tbuckley/cabot-search huggingface dataset:
Effects of temozolomide combined with bevacizumab in patients with relapsed uterine sarcoma.
Authors: Naoki Sasaki, Hiroko Kouta, Yuji Ikeda, Masashi Takano, Ryoko Kikuchi, Kazuya Kudoh, Tsunekazu Kita, Kenichi Furuya, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2013)

e21520 Background: Common treatment for patients with unresectable relapsed uterine sarcoma is anthracycline-based combination chemothersapy, but the response is not satisfactory. We evaluated the effects of temozolomide combined with bevacizumab in patients with relapsed uterine sarcoma. Methods: From 2009 to 2012, nine patients with relapsed uterine sarcoma were treated with weekly bevacizumab (2mg/kg; days1,8, and 15, q4 weeks) and temozolamide (80mg/body, daily), and treatment continued until disease progression. The response and adverse effects were evaluated using the response evaluation criteria in solid tumors (RECIST), and common terminology criteria for adverse events (CTCAE) version 3.0. Results: In RECIST evaluation, 1 (11%) of 9 patients had complete response (CR) and 1 (11%) had partial response (PR). Four patients (44%) had stable disease (SD) for at least three months. The response rate (RR; CR+PR) and clinical benefit rate (CBR; CR+PR+SD) were 22% and 66%, respectively. The median progression-free survival was 9.8 months (range from 3 to 32 months). There were no treatment-related deaths or CTCAE grade 4 toxicities, and no patients were dose-reduced due to toxicity. Conclusions: Temozolomide combined with bevacizumab provided disease stabilization in some patients with relapsed uterine sarcoma with tolerable toxicities. These results suggested that this combination would offer another option in the treatment of unresectable relapsed uterine sarcoma.
Stage I seminoma: Treatment outcomes in a low-income country.
Authors: Yazan Asad Abuodeh, Fadwa Abdelrahman, Ahmed Abdel-Fattah Salem, Naim Farah, Abdelatif Al-Mousa, Jamal Khader
Journal: Journal of Clinical Oncology (2012)

e15024 Background: The aim of this report is to address treatment outcomes of patients with early-stage seminoma in a developing country with special reference to patients with history of surgical violation of the scrotum and the potential predictors of disease relapse. Methods: Seventy four patients with pure seminoma were treated at King Hussein Cancer Center (Amman, Jordan) between 2003 and 2010. All patients underwent orchiectomy. All but 3 patients received adjuvant radiotherapy. Patients who underwent surgical violation of the scrotum prior to referral were managed by further excision or irradiation of the scrotal scar. The follow-up ranged from 1 to 200 months (mean, 33 months). Results: At the time of follow-up; all but one patient remain alive. The 3-year relapse-free survival for the entire cohort was 95.9%. Three patients were burdened by relapse, all of whom received adjuvant irradiation following inguinal orchiectomy and initially harbored tumors larger than 4cm upon pathological examination. Median time to relapse was 14 months (range, 8-25 months). None were associated with elevated tumor markers prior to detection of relapse. All but one patient were successfully salvaged by chemotherapy. Conclusions: Our results confirm the excellent prognosis for patients with early-stage seminoma treated by orchiectomy and adjuvant radiotherapy in a developing country. Although all patients burdened by relapse demonstrated adverse pathological findings upon initial assessment, no consistent predictor of relapse was found. Scrotal scar re-excision or irradiation in patients with prior history of surgical violation of the scrotum are effective in preventing local failure.
A phase II study of high-dose cetuximab plus irinotecan in colorectal cancer patients with KRAS-wild type tumors who progressed on prior standard dose cetuximab and irinotecan.
Authors: Ahmad Ali Fora, Jeanne A McMahon, Greg Wilding, Adrienne E. Groman, Wen Wee Ma, Karen S. Romano, Marwan Fakih
Journal: Journal of Clinical Oncology (2012)

