tbuckley/cabot-search huggingface dataset:
Precision radiotherapy in the treatment of haemangiopericytomas of the central nervous system
Authors: S. E. Combs, D. Schulz-Ertner, C. Thilmann, M. van Kampen, J. Debus
Journal: Journal of Clinical Oncology (2005)

1545 Background: Haemangiopericytomas (HAP) are rare tumors, that arise from pericytes, the contractile cells surrounding capillaries, also referred to as the pericytes of Zimmermann. Intracranial HAP have been classified as “angioblastic” members of the meningioma family. They have a high tendency to recur locally and they are associated with a high risk to metastasize. Radiotherapy (RT) plays a major control in the management of HAP. The present analysis evaluates the role of high precision RT in the management HAP of the CNS. Methods: Thirty-seven consecutive patients with histologically diagnosed HAP were treated at our institution between 1984 and 2004. The majority of the tumors was localized within the skull (n=25), and 2 tumors were localized at that spine. Out of these 37 patients, we selected 25 patients with tumors of the CNS and the spine for analysis which were treated with high precision radiotherapy delivered as Fractionated Stereotactic RT (FSRT) or Intensity Modulated Radiotherapy (IMRT). Median age at primary diagnosis was 40.5 years (range 10–77 years). After primary diagnosis, surgical resection was performed in 23 patients. Median time between primary diagnosis and RT was 20 months (range 1–382 months). For treatment planning, patients were immobilized by an individual precision head mask or a whole body fixation system made of Scotch Cast. Target delineation and treatment planning were performed in a stereotactic setup. A median total dose of 56.4 Gy was delivered in a fractionation of 5 x 1.8–2 Gy per week, with a median Planning Target Volume (PTV) of 58.2 ml. Median follow-up time was 34 months (range 3–166 months). Results: Seventeen patients out of 25 of this series remain alive. Overall survival rates at 5 and 10 years were 100% and 64%, respectively. Actuarial survival rates after RT were 85% and 69% at 3 and 5 years, respectively. Progression-free survival rates after RT were 80% and 61% at 3 and 5 years, respectively. No severe late toxicities could be observed. Conclusions: High precision radiotherapy is an effective and safe treatment modality for patients with HAP of the CNS with highly acceptable tumor control while sparing normal tissue. No significant financial relationships to disclose.
Duration of response in three phase III studies of denileukin diftitox in cutaneous T-cell lymphoma (CTCL).
Authors: M. Duvic, H. M. Prince
Journal: Journal of Clinical Oncology (2010)

8055 Background: Although responses to systemic chemotherapy or electron beam radiation in CTCL patients can be relatively high, the duration of response (DOR) can be disappointingly short since patients may relapse, develop resistance, or become refractory to therapy. Outcome for patients with CTCL worsens with higher disease stage and number of prior therapies. We looked at DOR to denileukin diftitox (DD), a fusion protein targeting the IL-2 receptor in malignant T cells. Methods: DOR in pooled intent-to-treat populations of patients with recurrent/persistent CTCL was calculated from three phase III trials of DD in patients with stage Ia-III disease. DD patients were categorized as 1) patients naive to DD (n= 198), 2) patients retreated with DD (n= 29), and 3) CD25 negative patients (n=36). In all three trials, DD was administered as courses of 9 or 18 μ g/kg IV daily for 5 days, repeated every 21 days, up to 8 courses. DOR was defined as date of first evidence of documented response until date of relapse, the initiation of new anticancer treatment, or the last observation on study. Results: The current analysis included 263 DD-treated patients and 44 placebo (PBO) patients. The median DOR in patients receiving DD was approximately 3 times higher than DOR for patients receiving placebo (277 days vs. 81 days, <0.0001). Incidence of drug-related immunosuppression, cumulative toxicity, or myelotoxicity was minimal. Overall response rates were 16% for placebo, 31% for 9 μ g/kg DD, 41% for 18 μ g/kg DD, 28% for retreated, and 31% for CD25 negative patients. Conclusions: DD appears to improve DOR in patients with CTCL. The estimated median duration of the response in all DD arms was more than triple that of patients receiving placebo. Placebo(N=44) All DDtreated(N=263) CD25+ CD25− 9 μ gDD naive(N=80) 18 μ gDD naive(N=118) 18 μ gretreated(N=29) 18 μ gDD naive(N=36) All 18 μ gtreated(N=183) No. of patients 7 100 25 56 8 11 75 Baseline stage ≤IIa 3 68 18 37 6 7 50 Baseline stage ≥IIb 4 32 7 19 2 4 25 Median DOR (Days) 81 277 277 267 274 340 274 95% CI for median (52, 92) (220, 820) (127, —) (197, —) (131, —) (141, — ) (203, —) Min, max 43, 127 42, 1325 42, 1325 43, 1247 75, 321 58, 400 43, 1247 P value (vs. PBO) – < 0.0001 0.0297 < 0.0001 0.0082 0.0036 < 0.0001 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai, Ligand Eisai
KEYNOTE-062: Phase III study of pembrolizumab (MK-3475) alone or in combination with chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Josep Tabernero, Yung-Jue Bang, Charles S. Fuchs, Atsushi Ohtsu, Uma Kher, Baohoang Lam, Minori Koshiji, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2016)

