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The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma.This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18-65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0-N1 disease (according to International Union Against Cancer-American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66-70 Gy (for the involved cervical lymph nodes), 60-62 Gy (for the high-risk target volume), and 54-56 Gy (for the low-risk target volume) were administered in 30-33 fractions, five fractions per week. Patients with stage II-IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed.Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46-59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% [95% CI 95·7-99·7] in the UNI group vs 96·3% [93·8-98·8] in the WNI group; difference -1·4% [95% CI -4·6 to 1·8]; pElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0-N1 nasopharyngeal carcinoma.Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation.For the Chinese translation of the abstract see Supplementary Materials section.

PURPOSE To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution. METHODS AND MATERIALS NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) and rENE-negative (rENE-) patients. Multivariable analysis (MVA) confirmed the prognostic importance of rENE and its grade. Staging schemas including rENE in N-classification were proposed and their performance evaluated. RESULTS A total of 274 patients were eligible (43 cN0; 231 cN-positive). rENE was identified in 83/231 (36%) cN-positive, including grade 1/2/3 rENE in 14/58/11 cases. Compared to rENE-, rENE+ patients had a lower OS (68% vs 89%, p

In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT).OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison.In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P0.001). Distant control was 97%, 87%, 68% (P0.001) and overall survival was 75%, 53% and 39% (P0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b.When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

To describe the utilization pattern of head and neck (HN) surveillance imaging and explore the optimal strategy for radiologic "residual" lymph node (LN) surveillance following definitive (chemo)radiotherapy (RT/CRT) in human papillomavirus (HPV)+ oropharyngeal carcinoma (OPC).All HPV+ OPC patients who completed RT/CRT from 2012 to 2015 were included. Schedule and rationale for post-treatment HN-CT/MRI were recorded. Imaging findings and oncologic outcomes were evaluated.A total of 1036 scans in 412 patients were reviewed: 414 scans for first post-treatment response assessment and 622 scans for the following reasons: follow-up of radiologic "residual" LN(s) (293 scans/175 patients); local symptoms (227/146); other (17/16); unknown (85/66). Rate of scans with "unstated" reason varied significantly among clinicians (3-28%, p 0.001) and none of them yielded any positive imaging findings. First post-treatment scans identified 192 (47%) patients with radiologic "residual" LNs. Neck dissection (ND) was performed in 28 patients: 16 immediately (6/16 positive), 10 after one follow-up scan (2/10 positive), and 2 after 2nd follow-up scan (1/2 positive). Thirty patients had2 consecutive follow-up scans at 2-3-month intervals, and none showed subsequent imaging progression or regional failure.Pattern of HN imaging utilization for surveillance varied significantly among clinicians. Imaging surveillance reduces the need for ND. However, routine HN-CT/MR surveillance without clinical symptoms/signs does not demonstrate proven value in identifying locoregional failure or toxicity. Radiologic "residual" LNs without adverse features are common. If two subsequent follow-up scans demonstrate stable/regressing radiologic "residual" LNs, clinical surveillance without further imaging appears to be safe in this population.

Highlights • Different trial types require different sample size calculation and interpretation. • Statistical modeling may help to minimize confounding effects and bias. • Statistical pitfalls can be avoided by following correct statistical guidance., Purpose To facilitate understanding statistical principles and methods for clinicians involved in cancer research. Methods An overview of study design is provided on cancer research for both observational and clinical trials addressing study objectives and endpoints, superiority tests, non-inferiority and equivalence design, and sample size calculation. The principles of statistical models and tests including contemporary standard methods of analysis and evaluation are discussed. Finally, some statistical pitfalls frequently evident in clinical and translational studies in cancer are discussed. Results We emphasize the practical aspects of study design (superiority vs non-inferiority vs equivalence study) and assumptions underpinning power calculations and sample size estimation. The differences between relative risk, odds ratio, and hazard ratio, understanding outcome endpoints, purposes of interim analysis, and statistical modeling to minimize confounding effects and bias are also discussed. Conclusion Proper design and correctly constructed statistical models are critical for the success of cancer research studies. Most statistical inaccuracies can be minimized by following essential statistical principles and guidelines to improve quality in research studies.

