Post-operative progress of arm abduction function and rate of lymph node metastasis around the region of the accessory nerve: a multicentre prospective observational study.

OBJECTIVE: Although neck dissection is an essential technique in the surgical treatment of head and neck carcinoma, arm abduction disorders occurring after neck dissection reduce the patient's quality of life. METHODS: We prospectively evaluated the rate of lymph node metastasis in Levels IIB and V in head and neck cancer patients who underwent neck dissection at eight centres in Japan. In addition, post-operative arm abduction disability was classified according to functional assessment values at 1 month post-operatively, and the rate of maintained function at 6 and 12 months was evaluated. RESULTS: Lymph node metastasis occurred in Level IIB in 12 of 242 cases (4.9%) and in Level V in 5 cases (2.1%) during the 12-month post-operative course. In patients with preservation of the ipsilateral accessory nerve, arm abduction function was maintained in 142 of 209 patients (67.9%) at 12 months after surgery. Post-operative radiotherapy and Level V dissection had no statistically significant effect on the recovery of arm abduction function. Level V dissection caused a temporary loss of abduction function post-operatively. A higher arm abduction test score at 1 month post-operatively was associated with a higher rate of subsequent ability to maintain arm abduction function. CONCLUSIONS: In patients classified as cN0, metastatic rate at Levels IIB and V was low. In this cohort, omitting Level V dissection may be an option in strategies aimed at maintaining arm abduction function.

Effect of mammalian-target-of-rapamycin inhibitors on the cancer risk in patients receiving calcineurin inhibitors: Data mining of a spontaneous reporting database.

OBJECTIVE: Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database. MATERIALS AND METHODS: Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 - 2019) with reporting odds ratio and information component being used to indicate a signal. RESULTS: Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi's sarcoma. CONCLUSION: mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi's sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi's sarcoma.

Surgical management around the paratracheal area of hypopharyngeal cancer.

OBJECTIVE: We aimed to clarify the suitable surgical management around the paratracheal area of patients who undergo total pharyngolaryngectomy based on the pathological results of hypopharyngeal cancer. METHODS: The study was conducted under a multicenter, retrospective observational design in Japan. We analyzed histopathological paratracheal lymph node metastasis and thyroid invasion, and recurrence around the paratracheal area for 184 patients who underwent initial surgery among 280 participants. RESULTS: There were significant differences in the frequency of metastasis to paratracheal lymph nodes as cN advances (P = 0.0344) and cT advances (P = 0.00028). By subsite, the paratracheal lymph node metastasis ratio was 22/130 patients (16.9%) in piriform sinus (PS), 8/32 (25.0%) in PW, 5/22 (22.7%) in PC and 10/17 (58.8%) in cervical esophagus (Ce+). The ratio of cases with bilateral paratracheal metastasis tended to be higher in cN2c, posterior wall (PW) and postcricoid (PC). Invasion to the thyroid was histopathologically confirmed in 16/184 patients (8.7%). Invasion from the primary lesion was in 15 patients. CONCLUSION: This study indicates that it is better for patients with advanced hypopharyngeal cancer at minimum undergo ipsilateral paratracheal lymph node dissection. Tumor subsite of PW, PC or cN2c disease or disease extending to the Ce+ should be treated with bilateral paratracheal neck dissection. In order to more reliably perform paratracheal dissection, there is also an option to resect the thyroid lobe in the range of dissection. Preservation of the thyroid gland can be considered if invasion into the thyroid gland has been clearly ruled out.

Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study.

BACKGROUND: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. METHODS: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. RESULTS: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT. CONCLUSION: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis.

Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2. In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.

MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts.

