tbuckley/cabot-search huggingface dataset:
Stereotactic body radiotherapy for hepatocellular carcinoma in the setting of poor liver function: A case series.
Authors: Vladimir Valakh, Graeme Williams
Journal: Journal of Clinical Oncology (2017)

493 Background: Role of stereotactic body radiotherapy (SBRT) to the liver for patients with poor hepatic function after transcatheter arterial chemoembolization (TACE) has not been established. We reviewed results of SBRT for men with hepatocellular carcinoma (HCC) and Child-Pugh (CP) score ≥ 8 cirrhosis after TACE. Methods: Following a median of 3 TACE treatments, five males with severe cirrhosis received SBRT for persistent or progressive HCC in 2011-14. Clinico-pathologic characteristics and treatment details were retrospectively retrieved. Results: Median age at diagnosis was 55 years (range, 48 – 55). Median interval between cancer diagnosis and SBRT was 38 months (range, 3 – 60). All 5 patients experienced decline in CP score after TACE, for a median of drop of 1 point (range, 1 – 3) between the initiation of TACE and referral for radiotherapy. At time of SBRT, 4 had CP class B and 1 class C cirrhosis with median CP score of 9 (range, 8 – 11). There were no distant metastases and one patient had extrahepatic tumor extension. Three of 5 exhibited clinical symptoms of decompensated cirrhosis within 30 days before radiotherapy and one had portal vein thrombosis. Median MELD score at SBRT was 15 (range, 12 – 18). SBRT to a median total dose of 27.5 Gray (range, 27.5 – 30) was delivered in 5 once daily fractions. Median radiotherapy course duration was 9 days (range, 5 – 18). All patients had single radiation therapy targets with median largest tumor dimension of 3.6 cm (range, 2.4 – 6.2). Median planned target volume was 24 cm 3 (range, 17 – 197). Sorafenib was given prior to SBRT to one patient, concurrently to one, and sequentially after radiotherapy to another. There were no acute complications. Two patients died within 20 days from completion of SBRT. Median follow up for surviving &gt; 20 days was 10 months (range, 5 – 13). None experienced radiographic tumor progression after radiotherapy. Estimated overall survival was 40% at 6 months (95% confidence intervals, 0 – 83.8%). Conclusions: For HCC patients with CP score ≥ 8 following TACE, prognosis after liver SBRT was poor.
Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Inder S Anand, Brian Claggett, Jiankang Liu, Amil M Shah, Thomas S Rector, Sanjiv J Shah, Akshay S Desai, Eileen O'Meara, Jerome L Fleg, Marc A Pfeffer, Bertram Pitt, Scott D Solomon
Journal: JACC Heart Failure (2017)
A randomized phase II/III study, comparing perioperative adriamycin plus ifosfamide versus gemcitabine plus docetaxel for operable high grade soft tissue sarcomas in extremity or trunk: JCOG1306.
Authors: Kazuhiro Tanaka, Kozo Kataoka, Junki Mizusawa, Tsukasa Yonemoto, Hideo Morioka, Hiroaki Hiraga, Hirokazu Chuuman, Takatoshi Ohno, Akihiko Matsumine, Satoshi Abe, Kosuke Matuso, Mitsuru Takahashi, Koji Hiraoka, Haruhiko Fukuda, Yukihide Iwamoto
Journal: Journal of Clinical Oncology (2015)

