tbuckley/cabot-search huggingface dataset:
Phase II study of simultaneous radiochemotherapy (RCT) with cisplatin/etoposide followed by consolidation chemotherapy (CT) with platin/gemcitabine for unresectable non-small cell lung cancer (NSCLC)
Authors: T. H. Fink, W. Melzner, V. Strnad, R. Sauer, C. Albrecht, S. Birkenhake, J. H. Ficker
Journal: Journal of Clinical Oncology (2007)

18103 Background: This phase II study has been conducted to determine the feasibility, toxicity, response rate, local control, distant metastases, and survival of simultaneous RCT (3D conformal radiotherapy with cisplatin/etoposide) followed by consolidation CT with platin/gemcitabine in unresectable NSCLC. Methods: From April 2001 to April 2005, 30 patients with unresectable NSCLC were entered into this trial. All patients had a histological confirmed unresectable non-small cell lung cancer. One patient had stage II, but was functionally unresectable; all other patients had locally advanced NSCLC (IIIA and IIIB). Noncoplanar 3D conformal radiotherapy was given to a total dose of 66.6 Gy (1.4 - 1.8 Gy per day) together with 2 cycles of CT (cisplatin 20 mg/m 2 d1–5, d29–33 plus etoposide 90 mg/m 2 d1–3, d29- 31). After completion of RCT patients received 4 courses of gemcitabine 900 mg/m 2 d1 and d8 with cisplatin 70 mg/m 2 d2 (or carboplatin AUC 5 d1) every 21 days. Results: 27 patients went through RCT, 22 patients received consolidation CT. The predominant hematological toxicity was grade 3/4 leukopenia, reported in 33% of patients during the RCT and 36% during the consolidation CT. One patient showed grade 3 radiation pneumonitis during concurrent RCT. No patient died of treatment related toxicity. The response rate was 83% with 2 CR and 23 PR. With a follow up of 24 months median survival was 17.5 months, 2 year survival rate was 40%. We will present median survival and 3 year survival rate with a follow up of 36 months. Conclusions: The simultaneous RCT with cisplatin/etoposide followed by consolidation CT with platin/gemcitabine is feasible and well tolerated. This study should prompt further investigation in a phase III randomized trial. No significant financial relationships to disclose.
Recombinant scAAV2 Vector-Mediated Ex Vivo Transduction of Primary Human Hematopoietic Stem Cells from a β-Thalassemia Patient and Human β-Globin Gene Expression in a Murine Xenograft Model in Vivo
Authors: Liu-Jiang Song, Xin-Hua Zhang, Jun Zhu, Jue-Lian Wu, Xiao-Ling Yin, Meng-Qun Tan
Journal: Blood (2014)
Impact of pre-operative chemoradiotherapy on post-esophagectomy morbidity and mortality
Authors: N. P. Rizk, M. Bains, R. Flores, B. Park, B. Minsky, D. Ilson, V. Rusch
Journal: Journal of Clinical Oncology (2006)

4025 Background: While multimodality therapy prior to surgical resection for locally advanced esophageal cancer is increasingly utilized, there remains the perception in the literature that its use may contribute to increased peri-operative morbidity and mortality. The purpose of this study was to compare our experience with the use of pre-operative chemoradiation with surgery (CRT) to patients who underwent surgery alone (S). Methods: We performed a retrospective review of a prospectively maintained database of all patients in our institution who underwent either (S) or (CRT) between 1/96 and 5/05. Data collected included demographics (age, sex), co-morbidities (cardiac, pulmonary, diabetes), pre-operative treatment details (chemotherapy type, radiation dose), procedure type, post-operative complications (pneumonia, anastomotic leak), length of stay (LOS), and hospital mortality. Statistical analysis included chi-square analysis for categorical variables and analysis of variance for continuous variables, and multivariate analyses was done using a logistic regression model. Results: There were 701 patients who were appropriate for this analysis, 332 (47.3%) (CRT) and 369 (52.7%) (S). 76% of CRT patients received 5040cGy of radiation and 90% received concurrent cisplatin based chemotherapy. CRT patients were younger (p&lt;0.001) and more often male (p=0.003). Univariate analysis indicated a similar incidence of pneumonia (p=0.78), leak rate (p=0.41), hospital length of stay (0.97), and hospital mortality (0.48). Multivariate analysis, controlling for demographics, co-morbidities, procedure type, and tumor location showed no significant difference in hospital mortality (p=0.84). Conclusions: The use of CRT does not appear to result in increased peri-operative morbidity or mortality. No significant financial relationships to disclose.
Abstract 13039: Combination and Hierarchical Use of Echocardiographic Parameters for Predicting Favorable Hemodynamic Response after Drainage of Pericardial Effusion
Authors: Kazuaki Negishi, Nael H Aldweib, Tomoko Negishi, Zoran B Popovic, Allan L Klein, Thomas H Marwcik
Journal: Circulation (2012)

