bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal repopulation dynamics in recurrent human papillomavirus-associated head and neck cancer.
Authors: Harbison Richard A. , Kubik Mark , Konnick Eric , Faden Daniel , Xu Chang , Pritchard Colin , Rodriguez Cristina P. , Zhang Qing , Delrow Jeffrey J. , Chen Chu , Mendez Eduardo , Duvvuri Umamaheswar 
Published: September 2018

e17517 Background: Despite the better prognosis for human papillomavirus (HPV)-associated head and neck cancer (HNC) relative to HPV-negative HNC, 10 to 25% of HPV-associated cases recur within 3 years of completing therapy. We sought to investigate clonal repopulation dynamics in recurrent HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Methods: Deep sequencing ( > 500X) using a CLIA-certified, targeted 262-gene multiplexed assay was performed on DNA extracted from 11 pairs of matched FFPE-preserved primary and subsequent recurrent p16-positive OPSCC samples including two pairs from the University of Washington and nine from the University of Pittsburgh. Results: 82% of patients were male with a median (IQR) age of 62 (15) years. Nine of eleven patients presented with advanced stage disease. Five were initially treated with surgery and concurrent chemoradiation, two with surgery, and four with concurrent chemoradiation. Median (IQR) time to recurrence was 10 (10.5) months. Four patients reported a history of tobacco use. The mean (SD) number of somatic nucleotide variants (SNVs) per tumor was 16.4 (12.2). 42% of SNVs occurred in the primary alone while 28% were unique to recurrences. 28% of SNVs were shared between primary-recurrent pairs. Three patients with distant or regional recurrences had different mutational profiles between the primary and recurrence suggesting repopulation by an early-appearing clone vs sampling error. One patient developed two local recurrences with conserved mutations in addition to de novo mutations in each subsequent recurrence suggesting repopulation by early and late evolving clones. Genes with a substantial functional impact that were frequently mutated in primary tumors include IDH2 and FBXW7. Recurrently mutated genes found in recurrent tumors include TET3, PIK3CA, STK11, and HDAC4. Conclusions: In thistargeted exome sequencing study of matched primary-recurrent OPSCC tumor pairs, we observed clonal repopulation with both transmitted and de novo mutations. Intriguingly, we noted a predilection for mutations involving genes regulating metabolism including IDH2 among primary tumors which has potential implications for precision medicine approaches.
Treatment of radioiodine refractory high-differentiated thyroid cancer with lenvatinib.
Authors: Romanov Ilya , Mudunov Ali , Isaev Pavel , Bychkov Yury , Odzharova Akgul 
Published: September 2018

e17518 Background:Long time the patients with high-differentiated thyroid cancer with distant metastases had only one type of treatment. It was radioiodine therapy courses and follow-up. In cases of revealed radioiodine (RAI) refractory process we did not have possibilities for treatment this category of patients. Results of trials DECISION and SELECT gave to oncologist new keys for successful treatment. We present our group of RAI refractory thyroid cancer patients, which was treated by Lenvatinib like routine clinical practice. Methods:We have on treatment 8 patients (3-male, 5-female). Histologically – papillary thyroid carcinoma. Provisions of national clinical recommendations were considered as criteria of a RAI-refractory status. Existence of a symptomatic progression of a tumor was main criterion. Results:Six patients received from 7 to 14 month courses of treatment. All these patients are revealed partial response of the tumor lesions by PET-FDG-CT and the dramatically decrease of thyroglobulin level is noted. Two patients stopped treatment after 1 month of therapy. One patient due to destructive pneumonia, other patient – death due to myocardial infarction. Adverse events not related with Lenvatinib. The adverse events were controllable. We noted the expressed arterial hypertension. Before correction of a dose of a drug increase of arterial pressure more than 160/100 mm Hg is noted. Arterial pressure managed to be corrected the combined scheme of therapy (amlodipin, bisoprolol, hydrochlorthiazide). Correction of a dose of lenvatinib is made at 3 patients to 20 mg daily, 2 patient – 14. Conclusions:Introduction of a lenvatinib clinical practice is very successful. But we noted of important accurate expert selection of patients for treatment after establishment of a condition of a RAI-refractory and revealed really symptomatic progression, adequate correction of the adverse effects (arterial hypertension) and well-timed correction of a dose of a lenvatinib.
