Oral Oncology

Patient-reported outcomes of symptom burden in patients receiving surgical or nonsurgical treatment for low-intermediate risk oropharyngeal squamous cell carcinoma: A comparative analysis of a prospective registry Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Moran Amit, Kate Hutcheson, Jhankruti Zaveri, Jan Lewin, Michael E Kupferman, Amy C Hessel, Ryan P Goepfert, G. Brandon Gunn, Adam S Garden, Renata Ferraratto, C. Dave Fuller, Samantha Tam, Neil D. Gross Abstract Purpose To explore treatment-related changes in symptom burden and quality of life (QOL) in oropharyngeal squamous cell cancer (OPSCC) patients treated surgically and non-surgically. Patients and Methods Eighty-six patients with human papillomavirus–associated OPSCC treated at the Head and Neck Center at The University of Texas MD Anderson Cancer Center were recruited to a prospective registry study between 2014 and 2016 and completed the core, head and neck-specific, and symptom interference sections of the MD Anderson symptom inventory (MDASI) multi-symptom questionnaire and the EQ-5D health status assessment as a measure of QOL at four time points. Results Longitudinal improvements from post-treatment nadir were observed across all groups. For patients treated with single modality, symptom interference, but not core and head and neck specific, MDASI scores were significantly better at 6 months in patients treated with surgery than radiation (P = 0.04). For patients treated with multiple modalities, scores for each of the three domains (i.e., core, head and neck -specific, and interference MDASI) were significantly better in the surgical group than the nonsurgical group at treatment completion (P = 0.0003, P = 0.0006 and P = 0.02) and 6 weeks (P = 0.001, P = 0.05 and P = 0.04), but not 6 months (P = 0.11, P = 0.16 and P = 0.040). No significant differences in EQ5D health status were observed between groups at any time point, reflecting similar overall QOL in all groups. Conclusion Symptom burden and QOL improves after treatment in OPSCC survivors over time regardless of whether primary surgical or nonsurgical treatment is used, although acute symptom profiles may differ.

Human papillomavirus detection in matched oral rinses, oropharyngeal and oral brushings of cancer-free high-risk individuals Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Maria Gabriella Donà, Barbara Pichi, Francesca Rollo, Maria Benevolo, Alessandra Latini, Valentina Laquintana, Raul Pellini, Manuela Colafigli, Mirko Frasca, Massimo Giuliani, Antonio Cristaudo Abstract Objectives The detection of oral Human Papillomavirus (HPV) may be of clinical utility because of the major role HPV plays in the etiology of oropharyngeal cancer. However, oral HPV testing is not standardized and the best sampling method has yet to be identified. We aimed to compare HPV findings in matched oral rinse-and-gargles (rinses), oropharyngeal brushings and oral brushings. Materials and methods HPV-DNA was investigated using Linear Array in samples collected from cancer-free individuals at increased risk for oral HPV. Results 163 oral rinses already tested for HPV were selected. The matched oropharyngeal (n = 163) and oral brushings (n = 100) were analyzed. The detection rate for any HPV, high-risk (HR)-HPVs and HPV16 was significantly higher in rinses than brushings. The overall agreement for any HPV between rinses and oropharyngeal brushings was 51.2% (Cohen K: 0.14, 95% CI: 0.07–0.21). The proportion of positive agreement was 16.8%. The overall agreement for HR-HPVs was 74.1% (Cohen K: 0.20, 95% CI: 0.07–0.33). The genotype-specific profile of rinses and brushings which were concomitantly HPV-positive only partially overlapped in cases with multiple infections, with more genotypes detected in the rinse, which were not isolated in the corresponding brushings. Conclusion The agreement for HPV status between rinses and brushings is poor, particularly for the HPV-positive findings. Despite the fact that the origin of the HPV-infected cells present in the oral rinse is unclear, since they could not be traced back to the oropharynx or oral cavity, oral rinses provided the highest detection rate for HR-HPVs and HPV16.

