bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicenter randomized controlled trial (RCT) of adjuvant chemotherapy (CT) in nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA (EBV DNA) following primary radiotherapy (RT) or chemoradiotherapy (CRT).
Authors: Chan Anthony T. C. , Ngan Roger K.C. , Hui Edwin Pun , Leung Sing Fai , Poon Patricia , Sin VC , Tung Stewart Yuk , Cheng Ashley Chi Kin , Yau Tsz Kok , Lee Victor , Ma Brigette , Cheng HC , Yuen Kwok Keung , Lee Conrad , Kam Michael K. , Yau Stephen , Ng Alice Wan-ying , Mo Frankie , Zee Benny C.Y. , Lo Dennis YM ,   Hong Kong NPC Study Group
Published: March 2020

5511

Background: The benefit of adjuvant CT in NPC is unclear. Administering CT after full-dose CRT presents challenges in treatment compliance and toxicity. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using EBV DNA to select high risk NPC patients (pts) for adjuvant CT while sparing low risk pts from unnecessary toxicity. Methods: Biopsy proven NPC, AJCC stage IIB-IVB, detectable EBV DNA at 6-8 wks post-RT, no persistent locoregional disease or distant metastasis, ECOG 0 or 1, adequate organ function. Randomised with stratification for primary therapy (RT Vs CRT) and tumor stage (II/III Vs IV) to arm A (adjuvant cisplatin 40 mg/m2 and gemcitabine 1000mg/m2, both given on D1+8 q3w x 6 cycles) or arm B (clinical follow-up). EBV DNA and PET scan were performed before and 6 months after randomization. Primary endpoint was relapse free survival and secondary endpoints included toxicity of adjuvant CT. With a hazard ratio of 2, 100 pts were required with a power of 0.8 and an alpha at 0.05. This safety analysis was approved by DMSC. Results: From 9/2006 to 12/2011, 514 pts consented for EBV DNA screening, 95 with detectable EBV DNA consented for adjuvant study. After work-up, 74 were eligible for randomization (37 to arm A; 37 to arm B). The two arms were well balanced in baseline characteristics. 80% received prior neoadjuvant and/or concurrent CT. Staging: IIB (36.5%), III (29.7%), IVA (18.9%), IVB (14.8%). Five pts refused adjuvant CT after randomization. Overall 65% and 57% completed 5 and 6 cycles respectively. Mean dose intensity (DI): 84% for cisplatin (22.5 mg/m2/wk, range 0.0-26.7), 92% for gemcitabine (612.8 mg/m2/wk, range 333.3-777.8). Treatment related adverse events above CTC G2 were summarized in Table. Conclusions: Delivery of 6 cycles of adjuvant CT is feasible with acceptable toxicity after full dose RT or CRT. [Table: see text]
Exploratory pharmacodynamics (PD) trial to investigate the mechanism of action of RG7160 (GA201), a novel dual-acting, monoclonal antibody (mAb) designed to enhance antibody-dependent cellular cytotoxicity (ADCC), compared with cetuximab (C) in neoadjuvant head and neck squamous cell carcinoma (HNSCC).
Authors: Temam Stéphane , Spicer James F. , Gomez-Roca Carlos , Berge Yann , Jeannon Jean-Pierre , Soria Jean-Charles , Soehrman Brossard Sophia , Delmar Paul , Golding Sophie , Oppenheim David , Passioukov Alexandre , Manenti Luigi , Delord Jean-Pierre
Published: March 2020

5522

Background: GA201 efficacy was superior to C in orthotopic xenograft models in terms of activity and PD. In a phase I study, objective responses and long lasting stable disease were observed in heavily pre-treated patients (pts). Methods: HNSCC pts (T2-4, any N, M0) received i.v. neo-adjuvant 700/1400 mg GA201 or C (as per SPC), on D1 and 8. Tumor biopsies were taken at baseline (BL) and pre-surgery. The primary objective was determination of changes in tumor immune cell infiltration after treatment. Peripheral CD3+, CD16+, CD56+ cells, plasma cytokines, tumor EGFR and 18F-FDG-PET avidity were also studied. Results: To date, 39 pts (15/10 vs 14 pts for 700/1400 GA201 vs C, respectively) were evaluable for the primary objective and 4 pts are on-going. Patient characteristics at BL were as follows: median age, 57/62 vs 62 years; gender, 11/10 vs 12 male; tumor size ≤ 4 cm, 7/3 vs 3 pts. A greater proportion of pts receiving GA201 compared to C had metabolic tumor reduction (> 25% of SUVmax) (10/15 at 700 mg [1 pathological CR], 7/10 at 1400 mg GA201 vs 7/14 C pts) and symptomatic relief (6/12 at 700 mg, 6/7 at 1,400 mg GA201 vs 2/10 C pts). Table shows changes in PD markers. Conclusions: GA201 treatment, compared to C, exhibited more extensive tumor immune cell infiltration and a greater metabolic response. Consistent with the proposed mechanism of action of GA201, peripheral NK cells dropped and a unique cytokine profile was observed. The data support the immunomodulatory superiority of GA201 - a mAb designed to enhance ADCC compared to C. [Table: see text]
Hearing evaluation of head and neck cancer patients (HNCP): Comparison of adverse event (AE) criteria.
Authors: Colevas A. Dimitrios , Lira Ruth R , Colevas Electra A , Lavori Philip W. , Chang Kay W
Published: March 2020