Change of three-dimensional DW-MRI for primary tumor and cervical lymph nodes in head and neck cancer during radiotherapy: A phase II prospective study.
Authors: Feng Mei , Lang Jinyi , Wu Fei , Chen Xiaochun , Xu Peng , Huang Yecai , Li Lu , Ren Jing 
Published: September 2018

e17522 Background: DW-MRI become more important, recent study find it help to discriminate metastatic lymph node and distinguish recurrent tumor. However, we still poorly understand the dynamic change of it during treatment, especially for 3D-apparent diffusion coefficient (ADC). It is urgent to study the dynamic change of 3D-ADC for head and neck cancer during radiotherapy, and to investigate the correlation between the ADC change, radiation dose and volume reduction. Methods: 60 head and neck cancer patients treated with image guided IMRT were enrolled. DW-MRI were performed on 3.0T MRI (b = 0, 500, 800 s/mm2) at pre-radiation, the 15th, the 25thand post-radiation. Region of interest was primary tumor (GTV-T) and cervical lymph node (GTV-N). The volumes and the maximum, mean and minimum of 3D-ADC value were automatically measured by MIM software. Pearson analysis was used to assess the correlation between 3D-ADC values, delivered radiation dose and tumor volume reduction. Results: All the patients exhibited the mean 3D-ADC increase in GTV-T (0.64±0.24 x10-3 mm2/s) and GTV-N (0.35±0.09 x10-3 mm2/s), with the mean increased ratios of 0.50±0.20 and 0.44±0.08 between pre- and post-radiation. However, the changes of the maximum and minimum 3D-ADC values for GTV-T and GTV-N had no correlation with delivered dose and volume reduction. The maximum, mean and minimum 3D-ADC changes in spinal cord were almost invisible (≤ 0.04 x10-3 mm2/s). The increased mean ADC had a strong positive correlation with the increased radiation delivered dose for GTV-T and GTV-N respectively (r = 0.977, p= 0.023; r = 0.974 , p= 0.026), and a significantly negative correlation with the volume reduction (r = -0.989, p= 0.011; r = -0.969 , p = 0.031) . Conclusions: The mean 3D-ADC value of primary tumor and cervical lymph node can be increased greatly for head and neck cancer during radiotherapy. It had a strong negative correlation with the volume reduction, and a positive correlation with the increased delivered dose. Dynamic 3D-ADC changes during radiotherapy might be an early indicator to assess the treatment response and helps to make treatment strategy for head and neck cancer.
Gene expression subtypes in early stage oral cavity squamous cell carcinoma and subclinical nodal metastasis.
Authors: Mazul Angela , Zevallos Jose , Wang Lin , Walter Vonn , Hayes David N. 
