tbuckley/cabot-search huggingface dataset:
Long term survival following cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for disseminated appendiceal tumors
Authors: Y. Baraki, P. N. Kostuik, B. Merriman, C. Nieroda, A. Sardi
Journal: Journal of Clinical Oncology (2006)

4128 Background: Appendiceal tumors represent 2.8% of gastrointestinal tumors and less than 0.5% of gastrointestinal malignancies, but frequently involve intraperitoneal spread. Controversial treatment of disseminated tumor has consisted of extensive debulking surgery, peritonectomy, and intraperitoneal chemotherapy. We evaluated the disease free and overall survival, morbidity and mortality of patients with disseminated appendiceal tumors treated by cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (IPHC). Methods: A retrospective review of a prospective database was performed between 1999 and 2005. Thirty-one patients underwent CRS followed by IPHC using mitomycin 40 mg infused over 90 minutes at 40–42°C. Patients were given a Peritoneal Carcinomatosis Index (PCI) score pre and post operatively. Postoperatively, patients were assigned cytoreductive scores, indicating completeness of resection: CC-0 = no residual disease, CC-1 ≤ 0.25 cm, CC-2 = 0.25–2.5 cm, CC-3 ≥ 2.5 cm. Cox proportional-hazards models were used to test the influence of different variables on survival. The models were adjusted for age, grade of differentiation, histology and cytoreductive score. Results: There were 14 females and 17 males with a mean age 50 years (range 33–80). Two-thirds of all patients had a preoperative PCI score of &gt;20. The overall survival at 1 year was 96% (95% CI, 74% to 99%) and at 3 years was 69% (95% CI, 38% to 86%). Disease free survival at 3 years was 30% ( 95% CI, 8% to 56%). There was no mortality from the procedure. Overall morbidity, including Grades 1–5 as described by the CTCAE guidelines, was 48%. A multivariate analysis was performed for grade of differentiation and was not found to be statistically significant. However, log rank test for equality of survivor functions in patients with CC scores of 0 or 1 experience recurrence of disease at a slower rate than patients with scores of 2 or 3 (p &lt; 0.001). Conclusions: Although further study is necessary, Cytoreductive surgery followed by IPHC, where a low PCI score and a CC score of ≤1 is achieved, can lead to increased survival for selected patients having advanced appendiceal cancer with peritoneal dissemination. No significant financial relationships to disclose.
Phase I study of intraperitoneal (IP) epinephrine in association with IP cisplatin in recurrent peritoneal carcinomatosis
Authors: C. Molucon-Chabrot, L. Benoit, S. Zanetta, J. Fraisse, P. Fargeot, N. Isambert, P. Monin-Baroille, M. Flesch, B. Coudert, B. Chauffert
Journal: Journal of Clinical Oncology (2004)

5049 Background: IP epinephrine (EPI) has been shown to enhance the accumulation and antitumor activity of IP cisplatin (CDDP) in rats with peritoneal carcinomatosis (Duvillard et al., Int J Cancer, 1999). EPI activity was related to the vasoconstriction of the peritoneal vascular bed which limits CDDP peritoneal leakage and enhances drug penetration into tumor nodules. A phase I study was conducted to evaluate the local and systemic tolerance of IP EPI in association with IP CDDP. Methods: Between 02/2000 to 06/2003, 17 patients (pts) with refractory peritoneal carcinomatosis (15 ovarian, 1 colorectal, 1 mesothelioma; 1 M/16 F), median age of 64 years (range 52–77), PS 0–1, and normal organ and cardiovascular function were enrolled. CDDP (total dose of 100 or 120 mg), associated with increasing concentrations of EPI, was given intraperitoneally in 2 or 3 liters of saline solution over 3 hours. Plasma and peritoneal concentrations of EPI were determined by HPLC. Results: A total of 52 intraperitoneal courses were performed. EPI was escalated at the following concentrations: 1 mg/L (24 courses), 2 mg/L (12), 3 mg/L (11), 4 mg/L (2) or 5 mg/L (3). Dose-limiting cardiovascular toxicity [systolic blood pressure ≥ 190 mm Hg (4 cases), tachycardy ≥ 120/min (6), or ventricular extrasystoles ≥ 2/min (2)] was encountered at all EPI levels, but was rapidly reversible after the transitory cessation of the IP infusion. An episode of non-complicated angina pectoris lead to the definitive withdrawal of treatment in one patient. A moderate and transitory increase of serum creatinine (1.6 and 1.9 mg/dL) was registered in 2 pts. No hematological toxicity occurred. Abdominal pain was the most frequent side effect (30 grade III, 8 grade IV). Nausea and vomiting were moderate (16 grade II). Clinical or biological responses were recorded in 8/17 pts. Conclusions: The combination of IP epinephrine with IP cisplatin is feasible and potentially efficient in refractory peritoneal carcinomatosis. A 3 mg/L epinephrine concentration which results in an optimal cisplatin accumulation in rat tumor nodules is often reached with few side effects in humans. No significant financial relationships to disclose.
Tumor microsatellite-instability status to predict benefit of adjuvant chemotherapy for stage III colon cancer
Authors: G. J. Chang, K. Y. Lee, C. Eng, K. M. Kattepogu, S. Richey, J. M. Skibber, M. A. Rodriguez-Bigas, S. R. Hamilton
Journal: Journal of Clinical Oncology (2007)

