tbuckley/cabot-search huggingface dataset:
A phase II multicenter study of the IGF-1 receptor antibody cixutumumab (A12) and the mTOR inhibitor temsirolimus (TEM) in patients (pts) with refractory IGF-1R positive (+) and negative (-) bone and soft tissue sarcomas (STS).
Authors: Gary K. Schwartz, William D. Tap, Li-Xuan Qin, Michael B. Livingston, Samir D. Undevia, Bartosz Chmielowski, Mark Agulnik, Scott Schuetze, Damon R. Reed, Scott H. Okuno, Joseph A. Ludwig, Kenneth R. Hande, Petra Rietschel, Andrew S. Kraft, Douglas Adkins, Bruce Brockstein, Vincent Yim, Christiana Bitas, Cristina Antonescu, Robert G. Maki
Journal: Journal of Clinical Oncology (2012)

10003 Background: Preclinical studies demonstrate synergistic anti-tumor activity by inhibiting mTOR and IGF-1R. This study evaluated the safety and efficacy of A12 and TEM in 3 chemo-refractory cohorts: IGF-1R (+) STS (Arm A), IGF-1R (+) bone (Arm B), and IGF-1R (-) bone and STS (Arm C). Methods: An optimal Simon 2 stage design was used for each arm. The primary end-point was progression free survival (PFS) at 12 weeks. Based on historical data, a 40% PFS rate was considered promising and a 20% PFS non-promising (type I/ II error, 0.05/0.10). ≥5 PFSs at 12 weeks were required in the first 19 and ≥16 PFSs were required in a total of 54 pts to consider each arm positive. Key eligibility: measurable disease (RECIST 1.1), age ≥18, 1- 4 priors, ECOG status 0-1. A12 (6 mg/kg) and TEM (25 mg) were administered IV weekly. Pre and post treatment tumor biopsies and plasma for IGF-1 and IGFBP3 were obtained. 20 Sarcoma Centers participated. Results: Starting in 02/2010, 383 pts were tested for IGF-1R by immunohistochemistry (IHC; 54% +) and 171 were treated: mean age 47 (range: 18-80), mean # priors 2.2 (range: 1-4). Grade 3/4 toxicities ≥10%: lymphopenia (12%), mucositis (10%). By intent to treat (ITT) analysis, each arm of the study achieved its primary 12 week PFS end-point (≥16 PFSs): Arm A: 18/56 (32%), Arm B: 19/50 (38%) (4 too early), Arm C: 27/63 (43%). The one-sided 95% CI for 12-week PFS is (0.22, 1), (0.27, 1), and (0.32, 1), respectively. By ITT the median PFS (95% CI) in weeks for each arm is 6.3 (5.9, 12.0), 11.0 (8.0, 18.0) and 11.6 (9.0, 17.9), respectively, and for chondro (n=18), Ewing’s (n=24), and osteo (n=23) only it is 22.6 (5.7, 40.9), 10.4 (5.7, 17.9) and 6.0 (6.0, 18.0), respectively. Westerns on 32 matched pair tumor biopsies indicate inhibition of IGF-1R, pAKT and pS6. Of biopsies on 7 IGF-1R (-) IHC pts (Arm C), 5 were IGF-1R (+) by western. Plasma biomarkers did not correlate with PFS. Conclusions: A12 and TEM met its primary end-point of improved PFS in pts with metastatic sarcoma. This effect was independent of IGF-1R status by IHC. These results support further clinical development of this combination in bone and STS.
Tofacitinib improves pruritus and health-related quality of life up to 52 weeks: Results from 2 randomized phase III trials in patients with moderate to severe plaque psoriasis
Authors: Steven R. Feldman, Diamant Thaçi, Melinda Gooderham, Matthias Augustin, Claudia de la Cruz, Lotus Mallbris, Marjorie Buonanno, Svitlana Tatulych, Mandeep Kaur, Shuping Lan, Hernan Valdez, Carla Mamolo
Journal: Journal of the American Academy of Dermatology (2016)
Primary tumor location and bevacizumab effectiveness in metastatic colorectal cancer patients.
Authors: Wen-zhuo He, Chang Jiang, Fang-xin Liao, Qiong Yang, Peng-fei Kong, Liang-ping Xia
Journal: Journal of Clinical Oncology (2016)

