bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical behavior of stage IVC squamous cell carcinoma of the head and neck.
Authors: Wookey Vanessa , Kusi Appiah Adams , Kallam Avyakta , Ernani Vinicius , Smith Lynette , Ganti Apar Kishor 
Published: September 2018

e17511 Background: Squamous cell carcinoma of the head and neck (HNSCC) with distant metastasis at diagnosis (stage IVC) is rare, and outcomes are often lumped together with those of patients who relapse following initial treatment. We evaluated prognostic factors in patients presenting with stage IVC HNSCC. Methods: Data was extracted from the National Cancer Database to determine prevalence, overall survival (OS), and prognostic factors of stage IVC HNSCC (oral cavity, gum, lip, oropharynx, tongue, tonsil and hypopharynx) in adults, using SAS software for analysis. OS curves were estimated using the Kaplan-Meier method and differences were compared using a log-rank test. Significant parameters in the univariate Cox proportional hazards regression model analyses were included in the multivariate model, and hazard ratios, p-values and 95% confidence intervals were presented. Results: Of 226,302 patients with HNSCC, 5458 had distant metastases at diagnosis (2.40%); 5238 had complete data and were included in further analyses. Median survival of the entire cohort was 9.07 months, and one-year survival was 41%. Age > 70 years, Black race and higher Charlson-Deyo comorbidity score were associated with worse OS, while HPV positive status, tonsil and tongue (not including base) primary, private insurance and receipt of any treatment were associated with improved OS on univariate analysis. In multivariate analysis, HPV positive tumors were associated with improved OS compared to HPV negative tumors (HR 0.63, 95% CI 0.48-0.82; p= 0.001), even after adjusting for site of tumor origin. Only patients with a Charlson-Deyo score of ≥2 had worse OS compared to those without comorbidities. Hypopharynx, lip, tonsil and base of tongue primaries had significantly worse OS compared to gum and other mouth. Except for radiation alone and radiation with surgery, treatment demonstrated significant improvement in OS compared to no treatment, a combination of chemotherapy, radiation and surgery provided the largest survival benefit (HR 0.23, 95% CI 0.20-0.28). Conclusions: HPV positivity seems to predict for better prognosis, regardless of site of origin. Patients with metastatic HNSCC should be offered multimodality therapy in order to improve outcomes.
Open label, non randomized, interventional study to evaluate response rate after induction therapy with docetaxel and cisplatin in unresectable locally advanced squamous cell carcinoma of head and neck (NCT02061631).
Authors: Zaidi S. H. Manzoor , Masood Ahmed I. , Shah Syed Ijaz Hussain , Hashemy Irfan 
Published: September 2018

e17513 Background: This single arm, multicenter, phase 2 study was conducted to evaluate overall response (OR) rate and safety of subjects treated with induction regimen docetaxel + cisplatin, followed by chemoradiotherapy (CRT), in patients with locally advanced squamous cell carcinoma of oral cavity (stage III or IV) without distant metastasis. Methods: Induction regimen consisted of docetaxel 75mg/m2 and cisplatin 75mg/m2 on day 1; cycles were repeated every 21 days for 3 cycles with supportive G-CSF treatment beginning at first cycle. CRT consisted of weekly cisplatin 30mg/m2 for 4 weeks starting concomitantly with 60 Gy/30 fractions of conventional radiotherapy for 6 weeks. Primary and secondary efficacy criteria were OR rate at 3 weeks after cycle 3 and 8 weeks after last cycle of CRT respectively. Results: Three centers enrolled 35 patients. Primary efficacy endpoint: OR rate of evaluable patients (n = 27) was 88.9% (95% CI:71.9-96.2). Complete response (CR) was not achieved by any patients; partial response (PR) was achieved by 88.9% (24 of 27). From intent to treat (ITT) analysis OR rate was 68.6% (24 of 35). Secondary efficacy endpoint: OR rate of evaluable patients (n = 19) was 78.9% (95% CI:56.7-91.5) with CR and PR achieved by 2 (10.5%) and 13 (68.4%) patients respectively. Progressive disease (PD) was present in 4 patients. From ITT analysis CR rate was 5.7% (2 of 35) and OR rate was 42.9% (15 of 35). During induction most common hematological toxicity was leukopenia in 8 patients, with ≥Grade 3 leukopenia in 3 patients. Common non hematologic toxicities (all grades) were nausea, stomatitis and alopecia in 21, 18 and 18 patients respectively. During CRT most common adverse events were alopecia, stomatitis and nausea in 14, 13 and 13 patients respectively. Overall, leukopenia met seriousness criteria in 4 patients, and there was 1 case of febrile neutropenia. Overall, 7 patients died. Fatal events were not associated to investigational drugs. Conclusions: We observed an ITT response rate of 68.6% with docetaxel + cisplatin, suggestive of an active induction regimen with manageable safety profile. Clinical trial information: NCT02061631.
Relevance between PD-L1 expression combined with tumor infiltrating lymphocytes and prognosis in advanced hypopharyngeal squamous cell carcinoma.
Authors: Ono Takeharu , Azuma Koichi , Kawahara Akihiko , Sasada Tetsuro , Hattori Satoshi , Sato Fumihiko , Chitose Shun-ich , Shin Buichiro , Akiba Jun , Umeno Hirohito 
Published: September 2018