Background: Echocardiography has a major role in decision-making for pericardial drainage. The individual accuracy of echocardiographic parameters is variable and their additive value is unknown. We sought how best to combine them together or in a hierarchy. Methods: After excluding patients with mechanical respiratory ventilation or arrhythmia at the time of echocardiography, we assessed 184 consecutive patients (age 59±16 yrs; 81 post-operative, 21 malignant and 82 others) who had moderate or greater pericardial effusion. Response to pericardial drainage (61/82 patients) was defined by reduction of heart rate after the procedure. A Classification and Regression Tree (CART) algorithm was used to combine parameters for prediction of response. We evaluated selection by; 1) combination of these variables and 2) application of decision tree. Results: There were 40 patients who had pericardiocentesis, 38 pericardial window and 4 had both procedures. Out of 82 those who were drained, indices chosen by CART wer...
Non-small cell lung cancer: Do African Americans really do worse?
Authors: K. R. Chan, J. C. Leighton, K. Pincus, W. J. Tester
Journal: Journal of Clinical Oncology (2004)

7293 Background: The Surveillance, Epidemiology, and End Results Medicare database (SEER), a population-based study, reported lower resection and survival rates for African-Americans with non-small cell lung cancer (NSCLC). This study was designed determine if such disparity also exists at Albert Einstein Medical Center (AEMC), a tertiary-care urban hospital. The study objectives are (1) to compare resection and 5-year survival rates for non-Hispanic whites (W) and African-Americans (AA); (2) to learn why eligible patients did not have surgery; and (3) to compare resection and survival rates with SEER. Methods: Demographic data was collected from AEMC tumor registry for stage I and II NSCLC from 1997–2001. From retrospective chart review, comorbidity score was determined using the Charlson Index. Actuarial survival curves were computed using Kaplan-Meier method and compare by log-rank statistic. The comparison population was the SEER data (NEJM 341:1198–1205, 1999). Results: Of 176 patients, 90 (51% W and 987 (49%) AA, no difference was found in resection rate and 5-year survival (56% W vs. 52% AA; 27%W vs. 28% AA). Among those not operated, 65% had medical contraindications, 12% refused, 3% had psychiatric contraindications, and the other reasons were unknown. Reasons given for refusal included: concerns of age, adverse experiences of others, and misconceptions of tumor spread with surgery. Compared to the SEER data, resection rate and 5-year overall survival was lower at AEMC (76% vs. 54%, p<0.01; 33% vs. 27%). Conclusions: The AEMC data show no difference in the resection rates or survival for AA, compared to W. However, our resection rate is lower than that of the SEER. This apparent difference may largely be related to greater medical comorbidity in the AEMC study population when compared with the SEER. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Phase II trial of oral gimatecan in adults with recurrent glioblastoma
Authors: J. Hu, P. Y. Wen, L. E. Abrey, C. Fadul, J. Drappatz, N. Salem, A. Amato, P. Carminati, J. Supko, F. Hochberg
Journal: Journal of Clinical Oncology (2009)

