such as diabetes, poor performance status, chronic steroid use, or undergo radiation therapy.
Efficacy of cabazitaxel second-line and beyond.
Authors: Salil Vengalil, Emma Nolan, Nasira Sultana, Shibu Joseph, Rajanee Bhana, Loaie El-Helw
Journal: Journal of Clinical Oncology (2020)

226 Background: Prostate cancer accounts for the 2nd most common cause of cancer deaths in males in the UK. Cabazitaxel (CBZ) is a third generation taxane with activity demonstrated even in docetaxel resistant cases. Results of the TROPIC study established survival benefit for CBZ in metastatic castrate resistant prostate cancer (mCRPC) patients but there was also a higher incidence of febrile neutropenia (FN) reported. We studied the efficacy of CBZ in mCRPC patients treated in our centre and assessed FN rates with the use primary granulocyte colony stimulating factor (GCSF) support. Methods: We conducted a retrospective audit of mCRPC patients treated with CBZ from January 2016 – January 2019. We analysed treatment outcomes, FN rates and potential prognostic factors. Results: There were 42 patients in total with a median age of 70 years (range; 54-91). The median follow up was 9.5 months (range; 2-34 months). Most of our patients had extensive disease, with bone and visceral metastases seen in 88% and 31% respectively. CBZ was given as second line treatment in 15 (35.7%) patients on progression following docetaxel and as third line in 27 (64.3%) patients. Majority of our patients (95%) had WHO PS of either 0 or 1. Median number of cycles of CBZ administered was 6 and 31% of patients completed 10 cycles of treatment. Median biochemical progression free survival (PFS) for patients who received at least 3 or more cycles of CBZ was 6 months and median overall survival (OS) was 11 months. Median OS for patients who received CBZ as 2nd line and 3rd line treatments were 9 and 13 months respectively. Patients with visceral metastases had a median OS of 9 months. Median OS for patients with Haemoglobin (Hb) ≥12gm/dl and lower Hb were 19 and 9 months respectively (p = 0.004). Patients in favourable prognostic group (Normal Hb, Normal albumin and no visceral metastases) had a median OS of 24 months compared to 10 months for those in less favourable group. There were no episodes of FN reported in our group with the use of primary GCSF prophylaxis. Conclusions: CBZ is effective as a 2nd or 3rd line treatment option in patients with mCRPC. Neutropenic complications can be significantly reduced with the use of primary GCSF prophylaxis. Low pre-treatment Hb seems to be a predictor for poor overall survival.