Publications by authors named "Daisuke Nishikawa"

41 Publications

Clinical impact of weekly paclitaxel plus cetuximab is comparable to the EXTREME regimen for recurrent/metastatic head and neck squamous cell carcinoma.

Int J Clin Oncol 2021 Apr 5. Epub 2021 Apr 5.

Department of Head and Neck Surgery, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.

Background: Until the emergence of immune checkpoint inhibitors, the EXTREME regimen comprising platinum-based chemotherapy plus cetuximab was the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Recent reports suggest the usefulness of regimens including taxanes in combination with cetuximab as treatment options for R/M HNSCC patients with contraindications for platinum. However, comparisons of weekly paclitaxel plus cetuximab (wPTX-Cmab) to the EXTREME regimen are limited.

Materials And Methods: We compared the clinical impact of wPTX-Cmab to EXTREME as first line treatment for R/M HNSCC in Aichi Cancer Center Hospital. The primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Propensity score-adjusted Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: From 2012 to 2018, 77 patients, including 55 treated with EXTREME and 22 refractory or intolerant to platinum treated with wPTX-Cmab, were analyzed. wPTX-Cmab was comparable to EXTREME on OS [adjusted HR 0.82 (95% CI 0.39-1.48)], PFS [adjusted HR 0.90 (95% CI 0.49-1.65)], ORR [wPTX-Cmab 34.7% (12-43), EXTREME 30.9% (18-43), p = 0.877] and DCR [wPTX-Cmab 72.7% (52-92), EXTREME 65.4% (52-78), p = 0.337]. Survival trends remained similar after stratification by platinum-refractory or intolerance status. Disease control with wPTX-Cmab was significantly associated with better OS [adjusted HR 0.18 (0.05-0.57)].

Conclusion: wPTX-Cmab may be a suitable treatment option for R/M HNSCC patients with contraindications for platinum.
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http://dx.doi.org/10.1007/s10147-021-01907-xDOI Listing
April 2021

Treatment outcome and pattern of recurrence of sinonasal squamous cell carcinoma with EGFR-mutation and human papillomavirus.

J Craniomaxillofac Surg 2021 Feb 22. Epub 2021 Feb 22.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, Japan. Electronic address:

The objective of our study was to clarify the clinical features of EGFR-mutated sinonasal squamous cell carcinoma (SNSCC) and human papilloma virus (HPV)-related SNSCC. Patients with SNSCC treated from April 2008 to June 2019 at our institution were retrospectively reviewed. We examined EGFR mutation and HPV status for all patients. Main outcomes were overall survival, recurrence, and outcome of each treatment modality. A total of 85 patients with SNSCC were enrolled in this study. EGFR mutations and HPV DNA were detected in 24 (28%) and 7 (8%) patients, respectively. Patients with EGFR-mutated SNSCC showed a worse overall survival (OS) than those with EGFR wild-type in the multivariate analysis (p = 0.037). No death was observed in HPV-positive SNSCC. The cumulative incidence of local recurrence was significantly higher in EGFR mutant than EGFR wild-type tumors (p = 0.03). In patients with EGFR mutations, treatment with induction chemotherapy significantly improved OS (p = 0.01). EGFR-mutated SNSCC have a high-risk feature for recurrence and requires intensive attention for treatment and observation. A new treatment approach, such as EGFR tyrosine kinase inhibitors, may be needed.
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http://dx.doi.org/10.1016/j.jcms.2021.02.016DOI Listing
February 2021

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan.

Auris Nasus Larynx 2021 Jun 22;48(3):502-510. Epub 2021 Feb 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC).

Materials And Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy.

Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177).

Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.
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http://dx.doi.org/10.1016/j.anl.2021.01.024DOI Listing
June 2021

Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma.

Cancer Med 2021 Feb 9;10(4):1335-1346. Epub 2021 Feb 9.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC).

Methods: The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme-linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed.

Results: The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis-positive and stage IV disease, in comparison to those with node metastasis-negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse-free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels.

