tbuckley/cabot-search huggingface dataset:
Results from a phase 2 trial of bortezomib (B) and sorafenib (S) in unresectable or metastatic renal cell cancer.
Authors: Richard C. Lauer, Ian Rabinowitz, Terry Novak, Martin J. Edelman
Journal: Journal of Clinical Oncology (2014)

495 Background: B is a small molecule proteasome inhibitor that affects multiple signaling pathways. S is an orally active multikinase inhibitor with known activity in renal cell cancer. In vitro data has shown that S and B interact synergistically in a number of neoplastic cell lines to cause apoptosis. A phase 1 trial of S and B demonstrated no unexpected toxicities. We now report the results of this phase 2 efficacy trial. Methods: Eligibility included cytologically confirmed clear cell cancer with no prior chemotherapy, PS 0-1, Cr &lt; 1.5 mg/dl, normal LFTs. Regimen: S 200 mg PO BID and B 1mg/m2 IV days 1,4,8, &amp; 11 every 21 days. Patients were treated until disease progression or unacceptable toxicity. The primary objective of the study was to achieve a PFS of 70 weeks. Results: Seventeen patients were enrolled between April of 2011 and January of 2013. Median age was 62y (range 44-75). Four of 17 patients had known brain metastasis on entry to the trial. Median number of cycles = 4 (range 1-45+). Response: CR/PR/SD/PD =0/1/12/4 (RR: 6%, 95% CI = 0%, 29%) Median progression free survival was 13.7 weeks; median overall survival was 110 weeks Toxicity: See table. Only 1 pts. treatment was stopped due to an AE of pancreatitis. There were no toxic deaths. The study was halted for futility. Conclusions: 1.The combination of S and B was well tolerated. 2. The RR of 6% and PFS of 13.7 weeks is not superior to S as a single agent. 3. The combination of SB is not recommended for further development. Clinical trial information: NCT 01100242.
Safety and feasibility of salvage robot-assisted radical prostatectomy for recurrent prostate cancer.
Authors: Andre Luis de Castro Abreu, Sanket Chauhan, Adrian Stuart Fairey, Ignacio Camacho, Alvin Goh, Daniel Park, Mihir Desai, Vipul Patel, Inderbir S Gill, Monish Aron
Journal: Journal of Clinical Oncology (2012)

e15171 Background: The safety and feasibility of salvage robot-assisted radical prostatectomy (sRARP) for recurrent prostate cancer is unclear. Herein we report short-term cancer control, functional, and perioperative outcomes in a multi-institutional cohort. Methods: Between July 2007 and October 2011, 38 consecutive men underwent sRARP for recurrent prostate cancer at the University of Southern California (n=14) or Global Robotics Institute (n=24). Failed primary therapy was varied (external beam radiotherapy [EBRT; n=14]; interstitial brachytherapy [IBT; n=11]; EBRT + IBT [n=5]; high-intensity focused ultrasound [n=3]; cryoablation [n=3]; other [n=2]). The main outcomes were immediate biochemical failure (IBF), positive surgical margins (PSM), urinary continence and erectile function at 3 months, and complications within 90 days of surgery. Immediate biochemical failure was defined as a PSA &gt; 0.2 ng/ml. Urinary continence was defined as the use of no pads and erectile function was defined as a SHIM score &gt; 21. Complications were classified and graded using the Clavien system. Results: The median age was 68 years (50-83 years) and median preoperative PSA was 4.1 ng/ml (0.4-15.2 ng/ml). Preoperative biopsy Gleason score was ≤6 (n=7), 7 (n=18), and ≥8 (n=12). All procedures were completed without the need for open conversion. No patient experienced an intra-operative complication. Median estimated blood loss was 100 ml (30-300 ml) and operative time was 1.5 h (1-6h). Median length of hospital stay was 1 day (1-7 days). The median duration of urethral catheterization was 12 days (4-48 days). IBF occurred in 9 (29%) patients and PSM occurred in 7 (18%) patients. Urinary continence and erectile function occurred in 9 (34%) and 0 patients, respectively. One or more postoperative complications occurred in 12 (31%) patients. Low grade (I-II) and high grade (III-IV) complications occurred in 8 (21%) and 4 (10%) patients, respectively. No patient died. Conclusions: Salvage robot-assisted radical prostatectomy is safe and feasible. Short-term cancer control and perioperative morbidity were acceptable; however, functional recovery was poor. To date, this is the largest series worldwide.
Characterization and Novel Treatment for Therapy-Resistant Mantle Cell Lymphoma Isolated from Liver and Kidney
Authors: Ganapati V. Hegde, Tara M. Nordgren, Corey M. Munger, Amit K. Mittal, Philip J. Bierman, Dennis D. Weisenburger, Graham Sharp, Julie M. Vose, Shantaram Joshi
Journal: Blood (2008)
Defining heminephrectomy for cancer.
Authors: Joseph C. Klink, Ali Khalifeh, Dinesh Samarasekera, Kamol Panumatrassamee, Jihad Kaouk
Journal: Journal of Clinical Oncology (2013)

