tbuckley/cabot-search huggingface dataset:
Bevacizumab administered intraperitoneally as palliative treatment of malignant refractory ascites.
Authors: Cristian Mateescu, Aymeric Becq, Mohamed Bouattour, Chantal Dreyer, Sandrine J. Faivre, Eric Raymond
Journal: Journal of Clinical Oncology (2014)

e20617 Background: Intra-peritoneal administration of Bevacizumab (IP-Beva) in refractory malignant ascites seems to be well tolerated and efficient in small clinical series. We aim to evaluate the activity of IP-Beva in refractory malignant ascites patients with solid malignancies. Methods: Patients with symptomatic malignant ascites requiring iterative paracentesis (at least every 4 weeks) were treated with IP-Beva 5mg/kg in 90 minutes perfusion after ultrasound guidance if necessary. A retrospective analysis of demographical, clinical and biological data was performed. Punction-free interval and evacuated volume per punction before and after IP-Beva, and safety were reported. Results: Thirty-four patients were treated between 2007 and 2013. Median age was 63 years. Primitive tumoral localizations were: pancreas (n=12), ovary (n=8), colorectal (n=4), biliary tractus (n=4), stomach (n=2), HCC (n=1), breast (n=1), kidney (n=1), unknown (n=1). Patients received IP-Beva once in 79% (n=27), twice in 15% (n=5) and more than twice in 6% (n=2). Concomitant systemic chemotherapy was administrated in 76% of cases (n=26). Ascites were exsudative (protides > 20g/L) and transsudative (≤ 20g/L) in 73% (n=24/33) and 27% (n=9/33) of patients respectively. Mean punction-free interval was doubled in exsudative (14 to 28 days) whereas unchanged in transsudative ascites patients (14 to 14 days). Mean evacuated volume was reduced in exsudative (4.2 to 2.1L) whereas none significantly modified in transsudative ascites patients (6.3 to 5.6L). Adverse effects were grade 1 or 2 abdominal pain (n=6), duodenal perforation 7 days after IP-Beva in 1 patient with duodenal stent and asymptomatic pulmonary embolism 4 weeks after IP-Beva in 1 patient. Conclusions: Intraperitoneal Bevacizumab appears well tolerated and active in patients with refractory malignant ascites especially in case of exsudative ascites. Intraperitoneal Bevacizumab seems to be useful for symptom management and palliative care in patients with refractory malignant ascites.
A pilot study of tremelimumab, a monoclonal antibody against CTLA-4, in combination with either transcatheter arterial chemoembolization (TACE) or radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC).
Authors: Austin G. Duffy, Susanna Varkey Ulahannan, Suzanne Fioravanti, Melissa Walker, William Douglas Figg, Kathryn Compton, Aradhana Venkatesan, Nadine Abi-Jaoudeh, Bradford J. Wood, Tim F. Greten
Journal: Journal of Clinical Oncology (2014)

e15133 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and results in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Both transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) have been shown to induce a peripheral immune response. The underlying hypothesis of this study is that the effect of anti-CTLA4 treatment can be enhanced by TACE or RFA in patients with HCC. Methods: Patients with HCC (Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage C; ECOG 0/1; post-sorafenib) are being enrolled in a pilot study of Tremelimumab at 2 dose levels (DL1 and DL2) until disease progression (irRECIST). Subtotal TACE or RFA is performed during study week 6 with DLT evaluation period encompassing first 8 weeks of study. Primary endpoint comprise safety and feasibility with secondary efficacy endpoints of time to tumor progression and overall survival. Exploratory objectives will evaluate changes in immune parameters in the peripheral blood of patients undergoing anti-CTLA4 therapy pre- and post-RFA or TACE. Results: 6 pts have been treated so far at DL1; M:F 4:2; Median age = 54(range 42-75); Cirrhosis present in 5pts. Hepatitis B/C/neg: 2/3/1. 3 pts received TACE, 3 underwent RFA. One patient experienced G3 hyperbilirubinemia. This occurred beyond the 8-week DLT period (5 weeks post-RFA) and was adjudicated as possibly related to treatment, but most likely related to concomitant medication. It followed a fluctuant course with subsequent resolution to G1/baseline. No other grade 3/4 treatment-related toxicities observed. No patient discontinued treatment due to toxicity. N=3 patients developed mild treatment-related rash requiring topical treatment. Conclusions: Tremelimumab in combination with TACE or RFA in patients with advanced HCC is feasible at the first of two planned dose levels with safety profile supporting continued development. Enrollment continues to the final planned dose level. Full safety data for both dose levels will be presented. Clinical trial information: NCT01853618.
Effect of a supportive group-based intervention for family caregivers of acute leukemia patients.
Authors: Megan Pailler, Teresa M Johnson, Michael Zevon, Sarah Kuszczak, Elizabeth A. Griffiths, James E. Thompson, Eunice S. Wang, Meir Wetzler
Journal: Journal of Clinical Oncology (2014)

