bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a phase II randomized controlled clinical trial comparing efficacy of cabazitaxel versus docetaxel as second-line or above therapy in recurrent head and neck cancer.
Authors: Joshi Amit , Patil Vijay Maruti , Noronha Vanita , Dhumal Sachin , Chandrasekharan Arun , Pande Nikhil , MV Chandrakanth , Talreja Vikas , Vallathol Dilip , Srinivas Sujay , Chanana Raajit , Gupta Kushal , Parthiban Sangeetha , Prabhash Kumar 
Published: September 2018

6018 Background: Cabazitaxel has shown activity in squamous cancer cell lines and in taxane resistant cell lines. Hence we planned a randomized phase 2 study to evaluate the efficacy and safety of cabazitaxel against docetaxel in recurrent head and neck cancer, post first line treatment. Methods: This was a phase 2 open label, investigator initiated, randomized controlled trial of Docetaxel (75 mg/m2) versus Cabazitaxel (20 mg/m2), in adult patients with head and neck cancer, ECOG performance status 0-2, with measurable disease, who have been exposed to at least one line of chemotherapy (CTRI/2015/06/005848). 1:1 central randomization was performed and chemotherapy was administered till progressive disease or until patient had intolerable side effects. The sample size of 92 (46 per group) was determined based on an assumption for a difference in disease control rate of 25%, an alpha of 0.05 and 80% power. The data was censored for analysis on 3rd March 2017. Primary analysis of disease control at 6 weeks (CR/PR/SD) was assessed and compared using the chi-square test. Progression free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. Cox proportional hazard model was used for comparison of PFS and OS between the 2 arms. Results: 92 patients were accrued in the study with 46 in each arm. The disease control rate at 6 weeks was better in the docetaxel arm which was statistically significant over the cabazitaxel arm (13.6% versus 52.3%, p = 0.017). The median PFS was 21 days (95% CI 5.28-36.72 days) in the cabazitaxel arm versus 61 days (95% CI 16.21 to 105.79 days) in the docetaxel arm (HR = 1.466, 95% CI 0.923-2.328, p = 0.105). The median OS was 172 days (95% CI 111.78 to 232.22 days) in the cabazitaxel arm versus 188 days (95% CI 134.4 to 241.6 days) in the docetaxel arm (HR-1.408, 95% CI 0.738-2.688, p = 0.299). Conclusion: In this phase 2 study, docetaxel had a superior disease control rate at 6 weeks and PFS compared to cabazitaxel. Clinical trial information: CTRI/2015/06/005848.
PREDICTOR (UNICANCER GEP11): Randomized phase II study of preoperative afatinib in untreated head and neck squamous cell carcinoma (HNSCC) patients.
Authors: Le Tourneau Christophe , Delord Jean-Pierre , Dolivet Gilles , Malard Olivier , Fayette Jérôme , Capitain Olivier , Even Caroline , Hoffmann Caroline , Vergez Sebastien , Geoffrois Lionnel , Rolland Frederic , Zrounba Philippe , Laccourreye Laurent , Guigay Joel , Bieche Ivan , Klijanienko Jerzy , Aide Nicolas , Benavent Valerie , Gal Jocelyn , Temam Stephane 
Published: September 2018

6021 Background: Afatinib, a pan-HER irreversible tyrosine kinase inhibitor, demonstrated limited antitumor activity compared to methotrexate in unselected recurrent and/or metastatic HNSCC patients (LUX-HN1, Machiels et al, Lancet Oncol 2015). The UNICANCER (GEP 11) PREDICTOR study’s objective was to identify predictive and pharmacodynamic biomarkers of biological activity and efficacy of afatinib (EUDRACT N° 2010-024046-29). Methods: This open-label, randomized, multicentric, controlled, phase II study included untreated patients with operable T2-4N0-2M0 HNSCC of the oral cavity, pharynx and larynx, with a PS < 2, adequate organ function and LVEF > 50%. Patients were randomized (2:1) to: oral afatinib (A) 40mg/day (d) for 14-28d or no treatment (NT). Patients had pre-treatment tumor biopsies, tumor imaging, and PET CT scan, with a 2nd tumor imaging before surgery and a PET scan at D15. Adverse events were classified by NCI CTCAE criteria. Based on the biological primary endpoint of tumor reduction the sample size was designed to identify biomarkers associated with a 20% difference between the study arms. Results: 61 patients were included (A: 41/NT: 20). 