bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of everolimus (E) plus weekly cisplatin (CDDP) plus intensity-modulated radiation therapy (IMRT) in head and neck (HN) cancer.
Authors: Fury Matthew G. , Sherman Eric Jeffrey , Ho Alan Loh , Rao Shyam S. , Shen Ronglai , Korte Susan H. , Lisa Donna M. , Ganly Ian , Katabi Nora , Patel Snehal G. , Wong Richard J. , Kraus Dennis , Shaha Ashok R. , Shah Jatin P. , Haque Sofia , Lee Nancy Y. , Pfister David G. 
Published: March 2020

5545^ Background: The PI3K/mTOR/eIF4E pathway is upregulated in many HN cancers, and expression of eIF4E in surgical margins has been associated with increased risk of recurrence (Cancer Res 2007; 67:2160. Clin Cancer Res 2004; 10:5820. JCO 1999; 17:2909). Daily E + weekly CDDP was well tolerated in a phase I study for patients with advanced solid tumors (Cancer Chemother Pharmacol 2011 Sep 13; Epub ahead of print]. E achieves radiosensitization in pre-clinical models. This study evaluated weekly CDDP + daily E given concurrently with IMRT in HN cancer. Methods: This was a single institution phase I study with a standard 3 + 3 dose escalation plan. Patients (pts) received standard definitive IMRT (66 Gy resected tumors, 70 Gy unresected tumors) concurrent with CDDP 30 mg/m2 weekly X 6 and daily oral E according to the dose escalation plan. Four dose levels (DLs) of daily oral E were planned: 2.5 mg, 5 mg, 7.5 mg, and 10 mg. Toxicities were recorded according to NCI CTCAE v.3. Results: Thirteen (9M, 4F) pts enrolled, with median age 52y (range, 37 – 65y) and median KPS 90 (range, 80-100). Primary sites: oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), unknown primary (1). Stage: IVA (11), IVB (1), II (1). Prior treatment: surgery (10), chemotherapy (2). The most common ≥ G.3 treatment related AEs were mucositis (functional 62%, clinical 31%), oral pain (31%), and lymphopenia (31%). There were no DLTs among 3 patients at DL1 or the first 3 patients at DL2. Among 4 pts at DL3, there were 2 DLTs: grade 3 mucositis with failure to thrive, and grade 3 mucositis with hypoxia. Among 3 additional patients enrolled at DL2, there was one 1 DLT: grade 3 mucositis with inability to tolerate E. There were no treatment-related deaths. With a median follow-up of 8.9 months, 3 patients have experienced recurrent disease, one of whom has died of disease. Median PFS has not been reached. Tissue correlates in process. Conclusions: When administered with weekly CDDP (30 mg/m2) and definitive IMRT for HN cancer, the phase II recommended dose of E is 5 mg/day.
Association of smoking status with p16 and cyclin D1 (CCND1) expression with clinical characteristics and overall survival (OS) in oropharyngeal squamous cell carcinoma (OSC).
Authors: Ang Mei-Kim , Ang Siok Hoon , Krishna Sai Sakktee , Chen Wallace Jian Jun , Thu Minn Minn Myint , Tai Wai Meng David , Tan Daniel S. W. , Tan Eng-Huat , Tan Puay Hoon , Hwang Siok Gek Jacqueline , Lim Wan-Teck 
Published: March 2020

