A Head-to-Head Comparison of the Medial Sural Artery Perforator versus Radial Forearm Flap for Tongue Reconstruction.

BACKGROUND: For tongue reconstruction, the radial forearm flap (RFF) is commonly used. In the last decade, the medial sural artery perforator (MSAP) flap has been successfully used with reportedly superior donor-site outcomes. Our study is the first to compare the RFF and MSAP for reconstruction of partial glossectomy defects (<50% of tongue). METHODS: We conducted a retrospective review of 20 patients with partial glossectomy defects reconstructed at a tertiary referral center. Patient demographics, perioperative data, and postoperative complications were analyzed. Objective measures of speech, swallowing, and subjective patient satisfaction with their donor site were recorded. RESULTS: Ten RFF and MSAP were each used, with a mean partial glossectomy defect size of 40.5 and 43.5%, respectively. The MSAP was significantly thicker (7.8 vs. 4.3 mm, p < 0.05) with a longer harvest time (122.5 vs. 75.0 minutes, p < 0.05). There were no cases of free flap failure. Donor-site healing times were comparable, but the MSAP group experienced significantly less donor-site complications (n = 1 vs. n = 7, p < 0.05). Functional outcomes were comparable with 13 patients achieving normal speech and diet after 3 months (MSAP = 6 vs. RFF = 7, p = 1.00). All patients were satisfied with their donor-site outcome with the MSAP group having a marginally higher score. CONCLUSION: Both flaps are good options for partial glossectomy reconstruction. Though more challenging to harvest, the MSAP gives comparable functional results and has become our first reconstructive option given its superior donor-site outcomes.

Implementing the Biodesign Process for Medical Device Innovation in Head and Neck Surgery.

Introduction. The Stanford Biodesign process is a needs-driven approach to innovation which begins in the clinical setting and environment and is championed by practicing clinicians and surgeons. Here, our team applied the Stanford Biodesign process through clinical immersion to identify potential unmet clinical needs in the field of head and neck surgery, brainstormed and prototyped solutions to solve the top unmet need, and developed a commercialized medical device. Methods. The team underwent the 3 phases of the Biodesign process: identify, invent, and implement. The team underwent clinical immersion and followed head and neck surgeons from the Department of Head and Neck Surgery for a duration of 1 month. The needs identified were then filtered through a structured process using predefined filters, and a top need was chosen. After multiple rounds of brainstorming and prototyping, a final concept was developed. Results. The team collected 111 unmet needs and designed the in vivo surgical lighting concept that eventually led to the development of the KLARO™ in vivo surgical lighting device with a commercial partner. KLARO™ is a fully flexible 4.6-mm diameter light-emitting diode light strip that is freely bendable to be safely placed into deep cavities during open surgeries. Conclusion. The Biodesign process provides a standardized way to turn these needs into solution to advance the field of head and neck surgery and improve the outcome of patients.

Comparing the Utility and Surgical Outcomes of Harmonic Focus Ultrasonic Scalpel with Ligasure Small Jaw Bipolar Device in Thyroidectomies: A Prospective Randomized Controlled Trial.

BACKGROUND: Ultrasonic or bipolar radiofrequency energy devices are routinely used for dissection and hemostasis during thyroidectomy. We report a single-center, prospective, randomized controlled trial comparing the utility and outcomes of Harmonic Focus, an ultrasonic coagulating shear device (UCSD), versus Ligasure Small Jaw, an electrothermal bipolar vessel sealer (EBVS) in thyroidectomy (NCT01765686). METHODS: Between December 2012 to January 2016, eligible patients were randomized to undergo hemithyroidectomy using either a UCSD or an EBVS. The primary outcome was duration of surgery. Secondary outcomes included blood loss, postoperative complications, ease of device use, ease of device set-up, vocal cord function, postoperative wound drainage, pain score, and adverse events. RESULTS: Of 110 patients assessed for eligibility, 100 were randomly allocated (UCSD: 49 patients; EBVS: 51 patients) and analyzed by intention-to-treat. There were no differences in specimen delivery time, total duration of surgery, wound drainage, and adverse events between the two groups. The UCSD group had a greater proportion of patients with higher postoperative pain scores in the first 72 h (8.1% vs. 2.0%, p = 0.043). Surgeons reported greater ease of use for the UCSD (49% vs. 27%; p = 0.005), while operating room staff favored the EBVS (60% vs. 33%, p = 0.005). CONCLUSIONS: Energy devices are equally effective in reducing thyroidectomy operative times, with no differences in the duration of surgery, drainage, or adverse events. Use of the UCSD was associated with higher postoperative pain scores, but was favored by the surgeons, likely due to the ability to perform fine dissection with the device itself.

