tbuckley/cabot-search huggingface dataset:
The effect of structured exercise during chemotherapy on chemotherapy-induced peripheral neuropathy (CIPN): A role for interoceptive brain circuitry.
Authors: Ian Kleckner, Jennifer S. Gewandter, Charles E. Heckler, Susan Staples, Ann Colasurdo, Po-Ju Lin, Michelle Shayne, Alissa Huston, Allison Magnuson, Mohamedtaki Abdulaziz Tejani, Richard Francis Dunne, Chunkit Fung, Brea Lipe, Frank Charles Passero, Nimish Mohile, Gary R. Morrow, Michelle Christine Janelsins, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2019)

11590 Background: Over half of patients receiving “neurotoxic” taxane, platinum, or bortezomib chemotherapy experience CIPN—a dose-limiting toxicity involving numbness and pain in the extremities. There are no FDA-approved drugs for CIPN, but exercise may help. This randomized pilot study explored whether structured exercise during chemotherapy ameliorates CIPN symptoms and whether improvements involve changes in the brain’s sensory processing (interoceptive) circuitry. Methods: Nineteen patients scheduled to receive taxane, platinum, or bortezomib were randomized to exercise (home-based, low-moderate intensity, walking and resistance training; EXCAP) or nutrition education (control) for 12 weeks starting at their first infusion. At 0, 6, and 12 weeks, we assessed CIPN symptoms using the CIPN-20 questionnaire (sensory scale, ranges 9-36, higher is worse) and a finger tactile sensitivity task. We assessed resting functional connectivity between the insula and thalamus via fMRI at 0 and 12 weeks. We used linear regression to model each outcome, tested for an effect of exercise, and controlled for baseline value and age because controls were older. Given the pilot nature of this study we present effect sizes, not p-values. Results: The 19 patients were 65±11 years old, 52% women, with cancer: 42% breast, 32% gastrointestinal, 16% myeloma, and 10% genitourinary. Exercise mitigated CIPN symptoms per the CIPN-20 sensory scale. At 6 weeks, exercisers increased from 11.0 to 12.5 whereas controls increased from 11.0 to 15.5 (+1.5 vs. +4.5; ES = 0.81). At 12 weeks, exercisers increased from 11.0 to 14.8 whereas controls increased from 11.0 to 16.2 (+3.8 vs. +5.2, ES = 0.46). The finger-touching test corroborated results at 6 and 12 weeks (ES = 1.03 and 0.07). Exercisers showed better (reduced) insula-thalamus connectivity vs. controls (ES = 0.41). Reductions in connectivity were correlated with smaller increases in CIPN symptoms (r = 0.74). Conclusions: Exercise during neurotoxic chemotherapy mitigated CIPN symptoms, perhaps via improvements in interoceptive brain circuitry. Future work should test for replication with a larger sample. Clinical trial information: NCT03021174.
Ugly is not only skin deep: A case of osteogenic melanoma.
Authors: Joshua C.M. Williams, Natale Tate Sheehan, Pierre DeDelva, Jennifer Barr
Journal: Journal of Clinical Oncology (2013)

e20009 Background: Although the incidence of malignant melanoma is high, the incidence of metaplastic malignant melanoma is low. Within the various subtypes of malignant metaplastic melanoma, the manifestation of osteogenic melanoma remains a rarer event. Current review of the literature reveals only 12 reported cases. Of these reported cases, scant discussion is made on treatment whereas the histopathology is discussed in great detail. Methods: We present the case of a 64 year old Caucasian man that was diagnosed with synchronous tumors of the foot and lung. Initial biopsy of the foot revealed metastatic osteogenic melanoma. As a result of the initial biopsy results and imaging, the patient underwent a right lower lobe resection and lymph node dissection followed by a left lower extremity Pirigoff’s amputation and inguinal lymph node dissection. Results: Immunohistochemical staining of the extirpated tissue from the lung revealed strong reactivity to S100, vimentin, Sox10, diffuse reactivity to low molecular weight cytokeratin and HMB-45/MART-1 and no lymph node involvement. Whereas the IHC of the extirpated tissue of the left foot remained consistent with the initial biopsy of strong reactivity to S100 and MART-1 and negative to pancytokeratins, CD34, Desmin, and SMA. Conclusions: Given the features of the patient’s pathology and resected metastatic disease, he was administered adjuvant alpha interferon therapy.
Results at 5 years of intra vesical gemcitabine (G) single agent as adjuvant chemotheray in superficial transitional cell carcinoma (TCC) of the bladder
Authors: F. Smaili, A. Bounedjar, R. Ferhat, K. Bouzid
Journal: Journal of Clinical Oncology (2009)