e20721 Background: Distress among family caregivers of cancer patients is common, and may be particularly heightened among caregivers of acute leukemia patients. We developed a supportive group-based intervention for family caregivers and assessed the feasibility, acceptability and efficacy of the group on caregiver distress and quality of life, as well as patient distress. Methods: We employed a sequential cohort design comparing a pre-intervention control group with the intervention group. Patients and caregiver dyads completed measures at four time points: within one week of diagnosis (T1), two week follow-up (T2), six week follow-up (T3) and twelve week follow-up (T4). Results: Significant interaction effects were observed for both caregiver distress and quality of life, whereby those receiving the intervention evidenced improved quality of life and reduced distress over time, compared with the control group, with group differences in caregiver quality of life emerging at T3 and in distress emerging at T4. Conclusions: Overall, results support the acceptability, feasibility and preliminary efficacy of the group intervention. Examination of the group with a larger sample and across multiple settings is warranted.
Image Gallery: A case of porokeratosis ptychotropica
Authors: J.R. Sun, Y.R. Li, P. Tu, X.X. Chen, Y. Wang
Journal: British Journal of Dermatology (2019)

Funding sources: none. Conflicts of interest: none to declare. Dear Editor, A 23‐year‐old‐man presented with a 5‐year history of progressive pruritic brown hyperkeratotic plaques on his buttocks with slightly elevated borders. Scattered hyperkeratotic satellite lesions could be observed peripherally (a). Histopathological examination showed multiple cornoid lamellae with underlying dyskeratotic keratinocytes in the epidermis (b). The diagnosis of porokeratosis ptychotropica was established. Porokeratosis ptychotropica is a rare and under‐recognized variant of porokeratosis, characterized by brown itching verrucous plaques in the genitogluteal region with multiple cornoid lamellae seen in histology. Lucker and colleagues first coined this diagnosis in 1995, using the Greek words ptyche (fold) and trope (turning) to describe the flexural distribution of the disease.1 The pathogenesis of this disease remains unknown. Malignant transformation of the porokeratotic lesion can occur in 7·5% of cases, mostly associated with long‐term, linear, large‐size lesions.2
Long-term quality of life among localized prostate cancer survivors: Qalipro population-based study.
Authors: Anne-Valérie Guizard, Clarisse Kerleau, Pascale Grosclaude, Mariette Mercier, Natacha Heutte, Florence Joly
Journal: Journal of Clinical Oncology (2014)