5551 Background: Smoking-related head and neck cancer (HNC) is genetically different, with higher mutation rates compared with non-smokers (NS). Human papillomavirus (HPV)-positive (+) OSC has a superior prognosis independent of treatment. Among HPV+ patients (pt), current or prior smokers (CS) have poor OS compared with NS. Expression of p16, a known HPV surrogate, and CYD1, a cell cycle marker often dysregulated in HNC, was evaluated with respect to smoking status and OS. Methods: Expression of p16 and CYD1 was assessed by immunohistochemistry in 108 OSC pt treated between 1999-2009, using cutoffs of ≥70% (p16+) and ≥10% (CYD1+) stained tumor cells. Associations between expression, clinical characteristics and OS were evaluated by Kaplan-Meier method and compared by log rank test. Hazard ratio (HR) for death was estimated using Cox models. Results: 31 pt (28.7%) were p16+ and 80 pt (75.5%) were CYD1 negative(-). p16+ pt were younger (median age 57 v 66 yrs, p=0.002), more likely female (35.5% v 15.2%, p=0.035), NS (51.6% v 13.9%, p<0.001) with lower combined age-comorbidity score (ageCS) (p=0.003). CYD1+ pt were older (median 66 v 57 yrs, p=0.015), more likely CS (81.5% v 48.1%, p=0.002) with higher ageCS (p=0.018). At a median f/u of 65.7 months, median OS was 57.3 months. p16+ pt had better OS than p16- pt (median OS not reached (NR) v 22.3 mths, p<0.001). CYD1+ pt had poorer OS than CYD1- pt (median OS NR v 17.7 mths, p<0.001). On multivariable analysis p16 and CYD1 status were independently associated with OS (HR 0.412, p=0.045 and HR 4.06, p=0.011 respectively), independent of smoking status (HR 5.01, p=0.008), ageCS (HR 1.32 per 1 point increase, p<0.001) and stage. Strikingly, among NS, 5-year OS in p16+ compared with p16- pt was 100% vs 67% (p<0.001). In contrast, among CS, p16 status had no association with OS (HR 0.97, p=0.943), while CYD1 status and ageCS were independent predictors of death (HR 4.70, p=0.025 and HR 1.28, p<0.001 respectively). Conclusions: In OSC, NS with high p16 expression have excellent prognosis. Among CS, pt with fewer comorbidities and low CYD1 expression have better OS. p16 status was not prognostic in the latter group of patients.
Expression and prognostic significance of directed therapy targets and mutational analysis of the EGFR pathway in malignant salivary gland tumors.
Authors: Cros Jerome F , Blons Helene , Sbidian Emilie , Tartour Eric , Hans Stephane , Brasnu Daniel , Laurent-Puig Pierre , Bruneval Patrick , Badoual Cecile 
Published: March 2020

5554 Background: Malignant salivary gland tumors are rare and pleomorphic entities (24 sub types, WHO 2005). Curative treatment relies on surgery sometimes completed by radiotherapy. Management of non-surgical, locally advanced or metastatic tumors is difficult as conventional chemotherapies are ineffective. Directed therapies may provide important benefits for these patients. The aim of this work was to assess the expression and prognostic value of directed therapy targets on salivary gland tumors and search for mutations within the key players of the EGFR pathway. Methods: Immunochemistry on formalin fixed paraffin embedded (FFPE) samples from 124 patients for c-KIT, EGFR, c-ERBB2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was performed and related to progression free interval and survival. DNA was extracted from FFPE samples and conditional for treatment mutations of EGFR/KRAS/BRAF were assessed. An additional high throughput screening for mutations of key oncogenic genes was performed. Results: EGFR was the most expressed marker, found across almost all histotypes. Expression of the other markers was heterogeneous but some potential therapy leads were suggested by high levels of C-ERBB2 and androgen receptors in salivary duct carcinomas or C-KIT over expression in myoepithetial carcinomas. Tumor grade and a high proliferation index (Ki67>20%) were associated with progression free interval and survival. None of the other marker was. No mutation was found in EGFR/KRAS/BRAF. 7% (7/104) of the tumors harbored a mutation at the codon 61 of HRAS. In epithelial and epithelial-myoépithélial carcinoma, the mutation rate reached 33%. Mutations of PI3K and p53 were the most frequently found in the broader screen. Conclusions: Several tumor subtypes expressed frequently some targets of directed therapies suggesting potential therapy leads. The EGFR/MAPK pathway seems intact suggesting a low efficacy of small kinase inhibitors such as erlotinib or gefitinib. The mutation of H-RAS, known to be important but not sufficient to trigger urothelial carcinoma, could be a key oncogenic event in tumors with a myoepithelial component.
Association between salivary cytokine levels and chemoradiotherapy-induced toxicities in head and neck cancer patients.
Authors: Bossi Paolo , Filipazzi Paola , Resteghini Carlo , Miceli Rosalba , Orlandi Ester , Locati Laura , Fallai Carlo , Tana Silvia , Cova Agata , Squarcina Paola , Rodolfo Monica , Bergamini Cristiana , Granata Roberta , Mirabile Aurora , Rivoltini Licia , Licitra Lisa F. 
Published: March 2020