e16087 Background: Systemic intravenous gemcitabine is usually used in advanced bladder carcinoma, intravesical G is a novel treatment approach for TCC. In this study we evaluate the efficacy of intravesical Gemcitabine in patients (pts) with superficial bladder carcinoma. Methods: From February 2003 to June 2004, 60 pts (57M/3F) were enrolled in the study (M/F = 57/3). The median age was 59,5 years old (24–84). Nine pts had a carcinoma in situ (Cis) and 51 had pT1 lesions. Three weeks after a total transurethral resection (TUR), patients receive intravesical instillation of 2000 mg G every week for 6 weeks, than every month for six months. They received a total of 720 instillations, Follow up was with cystoscopy and urine cytology every six months. Results: At a median follow-up time 60 months, all patients were evaluable for tumor response: 23(38, 3%) patient had a persistant complete remission after treatment, 26 patients (43,3%) had a superficial relapse of TCC, six patients (10%) had progressive disease: four with muscle invasion and two with distant metastasis. Conclusions: Intravesical therapy with gemcitabine is active and well tolerated treatment in patients with superficial TCC carcinoma of the bladder. A phase III trial comparing GEM with intravesical BCG or MMC is warranted No significant financial relationships to disclose.
Combinatorial treatment using CTO with paclitaxel or paclitaxel orotate in sc-implanted human OVCAR-5 ovarian tumor model.
Authors: Yulia Maxuitenko, Greg Gorman, Rashida A. Karmali
Journal: Journal of Clinical Oncology (2012)

e15515 Background: Paclitaxel (PXL) was converted to paclitaxel orotate (PXLO). Different combinations of Carboxyamidotriazole orotate (CTO) and PXL or PXLO were first evaluated in female non-tumored athymic NCr-nu/nu mice to determine the tolerance of the combinations. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor-operated calcium channel-mediated calcium influx. CTO can inhibit calcium sensitive signal transduction in the VEGF and the PI3K pathways, and inhibit FGF-2-induced tyrosine kinase. Methods: The antitumor effect of combinations was tested for: i) PXLO compared to PXL, ii) combinatorial effect of low (342mg/kg/dose) and high (513mg/kg/dose) doses of CTO (Q1Dx14, PO) with low (11.6 and 10mg/kg/inj, Q2Dx3/2 weeks, IV) and high (23.2 and 20mg/kg/inj, Q2Dx3/2 weeks, IV) respectively, doses of PXLO or PXL, against sc-implanted human OVCAR-5 ovarian tumor xenografts. Results: Results obtained in non-tumored mice show high PXLO plus CTO was better tolerated than high PXL plus CTO. In tumor bearing mice, oral CTO at doses of 513 or 342mg/kg/dose Q1Dx14 given alone resulted in slight inhibition of tumor growth, reaching statistical significance only when administered at a low dose (two tumor mass doubling: p=0.036 for 342mg/kg/dose). PXLO at 23.2 and 11.6mg/kg/inj. given alone inhibited tumor growth (p&lt;0.001, 0.029, respectively). PXL at 20 and 10mg/kg/inj inhibited tumor growth (p&lt;0.001 and 0.011, respectively). Since body weight loss was less with the orotate form of PXL, PXLO should be the preferred drug over PXL. Addition of oral CTO 513 or 342mg/kg/dose to PXLO 23.2 or PXL 20mg/kg/inj resulted in comparable tumor inhibition to PXLO or PXL alone. However, combination of PXLO 11.6 and PXL 10mg/kg/inj with CTO 513 or 342mg/kg/dose resulted in tumor inhibition suggesting that a low dose of PXL or PXLO may be combined with CTO to achieve tumor inhibition and to allow the use of the lower doses of PXL to reduce toxicity. Conclusions: Results suggest that PXLO is less toxic than PXL and CTO influences the sensitivity of PXL suggesting a role for combinatorial therapy with low doses of PXL and CTO in this ovarian tumor model.
CD23 provides a noninflammatory pathway for IgE-allergen complexes
Authors: Paul Engeroff, Flurin Caviezel, David Mueller, Franziska Thoms, Martin F. Bachmann, Monique Vogel
Journal: Journal of Allergy and Clinical Immunology (2019)