Conclusions: The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis.
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http://dx.doi.org/10.1002/cam4.3737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926025PMC
February 2021

A study of 17 cases for the identification of prognostic factors for anaplastic thyroid carcinoma.

Mol Clin Oncol 2021 Jan 30;14(1). Epub 2020 Oct 30.

Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.

Anaplastic thyroid cancer (ATC) has a poor prognosis. ATC accounts for only 1-2% of all thyroid carcinomas, yet it is one of the most lethal neoplasms in humans. Notably, there are no established treatment protocols for ATC. The present study investigated the prognostic and predictive factors of ATC. A retrospective analysis was conducted on 17 patients with histologically confirmed ATC. The median overall survival of all patients was 3.8 months. In patients under the age of 70 years, the statistically significant prognostic factors indicating longer survival were the absence of distant metastasis and treatment by radical resection. Furthermore, in contrast to previous findings, tumor size and white blood cell count were not associated with ATC prognosis in the present cohort. Importantly, tracheostomy did not contribute to improvement of prognosis and should perhaps not be considered, when unnecessary, to preserve the patient's quality of life. Prognostic factors for ATC are critical to clinicians to enable them to determine which patients will benefit from aggressive treatment strategies, as opposed to supportive care.
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http://dx.doi.org/10.3892/mco.2020.2163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678632PMC
January 2021

Eosinophil prognostic scores for patients with head and neck squamous cell carcinoma treated with nivolumab.

Cancer Sci 2021 Jan 4;112(1):339-346. Epub 2020 Nov 4.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Although nivolumab, a programmed cell death 1 (PD-1) inhibitor, is a standard therapy for platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), no definitive biomarkers have been reported thus far. This study aimed to select promising prognostic markers in nivolumab therapy and to create a novel prognostic scoring system. In this retrospective cohort study, we reviewed patients with R/M HNSCC who were treated with nivolumab from April 2017 to April 2019. We developed a prognostic score for immune checkpoint inhibitor (ICI) therapy that was weighed using hazard ratio-based scoring algorithms. Significant variables were selected from the multivariate Cox proportional hazard analyses on overall survival (OS). A total of 85 patients with HNSCC were analyzed in the present study. The relative eosinophil count (REC), the ratio of eosinophil increase (REI), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were selected as variables affecting the prognostic score. The patients were divided into four groups: very good (score = 0), good (score = 1), intermediate (score = 2), and poor (score = 3). The OS hazard ratios were 2.77, 10.18, and 33.21 for the good, intermediate, and poor risk groups compared with the very good risk group, respectively. The Eosinophil Prognostic Score is a novel prognostic score that is effective for predicting the prognosis of HNSCC patients treated with nivolumab. This score is more precise as it includes changes in biomarkers before and after the treatment.
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http://dx.doi.org/10.1111/cas.14706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780035PMC
January 2021

Patients with vertigo/dizziness of unknown origin during follow-ups by general otolaryngologists at outpatient town clinic.

Auris Nasus Larynx 2021 Jun 3;48(3):400-407. Epub 2020 Oct 3.

Department of Otolaryngology-Head and Neck Surgery, Nara Medical University,840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address:

Objectives: The purpose of this study was to access the contribution of vertigo/dizziness-related patients' interview and examinations during short-term hospitalization in determining the accurate final diagnosis of vertigo/dizziness of unknown origin.

Methods: We reviewed 1905 successive vertigo/dizziness patients at the Vertigo/Dizziness Center of Nara Medical University, who were introduced from general otolaryngologists at outpatient town clinic from May 2014 to April 2020. However, 244 patients were diagnosed with vertigo/dizziness of unknown origin (244/1905; 12.8%). Of these patients, 240 were hospitalized and underwent various examinations, including caloric test (C-test), video head impulse test (vHIT), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV), inner ear magnetic resonance imaging (ieMRI), Schellong test (S-test), and self-rating questionnaires of depression score (SDS).

