tbuckley/cabot-search huggingface dataset:
Quality of care improvement in breast and lung cancer.
Authors: Douglas D. Letson, Johnathan M. Lancaster, Alberto Chiappori, John W. Peabody, Lisa DeMaria, Marife Bacate, Timothy Edward Kubal
Journal: Journal of Clinical Oncology (2014)

252 Background: Despite the growing call for use of guidelines in cancer care, adherence to clinical pathways and clinical care transformation is a challenge. Moffitt Cancer Center (MCC) has addressed this challenge, in multiple service lines, using its clinical pathways and serial measurement in a broad-based initiative to improve quality of clinical care. Methods: Moffitt launched an initiative focused on quality and improvements in care using Clinical Performance and Value (CPV) vignettes to measure multiple aspects of quality including: clinical decision-making, pathway adherence and appropriate utilization of tests/procedures. The CPVs—simulated patients cared for by providers on-line—are based upon the Moffitt Clinical Pathways. CPVs are given serially to benchmark, motivate providers, and provide confidential individual feedback. Data have been collected every 4 months since mid-2013. We report on three rounds in breast cancer and two rounds in lung cancer. Results: A total of 18 providers at MCC completed the breast cancer CPVs and 19 providers at MCC completed the lung cancer CPVs. Overall scores improved significantly and pathway adherence improved significantly for staging work-up and chemotherapy between rounds 1 and 3 for breast cancer (Table). Conclusions: Adherence to Moffitt Clinical Pathways for breast and lung cancer, using serial measurement and feedback with CPVs, improved across multiple providers and two diseases. This may have potential to transform practice. [Table: see text]
Adverse Reactions to PEG and Erwinia Asparaginase and Correlation with Anti-Asparaginase Antibody Data and Survival in Children with Acute Lymphoblastic Leukemia (ALL): A Report From the Children's Oncology Group Study CCG 1961.
Authors: Girish Dhall, Tamekia Jones, David Radvinsky, Nathan Robison, Anna Butturini, Joan I Rubin, Paul S. Gaynon, Eduard H Panosyan, Ioannis A Avramis, Vassilios I Avramis, Lawrence J. Ettinger, Nita L. Seibel
Journal: Blood (2009)
Sunitinib in combination with gefitinib in patients (pts) with metastatic renal cell carcinoma (mRCC): Updated results from a phase I/II study
Authors: B. G. Redman, G. R. Hudes, S. T. Kim, I. Chen, R. J. Motzer
Journal: Journal of Clinical Oncology (2008)

16014 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs that has shown substantial efficacy in pts with mRCC (JAMA 2006;295:2516; NEJM 2007;356:115). Here, we present updated safety and efficacy data from the phase II part of a study of sunitinib in combination with gefitinib, an EGFR inhibitor. Methods: Eligibility included mRCC with a clear cell component, measurable disease, and ECOG performance status (PS) of 0 or 1. In phase II, pts received sunitinib 37.5 mg (the maximum tolerated dose [MTD] determined in phase I) orally, once-daily in 6-wk cycles (4 wks on treatment, 2 wks off) plus gefitinib 250 mg/day. The primary endpoint of phase II was RECIST-defined objective response rate (ORR). Sample size was determined using a one-sided, single-stage phase II design with a 10% alpha level and 85% power. Results are reported for all pts treated at MTD (N=35) from phase II (n=31) and phase I (n=4). An exploratory analysis of VEGF pathway biomarkers was performed for phase II. Results: Median age was 62 yrs (range: 29–78); 24 pts (69%) had ECOG PS of 0; and 24 pts (69%) had prior immunotherapy. The ORR was 34% (95% CI: 19–52), and 11 pts (31%) had stable disease. Median response duration was 18 mo (95% CI: 18-NR). Median progression-free survival was 11 mo (95% CI: 6-NR), and median overall survival had not been reached; 1-year survival probability was 82% (95% CI: 71–90). The most common grade 3 treatment-related AEs included diarrhea (14%) and gastrointestinal hemorrhage (6%); 3 pts were withdrawn due to treatment- related AEs (ejection fraction decline, cardiac arrhythmia, and asymptomatic ventricular tachycardia). Increases in plasma VEGF-A levels and decreases in plasma VEGF-C and soluble VEGFR-2 and VEGFR-3 levels were observed in patterns generally consistent with those for sunitinib monotherapy. In a preliminary analysis, no statistically significant correlations between these protein levels and efficacy were noted. Conclusions: Updated results from a study of sunitinib plus gefitinib further demonstrate the feasibility of this combination, with similar efficacy and tolerability to that observed with sunitinib monotherapy, along with similar patterns of biomarker modulation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
Understanding the psychosocial needs of young adults with cancer: Identifying targets for clinical intervention.
Authors: K. M. Trevino, K. Fasciano, A. H. Partridge, P. Maciejewski, E. Kacel, R. Jimenez, S. Block, H. G. Prigerson
Journal: Journal of Clinical Oncology (2011)