473 Background: The word heminephrectomy originally referred to the removal of half of a kidney with a duplicated collecting system. In the era of partial nephrectomies, heminephrectomy is sometimes used to describe the removal for tumor of &gt;30% of the parenchyma of a non-duplicated kidney. We herein propose a new definition of heminephrectomy: excision of the upper or lower pole of the kidney, removing at least 30% of the parenchymal mass, cutting to hilar fat, and transecting the collecting system. Methods: Our institutional database of robotic and laparoscopic partial nephrectomies was queried for patients who underwent a partial nephrectomy for tumor between 2002 and 2011. Patients who had a heminephrectomy for obstruction in a duplicated collecting system were excluded. The patients who had a heminephrectomy by our strict definition were compared to the remainder of patients who had a partial nephrectomy. Logistic regression was used to compare outcomes between the two groups. Results: 61 patients met our strict definition of heminephrectomy out of 643 patients who underwent a partial nephrectomy for tumor. Heminephrectomy and non-heminephrectomy patients were similar in age, gender, BMI, ASA score, proportion of left- versus right-sided tumors, solitary kidney status, preoperative creatinine and GFR. (all p&gt;0.1). The tumors in the heminephrectomy group were larger (5.1 vs. 2.8 cm, p&lt;0.001) and had a higher R.E.N.A.L nephrometry score (8.5 vs. 6.5, p&lt;0.001). Operative outcomes reflected the high complexity of performing a heminephrectomy. Estimated blood loss was greater (373 vs. 267 ml, p=0.04), operative time was longer (214 vs. 185 minutes, p&lt;0.001), warm ischemia time was longer (25 vs. 20 minutes, p=0.002), and the rate of intra-operative complications was greater (11% vs. 4%, p=0.02) in the heminephrectomy group. On multivariable analysis adjusted for age, preoperative GFR, R.E.N.A.L. score, and warm ischemia time, heminephrectomy was a significant predictor of lower post-operative GFR (p&lt;0.001). Conclusions: Our strict definition of heminephrectomy performed for tumor in a non-duplicated system will allow precise clinical and research communication about heminephrectomy patients and may aid in the prediction of outcomes after partial nephrectomy.
Screening for family members of patients with nasopharyngeal carcinoma—does early detection improve outcome?
Authors: A. L. Law, W. Ng, C. W. Choi, T. K. Yau, A. W. Lee
Journal: Journal of Clinical Oncology (2008)