Highlights • Definitive RT/CRT for OSCC achieved acceptable rate of locoregional control. • Definitive RT is a reasonable alternative treatment strategy if surgery is not possible. • cN2-3 is associated with poor distant control, DFS, and OS., Purpose To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). Methods All OSCC patients treated radically with IMRT (without primary surgery) between 2005–2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. Results Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p

This study examines outcome heterogeneity and potential to refine the TNM-8 cN-classification using radiologic extranodal extension (rENE) in a contemporary HPV-positive (HPV+) oropharyngeal carcinoma (OPC) cohort.All HPV+ OPC treated with definitive IMRT from 2010-2015 were included. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist for rENE. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) vs rENE-negative (rENE-). Multivariable analysis (MVA) for OS confirmed the prognostic value of rENE. Refined cN-classifications for new TNM staging proposals were evaluated against TNM-8 using established criteria.A total of 517 cN+ (rENE+: 97; rENE-: 420) and 41 cN0 cases were identified. The rENE+ proportion increased with rising N-category (N1/N2/N3: 11%/19%/84%, p 0.001). Median follow-up was 5.1 years. Compared to rENE-, rENE+ patients had a lower 5-year OS (56% vs 85%) and DFS (46% vs 83%) overall, and in N1 (OS: 57% vs 89%; DFS: 51% vs 87%) and N2 subsets (OS: 45% and 76%; DFS: 33% vs 74%) (all p 0.001). MVA confirmed the prognostic value of rENE for OS (HR = 3.86, p 0.001) and DFS (HR = 3.89, p 0.001). We proposed two new cN-classifications: Schema1 reclassified any N_rENE+ as New_N3; Schema2 reclassified N1_rENE+ as New_N2 and N2_rENE+ as New_N3. Stage incorporating either Schema1 (ranked 1st) or Schema2 (ranked 2nd) cN-categories outperformed TNM-8.This study confirms that rENE is prognostically important and facilitates understanding of known outcome heterogeneity within TNM-8 in HPV+ OPC patients. rENE is a promising parameter to refine the TNM-8 cN-classifications.

The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC.Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively.In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P0.01); this was similar in the validation cohort (44% versus 4%; P0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P0.01) and late (2 years post surgery) DM (22% versus 4%; P0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P0.01).This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.

To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW).This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status.Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P = .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW.The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC.

It is unclear whether postoperative wound infections after head and neck cancer surgery are associated with cancer progression.Patients undergoing surgery for oral cancer from 1998 to 2011 were reviewed. Univariable analyses and multivariable were performed. Propensity scores were used to create matched cohorts for infection and non-infection groups. Neutrophil-to-lymphocyte ratios (NLR) were determined prior to surgery and at the time of infection.Of 551 patients with oral cancer treated with surgery, 98 developed wound infections (18%). Tumor factors associated with wound infections included higher T and N category, extranodal extension, depth of invasion, lymphovascular and perineural invasion (p 0.02 for all). On univariable analysis, wound infection was a predictor for recurrence free survival (p 0.001), locoregional control (p = 0.01), and distant control (p 0.001). Wound infection was not a predictor of overall survival (p = 0.88), recurrence free survival (p = 0.17), locoregional control (p = 0.79) or distant control (p = 0.18) on multivariable analysis. Using a propensity score matched cohort of 83 patients with and without infection, wound infection was not associated with recurrence free survival (p = 0.21), overall survival (p = 0.71), and locoregional control (p = 0.84), although there was a trend towards increased distant metastases (p = 0.10). Patients with wound infection had a greater preoperative NLR as well as a greater rise in the NLR after surgery, but these were not associated with survival or recurrence.Patients with wound infections have more adverse pathologic features. However, wound infection was not associated with poorer cancer outcomes although a trend towards increased distant metastases should be investigated.

To evaluate outcomes in oropharyngeal cancer (OPC) patients who did not complete their planned curative radiation therapy (RT).OPC Patients who received less than planned curative RT dose between 2002 and 2016 were identified for analysis. HPV status was assessed. Radiation dose was normalized for fractionation variations using biological effective doses assuming tumor α/β = 10 Gy [BED10]. Outcomes were compared using BED10. Multivariable and univariable analysis identified OS predictors.From a total of 80 patients who did not complete therapy, 64 patients were eligible for analysis. RT incompletion was due to: RT side effects (n = 23), patients' decision (n = 21), disease progression or metastases (n = 3), and other causes (n = 7). Median BED10 (Gy) was 56.2 for the HPV-positive and 58 for the HPV-negative. Three-year OS was 74% vs 13% (p 0.001) for the HPV-positive (n = 29) and HPV-negative (n = 24), respectively. HPV-positive patients who received BED10 ≥55 had higher OS than those received BED1055 (94% vs 47%, p = 0.002) while no difference in OS by BED10 ≥55 vs55 for the HPV-negative (12 vs 13%, p = NS). HPV-positive status was associated with a higher OS (HR 12.5, 95% CI, 4.54 to 33.3, p 0.001). A total of 37 patients were available to estimate TDOverall, in patients with incomplete treatment, HPV-positive OPC patients demonstrated a better OS compared to HPV-negative patients. HPV-positive patients who received BED10 ≥55 have higher rates of OS.

