tbuckley/cabot-search huggingface dataset:
Radiotherapy protocol deviations and clinical outcomes: A meta-analysis of cooperative group clinical trials.
Authors: Nitin Ohri, Xinglei Shen, Adam Dicker, Laura Doyle, Amy Harrison, Timothy Norman Showalter
Journal: Journal of Clinical Oncology (2012)

181 Background: Several reports have linked noncompliance with radiotherapy (RT) protocol guidelines with inferior clinical outcomes. Here we perform a meta-analysis of prospective cooperative group trials to determine the impact of RT quality assurance (QA) deviations on disease control and overall survival (OS). Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for multi-institutional trials that reported clinical outcomes in relation to RT quality assurance (QA) results. Hazard ratios (HRs) describing the impact of RT protocol noncompliance on outcomes were extracted directly from the original studies or calculated from survival curves. Analyses were performed to assess the impact of RT QA deviations on OS and secondary outcomes (local/locoregional control, event-free survival, relapse), which were grouped together. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p&lt;0.10 using Q test). Results: Eight studies met all inclusion criteria and were incorporated into this analysis. Four were pediatric trials (POG 8346, SFOP.TC 94, POG 9031, SIOP/UKCC PNET-3), and four studied adult patients (RTOG 73-01, SWOG 7628, TROG 02.02, RTOG 97-04). Six of these trials reported the impact of RT QA deviations on overall survival, and six described the effects of RT QA deviations on secondary endpoints. The frequency of RT QA deviations ranged from 8% to 71% (median: 40%). Using a random effects model, RT deviations were associated with a significant decrease in OS (HR = 1.74, 95% CI: 1.28 to 2.35, p&lt;0.001). A similar effect was seen for secondary endpoints (HR = 1.79, 95% CI: 1.15 to 2.78, p=0.009). No evidence of publication bias was detected using the Egger test (p=0.361 for OS, p=0.468 for secondary endpoints). Conclusions: In clinical trials, RT protocol deviations are associated with increased risk of treatment failure and overall mortality. The magnitude of these effects demonstrates that RT QA results should be considered in the interpretation of clinical trial results. More importantly, the delivery of high-quality RT is critical for the successful treatment of cancer patients.
A phase I study of MORab-009, a monoclonal antibody against mesothelin, in mesothelioma, pancreatic and ovarian cancer
Authors: D. A. Laheru, S. J. Cohen, M. Phillips, D. K. Armstrong, J. Brahmer, E. M. Jaffee, S. Weil, I. Pastan, R. Hassan
Journal: Journal of Clinical Oncology (2008)

3578 Background: MORAb-009 is a monoclonal antibody that targets mesothelin, a cell surface adhesion protein over-expressed in pancreatic cancer, mesothelioma and other malignancies, with minimal expression in normal human tissue. In vitro MORAb-009 inhibits tumor cell adhesion and mediates tumor cell killing. We initiated this phase I study to determine the safety of MORAb-009 administered weekly. Methods: Cohorts of 3 subjects received MORAb-009 intravenously on days 1, 8, 15 and 22 at doses of 12.5, 25, 50 100, 200 and 400 mg/m2. Disease evaluation with CT occurred on day 35. Serum drug levels were measured throughout the study. Subjects with stable disease or better by RECIST could receive additional cycles. Results: Enrollment is complete. 24 subjects were enrolled: advanced mesothelioma (13), pancreatic cancer (7), and ovarian cancer (4). Adverse events thought to be possibly, probably or definitely related to MORAb-009 included 2 allergic reactions, 4 acute infusion reactions (all grade 1 or 2), a thromboembolic event (grade 4), mild transient thrombocytopenia (grade 1) and dysgeusia (grade 1). At the 400 mg/m2 dose, 2 SAEs were observed: grade 4 elevation of liver enzymes and grade 3 serum sickness. These episodes were thought to have been related to the subjects’ conditions, but were conservatively called DLTs and thus the MTD was determined to be 200 mg/m2. Six subjects had stable disease and received additional cycles of therapy. One subject with previously progressive metastatic pancreatic cancer received 5 additional cycles of MORAb-009 and demonstrated stable disease for over 6 months. Another subject with pancreatic cancer, 2 with mesothelioma and 2 with ovarian cancer each received 1 additional cycle, a third subject with ovarian cancer received a partial additional cycle. Conclusions: MORAb-009 is well tolerated and the MTD when administered weekly is 200 mg/m2. Six subjects demonstrated stable disease warranting additional therapy. Given the favorable safety profile and possibility of clinical benefit, a phase II study of the efficacy of MORAb- 009 with gemcitabine in unresectable pancreatic cancer is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Morphotek Morphotek Morphotek
Radiological markers of treatment responsiveness in patients (pts) with metastatic pancreatic ductal adenocarcinomas (mPDAC) receiving systemic chemotherapy.
Authors: Peter Yong Soo Park, Kenyon Verner McAferty, Michael Ahmadi, Kewei Chen, John Chang, Tomislav Dragovich, Madappa N. Kundranda
Journal: Journal of Clinical Oncology (2016)