TPS185 Background: Pembrolizumab (pembro) is a monoclonal antibody against PD-1 designed to block its interaction with PD-L1 and PD-L2 and permit an antitumor immune response. In KEYNOTE-012, pembro showed a 22% ORR (RECIST v1.1, central review) and a manageable safety profile in patients (pts) with advanced gastric cancer. The randomized, phase 3 KEYNOTE-062 study (NCT02494583) is designed to compare the efficacy and safety of pembro alone or in combination with cisplatin + a fluoropyrimidine with those of cisplatin + a fluoropyrimidine as first-line therapy for PD-L1 + /HER2 – advanced gastric or GEJ adenocarcinoma. Methods: Key eligibility criteria include age ≥ 18 y, locally advanced or metastatic PD-L1 + /HER2 – gastric or GEJ adenocarcinoma, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for advanced disease. Pts are randomized 1:1:1 to pembro 200 mg Q3W (arm 1), pembro + cisplatin 80 mg/m 2 Q3W + 5-fluorouracil (5-FU) 800 mg/m 2 on days 1-5 of each Q3W cycle (arm 2), or placebo Q3W + cisplatin + 5-FU (arm 3); 5-FU may be replaced with capecitabine 1000 mg/m 2 twice daily on days 1-14 of each cycle. Randomization is stratified by region (Europe/North America/Australia vs Asia vs rest of world), disease status (locally advanced vs metastatic), and chosen fluoropyrimidine (5-FU vs capecitabine). Arm 1 is open label; in arms 2 and 3, assignment to pembro vs placebo is double blind. In all arms, treatment will continue for 35 cycles or until progressive disease, unacceptable toxicity, or pt/investigator decision. Response will be evaluated every 6 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns; eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 d thereafter (90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 3 mo. OS and PFS per RECIST v1.1 are the primary study end points; secondary end points include ORR and duration of response. Enrollment in KEYNOTE-062 is ongoing and will continue until ~750 pts have enrolled. Clinical trial information: NCT02494583.
Predictors for Response to Ruxolitinib in Real-Life: An Observational Independent Study on 408 Patients with Myelofibrosis
Authors: Francesca Palandri, Giuseppe A. Palumbo, Massimiliano Bonifacio, Mario Tiribelli, Giulia Benevolo, Bruno Martino, Elisabetta Abruzzese, Mariella D'Adda, Nicola Polverelli, Micaela Bergamaschi, Alessia Tieghi, Francesco Cavazzini, Adalberto Ibatici, Monica Crugnola, Costanza Bosi, Roberto Latagliata, Ambra Di Veroli, Luigi Scaffidi, Federico De Marchi, Elisa Cerqui, Barbara Anaclerico, Francesco Di Raimondo, Umberto Vitolo, Roberto M Lemoli, Renato Fanin, Francesco Merli, Domenico Russo, Antonio Cuneo, Michele Cavo, Nicola Vianelli, Massimo Breccia
Journal: Blood (2016)
A phase I trial of LBH589 and bevacizumab for recurrent high-grade glioma (HGG).
Authors: J. Drappatz, J. J. Raizer, D. Schiff, A. S. Chi, T. Batchelor, S. M. Snodgrass, E. C. Quant, A. D. Norden, R. Beroukhim, S. A. Grimm, L. M. Doherty, A. S. Ciampa, D. C. LaFrankie, S. Ruland, M. Gerard, S. Hammond, P. Y. Wen
Journal: Journal of Clinical Oncology (2011)