2009 Background: Gimatecan is a highly lipophilic oral camptothecin analogue with impressive preclinical activity in glioma models. Methods: We conducted a multicenter two-stage phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, ECOG performance status 0 or 1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m 2 was given orally once daily for 5 consecutive days during each 28-day cycle. Radiographic response was evaluated by MRI after every second cycle. The primary endpoint of the study was 6 months PFS. A Simon's 2-stage design was used in which 19 patients were evaluated in the first stage, with an additional 36 patients accrued if &gt; 4 patients in stage 1 achieved 6 month PFS. Results: A total of 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6% female; all of whom had received prior surgery, radiation therapy, and at least one regimen of chemotherapy. The daily dose was reduced to 1.0 mg/m 2 after four of the first 10 patients experienced grade 4 hematologic toxicity. One patient was removed from trial due to toxicity (grade 3 leukopenia and thrombocytopenia). Treatment delay occurred in 11 patients (38%) and dose reduction was necessary in eight patients (28%). Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2%), leukopenia (17.2%), and neutropenia (10.3%). Only 1/19 patients treated with 1.0 mg/m 2 /day experienced grade 3/4 hematologic toxicity. The 18% reduction in the daily dose resulted in a 19% decrease in the concentration of total gimatecan in plasma prior to administration of the fifth daily dose (56 ± 23 vs. 45 ± 20 ng/mL) and a 33% decrease in the AUC for dose 5 (8.0±4.8 vs. 5.3±4.2 ng*h/mL). Only one patient had a partial radiographic response by the modified Macdonald criteria and stable disease was the best response in 13 patients. All other patients had progressive disease after two cycles of therapy. Only three patients (12%) were progression-free at 6 months. Median time to progression was 12.0 weeks (95% CI: 7.0, 17.0). Conclusions: Treatment with single-agent gimatecan 1.0 mg/m 2 /day for 5 days, repeated every 28-days showed minimal efficacy. [Table: see text]
Utilization of accelerated partial-breast irradiation (APBI) and guideline concordance: Analysis of the National Cancer Database.
Authors: Simona Flora Shaitelman, Heather Lin, Yu Shen, Isabelle Bedrosian, Elizabeth S. Bloom, Gildy Babiera
Journal: Journal of Clinical Oncology (2013)

54 Background: ASTRO published a consensus statement on patient suitability for APBI treatment to guide physician practice. The purpose of this study was to examine utilization trends of APBI in the American College of Surgeons’ National Cancer Database and to assess changes in APBI use following publication of the ASTRO guidelines in 2009. Methods: A total of 337,910 women were identified who were diagnosed from 2004 to 2010 with non-metastatic invasive breast cancer or ductal carcinoma in situ who were treated with breast conserving surgery and radiation therapy (RT) to the breast. Patients were divided by the type of treatment received (whole breast irradiation (WBI) or APBI) and by suitability to receive APBI as defined by the ASTRO Consensus Statement. Logistic regression was applied to study APBI use overall and within consensus statement categorization. All p-values are two-sided. Results: For all patients, APBI usage increased as an alternative to WBI over time, from 3.8% in 2004 to 10.8% in 2008, with a subsequent decline to 9.9% in 2010, due to a decline in APBI use for “cautionary”/“unsuitable” patients (p&lt;0.0001). Overall rates of APBI utilization were higher among “suitable” than “cautionary”/“unsuitable” patients (range 6.9% to 16.9% vs. 3.1% to 7.8%, p&lt;0.0001). Among all patients, the most common modality of delivering APBI was brachytherapy (82%), followed by external beam RT (17%) and intraoperative RT (1.0%). For both “suitable” and “cautionary”/“unsuitable” patients, factors associated with treatment with APBI included treatment after 2004 (p&lt;0.0001), well differentiated histology (p&lt;.0001), and smaller tumor size (p&lt;0.0001). For “cautionary”/“unsuitable” patients, those with grossly negative tumor margins were more likely to receive APBI, as were “suitable” patients treated at an academic or comprehensive community cancer program compared to a community cancer program (both p&lt;0.0001). Conclusions: The highest absolute rate of use of APBI was seen in the group considered “suitable” by ASTRO guidelines. Although significant increases have also been seen among less suitable cohorts, these rates have declined since the publication of the ASTRO guidelines in 2009.
Correlation between quality of prostate biopsy and pathological diagnosis in the REDUCE study after 2 and 4 years of treatment with dutasteride.
Authors: K. Drewnowska, D. G. Bostwick, J. Qian, S. A.arvel, K. C. Bostwick, M. Sigler, M. Marberger, R. S. Rittmaster
Journal: Journal of Clinical Oncology (2010)

