Correction: Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: a multicenter clinical study.

[This corrects the article DOI: 10.1371/journal.pone.0271907.].

Acquired tracheobronchomalacia developed following voice prosthesis implantation.

Acquired tracheobronchomalacia (ATBM) is a condition in which the tracheobronchial wall and cartilage progressively lose their rigidity, resulting in dynamic collapse during exhalation. In this report, we present a case of ATBM that developed following voice prosthesis implantation. To the best of our knowledge, this is the first documented case of such a condition in the medical English literature based on a PubMed search. A 63-year-old man was referred to National Kyushu Cancer Center in Japan with complaints of pharyngeal pain and a laryngeal tumor. The tumor was diagnosed as laryngeal cancer, and the patient underwent laryngectomy. Three months after the surgery, we implanted a voice prosthesis through a tracheoesophageal puncture. Two months after implantation, the patient experienced dyspnea. This condition was subsequently diagnosed as ATBM through computed tomography and bronchofiberscope examinations. After the removal of the voice prosthesis, there has been no progression of ATBM for over five years. While ATBM may not be a common occurrence in the practice of head and neck surgeons, it should be considered as a potential complication when patients report dyspnea following voice prosthesis implantation.

Efficacy of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine for the prevention of mucositis induced by platinum-based chemoradiation in head and neck cancer: A phase II study.

BACKGROUND & AIMS: The current standard treatment modality for advanced head and neck squamous cell carcinoma (HNSCC), namely platinum-based (PB) concurrent chemoradiotherapy (CRT), is associated with frequent severe mucositis which is responsible for the multiple acute and late adverse events. So far, effective preventive methods for this CRT-induced mucositis are not identified. In the current study, we examined the prophylactic effects of beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) (HMB/Arg/Gln) mixture. METHODS: Patients with HNSCC who were subject to PBCRT were randomly assigned to HMB/Arg/Gln intervention (Group I) and non-intervention (Group NI) cohort. The incidences of ≧ grade 3 mucositis (primary endpoint), ≧ grade 2 mucositis, and opioid usage and the degree of body weight loss (secondary endpoints) were compared between Group I and Group NI. RESULTS: A total of 75 patients were enrolled to this study and 38 patients were assigned to Group I, while 37 patients were to Group NI. After excluding patients who failed to complete CRT (3 in Group I and 2 in Group NI) or withdrew consents (11 in Group I and 1 in Group NI), 24 patients in Group I and 34 patients in Group NI were evaluated. HMB/Arg/Gln failed to reduce the incidences of ≧ grade 2 mucositis, but significantly (p = 0.0003) inhibited grade 3 mucositis in the late phase CRT, reducing the incidence from 64.6% (Group NI) to 25% (Group I) at 70Gy. The degree of body weight loss was significantly (p = 0.0038) lower in Group I (5.6%) compared to Group NI (8.9%), preventing the progression of PBCRT-induced cachexia. CONCLUSIONS: HMB/Arg/Gln administration demonstrated inhibitory effects on the progression of grade 3 mucositis and cancer cachexia in HNSCC patients treated with PBCRT. A larger scale phase III study is encouraged. CLINICAL TRIAL REGISTRATION: This study is registered to the UMIN Clinical Trial Registry: UMIN000050011.

Effectiveness and safety of weekly paclitaxel and cetuximab as a salvage chemotherapy following immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter clinical study.

OBJECTIVES: The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45). RESULTS: The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B. CONCLUSION: Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.

Real-world Experience With Pembrolizumab for Advanced-stage Head and Neck Cancer Patients: A Retrospective, Multicenter Study.