Patterns of EBV-positive cervical lymph node involvement in head and neck cancer and implications for the management of nasopharyngeal carcinoma T0 classification Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Wei-Jie Luo, Yan-Fen Feng, Rui Guo, Ling-Long Tang, Lei Chen, Guan-Qun Zhou, Wen-Fei Li, Xu Liu, Ying Sun, Ai-Hua Lin, Jun Ma, Yan-Ping Mao Abstract Objectives Epstein-Barr virus (EBV)-positive cervical lymph node (CLN) metastasis of unknown primary origin is classified as nasopharyngeal carcinoma (NPC) T0 by the American Joint Committee on Cancer staging manual (8th edition). We aimed to investigate the possible primary sites and patterns of EBV-positive CLN metastases and to provide implications for the management of NPC T0 classification. Materials and methods We retrospectively reviewed 269 patients with newly diagnosed EBV-positive CLN metastatic disease who underwent EBV detection via EBV-encoded RNA in situ hybridization. Fifteen patients with unknown primary tumors underwent follow-up after initial treatment. Results In patients with EBV-positive CLNs, the most common primary sites after the nasopharynx (51.7%) were the salivary gland (24.5%), lung (7.8%), oropharynx (3.3%), nasal cavity/maxillary (3.3%), oral cavity (2.2%), orbit (1.1%), and liver (0.4%). No primary site was found in 15 patients (5.6%). For salivary gland malignancies, level II and I were the most frequently involved regions. Tumors arising from the lung or liver metastasized to the lower neck (level IV, V, and VI) rather than the upper neck. After initial treatment, 2/15 patients with EBV-positive CLNs of unknown primary exhibited primary NPC and oropharyngeal tumor, respectively. Further, even without prophylactic irradiation to the nasopharynx, only one of 13 unknown primary patients developed NPC. Conclusions The origins of EBV-positive CLNs may not be restricted to the nasopharynx alone, and are likely to involve the head and neck or non-head and neck regions. NPC T0 classification should be cautiously assigned to such tumors.

Organ preservation in laryngeal and hypopharyngeal cancer Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Stephen Kang

Cervical nodal metastasis after malignant conversion of sinonasal inverted papilloma: Report of a rare case and literature review Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Daniel Sharbel, Vipawee Chat, Daniel Blumenthal, Paul Biddinger, J. Kenneth Byrd Abstract Malignant conversion of sinonasal inverted papilloma (SNIP) occurs in approximately ten percent of cases. These tumors are classically described as locally destructive, but without metastatic potential. Only four cases of malignant conversion with cervical nodal metastases have been described in the English literature. We present the rare case of a 61-year-old Caucasian male with a nasopharyngeal recurrence of malignant SNIP with cervical and retropharyngeal nodal metastases. The patient underwent endoscopic transpterygoid with nasoseptal flap reconstruction, followed by staged bilateral and retropharyngeal node dissection. Histopathology of the specimens demonstrated poorly differentiated invasive nonkeratinizing squamous cell carcinoma with inverted-type features. Three months after surgery, the patient suffered from C1-C2 fractures consistent with osteoradionecrosis and expired. Although the rate of malignant conversion of SNIP is low, this case highlights the need for aggressive, definitive treatment and surveillance.

Survival outcomes after treatment of cancer of the oral cavity (1985–2015) Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Daniella Karassawa Zanoni, Pablo H. Montero, Jocelyn C. Migliacci, Jatin P. Shah, Richard J. Wong, Ian Ganly, Snehal G. Patel Abstract Objectives To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015. Materials and methods A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16–100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1–382). Results The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05). Conclusion pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy.

Atorvastatin increases oxidative stress and inhibits cell migration of oral squamous cell carcinoma in vitro Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Patrícia Matos Biselli-Chicote, Amanda Trabachini Lotierzo, Joice Matos Biselli, Érika Cristina Paravino, Eny Maria Goloni-Bertollo Abstract Objective This study aimed to evaluate the effect of atorvastatin treatment on reactive oxygen species (ROS) production and tumor angiogenesis in oral squamous cell carcinomas. Material and Methods An HN13 cell line was treated with 1 µM, 5 µM, and 10 µM of atorvastatin. VEGF-A gene expression was evaluated by quantitative real time PCR. VEGF-A protein expression was quantified from total protein and conditioned media by ELISA. Cellular oxidative stress was measured using 2′,7′-dichlorfluorescein-diacetate (DCFH-DA). Angiogenesis assay was performed using human umbilical vein endothelial cells (HUVEC). The effect of atorvastatin on cell migration was evaluated by wound healing assay. Results 5 µM and 10 µM of atorvastatin significantly increased VEGF-A gene expression in the HN13 cell line. Intracellular expression of the VEGF-A protein was higher in the cells treated with 5 µM and 10 µM than in the control cells. VEGF-A protein expression was also higher in the conditioned media from the atorvastatin-treated cells than in the media from the DMSO-treated cells. 5 µM and 10 µM of atorvastatin increased oxidative stress. Regarding angiogenesis assay, 5 µM of atorvastatin resulted in higher numbers of branch points, compared to the solvent. 10 µM of atorvastatin treatment resulted in significantly reduced cell migration. Conclusions This study showed that atorvastatin increases the oxidative stress and angiogenesis in oral squamous cell carcinomas. The decrease of cell migration indicates atorvastatin's inhibitory effect in oral tumors. These results suggest that atorvastatin could increase the intracellular oxidative stress in these cells, leading to a toxic microenvironment and inhibiting their metastasis.