Comparison of Outcomes of Fasciocutaneous Free Flaps and Jejunal Free Flaps in Pharyngolaryngoesophageal Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: The literature reports a wide variety of reconstructive methods for pharyngolaryngoesophageal (PLO) defects, the most widely used being anterolateral thigh (ALT), radial forearm (RFF), and jejunal free flaps (JFF). However, there is a lack of uniform agreement among head and neck surgeons as to which technique offers the best results. With an increasing number of salvage PLO extirpations, determining the role of radiotherapy in influencing postoperative complication rates is becoming ever more important. Hence, this study aims to provide an up-to-date comparison of surgical and functional outcomes of the fasciocutaneous ALT and RFF versus the intestinal JFF for circumferential and partial PLO defects and determine whether radiotherapy, both preoperative and postoperative, influences the postoperative fistula and stricture rates in circumferential defects. METHODS: A systematic review and meta-analysis were performed using PubMed for reports published in the most recent 10 years between 2007 and 2017. RESULTS: A total of 33 articles comprising 1213 patients were reviewed. For circumferential defects, fistula and stricture rates were significantly lower in JFF than ALT and RFF. Of note, there was no statistical difference in tracheoesophageal speech and oral alimentation rates between JFF and the FC flaps. For near-circumferential and partial defects, ALT has a significantly lower fistula rate than RFF. There was no statistical difference in stricture and oral alimentation rates between ALT and RFF [corrected]. Fistula rates were significantly higher in patients who had preoperative radiotherapy than those without. However, there was no significant difference in fistula and stricture rates for postoperative radiotherapy. CONCLUSIONS: Jejunal free flaps still remain an excellent first choice for PLO reconstruction of circumferential defects. For near-circumferential and partial defects, ALT seems to have a better performance than RFF. Preoperative radiotherapy was associated with an increased risk of fistula formation in circumferential PLO defects but not postoperative radiotherapy.

Nasopharyngectomy with operating microscope: A case series.

BACKGROUND: Nasopharyngectomy for excision of nasopharyngeal tumors is challenging, as access to the nasopharynx is difficult. Recently our institution embarked on two new approaches - robotic nasopharyngectomy and open nasopharyngectomy with operating microscope (NOM) via maxillary swing approach. This article proposes that the novel approach of NOM via maxillary swing aids visualization for resection of locally invasive nasopharyngeal tumors. METHODS: Over a thirteen-month period, eight patients required nasopharyngectomy in our single Asian institution. Four underwent robotic nasopharyngectomy and four underwent NOM via maxillary swing approach. The latter four were retrospectively reviewed, and their clinical characteristics and surgical outcomes reported. Tips and pearls for operative setup and patient selection were also discussed. RESULTS: All four patients who underwent NOM had negative intraoperative frozen sections with subsequent negative paraffin sections. All patients remained disease free post-salvage surgery. CONCLUSION: NOM via maxillary swing allows better visualization and aids in augmentation of open nasopharyngectomy. This enables achievement of adequate resection margins and fewer surgical complications in locally invasive nasopharyngeal tumors.

Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma.

