tbuckley/cabot-search huggingface dataset:
Sorafenib (S) in HCC: Is there a role for starting at a total daily dose of 400mg?
Authors: Olugbenga Olanrele Olowokure, Brian Singeltary, Abhimanyu Ghose, Michelle Lynn Mierzwa, Tahir Latif, Shimul Shah, Ross Ristagno, Alok kumar Dwivedi
Journal: Journal of Clinical Oncology (2014)

e15126 Background: S at a starting dose of 400 mg twice daily (800 mg) is considered the standard systemic therapy for HCC, in patients(pts) with well-preserved liver function and advanced stage HCC, based largely on data reported by the SHARP and Asia-Pacific trials. Due to concerns related to SE and reluctance to start at full dose, this single institution retrospective review, evaluated the impact of starting Sat 400mg daily (200 mg twice daily). Methods: From 06/01/09-09/01/13, using ICD code 155, newly registered advanced HCC pts, ECOG PS 0-2, Childs Pugh (CP) A or B who were started on S400mg daily with at least 2 clinic visits were identified. CT scans and AFP levels were followed. Progression free survival (PFS) was estimated from the date of commencing therapy to date of progression or death or loss to follow up if this occurred first and overall survival (OS) was estimated from date of commencing therapy until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval. Log rank test was used to compare the PFS according to CP class. Results: 33 pts (M:F, 21:12), mean age of 59.8 y (SD: 12.40) met inclusion criteria, the median duration (MD) of follow up was 8.7 m, (range: 1.07-27.43). 23 (69.7%) pts were CP-A. 70% had Abnormal AFP and this decreased > 50% in 8 (35%). 96% of the pts received prior locoregional therapy in CP-A and 50% in CP-B. Initial dose tolerance was observed in 69.7%. 16 pts (48.5%) needed dose reduction (CP-A: 56.5%, CP-B: 30%) while 19pts (57.6%) were able to escalate their dose at some point during therapy (CP-A: 60.9%, CP-B: 50%). MD on 400 mg/d was 3m prior to any adjustment (CP-A: 3, CP-B: 2). MD of S use was 8.88 m (CP-A=10.04, CP-B=6.2). During follow up, 26 pts had POD and 24 died. Following POD 10/19 evaluable pts continued S. PFS and median OS was 5.8 m and 9 m respectively, while the OS for CP-A population was 12 m. OS was 79% (CI: 61-89%) at 3 m, 67% (CI: 48-80%) at 6 m, 50% (CI: 32-66%) at 9 m, and 40% (CI: 23-57%) at 12 m. The most common pt reported toxicities were fatigue 87.5%, diarrhea 53.1% and HFS/rash 43.8%. Conclusions: In this cohort of pts, S started at 400mg/d did not seem to result in worse outcomes compared to historic controls possibly due to the ability to tolerate therapy for a longer period of time.
Biomarkers to predict sensitivity to HER2-targeting treatment in HER2-positive advanced gastric cancer.
Authors: Tae Yong Kim, Chan-Young Ock, Do-Youn Oh, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2014)

4062 Background: Trastuzumab-based chemotherapy is considered as standard treatment for patients with HER2-positive advanced gastric cancer (AGC). However, the biomarkers to predict the sensitivity to this HER2-targeting treatment have not been clarified. We evaluated the association of sensitivity to HER2-targeting treatment with HER2 status and tumor metabolic activity in HER2-positive AGC. Methods: We consecutively enrolled 133 patients with HER2-positive AGC treated with trastuzumab-based chemotherapy. HER2 IHC status, HER2/CEP17 ratio, HER2 copy number and maximum standardized uptake value (maxSUV) from 18F FDG-PET were analyzed for the clinical outcomes. Results: Overall survival (OS) of patients with HER2 IHC 3+ was significantly longer than that of IHC 2+/FISH+ (26.9 vs 15.2 months, p=0.012). A median number of HER2/CEP17 ratio and HER2 gene copy number were 5.4 (95% CI, 1.1-14.6) and 10.2 (95% CI, 2.1-30.3), respectively. A higher HER2/CEP17 ratio more than 5.4 was identified as a good predictor to treatment sensitivity (<5.4: OS 11.9 vs ≥5.4: OS 25.7 months, p=0.040). For HER2 copy number, patients with higher HER2 copy number showed the tendency for better OS (HER2 copy number <10.2: 14.7 vs ≥10.2: 25.7 months, p=0.20). Patients with HER2/CEP17 ratio>5.4 and HER2 copy>6 showed best OS than the others (26.9 vs 11.9 months, p=0.044). Contrary to this, patients with IHC same or less than 2+ and HER2/CEP17 ratio<5.4 showed worst prognosis than the others (7.7 vs 26.9 months, p<0.001). However, there was no significant impact of maxSUV on predicting treatment sensitivity so far, even though tendency of higher response rate in high maxSUV patients. Conclusions: The higher HER2/CEP17 ratio and higher HER2 copy number could be biomarkers for sensitivity to HER2 targeting treatment in HER2-positive AGC. Further study on the role of tumor metabolism in this area is needed.
