tbuckley/cabot-search huggingface dataset:
Morbid mortality associated with total thyroidectomy for differentiated carcinoma in a training institute.
Authors: RaÃºl Alejandro López Saucedo, Roberto Rodirguez, Sergio Infante, Alejandra Salazar, Martin Granados-Garcia
Journal: Journal of Clinical Oncology (2017)

e17586 Background: Total thyroidectomy is now a common and relatively safe procedure. In the context of malignant pathology: It optimizes local control, facilitates adjuvant therapy with iodine 131, increases thyroglobulin sensitivity in patient surveillance and improves survival in patients at high risk. The reported morbimortality is related to Transient or definitive hypocalcemia, unilateral or bilateral recurrent laryngeal nerve injury (RLN), postoperative hemorrhage, wound infection, chylous fistula, tracheal injuries or esophageal perforations, cervical sympathetic chain lesions, among others Although death is rare as a result of the procedure and its complications. Methods: The present retrospective, descriptive, observational, cross-sectional, analytical study was performed based on an analysis of the records opened to patients at the National Cancer Institute between November 23, 2012, and January 5, 2015 corresponding to 100 consecutive cases with diagnosis of differentiated thyroid cancer, submitted to at least total thyroidectomy. Results: According with the AJCC 7 th edition TNM distribution was: pT1 n = 13, pT2 n = 14, pT3 n = 63, pT4a n = 10, pN1a n = 12, pN1b n = 51, M1 n = 12. In 73 patients, no complications developed, and of the complications presented, 8 patients developed transient hypocalcemia, 19 permanent hypocalcemia, 3 resections of the RLN in a planned manner, 1 accidentally identified intraoperative lesion, 7 unconscious lesions of the RLN, 11 developed dysphonia, 1 Horner's syndrome, 2 Vagus lesions, 2 patients with tracheal or pharyngeal fistula, 1 chylous fistula, 1 transoperative hemorrhage and 1 hematoma. Mortality in one of the patients. Conclusions: Our results translate morbidity and mortality associated with locally advanced tumors, where the only correlation identified were the relationships with the presence of parathyroid glands in the pathology report and the development of hypocalcemia. With the above, we can assure that the best ally of the surgeon is the careful dissection based on a deep knowledge of anatomy, which could reduce the morbidity due to the surgery.
Lymphopenia and changes on peripheral blood immunophenotype in patients with hepatobiliarypancreatic tumors treated with chemoradiotherapy.
Authors: Adelaida Garcia-Velasco, Natalia Lloveras, Raquel Guardeño, Bernardo Queralt, Xavier Hernandez Yague, Carmen Auñon, Elia Sais, Cristina Urbano, Miguel Sagues, Alejandro Hernandez, Hanan Ahmed-Ouahid, David Gallardo, Eugeni Canals
Journal: Journal of Clinical Oncology (2016)

e15610 Background: Chemoradiation-related lymphopenia has been linked to prognosis in retrospective studies. The aim of this trial was to prospectively assess the clinical significance of lymphopenia and the changes on lymphocyte subsets in peripheral blood in patients (pts) with hepatobiliarypancreatic (HBP) tumors treated with CRT. Methods: Pts with primary HBP adenocarcinoma (ADC) treated with CRT in our institution from January 2014 to October 2015 were enrolled. Peripheral venous blood samples were obtained before CRT, immediately after treatment and two months later. All clinical and serological data were recorded in a database system using SPSS 20.0 statistics package. Results: Of 33 pts included, 23 had pancreatic ADC, 6 ampullary carcinoma and 4 cholangiocarcinoma. All of them had peripheral blood samples available at the 3 time points, but only 27 pts had paired immunophenotyping. CRT was given as adjuvant treatment in 18 pts, and as sequential CRT after 6 cycles of GEMOX in 15 pts. Pre-CRT health status and total lymphocyte counts (TLC) were similar in both groups. Concomitant 5-FU continuous infusion was used in all but 4 cases, treated with gemcitabine. Median RT dose was 50,4Gy and median PTV 322.39cm3. A decrease in TLC after CRT was observed in all pts, with a mean reduction in TLC per patient of 54% (SD 31.8%), and an increase in the neutrophil/lymphocyte ratio (NLR) > 50% in 74% of cases. Absolute CD4 lymphocyte counts (CD4lc) dropped after CRT, with a mean reduction per patient of 57% (SD 19%), being < 200 cells/mm3 in 11 pts (30%). Two months after CRT, 7 pts (20%) had < 200 cells/mm3 CD4lc. CD8 and NoBnoT lymphocytes showed a nonsignificant increase after CRT. Changes on serum albumine and creatinin levels were not observed. Three Cytomegalovirus reactivations were registered after CRT in patients with CD4lc < 200 cells/mm3, without clinical infection. Conclusions: Severe treatment-related lymphopenia, mainly due to a decline in CD4 lymphocytes, is frequent in patients with HBP tumors treated with CRT. In our series this is not related to the nutritional status nor does it entail an increase in opportunistic infections. It is too early to make any prognostic correlation.
P01.023 Intraoperative mapping of long associated tracts in surgery of brain gliomas
Authors: S Goryaynov, V Jukov, S Buklina, D Pitzhelauri, A Potapov, A Ogurtsova, A Batalov, N Zakharova
Journal: Neuro-Oncology (2018)

