bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II/III randomized study of hyperfractionated radiotherapy with concomitant cetuximab versus concomitant chemotherapy in advanced nonmetastatic head and neck cancer: Preliminary report.
Authors: Al Saleh Khalid , Safwat Reham , Bedair Ahmed , AL Basmy Amany , Hooda H.S. , Shete Jitendra
Published: March 2020

e16002

Background: This is a randomized study to compare the use of cetuximab versus platinum based chemotherapy with concurrent hyperfractionated radiation therapy (HRT). Acute and late morbidity, locoregional control (LC) and disease free survival (DFS) were set as primary end points, while overall survival (OS) was set as secondary end point. Methods: Between December 2009 and May 2011, 24 patients were randomly assigned to HRT consisting of 120 cGy twice daily, for a total of 69.6 Gys in 58 fractions over 6 weeks, plus either cisplatin chemotherapy at weeks 1, 4, 6 (Arm A: 14 patients) or weekly cetuximab (Arm B: 10 patients). The overall radiation dose was the same for the two groups. The median follow up time of the whole group was 14.07 months (IQR: 5.8- 25.0 ms). Results: Overall treatment time was 72 days in arm A and 63 days in arm B (p= 0.64). Grade 3 skin toxicity was experienced in 42.9% of patients in arm A and 9.1% in arm B (p= 0.09). Grade 3 mucositis was 64.3% in arm A and 45.5% in arm B (p= 0.43). Hematologic toxicity of G3-4 occurred in 21.4% and 18% of the cases respectively (p= 0.06). The mean percent of weight loss was (13 % +/- 0.1%) in group A, and (10.75 % +/- 0.1%) in group B respectively (p=0.56). Complete response was observed in 12 (85.7%) and 100% of patients of arm A and B respectively. Partial response was achieved in the remaining 2 (14.2%) patients in arm A. Loco-regional recurrence occurred in 2 (14.2%) of the patients in arm A after partial response, and one of them died eventually due to progressive disease. Two patients developed distant metastasis, one patient in arm A and another one in arm B. As the sample size was small and events were limited, survival analysis could not be computed at this stage of the study Conclusions: Hyperfractionated radiotherapy and concurrent cetuximab seems to have less side effects compared to concurrent platinum. There's a trend of less skin, mucosal and haematological toxicity with cetuximab that might become significant as the number of patients increase. We will be able to evaluate the outcomes of the patients regarding LC, DFS and OS within 2 years.
Gender associations in head and neck squamous cell carcinoma (HNSCC).
Authors: Hoang Tien , Zhang Chong , Geye Heather M , Speer Tod , Yu Menggang , Wiederholt Peggy A , Kakuske Jennifer C , Traynor Anne M. , Cleary James F. , Dailey Seth H , Ford Charles N , McCulloch Timothy M , Hartig Gregory K , Harari Paul M.
Published: March 2020

e16010

Background: The primary objective of this analysis was to examine the association of gender with various presentation and outcome parameters in HNSCC. Methods: We queried the head and neck cancer (HNC) database at the University of Wisconsinand examined selected clinical, treatment and outcome data for all patients (pts) treated consecutively during the 10-year period (1/01-12/10). Results: From a total of 1,108 HNC pts, we identified 965 with SCC histology, including 252 women (26.1%) and 713 men (73.9%). Women were slightly older at presentation (mean age 62 vs. 60, p = 0.03); 29.6% of women vs. 19.6% of men were 70 years or older. There were no differences in race distribution. Smoking and drinking habits were frequently reported in both sexes, although seen more frequently in men. 74.1% of women vs. 83.1% of men had smoked cigarettes (p=0.003), while 74.9% and 90.6% respectively had consumed alcohol (p<0.0001). 16.3% women never smoked or drank in comparison to 4.6% in men (p<0.0001). There was a difference in primary tumor site distribution between genders (p=0.0003). Oral cavity (41.3%) and larynx (23%) were the most common sites in women vs. oropharynx (31.1%) and larynx (24.8%) in men. There appeared to be no difference in tumor T stage. However, more men presented with N2/3 (51.7% vs. 39.9%, p=0.01) and stage IV (63.1% vs. 53.2%, p=0.04). For initial treatment, more men received multi-modality therapy (56.2% vs. 48.4%, p=0.009) while more women received surgery as sole therapy (37.3% vs. 27.1%). Overall, 72.7% of men vs. 62.3% of women received radiation (XRT); 36.5% and 26.2% respectively received concurrent chemoradiation. There were no differences in baseline performance status, total XRT dose (mean 65.8 Gy), fractionation (mean 33), XRT technique (3D conformal, linac-based IMRT or tomotherapy), or chemotherapy delivered. Recurrence free outcome was achieved equally in both genders at the primary tumor site (~80%), neck (~84%) and distant sites (~88%). Median survival was 89.5 months in women and 84.2 months in men (p=0.65). Conclusions: Although there were no differences in overall survival,our analysis suggests that some gender differences may exist in risk factors and clinical presentation for HNSCC pts. Further study is warranted.
A phase II study of nimotuzumab and CDDP concurrent with radiation in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Lim Wan-Teck , Ang Mei-Kim , Ng Quan Sing , Wang Lan-Ying , Chau Noan-Minh , Tan Daniel S. W. , Chay Wen Yee , Leong Swan , Tan Eng-Huat
Published: March 2020