2 patients in the NT arm were not analyzed (consent withdrawal, no surgery). 7 patients in arm A received < 14d of treatment, including 6 patients with unacceptable toxicity. Afatinib-related toxicities were: grade (G)1 37%, G2 41%, G3 7%, G4 5%, and G5 0%. G≥3 toxicities were mainly gastrointestinal. Partial responses (RECIST1.1) were observed in 3 patients (7.3%) in arm A versus none in the NT arm (p = 0.018). Progressive disease was not observed in arm A versus 3 (16.6%) in the NT arm. Partial responses on PET CT scan by PERCIST were observed in 15/31 evaluable patients (48%) in arm A versus 1/15 (6.7%) in the NT arm (p = 0.005). Conclusions: Afatinib given to HNSCC patients in the preoperative setting is safe and is associated with improved response according to RECIST1.1 and PERCIST compared to no treatment. Clinical trial information: NCT01415674.
Efficacy of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated anaplastic thyroid cancer (ATC).
Authors: Subbiah Vivek , Kreitman Robert J. , Wainberg Zev A. , Cho Jae Yong , Schellens Jan H.M. , Soria Jean-Charles , Wen Patrick Y. , Zielinski Christoph , Urbanowitz Gladys , Mookerjee Bijoyesh , Wang Dazhe , Rangwala Fatima A. , Keam Bhumsuk 
Published: September 2018

6023 Background: ATC is a rare, aggressive malignancy with a dismal prognosis. Median overall survival (OS) is < 6 mo. Combined BRAF and MEK inhibition is efficacious in BRAF V600–mutated melanoma and lung cancer. One-fourth of ATCs harbor activating BRAF V600E mutations; thus, D (BRAF inhibitor) + T (MEK inhibitor) was evaluated as a treatment for pts with BRAF V600E–mutated ATC. Methods: In this phase 2, open-label trial (NCT02034110), pts with BRAF V600E mutations in 9 rare tumor types, including ATC, received continuous D (150 mg BID) + T (2 mg QD) until unacceptable toxicity, disease progression, or death. Eligible pts had advanced or metastatic cancer with no standard-of-care treatment options. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), OS, and safety. We report data from the ATC cohort. Results: 16 pts with BRAF V600E–mutated ATC had evaluable data with a median follow-up time of 47 wk (range 4-120 wk). BRAF V600E mutations were centrally confirmed in 15/16 pts. Median age was 72 y; all 16 pts had undergone prior tumor radiation and/or surgery and 6/16 pts (38%) had received ≥1 prior line of systemic therapy. Investigator-assessed confirmed ORR was 69% (11/16; 95% CI, 41%-89%), with 7/11 responses ongoing at the time of data cut. The Bayesian estimate of ORR was 69% (95% credible interval, 47%-87%) with a 100% probability that this ORR exceeded the 15% historical RR. Median DOR, PFS, and OS were not estimable due to insufficient progression and death events. Kaplan-Meier estimates of DOR, PFS, and OS at 12 mo were 90%, 79%, and 80%, respectively. The safety population comprised 100 pts enrolled in 7/9 histologies. Among all pts, 92% had an AE. Common AEs of any grade for all histologies were fatigue (38%), pyrexia (37%), and nausea (35%). In the ATC cohort, the most common grade 3/4 events were hyponatremia (19%), pneumonia (13%), and anemia (13%). Conclusions: D+T combination therapy significantly improved outcomes in ATC with a favorable safety profile. This regimen represents a clinically meaningful therapeutic advance for pts with advanced/metastatic BRAF V600–mutated ATC. Clinical trial information: NCT02034110.