Results: According to the examination data, together with interviewed vertigo/dizziness characteristics and daily changeable nystagmus findings, the final diagnoses were as follows: benign paroxysmal positional vertigo (BPPV: 107/240; 44.6%), orthostatic dysregulation (OD: 56/240; 23.3%), vestibular peripheral disease (VPD: 25/240; 10.4%), vestibular migraine (VM: 14/240; 5.8%), Meniere's disease (MD: 12/240; 5.0%), gravity perception disturbance (GPD: 10/240; 4.2%), psychogenic vertigo (Psycho: 10/240; 4.2%), and unknown (Unknown: 6/240; 2.5%). Supporting factors of final diagnosis was seen in gender, evoked dizziness, and positional nystagmus as BPPV; in evoked dizziness, S-test, and hypertension as OD; in evoked dizziness, head shaking after nystagmus, C-test, and vHIT as VPD; in gender, headache, and S-test as VM; in ear fullness and ieMRI as MD; in gender, evoked dizziness, and SVV as GPD; and in SDS as Psycho. To sum up, the ratios of Unknown were significantly reduced by this short-term hospitalization (244/1905→6/240).

Conclusions: The answer lists for vertigo/dizziness of unknown origin obtained in the present study may be helpful for future general otolaryngologists at outpatient town clinic to better attain an accurate final diagnosis.
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http://dx.doi.org/10.1016/j.anl.2020.09.012DOI Listing
June 2021

Association between treatment package time and clinical predictors in oropharyngeal cancer.

Medicine (Baltimore) 2020 Sep;99(39):e22244

Department of Head and Neck Surgery, Aichi Cancer Center Hospital.

The aim of the present study is to investigate the association of treatment package time with the survival outcomes and clinical parameters in patients with oropharyngeal squamous cell carcinoma.A total of 49 patients who underwent definitive treatment were enrolled. The treatment package time was calculated in days from the start of any treatment to the completion of all treatments, including postoperative treatment and salvage surgery for residual tumor.On univariate analyzes, treatment package time ≥118 days, sake index ≥60, Brinkman index ≥450, maximum standardized uptake value ≥42.45, and the presence of synchronous cancer were significantly associated with shorter oropharyngeal squamous cell carcinoma-specific survival. Moreover, a treatment package time of ≥118 days was significantly correlated with shorter overall survival and distant metastasis-free survival. On multivariate analyzes, Brinkman index ≥450 was significantly associated with shorter oropharyngeal squamous cell carcinoma-specific and locoregional recurrence-free survival, and the presence of synchronous cancer was significantly associated with shorter overall and distant metastasis-free survival.In conclusion, a relatively long treatment package time was a predictor of low survival outcomes in oropharyngeal squamous cell carcinoma by univariate analysis.
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http://dx.doi.org/10.1097/MD.0000000000022244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523759PMC
September 2020

Comparison of the video head impulse test results with caloric test in patients with Meniere's disease and other vestibular disorders.

Acta Otolaryngol 2020 Sep 21;140(9):728-735. Epub 2020 May 21.

Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Nara, Japan.

The caloric test has been used to evaluate the semi-circular canal function for decades. In 2009, the video head impulse test (vHIT) was introduced, which can be used to evaluate the semi-circular canal function within a short time. Although both tests examine the semi-circular canal, the stimulation methods differ and it is unclear whether the vHIT is equivocal to the caloric test. This study aimed to discern the differences between the vHIT and caloric test. This study comprised 112 patients with vertigo who visited the vertigo/dizziness centre at our university hospital. Each of these patients underwent a caloric test and vHIT within the same day, and their results were compared. Additionally, an electrocochleography (EcoG) examination, glycerol test (G test), and MRI (performed 4 h after an intravenous gadolinium injection) were conducted to evaluate the influence of endolymphatic hydrops (EH) on the caloric test and vHIT results. Differences in the caloric test and vHIT results, among those with and without EH, were observed in 66.7 and 35.3% of patients, respectively. EH resulted in a difference in results between the caloric test and vHIT. Activated hair cell type may also be implicated.
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http://dx.doi.org/10.1080/00016489.2020.1766700DOI Listing
September 2020

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

J Med Invest 2020 ;67(1.2):189-191

Department of Head and Neck Surgery.

