Pterygoid Muscle Necrosis Caused by Radiation and Intra-Arterial Cisplatin Infusion Chemotherapy (RADPLAT): A Case Report.

Introduction: Radiation and intra-arterial cisplatin infusion chemotherapy (RADPLAT) for advanced maxillary sinus cancer has accumulated evidence as a treatment with fewer complications and better 5-year survival rates. In this study, we report a case in which pterygoid muscle necrosis occurred 6 months following RADPLAT treatment for maxillary sinus cancer. Case Presentation: The 45-year-old woman had a long history of taking immunosuppressants against rheumatoid arthritis (RA) prior to treatment. Although achieving complete response (CR) to RADPLAT, the patient developed trismus (1 fingerbreadth or less) 6 months following treatment. Abscess formation and recurrence were suspected from the imaging findings; however, the biopsy with endoscopy indicated necrotic tissue. Currently, 18 months have passed without cancer recurrence. Although trismus temporarily improved with rehabilitation, the width of the mouth opening is currently a few millimeters, so the patient can only take liquid food. Conclusion: Pterygoid muscle necrosis should be recognized as a new major complication.

Clinical outcomes and failure patterns after postoperative radiotherapy for oral cavity squamous cell carcinoma.

PURPOSE: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). METHODS: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50-66) administered in 30 fractions (range 25-33). RESULTS: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC.

The Usefulness of Total Laryngectomy in Sarcopenic Patients With Hypopharyngeal and Laryngeal Cancer.

BACKGROUND/AIM: Sarcopenia has an adverse effect on postoperative complications and prognoses in head and neck cancer. This study focused on hypopharyngeal and laryngeal cancer patients with sarcopenia and analyzed the body composition following treatment when the larynx was preserved and when total laryngectomy was performed to examine the usefulness of laryngectomy. PATIENTS AND METHODS: We retrospectively reviewed 88 primary hypopharyngeal and laryngeal cancer patients aged 65 years or older with cT2N0M0 or higher who visited our department. RESULTS: There were no significant differences in the 3-year overall survival rate and the 1-year local control rate between the laryngeal preservation group and laryngectomy group. The average change one year following treatment in the laryngeal preservation group, when compared to prior to treatment, was a significant decrease in the body weight (BW) of -0.035, skeletal muscle mass (SMM) of -0.030, skeletal muscle mass index (SMI) of -0.026, body mass index (BMI) of -0.034, and grip strength (GS) of -0.066. The average change one year following treatment in the laryngectomy group, compared with prior to treatment, was an increase in BW of +0.028, SMM of +0.026, SMI of +0.008, BMI of +0.032, and GS of +0.026. Although no changes in serum biochemical testing after treatment were observed in the laryngeal preservation group, albumin, transferrin, and transthyretin all exhibited significant improvement or a tendency toward improvement in the laryngectomy group. The patients with sarcopenia before treatment in the laryngeal preservation group had a significantly higher incidence of aspiration pneumonia. CONCLUSION: The presence or absence of sarcopenia before starting treatment is considered to be an index for selecting total laryngectomy.

Up-front neck dissection followed by chemoradiotherapy for T1-T3 hypopharyngeal cancer with advanced nodal involvement.

BACKGROUND: The advantage of up-front neck dissection (UFND) followed by chemoradiotherapy (CRT) for hypopharyngeal cancer (HPC) with advanced neck involvement remains controversial. We aimed to determine the indications. METHODS: The data of 41 and 14 patients with stage IVA/B (T1-T3 and ≥N2a) HPC who underwent UFND followed by CRT and received CRT, respectively, were retrospectively analyzed and compared. RESULTS: The 5-year overall survival (OS) and disease-specific survival rates for the UFND and CRT groups were 61% and 52% (p = 0.1019), and 89% and 74% (p = 0.2333), respectively. Moreover, patients aged ≥70 years or those with a pulmonary disease history had a significantly poorer prognosis due to aspiration pneumonia in the UFND group. The 5-year regional control (RC) for the UFND and CRT groups were 92% and 57%, respectively (p = 0.0001). CONCLUSIONS: UFND followed by CRT was feasible with satisfactory RC. To further improve OS, aspiration pneumonia prevention is essential.

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study.

Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

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 .

Patterns of bone metastases from head and neck squamous cell carcinoma.