2050 Background: Bevacizumab has activity against recurrent HGG but responses are rarely durable. The histone deacetylase (HDAC) inhibitor panobinostat (LBH 589) induces apoptosis of glioma cells and may enhance the effects of bevacizumab. We conducted a phase I study to determine the safety and toxicity when combining panobinostat with bevacizumab in recurrent HGG. Methods: Eligibility criteria included histologically proven high grade gliomas (HGG) with documented radiographic progression with any number of prior relapses, >18 years old, KPS≥60, and adequate bone marrow reserve and organ function. Prior treatment with VEGF targeted therapies or HDAC inhibitors was not permitted. Patients on enzyme inducing anticonvulsants and valproic acid were excluded. We used a standard 3+3 dose finding design with the MTD being defined as the dose with DLTs in 1/6 or fewer patients after cycle 1 using NCI CTCAE v3. Three dose levels of panobinostat were tested: 20 mg on days 1, 3 and 5 weekly (cohort 1); 20 mg on days 1,3 and 5 every other week (cohort 2) and 30 mg on days 1,3 and 5 every other week (cohort 3). Bevacizumab (10 mg/kg IV) was administered on days 1 and 15 every 28 days. Results: A total of 12 patients have been accrued (10 GBM, 2 anaplastic astrocytoma; 6 men, 6 women, median age 50). Dose-limiting toxicities (DLT) in cohort 1 was gr. 3 thrombocytopenia in 1 patient. No DLTs have been observed in cohorts 2 (3 patients) and 3 (6 patients). Toxicities of at least grade 2 or higher included QTc prolongation, diarrhea, fatigue and deep vein thrombosis in one subject each, minor and reversible hematologic toxicities in 4 subjects and hypophosphatemia in 3 subjects. 3 patients achieved a partial response. Conclusions: The combination of panobinostat and bevacizumab is well tolerated. The recommended phase II dose is 30 mg panobinostat on days 1, 3 and 5 every other week with bevacizumab at 10 mg/kg on days 1 and 15 every 28 days. Additional efficacy data will be presented.
Successful Control of Massive Gastrointestinal Bleeding Following Umbilical Cord Blood Transplantation (UCBT) by Use of Recombinant Activated Factor VII (rFVIIa) and Octreotide Infusion
Authors: Satya Prakash Yadav, Anupam Sachdeva, Madasu Anjan, Nita Radhakrishnan, Sunil Bhat, Manas Kalra, Satyendra Katewa
Journal: Blood (2008)
The impact of body mass index on the surgical staging and outcome in women with intermediate risk endometrial cancer
Authors: A. Olawaiye, A. Rauh-Hain, M. Del Carmen, A. Goodman
Journal: Journal of Clinical Oncology (2008)

16517 Background: To test the null hypothesis that morbid obesity has no influence on the surgical staging and outcome in women with intermediate risk endometrioid adenocarcinoma. Methods: We reviewed the charts of all women diagnosed with intermediate risk endometrioid adenocarcinoma in our institution between January 1, 1995 and January 1, 2005. There were 200 eligible women out of whom 9 were excluded because of incomplete medical records. Statistical analysis was performed by SPSS. Median follow up was 50.8 months (range 2 - 152 months). Results: Patients were divided into 3 groups according to their BMI, normal or overweight (<30), obese (>30<40) and morbidly obese (>40). Morbid obese patients accounted for 26 % of the study group. The morbidly obese patients were younger than patients with BMI of < 30 (61.53 vs. 68.81, p<0.001). Other medical co-morbidities (hypertension, lung disease, hypothyroidism and diabetes) were more common among the morbidly obese patients (P<0.01). There was no difference in the number of patients with grade III histology between morbidly obese and patients with BMI of <30 (18% vs. 29% p = 0.14). The proportion of patients who had adjuvant radiotherapy was similar across groups). Surgical staging was less complete among morbidly obese patients as suggested by a lower lymph node count compared to all other groups combined (11 vs. 16, p < .05). However, compared to patients with BMI < 30, morbidly obese patients did not show any difference in disease free survival (p = 0.83) and their overall survival was superior (124 vs. 111 months, p = 0.036). Conclusions: Morbidly obese women with intermediate risk endometrioid adenocarcinoma may have a better outcome even though their BMI precludes thorough surgical staging. Factors other than tumor grade may account for the better outcome in this group. No significant financial relationships to disclose.
Phase I clinical evaluation of AZD2171 in combination with gefitinib, in patients with advanced tumors
Authors: H. van Cruijsen, E. E. Voest, C. M. L. van Herpen, K. Hoekman, P. O. Witteveen, C. J. A. Punt, T. A. Puchalski, N. Fernandes, M. Koehler, G. Giaccone
Journal: Journal of Clinical Oncology (2005)