Thyroid carcinoma usually presents as a neck lump. Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma (WDTC) is rare and little is known about these patients. The aim of this study is to characterize patients who present with distant metastasis as the sole initial manifestation of WDTC. Retrospective review of case records of WDTC seen at the National Cancer Centre Singapore from 2002 to 2015 was performed. Patients with no prior complaint of neck swelling and whose first presentation was distant metastatic WDTC were included. Patient demographics, disease characteristics, radiological imaging, histopathology, types of treatment administered, and survival outcomes were examined. Nineteen out of seven hundred and thirty-two cases fulfilled inclusion criteria. Mean age was 65.4 years. All patients presented with osseous (36.8%), pulmonary (31.6%), cerebral metastases (5.3%), or a combination of two out of three aforementioned sites (26.3%). Follicular thyroid carcinoma was most common (47.4%), followed by papillary (36.8%) and medullary (15.8%). More than two-thirds of patients had multiple metastatic foci. Thirteen out of nineteen patients (68.4%) underwent total thyroidectomy with or without neck dissection and adjuvant RAI, while the rest declined surgery. The mean length of follow-up was 40.1 ± 5.1 months and 5-year disease-specific survival was 48.0 ± 17.2%. Distant metastasis without a history of neck swelling as the initial presentation of WDTC is extremely rare. Osseous metastasis and follicular thyroid carcinoma are the most common metastatic site and etiology, respectively. Disease-specific survival at 5-year post-diagnosis is lower compared to patients with thyroid carcinoma diagnosed with distant metastasis on further work-up.

Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis.

BACKGROUND: The current study was performed to report the long-term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery and adjuvant radiotherapy (RT) in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma. METHODS: Patients with stage III/IV resectable head and neck squamous cell carcinoma were randomized to surgery followed by RT or CCRT. The trial was halted prematurely due to poor accrual. Human papillomavirus status was tested on archival material using polymerase chain reaction sequencing. RESULTS: Of the total of 119 patients, 60 patients were randomized to primary surgery (S arm) and 59 patients were randomized to CCRT (C arm). Human papillomavirus status was tested in 75 patients, and only 3 were found to be positive. The median follow-up for surviving patients was 13 years. Analysis of the entire cohort demonstrated no statistically significant difference in overall survival and disease-specific survival (DSS): 5-year rates were 45% versus 35% for overall survival (P = .262) and 56% versus 46% for DSS (P = .637) for the S arm and C arm, respectively. Analysis by subsites indicated that this difference favoring the S arm was mainly driven by survival data among patients with cancers of the oral cavity and maxillary sinus. For patients with oral cavity cancer, survival was significantly better in those who underwent primary surgery compared with CCRT; the 5-year DSS rate was 68% versus 12% for the S arm and C arm, respectively (P = .038). For patients with cancers of the maxillary sinus, the 5-year DSS rate was 71% for patients on the S arm and 0% for patients on the C arm (P = .05). CONCLUSIONS: These long-term results demonstrate a significant advantage for primary surgery in patients with cancers of the oral cavity or maxillary sinus, providing strong support for primary surgery as the main modality of treatment for these subsites. In other subsites, CCRT and surgery with adjuvant RT were found to demonstrate similar efficacy for survival in patients with advanced resectable tumors.

An objective comparison regarding rate of fistula and stricture among anterolateral thigh, radial forearm, and jejunal free tissue transfers in circumferential pharyngo-esophageal reconstruction.

BACKGROUND: The three commonly used free flaps for circumferential pharyngeal reconstruction after total pharyngo-laryngectomy are the radial forearm flap (RFF), the anterolateral thigh (ALT) flap, and the jejunum flap. This study was to objectively compare three different flaps for pharyngeal reconstruction during the past 10 years. Stricture and fistula were assessed using esophagogram and esophagoscopy. METHODS: Forty-five patients with pharyngeal reconstructions had esophagram and esophagoscopy done postoperatively to assess for strictures and fistulas. These patients were divided into three groups based on pharyngeal reconstruction by ALT, RFF, and jejunal flaps. From the results of the esophagogram and esophagoscope, the presence of a fistula or stricture was compared and analyzed. RESULTS: There was only one ALT flap failure. The rate of fistula was 33%, 50%, and 30% in the ALT, RFF, and jejunal flap group respectively. The fistula rate revealed no significant difference between ALT, RFF, jejunal flap groups (P = 0.63). The rate of stricture was 38.1%, 57.1%, and 0% in the ALT, RFA, jejunal flap groups respectively. The stricture rate in jejunal flap group revealed significant decrease (P = 0.0093). CONCLUSION: Jejunal flap has a significantly lower rate of stricture for reconstruction of circumferential pharyngeal defects when compared with RFF or ALT flaps.

