tbuckley/cabot-search huggingface dataset:
Single immediate preoperative intravesical instillation of electromotive mitomycin-C for low risk superficial bladder cancer: A prospective randomized study
Authors: S. M. Di Stasi, L. Storti, A. Giurioli, M. Brausi, M. Sciarra, G. Zampa
Journal: Journal of Clinical Oncology (2008)

5027 Background: To evaluate and compare the results of electromotive mitomycin-C (MMC) instillation administered before transurethral resection (TUR) with TUR alone or TUR plus single immediate MMC instillation on recurrence rate and time to first recurrence in patients with pTa bladder tumors. Methods: From 1994 to 2002, 167 patients with stage pTa and grade G1-G2 primary bladder tumors entered the study and were randomized to receive: TUR alone (Group-1; n=57), TUR plus one single immediate MMC 40 mg passive diffusion instillation with a dwell time of 60 minutes (Group-2; n=56) and one single immediate electromotive MMC 40 mg instillation with 20 mA electric current for 30 minutes before TUR soon after the induction of anesthesia (Group-3; n=54). All the patients were followed with ultrasound, urinary citology and cystoscopy. Clinical analyses were performed on an intent to treat basis. Results: During a median followup of 84.7 months (IQR 56.6) there was recurrence in 88/167 patients (52.7%), including 38/57 (66.7%) in Group-1, 30/56 (53.6%) in Group- 2 and 20/54 (37%) in Group-3 (p=0.007). In 58 patients with grade G1 tumors, 11 (19.0%) had recurrence, 6/20 (30%) in Group-1, 4/24 (20%) in Group-2 and 1/18 (5.6%) in Group-3 (p=0.157). In 109 patients with grade G2 tumors, 77 (70.6%) had recurrence, 32/37 (86.5%) in Group-1, 26/36 (72.2%) in Group-2 and 19/36 (52.8%) in Group-3 (p=0.007). In 71 patients with single tumors, 26 (36.6%) had recurrence, 12/24 (50%) in Group- 1, 9/24 (37.5%) in Group-2 and 5/23 (21.7%) in Group-3 (p=0.132). In 96 patients with multiple tumors 62 (64.6%) had recurrence, 26/33 (78.8%) in Group-1, 21/32 (65.6%) in Group 2 and 15/31 (48.4%) in Group-3 (p=0.039). Median time to first recurrence was 12.8 months for the Group-1, 14.7 months for the Group-2 and 36.8 for Group-3 (p=0.009). Irritative bladder symptoms were the most frequent side effects occurring in approximately 15% of patients in Group-2. Conclusions: In patients with single or multiple pTa bladder tumors one immediate preoperative intravesical instillation of electromotive MMC significantly decreases the risk of recurrence compared with TUR alone or with one immediate postoperative instillation of passive diffusion MMC. No significant financial relationships to disclose.
Retrospective analysis of treatment effects and prognostic factors associated with overall survival in patients with resected adenocarcinoma of the pancreas.
Authors: Dai Chu Nguyen Luu, Xiaobai Li, Julia Ojcius, Peter Muscarella, Edwin Christopher Ellison, Lavina Malhotra, Mark Bloomston, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2012)

359 Background: The role of adjuvant chemotherapy in pancreas cancer has been well established. The role of radiation therapy however remains controversial. The ESPAC-1 study showed a possible deleterious effect for radiation on survival of patients with resected pancreas cancer, although the study was limited by lack of compliance and quality control. Methods: We performed a retrospective analysis of patients who underwent curative resection of their cancer of the pancreas over the last 2 decades at the Ohio State University. 333 patients with adenocarcinoma of the pancreas were identified from our database and 148 subjects were found with complete treatment information available. Thirty patients had no treatment after resection. Log-rank test was used to compare the overall survival (OS) of two groups of patients: treated with chemotherapy (C, N=68) or fluoropyrimidine-based chemoradiation (CRT, N=50). Demographics of the CT and CRT groups were balanced. Patient characteristics including age, sex, tumor size, tumor location, tumor grade, nodal status, margins (R0 vs. R1) and number of hospitalizations within a six-month period of discharge from the hospital after surgery were compared across all groups. The effect of these variables on OS was assessed using log-rank test. Results: The mOS for C (21.5 months, 95% CI; 13.5, 24.6) and CRT (16.8 months, 95% CI; 13.9, 23.1) were similar. There was no statistically significant difference observed for C vs. CRT (p&gt;0.8). Out of all the characteristic variables tested (N= 148), only the presence of at least one positive lymph node vs. none had a statistically significant negative effect on survival (mOS of 12.20 months vs. 23.10 months; p=0.0053). Conclusions: In patients with resected adenocarcinoma of the pancreas, the addition of radiation does not seem to add benefit. The presence of positive lymph nodes is an adverse prognostic factor on overall survival.
Final results of a phase II study of sunitinib in patients (pts) with relapsed or refractory urothelial carcinoma (UC)
Authors: D. J. Gallagher, M. I. Milowsky, S. R. Gerst, A. Iasonos, M. G. Boyle, A. Trout, J. Riches, D. F. Bajorin
Journal: Journal of Clinical Oncology (2008)