3030 Background: AZD2171 is a highly potent inhibitor of VEGF receptor-2 tyrosine kinase activity. This Phase I trial assessed the safety, tolerability and pharmacokinetics (PK) of ascending once-daily oral doses of AZD2171 in combination with the EGF receptor tyrosine kinase inhibitor gefitinib (Iressa). Methods: Patients with advanced solid tumors refractory to standard therapies and a WHO performance status of 0–2 received once-daily oral dosing with AZD2171 (20, 30 or 45 mg) and gefitinib 250 mg until dose-limiting toxicity (DLT) was observed (Part A1). The PK interaction of AZD2171 30 mg with gefitinib 250 mg was studied in an expanded cohort (Part A2). Parts B1 and B2 will follow the design of Parts A1 and A2, respectively, with a gefitinib dose of 500 mg. Results: As of October 8, 2004, 16 patients (31–66 years) have received AZD2171 (20, 30, and 45 mg; n = 3, 5 and 8, respectively) plus gefitinib 250 mg (Part A1), and 14 patients have received AZD2171 30 mg plus gefitinib 250 mg (Part A2). AZD2171 at doses ≤30 mg/day was generally well tolerated in combination with gefitinib. The most frequently reported adverse events (AEs) were diarrhea (14/16), rash (9/16), abdominal pain (9/16), and hypertension (8/16). Hypertension and diarrhea were the most commonly reported CTC grade ≥2 AEs considered to be related to treatment, with the majority occurring in the AZD2171 45 mg cohort. In general, causality for diarrhea and rash was assigned to gefitinib, while causality for hypertension was assigned to AZD2171. DLTs (CTC grade ≥3) were hypertension (1/5 patients, 30 mg cohort; 3/8 patients, 45 mg cohort), and anorexia and dyspnea (both experienced by one patient with NSCLC in the 45 mg cohort). Based on preliminary data, AZD2171 30 mg steady-state plasma PK data were not substantially different when given alone or with gefitinib 250 mg for 14 consecutive days. The gefitinib 250 mg steady-state plasma PK data were within the range previously reported for gefitinib 250 mg alone. Clinical response data (RECIST) will be presented. Conclusions: The study has reached the MTD of AZD2171 (30 mg) in combination with gefitinib 250 mg. Part B1 of the study is now ongoing. Iressa is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca AstraZeneca
The correlation between the decrease of intratumoral arterial enhancement and time-to-tumor progression in patients with hepatocellular carcinoma treated with sorafenib.
Authors: Y. Kojima, S. Mitsunaga, M. Ikeda, H. Takahashi, S. Shimizu, I. Ohno, K. Nakachi, A. Imoto, T. Okusaka, A. Ochiai
Journal: Journal of Clinical Oncology (2011)

167 Background: In the diagnostic work-up of hepatocellular carcinoma (HCC), intratumoral enhancement in the arterial phase (IE) of dynamic computed tomography (CT) or magnetic resonance imaging (MRI) represents tumor viability. Although such IE has been known to disappear during the course of sorafenib therapy, the precise impact of decreased IE has not yet been elucidated. Therefore, we focused on the impact of decreased IE on the time-to-tumor progression (TTP) in HCC patients (pts) treated with sorafenib. Methods: The change in IEduring the course of sorafenib therapy was reviewed in 52advanced HCC patients treated between January 2004 and April 2010. decreased IE was defined as the disappearance of arterial enhancement to a level equal to or less than that of the surrounding cancer-free hepatic parenchyma on dynamic CT or MRI. Even if one of the HCC tumors in a patient showed decreased IE, that patient was regarded as showing decreased IE. The impact of the pretreatment variables, decreased IE, and adverse events on the TTP were evaluated by the log-rank test. The Cox proportional hazard model was used to determine the most significant variables related to TTP. Results: Of the 52 pts, 48 were males and 4 females, and the median age was 70.5 years. The Child-Pugh classification was A in 28 pts and B in 24 pts. HCV Ab positivity, HBs Ag positivity, and seronegativity for both were observed in 39 pts, 7 pts and 6 pts, respectively. Decreased IE was found in 23 patients. The median TTP was 114 days in all patients, 165 days in patients showing decreased IE, and 89 days in patients who did not show decreased IE. The median time to decreased IE was 41 days. In the univariate analysis, decreased IE, female, prothrombin time, and serum PIVKA II were identified as being significantly associated with the TTP. Multivariate analysis using the Cox proportional hazards model revealed decreased IE (p=0.04) and prothrombin time (p=0.04) to be independently associated with a favorable TTP. Conclusions: Decreased IE is correlated with a favorable time-to-tumor progression in HCC pts treated with sorafenib. No significant financial relationships to disclose.
Brain metastases in non-small cell lung cancer patients at the time of first diagnosis: Therapy and outcome.
Authors: A. H. Schmittel, S. H. Hoecht, K. Schiemenz, W. Hinkelbein, E. Thiel, U. Keilholz
Journal: Journal of Clinical Oncology (2010)