Influence of neck dissection and preoperative irradiation on microvascular head and neck reconstruction-Analysis of 853 cases.

BACKGROUND: Previous neck dissection and irradiation is believed to affect the success of free tissue transfers in head and neck reconstruction, but evidence is scarce and conflicting. This study seeks to evaluate flap success rates in the presence of these two factors. METHODS: Over a ten-year period, a total of 853 free flap cases were evaluated. Success rates were compared between a control group with no prior intervention (non-irradiation and neck dissection, NRTND) against three other groups: irradiation only (RT), previous neck dissection only (ND), and both (RTND). The choices of recipient vessel used were also compared. RESULTS: The flap failure rate was 6.3% (4/63) in the RTND group; 4.8% (1/21) in the ND group; 5.2% (6/115) in the RT group; and 2.1% (14/654) in the NRTND group. There was no statistical significance among the four groups (P = 0.254). Ipsilateral neck vessels (92.7%) were more frequently used in the NRTND group. In contrast, the superficial temporal vessels, contra-lateral neck vessels were more likely to be selected in the groups with irradiation and/or neck dissection. CONCLUSIONS: Free tissue transfer in head and neck patients with previous irradiation and neck dissection is feasible and can be safely done. In addition, superficial temporal vessel could be the first choice in patients with previous radiotherapy and neck dissection.

The outcome of prostaglandin-E1 and dextran-40 compared to no antithrombotic therapy in head and neck free tissue transfer: analysis of 1,351 cases in a single center.

Free tissue transfer has become a popular technique for soft tissue defect reconstruction in head and neck cancer ablation. Although high success rates and good reliability of free flaps are proven, microvascular thrombosis is still the most critical issue for microsurgeons. Pharmacological antithrombotic agents are widely used but their efficacy is still debated. In this study, we analyzed whether prostaglandin-E1 (PGE1) and dextran-40 can improve the outcomes compared to no antithrombotic therapy at all. We retrospectively reviewed 1,351 free flaps performed for head and neck reconstruction after cancer ablation. Three groups defined were 232 flaps received PGE1, 283 flaps received dextran-40, and 836 received no antithrombotic therapy. The demographics of these three groups indicated no statistical differences. The results showed that flap survival revealed no significant difference among PGE1, dextran-40, and control group (P = 0.734). There was a tendency to hematomas in PGE1 group (P = 0.056) when compared with other two groups. Dextran-40 significantly increased flap failure rate in high-risk patients with diabetes mellitus (P = 0.006) or hypertension (P = 0.003), when compared with PGE1 and control group. These results revealed antithrombotic therapy with PGE1 and dextran-40 do not determine a significant improvement in flap survival.

Single free anterolateral thigh flap for simultaneous reconstruction of composite hypopharyngeal and external neck skin defect after head and neck cancer ablation.

Single flap for complex hypopharyngoesophageal and anterior neck skin defect reconstruction is still a challenge for reconstructive surgeons. Herein, we present five patients, with advanced hypopharyngeal cancer and anterior neck skin invasion, which received a single anterolateral thigh (ALT) fasciocutaneous flap for composite inner pharyngeal and outer skin defect reconstruction after wide composite resection. Two ALT flaps were divided into two distinct paddles supplied by two or more separate perforators, one part for reconstructing the inner pharyngeal defect and another for neck skin coverage. Three ALT flaps only supplied by one sizable perforator could not be divided and de-epithelization of mid-part had to be done to reconstruct both defects with the single flap. The results revealed survival of all flaps. There were no flap loss, fistulas, or bleeding complications. All patients recovered uneventfully and could eat a soft diet to regular diet postoperatively. In conclusion, one-staged reconstruction of complex pharyngoesophageal and external skin defects after extensive oncological resection is feasible using a single ALT fasciocutaneous free flap.

