tbuckley/cabot-search huggingface dataset:
Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome
Authors: Daniela Pedicino, Ramona Vinci, Ada F. Giglio, Eugenia Pisano, Italo Porto, Rocco Vergallo, Giulio Russo, Aureliano Ruggio, Alessia D’Aiello, Davide Flego, Gianmarco Annibali, Francesco Trotta, Roberto Piacentini, Giampaolo Niccoli, Giovanna Liuzzo, Filippo Crea
Journal: Journal of the American College of Cardiology (2018)
Timing of percutaneous endoscopic gastrostomy (PEG) tube placement as supportive care in HNSCC patients (Pts) receiving concurrent chemoradiotherapy (CRT).
Authors: Oleksandra Lupak, Michael Bazydlo, Farzan Siddiqui, Steven Chang, Bryan Coniglio, Ding Wang
Journal: Journal of Clinical Oncology (2017)

e17571 Background: Concurrent CRT with curative intent is the standard of care treatment for Pts with locally advanced or local recurrent head and neck squamous cell carcinoma (HNSCC). The CRT is associated with significant toxicities including nausea/vomiting, dysphagia and/or odynophagia, which prevent Pts from tolerating oral hydration and nutrition intakes. Treatment frequently leads to weight loss, renal injury and unexpected emergent care or hospitalizations along with therapy interruptions. This study is to determine the timing of PEG tube placement and its impact on the safety and tolerability from HNSCC patients receiving CRT. Methods: We retrospectively reviewed 413 electronic medical records (EMR), of which 335 of HNSCC Pts who had complete EMR during CRT period were included in this study. 127 of these 335 Pts (38%) required no PEG tube placement, 208 (62%) required PEG placement. The timing of PEG placement has been observed as two groups: 1) 109 Pts had PEG tube placement before initiation of CRT (Prophylactic Group PG); 2) 89 Pts had PEG tube during CRT period in reaction to a serious toxicity event (Reactive Group_RG). Logistic regressions were used to estimate the effect of PEG timing on Emergency Department (ED) visits, hospitalization, and experiencing treatment interruptions. Results: Our study showed that patients in PG demonstrated 43% less likely on their visiting ED or 42% less likely for hospitalization than Pts of RG with an odds ratio (OR) at 0.396 (95% CI: 0.165~0.952, p = 0.038) for PG over RG from toxicity-related therapy interruptions. Pts in PG also showed an OR at 0.40 from improving hypoalbuminemia over RG Pts (95% CI: 0.16~0.64, p = 0.001) which associated with 23% of chance of maintaining pre-CRT body mass index (BMI) for Pts in PG over those in RG. Conclusions: We observed the prophylactic PEG tube placement prevented unexpected ER visits and hospitalizations through reducing the risk of malnutrition and dehydration, which improved Pts in PG through the CRT with less therapy interruptions and preserved BMI, especially for those Pts of older age, pre-therapy dysphagia, hypoalbuminemia and receiving cisplatin in CRT.
Paraprotein levels in assessing effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma patients.