BACKGROUND/AIM: This study investigated the effectiveness of pembrolizumab with or without chemotherapy on advanced-stage head and neck cancer (HNC), including nasopharyngeal, sinonasal cavity and external auditory canal cancer, in a real-world setting. PATIENTS AND METHODS: We retrospectively collected data from 97 HNC patients who were treated with pembrolizumab alone (n=60) or with chemotherapy (n=37), and we investigated the association between clinicopathological findings and treatment response or prognosis. RESULTS: Patients treated with pembrolizumab and chemotherapy had a 1-year overall survival (OS) of 72.8%, objective response rate (ORR) of 48.6%, and serious (≥G3) adverse events (AEs) of 29.7%. Patients treated with pembrolizumab alone had a 1-year OS of 51.9%, ORR of 21.7%, and ≥G3 AEs of 6.7%. Both the ORR and disease control rate (DCR) in the pembrolizumab with chemotherapy group were significantly better than those in the pembrolizumab group (p=0.074 and p=0.00101, respectively). Among patients with distant metastasis, patients on pembrolizumab with chemotherapy achieved significantly better OS than pembrolizumab alone (p=0.0039). Among patients in the pembrolizumab group, both AE-positive and better performance status were associated with longer OS (p=0.011 and p=0.0037, respectively). CONCLUSION: Our real-world experience reinforces the durability and effectiveness of pembrolizumab for HNC patients. Additionally, our results suggest that pembrolizumab with chemotherapy might be recommended for patients with distant metastasis and no prior treatment. Further studies are needed to determine the optimal treatment strategy for HNC.

Inflammation-based Prognostic Score as a Prognostic Biomarker in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With Nivolumab Therapy.

BACKGROUND/AIM: The inflammation-based prognostic score (IBPS) has attracted attention recently as a prognostic biomarker for head and neck cancer patients. However, as the IBPS often changes after anticancer drug therapy, its independent prognostic value remains controversial. We aimed to investigate the relationship between the IBPS and prognosis in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with nivolumab, and investigate changes in the IBPS before and after nivolumab treatment. PATIENTS AND METHODS: Total of 164 patients with RMHNSCC received nivolumab therapy were retrospectively analyzed. RESULTS: Univariate analysis among the 164 patients revealed that the performance status (PS), immune-related adverse event (irAE) status, pre- and post-therapy Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and post-eosinophil count, were all significant predictors of overall survival (OS) (p<0.05). A multivariate analysis revealed that PS, irAEs, post-GPS, post-NLR, post-CAR, and post-eosinophil count were independent prognostic factors for overall survival. CONCLUSION: Post-treatment factors were identified as independent prognostic factors for RMHNSCC and can more accurately predict prognosis compared to nivolumab-treated RMHNSCC pre-treatment factors.

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer.

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma.

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Is chemoimmunotherapy a game changer in the treatment of locally advanced head and neck squamous cell carcinoma?

Pembrolizumab and chemotherapy (chemoimmunotherapy) were administered to 2 head and neck squamous cell carcinoma (HNSCC) patients with extremely advanced local tumors and distant metastases with palliative intent. However, they demonstrated strikingly good responses and achieved remission. Expanded application of induction chemoimmunotherapy may be useful for locally advanced HNSCC.

Genetic and transcriptomic analyses in a rare case of human papillomavirus-related oropharyngeal squamous-cell carcinoma combined with small-cell carcinoma.

Human papillomavirus (HPV)-related oropharyngeal small-cell carcinoma (OPSmCC) is a rare malignancy with aggressive behavior, whereas HPV-related oropharyngeal squamous-cell carcinoma (OPSqCC) displays a favorable prognosis. Notably, these two malignancies occasionally arise in an identical tumor. In this case study, we explored the molecular characteristics that distinguishes these two carcinomas using a rare case of HPV-related oropharyngeal carcinoma (OPC) with the combined histology of SmCC and SqCC. Immunohistochemical analysis and HPV-RNA in situ hybridization (ISH) suggested that both SmCC and SqCC were HPV-related malignancies. Targeted exome sequencing revealed that SmCC and SqCC had no significant difference in mutations of known driver genes. In contrast, RNA sequencing followed by bioinformatic analyses suggested that aberrant transcriptional programs may be responsible for the neuroendocrine differentiation of HPV-related OPC. Compared to SqCC, genes up-regulated in SmCC were functionally enriched in inflammatory and immune responses (e.g., arachidonic acid metabolism). We then developed a SmCC-like gene module (top 10 up-regulated genes) and found that OPC patients with high module activity showed poor prognosis in The Cancer Genome Atlas (TCGA) and GSE65858 cohort. Gene set enrichment analysis of the SmCC-like gene module suggested its link to MYC proto-oncogene in the TCGA data set. Taken together, these findings suggest that the SmCC-like gene module may contribute to acquisition of aggressive phenotypes and tumor heterogeneity of HPV-related OPC. The present case study is the first report of genetic and transcriptomic aberrations in HPV-related OPSmCC combined with SqCC.

