Predictive factors for dissection-free sentinel node micrometastases in early oral squamous cell carcinoma.

This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria.

Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

p16-positive oropharyngeal cancer with rare thyroid metastasis†: A case report.

Thyroid metastasis is rarely diagnosed, and the treatment outcomes in p16-positive oropharyngeal squamous cell carcinoma patients with rare thyroid metastasis have not been fully investigated. Here we describe the case of a patient with p16-positive oropharyngeal squamous cell carcinoma who was diagnosed with cT4 N2M1 with rare thyroid metastasis. The patient was a current smoker and was positive for human papillomavirus DNA, with disease progression at 49 days and death at 113 days after completion of cisplatin-based concurrent chemoradiotherapy. J. Med. Invest. 67 : 189-191, February, 2020.

Prognostic value of lymph node density for major salivary gland carcinoma without clinical lymph node metastasis.

BACKGROUND AND OBJECTIVE: This study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis. METHODS: Sixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes. RESULTS: An LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS. CONCLUSION: Results demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis.

Combination of Cetuximab and Oncolytic Virus Canerpaturev Synergistically Inhibits Human Colorectal Cancer Growth.

The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro. Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer.

Epithelioid hemangioendothelioma of the parotid gland: a case report.

We present the case of a patient with epithelioid hemangioendothelioma of the parotid gland. A 70-year-old female developed swelling and pain in the lower part of the left ear 18 months previously and had visited a local hospital. Fine-needle aspiration cytology revealed no definitive diagnosis, but incisional biopsy under local anesthesia suggested epithelioid hemangioendothelioma. She was then transferred to our hospital, where she underwent total extirpation of the left parotid gland, left cervical lymph node dissection, and postoperative radiation therapy. However, she died from distant metastases 13 months after surgery. No previous study has reported any case of distant metastasis or death due to epithelioid hemangioendothelioma of the parotid gland. To the best of our knowledge, this is the first case report on distant metastasis and death due to the development of parotid gland cancer.

Uptake of 18F-Fluorodeoxyglucose in Major Salivary Gland Cancer Predicts Survival Adjusting for Pathological Stage.

AIM: To investigate whether 18F-fluorodeoxyglucose uptake is associated with overall survival in patients with major salivary gland cancer using univariate and multivariate analyses after adjusting for pathological stage (eighth edition of the International Union Against Cancer). PATIENTS AND METHODS: A total of 32 patients with major salivary gland cancer treated with curative surgery were enrolled. Parameters for 18F-fluorodeoxyglucose uptake were assessed by positron-emission tomography combined with computed tomography. RESULTS: Using univariate and multivariate analyses after adjusting for pathological stage, a maximum standardized uptake value ≥26, peak standardized uptake value ≥20.3, metabolic tumor volume ≥9.7, and total lesion glycolysis ≥263 were significantly correlated with shorter overall survival. CONCLUSION: Parameters of 18F-fluorodeoxyglucose uptake in major salivary gland cancer are predictive of overall survival after adjusting for the pathological stage.

Treatment package time predicts cancer-specific survival and distant metastasis in laryngeal cancer.

We investigated whether treatment package time was significantly associated with survival outcomes of resectable locally-advanced laryngeal squamous cell carcinoma in patients who consecutively underwent various treatments, including surgery alone and salvage surgery for residual tumor. A total of 100 patients with clinical T3-T4 resectable laryngeal squamous cell carcinoma were enrolled in this study. The treatment package time was calculated in days between the start of any treatment and the end of all treatments, including postoperative radiotherapy and salvage surgery for residual tumors. Using a log-rank test, a treatment package time of ≥68 days showed significantly shorter cancer-specific (P=0.0013) and distant metastasis-free survival (P=0.0017), compared with a treatment package time of <68 days. Multivariate survival analyses of two Cox's hazards proportional models was conducted. In both model-1, which adjusted for cT3/cT4, cN0-1/cN2-3 and total laryngectomy/non-total laryngectomy, and model-2, which adjusted for cT3/cT4, cN0-1/cN2-3 and induction therapy/non-induction therapy, the cancer-specific survival and distant metastasis-free survival, according to treatment package time, were significantly longer with <68 days compared with ≥68 days (P<0.01). The present study demonstrated that a prolonged treatment package time is a prognostic factor for shorter cancer-specific and distant metastasis-free survival after various treatments for resectable locally-advanced laryngeal cancer.