9068 Background: The NCI has recognized the unique burden of cancer for young adults (YAs) and called for specialized services to address their needs. Few studies have investigated the nature of distress in YAs, making development of targeted psychosocial interventions difficult. The present study advances understanding of YA psychosocial needs by examining correlates of quality of life, suicidal ideation, and disruption of work, social, and family life in patients with advanced cancer. Methods: Structured clinical interviews were conducted between April 2010 and January 2011 with 40 YA advanced cancer patients (age range 20-40 yrs, M=35.2, SD=5.16) receiving care at Dana-Farber Cancer Institute. Validated measures assessed quality of life (e.g. Global McGill Quality of Life Questionnaire), psychopathology, grief over cancer-related losses, coping methods, and psychosocial variables of clinical interest. Quality of life scores were regressed individually on grief, psychopathology, illness acceptance, patient-oncologist therapeutic alliance, social support, and coping methods. Significant bivariate associations were entered into multivariate models to identify the most significant set of influences. The same set of independent variables was used in models of life disruption and suicidal ideation. Results: In bivariate analysis, grief, illness acceptance, therapeutic alliance, social support, depression, and coping methods were associated with quality of life (p<.05). In multivariate analysis, less grief (B=-.54, SE=.43, df=29, p<.01) and more social support (B=.32, SE=.62, df=29, p<.05) remained significant predictors of better quality of life. In multivariate analysis, more grief predicted more suicidal ideation (B=.54, SE=.036, df=29, p<.01) and less illness acceptance predicted more life disruption (B=.51, SE=.31, df=29, p<.01). Conclusions: For YAs with advanced cancer, grief, social support, and illness acceptance are critical to quality of life, functionality, and will to live. Clinical interventions that reduce grief, promote illness acceptance, and enhance social support may address the unique psychosocial needs of YA cancer patients.
Patterns of radiotherapy and its impact on survival in patients with locally advanced gastric and gastroesophageal junction adenocarcinoma: Before and after the publication of the MAGIC trial.
Authors: Chi Lin, Abhijeet Bhirud, Nathan Ronald Bennion
Journal: Journal of Clinical Oncology (2016)

125 Background: The intergroup 0116 trial for locally advanced gastric (GA) and gastroesophageal junction adenocarcinoma (GEJA) established postoperative chemoradiation therapy as the standard of care. However, since the publication of the MAGIC trial in 2006, some physicians prefer perioperative chemotherapy rather than postoperative chemoradiation. The goal of this study is to examine the use of radiotherapy (RT) and its impact on survival in patients diagnosed 3 years prior to and after the publication of the MAGIC trial. Methods: Patients with stage T2-4 or N+ and M0 GA (3339) or GEJA (1868) diagnosed between 2004 and 2009 who have had a primary tumor resection with at least 3 years of follow up were identified from the SEER database. Regression models were used to analyze factors influencing the use of RT and its effect on survival. Kaplan Meier plots and log-rank tests were used for survival comparisons. Results: From 2004 to 2009, there was no change in the ratio of RT/no RT. About 33% of patients with GA and 53% with GEJA received RT. Multivariate regression analysis showed that patients with T2-3 disease, N+ disease, and younger patients were more likely to receive RT in both GA and GEJA. The median follow-up for GA and GEJA, was 73 and 68 months and median survivals of 27 and 26 months respectively. RT improved median survivals from 20 to 46 months for GA and from 20 to 31 months for GEJA (p &lt; 0.0001). After adjusting for stage and age, patients who received RT had higher odds of surviving 3 years or longer for both GA (OR 2.20, 95% CI 1.86-2.60) and GEJA (OR 1.46, 95% CI 1.19-1.80). Further analysis revealed that RT improved survivals in patients diagnosed either before or after 2006 for both GA and GEJA. Conclusions: The publication of MAGIC trial in 2006 has not affected the patterns of using RT on locally advanced GA or GEJA. Patients who did not receive RT after 2006 continue to have worse survival rates compared to those who have had RT. Further studies are warranted to evaluate the effect of combining the MAGIC chemotherapy regimen and RT on survival and quality of life of these patients.
A molecular tool to distinguish breast carcinoma metastases to the ovary and primary ovarian carcinomas
Authors: J. Meyniel, N. Servant, I. LeBigot, M. Bollet, C. Decraene, E. Barillot, J. Couturier, S. Roman-Roman, P. Cottu, X. Sastre-Garau
Journal: Journal of Clinical Oncology (2008)