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.
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http://dx.doi.org/10.2152/jmi.67.189DOI Listing
January 2020

Safety and Efficacy of Salvage Neck Dissection Following Carbon-ion Radiotherapy with Chemotherapy for a Patient with Mucosal Malignant Melanoma of Head and Neck.

Diagnostics (Basel) 2020 Feb 3;10(2). Epub 2020 Feb 3.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya 464-0021, Japan.

Mucosal malignant melanoma of the head and neck is a rare diagnosis. The safety and efficacy of salvage neck dissection following carbon-ion radiotherapy with concurrent chemotherapy are not well described, and carbon-ion radiation protocols have not been fully developed. A 77 year old woman with crT0N1M0 mucosal melanoma of the head and neck achieved a complete response following initial treatment with carbon-ion radiotherapy and concurrent chemotherapy. She was treated with salvage neck dissection for as a cervical lymph node metastasis 16 months after initial treatment. She experienced neither Clavien-Dindo Grade 3 or 4 postoperative complications nor subsequent recurrence of disease at 3 months following salvage neck dissection. Surgical specimens may be useful for future precision oncology based on the molecular biology of recurrence melanoma with poor prognosis.
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http://dx.doi.org/10.3390/diagnostics10020082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169450PMC
February 2020

An examination of the cutoff value of the depth of invasion for prophylactic neck dissection in stage I/II tongue cancer.

Acta Otolaryngol 2020 May 5;140(5):422-426. Epub 2020 Feb 5.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

In stage-I/stage-II oral tongue cancer, the cutoff value of depth of invasion (DOI) for prophylactic neck dissection is controversial. To examine the relationship between the DOI and the rate of occult lymph node metastasis. In addition, to examine the relationship between the DOI evaluated by magnetic resonance imaging (MRI) and pathological DOI. In this retrospective study, 95 patients with clinical T1-2/N0M0 oral tongue cancer were enrolled. The rate of occult lymph node metastasis per DOI between 2 and 11 mm was calculated from the total pathological lymph node metastasis and delayed neck metastasis cases. We measured DOI using MRI and compared DOI obtained from pathology. The total rate of occult lymph node metastasis was 23.9%. In the rate of occult lymph node metastasis per DOI, there were two peaks at point of 5 to 6 mm and 9 to 10 mm. And there was a significant correlation between the DOI evaluated by MRI and the pathological DOI (Pearson's correlation coefficient was 0.87). There was no consistent increase in the rate of occult lymph node metastasis per DOI. MRI was a useful modality to measure the DOI.
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http://dx.doi.org/10.1080/00016489.2020.1717606DOI Listing
May 2020

Prognostic Value of Age and Distant Metastasis in Differentiated Thyroid Carcinoma Undergoing Salvage Surgery.

Anticancer Res 2020 Feb;40(2):1127-1133

Department of Head and Neck Surgery, Aichi Cancer Center, Nagoya, Japan.

Aim: To investigate the association between survival outcomes and clinicopathological factors, including pathological restaging based on the UICC8, among patients with recurrence differentiated thyroid carcinoma undergoing salvage surgery of local site.

Patients And Methods: A total of 54 patients who underwent salvage surgery of local site for recurrence differentiated thyroid carcinoma were enrolled. The optimal cutoff ages at salvage surgery for predicting death and cancer-specific death were determined by receiver operating curve analysis. Overall and cancer-specific survivals were determined using log-rank test and Cox's proportional hazards model.

Results: Univariate analysis showed that age and the presence of distant metastasis at salvage surgery were significantly associated with overall survival (p=0.01 and p<0.05, respectively) and cancer-specific survival (p=0.02 and p=0.01, respectively). The optimal cutoff age at salvage surgery for predicting the detection of both death (p=0.01) and cancer-specific death (p=0.02) was 65 years. Multivariate analysis showed that age ≥65 years and the presence of distant metastasis were significantly associated with shorter overall survival (p<0.01 and p=0.03, respectively) and shorter cancer-specific survival (p<0.01 and p=0.01, respectively).

