tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Metreleptin Therapy in Patients With Type 1 Diabetes: A Pilot Study
Authors: Chandna Vasandani, Gregory O. Clark, Beverley Adams-Huet, Claudia Quittner, Abhimanyu Garg
Journal: Diabetes Care (2017)

OBJECTIVE To study the efficacy and safety of metreleptin therapy in patients with suboptimally controlled type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS After a baseline period of 4 weeks, five female and three male patients with T1DM (mean age 33 years, BMI 23.8 kg/m2) received metreleptin (0.08 mg/kg/day in females and 0.04 mg/kg/day in males) subcutaneously twice daily for 20 weeks followed by an off-therapy period of 4 weeks. RESULTS Metreleptin therapy did not lower HbA1c significantly compared with the baseline value (mean difference −0.19% [−2.0 mmol/mol] and −0.04% [−0.5 mmol/mol] at 12 and 20 weeks, respectively). Mean body weight reduced significantly by 2.6 and 4.7 kg (P = 0.003) and daily insulin dose by 12.6% and 15.0% at week 12 and 20 (P = 0.006), respectively. CONCLUSIONS Metreleptin is safe but may not be efficacious in improving glycemic control in patients with T1DM, although it reduces body weight and daily insulin dose modestly.
Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection
Authors: Sarina Ravens, Christian Schultze-Florey, Solaiman Raha, Inga Sandrock, Melanie Drenker, Linda Oberdörfer, Annika Reinhardt, Inga Ravens, Maleen Beck, Robert Geffers, Constantin von Kaisenberg, Michael Heuser, Felicitas Thol, Arnold Ganser, Reinhold Förster, Christian Koenecke, Immo Prinz
Journal: Nature Immunology (2017)
Preoperative chemoradiotherapy (CRT) in gastric cancer.
Authors: Anouk Kirsten Trip, Boelo Jan Poppema, Mark I. van Berge Henegouwen, Edwin PM Jansen, Ester Siemerink, Dirk Richel, Jannet C. Beukema, John Theodorus Plukker, Johanna W. van Sandick, Maarten C. Hulshof, Annemieke Cats, Marcel Verheij, Geke Hospers
Journal: Journal of Clinical Oncology (2013)

89 Background: The prognosis of gastric cancer patients remains poor even after radical surgery. Although local control and survival are significantly improved by postoperative CRT, treatment compliance is frequently compromised due to severe toxicity. On the other hand, treatment compliance is good with preoperative chemotherapy (CT) in gastric cancer and preoperative CRT in esophageal cancer. The current study was initiated to investigate the feasibility and efficacy of preoperative CRT for marginally resectable and initially irresectable gastric cancer. Methods: Patients with marginally resectable and initially irresectable gastric cancer, without signs of peritonitis carcinomatosa, stage IB-IV(M0) were treated with CRT. Treatment consisted of irradiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy combined with concurrent weekly carboplatin (AUC 2) and paclitaxel (50mg/m 2 ) on days 1, 8, 15, 22 and 29 of irradiation, followed by standardized surgery 4-6 weeks after the last irradiation. Results: Between December 2007 and January 2012, 25 patients with stage II-IV(M0) marginally resectable (n=13) or initially irresectable gastric cancer received preoperative CRT. One patient discontinued concurrent CT in the 4 th week due to toxicity, but completed radiotherapy, and another patient stopped CRT after the 3 rd week due to progressive disease. During CRT, grade III gastrointestinal adverse events (AE) occurred in 3 patients (12%), grade III hematological AE in 3 (12%) and grade III other AE in 2 (8%). Twenty-four patients (96%) were operated following CRT. Surgery-related complications consisted of anastomotic leakage in 3 patients (12%) and bowel perforation in 2 (8%). Postoperative mortality was 4%. A microscopically radical resection was achieved in 18 patients (72%), 8 of whom had initially irresectable gastric cancer. The pathologic complete response rate was 16% (4/25 patients). Conclusions: In this study, preoperative CRT for marginally resectable and initially irresectable gastric cancer was associated with manageable toxicity and resulted in an encouraging pathologic response rate. A multicenter phase II study has recently been initiated.
Induction of breast cancer progression and metastasis by HOXB9 gene’s activation by sequence specific binding factors.
Authors: Aisulu Zhussupova, Tetsu Hayashida, Maiko Takahashi, Hiromitsu Jinno, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2013)