e15056 Background: Early detection and treatment of prostate cancer improves patient outcomes. Cancer detection rate is associated with the quality of prostate biopsy. The REDUCE study provided a unique opportunity to evaluate the relationship between biopsy quality and likelihood of cancer detection in a large, geographically diverse population. Methods: Subjects were randomized to placebo or dutasteride. Study protocol required collection of 10-core prostate biopsy samples at 2 time points of treatment: Year 2 and 4, respectively. Biopsy cores from 6300 subjects at Year 2, and 4630 at Year 4 were processed and diagnosed by a central pathology laboratory. The following quality parameters were evaluated: number, length, and fragmentation of biopsy cores at 2 time points, regardless of the treatment arms. Logistic regression analysis was used to assess the relationship between quality parameters and the detection rate of prostate cancer (PC), high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical acinar proliferation (ASAP). Results: Mean patient age was 65 at Year 2, and there was no difference for PSA level at both time points (5.14 ng/ml and 5.15 ng/ml, p=0.91). A remarkable consistency in quality parameters was observed between specimens collected; no significant differences were detected between core lengths (16.54 cm and 16.57 cm, p=0.73), number of cores (10.00 and 10.00, p=0.89) or fragments of tissue per vial (1.20 and 1.21, p=0.25) at Year 2 and 4, respectively. No effects of any of the quality parameters were found to alter the rate of diagnosis of PC and HGPIN. However, there was a significant association between detection rate of ASAP with core length (χ2=7.5, p<0.01, N=106,878 cores). Conclusions: Our data indicate that variation in core length is associated with ASAP detection. Protocol-standardized collection of prostate biopsy decreases the variation in biopsy quality, and utilization of central pathology laboratory eliminates the variability in pathological evaluation. This process also allows the accurate assessment of study treatment effects independent of confounding factors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, MSD GlaxoSmithKline
Distribution of FDG-avid nodes in esophageal cancer: Implications for radiotherapy target delineation.
Authors: Brandon Garcia, Karyn A. Goodman, Lajhem Cambridge, Mark Dunphy, Abraham Jing-Ching Wu
Journal: Journal of Clinical Oncology (2015)

151 Background: Clinical target volumes (CTV) for radiation therapy (RT) in esophageal cancer (EC) are based on standard expansions of the primary tumor volume. Data is needed to better define the regions at highest risk for occult disease, based on histology and location of the primary tumor. We therefore reviewed PET scans in EC patients to characterize the frequency and location of FDG-avid lymph node metastases (LNM). Methods: We identified 474 EC patients with reviewable pre-treatment PET-CT scans who received RT. Tumors were classified by histology and location: upper esophageal (above carina, 15%), or lower/GE junction (85%). Locations of suspicious LNM were classified using standard radiographic nodal atlases, and distances from primary tumor to paraesophageal LNM were also measured. Results: FDG-avid LNM were identified and characterized in 204 patients. The most common LNM in upper EC were supraclavicular (1), retrotracheal (3P) and paratracheal (4). The most common LNM in lower EC were paraesophageal (8), and those in the gastrohepatic space (abdominal stations 1, 3 and 7). Overall, 55% of paraesophageal LNM were adjacent to the primary tumor. Of upper esophageal tumors with paraesophageal LNM, 87% were adjacent to the tumor and none were &gt;6cm from tumor. However, 57% of lower esophageal tumors with paraesophageal LNM had non-adjacent paraesophageal nodes, half of which were &gt;5cm from the tumor. Conclusions: A more data-driven and individualized approach to CTV delineation could improve the therapeutic ratio of RT in esophageal cancer. These results can guide CTV delineation by indicating the potential distribution of nodal involvement in esophageal cancer according to tumor location and histology. Because most paraesophageal LNM are adjacent to primary tumor, the necessity for uniformly large, longitudinal CTV expansions along the esophagus is unclear. [Table: see text]
Panobinostat plus lenalidomide and dexamethasone phase I trial in multiple myeloma (MM)
Authors: A. Spencer, K. Taylor, S. Lonial, M. V. Mateos, M. Jalaluddin, K. Hazell, P. M. Bourquelot, J. F. San Miguel
Journal: Journal of Clinical Oncology (2009)