9594 Background: If treatments can cure localized prostate cancers (LPC) they often induce acute toxicities and definitive sequelae with impact on quality of life (QoL). However, very few studies focused on the long-term QoL of survivors of LPC. The goal of this population based case-control-study was to evaluate QoL 10 years after treatments for LPC in comparison with aged-matched healthy controls. Methods: LPC patients diagnosed in 2001 were issued from 11 French Cancer Registries. Controls were recruited among the general population and were matched to patients on age and geographic area. EORTC QLQ-C30, EPIC, HADS and MFI self-reported questionnaires were used to measure QoL, anxiety and fatigue. Patients were identified into 3 groups according to previews treatments: radical prostatectomy (RP), radiotherapy (RT) and radical prostatectomy plus radiotherapy (RP+RT). Patients could receive hormonotherapy (HT). Student’s paired t and McNemar χ² tests were used for the analysis between patients and controls. Analysis between treatments groups were performed with ANOVA. Only clinically relevant QoL score differences (≥ 5 points) were reported. Results: There were 287 patients and 287 controls. The participation rate of patients was of 46. Among LPC patients 143 (50%) were treated with RP, 78 (27%) with RT and 33 (11%) with RP+RT. 60 (21%) and 47 patients (16%) received HT at baseline and at the time of the study respectively. There was no socio-demographic difference between patients and controls. Patients didn’t report more anxiety, depression and fatigue than controls, but lower EORTC-QLQ social functioning score (p=0.003). LPC long-term survivors reported more urinary troubles (urinary function and incontinence) (p<0.0001) and more sexual dysfunctions (p<0.0001) than controls, whatever the treatment group. RP and RP+RT groups had worse urinary function and incontinence than RT (p<0.01). LPC survivors treated with HT at the time of study reported more sexual dysfunction (p<0.0001) and hormonal troubles (dysfunction and bother) (p=0.002) than the other survivors. Conclusions: 10 years after treatments, long term survivors of LPC reported important urinary and sexual dysfunctions with poor social QoL.
Genomic Determinants of Response to Blinatumomab in Relapsed/Refractory (R/R) B-Cell Precursor Acute Lymphoblastic Leukemia in Adults
Authors: Yaqi Zhao, Ibrahim Aldoss, Chunxu Qu, Guido Marcucci, Anthony S. Stein, Ravi Bhatia, Charles G. Mullighan, Stephen J Forman, Kathryn G. Roberts
Journal: Blood (2018)
Aberrant Cytokine Production in Myelofibrosis Is Not Rectified By Ruxolitinib and Is Differentially Sensitive to Inhibition of JAK/STAT, MAP Kinase, and NFκB Signaling
Authors: Daniel A.C. Fisher, Cathrine Miner, Elizabeth Engle, Hengrui Hu, Taylor B. Collins, Amy Zhou, Maggie J. Allen, Olga Malkova, Stephen T Oh
Journal: Blood (2018)
Population pharmacokinetic (PK) analysis from phase 1 and 2 studies of the HER3 inhibitor patritumab in patients with advanced non-small cell lung cancer (NSCLC) or solid tumors.
Authors: Satoshi Yoshiba, Mendel Jansen, Nobuko Matsushima, Xiaoping Jin, Jeanne Mendell-Harary
Journal: Journal of Clinical Oncology (2014)

2587 Background: Patritumab is a fully human antibody specific to HER3, a HER family receptor implicated in tumor resistance to anticancer treatment. In order to support patritumab dose recommendations, a population PK model was developed for phase 1 and 2 patritumab studies to characterize its PK and identify influencing factors. Methods: Population PK analysis was performed using data from the international phase 1b/2 HERALD study of patritumab (18 mg/kg every three weeks [q3w] or 18 mg/kg loading dose followed by 9 mg/kg q3w maintenance dose) in combination with erlotinib in EGFR treatment-naïve patients with advanced NSCLC after failure of ≥1 prior chemotherapy. Data from an open-label, phase 1 study of patritumab (9 mg/kg q3w or 18 mg/kg q3w) in Japanese patients with advanced solid tumors were also included. The effects of gender, baseline body weight (BW), creatinine clearance, eGFR, and albumin as covariates for clearance (CL), and gender and baseline BW as covariates for volume of central compartment (Vc) were investigated. PK simulations were performed to compare interpatient variability of patritumab exposure following fixed or BW-based dosing. Results: In total, 833 serum concentrations from 145 patients (136 NSCLC, 9 solid tumor) were included in the analysis. Serum patritumab concentrations were described by a two-compartment intravenous model with first-order elimination. Linear PK were observed at doses of 9 mg/kg and 18 mg/kg. CL, Vc, and volume of peripheral compartment were estimated as 0.0238 L/h, 3.62 L, and 2.50 L, respectively. BW and baseline albumin were significant covariates of CL (p<.05) and BW was a significant covariate of Vc (p<.05). PK simulations showed that BW-based dosing reduces interpatient variability in exposure compared with fixed dosing. Conclusions: Results showed that Vc was approximately serum volume and that CL was relatively low, indicative of a long terminal half-life. BW and albumin were significant factors affecting PK. The analysis supports an 18 mg/kg loading dose and 9 mg/kg q3w maintenance dose, and suggests that BW-adjusted dosing reduces interpatient variability. Clinical trial information: NCT01211483.
Hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: Treatment outcome and prognostic factor analysis.
Authors: Youwu Shi, Yuankai Shi, Shengyu Zhou, Xiaohui He, Xiaohong Han, Shikai Wu, Feng Pan, Peng Liu, Yinyu Liu, Yingheng Lei, Hongzhi Zhang, Jianliang Yang, Yan Qin, Changgong Zhang, Sheng Yang, Liya Zhao, Kehuan Luo, Guanqing Wu, Yan Sun
Journal: Journal of Clinical Oncology (2014)

e19560 Background: The role of high-dose therapy followed by hematopoietic stem cell transplantation (HSCT) in the treatment of lymphoblastic lymphoma (LBL) has not been fully defined. Methods: This retrospective study analyzed data from 41 patients with chemotherapy-sensitive lymphoblastic lymphoma who underwent high-dose therapy followed by HSCT from December 1989 to December 2009 in Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College. Results: Initial treatments were conducted in 36 patients, of which 26 were in first complete remission (CR1) at transplantation; and 5 patients had had relapsed diseases. The median follow-up was 97.1months (range 24.6-173.1) for surviving patients. The 5-year overall survival (OS) and event-free survival (EFS) were 64% and 47%, respectively, for initial patients; and were both 20% for relapsed patients. The 5-year OS for patients in CR1 and in other disease status were 73% and 33%, respectively (p=0.033), and 5-year EFS were 49% and 33%, respectively (p=0.076). Age (cut-off value as 20 years), bone marrow involvement and chemotherapy cycles (cut-off value as 4) prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Of the 8 bone marrow involved patients, 3 underwent allogeneic HSCT and remained disease-free in the following 25, 40 and 144 months, respectively; while the other 5 received autologous HSCT and all died of disease progression within 25 months after the transplantation. Conclusions: These results confirm that high-dose treatment followed by hematopoietic stem cell transplantation is a reasonable option for chemotherapy-sensitive LBL patients in CR1. Allogeneic HSCT is superior to autologous HSCT in LBL patients with bone marrow involvement.
Are manufacturers targeting smaller patient populations and are they being rewarded for it?
Authors: Sydni Meyrowitz, Mariana Ricci, Alex Bastian
Journal: Journal of Clinical Oncology (2014)

e17621 Background: Between 1965 and 2013 over 132 oncology drugs received regulatory approval in Europe. Only recently, with the unlocking of the genome, has the advent of personalized medicine delivered a shift in the targetable populations addressed by these medications. This study aimed to analyze trends in oncology therapy development related to manufacturer use of biomarkers and targeting of niche populations, as well as the French payer reaction and subsequent assessment of these therapies within oncology. Methods: Oncology drugs (N=132) were identified from a literature search and the Medicines Complete reports. Pediatric oncology drugs, launch extensions, drugs not targeting tumor treatment, and reimbursement renewals were excluded. Information for each drug, including: indication, Amélioration du Service Médical Rendu (ASMR) score, target population, line-of-therapy, and presence of a genetic biomarker were obtained from the Haute Autorité de Santé (HAS) drug assessments for selected drugs in their first indication (n=62). An analysis was conducted across these variables to identify trends relating to average calculated estimates for eligible populations, line-of-therapy, inclusion of a companion biomarker, and the ASMR score determinations from HAS. Results: In 2001, oncology drugs targeted an average population of 10,175 French patients; by 2013 that number dropped to 2,015. This decline can be attributed to an increase in targeting of later-line settings and the use of biomarkers, which selected patient sub-populations. In 2013, 60% of drugs targeted second-line, compared to 80% in first-line in 2001. Biomarkers were present in 40% of assessments in 2013; none in 2001. Since 2007, no assessments received an ASMR I and since 2009 no ASMR II has been awarded. Since 2001, only 5% and 27% of assessments have received an ASMR I or II, respectively, while 19%, 23%, and 16% have received ASMR III, ASMR IV or ASMR V. Conclusions: Recently, new oncology drugs have, on average, targeted smaller patient populations. This is a result of a focus on biomarkers and later-line therapy. HAS has become more critical during this time, perhaps not finding smaller, niche populations attractive.
Lung cancer detection by low-dose computerized tomography (LDCT) and digital tomosynthesis (DT) for lung cancer screening in a high-risk population: A comparison of detection methods.
Authors: Natthaya Triphuridet, Sutida Singharuksa, Onousa Sangfai, Sirachat Vidhayarkorn, Tanachai Leelapisut, Pavinee Nantavithya, Thaniya Sricharunrat, Narongchai Teerayathanakul, Naree Chungklay, Supapun Luengingkasoot, Wisut Lamlertthon
Journal: Journal of Clinical Oncology (2014)