3582 Background: Prior clinical data suggest a dose-related response to cetuximab (cmab) when combined with irinotecan in patients (pts) with KRAS WT tumors who do not develop grade ≥ 2 rash with standard cmab dosing. However, the investigation of higher doses of cmab in the setting of acquired or innate resistance to standard dose cmab has not been previously investigated. We conducted a phase II clinical trial of high-dose cmab plus irinotecan in KRAS WT pts who progressed on standard-dose cmab plus irinotecan. Methods: Pts who progressed within 4 weeks from receiving a minimum of 6 weeks of standard dose cmab plus irinotecan were included in this study. Cmab was administered at 500 mg/m 2 /week and irinotecan was administered at the same dose/schedule on which each individual patient previously progressed. All pts received doxycyline 100 mg PO bid starting day 1 of treatment. 12-week PFS rate was the primary endpoint. The regimen was considered interesting if 7/36 patients had stable disease or response at 12 weeks. The study was closed early after meeting its primary endpoint. Results: 20 pts were treated on study: median age 65.5 yrs (44-84), 14 pts were males. 8 pts had grade ≥ 2 hypomagnesaemia (3 grade 3 and 2 grade 4), 6 pts had grade ≥ 2 skin rash (1 grade 3, 0 grade 4), and 4 pts had grade ≥ 2 diarrhea (1 grade 3, 0 grade 4). 1 pt had a confirmed PR and 12 pts had a SD (at 6 weeks). In 9 pts, SD was confirmed at 12 weeks (3 pts&gt; 24 weeks). Median PFS and OS were 2.8 and 6.6 months, respectively. The 1-year survival was 25%. Conclusions: High-dose cmab plus irinotecan is well tolerated with an acceptable rate of diarrhea and skin toxicities but with an increased rate of grade 3-4 hypomagnesemia. The prolonged disease stabilization and single response suggest that resistance to standard dose cmab plus irinotecan can be overcome by cmab dose escalation. The identification of predictive markers of response from dose escalation will be necessary to implement this strategy selectively in KRAS WT colorectal cancer patients.
Philadelphia-positive acute lymphoblastic leukemia in daily practice: A multicenter experience.
Authors: Hakan Goker, Emre Tekgunduz, Ismail Sari, Cigdem Pala, Mehmet Hilmi Dogu, Erman Ozturk, Burhan Turgut, Serdal Korkmaz, Itir Sirinoglu Demiriz, Yahya Buyukasik, Sibel Kabukcu Hacioglu, Leylagul Kaynar, Sinem Civriz Bozdag, Fevzi Altuntas
Journal: Journal of Clinical Oncology (2013)

e18014 Background: The prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) is generally poor. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only accepted therapy with curative potential. Herein, we report our experience with Ph + ALL patients treated off-study. Methods: Data were collected from medical records of Ph + ALL patients diagnosed between 2005 and 2012. Survival rates were calculated using the Kaplan-Meier method and the log-rank test was used for comparison between groups. Results: This retrospective study included 41 patients (21 females and 20 males) from 7 centers in Turkey. The median age of the patients was 42 years (range, 19-70 years). Thirty (73%) patients received TKI and concurrent chemotherapy, 10 (24%) patients received chemotherapy alone and 1 (3%) patient received TKI alone. Of the patients receiving TKI, 24 (77%) received imatinib and 7 (23%) received dasatinib as induction therapy. Following induction therapy, 77% and 10% of the patients achieved complete hematologic remission and complete response with incomplete hematologic recovery, respectively. Eight (20%) patients had relapsed/resistant disease and received rescue therapy. The most common complication during therapy was febrile neutropenia (n=7, 17%). The induction mortality rate was 5% (n=2). Allo-HSCT was performed in 16 (39%) patients, 12 (75%) of whom underwent HSCT in first complete remission. Donor sources were matched siblings in 14 (88%) and unrelated donors in 2 (12%) patients. Fifteen (37%) patients died during follow-up. The Kaplan-Meier analysis revealed a median overall survival (OS) period of 12 months (range, 1-86 months) for all patients. The median OS period was 17 months (range, 5-86 months) and 2 months (range, 1-24 months) for patients who did or did not undergo HSCT, respectively (p=0.014). The Kaplan-Meier estimate of OS was 69.3% at 12 months and 49.1% at 24 months, for all patients. Conclusions: Allo-HSCT is the most important denominator of survival and the only curative therapy for Ph + ALL patients. For patients without a suitable donor or who are unable to undergo HSCT, TKI with concurrent chemotherapy is a reasonable alternative.
Allergy to sunscreen and leave‐on facial products is not a likely causative mechanism in frontal fibrosing alopecia: perspective from contact allergy experts
Authors: C. Felmingham, L. Yip, M. Tam, R.L. Nixon
Journal: British Journal of Dermatology (2019)

