tbuckley/cabot-search huggingface dataset:
Overall survival of liver transplantation for hepatocellular carcinoma in the elderly.
Authors: Tanmay Sahai, George Cholankeril, Rosann Cholankeril, Caitlin Farrell, Ponnandai Sadasivan Somasundar
Journal: Journal of Clinical Oncology (2016)

e15639 Background: Currently liver transplantation (LT) is the gold standard treatment for hepatocellular carcinoma (HCC) confined to the liver. While many prognostic factors have been identified, there is a lack of data in HCC LT survival outcomes in the elderly patients (65+). We aim to evaluate and compare survival outcomes in this age population to younger patient populations. Methods: We identified 1765 patients with hepatocellular carcinoma who underwent liver transplantation using Surveillance, Epidemiology and End Results (SEER) database between 1998-2007. We characterized age at diagnosis as 15-44, 45-64 and 65+. Patients were stratified by gender, AFP elevation ( > 20), and single tumor size ( < 5cm) and histologic grade. 1-year and 5-year relative survival (RS) rates were calculated using the Kaplan-Meir method. Results: Of the 1,765 HCC LT patients, 6.3% of patients were from 15 to 44 yoa (n = 111), 81% of patients were from 45 to 64 yoa (n = 1431), and 12.6% of patients were above 65 yoa (n = 223). 84.6% (n = 1489) of LT recipients were males. The five-year RS for all patients was 75.7% (95% CI: 73.8% > 77.6%). Five-year RS rates for specific age populations are as follows: 15-44: 74.5 %(95% CI: 71.8% > 76.7%), 45-64: 74.4% (95% CI: 65% > 81.8%), and 65+ yoa: 71.6% (64.0% > 77.9%). Table below lists various prognostic factors in relation to RS. Conclusions: Similar RS was seen in each age population for their corresponding variable. HCC LT in females had a worse RS than males, most notably in the elderly. Our results suggest in carefully selected patients, HCC in LT have comparable survival outcomes to that of younger patient populations and that advanced age should not be the deciding factor to exclude patients from LT. 5-year RS 15-44 45-64 65+ Overall 74.5 (68-79.3) 74.4 (70.2 - 79.1) 71.6 (68.4-72.3) Male 74.8(63.6-83) 75.5 (72.7-78) 75.4 (69.2-84.6) Female 73.5 (52-86.5) 71 (64.9-76.2) 62 (69.2-84.6) AFP > 20 70 (50.6-83.7) 72.6 (67-77) 71.8 (57.2-82.2) Milan Criteria 72.8 (58.9-82.7) 76.2 (72.9-79.2) 70.7 (60.4-78.4) Well Diff Grade 1 78 (63-88.3) 82.1 (77.2-86) 70.7 (55.6-81) Mod. Diff Grade II 75 (53.6-87.6) 75.8 (71.3-79.7) 71.8 (57.3-82.1) Poor Diff Grade III 88.1 (27-98) 64.2 (52.9-70.6) 65.2 (38.1-82.7)
Transcatheter Aortic Valve Implantation
Authors: John G. Webb, Lukas Altwegg, Robert H. Boone, Anson Cheung, Jian Ye, Samuel Lichtenstein, May Lee, Jean Bernard Masson, Christopher Thompson, Robert Moss, Ron Carere, Brad Munt, Fabian Nietlispach, Karin Humphries
Journal: Circulation (2009)

