bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of weekly bevacizumab and gemcitabine/oxaliplatin with or without dasatinib on heavily pretreated patients with recurrent or persistent cervical cancer.
Authors: Takano Masashi , Kikuchi Yoshihiro , Ikeda Yuji , Sasaki Naoki , Goto Tomoko , Kouta Hiroko , Kikuchi Ryoko , Kudoh Kazuya , Kita Tsunekazu , Furuya Kenichi
Published: March 2020

e15579

Background: Prognoses of patients with recurrent and metastatic cervical cancer who received treatment including radiotherapy are commonly dismal. In such clinical settings effective treatment modalities are waited. Thus, we attempted to explore effects of weekly bevacizumab (B) and gemcitabine/oxaliplatin (GEMOX) with or without dasatinib (D). Methods: Ten cases with recurrent and metastatic CC after intensive treatment including radiotherapy were treated by weekly B (2mg/kg) and GEM (300mg/m2)/ OX (30mg/m2) with or without D (50mg/day) (3 weeks, one week rest) with written informed consents. The treatment was continued until development of progressive disease (PD) or unmanageable adverse effects. Adverse effects were analyzed according to NCI-CTCAE v3. The responses were evaluated by RECIST criteria. Results: In RECIST evaluation, one (10%) of 10 patients had complete remission (CR) and 4 (40%) had partial remission (PR). Overall response rate was 50%, and response was observed in four (80%) of 5 cases combined with D, and 1 (20%) of 5 patients without D. It is noteworthy that response was observed in 3 (60%) of 5 adenocarcinoma patients. Median progression-free survival (PFS) and overall survival (OS) were 6 months and 13 months, respectively. Hematological adverse effects more than grade 1 were not observed. Neurotoxicity, nasal bleeding, and general fatigue were frequently observed, but these were all grade 1. There was no toxicity-related death, and the regimen was well tolerated. Conclusions: The present preliminary study demonstrated weekly B and GEMOX with or without D was effective in heavily pretreated cervical cancer patients with tolerable toxicities, especially in patients with adenocarcinoma. These results warrant further study in such clinical settings.
Concurrent chemoradiotherapy using carboplatin/cetuximab regimen in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) not eligible for high-dose cisplatin (HD-DDP).
Authors: Saigal Kunal , Warsch Sean , Mandalia Amar , Samuels Michael , Tolba Khaled A. , Ikpeazu Chukwuemeka , Kwon Deukwoo , Santos Edgardo S.
Published: March 2020

e16001

Background: Cetuximab (Cx) + radiation therapy (RT) is well tolerated and has improved survival in patients (pts) with LA-HNSCC. However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin (Carbo) is added to Cx + RT for pts unsuitable for HD-DDP. Methods: We reviewed records of 16 pts with LA-HNSCC treated with definitive Cx + Carbo + RT at the University of Miami from 2007-2011. Median follow-up was 9.4 months (range: 1-50 months). Results: Median age: 71.5 years (range: 57-90 years); 15 male, 1 female.ECOG PS 0=15, 1=1. TNM staging was: T1= 1, T2= 5, T3=8, T4=2; N stage: N0=8, N1=5, N2a=2, N2b=1. All pts received weekly Carbo (AUC 1.5-2), Cx given conventionally and daily conventionally-fractionated RT. Median total weeks of concurrent systemic therapy= 7 (range: 3-8 weeks). RT was delivered to a median total dose of 70 Gy (range 30-74 Gy). Of the 15 evaluable pts, there were: 12 CR, 2 PR, and 1 PD. There were 2 local in-field failures, 1 regional failure, and 3 distant failures. At last follow-up, 11/16 pts remained with NED. 3-year locoregional recurrence was 29.5% (95% CI: 5.3%-45.9%). Toxicity (NCI-CTCAE v4.0): Mean percentage of weight loss was 14% (range: 6-26%). Two pts required systemic therapy dose-reduction. Three pts experienced a treatment delay and 3 did not finish RT as planned including one pt who received only 30Gy due to death secondary to MI during treatment. Conclusions: In this small retrospective series, Carbo/Cx/RT was well-tolerated and efficacious in pts unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well-tolerated cytotoxic chemotherapy agent may improve the therapeutic ratio of Cx + RT in pts who are poor candidates for more aggressive therapies and warrants evaluation in a prospective manner. [Table: see text]
Docetaxel (T), cisplatin (P), and TP 5-fluorouracil (F) with or without cetuximab in head and neck squamous cell carcinoma (HNSCC): Simulation of ex vivo results in the FLAVINO-assay.
Authors: Dietz Andreas , Boehm Andreas , Niederwieser Dietger , Wichmann Gunnar
Published: March 2020