A phase II multicenter trial of the multitargeted kinase inhibitor sulfatinib in advanced medullary thyroid cancer (MTC) and radioiodine (RAI)-refractory differentiated thyroid cancer (DTC).
Authors: Chen Jiaying , Ji Qinghai , Cao Junning , Ji Dongmei , Bai Chunmei , Lin Yansong , Pan Bin , Sun Guofang , Li Jing , Qi Chuan , Hua Ye 
Published: September 2018

6037 Background: Sulfatinib is an oral tyrosine kinase inhibitor targeting Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor 1 (FGFR 1), and Colony Stimulating Factor 1 Receptor (CSF1R). In a proof of concept (PoC) phase II study, sulfatinib showed promising efficacy in patients (pts) with neuroendocrine tumors (NETs). Methods: This is an open label, two cohorts phase II study using Simon's two-stage design. In stage I, 15 pts will be enrolled in each cohort (advanced MTC or iodine-refractory DTC), and 10 more pts will be enrolled in a cohort in stage II if at least 2 PR observed in that cohort in stage I. Pts are required to have progressive disease in the past 12 months, but could not have received > 1 prior anti-angiogenesis therapy. Pts are treated with oral sulfatinib 300 mg once daily until disease progression, death, or intolerable toxicity. Primary endpoint is Objective Response Rate (ORR) by investigator per RECIST 1.1. Results: As of Dec 31 2016,the studyenrolled 18 pts (MTC: 6, DTC: 12), amongst whom 17 pts were efficacy evaluable. There were a total of 4 confirmed PRs, 1 in the MTC cohort and 3 in the DTC cohort, respectively. The others best response was stable disease (SD). 11 pts (61.1%) had dose interruption due to adverse events (AEs) and 5 pts (27.8%) had dose reduction. Two pts discontinued therapy (1 patient due to disease progression, another due to subject's decision). The most commonly reported AEs were proteinuria 72.2% (Grade 3-4: 22.2%), hypertriglyceridemia 50.0% (Grade 3-4: 0%), hypertension 44.4% (Grade 3-4: 16.7%), blood bilirubin increased 44.4% (Grade 3-4: 5.6%), and diarrhea 33.3% (Grade 3-4: 0%). No Grade 5 AE was reported by the time of data cut-off. Conclusions: Sulfatinib appears to be well tolerated in the pts with advanced MTC and RAI refractory DTC. Safety profile seems to be consistent to previous report, with mostly manageable AEs. Efficacy is encouraging in both indications. Further investigation is warranted. Clinical trial information: NCT02614495.
Population assessment of head and neck cancer outcomes by race and HPV status in chance.
Authors: Sheth Siddharth , Farquhar Doug , Mazul Angela , Hayes David N. , Zevallos Jose , Olshan Andrew F 
Published: September 2018

6045 Background: Growing literature suggests that racial disparities exist in patients with head and neck squamous cell carcinoma (HNSCC). Currently, there are many hospital-based cohorts assessing racial disparities, however only a limited number of population-based cohorts exist. This study aims to explore the association between clinical characteristics and patient demographics with overall survival by race and HPV status. Methods: Patients were identified from the Carolina Head and Neck Cancer Study (CHANCE), a population based case-control study with enrollment from 2001-2006 in North Carolina. Vital status was determined by linkage with the National Death Index. Survival was considered at 5 years after diagnosis or study enrollment. We used Kaplan-Meyer analyses and Cox proportional hazards regression modeling to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 1361 HNSCC patients with no baseline metastasis and adequate survival time were identified. Of these, 1010 patients were white while 351 patients were black. Black patients were statistically more likely to be younger at age of diagnosis, have a history of tobacco or alcohol use, be uninsured, and not have completed high school (p-value < 0.001). In an unadjusted cox regression analysis, blacks had 1.50 times (95% CI 1.01-1.57) decreased overall survival than whites. Adjusting for gender, stage of disease, age, treatment, and smoking status, this relationship remained (HR 1.30, CI 1.1-1.6). In a subset analysis of male patients by disease site, there was decreased overall survival in black patients in oral cavity cases (p < 0.01). This relationship trended towards significant in pharynx cancer (p = 0.054) and was not found in laryngeal cancer. In pharyngeal cases only, there was decreased overall survival in black patients with HPV+ disease (p = 0.03) but not in HPV- cases (p = 0.33). Conclusions: This is the first population-based study that confirms racial disparities in HPV+ HNSCC. We also found worse overall survival prognosis for black patients with oral cavity cancer and a similar trend in pharynx cancer. Further studies are needed to evaluate if this difference is driven by either biological or socioeconomic factors.
