Deep learning-based multimodal segmentation of oropharyngeal squamous cell carcinoma on CT and MRI using self-configuring nnU-Net.

PURPOSE: To evaluate deep learning-based segmentation models for oropharyngeal squamous cell carcinoma (OPSCC) using CT and MRI with nnU-Net. METHODS: This single-center retrospective study included 91 patients with OPSCC. The patients were grouped into the development (n = 56), test 1 (n = 13), and test 2 (n = 22) cohorts. In the development cohort, OPSCC was manually segmented on CT, MR, and co-registered CT-MR images, which served as the ground truth. The multimodal and multichannel input images were then trained using a self-configuring nnU-Net. For evaluation metrics, dice similarity coefficient (DSC) and mean Hausdorff distance (HD) were calculated for test cohorts. Pearson's correlation and Bland-Altman analyses were performed between ground truth and prediction volumes. Intraclass correlation coefficients (ICCs) of radiomic features were calculated for reproducibility assessment. RESULTS: All models achieved robust segmentation performances with DSC of 0.64 ± 0.33 (CT), 0.67 ± 0.27 (MR), and 0.65 ± 0.29 (CT-MR) in test cohort 1 and 0.57 ± 0.31 (CT), 0.77 ± 0.08 (MR), and 0.73 ± 0.18 (CT-MR) in test cohort 2. No significant differences were found in DSC among the models. HD of CT-MR (1.57 ± 1.06 mm) and MR models (1.36 ± 0.61 mm) were significantly lower than that of the CT model (3.48 ± 5.0 mm) (p = 0.037 and p = 0.014, respectively). The correlation coefficients between the ground truth and prediction volumes for CT, MR, and CT-MR models were 0.88, 0.93, and 0.9, respectively. MR models demonstrated excellent mean ICCs of radiomic features (0.91-0.93). CONCLUSION: The self-configuring nnU-Net demonstrated reliable and accurate segmentation of OPSCC on CT and MRI. The multimodal CT-MR model showed promising results for the simultaneous segmentation on CT and MRI. CLINICAL RELEVANCE STATEMENT: Deep learning-based automatic detection and segmentation of oropharyngeal squamous cell carcinoma on pre-treatment CT and MRI would facilitate radiologic response assessment and radiotherapy planning. KEY POINTS: • The nnU-Net framework produced a reliable and accurate segmentation of OPSCC on CT and MRI. • MR and CT-MR models showed higher DSC and lower Hausdorff distance than the CT model. • Correlation coefficients between the ground truth and predicted segmentation volumes were high in all the three models.

Are second primary head and neck cancers with previous hematological malignancy more aggressive than de novo head and neck cancers?

OBJECTIVES: Secondary solid tumors can occur after the treatment of hematological malignancies and are associated with a poor prognosis. We evaluated the survival outcomes of patients with second primary head and neck cancers according to the site of cancer origin, type of hematological malignancy, and age. MATERIALS AND METHODS: We enrolled all patients who underwent surgery for second primary head and neck cancer and were previously treated for hematological malignancy between 1997 and 2020. We analyzed the survival outcomes of patients with second primary head and neck cancer, and compared them with 3126 de novo head and neck cancer patients diagnosed during the same period at our hospital. RESULTS: The 5-year overall survival (OS) rate was significantly worse for second primary head and neck cancer patients than de novo cancer patients (52.0 % and 77.9 %, respectively; p = 0.04) and those results were similarly observed in second primary oral cavity cancer (33.3 % and 75.7 %, respectively; p < 0.01). Patients with myelodysplastic syndrome and acute myeloid leukemia showed significantly worse 5-year OS rate than those with other types of hematological malignancies (p = 0.036). Multivariate analysis showed that bone marrow transplantation (BMT) was a risk factor for the recurrence of head and neck cancers (odds ratio = 6.635, p = 0.042). CONCLUSION: Patients with second primary head and neck cancer, particularly of the oral cavity, had a worse prognosis than patients with de novo head and neck cancer. BMT predicts recurrence in second primary head and neck cancer patients.

Persistent subjective voice symptoms for two years after thyroidectomy.

BACKGROUND: Voice change after thyroidectomy is an important issue in thyroid surgery. However, little is known about long-term voice outcomes after thyroidectomy. This study investigates the long-term voice outcomes of thyroidectomy up to two years after surgery. Also, we analyzed the pattern of recovery through acoustic tests over time. METHODS: We reviewed data from 168 patients who underwent thyroidectomy between January 2020 and August 2020 at a single institution. The Thyroidectomy-related Voice and Symptom Questionnaire (TVSQ) score and acoustic voice analysis results were examined preoperatively and postoperative one, three, and six months, and one and two years after surgery. We divided patients into two groups based on the TVSQ score (≥15 or <15) at two years postoperatively. We investigated the difference of acoustic characteristics between the two groups and analyzed correlations between acoustic parameters and various clinical and surgical factors. RESULTS: Voice parameters tended to recover, but some parameters and TVSQ scores exhibited deterioration two years after surgery. In the subgroups, among the many clinicopathologic factors examined, voice abuse history including professional voice users (p = 0.014), greater extent of thyroidectomy and neck dissection (p = 0.019, p = 0.029), and high pitch voice (F0; p = 0.005, SFF; p = 0.016) were associated with high TVSQ score at two years. CONCLUSIONS: Patients frequently experience voice discomfort after thyroidectomy. After surgery, voice abuse history including professional voice users, greater extent of surgery, and higher pitch voice are associated with worse voice quality and increased risk of persistent voice symptoms over the long-term.