e16016

Background: Individual response evaluation in head and neck squamous cell carcinomas (HNSCC) would be welcome for better biology-based decision making since therapy strategies like concurrent radio-chemo and induction-chemo (IC) compete with surgery e.g. of resectable advanced HNSCC. However, inter-individual differences in response to mixtures of chemotherapeutics and biologicals are not exactly known even in guideline-conform treatments. The purpose was to analyze combined effects of T, P, F, and cetuximab (E) on colony formation (CF) of HNSCC in the FLAVINO assay and the comparison with the clinical response to IC. Methods: Before starting IC, biopsies were taken, collagenase-digested and exposed to T and/or P at quarter, half, and exact their tolerable plasma (TPL) levels (6.6 and 0.55 µM) in presence or absence of F (1.5 µM)±E, and controls. To facilitate counting of colonies formed within 72h, epithelial cells were stained by Cy2-labeled pan-cytokeratin antibodies. The 28-d response to the first cycle of IC (reduction in surface and volume of the primary) was compared with CF. Results: Poorest response to IC was observed in patients with HNSCC unable to form epithelial colonies (13/36). Of the 63.9% ex vivo growing HNSCC, 34.8% (8/23) and 8.7% (2/27) responded to C and T in concentrations ≤TPL with completely inhibited CF. This rate was increased in presence of E. 22/23 (95.6%) HNSCC formed >4 epithelial colonies and allowed for IC50 calculation. TP+E and TPF+E proved to be more effective than binary combinations. Combined with increasing doses of P, the IC50 of T decreased and indicated superiority compared to treatment with T in binary combination with F. We found a high correlation of ex vivo and in vivo response of HNSCC. Conclusions: Complete suppression of CF and failure to form colonies ex vivo best predicted responsiveness or resistance to IC. Despite mostly additive or synergistic effects of TP and TPF ex vivo, identification of HNSCC probably failing to benefit from IC prior to starting therapy could reduce the risk of choosing inappropriate treatment modalities for HNSCC.
Distant metastasis in head and neck cancer: Baseline factors.
Authors: Krishnatry Rahul , Gupta Tejpal , Murthy Vedang , Nair Sudhir Vasudevan , Nair Deepa , Chaturvedi Pankaj , Dcruz A. K. , Prabhash Kumar , Ghosh Sarbani Laskar , Budrukkar Ashwini Narsingrao , Agarwal Jaiprakash
Published: March 2020

e16021

Background: Loco-regional relapse is predominant pattern of failure in locally advanced head & neck squamous cell cancer (HNSCC). Distant metastasis (DM) is increasingly detected on follow-up. this study attempts to identify baseline patient, tumor & treatment characteristics which determine poor survival in radically treated HNSCC patients developing DM. Methods: Clinical outcome audit of HNSCC receiving radical treatment from 1990-2010 in a single HNCC radiotherapy (RT) clinic who developed DM, using electronic search of a prospectively maintained database. The Disease free survival (DFS) & overall survival (OS) were calculated using Kaplan Meier method. The Log rank test & Cox regression (p< 0.05 significant) were used for univariate & multivariate analysis respectively. Results: 104 HNC patients developed DM, baseline characteristics are shown in table 1. DM was detected at a median of 7(IQR 3-14) months from treatment completion & median survival after diagnosis of DM was 2.6 (0-6) months. The median DFS & OS were 19(13-26), 21.5(16-29) months respectively. On univariate analysis, factors affecting DFS & OS were advanced tumor and nodal stage, perinodal extension & treatment factors (surgery & RT gap >30 days). On multivariate analysis stage and PNE remained significant for DFS while only stage showed significance for OS. Conclusions: Locally advanced stage of presentation (stage IV, T4, N2+) is the most important baseline factor determining poor outcome in HNC patients developing DM. Trials for aggressive primary systemic treatment (chemotherapy, targeted agents) are needed. [Table: see text]
Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer.
Authors: Dalal Jay S. , Greene Joshua B. , Hofmeister Craig C. , Clark Ann Lau , Clark Joseph
Published: March 2020

e16027

Background: Platinum-based chemotherapy including cisplatin, 5-fluorouracil (5-FU), and the EGFR-directed monoclonal antibody cetuximab, are active in the treatment of head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis and many have difficulty tolerating cisplatin-based regimens. Oxalipatin, a third-generation platinum derivative, has demonstrated antitumor activity and lacks many of the limiting side effects of cisplatin. We conducted a phase I pilot study to investigate the dose-limitation of oxaliplatin in addition to infusional 5-FU and cetuximab in patients with untreated recurrent or metastatic HNSCC. Methods: The planned dose escalation schedule included: dose level 1: oxaliplatin 100mg/m2 day 1, 5-FU CIV 750mg/m2 over 96 hours beginning day 1, and cetuximab 400mg/m2 cycle 1, day 1 (and 250mg/m2 weekly thereafter) on a 21-day cycle. Dose level 2: oxaliplatin 130mg/m2 day 1, 5-FU CIV 1000mg/m2 over 96 hours beginning day 1 and the same dose and schedule of cetuximab. Results: A total of 10 patients were accrued, consisting of 4 females and 6 males. The first seven were enrolled onto dose level 1 and the following three onto dose level 2. Dose level 1 was tolerated well with acceptable toxicity, including grade 1-2 oral mucositis, grade 1-2 fatigue, grade 1-2 acneiform rash, grade 1 nausea, grade 1-2 anemia and grade 1 transaminitis. All responses observed, (1 MR, 1 PR, 1 CR), were short-lived. Dose level 2 was more toxic than anticipated; 2 of 3 patients experienced grade 4 toxicities (mucositis, diarrhea, acute renal failure) requiring hospitalization with a treatment-related death in one of these patients. The phase I portion of the trial was therefore closed and dose level 1 is considered the maximum tolerated dose. Conclusions: The regimen of oxaliplatin 100mg/m2 day 1, infusional 5-FU 750mg/m2 over 96 hours beginning day 1, and cetuximab 400mg/m2 cycle 1, day 1 (with 250mg/m2 weekly thereafter), given on a 21-day cycle, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment of unresectable or metastatic HNSCC.
Retrospective analysis of the use of cetuximab (CTX) and paclitaxel (PTX) combination in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Authors: Soria Rivas Ainara , Rodriguez Garrote Mercedes , Olmedo Garcia Maria Eugenia , López Maria , Garrido López Pilar , Carrato Alfredo
Published: March 2020