TPS10575 Background: Based on the results of JCOG0304, which showed sufficient efficacy of perioperative chemotherapy with adriamycin plus ifosfamide (AI) for operable high-grade soft tissue sarcomas (STS), AI has been considered acceptable as standard regimen for operable STS in Japan. Recent studies have reported gemcitabine plus docetaxel (GD) is effective for advanced STS. A new clinical question has thus arisen of whether less toxic GD has a compatible efficacy to AI as perioperative therapy. Therefore, we have commenced a phase II/III trial to confirm the non-inferiority of perioperative GD to AI. Methods: Eligibility criteria include operable, histologically proven STS, primary tumor (T2bN0M0 or anyTN1M0) based on the 7th AJCC/UICC-TNM or first local recurrent tumor, arising in the extremities or trunk, FNCLCC grade 2 or 3, and aged 20 to 70. Patients are randomized to the AI or the GD. Patients in the AI arm receive preoperative 3 courses and postoperative 2 courses of adriamycin at 30 mg/m2 on days 1-2 and ifosfamide at 2 g/m2 on days 1–5, every 3weeks. Patients in the GD arm receive preoperative 3 courses and postoperative 2 courses of gemcitabine at 900 mg/m2 on days 1 and 8, and docetaxel at 70 mg/m2 on day 8, every 3 weeks. In the phase II part, the primary endpoint is the proportion of completion of preoperative chemotherapy without progressive disease in the GD arm. The planned sample size is 28 patients in the GD arm, which was calculated based on an expected proportion of completion of preoperative GD without progressive disease of 85% and a threshold of 65%, with a one-sided alpha of 0.1 and a beta of 0.2. In the phase III part, the primary endpoint is overall survival. The sample size was calculated as a total of 140 patients with a one-sided alpha of 0.1, power of 0.7 and a non-inferiority margin of 8% at 3 year survival, assuming 3 year survival of AI to be 85% and that of GD as 87%. The accrual period is 6 years and the follow-up period is 5 years. This trial has started in February 2014 and the current enrollment is 18 as of January 2015 (UMIN000013175). Clinical trial information: 000013175.
Prevention of 5-FU-induced health-threatening toxicity by pretherapeutic DPD deficiency screening: Medical and economic assessment of a multiparametric approach.
Authors: Michele Boisdron-Celle, Olivier Capitain, Jean-Philippe Metges, Roger Faroux, Christophe Borg, Marie-Pierre Galais, Mehdi Kaassis, Jaafar Bennouna, Karine Bouhier Leporrier, Eric Francois, Isabelle Baumgaertner, Veronique Guerin-Meyer, Oana Cojocarasu, Celia Roemer-Becuwe, Claire Stampfli, Ludovic Rosenfeld, Thierry Lecomte, Virginie Berger, Alain Morel, Erick Gamelin
Journal: Journal of Clinical Oncology (2013)

3601 Background: While 5-FU is the foundation of many in GI oncology treatments, pts with DPD deficiency can experience early-onset severe (5%) even fatal (0.3%) toxicities. This study aimed to confirm the pharmaco-economic benefits of pre-therapeutic screening for DPD deficiency using a multiparametric approach in a multicenter prospective cohort study (NCT01547923). Methods: Two parallel cohorts of pts treated with 5-FU-based chemotherapy for colorectal carcinoma were compared: Group A: initial DPD deficiency screening; Group B: no evaluation. Enrollment was based on 5-FU administration guidelines of each institution. DPD deficiency screening combined genotyping and phenotyping (ODPM Tox) (1,2,3). The 2 groups were to be compared in terms of early 5-FU-induced toxicity grade, toxicity cost and DPD screening cost. The enrollment was to be immediately closed in the case of proven 5-FU-related toxic death. Results: 1,130 pts were included from 06/01/2008 to 07/31/2012. Group A: no severe toxicity despite 1 pt with complete deficiency (pt not treated with 5-FU), 20 pts with partial deficiency had safe PK-monitored 5-FU (ODPM Protocol) with only one hospitalization due to toxicity. Group B: One death due to complete DPD deficiency, confirmed retrospectively. Enrollment prematurely closed after experts’ unanimous decision citing ethical concerns. 21 pts with partial DPD deficiency. 5 reported toxicity-related hospitalizations. Data treatment is ongoing. Conclusions: One complete deficiency occurred in both groups: Group A pt had safe treatment whereas Group B pt died due to 5-FU toxicity. Pre-therapeutic DPD deficiency screening using this multi-parametric approach should be performed before 5-FU-based treatment and PK-guided dose adaptation allows for safe treatment of even partially DPD deficient patients. Clinical trial information: NCT01547923. [Table: see text]
Predictors of declining levels of physical activity among adult survivors of childhood cancer.
Authors: Carmen L Wilson, Wendy M. Leisenring, Kevin C. Oeffinger, Paul C. Nathan, Karen Wasilewski-Masker, Melissa M. Hudson, Sharon M. Castellino, Marilyn Stovall, Gregory T. Armstrong, Tara M. Brinkman, Leslie L. Robison, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2013)