PD-L1 expression, tumor-infiltrating lymphocytes, mismatch repair deficiency, EGFR alteration and HPV infection in sinonasal squamous cell carcinoma.

The antitumor efficacies of immune checkpoint inhibitors (ICIs) and the usefulness of potential predictive markers such as programmed death-ligand 1 (PD-L1) expression, density of tumor-infiltrating lymphocytes (TILs) and microsatellite instability (MSI) in sinonasal squamous cell carcinoma (SNSCC) have not been fully elucidated. We retrospectively analyzed 131 SNSCCs with immunohistochemistry for PD-L1 expression, TIL subpopulations and loss of mismatch repair (MMR) proteins as a surrogate for MSI-high. We also comprehensively evaluated the mutual relationships among these immuno-markers, high-risk human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) gene status, and KRAS mutation. PD-L1 expression (tumor proportion score ≥ 1%) was detected in 60 (45.8%) SNSCC cases and was significantly associated with worse overall survival (OS) (p = 0.0240). High density of cluster of differentiation 8 (CD8)-positive TILs was significantly associated with better progression-free survival (PFS) (p = 0.0368), and high density of forkhead box protein P3-positive TILs was significantly associated with better PFS and OS (p = 0.0007 and 0.0143, respectively). With respect to the combination of CD8 + TIL and PD-L1 expression, the high-CD8/PD-L1-negative group showed the most favorable prognosis, whereas the low-CD8/PD-L1-positive group showed the worst prognosis. MMR loss was detected in 3 (2.3%) of the 131 cases. HPV infection (6.1%), EGFR mutation (14.5%), EGFR copy number gain (26%), and MMR loss were essentially mutually exclusive; patients in these molecular groups showed significant differences in prognosis but not in the degree of PD-L1 expression or TILs. Among the nine ICI-treated patients, three (33.3%) were responders, and the EGFR-wild type cases (n = 7) showed better clinical responses to an ICI compared to the EGFR-mutant cases (n = 2). Among the patients with residual/recurrent EGFR-wild type tumors (n = 43), ICI treatment significantly improved OS (p = 0.0281). The results suggest that the evaluation of immuno-markers and molecular subclassification may be helpful for prognostic prediction and selecting an individualized therapeutic strategy for patients with SNSCC.

Anterior Fusion using a Vascularized Fibular Graft for Cervical Kyphosis Associated with Neurofibromatosis Type 1: A Report of Two Cases with Long-term Follow-up.

INTRODUCTION: Vascularized fibular grafts (VFG) in the cervicothoracic spine have been used for patients with progressive neurofibromatosis (NF) type-1-related kyphosis, but the long-term outcomes of VFG with NF-1 are not well described. We describe the long-term follow-up of two cases of cervical kyphosis related to NF-1 treated with VFG in the cervical spine. CASE REPORT: Case 1 was that of a 33-year-old man with a large neurofibroma at the back of his neck and an arteriovenous malformation at C2-7. The neurofibroma was resected by durotomy and intradural neurofibromas were extirpated through O-C6 laminectomy. Anterior fusion with VFG was performed 6 months later, and bone union was confirmed after 4 months. Cervical alignment was maintained with 50° kyphosis 15 years after the operation. The man suffered a subarachnoid hemorrhage 22 years after the operation. Case 2 was a 23-year-old woman with diastematomyelia at C6-T1 who was treated by anterior fusion with VFG at C4-T1. The diastematomyelia septum was resected through a C4-T1 laminectomy with simultaneous posterolateral fusion at C3-T2. Cervical alignment was maintained with 50° kyphosis 18 years later. The left vertebral artery ruptured and was embolized 10 years after the operation. CONCLUSION: Anterior fusion with VFG can achieve good bone union and maintains long-term alignment. However, it is important to watch for vascular events related to NF-1.

