Incurable locoregional disease is a strong poor prognostic factor in recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Distant metastasis is a poor prognostic factor in recurrent/metastatic squamous cell carcinoma of the head and neck. However, limited information on the prognostic impact of locoregional disease is available, despite its life-threatening features. We investigated the prognostic impact of incurable locoregional disease and distant metastasis in recurrent/metastatic squamous cell carcinoma of the head and neck. METHODS: We retrospectively analyzed 156 patients with recurrent/metastatic squamous cell carcinoma of the head and neck who received palliative chemotherapy between August 2006 and December 2019. RESULTS: The median follow-up time for all censored patients was 12.1 (range 1.9-63.5) months. The median overall survival was 12.4 (95% confidence interval 10.1-15.1) months. Incurable locoregional disease (hazard ratio: 2.31, P = 0.007), liver metastasis (hazard ratio: 2.84, P = 0.006), disease-free interval > 13 months (hazard ratio: 0.51, P = 0.041), cetuximab use (hazard ratio: 0.59, P = 0.007), and immune checkpoint inhibitor use (hazard ratio: 0.56, P = 0.006) were associated with prognosis. The number of distant metastatic sites was not associated with overall survival (1-2: hazard ratio: 0.60, P = 0.16; 3-4: hazard ratio: 1.34, P = 0.50). Patients with incurable locoregional disease had more life-threatening events than those with curable locoregional disease. CONCLUSION: The presence of incurable locoregional disease had a significant prognostic impact, whereas the number of distant metastatic sites had no prognostic impact. Liver metastasis was a poor prognostic factor for recurrent/metastatic squamous cell carcinoma of the head and neck.

Triplet induction chemotherapy followed by less invasive surgery without reconstruction for human papillomavirus-associated oropharyngeal cancers: Why is it successful or unsuccessful?

BACKGROUND: De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation. METHODS: This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab. RESULTS: Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy. CONCLUSIONS: Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Chemoradiotherapy for high-risk stage II laryngeal cancer.

BACKGROUND: Definitive radiotherapy (RT) for stage II laryngeal cancer is known to be less effective for locoregional control and survival (LRCS) in patients with high-risk factors (e.g., subglottic extension, impaired cord mobility, or bulky tumor size) than in low-risk patients. The purpose of this study was to evaluate the safety and efficacy of chemoradiotherapy (CRT) for stage II laryngeal cancer patients with high-risk factors METHODS: Sixty-five consecutive patients with stage II laryngeal cancer who received radiotherapy (RT) alone or CRT were retrospectively analyzed. The patients were classified into three groups: RT, low risk (RT-low, n = 26); RT, high risk (RT-high, n = 25); and CRT, high risk (CRT-high, n = 14). RESULTS: The glottis was the most common primary tumor site in all groups. Most patients in the CRT-high group received platinum-based CRT. The 5-year locoregional control and survival (LRCS) rates were 88.3, 44.2, and 85.7% in the RT-low, RT-high, and CRT-high groups, respectively. In multivariate analysis, high-risk disease and CRT were significantly associated with 5-year LRCS rates. CONCLUSION: CRT may provide better locoregional control than RT alone in high-risk stage II laryngeal cancer.

Pretreatment predictive factors for feasibility of oral intake in adjuvant concurrent chemoradiotherapy for patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Prophylactic percutaneous endoscopic gastrostomy (PEG) has been widely performed before concurrent chemoradiotherapy (CCRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) because severe oral mucositis and dysphagia induced by CCRT lead to difficulty with oral intake. However, it is controversial whether all patients require prophylactic PEG for adjuvant CCRT. This study evaluated predictive factors for the feasibility of oral intake in adjuvant CCRT for patients with LASCCHN. METHODS: This study retrospectively analyzed 117 LASCCHN patients who underwent surgery followed by adjuvant CCRT with cisplatin at Shizuoka Cancer Center between April 2008 and December 2018. To investigate predictive factors for the feasibility of oral intake, tumor factors, treatment factors and social factors were included in multivariate analyses. RESULTS: Of the 117 patients, 25 received total laryngectomy and 92 received other surgery. In multivariate analysis, total laryngectomy [HR (hazard ratio) 0.09, P = 0.001] and oral cavity of primary tumor location (HR 0.21, P = 0.031) were significantly associated with the feasibility of oral intake. Difficulty obtaining adequate nutrition via oral intake from initiation of CCRT until 1 year after its completion was significantly rarer in the total laryngectomy group than in the other surgery group (16% vs. 57%, P < 0.001). CONCLUSION: Our study suggests that majority of patients who underwent total laryngectomy are able to maintain oral intake during adjuvant chemoradiotherapy.

Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin.

BACKGROUND: Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment. METHODS: We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015. RESULTS: Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0-1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis. CONCLUSIONS: CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.

Comparison of Salvage Total Pharyngolaryngectomy and Cervical Esophagectomy Between Hypopharyngeal Cancer and Cervical Esophageal Cancer.

BACKGROUND: Total pharyngolaryngectomy and cervical esophagectomy (TPLCE) after chemoradiotherapy remains a challenge because of the high rate of complications and few available data on outcomes and safety. The purpose of this study was to evaluate the clinical significance of salvage TPLCE and to compare treatment outcomes between hypopharyngeal cancer and cervical esophageal cancer. METHODS: Data from 37 consecutive patients who were diagnosed with potentially resectable hypopharyngeal and cervical esophageal cancer after chemoradiotherapy were retrospectively analyzed. The survival and surgical outcomes were investigated between the hypopharyngeal cancer and cervical esophageal cancer groups. RESULTS: Twenty-six patients were included in hypopharyngeal cancer group and 11 patients were included in cervical esophageal cancer group. The baseline characteristics were balanced between the two groups. Compared to the hypopharyngeal cancer group, the cervical esophageal cancer group had significantly more frequent tracheal-related complications (p < 0.05) and stronger association of distal margin of the cervical esophagus and radiation field with tracheal ischemia after salvage surgery. CONCLUSIONS: Salvage TPLCE can offer the exclusive chance of prolonged survival. Association of tracheal ischemia with salvage TPLCE was seen more frequently for cervical esophageal cancer. Therefore, the indication for salvage TPLCE must be carefully considered to maintain the balance between curability and safety.

MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma.

AIMS: Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of AdCC-associated genes, MYB, MYBL1, MYBL2 and NFIB, and their target molecules, including MYC. The results were correlated to clinicopathological profile of the patients. METHODS AND RESULTS: Using paraffin tumour sections from 33 cases of salivary gland AdCC, we performed a detailed fluorescence in-situ hybridization (FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2 and NFIB. We found that 29 of 33 (88%) AdCC cases showed gene splits in either MYB, MYBL1 or NFIB. None of the cases showed an MYBL2 gene alteration. AdCCs were divided genetically into six gene groups, MYB-NFIB (n = 16), MYB-X (n = 4), MYBL1-NFIB (n = 2), MYBL1-X (n = 1), NFIB-X (n = 6) and gene-split-negative (n = 4). AdCC patients showing the MYB or MYBL1 gene splits were associated with microscopically positive surgical margins (P = 0.0148) and overexpression of MYC (P = 0.0164). MYC expression was detected in both ductal and myoepithelial tumour cells, and MYC overexpression was associated with shorter disease-free survival of the patients (P = 0.0268). CONCLUSIONS: The present study suggests that (1) nearly 90% of AdCCs may have gene alterations of either MYB, MYBL1 or NFIB, suggesting the diagnostic utility of the FISH assay, (2) MYB or MYBL1 gene splits may be associated with local aggressiveness of the tumours and overexpression of MYC, which is one of the oncogenic MYB/MYBL1 targets and (3) MYC overexpression may be a risk factor for disease-free survival in AdCC.

Expression of cancer/testis antigens in salivary gland carcinomas with reference to MAGE-A and NY-ESO-1 expression in adenoid cystic carcinoma.

