bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of docetaxel combined with cisplatin as induction chemotherapy followed by cisplatin concurrent chemoradiotherapy plus gemcitabine as adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A prospective and multicenter phase II trial.
Authors: Wang Zhi Hui , Peng Peijian , Wang Siyang , Liu Yumeng , Lin Zhong 
Published: May 2019

6064 Background: Radiation therapy is the only curative treatment modality for nonmetastatic nasopharyngeal cancer (NPC). Concurrent chemoradiation (CCRT) is the standard treatment strategy for NPC in locally advanced stages. However, the results after such treatment are suboptimal. Clearly, novel treatment strategies are needed to further improve patients’ survival rates. This trial aimed to determine the safety and efficacy of a new treatment strategy. Methods: Patients with stage III – IVa-b NPC received TP (docetaxel 75 mg/m2, cisplatin 75 mg/m2 every 3 weeks for 2-3 cycles) followed by cisplatin chemotherapy concurrently with either 3-dimentional conformal radiation therapy or intensity-modulated radiation therapy plus gemcitabine (1000mg/m2 every 2 weeks for 2 cycles) as adjuvant chemotherapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.4.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-OIC-17011464. Results: From July 2010 to July 2017, 20 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 90% (3 complete responses [CRs] and 15 partial responses [PRs]) after two or three cycles of induction chemotherapy (ICT) and 100% (17 CRs and three PRs) after CCRT plus gemcitabine adjuvant chemotherapy, respectively. With a median follow-up time of 41 months, the 3-year overall survival rates were 90% (18/20,95% confidence interval [CI], 76.9%-100%).The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 80% (16/20,95% CI, 62.5%-97.5%), 85% (17/20,95% CI, 69.4%-100%),95% (19/20,95% CI, 85,4%-100%), respectively. The most frequent grade 3–4 toxicities were neutropenia (3/20,15%) and nausea (2/20,10%) after ICT and thrombocytopenia (6/20,30%) and leukopenia (6/20,30%) after CCRT plus gemcitabine adjuvant chemotherapy. Conclusions: Neoadjuvant TP followed by concurrent chemoradiation plus gemcitabine as adjuvant chemotherapy was well tolerated and produced promising outcomes in patients with LA-NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy. Clinical trial information: ChiCTR-OIC-17011464.
A randomized trial of laryngeal organ preservation evaluating two cycles of induction chemotherapy with platinum, docetaxel, and a novel Bcl-xL inhibitor.
Authors: Swiecicki Paul , Bellile Emily , Casper Keith , Malloy Kelly M , Kupfer Robbi , Spector Matthew E , Shuman Andrew , Chinn Steven Bennett , Stucken Chaz , Srinivasan Ashok , Owen Dawn , Dragovic Aleksandar Filip , Mierzwa Michelle , Jolly Shruti , Bradford Carol Rossier , Eisbruch Avraham , Carey Thomas E. , Prince Mark E , Wolf Gregory T. , Worden Francis P. 