16599 Background: Breast cancer often metastasizes to the ovary. Pathological differential diagnosis between primary ovarian carcinoma and breast cancer metastases may be difficult. We developed a molecular tool to discriminate between these diagnoses. Methods: The pangenomic profiles of 13 pairs of primary breast carcinoma and ovary tumors (primary tumors or breast metastases) from the same patients were analyzed using the Affymetrix GeneChip Mapping 50K (XbaI) SNP arrays. The data were normalized with ITALICS algorithm (Rigaill et al., Bioinformatics, 2008). A partial identity score developed using DNA breakpoint information was used to quantify partial identity between two tumors (Bollet et al., JNCI, 2008). The nature of ovary tumors (primary tumor or breast metastasis) as defined using the partial identity score was compared with that based on pathological characteristics. Results: For ten pairs, the pathological diagnosis agreed with the result of the partial identity score. For the three remaining pairs, the discordance could be explained by the fact that genomics profiles of the breast tumors were little altered. The low number of breakpoints in these tumors induces a score less robust than in tumors with profound genomic alterations. Conclusions: These preliminary results show the potential of such a genome wide molecular based approach to solve difficult diagnostic issues. Further studies will improve the robustness of this score and confirm its usefulness. No significant financial relationships to disclose.
Long term results and patterns of recurrence from SCOPE 1: A phase II/III randomised trial of definitive chemoradiotherapy (dCRT) plus or minus cetuximab (dCRT+C) in esophageal cancer.
Authors: Somnath Mukherjee, Chris Hurt, Stephen Falk, Simon Gollins, John Staffurth, Ruby Ray, John A. Bridgewater, David Cunningham, Jane M. Blazeby, Rajarshi Roy, Tim Maughan, Gareth Griffiths, Tom David Lewis Crosby
Journal: Journal of Clinical Oncology (2016)

118 Background: One of the largest trials in dCRT for localised oesophageal cancer, SCOPE 1 tested the role of adding cetuximab to conventional dCRT, and showed that this was associated with greater toxicity and worse survival. Here we present the long-term outcomes. Methods: Phase II/III trial. Randomisation: cisplatin 60mg/m 2 D1 and capecitabine 625mg/m 2 daily D1-21 for 4 cycles with/without Cetuximab 400mg/m 2 D1 followed by 250mg/m 2 weekly. RT: 50Gy in 25 fractions given concurrent with cycles 3 and 4. Recruitment: Feb 2008 - Feb 2012, when the IDMC recommended trial closure on the basis of futility. Results: 258 patients (dCRT = 129; dCRT+C = 129) were recruited from 36 centres. Median follow-up (IQR): 46.7 (36.0-49.0) months for all surviving pts. 65.1% (dCRT arm) and 69.8% (dCRT+C arm) of patients had died. Esophageal cancer was the cause in 82.1% and 86.7% of deaths respectively (p = 0.41). Median OS months (95% CI) was 34.5 (24.7-42.3) in dCRT and 24.7 (18.6-31.3) in dCRT+C (HR 1.25, p = 0.137); corresponding 3-year OS (95% CI) was 47.2% (38.2%-55.7%) and 37.6% (29.1%-46.0%). Median PFS (95% CI): 24.1 (15.3-29.9) and 15.9 (10.7-20.8) months respectively (HR1.28, p = 0.114). There was some evidence that local PFS (within RT field) was lower in the dCRT+C arm (HR1.38, p = 0.051). On multivariable analysis including treatment arm, Stage I-II ds (vs Stage III), full-dose RT and higher cisplatin dose intensity ( ≥ 75% vs &lt; 75%) were associated with improved OS and PFS. Patterns of recurrence (n [%]) were similar in both arms (see table). In dCRT arm, 31/38 pts (81.6%) with local relapse within the RT field compared to 40/48 (83.3%) in the dCRT+C arm (p = 0.8). Conclusions: The mature analysis shows unprecedented survival in dCRT arm, comparable to surgical trials (e.g. 3-year OS % [95% CIs] in OE05: CF 39 [35, 44] and ECX 42 [37, 46], in OE02: 31 [27, 36]). OS inferiority of dCRT+C is no longer statistically significant. The lower PFS (within RT field) in the dCRT+C arm was consistent with the lower number of patients receiving full dose of RT in the dCRT+C arm. Clinical trial information: 47718479. [Table: see text]
Anti-angiogenic therapies for metastatic colorectal cancer (MCRC): Preliminary results of a systematic review and meta-analysis
Authors: A. D. Wagner, D. Arnold, A. Grothey, J. Haerting, S. Unverzagt
Journal: Journal of Clinical Oncology (2008)