5525

Background: The incidence and severity of baseline hearing abnormality in HNCP is poorly characterized, as is the subsequent CDDP associated hearing loss. While formal behavioral audiograms can characterize CDDP associated hearing loss in great detail, most oncologists either rely on subjective evaluation of hearing loss or grade hearing impairment using the CTCAE. Two new grading systems for grading cisplatin ototoxicity have been developed for use in pediatrics, the Brock and Chang systems. This report is the first evaluation of these 3 hearing loss criteria in an adult cancer patient population. Methods: We conducted an electronic medical records (EMR) search for all HNCP between 2004 and 2010 treated at the Stanford Cancer Institute (SCI) and identified which patients had audiograms in the EMR, and who had received CDDP. Three investigators (RL, ADC, KC) independently graded these audiograms using the CTCAE v3 and v4, Brock and Chang criteria. Baseline distributions, changes following CDDP dosing, and inter-observer variability were calculated for hearing impairment grading using all four criteria. Results: We evaluated 460 audiograms in 111 patients. Because 282/460 of the audiograms did not have threshold shifts measured at 1,2,3,4,6 and 8 kHz, CTCAE v4 could not be applied to them . We therefore limited all further comparisons to CTCv3, Brock and Chang criteria. The table below summarizes the analysis. Conclusions: The Brock and Chang ototoxity criteria scales deliver a distribution of hearing AE grades at baseline more compatible than the CTCAE v3 with respect to the expectation that most HNCP do not have severe baseline hearing loss. Both the Brock and Chang scales are more sensitive than the CTCv3 to CDDP associated hearing changes. The Brock scale, followed by the Chang scale, demonstrated highest inter-rater agreement. Additional data concerning performance characteristics and utility of these three grading systems will be presented. Replacement of the present hearing impairment criteria in the CTCAE with either the Brock or Chang scales should be considered. [Table: see text]
Prognostic significance of the AJCC staging in patients with squamous cell carcinoma of the oropharynx.
Authors: Acevedo-Gadea Carlos Rodrigo , Baumgart Megan Ann , Wang Zuoheng , Deshpande Hari Anant , Davies Marianne , Decker Roy H. , Sasaki Clarence , Judson Benjamin , Herbst Roy S. , Morgensztern Daniel
Published: March 2020

5529

Background: There have been significant changes in the epidemiology of head and neck squamous cell carcinomas (HNSCC), with an increase in the incidence of oropharyngeal (OP) cancer and opposite effect in other sites. Since the rise in OP cancer incidence is attributed to human papillomavirus (HPV), which is associated with a different biology and clinical behavior, we evaluated whether the current AJCC system retained its prognostic impact in this patient population. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with HNSCC diagnosed between 2004 and 2007. Overall survival (OS) was estimated by the Kaplan-Meier method and the Cox model was used to compare the survival curves for each AJCC stage. Patients were grouped into three anatomical locations: oral cavity (OC), larynx (L) and OP. Results: There were 26,520 patients meeting eligibility criteria, including 8622 OP, 7332 OC, and 10566 L. The AJCC staging retained its prognostic significance across all stages for patients with HNSCC of the OC and L. Patients with OP cancer, however, had similar 4-year survival for stages I through IVA, whereas stage IVB and IVC had a significantly decrease survival compared to IVA and IVB respectively (Table). Conclusions: The OS for stages III and IVA OP cancer is similar to those with stages I and II, in an effect that may be attributed to the increased frequency of HPV in this population, rendering the tumors more sensitive to chemotherapy and radiation. Therefore, the AJCC stage in OP cancer may be more useful in guiding the therapy than as a prognostic factor. [Table: see text]
Phase II trial of chemoradiotherapy concurrent with S-1 plus cisplatin in patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN): Results of the Japan Clinical Oncology Group study, JCOG 0706.
Authors: Tahara Makoto , Kiyota Naomi , Mizusawa Junki , Nakamura Kenichi , Hayashi Ryuichi , Akimoto Tetsuo , Hasegawa Yasuhisa , Iwae Shigemichi , Monden Nobuya , Matsuura Kazuto , Fujii Hirofumi , Onozawa Yusuke , Homma Akihiro , Kubota Akira , Fukuda Haruhiko , Fujii Masato
Published: March 2020

5542

Background: To evaluate the efficacy and safety of chemoradiotherapy (CRT) concurrent with S-1 plus cisplatin in patients with unresectable locally advanced SCCHN. Methods: Eligibility criteria included histologically proven SCCHN with unresectable locally advanced lesions, PS 0-1, aged 20 to 75 years old, adequate organ function, and no prior treatment. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at 60 mg/m2/day, and cisplatin at 20 mg/m2/day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently startingon day 1. For patients achieving an objective response after CRT, two additional cycles of chemotherapy wereadministered. The primary endpoint was clinical complete response rate (%CR), which was the proportion of complete response (CR) and good partial response (good PR). Good PR was defined as remaining tissue with tumor shrinkage, which was not regarded as residual tumor but rather as scar material.The planned sample size was 45 patients, which was calculated by SWOG's two-stage attained design based on an expected %CR of 60% and a threshold of 45%, with a one-sided alpha of 0.1 and a power of 0.9. Results: From July 2008 to July 2010, 45 eligible subjects were accrued, including 43 males, with median age 63 years, ECOG PS 0/1 (36/9), oropharynx/ hypopharynx/larynx (26/15/4), T1/T2/T3/T4a/T4b (1/11/7/17/9) and N0/N2a/N2b/N2c/N3 (2/3/10/24/6). %CR was 64.4% (8 CR, 21 good PR) on central review. After a median follow-up of 1.56 years, 1-year local progression-free survival was 77.8%, with 1-year progression-free survival of 70.9%, 1-year overall survival of 93.3% and 1-year time to treatment failure of 57.6%. Grade 3 or 4 toxicity included mucositis (46.7%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%) and febrile neutropenia (4.4%). No treatment-related deaths were observed. Conclusions: This combination showed promising efficacy with acceptable toxicities. Further investigation in a phase III trial is planned.
Validation for a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma.
Authors: Ma Xiao-Jun , Schache Andrew , Liloglou Triantafilos , Risk Janet , Jones Terence , Wang Hongwei , Bui Son , Luo Yuling , Sloan Philip , Shaw Richard , Robinson Max
Published: March 2020