Published: September 2018

e17525 Background: Patients with early stage oral cavity squamous cell carcinoma (OCSCC) without clinical or radiographic evidence of cervical lymphadenopathy present as a therapeutic dilemma. Although studies show a survival advantage with elective neck dissection, about 70% of patients have pathologically negative nodes. In this study, we examine four previously described head and neck squamous cell carcinoma gene expression subtypes [basal (BA), mesenchymal (MS), atypical (AT), and classical (CL)] and subclinical nodal metastasis in early stage, clinically node negative OCSCC. Since the MS subtype is characterized by expression of epithelial to mesenchymal transition (EMT) genes, which is important in the initiation of nodal metastasis, we hypothesize the MS subtype is associated with higher rates of nodal metastasis and worse overall survival. Methods: Using a previously validated integrative genomic analysis, we determined gene expression subtype for T1-T2, clinically node negative OCSCC cases undergoing elective neck dissection from the Cancer Genome Atlas (TCGA) database. We compared rates of pathologically positive lymph nodes and survival in stage by gene expression subtype. Results: We identified 67 T1-T2, clinically N0 cases with pathologic node data. Most of OCSCC cases were BA (N = 24) or MS (N = 26) subtype. Few were either AT (N = 9) or CL (N = 8) subtype. Three of the BA subtype and 11 of the MS subtype tumors were pathologically node positive. MS tumors were 3.38 times (95% Confidence Interval (CI): 1.08-10.69) as likely to have pathologically positive lymph nodes compared to the BA subtype. The MS subtype was associated with worse overall survival (hazard ratio: 2.33, 95% CI 0.79-6.87) compared with the BA subtype. Conclusions: Our findings suggest gene expression subtypes can potentially identify early stage OCSCC patients at higher risk for subclinical nodal metastasis and may reflect high EMT gene expression associated with this phenotype. Gene expression subtype, along with tumor mutation and clinical profiles, could be used to determine the need for neck dissection in early stage OCSCC, and could translate into a reduction in treatment morbidity and length of hospitalization.
Compliance of elderly head and neck squamous cell carcinoma (HNSCC) patients (pts) with concurrent chemoradiotherapy (CRT) in cetuximab versus cisplatin.
Authors: Kazan Eyad , Kleihneny Tiffanie , Sakek Nacera , Thomas Alice , Milian Lucia , Edel Magali 
Published: September 2018

e17553 Background: Cisplatin toxicities substantially increased in elderly patients with head and neck cancer, when it is given as CRT. Bio-radiotherapy using cetuximab could offer a less toxic alternative. The purpose of this retrospective study is to evaluate the compliance of cetuximab versus cisplatin in CRT for HNSCC pts 70 years of age or old pts. Methods: We included over 70 years old patients treated by radio chemotherapy in head and neck cancer. Severity of AE was measured by the percentage of the drug dose reduction. Dose is considered reduced if patient did not receive 200mg/m² in cisplatin group, and if he did not receive the seven planned cycles in cetuximab group. We recalculated the dose reduction percentage including over 65 years old patientes. Results: We enrolled 37 over 70 years pts, middle age 74.5(from 70 to 88). 23 pts were treated by cetximab-RT compared to 14 treated by cisplatin-RT. 30% of pts (7 of 23 pts) in cet-RT group received a dose reduction versus 28% (4 of 14 pts) in cisplatin-RT group. Then, compliance to cetuximab is comparable to cisplatin and dose reduction is close.This finding disclaim a general assumption that cetuximab is better tolerated than cisplatin concurrently to radiotherapy in elderly pts. When we recalculated the dose reduction including also over 65 years old pts, we endrolled 64 pts, dose reduction in cet-RT pts remains about 28% (10 of 35pts) versus only 17% (5 of 29) in cisplatin-RT group. A clear increasing in dose reduction of cisplatin appears once pts passed 70 years old. Finally, we redistributed the 35 cetuximab-RT pts according to period of treatment, the first group included pts treated between 2007 and 2011, dose reduction was 35% (7 of 20patients),the second group included pts treated between 2012 and 2016, dose reduction was only 20% (3 of 15). This supports that good handling of cetuximab's toxicities improves the treatment's compliance. Conclusions: Dose reduction in elderly pts is equal in cetuximab and cisplatin. Dose reduction to cisplatin clearly increases among over 70years old pts. Good handling of cetuximab improves the compliance to treatment
Induction chemotherapy (IC) with EXTREME study regimen for locally advanced head and neck cancer (LAHNC) frail patients.