Transcatheter aortic valve implantation is an alternative to open heart surgery in patients with aortic stenosis. However, long-term data on a programmatic approach to aortic valve implantation remain sparse.Transcatheter aortic valve implantation was performed in 168 patients (median age, 84 years) in the setting of severe aortic stenosis and high surgical risk. Access was transarterial (n=113) or, in the presence of small iliofemoral artery diameter, transapical (n=55). The overall success rate was 94.1% in this early experience. Intraprocedural mortality was 1.2%. Operative (30-day) mortality was 11.3%, lower in the transarterial group than the transapical group (8.0% versus 18.2%; P=0.07). Overall mortality fell from 14.3% in the initial half to 8.3% in the second half of the experience, from 12.3% to 3.6% (P=0.16) in transarterial patients and from 25% to 11.1% (P=0.30) in transapical patients. Functional class improved over the 1-year postprocedure period (P<0.001). Survival at 1 year was 74%. The bulk of late readmission and mortality was not procedure or valve related but rather was due to comorbidities. Paravalvular regurgitation was common but generally mild and remained stable at late follow-up. At a maximum of >3 years and a median of 221 days, structural valve failure was not observed.Transcatheter aortic valve implantation can result in early and sustained functional improvement in high-risk aortic stenosis patients. Late outcome is determined primarily by comorbidities unrelated to aortic valve disease.
Psychiatric comorbidities among esophageal cancer survivors in South Korea: A nationwide population-based, longitudinal study.
Authors: Jaesung Heo, O Kyu Noh, Mison Chun, Young-Taek Oh, Oyeon Cho
Journal: Journal of Clinical Oncology (2018)

4037 Background: Esophageal cancer has a relatively poor prognosis ( < 15% overall 5-year survival), owing to a lack of initial symptoms and delayed diagnosis. Also, patients with this fatal cancer tend to have a high rate of mental disorders. The psychological problems can affect treatment compliance and could increase mortality in cancer survivors. Methods: The aim of this longitudinal study was to analyze the prevalence of mental disorders in esophageal cancer survivors using claims data in South Korea. We confirmed mental disorders in a nationwide cohort of 8,879 patients who were diagnosed with esophageal cancer between January 1, 2010 and December 31, 2014. We categorized the prevalence of mental disorders based on the age and the time of diagnosis. Results: In esophageal cancer, a total of 738 patients were diagnosed with a mental disorder, 1 year prior to the cancer treatment. Of those patients, 231 were diagnosed with depression (31.3%) and 245 with anxiety (33.2%) during their first visit. The overall frequency of mental disorders peaked within 2 months after the cancer treatment. The highest rate of increase after treatment was confirmed in stress reaction/adjustment disorders. Age and sex was a significant predictive factor for mental disorders (p < 0.05). Female patients were at a higher risk for mental disorders (hazard ratio: 1.30, p = 0.002), whereas patients with initial treatment as surgery were more likely to have mental disorders compared with radiotherapy (hazard ratio: 1.33, p < 0.001). Conclusions: Mental disorders in esophageal cancer survivors showed different patterns of prevalence depending on the nature of disease. Timely diagnosis and intervention for psychological distress could increase the quality of life for esophageal cancer survivors. The frequency of mental disorders in esophageal cancer survivors (N = 8,879). Age Total number of esophageal cancer Mental disorder Substance abuse Depressive disorder Anxiety disorder Stress/ adjustment disorder Somatoform/ conversion disorder 10-39 25 2 1 1 0 0 0 40-49 367 34 14 7 8 3 2 50-59 2,072 174 51 53 41 9 20 60-69 3,212 285 50 83 91 29 32 70-99 3,203 243 13 87 92 22 29 Total 8,879 738 129 231 232 63 83
Suppression of tumor progression and angiogenesis in two Lewis lung carcinoma mouse models by shRNA knockdown of fibroblast activation protein.
Authors: Shuang Xian, Feng Peng, Chunting Wang, Fan Cai, Yuquan Wei
Journal: Journal of Clinical Oncology (2013)