PURPOSE To identify adverse radiologic nodal features in cN+ TNM-8 stage I human papillomavirus-related (HPV+) oropharyngeal cancer (OPC). METHODS AND MATERIALS All patients with HPV+ cT1-T2cN1 OPC treated with definitive intensity modulated radiation therapy from 2008 to 2015 were included. Radiologically involved lymph node number (LN), radiologic extranodal extension (rENE), retropharyngeal LN (RPLN), and lower neck (level 4 or 5b) LN involvement were assessed on pre-treatment computed tomography/magnetic resonance imaging by a specialized head and neck neuroradiologist. Disease-free survival (DFS), locoregional control, and distant control were compared between those with versus without rENE. Univariable and multivariable analysis with stepwise modal selection were applied to identify prognostic factors for DFS. RESULTS A total of 45 rENE+ and 234 rENE- were identified. The rENE+ cohort had a higher number of LNs per patient (median: 6 vs 2, P

Highlights • Tissue segmentation can be achieved using a spatially registered cytokeratin mask. • Automated and manual cell counts and stain intensities were highly correlated. • Smokers had significantly stronger PD-L1 stain intensity and higher numbers TILs. • After radiotherapy, greater CD8+ TILs was associated with inferior survival., Oral tongue squamous cell carcinoma (OTSCC) displays variable levels of immune cells within the tumor microenvironment. The quantity and localization of tumor infiltrating lymphocytes (TILs), specific functional TIL subsets (e.g., CD8+), and biomarker-expressing cells (e.g., PD-L1+) may have prognostic and predictive value. The purpose of this study was to evaluate the robustness and utility of computer-assisted image analysis tools to quantify and localize immunohistochemistry-based biomarkers within the tumor microenvironment on a tissue microarray (TMA). We stained a 91-patient OTSCC TMA with antibodies targeting CD3, CD4, CD8, FOXP3, IDO, and PD-L1. Cell populations were segmented into epithelial (tumor) or stromal compartments according to a mask derived from a pan-cytokeratin stain. Definiens Tissue Studio was used to enumerate marker-positive cells or to quantify the staining intensity. Automated methods were validated against manual tissue segmentation, cell count, and stain intensity quantification. Univariate associations of cell count and stain intensity with smoking status, stage, overall survival (OS), and disease-free survival (DFS) were determined. Our results revealed that the accuracy of automated tissue segmentation was dependent on the distance of the tissue section from the cytokeratin mask and the proportion of the tissue containing tumor vs. stroma. Automated and manual cell counts and stain intensities were highly correlated (Pearson coefficient range: 0.46–0.90; p

Purpose/objective(s) Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. Materials/methods A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. Results Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for Conclusion HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Purpose/Objective(s) Only 9% of adult Rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS), often as a paranasal mass with proptosis, orbital and skull base invasion, and a prodigious risk of regional node involvement and distant metastatic dissemination to unusual locations in the young adult with the embryonal/alveolar (E/A) subtype. E/A-RMS respond rapidly to chemotherapy and radiotherapy (RT) and management is extrapolated from the pediatric experience where prognosis is better but treatment imperatives differ. We report on adults with HNRMS treated over 3 decades. Materials/Methods We reviewed adult patients treated from 1984 – 2017 via chart review and a prospectively maintained database from 1989 onward. RMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-RMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. Chemotherapy regimens included VAC and VAC/IE, with VC given concurrently with RT. P-RMS were treated with surgery +/- RT. IMRT was adopted from 2005 onward. Results Fifty-eight patients met inclusion criteria; median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were > 5cm. Of 45 patients with M0 disease treated with curative intent, 33 (73%) had E/A-RMS and 12 (27%) had P-RMS. All E/A-RMS patients received definitive RT with either 66 Gy or 70 Gy in 2 Gy per fraction, except 2 who had surgery for diagnostic purposes. Involved nodal regions were treated with radical dose RT and elective nodal RT was routinely delivered. In the IMRT-era, patients with primary disease in the nasopharynx or paranasal sinuses were treated with bilateral neck RT, while patients with well lateralized primary disease were generally treated with ipsilateral neck RT. Pre-IMRT, out of 23 patients with initial M0 E/A-RMS, 12 (52%) had a loco-regional recurrence. Post-IMRT, out of 10 patients with initial MO disease, only 1 (10%) had a local recurrence; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy due to local toxicity, but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was statistically superior in the IMRT era as compared to pre-IMRT (Fisher's exact test, P = 0.049). Overall, distant metastasis was the predominant mode of treatment failure (n = 17/33, 52%). Conclusion In our experience, the rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT is excellent. As such CRT should be considered the treatment of choice in this population to avoid extensive surgery including craniofacial resection and orbital exenteration, which would be needed for many of these patients but has functional and cosmetic consequence; it would also interrupt ongoing maintenance chemotherapy which has proven survival benefit. In contrast P-RMS is distinct and requires surgery +/- RT.