5082 Background: Second-line chemotherapy has limited activity in advanced UC. Preclinical evidence demonstrates a role for angiogenesis in UC growth thus supporting this study of the novel VEGF targeted agent, sunitinib, in pts with UC. Methods: The primary objectives of this single institution phase II trial of sunitinib in pts with UC who have failed prior chemotherapy were: 1) to determine the response rate (by RECIST); and 2) to evaluate toxicity. Prior therapy was restricted to ≤ 4 chemotherapy drugs. Pts received sunitinib in 6 week cycles 50 mg orally daily (4 weeks on / 2 weeks off). Response was assessed after each of the initial 4 cycles and every other cycle thereafter. A Simon 2-stage design was used with stage 2 requiring a maximal accrual of 41 evaluable pts. Results: 45 pts (32 male, 13 female) with median age of 64 yrs (39–82) and median KPS of 80 (60–90) were enrolled between 9/15/06 and 9/25/07. Primary sites included bladder (28 pts), ureter/renal pelvis (16 pts) and urethra (1). Prior therapy included 19 pts with 2 drugs, 14 with 3 and 12 with 4. 33 pts had visceral metastases and 12 pts had only lymph node metastases. 41 pts were evaluable for response after completing at least 1 cycle; 4 pts discontinued treatment due to toxicity in cycle 1. One pt experienced a treatment-related death. 3 patients achieved PR and 1 additional pt had > 30% reduction but other scans showed 28% reduction. 11 pts had SD, 24 had PD and 3 are too early (SD after cycle 1 but no confirmatory scans). Radiographic regression was observed in liver, lung, bone, bladder, soft tissue and lymph node lesions. Clinically significant toxicity (Grade 3/4) included: abdominal pain (1 pt), anorexia (1), diarrhea (1), fatigue (4), hand and foot syndrome (2), hemorrhage (2), hypertension (2), mucositis (2), skin ulceration (1), thrombosis (2), and emesis (1). Conclusion: Sunitinib has single agent activity in pts with advanced urothelial cancer. Accrual at this dose and schedule is complete; time to progression, duration of response, and survival data are pending. Tumor analysis of phospho-S6, phospho-4E BP1, HIF-1 alpha and VEGF R2 are ongoing to attempt to correlate expression with response. The trial is also being extended with another cohort of pts treated with continuous daily dosing at 37.5 mg. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, GPC biotech Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer
Incidence and risk factors of cetuximab-induced hypersensitivity infusion reactions (HIRs).
Authors: S. Hopps, E. Borders, P. Medina, M. Moorman, R. Webb, C. Kurkjian, S. Pant
Journal: Journal of Clinical Oncology (2011)

