Comprehensive genomic profiling from C-CAT database unveiled over 80% presence of oncogenic drivers in anaplastic thyroid carcinoma including BRAF, RAS family, NF1, and FGFR1.

OBJECTIVE: Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the BRAF V600E mutation, and its clinical implications. DESIGN, PATIENTS AND MESUREMENT: A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and χ2 tests, were employed for survival analysis and gene mutation comparisons. RESULTS: Among 102 ATCs, BRAF, RAS, and other driver mutations were found in 83 cases (81.2%). The prevalence of BRAF V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the BRAF, RAS, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that RAS mutations had a poorer prognosis. In the BRAF/RAS wild-type group, FGFR1 and NF1 were identified as driver mutations, with an accumulation of copy number variations and less TERT promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data. CONCLUSIONS: Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of BRAF V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.

Surgical approach through the anterior scalene muscle resection for invasive tumours in the supraclavicular fossa (with video).

BACKGROUND: The supraclavicular fossa contains many vital organs to be preserved, such as the brachial plexus, subclavian artery and vertebral artery. Various surgical methods have been reported. However, no well-standardized surgical procedure has been established. METHODS: Between 2010 and 2020, we performed 28 surgical treatments of the superior mediastinum and supraclavicular fossa. Of these, we retrospectively reviewed seven cases of supraclavicular invasion using a unified surgical technique in which the anterior scalene muscle was resected, and the inter-scalene triangle was approached. RESULTS: We performed claviculectomy in four cases and a transmanubrial approach in three cases. In all cases, by resecting the anterior scalene muscle, the brachial plexus, subclavian artery and vertebral artery were preserved. There were no critical postoperative complications other than tracheostomy and lymphatic leakage. Median bleeding amount and operative time were 438 (range; 76-1144) ml and 328 (range; 246-615) minutes, respectively. CONCLUSIONS: The anterior scalene muscle resection method might be a safe and standardized method for preserving the brachial plexus, subclavian artery and vertebral artery.

Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland.

Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of 6 cases of HCCC, including 2 atypical subtypes-a case of "high-grade transformation" and 1 "possessing a novel partner gene for EWSR1." We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the "high-grade transformation," harbored a known EWSR1::ATF1 fusion gene; however, 1 case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4-fused HCCC has a SOX10-positive staining, which is different from the EWSR1::ATF1-fused HCCC. According to whole-exome sequencing and fluorescence in situ hybridization analysis, the "whole-genome doubling" and focal deletion involving CDKN2A, CDKN2B, and PTEN were detected in HCCC with "high-grade transformation." Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, "high-grade transformation" and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations.

Comparison of Survival Outcomes Between Larynx-Preserving Open Partial Pharyngectomy and Radiotherapy or Chemoradiotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Single-Center Retrospective Analysis with Inverse Probability of Treatment Weighting Adjustments.

BACKGROUND: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies. METHODS: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted. RESULTS: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models. CONCLUSION: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC.

Current topics and management of head and neck sarcomas.

Given the low incidence, variety of histological types, and heterogeneous biological features of head and neck sarcomas, there is limited high-quality evidence available to head and neck oncologists. For resectable sarcomas, surgical resection followed by radiotherapy is the principle of local treatment, and perioperative chemotherapy is considered for chemotherapy-sensitive sarcomas. They often originate in anatomical border areas such as the skull base and mediastinum, and they require a multidisciplinary treatment approach considering functional and cosmetic impairment. Moreover, head and neck sarcomas may exhibit different behaviour and characteristics than sarcomas of other areas. In recent years, the molecular biological features of sarcomas have been used for the pathological diagnosis and development of novel agents. This review describes the historical background and recent topics that head and neck oncologists should know about this rare tumour from the following five perspectives: (i) epidemiology and general characteristics of head and neck sarcomas; (ii) changes in histopathological diagnosis in the genomic era; (iii) current standard treatment by histological type and clinical questions specific to head and neck; (iv) new drugs for advanced and metastatic soft tissue sarcomas; and (v) proton and carbon ion radiotherapy for head and neck sarcomas.

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database.