10062 Background: Childhood cancer survivors are at increased risk of developing obesity-related diseases, yet many survivors do not meet established guidelines for physical activity. We aimed to identify demographic and health-related predictors of declining physical activity among participants in the Childhood Cancer Survivor Study (CCSS). Methods: Analyses included 6617 &gt;5 year childhood cancer survivors diagnosed between 1970-86 who completed the CCSS 2003 and 2007 follow-up questionnaires, and1992 siblings. Participants were classified as active if they reported engaging in any physical activity other than their regular job duties in the prior month. Generalized linear models using a log-link and Poisson distribution were used to compare participants whose physical activity levels fell from active to inactive over the study interval to those who remained active or whose activity levels improved. In addition to analyses comparing survivors to siblings, selected demographic factors and chronic conditions (CTCAE v4.0 Grade 3 and 4) were evaluated as risk factors in an analysis among survivors alone. Risk ratios (RR) with 95% confidence intervals (CI) are reported. Results: The median age at last follow-up among survivors and siblings was 36 (range: 21-58) and 38 (range: 21-62) years, respectively. Approximately 14% of survivors and 9% of siblings reported declines in physical activity across the study interval (p&lt;0.01). Factors that predicted declining levels of physical activity included BMI≥30kg/m 2 (RR=1.4, 95% CI=1.3-1.7, p&lt;0.01), BMI&lt;18.5kg/m 2 (RR=1.4, 95% CI=1.0-1.8, p=0.03), not completing high school (RR=1.7, 95% CI=1.2-2.2, p&lt;0.01), and black race (RR=1.6, 95% CI=1.2-2.1, p&lt;0.01). In a model limited to survivors, declining levels of physical activity were more likely among survivors who reported the presence of Grade 3 or 4 neurological (RR=1.5, 95% CI=1.2-1.8, p&lt;0.01) or cardiac conditions (RR=1.5, 95% CI=1.3-1.9, p&lt;0.01). Conclusions: Childhood cancer survivors are at increased risk of becoming inactive over time compared to siblings. Interventions targeting survivors at highest risk of decline are required to reduce the risk of chronic diseases associated with an inactive lifestyle.
Are XELOX and FOLFOX equivalent in colorectal cancer? Dose intensity, toxicity, and treatment duration in clinical practice.
Authors: Ya Ning Gao, Aline Mamo, Michael Ostaric Palumbo, Gerald Batist, Prosanto Chaudhury, David Melnychuk, Peter Metrakos, Lawrence Panasci, Petr Kavan
Journal: Journal of Clinical Oncology (2013)

e14556 Background: Xelox and Folfox regimens have been shown to be equivalent in clinical trials for colorectal cancers. However, concerns about toxicity induced by Xelox in clinical practice have been reported, resulting in reduced dose intensity. In this retrospective analysis, we compared the dose intensity of Xelox to Folfox in relation to toxicity. Methods: 208 patients were treated in adjuvant (Xelox: n=56, median age 65 years; Folfox: n=40, median age 66 years) or metastatic (Xelox: n=65, median age 66 years; Folfox: n=47 median age 62 years) settings. 90% of patients had ECOG 0-1. Results: In the adjuvant setting, 86% of patients treated with Xelox received a lower dose of the drug up front, compared to only 10% of Folfox-treated patients. Additional dose reductions occurred in subsequent cycles in 23% of Xelox-treated patients (mean relative dose intensity (RDI) Oxaliplatin: 72%; Capecitabine: 74%) but not Folfox-treated patients (mean RDI Oxaliplatin: 85%, 5-FU: 86%). A higher percentage of Folfox-treated patients had toxicities compared to Xelox-treated patients: nausea (30% vs 18%), diarrhea (47% vs 24%), and peripheral sensory neuropathy (32% vs 3%). Treatment delays were more frequent in Folfox (40%); mean cumulative delay, 9.4 (range 2.1-52.4) weeks, compared to Xelox (20%); mean cumulative delay, 10.2 (3.1-48.1) weeks. Mean treatment duration was equal (Xelox: 22.8 (3.0-78.1); Folfox: 22.6 (2.3-64.4) weeks). In the metastatic setting, results followed a similar pattern. 75% of Xelox-treated patients received a lower dose up front compared to 33% of Folfox-treated patients. Further dose reductions occurred in 31% of Xelox-treated patients (mean RDI Oxaliplatin: 70%; Capecitabine: 67%) compared to 20% of Folfox-treated patients (mean RDI oxaliplatin: 75%; 5-FU: 69%). Treatment delays occurred in 60% of Folfox-treated patients and 43% of Xelox-treated patients becauseof toxicities. Mean treatment duration was 24.9 (3.0-65.0) and 26.1 (4.0-60.1) weeks respectively. Conclusions: The higher dose reduction of Xelox compared to Folfox appeared to enable treatment completion with less toxicities. The impact on survival and cost of treatments will be presented.
Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: A Japanese nationwide survey.
Authors: Takashi Kokudo, Kiyoshi Hasegawa, Yutaka Matsuyama, Tadatoshi Takayama, Namiki Izumi, Masumi Kadoya, Masatoshi Kudo, Shoji Kubo, Michiie Sakamoto, Osamu Nakashima, Takashi Kumada, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2017)