e19531 Background: The reported national incidence of grade 3/4 hypersensitivity infusion reactions (HIRs) with cetuximab is approximately 3%. The purpose of this study is to estimate the incidence of HIRs at the University of Oklahoma and to identify risk factors for developing HIRs. Methods: This is a retrospective chart review of patients who received cetuximab at the University of Oklahoma from July 2005 to August 2010. The incidence proportion of HIRs in this population was calculated. A reverse step-wise poisson regression analysis was performed on all factors with a bivariate analysis alpha value ≤0.2 and any logical interaction term. The outcome variable for all analyses was either HIR or severe HIR (defined as reaction grade 3 or 4 per CTCAE v.4.03). An alpha value of 0.05 was considered significant. Results: In the specified time period, 153 patients were identified that received cetuximab. Head and neck (50.33%) and cervical cancer (37.25%) were the most common malignancies. Other malignancies included non-small cell lung cancer, colorectal cancer, and ovarian cancer. The overall incidence proportion of severe HIRs was 12.42%. The incidence of severe HIRs in patients with head and neck cancer was 18.18% and the incidence in patients with cervical cancer was 5.26%. The incidence of HIRs in patients with cervical cancer was significantly less than all other malignancies combined (p = 0.0387). According to poisson regression, the risk factors most strongly associated with HIRs included current smoking (RR = 3.6, p=0.0093) and receiving cetuximab as a single agent (RR = 3.2, p=0.0391), after adjusting for cancer type. Conclusions: Regionally, there is an increased incidence of severe HIRs as compared to the national average. Interestingly, the incidence of cervical cancer was significantly lower than head and neck cancer and other malignancies in patients receiving cetuximab. To our knowledge, the incidence of HIRs in patients with cervical cancer has not been reported. Additional risk factors associated with higher incidence of HIRs included current smokers and use of single agent cetuximab. Further investigation is warranted to better predict who is a risk for cetuximab-induced hypersensitivity reactions.
FGFR1, a new FISH biomarker, to predict recurrence of prostate cancer after prostatectomy.
Authors: Ying Zhang, Jing Du, Ping Liu, Lela Buckingham, Tracey Colpitts, Ekaterina Pestova
Journal: Journal of Clinical Oncology (2015)

100 Background: To identify prostate cancer (CaP) with high recurrence risk after Radical Prostatectomy (RP) is a challenge. FGFR1 (Fibroblast Growth Factor Receptor 1) plays a critical role in prostate development and tumorigenesis. In this study, we explored the possibility of using FGFR1 fluorescence in situ hybridization (FISH) to predict recurrence after RP in the Formalin fixed paraffin embedded (FFPE) tissue from CaP patients. Methods: FFPE histological specimens from 52 RP cases were evaluated with FGFR1 (8p12) / CEP 8 probe mix. While 32 of the 52 patients recurred within 5 years (PSA progression or death of disease), and 20 remained disease-free with 8 to 15 years. Median age of patients was 62 with Gleason Score range from 4 to 9. Percent of FGFR1 gain and FGFR1 loss per specimen, as well as mean number of FGFR1 signals per specimen were calculated. CEP8 was used as a control to assess hybridization quality. Statistical analysis (Cox Proportional Hazards model) was conducted using SAS 9.2. Results: Survival analysis demonstrated that percent FGFR1 loss in a specimen could identify recurrent CaP with the Harzard Ratio (HR) of 3.34 (p=0.0011), which indicated that the risk of recurrence for FGFR1 loss-positive group is 3.34 times than that for FGFR1 loss-negative group. On the other hand, survival analysis of the percent FGFR1 gain showed that FGFR1 gain (amplification) is favorable for survival with HR of 0.36 (p=0.0043), which indicated that the risk of recurrence for FGFR1 gain-positive group is 0.36 times than that for FGFR1 gain-negative group. By using mean FGFR1 signals per specimen in the Kaplan-Meier analysis, the patient specimens stratified into three distinct groups (overall logrank p=0.0011): normal for FGFR1, FGFR1 gain (more favorable outcome), and FGFR1 loss (highest risk of recurrence). Conclusions: This study shows the utility of FGFR1 copy number abnormalities in CaP. Our results indicate that gain and loss of FGFR1 may have a different effect on disease recurrence. Therefore, FGFR1 FISH may provide predictive value for CaP recurrence in post RP patients, either by itself, or as an adjunct to the currently clinical prognostic indicators.
Installing FVIII-Specific Tolerance in Hemophilia Via Engagement of the Aryl Hydrocarbon Receptor By Tryptophan Derivatives
Authors: Davide Matino, Marco Gargaro, Giulia Scalisi, Antonella Turco, Francisco Javier Quintana, Paolo Puccetti, Alfonso Iorio, Francesca Fallarino
Journal: Blood (2016)
A first-in-human phase I clinical trial of CXR1002 in patients (pts) with advanced cancer.
Authors: I. R. MacPherson, D. Bissett, R. D. Petty, B. Tait, L. M. Samuel, J. MacDonald, M. Smith, J. A. Birse-Archbold, A. L. Barnett, C. R. Wolf, C. R. Elcombe, A. Jeynes-Ellis, T. R. J. Evans
Journal: Journal of Clinical Oncology (2011)

