Role of radiation therapy in primary tonsil large B cell lymphoma: a SEER-based analysis.

BACKGROUD: Primary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Data of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM). RESULTS: The entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241). CONCLUSIONS: This population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis.

Prevalence and prognosis of synchronous distant metastatic tonsil squamous cell carcinomas.

BACKGROUND: To analyze the prevalence proportions and prognostic factors of synchronous distant metastases in patients with tonsil squamous cell carcinomas (TSCC). METHODS: TSCC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2014. We examined the association between clinical manifestations and distant metastases using Chi-squared tests. Predictors of 5-year survival were assessed using univariate and multivariate analyses. RESULTS: A total of 6193 patients were analyzed and lung was the most common site of distant metastases. Poorly/undifferentiated differentiation was found to be significantly correlated with lung metastasis (p=0.033) and liver and bone metastases were associated with African American (p=0.000 and p=0.000, respectively). A higher T classification was associated with higher prevalence of lung, liver, bone and brain metastasis (p=0.000, p=0.000, p=0.000 and p=0.007, respectively). The same results were found in N classification in lung, liver, and bone metastasis (p=0.000, p=0.000, and p=0.000, respectively). Worse prognosis was associated with older age, Blacks, lower grade, higher T and N classification, no surgery therapy and more metastatic sites. CONCLUSION: Lung was the most frequent lesion of synchronous distant metastases and liver and bone metastases were associated with African American. Higher T and N classification were independent prognostic parameters for higher prevalence of lung, bone, liver and brain metastasis. Worse prognosis was associated with older age, African Americans, lower grade, higher T and N classification, no surgery therapy and more metastatic sites.

Treatment of Early Stage Tonsil Cancer in the Age of Human Papillomavirus-Associated Malignancies.

OBJECTIVE: To investigate the patterns of care and outcomes of treatment of early stage tonsil cancers, controlling for human papillomavirus (HPV) status. STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database (NCDB). METHODS: Review of the NCDB between 2010 and 2017 for all T1-2N0M0 tonsillar squamous cell carcinoma (SCC). Demographics, clinical characteristics, HPV status, treatment regimens, and survival were analyzed. RESULTS: A total of 4720 patients were identified with early stage SCC of the tonsil. Most were tested for HPV (2759 [58.5%]). Among tested patients, 1758 (63.7%) were positive for HPV and 1001 (36.3%) were negative for HPV. HPV-positive patients had higher 3-year survival compared to HPV-negative patients (93.2% vs 77.8%, P < .001). Among HPV-positive patients, there was no significant difference in survival between treatment cohorts. However, in the HPV-negative cohort, 3-year survival was higher in both bimodality surgical-based settings (tonsillectomy + neck dissection + radiotherapy, 86.0% vs chemoradiotherapy, 69.6%, P = .01) and for all surgical-based treatments when compared to nonsurgical management (84.6% vs 69.3%, P < .001). This difference was maintained in multivariable regression controlling for age, sex, comorbidities, clinical T stage, and treatments. In a subpopulation of HPV-negative patients propensity score matched by all factors significant in multivariable analysis, 3-year survival remained higher in the surgically treated group compared to the nonsurgically treated cohort (84.9% vs 67.1%, P < .001). CONCLUSIONS: Surgical- or radiation-based treatment resulted in similar survival in early stage HPV-positive tonsil cancer. Surgical-based treatments were associated with longer survival in HPV-negative cancers. These findings should be further investigated in a randomized prospective trial.

Prognostic impact of resection margin involvement in surgically managed HPV-positive tonsil cancer.

OBJECTIVES: To find out the role of resection margin involvement in surgically managed HPV-positive tonsil cancer. MATERIALS AND METHODS: The study included 94 subjects with HPV-positive tonsil cancer undergoing surgical treatment. We evaluated the relationships between the resection margin status, clinicopathological factors, and oncological outcome. RESULTS: The rate of resection margin involvement was 22.3% (21/94) after ablative surgery. Margin involvement, lymphatic invasion, and extracapsular spread were associated with the 5-year disease-free survival (DFS) and disease-specific survival (DSS) rate in univariate analysis. Multivariate Cox regression analysis confirmed a significant association between the margin involvement and 5-year DFS rate (HR = 4.602; 95% CI = 1.202-17.620; p = 0.026) and 5-year DSS rate (HR = 12.826; 95% CI = 1.399-117.593; p = 0.024). The incidence of resection margin involvement was significantly higher in patients with larger tumors (35.19 ± 15.07 mm vs. 25.53 ± 10.32 mm, p = 0.011) and more invasive tumors (17.84 ± 7.90 mm vs. 13.46 ± 6.88 mm, p = 0.037). The cutoff value of tumor size and depth of invasion for resection margin involvement was 29.5 mm (74% sensitivity and 63% specificity) and 14.5 mm (74% sensitivity and 61% specificity), respectively. CONCLUSION: Resection margin involvement was significantly correlated with tumor size and the depth of invasion in HPV-positive tonsil cancer. Furthermore, resection margin involvement was associated with adverse outcomes.