Authors: Cochin Valérie , De-Mones-Del-Pujol Erwan , Digue Laurence , Garcia-Ramirez Muriel , Dupin Charles , Majoufre-Lefebvre Claire , Daste Amaury 
Published: September 2018

e17564 Background: IC with TPF (docetaxel, cisplatin, 5FU) in LAHNC is limited to fit patients (pts). We conducted a retrospective cohort study to evaluate the use of EXTREME regimen (platinum, 5FU, cetuximab) as IC in LAHNC frail pts. Methods: Retrospective analysis of all consecutive pts with unresectable LAHNC treated with EXTREME regimen with or without 5FU as IC from two French centers from 2008 to 2015. We evaluated the rate of realization of the complete sequence (at least 2 cycles of IC and all radiation courses). Tolerance and efficacy, including clinical benefice, median progression free survival (PFS) and median overall survival (OS) were estimated. Results: We included 34 pts with average age of 56 years [46-70] (Table). Patients presented decreased weight (10% in one month or 15% in 6 months): 74% (n=25), pain: 76% (n=26), feeding tube: 82% (n=28), tracheotomy: 15% (n=4), fistula: 15% (n=4) and low albumin <35g/l: 41% (n=14), <25g/l: 12% (n=4). Six pts (17%) not received 5FU (cardiovascular history). Grade 3 toxicities were seen in 50% pts principally due to cisplatin. 5FU dose was decreased in 9% (n=3) and cisplatin switched to carboplatin in 15% (n=4). The sequence was achieved for 76% (n=26) of pts and 80% (n=27) presented clinical response with improvement of symptoms (increased weight: 32%, n=11). Six pts (17%) have a progression disease (PD) under IC, one patient (3%) died during bioradiotherapy (BRT) (stomach perforation) and one (3%) stopped IC after one cycle (infection) but achieved BRT. BRT with cetuximab was used in 85% (n=23) (average of 6 cycles [2-8]). PET-FDG at 3 months showed 9% (n=3) of complete response (CR) and 44% (n=15) of PD. Median PFS and OS were 5.7 and 15.5 months respectively. PD at 3 months was associated with decreased median OS: 21.9 versus 13.6 months, p=0.01. Conclusions: This is the first report of use of the EXTREME regimen as IC. This IC was used in a very frail population and the majority achieved sequence with significant clinical benefice. [Table: see text]
Effect of cabozantinib on bone turnover markers (BTM) and bone metastases (BM) in radioiodine refractory (RAIR)-differentiated thyroid cancer (DTC).
Authors: Konda Bhavana , Knopp Michael V. , Martin Peter R. , Geyer Susan , Cabanillas Maria E. , De Souza Jonas A. , Wirth Lori J. , Menefee Michael E. , Liu Stephen V. , Shah Manisha H. 
Published: September 2018

e17580 Background: Cabozantinib is a small molecule multiple-receptor tyrosine kinase inhibitor that primarily targets MET and vascular endothelial growth factor receptor 2 (VEGFR2). We evaluated the effect of cabozantinib on BTM in RAIR DTC. We also assessed the response of BM to cabozantinib using 18F Sodium Fluoride (NaF) PET and radionuclide bone scans. Methods: This prospective analysis was performed as part of a multicenter International Thyroid Oncology Group phase II study of cabozantinibin patients with RAIR DTC who progressed on prior VEGFR-targeted therapy (NCT01811212). BTM [serum C-telopeptide (CTx), osteocalcin, N-telopeptide (NTx), procollagen type 1 (Pc1) and urinary NTx] and NaF PET or Tc-MDP scans were done at baseline and after 8 weeks of therapy. A paired t-test was used between baseline and week 8 BTM. Results: Primary study results were presented elsewhere (Shah, et al. 2015, International Thyroid Congress) showing a response rate of 36% with cabozantinib. Of 25 patients (pts) enrolled, 21 had BM, 10 of whom were on bone-modifying agents (BMA) prior to week 8. Only 2 pts had elevated BTM at baseline. In all pts who had paired BTM, there was a statistically significant decline in all BTM except NTx by week 8 (table). Pts not on BMA also had a significant decline in CTx (p 0.0003), urine NTx (p 0.0300), and Pc1 (p 0.0030) compared to baseline. 19 pts were evaluable for overall response and there was no correlation between BTM and response rate. 6/21 patients underwent paired NaF PET scans and 4/6 had minor reduction in lesion uptake at 8 weeks. Conclusions: Interestingly, most of our patients had normal baseline BTM despite BM. Cabozantinib was associated with a strikingly significant reduction in all BTM (even when BTM were within normal limits at baseline) except NTx by week 8. Minor decreases in bone lesion uptake was noted on NaF PET in 4/6 evaluable patients. Clinical trial information: NCT01811212. [Table: see text]
Morbid mortality associated with total thyroidectomy for differentiated carcinoma in a training institute.