e16029

Background: Combination of platinum/5-FU and cetuximab is a 1st line standard treatment approach for R/M SCCHN. Results of a phase II study (Ann Oncol Aug 23, 2011) have shown an encouraging activity and tolerability of the combination of CTX and weekly PTX in this setting suggesting an alternative for unfit patients (pts) or when platinum-based chemotherapy is contraindicated. Methods: A retrospective analysis of our database was performed to evaluate outcomes in pts with R/M SSCHN who were treated under compassionate use with weekly PTX (80 mg/m2 IV) and CTX (initially 400 mg/m2 followed by 250 mg/m2) until progression or intolerance in a single institution in Madrid (Spain) between November, 2008 and July, 2011. Results: 16 pts were included (73% male) with a mean age of 58 years. Mainly squamous carcinomas: pharynx (7), larynx (2), tonsil (2), tongue (3), paranasal sinuses (1) and cavum lymphoepithelioma (1). Twenty percent of the pts received this treatment in 1st line; 67% in 2nd line treatment and only 2 pts received it as 3rd line treatment. Out of those who received PTX-CTX as 2nd or 3rd line treatment, 40% had received CTX as part of the 1st line treatment. Pts received a median of 13.87 cycles. All pts were evaluable for response and toxicity. Disease control rate was 47% (7% CR, 27% PR and 13% SD). With a median follow up of 10.3 months the median PFS was 4.7 months. PFS was 5.2 months for 1st line and 4 months for 2nd line after CTX. Acne-like rash appeared in 100% of the pts. It was G 1-2 in 87% of the pts and G 4 only in one patient, forcing to discontinue CTX. Main related toxicities (G 2-3) were diarrhea (13.34%) and hand-foot syndrome (13.33%). Hematological toxicity was mild, more remarkable in 3rd line treatment, and being managed with dose delays and, in two cases, with a 20% reduction of the PTX dose. Conclusions: The combination of cetuximab and weekly paclitaxel was active, well tolerated and manageable. It may be a first-line option for pts with poor performance status or non eligible for platinum as well as second line treatment for those who have failed first line platinum +/- cetuximab containing chemotherapy.
Functional organ preservation in larynx cancer: Correlation with baseline clinical and pathological features.
Authors: de Miguel Luken Maria Jose , Diaz Pena Elena , Chaves-Conde Manuel , de Miguel Luken Veronica , Chinchon Espino David , Carnero Moya Amancio , Pachon Ibanez Jeronimo , Menoyo Bueno Alicia , Paz-Ares Luis
Published: March 2020

e16037

Background: Functional organ preservation in larynx cancer has become a treatment quality aim. The goal of our study was to evaluate the potential association between clinical and pathological features and functional larynx preservation (FLP). Methods: Clinical and pathological features were registered from 43 consecutive patients who were diagnosed of squamous cell larynx cancer between Feb 2008 and Sep 2011 and were candidates to organ preservation approaches: surgery (1), radiotherapy (10), chemo/bioradiotherapy (26) or chemo/bioradiotherapy following induction chemotherapy (6). Kaplan Meier procedure was used to estimate FLP and OS. Log-rank test and Cox proportional hazards regression were performed to assess prognostic factors for FLP. Results: Median age was 62 years (23% >70 years). Former smokers 28% and alcohol consumers 70%. Most of the tumors were supraglottic (63% supraglottic/35% glottic/2% subglottic), T3 (T4 9%/T3 67%/T2 19%/T1 5%), N0 (N0 74%/N+ 26%), well/moderated differentiated histologic grade (HG) (I 23%/II 49%/III 14%) and stage III or IV (I 2%/II 16%/III 58%/IVA 23%). 33% required pretreatment tracheostomy. At the time of the analysis, with a median follow-up of 21 months, 7(16%) deaths and 18(42%) recurrences had occurred. The cumulative proportion of patients with larynx preservation at 2 years was 48%, and the median FLP survival was 21 months (CI 95%: 10.5-31.5). The most common cause of FLP failure was recurrence, that required salvage laryngectomy in 77% of cases. The following features were found to have a significant negative impact on FLP: T4 (HR: 9.04), former smoker (HR: 2.45), N+ (HR 1.36) and stage IV (HR: 2.44). Other factors such as tumor location, age, alcohol consumption, HG and pretreatment tracheostomy were not significant. Conclusions: The most relevant risk factors for FLP in our analysis were T4 stage, lymph node status, former smoker status and stage IVA. Therefore, patients presenting these features would not be optimal candidates for organ preservation approaches. Correlation of these prognostic factors with predictive biomarkers for specific treatments is warranted.
Induction TPF followed by chemoradiation or radiotherapy-cetuximab in nonresectable advanced head and neck squamous cell carcinoma: A retrospective study in 164 patients.
Authors: Borchiellini Delphine , Dupuis Charlotte , Gal Jocelyn , Lallemant Benjamin , Alfonsi Marc , Benezery Karen , Righini Christian , Guelfucci Bruno , Beltran Michel , Bozec Alexandre , Poissonnet Gilles , Dassonville Olivier , Giovanni Antoine , Morvan Francois , Peyrade Frederic ,   for the GRROC
Published: March 2020