A Survival Analysis of Pediatric Tonsillar Malignancies and Review of a Rare Case.

OBJECTIVE: To examine the survival of pediatric tonsillar cancer patients and review a rare case of pediatric tonsillar cancer. METHODS: Pediatric patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of tonsillar malignancy using the ICD O-3 tonsil primary site codes of: C09.0, C09.1, C09.8, and C09.9. Patients were included from birth-18 years. Survival analysis was performed using Kaplan-Meier analysis. Additionally, a case of pediatric natural killer (NK) cell tonsillar lymphoma diagnosed and treated at the Nemours Children's hospital in Orlando, Florida is presented. RESULTS: One hundred forty-one cases of tonsil cancer were identified. The mean age at diagnosis was 9.9 years (SD: 5.1, range: 0.0 (months)-18.0). Ninety five (67.4%) patients were male and 116 (82.3%) had unilateral malignancies. Burkitt lymphoma (32.6%) followed by diffuse large B-cell lymphoma (DLBCL) (27.0%) were the two most common histological types of tonsillar cancers. 79.4% of patients received chemotherapy and 81.6% received surgery as a part of their care. The 5-year disease-specific survival rate was >90% for patient cohorts diagnosed from 1984 to 1993, 1994-2003, and 2004-2014 as compared to 64% for patients diagnosed from 1973 to 1983 (p = 0.01). CONCLUSIONS: Survival rates for pediatric patients with tonsillar cancer are excellent. Pediatric primary tonsil cancer occurred most commonly in adolescent males and usually presents as a unilateral mass. Lymphoma remains the predominant histological type of cancer. Most patients are likely to receive surgery and chemotherapy.

Extranodal involvement of diffuse large B-cell lymphoma in the head and neck: An indicator of good prognosis.

OBJECTIVE: In this study, we analyzed clinicopathological characteristics and survival outcomes according to extranodal involvement of diffuse large B-cell lymphoma (DLBCL) in the head and neck. METHODS: A retrospective analysis was conducted on 110 patients from 2004 to 2014 with CD20-positive DLBCL involving the head and neck area. Patients were categorized into two groups, extranodal and nodal, according to involvement of extranodal sites in the head and neck. Outcome measurements for the groups included clinical response to treatment and recurrence rates. RESULTS: Palatine tonsils were the most frequently involved extranodal site in the head and neck (29.1%). Among clinicopathological parameters, proportion of patients with lactate dehydrogenase over 350 IU/L (p=0.033), cell of origin (p<0.001), and treatment outcomes (p=0.007) were significantly different between the two groups. Among cell origin markers CD10, Bcl6, and MUM1, MUM1 was significantly correlated with extranodal involvement (p=0.029). Recurrence rates were similar between groups, while disease-specific survival was significantly higher in the extranodal group (p=0.011). Disease-specific survival of the extranodal group was also higher than the nodal group with extranodal involvement of other body sites (p=0.010). Among patients with negative expression of CD10 (p=0.015), Bcl6 (p=0.018), and MUM1 (p=0.005), survival was longer in the extranodal than the nodal group. CONCLUSIONS: DLBCL patients with extranodal involvement of the head and neck may have longer survival outcomes than patients with solely nodal involvement. Increased survival may be more prominent in patients with negative expression of CD10, Bcl6, and MUM1.

Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy.