Surgery of intracerebral tumors involving long associated tracts is a complicated task. This study is devoted to intraoperative mapping of the upper longitudinal, arcuate and frontal aslant tracts in surgery of brain gliomas. Intraoperative mapping and postoperative speech function was analyzed in patients operated for premotor cortex gliomas of the left frontal lobe involving upper longitudinal, arcuate and frontal aslant tracts by method of awake craniotomy. A series of 12 clinical observations is reported, enrolling patients with gliomas located in the functionally meaningful left frontal lobe; 11 of them were right-handed. All patients had MRI with a long associated tract reconstruction; the tumor-tract topographic anatomical correlations were established before and after surgery. All 12 operations were performed by awake-asleep-awake protocol. Also, cortical and subcortical stimulation was used in all cases to control the tumor resection size. Speech impairment before, during and after surgery was evaluated by an experienced neuropsychologist. Mean electrical stimulation voltage made up 3 мА (1,9-6,5). 12 patients during surgery revealed associative tracts (11 pts - SLF/AF and 1 pts - FAT); 4 patients (33%) had intraoperative Broca’s area mapping; 3 patients developed speech impairment without electrical stimulation (paraphasia, preservations) during tumor removal; direct electrical stimulation revealed speech impairment in 7 cases (66%). MRI control within the first 48–72 hours was performed in all patients: total tumor resection (over 90% of tumor) was conducted in 7 cases, subtotal - in 2, and partial - in 2 cases. According to MR-tractography findings the removed tumor сavity was tightly adjacent to SLF/AF complex in 7 cases, was located in the vicinity of SLF/AF complex (at some distance) - in 4 cases and was directly adjoined to FAT in 1 cases. Ten of 12 patients developed neurologic aggravation manifesting in different aphatic disturbances. The postoperative period after premotor region tumor removal in the speech-dominant hemisphere is likely to be characterized by a high incidence rate of complicated speech disorders as a result of SLF/AF and FAT damage. Intraoperative mapping along the long associated tracts is the required procedure in those cases. Use of preoperative tractography in combination with intraoperative speech recordings (mapping) allows us to reveal associative SLF/AF and FAT complex fibers, thus allowing avoiding of marked conductive aphasia with poor speech recovery after tumor removal.
Prospective cross-sectional-study on influence of immigration background and education on breast cancer survival in a real-world setting.
Authors: Elna Kuehnle, Wulf Siggelkow, Kristina Luebbe, Iris Schrader, Stefanie Noeding, Karl-Heinz Noeding, Thomas Noesselt, Momme Arfsten, Christoph Busch, Regina Meier, Peter Hillemanns, Thilo Dörk, Tjoung-Won Park-Simon
Journal: Journal of Clinical Oncology (2018)