5555 Background: Mucositis is a common complication of chemoradiotherapy (CTRT) for head and neck cancer (HNC), linked to a balance between pro- and anti-inflammation serum cytokines. No study has yet addressed the role of salivary cytokines in influencing toxicity severity. Methods: Twenty consecutive stage III (15%) and IV (85%) HNC patients (pts) were treated with radiotherapy (64-70 Gy) plus cisplatin (n=15), carboplatin (n=4) or cetuximab (n=1). Primary tumor site was oral cavity (15%), oropharynx (55%), nasopharynx (15%), larynx or hypopharynx (15%). Unstimulated saliva samples were collected according to standardized protocols before CTRT, during (3rd, 5th and 7th weeks) and two weeks after; concomitantly, mucositis grade (WHO classification), weight loss and need for feeding tube were evaluated. The salivary levels of 11 different cytokines (IFNγ, IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNFα and TNFβ) were analysed both in pts and in healthy donors (HD, n=10) by optimized bead-based multiplex immunoassay. The cytokine change during treatment was calculated as the difference between the mean of individual values and the baseline value. The Wilcoxon rank sum test was used for between-groups comparisons. Results: At baseline, no difference in cytokine levels was observed in pts as compared with HD, except IL8. A significant and progressive increase of IL1β, IL6, IL8, TNFα and IL10 levels was observed during treatment, with high levels persisting two weeks after treatment for all cytokines but IL1β. Significant association was shown between IL6 increase and G3/4 mucositis (p=0.009) or feeding tube need (p=0.04). The same trend was observed for TNFα. Interestingly, IL8 increase appeared to be specifically linked to weight loss (>10%, p=0.003). In contrast, baseline cytokine salivary levels were not predictive of treatment-induced toxicities. Conclusions: The increase of IL6, IL8 and TNFα salivary levels occurring in HNC patients with CTRT seems to be directly associated with mucositis severity, feeding tube prevalence and weight loss. Cytokines may represent a potential new target for preventive and/or therapeutic intervention.
Outcomes of occult primary (OP) of the head and neck squamous cell carcinoma (HNSCC) treated with oropharynx (OPX)-targeted radiotherapy (RT) and concurrent chemotherapy (CCRT).
Authors: Hu Kenneth , Harrison Louis Benjamin , Shourbaji Rania Ayman , Culliney Bruce , Li Zujun , Mourad Waleed Fouad 
Published: March 2020

5559 Background: OP of HNSCC is commonly treated with comprehensive mucosal RT including nasopharynx, OPX, hypopharynx and larynx and bilateral neck. We are reporting the long term outcomes of a conservative mucosal sparing technique consisting of targeting only the OPX mucosa and bilateral necks. Methods: This is a single-institution retrospective study. From January 1998-2010, a total of 68 patients with OP of HNSCC were treated with CCRT (90%) or RT alone (10%), 40% with IMRT. RT fields comprehended OPX mucosa only and bilateral necks. Gross disease in the neck received 70Gy, involved neck 63 Gy, OPX 60 Gy, uninvolved neck and ipsilateral retropharyngeal nodes 54 Gy. All fractions were given at the rate of 1.8-2 Gy/fraction. The median age was 58 (21-87), 80% Caucasian, and 75% males. Stage IVa (N2) was 75% of the population, while stages III (N1), and IVb (N3) were 9, and 16% respectively. 16 patients (9N3+7 bulky N2) underwent neck dissection (ND). The median time interval from diagnosis to RT and RT duration were 60 (13-70) and 50 days (49-63) respectively. The Median number of Chemotherapy cycles was 2 (1-3). Cisplatin was given to 70% of pts, while Carboplatin and Cetuximab were 10 and 20% respectively. Results: With a median follow-up of 5.3 years (1– 13.6), the loco-regional control, (LRC) for all stages is 95.6 %. The median time to LRF is 18 months (12 - 63). Chronic CCRT toxicity was; grade (1) xerostomia (67%), dysphagia (35%), altered taste (28%), neck stiffness (15%), skin toxicity (12%), dysphonia (9%), and trismus (6%). One HIV patient developed grade 4 dysphagia. No patients experienced distant metastases. The emergence of primary was (1.5%) 1 patient developed subglottic SCC 2 years after CCRT, 2 patients failed in the neck (originally N3) all the 3 patients were salvaged successfully by surgery. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100. Conclusions: Our data show that CCRT or definitive RT alone to the OPX and bilateral neck provides excellent oncologic and functional outcomes. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable and likely reduces toxicity.
Young adults with squamous cell head and neck cancer: Ten years of a single institution’s experience (1999-2008).
Authors: Alves Marcos Pantarotto , Martins Ferreira Castro Ana Filipa , Lombo Liliana , Rodrigues Helena , Silva Jose D. , Azevedo Isabel 
Published: March 2020