371 Background: Because of the rarity of hepatic vein tumor thrombus (HVTT), compared with portal vein tumor thrombus (PVTT), in patients with hepatocellular carcinoma (HCC), little is known about this disease entity. The aim of this study was to evaluate the prognosis of each treatment modality for HVTT through an analysis of data collected in a Japanese nationwide survey. Methods: We analyzed data for 1,021 Child-Pugh A HCC patients with HVTT without inferior vena cava invasion registered between 2000 and 2007. Of these patients, 540 patients who underwent liver resection (LR) and 481 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 244 patients (52.5% of the LR group). Results: The median survival time (MST) in the LR group was 2.89 years longer than that in the non-LR group (4.47 years vs 1.58 years; P &lt; 0.001) and 1.17 years longer than that in the non-LR group (2.93 years vs 1.76 years; P = 0.009) in a propensity score-matched cohort. After curative resection, the MSTs were similar between patients with HVTT in the peripheral hepatic vein and those with HVTT in the major hepatic vein (4.85 years vs 4.67 years; P = 0.974). In the LR group, the postoperative 90-day mortality rate was 3.4% (16patients). In patients without PVTT, the MST was significantly better than that in patients with PVTT (5.67 years vs. 1.88 years; P &lt; 0.001). Conclusions: LR is associated with a good prognosis in HCC patients with HVTT, especially in patients without PVTT.
The effect of tissue factor pathway inhibitor release and interactions with growth factors on the antitumor effects of ultra low molecular weight heparin semuloparin.
Authors: Jawed Fareed, Angel Gray, Daniel Kahn, Josephine Cunanan, Hussein Khan, Christian Viskov, Debra Hoppensteadt
Journal: Journal of Clinical Oncology (2012)

e13117 Background: Heparins are known to produce anti-tumor effects beside other pharmacologic actions. More recently an ultra LMWH has been developed for the prevention of thrombosis in cancer patients. Initial studies demonstrated that this agent also exhibits anti-tumor effects in animal models. To understand the mechanism of anti-tumor effects of this agent studies were designed to fractionate this ULMWH in to various AT affinity fractions. Methods: An ULMWH (semuloparin, Sanofi-aventis) and its high (HAF) and low (LAF) affinity fractions were prepare by AT affinity chromatography. These agents were administered at 1 mg/kg to primates via intravenous route. Blood samples were collected for a period of up to 6 hours. TFPI release and anti-Xa activities were measured. The interactions of ULMWH and its fractions with various growth factors such as FGF, VEGF, EGF and beta TGF were measured using a mass spectral method employing SELDI technique. The anti-tumor effects of each of these agents were measured using the mouse model of Lewis lung carcinoma. Results: In comparison to ULMWH the LAF showed minimal anti Xa activity whereas HAF exhibited a higher activity. All agents exhibited a similar release of the TFPI; however, HAF exhibited slightly higher release. All agents also showed varying degrees of binding to growth factors as measured by peak intensities. All agents produce anti-tumor effects in the mouse model resulting in a significant reduction in tumor size. Conclusions: Semuloparin has been clinically proven to prevent venous thromboembolism in patients with cancer (SAVE ONCO). These effects are attributable to the inhibition of factor Xa and the generation of thrombin. The fact that LAF mediates its anti-tumor effects without producing anti Xa effects suggest that these may be related to the release of TFPI. Furthermore the ULMWH, HAF and LAF all interact with growth factors suggest that these interactions may also contribute to anti-tumor effects of semuloparin, therefore, beside antithrombotic effects this agent also exhibits oncostatic effects.
Focal cryo-hemiablation to treat unilateral localized prostate cancer: A prospective midterm oncologic and functional outcomes.
Authors: Mohammed Baghdadi, Eric Barret, Arjun Sivaraman, Rafael Sanchez-Salas, Igor Nunes-Silva, Victor Srougi, Youness Ahallal, Gregory Rembeyo, Silvia Garcia Barreras, François Rozet, Marc Galiano, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