ACUTE THROMBOCYTOPENIC PURPURA DUE TO NEOARSPHENAMINE: REPORT OF A CASE WITH EXAMINATION OF THE MARROW
Authors: P G HATTERSLEY
Journal: Annals of Internal Medicine (1948)

Case Reports1 February 1948ACUTE THROMBOCYTOPENIC PURPURA DUE TO NEOARSPHENAMINE: REPORT OF A CASE WITH EXAMINATION OF THE MARROWPAUL G. HATTERSLEY, M.D.PAUL G. HATTERSLEY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-28-2-452 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAcute thrombocytopenic purpura is a well known complication of the arsenical treatment of syphilis. Although occurring rather rarely, it is the most common of the blood dyscrasias arising from the use of the arsphenamines, and it has been seen at least once in most clinics where sizeable numbers of luetics are treated. The disorder usually occurs after a number of doses of the drug have been given, although it may follow the first injection. It is characteristically acute in onset, and often is preceded by a nitritoid type of reaction immediately after injection. The platelets may entirely disappear from the...Bibliography1. FARLEY DL: Depressed bone marrow function from the arsphenamines, Am. Jr. Med. Sci., 1930, clxxix, 214. CrossrefGoogle Scholar2. MU JW: The effect of neoarsphenamine on number of platelets, Proc. Soc. Exper. Biol. and Med., 1929, xxvi, 407. CrossrefGoogle Scholar3. MCCARTHYWILSON FPR: The blood dyscrasias following the arsphenamines, Jr. Am. Med. Assoc., 1932, xcix, 1557. CrossrefGoogle Scholar4. FALCONEREPSTEINWEVER EHNNGK: Purpura hemorrhagica following the administration of neoarsphenamine, Arch. Int. Med., 1936, lviii, 495. CrossrefGoogle Scholar5. FALCONEREPSTEIN EHNN: Purpura hemorrhagica following neoarsphenamine and bismarsen therapy, Arch. Int. Med., 1940, lxv, 1158. CrossrefGoogle Scholar6. Ibid.: Purpura hemorrhagica due to the arsphenamines, Arch. Int. Med., 1940, lxvi, 319. Google Scholar7. EPSTEINFALCONER NNEH: Effects of neoarsphenamine on formed elements of the blood, Arch. Dermat. and Syph., 1940, xlii, 909. CrossrefGoogle Scholar8. SCHWARTZVANDER HEIDE MEC: Purpura hemorrhagica due to mapharsen, Jr. Am. Med. Assoc., 1945, cxxviii, 657. CrossrefGoogle Scholar9. FERGUSON JW: Agranulocytosis and aplastic anemia after arsphenamines: Report of six cases, Lancet, 1944, i, 334. CrossrefGoogle Scholar10. GORRIE DR: Purpura hemorrhagica after arsenic (neoarsphenamine) therapy treated with vitamin P, Lancet, 1940, i, 1005. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Francisco, California*Received for publication October 15, 1946.From the Department of Medicine, Stanford University Medical School. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHemopoietic System 1 February 1948Volume 28, Issue 2Page: 452-456KeywordsBloodBone marrowDrugsPlateletsSyphilis ePublished: 1 December 2008 Issue Published: 1 February 1948 PDF downloadLoading ...