Authors: Irina B. Lysenko, Nailya Guskova, Oleg Ivanovich Kit, Natalya Dmitrievna Ushakova, Nadezhda Golomeeva, Natalia Zuderman, Ekaterina Guskova, Anastasia Nozdricheva, Svetlana V. Abakumova, Aliya K. Donskaya, Marina A. Gusareva, Kristina Avanesova, Izabella Torpudzhyan, Irina V. Tselishcheva, Viktoria Zakharchenko, Svetlana V. Belgova, Ekaterina Gornostaeva
Journal: Journal of Clinical Oncology (2017)

e19511 Background: Our purpose was to analyze levels and types of paraprotein in polychemotherapy combined with selective plasma exchange in patients with multiple myeloma. Methods: Blood levels of paraprotein (PP) were studied by capillary electrophoresis (Helena Bioscience V8), and content of plasma cells was determined in the bone marrow of 16 patients (main group) with multiple myeloma (MM) during polychemotherapy (PCT) plus selective plasma exchange (SPE). 14 patients receiving standard PCT were the controls. Results: MM patients in both groups were characterized with the presence of PP in the blood serum with the M-peak in the gamma-globulin zone. Only heavy IgG chains were found, bound to lambda (λ) light chains in 48% and to cappa (κ) light chains in 57.15%. The initial PP level in MM-IgGλ was 91.01±0.79 g/L and was 2.4 times higher than in MM-IgGκ (38.3±0.34 g/L). Significant differences in were found in PP reduction rate and intensity depending on the treatment. PP in the main group reduced by 42.4% after course1, by 41.4% after course 2, by 52.2% after course 3 and by 24% after course 4; in the control group – by 17.2%, 19.3%, 27.9% and 47.3%, respectively. PP levels decreased by 87.4% and 74.6% by the end of the treatment, respectively. The data were confirmed by a decrease in plasma cell content in the bone marrow of patients: up to 1.2% in the main group and 6.2% in the controls. Response to treatment in the main group was registered at the early stages of therapy, and at the late stages in the control group. Treatment effect was associated with the type of secreted PP. In MM-IgGκ, PP levels in the main group decreased by 59.7% after course 1, by 40.6% more after course 2 and by 51.9% after course 3; in MM-IgGλ – by 25.1%, 42.1% and 52.5%, respectively. Treatment effect was noted earlier and PP reduction was more intensive in MM-IgGκ than in MM-IgGλ. PP levels decreased by the end of the treatment by 85.4% in MM-IgGκ and by 73% in MM-IgGλ. Similar changes were observed in the control group. Conclusions: Increased rates and intensiveness of paraprotein reduction reflect effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma. Patients with MM-IgGκ are more sensitive to the therapy.
An integrated medical oncology-physiatry practice model improves overall patient functionality of prostate cancer patients by identifying, quantifying and treating the pre-existing non-cancer co-morbidities.
Authors: Lisa Marie Ruppert, Erica Simone Dayan, Abigail Bacharach, Howard I. Scher
Journal: Journal of Clinical Oncology (2018)

e22051 Background: Prostate cancer bone metastases can produce pain, fractures and spinal cord compromise, severely limiting function. ADT needed to treat disease can result in bone loss, decreased lean body mass and muscle weakness. Underappreciated and under-discussed is morbidity of pre-existing non-cancer conditions including age related disc disease, facet arthropathy, muscle weakness, joint degeneration, bone loss and neuropathies from diabetes and vascular disease, all of which contribute to spinal complications and impaired function. Methods: Medical oncologist and physiatrist integrated practices with same day referrals when possible. All neurologic and musculoskeletal symptoms were discussed with pts and real time physiatric recommendations were provided. Results: 123 pts were evaluated (83/123 same day). The average age was 70 and most frequent referral was back pain (84%). Pts also commonly reported joint pain, weakness, gait/balance impairments and bowel/bladder dysfunction. 88 had documented metastases and 18 localized disease at time of evaluation. 25 patients had diabetes mellitus, 67 vascular disease, 34 arthritis and 18 prior surgery for disc/facet disease. On examination 42 pts had weakness, 21 sensory impairments, 67 abnormal posture and 52 gait abnormalities. Imaging revealed that 83 had metastases of the spine/pelvis, 16 had fractures and 95 had degenerative changes in the spine. Given these findings, non cancer related co-morbidities were thought to contribute to symptoms in 54% of evaluations. Common management recommendations included formal physical therapy, bracing, and self exercise. 29% of patients were referred for further imaging to evaluate extent of disease. Conclusions: Over half of the patients had non-cancer related morbidities optimally served with an integrated practice model where all symptoms are addressed. In addition to symptom management, the model enables prevention of further complications and improvement in overall patient function.
Objective measurement and significance of PD-L1, B7-H3, B7-H4 and TILs in small cell lung cancer (SCLC).