PURPOSE/OBJECTIVE(S) Patient-derived xenografts (PDX) can help identify oral cavity squamous cell carcinoma (OSCC) patients at risk for disease recurrence and optimize clinical decision-making. In this study, we develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors. MATERIALS/METHODS PDX models were generated from OSCC patients. Patients were scored as a ''non-engrafter" if PDX formation did not occur within 6 months. Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups using a 10-fold cross-validation approach. RESULTS Overall 288 OSCC patients were analyzed. MVA identified pT3-4, pENE, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (HR 1.98, 95% CI: 1.24-3.18, P < 0.01), and DM (HR 2.64, 95% CI 1.21-5.75, P < 0.01) compared to non-engrafters. A prediction score based on the aforementioned variables identified patients at high-risk (defined as having at least two of the three high risk features i.e., engraftment, pT3-4, pENE) and low-risk for LRF (43.5% vs 26.5% at 5-years, P < 0.001), DM (38.2% vs 8.4% at 5-years, P < 0.001), and poorer 5-year OS (34% vs 66%, P < 0.001). The prediction model that included engraftment had the highest discriminatory capacity in the cross-validation analysis (AUC: 67.8 [63.5-72.9]), while removal of engraftment as a predictor resulted in a lower c-index (AUC: 62.7 [57.0-68.4]). In patients classified based on a clinical score only (i.e., presence or absence of pT3-4 and pENE), engraftment remained useful in identifying those with worse outcomes. Compared to non-engrafters, engraftment was associated with higher rates of DM (15.8% vs. 5.4%, P < 0.05) in clinically "high risk" patients as well as higher rates of LRF (31.9% vs. 13.8%, P < 0.05) in clinically "low risk" patients at 5-years. Finally, engraftment was associated with poorer 5-year OS in both clinically "high risk" (36% vs. 65%, P < 0.05), and "low risk" patients (57% vs. 78%, P < 0.01). CONCLUSION A prediction score utilizing OSCC PDX engraftment, in conjunction with pT3-4 and pENE, improves the prognostic utility of existing clinical models and predicts patients at risk for LRF, DM and poor survival.

Purpose To assess the impact of the radiation therapy (RT) regimen and image guidance (image guided radiation therapy [IGRT]) protocol on local control (LC) for T2N0 glottic cancer treated with partial laryngeal intensity modulated radiation therapy (IMRT). Methods and Materials All patients with T2N0 glottic cancer treated with IMRT from 2006 to 2013 at a single institution were retrospectively reviewed. The gross tumor volume (GTV), delineated from endoscopic and/or radiologic findings, was expanded 0.5 cm for the high-dose clinical target volume and an additional 0.5 cm for the lower-dose clinical target volume (total of 1.0 cm from GTV). The planning target volume margin was 0.5 cm radially and 1 cm superiorly and inferiorly. RT regimens evolved from hypofractionated IMRT (RT-hypo, 60 Gy in 25 fractions over a period of 5 weeks) to moderately accelerated IMRT (RT-acc, 66-70 Gy in 33-35 fractions over a period of 5.5-6 weeks) since 2010. The IGRT matching surrogate changed from cervical vertebral bone (IGRT-bone) to laryngeal soft tissue (IGRT-larynx) in 2008. LC was compared between 3 sequential cohorts: RT-hypo/IGRT-bone, RT-hypo/IGRT-larynx, and RT-acc/IGRT-larynx. Multivariable analysis assessed the relative impact of RT regimen and IGRT technique on local failure separately. Results Among 139 eligible patients (median follow-up period, 5.03 years [range, 0.8-10.5 years]), we identified 28 local, 6 regional, and 2 distant failures. A higher 3-year LC rate was observed for RT-acc/IGRT-larynx (89% [95% CI: 78%-95%]) versus RT-hypo/IGRT-larynx (80% [95% CI: 54%-91%]) and RT-hypo/IGRT-bone (70% [95% CI: 53%-80%]) (P = .02). Multivariable analysis adjusted for GTV (in cubic centimeters) and smoking status confirmed that IGRT-larynx versus IGRT-bone (hazard ratio, 0.40; P = .019) and RT-acc versus RT-hypo (hazard ratio, 0.34; P = .012) both reduced the risk of local failure. Conclusions This single-institution cohort study shows a high LC rate (89%) for T2N0 glottic cancer following moderately accelerated partial laryngeal IMRT with daily laryngeal soft tissue matching IGRT. These results appear to represent an improvement attributable to changes in both IGRT matching and dose delivered, but their independent significance is unknown and further confirmation in a larger cohort is warranted.