AIMS: Cancer/testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE-A and NY-ESO-1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome. METHODS AND RESULTS: We used immunohistochemistry to examine the expression of four CTAs (MAGE-A, NY-ESO-1, CT7, and GAGE7) in various types of salivary gland carcinoma (n = 95). When carcinoma cases were divided into low-grade and intermediate/high-grade types, NY-ESO-1 and CT7 were expressed more frequently in intermediate/high-grade carcinomas. We then focused on MAGE-A and NY-ESO-1 expression in a large cohort of adenoid cystic carcinomas (AdCCs) (n = 46). MAGE-A and NY-ESO-1 were frequently expressed in AdCC; specifically, MAGE-A was expressed in >60% of the AdCC cases. MAGE-A expression and tumour site (minor salivary gland) were identified as independent risk factors for locoregional tumour recurrence. CONCLUSIONS: These findings suggest that CTAs may be expressed in a variety of salivary gland carcinomas, especially in those with higher histological grades. In addition, MAGE-A, which is frequently expressed in AdCC cases, may be a useful prognostic factor for poorer locoregional recurrence-free survival.

Survival benefit of adding docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with nodal Stage N2-3.

BACKGROUND: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) has been established as the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC). The survival benefit of induction chemotherapy (ICT) for LA-NPC remains controversial. We analyzed the efficacy and feasibility of docetaxel, cisplatin and 5-fluorouracil (TPF) ICT followed by CCRT for LA-NPC with nodal Stage N2-3. METHODS: We performed a retrospective analysis of 28 LA-NPC patients with nodal Stage N2-3 receiving induction TPF followed by CCRT (TPF group; n = 12) or CCRT-AC (CCRT group; n = 16) between October 2006 and May 2016. RESULTS: The median follow-up periods were 36.4 (range 6.7-55.2) and 40.1 months (range 4.3-99.0) for the TPF and CCRT groups, respectively. One- and three-year overall survival for the TPF group vs. the CCRT group were 100% and 100% vs. 94% and 75%, respectively (P = 0.21). The cumulative one- and three-year incidences of locoregional recurrence or progression for the TPF group vs. the CCRT group were 10% and 21% vs. 16% and 32% (P = 0.49), and those of distant metastasis were 0% and 0% vs. 26% and 26%, respectively (P = 0.08). The common Grade 3-4 acute toxicities were neutropenia, anorexia, febrile neutropenia, and stomatitis in the TPF group. The Grade 3-4 late toxicities did not differ significantly between the two groups. CONCLUSIONS: This study suggests that induction TPF followed by CCRT might reduce distant metastasis, so this combination may be feasible for the treatment of LA-NPC with nodal Stage N2-3.

Prognostic Factors and Multidisciplinary Postoperative Chemoradiotherapy for Clinical T4a Tongue Cancer.

OBJECTIVE: The prognosis of patients with locally advanced squamous cell carcinoma (SCC) of the tongue is poor. Postoperative chemoradiotherapy (CRT) improves locoregional control and survival in high-risk patients. We investigated the prognostic factors for clinical T4a tongue SCC, and elucidated whether postoperative CRT has a benefit for patients with poor prognosis in terms of survival. METHODS: We performed a retrospective analysis of 61 patients with stage T4a SCC of the tongue who underwent primary resection and neck dissection. RESULTS: The median follow-up was 53.8 months. Multivariate analysis revealed a 4.26× relative risk of death for patients with the involvement of ≥5 regional lymph nodes (pN ≥5) compared with those with pN 0-4 (p = 0.002). In Kaplan-Meier analysis, patients with pN ≥5 who received CRT had longer overall survival rates than those who did not (hazard ratio = 0.31; p = 0.041). CONCLUSIONS: pN ≥5 is the most powerful prognostic factor for clinical T4a SCC of the tongue. Postoperative CRT is recommended in patients with pN ≥5.

Safety and efficacy of concurrent carboplatin plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin.