Authors: Kurt Alex Schalper, Daniel E. Carvajal-Hausdorf, Joseph Francis McLaughlin, Mehmet Altan, Anne C. Chiang, Vamsidhar Velcheti, Edward Kaftan, Jie Zhang, Liming Lu, David L. Rimm, Baohui Han, Hui Lu, Hongyu Zhao, Roy S. Herbst
Journal: Journal of Clinical Oncology (2016)

8566 Background: Small-cell lung cancer (SCLC) accounts for 10-15% of all lung malignancies and is characterized by its neuroendocrine differentiation, prominent association with tobacco, elevated somatic mutational load, aggressive clinical course and limited therapeutic options. Early studies have shown promising results of PD-1 axis blockers and diverse trials using PD-1 monotherapy or combinations are ongoing. However, the expression of PD-L1, additional potentially actionable immune targets and immune infiltration remain poorly understood. Methods: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, B7-H3, B7-H4 and different tumor infiltrating lymphocyte (TIL) subsets in 90 SCLC samples represented in tissue microarray format from 2 retrospective collections (YTMA57 and YTMA259). Tumor PD-L1 (clone E1L3N), B7-H3 (D9M2L) and B7-H4 (D1M8I) were detected in serial sections. The major TIL subsets were determined using multiplex staining of the markers DAPI, cytokeratin (AE1/AE3), CD3 (E272), CD8 (C8/144B) and CD20 (L26). Associations between the marker levels, major clinico-pathological variables and survival were established. Results: PD-L1 protein was detected in 7.3%, B7-H3 in 64.9% and B7-H4 in 2.6% of SCLC cases. PD-L1 and B7-H3 showed limited co-expression and a mutually exclusive expression pattern. In preliminary analysis using the median score as cutpoint, expression of the markers was not significantly associated with age, stage, TILs or 5-year overall survival. In SCLC, the levels of CD3, CD8 and CD20 were significantly lower than in lung adenocarcinomas and squamous cell carcinomas. The ratio of CD8/CD3 signal was also prominently lower in SCLC. Conclusions: PD-L1 and B7-H4 are infrequently expressed in SCLC. B7-H3 is present in nearly 65% of cases and shows limited co-expression with PD-L1. Despite having a high mutational rate, the level of TILs in SCLC is low, suggesting prominent immune regulation/suppression in this malignancy. Our findings support the blockade of B7-H3 and immune regulatory pathways as candidate immunotherapeutic alternatives in SCLC. Validation of the findings in an independent SCLC population is ongoing.
A single center experience with two decades of follow-up on patients with hairy cell leukemia.
Authors: Osman Ilhan, Erden Atilla, Pinar Ataca Atilla, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Selami Kocak Toprak, Pervin Topcuoglu, Taner Demirer, Onder Arslan, Muhit Ozcan, Hamdi Akan, Meral Beksac, Gunhan Gurman
Journal: Journal of Clinical Oncology (2017)

e18530 Background: HCL is a rare chronic lymphoid malignancy and frequency is 2% in all leukemia and diagnosed mostly in middle ages. Patients generally respond to purine analogues treatment. In this study our aim is to present our HCL patients with demographic features, treatment modalities and responses. Methods: 39 HCL patients who were diagnosed and treated at Ankara University Department of Hematology between 1984 and 2016 were retrospectively evaluated. Ki-square test and student t test were used in comparison. P &lt; 0.05 was considered statistically significant. Results: Median age of patients were 51 (range, 31-79). 30 of patients (77%) were male. The average leucocyte, hemoglobin, platelet, lactate dehydrogenase (LDH) levels and the spleen size at diagnosis were as follows: 5,1 x 10^9/L (range, 1,5-20), 12,5 g/dl (range, 9-17,5), 116x10^9/L (range,15-300), 178 IU (range,107-394), 155 mm (range,110-290). BRAF mutation could be evaluated in two patients and revealed as positive. 9 patients (23%) underwent splenectomy prior to chemotherapy. All patients received cladribine (0.1mg/kg, 7 days) as a first line treatment; 8 patients (21%) had two courses for remission. 11 patients (30%) had treatment related febrile neutropenia, 2 patients (0.05%) had transient skin rash after infusion. 8 patients (21%) had a relapse and 1 patients received pentostatin (4mg/m 2 , 1 dose every 2 weeks, 6 months), 7 patients were retreated with the first line treatment and achieved complete response. The overall survival was 67 months, respectively. Leucocyte, hemoglobin, platelet levels were lower, LDH levels were higher and spleen size was increased in patients with relapse however no statistical difference were detected. The patients with splenectomy had improved survival compared to patients without splenectomy (144 vs 329 months, P = 0.024). Conclusions: We detected 18% relapse rate in our series and all patients were followed in remisson after second line purine analogue treatment. Splenectomy has improved overall survival and possibly still has a role to play in HCL therapy. Generally, HCL is a chronic disease with a favorable prognosis.