Design and development of ferrocene-containing chitosan-cografted-branched polyethylenimine redox conjugates for monitoring free flap failure after reconstructive surgery.

We reported a proof-of-concept study of developing an electrochemical biosensor for prolonged continuous monitoring free flap failure caused by vascular occlusion after reconstructive surgery. Ferrocene (Fc)-containing Chitosan-cografted-Branched Polyethylenimine redox conjugates (CHIT-Fc-co-BPEI-Fc) were used as pH-tuneable matrix to attach the target enzymes (glucose oxidase ≡ GOD and lactate oxidase ≡ LOD, respectively) to build up the corresponding GOD-sensor and LOD-sensor. The sensitivity of GOD-/LOD-sensor was found to be 2.89(±0.06)µA/mM and 2.95(±0.19)µA/mM with a limit of detection (LOD) of 0.047 mM and 0.172 mM, respectively. The sensor performance was further pre-clinically validated via rabbit study, which confirmed that the designed biosensors could electrochemically detect the changes of metabolite levels caused by flap failure within minutes. This sensor protocol is able to be fabricated as embedded biosensor for prolong continuous detection for clinical application/research.

Factors associated with returning to work in head and neck cancer survivors in Singapore: A preliminary exploratory mixed-methods approach study.

BACKGROUND: Little is known about return-to-work (RTW) among Asian head and neck cancer (HNC) survivors. We investigated the prevalence and factors associated with RTW among HNC patients with in Singapore. METHODS: In this cross-sectional mixed-methods study, 80 HNC patients, who had been working prior to diagnosis, completed questionnaires and 15 participated in qualitative interviews to explore perceived barriers and facilitators of RTW. Multivariate logistic regression was used to evaluate factors associated with not-returning-to-work (NRTW) within 6 months of treatment completion. RESULTS: Thirty-five participants reported NRTW 43.8%. Multivariable analysis showed that patients with advanced stage (III-IV) cancer (odds ratios [OR] = 4.51, 95% confidence intervals [CI]: 1.15-13.28, p = 0.006), multi-modality treatment (OR = 4.62, 95% CI: 1.38-15.52, p = 0.013), and pink-collar jobs (OR = 9.30, 95% CI: 1.70-50.83, p = 0.010) had higher odds of NRTW. CONCLUSION: The factors associated with employment after HNC treatment are complex. Identification of key modifiable factors may lead to improved RTW outcomes.

Impact of Radiotherapy on Neck Dissection Nodal Count in Patients With Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: Our study aimed to review the impact of preoperative radiotherapy (RT) and other factors on the lymph node count of neck dissection (ND) specimens from patients with head and neck cancer (HNC). A retrospective study was conducted on all patients with head and neck cancers who had undergone NDs in Singapore General Hospital between 1992 and 2013. STUDY DESIGN: Retrospective study. METHODS: Patients were categorized into two groups: patients treated with RT with or without chemotherapy before ND and patients who had undergone ND surgery without previous history of RT. The primary endpoint for this study would be the lymph node count from ND. RESULTS: The study cohort consists of 1,024 NDs on 829 patients. There were 597 (58.3%) radical/modified radical NDs involving levels I-V. Within this group, 75 (12.6%) NDs had preoperative RT. Preoperative RT and age were found to significantly reduce nodal yield in both univariate and multivariate analysis in the radical/modified radical ND subgroup. In our multivariate analysis, preoperative RT was shown to decrease the nodal yield by 7.464 (P = .0002, 95% confidence interval [CI]: -11.35 to -3.58). Advanced age independently decreases nodal yield, even after accounting for the effect of RT (P = .0002, 95% CI: -0.27 to -0.08). In addition, preoperative RT has a more pronounced effect in reducing lymph node count in the older age group. CONCLUSIONS: Preoperative RT and advanced age are independent and synergistic factors that reduce nodal count from NDs in patients with head and neck cancers. LEVEL OF EVIDENCE: 4 Laryngoscope, 130: 1947-1953, 2020.