5543

Background: HPV testing is now widely advocated in the work up of oropharyngeal squamous cell carcinoma (OPSCC). The "gold standard" for oncogenic HPV detection is the demonstration of transcriptionally active high-risk HPV in fresh tumour tissue. For clinical utility, testing strategies have necessarily focused on formalin-fixed paraffin-embedded (FFPE) tissue, but this has been at the expense of reduced sensitivity and specificity for oncogenic HPV. This study evaluates a novel RNA-based in situ hybridisation test against the analytical gold standard; detection of high-risk HPV mRNA, derived from fresh frozen tissue samples, by quantitative reverse transcriptase polymerase chain reaction (qPCR). Methods: A tissue-microarray comprising FFPE cores from 79 OPSCC was tested using High Risk HPV RNAscope (Advanced Cell Diagnostics, USA) for HPV16, 18, 31, 33, 35, 52, and 58. Analytical accuracy and capacity for prognostic discrimination was determined by comparison with HPV RNA qPCR for HPV16, 18 and 33. Demographic and tumour parameters were compared by Chi-squared and Kruskal-Wallis tests. Test sensitivity and specificity were calculated against the standard. Kaplan–Meier survival estimates were constructed to assess prognostication. Results: High risk HPV RNAscope had sensitivity and specificity of 97% and 93% respectively (PPV 91%, NPV 98%) by comparison to the gold standard. Kaplan-Meier estimates of disease specific survival (DSS, p=0.002) and overall survival (OS, p<0.001) by RNAscope were similar to the gold standard (DSS, p=0.006, OS, p=0.002) and superior to p16 immunohistochemistry (IHC) or the combination of p16 IHC and DNA qPCR. Conclusions: We demonstrated that High Risk HPV RNAscope can be used to detect oncogenic HPV in FFPE OPSCC samples and has both excellent analytical and prognostic performance against the gold standard test for oncogenic HPV. These results raise the possibility that High Risk HPV RNAscope could be adopted as an ‘international standard’ test for OPSCC in clinical practice. As the oncology community approaches therapeutic de-escalation based on HPV status, such a reliable and efficacious test may have immediate application.
The role of family caregiver in the head and neck cancer: Psychological distress and quality of life evaluation.
Authors: Airoldi Mario , Garzaro Massimiliano , Raimondo Luca , Bartoli Claudia , Carnio Simona , Fora Gianluca , Giordano Carlo , Pecorari Giancarlo
Published: March 2020

5546

Background: The family caregiver (FCG) has become a hot topic. This figure among head and neck cancer patients is still largely un-investigated; aim of our study was: 1) to describe in a more detailed way the role of FCG, 2) to evaluate quality of life (QoL) and psychological distress of FCGs and patients 3) to investigate relationships between FCG’s wellbeing and patient’s QoL and emotional pattern. Methods: Sixty couples of patients and their caregivers were enrolled in this observational cross-sectional study between April 2007 and May 2011 at 1st ENT Division, 2th Medical Oncology Division and 2th Radiotherapy Division of San Giovanni Battista Hospital of Turin. Inclusion criteria were: diagnosis of SCC, advanced stage (III-IV), completion of curative treatment and no evidence of disease at the enrolment. Psycho-oncological assessment was performed using: Distress Thermometer (DT), Stay-Trait Anxiety Inventory Manual in Y1 and Y2 form (STAI Y1-Y2), Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MDRS), EORTC-QLQ-C30 and Head and Neck-35 module and Caregiver Quality of Life Index-Cancer (CQOLC). Results: Patients: state and trait anxiety are 46,7% (STAI Y1 mean value 40,2±10,2; cut-off 40) and 36,7% (STAI Y2 mean value 36,7±8,2; cut off 40) respectively; self reported and clinician rated depression are 31,6% (BDI mean value 8,2±5,3; cut-off 9) and 48,3% (MDRS mean value 7,9±5,9; cut-off 6) respectively.CGs: state and trait anxiety are 50% (STAI Y1 mean value 42,5±9,9; cut-off 40) and 41,7% (STAI Y2 mean value 39,1±8,7; cut off 40) respectively; self reported and clinician rated depression are 28.3% (BDI mean value 7,3±4,7; cut-off 9) and 41.7% (MDRS mean value 7,6±5,8; cut-off 6) respectively.Data analysis underlined a positive association among emotional scales of patients and caregivers. Patients’ psychological aspects are negatively associated with caregivers’ QoL and vice versa. Conclusions: Anxiety and depression are often present in FCGs and cured HNC patients. Long term patient's QoL is the result of a frail balance between FCG and patiet emotional and psychological distress. A psychological support for FCG could improve patient well-being.
The accuracy of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the staging of newly diagnosed nasopharyngeal carcinoma: A systematic review and meta-analysis.
Authors: Vellayappan Balamurugan A. , Soon Yu Yang , Earnest Arul , Zhang Qing , Koh Wee Yao , Tham Ivan Weng Keong , Lee Khai Mun
Published: March 2020