OBJECTIVE: Cisplatin-based chemoradiotherapy is the standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck. However, patients with advanced age, renal, cardiac or neurogenic dysfunction seem ineligible for cisplatin treatment. We evaluated the safety and efficacy of concurrent carboplatin plus radiotherapy in patients ineligible for cisplatin usage. METHODS: We retrospectively analyzed the records of 25 consecutive locally advanced squamous cell carcinoma of the head and neck patients who received concurrent carboplatin plus radiotherapy at Shizuoka Cancer Center between August 2006 and March 2014. Carboplatin was administered tri-weekly or weekly. RESULTS: Patient characteristics were analyzed. The median age was 75 years (range, 54-82), male:female ratio, 24:1; performance status, 0-1 (23) or 2 (2); primary tumor site, oropharynx (10), hypopharynx (12), larynx (1) or oral cavity (2); Stage III (3), IVa (19) or IVb (3); induction chemotherapy, with (2) or without (23); and a median creatinine clearance of 62 ml/min (range, 37-117). The main reasons for choosing carboplatin were age (40%), renal impairment (36%) and cardiac dysfunction (20%). All patients received a planned irradiation dose of 70 Gy. Median follow-up was 30.9 months. Complete response was observed 70% patients. Median progression-free survival duration was 42.7 months. Median overall survival could not be analyzed. The 2-year progression-free and overall survival rates were 68 and 74%, respectively. The main toxicity Grade 3 or 4 was oral mucositis (56%), thrombocytopenia (34%), neutropenia (28%) and infection (24%). CONCLUSIONS: Concurrent carboplatin plus radiotherapy is tolerated and may be an option in treating locally advanced squamous cell carcinoma of the head and neck patients ineligible for treatment with cisplatin.

Distinctive mucositis and feeding-tube dependency in cetuximab plus radiotherapy for head and neck cancer.

OBJECTIVE: Prophylactic percutaneous endoscopic gastrostomy may be considered before chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma, because severe mucositis is a common complication. We evaluated the mucosal findings and necessity of prophylactic percutaneous endoscopic gastrostomy in patients with head and neck squamous cell carcinoma receiving cetuximab and radiotherapy. METHODS: Fourteen consecutive patients with locally advanced head and neck squamous cell carcinoma receiving cetuximab and radiotherapy were analyzed. RESULTS: Patients' backgrounds were as follows: male/female, 8/6; median age, 64.5 years (range, 35-83 years); performance status, 0/1, 9/5. Primary tumor sites included the oropharynx, hypopharynx and larynx in four, seven and three patients, respectively. Patients completed a median of eight cetuximab cycles. All patients received three-dimensional conformal radiotherapy (median dose, 70 Gy). Thirteen patients were treated with elective neck irradiation at the ipsilateral (n = 3) or bilateral (n = 10) nodes. Grade ≥ 3 mucositis/stomatitis (clinical examination) occurred in 85.7% patients (n = 12). The median irradiation dose was 33 Gy at the Grade 3 mucositis onset. Eight patients showed mucositis with distinctive features, a wide range of white-coated lesions with a clear border; hypopharyngeal atresia was observed in two patients. Prophylactic percutaneous endoscopic gastrostomy was performed in 11 patients, and 11 patients (78.6%) actually required nutritional support because of Grade ≥ 3 mucositis/stomatitis (functional/symptomatic). CONCLUSIONS: Prophylactic percutaneous endoscopic gastrostomy is recommended because most patients receiving cetuximab and radiotherapy for locally advanced head and neck squamous cell carcinoma have Grade ≥ 3 mucositis with distinctive features.

Efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy for locally advanced head and neck squamous cell carcinoma classified as clinical nodal stage N2c, N3, or N2b with supraclavicular lymph node metastases.