4046 Background: Microsatellite instability (MSI) is an alternative pathway to colon cancer pathogenesis and may be categorized by the degree of MSI exhibited as MSI-high (MSI-H), MSI-low (MSI-L) or microsatellite stable (MSS). The aim of this study was to determine the prognostic impact MSI status on survival in stage III colon cancer. Methods: A total of 197 patients who received curative resection of stage III colon cancer from 1991 through 2002 were identified. Records of these patients were retrospectively evaluated to determine chemotherapy (CTx) use and vital status. DNA extracted from paraffin embedded tumor specimens was amplified by polymerase chain reaction using a panel of 7 markers. MSI-H was defined as instability in &gt;40% of markers and low as instability in &gt;0% but &lt;40% of markers. Overall survival based on MSI and CTx status was compared using Kaplan-Meier analysis and the log-rank test and Cox multiple regression to adjust for covariates. Results: Median follow-up was 5.4 years. There were 25 (13%) MSI-H, 38 (19%) MSI-L and 134 (68%) MSS patients. Median age was 56 years (MSI-H), 65 years (MSI-L) and 62 years (MSS). 5-fluorouracil adjuvant CTx was completed in 135 (69%), not completed in 36 (18%) and unknown in 26 (13%) patients. Tumors were left sided in 56% of the cohort, 72% among MSI-H, 60% among MSI-L, 51% among MSS. 5-year overall survival after adjuvant CTx ranged 71–82% and was not significantly different among the groups. Completion of CTx improved survival among MSS, HR 0.18 (95% confidence [CI] 0.07–0.42, p&lt;0.0001), but not among MSI- H, HR 0.83 (95% CI 0.19–3.60, p=0.79), with an intermediate effect among MSI-L, HR 0.36 (95% CI 0.09–1.47, p=0.0562). The effect of completing adjuvant CTx persisted after adjustment for age, sex, stage (IIIA, B, C), and histology, RR 0.19 (95% CI 0.089–0.41, p&lt;0.0001), RR 0.059 (95% CI 0.009–0.39, p=0.003), RR 0.26 (95% CI 0.01–13.3, p=0.31) for MSS, MSI-L, and MSI-H, respectively. Conclusions: 5-fluorouracil based adjuvant chemotherapy did not affect overall survival in patients with stage III colon cancer who are MSI-H due to a high baseline survival rate without adjuvant therapy. Adjuvant chemotherapy did improve survival in patients who are MSS and an intermediate effect was seen in paitents who are MSI-L. No significant financial relationships to disclose.
Abstract P041: Functional Status Modifies Treatment Effectiveness in the Systolic Hypertension in the Elderly Program Trial
Authors: Michelle C Odden, Christina Charlesworth, Carmen Peralta
Journal: Circulation (2014)