Authors: López Saucedo RaÃºl Alejandro , Rodirguez Roberto , Infante Sergio , Salazar Alejandra , Granados-Garcia Martin 
Published: September 2018

e17586 Background: Total thyroidectomy is now a common and relatively safe procedure. In the context of malignant pathology: It optimizes local control, facilitates adjuvant therapy with iodine 131, increases thyroglobulin sensitivity in patient surveillance and improves survival in patients at high risk. The reported morbimortality is related to Transient or definitive hypocalcemia, unilateral or bilateral recurrent laryngeal nerve injury (RLN), postoperative hemorrhage, wound infection, chylous fistula, tracheal injuries or esophageal perforations, cervical sympathetic chain lesions, among others Although death is rare as a result of the procedure and its complications. Methods: The present retrospective, descriptive, observational, cross-sectional, analytical study was performed based on an analysis of the records opened to patients at the National Cancer Institute between November 23, 2012, and January 5, 2015 corresponding to 100 consecutive cases with diagnosis of differentiated thyroid cancer, submitted to at least total thyroidectomy. Results: According with the AJCC 7th edition TNM distribution was: pT1 n = 13, pT2 n = 14, pT3 n = 63, pT4a n = 10, pN1a n = 12, pN1b n = 51, M1 n = 12. In 73 patients, no complications developed, and of the complications presented, 8 patients developed transient hypocalcemia, 19 permanent hypocalcemia, 3 resections of the RLN in a planned manner, 1 accidentally identified intraoperative lesion, 7 unconscious lesions of the RLN, 11 developed dysphonia, 1 Horner's syndrome, 2 Vagus lesions, 2 patients with tracheal or pharyngeal fistula, 1 chylous fistula, 1 transoperative hemorrhage and 1 hematoma. Mortality in one of the patients. Conclusions: Our results translate morbidity and mortality associated with locally advanced tumors, where the only correlation identified were the relationships with the presence of parathyroid glands in the pathology report and the development of hypocalcemia. With the above, we can assure that the best ally of the surgeon is the careful dissection based on a deep knowledge of anatomy, which could reduce the morbidity due to the surgery.
Outcomes and prognostic factors of localized, resected malignant salivary gland tumors: Examining a single institution’s 12-year experience to discover indications for adjuvant chemotherapy.