The pathogenesis of frontal fibrosing alopecia (FFA) is complicated and incompletely understood, and the cause for its increasing incidence over the last 10-15 years is unknown.
High‐Density Lipoprotein in Lupus: Disease Biomarkers and Potential Therapeutic Strategy
Authors: Sang Yeop Kim, Minzhi Yu, Emily E. Morin, Jukyung Kang, Mariana J. Kaplan, Anna Schwendeman
Journal: Arthritis & Rheumatology (2019)

Systemic lupus erythematosus ( SLE ) patients exhibit accelerated development of atherosclerosis and increased incidents of cardiovascular disease ( CVD ) that cannot be explained by traditional risk factors alone. Accumulating evidence suggests that reduced levels of high‐density lipoproteins ( HDL s), along with altered HDL composition and function, may contribute to the accelerated atherosclerosis in SLE patients. Normally, HDL s play various atheroprotective roles through facilitating cholesterol efflux, inhibiting vascular inflammation, and scavenging oxidative species. However, systemic inflammation, oxidative stress, and autoimmunity in SLE patients induce changes in HDL size distribution and proteomic and lipidomic signatures. These compositional changes in HDL s result in the formation of proinflammatory, dysfunctional HDL . These lupus‐altered HDL s have impaired antiatherogenic function with reduced cholesterol efflux capacities, impaired antioxidation abilities, and diminished antiinflammatory properties. In fact, dysfunctional HDL may promote atherogenesis by inducing inflammation. Thus, dysfunctional HDL s could be an important biomarker of accelerated atherosclerosis in lupus. Additionally, HDL ‐targeted therapies, especially infusion of reconstituted HDL s, may serve as a potential therapeutic intervention for SLE patients with CVD .
TRICC-c: BIBF 1120 versus placebo in patients receiving oxaliplatin plus fluorouracil and leucovorin (mFOLFOX6) for advanced, chemorefractory metastatic colorectal cancer (mCRC)—A multicenter, randomized phase II trial in progress.
Authors: Andreas Berger, Thomas Ettrich, Angela Marten, Thomas Seufferlein
Journal: Journal of Clinical Oncology (2012)

TPS3636 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in western countries. With advances in the treatment of metastatic CRC (mCRC) in the last decade using combination chemotherapy and bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), progression free survival (PFS) in first and second line setting was substantially improved. Tumour angiogenesis is also driven by other factors but VEGF including Platelet Derived Growth Factor (PDGF) and Fibroblast Growth Factor (FGF). BIBF1120 is a potent, orally available triple angiokinase inhibitor that blocks the receptor tyrosine kinase activity of human VEGFR1-3, FGFR1 and -3 and PDGFRα and -β. Thus, BIBF1120 could be an exciting addition to the treatment of patients with chemorefractory CRC. Methods: Randomized, double-blind, placebo-controlled, multicentre, phase II trial of BIBF1120 (orally, 200 mg, bid, d1-d14, Arm A) vs. placebo (Arm B) in patients receiving mFOLFOX6 (oxaliplatin, 85 mg/m 2 , fluorouracil, 400 mg/m 2 bolus and 2400 mg/m 2 over 46 h, leucovorin, 200 mg/m 2 ) q14 d for patients (ECOG performance status 0-1) with chemorefractory mCRC who received one prior line of chemotherapy. Scheduled are 90 patients per treatment arm. Primary endpoint: PFS, Secondary endpoints: objective response, overall survival, duration of overall response, safety. Additionally there will be an explorative analysis of predictive biomarkers for BIBF1120. 4 of planned 180 patients have been enrolled. We expect the last patient out in June 2013. (Trial identifier: NCT01362361.)
Risk of skeletal-related events (SREs) following initial diagnosis of bony metastases in breast, lung, and prostate cancer.
Authors: Lois Lamerato, Andrew Glass, Greg G. Wolff, Kathryn E. Richert-Boe, Charu Taneja, John Edelsberg, Natalie Czapski, Karen Chung, Akshara Richhariya, Gerry Oster
Journal: Journal of Clinical Oncology (2012)