5553

Background: The specific role of FDG-PET/CT in pretreatment staging of nasopharyngeal carcinoma (NPC) remains to be validated. We performed a systematic review and meta-analysis to assess the diagnostic accuracy of staging FDG-PET/CT for newly diagnosed NPC with reference to conventional staging modalities and/or clinical follow up. Methods: We searched MEDLINE, Cochrane central register of controlled trials, proceedings of ASTRO and ASCO as well as Chinese databases (Chinese National Knowledge Infrastructure and CBMdisc) from the date of inception to September 2011 for relevant studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. We determined the sensitivities and specificities across studies, pooled diagnostic odds ratios (DOR) and constructed summary receiver operating characteristic curves using hierarchical regression model. Results: We found 15 relevant studies (of which seven were in English) including 851 patients. Of the 15 studies: five addressed primary tumor (T), nine addressed regional lymph nodes (N) and seven addressed distant metastasis (M). The combined sensitivity estimate for FDG-PET/CT in T classification was 0.77(95% confidence interval (CI) 0.59-0.95). The combined sensitivity estimate for N classification was 0.88 (95% CI 0.86-0.90), specificity 0.85(95% CI 0.83-0.88), DOR 82.4 (23.2 to 292.6) and Q-index was 0.90. For M classification, the combined sensitivity estimate was 0.82(95% CI 0.65-0.93), specificity 0.98 (95% CI 0.96 – 0.99), DOR 120.9 (43.0 to 340.0) and Q-index was 0.89. Conclusions: FDG-PET/CT showed good accuracy in N and M but not T classification for newly diagnosed pre-treated NPC. FDG-PET/CT, together with Magnetic resonance imaging (MRI) of the nasopharynx, should be part of the routine staging investigations for NPC. Future research should evaluate the accuracy of FDG-PET/MRI fusion as a single staging modality for NPC.
Organ preservation with daily concurrent chemoradiotherapy using a new superselective intra-arterial infusion for stage III, IV tongue cancer.
Authors: Tohnai Iwai , Mitsudo Kenji , Kioi Mitomu , Koizumi Toshiyuki , Oguri Senri , Iwai Toshinori , Hirota Makoto , Fuwa Nobukazu
Published: March 2020

5556

Background: Combined radiotherapy and intra-arterial chemotherapy, which delivers a very high concentration of anticancer agent to the tumor, is currently used to treat advanced head and neck cancer. However, chemotherapy and radiotherapy cannot be performed simultaneously on a daily basis under conventional methods because long-term catheterization is not possible. Therefore, we developed a new method using superselective intra-arterial infusions via the superficial temporal artery and the occipital artery, and used it to perform daily concurrent chemoradiotherapy for the treatment of advanced tongue cancer. Methods: Seventy-two patients with advanced tongue cancer underwent chemoradiotherapy using this superselctive intra-arterial infusion method. Catheters were inserted superselectively to the feeding arteries of the tumor via the superficial temporal artery and the occipital artery. Long-term catheterization is possible in this method. Daily concurrent combined therapy with radiotherapy (total dose: 60 Gy), superselective intra-arterial chemotherapy using DOC (total dose: 60 mg/m2) and CDDP (total dose: 150 mg/m2) was performed. The anticancer agent was injected in a bolus through the intra-arterial catheter simultaneously with radiotherapy. Results: No major complications were observed. Clinical efficacy was CR in 64 (88.9 %) patients and PR in 8 (11.1 %). With a median follow-up period of 31 months (range 6 to 72 months), the overall survive rate was 74.8 % and the local control rate was 93.7%. Conclusions: This superselective intra-arterial infusion allows for long-term catheterization, unlike the conventional method, so that chemotherapy can be performed simultaneously with radiotherapy on a daily basis. This treatment method promises to be the strategy of choice for the treatment of advanced tongue cancer.
Gemcitabine versus cisplatin concurrent with radiation therapy in locally advanced head and neck squamous cell carcinoma.
Authors: Mostafa Magda , Atif Hesham , Fawzy Mahmoud , Sakr Amr Yehia , Alashwah Ahmed
Published: March 2020

5557

Background: In locally advanced head and neck squamous cell carcinoma (HNSCC) weekly cisplatin concurrent with radiation therapy is the standared treatment. However some patients cannot tolerate cisplatin. So we conduct a prospective randomized trial comparing cisplatin versus gemcitabine. Methods: This trial was done in Kasr El-Ainy Center of Clinical Oncology and Radiation therapy (NEMROCK), during the period from March 2010 till June 2011. Sixty patients with locally advanced HNSCC were randomized to receive Cisplatin (30 mg/m2) weekly for 6 consecutive weeks (30 patients) or Gemcitabine (50 mg/m2) weekly for 6 consecutive weeks (30 patients) both concomitant with radiation therapy reaching a dose of 70 Gy over 7 weeks. Primary end points include response rate, progression free survival and toxicity. Toxicities were graded according to NCI-CTCAE v3.0. Results: Thewhole study group included 48 (80%) males and 12 (20%) females. Mean age was 47.9 (± 6.5) years (range 26-61). Both arms were comparable regarding their age, gender, performance status and stage. There were 9 (30%) CR, 7 (23.3%) PR, 2 (6.7%) SD and 12 (40%) PD in cisplatin arm versus 12 (40%) CR, 4 (13.3%) PR, 1 (3.3%) SD and 11 (36.7%) PD in gemcitabine arm. Median progression free survival (PFS) in cisplatin arm was 9 months versus 11months in gemcitabine arm with a hazard ratio of 0.08 (95% CI 0.005 – 1.47). We did not reach median overall survival. Radiotherapy induced skin toxicity (slight or patchy atrophy), nausea, vomiting, mucositis, salivary gland affection and weight loss were equally distributed in both arms. Dysphagia and fatigue were markedly higher in gemcitabine arm. While infection and neutropenia were slightly higher in cisplatin arm. Conclusions: Weekly gemcitabine 50mg/m2 concomitant with radiotherapy was found to be of equal efficacy and toxicity comparable with weekly cisplatin in the treatment of locally advanced HNSCC.
Nomogram for prediction of prognosis in patients treated for oral cavity squamous cell carcinoma.
Authors: Montero Pablo H. , Yu Changhong , Patel Purvi D. , Palmer Frank L. , Ganly Ian , Shah Jatin P. , Kattan Michael W. , Patel Snehal G.
Published: March 2020