e17528 Background: Little information has been available regarding immune-related prognostic factors in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). Expression of programmed cell death-ligand 1 (PD-L1) in tumor cells is known to be a mechanism whereby cancer can escape immune surveillance. We investigated the predictive relevance of PD-L1 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density in patients with locally advanced HPSCC receiving neoadjuvant chemotherapy (NAC). Methods: We retrospectively reviewed 83 consecutive patients with advanced HPSCC who had received NAC. PD-L1 expression and TIL density were evaluated by immunohistochemical analysis. Results: Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression free survival (PFS) and overall survival (OS), whereas PD-L1 expression was not correlated with PFS or OS. Subgroup analysis defined by PD-L1 expression in combination with CD8+ TIL density revealed that the PD-L1-/CD8high group showed the longest survival (median PFS and OS were not reached), whereas the PD-L1+/CD8low group showed the shortest PFS (median 7.9 months, p = 0.006) and OS (14.3 months, p = 0.011) by Kaplan-Meier curves. Conclusions: Although there was no significant correlation between PD-L1 expression and prognosis in stage III and IV HPSCC patients who received NAC, the subgroup analysis indicated that combination of lack of PD-L1 expression and higher CD8+ TIL density was significantly associated with favorable survival in these patients. These results suggested that PD-L1 expression levels in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III and IV HPSCC.
Characteristics and outcomes of head and neck cancer in solid organ transplant recipients.
Authors: Alsidawi Samer , Price Katharine Andress Rowe , Chintakuntlawar Ashish V. , Garcia Joaquin J. , Westin Gustavo Figueiredo Marcondes , Okuno Scott H. 
Published: September 2018

e17529 Background: The immune system plays a major role in anti-tumor surveillance in healthy individuals. Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients (pts) with post-transplant HNSCC are unknown. Methods: After Institutional Review Board approval, we retrospectively identified pts who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and good follow up were included. Cutaneous cancers were excluded. Median overall survival (mOS) and progression free survival (mPFS) were analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. Results: 33 pts met study inclusion criteria. The median time to HNSCC after transplant was 5.9 years. The primary site was the oral cavity in 15 pts, the oropharynx in 10, the larynx in 3, the hypopharynx in 2, the parotid in 2 and unknown in 1 pt. 58% of pts presented with locally advanced disease, 39% with localized disease and one pt with metastatic disease. 87% underwent upfront surgical resection. Of those, 66% received adjuvant therapy (38% radiation alone and 28% chemoradiation). 6% of pts had definitive chemoradiation. After a median follow up of 10.5 years, the 5-year OS rate was 45% and 37% for localized and locally advanced disease respectively. 75% of pts with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year OS rate of 67%). The mPFS for the cohort was 22.8 months (95% CI; 11.6-50.1) with a median time to relapse of 15.2 months. The pattern of relapse was local in 69% of pts, distant in 25% and local plus distant in 6%. In a multivariate analysis, age > 60 years was a negative predictor of survival (HR 2.7; 95% CI, 1.1 to 6.5; P = 0.03). Conclusions: This retrospective study evaluated the clinical course and outcomes of pts with non-cutaneous HNSCC after solid organ transplant. Pts had inferior survival compared to historical controls. older pts had poor prognosis. The risk of local and distant recurrence was high. HPV-positive oropharyngeal tumors continue to have better outcomes in this population.
Tumor expression of hypoxia-inducible factor and antimicrobial peptides in oral fluid for prediction of after-surgery suppurative complications in patients with oral mucosa cancer.
Authors: Komarova Ekaterina , Kit Oleg Ivanovich , Kononenko Vladimir , Maksimov Aleksey Yurievich , Pozdnyakova Victoria V. , Novikova Inna Arnoldovna , Demidova Aleksandra 
Published: September 2018