8542 Background: Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), affecting with epigenetic and non-epigenetic pathways of cancer. In vivo experiments demonstrated potent MM cytotoxicity of the triplet panobinostat + lenalidomide + dexamethasone. Methods: Trial started with 5 mg panobinostat (po, TIW) combined with fixed doses of lenalidomide (25 mg po, QD, Days 1–21) and dexamethasone (40 mg po, Days 1–4, 9–12, 17–20, Cycles 1–4), in a 28-day cycle. MTD of panobinostat in this combination for second-line MM will be established based on data from cohorts of ≥6 evaluable patients (pts). Safety, tolerability, PK/PD, and preliminary efficacy will be assessed. Results: Twenty-two pts with relapsed or relapsed refractory MM were treated in three dose levels to date. Dose escalation started at 5 mg panobinostat (po, thrice weekly) combined with fixed doses of 25 mg lenalidomide (po, qd, Days 1–21) and 40 mg of dexamethasone (po, Days 1–4, 9–12, 17–20, Cycles 1–4), in a 28-day cycle. Data from all eight patients in Cohort 1 were evaluated. The median number of prior lines of therapy was two (range 1–3). Six out of eight patients in Cohort 1 remain on therapy. Median follow-up is six cycles (range 4–8+). No DLT was observed. In Cohort 2, eight patients were treated at the dose level of 10 mg of panobinostat, with one single DLT: a Gr 1 increase of QT interval duration was detected on Day 3, persisting on Day 8 with therapy withheld, meeting DLT definition although not deemed clinically relevant. Cohort 3 is enrolling with six patients at 20 mg of panobinostat, thus far. SAEs included fever (two pts), anxious depressive syndrome, respiratory infection, atrial fibrillation, exertional dyspnea, cellulitis, superficial blood clot of thigh, phlebitis, hypokalemia. All, but fever in one patient, were assessed by the investigator as not study drug related. Conclusions: The potential for anti-myeloma activity of this triple combination is strongly supported by in vivo preclinical data. In this first clinical trial assessing this triple oral combination, the 5 and 10 mg dose level of panobinostat appear safe. Updated safety, early efficacy, and subsequent dose-level patient data will be presented. [Table: see text]
Transfusion outcomes in erythropoiesis-stimulating agent (ESA)-treated cancer chemotherapy patients based on achieved hemoglobin (Hb) levels
Authors: K. Larholt, T. Burton, D. Hoaglin, C. L. Pashos, B. K. Bookhart, M. Corral, C. T. Piech, R. S. McKenzie
Journal: Journal of Clinical Oncology (2008)

6637 Background: Recently, Medicare ESA coverage policy has been changed mandating ESA administration be limited to specific achieved Hb levels. To assess the clinical implications of these changes in ESA coverage policy, data from an ongoing ESA registry were evaluated. Methods: Observational data from an ongoing, prospective registry of ESA-treated patients in 55 US oncology clinics between 12/03–11/07 were analyzed. Hospital- and community-based outpatient practices were included. Data were analyzed from adult chemotherapy-treated oncology patients with ≥2 ESA doses and Hb level <10g/dL prior to ESA administration. Transfusion-related outcomes were categorized into three cohorts based on mean Hb values achieved during ESA treatment: 9.1–10, 10.1–11, or 11.1–12g/dL. Results: 330 patients met inclusion criteria with 36%, 45%, and 19% categorized into mean achieved Hb levels of 9.1–10, 10.1–11, and 11.1–12g/dL, respectively. Patients with lower mean achieved Hb levels were associated with greater transfusion requirements, including a higher proportion of patients requiring transfusion and higher blood utilization based on units/study patient (Table). Logistic regression analysis suggested that as the mean hemoglobin achieved increases, the risk of transfusion decreases (Odds Ratio= 0.580, 95% CI 0.401, 0.839). Conclusion: Lower mean achieved Hb level during ESA treatment was associated with increased transfusion requirements in cancer chemotherapy patients. Such findings are informative to decision-makers on the transfusion implications of limiting ESA coverage to defined Hb levels. Hb Cohort 9.1–10 g/dL (n=118) 10.1–11 g/dL(n=149) 11.1–12 g/dL (n=63) Mean (SD) Hb achieved, g/dL 9.6 (0.24) 10.5 (0.27) 11.4 (0.28) % Patients Transfused 39% 23% 19% Mean (SD) units/study patient 1.3 (2.2) 0.6 (1.2) 0.5 (1.1) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ortho Biotech Ortho Biotech Ortho Biotech