Surgical treatment for persistent second carpometacarpal joint pain.

The purposes of this study were to demonstrate the clinical characteristics of patients with persistent second carpometacarpal (CMC) joint pain without bony abnormalities known as the carpal boss, and to assess the clinical efficacy of surgical stabilization of the second CMC joint. Eleven patients had persistent wrist pain with characteristic symptoms, including tenderness over the second CMC joint, increased symptoms when the involved hand was placed on the ground or gripped strongly with the involved hand, a positive metacarpal stress test and temporary pain relief with the intra-articular injection of the lidocaine. The patients underwent arthrodesis of the second CMC joint. All cases showed radiologically confirmed fusion of the second CMC joint. At the final followup examination, 10 of 11 patients resulted in satisfactory clinical outcomes, excepting one patient with remnant pain and restricted range of wrist motions. This report highlights the importance of conducting a careful assessment of patients who present with persistent second CMC joint pain without the bony abnormalities, such as carpal bossing. Surgery to stabilize the second CMC joint may be an option to improve their symptoms when conservative treatment fails.

Drug-induced interstitial lung disease in recurrent and/or metastatic head and neck cancer patients treated with cetuximab and/or nivolumab.

BACKGROUND: Drug-induced interstitial lung disease (DI-IP) is one of the most serious adverse reactions associated with the use of anticancer drugs. DI-IP prevalence among molecular-targeting drugs and immune checkpoint inhibitors (ICIs) is relatively high in Japanese patients. To assess the risk of cetuximab and/or nivolumab-related IP is important. PATIENTS AND METHODS: The medical records of 138 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with cetuximab-containing chemotherapy and/or nivolumab monotherapy were retrospectively reviewed. RESULTS: The incidence of DI-IP with R/M HNSCC was 7.2%. DI-IP occurred more frequently in patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy than in patients with other regimens. However, tumor suppression was detected in all patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy, and two achieved a complete response. CONCLUSIONS: Although patients treated with cetuximab-containing chemotherapy following nivolumab showed dramatic efficacy, careful monitoring should be recommended.

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

OBJECTIVES: Immune-related adverse events (irAEs) have been shown to be associated with higher antitumor responses and a clinical benefit in non-small cell lung carcinoma, renal cell carcinoma, and melanoma patients. However, little is known regarding the association between irAEs and the clinical effect of nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC). MATERIALS AND METHODS: We evaluated 108 patients treated with nivolumab for R/MHNSCC at 2 participating institutions. IrAEs were identified and profiled. We analyzed the association of each immune-related adverse effect with the clinical outcome of the patients. RESULTS: Among 108 patients, the objective response rate (ORR) was 29.6% (32/108 patients), and the disease control rate (DCR) was 50.0% (54/108 patients). IrAEs were observed in 41 patients (38.0%). Patients with irAEs had a significantly higher ORR and DCR than those without irAEs (46.3% vs. 19.4%, P = 0.004 and 75.6% vs. 34.3%, P < 0.001, respectively). The median progression-free and overall survival rates in patients with irAEs were significantly longer than in those without irAEs. CONCLUSIONS: There was a significant relationship between irAEs and efficacy in R/MHNSCC patients treated with nivolumab. Our results indicate that the development of irAEs may aid in the earlier prediction of anticancer effects in patients with recurrent or metastatic HNSCC during nivolumab monotherapy.

Larynx-preserving reconstruction after extended base of the tongue resection.