Published: May 2019

6066 Background: Laryngeal bio-selection with induction chemotherapy (platinum + 5-FU infusion: PF) has been demonstrated to result in impressive rates of survival and organ preservation with moderate toxicities. We sought to reduce the toxicity of PF by substituting docetaxel (T) for 5-FU and improve the tumor response rate with the addition of the Bcl-xL inhibitor AT-101. Methods: Pts with advanced stage laryngeal cancer were treated with 1 cycle of T 75 mg/m2 + platinum (P) (cisplatin 100 mg/m2 or carboplatin AUC 6) and were randomized 2:1 to the addition of AT-101. Patients with a CR proceeded to chemoradiation (CRT) with concurrent weekly P. All pts with PR or NR underwent a second cycle of induction with TP + AT-101. Pts with a > 50% response (CR or PR) after the second cycle of induction chemotherapy underwent CRT. Pts with a ≤ 50% response (NR) underwent laryngectomy. PET-CT was performed 12 weeks after CRT. Pts with residual disease underwent salvage laryngectomy (SL). Results: 54 eligible pts were enrolled; 46 M, 8 F; median age 59; 26 T4; stage III 16, stage IV 38; site: 2 hypopharyngeal, 39 supraglottic, 11 glottic, 2 subglottic. After cycle 1 of induction, 2/54 (4%) died prior to assessment by DL and 2 were removed from protocol due to adverse events (AEs). 29/50 pts (58%) had ≥ 50% response, 3 of which had CR; 2 proceeded to CRT & 1 received a 2nd cycle of IC. 21/50 pts (42%) had < 50% response. A total of 48 pts received cycle 2 of IC. After the 2nd cycle, a total of 39/50 pts (78%) had ≥ 50% response & received CRT. No difference in response was seen with addition of AT-101. 11/50 pts (22%) had < 50% response- 8 had laryngectomy & 3 refused. Following CRT, 10 pts underwent SL, 2 for residual disease & 8 late SL. The organ preservation rate was 31/50 (62%). The most common grade 3/4 toxicities associated with IC were nausea 9%, neutropenia 9%, & infection 7%. 1 pt died of CNS hemorrhage unrelated to therapy & 1 from sepsis. The median follow-up time is 28 months. The 2 yr laryngectomy-free survival is 54% (95% CI:38-68) & 2 yr overall survival is 81% (95% CI: 64-90). Conclusions: AT-101 did not improve responses to P. Treatment with 2 cycles of IC with PT produced similar response rates to our institutional controls, but organ preservation was somewhat less following treatment with weekly P + RT. Toxicities were overall improved with this treatment strategy. Clinical trial information: NCT01633541.
Hafnium oxide nanoparticles NBTXR3 activated by radiotherapy as a new therapeutic option for elderly/frail HNSCC patients.
Authors: Le Tourneau Christophe , Moreno Victor , Salas Sebastien , Mirabel Xavier , Calvo Emiliano , Doger Bernard , Florescu Carmen , Thariat Juliette , Fijuth Jacek , Rutkowski Tomasz , Magné Nicolas , Liem Xavier , Fakhry Nicolas , Wong-Hee-Kam Stéphanie , Calugaru Valentin , Hoffmann Caroline 
Published: May 2019

6069 Background: New therapeutic approaches are needed for elderly or frail head and neck squamous cell carcinoma (HNSCC) patients (pts) ineligible for standard of care treatment. NBTXR3, a crystalline solution of hafnium oxide nanoparticles may represent such an option. Injected intratumorally, NBTXR3 enters tumor cells and yields an increased cell-localized energy deposit upon exposure to radiotherapy (RT), leading to increased tumor cell death compared to the same dose of RT alone. Methods: Phase I study of NBTXR3 activated by RT in pts ≥70 years old or ≥65 years old and unable to receive cisplatin, eligible for exclusive RT with stage III or IV HNSCC of the oral cavity or oropharynx [NCT01946867]. A 3+3 dose escalation design was implemented with dose levels corresponding to 5%, 10%, 15% and 22% of baseline tumor volume, followed by an expansion phase. Pts received an intratumoral (IT) injection of NBTXR3 and intensity modulated RT (IMRT; 70 Gy/35 fractions/7 weeks). Determination of Recommended Phase 2 Dose (RP2D) and Dose Limiting Toxicities (DLT) were primary endpoints of phase I. Absence of NBTXR3 leakage and preliminary efficacy using RECIST 1.1 principles were also evaluated. Results: The dose-escalation is complete. Nineteen pts were enrolled: 3 at 5%, 3 at 10%; 5 at 15% and 8 at 22% with no observed DLT or SAE related to NBTXR3 or IT injection. One grade 1 NBTXR3-related AE (asthenia at 22%) and four IT injection-related AE (grade 2 oral pain; grade 1 tumor hemorrhage; grade 1 asthenia, and grade 1 injection site hemorrhage) were reported. RT-related toxicity was as expected with IMRT. RP2D has been determined to be 22%. CT-scan assessment between 24h and 7 weeks post-IT injection demonstrated absence of NBTXR3 leakage in the surrounding tissues. Among 13 evaluable pts treated at doses ≥10%, 9 achieved a complete response of the injected lesion. Conclusions: These results show that NBTXR3 activated by RT is safe and well tolerated at all doses with preliminary encouraging efficacy results. It thus represents a promising future treatment for frail and elderly pts with locally advanced HNSCC with limited therapeutic options. Expansion phase has started at the RP2D. Clinical trial information: NCT01946867.