Validity and reliability of the MD Anderson dysphagia inventory in English and Chinese in head and neck cancer patients.

AIMS: Patient-reported outcome measures are important in assessing the impact of dysphagia on quality of life. Our aim was to adapt and examine the cultural validity and reliability of a swallowing-related quality of life measure, the MD Anderson Dysphagia Inventory (MDADI), in English and Chinese, with head and neck cancer patients. METHODS: We adapted the MDADI to Chinese through formal forward-backward translation. Sixty-six head and neck cancer survivors completed the MDADI, Swallowing Quality of Life (SWAL-QOL) questionnaire and Hospital Anxiety and Depression Scale (HADS) in English or Chinese. Swallowing status was scored on the Functional Oral Intake Scale (FOIS). Seventy-four percent (n = 49) of participants completed a repeat administration of the MDADI for test-retest reliability analysis. RESULTS: The MDADI showed high internal consistency reliability (Cronbach's α , 0.82 ≤ α ≤ 0.94), and test-retest reliability in both English (intraclass correlation coefficient, ICC = 0.81) and Chinese (ICC = 0.72). Criterion validity was established through moderate to strong correlations with relevant SWAL-QOL domains. Convergent validity was determined by significant correlations to the HADS and FOIS. Divergent validity was determined by nonsignificant association to the SWAL-QOL Sleep domain. The MDADI also presented as hypothesised to most known-group theoretical constructs. CONCLUSIONS: The MDADI showed good psychometric properties in English and Chinese. This avails a reliable and psychometrically valid MDADI for Chinese speakers.

Adherence of head and neck squamous cell carcinoma patients to tumor board recommendations.

BACKGROUND: Multidisciplinary team (MDT) meetings or tumor boards (TBs) are fundamental components of cancer treatment. Although their primary function is improved outcomes, this aspect is often underreported. The main objective of this study was to analyze the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) discussed at TBs, and to compare the effect of adherence and nonadherence to recommended treatment plans on outcomes. METHODS: Retrospective data analysis was conducted of HNSCC patients those who were adherent and nonadherent to TB therapy recommendations during 2008-2009 at a comprehensive cancer center. Fisher's exact test and t test were used for group-wise comparison, and Kaplan-Meier and logistic regression models, for survival analysis and determination of the contributing factors to nonadherence. RESULTS: Comprehensive Treatment plans were recommended by TBs in 293 HNSCC patients with curative intent. Seventy-two patients were excluded based on the selection criteria. Among the remaining 221 patients, 172 (77.9%) were adherent to TB recommendations, while 49 (22.1%) failed to comply. Patient (n = 36; 73.5%), clinician (n = 2; 4.1%), and disease-related (n = 11; 22.4%) factors were significant contributors to nonadherence. Mean (±standard deviation (SD)) survival time was 55.6 ± 2.32 and 29.1 ± 4 months in the adherent and nonadherent groups, (P < .0001, respectively). Multivariate analyses showed that gender, ethnicity, higher T-stage, and multimodal treatment were associated with nonadherence. CONCLUSION: Adherence to TB recommendations improved overall survival, reflecting the importance of interdisciplinary expertise in contemporary cancer treatment. Early identification and intervention is crucial in "at risk" patients to prevent subsequent drop-out from optimal cancer care.

Electronic tumor board presentations as the basis for the development of a head and neck cancer database.