5562

Background: TNM staging is an effective tool for prognostic prediction in patients with oral cavity cancer, but it disregards variables such as the anatomic subsite, medical comorbidity, lifestyle, etc. A nomogram has the ability to take into account many factors predictive of outcome for an individual patient, beyond the traditional TNM. We have developed a nomogram to accurately predict overall mortality (OM) and disease specific mortality (DSM) in individual patients treated for oral cancer. Methods: Demographic, host, and tumor characteristics of 1,617 oral cancer patients treated with surgery and adjuvant treatment between 1985 and 2009 were available from a preexisting database. Recurrent disease was recorded in 509 patients, 328 died of cancer-related causes and 542 died of other causes. The median follow-up was 42 months (range 1-300 months). Cox proportional hazards regression model was used for OM and competing risk regression was used for DSM. Death from other causes was treated as competing risk for DSM. Missing values in the predictors were multiply imputed before analysis. Variables analyzed as prognosis predictors included age, gender, race, alcohol/tobacco use, anatomic subsite, comorbidity, tumor size/thickness, bone/deep muscle invasion, nodal status/level, grade, vascular/perineural invasion, margin status and adjuvant therapy. Step-down method was used to select the statistically most powerful predictors for inclusion in the final nomogram for each outcome. Results: Age, severe comorbidity, subsite, tumor size, bone/deep muscle invasion, margin status, vascular and perineural invasion, nodal status and level, and adjuvant therapy were the variables with highest predictive value for OM. The most influential predictors of DSM were gender, tumor size, nodal status and location, subsite, margin status, grade and vascular invasion. Nomograms were generated for prediction of OM and DSM. The nomograms were internally validated with correction for over-fitting; bias-corrected concordance index for OM was 75% and DSM 76%. Conclusions: We have developed nomograms that can accurately estimate OM and DSM based on tumor and host characteristics of an individual patient treated for oral cancer.
The impact of advanced age on outcomes in squamous cell carcinoma of the head and neck.
Authors: Moye Virginia Ann , Chandramouleeswaran Sindhu , Zhao Ni , Muss Hyman , Weissler Mark C , Brossoie Susan M , Hayward Michele C , Hayes David N.
Published: March 2020

5577

Background: Limited data are available regarding outcomes in elderly head and neck cancer patients. This retrospective study was designed to characterize head and neck cancer in geriatric patients in the UNC Tumor Registry. Methods: Of 1,598 patients identified from the registry, 1,291 patients were <70 years old (young group, YG) and 307 patients were > 70 (elderly group, EG) at diagnosis. Both overall survival (OS), calculated from diagnosis to death or the last follow up, and relapse free survival (RFS) were censored at 60 months. Log-rank test was used to compare survival difference. Cox proportional hazard model was used to estimate hazard ratio, adjusting for potential confounding factors. All tests were performed in R 2.13.1. Results: EG patients were more likely to present at an early stage with 25% presenting at stage I and 37% presenting at stage IV compared to 17% and 51% respectively in YG. EG had a median OS of 35 months (95% CI: 28-41 months) compared to approximately 60 months in YG (p < 0.0001 log rank test). The median RFS for EG and YG are 25 (95% CI: 20-32 months) and 44 (95% CI: 38-52 months) months respectively (p < 0.0001 log rank test). When controlling for possible confounders, EG patients were nearly twice as likely to die (HR 1.94, 95% CI 1.635-2.302, p<0.0001) and 70% more likely to relapse in 5 years compared to YG (HR 1.704, 95% CI 1.449-2.004, p<0.05). The median life expectancy for elderly patients in our study was nearly 5 years for stage I/II and <2 years for stage III/IV. Conclusions: Poor OS and RFS in elderly patients compared to younger patients in this study indicate a need for further investigation considering comorbidities and aggressiveness of treatment. Significant differences in life expectancy in elderly patients with early versus late disease may help guide patients and clinicians in determining how aggressively to treat.
Sentinel lymph node biopsy for clinically N0 oral squamous cell carcinoma.
Authors: Goda Hiroyuki , Nakashiro Koh-ichi , Oka Ryota , Shintani Satoru , Hamakawa Hiroyuki
Published: March 2020