Type I hypersensitivity is mediated by allergen-specific IgE, which sensitizes the high-affinity IgE receptor FcεRI on mast cells and basophils and drives allergic inflammation upon secondary allergen contact. CD23/FcεRII, the low-affinity receptor for IgE, is constitutively expressed on B cells and has been shown to regulate immune responses. Simultaneous binding of IgE to FcεRI and CD23 is blocked by reciprocal allosteric inhibition, suggesting that the 2 receptors exert distinct roles in IgE handling.We aimed to study how free IgE versus precomplexed IgE-allergen immune complexes (IgE-ICs) target the 2 IgE receptors FcεRI and CD23, and we investigated the functional implications of the 2 pathways.We performed binding and activation assays with human cells in vitro and IgE pharmacokinetics and anaphylaxis experiments in vivo.We demonstrate that FcεRI preferentially binds free IgE and CD23 preferentially binds IgE-ICs. We further show that those different binding properties directly translate to distinct biological functions: free IgE initiated allergic inflammation through FcεRI on allergic effector cells, while IgE-ICs were noninflammatory because of reduced FcεRI binding and enhanced CD23-dependent serum clearance.We propose that IgE-ICs are noninflammatory through reduced engagement by FcεRI but increased targeting of the CD23 pathway.
Abstract LB-166: Antibiotic prescriptions and colorectal cancer recurrence risk: A Danish nationwide prospective cohort study
Authors: Veronika Fedirko, Deirdre Cronin-Fenton, Anders Hammerich Riis, Henrik Toft Sørensen, Claus Lindbjerg Andersen, Ole Thorlacius-Ussing, Timothy Lash
Journal: Cancer Research (2018)

Abstract The large number of colorectal cancer survivors, coupled with the financial burden of colorectal cancer, makes it critical to identify factors associated with cancer recurrence. The human gut microbiome is one of the most densely populated bacterial communities known to exist. It plays a vital role in the host's gut physiology and potentially contributes to colorectal cancer progression. Given the prevalence and often overuse of antibiotics in the population, and their effects on the gut microbiome, the potential influence of antibiotics on the clinical course of colorectal cancer is of great public health importance. Using data from Danish medical registries, we followed 21,152 patients (5,036 with recurrences) diagnosed with stage I-III colorectal cancer from 2001 to 2011. We examined the association between pre- and post-diagnostic antibiotic use and cancer recurrence. After adjustment for potential confounders (age at diagnosis, sex, year of diagnosis, stage, tumor location, cancer treatment, comorbidities, inflammatory bowel disease, and use of statins, non-steroidal anti-inflammatory drugs and aspirin), any antibiotic prescription 90 days prior to colorectal cancer diagnosis was not associated with recurrence [adjusted hazard ratio (aHR) = 1.06, 95% confidence interval (CI): 0.98, 1.14]. However, antibiotic use after cancer diagnosis was associated with a higher risk of recurrence (aHR = 1.23, 95% CI: 1.16, 1.31). Additional ongoing analyses address cancer-specific and all-cause mortality and different time-lag periods. Their results also will be presented at the meeting. Our preliminary findings support further investigation into the possible roles of the gut microbiome and agents that alter its composition and diversity in colorectal cancer progression. Citation Format: Veronika Fedirko, Deirdre Cronin-Fenton, Anders Hammerich Riis, Henrik Toft Sørensen, Claus Lindbjerg Andersen, Ole Thorlacius-Ussing, Timothy Lash. Antibiotic prescriptions and colorectal cancer recurrence risk: A Danish nationwide prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-166.
Surgical outcome score (SOS), a new algorithm based on HE4 and CA125, to predict surgical outcome in primary epithelial ovarian cancer (EOC) patients (pts).
Authors: Elena Ioana Braicu, Toon van Gorp, Rolf Richter, Radoslav Chekerov, Dirk Timmerman, Mani Nassir, Jalid Sehouli, Ignace Vergote
Journal: Journal of Clinical Oncology (2013)