OBJECTIVE: To report clinical features of bone metastases (BM) from head and neck squamous cell carcinoma (HNSCC). METHODS: Among 772 patients with HNSCC diagnosed at our hospital over 9 years, 30 patients (3.9%) had clinical evidence of BM (24 men and 6 women; mean age: 63 years). We assessed the time interval from the primary diagnosis to BM development, symptoms attributable to BM, presence of distant metastases to other organs, number of BM, sites of BM, morphologic changes on computed tomography (CT) images, treatment for BM, and overall survival (OS). RESULTS: BM at the initial stage were found in 9 patients with HNSCC (30%), and in 21 patients (70%) with HNSCC during the course of the disease. In the later patients, the median time interval from the primary diagnosis was 11.5 months. Nineteen patients (63%) did not have BM-related symptoms, 6 (20%) had pain, 3 (10%) had neurologic symptoms resulting from vertebral or skull metastases, and 2 (7%) had hypercalcemia. Seventeen patients (57%) showed bone-exclusive metastases, and 13 (43%) had distant metastases in other organs. Eleven patients (37%) had monostotic metastases (solitary BM), and 19 patients (63%) had polyostotic metastases (multiple BM). When combined, 9 patients (30%) showed bone-exclusive and monostotic metastases. The most commonly affected site was the thoracolumbar spine, accounting for 34% of total BM, followed by the pelvis (24%), shoulder and thorax (21%), and the extremities (17%). Notably, metastases to bones above the clavicle (craniofacial bones and cervical spine) accounted for only 3% of all bone lesions. CT images showed variable morphologic patterns with osteolytic type in 17 patients (57%), intertrabecular in 7 (23%), osteoblastic in 4 (13%), and mixed in 2 (7%). Systematic chemotherapy for BM was performed in 19 patients and radiotherapy in 18. The median survival time for patients with bone-exclusive and monostotic metastases was significantly longer than that for patients with multi-organ metastases or polyostotic metastases at 18.2 months vs. 5.7 months (p=0.02). Neither chemotherapy nor radiotherapy extended OS. CONCLUSION: Thirty percent of BM cases from HNSCC showed bone-exclusive and monostotic metastases. These patients tended to show a more favorable prognosis than patients with multi-organ metastases or polyostotic metastases.

Aberrant HER3 ligand heregulin-expressing head and neck squamous cell carcinoma is resistant to anti-EGFR antibody cetuximab, but not second-generation EGFR-TKI.

The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is standard therapy for head and neck squamous cell carcinoma (HNSCC). However, most HNSCC tumors are resistant to it and require alternative treatments. Here, we explored the mechanism of cetuximab resistance and evaluated its clinical relevance in HNSCC. An unbiased comprehensive transcriptome analysis was performed on cetuximab-resistant HNSCC FaDuCR cells. The causative resistance genome was knocked down with siRNA, cell signaling was immunologically analyzed, and drug efficacy was evaluated in vitro and in vivo. The mRNA in situ hybridization (ISH) of the causative genome was performed using 28 excised HNSCC tumors and its relationship with cetuximab efficacy was analyzed. FaDuCR cells were resistant to cetuximab, whereas parental FaDu cells were susceptible to it. FaDuCR cells expressed consistently higher levels of phosphorylated Akt than FaDu cells despite cetuximab exposure. A comprehensive transcriptome analysis revealed that the HER3-ligand heregulin was upregulated in FaDuCR cells compared to FaDu cells. Heregulin knockdown in FaDuCR cells repressed HER3 and Akt phosphorylation and recovered cetuximab anticancer efficacy. In contrast, pan-HER family tyrosine kinase inhibitors such as afatinib decreased HER3 and Akt phosphorylation in FaDuCR cells and inhibited FaDuCR tumor growth. Two of the 28 HNSCC tumor samples presented aberrant heregulin expression comparable to that of FaDuCR cells and were resistant to cetuximab therapy. In HNSCC, heregulin-mediated HER3-Akt activation causes resistance to cetuximab but not to second-generation EGFR-tyrosine kinase inhibitors. Subpopulations with aberrant heregulin-expressing HNSCC might be resistant to cetuximab.

Spontaneously infarcted parotid tumours: MRI findings.

OBJECTIVES: To report MRI findings of spontaneous infarction in parotid tumours. METHODS: 14 patients (13 male, 1 female; mean age 73 years) with spontaneously infarcted parotid tumours were reviewed retrospectively. MR images were assessed for the location, the presence of synchronous parotid masses, margin characteristics, signal intensity on T 1 and T 2 weighted images, and internal architecture according to the distribution of T 2 signal hyperintensity. RESULTS: 12 tumours were located in the parotid tail and 2 in the superficial lobe. Synchronous parotid masses were seen in four tumours, three of which were located in the ipsilateral parotid tail and one in the contralateral parotid tail. Seven tumours had well-defined margins and seven had ill-defined margins. The signal intensities on T 1 weighted images were a mixture of high and intermediate in all cases; in 11 tumours, hyperintense areas were dominant. On T 2 weighted images, all tumours also showed a mixture of high and intermediate signal intensities. Internal architectures on T 2 weighted images were mosaic hyperintensity in three tumours, central hyperintensity in five, and multiseparated hyperintensity in six. CONCLUSIONS: Spontaneously infarcted parotid tumours were mostly located in the parotid tail and showed mixed signal intensities with predominant hyperintensity on T 1 weighted images. Half of the tumours had ill-defined margins, and the internal architectures varied.

Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial Clinical Experience and Validation of Clinical Staging.