e18650 Background: Although immigrant health is an important issue in worldwide health policy there is a serious shortage of data in many countries, especially survival data. In this prospective cross-sectional-study we analyzed the influence of immigration background and educational status on breast cancer survival in a real-world-setting in Lower-Saxony, Germany. Methods: Data collection was conducted from 2012-2017 in six certified breast cancer centers using a personal questionnaire and data from the patients’ medical records for example tumor stage, grading, hormone and her2neu receptor status, mode of detection, country of origin and educational status. Classification into subgroups was carried out according to first- and second-generation immigrants and country of origin. Results: 2318/3519 patients (224 first-generation immigrants, n = 184 second-generation immigrants and n = 1910 native Germans) were analyzed. Mean duration of follow-up was 15.68 months (0-70months). No difference in mode of tumor detection was seen in the 3 groups. No difference in DFS and OS according to tumor biology was detected in between the 3 groups. Overall DFS was 97.1%. DFS between all 3 groups revealed no significant difference (p = 0.848). Also, OS (98.5%; 2283/2318) showed no significant difference between natives and first- and second-generation immigrants (p = 0.133). Death due to breast cancer was seen in 48.4% (18/35) of all deaths. A subgroup analysis for natives and second generation-immigrants revealed no influence of educational status on DFS (p = 0.368) and OS (p = 0.461). Conclusions: No difference was seen between immigrants and natives with regard to tumor biology. DFS and OS were similar and high in all subgroups. In this real-world setting immigration status did not influence tumor biology or survival. Indicating that immigration background is no limitation for diagnostic and treatment access. Also, educational status had no impact on breast cancer survival for the subgroups with comparable education. These findings mainly relate to immigrants from EU27 Member states rather than immigrants from non-EU countries.
Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON
Authors: Bruno Crestani, John T Huggins, Mitchell Kaye, Ulrich Costabel, Ian Glaspole, Takashi Ogura, Jin Woo Song, Wibke Stansen, Manuel Quaresma, Susanne Stowasser, Michael Kreuter
Journal: The Lancet Respiratory Medicine (2018)
Hope and benefit-finding among adolescents and young adults with cancer: Results from the PRISM randomized controlled trial.
Authors: Abby R. Rosenberg, Miranda Bradford, Krysta S. Barton, Nicole Etsekson, Elizabeth McCauley, J. Randall Curtis, Joanne Wolfe, Kevin Scott Baker, Joyce P. Yi-Frazier
Journal: Journal of Clinical Oncology (2018)

10517 Background: Adolescents and Young Adults (AYAs) with cancer are at risk for poor psychosocial outcomes, perhaps because they have not acquired the skills to navigate illness. We previously reported that a novel, brief, age-appropriate, skills-based intervention [“Promoting Resilience in Stress Management” (PRISM)] was associated with improved quality of life and psychological distress. In this secondary analysis, we aimed to determine if PRISM also improved targeted skills of hopeful thinking, benefit-finding, and goal-setting. Methods: PRISM consists of 4, 30-60 minute, in-person, 1:1 sessions plus a facilitated family-meeting targeting stress-management, goal-setting, cognitive reframing, and meaning-making. English-speaking AYAs (ages 13-24 years) with cancer were randomized to receive either PRISM or psychosocial usual care (UC). Participants completed surveys upon enrollment and 6 months later. Mixed effects regression models estimated associations between PRISM and hopeful patterns of thought (Snyder Hope Scale), benefit-finding (benefit-finding scale for children), and goal-setting (queried with open-ended items about short- and long-term goals, then evaluated by 3 blinded coders with a 10-point, a priori defined tool to identify specific, measurable, and actionable goals) at 6 months. Results: Of N = 92 enrolled AYAs (48 PRISM and 44 UC), 73% were 13-17 years-old, 43% were female, and 62% had a diagnosis of leukemia or lymphoma. Attrition was similar in each arm and primarily due to medical complication or death; n = 36 (72%) PRISM and n = 38 (76%) UC participants completed 6 month surveys. After adjusting for baseline scores, PRISM was associated with improved hope and benefit-finding with moderate-to-large effect sizes: Hope: +3.6 points, 95% CI 0.7,6.4, Cohen’s d effect size = 0.6, p = 0.01; Benefit-finding: +3.1 points, 95% CI 0.0,6.2, d =0.6, p = 0.05. We did not detect changes in goal-setting (Goals: -0.5 points, 95% CI -1.2,0.3, d = -0.3, p = 0.23). Conclusions: A novel intervention targeting skills for AYAs with cancer was associated with significant improvements in hope and benefit-finding, 2 key skills which may mitigate later psychosocial risk. Clinical trial information: NCT023408.
Tumor volume score (TVS), modified recist, and tissue damage score (TDS) as novel methods for assessing response in tenosynovial giant cell tumors (TGCT) treated with pexidartinib: Relationship with patient-reported outcomes (PROs).
Authors: Charles Peterfy, Xin Ye, Heather Gelhorn, Rebecca M Speck, Peter J. Countryman, Vicki Leigh Keedy, Zev A. Wainberg, Arun S. Singh, Bartosz Chmielowski, Daniel D. Von Hoff, Hani M. Babiker, Vivek Khemka, Gregory Michael Cote, Geoffrey Shapiro, Andrew J. Wagner, John H. Healey, Henry Hsu, Paul S. Lin, Sandra Tong, William D. Tap
Journal: Journal of Clinical Oncology (2017)