403 Background: mPDAC is a deadly disease with dismal survival. Newer systemic therapies including gemcitabine/nab-paclitaxel (GA) and FOLFIRINOX (FF) have resulted in modest increases in median overall survival(mOS). Currently, no good predictors exist to prioritize the use of one regimen over the other. We investigated imaging patterns in patients receiving these two regimens. Methods: A single institution retrospective analysis of pts with mPDAC receiving either GA or FF as the front-line therapy between Jan 2012 - Dec 2014 was conducted. Data included demographics and systemic therapy.Baseline CT evaluated six imaging features; lung metastases, liver metastases, peripancreatic adenopathy, retroperitoneal adenopathy, mesentery/omentum infiltration and ascites. Statistical analysis included Kaplan Meier survival analysis with Chi-square test to compare imaging features that predict mOS or median response duration (mRD). Results: N = 27 pts; median age:GA-66 years( range: 52-76), FF-55 years (range: 40-67); 13 pts (48 %) were women and 24 pts had an ECOG performance status of ≤ 1. 18 pts received GA and 9 received FF. mOS with GA = 6.1 months(m) ( range: 1.9-15.7) and FF = 9.9 m (range: 2.5-24.1). 5/18 (28%) of the GA group and 7/9(78%) of the FF group received subsequent therapies. The presence of peripancreatic adenopathy in GA pts correlated with prolonged mRD (2.2 vs. 0.6 m; p &lt; 0.001) without statistical difference in mOS (8.5 vs. 2.9 m; p = 0.4). In pts receiving FF the absence of hepatic metastasis resulted in a significant mRD (2.3 vs. 0.9 m; p = 0.01) and mOS (7.9 vs. 1.9 m; p = 0.04). The remainder of the radiological features did not show any statistically significant difference. Conclusions: In patients with mPDAC receiving GA or FF in front-line therapy; we observed that metastasis to the liver predicts worse outcome with FF than GA. Interestingly, peripancreatic lymphadenopathy was predictive of longer mRD for GA pts, without difference in mOS. Our pilot data demonstrates the potential of using CT imaging features to predict likelihood of response to different chemotherapy regimens. A larger study is needed to confirm these findings.
Standardizing architecture and governance of radiology clinical checklist development.
Authors: Colleen Bedford, Priyanka Jain, Deanna Langer, David Kwan, Julian Dobranowski
Journal: Journal of Clinical Oncology (2016)

193 Background: To improve quality of radiology reporting, Cancer Care Ontario’s (CCO) Cancer Imaging Program established synoptic radiology reporting as a priority area. Program goals are to implement standardized radiology reports across the province, improving communication between referring and interpreting physicians and providing a standardized foundation for staging data collection and population health research. Although there are libraries of structured radiology clinical checklists, development methodologies quality vary. To support ongoing development and provide a framework to assess existing checklists, the program developed and published two white papers. Methods: To ensure checklists are consistent in format, the first white paper provides guidance on ‘architecture’ (high-level elements) of a cancer imaging report. To ensure the content of adopted checklists are based on high-quality evidence, the second white paper focuses on clinical checklist development governance. Both white papers were developed in consultation with multidisciplinary expert panels assembled by CCO and underwent peer review prior to being made available. Results: The architecture white paper outlines the minimum mandatory elements for cancer imaging reports. The elements to be included in these reports are: demographics, relevant clinical information, body of the report, and impression. This paper provides specific guidance for expert panels in the development of new clinical checklists as well as criteria for reviewing existing checklists. The governance white paper provides a clear methodology for a systematic approach to clinical checklist development for synoptic radiology. Included are recommendations on the constitution of the clinical expert panels, the level of evidence needed to support checklist items, external review of the checklist, and periodic checklist maintenance. Conclusions: CCO has developed two white papers that serve as a guide for both CCO and external parties in the creation of high-quality clinical checklists. Improved standardization of the structure and development approach for clinical checklists facilitates both in-house development and adoption of third party checklists.
SWITCH: A randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO)/sunitinib (SU) versus SU/SO in the treatment of metastatic renal cell cancer (mRCC).
Authors: Maurice Stephan Michel, Walter Vervenne, Maria de Santis, Ludwig Fischer von Weikersthal, Peter J. Goebell, Juergen Lerchenmueller, Uwe Zimmermann, Monique M.E.M. Bos, Werner Freier, Silke Schirrmacher-Memmel, Michael D. Staehler, Sascha Pahernik, Maartje Los, Marcus Schenck, Anne Flörcken, Cornelis Van Arkel, Kirsten Hauswald, Martin Indorf, Dana Gottstein, Christian Eichelberg
Journal: Journal of Clinical Oncology (2014)