BACKGROUND: As the base of the tongue (BOT) plays essential roles in speech and swallowing, surgical resection of BOT cancer is typically avoided. Moreover, standard reconstructive procedures for larynx-preserving BOT defects have not yet been established. We performed immediate flap reconstruction after wide resection of BOT cancer with laryngeal preservation. Herein, the functional and oncological results of our strategy were analysed. METHODS: We retrospectively evaluated patients who underwent extended BOT resection (including the oral tongue, upper/lateral oropharyngeal wall, epiglottis and false vocal cord) with laryngeal preservation between April 2006 and April 2016. We classified defects involving the oral tongue or upper/lateral oropharyngeal wall as the lateral extension type and those involving the epiglottis or false vocal cord as the laryngeal extension type. Lateral extension-type defects were closed primarily and filled with a deepithelialised skin or muscle flap. Laryngeal extension-type defects were reconstructed using a bulky skin flap plus hyo-thyroid-pexy to create a neo-epiglottis. Postoperative functional and oncologic outcomes were assessed. RESULTS: We enrolled 18 patients with extended BOT defects. Of them, 11 had a history of irradiation. The tracheal cannula was removed in all cases, although laryngeal extension defects were associated with a longer duration to removal. All patients achieved complete oral intake and retained intelligible speech, with preservation of laryngeal function. There was no local recurrence, and the 5-year overall survival was 88.9%. CONCLUSIONS: Following wide BOT resection, reconstruction with laryngeal preservation is feasible even in cases involving irradiated tumours with laryngeal extension.

Stress-triggered YAP1/SOX2 activation transcriptionally reprograms head and neck squamous cell carcinoma for the acquisition of stemness.

PURPOSE: The clinical importance of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) is well recognized. However, a reliable method for the detection of functioning CSC has not yet been established. We hypothesized that YAP1, a transcriptional coactivator, and SOX2, a master transcription factor of SCC, may cooperatively induce stemness through transcriptional reprogramming. METHODS: We immunohistochemically examined the expression of SOX2 and YAP1 in the CD44 variant 9 (CD44v9)-positive invasion front. A CSC-inducible module was identified through a combination of siRNAs and sphere formation assays. YAP1 and SOX2 interactions were analyzed in vitro. RESULTS: The triple overexpression of SOX2, YAP1, and CD44v9 was significantly associated with poor prognosis. TCGA data revealed that the CSC-inducible module, which was related to EMT and angiogenesis, was significantly correlated with poor prognosis. The KLF7 expression, representatively chosen from the module, also correlated with poor prognosis and was essential for sphere formation and CSC propagation. Sphere stress-activated YAP1 enhanced SOX2 activity. CONCLUSIONS: The stress-triggered activation of YAP1/SOX2 transcriptionally reprograms HNSCC for the acquisition of stemness. Triple SOX2, YAP1, and CD44v9 immunostaining assays may be useful for the selection of high-risk patients with functioning CSCs, and YAP1 targeting may lead to the development of a CSC-targeting therapy.

Prognostic value of programed death ligand-1 and ligand-2 co-expression in salivary gland carcinomas.

OBJECTIVES: The aim of the present study was to investigate the molecular basis for the use of immune checkpoint inhibitors to treat salivary gland carcinomas (SGC). MATERIALS AND METHODS: We examined the clinical and prognostic significance of programed death ligands 1 and 2 (PD-L1 and -L2) expression using immunohistochemistry and in situ hybridization, as well as microsatellite instability (MSI) status using polymerase chain reaction, along with tumor-infiltrating lymphocytes (TILs) in 30 cases of SGC. RESULTS: The SGC cases studied included adenoid cystic carcinoma (AdCC, 36.7%), salivary duct carcinoma (SDC, 26.7%), mucoepidermoid carcinoma (MEC, 23.3%), and carcinoma ex pleomorphic adenoma (CxPA, 13.3%). Either PD-L1 or PD-L2 overexpression was observed in 36.7% patients. PD-L2 expression was associated with reduced disease-specific survival (DSS) and disease-free survival (DFS) (P = 0.0266 and P = 0.0209, respectively). Simultaneous PD-L1 and PD-L2 overexpression was detected in 13.3% of cases, and was correlated with reduced DSS (P = 0.0113). Among non-AdCCs, all cases that developed distant metastasis were positive for PD-L2 (P = 0.001). Cases showing low-TILs that were positive for either PD-L1 or L2 were associated with poor DFS. No MSI was detected in the SGC cases studied. CONCLUSION: To our knowledge, this is the first comprehensive study examining PD-L1 and PD-L2 status, MSI status, and TILs in SGC. Our results indicate that the PD-1/PD-L1 or PD-L2 pathway, which is associated with poor clinical outcomes, may provide promising therapeutic targets against SGC in selected patients. Further experimental and clinical studies are encouraged.