5584

Background: Regionallymph node metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC). Sentinel lymph node biopsy (SLNB) is a widely accepted procedure in various human malignancies. In clinically N0 (cN0) OSCC cases, SLNB has received considerable attention for its role in deciding whether to perform neck dissection. In this study, we assessed the efficiency of SLNB for cN0 OSCC case in a single-institution experience. Methods: 100 patients with cN0 OSCC underwent SLNB between 2001 and 2011, of which 95 were clinically T1 and T2. The primary site was tongue, gingiva, oral floor, buccal mucosa, and lip in 50%, 36%, 8%, 5%, and 1%, respectively. The location of sentinel lymph node (SLN) was determined by radioisotope (RI) method with preoperative lymphoscintigraphy and intraoperative use of a handheld gamma probe and/or dye method, and evaluated by histopathological examination and genetic analysis. Results: SLNB was performed with RI and dye method (79%), only dye method (14%), or only RI method (7%). SLN was successfully identified with RI method (100%) and dye method (71%). The average number of SLN was 2.5 with dye method and 1.9 with RI method. The rate of SLN identified side was 84% in ipsilateral, 10% in bilateral, and 6% in contralateral. Fifteen of 100 patients (15%) had metastasis-positive SLN, and 3 patients was up-grade to stage III and others to stage IVA. Eight patients with negative SLN developed latent neck lymph node metastasis. The sensitivity, specificity, accuracy, and negative predictive value was 65% (15/23), 100% (77/77), 92% (92/100) and 91% (77/85). Disease specific survival rate for SLNB-negative patients were 98% (79/81), and for SLNB-positive patients were 73% (11/15), respectively. Conclusions: SLNB is a minimally invasive and highly reliable means of staging the cN0 neck for patients with OSCC. Patients with negative SLNB showed more excellent neck control rate and SLNB provides more accurate staging than elective neck dissection or wait and see.
TPF induction chemotherapy and pathologic response for patients with locally advanced and resectable oral squamous cell carcinoma.
Authors: Zhong Lai-ping , Zhang Chen-ping , Zhang Zhi-yuan , Ren Guo-xin , Guo Wei , Tu Wen-yong , Sun Jian , Zhu Han-guang
Published: March 2020

5593

Background: The role of induction chemotherapy in locally advanced and resectable oral squamous cell carcinoma has not been well issued. Methods: A prospective, open label, parallel, and interventional randomized control trail has been performed to evaluate the induction chemotherapy of TPF protocol in resectable oral squamous cell carcinoma (OSCC) patients at clinical stage III and IVA. The patients received two cycles of TPF induction chemotherapy (75 mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy with a dose from 54 to 66 Gy (the experimental group) or surgery and post-operative radiotherapy (the control group). Post-surgical pathologic examination was performed to determine a positive response or negative response. A positive response was defined as absence of any tumor cells (pathologic complete response) or presence of scattered foci of a few tumor cells (minimal residual disease with <10% viable tumor cells). The primary endpoint is the survival rate; the secondary endpoint is the local control and safety. This study has been approved by institutional ethics committee at Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University. Survival analysis was conducted with the Kaplan-Meier method. Results: 256 patients were enrolled in this trail and 224 patients (111 in experiment group and 113 in control group) finished the whole treatment protocol. After a median follow-up of 21 months (ranging 6-43 m). The pathologic positive response rate was 29.7% (33/111), and negative response rate was 70.3% (78/111). The patients with positive response had a better disease free survival (38.5±2.1m, 95%CI 34.4-42.6m, P=0.003) compared with those with negative response (24.6±2.1m, 95%CI 20.6-28.7m) and control group (31.0±1.6m, 95%CI 27.9-34.1m). The toxicity of induction chemotherapy could be tolerated. Conclusions: Pathologic positive response to TPF induction chemotherapy could benefit the patients with locally advanced and resectable OSCC. However, further long-term follow-up is needed to confirm the benefit on survival and local control.
Progressive increasing in the risk of second and subsequent malignant tumors in patients with a head and neck cancer: A validation study with SEER data.
Authors: Leon Xavier , Lopez-Pousa Antonio , Villatoro J Carlos , Quer Miquel , Sullivan Ivana , Murata Paola , Stradella Agostina , De Vega Josep M. , Farre Nuria , Gallego Rubio Oscar , Quintana Maria Jesus , Barnadas Agust , Alonso Martinez Milagros ,   Hospital Sant Pau
Published: March 2020

5595

Background: Patients with a head and neck squamous cell carcinoma (HNSCC) index tumor have a increased risk (2-4% per year) for appearance of a second malignant neoplasms (SMN) and higher risk for successive malignant tumors during the follow-up. The objective of our study was to validate this concept with data of patients included in the Surveillance Epidemiology and End Results (SEER) program (1973-2008). Methods: We performed a population-based cohort study of 149.328 patients with a primary oral cavity, oropharynx, hypopharynx and larynx squamous cell carcinoma index tumor, included in the SEER program, to analize the actuarial survival-free of second and successive tumors. A total of 11.948 (8%) patients had one or more malignant tumors before the diagnosis of HNSCC. Results: During the follow-up period, a total of 31.507 new SMN appeared. There was a progressive and significant increase in the risk of SMN. The annual hazard ratio for 2nd to 7th successive SMN was 2.3%, 2.7%, 3.9%, 5.4%, 8.9% and 19.1% annual risk respectively. Additionally 11 patients had 8th SMN. We observed a progressive increase in the risk of appearence of new malignant tumors located in and outside the aerodigestive tract. The increase in the risk of SMN was higher for tumors located in the aerodigestive tract than tumors located outside aerodigestive tract. It was a tendency towards the increase in the proportion of HNSCC with the appearance of new tumors, with a decrease in the proportion of the malignant tumors located in the lung and in locations outside the aerodigestive tract. There were significant differences inthe risk of SMN between second and third, third and fourth, fourth and fifth, and sist and seventh tumors (p<0.0001). Conclusions: In patients with HNSCC there is a progressive increase in the risk of appearance of successive tumors. Previous tobacco and alcohol consumption, persistence in the exposure to carcinogens and individual susceptibility (genetic) could play a role in the increased risk of SMN. We have validated this concept with data from the SEER program.
Clinical outcomes and prognostic factors of 582 nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.
Authors: Lang Jin Yi , Wang Weidong , Xu Peng
Published: March 2020