Authors: Gutschenritter Tyler , Machiorlatti Michael , Vesely Sara , Ahmad Bilal , Razaq Wajeeha , Razaq Mohammad 
Published: September 2018

e17587 Background: Survival outcomes remain poor in salivary gland malignancies (SGMs) with multiple poor prognostic factors despite adjuvant radiotherapy. We examined prognostic factors that portended poor survival in resected SGMs to determine possible indications for adjuvant chemoradiotherapy. Methods:Patients who underwent curative resection with or without adjuvant radiotherapy between 2002 and 2014 were identified and retrospective chart review was performed. Bivariate analysis was performed on continuous variables using Analysis of Variance. Chi-Square analysis and Fishers Exact Tests were performed on categorical variables. To evaluate the overall survival (OS) and disease-free survival (DFS), Kaplan-Meier curves and log-rank tests of homogeneity were used. Results: Overall, 99 patients met inclusion criteria. Median follow-up time was 46.8 months. Univariate analysis revealed male sex, smoking history ≥ 10 pack-years, high grade, stage III-IVB, squamous cell histology, and perineural invasion significantly impacted OS and DFS. High-risk histopathology significantly impacted DFS and trended towards poor OS. Positive resection margins trended towards significantly impacting DFS. Multivariate analysis revealed only male sex and perineural invasion significantly impacted OS and DFS. Conclusions: Survival outcomes remain poor for patients with high-grade, late-stage tumors with perineural invasion. Specifically, perineural invasion is a poor prognostic factor regardless of age, histology, stage, and grade. Males and patients with a smoking history ≥ 10 pack-years have worse survival outcomes with male sex being a more influential prognostic factor. Notably, this is the first study to quantify patient’s smoking history in malignant salivary gland tumors and assess the impact of pack-year smoking history on survival outcomes. Given our observed trend, positive resection margins would likely become significant influencer of DFS with larger sample size and longer follow up. Adjuvant chemoradiotherapy should be evaluated in patients with the above-mentioned characteristics.
Second or none: Many patients treated for refractory differentiated thyroid cancer with small molecular kinase inhibitors do not receive a second line of therapy.
Authors: Copher Ronda , Adejoro Oluwakayode , Byfield Stacey DaCosta , DuCharme Mary , Chatterjee Debanjana , Joshi Prashant Ramesh , Desai Avinash , Baig Mahadi Ali 
Published: September 2018

e17589 Background: Describe the treatment patterns of patients initiated on NCCN-recommended small molecular kinase inhibitors (SMKIs) for radioiodine-refractory differentiated thyroid cancer (DTC) approved in the United States. Methods: A large national US claims database was used to identify adult patients diagnosed with thyroid cancer (≥2 non-DX medical claims, ≥ 30 days apart) from 1/1/2006 - 6/30/2016 (study period) with claims for SMKIs from 1/1/2010 - 5/31/2016. Continuous enrollment required participation in a commercial or Medicare Advantage health plan ≥3 months before and ≥1 month following index date (date of first pharmacy claim for SMKI). Line of therapy (LOT) periods were defined by receipt and timing of SMKIs. Patient follow up was earliest disenrollment, death or end of the study period. Patient characteristics and SMKI treatment patterns were described. Results: A total of 217 DTC patients were identified; 63% commercially insured and 37% Medicare Advantage. Almost half were male (48%); mean age was 61.2 years (standard deviation SD 12.5 years) and mean follow-up period was 499 days (SD 414 days). In the study period, 35% (n = 77) of patients had ≥2 LOTs and 18% (n = 39) had ≥3 LOTs. Mean treatment duration was 5.4 months (SD 6.7 mos) for LOT1, 4.9 months (SD 3.8 mos) for LOT2, and 4.2 months (SD 4.9 mo) for LOT3. During the full study period, the most used regimens were Sorafenib for both LOT1 (37%) and LOT2 (25%), pazopanib (18%) and sunitinib (18%) in LOT3. Also, in the study period, 33 patients had sorafenib in LOT1 of which 16 were treated with sorafenib again (48%) in LOT2. Post FDA approval in 2015, Lenvatinib became the predominant first-line regimen (47%, n = 29) during study period. Across all first line therapies, for those patients with ≥12 months of follow-up, 53% (n = 60) initiated LOT2. Conclusions: Sorafenib was the most common first line of therapy for DTC, with Lenvatinib adoption increasing as first-line therapy since the drug’s approval in 2015. Depending on the period evaluated, almost half to 2/3 of patients are not receiving a second line of treatment, efficacious and patient appropriate therapy is of importance in treating this rare cancer.