e16024

Background: Nimotuzumab is a humanized monoclonal antibody (MAb) to EGFR. Concurrent cisplatin with radical radiotherapy (RT) is standard treatment for locally advanced SCCHN where it is unresectable or for organ-preservation. We explored the combination of nimotuzumab with concurrent CDDP and RT in these patients (pts). Methods: Pts with locally advanced stage III/IV SCCHN were eligible for study if: age > 18, ECOG 0-1, SCC, normal organ function. Analysis was by intention-to-treat (ITT). CDDP 100 mg/m2 on days 1, 22, and 43 was given with RT (70 Gy over 35 fractions). Nimotuzumab was given as a flat dose of 200 mg weekly on weeks 1 to 8 of treatment. Pts were followed up for RECIST response, progression free survival and toxicity. Results: Twenty-eight pts were available for analysis at the time of report. The median age was 58 (30-69). Most were Chinese (90%) and all ECOG 0-1. Twelve pts had oropharynx Ca, 16 had non-oropharyx Ca. Twenty-five pts were evaluable for response, 2 pts withdrew consent after 2 weeks, 1 pt died of undiagnosed Fanconi anemia. By ITT, the best overall response rate (CR/PR) was 78.6% (12 CR/10 PR), SD 3.6% (1), PD 7.2% (2). Pts with oropharynx Ca had higher PFS rate at 1 year than non-oropharynx (80% vs 48%). Major grade 3/4 toxicities were limited to mucositis, dysphagia, and fatigue. Grade 5 toxicity due to febrile pancytopenia occurred in 1 pt with undiagnosed Fanconi’s. Acneiform rash typical of EGFR inhibitors occurred in 1 pt. Conclusions: Nimotuzumab with concurrent CDDP/RT is feasible and there was minimal additional toxicity encountered. Final results will be updated at the meeting.
A phase I/II study of radiation therapy, paclitaxel poliglumex, and cetuximab in locally advanced head and neck cancer.
Authors: Hahn Seung Shin , Bogart Jeffrey , Chung Chung Taik , Hsu Jack , Kellman Robert , Kim Jung-AH , Graziano Steve , Martin Dena , Gajra Ajeet
Published: March 2020

e16047

Background: In patients with locally advanced head and neck cancer (LA-HNC), radiotherapy (RT) + cisplatin showed survival benefit over RT alone, but with significant toxicity. The addition of cetuximab to RT demonstrated survival benefit without increased RT-related toxicity. Paclitaxel poliglumex (PPX) is a novel conjugate consisting of paclitaxel linked to a biodegradable, water-soluble polymer of glutamic acid. PPX has a radiation enhancement factor of ≈8 and improved curability in a murine carcinoma model. In a phase I study of PPX + RT in esophageal cancer, no dose-limiting toxicities (DLTs) occurred at PPX doses up to 70 mg/m2/week and an encouraging rate of pathological CRs was observed. This phase I/II study addresses the combined use of intensity modulated RT (IMRT), PPX, and cetuximab in patients with LA-HNC. Methods: Eligible patients had untreated stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx; ECOG PS 0-1; and adequate bone marrow function. In the phase I portion, patients received cetuximab 400 mg/m2 day 1 and 250 mg/m2 days 8, 15, 22, 29, 36, 43, and 50. PPX was administered at 40 mg/m2 days 8, 15, 22, 29, 36, 43, and 50 for Cohort 1 (n = 3) then escalated or decreased for Cohorts 2-5 (3 patients each) until the maximum tolerated dose (MTD) was established. IMRT began on day 8 and consisted of 69.96 Gy delivered in 2.12 Gy daily fractions. In the phase II portion, patients received PPX at the MTD + cetuximab and IMRT at the phase I dose and schedule. Results: In total, 14 patients were treated (9 phase I, 5 phase II). The PPX MTD was determined to be 40 mg/m2. The majority of adverse events (AEs) were grade 1/2 and consistent with known toxicities of individual agents. The most common grade 3 AEs were mucositis (n = 8), radiation dermatitis (n = 4), and cetuximab rash (n = 3). Of 13 patients evaluable for response, 9 had CR and 4 had PR. After a median 17-month follow up, the local control rate was 11/11 and the median survival was 20 months. Two patients with stage IVC disease were excluded for local control and survival analysis. Conclusions: The combination of IMRT, PPX, and cetuximab is tolerable and shows promising clinical activity in patients with LA-HNC.
The impact of interventions on provider and treatment delays in head and neck cancer patients.
Authors: Lai Dominic W. , Kim June , Marciscano Ariel , Buckley Sarah A , Schmidt Brian L. , Cohen Richard F. , Nierodzik Mary Lynn R. , Myssiorek David , DeLacure Mark D. , Sanfilippo Nicholas , Seetharamu Nagashree
Published: March 2020