BACKGROUND: Multidisciplinary team meetings or tumor boards (TBs) form a pivotal component of oncology practice. The crux of a TB revolves around making treatment decisions based on succinct head and neck cancer (HNC) patient data presentations, which can be challenging and complex. Apart from meticulous TB presentations, discussions and treatment plan documentation is equally important. The aim of this study was to structure an electronic synoptic TB data presentation to address all these areas. The overarching benefits of systematic TB data collection include facilitating audits and research. METHODS: We utilized a secure web-based tool that was used for common scientific research purposes but customized to store HNC patient data. The data points were tabulated across eight TB pages: (a) TB scheduling, (b) patient biodata, (c) diagnosis details, (d) index presentation, (e) images, (f) management and histopathology, (g) TB presentation, and (h) TB discussion and decisions. Each data point leads to additional fields by branching logic to permit further relevant data entry. This was integrated within the patient electronic medical records allowing for a direct internal trajectory to recall TB data. RESULTS: From October 2015 to October 2018, we recorded over 2000 presentations for 1279 individual patients. This is a quality improvement initiative, and hence, the results are more of a broad analysis of our TB presentation process. The most common cancers were squamous cell (523, 41%), thyroid (207, 16%), and nasopharyngeal (139, 11%) carcinomas. Importantly, this system has formed the basis for a number of clinical and translational research projects and audit outcomes. CONCLUSION: Despite TBs being vital to oncologic practice, little attempt has been made to report TB data management. In this study, we present an efficient system that permits the integration of dual functions: TB data presentation and oncologic data collection for research, recall, and audit purposes.

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma.

Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15+), macrophages (CD68+), cytotoxic T cells (CD8+), Tregs (FOXP3+), and PD-L1+ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.

Pairing a prognostic target with potential therapeutic strategy for head and neck cancer.

OBJECTIVES: We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, and ANO1) for Head and Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the consequence of ATP13A3 dysregulation on signaling pathways, to aid in formulating a therapeutic strategy targeting ATP13A3-overexpressing HNSCC. MATERIALS AND METHODS: Gene Set Enrichment Analysis (GSEA) was performed on HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) to identify pathways associated with high expression of ATP13A3. Validation was performed using immunohistochemistry (IHC) on tissue microarrays (TMAs) of head and neck cancers (n = 333), staining for ATP13A3 and phosphorylated Aurora kinase A (phospho-T288). Short interfering RNA was used to knockdown ATP13A3 expression in patient derived HNSCC cell lines. Protein expression of ATP13A3 and Aurora kinase A was then assessed by immunoblotting. RESULTS: GSEA identified Aurora kinase pathway to be associated with high expression of ATP13A3 (p = 0.026). The Aurora kinase pathway was also associated with a trend towards poor prognosis and tumor aggressiveness (p = 0.086, 0.094, respectively). Furthermore, the immunohistochemical staining results revealed a significant association between Aurora kinase activity and high ATP13A3 expression (p < 0.001). Knockdown of ATP13A3 in human head and neck cell lines showed decrease in Aurora kinase A levels. CONCLUSION: Tumors with high ATP13A3 are associated with high Aurora kinase activity. This suggests a potential therapeutic role of Aurora kinase inhibitors in a subset of poor prognosis HNSCC patients with overexpression of ATP13A3.

Elderly Patients with Advanced Head and Neck Carcinoma: Does Aggressive Treatment Result in Better Outcomes?

OBJECTIVE: There are no well-defined treatment recommendations for elderly patients with advanced head and neck squamous cell carcinoma. This study aimed to investigate whether aggressive treatment among the elderly translated into better survival outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary institution. SUBJECTS AND METHODS: Elderly patients (≥60 years) with advanced-stage head and neck squamous cell carcinoma (stage III and IV) treated between January 1991 and May 2014 were reviewed. According to current National Comprehensive Cancer Network guidelines, they were classified to have received standard or substandard treatment. Overall survival (OS), locoregional recurrence-free survival, and distant recurrence-free survival were evaluated. RESULTS: A total of 355 patients were treated curatively: 194 with up-front surgery and 161 with radiotherapy or concurrent chemotherapy and radiotherapy. Median OS was higher among patients who received standard treatment (42.0 vs 16.0 months, P < .001). On multivariate analysis, standard treatment showed superior OS ( P < .001). Use of substandard treatment showed a hazard ratio of 2.09 (95% CI, 1.59-2.74) for poorer OS. CONCLUSION: Aggressive standard treatment protocols should be advocated for elderly patients, where comorbidities permit, as they confer better outcomes.