1512 Background: Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed distribution with highest incidence in Southern Chinese population. As familial aggregation is evident, screening is conducted in Hong Kong to first-degree relatives of patients with NPC to see whether it could result in better clinical outcomes. Methods: 1,216 asymptomatic family members of NPC patients were screened by yearly Epstein Barr Virus serology testing and endoscopic examination of the nasopharynx between the years 1994 to 2005. Stage distributions of screening-detected cases were compared with that of 1,185 consecutive symptomatic patients treated in the same period through general referral. The expected additional observation time due to lead time was subtracted from the survival of the screening-detected cases. Results: Seventeen cases of NPC were detected by screening. Comparison of these screening-detected cases against the symptomatic cases showed that their median age was 6 years younger (42 vs. 48, p=0.07). Regular screening results in early detection of cancer, with 50.0% presenting at early stage (stage I: 37.5%, stage II: 12.5%), compared to 23.9% (stage I: 0.7%, stage II: 23.2%) of symptomatic cancers (p < 0.01). The overall survival rate at 5-year is also substantially higher (94% vs. 69%). However, after correcting for lead time, the p-value was statistically insignificant (p = 0.49). Conclusions: These results strongly suggest that screening asymptomatic family members of NPC patients leads to early detection of NPC and clinically valuable survival advantage. However, a larger sample size will be needed for more precise estimates of this potential survival benefit. No significant financial relationships to disclose.
Comparison of MRI and 18F-FDG PET for Evaluation of the Response to Treatment of Patients Diagnosed with Multiple Myeloma: A Prospective Clinical Study
Authors: Catherine Phan, Veronique gaura Schmidt, Chaima Kellil, Souhila Ikhlef, Philippe Moreau, Anne Miquel, Clement Pradel, Norbert C. Gorin, jean Yves Devaux, Yves Menu, Laurent Garderet
Journal: Blood (2012)
ZAP-70 Expression in Acute Lymphoblastic Leukemia: Association with the E2A/PBX1 Rearrangement and with the Pre-B Stage of Differentiation.
Authors: Sabina Chiaretti, Anna Guarini, Maria Stefania De Propris, Stefania Intoppa, Antonella Vitale, Cristina Ariola, Jerome Ritz, Robert Foa
Journal: Blood (2004)
Do Elderly Myeloma Patients Benefit From High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT)?: A Comparative Survival Analysis using SEER Registry
Authors: Eden Hailemichael, Jonathan L. Kaufman, Christopher R. Flowers, Edmund K. Waller, Mary Jo Lechowicz, Amelia Langston, Michael Graiser, Lawrence H. Boise, Sagar Lonial, Ajay K. Nooka
Journal: Blood (2012)
Hypothyroidism may accompany SU11248 therapy in a subset of patients (pts) with metastatic (met) gastrointestinal stromal tumors (GIST) and is manageable with replacement therapy
Authors: J. Desai, P. Dileo, J. A. Morgan, P. R. Larsen, M. H. Chen, S. George, J. Jackson, C. Baum, G. D. Demetri
Journal: Journal of Clinical Oncology (2005)

3040 Background: SU11248 is an oral, multitargeted kinase inhibitor with antiangiogenic and antitumor activity due to inhibition of VEGFR, PDGFRα, KIT and FLT3. SU11248 has documented activity in pts with a variety of malignancies, including imatinib-resistant GIST and renal cell carcinoma. Thyroid function was tested serially to assess the tolerability of chronic dosing. Methods: Pts with met GIST treated at a single center with repeat cycles of SU11248 in a phase 1/2 trial underwent serial assessments of TSH levels at the end of each dosing cycle. Comprehensive thyroid function indices (TFTs), including T4, T3, free T4 index, were performed if TSH was abnormal. Results: To date, 64 sequential pts have received 344 dosing cycles of SU11248. 25/64 pts developed abnormal TSH levels (CTC grade (G) 1 = 6; 2 = 19; 3/4 = 0), after a median of 5.4 months of treatment (range 1–24). Of these pts, 13 demonstrated abnormally low T4/T3 levels. 19/25 pts were treated with thyroid hormone replacement (THR) due to persistent elevations of TSH and accompanying fatigue (G 0/1 = 6; 2 = 12; G3/4 = 1). Signs and symptoms of transient myxedema were noted in 5/20 pts. All pts treated with THR had TSH normalization with rapid resolution of fatigue and any other symptoms. 7/25 pts were not treated with THR due to a lack of symptoms (fatigue: G 0/1 = 6; G2 = 1; G3/4 = 0), or disease progression. 5 pts initially had elevated TSH levels prior to developing hypothyroidism, consistent with a thyroidititic process, but with otherwise normal TFTs and no associated clinical symptoms. No pts required cessation or delay of SU11248 treatment as a result of thyroid-related toxicity. Conclusions: A subset of pts may develop thyroid dysfunction, which may account, in part, for fatigue previously described with SU11248. Thyroid dysfunction is not dose-limiting and all pts could be treated effectively with THR, with rapid clinical improvements and resolution of TSH elevation. The mechanism by which SU11248 affects thyroid function is being investigated and may account for documented objective responses to SU11248 which have previously been reported in pts with thyroid cancer (Rosen, Proc ASCO 2003, a765). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
Identification of hypoxanthine and phosphoenolpyruvic acid as serum markers associated with chemoradiotherapy response in locally advanced rectal cancer.
Authors: Min-Jeong Kim, Byong Chul Yoo, Seung-Gu Yeo
Journal: Journal of Clinical Oncology (2014)