e16052

Background: Diagnosis and management of squamous cell carcinoma of head and neck (SCCHN) involves a multidisciplinary approach. Navigation at a public hospital can be difficult and lead to delays. In a previous study, we reported English-speaking and employed patients having longer provider delays (Lai 2011). In July 2010, we instituted the use of patient navigators, bimonthly management conferences, and improved inter-disciplinary communication in order to improve the patient experience. Aims: 1. Study differences in “provider delay” (time between first contact with health care provider and positive biopsy) between patients in cohort A (diagnosed between 1/2007 and 6/2010) and cohort “B” (diagnosed between 7/2010 and 6/ 2011). 2. Study differences in “treatment delay” (time between biopsy and initiation of treatment) between the two cohorts. 3. Determine what factors influence delays in both cohorts. Methods: The delays of the two cohorts were compared using the student t-test. Independent t-test and chi-square tests were used to examine associations between delays and the following characteristics: language, employment, presence of partner, gender, ethnicity, age, cancer sub-site, staging, number of co-morbidities, tobacco use, and alcohol use. The likelihood ratio test was used for multivariate analysis. Results: 133 patients in cohort A and 20 patients in cohort B were evaluable. Both provider and treatment delays in cohort B (50.5 and 39.3 days, respectively) were shorter than cohort A (60.2 and 41.6 days), but this was not statistically significant. The standard deviations of both delays were lower in cohort B, pointing towards a greater consistency in this group. In cohort A, provider delay was significantly shorter (p-value=0.003) for non-English speakers than English speakers on univariate and multivariate analysis. Other trends were not observed. Conclusions: Simple interventions can reduce provider and treatment delays. Our observations suggest that these interventions can mitigate the effect of patient factors on provider and treatment delay. However, our results may be affected by small sample size and demographic shifts. With time, we will accrue more patients to address these issues.
A prospective, multicentric clinical study of intensity modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC): A 4-year follow-up report.
Authors: Wu Fang , Wang Ren-sheng , Feng Guosheng , Li Guisheng , Liu Meilian , Yan Haolin , Zhu Jinxian , Hu Kai , Zhang Yong
Published: March 2020

e16054

Background: To evaluate the treatment efficacy, toxicity and prognostic factors of patients with NPC treated with IMRT. Methods: Between January 2006 and August 2008, 300 patients with pathologically diagnosed NPC from 6 medical center received IMRT. The number of patients with stage I, II, III, IVa-b disease (UICC/AJCC 2002 staging system) was 6, 45,141, and 108, respectively. The prescription doses were as follows: 70~74Gy/30 fraction to GTVnx, 68~70Gy/30 fraction to GTVnd, 60~64Gy/30 fraction to CTV1,50~54Gy /30 fraction to CTV2. Patients with stage III, IVa-b disease also received cisplatin-based chemotherapy. Results: The median follow-up time was 47.1 months (range,11-68 months). There were 18,15 and 42 patients who had developed local, regional recurrence and distant metastasis, respectively. There were 45 patients died. 34 patients died of distant metastasis,6 died of local and regional recurrence, 2 died of re-treatment, one died of hemorrhage complications of nasopharynx,one died of second primary tumor, and the other one died of unknown cause.The 4-year rate of local control (LC), regional control(RC), metastasis-free survival(DMFS),disease-free survival(DFS) and overall survival(OS) was 94.0%, 95.5%, 87.4%, 80.8%, 86.1%, respectively. Multivariate analysis showed that N stage was the only prognostic factor for OS (x2=3.912, p=0.048, HR=14.565), DMFS (x2=5.195, p=0.023, HR=8.737)and DFS (x2=7.613,p=0.006, HR=7.628), in these patients. Mucositis was the most severe acute toxicity, with 18.1% grade 1, 48.6% grade 2, 33.3% grade 3 . No patient suffered from grade 4 mucositis. Xerostomia was the most common seen late toxicity, with 8% grade 0, 50.5% grade 1, 4.6% grade 2. No grade 3-4 xerostomia was observed. Conclusions: IMRT can improve the treatment efficacy of patients with NPC. The acute and late toxicities were tolerated. Distant metastasis becomes the main treatment failure. N stage is a significant prognostic factors.
Global survey on barriers to clinical cancer research.
Authors: Cufer Tanja , Cazap Eduardo L. , Delgado Lucia Beatriz , Digumarti Raghunadharao , Leighl Natasha B. , Meshref Mohamed M. , Minami Hironobu , Robinson Eliezer , Yamaguchi Nise Hitomi , Sadikov Aleksander , Seruga Bostjan , Pyle Doug
Published: March 2020

e16505

Background: Many authorities, including ASCO, have raised concerns about growing barriers to clinical cancer research. We believe this is the first global survey of perceived barriers to clinical cancer research from the investigator perspective. Methods: The ASCO International Affairs Committee invited 300 oncologists in 19 countries to complete a web-based survey. Eighty responded, with 41 from high-income countries (HIC) and 39 from low- and middle-income countries (LMIC). Most responders were medical oncologists (62%), at academic hospitals (90%). Barriers were ranked from 1 (most) to 8 (least) important. Results: Most responders reported participating in academia-driven (ADCT) (92%) and industry-driven clinical trials (IDCT) (89%) in the last 5 years, with a significantly higher proportion from HIC compared to LMIC involved in more than 10 ADCT (71% vs. 29%; p=0.008) and IDCT (71% vs. 29%; p=0.017) in that time. Most of the responders (45% from HIC vs. 55% from LMIC; p=NS) reported “no change” in the last 5 years in the proportion of their trials that were IDCT. Of those who said it has become more difficult to conduct ADCT (40/80) and IDCT (27/80), a significantly higher share came from HIC than from LMIC in the case of both ADCT (29/40; 73% vs. 11/40; 28%; p=0.001) and IDCT (19/27; 70% vs. 8/27; 30%; p=0.009). Average time reported from regulatory initiation to the first-patient-in was up to 90 days for 39% of responders, 90-120 days for 26% and more than 120 days for 30%, with extremes reported most frequently by LMIC responders. A lack of funding was ranked the most important barrier to ADCT by both HIC (3.15) and by LMIC (3.18) responders, and a lack of patients the least important by both HIC (5.27) and LMIC (5.59) responders. LMIC responders considered competent authorities (regulatory) procedures a more important barrier than HIC responders (3.87 vs. 4.67). Conclusions: Though investigators from HIC are involved in more ADCT and IDCT than LMIC counterparts, they are more likely to perceive the barriers to conducting trials as worsening. Of note, no major shift towards greater IDCT was reported in our survey. With regards to ADCT, the main barrier that should be improved globally is financing, with an additional focus in LMIC on regulatory procedures optimization.
Comparative effectiveness assessment of a lung cancer multidisciplinary practice to improve patient care.
Authors: Mirshahidi Hamid R. , Hernandez Elvin , Ta Matthew , Baylon Sheley M , Pham Minh Thy , Lee Bonnie , Jahng Patrick , Kung Ling , Wong Siu-Fun
Published: March 2020