Transoral surgery (TOS) and IMRT represent two primary local ablative treatment modalities for oropharyngeal cancer (OPC). The choice of one over the other represents an interplay between the chance of cure vs risk of late sequelae. HPV-mediated (HPV+) OPC patients generally have excellent outcomes, especially in TNM-8 stage I disease. Controversies exist over which treatment has a more favorable toxicity profile and equal efficacy in the management of this population. Non-randomized retrospective data show comparable oncological and functional outcomes between TOS-based vs IMRT-based treatment for this disease. Several de-intensification concepts have been explored in this subset in both primary surgery-based vs primary radiotherapy-based trials. However, no robust mature trial data are available to convincingly guide treatment selection. TOS is often presented as one of the de-intensification options although the majority of series also describe the use of adjuvant treatments which inevitably result in non-negligible toxicities. Patient selection and surgeons' training are paramount. Understanding tumor biology and the prognostic value of traditional 'adverse' features will further guide trial design for refinement of risk tailored approach. In conclusion, comparative data suggests TOS and IMRT are both effective treatment for TNM-8 stage I HPV+ OPC with similar oncological and functional outcomes. TOS as a single modality has potential advantages in mitigating radiation included toxicities. TOS should be avoided in the presence of clinically overt extranodal extension or when negative margins are unlikely to be achieved. TOS is also less ideal for cases with radiological features predicting a high risk of distant metastasis.

Distant metastasis (DM) is the main cause of death for patients with human papillomavirus (HPV)-related oropharyngeal cancers (OPCs); yet, there are few reliable predictors of DM in this disease. The role of quantitative imaging (ie, radiomic) analysis was examined to determine whether there are primary tumor features discernible on imaging studies that are associated with a higher risk of DM developing.Radiation therapy planning computed tomography scans were retrieved for all nonmetastatic p16-positive OPC patients treated with radiation therapy or chemoradiation therapy at a single institution between 2005 and 2010. Radiomic biomarkers were derived from each gross tumor volume. The biomarkers included 4 representative radiomic features from tumor first-order statistics, shape, texture, and wavelet groups, as well as a combined 4-feature signature. Univariable Cox proportional hazards models for DM risk were identified. The discriminative performance of prognostic univariable and multivariable models was compared using the concordance index (C-index). Subgroup analyses were performed.There were 300 HPV-related OPC patients who were eligible for the analysis. A total of 36 DM events occurred within a median follow-up period of 5 years. On univariable analysis, top results included the 4 representative radiomic features (C-index, 0.670-0.686; P .001), the radiomic signature (C-index, 0.670; P .001), tumor stage (C-index, 0.633; P .001), tumor diameter (C-index, 0.653; P .001), and tumor volume (C-index, 0.674; P .001), which demonstrated moderate discrimination of DM risk. Combined clinical-radiomic models yielded significantly improved performance (C-index, 0.701-0.714; P .05). In subgroup analyses, the radiomic biomarkers consistently stratified patients for DM risk, particularly for those cohorts with greater risks (C-index, 0.663-0.796), such as patients with stage III disease.Radiomic biomarkers appear to classify DM risk for patients with nonmetastatic HPV-related OPC. Radiomic biomarkers could be used either alone or with other clinical characteristics in the assignment of DM risk in future HPV-related OPC clinical trials.

In the effort to control human papillomavirus-related oropharyngeal cancer, the head and neck oncology community has devoted much effort to understanding its disease biology and clinical behavior, and refining strategies to address early diagnosis and optimal management for the affected population. This review identifies articles published up to March 2017 on tumor biology and clinical implications of human papillomavirus-related oropharyngeal cancer, and summarizes the findings in some key areas. These include potential screening strategies, possible anatomical features responsible for early lymph node involvement and its implication for staging, biological mechanisms to explain superior outcomes compared to traditional nonviral-related mucosal cancers, re-appreciation of traditional prognostic factors (eg, hypoxia, extranodal extension, and smoking), and current efforts to optimize management for this patient population. The review reflects the global effort to mitigate the influence of this burgeoning disease.