3593 Background: We previously reported that bevacizumab effectiveness was associated with the primary tumor location of metastatic colorectal cancer (mCRC). However, several important clinical and pathological features were not balanced when patients were grouped by the primary tumor location. Methods: From 2004 to 2013, we identified 740 patients with mCRC treated with oxaliplatin or irinotecan based chemotherapy (CT group) and 244 patients treated with bevacizumab plus oxaliplatin or irinotican based chemotherapy as first-line setting (CT + B group) from Sun Yat-sen university cancer center. We selected patients using propensity score analyses based on unbalanced characteristics (gender, mucinous histology, stage at diagnosis, and lactate dehydrogenase). The primary outcome was overall survival (OS). Kaplan-Meier curves with log-rank tests were used to detect difference. The last time follow-up was conducted at 30th December 2015. Results: 58 right-side colon, 86 left-side colon and 99 rectal cancer patients were included in CT group (total: 243) while 78 right-side colon, 86 left-side colon and 80 rectal cancer patients were included in CT + B group (total: 244). Patients in CT + B group had a similar OS in comparison with CT group only when the primary tumor located at right-side colon (median OS were 20.2 months for CT + B group versus 20.5 for CT group, P = 0.851). For left-side colon cancer patients, those in CT + B group had longer OS than CT group (26.3 versus 23.1 months, P = 0.021). For rectal cancer patients, significantly longer OS were also observed in CT + B than CT group (26.3 versus 21.1 months, P = 0.014). Conclusions: Our data suggested that patients with right-side colon cancer could not get survival benefit from the addition of bevacizumab, and the different response to bevacizumab between right-side and left-side colon cancer were not caused by routinely clinical and pathological features.
Follicle stimulating hormone (FSH) as a surrogate parameter for the effectiveness of endocrine therapy with or without zoledronic acid in premenopausal patients with breast cancer: An analysis of the prospective ABCSG-12 trial.
Authors: Georg Pfeiler, Robert Königsberg, Lidija Filipcic, Richard Greil, Herbert Stoger, Christian F. Singer, Michael Knauer, Guenther G. Steger, Michael Seifert, Peter Christian Dubsky, Florian Fitzal, Marija Balic, Vesna Bjelic-Radisic, Brigitte Mlineritsch, Christian Marth, Michael Gnant
Journal: Journal of Clinical Oncology (2014)

577 Background: Endocrine therapy is an effective, targeted therapy in patients with hormone receptor positive breast cancer (BC). However, in the adjuvant setting no indicator exists visualizing its effectiveness during therapy. In this analysis we test whether FSH serum levels during therapy might be a surrogate parameter for the effectiveness of adjuvant endocrine therapy. Methods: ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6mgq4wSC) in combination with anastrozole or tamoxifen ± zoledronic acid (ZOL, (4mgIVq6mo) in premenopausal women with endocrine-responsive BC. Prospective collected data on FSH serum levels were used for the analyses. Disease-free survival (DFS), distant metastasis free survival (DMFS) and overall survival (OS) were calculated by Kaplan-Meier method, results were compared by using the log-rank test and Cox proportional hazard modelling. Results: Analyses are based on 503 patients with FSH levels at baseline, 562 patients with FSH levels during therapy and 641 patients with FSH levels during follow up. Mean FSH levels were significantly lower during therapy, when compared to baseline and follow up, respectively (4.87mIU/ml vs. 14.16mIU/ml vs. 22.28mIU/ml, p<0.001). Patients treated with anastrozole had significantly higher FSH levels during therapy compared to patients treated with tamoxifen (7.05mIU/ml vs. 2.45mIU/ml, p<0.001). Patients with FSH levels above the mean during therapy (4.87mIU/ml) had a worse outcome compared to patients with FSH levels below 4.87mIU/ml (DFS HR 1.347, p=0.18; DMFS HR 1.939, p=0.035; OS HR 2.208, p=0.096). This could be confirmed with borderline significance in the subgroup of patients treated with ZOL (DFS HR 1.886, p=0.075; DMFS HR 2.537, p=0.077; OS HR 1.306, p=0.726). BMI had no impact on FSH serum levels in any group during therapy. Conclusions: This study suggests that FSH serum levels during therapy might be a good surrogate parameter for the effectiveness of adjuvant endocrine therapy.
Erythropoiesis In SF3B1 Mutated RARS Is Disrupted During Terminal Erythroid Maturation
Authors: Simona Conte, Liselotte Vesterlund, Shintaro Katayama, Mohsen Karimi, Elli Papaemmanuil, Monika Jansson, Teresa Mortera-Blanco, Marios Dimitriou, Birgitta Sander, Tiina Skoog, Peter J. Campbell, Juha Kere, Per Unneberg, Eva Hellström-Lindberg
Journal: Blood (2013)
The prognostic importance of biopsy proven unilateral versus bilateral disease in patients treated with I-125 seed implant for localized prostate cancer: A single institution retrospective study
Authors: N. Dunlap, R. Shirazi, A. Naghavi, W. Barrett
Journal: Journal of Clinical Oncology (2004)