A longitudinal study investigating quality of life and nutritional outcomes in advanced cancer patients receiving home parenteral nutrition.
Authors: Pankaj G. Vashi, Sadie Dahlk, Brenten Popiel, Carolyn Lammersfeld, Carol Ireton-Jones, Maurie Markman, Digant Gupta
Journal: Journal of Clinical Oncology (2014)

e17591 Background: In cancer patients where gastrointestinal function is marginal and malnutrition significant enough to result in the requirement for intensive nutrition support, parenteral nutrition (PN) is indicated. This longitudinal study examined the quality of life (QoL) and nutritional outcomes in advanced cancer patients with a life expectancy >90 days receiving home PN (HPN). Methods: Fifty-two adult cancer patients (21 males, 31 females, average age 53 years) treated at a specialized cancer facility between April 2009 and November 2011 met criteria. QoL and nutritional status were measured at baseline and every month while on HPN using EORTC-QLQ-C30, Karnofsky Performance Status (KPS), and Subjective Global Assessment (SGA). Repeated measures ANOVA and Generalized Estimating Equations (GEE) were used to evaluate longitudinal changes in QoL and SGA. Results: Cancer diagnoses included pancreatic (n=14), colorectal (n=11), ovarian (n=6), appendix (n=5), stomach (n=4) and others (n=12). Average weight loss 6-months prior to HPN was 13.2 kg (16.9%). Average weight at initiation of HPN was 62.2 kg. In patients with available follow-up data after 1 month (n=39), there was a significant improvement in SGA (10 to 7.9), weight (61.5 to 63.1 kg) and KPS (61.6 to 67.3) from baseline. Similarly, after 2 months (n=22), there was an improvement in global QoL (37.1 to 49.2), SGA (10 to 6.5), weight (57.6 to 60) and KPS (63.2 to 73.2) from baseline. Finally, after 3 months (n=15), there was an improvement in global QoL (30.6 to 54.4), SGA (10.1 to 5.5), weight (61.1 to 65.9) and KPS (64.0 to 78.7) from baseline. Upon GEE analysis, every 1 month of HPN was associated with an increase of 6.3 points in global QoL (p<0.001), 1.3 kg in weight (p=0.009), 5.8 points in KPS (p<0.001) and a decrease of 1.5 points in SGA (p<0.001). Conclusions: HPN is associated with an improvement in QoL, KPS and nutritional status in advanced cancer patients, irrespective of their tumor type, who have compromised enteral intake and malnutrition. The greatest benefit was seen in patients with 3 months of HPN, although patients receiving HPN for 1 or 2 months also demonstrated significant improvements.
Hemoglobin S Induces Exposure of Red Blood Cell Membrane Skeleton Microdomains Bearing Mannose That Stimulate Phagocytosis By Macrophages: A Molecular Basis for Hemolysis in Sickle Cell Disease but Protection Against Plasmodium Falciparum malaria
Authors: Huan Cao, Heather J Wassall, Megan A Forrester, Lindsay S Hall, Heather M Wilson, Jenna Shepherd, Bhinal Patel, Alanna Masson, Sadie Henderson, Gabriela Konieczny, Minter Beverly, Dimitrios Tampakis, Aristotelis Antonopoulos, Stuart M Haslam, Anne Dell, Alexandra J Rowe, John Brewin, David C Rees, Robert N Barker, Mark A Vickers
Journal: Blood (2018)
Incidence of colorectal neoplasia in a high-risk population screened for colorectal cancer: Result of five consecutive mass screening campaigns in a well-defined population.