Purpose/Objective(s) To evaluate the association of contralateral nodal involvement (CNI) with automatically defined midline proximity in patients (pts) with head and neck cancer based on treatment planning (TP) real world data (RWD). Materials/Methods All available TPs for head and neck cancer pts between 2010 and 2017 were analyzed in an automated data analysis pipeline where the pt's midline was determined objectively using their external contour and discounting distortion due to neck lymphadenopathy via linear modeling. Primary gross tumor volumes (GTVp) and nodal volumes (GTVn) were contoured by treating radiation oncologists. Objective tumor laterality (OTL) was calculated as the difference between the GTVp center of mass and the midline in the R/L direction. OTL accuracy compared to the clinically assigned laterality (when available) was assessed. Midline proximity (MP) was the difference between the medial edge of the GTVp bounding box to the patient midline with positive values representing progressively lateralized tumors and negative values representing tumors crossing midline. Nodal involvement (ipsilateral and contralateral levels 1-5 and retropharyngeal) was determined using the TP nodal target contours labeled by neck level as is standard practice at our institution during treatment planning. The primary endpoint, CNI, was defined based on these TP contours. Volumes of GTVp were calculated from the TP. Clinical variables including HPV status, age, smoking, disease site and subsite were used for model development. The factors predictive of CNI were assessed using logistic regression (LR). Results Of 2458 pts available for analysis, 2031 had a clinically assigned laterality. The accuracy of automatically assigned laterality was 0.91 when compared with the clinically assigned laterality. Using the automatically assigned laterality (n = 2458), the overall rate of CNI was 45% and varied by disease site and nodal level involved: oropharynx (55.1%, n = 629/1142), larynx (17.6%, n = 124/703), nasopharynx (79.7%, n = 231/290). Multivariable logistic regression (LR) including subsite, HPV status, GTVp, GTVp center of mass relative to midline, GTVp midline proximity, and ipsilateral nodal involvement was performed. In the oropharynx, multivariable LR demonstrated GTVp volume (P Conclusion Automated TP analysis can be used to generate RWD-based predictions of CNI. CNI risk remains a critical radiotherapy endpoint and RWD may help determine CLI risk using combinations of anatomic and clinical features.

Objectives The literature demonstrates that ‘aggressive’ head-and-neck basal cell carcinomas (HN-BCC) have a higher than expected relapse rate with unfavorable outcomes. We report outcomes following definitive (dRT) or post-operative radiotherapy (PORT) for these tumors. Methods We reviewed all HN-BCC patients with ‘aggressive’ features (primary lesions diameter >10 mm, >2 recurrences, or extra-cutaneous extension), treated with megavoltage dRT or PORT between 1998 and 2013. Loco-regional control (LRC) and relapse-free survival (RFS) were estimated using the competing risk method, and overall survival (OS) by Kaplan-Meier method. Univariable analysis explored factors associated with relapse. Results A total of 108 histologically confirmed ‘aggressive’ HN-BCC patients were identified, including 38 (35%) presenting de novo and 70 (65%) treated for recurrence (rBCC). dRT was offered to 72 (66.7%) patients and PORT to 36 (33.3%). Median follow-up was 3.5 years. Actuarial 3-year LRC, RFS, and OS were 87% (95% confidence interval: 77–92), 82% (72–89), and 87% (80–94), respectively. LRC rates for dRT and PORT were similar [hazard ratio (HR) 0.61 (0.17–2.23), p = 0.46]. Factors associated with higher risk of relapse were: rBCC [HR 7.96 (1.03–61.71), p = 0.047], ‘H-zone’ (mid face, eyes, and ears) location [HR 3.13 (1.07–9.19), p = 0.04], tumor size [HR 1.32 (1.08–1.6), p = 0.006], nodal involvement [HR 3.68 (1.11–12.2), p = 0.03] and stage [HR 3.13 (1.19–8.26), p = 0.02]. Conclusion RT is an effective treatment for ‘aggressive’ HN-BCC when used as a definitive modality or as PORT. Non-surgical management with definitive radiotherapy provides an alternative effective option if surgery is not used.

Purpose We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age ( P =.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P =.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P =.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P =.061). OS between P1 and P2 did not differ ( P =.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P =.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P =.008). Conclusions The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

Background/objectives We evaluate the performance between the TNM-8 versus TNM-7 cN-classification and explore the relative prognostic contribution of radiologic extranodal extension (rENE) for HPV-negative oropharyngeal cancer (HPV–OPC). Materials/methods All HPV– OPC treated with IMRT between 2005 and 2016 were included. cENE was defined as unambiguous “fixation” of a neck mass or “skin involvement” on clinical examination. rENE was recorded by re-reviewing pre-treatment CT/MR. Disease-free survival (DFS) stratified by cENE or rENE were compared. Multivariable analyses (MVA) calculated the adjusted hazard ratio (aHR) for the separate cENE and rENE attributes and their combination. A refined cN-category incorporating both cENE and rENE parameters was proposed. The performance of the revision was compared to TNM-8 and TNM-7. Results Of 361 HPV– OPC, 97 were cN0 and 264 were cN+ with 48 cENE+ and 72 rENE+ respectively. Median follow-up was 5.4 years. The 3-year DFS was lower in cENE+ vs cENE-negative (cENE–) (23% vs 45%; aHR = 1.68, p = 0.008) and rENE+ vs rENE-negative (rENE–) patients (29% vs 45%; aHR = 1.44, p = 0.037). The cENE+/rENE+ subset had the worse DFS vs cENE–/rENE+ or cENE–/rENE– (24%/37%/46%, p = 0.005). We propose a refined cN-category wherein any cENE–/rENE+ case is reclassified one N-stratum higher while any cENE+ case remains cN3b. The stage schema with the refined N-categorization outperformed TNM-8, and both outperformed TNM-7. Conclusions cENE and rENE are both prognostic but the cENE+/rENE+ subset has the worst outcome. The TNM-8 cN-categories improves outcome prediction compared to the TNM-7. Incorporation of rENE into TNM-8 cN-categories may further augment performance.