5549 Background: There are no clinical or biomolecular algorithms to predict surgical outcome in EOC pts. Recently, we showed that the combination of HE4 and CA125 predict surgical outcome in advanced primary EOC (ASCO 2012). We validated the cut-off values in an independent cohort and developed a new algorithm to predict surgical outcome-SOS. Methods: Pts with primary EOC (n = 193) were selected for a retrospective study between 2003 and 2011. Preoperative serum HE4 and CA125 levels were measured. The predictive values of HE4 and CA125 were analyzed using the receiver operator characteristic (ROC) with the corresponding area under the curve (AUC). Separate logistic regression algorithms for pre- and postmenopausal women were utilized to categorize pts into low and high-risk for residual disease, using CA125 and HE4 within SOS algorithm. Furthermore we performed a multivariate analysis for prediction of progression free- (PFS) and overall survival (OS). Results: Maximal cytoreduction was achieved in 67.4% pts. Serum HE4 expression correlated with residual disease (p&lt;0.001, RR: 2.74, 95%CI 1.65-4.54), reaching a 76.2% sensitivity (Se), 56.9% specificity (Sp) and 83.1% negative predictive value (NPV), with 235 pM cut-off value. CA125 correlated with residual disease in premenopausal pts (p=0.031, RR: 3.13, 95%CI 1.28-7.65). For a CA125 cut-off of 500 IU/l, the Se, Sp and NPV were 39.7%, 69.8%, and 70.3%, respectively. ROMA predicted surgical outcome (AUC = 0.70, p &lt;0.001, 95% CI = 0.624-0.776, RR = 2.54), reaching a 76.2% Se, 53.5% Sp for 81% cut-off value. SOS algorithm performed better than HE4 or CA125 alone, and ROMA (AUC= 0.741, p &lt; 0.001, 95% CI 0.670-0.812, RR = 4.98). The Se, Sp and NPV was 90.5%, 46.5% and 90.9%, respectively, for a SOS cut off value of 21.5%. FIGO stage and residual disease were the only prognostic factors for both PFS and OS. SOS was an independent prognostic for PFS (p = 0.009, HR = 1.014, 95% CI = 1.004-1.025), but not for OS. Conclusions: This independent validation study confirm the predictive value of CA124 and HE4 on surgical outcome. The combination of HE4 and CA125 within the SOS score improve the prediction of surgical outcome, and therefore of PFS.
Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma
Authors: Zi-Xun Yan, Li Li, Wen Wang, Bin-Shen OuYang, Shu Cheng, Li Wang, Wen Wu, Peng-Peng Xu, Muharrem Muftuoglu, Ming Hao, Su Yang, Mu-Chen Zhang, Zhong Zheng, James Li, Wei-Li Zhao
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Anti-CD19 chimeric antigen receptor (CAR) T cells represent a novel immunotherapy and are highly effective in treating relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL). How tumor microenvironment influences clinical response to CAR T therapy remains of great interest. Patients and Methods: A phase I, first-in-human, dose-escalation study of anti-CD19 JWCAR029 was conducted in refractory B-NHL (NCT03355859) and 10 patients received CAR T cells at an escalating dose of 2.5 × 107(n = 3), 5 × 107(n = 4), and 1 × 108(n = 3) cells. Core needle biopsy was performed on tumor samples collected from diffuse large B-cell lymphoma patients on Day −6 (1 day before lymphodepletion) and on Day 11 after CAR T-cell infusion when adequate CAR T-cell expansion was detected. Results: The overall response rate was 100%, with 6 of 9 (66.7%) evaluable patients achieving complete remission. The most common adverse events of grade 3 or higher were neutropenia (10/10, 100%), anemia (3/10, 30%), thrombocytopenia (3/10, 30%), and hypofibrinogenemia (2/10, 20%). Grade 1 cytokine release syndrome occurred in all patients and grade 3 neurotoxicity in 1 patient. The average peak levels of peripheral blood CAR T cells and cytokines were similar in 3 different dose levels, but CAR T cells were significantly higher in patients achieved complete remission on Day 29. Meanwhile, RNA sequencing identified gene expression signatures differentially enriched in complete and partial remission patients. Increased tumor-associated macrophage infiltration was negatively associated with remission status. Conclusions: JWCAR029 was effective and safe in treating refractory B-NHL. The composition of the tumor microenvironment has a potential impact in CAR T therapy response.
Trends in the quality of abstracts of articles describing randomized controlled cancer trials (RCTs) from 1975–2004
Authors: D. W. Cescon, C. M. Booth, L. Wang, I. F. Tannock, M. K. Krzyzanowska
Journal: Journal of Clinical Oncology (2007)