Long-term survival of adjuvant high-dose (HDC) vs weekly cisplatin (WC) for human papilloma-virus (HPV) and non-HPV head and neck squamous cell carcinoma (HNSCC).
Authors: Price Katharine Andress Rowe , Chintakuntlawar Ashish V. , Foote Robert Leonard , Garces Yolanda I. , Ma Daniel , Neben-Wittich Michelle A. , Moore Eric J. , Kasperbauer Jan C. , Price Daniel L. , Janus Jeffrey R. , Van Abel Kathryn M. , Geiger Jessica Lyn 
Published: May 2019

6071 Background: Phase III data suggests a benefit of HDC in the adjuvant setting, but the effect of HDC and WC on long term survival and for HPV+ HNSCC is unknown. Methods: Data from a published retrospective study (Geiger Oral Onc 2013) of HDC vs WC in resected HNSCC was updated. Overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier method for all pts and by HPV status. Multivariate analyses were performed to assess impact of HPV status, smoking, age, HDC vs WC, and cumulative cisplatin dose ( < 200mg/m2 vs ≥200 mg/m2). Results: 51 patients (pts) received HDC and 53 WC. Median follow-up was 8.7 yrs (0.8-13.7). For the whole cohort, HDC had significantly improved OS over WC (p = 0.0095; 5- and 10-yr OS 84% and 80% vs 72% and 60%). No OS benefit for HDC was seen in pts with HPV+HNSCC (5- and 10-yr OS 90% and 87% for HDC and 81% and 81% for WC; p = 0.51). For HPV-negative HNSCC, OS had borderline significance with HDC vs WC (5- and 10-yr OS 73% and 68% vs 65% and 44%; p = 0.06). For the whole cohort, there was no difference in 5- and 10-yr RFS (78% and 74% for HDC vs 72% and 62% for WC; p = 0.32). When analyzed by HPV status, there was no difference in RFS with HDC or WC for either HPV+ (p = 0.43) or HPV-negative HNSCC (p = 0.97). On multivariate analyses of OS for all pts, only HPV status was significant (p = 0.0011; HR 0.27, CI 0.12-0.62). For HPV+ HNSCC, there was no significant predictor of OS. For non-HPV HNSCC, the benefit of HDC approached significance with a decreased risk of death (HR 0.38; p = 0.07). For all pts, those who received ≥200mg/m2 had significantly improved OS (5-yr 90% vs 72% and 10-yr 86% vs 61%; p = 0.004). By HPV status, cumulative dose had no significant effect on OS. Conclusions: OS is better with HDC and with cumulative dose > 200 mg/m2 in unselected patients. The benefit of cisplatin is likely higher for non-HPV HNSCC. A difference in OS with no difference in RFS suggests non cancer-related causes of death in the WC cohort. Ability to receive HDC could be a surrogate marker of comorbidity. [Table: see text]
Is there a benefit of adding surveillance imaging to frequent history and physical exams in patients treated definitively for head and neck squamous cell carcinoma?