5567 Background: Head and neck cancer of squamous cell type (SCHNC) is characterised by its aggressiveness and strong relationship with smoking and drinking habits. It is generally diagnosed in locally advanced stages, mainly in middle-aged men. People younger than 35yo are rarely affected by this disease, and little is known about its behaviour among young Portuguese adults. Our aim was to describe the clinical and epidemiological features of young adults with diagnosis of SCHNC in a single oncological centre in Portugal. Methods: Retrospective cohort including clinical registries’ databases for patients (pts) with diagnosis of SCHNC, with 3391 eligible pts from 1999 to 2008. Pts aged ≧18yo and ≤35yo at diagnosis with histopathological diagnosis in our Institution were included. Pts admitted to radiation therapy with no follow-up information were excluded. 39 pts fulfilled the criteria described, comprising the study population. Statistical analysis was carried out using SPSS v19.0 for Mac (IBM, 2010, EUA), with values of p<0,05 considered significant. Results: Male sex predominance (82%) was observed. The median age of presentation was 33 yo [22; 35], with 90% smokers with a median of 18,5 package-years [1; 48]. Alcohol consumption was mild to moderate (n=9; 23%) or heavy (n=15; 38%). The median of follow-up time was of 24 months [1;151]. Locally advanced diseased was present at diagnosis in 24 pts, where localised disease was commonest among women (57%) than in men (29%). Median overall survival (OS) was not reached on this population, although K-M graphs seems to show a significant difference in survival between sexes. Alcohol consumption was the most significant variable to influence the survival (p<0,01). Conclusions: SCHNC in young people is a rare condition, with distinct epidemiological and clinical features. Women seems to have greater survival rates, which may be explained by other risk factors already reported for this gender, namely HPV infection. The finding of an apparent relationship between alcohol consumption and OS, and the high prevalence of alcoholic intake habits on this parcel of the population, urge the need of development of public health programs addressed to this specific age group.
Impact of p16 status on the QOL effects of chemoradiation for locally advanced oropharynx cancer: Results of TROG 02.02.
Authors: Ringash Jolie , Fisher Richard , Peters Lester J. , O'Sullivan Brian , Trotti Andy , Kenny Lizbeth M. , Young Richard J. , Rischin Danny 
Published: March 2020

5571 Background: We report the impact of p16 status on quality of life (QOL) for patients with stage III or IV (excluding T1-2N1 and M1) squamous cell carcinoma of the oropharynx (OPC) treated with concurrent chemoradiotherapy in a large international phase III trial (TROG 02.02/HeadSTART). Methods: The 861 patients accrued received definitive radiotherapy (RT) (70 Gy/7 weeks) concurrently with 3 cycles of either cisplatin (100mg/m2) or cisplatin (75 mg/m2) plus tirapazamine (290 mg/m2/day) by random assignment, as previously described. QOL was measured with the FACT-H&N at baseline, 2,6,12, 23 and 38 months. No significant difference in overall or subscale QOL score change from baseline was observed between arms at any subsequent time point; results for the oropharynx subgroup by p16 status are reported for both treatment arms combined. Results: Of 853 eligible participants, 465 had OPC, for whom p16 status could be determined in 206. Of 179 who received adequate RT (≥ 60 Gy, no major deviations) and completed baseline QOL, 104 were p16+ and 79 were p16-. p16+ patients had better baseline ECOG PS, lower T-category, higher N-category, were younger and were less likely to be current smokers. Baseline mean FACT-H&N score was statistically and clinically significantly better in p16+ patients (111 vs. 102, p=0.001). The drop in QOL from baseline to 2 months was more severe in p16+ cases (-20.4 vs -9.1, p=0.001), resulting in an equalization of 2 month scores (p16+: 90.6, p16-: 93.6, p=0.16). At 6 and 12 months post-treatment, no difference in score changes from baseline by p16 status was seen (6 mo, p16+: -6.2, p16 -:-1.2, p=0.22; 12 mo, p16 +: -0.3, p16 -: +2.0, p=0.82). Conclusions: p16 associated oropharyngeal cancer has been shown to be a distinct entity with different demographic features. In our study, such patients exhibited better baseline QOL and a more severe drop immediately after treatment, but did not differ in long-term QOL response to the effects of aggressive concurrent chemoradiation. Given the favorable prognosis of p16-associated oropharyngeal cancer, efforts to reduce the QOL burden of treatment are warranted.
Importance of HPV involvement and FOXP3+ T-cell status as prognostic factors in tonsilar squamous cell carcinoma.
Authors: Park Kwonoh , Cho Kyung-Ja , Yoon Dok Hyun , KIM Jiyoun , Kim Sang Yoon , Nam Soon Yuhl , Choi Seung-Ho , Han Myung Woul , Lee Sang-wook , Song Si Yeol , Kim Sung-Bae 
Published: March 2020