Introduction: We have previously demonstrated that high blood pressure is not associated with mortality in elders with impairments in functional status. Whether functional status modifies the effectiveness of treatment to lower blood pressure is not known. Methods: The Systolic Hypertension in the Elderly Program (SHEP) was a multicenter, randomized, double-blind, placebo-controlled trial of 4,736 adults aged 60 and older with isolated systolic hypertension. Participants were randomized to chlorthalidone +/- atenolol or reserpine or matching placebo and followed for an average of 4.5 years. Functional limitation was assessed by the self-reported inability to do any one of the following activities: i) heavy work around the house, ii) walk up and down stairs, or iii) walk a half a mile. Analyses were conducted by intention-to-treat within the post-hoc subgroups. Results: There was a pattern of effect modification by functional limitation, where the association of active treatment was attenuated or inverted in persons with functional limitation compared with those without (Table). The interaction of treatment and functional limitation was strongest for the outcomes of myocardial infarction: hazard ratio = 0.57 (95% confidence interval (CI): 0.40, 0.81) and 1.33 (95% CI: 0.57, 3.07) in persons without and with functional limitation, respectively; and for mortality: 0.78 (95% CI: 0.66, 1.01) and 1.27 (95% CI: 0.83, 1.95) in persons without and with functional limitation, respectively. Conclusions: Antihypertensive therapy appears less effective in persons with self-reported functional limitation. More evidence is needed to guide optimal blood pressure control in elderly adults with functional limitation.
Early (<sup>18</sup>F) fluoro-2-deoxy-D-glucose positron emission tomography/computerized tomography (PET/CT) imaging as a tool for response assessment in T-cell non-Hodgkin’s lymphoma (TCL): An update to a phase II study of HCVIDD alternated with methotrexate (MTX) and cytarabine (Ara-C)
Authors: J. L. Cultrera, R. F. Nunez, J. E. Romaguera, F. B. Hagemeister, M. A. Rodriguez, L. E. Fayad, B. Pro
Journal: Journal of Clinical Oncology (2008)

8538 Background: TCLs have a worse prognosis than their B-cell counterparts. Despite the information available regarding PET/CT in B-cell lymphomas, there is virtually no data for its role in TCL. In this study we evaluated the utility of using PET/CT imaging during induction therapy as a predictor of progression free survival (PFS). Methods: From October 2003 to July 2007, 41 patients were enrolled in a phase II study examining the efficacy of HCVIDD (therapy consisted of using pegylated liposomal doxorubicin on day 2 as a substitute for adriamycin in the HyperCVAD regimen - cyclophosphamide, vincristine, adriamycin, dexamethasone) alternated with MTX and Ara-C in TCL patients (pts). Pts were evaluated with PET/CT from 3 weeks prior to induction treatment, after 2–4 cycles, and at 6–8 cycles. Four pts were removed from study due to intolerance and received the standard CHOP regimen. Median age of the patients was 54 (23–71), 85% were stage III/IV while only 6 patients were stage I/II. Sixty percent had extranodal involvement and 29% presented with bone marrow involvement. A median of 4 cycles were delivered with eight pts excluded from analysis due to insufficient imaging or treatment. Results: At cycles 2–4 PET/CT imaging was considered negative in 25 of 33 evaluable pts. Of those 25, 15 pts (60%) relapsed with a progression free survival of 222 days. There were 8 pts in the PET/CT positive cohort all of which developed progression of disease (median PFS = 92 days) except for 1 who developed a CR as of last visit after 6 cycles. Log-rank analysis demonstrates no difference between either the PET/CT positive or negative set (p=0.256). Conclusions: It is evident that PET/CT may not be a useful predictor of a durable response in T-cell lymphoma. Patients with PET/CT imaging indicating CR at 2 or 4 cycles are likely to relapse before 8 months. In short, unlike in B-cell lymphomas, PET/CT is not a useful tool for response assessment to chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ortho Biotech
Biofilm Formation by <i>Mycobacterium abscessus</i> in a Lung Cavity
Authors: Kevin P. Fennelly, Carolyn Ojano-Dirain, Qingping Yang, Lin Liu, Li Lu, Ann Progulske-Fox, Gary P. Wang, Patrick Antonelli, Gregory Schultz
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Biofilm Formation by Mycobacterium abscessus in a Lung Cavity Kevin P. Fennelly, Carolyn Ojano-Dirain, Qingping Yang, Lin Liu, Li Lu, Ann Progulske-Fox, Gary P. Wang, Patrick Antonelli, and Gregory Schultz Department of Medicine, Emerging Pathogens Institute, Department of Otolaryngology, Institute for Wound Research, and Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, and Center for Molecular Microbiology, Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida; and Medical Service, North Florida/South Georgia Veterans Health System, Gainesville, Florida
The role of FLT3 in sole trisomy 8 acute myeloid leukemia.
Authors: A. W. Block, A. E. Groman, G. E. Wilding, L. Ford, S. N. Sait, G. Deeb, P. Starostik, E. S. Wang, J. E. Thompson, M. Wetzler
Journal: Journal of Clinical Oncology (2010)