Authors: Sylvain Manfredi, jean-Francois Bretagne, Gerard Durand, Christine Piette, Gaud Mallard, Jean Faivre
Journal: Journal of Clinical Oncology (2014)

e12509 Background: Colorectal cancer mass screening with FOBT permit to screen average risk population aged 50-74 years. Some colorectal neoplasia history is revealed by the pre-screening procedure. Patients were then excluded from FOBT screening and a screening colonoscopy was offered. We studied this population at high risk colorectal neoplasia naïve for previous colorectal exploration, from 5 consecutive colorectal cancer screening campaigns. Methods: Variables: age, campaign, source of exclusion (general practitioner (GP) or gastroenterologist), colonoscopy completion rate, positive predictive value (PPV) of neoplasia (cancer, advanced adenoma, adenoma). Results: 1179 patients studied (0.1-0.3% of the target population), mean age 59.6 years. Colonoscopy performed for 890 patients, complete in 97.5% of cases. In 69% of cases the history was revealed by the GP. Colonoscopy was achieved in 70% of cases when history was detected by the GP and in 87.7% when detected by the gastroenterologist. 253 Colorectal neoplasias were diagnosed; 34 cancers (TNM stage 0-1: 73.5%, TNM stage 2: 8.6%, TNM stage 3: 14.7%, TNM stage 4: 2.9%), 18 resected endoscopically; one or more adenomas diagnosed in 219 patients and a total of 367 adenomas resected, endoscopically in 96.6% of cases. The average number of adenoma per patient was 2.8 (1 to 50) and the average size was 8.1 mm (1 to 75). Size was ≥10 mm for 25.4% of cases, 37.1% had a villous component and 7.4% were high grade dysplasia. A total of 210 advanced adenomas (size≥10 mm and/or villous component and/or high grade dysplasia and/or number≥3) were diagnosed in 122 patients. PPV of cancer was 3.8%, PPV of advanced adenoma was 13.7%, and PPV of adenoma was 24.6%. Conclusions: In this population with a history of colorectal neoplasia revealed by the mass screening campaign, the rate of participation in screening is very high (75.5%). The PPV of neoplasia is lower than in the average risk population selected by a positive FOBT (PPV of cancer range 7.5 to 10%, PPV of advanced adenoma range 15 to 27% and PPV of adenoma range 32 to 37% in our administrative area). This population might probably also benefit from screening with FOBT.
Phase II study of cabazitaxel as second-line therapy in stage IV non-small cell lung cancer (NSCLC).
Authors: Devika Das, Francisco Robert, Rodolfo Bordoni, Stefan C. Grant, Mansoor N. Saleh, Vishnu Reddy, Mary Jerome, Debi Miley, Karan P. Singh
Journal: Journal of Clinical Oncology (2014)

e19107 Background: Cabazitaxel (C) is a novel semisynthetic taxane with in vitro sensitivity against resistant cell lines to docetaxel due to its lower affinity for P-glycoproteins. In addition, preclinical models indicated that C was able to cross the blood brain barrier. Based on these data, we designed a two-stage phase II study with the primary objective of achieving an objective response rate (ORR) of ≥15%. Methods: Patients (pts) were randomly treated with schedule A (20-25 mg/m2, IV, every 3 weeks) or schedule B (8.4-10 mg/m2, IV on days 1, 8, 15 and 22 of a 5 week cycle). Fourteen pts in each schedule were accrued in the first stage, with the assumption to terminate the study if no objective responses were observed. Secondary objectives include: time to progression (TTP), overall survival (OS), safety, and exploratory correlation of tumor expression of P-glycoprotein (and other ABC transporters) with clinical endpoints. Pts with performance status 0-2, asymptomatic brain metastasis, and previous therapy with paclitaxel were allowed in this study. Results: Fourteen pts were enrolled in each schedule, but 3 are too early for evaluation for response. The median number of treatment cycles were 4 (1-14) for schedule A and 2 (1-4) for schedule B. The average dose intensity for schedule A was 0.98 and for schedule B was 0.83. The most common grade 3+ adverse events (AEs) in A vs B were: neutropenia (66% vs 0), febrile neutropenia (25% vs 0), thrombocytopenia (8% vs 0), anemia (16% vs 0), fatigue (16% vs 14%), diarrhea (8% vs 0), and hematuria (8% vs 7%). No objective responses have been observed among 25 evaluable pts. Stable disease and progression were: A: 64% and 36%; B: 36% and 64%. Median TTP and OS were: A: 3m and 7m, B: 2m and 5.5m, respectively. Conclusions: C was well tolerated when administered in 2 different schedules. Hematuria was an unexpected AE in this patient population. So far, the trial did not meet its primary endpoint of ORR. Clinical trial information: NCT01438307.
Leukocyte telomere length and risk of secondary primary tumors in long-term breast cancer survivors.