26 Background: HOXB9 is a member of class I HOX genes and is known to be overexpressed in human breast cancer and related to EMT, tumor angiogenesis, and radio-resistance (PNAS 2010), being significant prognostic factor in breast cancer patients. (Ann Surg Oncol 2012). Methods: We analyzed the upstream promoter region to determine the critical sequence for HOXB9 transcription. The multiple lengths of HOXB9 promoter region were cloned into pGL3 luciferase vector and each of them were checked by luciferase assay. Then made E2F1 overexpressed cell-lines: MCF7, MCF10A and MDA-MB231 to check HOXB9 gene expression. ChIP assay performed using E2F1 induced MCF7 cell-line model and EMSA made with T47D cells and E2F1 antibody. Results: We demonstrated luciferase activity of MDA-MB231 cells and overexpressed HOXB9 was determined at the region from -404 to -392 bps, showing that the mentioned region plays the critical role for the transcription of HOXB9. Computer prediction system for the binding ability to critical sequence raised several candidate: E2F1, PAX-5, P53, ETS-1, NFY-A, Sp-1, which are known to be related with cancer progression and we confirmed these genes could induce HOXB9. E2F1 overexpressed breast cancer cell-lines indicate high expression of HOXB9 show the correlation between E2F1 and HOXB9 expression. Luciferase assay method done by constructing pGL3 with HOXB9 critical sequence and analyzed using wild-type MCF7 and E2F1 induced MCF7 cells showed high luciferase activity of HOXB9 critical sequence plasmid in E2F1 induced MCF7 cell-line by compare to WT. ChIP assay and EMSA assay methods performed using E2F1 overexpressed MCF7 and T47D cell-lines model revealed high precipitation rate with E2F1 antibody and HOXB9 expression than negative control. Conclusions: HOXB9 is plays the role as the accelerator of breast cancer progression and discovering the properties of the gene and related factors will help to understand new signaling pathways of breast cancer development. E2F1 is a strong candidate direct binds to HOXB9 critical sequence and correlates with HOXB9 expression. Manipulating of E2F1 expression may regulate HOXB9 and reduce cancer progression and metastasis.
Phase I study of pazopanib in combination with interferon alfa in patients with advanced renal cell carcinoma (RCC) and other primary tumors: A Spanish Oncology Genitourinary Group (SOGUG) study.
Authors: Xavier Garcia del Muro, Ignacio Duran, Jesús García-Donas, Juan Francisco Rodriguez-Moreno, Marta Gil-Martin
Journal: Journal of Clinical Oncology (2014)

450 Background: Pazopanib is a VEGF receptor inhibitor active in the treatment of advanced RCC treatment, and Interferon has been a long-standing treatment option for metastatic RCC with a modest overall survival benefit. The purpose of this study is to assess the feasibility and safety of the combination of pazopanib and interferon in the treatment of advanced RCC and other tumor types. Methods: This is a phase I study of the combination of pazopanib and interferon alfa-2A. It has been developed in a 3+3 standard escalating design with cohorts of 3-6 patients (pts) to identify the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD). Pazopanib is given po daily and interferon is given subcutaneously 3 times a week. Dose levels 1, 2, 3, 4 and 5 corresponded to pazopanib 400, 600, 800, 800 and 800 mg per day plus interferon 3, 3, 3, 6 and 9 million U. Patients with previously treated RCC and also other primary tumors could be included. Results: 19 pts were included and treated in 4 dose levels. Patients’ median age was 60 years old, 13 men and 6 women. Six of them were diagnosed with RCC; other pts presented metastatic tumors as ovarian carcinoma, peritoneal mesothelioma, breast cancer (2), liposarcoma, breast angiosarcoma, uterine sarcomas (3), endometrial carcinoma (3) and melanoma. MTD was reached at level 4, and the RD was Pazopanib 800mg with IFN 3MUI. Three pts experienced DLT, one in level 2 and two in level 4: grade 4 transaminitis, grade 3 transaminitis and grade 3 liver hematoma, respectively. Other toxicities (grade 3 and 4) included anemia, neutropenia, thrombocytopenia, asthenia, arthromialgia, anorexia, diarrhea and Raynaud’s syndrome. Additional mild but common toxicities were fever and proteinuria. One partial response was observed in a uterine sarcoma patient. In RCC, 4 pts achieved stable disease lasting a median of 5 cycles. Conclusions: Combination of pazopanib and interferon alfa is feasible and safe, allowing administration of active doses of both agents. A phase II study to assess this combination activity in RCC is assured. Clinical trial information: NCT01513187.
A phase II trial of gefitinib in patients with malignant pleural mesothelioma (MPM)
Authors: C. W. Lee, H. Anderson, H. Martins, S. C. Rao, D. Sauciuc, S. A. Laurie, W. Morzycki, M. V. MacNeil
Journal: Journal of Clinical Oncology (2008)

