Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches.

PURPOSE: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population. METHODS: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm). RESULTS: EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively. CONCLUSION: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

BACKGROUND: A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. METHODS: Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. RESULTS: The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). CONCLUSIONS: The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.

Delta-volume radiomics of induction chemotherapy to predict outcome of subsequent chemoradiotherapy for locally advanced hypopharyngeal cancer.

INTRODUCTION: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. METHODS: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). RESULTS: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<-0.16) was associated with improved PFS (p < 0.05). CONCLUSIONS: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

Cigarette smoking increases the risk of nasopharyngeal carcinoma through the elevated level of IgA antibody against Epstein-Barr virus capsid antigen: A mediation analysis.

BACKGROUND: The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein-Barr virus (EBV) infection for NPC risk. METHODS: 1235 male NPC cases and 1262 hospital-based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti-EBV VCA IgA and anti-EBV EA-EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders. RESULTS: 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60-fold (95% CI = 1.30-1.97) and former smokers a borderline significant 1.27-fold (95% CI = 1.00-1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack-years of cigarette smoking but not with age at smoking initiation. Among controls, anti-EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19-2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti-EBV VCA IgA. CONCLUSION: This study confirms the association between long-term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti-EBV VCA IgA antibodies.

Evaluation of Rare and Common Variants from Suspected Familial or Sporadic Nasopharyngeal Carcinoma (NPC) Susceptibility Genes in Sporadic NPC.

BACKGROUND: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC. METHODS: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted. RESULTS: We found that NPC was associated with combined common and rare variants in CDKN2A/2B (P = 1.3 × 10-4), BRD2 (P = 1.6 × 10-3), TNFRSF19 (P = 4.0 × 10-3), and CLPTM1L/TERT (P = 5.4 × 10-3). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10-4; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU (P = 3.8 × 10-3) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs. CONCLUSIONS: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC. IMPACT: NPC-associated genes, including CLPTM1L/TERT, BRD2, and HNRNPU, suggest a role for telomere length maintenance in NPC etiology.

Caffeic acid phenethyl ester upregulates N-myc downstream regulated gene 1 via ERK pathway to inhibit human oral cancer cell growth in vitro and in vivo.

SCOPE: Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, is considered as a new anti-cancer agent. Oral squamous cell carcinoma (OSCC) is the most common oral cancer with unsatisfying survival. N-myc downstream regulated family genes (NDRGs) involve in numerous physiological processes. We investigated the anti-cancer effect of CAPE on OSCC and related mechanisms. METHODS AND RESULTS: Cell proliferation assay, western blot, gene transfection and knockdown, and reporter assay were applied. We showed that CAPE attenuated OSCC cell proliferation and invasion in vitro, and safely and effectively inhibited OSCC cell growth in a xenograft animal model. CAPE treatment induced NDRG1, but not NDRG2 and NDRG3, expression in OSCC cells as determined by western blot, RT-qPCR, and reporter assay. The 5'-deletion assay demonstrated that CAPE increased NDRG1 promoter activity depending on the region of -128 to +46 of the 5'-flanking of NDRG1 gene. NDRG1 gene knockdown attenuated CAPE anti-growth effect on OSCC cells. CAPE activated mitogen-activated protein kinase (MAPK) signaling pathway. The extracellular signal regulated kinase (ERK) inhibitor (PD0325901) and ERK1 knockdown blocked CAPE-induced NDRG1 expression in OSCC cells. CONCLUSION: CAPE activated MAPK signaling pathway and increased NDRG1 expression through phosphorylation of ERK1/2 to repress OSCC cells growth.

The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo.

Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.

Multiple analyses of factors related to complications in endoscopic sinus surgery.