e537 Background: We report our mid-term oncologic and functional outcomes of focal cryo-hemiablation (FC-HA) for unilateral localized low-risk prostate cancer (PCa). Methods: Prospective single-arm interventional study analyzing mid-term data of PCa patients treated at our institution with FC-HA of diseased lobe. Inclusion criteria‎ were men with unilateral localized cancer, PSA &lt; 15 ng/ml, clinical stage T1c-T2a, Gleason score ≤ 7 (3+4), maximum number of cancer-cores &lt; 33%, maximum cancer involvement in a single core &lt; 50%, no extra prostatic extension in mp-MRI, no previous PCa-related treatment and life expectancy ≥10 yr. PSA was measured every 3 mo during 1st yr post treatment, and biannually thereafter. mp-MRI and biopsy of both lobes were routinely done at 12 mo, while repeat biopsies were driven by PSA elevations. Continence, urinary and erectile functions were assessed using ICS, IPSS and IIEF-5 questionnaires, respectively. Treatment failure (primary outcome) was defined as residual cancer in treated lobe at follow up. Results: We studied 52 men with mean (SD) age of 65.8 (7.2) yrs and median (IQR) follow-up of 31 (21-44) mo. Baseline criteria were: median (IQR) of PSA of 6.8 (5.4–8.0) ng/ml, total number of cancer-cores of 2 (1-3) and percentage cancer-cores of 17% (8-25), and total cancer-core length of 7 (3-12) mm. Gleason score was 6 (3+3) in 33 (63.5%) and 7 (3+4) in 19 (36.5%) patients. Follow-up biopsies were done in 1st, 2nd and 3rd yrs for 52 (100%), 28 (53.8%) and 15 (28.8%) patients, respectively, revealing cancer-cores in 13/52 (25%) patients. 6 (11.5%), 5 (9.6%) and 2 (3.8%) patients showed cancer in ipsilateral lobe, contralateral lobe and bilaterally, respectively. Treatment failure was observed in the treated lobe in 8 (15.4%) patients. Median (IQR) PSA significantly (p &lt; 0.0001) declined to nadir PSA of 2.9 (1.5-4.2) ng/ml (57.4% reduction) at 3 mo. None of patients demonstrated undetectable PSA. All patients maintained continence with insignificant worsening of IPSS (p &lt;0.92) and IIEF-5 (p &lt;0.07) and low toxicity. Conclusions: FC-HA appears to maintain acceptable oncologic control in mid-term follow-up with preserved genitourinary functions and low toxicity.
Genetic variations in miRNA binding site of <i>TPST1</i> and <i>ZG16B </i>associated with prognosis for patients with colorectal cancer.
Authors: Byung Woog Kang, Soo Jung Lee, Yoo Jin Lee, Jong Gwang Kim, Yee Soo Chae, Sang Kyun Sohn, Joon Ho Moon
Journal: Journal of Clinical Oncology (2013)

3553 Background: MicroRNAs (miRNA) may play important roles in tumorigenesis by regulating the expressions of proto-oncogenes or tumor suppressor genes. Single nucleotide polymorphisms (SNP) located in the 3’-UTR of miRNA target genes might affect miRNA-mediated gene regulation, thereby contributing to the susceptibility or prognosis of cancer. Accordingly, the present study analyzed SNPs located in the putative miRNA-binding sites of the 3’-UTR of various genes and their impact on the prognosis for patients with colorectal cancer by altering miRNA binding efficiency. Methods: Eight hundred and thirty-one consecutive patients (discovery cohort, n=309; validation cohort, n=522) with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue. One hundred fifty-seven SNPs were selected in Silico analysis for the current study, which was based on several miRNA database and HapMap database. The SNP genotyping was performed using the Sequenom MassARRAY. Results: The median age of all patients was 65 years, and 468 (56.3%) patients had colon cancer, while 363 (45.1%) patients had rectal cancer. The pathologic stages after the surgical resection were as follows: stage I (n=150, 18.1%), stage II (n=332, 40.0%), stage III (n=333, 40.1%), and stage IV (n=16, 1.9%). In the discovery cohort, 19 SNPs were identified as possible prognostic biomarkers in a multivariate survival analysis [disease-free survival (DFS) and/or overall survival (OS)] adjusted for age, preoperative CEA level, and pathologic stage. In the validation cohort, the TPST1 rs3757417T&gt;G and ZG16B rs12373A&gt;C were significantly associated with prognosis as same direction in the discovery cohort (discovery + validation cohort; TPST1 rs3757417T&gt;G, DFS, p value=0.0007, OS, p value=0.0091 in recessive model; ZG16B rs12373A&gt;C, DFS, p value=&lt;0.0001, OS, p value=0.0009 in dominant model). Conclusions: The current study provides evidence that the rs3757417T&gt;G and rs12373A&gt;C polymorphism in the 3’-UTR of TPST1 and ZG16B, respectively, are possible prognostic biomarker for patients with colorectal cancer.