Associations between pre-, post-, and peri-operative variables and health resource use following surgery for head and neck cancer Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Hoda Badr, Maximiliano Sobrero, Joshua Chen, Tamar Kotz, Eric Genden, Andrew G. Sikora, Brett Miles Abstract Objective We examined associations between pre-, post-, and peri-operative variables and health resource use in head and neck cancer patients. Methods Patients (N = 183) who were seen for a pre-surgical consult between January 2012 and December 2014 completed surveys that assessed medical history, a patient-reported outcome measure (PROM) of dysphagia, and quality of life (QOL). After surgery, peri-operative (e.g., tracheostomy, feeding tube) and post-operative (e.g., complications) variables were abstracted from patients' medical records. Results Multivariate regression models using backward elimination showed that pre-surgical University of Washington Quality of Life (UW-QOL) Inventory and M.D. Anderson Dysphagia Inventory (MDADI) composite scores, documented surgical complications, and having a tracheostomy, were all significant predictors of hospital length of stay, explaining 57% of the total variance (F(5, 160) = 18.71, p < .001). Male gender, psychiatric history, and lower pre-surgical MDADI scores significantly predicted thirty-day unplanned readmissions (30dUR). Pre-surgical MDADI composite scores also significantly predicted emergencey department (ED) visits within 30 days of initial hospital discharge (p = .02). Conclusions Assessment of PROMs and QOL in the pre-surgical setting may assist providers in identifying patients at risk for prolonged LOS and increased health resource use after hospital discharge.

A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Loris De Cecco, Mara Serena Serafini, Carla Facco, Roberta Granata, Ester Orlandi, Carlo Fallai, Lisa Licitra, Edoardo Marchesi, Federica Perrone, Silvana Pilotti, Pasquale Quattrone, Cesare Piazza, Fausto Sessa, Mario Turri-Zanoni, Paolo Battaglia, Paolo Castelnuovo, Paolo Antognoni, Silvana Canevari, Paolo Bossi Abstract Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8+ effector memory cells, in SNUC) and "other cells": keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic β-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities.

A competing risk nomogram to predict severe late toxicity after modern re-irradiation for squamous carcinoma of the head and neck Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Matthew C. Ward, Nancy Y. Lee, Jimmy J. Caudell, Alexander Zajichek, Musaddiq J. Awan, Shlomo A. Koyfman, Neal E. Dunlap, Sara J. Zakem, Comron Hassanzadeh, Samuel Marcrom, Drexell H. Boggs, Derek Isrow, John A. Vargo, Dwight E. Heron, Farzan Siddiqui, James A. Bonner, Jonathan J. Beitler, Min Yao, Andy M. Trotti, Nadeem Riaz Abstract Purpose Severe late toxicity is common after re-irradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck. However, many patients experience complications from tumor progression before manifesting late effects. We constructed a nomogram to examine this relationship between late toxicity and competing risks. Methods and materials Patients with RSP squamous carcinoma originating in a field previously irradiated to ≥40 Gy and treated with IMRT-based re-irradiation to ≥40 Gy were collected. Grade ≥3 late toxicity developing ≥90 days after re-irradiation was collected. A multivariable competing-risk model was fit to the actuarial risk of late toxicity with progression or death as the competing risk. The final bootstrap optimized model was converted into a nomogram. Results From 9 institutions, 505 patients were included. The 2-year incidence of grade ≥3 late toxicity was 16.7% (95% CI 13.2–20.2%) whereas progression or death was 64.2% (95% CI 59.7–68.8%). The median freedom from late toxicity, progression or death was 10.7, 5.5 and 3.2 months for RPA class I-III patients respectively, whereas the median OS was 44.9, 15.9 and 7.9 months, respectively. The final model included six clinical factors. Notably, dose, volume and fractionation did not significantly impact toxicity. Conclusions After re-irradiation, the risk of progression or death is approximately four times the risk of radiation-related severe late toxicity. The risk of late toxicity may be more dependent on patient and disease factors than modifiable treatment factors. This model is useful for patient selection, pre-treatment consent and post-treatment survivorship following re-irradiation.