e16523

Background: Multidisciplinary focused-care teams have shown beneficial outcomes in diagnosis and treatment in cancer patients as well as assist in providing accessible, cohesive and continuous care. The multidisciplinary team specializing in thoracic cancer at our institution includes thoracic surgeons, pulmonologists, medical oncologists, radiation oncologists, pathologists, radiologists and a weekly tumor board with the inclusion of a dietician, a pharmacist, and a psych/social worker. This study examined the effectiveness of a multidisciplinary focused program in improving overall care in lung cancer patients. Methods: Lung cancer patient data between January 2000-December 2009 were abstracted from the institutional cancer registry. Patient demographics, treatment received, and survival (1-year and 2-year) were compared between Group A (January 2000-July 2005) and Group B (August 2005-December 2009) using Fisher’s exact test. Results: 1202 patients (Group A = 760; Group B = 442) were evaluated. Majority of patients were > 60 years old, male, and has stage IV adenocarcinoma. Missing stage was less in Group B (13.8% vs 17.4%). Early stage patients in Group B received more surgeries and less inappropriate treatments. More palliative chemotherapy/radiation treatments were given in Group B late stage disease. More stage II (21.1% vs 2.3%) and IIIA (12% vs 1.5%) patients in Group B were treated with wedge resection and chemotherapy. One-year survival differences were seen between 2 groups in stage I, IIIA, and IV (P <0.05). 2-year survival difference was seen in stage IV disease (P<0.05). Conclusions: Introduction of multidisciplinary lung care team between 2005-2009 was associated with an increased patients being staged and more appropriate treatments. One year survival almost doubled in stage I patients where stage IV pts experienced up to 4 times improvement in 1- and 2-year survival. The results of the present evaluation appear to confirm the value of a multidisciplinary approach to the management of patients with lung cancer.
Use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.
Authors: Arlen Aimee Ginsburg , Cartwright Thomas H. , Wilfong Lalan S. , Hoverman J. Russell , Nelson Greg C , Turnwald Brian , Beveridge Roy A. ,   on behalf of The US Oncology Pathways Task Force
Published: March 2020

e16536

Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 43,920 patients will be diagnosed in 2012 and 37,390 will die (Siegel, CA Cancer J Clin, 2012). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment options have led to the utilization of a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) in patients with good Karnofsky performance status (PS). This regimen was compared to single-agent gemcitabine, presented at ASCO 2010 and recently published (Conroy, NEJM, 2011). This retrospective analysis was conducted to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. Methods: Patients with advanced PC treated within The US Oncology Network and entered into the iKnowMed (iKM) database between June 2010 and November 2011 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Of the 717 patients identified within the iKM database, 13% received FOLFIRINOX and 87% gemcitabine-based therapy. Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (54% male), the median age at diagnosis was 67 years and the majority of patients (89%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (8.4 months) versus gemcitabine (6.4 months) (p=0.036). OS was also significantly longer for PS of 70% or greater given FOLFIRINOX (9.0 months) versus gemcitabine (6.7 months) (p=0.022). After controlling for PS, the use of gemcitabine led to a shorter OS (HR 1.4; 95% CI: 1.02-2.01). Conclusions: Utilization of FOLFIRINOX has rapidly been adopted in patients with good PS after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community setting, we agree that should FOLFIRINOX become a standard of care for good PS patients.
Estimation of hypertension (HTN) occurrence, severity changes, and patterns of antihypertensive (AH) use in patients (pts) receiving VEGF inhibitors for the treatment of cancer.
Authors: Thompson Lisa A. , Saseen Joseph , O'Bryant Cindy L. , Allen Richard Read , Nair Kavita V.
Published: March 2020

e16541

Background: Reports have examined the occurrence and management of HTN in pts receiving VGEF inhibitors, but typically have small samples and represent single institutions. This study used a large claims database to describe how the use of VGEF inhibitors impacted the occurrence, severity and management of HTN. Methods: Claims data (2004-2009) from Medstat’s MarketScan database identified pts with bevacizumab (BEV), sorafeninb (SO) and sunitinib (SU) claims and an approved cancer indication. First prescription claim for a VGEF inhibitor was the index date; treatment period began on this date and ended 30-60 days after the last VEGF inhibitor claim. Pts were followed for 12 months pre and post index date. HTN was defined as at least one ICD-9 (401.xx) or AH prescription claim. Cohort A (A) included pts with no HTN prior to index date; Cohort B (B) included pts with HTN prior to index date. A was divided into cohort A1 (A1): no HTN pre or post index date; and cohort A2 (A2): HTN post index date. HTN severity was defined in accordance with CTCAE v4.0 as: pre-HTN and no AH claims (grade [gr] 1); 1 or 2+ AH claims within 90 days (gr 2, 3); or life threatening complications (gr 4). Cardiac complication ICD-9 codes were collected. Results: 2177 pts received BEV (89.3%), SO (4.9%) and SU (5.8%). A had 1041 pts; 32% (A2) had HTN. B had 1136 pts. Gr 1 HTN incidence increased during the treatment period in A1 (0.1 to 0.7%) and A2 (0.9 to 12.3%), but decreased in B (12 to 7.5%). Gr 2 HTN increased from 1.2 to 48% (A2) and 26.4 to 32.4% (B). Gr 3 HTN increased from 0 to 18.6% (A2) and 33.5 to 41% (B). Gr 4 HTN occurred in 3.4% (A1), 8.4% (A2) and 6.3% (B) of pts within one year post index date. B had higher complication rates (16.7%) than A1 (2.3%) and A2 (9.6%). 286 (85.9%) pts in A2 received AH; median time to AH initiation was 96 days. Pts in A2 required 0.9 AH during the treatment period compared to 1.3 in B. Initial AH class did not affect complication rates in A2. Conclusions: We observed clinically relevant HTN in a significant proportion of pts receiving VEGF inhibitors with real world data. HTN incidence increased in all cohorts, regardless of baseline HTN. Pts should be monitored carefully for HTN.
Development and validation of a clinical trial feasibility assessment (CTFA) tool and evaluation of the NCI clinical trial evaluation and scoring (NCI-CTES) model.
Authors: Weiss Matthias , Bulgrin Angela , Liang Hong , Fuehrer Kim , Choudhary Vidhu , Yale Steven
Published: March 2020