e16044

Background: Induction chemotherapy with docetaxel, cisplatin, and 5FU (TPF) followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced head and neck squamous cell carcinoma (LASCC). Radiotherapy (RT) associated with cetuximab (RT-cetux) is superior to RT alone and has less systemic toxicity than CRT. Recent data suggest RT-cetux could be an alternative treatment to CRT after induction TPF. The aim of this study was to report the outcome of these pts in clinical practice. Methods: A multicentric retrospective analysis was conducted in LASCC pts treated with induction TPF (T 75mg/m2 day 1, P 75mg/m2 day 1, F 750mg/m2/d day 1 to 4 – q3w), followed by CRT (cisplatin 100mg/m2 – q3w) or RT-cetux (400mg/m2 loading dose and 250mg/m2 – q1w). Exploratory endpoints were progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Results: 164 pts treated from October 2005 to June 2010 were eligible. 113 pts had TPF followed by CRT and 51 pts had TPF followed by RT-cetux. Clinical characteristics were similar in each group, regarding gender (men 84% vs 92%), mean age (56 vs 57 yrs), BMI (23.4 vs 23 kg/m2), alcohol consumption under treatment (41% vs 49%), non laryngeal tumor site (77% vs 73%), T3-T4 tumor size (84% vs 80%) and N+ status (71% vs 77%). There was a difference in performance status 0 and 1 between pts in CRT group (73% and 26%) and RT-cetux group (47% and 51%) (p=0.005). 2-yr PFS rate was 68% in CRT group vs 42% in RT-cetux group (p=0.002). After a median follow-up of 23 months, the median PFS was not reached in CRT pts vs 13 months (95% CI : 8.1-17.9 months) for RT-cetux group. At 2 years, CSS and OS rate was 84% and 78% vs 54% and 50%, respectively (p<0.0001). Median CSS ans OS were not reached in CRT group as compared to 25 months (95% CI : 14.6-35.4 months) and 23 months (95% CI : 10.7-35.3 months) in the RT-cetux group, respectively. Conclusions: In daily practice, outcome after induction TPF for LASCC pts seems to be superior with standard CRT than RT-cetux. The higher proportion of PS 1 pts in the RT-cetux group could explain this difference. These data suggest that selection of pts should be carefully considered.
A phase II study of cetuximab-based neoadjuvant and adjuvant treatment strategies, with or without surgery, in patients with locally very advanced squamous cell carcinoma of the oral cavity.
Authors: Lou Pei-Jen , Liao Chun-Ta , Wang Cheng-Ping , Huang Shiang-Fu , Cheng Shin-June , Hsu Cheng-Lung , Wang Chun-Wei , Chang Tung-Chieh , Chen Ya-Fang , Lin Chien-Yu , Wang Hung-Ming , Hong Ruey-Long
Published: March 2020

e16050

Background: The purpose is to evaluate the efficacy of sequential regimen using cetuximab-based doublet neoadjuvant chemotherapy, followed by surgery, if tumors resectable, and adjuvant cetuximab-based chemoradiotherapy in locally very advanced OSCC patients. Methods: Patients with T4a/b or N2b/c or N3 OSCC were enrolled to determine the response rate of cetuximab, cisplatin, and 5-FU neo-adjuvant chemotherapy. Cetuximab (400 mg/m2 loading, followed by 250 mg/m2 weekly x 6 weeks) was combined with 2 3-weekly cycles of cisplatin (100 mg/m2) and 5-FU (1000 mg/m2 x 3 days) as neo-adjuvant. Patients whose tumors became operable after neoadjuvant underwent radical surgery followed by adjuvant weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Patients whose tumors remained inoperable after neoadjuvant received weekly cetuximab (250 mg/m2), cisplatin (30 mg/m2) and XRT (up to 70 Gy). Results: 33 patients were enrolled from Dec. 2009 to Jan. 2011. Average age was 47.3 years. 51.5% had primary lesion in buccal mucosa and 21.2% on tongue. 66.7% and 27.2% had T4b or T4a disease respectively, while 72.7% had N2b/N2c/N3 disease. 28/33 completed treatment course. On ITT analysis, 39.4% (13/33) had partial response and 48.5% (16/33) had stable disease after neoadjuvant. 42.4% (14/33) underwent radical surgery after neoadjuvant, while another 9% (3/33) underwent surgery after bio-chemoradiation. The 1 year disease free survival (resected group), progression free survival (ITT group), and overall survival (ITT group) were 48.8%, 73.2%, and 51.7% respectively. The most common grade 3/ 4 adverse event in neo-adjuvant phase was vomiting (16.1%), while mucositis (75%) and dermatitis (42.8%) accounted for major grade 3/ 4 adverse events during bio-chemoradiation. Conclusions: Cetuximab based sequential regimen was efficacious and well tolerated in improving treatment outcomes in locally very advanced OSCC patients with manageable side effects.
Safety and feasibility of outpatient TPX regimen.
Authors: Pendharkar Dinesh , Ahmad Hilal
Published: March 2020

e16057

Background: TPF has emerged as standard induction regimen in head and neck cancers. Along with docetaxel and platinum it involves continuous infusion of 5FU, which requires a prolonged admission or use of infusional devices, with added cost of treatment, not practical in many clinical situations and situations with limited resources. Keeping this in view, to make the schedule cost effective and outpatient based, we attempted to replace 5FU with oral capecitabine and study the safety and feasibility of TPX regimen (docetaxel, carboplatin and capecitabine) in advanced cancer patients. Methods: 12 patients (8 male, 4 female, age 51-67, median 58) with advanced metastatic disease, where palliative TPF regimen is generally used ,were prospectively planned to receive fixed dose combination of TPX regimen- docetaxel 120 mg day 1, carboplatin 450 mg day 2 and tab capecitabine 2000mg per day, in two divided doses, for five days q 3 weeks. There were 2 cases of cervical cancer, 3- GI tract and rest 7 had head and neck cancer. They were analysed for toxicity and tolerability. Results: In all 12 patients were given 39 courses of TPX regimen. The toxicities included weakness in 2/39 courses, loss of appetite 2/39, neutropenia grade 1 in 3/39, grade 2 in 3/39. During two course grade 3 neutropenia requiring intervention was recorded. The mucositis grade 1-2 was seen only on two occasions in previously radiated patients. There was no incidence of diarrhea. The treatment was well tolerated. All courses were given on time, and there were no treatment delays related to toxicity. Conclusions: TPX appears to be safe and feasible outpatient alternative to TPF. It has no infusional component allowing it to be used in day care setting. Efficacy data in bigger cohort is warranted.
Oral anticancer therapy: Does the patient understand?
Authors: Graham Donna M. , Bambury Richard Martin , Ismail Jeffri R. M. , O'Keefe Margaret , Drake Catherine , O'Shea Alan , Moylan Eugene J. , Power Derek Gerard , O'Reilly Seamus
Published: March 2020