Authors: Maria Alma Rodriguez, Beatriz Sanchez-Espiridion, Jian Gu, Xifeng Wu, Frances Ann Zandstra, Guadalupe R. Palos
Journal: Journal of Clinical Oncology (2014)

9599 Background: Leukocytetelomere length (LTL) has been associated with cancer risk including breast cancer. Telomere shortening is observed in response to chemotherapy and/or ionizing radiation exposure. More recently, a report has shown a significant association between short LTL and increased risk of treatment-related thyroid cancer, whereas a suggestive, non-significant association was found between LTL and treatment-related breast cancer (Gramatges MA, et al. Clin Cancer Res, Nov. 2013). We hypothesize that LTL at diagnosis may be associated with breast cancer survival and risk of developing secondary primary tumors (SPT) in long-term breast cancer survivors. We used a case-control study to test this hypothesis. Methods: We used a quantitative real-time PCR method to measure LTL in 168 long term breast cancer survivors (including 68 with SPT, and 100 without SPT), 96 newly diagnosed breast cancer cases, and 97 controls. Cases and controls were matched by years since diagnosis, age at time of sample collection and race. Wilcoxon-rank sum test was used to compare LTL among these three groups and between those long-term survivors with and without SPT. Results: We found that LTL was significantly longer in long-term breast cancer survivors than newly-diagnosed breast cancer patients (Mean (SD), 1.31 ±0.26 vs 1.22 ±0.31; p=0.005), and healthy controls (1.31±0.26 vs 1.10±0.30, p<0.001). Overall, there were no significant differences in LTL between long term survivors with SPT and without SPT. However, in stratified analyses, we observed that breast cancer survivors with SPT had significantly or borderline significantly shorter LTL than those without SPT in individuals with low BMI (<=25) (1.23±0.19 vs 1.44±0.25; p<0.006) and in ever smokers (1.21±0.31 vs 1.36 ±0.32, p =0.071). Conclusions: Longer telomeres were observed in long term breast cancer survivors when compared to new diagnosed cases and healthy controls. A relation between short LTL and increased risk of SPT in long term breast cancer survivors was observed in individuals with low BMI and ever smokers. These results suggest a role of telomere dysfunction in long term breast cancer survivorship.
Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study
Authors: Jacoline E C Bromberg, Samar Issa, Katerina Bakunina, Monique C Minnema, Tatjana Seute, Marc Durian, Gavin Cull, Harry C Schouten, Wendy B C Stevens, Josee M Zijlstra, Joke W Baars, Marcel Nijland, Kylie D Mason, Aart Beeker, Martin J van den Bent, Max Beijert, Michael Gonzales, Daphne de Jong, Jeanette K Doorduijn
Journal: The Lancet Oncology (2019)
Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era
Authors: James N. Gerson, Elizabeth Handorf, Diego Villa, Alina S. Gerrie, Parv Chapani, Shaoying Li, L. Jeffrey Medeiros, Michael I. Wang, Jonathon B. Cohen, Oscar Calzada, Michael C. Churnetski, Brian T. Hill, Yazeed Sawalha, Francisco J. Hernandez-Ilizaliturri, Shalin Kothari, Julie M. Vose, Martin A. Bast, Timothy S. Fenske, Swapna Narayana Rao Gari, Kami J. Maddocks, David Bond, Veronika Bachanova, Bhaskar Kolla, Julio Chavez, Bijal Shah, Frederick Lansigan, Timothy F. Burns, Alexandra M. Donovan, Nina Wagner-Johnston, Marcus Messmer, Amitkumar Mehta, Jennifer K. Anderson, Nishitha Reddy, Alexandra E. Kovach, Daniel J. Landsburg, Martha Glenn, David J. Inwards, Reem Karmali, Jason B. Kaplan, Paolo F. Caimi, Saurabh Rajguru, Andrew Evens, Andreas Klein, Elvira Umyarova, Bhargavi Pulluri, Jennifer E. Amengual, Jennifer K. Lue, Catherine Diefenbach, Richard I. Fisher, Stefan K. Barta
Journal: Journal of Clinical Oncology (2019)

Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger.We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed.Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2).In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.