e17530 Background: It is believed that hypoxia-inducible factor (HIF-1α) hyperactivity promotes synthesis of protective factors and increases bacterial growth-inhibitory activity, provides enhancement methods of the congenital immune response to microbial infection. Methods: Lactoferrin and α-defensin were detected in saliva of 41 patients with oral mucosa (OM) cancer (T2N0-2M0) before a comprehensive treatment; enzyme immunoassay (EIA) method was used. A level of hypoxia-inducible factor (HIF-1α) was evaluated by EIA method in tumor tissues after surgical treatment. The patients were divided into two groups according to an after-surgery period: the main group (n = 16) had after-surgery suppurative complications. An after-surgery period proceeded without infectious complications in patients of a control group (n = 25). Results: It was found that Lactoferrin content in saliva statistically was significantly higher by 36,4% (p < 0,05) (3,0±0,24 µg/ml against 2,2±0,19 µg/ml) if to draw a comparison between the main group and the control group with respect to development of suppurative complications and absence of a inter-group difference according to α-defensin concentration (4,1±0,35 pg/ml against 3,8±0,19 pg/ml). HIF-1α expression index in the main group (8,4±0,79 CU/mg protein in a well) exceeded this index by 18,3% (p < 0,05) in the control group (7,1±0,79 CU/mg protein). A positive correlation between HIF-1α expression and Lactoferrin content (R = 0,53 at р = 0,0001) was detected in patients with OM cancer. Conclusions: Detected HIF-1α hyperexpression in tumor tissues and Lactoferrin content in saliva, as well as their interaction allows suggesting significance of these factors for their progression prediction in patients with OM cancer in case of after-surgery suppurative complications.
In-human activity and pharmacology of homemade silver nanoparticles in highly refractory metastatic head and neck squamous cell cancer.
Authors: Singh Jasmine , Fattah Farjana , Burks Tam , Zheng Jie , Jiang Xingya , Kurian Pamela , Saleem Sehresh , Pearson Jean , Khan Saad A. 
Published: September 2018

e17533 Background: Silver nanoparticles (SNPs) show high efficacy as targeted therapy against cancer cell lines, but have never been tested in patient clinical trials. We present the first in-human trial of SNPs in a cancer patient with a dramatic outcome. Methods: Homemade SNP solution is prepared by the patient with online instructions. Current from 3 9-volt batteries is passed across 99.99% pure silver-bar electrodes in distilled water, until the metal content of the water measures 0.09-0.15 parts per million. The manufacturer is a 77-year old male who developed multiple recurrences of nasal cavity squamous cell cancer. Over 2 years he progressed on platinum and taxane based-chemotherapy, radiation twice and 2 surgical resections. Large hepatic and pulmonary metastases were observed on PET, MRI and CT; he was initiated on hospice. Without informing his oncologist he subsequently began manufacturing and consuming the SNP solution. Results: The patient ingested 120 ml daily of the solution for 3 months leading to clinical recovery and complete resolution of cancer at all sites, persisting for 18 months. Electron microscopy of the silver solution revealed bimodal SNP size distributions; 3 & 12 nm. Inductively coupled plasma mass spectrometry showed the basal blood silver ion concentrations of 32 ng/g. One hour after ingesting 60 ml of silver solution it rose to 46 ng/g. Urine showed no SNPs. Toxicities were not noted with this silver solution, with no evidence of myelosuppression, liver or kidney abnormalities on repeated testing. The patient underwent reconstructive surgery with excellent wound healing, and his performance status continues to improve. Conclusions: Ingestion of a SNP solution is associated with complete regression of highly refractory head and neck cancer in the absence of other anticancer therapy. Ingesting silver solution causes a noticeable and nearly immediate rise in blood silver concentration. Urinary excretion is not a major path of clearance from the body. Given these dramatic results that may be attributed to SNP in conjunction with strong preclinical data, further patient testing of SNP should be done to confirm its safety and efficacy in head and neck cancer.
Correlation of outcome with early metabolic response on FDG-PET in treatment of locally advanced nasopharyngeal carcinoma.
Authors: Kwong Dora Lai Wan , Lee Victor HF , Khong Pek lan 
Published: September 2018