4673 Background: The prognostic value of prostate disease laterality has rarely been assessed. The objective of this retrospective study was to determine the significance of biopsy proven unilateral versus bilateral prostate cancer as a prognostic indicator of biochemical control in patients treated with I-125 seed implant for localized prostate cancer. Methods: Between 1996 and 2001, 159 consecutive patients with clinically localized prostate cancer were treated with I-125 seed implant at our institution. As part of the initial workup, all patients underwent bilateral prostate biopsies, pretreatment PSA, and Gleason score determination. Based on biopsy results, the patients were divided into two groups according to positive biopsies from one versus both lobes of the prostate. Biochemical control was assessed according to the ASTRO consensus definition of biochemical failure and by determining the number of patients achieving and maintaining a PSA nadir of ≤1.0, ≤0.5, or ≤0.2. Results: Mean pretreatment PSA level for patients exhibiting unilateral disease was 7.32 versus 8.20 in patients with bilateral disease (p=.1151). Mean Gleason score was 6.03 for patients with unilateral disease versus 6.27 for patients with bilateral disease (p=.0778). Biochemical control according to the ASTRO consensus definition was achieved in 91% of the patients with unilateral disease compared to 77% of patients with bilateral disease (p=.0069). PSA nadirs of ≤1.0, ≤0.5, or ≤0.2 were achieved in 94% versus 79% (p=.0026), 89% versus 68% (p=.0006) and 72% versus 53% (p=.0096) of patients with unilateral disease versus bilateral disease respectively. Conclusions: Unilateral versus bilateral disease is an important prognosticator for biochemical control in patients with early stage localized prostate cancer treated with I-125 seed implant. Patients with positive biopsies from both lobes of the prostate have worse prognoses compared to patients with only unilateral biopsy proven disease. No significant financial relationships to disclose.
MSF urges world leaders to act over bombing of hospitals in Aleppo
Authors: Anne Gulland
Journal: BMJ (2016)

Medecins Sans Frontieres’ president, Joanne Liu, has urged world leaders to stop the bombing of hospitals in the Syrian city of Aleppo.

In a speech to the United Nations Security Council on 28 September Liu said that the conduct of war was “ever boundless.” She continued, “It is a race to the bottom. The unremitting assault on Aleppo by Russian and Syrian forces over recent days is certainly testament to that.”

Liu added, “In Syria the government and its allies relentlessly—deliberately—attack hospitals, doctors, first responders, and patients. Doctors in Aleppo tell …
Dose-dense chemotherapy in nonmetastatic breast cancer patients: A systematic review and meta-analysis.
Authors: L. F. Bonilla, I. Ben-Aharon, L. Vidal, A. Gafter-Gvili, L. Leibovici, S. M. Stemmer
Journal: Journal of Clinical Oncology (2010)

645 Background: Dose-dense chemotherapy (DDC) has become the standard of care in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of existing data regarding the efficacy and toxicity of DDC approach in nonmetastatic breast cancer. Methods: Relevant RCT's were identified by searching The Cochrane Cancer network register of trials, The Cochrane Library, LILACS and MEDLINE (1.1966 and onwards). The terms adjuvant or neoadjuvant DDC and similar, breast cancer and similar where crossed. Two reviewers independently appraised the quality of trials and extracted data. Results: Eleven trials met the inclusion criteria and were classified into two categories. Three compared DDC to standard schedule. DDC showed superiority in overall survival (OS) and disease free survival (DFS) (HR 0.84; 95% CI 0.72 -0.98, p = 0.03 and HR 0.83 95% CI 0.73-0.94, p = 0.005). No benefit was observed in patients with positive hormonal receptor status. Six trials compared DDC with regimens using standard intervals, but the agents in the 2 arms were not similar nor their dosages. Similar results were obtained for these trials with improvement in OS (HR 0.85; 95% CI 0.75-0.96 p = 0.01) and DFS (HR 0.81; 95% CI 0.73-0.88 p = 0.0003) respectively. Toxicity evaluation depicted a higher non-hematological adverse events rate for DDC arms. One study was included in the systematic review only due to lack of any survival data. Conclusions: Current data indicate a favorable outcome for DDC in OS and DFS. Hormonal receptor status may play a role when using DDC. The acceptance of DDC as standard of care is based upon limited but encouraging data and warrants more randomized controlled trials to further validate this concept. No significant financial relationships to disclose.
Laparoscopic Rectal Resection—Ready for Prime Time?
Authors: Martin R. Weiser
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
A phase I study of the anti-insulin like growth factor type 1 receptor (IGF-1R) antibody dalotuzumab in pediatric patients with advanced solid tumors.
Authors: Didier Frappaz, Lisa M. McGregor, Andrew DJ Pearson, Lia Gore, Steven G. DuBois, Isabelle Aerts, Robert Iannone, Ryan Geschwindt, Arne Van Schanke, Ruixue Wang, Birgit Geoerger
Journal: Journal of Clinical Oncology (2013)