e16549

Background: The ability to predict accrual success of a specific NCI sponsored clinical trial (CT) in the setting of a Community Clinical Oncology Program (CCOP) is typically based on the experience of the local principal investigator (PI) and research staff. This study was designed to develop an objective method to predict accrual success based on CT and institution specific factors. Funded by ARRA grant #3U10CA35412-26S1. Methods: 27 potential barriers to successful CT accrual were identified by Marshfield Clinic CCOP and validated by Eastern Cooperative Oncology Group (ECOG) PI and research staff (Cronbach alpha 0.922). This 27 item CTFA tool and the NCI-CTES model were prospectively applied to 32 consecutive NCI sponsored CT which opened at Marshfield Clinic CCOP (2009-11). Incorporating PI and research staff input each CT was scored (CTFA range 27-135; NCI-CTES 0-22). These scores were correlated with accrual outcome (Wilcoxon`s rank-sum test). Statistical analysis included CTFA item content validity testing via item-test correlation and CTFA/NCI-CTES internal consistency reliability testing via Cronbach alpha. Results: 28/32 CT were available for analysis; 4 CT were excluded (never opened to accrual). Duration of time open to accrual ranged from 1-27 months (mean=13.5). 21/28 CT achieved accrual ranging from 1-50 subjects (1-5 accrual=13; 5-10=4; >10=4). Median time to complete the 27 item CTFA tool was 16 minutes and 8 minutes for the NCI-CTES model. After eliminating 6/27 CTFA items due to low content validity (<0.2), the remaining 21 item final CTFA tool indicated very high internal consistency reliability (Cronbach alpha 0.872). Wilcoxon`s rank-sum test revealed that the differences in NCI-CTES and CTFA scores between the groups with <=0.25 and >0.25 subject accrual per month were significant (CTFA P-value=0.0418; NCI-CTES P-value=0.0032). Conclusions: Application of the CTFA tool and the NCI-CTES model proved to be feasible and predictive of accrual success of NCI sponsored clinical trials at Marshfield Clinic CCOP.
Physician participation and compliance with cancer clinical care pathways: A successful model of collaboration between payers and providers.
Authors: Ruane Thomas , Stella Philip J. , Scott Jeffrey A. , Feinberg Bruce A. , Cooper Joseph
Published: March 2020

e16552

Background: Blue Cross Blue Shield of Michigan (BCBSM), Physician Resource Management (PRM), and Cardinal Health Specialty Solutions (CHSS), partnered to develop a clinical pathway program that would benefit all parties by improving the consistency and quality of patient care while reducing costs. A major obstacle to clinical pathway adoption is physician participation and compliance. Incentives were provided to physicians to join and comply with this clinical pathways program. We report the rates of physician participation and compliance after 1 year. Methods: In 2009, treatment and supportive cancer care clinical pathways moderated by PRM and CHSS chief medical officers were developed by a 12-member steering committee of BCBSM network oncologists. The non-steering committee physicians within the BCBSM network then provided input and review prior to implementation. Physician financial incentives were provided by BCBSM to encourage adoption of the cancer pathways: (1)$5,000 (2) an increased reimbursement rate for certain generic therapies associated with the pathways (3) a share of the savings realized in expenditures for chemotherapy and supportive medications directly attributable to pathways. Rates of participation and compliance by physicians were evaluated after the first year. Compliance was measured using insurance claims data from BCBSM and a proprietary CHSS claims management software tool. Results: Out of 228 Michigan private practice medical oncologists, 187 (82%) participated in the first year of BCBSM’s cancer pathways program. Average compliance rates for the cancer treatment and supportive care pathways over the year 2010 were 96% and 92.5% respectively. Conclusions: Effective clinical care pathway programs require robust physician participation and compliance. Involving physicians in the pathway development process and providing financial incentives led to high rates of physician involvement and “buy-in”, a crucial step in developing our successful clinical care pathway program.
Supportive simultaneous care: A novel approach to frail cancer patients.
Authors: Quirino Michela , Cassano Alessandra , Corallo Salvatore , Turriziani Adriana , Orlandi Armando , Schinzari Giovanni , Basso Michele , Barone Carlo
Published: March 2020