14614 Background: The incidence of MPM is increasing and treatment options are limited. Expression of the epidermal growth factor receptor (EGFR) in MPM makes it a potential therapeutic target. A phase II trial was performed to examine the impact of the oral EGFR tyrosine kinase inhibitor (TKI), gefitinib, as first-line systemic therapy. Methods: A two-stage study design was planned, with the primary endpoint tumour response. Initial enrollment was to consist of 18 evaluable subjects. Eligibility included biopsy-proven MPM and no prior systemic therapy. Gefitinib was taken at a dose of 250 mg daily on a four-week cycle. Tumour response was determined according to published Australian criteria, and toxicity was assessed by the National Cancer Institute Common Toxicity Criteria version 2.0. Results: From October 2003 to September 2006, 21 individuals with MPM were enrolled and response was evaluable in 20. The median number of cycles completed was 4 (mean 4, range <1–24), with 9 off study by the end of the first cycle. A partial response was seen in only 1 (5%). A best response of stable disease and progression occurred in 10 (50%) and 9 (45%), respectively. The median overall survival was 14.1 months (95% CI, 13.5–14.8), with 1- and 2-year survival rates of 0.69 and 0.38. The most common side effects were grades 1/2/3 skin rash (25/35/5%) and diarrhea (15/20/0%). The most common biochemical toxicity was grades 1/2 elevation in the transaminases (30/10%), with grade 3 elevation of the ALT seen only in 1 (5%). Conclusions: Gefitinib has very modest activity in MPM. The toxicity encountered was as expected with the dose of gefitinib employed. Survival outcomes likely reflect patient selection, and possibly the effect of chemotherapy as salvage therapy. As other phase II trials of EGFR TKIs have produced similar response data, there are no plans to expand the study cohort. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology AstraZeneca Oncology
Induction cisplatin, paclitaxel, and 5FU (PTF) before definitive local therapy for locally advanced esophageal squamous cell carcinoma (SCC).
Authors: R. Fernandez, G. Lopez de Argumedo, N. Fuente, J. Ferreiro, M. Martinez, E. Azkona, E. Gutierrez, E. Iza, R. Casas, J. Mane
Journal: Journal of Clinical Oncology (2011)

115 Background: Induction chemotherapy for locally advanced oesophageal SCC is controversial. Triple combination is under study with promising results. We analyse induction therapy with PTF before local definitive therapy in terms of response, resectability, toxicity and survival. Methods: Pts diagnosed of locally advanced oesophageal SCC have been included. Treatment schedule: paclitaxel 175 mg/m 2 and CDDP 75 mg/m 2 on day 1 and 5FU 800 mg/m 2 /day days 1-4, every 28 days. After 2-3 cycles surgery is considered. If unresectable, radical radiotherapy (64 Gy) and concomitant carboplatin (60 mg/m 2 , d 1–5 during 1st, 4th and, if feasible, 7th week of RT) are administered. Results: From May-02 to Feb-10 48 pts have been treated (44M, 4F). Age: 56,7 (32–70). PS 0-1: 8-40. Location: Upper: 14, Middle: 25, Distal: 8, Whole: 1. T2/3/4:1/26/21, N0/1: 12/36. M1a: 6. Weight loss over 10 kg: 11 pts. Cycles delivered: 140; median 3. Toxicity (episodes): Anemia 3: 1. Emesis 3: 2. Mucositis 3: 2. Asthenia 2-3: 8. Two pts died in remission (one of them with a pCR at necropsy) due to gastrostomy complications and oesophagus-tracheal fistula, treatment related. Two pts developed oesophagus-tracheal fistula as a late event after response to therapy. Response rates: CR 7 (14.6%), PR 16 (33.3%), SD 18 (37.5%), PD 7 (14.6%). Treatment after PTF: Surgery 14 pts (1 upper, 9 middle, 4 distal). One (distal) unresectable at surgery, one (middle) not resected because of liver cirrhosis, two not resected because of liver metastases, unexpected findings at surgery. pCR: 2. pPR 8 (R0: 7, R1: 1). Chemoradiation: 25, improving 2 SD to PR, 4 PR to CR and 3 SD to CR. One PR and 4 SD progressed immediately after chemoradiation. Progression: 33 (local 14, systemic 11, both 8); died: 34. Median progression free survival: 35.7 weeks (95% CI 30.2-41.2). Median overall survival: 50.7 weeks (95% CI 35.2-66.1). Conclusions: Induction PTF has a good toxicity profile with a high response rate and disease control during therapy. Surgical rescue is possible in middle and distal tumours. Local definitive therapy with chemoradiation is the best approach for unresectable or upper third tumours. No significant financial relationships to disclose.
The efficacy of capecitabine and temozolomide for the treatment of metastatic neuroendocrine tumors: Memorial Sloan-Kettering Cancer Center experience.
Authors: Alex Ganetsky, Nelly G. Adel, Kinh Gian Do, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2012)