5597

Background: To evaluate the 5-yrs clinical outcomes and prognostic factors of 582 nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). Methods: 582 NPC patients primarily treated with IMRT in Sichuan Cancer Hospital from Jan.2001 to Dec.2004 were analyzed retrospectively, including 460 males and 122 females. The prescription dose was delivered as follows: gross target volume (GTVnx) 67-76Gy in 30-33 fractions, positive neck lymph nodes (GTVln-R/L) 60-70Gy in 30-33 fractions, The lower neck and the supraclavicular fossae were irradiated with the conventional 2D technique using an anterior field. The Kaplan-Meier method was used to calculate the local-regional control rate (LRC) and overall survival rate (OS). Acute and late toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria, meanwhile analyze the prognostic factors. Results: The median follow-up interval was 66.4 months. The 5-year local control, regional control, distant metastasis-free survival, disease free survival, disease specific survival and overall survival rate was 89.8%, 95.2%, 74.1%, 69.6%, 83.2% and 77.1%. 133 patients died during the follow-up. The 5-year DMFS of IMRT and IMRT combined with chemotherapy was 62.1% and 70.9%, the OS of them was 75.9% and 79.1%. The incidence of grade 3 acute and late toxicity was 38.3% and 4.2% respectively.Univariate analysis revealed that gender, T/N stage, clinical stage, radiotherapy interruption, anemia and weight loss was the significant prognostic factor for the OS. Multivariate analysis showed that N stage, radiotherapy interruption, chemotherapy, the volume of GTVnx, age, anemia and weight loss was the independent prognostic factors for the OS. Conclusions: The 5-year local control and overall survival rate of NPC treating with IMRT was 89.8% and 77.1%. The clinical stage, N stage , volume of GTVnx and chemotherapy was the main prognostic factor for the OS. The acute and late toxicities were mainly grade I and II. Distant metastasis was the main pattern of failure.
Prognostic significance of PI3K pathway (PI3Kp) dysregulation in metastatic breast cancer (MBC) patients (pts).
Authors: Navarro Alejandro , Oliveira Mafalda , De Mattos-Arruda Leticia , Sánchez-Ollé Gessamí , Bellet Meritxell , Balmaña Judith , Gómez-Pardo Patricia , Perez-Garcia Jose Manuel , Muñoz-Couselo Eva , Vidal Maria , Ortega Vanesa , Dienstmann Rodrigo , Aura Claudia , Hernandez-Losa Javier , Rodon Jordi , Ramon y Cajal Santiago , Baselga José , Tabernero Josep , Cortes Javier , Saura Cristina
Published: March 2020

566

Background: PI3Kp dysregulation represents a potential target for therapies that are currently being tested in clinical trials. This observational retrospective study aims to evaluate the prognostic implications of PI3Kp dysregulation in MBC. Methods: MBC pts with PI3Kp status assessment from Sep09 to Sep11 were reviewed. PIK3CA mutation status analyzed in paraffin-embedded tissue by DxS PI3K Mutation Test Kit or Sequenom MassARRAY. PTEN status determined by IHC. PI3Kp status: (a) No dysregulation: PIK3CA wt and PTEN normal; (b) PI3Kp dysregulation: PIK3CA mutation (PIK3CAmut) or PTEN low (HScore≤50). Results: 232 MBC pts screened, median age 49.8 (22.9-83.1) and median MBC lines 4 (1-15). Distribution: HR+/HER2- 99 (43%), HER2+ 52 (22%), triple negative 35 (15%), unclassified 46 (20%). Sites of metastasis: visceral 173 (75%), only skin 10 (4%), only bone 49 (21%). PIK3CA status assessed in 174 pts, 53 (22.8%) bearing a mutation (21 exon9, 32 exon20). PTEN status assessed in 229 pts, PTEN low 61 (26.6%). PI3Kp dysregulation in 103/185 pts (55.6%). Time to progression to first line MBC treatment (TTP) and overall survival after MBC diagnosis (OS) are shown. Disease free survival (DFS) and distant-disease free survival (DDFS) in pts initially diagnosed with early breast cancer (n=193) has also been calculated. Conclusions: These results suggest that PI3Kp dysregulation, either by PIK3CA mutation or PTEN low, does not seem to have impact on disease recurrence, response to first line MBC treatment or overall MBC survival.[Table: see text]
Evaluation of Oncotype DX testing and subsequent patterns of care in patients (pts) with early-stage breast cancer (ESBC).
Authors: Fitzgerald Meghan , Hassell Robert , Haislip Sally , Gilmore James W. , Richardson Steve , Cooper Joseph , Szabo Stephen , Feinberg Bruce A.
Published: March 2020