MYB-NFIB and MYBL1-NFIB have been reported in ~60% of adenoid cystic carcinoma cases, but driver alterations in the remaining ~40% of adenoid cystic carcinoma remain unclear. We examined 100 adenoid cystic carcinoma cases for MYB and MYBL1 locus rearrangements by fluorescence in situ hybridization (FISH) with originally designed probe sets using formalin-fixed paraffin-embedded materials. Approximately one-third of samples were also analyzed by fusion transcript-specific RT-PCR and capture RNA sequencing. In the 27 cases with frozen materials, MYB-NFIB and MYBL1-NFIB fusion transcripts were detected in 9 (33%) and 6 cases (22%) by RT-PCR, respectively. Meanwhile, high expression of MYB (18 cases, 67%) or MYBL1 (9 cases, 33%) was detected in all 27 cases in a mutually exclusive manner, regardless of its form (full-length, truncation, or fusion transcript). Interestingly, genomic rearrangements around the corresponding highly-expressed gene were observed in all 27 cases by FISH, suggesting a causative relationship between genomic rearrangements and gene expression. Among the 100 cases, including additional 73 cases, 97 harbored genomic rearrangements in the MYB (73 cases) or MYBL1 locus (24 cases) including 10 cases with atypical FISH patterns undetectable through ordinary split FISH approaches: breakpoints far distant from MYB (5 cases) and a small NFIB locus insertion into the MYB (3 cases) or MYBL1 locus (2 cases). In clinicopathological analyses, histological grade, primary tumor size, and lymph node metastasis were identified as prognostic factors, whereas MYB/MYBL1 rearrangements were not, but were associated with histological grade. In the present study, MYB or MYBL1 locus rearrangement was detected in nearly all adenoid cystic carcinoma cases, and therefore it would be a good diagnostic marker for adenoid cystic carcinoma. However, fusion transcript-specific RT-PCR for MYB-NFIB and MYBL1-NFIB and ordinary split FISH assays for MYB and MYBL1 were less sensitive, and thus detection methods should be judiciously designed because of the diversity of rearrangement modes in adenoid cystic carcinoma.

Thick tumor capsule is a valuable risk factor for distant metastasis in follicular thyroid carcinoma.

OBJECTIVE: While the biological behavior of follicular thyroid carcinoma (FTC) has been studied in great detail using clinical experience, few studies have investigated pre- or intraoperative factors related to the risk of distant metastasis (DM) among patients with FTC. The aim of this study was to analyze the characteristics of FTC with DM. METHODS: This study retrospectively investigated 102 patients with FTC who underwent surgery between 1988 and 2013. We compared clinicopathological characteristics between FTC with and without DM. RESULTS: Univariate analysis revealed nodal metastasis (p=0.045), serum thyroglobulin (Tg) at initial operation (≥1000ng/ml; p<0.0001), widely invasive appearance according to macroscopic findings (p<0.0001), thick tumor capsule (≥1mm; p<0.0001), vascular invasion (p=0.0003), extrathyroidal invasion (p=0.047), and venous tumor embolism (p=0.045) as significant risk factors for DM. Multivariate analysis conducted using pre- and intraoperative factors identified thick tumor capsule (≥1mm), serum Tg at initial operation (≥1000ng/ml), and macroscopically widely invasive appearance as risk factors independently associated with development of DM. CONCLUSION: Patients with these risk factors should undergo total thyroidectomy and radioactive iodine ablation.

Indwelling voice prosthesis insertion after total pharyngolaryngectomy with free jejunal reconstruction.

OBJECTIVES: Total pharyngolaryngectomy with free jejunal reconstruction is often performed in patients with hypopharyngeal carcinoma. However, postoperative speechlessness significantly decreases patient quality of life. We investigated whether Provox® insertion could preserve speech after total pharyngolaryngectomy with free jejunal reconstruction. STUDY DESIGN: Retrospective chart review. METHODS: A total of 130 cases of secondary Provox® insertions after total pharyngolaryngectomy with free jejunal reconstruction were analyzed. Communication outcomes were compared using the Head and Neck Cancer Understandability of Speech Subscale. Outcomes and complications associated with insertion site (jejunal insertion vs. esophageal insertion) and adjuvant irradiation therapy were also evaluated. RESULTS: Provox® insertion had favorable communication outcomes in 102 cases (78.4%). Neither the insertion site nor irradiation affected the communication outcome. Complications were observed in 20 cases (15.4%). Local infection was the most common complication. Free jejunal insertion, in which the resection range was enlarged, had a lower complication rate than did esophageal insertion, and its complication rate was unaffected by previous irradiation. For all patients, the hospitalization duration and duration of speechlessness were 13.4 days and 14.6 months, respectively. Patients receiving jejunal insertions had a significantly shorter hospitalization duration than did those receiving esophageal insertions. Unlike Provox®2, Provox®Vega significantly reduced the complication rate to zero. CONCLUSION: For jejunal inserson of a Provox® prosthetic, a sufficient margin can be maintained during total pharyngolaryngectomy and irradiation can be performed, and satisfactory communication outcomes were observed. Provox® insertion after total pharyngolaryngectomy with free jejunal reconstruction should be considered the standard therapy for voice restoration. LEVEL OF EVIDENCE: 4.