3063 Background: CXR1002, an ammonium salt of perfluorooctanoic acid, is a lipid mimetic that causes ER stress and inhibits PIM kinases. Aims of this study were to assess the tolerability, safety and pharmacokinetics (PK) and to identify the recommended phase II dose (RP2D) of CXR1002 administered orally once weekly. Methods: Sequential cohorts of pts with advanced refractory solid tumors were enrolled. Cohort 1 received a single dose of CXR1002 followed by once weekly dosing commenced 6 weeks (wks) later. Subsequent cohorts received CXR1002 once wkly. Dose escalation followed a standard 3+3 design until dose-limiting toxicity (DLT) was observed in ≥ 2/6 pts. Plasma levels of CXR1002 were determined by LC-MS/MS at the following time-points: pre-dose, 2, 3, 4, 24 hours post-dose for the first 6 wks then 6 wkly. Exploratory PD analyses included: serum leptin; plasma lipids, glucose and insulin. Results: 41 pts have been enrolled (23M / 18F); median age 63 (range 36-75); PS < 2; colorectal (n=16); pancreatic (n=5); other (n=20). CXR1002 was administered at 10 dose levels [mg (pts entered/evaluable)]: 50 (4/3), 100 (3/3), 200 (3/3), 300 (4/3), 450 (3/3), 600 (8/6), 750 (3/3), 950 (4/3), 1000 (3/3), 1200 (6/6). Median duration of therapy was 6.5 wks (range 0-40). DLT (grade 5 renal failure / grade 4 transaminitis; possibly drug-related) occurred in 1 pt at the 600mg dose. Protocol-defined MTD was not reached and the RP2D of 1,000mg wkly was based on tolerability of common cumulative drug-related toxicities, primarily: fatigue, nausea, vomiting, and diarrhea. Cmax was reached 1.5 hours after administration of a single dose of CXR1002 and maintained at a constant level over a 6 wk sampling period. CXR1002 was cumulative with wkly dosing with increased exposure seen with increasing dose level and duration. Reductions in LDL-cholesterol consistent with a PD effect were observed. Stable disease >12 wks was observed in 8 pts including pts with anaplastic thyroid (40 wks), pancreatic (35 wks), and cervical cancer (34 wks). Conclusions: The RP2D of CXR1002 when administered orally once wkly is 1,000mg. An expansion phase at this dose level will investigate biomarkers of PIM kinase inhibition. CXR1002 exhibits unusual PK with an extremely long t1/2.
Prognostic factors in patients with bulky stage Ib or II cervical carcinoma undergoing neoadjuvant chemotherapy and radical hysterectomy
Authors: K. Takehara, Y. Kawakami, M. Egawa, M. Hanaoka, O. Samura, M. Kumagai, T. Mizunoe, F. Saji
Journal: Journal of Clinical Oncology (2008)

16548 Background: The purpose of this study was to investigate the prognostic factors in patients with bulky stage Ib or IIb cervical carcinoma undergoing neoadjuvant chemotherapy and radical hysterectomy. Methods: All the patients with bulky (≥4 cm) stage Ib or II cervical carcinoma were treated at Kure Medical Center from 1993 to 2004, using a strategy of neoadjuvant chemotherapy, which regimen is PIP (Carboplatin, Ifosfamide, Peplomycin), BOMP (Bleomycin, Vincristine, Mitomycin, Cisplatin) or CPT-11+MMC (Irinotecan hydrochloride, Mitomycin). Twenty-two patients underwent one to four courses of chemotherapy, and all patients subsequently underwent radical hysterectomy.Prognostic factors were examined for age, histologic type, stage, tumor size, SCC value, courses of chemotherapy, pelvic lymph node metastasis and post-operative pathological findings. Clinical responsiveness to chemotherapy was evaluated according to the World Health Organization criteria. Logrank test was used to identify predictors for outcome. Results: Pre-chemotherapy MRI confirmed that the tumor size was >4 cm in all cases. The tumor-size was reduced by NAC by an average of 51.0%. The overall clinical response rate was 77.3% (17/22) with 4.6% completely responsive (CR) and 72.7% partially responsive (PR). Histologically proven pelvic node metastasis was noted in 31.8% (7/22). Ten cases underwent postoperative radiotherapy. Six cases exhibited recurrence during subsequent observation. The 5-year survival rate of the patients was 68.0%. Among the variables that could be assessed before treatment, clinical stage, tumor size, histologic type, Pretreatment SCC, course of chemotherapy and lymph node swelling were independent predictor of clinical response. Postoperative lymph node metastasis was only the prognostic factor for decreased survival in pre- and post-operative factors. Conclusions: Even if surgical resection is performed after NAC, cases with pelvic lymph node metastases exhibit significantly poorer prognosis. No significant financial relationships to disclose.
New conditions identified through a comprehensive geriatric assessment in cancer patients.
Authors: Beatrice Jara-Almonte Edwards, Holly Michelle Holmes, Heather Valladarez, Ming Sun, Peter Khalil, Vu Nguyen, Juhee Song
Journal: Journal of Clinical Oncology (2016)