e16506

Background: Oral anti-cancer therapy (OAT) prescribing is increasing. Safety and adherence issues surrounding OAT are causing a shift in the traditional roles and responsibilities of oncologists, nurses and pharmacists. This study aims to investigate patients’ perception of education and safety surrounding OAT use. Methods: Over a 6-month period an anonymous cross-sectional survey was offered to all patients (pts) attending for cancer treatment with OAT at Irish hospitals with cancer services in the South-West region. Data was prospectively analyzed using standard statistical tools for non-parametric data. Results: A total of 172 surveys were distributed and 101 pts responded (59%). Of these, 53 (54%) were female. Median age was 62 (range 29-80 yrs). Diagnosis was colorectal cancer in 49 pts (48%), breast cancer in 13 (13%) and glioma in 12 (12%). Of treatments used, 85% were oral chemotherapy and 15% oral biological therapy. The most commonly used agent was capecitabine (61%). When commencing OAT, 17 (17%) of respondents felt they did not understand it. Understanding was improved by pt education by a doctor (p=0.03) or hospital-based nurse (p=0.04) and provision of information booklets (p=0.04). Pts were unaware of interactions in 30% of cases and 20% were not aware of any safety issues. Pts who had been given information leaflets were significantly more aware of safety including careful handling (p<0.001), storage conditions (p=0.02) and safe disposal (p<0.001). Pts attending nurse-led oral chemotherapy clinics (NOCC) were significantly more aware of safety issues (p=0.04). Of respondents, 1% reported taking too many tablets and 15% had forgotten to take OAT on ≥1 occasion. NOCC improved adherence (p=0.03). Conclusions: OAT, when indicated, is an option for selected pts who are compliant and educated about complications. This study highlights issues with pt education and safety awareness. To our knowledge the factors influencing this have not been previously explored. A significant proportion of our pts were sub-optimally educated regarding medication interactions, storage needs, handling and disposal precautions. Educational tools to aid healthcare professionals in pt instruction and NOCC significantly improve patient understanding.
Strategies to increase efficiency in protocol development.
Authors: Stoermer Kati M ,   SWOG
Published: March 2020

e16508

Background: In 2010, the NCI’s Operational Efficiency Working Group recommended changes aimed at compressing the timeline for cancer clinical trial activation. SWOG implemented multiple changes prior to and since that report, intended to increase protocol development efficiency. Two protocol development interventions were piloted; weekly meetings of SWOG leadership and the study team, or SWOG Activation Team (“SWAT”), which began in 2007, and intensive RaPID Protocol Development Meetings, beginning in 2010. Methods: The highest priority developing trial was selected for SWAT, with only one trial using this mechanism at a time. RaPID trials were chosen based on trial complexity and urgency. We reviewed all protocol development milestones across SWOG protocols activated between 2007 and 2011. Results of the review were compared and contrasted for 1) the two piloted interventions 2) pre- and post-OEWG implementation and 3) time from trial activation to first patient entered. Results: Time to activation results are outlined in the table. Within SWAT, the median time to activation was 400 days, 190 days sooner that all trials developed in the same time period. RaPID trials median time to activation was 225 days, 365 days sooner than others developed in the same timeframe. Regardless of intervention type, median time from concept submission to trial activation was 724 days pre-OEWG and 286 days post-OEWG. The median time from trial activation to first patient accrued was 106 days pre-OEWG implementation and 75 days post-OEWG. Conclusions: While barriers to timely trial activation still exist, SWOG programs aimed at enhancing the efficiency of protocol development, in partnership with the implemented OEWG recommendations, have been successful. SWOG has developed effective and timely protocol develop strategies among diverse, and geographically dispersed, study teams with only modest increases in effort and cost. Supported in part by PHS Cooperative Agreement grant awarded by the National Cancer Institute, DHHS: CA032102. [Table: see text]
The 2010 National Comprehensive Cancer Network (NCCN) risk assessment and genetic counseling (RA/GC) study: Operational aspects of RA/GC programs at academic medical centers.
Authors: Sherman Stephen L. , Crawford Beth , Giammicchio Karen , Kimbro Lisa , Masny Agnes , Mahoney Shannon Kristen
Published: March 2020