393 Background: The sequential use of SO and SU has been investigated retrospectively in patients with mRCC. We report here results from the first randomized study to prospectively compare SO/SU versus SU/SO. Methods: Pts with mRCC unsuitable for cytokines without prior systemic therapy, ECOG PS 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion were randomized to receive open-label SO/SU (arm A) or SU/SO (arm B) in standard dosage. Primary endpoint: total PFS (T-PFS) from randomization to event during 2 nd line therapy. Therapy continued until progression or intolerability. The study was powered to detect a 47% increase in T-PFS with SO/SU compared to SU/SO using log-rank testing and Cox proportional hazard regression model. ( NCT00732914 ). Results: A total of 365 pts were enrolled: 182 arm A, 183 arm B.The two arms were well balanced: median age (A/B): 64/65 yrs; prior nephrectomy: 74/65%; MSKCC intermediate: 59/51%, low: 39/45%; clear cell histology: 90/84%. At time of final T-PFS analysis 220 events had occurred (A, n=117 [64%]; B, n=103 [56%]). There was no statistically significant difference in T-PFS across arms: HR 1.01, p=0.54, arm A and arm B, respectively. Likewise, there was no statistically significant difference in OS: HR 0.997, p=0.49, nor in the first PFS across arms: HR 1.19, p=0.92. Fewer pts crossed over to receive SO in arm B (n=76) than to receive SU in arm A (n=103). Overall DCR was 72/67%. There was a marked difference in AEs leading to permanent discontinuation between the two groups (18.6/29.5%). Most frequent (&gt;20%) side effects under 1 st -line treatment SO vs SU were alopecia (29/4%), diarrhea (43/29%), dysgeusia (8/21%), fatigue (21/34%), HFSR (37/20%), hypertension (24/24%), nausea (18/24%) and rash (22/3%). AEs were generally lower during 2 nd -line therapy. Conclusions: There was no significant difference in T-PFS, OS, DCR and 1 st -line PFS between the two sequential treatments. Both drugs provided overall benefit regardless of sequence. Side effect profiles differ, but were generally less frequent during 2 nd -line therapy. More patients reached 2 nd -line in the SO/SU arm. Clinical trial information: NCT00732914.
Clinical utility of the radiation dose management system for full field digital mammography (FFDM): In Asian women with dense breast tissue.
Authors: Bong Joo Kang, Ji Eun Baek, Hyun Sil Lee, Sung Hun Kim
Journal: Journal of Clinical Oncology (2015)

70 Background: In the perspectives on radiation dose, there are consensus of importance on radiation dose management for patient safety and trends to reduce radiation dose for patient safety. Radiation dose management system like Radimetrics helps radiologists optimize protocols and reduce radiation dose. There is no previous data applying the radiation dose management system in mammography.We investigated the clinical usefulness of the radiation dose management system in full field digital mammography (FFDM) using commercial Radiation dose management system. Methods: We did radiation dose tracking, monitoring, and statistics through the existed radiation dose management system (Radimetrics). The utilization data, parameter, and dose report were sent to the conventional picture archiving and communication system (PACS) and the Radimetrics enterprise flat form. And we could review the data including age, kVp, mAs, breast thickness, and compression force under the web base. We analyzed the breast composition depending on the BI-RADS assessment categories. We evaluated the correlation of the age, kVp, mAs, breast thickness, compression force, and breast composition with organ dose of breast. Additionally, in patients with above diagnostic reference level ( ≥ 75%) of radiation dose, the causes were analyzed. Results: From February to May 2015, 3076 sets of FFDM were performed and sent to PACS and the radiation dose management system (Radimetrics). In total 3076 sets, 2520 were routine bilateral FFDM with 4 views. The mean glandular dose was 6.59± 2.87 mGy (2.63-18.46). In the correlation analysis, the age had moderate negative linear relationship with organ dose. The mAs and breast composition had moderate positive linear relationship with organ dose. The kVp, breast thickness, and compression force had weak positive linear relationship with organ dose. Patients with above diagnostic reference level ( ≥ 75%) of radiation dose showed dense breast composition and thicker breast. Conclusions: The radiation dose management system is useful in FFDM. Especially in Asian women with thick and dense breasts, radiation dose should be carefully managed.
Outcomes and toxicities for the treatment of stage IVB cervical cancer.
Authors: J. H. Hwang, M. C. Lim, S. Seo, S. Kang, S. Park, J. Kim
Journal: Journal of Clinical Oncology (2011)