BACKGROUND: This study was undertaken to evaluate whether endoscopic sinus surgery (ESS) with a microdebrider had an impact on complication rates, and to facilitate the determination of factors associated with complications in patients who underwent ESS at a tertiary referral center in Taiwan. METHODS: This investigation was a retrospective study and literature review. We analyzed 997 consecutive patients who underwent ESS at Mackay Memorial Hospital in Taipei, Taiwan from January 2006 through February 2010. All data including those of patient medical information, and peri- and postoperative complications were provided by the surgeons involved in patient medical care. We analyzed the complication rates using the following 10 variables by univariate analysis and multivariate logistic regression: sex, age, Lund-Mackay score, polyp grading, previous sinonasal surgery, surgeon skill, adjunctive sinonasal surgery, mesenteric type of anterior ethmoid artery, Keros skull base type, and the use of a microdebrider. RESULTS: Of the 997 patients in our study, 78 (7.8%) had complications. Major complications occurred in five patients (0.5%): two with cerebrospinal fluid rhinorrhea, one with medial rectus muscle damage, and two with retrobulbar hematoma. Minor complications were found in 73 patients (7.3%), which included 32 patients with perioperative estimated blood loss > 15% of the total estimated blood volume, 26 with lamina papyracea damage, two with orbital cellulitis, and 13 with postoperative bleeding. Univariate analysis showed that risk factors related to complication rate were advanced Lund-Mackay scores (scores 19-24), advanced polyp grading (Grades 2 and 3), inexperienced surgeon (resident), and microdebrider usage. However, multivariate analysis revealed that complication rate was linked to advanced Lund-Mackay scores (Scores 19-24), mesenteric type of anterior ethmoid artery, and inexperienced surgeon. CONCLUSION: Overall, the results of our study showed that the ESS complication rate was 7.8%, with risk factors including advanced Lund-Mackay scores (19-24, odds ratio 10.4) and inexperienced surgeon. It was also noted that ESS with a microdebrider had no impact on complication rates, although the presence of a mesenteric type of anterior ethmoid artery proved to be a protective factor.

Upregulation of B-cell translocation gene 2 by epigallocatechin-3-gallate via p38 and ERK signaling blocks cell proliferation in human oral squamous cell carcinoma cells.

Oral squamous cell carcinoma (OSCC) is a well-known malignancy that accounts for the majority of oral cancers. B-cell translocation gene 2 (BTG2) is an important regulator of cell cycle dynamics in cancer cells. However, the role of BTG2 in OSCC cells and the influences of epigallocatechin-3-gallate (EGCG) on BTG2 gene expressions have not been well evaluated. The objectives of this study were to examine the effect of EGCG-induced BTG2 expression and the potential signal pathways involved. The (3)H-thymidine incorporation and Western-blot assays revealed cell proliferation was attenuated by EGCG via upregulation of BTG2 expression causing cell cycle G1 phase arrest in OSCC cells. BTG2 overexpression decreased tumor cell growth, while BTG2 knockdown illuminated the opposite effect in xenograft animal studies. Overexpressed BTG2 arrested the cell cycle at the G1 phase and downregulated protein expressions of cyclin A, cyclin D, and cyclin E. Western-blot assays indicated that EGCG induced phosphorylation of p38, JNK, and ERK. However, pretreatments with selective mitogen-activated protein kinase (MAPK) inhibitors, SB203580 (p38 inhibitor) and PD0325901 (ERK1/2 inhibitor), significantly suppressed the activation of EGCG on BTG2 expression. Our results indicate that EGCG attenuates cell proliferation of OSCC cells by upregulating BTG2 expression via p38 and ERK pathways.

Prolonged radiation time and low nadir hemoglobin during postoperative concurrent chemoradiotherapy are both poor prognostic factors with synergistic effect on locally advanced head and neck cancer patients.