Association of muscle mass with pathologic response and toxicity in localized bladder cancer patients treated by neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).
Authors: Charlotte Fenioux, Olivier Huillard, Evanguelos Xylinas, Camille Tlemsani, Pascaline Boudou-Rouquette, Edith Carton, Michael Peyromaure, Jerome Alexandre, Francois Goldwasser
Journal: Journal of Clinical Oncology (2017)

e16022 Background: Sarcopenia, the condition of low muscle mass, is a prognostic factor across many cancer types including bladder cancer. Moreover, sarcopenia was shown to predict severe toxicity induced by many anticancer agents. Conversely, NAC may increase the prevalence of sarcopenia before surgery. This retrospective study aimed to investigate the association of sarcopenia with pathologic response and toxicity in localized bladder cancer patients treated by NAC and RC. Methods: Among the 52 patients who underwent RC after NAC between Jan 2010 and Dec 2016, the preoperative sarcopenia status could be determined for 39 patients. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured on CT scan images, and sarcopenia was defined as skeletal muscle index of &lt; 43 cm2/m2 for men with body mass index (BMI) &lt; 25 kg/m2, SMI &lt; 53 cm2/m2 for men with BMI &gt; 25 kg/m2, and SMI &lt; 41 cm2/m2 for women. The criteria for efficacy was pathologic response defined by pathological down-staging to ≤ pT1N0. Patients were compared using χ2 or Fischer’s exact test when appropriate. Results: 48% of patients were sarcopenic before RC. A significant higher rate of pathological response was found in non-sarcopenic patients compared to sarcopenic patients (13/20 vs 5/19, P = 0.01). More severe chemotherapy related toxicity was found in sarcopenic patients compared to non-sarcopenic patients for neutropenia (P = 0.06), thrombopenia (P = 0.15), and neuropathy (P = 0.23). Among the 21 patients for whom sarcopenia status before chemotherapy was available, 3 patients became sarcopenic and 4 patients initially sarcopenic gained muscle mass on post-chemotherapy CT scan. Conclusions: Sarcopenia is frequent in localized bladder cancer patients. Muscle mass correlates with pathological response to NAC.
A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of head and neck (LASCCHN).
Authors: Keemo Delos Santos, Katarzyna Joanna Jerzak, Ronak Saluja, Kelly Lien, Justin Lee, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2016)

6082 Background: Many randomized controlled trials (RCTs) have evaluated definitive radiotherapy (RT) with different sequencing (induction (I+RT), concurrent (CRT), adjuvant, induction + concurrent (I+CRT)) and types of systemic therapies (chemotherapy (chemo), EGFR inhibitors) in the treatment of LASCCHN. Some therapies have not been compared directly. We performed a network meta-analysis to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously. Methods: A systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and Cochrane Central of Registered Trials using Cochrane methodology to identify RCTs up to February 2015 investigating sequencing or types of systemic treatments that involved the same definitive radiotherapy in the arms for the RCT. Two reviewers independently reviewed the RCTs and discrepancies were resolved either by discussion or by a third reviewer. The Parmar method was used to extract OS hazard ratios (HR). A Bayesian network meta-analysis (NMA) with random effects was constructed using WinBUGS to compare the relative efficacy of different sequencing and types of systemic therapies simultaneously. Results: Fifty-nine RCTs involving 11,991 patients and 13 different treatment strategies were identified. Selected comparisons are shown in the table. Conclusions: Our findings support that CRT remains the standard treatment for LASCCHN. Concurrent radiotherapy with an EGFR inhibitor does not confer an OS benefit for patients who are eligible for CRT (chemo). Induction taxane-based chemotherapy followed by CRT showed a strong trend for OS benefit when compared with CRT; this warrants further evaluation in RCTs. Comparisons HR 95% CrI CRT (chemo) vs. RT 0.72 0.66-0.78 CRT (EGFR) vs. RT 0.77 0.55-1.08 CRT (EGFR) vs. CRT (chemo) 1.06 0.75-1.52 I (no taxane) + RT vs. RT 0.88 0.66-1.00 I (taxane-based) + RT vs. RT 0.64 0.43-0.95 I (taxane-based) + RT vs. CRT (chemo) 0.89 0.59-1.33 I (taxane-based) + CRT (chemo) vs. RT 0.60 0.48-0.74 I (no taxane) + CRT (chemo) vs. CRT (chemo) 1.02 0.82-1.24 I (taxane-based) + CRT (chemo) vs. CRT (chemo) 0.83 0.67-1.01
Differences in plasminogen activation in primary rectal adenocarcinoma with and without liver metastasis.