11048 Background: TGCT is a locally aggressive neoplasm of joint and tendon sheath synovia that may cause pain, limit joint function and destroy bone and local tissues. Measuring TGCT with RECIST is a challenge due to irregular shape and asymmetrical growth, and local tissue damage is not assessed. We reported earlier results of a longitudinal trial of pexidartinib, a selective CSF1R kinase inhibitor, using RECIST as well as novel TVS, modified RECIST and TDS. Here we examine concordance of these MRI measures with PROs. Methods: Patients (pts) with progressive TGCT in a single-arm, multi-center trial of pexidartinib (1000 mg po daily) were assessed by MRI every 2 months by 2 central radiologists (blind to visit order). For RECIST, longest measurable dimensions of up to 2 tumors per joint or tendon sheath were summed (SLD). Modified RECIST summed short axis dimensions (SSD). TVS was based on 10% increments of the estimated maximally distended normal synovial cavity or tendon sheath. TDS scored bone erosion (ERO), cartilage loss (CAR) and bone marrow edema (BME) in multiple regions of each joint. The relationship with PROs (Worst Pain numerical rating scale [NRS] and Worst Stiffness NRS) was assessed. Results: 15 pts (7 knees, 3 hips, 2 ankles, 1 elbow, 1 wrist, 1 thigh) with PRO data and evaluable MRI scans at baseline and Month 7 were assessed. All SLD, SSD and TVS scores improved with respective median changes of -25%, -39% and -50%. Baseline ERO, CAR, and BME ranged 0-19, 0-34, and 0-15, respectively. Median change for each was 0%: ERO worsened in 1 pt, CAR did not change, and BME improved in 4 and worsened in 2. Worst Pain NRS and Worst Stiffness NRS improved in 11 and 9 pts, respectively. Conclusions: TVS demonstrated the greatest pexidartinib effect size, followed by SSD and then conventional RECIST. All had good concordance with PROs. Clinical trial information: NCT01004861. [Table: see text]
Price trajectories assessment for Medicare Part B generic anti-cancer drugs.
Authors: Noa Gordon, Omer Ben-Aharon, Salomon M. Stemmer, Dan Greenberg, Daniel A. Goldstein
Journal: Journal of Clinical Oncology (2017)

6624 Background: Patented anti-cancer drugs launch prices have increased in recent years with subsequent increases after launch. Recently, large price increases of generic drugs were at the center of public attention in the United States. Our aim was to assess price changes with time for Medicare part B anti-cancer generic drugs and to understand how drug characteristics and market structure influence price trajectories. Methods: We included all Medicare part B anti-cancer drugs with price reported in both 2006 and 2016. Patent expiration dates were attached using the Medicare Drug Patent Expiration engine and drugs with a patent expiration date later than 2006 were excluded. Generic manufacturers' FDA approvals for each drug were extracted from the FDA Orange Book. For each drug we extracted the Average Sales Price (ASP) history from October 2006 to October 2016, published by the Center for Medicare and Medicaid services (CMS). Prices were adjusted for inflation, using information obtained from the United States Department of Labor. For each drug we calculated the cumulative ASP change during the follow-up period. Data were analyzed using IBM SPSS Statistics software. Results: We identified 31 anti-cancer generic drugs that met the inclusion and exclusion criteria. During the follow-up period, 15 (48%) drugs had increases in price (median 139%, range 18-2632%). Seven (23%) drugs increased by more than 200% (Table 1). Both gradual price and acute price increases were observed. Some of the drugs which had substantial price increases had no market competition market. Conclusions: Generic drug prices may change substantially with time. Gradual or rapid price increases may be due to lack of generic drug competition, substitution shortages or marketing reasons. New regulations may be needed to prevent further increases in generic drug costs, while balancing the need to maintain financial incentives for drug production and competition. [Table: see text]
Phase II trial of circulating cytokines as markers of docetaxel (DTX) resistance in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Kate Lynette Mahon, Hui-Ming Lin, Calan Spielman, Michelle Lee-Ng, Howard Gurney, Girish Mallesara, Martin R. Stockler, Karen P. Briscoe, Gavin M. Marx, Samuel N. Breit, David A. Brown, Lisa Horvath
Journal: Journal of Clinical Oncology (2016)

5039 Background: DTX improves symptoms and survival in mCRPC; however, ~ 50% of patients have DTX resistant disease. Early markers of DTX resistance will allow rapid cessation of ineffective therapy and enable progression to other available treatments. Increased levels of circulating macrophage inhibitory cytokine 1 (MIC1), interleukins 4 (IL4) and 6 (IL6) after cycle 1 (C1) of DTX predicted chemoresistance in a phase I cohort of men with mCRPC. This phase II study aims to validate these biomarkers in an independent patient cohort. Methods: Plasma samples pre C1 and pre C2 DTX were collected from 121 men with mCRPC. MIC1, IL4 and IL6 levels were measured by ELISA. Patients were grouped as partial responders (PR) and non-responders based on PSA response criteria (PR ≥ 50% reduction in PSA within 3 months of commencing DTX). Associations between cytokine levels, response groups and overall survival (OS) were assessed by non-parametric tests and Cox regression analysis. Results: After C1 DTX, non-responders had significantly greater increases in MIC1 (p < 0.001) and IL6 (p = 0.048). On ROC analysis DTX resistance was predicted by early changes in MIC1 (AUC 0.7; p < 0.001). In contrast to our phase I analysis, IL4 was not associated with response. Furthermore, combinations of cytokine changes did not improve on MIC1 alone as an early biomarker of response. With a median survival of 16 months with 84 deaths, higher levels of MIC1 pre C1 and pre C2 DTX predicted shorter OS (HR 1.2, 95%CI 1.0-1.4; p = 0.03 and HR 1.3, 95%CI 1.1-1.5; p = 0.004, respectively). In a multivariable model including presence of visceral metastases (p = 0.16), baseline ALP (p = 0.13), baseline Hb (p = 0.01), baseline PSA (p = 0.9) and baseline MIC1 (p = 0.08), post DTX MIC1 level was an independent predictor of OS (HR 1.9, 95% CI 1.1-3.4; p = 0.02). Conclusions: This phase II biomarker study has validated the utility of MIC1 as an early predictor of DTX resistance and OS in mCRPC. Conversely, IL4 and IL6 have not demonstrated additional value, emphasizing that adherence to a standardized biomarker development pathway is essential to efficiently move biomarkers into clinical practice. Independent phase III validation of MIC1 is now underway.
A model system to characterize the personalized immunotherapy, AGS-003, and predict functional activity in combination with other therapeutic agents.
Authors: Olga A. Zubkova, Larissa S. Agapova, Marina V. Kapralova, Liudmila A. Krasovskaia, Armen A. Ovsepyan, Maxim V. Lykov, Artem V. Eremeev, Vladimir E. Bokovanov, Olga V. Grigoryeva, Andrey P. Karpov, Sergey V. Ruchko, Charles A. Nicolette, Alexander M. Shuster
Journal: Journal of Clinical Oncology (2016)

e14532 Background: AGS-003 is an immunotherapy consisting of autologous dendritic cells electroporated with amplified total tumor RNA plus synthetic CD40L RNA and is currently being tested in combination with standard of care to extend survival of newly diagnosed metastatic RCC patients in the Phase 3 ADAPT clinical trial. We set out to establish an animal model system to more thoroughly study the AGS-003 mechanism of action and assess the functionality in combination with other therapeutic agents. Methods: Mouse DC precursors were processed in a similar manner to how human monocytes are processed to manufacture AGS-003. Bone marrow cells from 5-8 week old Balb/c mice were incubated with GM-CSF and IL-4 and matured with TNFa, IFNg and PGE2 . Mature DCs were electroporated with total tumor RNA from RENCA tumor plus synthetic mCD40L RNA and injected i.p. to treat syngeneic BALB/c mice in an orthotopic RCC model. This model system was utilized to test the AGS-003-like mouse DCs as a single agent or in combination with an anti-mPD-1 checkpoint inhibitor. Results: Here we report on successfully developing a murine DCs with similar properties to AGS-003, including phenotype (CD80, CD83, CD86, MHCI, CCR7), secretion of IL-12 induced by CD40L RNA and induction of CD8+CD28+CD45RA- memory T cells in vivo.Results showed that, as a single agent, the DC therapy was superior to PBS controls at increasing survival, slowing tumor growth and decreasing lung metastases. These effects were dependent on inclusion of the amplified total RENCA cell RNA based on comparison with irrelevant RNA controls. In addition, the greatest control of tumor growth rate and median survival occurred when combined with the PD-1 checkpoint inhibitor. Conclusions: These data demonstrate the importance of amplified total tumor RNA in directing immune responses against the corresponding tumor target and support the strategy of generating and/or augmenting pre-existing anti-tumor immune responses with active immunotherapy to maximize clinical benefit when combined with checkpoint inhibition. This model system may useful to explore additional combination therapies with other therapeutic agents.