e17555 Background: Skull base changes often persist on CT and MRI after treatment in locally advanced nasopharyngeal carcinoma (NPC) and cannot be differentiated from active tumor. We prospectively evaluated the metabolic response of T3/T4 NPC during treatment with PET scans. Early metabolic response was correlated with outcome after treatment. Methods: 50 patients with T3/T4, N0-3, M0 NPC were recruited. All patients had 3 cycles of induction chemotherapy (IC, physician’s choice of regime) before concurrent chemoradiation (CRT) with cisplatin 100mg/sqm for 3 cycles. PET scans were performed before and after IC and at 30Gy of CRT. For primary tumor that showed complete metabolic response (mCR, defined as SUV max in tumor ≤1.25x liver background activity) on reassessment PET, the dose to tumor stopped at 70Gy. For those who did not achieve mCR, a boost dose was given to the residual tumor to total 76Gy. Results: On post-IC PET scan, 2 patients with extensive intracranial disease showed no response with static and progressive disease respectively and did not proceed to CRT. 48 patients showed regression of tumor and decreased metabolic activity on post-IC PET, 16 of whom achieved mCR. One patient with mCR after IC refused CRT. 47 patients proceeded to CRT. 44 patients had reassessment PET at around 30Gy and 25 patients had mCR during CRT. 47 patients who completed CRT were included in survival analysis. Median follow up after completion of CRT was 28 months. Among the 15 cases who achieved mCR after IC, all patients were disease free without relapse at time of analysis. Among the 32 patients who did not achieve mCR after IC, there was 1 persistent loco-regional disease, 1 local and 1 regional relapse and 6 developed distant metastases. The 3 year NP control, regional control, distant metastases free, progression free survival and overall survival were 89.4%, 96.9%, 79.5%, 49.2% and 81% respectively compared with 100% corresponding survival rates among patients who achieved mCR after IC. The difference in progression-free survival was statistically significant (p = 0.045) Conclusions: Early mCR was observed in 32% patient after IC and 56.8% of patients during CRT. mCR after IC predicts for very favourable outcome.
Evaluation of feasibility of preoperative concurrent chemoradiotherapy in locally advanced operable oral cancer and resection and reconstruction of mandibular/maxillary segment with prefabricated free fibular graft.
Authors: Deshmukh Sanjay P 
Published: September 2018

e17558 Background: Every year more than 500,000 patients are diagnosed with oral cancer worldwide and majority require surgery and radiotherapy as a definitive curative treatment. Loss of bony segment of mandibular/maxillary bone with resultant loss of shape, function and ability to chew the food is known. Neoadjuvant chemoradiotherapy is known to have improved disease outcomes in many solid tumours. Methods: Total Seven patients underwent the planned protocol of 100 days. All patients were male and median age was 46 years. Six patients had disease involving lower alveolus and one had upper alveolus. All had no palpable nodes clinically. Step 1 a. Neoadjuvant treatment of Radiotherapy to Primary disease and draining lymph nodes dose of 45 to 50 Gy in 25 fractions over 5 weeks along with concurrent weekly Cisplatin 40mg/m2 for 5 cycles b. Mock surgery on 3D models with defining of insertion site of implants on fibular segment. Step 2 Insertion of dental implants in fibula and split skin graft in the desired fibular site in second week of radiotherapy. Step 3 Definitive surgery 6 weeks after completion of chemoradiotherapy and reconstruction by free fibular segment with primary dental prosthesis checking occlusion of oral bite. Results: Six patients(85.7%) are alive and free of disease at median follow up of 6.7 months. Three(42.8%) patients underwent prosthetic placement with acceptable outcome. Two patients had trismus and undergoing oral physiotherapy. Six patients had orocutaneous fistula. One had extrusion of fibular graft and one patient died. Five(71.4%) patients had complete response on final histopathology report and two had partial response. Conclusions: : A novel technique for better functional and aesthetic results with possible improved survival in operable oral cancer. Future randomized studies are needed for validation.
Outpatient intra-arterial chemotherapy without radiation therapy for stages II and III oral cancer: A new treatment to improve quality of life and reduce irradiation-related complications.
Authors: Ohmae Masatoshi , Kato Itsuro , Fujita Yusei , Takaoka Hiroo , Meshii Noritoshi , Takasu Ayako , Nakazawa Mitsuhiro 
Published: September 2018