Superficial Esophageal Cancer in a Fanconi Anemia Patient That Was Treated Successfully by Endoscopic Submucosal Resection.

Fanconi anemia (FA) is a disorder of chromosomal fragility characterized by progression to aplastic anemia, myelodysplastic syndrome, and leukemia. FA patients are also predisposed to solid cancers. A case of FA in an adult patient who developed tongue and superficial esophageal cancers following hematopoietic stem cell transplantation is reported. This case was considered significant because it is the first reported case of superficial esophageal cancer in an FA patient that was treated successfully by endoscopic submucosal resection.

Primary Tumor Size Predicts Distant Metastasis of Mucosal Malignant Melanoma in Head and Neck.

BACKGROUND/AIM: To investigate the possible association between primary tumor size and overall survival and/or distant metastasis-free survival of patients with mucosal malignant melanoma of the head and neck. PATIENTS AND METHODS: A total of 25 patients that have had primary tumor resection were enrolled in this study. Primary tumor size was assessed as the maximum size of the primary tumor in pathological and surgical reports. RESULTS: Patients with a primary tumor size of ≥43 mm showed a significant association with shorter overall survival (p=0.007) and distant metastasis-free survival (p=0.005) by the log-rank test. Multivariate survival analyses of two Cox's hazards proportional models showed that, in model1, pT4a-4b (p=0.01) and primary tumor size ≥43 mm (p=0.03) were significantly associated with shorter overall survival, and primary tumor size ≥43 mm (p=0.02) was significantly associated with shorter distant metastasis-free survival. In model2, pStage IVA-IVB (p=0.02) and primary tumor size ≥43 mm (p=0.03) were significantly associated with shorter overall survival, and primary tumor size ≥43 mm (p=0.02) was significantly associated with shorter distant metastasis-free survival. CONCLUSION: Large tumor size (≥43 mm) is a predictor of shorter overall survival and distant metastasis-free survival after primary tumor resection of mucosal malignant melanoma of the head and neck.

Prognostic Markers in Head and Neck Cancer Patients Treated with Nivolumab.

To investigate whether peripheral blood biomarkers predict the outcome of anti-PD-1 antibody treatment for head and neck squamous cell carcinoma (HNSCC). Patients treated with nivolumab for platinum-refractory recurrent or metastatic HNSCC were retrospectively reviewed. Fifty-three patients treated between April 2017 and March 2018 were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 2.5 and 8.7 months, respectively. In the univariate analysis, performance status (PS) ≥ 3, relative neutrophil count ≥ 0.65, relative lymphocyte count ≥ 0.17, and relative eosinophil count (REC) ≥ 0.015 were significantly associated with both PFS and OS. On multivariate analysis, PS ≥ 3 and REC ≥ 0.015 were significantly associated with PFS and OS. Low REC and poor PS were independent poor prognostic factors for both PFS and OS in patients with recurrent or metastatic HNSCC treated with nivolumab.

Gross tumor volume in sinonasal tract cancer as a predictor of local recurrence after chemoradiotherapy.

OBJECTIVE: This study investigated whether gross tumor volume of the primary tumor before treatment was a predictor for local recurrence in patients with resectable sinonasal tract squamous cell carcinoma who were treated by chemoradiotherapy. METHODS: A total of 24 patients were enrolled. Pretreatment gross tumor volume of primary tumor was assessed by palpitation, perception and imaging. The cut-off value of the gross tumor volume for local recurrence was determined by receiver-operating curve analysis. A log-rank test and Cox's proportional hazards model were used for univariate and multivariate analyses with adjustment for the clinical T category (cT1-T4a/cT4b), respectively. RESULTS: In the univariate analysis, patients with the gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.0023) and disease-free survival (P = 0.0064) than those with gross tumor volume <83.7 ml. In the multivariate analysis, gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.041). CONCLUSIONS: Pretreatment gross tumor volume of primary tumor ≥83.7 ml was significantly associated with local recurrence-free rate in resectable sinonasal tract squamous cell carcinoma.