BACKGROUND: Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed. METHODS: We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher's exact test, Kaplan-Meier analysis, log-rank test and Cox regression models were used for statistical analysis. RESULTS: In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival. CONCLUSION: CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.

Clinical outcomes of head and neck mucosal melanoma treated with surgery: a single-center study in Japan.

BACKGROUND: Head and neck mucosal melanomas are rare malignancies. Although the prognosis is poor owing to the high incidence of distant metastases, locoregional control remains important. It is difficult to obtain results in a large cohort because of its rarity. This study aimed to elucidate the survival outcomes of patients with head and neck mucosal melanoma treated with surgery in Japan. METHODS: Patients with head and neck mucosal melanoma who were surgically treated between 2007 and 2021 at the National Cancer Center Hospital were retrospectively analyzed. RESULTS: A total of 47 patients were included in this study. The 5-year overall survival, disease-specific survival, locoregional control and relapse-free survival rates were 42%, 50%, 79% and 13%, respectively. The disease-specific survival of the oral mucosal melanoma group was significantly better than that of the sinonasal mucosal melanoma group (5-year disease-specific survival rate: 70% versus 37%, respectively; P = 0.04). Multivariate analyses revealed that sinonasal mucosal melanoma were independently significant adverse prognostic factor, for overall survival and disease-specific survival. Patients with oral mucosal melanoma patients had a higher incidence of lymph node metastasis than those with sinonasal mucosal melanoma patients (P < 0.0001). CONCLUSION: This study demonstrated the survival outcomes of the largest cohort of patients with head and neck mucosal melanomas treated surgically at a single institution within the past 20 years in Japan. We found that survival outcomes and incidence of nodal metastases varied by site.

Risk factors for incomplete resection with pharyngeal endoscopic submucosal dissection and long-term prognosis after resection.

BACKGROUND: Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD. METHODS: This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed. RESULTS: The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection. CONCLUSION: Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.

Elective neck dissection for T3-T4N0 laryngeal carcinoma: evidence from Japan's National Head and Neck Cancer Registry.

BACKGROUND: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. METHODS: We conducted a retrospective nationwide observational study on patients with T3-T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. RESULTS: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%-19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. CONCLUSION: Omission of END during laryngectomy for T3-T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time.

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade.

BACKGROUND: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. METHODS: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. RESULTS: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. CONCLUSION: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma.

There is an unmet need for improving survival outcomes of locally advanced nasopharyngeal carcinoma, for example, T4/ N3 stage disease. To this end, we administered induction chemotherapy (IC) with TPF (docetaxel, cisplatin, and fluorouracil) because this stage of disease is associated with a high risk of recurrence and is difficult to control with standard treatments, such as chemoradiotherapy (CRT) alone or CRT followed by adjuvant chemotherapy. The aim of this retrospective single-center study was to clarify the short-term outcomes of locally far-advanced nasopharyngeal carcinoma patients treated with IC-TPF, followed by CRT with cisplatin. Data from 11 patients were extracted from our database, indicating that the overall response rate to IC-TPF, clinical complete response rate after CRT, 1-year progression-free survival, and 1-year overall survival were 73%, 91%, 68%, and 89%, respectively. Hematological toxicity was the most common adverse event reported during IC-TPF with 64% of patients suffering grade 3 or 4 neutropenia, 55% grade 3 or 4 leucopenia and 9% febrile neutropenia. Despite the small number of patients, these data are important because there is a limited number of studies investigating IC-TPF followed by CRT in Japanese patients. This pilot study provides some indication of the short-term effectiveness and toxicity of this therapeutic approach, which may be superior to standard treatments. Long-term follow-up is warranted to assess the effectiveness of IC-TPF in terms of clinical outcome and late-phase toxicity.