133 Background: Chronologic age cannot be used to predict the degree of comorbidity and of functional deterioration of older adults. Assessment of older adults includes health, functional status, nutrition, cognition, socio-economic and mood disorders evaluations. This multidisciplinary assessment is referred to as comprehensive geriatric assessment (CGA). The risk of comorbid conditions increases with age and may result in under diagnosis: in older patients, new symptoms may not be clearly recognized by the patient and may be dismissed by practitioners as manifestations of preexisting conditions. Methods: We conducted a retrospective cohort analysis, of older adult patients (aged 70 years of age and older) evaluated at the Program for Healthy Aging at MD Anderson from January 1, 2013 through December 31, 2014. Assessment was conducted using Katz’ ADLs, Lawton’s IADLs, PHQ-9, the short physical performance battery, the Montreal cognitive assessment, mini nutritional assessment and Charlson co-morbidity index. Medication review and social assessment were also included. Analysis: cross tabulations were performed in SAS 9.4 (SAS Institute INC, Cary, NC) Results: We evaluated 198 patients, (n = 99, 51.6% females). Most common malignancies evaluated included hematologic malignancies (n = 62, 33%), breast cancer (n = 32, 13.2 %), prostate cancer (n = 19, 10 %) and other solid malignancies (n = 85, 43%). The comprehensive geriatric assessment identified a mean of 3 new conditions (range 1-10). The most commonly identified conditions included cognitive impairment and dementia (n = 148, 77%), low bone mass and osteoporosis (n = 67, 34%), malnutrition (n = 65, 34%), frailty (n = 58, 30.2%), and polypharmacy (n = 64, 33%). These conditions are relevant in the management of such patients and could lead to recurring admissions if left unaddressed. Conclusions: A CGA program in a cancer center allows for the identification of medical conditions that directly contribute to clinical outcomes. A CGA allows for the development of a comprehensive plan of care that addresses such issues preventing adverse consequences.
Surgical management for local retroperitoneal recurrence after radical nephrectomy in the targeted therapy era.
Authors: Arun Z. Thomas, Mehrad Adibi, Leonardo Borregales, Ly N Hoang, Pheroze Tamboli, Surena F. Matin, Jose A. Karam, Christopher G. Wood
Journal: Journal of Clinical Oncology (2015)

431 Background: Isolated local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) for renal cell carcinoma (RCC) poses a therapeutic challenge. We examined the role of aggressive surgical resection of localized RPR in the modern era of targeted therapy for metastatic RCC. Methods: We retrospectively reviewed clinico-pathological data of patients from our RCC database from 2004-2014. We identified 67 patients with localized RPR after radical nephrectomy (RN) who underwent surgical resection. We assessed patient demographics, clinical and pathological features, location of RPR, perioperative complications and outcomes, recurrence free, cancer-specific and overall survival. Results: Median follow up after RPR resection was 33 months (range 3-120). Median recurrence free survival after RPR was 20 months (range 1-120). One, 3 and 5-year cancer specific survival was 95% 77% and 50%, respectively. Neoadjuvant and salvage targeted therapy were administered in 29 (43.3%) and 28 (41.8%) patients, respectively. Multivariate analysis identified that pathological tumor stage and nodal stage at nephrectomy, maximum diameter of RPR mass and abnormal lactate dehydrogenase levels were associated with an increased risk of cancer specific death. Patients with 0, 1, and greater than 1 adverse risk factors demonstrated cancer specific survival of 100%, 74%, 50% at 3 years and 100%, 57%, 19% at 5 years. Conclusions: This study is the largest series of patients to undergo RPR resection in the targeted therapy era. We found that clinic-pathological factors at the time of nephrectomy as well as RPR resection are important prognosticators. Aggressive surgical resection offers potential cure in a substantial number of patients with RPR.