e15586 Background: The prognosis of stage IVB cervical cancer is generally poor. In the current study, treatment outcomes were evaluated in patients with International Federation of Gynecologic Oncology (FIGO) stage IVB cervical cancer treated with radiotherapy and chemotherapy for progression-free survival (PFS) and treated-related toxicities. Methods: The medical records of the patients with stage IVB cervical cancer who were treated at the National Cancer Center in the Republic of Korea were reviewed retrospectively. From February 2002 to February 2010, 45 patients were diagnosed with FIGO stage IVB cervical cancer. Survival and toxicities were compared between the 13 patients with concomitant chemoradiotherapy (CCRT) with weekly cisplatin (CP) vs. 20 patients with CCRT with 5-fluorouracil/cisplatin (FP). Results: Initial treatment included CP-CCRT, FP-CCRT, neoadjuvant chemotherapy, and radiotherapy with subsequent combination chemotherapy in 13, 20, 4, and 5 patients, respectively. Overall survival (OS) and PFS were 26.2 months and 6.7 months, respectively. There was no statistical difference in OS (p=0.47) and PFS (p=0.64) between the CP-CCRT and FP-CCRT groups; however, the incidence of anemia > grade 3 as an acute toxicity was higher in the FP-CCRT chemotherapy regimen group than the CP-CCRT group (p=0.03). Acute toxicity > grade 2 showed a tendency to be higher in the FP-CCRT group. Gastrointestinal toxicity, anemia, leukopenia, and thrombocytopenia > grade 2 were 38.5 % vs. 65% (p=0.13), 84.6 % vs. 100 % (p=0.15), 84.6 % vs. 95 % (p=0.34), and 23.1 % vs. 50 % (p=0.12) in the CP-CRRT and FP-CRRT groups. Based on multivariate analysis, poor performance status was the only independent prognostic factor of OS (p=0.03, 9.77; 95% CI, 1.3-73.3) and PFS (p=0.04, 9.58; 95% CI, 1.14-81.26). Conclusions: CCRT using combination chemotherapeutic agents may not have survival advantage over single agent cisplatin-based CCRT. The incidence of treatment-related acute and late toxicities tend to be higher in the former group. Further improvement in treatment is needed to increase survival outcomes and to decrease treatment-related toxicities for the patients with stage IVB cervical cancer.
Integration of a cancer registry dataset into a hospital-wide central data warehouse.
Authors: Stephen Flaherty, Robert Savage, Ingrid Stendhal, Susan Roston, Abhijeet Makhe, Veronica Mead
Journal: Journal of Clinical Oncology (2014)

212 Background: The ability to link cancer registry data to clinical and administrative data sets for quality improvement has long been desired. We sought to integrate registry data into a central data warehouse in an effort to make available for the first time consistent and reliable diagnosis and staging data to a broad hospital user group. Methods: After a short period of data analysis, the tables for Cancer Registry data (Oracle) were modeled. The source data (SQL Server) was conformed and integrated using an ETL tool (Informatica). All ETL QA work was performed with SQL queries. Cancer registry data was integrated into reporting architecture (Microstrategy) to facilitate design of standardized and ad hoc reports. Results: 140 distinct fields on demographics, staging (clinical, pathological, collaborative), site specific categories, diagnosis, and treatment were integrated into the Dana-Farber Analytics Reporting Tool (DART) for historic Cancer Registry data beginning with January 2010 newly diagnosed cancers. All Cancer Registry data and patient files (new and old) are updated in DART on a monthly basis. Conclusions: Individuals across the hospital now have the ability to link clinical and administrative data from our EMR, institutional QI data from varied systems, and pharmacy data to Cancer Registry data in the DART tool. One example of the integration of these multiple data sets is the linkage of staging data from the Cancer Registry data set and time to referral data from the administrative data set by patient MRN. As DFCI aims to cohort its patients based on their primary diagnosis for quality improvement and other internal reporting needs, the ability to analyze patients in this way becomes critical. This project sets an example for other centers as they integrate Cancer Registry data into user friendly business intelligence systems to help meet federal reporting mandates and aid internal improvement work. [Table: see text]
Multicentre phase II study of imatinib mesylate in patients with recurrent anaplastic oligodendroglioma (AOD)/mixed oligoastrocytoma (MOA) and anaplastic astrocytoma (AA)/low grade astrocytoma (LGA): An EORTC New Drug Development Group (NDDG) and Brain Tumor Group (BTG) study
Authors: M. van den Bent, A. Brandes, M. Frenay, P. Fumoleau, R. Stupp, C. Dittrich, B. Coudert, P. Clement, D. Lacombe, E. Raymond
Journal: Journal of Clinical Oncology (2005)