OBJECTIVE: To evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Patients who underwent TORS at the University of Washington from 2010 to 2017 (n = 150) were identified. All patients who were diagnosed with tonsillar carcinoma following a nononcologic tonsillectomy and subsequently underwent TORS radical tonsillectomy were included (n = 14). Tumor stage-matched subjects (n = 44) were included who did not undergo standard tonsillectomy prior to TORS. Our primary outcome was final margin status. Secondary outcomes were presence of residual tumor, receipt and dose of postoperative adjuvant therapy, disease-free survival (DFS), and disease-specific survival. Patients with <6 months of follow-up following definitive treatment were excluded from survival analyses. RESULTS: Final margin status was clear in all subjects. Residual tumor was not identified in 13 of 14 (92.9%) prior-tonsillectomy subjects following TORS radical tonsillectomy. Seven of 14 (50%) prior-tonsillectomy subjects and 12 of 44 (27.3%) TORS-matched subjects did not require adjuvant therapy due to favorable pathology. Among subjects who received post-TORS radiation therapy (RT) at our institution, RT dose reduction was achieved in 3 of 4 (75%) prior-tonsillectomy subjects and 21 of 24 (87.5%) TORS-matched subjects. Ten of 14 (71.4%) prior-tonsillectomy subjects and 31 of 44 (70.5%) TORS-matched subjects avoided post-TORS chemotherapy. DFS was not significantly different ( P = .87) between prior-tonsillectomy and TORS-matched groups, and no subjects died of related disease. CONCLUSIONS: Patients diagnosed with tonsillar carcinoma following a prior nononcologic standard palatine tonsillectomy are suitable candidates for revision surgery with TORS radical tonsillectomy.

Role of palatine tonsillectomy in the diagnostic workup of head and neck squamous cell carcinoma of unknown primary origin: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aims to evaluate the effectiveness of palatine tonsillectomy in patients with cervical metastasis from squamous cell carcinoma of unknown primary (SCCUP) origin. METHODS: A systematic review including studies that encompassed palatine tonsillectomy in the SSCUP diagnostic evaluation was conducted. A single arm meta-analysis was then made to obtain the overall identification rate of tonsillectomy. RESULTS: Fourteen studies were included, comprising 673 patients who underwent 416 palatine tonsillectomies, 338 preformed during examination under anesthesia (EUA) and 78 managed with transoral robotic surgery (TORS). A total of 140 occult tonsillar malignancies were identified; of these, 124 (89%) were ipsilateral, 2 (1%) contralateral, and 14 (10%) synchronous bilateral. Meta-analysis of 11 studies showed an overall detection rate of tonsillectomy of 0.34 (99% confidence interval 0.23-0.46). CONCLUSION: Palatine tonsillectomy is a valuable diagnostic tool in the management of patients with head and neck SCCUP. Bilaterality of tonsillectomy should be taken into consideration.

Post-operative radiation effects on lymphopenia, neutrophil to lymphocyte ratio, and clinical outcomes in palatine tonsil cancers.

OBJECTIVE: To evaluate radiation-induced lymphopenia associated with unilateral vs. bilateral neck radiation and to test post-treatment neutrophil to lymphocyte ratio (NLR) as a prognostic clinical biomarker. METHODS: This was a single academic center retrospective review of palatine tonsil squamous cell cancer patients treated with post-operative intensity modulated radiation therapy (IMRT) from 1997 to 2013. Absolute lymphocyte count (ALC) and NLR were evaluated during and after radiation for up to a year. Correlations of lab values with loco-regional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were assessed. RESULTS: Ninety-nine patients with median follow up 5.8 years had ALC recorded at least at baseline and within one year of starting RT. Acute grade 3-4 lymphopenia (<10 weeks from RT start) occurred in 79% of bilateral neck RT patients (n = 70) and 58% of unilateral neck RT patients (n = 29), p = 0.03. There was no significant difference in late grade 3-4 (p = 0.12) lymphopenia. In a multivariable Cox regression model, acute NLR > 11.875 correlated with worse OS (HR = 4.4, 95% CI 1.2-16). Late NLR > 6.875 independently correlated with significantly worse FFDM (HR = 16, 95% CI 1.9-137) and OS (HR = 12, 95% CI 3.0-48). CONCLUSIONS: Unilateral neck radiation may prevent acute iatrogenic immunosuppression. In exploratory analyses, elevated post-treatment NLR was associated with risk for distant metastases and death.

[Clinicopathologic characteristics and prognositic indicators of tonsillar mantle cell lymphoma].