BACKGROUND: We evaluated the efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) with a high risk of distant metastases compared with CRT alone. METHODS: We retrospectively analyzed 29 HNSCC patients with clinical nodal stage N2c, N3, or N2b disease and supraclavicular lymph node metastases receiving CRT alone (CRT group; n = 16) or TPF induction chemotherapy followed by CRT (TPF group; n = 13) between April 2008 and May 2012. RESULTS: The median follow-up periods were 14.5 (range 5.0-65.0) and 25.0 (range 14.0-32.0) months for CRT and TPF groups, respectively. A greater proportion of patient characteristics in the CRT group had advanced T and N stages. The overall response rate to induction TPF was 50.0%; grade 3-4 toxicities included neutropenia, febrile neutropenia, anorexia, and hyponatremia. Complete response rates after CRT completion were 55.5% in the TPF and 42.9% in the CRT group; median overall survival was not reached in the TPF group and was 14.0 months in the CRT group (p = 0.037). Multivariate analysis revealed that induction TPF and T stage were independent prognostic factors [hazard ratio (HR) = 0.196; 95% confidence interval (CI) 0.043-0.898; p = 0.036, HR = 9.966; 95% CI 2.270-43.75; p = 0.002, respectively). CONCLUSION: TPF followed by CRT is tolerated and may be an option for the treatment of locally advanced stage N2c, N3, or N2b HNSCC.

MUC expression in adenosquamous carcinoma of the head and neck regions of Japanese patients: immunohistochemical analysis.

Adenosquamous carcinoma (ASC) is a rare malignant neoplasm of the head and neck regions. We elucidated the relationship between ASC and MUC molecule expression. We selected 14 cases of ASC in the head and neck, and examined them immunohistohcmically. Seven cases of tongue, 3 cases of larynx and 4 cases of hypopharynx carcinoma were selected. Nine (64.3%) of 14 cases showed lymph node metastasis at the diagnosis. Laryngeal and hypopharyngeal cases showed a higher stage. Six cases (66.7%), all of which showed lymph node metastases, died of disease. Immunohistochemical examinations showed that ASC was positive for both markers of squamous cell carcinoma and adenocarcinoma. ASC showed positivity for MUC1 (13 cases: 92.3%), MUC1core (12 cases: 85.2%) and MUC4 (12 cases: 85.7%). In rare ASC of the head and neck region, it was revealed that MUC1 and MUC4 expression might be associated with its nodal status.

Is postoperative adjuvant chemoradiotherapy necessary for high-risk oropharyngeal squamous cell carcinoma?

BACKGROUND: High-risk factors for recurrence of head and neck squamous cell carcinoma after surgical resection include involvement of ≥ 2 regional lymph nodes, extracapsular spread, and microscopic involvement of resected mucosal margins. Adjuvant chemoradiotherapy is thought to improve postoperative locoregional control and survival. In this paper, we evaluate the efficacy of adjuvant therapy for high-risk oropharyngeal squamous cell carcinoma (OPSCC) (i.e., with ≥ 2 lymph nodes, positive extracapsular spread, or positive margins). METHODS: This is a retrospective analysis of 45 high-risk OPSCC patients who underwent surgery without adjuvant therapy (n = 19), with radiotherapy (n = 17), or with chemoradiotherapy (n = 9). RESULTS: The median follow-up period was 41.0 months. Radiotherapy patients showed a trend toward longer overall survival than patients without adjuvant therapy [hazard ratio (HR) = 0.32, p = 0.176]. However, overall survival for the chemoradiotherapy group seemed to be the same as that for the no adjuvant therapy group (HR = 0.79, p = 0.779). Multivariate analysis found that the relative risk of recurrence for patients without adjuvant therapy compared with any adjuvant therapy was 3.02 (p = 0.101). The relative recurrence risk in radiotherapy patients was 0.95 compared with that in chemoradiotherapy patients (p = 0.971). However, pathological T-stage was significantly associated with disease-free survival for high-risk OPSCC. CONCLUSIONS: Although the current study uses data from a small retrospective sample of patients, our results suggest that the addition of chemotherapy to radiotherapy may not be necessary as an adjuvant therapy for all high-risk OPSCC. A novel prognostic factor, such as pathological T-stage, should be considered for selecting those patients with high-risk OPSCC who would benefit from adjuvant therapy.

Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology.

Squamous cell carcinoma (SCC) with rhabdoid features (SCCRF) is extremely rare in the oral cavity. We report herein a case of oral SCCRF. The patient was a 69-year-old Japanese woman who had been suffering from a mass in the right lower gingiva. Right hemi-mandibulectomy was performed. The gingival tumor was composed of pleomorphic, non-cohesive ovoid tumor cells with abundant cytoplasm and eccentric nuclei, which were positive for both pan-cytokeratin and vimentin. In another portion, moderately differentiated SCC and carcinoma in situ were also seen. A transition zone existed between the components. Finally, we diagnosed SCCRF. Four months after the operation, multiple bone metastases, lung and skin metastases and marked hypercalcemia were found. SCCRF, therefore, might be more aggressive than the usual type of oral SCC.

Clinicopathological Features of Buccal Squamous Cell Carcinoma with Focus on Patients Who Never Smoke and Never Drink.

Introduction Oral carcinoma has been reported at a substantial proportion in patients who never smoke and never drink. However, the proportion may vary by subsite and ethnicity. Objective We aimed to determine the clinicopathological features of buccal squamous cell carcinoma (SCC) in a Japanese population. Methods We retrospectively analyzed the records of patients diagnosed with buccal SCC at our institution from September 2002 to November 2015. We reviewed the gender, age, tumor status, treatment, smoking, alcohol drinking, multiple primary cancers, and prognosis of the patients. The overall and cause-specific survival rates were calculated, and the effects of clinicopathological variables were assessed by univariate analysis. Furthermore, the cause of death was evaluated. Results Among the 63 patients (men: 38; women: 25) included in the present study, 29 (46.0%) never smoked or drank. Women were almost 5 years older than men ( p = 0.014). The number of women in the group who never smoked or drank was disproportionately higher than that of those in the smoker or drinker groups ( p < 0.001). In total, 29 patients (46.0%) had 59 multiple primary cancers, including 26 oral cancers. Surgeries and radiotherapy were performed in 57 (90.5%) and 6 (9.5%) cases, respectively. The 5-year overall survival and disease-specific survival rates were 74.6 and 78.8%, respectively. Conclusion Our study confirms that buccal SCC may develop in older adult Japanese patients, especially in women who have never smoked or drank. These patients could be at risk for second primary malignancy.

Molecular profile of a pleomorphic adenoma of the hard palate: A case report.

RATIONALE: Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. PAs have the potential for regional and distant metastases that preserve their benign phenotype; they also have the potential for malignant transformation. The molecular pathogenesis of malignant neoplasms has been studied extensively in recent years, unlike that of benign tumors, such as PA. PATIENT CONCERNS: In this case report, we identified the molecular signatures of a 57-year-old Japanese woman. Our patient presented with a swelling of the hard palate with an erosive appearance. DIAGNOSES: The patient was diagnosed with a right hard palate tumor suspected to be a malignant neoplasm. INTERVENTIONS: Partial maxillary resection and reconstruction were performed. OUTCOMES: There was no obstacle to swallowing or dysarthria after surgery. There was no sign of recurrent palatal tumor 4 years after the operation. Using next generation sequencing, 5 nonsynonymous mutations and CHCHD7-PLAG1 fusion genes were detected. Moreover, gene expression profiling indicated the possibility of the activation of several cancer-related signaling pathways. Although the PLAG1 gene is predicted to play a crucial role in PA tumorigenesis, its over-expression is reported to mediate multiple downstream factors. In this case, various up- and downregulated RNA signaling pathways, including MAP kinase signaling, PI3K/AKT1/MTOR signaling, JAK/STAT signaling, and PD-L1 signaling, were revealed. LESSONS: These molecular profiles of PA may elucidate the mechanism of metastasis, preserving its benign phenotype and carcinoma ex PA.