Authors: Evgeniy N. Kolesnikov, Elena Alekseevna Nikipelova, Elena Mikhaylovna Frantsiyants, Larisa Kozlova, Valeria Bandovkina, Irina V. Kaplieva, Lidia K. Trepitaki, Lyudmila Dmitriyevna Tkalya, Alexander V. Snezhko, Michail Averkin, Mikhail Anatolievich Kozhushko, Sergey Vladimirovich Sanamyanc, Roman E. Myagkov, Leonid Kharin, Vladimir Trifanov, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e15111 Background: Plasminogen activators play a key role in the cascade fibrinolytic system as they catalyze plasmin formation from plasminogen (PG). Plasminogen activators together with plasmin are directly or indirectly involved in tumor growth. The purpose of the study was to compare the plasminogen activation system in primary adenocarcinomas (РА) of the rectum (R) with and without liver metastases (LM). Methods: Tissues of tumors (РА, st. III, G2, 38-74 years) and their perifocal zone (PZ) with LM (T 2-3 N х M 1 , n = 24) and without them (T 2-3 N 0 M 0 , n = 32) were studied by ELISA. Results: The studied parameters did not differ in apparently intact R tissues in the resection line (RL) with and without LM. Plasmin-α2-antiplasmin complex (PAP) was 1.4 times higher in PA with LM than without LM (p &lt; 0.05). Prourokinase and urokinase levels (uPA-Ag and uPA-act) were 12.4 and 3.7 higher than in RL. uPA-Ag and uPA-act in PA+LM were higher than without LM by 1.4 and 1.6 times. PG levels and α2-macroglobulin (α 2 M) activity in PA+LM were lower by 1.5 and 2.7 times than in PA without LM and lower than in RL (p &lt; 0.01). All studied parameters, except α 2 M, in PA+LM were activated more than in PA without LM. Low α 2 M content supposed realization of effects of uPA and plasmin in insufficient inhibitory control. Most parameters in PZ+LM were between the levels in PA and RL being significantly different from both and significantly exceeding the values in PZ of PA without LM. α 2 М was an exception being 1.8 times lower in PZ of PA+LM than in PZ of PA without LM. The results demonstrated higher uPA and РАР levels in PA and its PZ with LM than without them, with increased PG consumption and decreased α 2 M activity in these parts of the rectum. Activation of plasminogen system in tissues of PA+LM and in PA without LM was unidirectional. Conclusions: Levels of uPA and PAP, as well as low α 2 M content in PA and PZ with LM can be used as an indicator of tumor metastatic activity.
Clinical experiences of gene therapy.
Authors: Longjiang Li
Journal: Journal of Clinical Oncology (2017)

e17561 Background: Based on the theoretic and clinical development of modern medicine, gene therapy has been a promising treatment strategy for cancer and other patients. Methods: In the present paper, we reviewed the history and clinical experiences of gene therapy from the aspects of treatment protocol, administration cycle, dosage calculation and evaluation of therapeutic effects, in order to provide more information for the further development of this promising treatment. Results: Although the development of gene therapy has not gone smoothly since the beginning of the clinical trials, the results showed that this was a promising treatment for the cancer patients. There are still a lot of researches needed to be done to further solve the theoretic and clinical issues, and to improve the therapeutic effects. Conclusions: : In conclusion, although the development of gene therapy has not gone smoothly since the beginning of the clinical trials, the results showed that this was a promising treatment for the cancer patients. There are still a lot of researches needed to be done to further solve the theoretic and clinical issues, and to improve the therapeutic effects. But the future of the gene therapy will be bright, and it will become a new basic strategy to help more patients.