A comparison of weekly paclitaxel and cetuximab with the EXTREME regimen in the treatment of recurrent/metastatic squamous cell head and neck carcinoma.

BACKGROUND: The effectiveness of the combination chemotherapy of weekly paclitaxel and cetuximab has not yet been compared to that of the current standard regimen, EXTREME (combination of 5-fluorouracil, cisplatin and cetuximab). METHODS: We retrospectively reviewed the clinical records of R/M SCCHN patients who received cetuximab-containing chemotherapy as a first-line therapy; from these, patients receiving a weekly paclitaxel and cetuximab regimen (cohort A) and the EXTREME regimen (cohort B) were extracted. The responses, prognoses and adverse events of these two cohorts were evaluated. RESULTS: A total of 86 patients were included (cohort A, 49; cohort B, 36). Patients with histories of platinum-based chemotherapy were more frequently given the cohort A treatment. Though the response rates were similar in the two cohorts (45% in cohort A and 51% in cohort B; p=0.83), the progression-free survival (PFS) was significantly more favorable in cohort A by the log-rank test (6.0monthsvs 5.0months; p=0.027). In the Cox-regression hazard analyses, male gender (hazard ratio [HR]=2.1, p=0.010), older age (≥ 70 yo) (HR=5.0, p=0.018), PS 0 (HR=2.2, p=0.027), no history of platinum chemotherapy (HR=3.2, p=0.003) and the presence of a tracheostomy (HR=2.3, p=0.039) were favorable factors within cohort A. CONCLUSION: In selected R/M SCCHN patients, the combination of weekly paclitaxel and cetuximab could be the better treatment option than the EXTREME regimen.

Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy.

BACKGROUND: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. METHODS: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. RESULTS: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. CONCLUSIONS: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

Japanese Clinical Practice Guideline for Head and Neck Cancer.

OBJECTIVE: The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. METHODS: 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members. RESULTS: Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function. CONCLUSIONS: In this article, we described most relevant guidelines and CQs for the diagnosis and treatment of head and neck cancer in Japan. These guidelines are not intended to govern therapies that are not shown here, but rather aim to be used as a guide in searching for the most appropriate treatment for individual patient.

Two Cases of Ectopic Hamartomatous Thymoma Masquerading as Sarcoma.

Ectopic hamartomatous thymoma (EHT) is an extremely rare benign tumor. EHTs are difficult to differentiate from sarcomas, especially synovial sarcomas. We encountered two cases of EHT that were referred from other hospitals because sarcoma was suspected. In these cases, fusion gene detection via polymerase chain reaction or fluorescence in situ hybridization was useful for differentiating EHT from synovial sarcoma. EHT requires accurate diagnosis before surgery to avoid excessive treatment. Both tumor location and the presence of fat inside the tumor are important imaging findings for EHT, and confirmation of spindle cells, epithelial cells, and mature adipose cells in the tumor is an important pathological finding. It is important to exclude synovial sarcoma from the differential diagnosis via fusion gene analysis.

Efficacy of double-scope endoscopic submucosal dissection and long-term outcomes of endoscopic resection for superficial pharyngeal cancer.