e19630 Background: Bony metastases (mets) are a common source of morbidity in patients (pts) with cancer, cause spinal cord compression (SCC), pathological fracture (PF), and bone pain, and often require radiotherapy (RT) and/or surgery to bone (SB). Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 years with primary breast, lung, or prostate cancer diagnosed between 1995 and 2009. Registry and electronic medical records were then used to identify pts with diagnosis of bone mets at initial cancer diagnosis or at recurrence. Trained technicians reviewed medical records for occurrence of SCC, PF, RT and SB—outcomes that have been collectively referred to as SREs. Cumulative incidence of these events was calculated in the presence of competing risk of death. Results: We identified 378 pts with breast cancer and bone mets, 272 with lung cancer and bone mets, and 420 with prostate cancer and bone mets. SREs were present at initial diagnosis of bone mets in 23% of breast cancer pts, 24% of lung cancer pts, and 10% of prostate cancer pts (Table). At 12 months, cumulative incidence of SREs was 57.3% for breast cancer (SCC, 5.1%; PF, 37.9%; SCC and/or PF, 40.2%; SB, 5.9%; RT, 27.4%), 62.7% for lung cancer (SCC, 8.9%; PF, 37.8%; SCC and/or PF, 43.3%; SB, 3.5%; RT, 32.4%), and 38.4% for prostate cancer (SCC, 7.9%; PF, 21.3%; SCC and/or PF, 26.7%; SB, 4.0%; RT, 22.9%). Use of bisphosphonates was largely confined to pts with breast cancer. Conclusions: Though breast, lung, and prostate cancers differ considerably in presentation, clinical course, and treatment, SREs are a common and serious problem in all three cancers among patients with bone mets. [Table: see text]
177 Lu-Lilotomab Satetraxetan, a Novel CD37-Targeted Antibody-Radionuclide Conjugate in Relapsed Non-Hodgkin's Lymphoma (NHL): Updated Results of an Ongoing Phase I/II Study (LYMRIT 37-01)
Authors: Arne Kolstad, Ulf Madsbu, Matthew Beasley, Michael Bayne, Tim M. Illidge, Noelle O'Rourke, Ingemar Lagerlöf, Roman Hájek, Wojciech Jurczak, Ella Willenbacher, Johan Blakkisrud, Ayca Muftuler Løndalen, Lisa Rojkjaer, Laurie Baylor Curtis, Marianne Bloma, Simon Turner, Nils Bolstad, Signe Spetalen, Martin Erlanson, Unn Merete Fagerli, Renate Galleberg, Stine Nygaard Rudå, Harald Holte
Journal: Blood (2017)
Transfusion Volume for Children with Severe Anemia in Africa
Authors: Kathryn Maitland, Peter Olupot-Olupot, Sarah Kiguli, George Chagaluka, Florence Alaroker, Robert O. Opoka, Ayub Mpoya, Charles Engoru, Julius Nteziyaremye, Macpherson Mallewa, Neil Kennedy, Margaret Nakuya, Cate Namayanja, Julianna Kayaga, Sophie Uyoga, Dorothy Kyeyune Byabazaire, Bridon M’baya, Benjamin Wabwire, Gary Frost, Imelda Bates, Jennifer A. Evans, Thomas N. Williams, Pedro Saramago Goncalves, Elizabeth C. George, Diana M. Gibb, A. Sarah Walker
Journal: New England Journal of Medicine (2019)

Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level.In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality.A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days.Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.).
Gemcitabine (G) plus nab-paclitaxel (nab-P) plus chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC).
Authors: Olugbenga Olanrele Olowokure, Ivan Dario Bedoya, Michelle Lynn Mierzwa, Maria Patricia Torregroza, Alok kumar Dwivedi, Jiang Wang, Milton T Smith, Nathan Schmulewitz, Stephen Kucera, Kyuran Ann Choe, Ross Ristagno, Steven Rudich, Jeffrey J. Sussman, Syed A Ahmad
Journal: Journal of Clinical Oncology (2012)