e16553

Background: In the last decades, improvements in systemic therapies and advances in supportive and palliative care made pts, usually early referred to exclusive supportive care, suitable for integrated strategies of care. This approach responds to an increasing effort to integrate palliative care in the model of comprehensive cancer care. Its feasibility relies on cooperation between oncologists and palliative care providers along the period of disease until the death of the pt. We report the experience of our Simultaneous Care Unit in the period 2008-11. Methods: We observed 159 pts (76 M, 83 F), median age 72 years (29-95), affected by advanced solid tumors or hematological malignancies. All pts received assistance by the Simultaneous Care Unit (SCU) composed by oncologists, psychologists, palliative care providers, spiritual assistants. They all received palliative and supportive care in the home setting and cancer therapies as outpatient. All pts were monthly evaluated for clinical benefit, defined as follows: ESAS score decreasing from >4 to <4 cut points and PS ECOG decrease from ≥2 to <2. We also evaluated the rate of hospitalization as the number of pts requiring access to our Acute Palliative Care Unit (APCU) as inpatient for acute illness or uncontrolled symptoms. Costs analysis was performed on the basis of the DRG reimbursements. Results: The median length of simultaneous care was 88 days (95% C.I. 68.75-111.51). Clinical benefit rate was 63,5% (95% C.I. 55.96-71.09). Hospitalization rate was 23,27% (95% C.I. 16.63-29.91). Median length of hospitalization for each pt (until symptom improving or death, if occurred) was 22,5 days. Median cost for each pt hospitalized at our APCU was 4478 euros. Conclusions: Our experience within the SCU shows that the early integration of SC and active cancer treatments is effective. Our % hospitalization is lower than that reported by other authors in the same settings of pts (range 30-70%) with a significant saving of money. If confirmed in prospective pharmaco-economic studies, our data suggest that our model provides a high-quality assistance to frail patients and could be exportable also in other settings of chronic illness, potentially leading to a more wise way to use Health Care System resources.
Oncology education in Canadian undergraduate and postgraduate medical programs: A survey of educators and learners.
Authors: Tam Vincent Channing , Berry Scott R. , Hsu Tina , North Scott A. , Neville Alan John , Chan Kelvin K. , Verma Sunil
Published: March 2020

e16558

Background: Deficiencies in undergraduate (UG) oncology education have been documented and there is a lack of data on the quality and quantity of oncology education in postgraduate (PG) family medicine (FM) and internal medicine (IM) training programs. Methods: A self-administered web-survey was created to obtain information regarding the current oncology curriculum at medical schools and PG FM and IM training programs. Survey requests were sent to educators (undergraduate medical education curriculum committee members (UMECCM), family medicine (FMPD) and internal medicine program directors (IMPD), oncologists) and learners (final year medical students (MS), family medicine (FMR) and internal medicine residents (IMR)) at all 17 of Canada’s medical schools. Results: 159 of 961 educators (19 UMECCM, 7 FMPD, 10 IMPD, 54 medical oncologists, 67 radiation oncologists and 2 hematologic oncologists) and 518 of 1966 learners (342 MS, 95 FMR and 81 IMR) completed the survey. Overall response rate was 23% (educators 17%, learners 26%). Responses were received from at least one educator or learner from all 17 medical schools. The amount of oncology education was thought to be inadequate in their respective programs by 58% UMECCM, 57% FMPD and 50% IMPD. 82% of oncologists believed that oncology education was inadequate in their UG and PG FM and IM programs. For learners, oncology education was thought to be inadequate in their respective programs by 67% MS, 86% FMR and 63% IMR. Of 10 different categories of medical illness all groups agreed that their trainees were least adequately prepared to manage cancer. A standard set of oncology objectives was thought to be useful for UG learners by 59% of respondents and 61% for PG learners. The 3 topics considered most important as core competencies in oncology for both UG and PG learners are: cancer diagnosis, breaking bad news and cancer screening. Conclusions: Oncology education at the UG medical and PG FM and IM levels are currently thought to be inadequate by a majority of educators and learners. Developing a standard set of oncology objectives focusing on topics believed to be most important by educators may improve the quality of oncology education for learners.
Patients’ and health professionals’ perspectives on the outcomes, conduct, and medico-legal implications of multidisciplinary cancer meetings (MDMs).
Authors: Devitt Bianca Alix , Philip Jennifer , Singh Madhu Sudan , Mileshkin Linda R. , McLachlan Sue-Anne
Published: March 2020

e16562

Background: Multidisciplinary cancer meetings (MDMs) are a fundamental component of multidisciplinary cancer care. Guidelines relating to their conduct are largely based on expert opinion rather than empirical evidence. We examined patients and health professionals’ (HPs) attitudes to the outcomes, conduct and medico-legal implications of MDMs. Methods: Two study-specific questionnaires were developed based on qualitative research, published literature and guidelines, for health professionals who attend MDMs and patients with a current or previous diagnosis of cancer. The questionnaires were administered at 4 health services encompassing tertiary and regional centres in Victoria, Australia. Results: 170 HPs (response rate 62%) and 110 patients (response rate 83%) completed the questionnaire. 92% of patients want their case discussed at an MDM. HPs believe the focus of MDMs is to consider different treatment modalities (99%) and ensure patients receive evidence-based care (83%) rather than address psychosocial issues (52%). Similarly, patients allocated 71% of MDM discussion time to discussing possible treatment options, 15% to relevant social issues and 14% to psychological issues. More than 70% of patients and HPs thought no formal patient consent was required prior to discussion at MDM. 75% of HPs agreed MDMs provided them with increased medico-legal protection. 93% of HPs thought MDM discussions should result in a consensus on the proposed management plan. Patients would prefer to discuss the outcomes of the MDM personally with their treating doctor (81%) and 75% also desired written documentation. Conclusions: Patients and HPs agree the focus of MDMs is predominately medical with emphasis on treatment planning rather than the psychosocial needs of patients. Both groups believe MDM discussion forms part of standard care and formal consent is not required. HPs aim to develop an individualized, evidence-based management plan, agreed to by consensus. Strategies to improve communication of this plan to patients should be developed. This is the first empirical evidence on MDMs’ conduct and should help inform the development of future guidelines.
Outcomes of autologous stem cell transplant (ASCT) in multiple myeloma from a tertiary cancer center in India.
Authors: Bagal Bhausaheb Pandurang , Khattry Navin , Dongre Amol , Kanan Sadhana , Menon Hari , Sengar Manju , Nair Reena
Published: March 2020