Authors: Chi Jeffrey , Sugarman Ryan , Lee Matthew C. , Kamdar Dev , Frank Douglas K. , Pereira Lucio , Gabalski Edward Z. , Goncalves Priscila Hermont , Parashar Bhupesh , Teckie Sewit , Ghaly Maged , Seetharamu Nagashree 
Published: May 2019

6074 Background: In head and neck squamous cell carcinoma (HNSCC) patients (pts) who completed curative-intent definitive treatment (tx), close surveillance is important. Across all centers, pts are closely monitored for symptoms and undergo frequent dedicated head and neck evaluation. Role of surveillance imaging after the initial 12 week post-treatment PET/CT however is less clear. Our institutional practice is to follow pts with regular interval imaging for two years after treatment. However this carries a financial cost, and risk for false positives and unnecessary biopsies. Methods: This is a retrospective chart review of pts treated definitively for HNSCC at our institution from 2012 to 2016. Pts who had a biopsy (bx) post-tx due to suspicion for recurrence were included. Pts belonged to 3 groups: In the first group (A), biopsy was prompted by findings on surveillance imaging (SI); in the second (B), biopsy was prompted by symptom triggered imaging (STI) and in the third (C), biopsy was based on physical exam (PE). We recorded the aggregate results of bx in each group and calculated the positive predictive value (PPV) for each. Results: Of 353 HNSCC pts, 66 underwent post-tx bx for suspected recurrence of which 46 were positive. Of the 30 pts in group A, 21 had positive bx (PPV = 70%). Within this group, PPV was highest with PET/CT (81.82%) followed by magnetic resonance imaging (66.67%) and CT (62.5%). 20 out of 20 pts in group B had bx-proven recurrence (PPV = 100%). 27 out of 36 pts in group C had positive bx (PPV = 75%). While there was no overlap between groups A and B, there was some overlap between groups A and C; and B and C. 45.45% of all recurrences were captured because of SI. When both imaging and PE conducted were positive simultaneously, 54.35% of recurrences were detected first by PE and 45.65% by imaging. Conclusions: Bx triggered by STI has the highest PPV. SI has the lowest PPV, but 45.65% of recurrences were diagnosed because of SI alone. Our study suggests that routine SI for at least two years post treatment for HNSCC patients may add to the surveillance value of frequent PE but larger studies are needed to determine the optimal frequency and type of SI modality.
A retrospective analysis of cisplatin dosing strategies when used with radiation on outcomes in head and neck squamous cell carcinoma of the oropharynx.
Authors: Tchekmedyian Vatche , Ho Alan Loh , Dunn Lara , Fetten James Vincent , Pfister David G. , Lobaugh Stephanie , Zhang Zhigang , Kang Jung , Chen Linda , Riaz Nadeem , McBride Sean Matthew , Yu Yao , Tsai C. Jillian , Lee Nancy Y. , Sherman Eric Jeffrey 
Published: May 2019

6079 Background: Cis is the gold standard radiosensitizer for CRT to treat head and neck cancer. Prospective trials have required that cis be administered early in the week (Mon/Tues) to optimize radiosensitization without evidence to support this practice. This retrospective analysis considers the impact of cis day of week (DOW) administration and other variables on OPSCC pt outcomes. Methods: We reviewed OPSCC cases treated with primary CRT at our center. Pts treated with non-cis or induction chemotherapy were excluded. Data collected includes age, DOW (Mon/Tues vs Wed/Thurs/Fri), smoking status, total dose (TD) of cis (≤200mg/m2 vs > 200mg/m2), single dose (SiD) [100mg/m2 x1 day] vs split dose (SpD) [50mg/m2 x2 days] administration, T stage (0-2b vs 2c-3), N stage (0-2b vs 2c-3), overall survival (OS) (from start of RT), local/regional/distant failure, KPS and HPV/p16 status. Univariate Cox proportional hazards regression was used to analyze OS and multivariate Cox proportional hazard model investigated the relationships between OS and cis dosing variables while controlling for other factors. Results: 745 pts with OPSCC were treated with CRT from 7/31/2001-2/7/2014. 459 used cis based regimens and were included. Median age at start of RT was 55. 311 pts (67.8%) received SpD, 124 (27%) received SiD, 8 (1.7%) received weekly cis and 16 (3.5) received mixed cycles. 269 (58.6%) received ≤200mg/m2. 232 (50.5%) were HPV/p16 positive, 40 (8.7%) were negative and 187 (40.7%) were unknown. Median f/u was 7.9yrs (1.8m -18.9yrs). There were 92 (20%) deaths, and 75 (16.4%) recurrences (local/regional and distant) with 44 (9.6%) competing events. In univariate analysis, age, N stage, T stage, KPS and HPV/p16 status were significantly associated with OS, while DOW, TD, and SiD/SpD were not. In multivariate analysis (MVA), none of the associations between cis dosing and OS were significant (although MVA was limited by low number of events and total variables included). Conclusions: This retrospective analysis suggests that the DOW cis is given has no impact upon CRT outcomes for OPSCC pts. SpD cis represents an alternative administration approach.