Uniform infection screening allowed safe head and neck surgery during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: The purpose of this study was to determine whether a uniform infection screening protocol could be used to safely perform head and neck cancer surgery during the coronavirus disease 2019 pandemic and clarify how surgical treatment changed compared with the pre-pandemic period. MATERIALS AND METHODS: During the unprecedented coronavirus disease 2019 pandemic in Tokyo, we continued providing head and neck cancer care, guided by our own uniform screening protocol. In this study, medical records of 208 patients with head and neck malignancy, who underwent surgical treatment at our hospital during the first and second wave of pandemic for each 2-month period (first wave: 30 March 2020-30 May 2020, second wave: 14 July 2020-14 September 2020) and the 2-month pre-pandemic period (30 October 2019-30 December 2020), were analysed. RESULTS: A total of 133 patients were admitted for surgical treatment and all, except six patients with emergency tracheostomy, were screened according to the protocol. As a result, all 127 patients received surgical treatment as planned, and all 1247 medical staff members involved in the surgeries were uninfected by severe acute respiratory syndrome coronavirus 2. During the first wave of pandemic, 20% reduction of head and neck surgery was requited; however, restrictions of surgery were not necessary during the second wave. Surgical procedure, length of hospitalization, postoperative complications and number of medical staff were unchanged compared with pre-pandemic period. CONCLUSION: Our data indicate that continuation of head and neck anticancer surgical treatment in an epidemic area during the coronavirus disease 2019 pandemic were safe and feasible, if adequate and strict preventive measures are vigorously and successfully carried out.

Pull-through resection without free-flap reconstruction for lateral wall oropharyngeal cancer.

BACKGROUND: While transoral robotic surgery (TORS) is widely used for the management of lateral wall oropharyngeal carcinomas (OPC), open surgical techniques are still used in some cases. A pull-through method for open surgical resections of OPC has recently been introduced. We improved on this method by eliminating the need for subsequent free-flap reconstruction. METHODS: 16 patients with lateral wall OPC underwent pull-through resections. After resection, we used the digastric muscle, stylohyoid muscles, submandibular gland and the surrounding tissues to block the neck and oral cavity and to avoid reconstruction. RESULTS: This novel technique was performed without major complications or morbidities. The average post-operative hospital stay was 14.6 ± 6.1 days, and the average duration until initiation of oral intake post-operation was 6.5 ± 2.9 days. Oncological outcomes, post-operative course and function were acceptable. CONCLUSIONS: Our novel method provides an efficient and less invasive surgical technique than conventional open approaches.

All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens. METHODS: Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirus-associated oropharyngeal carcinomas, two risk categories were classified as "p53 adverse function" and "p53 favorable function" based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher's exact test. RESULTS: Multivariate analysis identified "p53 adverse function" as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin > 6 mm, the "p53 adverse function" group demonstrated significantly higher local recurrence rate than the "p53 favorable function" group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival. CONCLUSIONS: All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.

Common carotid artery ligation at the proximal side before rupture in patients with ligation or occlusion of the external carotid artery at risk of carotid blowout syndrome.

BACKGROUND: Carotid blowout syndrome (CBS) is among the fatal complications in head and neck cancer treatment. However, the optimal treatment for CBS has not been established yet. This study aimed to describe our experience with two patients at high risk of CBS who underwent common carotid artery (CCA) ligation at the proximal side of the bleeding point under local anesthesia and before CCA rupture, and to review and compare the medical records of these two patients against 10 CBS cases treated in our department. METHODS: The institutional electronic medical record was searched, and clinical information was extracted for all patients who showed CBS from 2007 to 2017. Our treatment method was performed as follows. Ligation of the proximal side of the CCA was performed under local anesthesia. The CCA was identified and clamped with two bulldog forceps for 10 minutes to check for any adverse neurological symptoms. Subsequently, the CCA was ligated using 2-0 silk threads and sutured with an absorbable suture between the silk threads. However, ligation or occlusion of the external carotid artery by previous treatment is a prerequisite for this method. RESULTS: Eight patients received interventions, with six patients undergoing prophylactic interventions before rupture. Four patients who did not undergo treatment died owing to CBS. Two patients who underwent treatment with the novel method did not experience re-bleeding, but their conditions deteriorated owing to cancer progression. CONCLUSION: The present method is one of the treatment choices for CBS, especially in patients with an 'impending' risk of CBS.

Enhancement of Binding Affinity of Folate to Its Receptor by Peptide Conjugation.