Management of the neck in oropharyngeal carcinoma varies due to a lack of clarity of patterns of lymphatic drainage and concern of failure in the contralateral neck. With recent advances in transoral surgical techniques, surgical management has become increasingly prevalent as the primary treatment modality. We compare international practice patterns between surgical and radiation oncologists.A survey of neck management practice patterns was developed and pilot tested by 6 experts. The survey comprised items eliciting the nature of clinical practice, as well as patterns of neck management depending on extent of nodal disease and location and extent of primary site disease. Proportions of surgical and radiation oncologists treating the neck bilaterally were compared using the chi-squared statistic.Two-hundred and twenty-two responses were received from 172 surgical oncologists, 44 radiation oncologists, 3 medical oncologists, and 3 non-oncologists from 32 different countries. For tongue base cancers within 1 cm of midline (67% vs. 100%, p 0.001), and for tonsil cancers with extension to the medial 1/3 of the soft palate (65% vs. 100%, p 0.001) or tongue base (77% vs. 100%, p 0.001), surgical oncologists were less likely to treat the neck bilaterally. For isolated tonsil fossa cancers with no nodal disease, both surgical and radiation oncologists were similarly likely to treat unilaterally (99% vs. 97%, p = NS). However, with increasing nodal burden, radiation oncologists were more likely to treat bilaterally for scenarios with a single node 3 cm (15% vs. 2%, p 0.001), a single node with extranodal extension (41% vs. 18%, p 0.001), multiple positive nodes (55% vs. 23% p 0.001), and node(s) 6 cm (86% vs. 33%, p 0.001). For tumors with midline extension, even with a negative PET in the contralateral neck, the majority of surgical and radiation oncologists would still treat the neck bilaterally (53% and 84% respectively).The present study demonstrates significant practice pattern variability for management of the neck in patients with lateralized oropharyngeal carcinoma. Surgical oncologists are less likely to treat the neck bilaterally, regardless of tumor location or nodal burden. Even in the absence of disease in the contralateral neck on imaging, them majority of practitioners are likely to treat bilaterally when the disease approaches midline.

Aim The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV−) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). Patients and methods A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000–2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV−. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV− cohorts separately. Results A total of 404 HPV+ and 255 HPV− LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5–11.9) years. Three-year OS for cisplatin 200 mg/m 2 subgroups were 52%, 60%, and 72% ( P = 0.001) for the HPV− and 91%, 90%, and 91% ( P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m 2 for the HPV− (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3–0.7, P P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset ( N = 107) with cisplatin >200 mg/m 2 (HR 0.5, 95% CI: 0.2–1.1, P = 0.07). Conclusions A survival benefit of cisplatin dose >200 mg/m 2 is evident for HPV− LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose.

Summary Purpose To report outcomes of postoperative radiotherapy (PORT) for major salivary gland carcinoma (SGC) and identify patients at high risk of distant metastases (DM). Methods and materials Patients with major SGC treated between 2000–2012 were identified. All patients underwent initial primary resection, with neck dissection (ND) therapeutically (if N+) or electively in high risk N0 patients. PORT was delivered using 3D-CRT or IMRT. Multivariable analysis (MVA) assessed predictors for DM, cause-specific (CSS) and overall survival. Results Overall 304 patients were identified: 48% stage III–IVB, 22% lymphovascular invasion (LVI), 50% involved margins and 64% high risk pathology. ND was performed in 154 patients (51%). Adjuvant chemotherapy was used in 10 patients (3%). IMRT was delivered in 171 patients (56%) and 3D-CRT in 133 (44%). With a median follow-up of 82 months, the 5-(10-) year local, regional, distant control, CSS and OS were 96% (96%), 95% (94%), 80% (77%), 83% (82%) and 78% (75%), respectively. DM was the most frequent treatment failure ( n = 62). On MVA, stage III–IVB and LVI significantly correlated with DM, CSS and OS, while positive margins predicted DM and CSS, and high risk pathology predicted DM. No grade ⩾4 RTOG late toxicity was reported; 9 patients had grade 3, including osteoradionecrosis ( n = 4), neck fibrosis ( n = 3), trismus ( n = 1) and dysphagia ( n = 1). Conclusions Surgery and PORT with 3D-CRT/IMRT produced excellent long-term outcomes. Further research is required for patients with stage III–IVB, LVI, positive margins and high risk pathology to determine the incremental benefit of systemic therapy in management of SGC.