5586 Background: Human papillomavirus (HPV) status is a strong and independent favorable prognostic factor for survival in tonsilar squamous cell cancer (TSCC). The reason for the improved survival in HPV associated TSCC is unclear. Recently, activation of immune surveillance mechanism against non-self Ag is postulated to one of reasonable causes as favorable prognosis of HPV associated with TSCC. Methods: We reviewed the medical records of histologically confirmed locally advanced TSCC patients, curatively treated in Asan Medical Center from January 2000 to December 2008. The immunohistochemistry (IHC) assays for p16 and FOXP3 were done in TSCC pafaffin-embedded samples. Results: We identified 79 patients who met the inclusion criteria. The median age was 54 years (range 32-76) and 16 (20%) patients were stage III and the others were all stage IV. With the median follow up of 62.9 months (95% CI, 59.2 - 66.7), sixty three (80%) were HPV-positive with p16 overexpression, and 38 (48%) were Treg-positive with FOXP3. Treg involvement was significantly related to HPV positive status (P=0.011). The result was the same after adjustment of age, T & N stage, smoking exposure and alcohol consumption. (Odd ratio = 6.54, 95% CI 1.58-27.1, P=0.01) Five-year overall survival (OS) rate in HPV-positive group was significantly higher than that of HPV-negative group (78% and 63%, Hazard Ratio (HR)=0.347, 95% CI 0.14-0.87, P=0.025), and 5-year OS of Treg-positive group was also higher than that of Treg-negative group (89% and 61%, HR=0.158, 95% CI 0.05-0.53, P=0.003). In multivariate analysis, the Treg status was an independent prognostic factor (HR=0.11, 95% CI 0.03-0.40, P=0.001), as well as HPV status. (HR=0.28, 95% CI 0.10 - 0.78, P=0.016). Conclusions: HPV positivity was associated with Treg positivity in TSCC and both were found to be favourable prognostic factors for survival.
Pretreatment neurocognitive function (NCF) status in head and neck cancer (HNC) patients (pts) with comparison to control cohort.
Authors: Abdul Razak Albiruni Ryan , Gan Hui Kong , Pond Gregory Russell , Tirona Kattleya M , Chen Eric Xueyu , Chan Kelvin , Hope Andrew J. , Kim Joon-Hyung J. , Siu Lillian L. , Bernstein Lori J 
Published: March 2020

5587 Background: There is increasing evidence that NCF abnormalities may occur in cancer pts. Data on pre-treatment NCF in HNC pts are lacking. This study reports NCF in pts with newly diagnosed, curable HNC compared to controls. Methods: HNC pts underwent a 2-hour battery of NCF tests prior to radio +/-chemo(bio)therapy. Domains tested were intelligence (IQ), memory, language, attention, processing speed, executive function and manual dexterity. Test performances were transformed into Z-scores using normative data (score < -1 signified deficit). Pts also had self-reported assessments for NCF, quality of life (QOL), fatigue and affect. Data obtained were compared to non-cancer controls who underwent the same tests. Results: Eighty HNC and 30 control subjects were assessed. Objective NCF testing demonstrated that HNC and control cohorts were similar across all domains, except for IQ, with pts having higher scores (mean 0.55 vs 0.12, p=0.03). However, individual analysis showed that 39% of HNC and 43% of control subjects had abnormal Z-scores in ≥ 2 domains. Multivariable analysis of factors associated with ≥ 2 abnormal NCF domains included: low education level, significant smoking history (≥ 10 pack year), previous mild brain injury, gender, and group (pt vs control). Amongst pts, HPV -ve status and non-oropharyngeal tumors were also associated with decreased NCF. Pts reported statistically worse subjective baseline symptoms compared to controls: NCF (mean FACT-COG 33.7 vs 18.2, p=0.002), QOL (FACT H&N 33.8 vs 14.9), fatigue (FACT-F 35.1 vs 15.1), anxiety (HADS 7.0 vs 3.1) and depression (HADS 3.9 vs 1.2), p<0.01 for all five parameters. Conclusions: Objectively assessed NCF was similar between HNC pts and controls, but a proportion of participants in both cohorts have multi-domain abnormal Z-scores. Several patient demographics and disease characteristics were associated with abnormal NCFs. Subjectively, pts reported worse NCF, QOL, fatigue and affect. These data suggest that participant and disease characteristics may play a larger role in determining NCF than previously shown. Whether such characteristics impact subsequent NCF is under investigation in a longitudinal study.