e17003

Background: ASCT is part of standard treatment in multiple myeloma (MM).We report the results of such transplants and evaluate the role of prognostic factors if any in our patients. Methods: Sixty-one patients who underwent ASCT between June 1993 and March 2010 were included. Twenty four patients received VAD like regimen. Nineteen patients received novel agent based therapies. Ten patients underwent cyclophosphamide based mobilisation while only G-CSF based mobilisation done in 51 patients. Stem cells were harvested from peripheral blood in all patients. Melphalan was used at 200 mg/m2 in 24 patients. Prognostic factors evaluated for overall (OS) and progression-free survival (PFS) were baseline hemoglobin and albumin, ISS stage, disease status at day 100 post transplant, use of maintenance treatment post transplant, response to first line chemotherapy, use of novel agents before transplant and time to transplant from diagnosis. Results: Median age was 46 years. Median baseline haemoglobin (Hb) and albumin were 9.7 g/dl and 3.9 g/dl respectively. At the time of transplant 36% were in complete remission (CR), 5% in very good partial response (VGPR) and 28% in partial remission (PR). Median time to engraftment of neutrophils and platelets was 12 and 17 days respectively. Grade III–IV oral mucositis was seen in 35%. Transplant related mortality was 8.0 %. The 5 year overall survival (OS) and progression free survival (PFS) were 73% and 33% respectively. OS was better for patients with pre-transplant Hb greater than 9.7 g/dl (P= .04) and those who achieved CR at day 100 post transplant (P= .03). Patients who received maintenance therapy showed trend towards better OS (P= .07). PFS was better for patients with baseline albumin greater than 3.9g/dl (P = .043), Hb greater than 9.7 g/dl (P = .027) and early stage disease by ISS staging system (P=.001). Conclusions: Our study confirms that ASCT in such patients is safe and effective. Baseline albumin and Hb, ISS stage, day 100 disease response and use of maintenance treatment are important prognostic factors affecting survival.
Recombinant human activated FVII as prophylaxis in surgical treatment of cancer patient with acquired hemophilia A.
Authors: La Verde Giacinto , Ferrari Antonella , Ziparo Vincenzo , Naso Virginia , Bianchi Maria Paola , Antolino Giusy , Saltarelli Francesca , Monarca Bruno , Resci Federica , De Benedittis Daniela , Moscetti Alessandro
Published: March 2020

e17006

Background: Acquired hemophilia A is caused by the development of factor (F)VIII autoantibodies and results in more serious haemorrhagic symptoms than in congenital severe HA. About 50% of cases, not identified as idiopathic, are related to autoimmune diseases, viral infections, pregnancy and also neoplasms. To treat bleeds recombinant factor VIIa and activated prothrombin complex concentrate are equally efficacious while immunosuppression with steroids alone or combined with cytotoxic agents should be started as soon as the diagnosis is made. Methods: In February 2010 a woman of 58 years with acquired hemophilia A, previously treated in 1978 with cyclophosphamide and steroids without clinical benefits, was admitted to the Hematology Department of Sant’Andrea Hospital in Rome for a recent episode of spontaneous massive enterorrhagia. The diagnostic exams revealed a colorectal carcinoma (moderately differentiated G3) associated with papillary urothelial neoplasia with low malignant potential. A coagulation panel showed an aPTT ratio of 3.75 (normal range 0.8-1.2), INR 1.03 (normal range 0.9-1.2), fibrinogen 327 mg/dL (normal range 238-500), FVIII activity level of 3% (normal reference 50-150%) and FVIII inhibitor titer > 100 Bethesda Units. Results: The patient was treated with left hemicolectomy and removal of the bladder lesion associated with chemotherapy XELOX (oxaliplatin 130 mg/sm day 1 q21, capecitabine 1000 mg/sm orally day 1-14 q21). From day -1 to day +15 post surgery, the patient was treated with intravenous recombinant human activated FVII at standard dose (NovoSeven®, 90 mcg/kg every 4 hours). Our treatment avoided both intra and post-operative surgical bleeding complications, while not changing the titer of the inhibitor nor by normalizing the aPTT ratio. Actually the patient is in good clinical conditions with no further hemorrhagic episodes, although the FVIII inhibitor titer still remains high. Conclusions: We have described this case to emphasize that the presence of acquired hemophilia A in cancer patients, thanks to its specific prophylactic treatment, cannot be a limit in performing routine diagnostic and therapeutic procedures, especially surgical ones.
Adherence and persistence to second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia.
Authors: Trivedi Digisha , Amin Shahla , Zhu Ling , Joo Sam , Kawabata Hugh , Darkow Theodore , Hebden Tony
Published: March 2020