BACKGROUND: Anemia, a common complication of head and neck cancer treatment, is regarded as a poor prognostic factor. We evaluated the impact of low hemoglobin (Hb) levels, measured at different time points, on a consecutive cohort of patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) who underwent postoperative concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From 2002 to 2009, 140 patients were enrolled and reviewed retrospectively. Preoperative (pre-op Hb), pre-CCRT Hb, and nadir Hb during CCRT were measured and recorded. The three Hb parameters were analyzed against several well-established pathologic risk factors and radiation-associated variables. Prognostic impacts were investigated with multivariate analysis by Cox proportional hazards model. RESULTS: On Cox regression analysis, significantly higher risk of death was associated with pre-op Hb ≦13 g/dL (hazard ratio [HR] =1.8; 95% confidence interval [CI], 1.1-3.1; P=0.023), nadir Hb ≦11 g/dL (HR =1.9; 95% CI, 1.1-3.3; P=0.020), radiation treatment time (RTT) >7 weeks (HR =1.9; 95% CI, 1.1-3.3; P=0.022), and multiple positive lymph nodes (HR =2.1; 95% CI, 1.2-3.7; P=0.010), after adjusting for primary tumor site and pathologic lymphovascular invasion. Patients with poor prognosticators including low nadir Hb ≦11 g/dL and RTT >7 weeks had a higher risk of death (HR =4.0; 95% CI =1.6-10.2; P=0.004). CONCLUSION: In the treatment setting of LA-SCCHN patients who underwent postoperative CCRT, coexistance of lower nadir Hb during CCRT and prolonged RTT resulted in reduced survival.

Guideline and preliminary clinical practice results for dose specification and target delineation for postoperative radiotherapy for oral cavity cancer.

BACKGROUND: Surgery followed by radiotherapy (RT) is indicated for patients with high-risk oral cavity cancer (OCC). Based on multi-institutional reports, we developed a guideline for postoperative RT for patients with OCC. METHODS: A multidisciplinary OCC team was recruited to develop a questionnaire concerning details of risk-factor categorization, target delineation, and dose specification. Thirty-one radiation oncologists from 18 institutions completed the questionnaire, and data were subjected to extensive review to establish the guideline by expert meeting. In this study, we also report the results for patients treated in accordance with the guideline at our institution between 2007 and 2011. RESULTS: Forty-one patients received RT compatible with this guideline with a median 26.8-month follow-up. Thirty-two patients (78%) remained disease-free, 6 (15%) developed locoregional recurrence (4 in-field, 1 marginal, and 1 out-field) and 4 (10%) developed distant metastasis. The overall 2-year survival rate was 86.7%. CONCLUSION: This guideline is promising and should be validated and refined in further clinical practice.

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN. MATERIALS AND METHODS: The patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan-Meier statistical method. RESULTS: We demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4-193.4; P=0.002). CONCLUSION: In this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy.

N-myc downstream-regulated gene 1 downregulates cell proliferation, invasiveness, and tumorigenesis in human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common phenotype of oral cancer. N-myc downstream regulated gene 1 (NDRG1) is a modulator for cell proliferation, differentiation, and invasion. The role and function of NDRG1 in OSCC cells remain inconclusive. The (3)H-thymidine incorporation and in vitro matrigel invasion assays revealed NDRG1-knockdown significantly enhanced OSCC cell proliferation and invasion. Overexpressed NDRG1 arrested the cell cycle at the S-phase, thus attenuated cell proliferation in OECM-1 cells. The NDRG1-knockdown enhanced tumorigenesis of OECM-1 cells in the xenograft animal model. Western-blot and zymographic assays revealed that NDRG1 downregulated the gelatinase activities and protein levels of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9). NDRG1 modulated epithelial-mesenchymal transition (EMT) through upregulation of the E-cadherin expression, but downregulation of the N-cadherin, Vimentin, Snail-1, and Slug. Immunofluorescence staining indicated knockdown of NDRG1 enhanced F-actin expression and polymerization. Our results indicated NDRG1 attenuated OSCC cell growth in vitro and in vivo. The downregulation of EMT, MMP-2, and MMP-9 may explain the role of anti-invasion of NDRG1 in human OSCC cells. The experiments recognize that NDRG1 is an antitumor gene in OSCC cells.

A fabricated forearm free flap with accompanying phonation tube for simultaneous reconstruction of a pharyngolaryngeal circumferential defect and voice loss: new surgical modification with functional phonation outcome.