Impact of p16 expression on induction taxotere-cisplatin-5 FU (TPF) followed by cetuximab-radiotherapy in N2b-N3 head and neck squamous cell carcinoma (HNSCC): Results of GORTEC 2007-02 phase III randomized trial.
Authors: Tao Yungan , Geoffrois Lionnel , Martin Laurent , De Raucourt Dominique , Miny Joelle , Maingon Philippe , Lafond Cedrik , Tuchais Claude , Sire Christian , Babin Emmanuel , Coutte Alexandre , Rolland Frederic , Girard-Calais Marie-Helene , Casiraghi Odile , Garaud Pascal , Bourhis Jean 
Published: September 2018

6070 Background: TPF is a reference induction chemotherapy regimen in non-operated locally advanced (LA) HNSCC. GORTEC 2007-02 phase III randomized trial was restricted to HNSCC patients with large nodal spread (N2b-N3). Results showed no benefit of 3 cycles of induction TPF followed by cetuximab-radiotherapy (RT), as compared to concurrent chemoradiotherapy (CRT) (Geoffrois et al ASCO 2016). Methods: Patients were randomized to receive concurrent CRT (arm A) or induction TPF followed by cetuximab-RT (arm B). RT was 70 Gy/35F/7 weeks. Concurrent chemotherapy was 3 cycles of carboplatin-5FU as previously described (Calais JNCI 1999). About 2/3 of patients had oropharyngeal cancers (OPC) and HPV status was determined in these patients using p16 expression as a surrogate (immunohistochemistry). Smoking status was also collected. Primary endpoint was progression free survival (PFS). Results: Between May 2009 and Aug 2013, 360 eligible patients were randomized including 231 (64%) OPC. Overall, p16 expression could be assessed in 172 / 231 OPC patients (74%) with 84 in arm A and 88 in arm B. 26 patients were found p16+ in arm A (31%) and 19 in arm B (22%). Only 8 out 45 (18%) p16+ patients were non-smokers showing that the large majority of OPC patients randomized were p16- (127/172) and smokers (117/129). A significant improvement in PFS was found in p16+ compared to p16- OPC (p < 0.0001). The absence of benefit in PFS associated with TPF + cetux-RT compared with CRT was suggested both in p16+ (HR: 0.78, 95% CI: 0.28 – 2.20) and in p16- OPC (HR: 1.28, 95% CI: 0.84 – 1.93), and the interaction between p16 and treatment modality was not significant (p = 0.35). A significant benefit was observed in favor of arm B regarding distant metastasis, but this effect was not different between the p16+ and p16- OPC, while there was no benefit of TPF + cetux-RT compared with CRT for loco-regional control, regardless of p16 status. Conclusions: The OPC p16 subpopulations were small. No benefit of induction TPF chemotherapy followed by cetuximab-RT compared with CRT in OPC patients regardless of p16 status. Clinical trial information: NCT01233843.