e17009

Background: Some studies have demonstrated the correlation between adherence and persistence to therapy and the effectiveness of that therapy, thereby reinforcing the need to optimize both as a core treatment strategy. Because available data are limited, we examined real world adherence and persistence to the 2nd generation tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). Methods: An observational retrospective study was conducted using pooled Invision Data Mart and Pharmetrics claims data. Adult CML patients with at least two prescriptions for a 2nd generation TKI between July 1, 2006 and December 31, 2010 were identified and followed for a maximum of 6 months from their index date (first observed prescription date). Dasatinib and nilotinib patients with prior imatinib use in 6 month pre-index period were classified as second-line and those with no prior use as first-line patients. Adherence to treatment was defined by the medication possession ratio (MPR) and persistence as the proportion of patients refilling prescriptions within 1.5 times the days supply during the follow-up period. Results: Of the 276 CML patients identified, 179 received dasatinib (n=50 first-line; n=129 second-line) and 97 received nilotinib (n=27 first-line; n=70 second-line). Patient characteristics were similar across treatment groups. Proportions with MPR ≥85% were 64% and 75% for first- and second-line dasatinib and 48% and 61% for first- and second-line nilotinib. Persistence rates were 36% and 47% for first- and second-line dasatinib and 26% and 39% for first- and second-line nilotinib. Conclusions: In both first- and second-line use, dasatinib was associated with higher adherence and persistence than the corresponding nilotinib-treated group. The reason for the difference between these TKIs is not known and will require further study.
Primary ovarian granulocytic sarcoma: A case report and literature review.
Authors: Njoh Roland Fokwen
Published: March 2020

e17011

Background: Granulocytic sarcoma, also known as myeloid sarcoma, myeloblastoma, and Chloroma are extramedullary manifestation of malignant myeloid precursor cells. Its occurrence as a primary ovarian tumor is a rare entity. Methods: A 49 y/o female presented to the clinic with right lower quadrant abdominal pain that had been present for 6 months. Eventually, a CT scan was obtained that showed a 6.5 cm mixed solid and cystic mass on the right adnexa that was felt to represent malignancy. Her history was positive for residing near a car-spraying garage. She was taken to the operating room and underwent a robotically assisted laparoscopic BSO, laparotomy, omentectomy, lymph node dissection and tumor debulking. Findings at surgery included a normal left ovary, adherent right ovary, normal omentum, nodular epiploicae, and tumor encasing the iliac vessels. Final pathology report of tumor cells showed granulocytic sarcoma with flow cytometry positive for CD 33 and CD 34. Bone marrow biopsy and peripheral blood flow cytometry was negative for leukemia. She subsequently underwent chemo-induction with cytarabine, idurubicin, and prednisone. Results: A PUBMED, MEDLINE/OVID database search revealed only three previously reported cases of primary ovarian granulocytic sarcoma without concurrent or subsequent hematological manifestation. Conclusions: Granulocytic sarcoma most frequently precedes or occurs in the setting of acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). The typical sites of isolated granulocytic sarcoma include bone, periosteum, soft tissues, and lymph nodes, and less commonly the orbit, intestine, mediastinum, epidural region, uterus, and ovary. In patients presenting with primary ovarian granulocytic sarcoma, the final diagnosis is obtained after tissue examination and often comes as a surprise to providers. Granulocytic sarcoma should therefore be included in the differential diagnosis of patients with isolated ovarian tumor.
Occult hepatitis B and occult hepatitis C viremia in patients with hematologic malignancies.
Authors: Torres Harrys A. , Mahale Parag , Kontoyiannis Dimitrios P , F. Blaine Hollinger F. Blaine
Published: March 2020

e17016

Background: Occult Hepatitis B (OHB)and Hepatitis C (OHC) in patients with hematological malignancies (HM) are understudied, mainly because biopsies to identify these viruses in the liver are often not performed due to an associated risk of complications (e.g., bleeding). We describe our retrospective experience of patients with HM tested for OHB and OHC. Methods: Between 09/09 and 11/10, 18 unselected consecutive patients with an abnormal liver panel were tested for both OHB and OHC which was defined as detectable viremia in the absence of HBsAg and anti-HCV, respectively. Severe liver dysfunction was defined as ALT >10 times the upper limit of normal (>560 IU/L) and/or a total bilirubin >6 mg/dL. Plasma samples were tested for HBV DNA and HCV RNA by using real-time PCR (Cobas Taqman HBV and HCV Tests-Roche Molecular Systems). Results: Most patients (12 or 67%) had leukemia, followed by lymphoma (5 patients or 28%). Two patients (11%) had OHB, and none had OHC.The 2 patients with OHB were born in areas with an intermediate to high prevalence of HBV; both had only low grade viremia (<29 IU/mL). At the time HBV DNA testing was performed, peak ALT levels in these 2 patients were 843 IU/L and 6,047 IU/L compared to a median peak ALT of 302 IU/L (range, 84-1,320 IU/L) among those without OHB (P=0.03). Severe liver dysfunction occurred in the 2 (100%) patients with OHB compared to 6 (38%) of the non-OHB cases (P=0.1). Durations of ALT elevation were 12 and 17 days in patients with OHB, compared to a median duration of 13 days (range, 5-73 days) in non-OHB patients. Co-infections were identified in 1 patient with OHB and in 10 (63%) without OHB. The 2 patients with OHB and 8 (50%) patients without OHB died within 6 months after HBV DNA testing. Conclusions: Although our data are limited, in a group of cancer patients in whom a liver biopsy is not available, detection of HBV DNA or HCV RNA in serum in the absence of HBsAg or anti-HCV identifies a subset of patients with occult viral hepatitis, a phenomenon of unclear clinical significance.