NISCAHN: A phase II, multicenter nonrandomized trial aiming at evaluating nivolumab (N) in two cohorts of patients (pts) with recurrent/metastatic (R/M) salivary gland carcinoma of the head and neck (SGCHN), on behalf of the Unicancer Head & Neck Group.
Authors: Fayette Jerome , Even Caroline , Digue Laurence , Geoffrois Lionnel , Rolland Frederic , Cupissol Didier , Guigay Joel , Le Tourneau Christophe , Dillies Anne-Francoise , Zanetta Sylvie , Bozec Lemoal Laurence , Borel Christian , Guyennon Aurélie , Couchon-Thaunat Sophie , Costes Valerie , Jallut Isabelle , Delaye Jessy , Lardy-Cleaud Audrey , Chabaud Sylvie 
Published: May 2019

6083 Background: SGCHN are rare tumors including adenoid cystic carcinoma (ACC) and non-ACC, with no standard systemic treatment for R/M pts. We evaluated N monotherapy in R/M SGCHN pts. Methods: R/M SGCHN pts (ACC or non-ACC) not eligible to local treatment and with centrally confirmed RECIST 1.1 disease progression over the last 6 months were enrolled and received N 3 mg/kg IV, every 2 weeks for a maximum of 12 months (mo). Possibility was given to re-start N in case of progression during the 2-year follow-up phase. Primary endpoint was 6-mo non-progression Rate (NPR6m) as per RECIST 1.1. Secondary endpoints included ORR, PFS, OS, and safety. Considering that N would be uninteresting if NPR6m ≤ 20% and promising if ≥ 40% and using a Fleming’s single-stage design (α: 5% unilateral, power: 90%), at least 14 successes/42 evaluable pts were required for each cohort to be positive. Results: 46 ACC and 52 Non-ACC pts (median age 61 yrs (range 29-81), 43.9% female, 55.1% PS1 and 2.0% PS2) were enrolled and received at least one dose of N. Median treatment duration was 5.5 mo (ACC) and 3.3 (Non-ACC). Median FU was 10.8 mo (ACC) and 8.3 mo (Non-ACC). 95 patients were evaluable for the primary endpoint. NPR6m was 15/45 pts (33.3%, 90%CI :21.8;46.6) and 7/50 pts (14.0%, 90%CI:6.8;24.7) for ACC and non-ACC pts respectively. 4 (8.7%) partial responses (PR) and 26 (56.5%) stable diseases (SD) were observed in ACC cohort while 2 (3.8%) PR and 22 (42.3%) SD were observed in non-ACC. Median PFS was 4.9 mo (95%CI = 3.4;5.6) in ACC pts and 1.8 mo (95%CI = 1.7;3.5) in non-ACC pts. The most common related adverse events (AE) ( > 10% by cohort) were asthenia, hyperthyroidism, diarrhea, rash, pruritus and hypothyroidism. 7/98 pts (7.1%) presented at least one related AE Grade 3-4 (mainly hepatic) and 9 pts (9.2%) prematurely discontinued Nivolumab due to toxicity. Conclusions: Limited efficacy was observed with N in R/M SGCHN pts. N in combination might be of interest and deserves exploration in ACC pts. Clinical trial information: NCT03132038.