6541 Background: Busy oncologists may rely on abstracts to obtain most of their information from published reports. Here we evaluate the quality of abstracts in articles reporting RCTs, and whether quality of reporting has changed over time. Methods: Reports of RCTs evaluating systemic therapy for breast, colorectal and non-small cell lung cancer published 1975–2004 in 6 major journals were identified. The quality of abstracts was evaluated using a scale which awards 1 point for full and 1/2 point for partial reporting of each of 6 items: study rationale, statement of primary endpoint, description of intervention, treatment effect size, P-values or confidence intervals (CI), and toxicity. The scale was a modification of one previously developed to assess quality of reporting of conference abstracts. Trends in the reporting of individual items and composite scores were evaluated over three 10-year periods (1975–84, 1985–94, 1995–2004) using descriptive statistics. Results: Of 326 eligible articles, 319 had an abstract. Unstructured abstracts were common before 1994 ( Table ). The minimum and maximum quality scores assigned were 0.5 and 6/6. Median quality scores improved significantly with time (from 2.5 to 4.5/6, P &lt; .001), as did inclusion of each of the individual items (P &lt; .001). In the most recent 10-year period, three variables were adequately reported in less than half of abstracts (primary endpoint 38.0%, rationale 38.6%, toxicity 40.4%). Since the publication of the revised CONSORT statement in 2001, reporting of these items has improved (58.2%, 47.8%, 44.8% for 2002–2004). Conclusions: Quality of abstracts for published RCTs has improved over time, but deficiencies still exist. Items requiring improved reporting include identification of the primary endpoint, description of rationale, and a summary of toxicity. No significant financial relationships to disclose. [Table: see text]
The ELDORADO study: A phase II randomised study of concurrent weekly docetaxel, IMRT, and ltadt in patients with high-risk prostate cancer.
Authors: Derek Wilke, Lori Wood, Heather Walker, David Bell, Ricardo A. Rendon, Helmut Hollenhorst, Robert Rutledge, David Bowes, James Robar, Arik Marc Drucker, Slawa Cwajna, Greg Bailly, Tetteh Ago
Journal: Journal of Clinical Oncology (2013)

5048 Background: Treatment intensification is warranted for ‘high risk’ prostate cancer. Docetaxel (DO) and radiotherapy (IMRT) may cause dose-limiting GI or GU toxicity. Treating the whole pelvis last (WP-L) versus the whole pelvic lymphatics first (WP-F) could reduce the number of dose delays or omissions of DO. Methods: We performed a double-blind, randomized trial, in patients with ‘high risk’ non-metastatic prostate cancer who had any one of the following: 1) ≥ T2c TNM category, 2) Gleason score ≥ 8, or PSA &gt; 20 and &lt; 50 µg/L, OR have a greater than 50% risk of recurrence after radical prostatectomy (RP), as predicted by the Kattan nomogram, with no evidence of metastatic disease. Patients receive long-term androgen deprivation therapy (LTADT), and after 4 months of neoadjuvant ADT, receive IMRT and concurrent DO 20 mg/m 2 x 8 weekly infusions. Patients were randomized to receive WP-F followed by a boost to the prostate/prostate bed, or to have WP-L. The primary outcome was to compare the number of DO dose reductions, delays or omissions due to GI or GU toxicity, between arms. Target sample size was 86 patients (pts). Results: 98 pts were registered, 88 were randomized, 2 withdrew consent, leaving 42 pts randomized to WP-F, and 44 pts to WP-L. The trial was closed to accrual Feb 2, 2012. Twenty-five pts had previous RP (29%). Seven pts (16.6%) allocated to WP-F had chemotherapy dose reductions/delays versus 3 pts (6.8%) allocated to WP-L , which was not statistically significant (p=0.19). Overall 80.2% of pts received all 8 weekly doses of DO and IMRT (WP-F vs. WP-L: 78.6% vs.81.8%, p=0.9). Actuarial overall survival at 4 years is 96 % (WP-F vs. WP-L: 94% vs.97%, p=0.6). Biochemical relapse-free survival at 4 years is 96.7% (WP-F vs. WP-L: 98% vs.97%, p=0.92). Two patients have needed surgical intervention for Grade &gt; 3 GU toxicity. Cumulative treatment-related grade 3 or 4 GI or GU toxicity was 36%. When patients were last seen, only 2/84 (2.3%) patients had ongoing grade 3 GI or GU toxicity at a median follow up of 2.7 years Conclusions: Concurrent use of DO and IMRT is feasible with reasonable toxicity. Sequence inversion does not enhance chemotherapy delivery. Clinical trial information: NCT00452556.