The Role of Open Conservation Surgery in the Era of Minimally Invasive Surgery for Hypopharyngeal Cancer.

Background and Objectives: Total laryngectomy with partial pharyngectomy is traditionally the principal curative treatment for hypopharyngeal cancer; however, conservative surgical approaches that minimize functional disability are attracting increasing interest. Thus, we evaluated the appropriateness and oncological outcomes of open conservation surgery for such patients. Materials and Methods: We reviewed the medical records of 49 patients who underwent vertical hemipharyngolaryngectomy from 1998 to 2018 at a single institution. Results: Locoregional recurrences developed in 19 patients (38.8%) and distant metastases in 6 (12.2%). Histopathologically, paraglottic space invasion was apparent in 13 patients (26.5%), pre-epiglottic space invasion in 4 (8.2%), thyroid cartilage invasion in 9 (18.4%), thyroid gland invasion in 2, perineural invasion in 11 (22.4%), and lymphovascular invasion in 35 (71.4%). The 5-year overall survival of patients who underwent open conservation surgery was comparable to that of patients who underwent total laryngectomy with partial pharyngectomy (68.7% vs. 48.4%, p = 0.14). Pre-epiglottic space invasion significantly decreased the 5-year disease-free survival rate after open conservation surgery (69.7% vs. 17.9%, p = 0.01). Conclusions: We found that pre-epiglottic space invasion negatively impacted disease control after open conservation surgery, emphasizing the crucial role played by a preoperative evaluation during patient selection.

Sonographicdetectionof a metastatic lingual lymph node in a patient with tongue cancer.

A 41-year-old male was diagnosed with tongue cancer. Preoperative imaging revealed no metastatic lymph nodes. Intraoperative sonography detected a minute hypoechoic lesion in the sublingual space. A pea-sized mass was found during dissection of that space and histopathology revealed a metastatic lymph node. The lingual lymph node should routinely be evaluated sonographically prior to surgical resection of tongue cancer.

Neoadjuvant chemotherapy followed by surgery for HPV-associated tonsillar cancer: Does imaging reflect the pathological response?

OBJECTIVES: The purpose of this study was to present our evaluation of the outcome of tonsillar cancer managed with neoadjuvant chemotherapy followed by surgery as definitive treatment. MATERIALS AND METHODS: Thirty-eight patients with human papilloma virus (HPV)-associated tonsillar cancer were treated with neoadjuvant chemotherapy followed by surgery. The volume reduction response of the tumor to neoadjuvant chemotherapy was evaluated and verified by histopathology. RESULTS: The complete pathologic response (pCR) rates at primary and nodal sites were 60 % and 45 %. Tumor volume reduction ≥78.8 % following neoadjuvant chemotherapy predicted pCR of the cervical node. In addition, the optimal cut-off value to predict pCR at the primary tumor site was 83.4 % volume reduction but was not a significant result. For pCR, neoadjuvant chemotherapy decreased the pathological adverse features, significantly reducing the need for adjuvant therapy. The overall survival of the adjuvant group was 79.2 %, and that of the non-adjuvant group was 87.5 %, with disease-free survival of 65.9 % and 54.2 %. There was no significant difference between the two groups. CONCLUSION: Neoadjuvant chemotherapy followed by surgery proved to be a good therapeutic option for management of HPV-associated tonsillar cancer. A greater reduction in tumor volume in post-neoadjuvant chemotherapy imaging predicts a complete pathologic response.

Perineural Invasion Predicts Local Recurrence and Poor Survival in Laryngeal Cancer.

(1) Background: Perineural invasion (PNI) in head and neck cancer is associated with a poor prognosis; however, the effect of PNI on the prognosis of laryngeal cancer remains under debate. This retrospective study aimed to investigate the effect of PNI in fresh or salvaged larynges on survival in patients who had undergone laryngectomy for squamous cell carcinoma. (2) Methods: This study enrolled 240 patients diagnosed with laryngeal cancer who had undergone open surgery at Seoul St. Mary's Hospital, Korea. The effects of PNI, other histopathologic factors, and treatment history on survival and recurrence patterns were assessed. (3) Results: PNI was observed in 30 of 240 patients (12.5%). PNI (HR: 3.05; 95% CI: 1.90-4.88; p = 0.01) was a significant predictor of poor 5-year disease-free survival. In fresh cases, preepiglottic invasion (HR: 2.37; 95% CI: 1.45-3.88; p = 0.01) and PNI (HR: 2.96; 95% CI: 1.62-2.96; p = 0.01) were negative prognostic factors for 5-year disease-free survival. In the salvage group, however, only PNI (HR: 2.74; 95% CI: 1.26-5.92; p = 0.01) was a significant predictor of disease-free survival. Further, PNI significantly influenced high local recurrence (HR: 5.02, 95% CI: 1.28-9.66; p = 0.02). (4) Conclusions: Independent of treatment history, PNI is a prognostic factor for poor survival and local recurrence in laryngeal cancer.

Oncologic and functional outcomes of neoadjuvant chemotherapy followed by surgery in human papillomavirus-positive tonsillar cancer.

BACKGROUND: Functional outcomes of neoadjuvant chemotherapy in human papillomavirus (HPV)-positive tonsillar cancer remained unclear. METHODS: We retrospectively reviewed the medical records of HPV-positive patients with tonsillar cancer. Of 112 patients, 38 were assigned to a neoadjuvant chemotherapy group and 74 were assigned to an upfront surgery group. RESULTS: Pathological analyses showed that the risks of close or positive resection margins and lymphovascular invasion were lower in patients who received neoadjuvant chemotherapy. The 5-year disease-free survival was significantly higher in the neoadjuvant chemotherapy group than in the upfront surgery group, but the 5-year overall survival was not. The time to commencement of oral feeding and the mean hospital stay were significantly shorter in the neoadjuvant chemotherapy group. The neoadjuvant chemotherapy group was more likely than the upfront surgery group to resume a regular diet. CONCLUSIONS: Compared with upfront surgery, neoadjuvant chemotherapy improved the functional outcomes and 5-year disease-free survival.

Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions.

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances.

Predictive Value of 18F-Fluorodeoxyglucose Positron-Emission Tomography Metabolic and Volumetric Parameters for Systemic Metastasis in Tonsillar Cancer.

Although the prognosis of tonsillar cancer (human papillomavirus-positive oropharyngeal squamous cell carcinoma) is improving, disease control failure (distant metastasis) still occurs in some cases. We explored whether several 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) parameters can predict metastasis. We retrospectively reviewed the medical records of 55 patients with tonsil squamous cell carcinoma who underwent pretreatment 18F-FDG positron-emission tomography/computed tomography (PET/CT) followed by primary surgery. During the follow-up period, systemic metastases were found in 7 of the 55 patients. The most common sites were the lungs (33%), bone (22%), brain/skull base (22%), small bowel (11%), and liver (11%). Pathologically, P53 mutation was less common in patients with systemic metastasis (41.7% vs. 14.3%, p = 0.054) than without systemic metastasis. In terms of PET parameters, the metabolic tumor volume (MTV2.5) and total lesion glycolysis (TLG2.5) values were lower in the primary tumor, and higher in the metastatic lymph nodes, of human papillomavirus (HPV)-positive compared to HPV-negative patients (all p < 0.05). The MTV2.5, TLG2.5, and tumor−to−liver uptake ratio were 36.07 ± 54.24 cm3, 183.46 ± 298.62, and 4.90 ± 2.77, respectively, in the systemic metastasis group, respectively; all of these values were higher than those of the patients without systemic metastasis (all p < 0.05). The MTV2.5 value was significantly different between the groups even when the values for the primary tumor and metastatic lymph nodes were summed (53.53 ± 57.78 cm3, p = 0.036). The cut-off value, area under the curve (95% confidence interval), sensitivity, and specificity of MTV2.5 for predicting systemic metastasis were 11.250 cm3, 0.584 (0.036−0.832), 0.571, and 0.565, respectively. The MTV2.5 of metastatic lymph nodes and summed MTV2.5 values of the primary tumor and metastatic lymph nodes were significantly higher in tonsillar cancer patients with than without systemic metastases. We suggest PET/CT scanning for pre-treatment cancer work-up and post-treatment surveillance to consider additional systemic therapy in patients with a high risk of disease control failure.

Use of a combination of N-acetylcysteine and clonazepam to treat burning mouth syndrome.

OBJECTIVE: This study was intended to evaluate the clinical efficacy of a combination of N-acetylcysteine (NAC) and clonazepam for treatment of burning mouth syndrome (BMS). STUDY DESIGN: A total of 160 patients with BMS were divided into 3 groups: group 1 received NAC (400 mg/d), group 2 received clonazepam (0.5 mg/d), and group 3 received both NAC and clonazepam. We evaluated symptom relief after 8 weeks of treatment using a visual analog scale (VAS). To assess oral health-related quality of life, we used the validated Korean version of an oral health impact profile (OHIP-14K). RESULTS: The overall response rates of the 3 groups were 60.3%, 51.3%, and 80.0%, respectively. The mean VAS and OHIP-14K scores significantly decreased in all groups after the 8-week treatments. The VAS score changes were -12.2 ± 19.5, -10.0 ± 14.1, and -21.0 ± 24.6, respectively (P = .001), in the 3 groups and the OHIP-14K changes were -2.3 ± 9.2, -4.4 ± 6.9, and -8.7 ± 10.3, respectively (P = .020). Group 3 showed significantly larger differences in VAS and OHIP-14K scores than group 2, before and after treatment. CONCLUSIONS: In the treatment of BMS, the NAC/clonazepam combination therapy was more effective than either monotherapy.