Development and validation of a prediction-score model for distant metastases in major salivary gland carcinoma.
Authors: Lukovic Jelena , Alfaraj Fatima , Mierzwa Michelle Lynn , Nader Marta Gustavo , Xu Wei , Su Jie , Ynoe de Moraes Fabio , Huang Shao Hui , Bratman Scott Victor , O'Sullivan Brian , Kim John , Ringash Jolie , Waldron John , de Almeida John R. , Goldstein David Paul , Rosko Andrew , Spector Mathew E , Kowalski Luiz Paulo , Hope Andrew , Hosni Ali 
Published: May 2019

6085 Background: We developed and validated a prediction-score for distant metastases (DM) in major salivary gland carcinoma (SGC). Methods: Patients with SGC treated with curative-intent surgery +/- postoperative radiation therapy (PORT) at 4 tertiary cancer centers were divided into discovery (institution A&B) and validation (institution C&D) cohorts. Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score. The optimal score cut-off for high vs low-DM risk was determined using a minimal p-value approach. The results were subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. Results: Overall, 1035 patients were included (Table). In the discovery cohort, DM predictors (risk score coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (LVI; 0.8), and high risk histology* (1.2). High DM-risk SGC was defined by sum of coefficients greater than 2. In the discovery cohort, the 5-year cumulative incidence of DM for high vs low risk SGC was 50% vs 8%; p < 0.01; these results were similar in the validation cohort (44% vs 4% at 5 years; p < 0.01). In the combined cohorts, this model predicted distant-only failure (40% vs 6%, p < 0.01) and late ( > 2yr post surgery) DM (22% vs 4%; p < 0.01). Patients with high DM-risk SGC had an increased incidence of DM in the subgroup receiving PORT (46% vs 8%; p < 0.01) or concurrent chemotherapy (71% vs 34%; p < 0.01). The 5-yr OS for high vs low risk SGC was 48% vs 92% (p < 0.01). Conclusions: This validated prediction score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies. Baseline characteristics. [Table: see text]
Comparison of normal saline versus heparin flush solutions for maintaining patency of central venous catheter in cancer patients.
Authors: Pai Amy , Ferrajoli Alessandra , Cheng Lee , Huynh Tam , Rodriguez Maria Alma 
Published: May 2019

6501 Background: Published guidelines recommend normal saline (NS) flushes for maintaining patency of central venous catheters (CVCs) in cancer patients. The practice at a large oncology ambulatory facility was modified to use NS flushes instead of heparin for CVC maintenance (centrally inserted catheters and peripherally inserted central catheters, excluding implanted ports). The number of catheter occlusion events, pre- and post-implementation, was utilized to determine the effectiveness and safety of this practice change. Methods: Retrospective data of patients aged 18 years and older who presented to the ambulatory centers were collected from the electronic health record (EHR). The number of alteplase instillations was used as a surrogate measure for occlusion events. Ambulatory line-days, defined as patients arriving for an appointment and with either an active CVC or a CVC placement, was the denominator. The numerator was the number of ambulatory line-days with a catheter line and alteplase dose(s) given. The pre-intervention CVC maintenance period using heparin flushes was March 2016 - April 2017. The post-intervention CVC maintenance period using NS flushes was May 2017 - September 2018. Results: 95,089 line-days and 4,452 unique patients were analyzed pre-intervention and compared to 115,194 line-days and 5,575 unique patients post-intervention. The baseline incidence rate of occlusion was 0.91%, compared to the post-intervention incidence rate was 2.67% ( p < 0.01). The increase started immediately within the first month of the practice change (2.26%) and continued throughout the post-implementation observation time. Conclusions: In an ambulatory oncology-practice setting with a high volume of CVC utilization, an increase in line occlusions rate was observed after implementing the practice change of flushing CVCs from heparin to NS. This raises concerns regarding safety and additional burdens to patients and caregivers, and additional analyses are ongoing to evaluate the further impact of this evaluation.