Conclusion: Older age and the presence of distant metastasis at salvage surgery of local site were identified as predictors for poor survival outcomes in recurrence differentiated thyroid carcinoma.
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http://dx.doi.org/10.21873/anticanres.14053DOI Listing
February 2020

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

Am J Otolaryngol 2020 Jan - Feb;41(1):102304. Epub 2019 Oct 5.

Department of Head and Neck Surgery, Asahi University Hospital, Gifu, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.amjoto.2019.102304DOI Listing
April 2020

Epithelioid hemangioendothelioma of the parotid gland: a case report.

Int Cancer Conf J 2019 Jan 29;8(1):39-42. Epub 2018 Nov 29.

1Department of Head and Neck surgery, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681 Japan.

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.
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http://dx.doi.org/10.1007/s13691-018-0351-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498246PMC
January 2019

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

Anticancer Res 2019 Feb;39(2):1043-1049

Department of Head and Neck Surgery, Aichi Cancer Center, Nagoya, Japan.

Aim: To investigate whether F-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 F-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 F-fluorodeoxyglucose uptake in major salivary gland cancer are predictive of overall survival after adjusting for the pathological stage.
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http://dx.doi.org/10.21873/anticanres.13211DOI Listing
February 2019

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

Oncol Lett 2019 Jan 5;17(1):1384-1390. Epub 2018 Nov 5.

Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan.

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.
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http://dx.doi.org/10.3892/ol.2018.9664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313000PMC
January 2019

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

Cancers (Basel) 2018 Nov 23;10(12). Epub 2018 Nov 23.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan.

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.
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http://dx.doi.org/10.3390/cancers10120466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316608PMC
November 2018

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

Anticancer Res 2018 Nov;38(11):6485-6490

Department of Head and Neck Surgery, Asahi University, Gifu, Japan.

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.
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http://dx.doi.org/10.21873/anticanres.13012DOI Listing
November 2018

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

Jpn J Clin Oncol 2018 Dec;48(12):1041-1045

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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.
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http://dx.doi.org/10.1093/jjco/hyy147DOI Listing
December 2018

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

In Vivo 2018 Sep-Oct;32(5):1193-1198

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background/aim: To predict survival outcomes of different patients with the same stage of disease is difficult. The possible correlation between F-fluorodeoxyglucose (F-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: F-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 F-FDG-PET/CT is a prognostic parameter of identifying lower survival outcomes.
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http://dx.doi.org/10.21873/invivo.11363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199585PMC
December 2018

Sinonasal squamous cell carcinoma and EGFR mutations: a molecular footprint of a benign lesion.

Histopathology 2018 Dec 23;73(6):953-962. Epub 2018 Oct 23.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.

Aims: Molecular targeted therapy against EGFR kinase domain mutations has been successfully established for lung cancer. These mutations have now also been reported in head and neck tumours, particularly in inverted sinonasal papillomas (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in head and neck squamous cell carcinomas and papillomas.

Methods And Results: We examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head and neck papillomas or polyps. EGFR mutations were detected in 24 (30%) of 80 sinonasal squamous cell carcinomas (SNSCCs) and in 19 (90%) of 21 ISPs. Notably, 15 (88%) of 17 SNSCCs that developed along with ISPs harboured EGFR mutations in both components, whereas EGFR mutations were detected in nine (14%) of 63 SNSCCs without any papilloma component. Analysis to detect other known driver oncogene mutations - KRAS, BRAF and HER2 - was also performed; none of these mutations was detected in SNSCCs. The other 208 non-sinonasal carcinomas and 37 non-ISP head and neck papillomas or polyps did not harbour EGFR mutations.

Conclusions: Taken together with the specific involvement of EGFR mutations in ISP, a molecular benign lesion trail suggests that 26 (33%) of 80 SNSCCs developed in association with an ISP. SNSCCs with EGFR mutations may be biologically distinct among head and neck cancers.
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http://dx.doi.org/10.1111/his.13732DOI Listing
December 2018

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

Oncotarget 2018 Jun 1;9(42):26670-26678. Epub 2018 Jun 1.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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.
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http://dx.doi.org/10.18632/oncotarget.25453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003559PMC
June 2018

Boerhaave syndrome due to hypopharyngeal stenosis associated with chemoradiotherapy for hypopharyngeal cancer: a case report.