e13592 Background: Fibroblast activation protein (FAP), a transmembrane serine peptidase, is expressed by tumor-associated fibroblasts. As an important factor in tumor microenvironment, it has been reported that FAP plays a dual role in tumor progression, both positive and negative. In a mouse model of breast cancer, FAP increasing microvessel densities had been experimentally demonstrated. The aim of the study was to determine the effect of FAP in tumor growth and tumor microenvironment in LLC mouse models, especially in lung metastasis model. Methods: Female C57 mice received i.v injection of LLC cells into tail vein or s.c into right flank to establish lung metastasis model or subcutaneous xenograft model. 21 mice were randomly divided into 3 groups (n=7, per group) and treated with 5% GS,control-shRNA or FAP-shRNA, respectively. Xenograft tumor size and weight, numbers of pulmonary metastatic nodules and lung weight were measured. FAP expression, microvessel density and collagen fiber were evaluated. Data were analyzed using one-way analysis of variance (ANOVA), and a value of P &lt;0.05 was considered to be statistically significant. Results: FAP-shRNA decreased significantly in the number of metastases on the lung surface and average lung weight, compared with 5%GS and control-shRNA (P&lt;0.05).The size of metastases in treatment group was large than those of the controls (P&lt;0.05). Moreover, FAP-shRNA showed a significant reduction of 44% in tumor volume and tumor weight, relative to other groups (P&lt;0.05). In both models, FAP expression and microvessel density were lower in treatment group compared to the controls. And FAP-shRNA indicated an increase in the accumulation of collagen fiber. Conclusions: The study suggests that shRNA targeting FAP inhabit tumor growth in LLC mouse models, especially in lung metastasis model. We hypothesize that the anti-tumor mechanism is related to angiogenesis reduction and alteration of collage fibro accumulation, which eventually change tumor microenvironment. These findings indicate the potential of FAP as a new therapeutic strategy for lung cancer.
c15-160: Enzalutamide (ENZA) plus CC-115 in men with metastatic castration-resistant prostate cancer (mCRPC): A phase 1b Prostate Cancer Clinical Trials Consortium study.
Authors: Dana E. Rathkopf, Karen A. Autio, Emmanuel S. Antonarakis, Heather H. Cheng, Gabrielle Arauz, Annelise Slack, Melanie Hullings, Howard I. Scher, Felix Y Feng, Karen E. Knudsen
Journal: Journal of Clinical Oncology (2018)

5045 Background: Studies in PTEN-deficient prostate cancer (PC) models have shown additive anti-tumor activity when ENZA is combined with PI3K pathway inhibition due to modulation of reciprocal feedback loops. In addition, interplay between AR and DNA-PK regulates hormone-dependent DNA repair and PC progression. This phase Ib trial aims to optimize therapy for mCRPC with the combination of ENZA and the dual mTOR/DNA-PK inhibitor CC-115. Methods: This was a phase Ib multicenter trial (NCT02833883) for first-line mCRPC patients. Treatment was fixed dose ENZA (160 mg PO QD) with escalating doses of CC-115 (5 mg and 10 mg PO BID) using a 3 x 3 design. The primary endpoints were safety, PK and the recommended phase 2 dose (RP2D) of the combination. Secondary endpoints were PSA response, time on study and exploratory correlates using tumor biopsies, CTCs and ctDNA. Results: 16 patients were treated: 9 in dose escalation and 7 in dose expansion, for a total of 13 patients treated at the RP2D of CC-115 10 mg PO BID. There were no drug-drug interactions. Median time on study was 26 (18-74+) weeks (wks), and 9 patients remain on active treatment. All evaluable patients had a > 50% PSA response, and 60% of patients achieved a ≥90% decline. The most common AEs were low grade fatigue (31%) and diarrhea (25%). At the RP2D, 8/13 (62%) patients developed rash: grade 3 (n = 6), grade 2 (n = 1) and grade 1 (n = 1) prompting dose reduction. 12 patients had baseline tissue analysis by IHC and/or NGS: 6 men had PTEN inactivation and 3 had DNA damage response and repair (DDR) alterations. Median time on study for those with PTEN deletions was 25 wks (7-57+), and was 29 wks (28-41+) for those with DDR alterations. Data on ctDNA and CTC biomarkers is pending. Conclusions: The combination of ENZA and CC-115 is safe and active in mCRPC, as demonstrated by all evaluable patients achieving a > 50% PSA decline and 60% achieving a ≥90% PSA decline. Due to a higher than expected incidence of rash, the protocol was amended to continue with CC-115 at 7.5 mg PO BID for the phase 2 expansion. Funding: Celgene and Gateway for Cancer Research. Clinical trial information: NCT02833883.
Infographic. International Ankle Consortium Rehabilitation-Oriented Assessment
Authors: Eamonn Delahunt, Chris M Bleakley, Daniela S Bossard, Brian M Caulfield, Carrie L Docherty, Cailbhe Doherty, Francois Fourchet, Daniel T P Fong, Jay Hertel, Claire E Hiller, Thomas W Kaminski, Patrick O McKeon, Kathryn M Refshauge, Alexandria Remus, Evert A Verhagen, Bill T Vicenzino, Erik A Wikstrom, Phillip A Gribble
Journal: British Journal of Sports Medicine (2018)