BACKGROUND AND AIM: Owing to increased awareness and use of narrow-band imaging, there are more opportunities to treat superficial pharyngeal cancer (SPC). The present study aimed to describe the short- and long-term outcomes of endoscopic resection (ER) for SPC. METHODS: This study included 166 consecutive SPC in 113 patients treated during 2006 to 2013 at one referral cancer center. In the first period, we treated patients using endoscopic mucosal resection (EMR), in the second period using conventional ESD (cESD) and in the recent period using double-scope ESD (dsESD), which involves a second thin endoscope for assistance to produce traction. Median follow-up period was 30 months. RESULTS: All lesions were diagnosed as squamous cell carcinoma. Complete resection rate of cESD and dsESD procedures was 56.4% and 82.3% (P < 0.01), and local recurrence rate was 2.6% and 0.0%, respectively. Procedure duration was significantly shorter for dsESD than for cESD (P < 0.05). Four cases of recurrent lymph node (LN) metastasis were observed; however, all patients with LN metastases survived to a 48-month median interval after neck dissection. Risk factors for LN metastasis included subepithelium invasion, tumor thickness >1000 µm, droplet infiltration, and lymphovascular invasion. Overall survival rate after 5 years was 79.5%; no patients died of SPC. Cumulative rate of metachronous SPC after 5 years was 46.5%. CONCLUSION: ER for SPC is a feasible and effective treatment, although metachronous SPC occurred frequently. For the technique of ER, dsESD was effective.

Comparison of synchronous versus staged surgeries for patients with synchronous double cancers of the esophagus and head-and-neck.

Esophageal and head and neck (H&N) cancers often occur synchronously, this study aimed to clarify the benefits and disadvantages of synchronous and staged operations for double H&N/esophagus cancers. We retrospectively reviewed 43 patients with synchronous double cancer of H&N and esophagus treated between July 2005 and July 2014, of whom 33 patients underwent synchronous operation (SYN) and 10 underwent staged operations (STG). We compared the short-term outcomes between the groups. Operation time was longer, amount of blood loss was larger, and hospital stay was longer in the SYN group than in each single surgery of the STG group. Incidence of postoperative complications did not differ between the groups. Tracheal necrosis was observed only in the SYN group. One patient died because of postoperative bleeding in the SYN group, whereas no mortality was seen in the STG group. Both the peripheral white blood cell counts and serum CRP levels during postoperative period were significantly higher in the SYN group than each single surgery of STG group. The staged surgery strategy for patients with synchronous esophagus/H&N cancers can attenuate surgical stress and thus may increase safety.

Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses.

BACKGROUND: A standard chemotherapy for recurrent/metastatic salivary gland cancers has not been established. Combination chemotherapy of carboplatin and paclitaxel should be evaluated as a treatment option. METHODS: This study retrospectively reviewed salivary gland cancer patients who received combination chemotherapy of carboplatin and paclitaxel. The differences in objective responses and in the prognoses according to the different pathological diagnoses were evaluated. RESULTS: A total of 38 patients were enrolled in the study; of them, 18 had salivary duct carcinomas (SDCs), nine had adenoid cystic carcinomas (ACCs), and 11 had other pathological diagnoses. Objective responses were observed in 15 (39%) patients. The median progression-free survival (PFS) was 6.5 months, and the median overall survival (OS) was 26.5 months. ACC patients had relatively low response rates (9%), but there were no significant differences in PFS or OS compared to other sub-types. The treatment was well tolerated, with few adverse events. CONCLUSION: Salivary gland cancer patients showed a moderate clinical response to the combination chemotherapy of carboplatin and paclitaxel. The objective response rates differed according to the pathological diagnoses, but there were no significant differences in prognoses.

Association of impaired renal function and poor prognosis in oropharyngeal squamous cell carcinoma.

BACKGROUND: Renal function influences decisions regarding treatment for patients with oropharyngeal squamous cell carcinoma (SCC). However, the importance of renal function in oropharyngeal SCC has not yet been reported. METHODS: Four hundred sixty patients with oropharyngeal SCC treated with curative intent between April 2005 and March 2007 in 12 institutions in Japan were analyzed retrospectively. RESULTS: Four hundred three patients (87.6%) showed a creatinine clearance (CrCl) ≥50 mL/min and 57 (12.4%) with a CrCl <50 mL/min. Age was associated with worse overall survival (OS), whereas stage IVB, radiotherapy (RT), and CrCl <50 were associated with worse OS on univariate analyses. Surgery and hypertension were associated with better OS on univariate analyses. On multivariate analysis, age, stage, hypertension, and CrCl were also found to be significantly associated with OS. CONCLUSION: Based on this retrospective study, impaired renal function is an independent predictor of increased risk of death in patients with oropharyngeal SCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1500, 2016.

Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy.

Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, ≥200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose ≥200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3-year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance.

Common carotid artery rupture during treatment with lenvatinib for anaplastic thyroid cancer.

Anaplastic thyroid cancer is a fatal disease for which no effective therapeutic strategies exist. Lenvatinib, a tyrosine-kinase inhibitor that targets vascular endothelial growth factor receptor, has recently been approved in Japan for the treatment of patients with unresectable thyroid cancer including anaplastic thyroid cancer. Although lenvatinib, like the other tyrosine-kinase inhibitors, sunitinib and sorafenib, might also confer a risk of bleeding, fatal bleeding as a result of lenvatinib treatment for anaplastic thyroid cancer has not been described. A 61-year-old woman presented with a 7-cm mass in the right lobe of the thyroid, lymph node metastases to the neck and multiple lung metastases. Fine needle aspiration revealed that the tumor was anaplastic thyroid cancer. The TNM classification was T4aN1bM1, stage IVC. Shortly after local curative surgery, a tumor recurred in her neck that was treated with lenvatinib (24 mg/day). Nineteen days later, the common carotid artery ruptured and the lenvatinib was stopped. She received the best possible supportive care but died 40 days after stopping the lenvatinib. Autopsy findings showed that the tumor had invaded the adventitia of the common carotid artery at the region of the neck surgery, and an aneurysm had developed. However, the adventitia of the common carotid artery was preserved at the non-dissected area. Lenvatinib might confer risk for fatal bleeding in patients with recurrent anaplastic thyroid cancer after neck surgery, particularly with dissection around the common carotid artery.

Natural History of Asymptomatic Papillary Thyroid Microcarcinoma: Time-Dependent Changes in Calcification and Vascularity During Active Surveillance.

BACKGROUND: Prospective trials of non-surgical observation have shown progression rates of only 5-10% in patients with asymptomatic papillary microcarcinoma (PMC). This study investigated time-dependent changes in calcification patterns and tumor vascularity on ultrasonography (US) to clarify the natural course of PMC. METHODS: We examined calcification patterns and tumor vascularity for 480 lesions in 384 patients. Calcification patterns were classified as: (A) none; (B) micro; (C) macro; or (D) rim. Tumor vascularity was classified as rich or poor via color Doppler US. RESULTS: After a mean of 6.8 years of observation, 29 lesions (6.0%) had increased in size. Mean age for initial calcification pattern was 52.1 years for A (n = 135), 54.2 years for B (n = 235), 56.3 years for C (n = 96), and 60.1 years for D (n = 14), and the incidence rates of tumor enlargement were 9.6, 5.5, 3.2, and 0%, respectively. The cumulative rate of upgrade in calcification pattern was 51.8% at 10 years. Lesions with initially rich vascularity (n = 70) had significantly higher rate of tumor enlargement than those with poor vascularity (n = 410); however, the majority of tumor (61.4%) with initially rich vascularity had decreased their blood supply during the follow-up. Multivariate analysis showed that strong calcification (C or D) and poor vascularity at last examination correlated significantly with non-progressive disease. CONCLUSIONS: PMCs in older patients showed significantly stronger calcification patterns and poorer vascularity. Both consolidation of calcification and loss of vascularity occurred in a time-dependent manner during observation and were significant indicators for non-progressive disease.