Surg Case Rep 2018 Jun 8;4(1):54. Epub 2018 Jun 8.

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.

Background: Spontaneous esophageal rupture, also known as Boerhaave syndrome, is a very serious life-threatening benign disease of the gastrointestinal tract. It is typically caused by vomiting after heavy eating and drinking. However, in our patient, because of a combination of hypopharyngeal cancer with stenosis and chemoradiotherapy (CRT), which caused chemotherapy-induced vomiting, radiotherapy-induced edema, relaxation failure, and delayed reflexes; resistance to the release of increased pressure due to vomiting was exacerbated, thus leading to Boerhaave syndrome. To the best of our knowledge, this is the first report of a patient with esophageal rupture occurring during CRT for hypopharyngeal cancer with stenosis.

Case Presentation: A 66-year-old man with a sore throat was referred to our hospital. He was found to have stage IVA hypopharyngeal cancer, cT2N2bM0, and underwent radical concurrent CRT consisting of weekly cisplatin (30 mg/m) and radiation (70 Gy/35fr), for larynx preservation. On day 27 of treatment, he vomited, which was followed by severe left chest pain radiating to the back and the upper abdomen. Enhanced computed tomography (CT) revealed extensive mediastinal emphysema and a small amount of left pleural effusion. Esophagography revealed extravasation into the left thoracic cavity, and the patient was diagnosed with an intrathoracic rupture type of Boerhaave syndrome. He underwent emergency left thoracotomy 21 h after the onset. The ruptured esophageal wall was primarily repaired by closure with two-layer suturing and covered by a pedicled omentum. A jejunostomy tube was placed for postoperative enteral nutrition. On postoperative day (POD) 16, the patient was transferred to head and neck surgery to finish CRT and was discharged on POD 56. He has survived without relapse for 11 months after surgery.

Conclusion: Patients with head and neck cancer are at risk for developing Boerhaave syndrome during CRT. In addition, since such patients often are in poor overall condition because of immunosuppression and protracted wound healing, Boerhaave syndrome can rapidly lead to severe life-threatening infections such as empyema and mediastinitis. Therefore, awareness of this condition is important so that appropriate treatment can rapidly be implemented to increase the likelihood of a good outcome.
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http://dx.doi.org/10.1186/s40792-018-0462-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993691PMC
June 2018

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

Oncotarget 2018 Apr 10;9(27):19115-19122. Epub 2018 Apr 10.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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.
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http://dx.doi.org/10.18632/oncotarget.24914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922381PMC
April 2018

Prospective randomized investigation implementing immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids during the perioperative period for head and neck carcinomas.

Jpn J Clin Oncol 2018 Apr;48(4):356-361

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi.

Objectives: The purpose of this study is to evaluate whether a nutritional supplement with a high blend ratio of ω-3 fatty acids can minimize weight loss and attenuate increases in inflammatory marker levels during the perioperative period in patients undergoing surgery for head and neck carcinoma.

Methods: Patients with ≥5% weight loss within 6 months were considered as targets for aggressive nutritional intervention. Among these patients, those with head and neck squamous cell carcinoma, who underwent major invasive surgery with free flap reconstruction were included in the present study. The patients were randomized into two groups: the 'nutritional supplementation group' and the 'non-intervention group'. The nutritional supplementation group received two packs of Prosure® (an eicosapentaenoic acid [EPA]-enriched oral nutritional supplement) per day for 28 days during the perioperative period.

Results: Compliance with the Prosure® dosage was very good at 6277/6720 ml (average) before surgery (93%) and 5229/6720 ml after surgery (78%), and a significant increase in EPA concentration was shown in the group that received Prosure® (P < 0.0001: Welch's t-test). However, 28 days of nutritional supplementation did not lead to further weight change or changes in the inflammatory marker levels of patients were already showing cachexia (based on weight loss). Interestingly, no further change in the mean weight was noted in these patients. The incidence of postoperative complications did not differ between the two groups.