1517 Background: Autocrine activation of PDGFα&β receptors yields strong mitogenic effects and activates tumor angiogenesis in malignant gliomas. Preclinical data showed tumor growth inhibition of ras and v-sis transformed BALB/c, 3T3U87 and U343 human glioma xenografts in mice using imatinib mesylate. Methods: To assess the antitumor activity (measured by response and 6-month PFS) and the safety of imatinib mesylate in patients (pts) with histologically proven, CT-scan or MRI documented measurable recurrent non GBM tumors, stable/decreasing doses of steroids, no more than one prior chemotherapy regimen given either in adjuvant or first line treatment, and no surgery or radiotherapy within 3 months prior to enrollment were entered. Imatinib mesylate was given until tumor progression at the daily dose of 600mg and 800mg in two cohorts of pts, group1: AOD/MOA and group 2: AA/LGA. A Fleming one sample/one stage testing procedure was used for each cohort independantly. Results: G3–4 neutropenia was reported in 1 patient (pt). Non hematological toxicity consisted of G3 fatigue in 3 pts, G3 vomiting in 1 pt, G2–3 liver enzyme disturbances in 6 pts, G1 palpebral edema was reported in 3 pts and G1 lower limb edema in 2 pts. Dose reduction: 4 pts; dose interruption: 6 pts. 35 patients are off-treatment, one was stable for more than 6 months. 25 are still too early to evaluate. The trial is closed for accrual. Conclusions: Imatinib mesylate as single agent displays a good safety profile in patients with AOD/MOD and AA/LGA. Final results including response rates and survival will be presented at the meeting. No significant financial relationships to disclose.
Contemporary evaluation of urography in diagnosis in patients with urothelial cell carcinoma.
Authors: Anna Maria Leliveld, Benjamin HJ Doornweerd, Igle De Jong
Journal: Journal of Clinical Oncology (2013)

312 Background: Upper urinary tract tumors (UUTT) can occur synchronous or metachronous (0.7 – 6%) with bladder tumors. The optimal imaging technique of the upper urinary tract is unclear. Studies on the accuracy of retrograde pyelography (RUP) and comparative studies on detection level are sparse. In this study we evaluated the effectiveness of a first RUP in patients with a first manifestation of urothelial cell carcinoma (UCC) in the urinary tract. Methods: In this retrospective study we evaluated all consecutive patients with pathologic proven UCC who underwent their first RUP between March 1998 and April 2008 in the University Medical Center Groningen, Netherlands. Data regarding patient and tumor characteristics, results from RUPs, use of alternative imaging techniques, treatment and outcome were collected from the electronically patient’s records. Follow up was calculated from the first RUP to the last registrated visit. Descriptive statistics have been used to evaluate the performance of the RUP. Results: A total of 156 patients underwent a first RUP because of a first manifestation of UCC of the bladder or upper urinary tract. A mean follow up of 5.09 years was achieved (range 0-13 years). On 17 RUPs (11%) abnormalities were detected. In 16 patients a malignancy was diagnosed. Except one renal cell carcinoma all tumors were UCC of the renal pelvis, ureters or both. Muscle invasive tumors were diagnosed in 7 of these 17 patients. In 30 patients (19%) no conclusive results were obtained because of failure of the RUP due to technical difficulties. In 19 of 30 patients alternative imaging was performed, with intravenous pyelography in 11 patients, computer tomography urography in 7 patients and with both in 1 patient. No UUTTs were diagnosed in this group. In 109 (70%) patients whit a negative RUP three patients developed a tumor after 8, 52, and 65 months. The latter two we consider as newly developed lesions. Conclusions: RUP in patients with a first manifestation of UCC is a very sensitive and accurate diagnostic tool in detecting UUTT.