e16510

Background: In 2010 NCCN conducted a Risk Assessment and Genetic Counseling (RA/GC) study focused on the operational aspects of RA/GC programs and services at NCCN Member Institutions (MIs). The primary aims were benchmarking of RA/GC operations and practice patterns. Methods: A survey instrument was developed by NCCN staff in consultation with RA/GC leaders at NCCN MIs. The survey collected quantitative and descriptive data on RA/GC program organization, staffing, and patient volume and also included questions on patient referral, test disclosure, and program funding. Results: 19/21 (90%) NCCN MIs participated. The mean number of patients seen annually for 17 MIs reporting data was 872 (range 130 – 2,200). The mean number of patients seen annually per 1.0 genetic counseling full-time equivalent was 272 (range 152 – 422). RA/GC services are made available to patients by scheduled appointment only at 5 MIs (26%) versus by appointment or with on-call genetic counselors at 14 MIs (74%). However, 11/19 (58%) MIs reported the time between initial patient contact and appointment was greater than 2 weeks. Self-sufficient RA/GC program funding was consistently cited by survey respondents as one of the greatest challenges, with 18 MIs indicating that they require institutional support, whereas only 11 indicated that reimbursement from third-party payors contributed to funding. Pertaining to disclosure, respondents estimated that 48% of test results were disclosed to patients via telephone and 39% in-person. The remaining disclosures were made based on patient preference. Conclusions: The availability of on-call RA/GC resources at most NCCN MIs likely indicates an effort to increase the number of patients that receive RA/GC services, but based on times to first appointment, access remains an issue. The 2011 recommendations of the National Society of Genetic Counselors state that the disclosure of test results in-person is often very helpful. However, the percentage given by telephone remains substantial. Dissemination of RA/GC benchmark data and identification of best practices will promote enhanced operations and patient access at NCCN MIs.
The burden of radiation therapy to the bone in patients with prostate cancer and bone metastases.
Authors: Hess Gregory P. , Barlev Arie , Hill Jerrold W. , Fonseca Eileen , Chung Karen
Published: March 2020

e16512

Background: Bone metastases (mets) occur in up to 80% of patients (pts) with advanced prostate cancer and are associated with considerable skeletal morbidity. Radiation therapy is often used to treat spinal cord compression, pathologic fractures, and pain associated with bone mets. However, the burden of radiation therapy, such as dosing, number of fractions, exposure period, and frequency has not been well described. We present the treatment patterns of radiation episodes of care (REOCs) in pts with bone mets secondary to prostate cancer. Methods: Claims-linked medical records at 98 US cancer centers in 16 states were analyzed. Key inclusion criteria included a diagnosis of prostate cancer and bone mets; ≥1 visit to a radiation center on or after bone met diagnosis date (study period: 1 Jul 2008 to 31 Dec 2009); and radiation therapy to ≥1 bone site. Pts with unknown age or REOCs including non-bone site radiation were excluded. Visits and procedures were stratified into radiation and radiation-related categories. Results: A total of 233 REOCs in 213 pts were analyzed. The mean (SD) age was 74 (8.4) years and the mean (SD) Charlson Comorbidity index was 6 (1.1). The mean (SD) number of visits for a REOC was 13 (5.8), over a mean (SD) of 30 (16.7) days (from planning visit to follow-up). 71.7% of REOC visits involved radiation therapy, with the remaining visits for radiation-related procedures (table). The mean (SD) number of fractions per REOC was 10 (4). Conclusions: Radiation to the bone is a well recognized treatment for management of bone mets. The use of multi-fraction schedules is common and is associated with substantial burden to pts and healthcare providers. [Table: see text]
Management of octogenarians with female breast cancer in a rural oncology program.
Authors: Alikhan Mir Asif , Limesand Dianne L , Schmelzel Mark , McGlone Thomas , Powers David , Khawaja Osmaan , Johnson Russell F. , Pikul Frank
Published: March 2020

e16513

Background: Despite the fact that chronological age alone does not determine tolerance to cancer treatment, there is a general perception that elderly cancer patients do not receive standard treatment. We sought to review breast cancer patients above 80 years in our practice. Methods: Retrospective analysis was performed ofall women with breast cancer over the age of 80 either at the time of diagnosis or at the time of relapse since July 2005 till July 2011. Results: There were total of 492 breast cancer patients seen during the study period, 207 below 65, 213 between 66-79 and 70 above 80. 59 women met the study criteria. The median age was 86 (81to 99 years). 47 had activities of independent living, 8 were in an assisted living facility and 4 in nursing homes. Median Charlson Co morbidity Index was 2 (0-5). Pathological types: DCIS 2, Invasive ductal carcinoma 50, invasive lobular carcinoma 6 and 1 had apocrine carcinoma. 50 had ER+, PR+ and Her-, 2 patients had triple negative disease and 4 Her+. 2 patients had stage 0, 22 stage I, 23 Stage II, 7 stage III and 5 stage IV. All patients stage 0-III had surgical management, 39 had breast conservative surgery with sentinel node biopsy and 15 had mastectomy. Out of 28 patients referred for adjuvant radiation therapy 17 received it. 49 patients received hormone treatment (39 aromatase inhibitors- AIs and 14 tamoxifen) Chemotherapy was offered but refused by two stage III patients. 2 Her + patients received and tolerated well trastuzumab based chemotherapy. After a median follow up of 48 months (8-120 months) there was 1 local recurrence, 1 distant relapse and 14 deaths ( 11 from other causes 3 from breast cancer). Conclusions: In ourpractice, a majority of octogenarians and nonagenarians live independently and have minimal co morbidities and tolerate standard surgical and hormonal treatment. Although radiation therapy would be considered optional in this group of women, it was offered based on predicted longevity. Mortality form other causes was higher than that from breast cancer ( 18% vs 5%).
Sociodemographic disparities in treatment receipt for prostate cancer: A population-based study.
Authors: De Camargo Cancela Marianna , Sharp Linda , Kelly Maria , Comber Harry
Published: March 2020