A multicenter phase II trial of docetaxel, cisplatin and cetuximab (TPE) followed by cetuximab concurrent with radiotherapy in patients with local advanced squamous cell carcinoma of the head and neck (ECRIPS study).
Authors: Zenda Sadamoto , Ota Yosuke , Kiyota Naomi , Okano Susumu , Fujii Masato , Kitamura Morimasa , Takahashi Shunji , Ueda Tsutomu , Monden Nobuya , Yamanaka Takeharu , Tahara Makoto 
Published: September 2018

6071 Background: Induction chemotherapy is a treatment option for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, Docetaxel, Cisplatin, and 5-FU (TPF) followed by Cisplatin with radiotherapy is currently not recommended due to toxicity concerns. The aim of this phase II study was to assess the feasibility of Docetaxel, Cisplatin, and Cetuximab (TPE) followed by Cetuximab with concurrent radiotherapy for LA-SCCHN. Methods: Patients were eligible if they had histologically proven SCC of oropharynx, hypopharynx or larynx, a PS of 0-1, adequate organ function, and no distant metastasis. Induction chemotherapy consisted of Cisplatin 75mg/m2 and Docetaxel 75mg/m2 on day1 and the induction regimen was repeated every 3 weeks up to a total of 3 courses. Cetuximab was administered at an initial dose of 400mg/m2 followed by 250mg/m2 weekly until the end of radiotherapy. Radiotherapy (70Gy/35fr/7w) was started after last administration of Docetaxel. Primary endpoint was the rate of treatment completion. The planned sample size was 55 with one-sided alpha of 0.025 and the power of more than 90% based on the expected and threshold treatment completion rates of 65% and 40%. Results: Between August 2013 and October 2015, 54 patients with a median age of 58 years were eligible and had the study treatment. There were 50 males, hypopharynx/oropharynx/larynx cancer of 28/19/7 cases, and 48 Stage IV disease. Response rate at induction chemotherapy was 72% while that after radiotherapy was 76% . Of 54 patients, 50 (93%) received > 2 courses of induction chemotherapy, and 41 (76%) had the full dose of radiotherapy. The rate of treatment completion was thus 76% (95%CI, 62–87%). The frequency of grade 3-4 neutropenia, febrile neutropenia, and allergy/infusion reaction was 93%, 39%, and 11%, respectively. One treatment-related death was observed. Conclusions: Induction TPE followed by Cetuximab with concurrent radiotherapy was feasible with a promising efficacy. A phase III study to evaluate this treatment strategy is warranted. Clinical trial information: UMIN000009928.
Cost-effectiveness of prophylactic antibiotics to prevent pneumonia in patients treated with chemoradiotherapy (CRT) for locally advanced head and neck carcinoma (LAHNC).