4060 Background: Anti-angiogenesis is one of the most exciting approaches in drug development. However, results from individual trials in MCRC are highly variable and the clinical value of this strategy needs further clarification. Therefore our objective was to assess the effect of targeted anti-angiogenic therapies in addition to chemotherapy (ctx) in patients (pts) with MCRC. Methods: Systematic review and meta-analysis were performed on the basis of a previously published protocol. Progression-free (PFS) and overall survival (OS) were primary endpoints, with OS being hierachically lower ranked. Response rates, toxicity and secondary resectability were secondary endpoints. Search strategy: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, proceedings from ECCO, ESMO, ASCO until 11/ 2007. Selection criteria: Randomized controlled trials on targeted anti-angiogenic drugs in MCRC. As individual patient data was not provided, aggregate data had to be used for the analysis. Results: 5 eligible trials using bevacizumab (bev) were identified (4 in 1st-line, 1 in 2nd- line). 1 trial was excluded due to insufficient data. The pooled HR’s for PFS and OS for the comparison of ctx with versus without bev (4 trials, 2999 pts) were 0.68 [95% CI 0.62 -0.74] and 0.79 [95% CI 0.73–0.87] in favour of the pts treated with bev. When only trials comparing 1st line ctx with versus without bev were included (3 trials, 2422 pts), the pooled HR’s for PFS and OS were 0.70 [95% CI 0.63–0.76] and 0.81 [95% CI 0.73–0.90]. The odds ratios (OR) for all-cause 60-day mortality (n=2,935 pts, OR= 0.790; 95% CI 0.53–1.18) and treatment-related deaths (n=2,335 pts, OR 0.99; 95% CI 0.58–1.68) had insignificant results. Two phase III trials using PTK787/ZK 222584 in 1st- and 2nd-line have been published, but final results are available for only one of them at present and will be included in the future for this reason. Conclusions: The addition of bev to ctx significantly improves PFS and OS in MCRC, although the initially observed magnitude of the treatment effect could not be reproduced in later studies. Supported by BMBF [FKZ 01 KG 0603]. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Roche Roche, sanofi-aventis Genentech™ BioOncology, Roche
Multicenter randomized phase II trial of combined radiotherapy and cisplatin with or without erlotinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCAHN): Preliminary toxicity results.
Authors: D. N. Hayes, L. E. Raez, A. K. Sharma, M. A. Papagikos, F. Yunus, U. Parvathaneni, K. D. Eaton, N. Futran, S. G. Wallace, R. Martins
Journal: Journal of Clinical Oncology (2010)

5580 Background: Cisplatin and radiotherapy is a standard therapy for patients with SCCAHN. Targeting the EGFR pathway in combination with radiotherapy improves survival over radiotherapy alone. Erlotinib has activity in advanced SCCAHN. Methods: Patients were randomized between cisplatin 100 mg/m2on days 1, 22, and 43 combined with 70Gy of radiotherapy (arm A) or the same treatment plus 150 mg of erlotinib starting one week before chemoradiotherapy and continued until the completion of radiotherapy (arm B). The primary objective of the trial was the comparison of the rate of complete response between the two arms. Quality of life, all grades of rash, all grades of pain, and grade III and higher toxicity data was collected. The accrual goal is 204 patients. Results: Between June 2006 and December 2009, 128 patients were randomized. Current analysis is restricted to the first 100 patients. Demographic characteristics: male 87%, median age 55.7 (36- 76), 80% Caucasian, 73% former or current smokers, 77% with N2 or N3 nodal disease. Eighty-two patients are evaluable for response and ninety-two patients are evaluable for toxicity. Eight patients never received any protocol therapy, 9 patients have incomplete response data and one patient was ineligible. Serious adverse events (SAEs) were observed in 16 patients in arm A (33 %) and 14 patients in arm B (32%). Most common serious adverse events were nausea, vomiting, and dehydration and accounted for 30% of all SAEs reported, with no difference between arms. There was 1 treatment related death (arm A). Fifty-eight patients had a complete response (71%). Efficacy data will only be evaluated for each arm at trial completion. Conclusions: Erlotinib does not increase the rate of serious adverse events associated with the use of cisplatin and radiotherapy in SCCAHN. Updated efficacy data will be presented at the Meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, OSI Genentech, OSI
Bi-fractionated oxaliplatin (L-OHP) plus 5-fluorouracil (5FU)/leucovorin (LV) for elderly patients (pts) with advanced colorectal cancer (CRC)
Authors: C. Massacesi, P. Lippe, F. Recchia, F. Marcucci, M. Rocchi, A. Cesta, A. Pilone, C. Cappelletti, M. Bonsignori, R. Mattioli
Journal: Journal of Clinical Oncology (2005)