e16514

Background: Prostate cancer (PC) treatment remains controversial. Little is known about how this controversy plays out in routine clinical practice. Most studies of treatment patterns are from the US, specialist centres, and/or involve selected patients. In a national, population-based analysis, using linked cancer registration and hospital in-patient data, we investigated associations between socio-demographic and clinical factors and PC treatment in Ireland. Methods: PC cases (ICD10 C61) diagnosed 2002-2008, and with a hospital in-patient episode within one year of diagnosis (n=9658) were included. Comorbidity (assessed by Charlson and Elixhauser indices) was determined from diagnoses on hospital episodes. Multinomial logistic regression was used to investigate associations between age, marital status, smoking status, area of residence, deprivation category, comorbidity, diagnosis period, stage and Gleason score, and receipt of different treatment modalities. Results: Age was a significant determinant of treatment receipt, after adjusting for socio-demographic and clinical factors. Compared to younger men, men aged ≥70 were significantly less likely to undergo radical prostatectomy (RP), and significantly more likely to be treated by TURPS, androgen deprivation therapy (ADT) or radiotherapy with ADT. Within the 40-69 age-group, likelihood of RP decreased with increasing age. After adjusting for age and other factors, presence of comorbidities, overall, had a moderate impact on treatment receipt. Some conditions had a stronger effect (e.g. congestive heart failure). There were strong variations in treatment by area of residence, which persisted after adjustment for age, comorbidity and other factors. Conclusions: These results suggest socio-demographic factors, including patient age and area of residence, strongly influence PC treatment. Strategies to reduce these disparities have potential to improve PC survival and mortality in the population.
Implementation of a team training program in the treatment of breast cancer patients.
Authors: Bunnell Craig A. , Gross Anne , Kalfin Michael , Partridge Ann H. , Lane Sharon , Burstein Harold J. , Fine Barbara , Hilton Nancy , Sullivan Clare , Colicchio Lynn , Hagemeister Erin , Kelly Anne , Szabatura Audrea , Winer Eric , Mann Susan , Weingart Saul
Published: March 2020

e16515

Background: Team Training (TT) principles, used in high-risk industries to reduce errors and improve communication and task coordination, have been applied in other areas of medicine, but never in an outpatient subspecialty setting. We piloted a TT program in a large, academic breast cancer program. Methods: Observations, interviews and anonymous adverse event reporting systems were used to identify areas of vulnerability warranting intervention: 1) communication of changes in chemotherapy orders on the day of treatment ("change orders") 2) missing orders on treatment days that patients were not also scheduled to see their physician (“unlinked” visits) 3) follow-up and communication to other team members on important patient issues (e.g. pending test results or changes in patient status) 4) conflict resolution between providers and staff. For each area, agreements about roles, responsibilities and behaviors were made. Using a train-the-trainer model, clinical leaders trained all providers and staff in TT principles, the agreements, and the tools to support them. Results: The program was evaluated six months after implementation. There was insufficient power to detect a significant difference in communication of change orders because of the infrequency of events (< 2% pre and post-training). However, 100% of providers reported it was easier to communicate change orders and 87% of infusion nurses reported a decrease in non-communicated changes. The incidence of missing orders for unlinked visits decreased from 30% to 2%. Press-Ganey patient satisfaction scores suggested improvement in patient perception of care coordination. Providers, infusion nurses and support staff reported strongly positive perceptions of improvement in efficiency (75%, 86%, 90%), quality (82%, 93%, 93%) and safety (92%, 92%, 90%) of patient care. Similarly, all groups reported improved relationships and more respectful behavior among team members (91%, 85%, 93%). Conclusions: Team Training improved communication, task coordination and perceptions of efficiency, quality, safety and interactions among team members as well as patient perception of care coordination. Widespread implementation of this strategy is ongoing at our institution.
Patterns of care according to treatment intent for metastatic colorectal cancer (mCRC): A 2.5-year review of routine practice.
Authors: Field Kathryn Maree , Desai Jayesh , Tie Jeanne , Kosmider Suzanne , Bae Susie , McKendrick Joseph James , Harold Michael , Gibbs Peter
Published: March 2020

e16516

Background: Cure is potentially achievable in select patients with mCRC with limited metastatic disease to liver and/or lung. To date the peri-operative strategies undertaken by oncologists in routine practice for such pts have not been well documented. Methods: A clinical database recording information on all pts diagnosed with mCRC since July 2009 from 5 hospitals was analysed. Management strategies where a curative-intent resection had occurred; was planned; or was a potential option were compared with those managed with palliative intent. Results: Status at the time of first review regarding systemic chemotherapy (CT) was documented for 354 pts. 15 (4.2%) had undergone curative-intent resection; 37 (10.5%) had a resection planned; 36 (10.2%) were considered potentially resectable if response to treatment was good; and 266 (75.1%) were treated with palliative intent. Only one patient (1.9%) already resected or planned for resection was >ECOG1, compared with 8% (3/36) potentially resectable and 20% (53/266) palliative pts. CT was delivered in 12 (80%) already-resected, 29 (78%) planned for resection, 33 (92%) potentially-resectable and 202 (76%) palliative-intent pts. Combination CT was the dominant strategy, although 5 of 12 (42%) resected pts received single agent treatment. 17% (n=2) resected pts received bevacizumab with CT, compared with 29% (n=18) of planned or potentially-curative pts and 55% (n=112) of those treated with palliative intent. At the time of analysis 17 pts (46%) with a planned resection and 7 (20%) considered potentially curative have had surgery, while 6 (2.3%) where treatment was initially considered palliative have had curative-intent surgery. Conclusions: Treatment strategies for pts with mCRC differ significantly based on the treatment intent, and may be affected by surgical preference and referral pattern. Bevacizumab was less likely to be used for already-resected pts and the use of single agent therapy in this group was also not uncommon. Many pts initially considered resectable do not ultimately undergo resection, whereas occasional ‘palliative’ pts may become resectable, confirming the importance of continued consideration of this option.
Representation of minorities in randomized lung cancer trials in the United States.
Authors: Mandadi Mounika , Kloecker Goetz H.
Published: March 2020