Peak of Standardized Uptake Value in Oral Cancer Predicts Survival Adjusting for Pathological Stage.

BACKGROUND/AIM: To predict survival outcomes of different patients with the same stage of disease is difficult. The possible correlation between 18F-fluorodeoxyglucose (18F-FDG) uptake parameters and survival outcomes was investigated in oral squamous cell carcinoma patients by multivariate analysis adjusted for the pathological stage according to the 8th edition of the tumor-node-metastasis (TNM) classification of the Union for International Cancer Contro. PATIENTS AND METHODS: 18F-FDG-uptake parameters of 28 patients were assessed by positron emission tomography with computed tomography (PET/CT). RESULTS: A peak of standardized uptake value of primary tumor (p-SUVpeak) of ≥14.1 was significantly correlated with shorter overall survival by univariate and multivariate analyses adjusted for the pathological TNM stage. A p-SUVpeak of ≥14.1 was significantly associated with shorter local recurrence-free survival and disease-free survival. CONCLUSION: A higher p-SUVpeak on pretreatment 18F-FDG-PET/CT is a prognostic parameter of identifying lower survival outcomes.

Lymph node density in papillary thyroid carcinoma is a prognostic factor after adjusting for pathological stage.

We investigated the possible association between the lymph node density and survival outcomes in differentiated papillary thyroid carcinoma, and examined whether the lymph node density was a predictor in a multivariate analysis adjusted for the pathological stage in the eighth edition of the Union for International Cancer Control Tumor-Node Metastasis Classification of Malignant Tumors. A total of 543 patients with papillary thyroid carcinoma were enrolled. We performed restaging according to the eighth edition. The lymph node density was the ratio between number of positive lymph nodes and total number of excised lymph nodes. A log-rank test and Cox's proportional hazards model were used for univariate and multivariate analysis with adjustment for the pathological stage in the eighth edition, respectively. In both the univariate and multivariate analyses of 150 patients with pN1bM0, the presence of a lymph node density of ≥ 0.3 with pN1b was significantly associated with shorter disease-specific survival. In both the univariate and multivariate analyses of all 543 patients, a lymph node density of ≥ 0.3 with pN1b were also significantly associated with shorter overall and disease-specific survival. In conclusion, these results suggest that the lymph node density can be used as a predictor for the survival outcomes after adjustment for the pathological stage in the eighth edition.

Total lesion glycolysis on FDG-PET/CT before salvage surgery predicts survival in laryngeal or pharyngeal cancer.

We investigated whether 18F-fluorodeoxyglucose uptake parameters using positron emission tomography combined with computed tomography predicts several survival outcomes, including lung metastasis-free survival, in patients with laryngeal or pharyngeal cancer who underwent salvage surgery. The maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were calculated as 18F-fluorodeoxyglucose uptake parameters in 51 patients with laryngeal or pharyngeal cancer before salvage surgery. In univariate analysis, the maximum standardized uptake value ≥ 22.8, metabolic tumor volume ≥ 2.4, and total lesion glycolysis ≥ 5.4 were significantly correlated with shorter overall survival. In multivariate analysis with adjustment for clinical stage, patients with total lesion glycolysis ≥ 5.4 exhibited significantly shorter overall survival. Furthermore, total lesion glycolysis ≥ 5.4 was significantly correlated with shorter disease-specific survival, distant metastasis-free survival, and lung metastasis-free survival in univariate analysis. In conclusion, total lesion glycolysis predicts the survival outcomes including lung metastasis in patients with laryngeal or pharyngeal cancer who underwent salvage surgery.