3619 Background: Delivering l-OHP over 2 days together with 5FU may enhance the synergism and reduce neurotoxicity. In this study we assessed activity, toxicity and both the activity of daily living (ADL) and instrumental activity of daily living (IADL) of a bi-fractionated l-OHP plus 5FU/LV regimen as first line chemotherapy for elderly pts with metastatic CRC. Methods: Eligibility criteria included no previous chemotherapy for advanced disease, age >= 70 yrs, ECOG PS <= 2. Schedule was: l-OHP 45 mg/m2 + bolus 5FU 400 mg/m2 + 24-h infusional 5FU 600 mg/m2 + LV 200 mg/m2, days 1 and 2, every 2 weeks. Responses (WHO criteria) and ADL/IADL were assessed every 6 cycles. A two-staged Simon accrual design was adopted for this phase II study, with response rate as main endpoint (p1 45%; p0 30%). Results: From Aug ‘01 to Jul ‘04, 78 pts entered the study: M/F 54/24, median age was 75 years (r. 70–85), PS 0/1/2 in 31/38/9, liver/lung/peritoneum metastases in 58%/31%/11% of pts. A total of 651 courses were administered, with a median of 8 cycles per pt (r. 1–19). The mean weekly DI of l-OHP was 34 mg/m2 (76% of the planned). Response (77 pts evaluable) was as follow: CR in 7 (9.0%) and PR in 32 (41.5%) pts, for an overall RR of 50.5%; SD and PD both in 19 (24.7%) pts. Median duration of response was 9.0 mo. Second-line chemotherapy was delivered to 47% of pts. With a median f-u of 12.5 mo, according K-M method, median TTP and OS was 8.1 (r. 0.3–21.9) and 20.1 (r. 0.8–29.5) mo, respectively. NCI-CTC grade 3/4 toxicities were: neutropenia in 32% of pts (febrile in 2 pts), diarrhea 10%, mucositis 4%, fatigue 4%. G2 and G3 sensory neuropathy occurred in 17% and 6% of pts, respectively. Median ADL/IADL scores at T0, T6 and T12 were 6/4, 6/4, and 6/5, respectively, without significant differences. Conclusions: l-OHP and 5FU/LV was highly active and did not interfere with ADL/IADL of elderly pts with advanced CRC. The bi-fractionated delivering of l-OHP demonstrated to reduce neurotoxicity. No significant financial relationships to disclose.
Radiotherapy and hyperthermia for NSCLC
Authors: H. J. Yang, G. L. Jiang, X. L. Fu, J. X. Liao
Journal: Journal of Clinical Oncology (2005)

7289 Background: Up to now, NSCLC with tumor(T) larger in lungs treated with irradation(RT) has poorly loco-regional control limited by tolerance dose of normal tissues. The aim of this study is to observe the toxicity, tolerance and efficacy of RT combined with hyperthemia(HT) for NSCLC with T in diameter >= 5cm. Methods: Patients(pts) satisfied NSCLC, karnofski performance status>=70, the least diameter of T >=5cm or volume of T>=125cm3 prior to irradiation, tolerable to radical irradiated doses, expected survival > 3 months were received RT and HT.The temperature of HT in the center of Ts was monitored between 430 C and 43.50 C by computer with ZRL-II radio-frequency capacitive. The total T dosage was 60–66Gy in 30–33 fractions. Results: From September 2001 to April 2004, 30 Pts were registered for this study. The last day of follow up was September 2004. There were 23 males and 7 female with median age of 61 years (32–81), 22 cases squamous cancer, 8 cases adenocarcinoma. And 6 cases were stage I b, 1 case stage II b, 10 cases stage III a, 8caes stage III b, 5cases stage IV. The mean volumes of T were 275.45cm3(125–900). None of pts had changed significantly in blood pressure, pause and frequency of the breath. And lipid nodules, acute radiation-induced responses in Grade III and over had not also been observed. CR was observed in 23%, PR in 50%, NC in 27% and PD in 0%. Local relapse-free survival rate was 83% with median loco-regional duration of 19.17months. The median survival duration was 19.69 months. And the 1-year survival rate was 75%. Conclusions: The regimen of RT combined with HT could be used for NSCLC with T in diameter >=5cm which has better efficacy and loco-regional control without serious sides. No significant financial relationships to disclose.