AIM: To evaluate the clinical results of two-step intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. PATIENTS AND METHODS: Eighty patients were treated with two-step IMRT between 2002 and 2014. Whole-neck radiotherapy (44.0-50.0 Gy/22-25 fractions) was delivered by IMRT, followed by boost IMRT to the high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Forty-seven patients received concurrent chemotherapy. Immunohistochemistry for human papillomavirus type 16 (HPV/p16) was performed for 64 patients. RESULTS: The 5-year overall survival and locoregional control rates for stage I, II, III, and IVA-B disease were 80.0%, 75.0%, 78.0%, and 64.0% and 100.0%, 75.0%, 92.0%, and 82.0%, respectively. Overall survival was significantly higher in HPV/p16-positive patients than in HPV/p16-negative patients (p=0.01). Xerostomia of grade 2 or more was noted in 10 patients. CONCLUSION: Favourable overall survival and locoregional control rates with excellent salivary preservation were obtained using the two-step IMRT method for oropharyngeal cancer.

Metastases to the parotid nodes: CT and MR imaging findings.

OBJECTIVES: To present and characterize CT and MR imaging findings of metastases to the parotid nodes. METHODS: CT (n = 10) and MR (n = 11) images from 14 patients with metastases to the parotid nodes were reviewed. The primary tumour sites were the ocular adnexa in five patients, facial skin in four patients, upper aerodigestive tract in four patients and thyroid gland in one patient. CT and MR images were evaluated with emphasis on the size and number of parotid tumours, their location in the parotid gland, the presence of associated clinically pathological cervical nodes or previous history of cervical node metastasis, margin characteristics and the presence of central necrosis. RESULTS: A total of 18 tumours were identified in 14 patients, with an average maximal cross-sectional diameter of 19 mm (7-44 mm). 12 patients had a single parotid tumour and 2 patients had unilateral multiple tumours; 12 tumours in 10 patients were located in the parotid tail, 6 tumours in 4 patients were located in the superficial lobe and no tumour was noted in the deep lobe. In the superficial lobe, four of six tumours were located in the pretragal area. Three of nine patients whose primary sites were the ocular adnexa or skin had associated clinically pathological cervical nodes. None of these patients had a previous history of cervical node metastasis. All five patients with other primary sites had associated pathological cervical nodes or a history of such. 11 tumours had well-defined margins and 7 tumours had ill-defined margins. Post-contrast images showed central necrosis in 2 of 11 tumours. CONCLUSIONS: Metastases to the parotid nodes tend to present as solitary parotid masses with two preferential sites.

Superselective intra-arterial chemotherapy with concurrent radiotherapy for advanced parotid squamous cell carcinoma: a case report.

A case of advanced parotid cancer in which long-term control was achieved by superselective intra-arterial cisplatin infusion with concomitant radiotherapy is reported. A 63-year-old woman with parotid squamous cell carcinoma was referred to our hospital. Magnetic resonance images revealed extraparotid extension of the tumor, indicating that complete resection would be difficult. Consequently, intra-arterial cisplatin infusion with concomitant radiotherapy was planned as an alternative therapy. Superselective intra-arterial infusion of cisplatin (100 mg/m(2)) was performed six times, at intervals of 7-9 days. The arteries chosen for superselective infusion were the posterior auricular artery, the transverse facial artery and the intrinsic parotid artery originating directly from the external carotid artery. Concurrently, external radiotherapy of a total of 50 Gy in 25 fractions was also performed. The patient achieved a complete response and has remained free of disease recurrence 5 years after treatment. Intra-arterial cisplatin infusion with concomitant radiotherapy can be a practical option for patients with unresectable parotid squamous cell carcinoma.

Cytopathological review of patients that underwent thyroidectomies based on the diagnosis of papillary thyroid carcinoma by fine needle aspiration cytology but were later found to have benign tumors by histopathology.

PURPOSE: The aim of this study is to evaluate the specificity of diagnosing PTC by fine needle aspiration (FNA) cytology. METHODS: This study retrospectively reviewed the cytopathological reports of 1066 patients that underwent thyroidectomy based on a diagnosis of PTC by FNA between January 1993 and December 2008. This study re-evaluated the cytology and histopathology of the patients that received false positive diagnoses of PTC by FNA. RESULTS: Ten patients (0.9 %) received false positive diagnoses of PTC by FNA. Three patients were overdiagnosed as having PTC by FNA cytology. In contrast, the nuclear features of PTC in the other seven cases were confirmed by the retrospective reviews of the patients' FNA cytology. Three of the seven patients showed follicular structures in their resection specimens, thus resulting in a diagnosis of either adenomatous goiter or follicular adenoma. However, PTC could not be diagnosed by histopathology in the remaining four patients, even though the histopathology showed the nuclear features of PTC. CONCLUSIONS: Most cases of PTC can be easily diagnosed by cytological and morphological atypia with certain limitations. The difficulty in diagnosing PTC by cytology is because the pathological features of PTC also occur in some benign thyroid tumors. Therefore, immunohistochemical or molecular biological approaches must be combined with current cytological diagnostic techniques for the diagnosis of PTC.