507 Background: Patients show variable responses to chemoradiotherapy (CRT), generally performed before surgery for locally advanced rectal cancer (LARC). We aimed to identify molecular markers predictive of CRT responses by analyzing low-mass ions (LMIs) in serum of LARC patients. Methods: LMIs (&lt;1000 m/z) in serum obtained before CRT from 73 LARC (cT3–4) patients were profiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs with higher weighting factors in discriminating CRT responses were selected using principal components analysis and discriminant analysis. Selected LMIs were identified using the Human Metabolome Database. The concentrations of identified LMIs were determined by colorimetric enzyme assay, and compared according to post-CRT pathological stage (ypStage) or Dworak’s tumor regression grade (TRG). Results: The nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and 169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP), respectively. The HX concentration was higher in patients with ypStage 0-I compared with ypStage II-IV (p = 0.034) or ypStage III-IV (p = 0.030); a similar difference was observed between TRG IV-III and TRG 1 (p = 0.035). In contrast, the concentration of PEP was significantly lower in TRG 4-3 compared to TRG 2-1 (p = 0.012), and a lower PEP level was also found in ypStage 0 compared to ypStage I-IV, with marginal significance (p = 0.061). Conclusions: This study demonstrated that pretreatment serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC.
The use of trastuzumab in Japanese patients with HER2-positive advanced or metastatic gastric cancer.
Authors: A. Sawaki, Y. Ohashi, Y. Omuro, T. Satoh, Y. Hamamoto, N. Boku, Y. Miyata, H. Takiuchi, A. Ohtsu
Journal: Journal of Clinical Oncology (2011)

102 Background: The Trastuzumab for Gastric Cancer (ToGA) study showed the efficacy of trastuzumab for HER2-positive gastric cancer (HGA). The aim of this study is to evaluate the benefit of trastuzumab for Japanese HGA patients. Methods: ToGA was an open-label, international, phase III, randomized controlled trial undertaken in 122 centers in 24 countries. Median overall survival (OS) was 13.8 months in those assigned to trastuzumab plus chemotherapy (C+T) compared with 11.1 months in those assigned to chemotherapy alone (C) with hazard (HR) ratio of 0.74. Subgroup analyses of patients enrolled from Japan were undertaken to estimate the hazard ratio (HR) for OS in the Japanese population. Based upon the prescribed protocol for Japan, we calculated HR using multiple Cox regression model with prespecified covariates in the ToGA study in order to make up for the small number of Japanese patients and reduce the bias in the baseline characteristics between two groups. Results: Sixteen institutes participated and 102 patients were enrolled, of which 101 patients were evaluable for this research. The median OS was 15.9 months in C+T arm versus 17.7 months in C arm. The HR for OS was 1.00 [95% CI: 0.59-1.69]. However, the HR for OS adjusted for the above covariates was estimated to be 0.68 [95% CI: 0.36-1.27]. There were differences between C+T arm and C arm in some baseline characteristics. Higher frequencies were seen in C arm as follow: intestinal type, prior gastrectomy, and smaller number of metastatic sites. For HER2 status, the percentage of patients with IHC0/FISH+ was lower in C+T arm (5.9%) than in C arm (18.0%), while that of patients with HER2 status IHC2+/FISH+ was higher in C+T arm (35.3%) than in C arm (26.0%). Conclusions: Although ToGA's overall OS HR = 0.74 (p = 0.0046), in the Japan patient subgroup, the unadjusted hazard ratio was 1.00. However, there was an imbalance of the baseline characteristics between the treatment arms in Japanese population. When adjusted for these characteristics, the HR was 0.68 which is similar to those in the ToGA study. Adding trastuzumab to chemotherapy in Japanese population appears to confer a similar magnitude of benefit compared to the whole population enrolled in the ToGA study. [Table: see text]
Costs and outcomes in stage IV non-small cell lung cancer at an urban safety net hospital.
Authors: Julian Lel, Edmund Folefac, Ken Scott Zaner, Kevan L. Hartshorn
Journal: Journal of Clinical Oncology (2014)