Background Both adjuvant chemotherapy and higher cumulative cisplatin dose (CDDP-D) given as part of multimodality therapy for locally-advanced nasopharyngeal carcinoma (LA-NPC) have improved survival in Asian series. We evaluated their impact in a contemporary single-institution Canadian cohort of LA-NPC. Methods Patients with EBV-related stage II-IV LA-NPC by 7th edition TNM (TNM-7) treated with IMRT plus high-dose CDDP followed by adjuvant chemotherapy with CDDP/Carboplatin − 5-FU (maximum total/adjuvant CDDP-D = 540/240 mg/m2) between 2003 and 2016 were analyzed. 5-year overall survival (OS) and recurrence-free survival (RFS) were calculated and compared using log-rank test by stage, adjuvant chemotherapy (yes/no) and total CDDP-D (>300 vs ≤300 mg/m2). Multivariable analysis (MVA) was performed to identify survival predictors. Results A total of 312 patients were evaluated: TNM-7 stage II/III/IV = 2%/51%/47%; T4 = 36%; N3 = 17%; adjuvant chemotherapy = 83% (79% 21% CDDP/carboplatin); median total/adjuvant CDDP-D = 380/160 mg/m2; median follow-up 76 years (range 06–149). 5-year OS differed by stage II–III vs IV (95% vs 80%, p 300 (n = 210) vs ≤300 (n = 102) mg/m2 (89% vs 83%, p = 0.02). Adjuvant chemotherapy and total CDDP-D impacted on 5-year OS in stage IV but not stage II–III. 5-year RFS was higher in stage IV patients with total CDDP-D >300 vs ≤300 mg/m2 (74% vs 59%, p = 0.03), with a trend seen in locoregional (LRC) (91% vs 80%, p = 0.05) but not distant control (DC) (78% vs 72%, p = 0.36). Conclusions Adjuvant chemotherapy and total CDDP-D >300 mg/m2 improved OS and RFS in stage IV but not stage II–III LA-NPC, mainly due to effect on LRC rather than DC.

Little information has been published in English about the epidemiology of tumours of the salivary glands in northeastern China. From August 2004 to March 2014, 2508 cases of primary epithelial salivary gland tumours were diagnosed in the Department of Oral and Maxillofacial Surgery, the Affiliated Stomatology Hospital of China Medical University. Tumours were analysed according to their histological type and site, and the age and sex of the patients. Ages ranged from 5 to 98 years, with a slight propensity in favour of men. The peak incidence was in the sixth decade for both sexes. The mean (SD) ages were 48 (16) years when the tumour was benign and 51 (15) years when it was malignant. The parotid gland and palate were the sites most commonly affected. There were 1934 (77.1%) benign and 574 (22.9%) malignant tumours, with the most common histological types being pleomorphic adenomas and mucoepidermoid carcinomas. A lesion that arises from the floor of the mouth (92.8%) or the tongue (86.2%) is more likely to be malignant than those from other minor salivary glands.

Purpose The relative frequency of individual minor salivary gland tumors (MSGTs) is not well documented in the literature. The aim of this study was to determine the range and demographics of all histologically diagnosed MSGTs in a northeastern Chinese population. Materials and Methods A total of 485 cases of MSGT were retrospectively studied. The files of the Department of Oral and Maxillofacial Pathology, School of Stomatology, China Medical University served as a source of material for this study. All epithelial tumors from minor salivary glands accessioned from August 2004 to April 2014 were analyzed for demographic features, anatomic location of tumors, and pathologic classification. Tumors were classified according to the 2005 World Health Organization classification of salivary gland tumors. Statistical analysis was performed using analysis of variance. Results MSGTs were identified in 485 (2.60%) of 18,670 accessed cases. There were 268 (55.26%) benign and 217 (44.74%) malignant tumors. Female outnumbered male patients (male-to-female ratio, 1:1.43). The mean ages of patients with benign and malignant MSGTs were 47.58 and 51.51 years, respectively. Pleomorphic adenoma and adenoid cystic carcinoma were the most frequent types of benign and malignant tumors, respectively. The palate was the most commonly affected site (64.74%), followed by the buccal mucosa (7.63%) and the tongue (5.98%). Conclusions From the results of this study and a review of the literature, it is suggested that MSGTs in the northeastern Chinese population may be characterized by a higher incidence of MSGTs than in the populations of other reviewed regions, a higher incidence of myoepithelioma, a rarer occurrence of polymorphous low-grade adenocarcinoma, and an absence of canalicular adenoma occurrence.