e18114 Background: Brain metastases frequently occur in non-small cell lung cancer (NSCLC). Most clinical trials in stage IV NSCLC have excluded patients with brain metastases therefore the outcome of this patient population remains unclear. We retrospectively analysed treatment and outcome of patients with brain metastases at the time of first diagnosis and descriptively investigated the outcome after resection and the role of systemic chemotherapy in addition to whole brain radiotherapy (WB-RT). Methods: All patients diagnosed and treated in the department of radiooncology between 2001 and 2006 were included into the analysis. Patients and disease characteristics, treatment, outcome and data on the systemic therapy were taken from the patient's charts and by contacting the general physicians. Results: Sixty-six patients with a median age of 59 years (range 38-80) were identified. Thirty-two (48%) were female, 7 were never-smokers, 22 (33%) had a Karnofsky performance status (KPS) of ≥ 70% and the majority of 54 (82%) had adenocarcinomas. Ten (15%) had a single brain metastasis, 6 (9%) had asymptomatic brain metastases. In ten of 66 (15%) metastases were resected (n = 10), all patients received WB-RT with a dose of 30 Gy given in 10 fractions. Fourty-one (62%) in addition received systemic chemotherapy. Median survival of the entire population was 7 months (95% CI 4.8-9.2). Univariate analysis revealed a significantly improved median survival for patients with resected brain metastases 19 (95% CI 1.8-36.2) versus 5 months (95% CI 2.9-7.1) (p < 0.01). Patients with a KPS ≥ 70% had a median survival of 9 (95% CI 5.0-13.0) versus 3 months (95% CI 0.7-5.3) in KPS < 70% patients (p = 0.005). Survival analysis did not show differences between genders, histology and patients receiving chemotherapy versus no chemotherapy. Conclusions: This analysis confirms earlier studies showing an improved survival for patients after resection of brain metastases and in patients with good performance status. This retrospective analysis failed to demonstrate a benefit from systemic chemotherapy and therefore is the basis for a prospective trial on chemotherapy in patients with brain metastases at the time of first diagnosis. No significant financial relationships to disclose.
Distress factors in the determination of palliative care for ethnically diverse women with gynecologic cancer.
Authors: Adebola Falae, William Robinson, William R. Robinson
Journal: Journal of Clinical Oncology (2015)

16 Background: Versions of the Distress Thermometer have been used and validated widely, but studies of ethnically diverse populations has been limited. A modifed version of the Thermometer is used to understand factors affecting an African American(AA), inner-city population in order to improve access and utilization of palliative care services in a large, ethnically diverse metropolitan area. Methods: A cross-sectional study of women recieving cancer therapy in New Orleans, LA in 2013-14 was conducted. Subjects completed modified Distress Thermometer surveys which captured levels of distress and assessed predefined factors that could impact distress.Demographics were collected, and descriptive and comparative analyses were performed. Results: 49 Caucasian and 34 AA subjects were analyzed. Overall distress rating distributions were similar between the two groups. AA subjects cited family factors as a cause of distress more often than Causasians. (p &lt; 0.006) AA subjects were also more likely to indicate difficulty with partners and overall lack of support as stressing factors than Caucasians. In subjects who reported distress scores greater than 4, AA subjects cited emotional and physical factors more frequently than Caucasians as a cause for distress. (p &lt; 0.05) 11.11% AA subjects vs 3.57% Caucasians cited spiritual factors as a cause of distress. Conclusions: AA women with gynecologic cancer are more likely to cite familial, emotional, physical and perhaps spiritual factors as factors affecting distress than Caucasian women. These findings could be used to target Palliative Care resources more effectively in an ethnically diverse population.