Objective: To investigate clinicopathological features and prognosis of tonsillar mantle cell lymphoma(TMCL). Methods: Clinical data of 25 patients with TMCL at Beijing Friendship Hospital, Capital Medical University from 2002 to 2016 were included. All the cases were reviewed microscopically. Various immunohistochemical stains were performed using the MaxVision two-step method. IgH/CCND1 gene fusion was detected by fluorescent in situ hybridization(FISH). Additionally, randomly selected 40 cases of non-tonsil MCL of the same period were compared. Results: Among all mantle cell lymphomas (MCL), TMCL accounted for 5.6%(25/449). The median age of the patients was 60 years(range: 44-82 years) with a M∶F ratio of 5.3 to 1.0. The main symptoms were sore throat and foreign body sensation and patients usually presented with enlargement or mass of tonsil. At the early stage of the disease, 18 cases(72.0%) were clinically misdiagnosed as tonsillitis. Lymph node involvement was present in 76.0%(19/25) of the patients. There were 4 cases(16.0%)with current splenic involvement, 11 cases(44.0%) with pharyngeal focal recidivism, and 3 cases(12.0%) with involvement of other non-lymphoid organs. Morphologically, tonsillar architectures were effaced at various degrees. Eighteen MCL cases showed classical type and 7 cases were blastoid variant. All tumors were positive for CD20 and cyclin D1. 92.0%(23/25) tumors showed weakly positive or positive expression for CD5. FISH test that IgH/CCND1 gene fusion was positive in two CD5 negative classical cases. 18 patients(72.0%) had a median follow-up time of 26 months(range: 6-81 months). The difference of survival rate between stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ patients was not statistically significant(P>0.05). Compared with NTMCL, TMCL was found to have higher proportion of stage Ⅰ-Ⅱ disease (χ(2)=12.789, P<0.01), lower the proportion of non-lymphatic organ involvement (χ(2)=8.125, P<0.01), and better prognosis (χ(2)=4.351, P=0.037). Conclusion: The incidence of TMCL is low and prone to be misdiagnosed as tonsillitis. Patients with TMCL are more likely at stage Ⅰ-Ⅱ at presentation and the prognosis is better than that of NTMCL.

Human papillomavirus and survival of patients per histological subsite of tonsillar squamous cell carcinoma.

Current data advocate that oropharyngeal squamous cell carcinoma (OPSCC) should be divided into subsites when evaluating the presence of human papillomavirus (HPV) and prognosis. More specifically, tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) have much higher HPV prevalence compared to other OPSCC. Moreover, patients with HPV positive (HPV+) TSCC and BOTSCC have a better prognosis as compared to patients with HPV negative (HPV-) corresponding tumors, while the prognostic role of HPV in other OPSCC is unclear. Furthermore, in a recent report from Denmark, TSCC was further subclassified into specified TSCC (STSCC) and nonspecified TSCC (NSTSCC), with HPV significantly more prevalent in STSCC. In this study, the histopathological influence of HPV prevalence and survival in TSCC was analyzed in a TSCC cohort with known HPV status, of patients diagnosed 1970-2002 in Stockholm. In total, 139 TSCC biopsies with both tumor and adjacent normal tissue were separated into STSCC and NSTSCC. HPV was significantly more commonly found in STSCC than in NSTSCC. Patients with HPV+ STSCC had a better disease-specific and overall survival as compared to patients with HPV+ NSTSCC, but no survival differences were observed in patients with HPV- STSCC and NSTCC. These findings confirm previous reports and suggest that TSCC subsite may also be of relevance for clinical outcome and should be further followed up in future studies.

Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study.

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure.

Re-evaluation of Ipsilateral Radiation for T1-T2N0-N2b Tonsil Carcinoma at the Princess Margaret Hospital in the Human Papillomavirus Era, 25 Years Later.