569

Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross BlueShield revealed that pts with estrogen receptor-positive ESBC who underwent Oncotype DX testing and were found to have high-risk Recurrence Scores (RS) received less chemotherapy than expected. To better understand physician behavior as it relates to Oncotype DX testing, CHSS examined patterns of Oncotype DX use in a large private practice oncology group with a robust electronic medical record (EMR), Georgia Cancer Specialists (GCS). We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using GCS EMR data from 2009 to 2011, the number of pts who were eligible to undergo Oncotype DX testing was compared to the number of pts who underwent testing. Pts were considered eligible for testing if they had node-negative, estrogen receptor-positive, HER2-negative ESBC. We determined the number of pts with a RS value in the low- (RS <18), intermediate- (RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received chemotherapy in each category. Results: Of the 1908 patients identified with ESBC, 788 were eligible for Oncotype DX testing and 288 (37%) underwent testing. Fifty percent of pts were in the low-, 34% in intermediate-, and 16% in the high-risk groups. Six percent of low-, 41% of intermediate-, and 83% of high-risk pts received chemotherapy. Seventeen percent of pts in the high-risk group did not receive chemotherapy. Conclusions: The use of chemotherapy in the low- and intermediate-risk groups was as expected based on adjuvant chemotherapy guidelines; however, an under utilization of chemotherapy was found in high-risk pts. There also appears to be a noteworthy underuse of Oncotype DX testing in eligible pts. Further data analysis is needed to understand the low use of Oncotype DX testing in eligible pts and to explain the lower than expected use of chemotherapy in high-risk pts.
Estrogen receptor (ER) signaling in normal, BRCA (B) 1 and B2 mutation associated, and ER-positive breast cancer (BC) mammary cells.
Authors: Lim Elgene , He Housheng Hansen , Chi David , Garber Judy Ellen , Richardson Andrea , Brown Myles
Published: March 2020

576

Background: ER is expressed in ≈70% of sporadic BC and activates genes driving cell proliferation and tumorigenesis. B1 and B2 mutation associated BC have predominant triple negative and ER+ phenotypes respectively, yet hormonal manipulation with oophorectomy reduces BC risk in both B1 and B2 carriers. We have previously performed genome-wide analysis of ER binding sites in MCF-7 BC cells, and identified distinct mechanisms of ER signaling. Here, we seek to elucidate differences in ER signaling between non-malignant (normal, B1 and B2) and ER+ BC mammary cells. Methods: Breast tissue were obtained from patients undergoing reduction mammoplasties (normal), prophylactic mastectomies (B1 and B2 carriers) and surgical excision of ER+ BC. After dissociation into a single-cell suspension, ER+ EpCAM+CD49f- mature luminal (ML) and EpCAM+CD49f+ luminal progenitor (LP) subpopulations were obtained by flow cytometry. Following estrogen stimulation, RNA was extracted for gene microarray analysis. ER chromatin immunoprecipitation and DNA sequencing (ChIP-seq) was performed and DNA libraries prepared and sequenced. Results: Triplicates ofnormal, prophylactic B1 and B2, and ER+ BC tissues were analyzed.Gene ontology analysis indicates different gene expression signatures between non-malignant tissue and MCF-7 BC cells following estrogen stimulation. Genes that promotes cell cycling and proliferation were downregulated in non-malignant tissue, but were upregulated in BC cells (P < 10-5). Hierarchical clustering of the gene microarray by mutation status revealed distinct LP gene signatures in normal, B1 and B2 breast tissue, whilst the ML signatures were largely indistinguishable between the three tissue types. Conclusions: There are contrasting differences in ER signaling between normal mammary and BC cells, with estrogen having anti-proliferative effects in normal luminal cells compared to pro-proliferative effects in BC. Our data suggest that alterations in ER signaling play a major role in breast tumorigenesis. Differences in the LP population between B1 and B2 breast tissue may account for their distinct BC phenotypes.
Molecular subtyping using MammaPrint and BluePrint as an outcome predictor in 180 U.S. breast cancer (BC) patients.
Authors: Stork-Sloots Lisette , Yao Katharine , Turk Mary , Kaul Karen , Weaver JoEllen , De Snoo Femke , Cristofanilli Massimo
Published: March 2020

577

Background: Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy (Glück SABCS2011). The aim of this study was to evaluate the prognostic value of Molecular Subtyping using MammaPrint and BluePrint in women with early stage BC treated at US Institutions following National Comprehensive Cancer Network (NCCN) standard guidelines. Methods: Frozen tumor samples from 180 BC patients (TI-III, N0-Ib) median age 57 years at diagnosis (range 28-89) were suitable for hybridization on full genome array. MammaPrint and BluePrint Molecular Subtypes were determined and survival for Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2-type and Basal-type patients was assessed. Patients were treated either with breast conserving therapy or mastectomy with axillary lymph node dissection between 1992 and 2005. The median follow-up is 12.7 years. 71% was ER positive and 20% Her2 positive by IHC/FISH. 58% received adjuvant endocrine therapy (ET) (excluding 13 patients unknown treatment), 64% received adjuvant chemotherapy (CT) (excluding 12 patients unknown treatment) and 33% received both. Results: 61 (34%) Patients with MammaPrint Low Risk/Luminal-type (Luminal A) showed 5-year DFS of 97% (34% received CT and 69% ET) and 50 (28%) patients with MammaPrint High Risk/Luminal-type (Luminal B) had a 5-year DFS of 98% (60% received CT and 68% ET). Patients with BluePrint Basal-type tumors (46 (26%)) had a 5-year DFS of 80% (78% received CT); HER2-type (23 (13%)) had a 5-year DFS of 78% (87% received CT without HER-2 targeted therapy). Conclusions: In this retrospective study evaluating 180 US patients with early BC treated according to standard guidelines we showed how combining BluePrint with MammaPrint can detect molecularly defined subgroups of patients who are at high risk of recurrence (HER2 and Basal-type). Furthermore, we confirmed that molecularly defined Luminal type disease is associated with excellent disease-free survival. MammaPrint and BluePrint molecular and prognostic stratification should be prospectively evaluated for therapeutic selection.