10026 Background: Insulin-like growth factor signaling plays an important role in several pediatric cancers. Dalotuzumab is a highly specific, humanized IgG1 monoclonal antibody against IGF-1R. This multicenter phase 1 study explored the safety and pharmacokinetics (PK) of dalotuzumab in pediatric patients with advanced solid tumors. Methods: Dalotuzumab was administered intravenously every 3 weeks. Dose-escalation was performed according to a modified Toxicity Probability Interval (mTPI) design starting at 900 mg/m 2 . The PK profile of dalotuzumab was evaluated with the primary goal of confirming that the Day 22 mean serum trough concentration exceeded 25 μg/mL. Results: 24 patients were enrolled and 20 treated (median age, 10.5 years; range, 3–17 years). Six patients had recurrent Ewing sarcoma. Patients received a median of 2 cycles (range, 1-10). No dose-limiting toxicity was observed in any of the three dose levels explored (900, 1200 and 1500 mg/m 2 ). Main treatment-related toxicities were Grade 3 elevated transaminases. PK data showed dose dependent increases in AUC 0-∞ (105,000, 164,000 and 281,000 hr*mg/mL, for the 900, 1200 and 1500 mg/m 2 dose levels, respectively), C trough (65.2, 71.6, 148 mg/mL) and C max (559, 643, 888 mg/mL). The mean half-life was 247, 394 and 376 hours respectively. The C max exhibited mild variability (4.8-35% Coefficient of Variation), whereas variability was moderate to high on the C trough (39-200%), apparent t 1/2 (28-154%), AUC 0-∞ (29-106%) and clearance (52-161%). Except for one patient at the 1200 mg/m 2 dose level, all patients met the PK target, a C trough of 25 μg/mL, suggesting 900 mg/m 2 as the recommended phase 2 dose (RP2D). One patient with Ewing sarcoma had a confirmed partial response; 2 patients with Ewing sarcoma and one with nephroblastoma had stable disease for at least 7, 5 and 6 months, respectively. Conclusions: Dalotuzumab is well tolerated in pediatric patients with advanced malignancies. The RP2D of 900 mg/m 2 was chosen based on tolerability and PK parameters. Preliminary data confirm prior reports suggesting activity in Ewing sarcoma. Clinical trial information: NCT01431547.
Case 52-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Jerome H. Shapiro, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of Case First admission. A 78-year-old man entered the hospital because of symptoms of prostatic obstruction.Fourteen years previously transurethral resection of the prostate gland had been performed at another hospital. Five years before admission he came to this hospital because of recurrent symptoms of bladder-neck obstruction. The urea nitrogen was 15 mg, and the creatinine 1.3 mg per 100 ml. An intravenous pyelographic study showed poor function bilaterally, with decrease in the size of the left kidney. Cystoscopic examination revealed enlargement of the lateral lobes of the prostate gland and hemorrhagic cystitis. Retrograde examination of the left . . .
Targeting HSP90 in breast cancer: Enchant-1 (NCT01677455) phase 2 proof of concept study of ganetespib in first-line treatment of women with metastatic breast cancer.
Authors: David A. Cameron, Neil Spector, Javier Cortes, Max S. Mano, Jean-Luc Re Canon, Tamas Hickish, Linda T. Vahdat, Sung-Bae Kim, Henry Leonidas Gomez, Iman El-Hariry, Vojislav M. Vukovic, Emily H Sheldon, Edith A. Perez, Ahmad Awada
Journal: Journal of Clinical Oncology (2014)