The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. METHODS: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. RESULTS: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. CONCLUSION: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.

Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma.

PURPOSE: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. MATERIAL AND METHODS: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. RESULTS: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. CONCLUSION: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.

Comparison between chemoselection and definitive radiotherapy in patients with cervical esophageal squamous cell carcinoma.

BACKGROUD: Laryngeal preservation is an important consideration when treating cervical esophageal cancers (CECs) such as laryngeal cancer. The standard treatment for CEC allowing laryngeal preservation is chemoradiotherapy. However, in cases of laryngeal cancer, chemoselection has also been applied as a treatment strategy that promotes larynx preservation. This strategy involves assigning the appropriate radical treatment according to the primary tumor's response to induction chemotherapy. Since there have been no studies of the application of chemoselection in CEC cases, the present study compared the results, including laryngeal preservation rates, obtained upon applying chemoselection and chemoradiotherapy to CEC. STUDY DESIGN: This was a retrospective cohort study of cervical esophageal squamous cell carcinoma patients treated using chemoselection or chemoradiotherapy at Aichi Cancer Center Hospital between January 2000 and March 2013. A total of 42 patients were enrolled. RESULTS: The 2-year overall survival and laryngeal preservation rates for the chemoselection group versus the primary radiotherapy group were 65.1 and 57.3 versus 40 and 83.3%, respectively (P = 0.017 and P = 0.122, respectively). The 2-year locoregional control rates for the chemoselection and primary radiotherapy groups were 68 and 25%, respectively (P = 0.045). CONCLUSION: The chemoselection group achieved favorable results. Therefore, chemoselection can be applied as a treatment strategy for CEC.

Lymph node ratio predicts survival in hypopharyngeal cancer with positive lymph node metastasis.

The lymph node density (LND) has been reported to be a significant prognostic factor in various types of carcinoma. This study investigated whether the LND is associated with survival in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who have positive lymph nodes without distant metastasis. Forty-six patients who were pathologically diagnosed with HPSCC with positive lymph nodes and without distant metastasis were enrolled in this study. The LND was defined as the ratio of positive lymph nodes to the total number of lymph nodes. An LND of ≥0.09 was found to be significantly correlated with a shorter overall (p = 0.044) and disease-specific (p = 0.019) survival according to a log-rank test. In a multivariate survival analysis using a Cox proportional hazards model adjusted for the pathological T category (pT3-4/pT1-2), pathological N category (pN2/pN1) and positive surgical margin and/or extracapsular spread (presence/absence), both an LND of ≥0.09 and pT3-4 category were associated with significantly shorter overall survival (p < 0.01) and disease-specific survival (p < 0.01). These results suggest that the LND functions as a prognostic factor for HPSCC patients with positive lymph nodes who do not have distant metastasis.

The Charlson comorbidity index is a prognostic factor in sinonasal tract squamous cell carcinoma.

OBJECTIVE: High Charlson comorbidity index values have been reported to be associated with shorter overall survival in various types of cancer. We investigated whether Charlson comorbidity index values were correlated with overall survival in patients with resectable sinonasal tract squamous cell carcinoma. METHODS: Seventy-nine patients with resectable sinonasal tract squamous cell carcinoma were treated with curative intent. The Charlson comorbidity index values were calculated by the summation of the weight scores of 19 medical conditions (other than sinonasal tract squamous cell carcinoma) before treatment. The survival rate was analyzed according to the Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Wilcoxon test and the Cox proportional hazards model, respectively. RESULTS: According to a univariate analysis, a Charlson comorbidity index value ≥6 was found to be significantly correlated with shorter overall survival (P < 0.02). In the multivariate survival analysis with adjustment for the clinical T and N classification, age, sex, anatomical location, treatment group (radiotherapy/surgery) and chemotherapy (presence/absence), a Charlson comorbidity index value ≥6 was found to be associated with the significantly shorter overall survival. CONCLUSIONS: These results suggest that the Charlson comorbidity index functions as a prognostic factor in cases of resectable sinonasal tract squamous cell carcinoma.