e16517

Background: The SEER data base shows a higher rate of lung cancer mortality for African Americans and a lower lung cancer mortality rate of Hispanics compared to Caucasians in the US. It is not clear if this is due to socioeconomic or biological factors. This study reviews the representation of Caucasians, African Americans (AA), Hispanics, and Asians in recent randomized trials published in the US. Methods: A systematic review was done of randomized trials in lung cancer published in the NEJM, JAMA, JCO. The percentage of patients of each race in the individual trials was listed. An average percentage with mean standard error for Caucasian, African-American, Hispanic and Asian race was obtained. The percentage for each group is compared to the racial distribution in the US Census data. Results: 30 randomized clinical trials were analyzed for racial distribution. A total of 227,411 patients were enrolled in the trials. Conclusions: African Americans and Hispanics have been significantly underrepresented in randomized trials published in the US. This affects the external validity of the trial results when generalizing the results to these minorities. Strategies to ensure accrual of people of all races are required to ameliorate the disparities clinical trial enrollment. [Table: see text]
Cost-effectiveness analysis of eribulin (E) versus treatment of physician’s choice (TPC) in patients (pts) with pretreated metastatic breast cancer (MBC).
Authors: Montero Alberto J. , Avancha Kiran Kumar Venkata Raja , Gluck Stefan , Lopes Gilberto de Lima
Published: March 2020

e16525

Background: Eribulin was FDA approved in 2010 for pts previously receiving >2 prior chemotherapeutic regimens for MBC. This approval was based on the phase 3 trial (EMBRACE) which demonstrated that E significantly improved median overall survival (OS) relative to different TPC by 2.5 months [HR 0.81; p=0.041]. Methods: The aim of this study was to assess the cost-effectiveness of E versus the 3 most commonly selected TPC in EMBRACE. We also evaluated the cost effectiveness of E compared to other approved drugs for MBC. We created a decision-analytical model using clinical data from the EMBRACE trial. Health utilities were derived from the published literature. Costs for drug acquisition, physician visits, and laboratory tests were obtained from Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2011 USD. Life-years saved (LY), Quality-adjusted life years (QALY), and Incremental Cost Effectiveness Ratio (ICER) were calculated using the EMBRACE median OS data. TPC cost was calculated with 3 most commonly used drugs: vinorelbine (V), gemcitabine (G), and capecitabine (X), comprising 60% of pts in the TPC arm. Other drugs analyzed included liposomal doxorubicin (D), nab-paclitaxel (A), and ixabepilone (I). Greater GCSF use with E vs. TPF was also accounted for in our model. Results: E added 0.208 LY and 0.119 QALY with an incremental cost over TPC of $24,035; and therefore a cost of $115,369/LY and an ICER of $201,790/QALY. The main drivers of the model were drug acquisition cost, OS, and health utility values. The results of the model were robust in sensitivity analyses. Because of the very low cost of V and G, we looked at the cost-effectiveness of E relative to several other drugs commonly used in this setting, but used in fewer pts in the pivotal trial. Relative to ixabepilone, liposomal doxorubicin, nab-paclitaxel, and capecitabine the ICER for E was $85,130, $98,538, $119,029, and $154,591, respectively. Conclusions: Using commonly accepted willingness-to-pay thresholds, E appears to be cost effective in the treatment of MBC relative to D, A, X, and I; with marginal cost effectiveness for less expensive drugs such as V and G.
Health state preferences associated with subcutaneous injections and intravenous infusions for treatment of bone metastases.
Authors: Matza Louis S. , Cong Ze , Chung Karen , Stopeck Alison , Tonkin Katia Sonia , Brown Janet Elizabeth , Braun Ada H. , Van Brunt Kate , McDaniel Kelly
Published: March 2020

e16528

Background: Although cost utility models are often used to estimate the value of treatments for metastatic cancer, limited information is available on the utility of common treatment modalities. Bisphosphonate treatment for bone metastases (BM) is frequently administered via intravenous (IV) infusion, while a recently approved treatment to prevent skeletal-related events (SREs) of BM is administered as a subcutaneous (SC) injection. This study estimated the impact of these treatment modalities on health state (HS) preference. Methods: Participants from the UK general population completed time trade-off interviews to assess the utility of HS vignettes. Respondents first rated a HS representing cancer with BM. Subsequent HSs added descriptions of treatment modalities (ie, injection or infusion) to this basic HS. To represent a range of possible treatment experiences, the two treatment modalities were presented with and without chemotherapy (chemotx), and infusion characteristics were varied by duration (30 minutes or 2 hours) and renal monitoring. Results: A total of 121 participants completed the interviews (47.9% male, 76.9% white). Cancer with BM had a mean utility of 0.40 on a standard utility scale (1 = full health; 0 = death). Adding an injection resulted in a mean utility decrease (ie, disutility) of -0.004. The 30 minute and 2 hour infusions had mean disutilities of -0.02 and -0.04, respectively. Mean disutility of the 30 minute infusion was greater with renal monitoring (-0.05 with same-day blood draw; -0.07 with blood draw 2 days prior). Chemotx was associated with substantial disutility (-0.17). For the HS of BM with chemotx, the mean disutilities of injection, 30 minute infusion, and 2 hour infusion, were -0.02, -0.03, and -0.04, respectively. Disutility associated with injection was significantly smaller than the disutility of both the 30 minute and 2 hour infusions (p < 0.05), regardless of chemotx status. Conclusions: Respondents perceived an inconvenience with each type of BM treatment, but injections were preferred over infusions. The resulting utilities may be used in cost utility models examining the value of treatments for the prevention of SREs in patients with BM.