Authors: Ham Janneke , Driessen Chantal , Hendriks Mathijs P , Fiets W. Edward , Kreike Bas , Hoeben Ann , Slingerland Marije , Opstal Claudia van , Kullberg Bart-Jan , Adang Eddy MM , Kaanders Johannes , Van Der Graaf Winette T.A. , Van Herpen Carla M.L.- 
Published: September 2018

6075 Background: Recently, we reported about a prospective randomized study (PANTAP-study) investigating the effect of prophylactic antibiotics in LAHNC pts treated with CRT. We did not show a reduction in pneumonias, but did find a significant decrease in the number of hospitalizations. Detailed quality of life (QoL) results have been reported elsewhere. Now we present the results of the cost-effectiveness analysis. Methods: A multicenter study was performed in LAHNC pts treated with CRT, i.e.cisplatin weekly or 3-weekly combined with radiotherapy for 42 or 49 days. The standard treatment group (STG) received no prophylactic antibiotics; the intervention group (IG) received prophylactic antibiotics, i.e. amoxicillin/clavulanic acid, from day 29 until 14 days after completion of CRT. QoL questionnaires, including EQ-5D, QLQ-C30, EORTC Head&Neck35 and PSSHN, were taken before start of CRT, before start of antibiotics, at the end of CRT and at the end of follow up. Costs of hospitalization, prophylactic antibiotics, pain medication and anti-emetics were taken into account for the cost-effectiveness analysis. Results: A total of 94 pts were randomized; 48 pts to the STG and 47 pts to the IG. Between the STG and IG we found a difference per patient in costs of hospitalization of €2076 and €682 (p = 0.03), respectively, but not in the costs for pain medication per patient €78 and €46, respectively, (p = 0.382). The total costs of hospitalization in combination with prophylactic antibiotics, pain medication and anti-emetics were €2462 and €1037 (p = 0.046) in the STG and IG respectively, leading to a difference in total costs per patient of €1425 in favor of the IG. There were no significant differences in QoL between the groups. Conclusions: Prophylactic antibiotics during CRT for LAHNC did not reduce the rate of pneumonias, but reduced the number of hospitalizations in the IG, which led to a significant reduction in costs. Given the lack of adverse clinical effects, the same QoL, the cost savings and the impact of costs of hospitalization on health care globally, we recommend the use of prophylactic antibiotics in LAHNC pts receiving CRT. Clinical trial information: NCT01598402.
Institutional treatment volume and outcomes in salivary gland cancer.
Authors: Steuer Conor Ernst , Switchenko Jeffrey M. , Griffith Christopher C , Patel Mihir , Cassidy Richard John , Gillespie Theresa Wicklin , McDonald Mark William , Higgins Kristin Ann , Beitler Jonathan Jay , Owonikoko Taofeek Kunle , Chen Zhuo Georgia , Shin Dong Moon , Saba Nabil F. 
Published: September 2018

6082 Background: Salivary gland cancer (SGC) is a rare malignancy and has been understudied in the literature. Given the rarity of SGC, we sought to compare outcomes of SGC within high volume (HV) and low volume (LV) centers, utilizing the National Cancer Database (NCDB). Methods: The NCDB was queried from 2004 to 2014 for SGC using ICD-O-3 codes for the 4 most common histologies: (mucoepidermoid carcinoma (ME), adenoid cystic carcinoma (AdCC), acinic cell carcinoma(ACC), and adenocarcinoma NOS(A)) for consistency. The number of cases treated at each facility was calculated, and the threshold for distinguishing high volume vs. low volume was determined using the 80th percentile of the number of cases treated per facility. Patient characteristics were compared using chi-squared tests and ANOVA. Overall survival was estimated using the Kaplan-Meier method, and was compared using log-rank tests. Statistical analyses were performed using SAS 9.4. Results: There were 31,189 SG patients overall; 16,373 were either ME, AdCC, ACC, or A and were included in the analysis. There were 6534 patients treated in LV (41%) and 9839 in HV (59%). HV centers were more likely to be academic and integrated network cancer programs (p < .001). The median age for LV vs. HV was 61y vs. 58y (p < .001), 49% vs. 47% male (p = .007), and 84% vs. 80% White (p < .001), respectively. Patients presented with slightly more advanced disease at HV, with 24.4% having stage 3-4 disease, vs 23% in LV (p = .004). The majority of patients underwent surgical resection (57% LV vs. 64% HV). HV had more negative margins (59% vs 55%, p < .001), more neck dissections (72% vs. 64%, p < .001), and longer hospital stays (mean 2.21d vs 1.55d, p < .001). More patients in LV received radiation than HV (55% vs. 52%, p < .001), but there was no difference in chemotherapy use (p = 0.650). Patients had better survival (m1 disease excluded) in HV as compared to LV (5-year OS HV 77.4% vs LV 75.5%, HR 0.89, p = 0.002). Conclusions: Our results indicate that survival of SGC is affected by institutional treatment volume and the significant differences in treatment at LV vs. HV institutions urges for the need of better standardization of care.