PURPOSE: To report the outcome of ipsilateral radiation therapy (RT) in human papillomavirus (HPV)-positive (HPV+) patients and HPV-negative (HPV-) patients with T1-T2N0-N2b tonsillar cancer treated 25 years after our initial historical cohort. METHODS AND MATERIALS: Patients with T1-T2N0-N2b tonsillar cancer who received ipsilateral RT or bilateral RT between 1999 and 2014 were reviewed. Overall survival (OS), local control (LC), regional control (RC), and grade 3 to 4 late toxicity (LT) were compared between ipsilateral RT and bilateral RT within HPV+ and HPV- patients, separately. RESULTS: HPV status was ascertained in 379/427 (88%) consecutive patients (ipsilateral RT: 62 HPV+, 34 HPV-; bilateral RT: 240 HPV+ 240, 41 HPV-). The proportion of ipsilateral RT by N category for HPV+ and HPV- patients were as follows: N0: 24/37 (65%) versus 28/48 (74%); N1: 21/49 (43%) versus 4/9 (44%); N2a: 10/39 (26%) versus 1/4 (25%); and N2b: 7/177 (4%) versus 1/24 (4%), respectively. Of the patients receiving ipsilateral RT, 94/96 (98%) were treated with RT alone. The median follow-up time was 5.03 years. The respective 5-year rates of OS, LC, RC, and LT were similar between ipsilateral RT and bilateral RT for the HPV+ patients (OS: 89% vs 87%, P=.55; LC: 97% vs 98%, P=.65; RC: 98% vs 97%, P=.27; LT: 17% vs 12%, P=.83) and HPV- patients (OS: 63% vs 48%, P=.27; LC: 90% vs 80%, P=.19; RC: 94% vs 83%, P=.14; LT: 15% vs 22%, P=.36). Of the 96 patients receiving ipsilateral RT, contralateral neck failure (CNF) occurred in 1/52 HPV+ patients and 1/34 HPV- patients. The 5-year CNF rates were 2% (95% CI: 1-9) (HPV+: 2% [0-14]; HPV-: 3% [0-21], P=.66). Five local failures (2 HPV+; 3 HPV-) and no distant failures were seen. The 5-year rates of LC, RC, and LT were 97% versus 90% (P=.24), 98% versus 94% (P=.25), and 18% versus 15% (P=.75) for the HPV+ and HPV- cohorts, respectively. Osteoradionecrosis occurred in 9 patients: 6/47 (13%) treated with conventional RT and 3/49 (6%) with intensity modulated RT (P=.32). CONCLUSION: Ipsilateral radiation to selected patients with T1-T2N0-N2b tonsillar cancer results in equally excellent outcomes regardless of tumor HPV status.

Comparison of the Clinical Outcomes of Patients with Squamous Cell Carcinoma of the Tonsil Receiving Postoperative Ipsilateral Versus Bilateral Neck Radiotherapy: A Propensity Score Matching Analysis (KROG 11-07).

PURPOSE: The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively. MATERIALS AND METHODS: Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patients were identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groups were similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively. CONCLUSION: INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.

Unilateral radiotherapy for surgically resected lateralized squamous cell carcinoma of the tonsil.

BACKGROUND: The purpose of this study was to determine the rate of contralateral neck recurrence after surgery and unilateral neck radiotherapy, for lateralized tonsillar cancers with ipsilateral neck disease, in order to inform future clinical trial protocols for this disease. METHODS: Patients with lateralized tonsillar squamous carcinoma (T1-T2, N0-N2b), treated with surgery and unilateral adjuvant radiotherapy in a single United Kingdom center were retrospectively identified. Rates of recurrence in the contralateral, unirradiated neck were analyzed, together with survival and toxicity data. RESULTS: Of 81 patients included, after a median follow-up of 5.7 years, no contralateral recurrences were identified. Five-year overall survival, progression-free survival, and locoregional control were 91.0%, 93.0%, and 95.4%, respectively. CONCLUSION: Unilateral radiotherapy is an effective and safe treatment option for the postoperative management of lateralized tonsillar cancers, even in patients with N2b disease, and should be recommended in future clinical trial protocols. © 2016 Wiley Periodicals, Inc. Head Neck 39: 17-23, 2017.

Subsite variation in survival of oropharyngeal squamous cell carcinomas 2004 to 2011.

OBJECTIVES/HYPOTHESIS: To evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors. STUDY DESIGN: Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011. METHODS: The cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival. RESULTS: The cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa. CONCLUSIONS: In this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1087-1092, 2017.

The Impact of Radiation Treatment Time on Survival in Patients With Head and Neck Cancer.

PURPOSE: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation. METHODS AND MATERIALS: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT was defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ2 tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status. RESULTS: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01). CONCLUSION: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies.

Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population-based study.