363 Background: Emerging literature has suggested the benefit of capecitabine/temozolomide (C/T) therapy in metastatic pancreatic NETs (pNETs) as first line therapy. We conducted a retrospective analysis of the efficacy of (C/T) therapy in all patients with metastatic NETs treated at MSKCC. Methods: Using the electronic pharmacy database, we included all patients’ ≥ 18 years of age who received C/T combination therapy for pNETs between 1/2003-10/2010. Primary endpoint was the overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Response rates were evaluated by a radiologist using CT scans and per RECIST 1.1. MGMT tumor expression was conducted to correlate with response. Results: Twenty patients (mean age 64, 35% female) were identified. There were 16 (80%) pNETs (1 functional, 15 nonfunctional), 2 (10%) carcinoid, 1 high grade biliary (5%) and 1 (5%) gastric neuroendocrine carcinoma. Eight tumors were low grade (1 carcinoid, 7 pNET), 8 intermediate grade (7 pNET, 1 carcinoid), and 4 high grade (2 pNET, 1 stomach, 1 biliary). Twelve (60%) received C/T in the first-line setting and 8 in the relapsed setting. Six (30%) had a partial response and 7 (35%) had stable disease. There were no complete responses ( Table 1 ). With a median follow-up of approximately 3 years, the PFS was 16.4 months. Four pNET patients had unresectable disease at presentation and 2/4 were resected and rendered free of disease after C/T therapy. There were no high grade responders. Liver tumor burden (0%, &lt;10%, 10-50%, &gt;50%), number of prior treatments, and tumor grade did not predict response. Grade 3-4 events potentially related to C/T included neutropenia (1/20, 5%), nausea (3/20 15%), diarrhea (1/20, 5%), and fatigue (3/20, 15%). Conclusions: Combination C/T for the treatment of pNETs is an effective regimen for well differentiated NETs irrespective of tumor burden and prior treatment. No responses were seen in our carcinoid patients. MGMT expression will be presented at the meeting. [Table: see text]
Implications for the American Joint Committee on Cancer staging systems on esophageal squamous cell cancer patients receiving multimodality therapy.
Authors: Motoo Nomura, Tetsuya Abe, Azusa Komori, Yukiya Narita, Shiori Uegaki, Sohei Nitta, Kazuhisa Yamaguchi, Hiroya Taniguchi, Ryosuke Kawai, Norihisa Uemura, Shigenori Kadowaki, Daisuke Takahari, Takashi Ura, Masashi Andoh, Yasumasa Niwa, Masayuki Shinoda, Kei Muro
Journal: Journal of Clinical Oncology (2014)