BACKGROUND: Total pharyngolaryngectomy is potentially ablative surgery, resulting in compromise of some most basic functions of life, including speech and swallowing. Tracheoesophageal puncture is the gold standard for voice restoration. But it still has prosthesis-related problems. OBJECTIVES/HYPOTHESIS: We designed a uniquely customized radial forearm free flap (RFFF), which also incorporated a region for phonation tube (PT) creation, for the dual purpose of circumferential laryngopharyngeal defect reconstruction and voice production. METHODS: From August 2005 to September 2010, there were 18 male patients with late-stage hypopharyngeal cancer (HPC) or laryngeal cancer (LC) who received one-stage reconstruction with the fabricated RFFF-accompanying PT after total pharyngolaryngectomy. We recorded the phonation outcome of phonation efficacy (PE) and maximal phonation time (MPT) postoperatively within 1 month and at least 1 year after surgery. RESULTS: Nine patients suffered from HPC and the others suffered from LC. Twelve patients received concurrent chemoradiotherapy after surgery. The follow-up time was 12 to 56 months (mean 28.7 months). There was no significant variance in the PE (79.72%, SD=21.93% vs. 62.50%, SD=39.60%, respectively; p = 0.115) and MPT (2.58 seconds, SD=1.80 vs. 2.97 seconds, SD=3.96, respectively; p = 0.878) between the first and last follow-up points, even when the patients were grouped by radiotherapy status after surgery or by disease group. CONCLUSIONS: The phonation outcome in our experience was satisfactory and it tolerated postoperative radiotherapy during at least the 12-month follow-up period.

Comparison of the efficacy and toxicity of two dose levels of cisplatin/5-fluorouracil as the chemoradiotherapy regimen for the treatment of locally advanced squamous cell carcinoma of the head and neck.

CONCLUSION: The low-dose regimen brought less grade 3?4 neutropenia and mucositis with similar treatment efficacy. It should be further investigated in prospective randomized clinical trials to confirm its effectiveness and tolerability. OBJECTIVES: This nonrandomized study compared the efficacy and toxicity profiles of two dose levels of cisplatin/5-fluorouracil (5-FU) as the chemoradiotherapy regimen for the treatment of locally advanced squamous cell carcinoma of the head and neck. METHODS: Concurrent chemotherapy consisted of two dose levels: a low dose (cisplatin 12 mg/m(2) + 5-FU 600 mg/m(2) per day) or a high dose (cisplatin 15 mg/m(2) + 5-FU 750 mg/m(2) per day). Both were administered as a 5-day continuous infusion in week 1 and week 5 during radiotherapy. RESULTS: With a median follow-up of 44 months, the overall survival and disease-free survival were 35 months and 22 months (n = 67) for the low-dose group and 36 months and 33 months for the high-dose group (n = 96). The 2-year locoregional control rate was 67.2% for the low-dose and 66.8% for the high-dose group. No statistically significant differences were demonstrated in the treatment efficacy end points. The high-dose regimen resulted in significantly more grade 3?4 neutropenia (31.5% vs 10.9%, p = 0.003) and a trend towards more mucositis (62.1% vs 49.3%, p = 0.066).

Voice and speech outcomes with radial forearm free flap-accompanied phonation tube after total pharyngolaryngectomy of hypopharyngeal cancer.

CONCLUSIONS: Radial forearm free flap (RFFF)-accompanied phonation tube (PT) for voice and speech restoration after pharyngolaryngectomy is promising, especially in phonation efficacy and intelligibility. It offers not only another safe surgical option but also a satisfactory result for such patients with advanced hypopharyngeal cancer. OBJECTIVES: We use RFFF with RFFF-accompanied PT for one-stage reconstruction both for tissue defect and voice reconstruction in patients undergoing total pharyngolaryngectomy. METHODS: Eight male patients with advanced hypopharyngeal cancer underwent total pharyngolaryngectomy. Voice restoration was done with RFFF-accompanied PT. Phonation outcomes and speech outcomes of the patients were evaluated and scored. RESULTS: The mean follow-up time was 13.7 months. All free flaps were successful without perioperative mortality. All the patients were able to produce sound. Phonation efficacy ranged from 70% to >90% postoperatively and 40% to >90% at the last follow-up. The speech intelligibility was graded as moderately good.