The aim was to explore the overall survival (OS) for palatine tonsillar squamous cell carcinoma (TSCC), subdivided, according to certainty of tonsillar tumour origin, into specified tonsillar squamous cell carcinomas (STSCCs) and nonspecified tonsillar squamous cell carcinomas (NSTSCCs), and base of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology Databank, 2000-2010. Patients were treated according to national guidelines (radiotherapy +/- concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry. Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV-/p16- (hazard ratio for death [HR], 0.15; 95% CI, 0.09-0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13-0.29); whereas, HPV-/p16+ showed an intermediate HR (0.39; 95% CI, 0.22-0.70). For NSTSCCs, HPV+/p16+ and HPV-/p16+ showed similar OS (HRs, 0.39; 95% CI, 0.26-0.59; and 0.48; 95% CI, 0.24-0.95, respectively). Combined HPV+/p16+ was a significantly better prognostic marker in BSCCs and STSCCs than HPV DNA and p16, alone (all p-values < 0.05). Whereas, combined testing in NSTSCC was not better than p16 (p = 0.53), alone. In conclusion, double positivity for HPV/p16 in conjunction with the certainty of tumour site improved prognosis.

Minimal benefit of tonsillectomy in T1-T2 tonsillar squamous cell carcinoma treated with chemoradiotherapy.

BACKGROUND: Chemoradiotherapy (CRT) has become the mainstay of treatment for tonsillar squamous cell carcinoma (SCC). Pre-CRT tonsillectomy is frequently performed, mostly for small primary tumors (T1-T2). However, the benefits of pre-CRT tonsillectomy remain unclear. METHODS: A retrospective review was performed in 66 patients with T1-T2 tonsillar SCCs treated by CRT from 1997 to 2009. The efficacy of pre-CRT tonsillectomy was analyzed with regard to oncological and functional outcomes. RESULTS: Thirty patients (45.5%) received tonsillectomy (pre-CRT tonsillectomy group), and 36 patients (54.5%) did not (CRT group). Except for a trend toward more T1 cases (33.3% vs. 13.9%, p = 0.061) and significantly less chemotherapy use (60% vs. 86.1%, p = 0.016) in the pre-CRT tonsillectomy group, there were no differences between the two groups in terms of age, gender, N classification (nodal status), overall stage, radiation dose, duration, or technique. In the pre-CRT tonsillectomy group, eight cases (26.7%) achieved an adequate operative margin judged by the surgeon, and only one (12.5%) had a negative pathological margin. In long-term follow-up, there were no statistically significant differences between the two groups regarding local (93.3% vs. 91.7%, p = 0.82) or regional control (93.3% vs. 94.4%, p = 0.84). The pre-CRT tonsillectomy group did not have a better 5-year disease-specific survival rate (83.3% vs. 94.4%, p = 0.177) or 5-year overall survival rate (70% vs. 94.4%, p = 0.017). There were no differences in complications or functional results (feeding tube and tracheostomy dependence), and quality of life demonstrated no significant difference. CONCLUSION: Pre-CRT tonsillectomy contributes little to oncological and functional outcomes in patients with T1-T2 tonsillar SCC.

Evaluation of the factors contributing to long-term survival in canine tonsillar squamous cell carcinoma.

OBJECTIVES: To identify any prognostic factors that may be associated with the long-term survival of dogs diagnosed with tonsillar squamous cell carcinoma (TSCC). METHODS: The medical records of 15 dogs treated for TSCC were reviewed retrospectively. The signalment, presenting signs, clinical stage, treatments and outcome were documented. RESULTS: The overall median survival time (MST) of the dogs in the study was 243 days. There was a 1-and 2-year survival of 40% and 20%, respectively. The results of initial staging had a significant effect on survival, as dogs with only one tonsil affected and no evidence of metastatic disease had a longer MST (637.5 days) than the dogs with local (MST: 134 days) or distant (MST: 75 days) metastatic disease or bilateral tonsillar involvement at the time of initial presentation. Prolonged survival times were reported for dogs undergoing surgery and adjunctive chemotherapy (MST: 464.5 days) for treatment of their TSCC. CLINICAL SIGNIFICANCE: This is the first veterinary study demonstrating an association between prognosis of patients with TSCC and stage at the time of presentation, with long survival times demonstrated for dogs with early-stage disease following an initial treatment protocol that included surgery and chemotherapy. There was no clear association between long survival and additional surgeries for progressive disease; however; further investigation is warranted.