Conclusion: In this trial, immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids from 2 weeks before surgery until 2 weeks after surgery was not effective for maintaining the nutritional status of head and neck carcinoma patients.
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http://dx.doi.org/10.1093/jjco/hyy008DOI Listing
April 2018

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

ORL J Otorhinolaryngol Relat Spec 2018 26;80(1):1-9. Epub 2018 Jan 26.

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.
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http://dx.doi.org/10.1159/000485515DOI Listing
November 2018

Treatment and Outcomes of Carcinoma of the External and Middle Ear: The Validity of En Bloc Resection for Advanced Tumor.

Neurol Med Chir (Tokyo) 2018 Jan 15;58(1):32-38. Epub 2017 Nov 15.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital.

Carcinoma of the external and middle ear is a very rare disease. Despite the various treatment modalities available, its prognosis is still poor. We aimed to analyze the treatment modalities, outcomes, and validity of surgical approaches, especially in advanced tumors in the ear. Twenty-five patients with carcinoma of the external and middle ear were retrospectively analyzed. The modified Pittsburgh staging system was used for staging of the patients. Overall and disease-free survival was estimated using of Kaplan-Meier method. In our cohort of 25 patients, the majority (76%) had tumor located in external auditory meatus. The most common histologic subtype was squamous cell carcinoma (80%). More than half of patients (56%) had tumor stage IV. In the stage IV group, five patients underwent subtotal temporal bone resection and ipsilateral neck dissection. Seven patients underwent definitive radiotherapy. The remaining two patients underwent palliative chemotherapy. The 2-year overall and disease-free survival for patients with tumor stage IV was 67.7% and 57.8%, respectively. In patients with tumor stage IV, the 2-year overall survival for patients who underwent surgery was 80.0% versus 53.6% for those who underwent radiotherapy (P = 0.16). The 2-year disease-free survival for patients who underwent surgery was 80.0% versus 28.6% for those who underwent radiotherapy (P = 0.15). In the present study, the outcome of patients who received surgical treatment tended to be better than that of patients who received radiation therapy. Our results suggest that en bloc resection could be the first choice even in the advanced disease stage.
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http://dx.doi.org/10.2176/nmc.oa.2017-0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785695PMC
January 2018

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

Jpn J Clin Oncol 2017 Dec;47(12):1141-1150

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya.

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.
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http://dx.doi.org/10.1093/jjco/hyx137DOI Listing
December 2017

Prognostic importance of pathological response to neoadjuvant chemotherapy followed by definitive surgery in advanced oral squamous cell carcinoma.

Jpn J Clin Oncol 2017 Nov;47(11):1038-1046

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa.

Objective: The clinical importance of neoadjuvant chemotherapy (NAC) followed by definitive surgery was retrospectively investigated in clinical Stage III/IV oral squamous cell carcinoma (OSCC).

Methods: Surgery was performed for OSCC in 164 patients, including 72 patients who had received NAC (two cycles of cisplatin and fluorouracil) prior to surgery from January 2004 to December 2014. The clinical characteristics and survival parameters of the groups that received and did not receive NAC were evaluated. The pathological response was classified as Grade 0 (no effect), 1a (very slight effect), 1b (slight effect), 2 (moderate effect) or 3 (marked effect), and its correlation with prognosis was investigated.

Results: There were no statistical differences in survival indicators between patients who received NAC and those who did not (overall survival, P = 0.75). The proportion of patients who received NAC in the effective NAC group (Grades 1b, 2, and 3) was 52.8%. After a median follow-up of 35 months, overall survival (P = 0.01), disease-free survival (P = 0.002), locoregional disease-free survival (P = 0.003), and distant disease-free survival (P = 0.01) were significantly better in the effective NAC group than in the less effective NAC group (Grades 0 and 1a).

Conclusion: Although NAC had a limited effect on disease prognosis in OSCC, the pathological response to NAC could be an important prognostic indicator for advanced OSCC.
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http://dx.doi.org/10.1093/jjco/hyx097DOI Listing
November 2017