e14714 Background: 30-40 % of PC pts present with LAPC. Optimal management remains controversial. Current NCCN guidelines, suggests clinical trial, FOLFIRINOX, G, G based combination therapy, chemo followed by CRT as options in pts with good PS. This single institution retrospective review, evaluated the UC experience of the impact of G+nab-p+/- CRT in LAPC. Methods: From 05/01/09-09/01/11,105 newly registered pts were identifiedusing ICD code 157, 13pts met inclusion criteria: ECOG PS 0-2, histologically proven LAPC, without prior therapy that received G + nab-P, pre or post radiation as part of their treatment. G+nab-p was given as cycles of G=1,000mg/m 2 and nab-P=100mg/m 2 weekly x3 every 4 weeks with appropriate modifications. CT scans and CA19-9 levels were followed. PFS was estimated from the date of diagnosis to date of progression or death if this occurred first and OS was estimated from date of diagnosis until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval (CI). Log rank test was used to compare the PFS according to categorical variables. Results: Median duration of follow up was estimated to be 14.4 months (M) range(R) (5.8-19). CA19-9 data was available for 12 pts, 2 had baseline &lt;1 (R&lt;1-12,861), CA19-9 decrease &gt; 50% from baseline was seen in 9/10. Mean # of G+nab-P cycles administered was 3, R (1-10). 77% received G based CRT with only 1pt receiving this post op. 38% (5/13) underwent resection, 4 post CRT with R0 margins and -ve LN’s and 1 pre CRT with R0 margins but 1/13 LN’s +ve. 11 pts were evaluable for response by RECIST (4PR, 6SD, 1PD). Disease control rate 91%. PFS 92% (CI: 57- 99%) at 6 M and 65% (CI: 31-85%) at 12 M. OS was 85% (CI: 51-96%) at 6M and 77 %(CI: 44-92%) at 12M. At 6M, 100% PFS was observed in resected group, whereas 88% PFS in non-resected group (p=0.12). There was no significant difference in PFS according to gender (p=0.44) and T lesion (p=0.49). Grade III/IV toxicity was mainly hematologic and gastrointestinal. (4/7) 57% received further therapy upon progression. Conclusions: Compared to contemporary G- based trials, the UC experience of G+ nab-P with CRT appears to be associated with improved survival in LAPC and warrants further study.
Results of monoclonal antibodies against EGFR-receptors application in patients with metastatic colorectal cancer (mCRC).
Authors: Liubov Yu Vladimirova, Oleg Ivanovich Kit, Elena A Nikipelova, Natalya A Abramova
Journal: Journal of Clinical Oncology (2013)

e14701 Background: Monoclonal antibodies against the epidermal growth factor receptor(EGFR)are standard components of treatment in mCRC.This study was designed to evaluate the tolerability and efficacy of the combinations of Panitumumab(P) and Cetuximab(C) with chemotherapy in patients with wild type(WT) KRAS tumors mCRC. Methods: Mutation analysis of KRAS(codons12,13) was done on samples at diagnosis. Key elegibility criteria included measurable mCRC stage IV, ECOG ≤2, adequate liver,kidney and bone marrow function, no brain metastases. P was administered 6mg/ kg 1 day q2w. C was administered 400mg/m² 1day and 250mg/m² q1w. Combination with FOLFOX-6 or FOLFIRI pegimens was allowed. Endpoints include response rate, OS, PFS and safety. Results: Of 38 testable samples there were 21(55.3%) WT KRAS tumors. All of these 21 (13male and 8female) pts were recruited. Mean age was 58.1±12.3. Synchronous metastases had 33.3%(7pts). Majority of pts benefited from anti-EGFR combined with cytotoxic chemotherapy 80.9% (17), mostly FOLFIRI – 57,1%(12).There were23.8%(5) in the 1st line CT, 76.1%(16) in the 2 nd line CT. 6 mos of the treatment were analyzed. Overall RR was76.1 %(16) including 6PR(28.5%) and 10SD(47.6%). Med OS= 9.1mo, Med PFS= 4.3mo. 8 pts(38.1%) are alive till the abstract submission. Most common toxicities were:skin rash 2/3Gd.-90.5%(19), xeroderma 2Gd.-42.9%(9),skin itch 1/3Gd.-42.9%(9), paronychia 2Gd. -14.2%(3), purulent psorophthalmia 2Gd.-14.2%(3). All kinds of toxicities were controlled by symptomatic medication if necessary and did not lead to anti-EGFR agents dalay. Besides,diarrhea 1/2Gd.- 66.7%(14), 3Gd.-14.3%(3), neutropenia 1/2Gd.-28.6%(6), 3/4Gd.-9.5%(2), nausea 3/4Gd.- 14.3%(3), vomiting 1/2Gd.- 42.9%(9), fatigue 1/2Gd.-47.6%(10). Conclusions: These results consider significant efficacy of anti-EGFR agents combined with CT in pts with mCRC. Controlled toxicity of the therapy allows to use it widely.