6562 Background: FLT3 (fms-related tyrosine kinase 3) with internal tandem duplication (ITD) is a known adverse prognostic factor in normal karyotype acute myeloid leukemia (AML). We asked whether FLT3 ITD carries any prognostic significance in sole trisomy 8 AML. Methods: A total of 37 AML patients (25 males:12 females) with sole trisomy 8 were seen at Roswell Park Cancer Institute between 1991 and 2008. Treatment differed according to available protocols at the time. Results: Nucleophosmin (NPM1) was detected in only one case (FLT3 ITD/D835 negative). Interestingly, FLT3 D835 was detected in five (20%) of the 25 patients without FLT3 ITD but was not detected in any of the 7 FLT3 ITD- positive patients. A total of 22 (59%) patients achieved complete remission (CR). There was no difference in achievement of CR, overall or disease-free survival between trisomy 8 patients with or without FLT3 ITD. Of interest, patients with FLT3 ITD were significantly younger (mean: 50 year old; 95% confidence interval [CI]: 33.51, 66.49) compared to patients without FLT3 ITD (mean: 69.8 year old; 95% CI: 65.87, 73.73) (p = 0.006). In addition, patients with FLT3 ITD were less likely to have normal metaphases in their karyotype than patients without FLT3 ITD (86.7% [95% CI: 0.693, 0.963] vs. 42.8% [95% CI: 0.099, 0.816]; p = 0.027). Conclusions: The presence of FLT3 ITD in trisomy 8 AML was associated with younger age and presence of trisomy 8 in all analyzed metaphases when compared to those without FLT3 ITD. AML patients with trisomy 8 and FLT3 ITD had similar CR, overall and progression-free survival as those without FLT3 ITD. No significant financial relationships to disclose.
Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation.
Authors: T E Goffman, L J Dachowski, H Bobo, E H Oldfield, S M Steinberg, J Cook, J B Mitchell, D Katz, R Smith, E Glatstein
Journal: Journal of Clinical Oncology (1992)

PURPOSE We report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd). METHODS For a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow-up) or until death. RESULTS The results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation. CONCLUSION The failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM.
Successful Treatment of Tuberculosis in Renal Transplant Recipients<sup>1</sup>
Authors: T J Bell, Grant B Williams
Journal: Journal of the Royal Society of Medicine (1978)

Tuberculosis is a rare and usually fatal complication of renal transplantation. From 82 transplants in seven years, 4 cases of tuberculosis are reported. All have been treated successfully, with no fatalities or deterioration in renal function.
Phase II study of vinorelbine (VRL) alternating i.v. and oral in combination with docetaxel (DTX) as 1<sup>st</sup> line chemotherapy (CT) of metastatic breast cancer (MBC)
Authors: M. Blasinska Moriawiec, M. Ułańska, O. Zambrano Quispe, P. Koralewski, A. Tekiela, E. Chmielowska, B. Longerey, S. Lafaye de Micheaux
Journal: Journal of Clinical Oncology (2005)