Lateral ankle sprains are one of the most prevalent lower limb musculoskeletal injuries incurred by individuals who participate in recreational physical activities and sports.1 2 

### Propensity for the development of chronic ankle instability

The misconception that acute lateral ankle sprains are innocuous injuries that require little treatment is common across patients and healthcare professionals; indeed, up to 50% of individuals who incur an acute lateral ankle sprain do not seek formal healthcare management for their injury.3 All too often colloquial terms such as a ‘rolled’ ankle or ‘twisted’ ankle are used to describe an acute lateral ankle sprain injury. In reality, acute lateral ankle sprains are rarely ever a ‘simple’ injury. …
Cortico-anorectal, Spino-anorectal, and Cortico-spinal Nerve Conduction and Locus of Neuronal Injury in Patients With Fecal Incontinence
Authors: Xuelian Xiang, Tanisa Patcharatrakul, Amol Sharma, Rachael Parr, Shaheen Hamdy, Satish S.C. Rao
Journal: Clinical Gastroenterology and Hepatology (2018)
Results of treatment of bilateral Wilms' tumor: The Instituto Nacional de Pediatria Experience—Mexico City, Mexico.
Authors: Araceli Castellanos-Toledo, Lourdes Romero-Rodriguez, Jose de Jesus Figueroa Carbajal, Jose Martin Palacios-Acosta, Daniel Hernandez-Arrazola
Journal: Journal of Clinical Oncology (2016)

e22005 Background: Treatment of bilateral Wilms tumor (BWT) presents the challenge of resecting the tumor while preserving nephrons to avoid renal failure. In the NWTSG experience, 14.5% patients with BWT developed endstage renal disease (ESRD) at 20 years, most commonly associated with progressive disease, genetic predisposition, nephrotoxic effects of treatment, and hyperfiltration injury. The 8-year EFS was 74%. Methods: Retrospective, longitudinal and clinical study performed from January/1995-December/2011 in children younger 18 years old with BWT included in a multimodal approach based in NWTSG as preoperative chemotherapy and nephron-sparing surgery for all patients, and radiation-therapy for select patients. Regimen DD-4A (Dactinomycin/Vincristine/Doxorubicin) was given. An initial biopsy was performed mainly to assess anaplastic histology. Results: 8 (16.3%) of 49 Wilms tumors registered were BWT. At diagnosis, all had synchronous disease, median age was 18 months (6-90 months), 5 (62.5%) were male, all had asymptomatic abdominal mass, 87.5% abdominal pain, 62.5% microscopic hematuria (no macroscopic hematuria was reported), 25% hypertension, 25% fever, 50% had metastatic disease (lung 50%, liver 25%, and distant lymph nodes 12.5%), and 50% had some known syndromic association (Denys-Drash and overgrowth-syndromes) or congenital anomalies (clubfoot-equinovarus, double renal pelvis and bilateral cystic renal dysplasia). Initial biopsy identified favorable histology in 7 patients and anaplastic histology in 1 patient. Nephrogenic rest was presented in 50%. Preservation of renal tissue with clear margins was obtained in nephron-sparing surgery. Unilateral nephrectomy was also required in 3 patients by extensive tumor, radiation-therapy to the involved flank was given. 5-year EFS was 86%. No ESRD, no important toxicity and no second malignancies were observed at 15-years follow up. Conclusions: Substantial differences were observed in our results. It is possible that addition of doxorubicin could have contributed to improve EFS and enhance nephron-sparing surgery. Identifying anaplastic histology at initial biopsy allowed the assignment of appropriate treatment.
Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine: A Pan-European study.
Authors: Muhammad Ahsan Javed, Georg Beyer, Nha Ngoc Hoa Le, Alessio Vinci, Helen Wong, Daniel H. Palmer, Robert Morgan, Angela Lamarca, Richard Hubner, Juan W. Valle, Salma Alam, Sumsur Chowdhury, Yuk Ting Ma, Livia Archibugi, Gabriele Capurso, Patrick Maisonneuve, Albrecht Neesse, Malin Sund, Marvin Schober, Sebastian Krug
Journal: Journal of Clinical Oncology (2017)

e15774 Background: Gemcitabine (GEM) based chemotherapy has been the standard of care for patients with metastatic PDAC with marginal effects on overall survival (OS). In recent years, FOLFIRINOX and Nab-paclitaxel (NAB) + GEM regimens have shown significant survival benefits compared to gemcitabine in clinical trial settings. This study aims to investigate the efficacy of FOLFIRINOX and NAB + GEM versus GEM monotherapy and GEM doublet combinations in real-life settings across different European institutions. Methods: Patients from UK, Sweden, Germany, Italy and Hungary with metastatic PDAC receiving palliative chemotherapy between 2012 and 2015 were included in a retrospective multinational study. Kaplan-Meier method was used for survival analysis. Results: Of the 1089 included patients, 576 (52.9%) were male and 170 (15.6%) underwent primary resection before systemic recurrence. GEM monotherapy was the most commonly used regimen (40.0%; n = 436), followed by combination treatments such as GEM + oxaliplatin, GEM + cisplatin, GEM + capecitabine (24.2%; n = 263), FOLFIRINOX (17,5%; n = 191) and NAB + GEM (7.3%; n = 80). Overall, 6-months and 12-months mortality rate was 48.9% and 72.5%, respectively. The median OS in different groups was: FOLFIRINOX 9.0 months (95% CI 7.1-10.9), NAB + GEM 7.0 months (95% CI 5.8-8.2), other GEM doublet combinations 7.0 months (95% CI 6.0-8.0) and GEM monotherapy 5.0 months (95% CI 4.3-5.7). Compared to GEM monotherapy, intensified chemotherapy either with FOLFIRINOX (p = 0.0001), NAB + GEM (p = 0.02) or GEM doublets (p = 0.0001) was associated with significantly improved survival. Comparison of the different combination regimens was as follows: NAB + GEM vs. FOLFIRINOX (OS: 7.0 vs 9.0 months, p = 0.25), NAB + GEM vs. GEM doublets (OS: 7.0 vs. 7.0 months, p = 0.79) and FOLFIRINOX vs. GEM doublets (OS: 9.0 vs. 7.0 months, p = 0.29). Conclusions: The use of FOLFIRIOX and NAB in clinical routine is variable in Europe. GEM based regimens seem to be the preferred standard of care. Compared to GEM monotherapy, combination treatments improved survival. No significant differences amongst combination therapeutic regimens were identified within our cohort.
P05.16 Successful high dose chemotherapy for recurrent pineoblastoma - cases report
Authors: C Lee
Journal: Neuro-Oncology (2018)

Pineoblastoma is a exceedingly rare highly malignant pineal gland neuroectodermal tumor in adult. Treatment strategies should have surgery, radiotherapy and chemotherapy. Treatment strategies for recurrent pineoblastoma is very limited. We discussed successful high dose chemotherapy for the recurrent pineoblastoma after GTR and/or CSI. We reviewed the chemo and radiotherapy for the recurrent pineoblastomas. Two young adult patients were undergone gross total resection of large pineal gland tumor. Histopathologic study revealed pineoblastoma. One patient received craniospinal irradiation(CSI) and the other refuse to radiation treatment. Both patient recurred the tumor, one who received CSI recurred at the multiple spinal cord and the other who did’nt CSI at the original site after one postoperative year. Both patient received high dose carboplatine plus ectoposide systemic chemotherapy with intrathecal methotraxate treatment. Both two patients successfully received high dose chemotherapy without major complication. Both patients had partial remission after 6 courses of induction chemotherapy. Both patients still have tumor cells on the MRI and received 6 courses of intensified chemotherapy. Both of the patients got complete remission. Short intensive hgh dose chemotherapy followed by surgery and CSI in young adult with pineoblastomas seems to be superior treatment results in recurrent cases.
The impact of osimertinib on function and health status for patients with EGFR mutation-positive advanced non-small cell lung cancer.
Authors: Katja Rudell, Konstantinos Papadakis, Carolyn Bodnar, Christopher Hoyle, Serban Ghiorghiu, Anna Ryden
Journal: Journal of Clinical Oncology (2016)

e20548 Background: The impact of osimertinib (AZD9291) on lung cancer symptoms (cough, pain and dyspnea) has been described in phase I and phase II trials (Ryden A et al. Poster P282 European Cancer Congress 2015.). We aimed to characterize the effect of treatment on additional and broader functioning domains using the patient-reported European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EuroQoL 5-Dimensions (EQ-5D-5L) questionnaires. Methods: At the start of a phase II trial (AURA2, NCT02094261), patients completed the QLQ-C30 (general cancer symptoms, functioning and global health status/quality of life [QoL]) and the EQ-5D-5L (general health status utilities). Both questionnaires were completed every 6 wks for 36 wks. Changes of 10 points or more were defined as clinically meaningful for the QLQ-C30 (Osoba D et al. J Clin Oncol 1998;16:139–44.). Results: In AURA2, approximately three-quarters of patients on treatment improved or stabilized in the functioning domains of the QLQ-C30. Table 1 shows the mean change from baseline in functioning domains and responders at 36 wks. Patients on treatment also showed improvement on the EQ-5D-5L visual analogue scale absolute scores, which increased from a mean of 65.2 (SD 20.33) at baseline (n = 175), to 73.7 (SD 17.33) at wk 36 (n = 102). Conclusions: Data suggest that patients treated with osimertinib show benefits in functioning and health status/QoL from baseline assessments up to the first 36 wks using two established health status instruments. This trial program is ongoing. Clinical trial information: NCT02094261.Changes from baseline (N = 186) in functioning domains of the QLQ-C30 at 36 wks in AURA2. Functioning domain of QLQ- C30 (n = 109) Change from baseline, mean (SD) Improved ≥ +10 n (%) Stable –9 to +9 n (%) Worse ≤ -10 n (%) Global health status 6.5 (24.85) 36 (33.0) 52 (47.7) 21 (19.3) Physical 4.9 (16.72) 37 (33.9) 59 (54.1) 13 (11.9) Role 4.7 (27.58) 37 (33.9) 51 (46.8) 21 (19.3) Emotional 7.0 (19.88) 31 (28.4) 68 (62.4) 10 (9.2) Cognitive 1.7 (19.24) 32 (29.4) 49 (45.0) 28 (25.7) Social 9.2 (26.59) 42 (38.5) 51 (46.8) 16 (14.7)