14 Background: Stage IV NSCLC is an incurable illness with significant morbidity. Chemotherapy prolongs average survival from 6 to 10 months and targeted therapies further reduce morbidity and prolong survival. These advances pose financial challenges for safety net hospitals, which may also disproportionately feel the impact of racial disparity. Outcomes in advanced lung cancer may thus differ in the underserved population and resources may not be allocated optimally. Methods: A retrospective review was conducted on all patients diagnosed with Stage IV NSCLC between 2005 and 2011 at Boston Medical Center, an urban safety net hospital. Data were collected on survival from time of diagnosis, type and duration of treatment, utilization of healthcare resources, as well as detailed personal characteristics. We calculated costs of treatment for all patients. We assessed the effect of treatment and patient characteristics on survival. Results: Of 198 patients analyzed, 57% were white, 32% were black, 6% were Hispanic. 11% were homeless. 57% did not receive antineoplastic therapy, 24% received cytotoxic chemotherapy, 18% received combined cytotoxic and targeted therapy. Median survival was 5.0 months without therapy, 7.0 months with cytotoxic chemotherapy and 9.2 months with combined therapy. Any therapy was associated with 56% longer survival. Hazard of death in white patients was 0.68 relative to non-white patients. Median total and monthly costs for patients on no therapy were $70,000 and $14,000, on cytotoxic chemotherapy were $112,000 and $19,000 and on combined therapy were $247,000 and $26,000. Cost per month of survival was $12,000 less for white patients and $15,000 more for homeless patients. Conclusions: The majority of patients did not receive antineoplastic therapy, despite robust survival gains associated with its use. Untreated patients nevertheless incurred a high cost of care. White patients showed better survival at a lower cost. Further topics for study and intervention in this population include barriers to therapy, early involvement of palliative and home-based care in patients not suitable for treatment, strategies for cancer care in the homeless, as well as closer inquiry into drivers of racial disparity.
Monitoring therapeutic response to TKIs in breast cancer by use of imaging peptides
Authors: D. Hallahan, Z. Han
Journal: Journal of Clinical Oncology (2008)

11002 Background: Rapid assessment of cancer response to a therapeutic regimen can determine efficacy early in the course of treatment. Here we simultaneously assess response in all sites of disease within days of starting therapy by use of peptide ligands selected for their ability to discern responding from non-responding cancers. Methods: MDA-MB-231 breast cancer was studied in the cerebrum, lung, Liver and axilla of nude mice. The tumor bearing mice were treated with VEGFR TKIs for one hour. Cy7-labeled HVGGSSV peptide was injected intravenously 4 hours after treatment. The peptide binding (relative radiance) was correlated to tumor response (tumor volume fold change). mice were treated with SU11248 doses of 0, 4 or 40 mg/Kg daily for 14 days. Tumor volumes were measured by use of calipers. Peptide was imaged by use of near infrared (NIR) using Xenogen IVIS. Results: HVGGSSV peptide binding was not detected in untreated tumors. Tumors treated with TKIs showed NIR imaging of peptide binding within 24 hours of injection. The NIR images show Cy7 labeled peptide binding within treated tumors but no binding to untreated control tumors. All tumors showed significant increase in radiance compared to untreated controls (p<0.05). The sensitivity of detecting responsive tumors was 40 out of 42 responding mouse tumors detected by HVGGSSV radiance. In comparison, 0 of 26 non-responding or untreated tumors showed increased peptide radiance within tumors (p<0.001). To determine whether radiance from peptide binding in tumors correlated with tumor response, we studied the dose-dependent response to SU11248 in MDA-MB231. Tumors responded to high dose treatment (40 mg/kg SU11248), but not 4 mg/kg, when treated with SU11248 alone. After the first treatment, Cy7-labeled peptide was injected intravenously into tumor-bearing mice. NIR images were captured and radiance from peptide binding in tumors was measured. A linear correlation (R2=0.8684) was found for peptide binding and tumor response to treatment. Conclusions: Rapid noninvasive assessment of cancer response promises to speed drug development and minimize the duration of treatment with ineffective regimens in cancer patients. No significant financial relationships to disclose.