123 Background: The 7 th edition of the American Joint Committee on Cancer (AJCC) staging system is based on pathologic data from esophageal cancers treated by surgery alone. The objective of this study was to evaluate the prognostic impact of the pretreatment clinical stage (cTNM) and posttreatment pathologic stage (ypTNM) on esophageal cancer patients undergoing neoadjuvant chemotherapy followed by surgery (NAC-S). Methods: Information on 245 consecutive esophageal squamous cell carcinoma patients undergoing NAC-S was reviewed. Data collected included demographics, cTNM, ypTNM, and survival. Statistical methods included the Cox regression model, Akaike information criterion (AIC) within the Cox proportional hazard regression model, and Kaplan-Meier analyses. Results: The overall three-year survival rate was 67.6%. There were significant differences between stages II and III in cTNM and ypTNM stage, respectively (P &lt; 0.01, respectively). There were no significant survival differences between stages I and II, between stages III and IV in each TNM stage. For all patients, cN stage (cN0 vs. cN1-3), ypT stage (ypT0-2 vs. ypT3-4), ypN stage (N0 vs. N1-3), and ypM stage were independent prognostic factors by multivariate analysis (P&lt; 0.05). Compared with cTNM stage, ypTNM stage has a smaller AIC value, which described the optimum prognostic stratification. Conclusions: Our study indicates that the ypTNM stage of the 7th edition of AJCC staging system has better performance than the cTNM stage in patients undergoing NAC-S.
Prospective observational study on chemotherapy-induced nausea and vomiting (CINV) for colorectal cancer patients by the CINV study group of Japan.
Authors: Yuji Miyamoto, Hideo Baba, Yasushi Tsuji, Ayako Doi, Koji Takeda, Michiya Kobayashi, Yoshihiko Maehara, Masahiro Gotoh, Kazuhiro Yoshida, Norihiro Kokudo, Yoshihiro Kakeji, Keisuke Aiba
Journal: Journal of Clinical Oncology (2014)

652 Background: The aim of this study is to investigate the incidence of Chemotherapy Induced Nausea and Vomiting (CINV) among moderately emetogenic chemotherapy-naive patients with colorectal cancer. We also assessed whether the medical staff accurately recognized the incidence of CINV in their own practices. Methods: A prospective observational study of patients receiving the first cycle of oxaliplatin or irinotecan-based chemotherapy was performed. A 7-day diary for CINV was provided to the patients prior to chemotherapy to record daily incidence of CINV. Observed incidence rates of acute (day1) and delayed (days 2-7) CINV were compared with medical staff's predictions. Results: A total of 191 patients (110 males and 81 females) were registered during the period from April 2011 to December 2012. All patients were treated with oxaliplatin-based (n = 175) or irinotecan-based chemotherapy (n = 16). Acute vomiting was observed in 4 patients (2.1%), while delayed vomiting was observed in 19 patients (10.0%). Acute nausea occurred in 14 patients (7.3%), while 63 patients (33%) were affected by delayed nausea. Irinotecan significantly induced acute nausea more frequently than oxaliplatin did (p = 0.019). The presence of motion sickness was significantly associated with the incidence of acute nausea (p &lt; 0.001) and vomiting (p = 0.003). Antiemetics were given along the guideline to all patients. 58 patients were administered a neurokinin-1 (NK1) receptor antagonist. Patients with NK-1 receptor antagonist showed significantly less incidence of delayed vomiting than patients without one (3% vs 13%, p = 0.048). 30 patients (15.7%) required rescue antiemetics. The staff had estimated the incidence of acute CINV in 91 patients (47.6%). However, only 14 patients (7.3%) really experienced acute CINV. Conclusions: CINV seems to be controllable with appropriate management, but delayed CINV still remains an important problem to be targeted. The presence of motion sickness should be affected by efficient antiemetic management. The extent of CINV in this patient group seems to be overestimated.
Diagnostic accuracy of PET scan in salvage lymph node resections in patients with prostate cancer (CaP).
Authors: David J. K. P. Pfister, Charlotte Piper, Daniel Porres, Theodor Klotz, Axel Heidenreich
Journal: Journal of Clinical Oncology (2013)

215 Background: PET-CT scans in patients with CaP are often used to identify either local recurrent disease or suspected lymph node metastases in early biochemical recurrent disease. The diagnostic accuracy is controversial. We want to show our experience of PET-CT and its diagnostic accuracy in salvage lymph node dissection. Methods: 21 patients treated with radical prostatectomy between 1997 and 2009 presented with PET-CT´s and biochemical recurrent disease and were treated by salvage lymph node dissection to prolong the time to either androgene deprivation or chemotherapy. Diagnostic accuracy was correlated per patient and per lymph nodes. Results: Mean PSA at time of lymph node dissection was 2,73 (0,4-8,4)ng/ml. 17 (81%) received prior radiotherapy and 6 (29%) received androgene deprivation. In total 203 lymph nodes were resected with 58 (29%) harbouring metastasis in 15 (71%) patients. This leads to a Sensitivity, Specifity, positive and negative predictive value of 69%, 12%, 76% and 88% concerning lymph node detection and 70%, 0%, 93% and 0% concerning the calculation per patient. At time of analysis follow-up was available in 5 patients with a biochemical recurrence free survival of 5 (3-12) months. Conclusions: The value of PET-CT in salvage lymph node dissection is under debate and must be questioned according to our results in this setting.