Successful management of recurrent adenoid cystic carcinoma in the deep infratemporal fossa by maxillo-orbito-zygomatic approach.

OBJECTIVE: In the case of deep invasion of an infratemporal fossa (ITF) tumor, surgeons find it difficult to gain sufficient visualization and working space by conventional surgical approaches. To overcome these limitations, we have developed a novel surgical technique, maxillo-orbito-zygomatic (MOZ) approach, by combining partial lateral maxillectomy with the conventional orbito-zygomatic approach. METHODS: A 63-year-old male presented with the fifth recurrent adenoid-cystic carcinoma in the right deep ITF. Using a Weber-Ferguson-type incision and partial dismasking, we elevated the skin and scalp flap, while preserving the facial nerve and orbicularis oculi muscle intact in the flap. Then, we performed MOZ osteotomy using three cut lines, the zygomatic arch, the frontozygomatic suture, and from the inferior orbital fissure to the anterolateral wall of the maxilla. Following this, we temporarily elevated the bone flap by partially opening the lateral maxillary sinus. We obtained an excellent surgical view of the ITF, middle skull base, and pterygopalatine fossa with this technique, which facilitated the safe removal of the tumor. RESULTS: The postoperative course remained almost uneventful, and we obtained favorable cosmetic results. CONCLUSIONS: Our novel MOZ approach could be a robust approach to remove deep ITF tumors.

Utility of chemoradioselection for the optimization of treatment intensity in advanced hypopharyngeal and laryngeal carcinoma.

Definitive concomitant chemoradiotherapy (CRT) with high-dose cis-platinum (CDDP) is a current standard protocol for advanced laryngeal and hypopharyngeal cancer sparing surgery for salvage. However, this modality is associated with limited feasibility and frequent sever toxicities. In the present study, a 'chemoradioselection' protocol with minimal toxicity was developed using initial response to CRT as a biomarker for patient selection. Between 2000, March and 2012, September 123 patients with stage III (44), IV (79) laryngeal (64) and hypopharyngeal carcinoma (59) excluding T4 cases were enrolled to this protocol. Two cycles of split (15 mg/m2 ×5 days, 2000-2008) or bolus (80 mg/m2, 2009-present) CDDP was concurrently administered. Tumor responses were evaluated after 40 Gy of CRT and 64 responders (chemoradioselected, CRS) received further CRT up to 70 Gy, while radical surgery was recommended for the 59 non-responders (N-CRS), and 34 underwent surgery (N-CRS-ope). The remaining 25 patients who refused surgery (N-CRS-refu) were treated with continuous CRT. The 5-year overall survival (OS) and disease-specific survival (DSS) were 67, and 77%, respectively. The CRS demonstrated favorable 5-year OS (73%) and laryngo-esophageal dysfunction-free survival (LEDFS, 69%) rates. In contrast, the N-CRS-refu showed significantly lower 5-year OS (47%) compared with CRS (73%) and N-CRS-ope (70%) (P=0.0193), and significantly lower 5-year LEDFS (20%) compared with the CRS (69%) (P<0.0001). On multivariate analyses, including T, N, primary site and planned treatment (CRS + N-CRS-ope) or not (N-CRS-refu), unplanned treatment alone showed a significant correlation with poor OS [hazard ratio (HR), 2.584; 95% confidence interval (CI), 1.313-4.354; P=0.007). Chemoradioselection reflects the biological aggressiveness of each tumor, and is able to segregate patients for functional laryngeal preservation with moderate intensity CRT (150-160 mg/m2 of CDDP) from those who would be better treated with surgery. This strategy may be useful for the optimization of the therapeutic intensity.