783 Background: VRL and DTX are targeting tubulin-microtubule system, either inhibiting tubulin polymerisation (VRL) or microtubule depolymerisation (DTX). Both agents have proven activity in MBC. Methods: This study was designed to evaluate the efficacy and the tolerance of the combination of i.v. VRL 20 mg/m2 with DTX 60 mg/m2 on day 1 and oral VRL 60 mg/m2 on day 15 of a three-week cycle in first line treatment MBC for a maximum of 6 cycles. Prior adjuvant CT was allowed if completed at least 12 months before study entry. At least one bidimensionally measurable lesion (WHO criteria) should be present. Results on the first 23 treated patients are as follows: median age was 56(y), 16 pts (69.6%) had received prior adjuvant chemotherapy, 22 pts (95.7%) had a KPS ≥80%, and 10 pts (43.5%) had ≥3 sites involved. All patients were eligible and evaluable for efficacy. A total of 129 cycles were given (median 6). Median relative dose intensities (RDI) of i.v.VRL and DTX were over 99% and median RDI of oral VRL was 81.6%. Neutropenia was the major side effect: G 4 in 43.5% of pts and 15% of cycles but only complicated in 3 pts: two febrile neutropenia (8.4%) and one neutropenic infection (4.3%). In terms of non haematological related toxicity, the more frequent events reported were mild to moderate fatigue and diarrhoea (21.7% of pts each), stomatitis and weight loss (17.4%). No G4 toxicity was seen. One toxic death occurred due to hypovolemic collapse secondary to inadequately treated G3 vomiting and diarrhoea. Other G3 events were stomatitis and infection with unknown ANC (8.7% each), fatigue and amenorrhea (4.3% each). The combination is highly effective with 14 PR validated by an external panel, yielding a RR of 60.9%[95%CI= 38.5 - 80.3] in the first 23 pts. Recruitment is now completed (44 pts), treatment and follow-up are ongoing. Conclusions: This combination with oral VRL on day 15 avoiding hospitalisation, is highly efficient (RR=60.9%) and safe. VRL iv./oral D1/D15 -DTX D1 every 3-week cycle is an attractive option to combine DTX and VRL in every day practice for MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IRPF
A retrospective comparison of 12 weeks versus 52 weeks of adjuvant interferon for patients with stage IIB, IIC, and IIIA (IIB-IIIA) melanoma (Mel).
Authors: R. J. Sullivan, A. Frankenthaler, W. Wang, V. J. Seery, M. Lee, H. B. Koon, M. B. Atkins
Journal: Journal of Clinical Oncology (2010)

e19013 Background: One year of adjuvant alpha-interferon (HD IFN) treatment is the FDA-approved standard for patients (pts) with stage IIB, IIC, and III Mel. Based on data suggesting that the major benefit of the HD IFN happens early, that the risk of relapse in the era of sentinel lymph node staging is less than previously thought for pts with IIB-IIIA Mel, and that benefit of HD IFN is likely proportionate to risk, we postulated that pts with IIB-IIIA Mel might receive largely equivalent benefit from an abbreviated HD IFN course. Methods: We identified 86 pts with IIB-IIIA Mel who initiated adjuvant IFN at BIDMC from 1/02 to 1/09. Each pt received the standard 4-week (wk) IV HD IFN induction. Pt treated prior to 1/06, received a planned 48 wks sq maitenance IFN (52-wk group), while the others received only 8 wks (12-wk group). The relapse-free and overall survival (RFS and OS) for the 2 groups were compared unadjusted and adjusted for other covariates (age, gender, stage, ulceration, mitosis status, and tumor depth). Results: 37 pts were identified in the 12-wk and 49 in the 52-wk group. Baseline characteristics and outcomes for each group are summarized in the Table. Pts in the 12-wk group were significantly older, more likely stage IIB, and trended toward having Mel with ulceration and/or a higher mitotic rate. Pts with stage IIB and IIIA appeared to have equivalent RFS and OS, while those with stage IIC trended toward worse RFS. There was no difference in OS (p=0.99) or RFS (p=0.41) in the 12-wk versus 52-wk groups adjusted for other covariates. Conclusions: Pts with IIB-IIIA Mel had similar RFS and OS whether treated with 12 wks or 52 wks of adjuvant IFN. These data support the use of an abbreviated course of adjuvant IFN in these intermediate risk pts. Use of this abbreviated course may encourage broader use of adjuvant IFN in this pt population. 12- week (n=37) 52-week (n=49) p value Median age 55 46 0.0007 Gender (M-F) 13-24 25-24 NS Breslow's depth (mean) 4.07 4.32 NS Ulceration (%) 16 (43) 11 (22) 0.063 Mitoses (<1/1/1-5/≥6) 2-3-13-16-1 5-14-14-12 0.078 Stage (IIB-IIC-IIIA) 18-7-12 8-6-35 0.009 RFS @ 1yr/3yr 91/80 98/87 0.41 OS @ 3yr/5yr 100/90 96/88 0.99 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough