Transoral robotic surgery (TORS) in Japan: procedures, advantages and current status.

Transoral robotic surgery (TORS), introduced by Weinstein et al. in 2005, has been widely adopted as a minimally invasive procedure, particularly for the treatment of patients with early stage oropharyngeal cancer. TORS is typically performed using the da Vinci Surgical System, similar to robot-assisted surgeries for other malignancies. The main difference between TORS and these other robot-assisted surgeries is that it is performed through the natural orifice of the mouth, which limits the surgical working space, and that it progresses from the lumen of the pharynx to the deeper tissues. The advantages of TORS are mainly due to the benefits of using the da Vinci Surgical System, such as three-dimensional high-definition images, magnification, multiple forceps articulation, tremor-stabilization function and motion scale function. To date, many big data and meta-analyses have shown that TORS is superior to conventional surgeries, such as open surgery, in terms of oncological outcomes, post-operative functionality and quality of life. In Japan, TORS is expected to spread across the country, as it has been covered by health insurance since April 2022. This review highlights the procedures of TORS, its unique aspects, its unparalleled advantages as a minimally invasive surgery for treating laryngeal and pharyngeal cancers, and its current status in Japan.

Ion transport its regulation in the endolymphatic sac: suggestions for clinical aspects of Meniere's disease.

Ion transport and its regulation in the endolymphatic sac (ES) are reviewed on the basis of recent lines of evidence. The morphological and physiological findings demonstrate that epithelial cells in the intermediate portion of the ES are more functional in ion transport than those in the other portions. Several ion channels, ion transporters, ion exchangers, and so on have been reported to be present in epithelial cells of ES intermediate portion. An imaging study has shown that mitochondria-rich cells in the ES intermediate portion have a higher activity of Na+, K+-ATPase and a higher Na+ permeability than other type of cells, implying that molecules related to Na+ transport, such as epithelial sodium channel (ENaC), Na+-K+-2Cl- cotransporter 2 (NKCC2) and thiazide-sensitive Na+-Cl- cotransporter (NCC), may be present in mitochondria-rich cells. Accumulated lines of evidence suggests that Na+ transport is most important in the ES, and that mitochondria-rich cells play crucial roles in Na+ transport in the ES. Several lines of evidence support the hypothesis that aldosterone may regulate Na+ transport in ES, resulting in endolymph volume regulation. The presence of molecules related to acid/base transport, such as H+-ATPase, Na+-H+ exchanger (NHE), pendrin (SLC26A4), Cl--HCO3- exchanger (SLC4A2), and carbonic anhydrase in ES epithelial cells, suggests that acid/base transport is another important one in the ES. Recent basic and clinical studies suggest that aldosterone may be involved in the effect of salt-reduced diet treatment in Meniere's disease.

[Significant factors for surgical site infection: analysis of 203 head and neck surgeries].

Surgical site infection (SSI) is a common complication in head and neck surgeries. The aim of this study was to assess the rate of, and risk factors for SSI following surgical procedures of the head and neck. The study population comprised 206 patients who underwent surgery of head and neck region in NTT West Osaka Hospital between 2009 and 2011. The incidence rate and risk factors were estimated by the chi-square test and a logistic regression analysis. SSI occurred in 22 cases (10.8%) of 203 patients. A broad range of putative risk factors was recorded in each patient and statistically analyzed to elucidate SSI related factors. Univariate analysis indicated that low BMI, diabetes mellitus, anemia, hypoalbuminemia, surgical wound classification, duration of operation, blood loss, left implants and preoperative radiotherapy were risk factors associated with SSI. Multivariate statistics revealed four independent risk factors: surgical wound classification (odds ratio (OR) 5.88, p = 0.02), hypoalbuminemia (OR 11.48, p < 0.01), duration of operation (OR 18.66, p < 0.01) and left implants (OR 20.24, p < 0.01). Thus, to achieve a reduction in SSI, we need to take care of not only the factors related with surgical technique such as the duration of the operation or left implants, but the preoperative nutrition status.

Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

The Utility of Glasgow Prognostic Score and Palliative Prognostic Index in Patients With Head and Neck Squamous Cell Carcinoma Under Palliative Care.

OBJECTIVES: Palliative care patients with head and neck squamous cell carcinoma (HNSCC) often experience dysphagia and airway trouble; thus, each patient requires a specific palliative care plan based on their prognostication. However, no established specific prognostic tool performed on the day of starting end-of-life care is available for such patients. We assessed the accuracy of Glasgow prognostic score (GPS) and palliative prognostic index (PPI) and their combination to establish a specified prognostic tool for patients with HNSCC in end-of-life setting. METHODS: A retrospective clinical chart review was undertaken on patients with HNSCC in end-of life setting who were decided in Kagawa University Hospital and National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. The patients were divided into 2 categories according to GPS (0-1 and 2) and PPI (groups A-B and C). These were combined into 4 categories (PPI group A-B and GPS score 0-1: good; PPI group A-B and GPS score 2: intermediate; PPI group C and GPS score 2: poor; and PPI group C and GPS score 0-1: others). The survival curves were compared for the former 3 categories. RESULTS: The median survival of the scores 0-1 and 2 on GPS were 114 (72-148) and 39 (25-52) days, respectively (P < .01). These of groups A-B and C on PPI were 79 (64-99) and 16 (9-29) days, respectively (P < .01). The median survival of the good, intermediate, and poor categories was 127 (73-149), 64 (44-80), and 15 (9-27) days, respectively (P < .01 among all categories). CONCLUSIONS: In this study, the survival of terminally ill patients with HNSCC can be predicted by the GPS, PPI, and their combination with sufficient probability.

Comparison of the accuracy of clinical prediction of survival and palliative prognostic index for patients with head and neck squamous cell carcinoma in the end-of-life setting.

OBJECTIVE: In the end-of-life stage of head and neck squamous cell carcinoma (HNSCC), predicting survival is essential to determine treatment procedure and place of care. Several reports have compared actual survival (AS) and clinical prediction of survival (CPS), a subjective prognostic prediction by attending physicians. However, specific studies focusing on patients with HNSCC are limited. Likewise, a comparison of the accuracy of CPS and palliative prognostic index (PPI), a prognostic tool using subjective assessment, has not been sufficiently investigated. This study aimed to clarify the correlation between AS and CPS/PPI and compare the accuracy of CPS and PPI in end-stage HNSCC. METHODS: This retrospective study included patients with HNSCC in the end-of-life setting. Patients were recruited from the National Hospital Organization Shikoku Cancer Center between April 2011 and March 2019. Data on basic demography and clinical parameters when patients decided to start end-of-life care at the head and neck oncology division were collected. We examined the correlation between AS and CPS using Spearman's correlation coefficients. The area under the receiver operating characteristic curve of CPS and PPI for 30-day survival prediction were compared for predictive accuracy. RESULTS: Among 98 eligible patients, 59 patients were enrolled in this study and analyzed. Of the 59 patients, CPS and PPI were calculated for 30 patients, whereas, only the PPI was calculated for 29 patients. The median AS and CPS were 35 (IQR: 9-73) days and 30 (IQR: 7-83) days, respectively. CPS and PPI (30 cases) were moderately correlated (r = 0.72, p<0.01). AS and CPS/PPI (30 cases) were significantly correlated (p<0.01) and showed a strong correlation (r = 0.86 and 0.80, respectively). In the 30-day survival prediction, the AUROCs of CPS and PPI (30 cases) were 0.967 (95%CI: 0.919-1) and 0.884 (95%CI: 0.767-1), respectively. Both CPS and PPI (30 cases) showed high accuracy in predicting the 30-day prognosis, with no significant difference (p = 0.077). The AUROC of PPI (59 cases) was 0.840 (95%CI: 0.711-0.969). CONCLUSIONS: AS and CPS/PPI showed significant correlations. The high accuracy of CPS may have been influenced by the fact that multiple head and neck cancer specialists at a comprehensive cancer center estimated CPS. Both CPS and PPI showed high prognostic accuracy in predicting 30-day survival. This suggests that PPI is useful in centers among physicians and healthcare workers unfamiliar with head and neck cancer.

Current Status of Transoral Surgery for Patients With Early-Stage Pharyngeal and Laryngeal Cancers in Japan.

As the laryngopharynx is closely related to swallowing, speech, and phonation, it is necessary to consider not only disease control but also a minimally invasive approach for the treatment of laryngopharyngeal cancer. Transoral surgery has been reported to be a minimally invasive method for treating these diseases. Transoral videolaryngoscopic surgery (TOVS) and endoscopic laryngo-pharyngeal surgery (ELPS) have been developed in Japan and recently emerged as treatments for patients with early stage pharyngeal and laryngeal cancers. However, securing an appropriate field of view and a narrow operating space during TOVS or ELPS are critical issues to be resolved for these surgeries. The clinical significance and safety of transoral robotic surgery (TORS) using the da Vinci Surgical System have been widely reported to provide surgeons with increased visualization and magnification, resulting in precise surgical margins and rapid functional recovery. In this context, a multi-institutional clinical study was conducted to evaluate the treatment outcomes of TORS for the treatment of laryngopharyngeal cancer in Japan, and the da Vinci Surgical System for oral robot-assisted surgery for these diseases was approved by the Pharmaceutical Affairs Agency in August 2018. This review provides an overview of the therapeutic effects of TOVS, ELPS, and TORS, with a particular focus on these therapeutic results in Japan.

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.

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.

In vitro and in vivo effects of D-allose: up-regulation of thioredoxin-interacting protein in head and neck cancer cells.

OBJECTIVES: This study was aimed to investigate the relationship between the antiproliferative effects of D-allose and the up-regulation of thioredoxin-interacting protein (TXNIP) in head and neck cancer cells. METHODS: For the in vitro study, 5 oral squamous cell carcinoma cell lines (Ca9-22, HSC-3, HSC-4, SAS, and KON) were treated with 25 mmol/L D-allose. For the in vivo study, HSC-3 cells were used in a xenograft model with female athymic nude mice (BALB/c nu/nu; 5 to 6 weeks old). RESULTS: Inhibition of cell growth by D-allose was noted in HSC-3 and Ca9-22 cells, along with significant induction of TXNIP. Although TXNIP up-regulation was also evident, albeit to a lesser extent, in the remaining cell lines, D-allose did not inhibit their growth. With the HSC-3 line, the cell survival fractions decreased and TXNIP expression increased in a D-allose dose-dependent manner. The antiproliferative effects were partially suppressed by concomitant D-glucose treatment, which also reduced TXNIP expression. In the in vivo experiment, the tumor volume at day 15 after D-allose treatment was reduced to 61% of that of the control group. CONCLUSIONS: This study showed that D-allose exerts growth inhibitory effects on head and neck cancer cells in vitro and in vivo. The sugar may act as an antiproliferative agent via TXNIP induction and thus may be useful as a novel anticancer drug.

Endolymphatic sac is involved in the regulation of hydrostatic pressure of cochlear endolymph.

To clarify the role of the endolymphatic sac (ES) in the regulation of endolymphatic pressure, the effects of isoproterenol, a beta-adrenergic receptor agonist, and acetazolamide, a potent carbonic anhydrase inhibitor, both of which decrease ES direct current potential on cochlear hydrostatic pressure, were examined in guinea pigs. When isoproterenol was applied intravenously, hydrostatic pressures of cochlear endolymph and perilymph were significantly increased with no change in endocochlear potential or the hydrostatic pressure of cerebrospinal fluid. Acetazolamide produced no marked change in the hydrostatic pressure of cochlear endolymph. In ears with an obstructed ES, the action of isoproterenol on the hydrostatic pressure of cochlear endolymph and perilymph was suppressed. These results suggest that the ES may regulate the hydrostatic pressure of the endolymphatic system via the action of the agents such as catecholamines on the ES.

Expression of prostaglandin E2 receptors in oral squamous cell carcinomas and growth inhibitory effects of an EP3 selective antagonist, ONO-AE3-240.

Prostaglandin E2 (PGE2) can stimulate tumor progression by both direct and indirect mechanisms. However, its influence on cell proliferation is still unclear. The present study characterized expression of subtypes of PGE2 receptors in oral squamous cell carcinomas, while also investigating the effects of EP3 and EP4 selective antagonists on oral carcinoma cell lines. EP1, EP2, EP3 and EP4 receptor mRNAs were detected in 4, 5, 10 and 10 of 11 surgical specimens respectively. Application of an EP3 antagonist (ONO-AE3-240) strongly inhibited cell growth in COX-2 and PGE2 high expression cells (Ca9-22) but not in COX-2 and PGE2 low expression cells (HSC4). The antagonist also reduced the production of endogenous PGE2 and induced G0/G1 phase cell arrest. Addition of exogenous PGE2 only partly abrogated the growth inhibition, indicating that the anti-proliferative effect via EP3 receptor signaling was not only due to PGE2-dependent but also PGE2-independent mechanisms. In contrast, an EP4 antagonist (ONO-AE3-208) did not inhibit growth in either of the cancer cell lines. In summary, PGE2 receptor EP3 signaling probably contributes to development of oral carcinomas and use of EP3 antagonist may be a new therapeutic strategy for head and neck cancer.

Expression of thiazide-sensitive Na+-Cl- cotransporter in the rat endolymphatic sac.

The endolymphatic sac (ES) is a part of the membranous labyrinth and is believed to absorb endolymph. It has been well-established that the endolymph absorption is dependent on several ion transporters in a manner similar to that in the kidney, and the ES is regulated by hormones such as aldosterone and vasopressin that also affect on the kidney. The thiazide-sensitive Na(+), Cl(-) cotransporter (TSC) is an electroneutral cotransporter specific to the kidney that plays an important role in absorption of NaCl in renal tubules. In the inner ear, TSC expression has never been examined. The expression of TSC in the rat ES was examined by RT-PCR, in situ hybridization and immunohistochemistry. These analyses indicated that TSC genes and proteins were expressed in the rat ES. In contrast, it was not observed in the rat cochlea by RT-PCR. This is the first report confirming the expression of TSC in the ES.

A new approach for selective rat endolymphatic sac epithelium collection to obtain pure specific RNA.

The endolymphatic sac (ES) is an organ that is located in the temporal bone. Its anatomical location makes ES tissue collection without any contamination very difficult, and sometimes accurate molecular analyses of the ES are prevented due to this matter. In the present study, a new selective ES epithelial tissue collection method was attempted using laser capture microdissection to obtain pure ES RNA without any contamination. The validity of this method was demonstrated by RT-PCR with three specific primer pairs against osteocalcin, calponin H1, and NKCC2, which are specific proteins in bone, smooth muscle, and kidney/ES cells, respectively. From the RT-PCR results, the high specificity and sufficient sensitivity of the new method was indicated. It is considered that the new method is optimal for ES collection without contamination and it will be able to contribute to future analyses of the ES.

Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer.

The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues.

Expression of the Na+-K+-2Cl- cotransporter in the rat endolymphatic sac.

The endolymphatic sac (ES) is a part of the membranous labyrinth that contains the cochlea, vestibular organs, an d semicircular canals, and is believed to absorb endolymphatic fluid. Na(+)-K(+)-2Cl(-) (NKCC) is a cotransporter that occurs as two isoforms (NKCC-1 and NKCC-2). Especially, NKCC-2 is suggested to participate in ES endolymph absorption. In the present study, the expression and cellular localization of NKCC-1 and NKCC-2 in the rat ES wer e examined by RT-PCR and in situ hybridization, respectively. The findings indicate that both NKCC-1 and NKCC-2 are expressed in the rat ES and suggest that NKCC is involved in ES homeostasis. NKCC-2 may be particularly involved in endolymph absorption. This is the first report confirming NKCC expression in the ES.

Influence of volumetric 4'-[methyl-11C]-thiothymidine PET/CT parameters for prediction of the clinical outcome of head and neck cancer patients.

OBJECTIVE: This prospective study compared the value of pretreatment 4'-[methyl-11C]-thiothymidine (11C-4DST) volumetric parameters and those of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) in predicting the clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Fifty patients with HNSCC underwent 11C-4DST PET/CT and 18F-FDG PET/CT prior to anticancer therapy. 18F-FDG metabolic tumor volume (18F-FDG MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET, and 11C-4DST MTV and total lesion proliferation (TLP) were calculated from 11C-4DST PET. All parameters were measured for the primary lesion and metastatic lymph nodes. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: Receiver-operating characteristic analysis revealed that MTV, TLG, and TLP acquired from the primary lesion and metastatic lymph nodes were good parameters for predicting disease relapse and death. The area under the curves (AUCs) ranged from 0.63 to 0.71 for 18F-FDG PET/CT parameters. The AUCs of 11C-4DST PET/CT parameters were larger than those of 18F-FDG (range 0.72-0.81). Univariate analysis revealed that individuals with tumors showing a high value for any PET/CT parameter were at a significantly increased risk of relapse. Upon multivariate analysis, 18F-FDG MTV, 11C-4DST MTV and 11C-4DST TLP were significant independent factors for relapse-free survival (P = 0.04, P = 0.0001 and P = 0.0005, respectively). CONCLUSION: Pretreatment 11C-4DST PET/CT volume-based parameters can provide important prognostic information about patients with HNSCC.

Prognostic value comparison between (18)F-FLT PET/CT and (18)F-FDG PET/CT volume-based metabolic parameters in patients with head and neck cancer.

PURPOSE: The present study compared the potential of pretreatment 3'-deoxy-3'-[F]-fluorothymidine (F-FLT) uptake parameters and those of F-FDG to predict the clinical outcome of head and neck squamous cell carcinoma treated with chemoradiotherapy. METHODS: A total 53 patients undergoing pretreatment F-FLT PET/CT and F-FDG PET/CT from May 2006 to April 2013 were evaluated. The SUVmax, metabolic tumor volume (MTV), total lesion glycolysis, and total lesion proliferation (TLP) were determined semiquantitatively. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: In univariate analyses, F-FLT SUVmax, MTV, TLP, F-FDG MTV, and total lesion glycolysis correlated with locoregional control (P = 0.02, P = 0.0007, P = 0.0001, P = 0.007, and P = 0.013, respectively). Clinical T stage, F-FLT SUVmax, MTV, TLP, and F-FDG SUVmax correlated with overall survival (P = 0.012, P = 0.0057, P = 0.0018, P = 0.0012, and P = 0.047, respectively). On multivariate analyses, F-FLT TLP was an independent factor for locoregional control (P = 0.002; hazards ratio [HR], 5.13; 95% confidence interval [CI], 1.81-14.54), as were F-FLT SUVmax and MTV for overall survival (P = 0.021; HR, 3.47; 95% CI, 1.2-10.01 and P = 0.029; HR, 3.17; 95% CI, 1.12-8.95). CONCLUSIONS: Pretreatment F-FLT PET/CT volume-based metabolic parameters are superior prognostic predictors to those of F-FDG PET/CT. F-FLT SUVmax and MTV can provide important prognostic information for patients with head and neck squamous cell carcinomas administered with chemoradiotherapy.

Clinical outcomes of nedaplatin and S-1 treatment with concurrent radiotherapy in advanced head and neck cancer.

CONCLUSION: Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients. OBJECTIVES: We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer. METHODS: Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed. RESULTS: Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers.

OBJECTIVE: The aim of this study was to investigate the predictive potential of pre-treatment 3'-deoxy-3'-[18F]-fluorothymidine (FLT) uptake parameters for short-term outcome of primary head and neck squamous cell cancer (HNSCC) patients. PATIENTS AND METHODS: A total of 32 patients undergoing pre-treatment FLT positron emission tomography/computed tomography (PET/CT) from May 2010 to May 2013 were evaluated. Semi-quantitative assessment was used to determine mean, peak and maximum standardized uptake values (SUVmean, SUVpeak and SUVmax), metabolic tumor volume (MTV) and total lesion proliferation (TLP). Clinicopathologic factors and PET/CT parameters were analyzed for their association with 2-year loco-regional control (LRC) and overall survival (OS). RESULTS: The mean (± SD) SUVmean, SUVpeak, SUVmax, MTV and TLP were 5.97 ± 3.16, 6.71 ± 3.75, 10.05 ± 5.37, 7.31 ± 8.05 and 44.95 ± 52.82, respectively. In univariate analyses, N category was associated with OS (P = 0.037). Increased MTV ≥13 ml was associated with decreased LRC and OS (P < 0.0001). TLP ≥69.3 g was also linked with both LRC and OS (P = 0.009 and 0.015, respectively). Regarding SUVs, only the SUVpeak was associated with LRC and OS (P = 0.035 and 0.049, respectively). CONCLUSIONS: Pre-treatment MTV is the most useful parameter with FLT PET/CT. TLP and SUVpeak may also provide important prognostic information for patients with HNSCCs.

The value of 18F-FLT PET for detecting second primary cancers and distant metastases in head and neck cancer patients.

OBJECTIVE: Diagnostic efficacy of (18)F-FLT PET was compared with that of (18)F-FDG PET regarding second primary cancers and distant metastases of head and neck squamous cell cancers (HNSCCs). METHODS: A total of 88 patients with HNSCCs were qualitatively examined with FLT PET and FDG PET for regions of focally increased metabolism. Final diagnoses of second primary cancer and distant metastasis were established on the basis of histological findings or clinical follow-up. RESULTS: FDG PET had 1 false-negative finding with lung metastasis, and FLT PET had 4 false-negative findings with 1 liver metastasis, 1 bone metastasis, and 2 lung metastases. There were no false-positive findings with FLT PET in contrast to 9 with FDG PET (1 in lung, 4 in mediastinum, 1 in rectum, and 3 in stomach). Overall accuracy of FDG PET and FLT PET for pretreatment metastasis staging was 92% and 98%, respectively. Five distant metastases in 3 patients occurred after the initiation of chemoradiotherapy. FLT PET missed 2 metastatic lesions (1 in liver and 1 in lung), whereas FDG PET could not discriminate intracranial metastasis because of FDG uptake in the brain. CONCLUSIONS: FLT PET does not appear to be recommendable to replace FDG PET for pretreatment metastasis staging in HNSCC cases because of its lower sensitivity and higher background activity in the liver and bone marrow. However, it might provide additional diagnostic specificity and biological information.