TPS665^ Background: Hsp90 is a chaperone protein required for the activation of several client proteins critical to breast cancer growth and aggressiveness, including HER2, HIF1-α, EGFR, ER, PI3K, AKT, p53 and VEGFR. Ganetespib, a novel Hsp90 inhibitor, has preclinical activity in HER2+, ER+/PR+ and triple negative breast cancer (TNBC) models. Clinical trials showed a favorable safety profile with early signals of activity in patients (pts) with HER2+ disease, as well as TNBC. The ENCHANT-1 trial aims to further evaluate ganetespib single-agent activity in metastatic breast cancer (mBC) and identify biomarkers predictive of outcome. Methods: ENCHANT-1 is an international, Phase 2 study in 1st line mBC. Pts are assigned to one of the following 3 cohorts: Cohort A, HER2 amplified (n=35), Cohort B, TNBC (n=35), Cohort D, Hormone receptor (HR) positive (n=35). Pts with previously untreated mBC are eligible for treatment with ganetespib twice weekly on a 3 out of 4 wk schedule, for a total of up to 12 wks. HER2+ and HR+ pts must have received prior anti-HER2 therapy and endocrine therapy, respectively. At disease progression, pts will receive combination therapy of weekly ganetespib (150 mg/m2) and weekly paclitaxel (80 mg/m2) on a 3 out of 4 wk schedule. Primary endpoint: ORR assessed using RECIST1.1 criteria. Key secondary endpoints include metabolic response assessed by PET/CT at wk 3 utilizing modified EORTC criteria. Tumor genetic signature and proteomic profiling are performed on patient’s tumors in an effort to develop biomarkers of response. At the time of submission, a total of 46 pts were enrolled; TNBC (n= 38) and HER2+ (n=8). Clinical trial information: NCT01677455.
The psychological projective test Wartegg-Zeichentest: A contribution to the knowledge of patients with cancer.
Authors: C. M. La Spina, C. Murasecchi, S. Stinco, A. Cassano, A. Strippoli, N. Trigila, M. Di Salvatore, A. Quaranta, E. Straffi, C. Barone
Journal: Journal of Clinical Oncology (2010)

e19678
Sorafenib in combination with local microtherapy guided by gadolinium-EOB-DTPA enhanced MRI in patients with inoperable hepatocellular carcinoma (HCC) (SORAMIC).
Authors: Jens Ricke, Kerstin Schuette, Olivier Rosmorduc, Augustinus Jakob, Chris Verslype, Bruno Sangro, Jerzy Walecki, Heinz-Josef Klumpen, Bora Peynircioglu, Bulent Yalcin, Carlo Bartolozzi, Holger Amthauer, Peter Malfertheiner
Journal: Journal of Clinical Oncology (2012)

TPS4148 Background: HCC is a leading cause of cancer-related mortality in both men and women. It represents the fifth most common cancer worldwide with an increasing incidence. For the individual patient tumor stage at diagnosis (number and size of nodules, presence or absence of vascular invasion, presence or absence of extrahepatic spread), liver function and general health status are the principal prognostic factors. The clinical management of HCC requires a comprehensive, multidisciplinary approach. In early HCC curative treatment can be achieved by local ablation, resection or liver transplantation. In intermediate stages patients (pts) are offered locoregional treatment with palliative intent (transarterial chemoembolisation (TACE), Yttrium-90-radioembolisation (SIRT)). In advanced disease systemic therapy with sorafenib (sor) has the potential to prolong survival of pts and is standard of care in pts with preserved liver function. Studies on the combined use of locoregional and systemic therapy with their potential of a beneficial synergism are few and conducted in a small number of pts. Methods: This phase II-study is composed of three substudies with the following primary objectives: 1. In pts in whom local ablation is appropriate to determine if sor in combination with RFA prolongs the time-to-recurrence in comparison with RFA plus placebo. Primary endpoint (PEP): time to recurrence, n = 290 pts 2. In pts in whom RFA is not appropriate (palliative treatment group) to determine if the combination of SIRT and sor improves the overall survival in comparison to sor alone. PEP: overall survival, n = 375 pts 3. To confirm in a 2-step procedure that Gd-EOB-DTPA enhanced MRI is non-inferior or superior compared with contrast-enhanced multislice CT for stratification of pts to a palliative or a local ablation treatment strategy. PEP: correct stratification of pts to a palliative versus local ablation treatment strategy; n = 830 pts The trial has started in December 2010 as a multinational and multicentric study. 90 pts have been enrolled until January 31 st 2012 with 51 pts randomized in the palliative arm and 14 pts treated in the curative arm.