1530 Background: Low-dose computerized tomography (LDCT) recommended as a screening tool for lung cancer in a high risk population has some limitations with respect to its high false positive rate, accumulated radiation exposure and relatively high costs. Digital tomosynthesis (DT) is a multi-section imaging technique which can improve detection ability of small lung nodules and renders much lower radiation dosage and operation costs. Methods: 624 Thai heavy smokers (>30 pack-years) were enrolled in a prospective study starting from July 2012 to October 2013. All participants underwent LDCT and DT on the same day while the results were independently viewed with 1-week interval apart. Abnormal findings were categorized into 3 groups: negative, indeterminate (maximum diameter of pulmonary nodule 5-9.9 mm or volume 50-500 mm3), and suspicious for primary lung cancer (maximum diameter of pulmonary nodule >10 mm or volume >500 mm3, consolidation, obstructive atelectasis, pleural effusion, or mediastinal lymphadenopathy). Results: Ten lung cancer cases were detected in this high-risk group (10/624, 1.6%). LDCT and DT classified 23 and 20 cases, respectively, as suspicious for primary lung cancer. DT detected 8 primary lung cancers as frequently as did LDCT. LDCT classified 68 cases as indeterminate while DT classified 21 as such cases. Two additional primary lung cancers were detected at a 3-month follow-up; all were identified as indeterminate by baseline LDCT and only one case was indeterminate by baseline DT. The positive predictive value (PPV) for all suspicious for primary lung cancer findings by LDCT and DT was 34.8% and 40%, respectively. The sensitivity and specificity of LDCT and DT was comparable at 80% and 98%, respectively. The PPV for pulmonary nodule >10 mm or volume >500 mm3 was 30% and 42% in LDCT and DT, respectively. The PPV for pulmonary nodule >5mm or volume 50-500 mm3 was 9% and 22.5% in LDCT and DT, respectively. Conclusions: DT is a lung cancer screening modality that is comparable to LDCT, particularly for pulmonary lesions of 10 mm. and larger.
Low levels of tumour suppressor miR-655 in plasma contribute to lymphatic progression and poor outcomes in oesophageal squamous cell carcinoma
Authors: Jun Kiuchi, Shuhei Komatsu, Taisuke Imamura, Keiji Nishibeppu, Katsutoshi Shoda, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Atsushi Shiozaki, Kazuma Okamoto, Hitoshi Fujiwara, Daisuke Ichikawa, Eigo Otsuji
Journal: Molecular Cancer (2019)

Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.
The Use of EUTOS Long-Term Survival Score Instead of Sokal Score Is Strongly Advised in Elderly Chronic Myeloid Leukemia Patients
Authors: Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Fabio Stagno, Giorgina Specchia, Luciano Levato, Bruno Martino, Mariella D'Adda, Elisabetta Abruzzese, Patrizia Pregno, Mario Tiribelli, Alessandra Iurlo, Tamara Intermesoli, Anna Rita Scortechini, Francesco Cavazzini, Carmen Fava, Massimiliano Bonifacio, Marzia Salvucci, Monica Bocchia, Giovanni Caocci, Antonella Gozzini, Micaela Bergamaschi, Simona Soverini, Robin Foà, Giovanni Martinelli, Michele Cavo, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2018)