e17567 Background: We developed a superselective intra-arterial chemotherapy (iaCT) approach to oral cancer, in which an intra-arterial catheter is retrogradely inserted through the superficial temporal artery and/or occipital artery with concurrent radiation therapy (RT). This approach remarkably improves the curative effect, but it decreases patients’ quality of life (QOL) because of prolonged hospitalization, severe stomatitis, lifelong dry mouth, dysgeusia, and radiation osteonecrosis of the maxillo-mandibular bone. Methods: This study assessed our new outpatient iaCT (op-iaCT) approach involving a subcutaneous infusion reservoir without concurrent RT. We included 23 patients, 11 with stage II and 12 with stage III oral cancer, and they were treated with the op-iaCT approach without concurrent RT. Using this approach, the chemotherapeutic agent was intra-arterially administered at the Outpatient Chemotherapy Center of Rinku General Medical Center. Results: The response rate to this approach was 100%, and all patients had a complete response. Four patients with secondary regional lymph node metastasis underwent neck dissection. Twenty patients were disease-free without an irradiation-related complication, whereas 3 patients died of distant metastasis (2) or local recurrence (1). With the exception of ambulatory visits twice per week for 3 weeks, patients’ activities of daily living (ADLs) were mostly unaffected. Moreover, patients rarely complained of dry mouth or dysgeusia, and they were free from radiation osteonecrosis after cancer therapy. Additionally, they did not develop oral dysfunction related to radical operation. Conclusions: In this approach, the catheter is implanted subcutaneously; therefore, common catheter-related issues rarely occur, resulting in good maintenance of ADLs. Moreover, patients can avoid the side effects of RT. Consequently, patient’s QOL improves and medical expenses decrease. Thus, our new op-iaCT approach improves QOL and the curative effect in patients with oral cancer if their ambulatory and performance status is good.
Timing of percutaneous endoscopic gastrostomy (PEG) tube placement as supportive care in HNSCC patients (Pts) receiving concurrent chemoradiotherapy (CRT).
Authors: Lupak Oleksandra , Bazydlo Michael , Siddiqui Farzan , Chang Steven , Coniglio Bryan , Wang Ding 
Published: September 2018

e17571 Background: Concurrent CRT with curative intent is the standard of care treatment for Pts with locally advanced or local recurrent head and neck squamous cell carcinoma (HNSCC). The CRT is associated with significant toxicities including nausea/vomiting, dysphagia and/or odynophagia, which prevent Pts from tolerating oral hydration and nutrition intakes. Treatment frequently leads to weight loss, renal injury and unexpected emergent care or hospitalizations along with therapy interruptions. This study is to determine the timing of PEG tube placement and its impact on the safety and tolerability from HNSCC patients receiving CRT. Methods: We retrospectively reviewed 413 electronic medical records (EMR), of which 335 of HNSCC Pts who had complete EMR during CRT period were included in this study. 127 of these 335 Pts (38%) required no PEG tube placement, 208 (62%) required PEG placement. The timing of PEG placement has been observed as two groups: 1) 109 Pts had PEG tube placement before initiation of CRT (Prophylactic Group PG); 2) 89 Pts had PEG tube during CRT period in reaction to a serious toxicity event (Reactive Group_RG). Logistic regressions were used to estimate the effect of PEG timing on Emergency Department (ED) visits, hospitalization, and experiencing treatment interruptions. Results: Our study showed that patients in PG demonstrated 43% less likely on their visiting ED or 42% less likely for hospitalization than Pts of RG with an odds ratio (OR) at 0.396 (95% CI: 0.165~0.952, p = 0.038) for PG over RG from toxicity-related therapy interruptions. Pts in PG also showed an OR at 0.40 from improving hypoalbuminemia over RG Pts (95% CI: 0.16~0.64, p = 0.001) which associated with 23% of chance of maintaining pre-CRT body mass index (BMI) for Pts in PG over those in RG. Conclusions: We observed the prophylactic PEG tube placement prevented unexpected ER visits and hospitalizations through reducing the risk of malnutrition and dehydration, which improved Pts in PG through the CRT with less therapy interruptions and preserved BMI, especially for those Pts of older age, pre-therapy dysphagia, hypoalbuminemia and receiving cisplatin in CRT.