(1) Background: The folate receptor (FR) is a target for cancer treatment and detection. Expression of the FR is restricted in normal cells but overexpressed in many types of tumors. Folate was conjugated with peptides for enhancing binding affinity to the FR. (2) Materials and Methods: For conjugation, folate was coupled with propargyl or dibenzocyclooctyne, and 4-azidophenylalanine was introduced in peptides for "click" reactions. We measured binding kinetics including the rate constants of association (ka) and dissociation (kd) of folate-peptide conjugates with purified FR by biolayer interferometry. After optimization of the conditions for the click reaction, we successfully conjugated folate with designed peptides. (3) Results: The binding affinity, indicated by the equilibrium dissociation constant (KD), of folate toward the FR was enhanced by peptide conjugation. The enhanced FR binding affinity by peptide conjugation is a result of an increase in the number of interaction sites. (4) Conclusion: Such peptide-ligand conjugates will be important in the design of ligands with higher affinity. These high affinity ligands can be useful for targeted drug delivery system.

The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma.

BACKGROUND: TP53 is the most frequently mutated gene in human cancers. Previous studies reported that TP53 mutations correlated with poor prognoses in patients with head and neck squamous cell carcinoma (HNSCC). However, the relationship between TP53 mutations and hypopharyngeal squamous cell carcinoma (HPSCC) is not known. The current study aimed to evaluate TP53 mutation status as a predictive biomarker in patients with HPSCC. METHODS: We retrospectively reviewed the clinical charts of 57 HPSCC patients treated with initial surgery between 2008 and 2014. TP53 mutation status was determined by Sanger sequencing, and patients were classified into wild-type, missense mutation, and truncating mutation groups. Additionally, p53 expression was determined using immunohistochemistry in surgical specimens. RESULTS: TP53 mutations were identified in 39 (68%) patients. The 3-year disease-specific survival (DSS) rate of wild-type, missense mutation, and truncating mutation group were 94%, 61%, and 43%, respectively. The TP53 mutation group displayed significantly worse DSS and overall survival rates than the wild-type group (P = 0.01 and P = 0.007, respectively). Multivariate analyses revealed that the presence of TP53 mutations and ≥4 metastatic lymph nodes were independent adverse prognostic factors for HPSCC. p53 immunopositivity was detected in 22 patients, including 5 (28%) and 17 (71%) patients in the wild-type and missense mutation groups, whereas none of the patients with truncating mutation exhibited p53 immunopositivity (P = 0.0001). CONCLUSION: The TP53 mutation status correlated with poor prognosis in surgically treated HPSCC patients. Specifically, truncating mutations which were not detected by p53 immunohistochemistry were predictive of worst survival.

Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

BACKGROUND: Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. METHODS: Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. RESULTS: Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. CONCLUSIONS: Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for patients with laryngeal/hypopharyngeal cancer than oral cancer.

Impact of microscopic orbital periosteum invasion in orbital preservation surgery.

OBJECTIVE: The orbital periosteum is considered to be a barrier to tumor spread; however, it is difficult to evaluate microscopic tumor spread during surgery. This study aimed to assess the impact of pathological status in orbital preservation surgery. METHODS: We retrospectively analyzed the 3-year local control rate and treatment outcomes of patients with malignant tumors invading the orbit who were treated between 2006 and 2012. RESULTS: In total, 27 patients were reviewed over a median follow-up period of 36 months. Pathologically, 19 had carcinomas and 8 had sarcomas. Treatment was by orbital exenteration in 6 patients and orbital preservation surgery in 21 patients. After orbital preservation surgery, poorer 3-year local control rates were significantly associated with positive surgical margins (negative vs. positive: 91% vs. 41%, P = 0.040) and microscopic orbital periosteum invasion (negative vs. positive: 90% vs. 39%, P = 0.010). These factors were independent risk factors in multivariate analysis. The locations of the positive margin were most common at the horizontal and vertical margins of the orbital periosteum and the posterior margin of the orbital apex. Moreover, in 24% of patients, invasion evaluation by preoperative imaging study was underestimated compared with postoperative microscopic evaluation. CONCLUSIONS: The positive surgical margin and microscopic orbital periosteum invasion were the risk factors of orbital recurrence. It is difficult to determine the indications for orbital preservation surgery by preoperative imaging studies because of the unpredictable accurate pathological status before surgery and the limitations of preoperative imaging evaluation.