Publications by authors named "Tsu-Hui Hubert Low"

52 Publications

Dentoalveolar outcomes in maxillary reconstruction: A retrospective review of 85 maxillectomy reconstructions.

ANZ J Surg 2021 Jun 14. Epub 2021 Jun 14.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: Although microvascular free flaps are often used to reconstruct maxillary defects, dentoalveolar rehabilitation is arguably less common despite its importance to midface function and aesthetics. The aim of this study is to review the contemporary management of maxillary defects in a single quaternary referral institution to identify factors that assist or impede dentoalveolar rehabilitation.

Methods: A retrospective review of maxillary reconstructions performed between February 2017 and December 2020 was performed. Patient characteristics, defect classification, operative techniques, complications and dentoalveolar outcomes were recorded.

Results: A total of 85 maxillary reconstructions were performed in 73 patients. Of the 64 patients where dental rehabilitation was required, 31 received a functional denture (48%) with 24 (38%) being implant-retained. Significant predictors of successful rehabilitation included the use of virtual surgical planning (VSP; 86% vs. 25%, p < 0.001), preoperative prosthodontic assessment (82% vs. 21%, p < 0.001), prefabrication (100% vs. 40%, p = 0.002) and use of the zygomatic implant perforator flap technique (100% vs. 39%, p = 0.001). Preoperative prosthodontic consultation was associated with 21-fold increase in the odds of rehabilitation (odds ratio 20.9, 95% confidence interval 6.54-66.66, p < 0.005).

Conclusion: Preoperative prosthodontic evaluation, VSP and reconstructive techniques developed to facilitate implant placement are associated with increased dental rehabilitation rates. Despite using an institutional algorithm, functional dentures are frequently prevented by factors including soft tissue constraints, disease recurrence and patient motivation.
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http://dx.doi.org/10.1111/ans.17001DOI Listing
June 2021

The significance of regional metastasis location in head and neck cutaneous squamous cell carcinoma.

Head Neck 2021 May 21. Epub 2021 May 21.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: Regional metastasis of head and neck cutaneous squamous cell carcinoma (HNcSCC) can be seen in either parotid and/or cervical lymph nodes. The aim of this study was to assess whether there was a difference in prognosis between parotid and cervical nodal metastases.

Methods: Patients with regional metastasis from HNcSCC were identified from an institutional database. Disease-specific (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method and Cox proportional hazards models.

Results: Five hundred and thirty-five patients were identified with median follow-up of 26.4 months (3-255 months). Two hundred and thirty-five patients had parotid metastasis, 96 patients had neck metastasis, and 204 patients had both. On multivariable analysis, any regional metastasis to the neck when compared to parotid alone conferred worse DSS (HR 1.8, p = 0.007) and OS (HR 1.3, p = 0.024).

Conclusion: Regional metastasis of HNcSCC to the neck confers worse outcomes compared to metastasis to the parotid alone.
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http://dx.doi.org/10.1002/hed.26744DOI Listing
May 2021

Combined approach for malignant tumours of the deep lobe of the parotid involving the stylomandibular tunnel and parapharyngeal space.

Oral Oncol 2021 Aug 26;119:105283. Epub 2021 Apr 26.

Head and Neck Oncology, Chris O'Brien Lifehouse, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.oraloncology.2021.105283DOI Listing
August 2021

Metrics of pN-staging in oral squamous cell carcinoma: An analysis of 1,905 patients.

Eur J Cancer 2021 Jun 19;150:33-41. Epub 2021 Apr 19.

Department of Otorhinolaryngology, Region Hospital West Jutland, Holstebro, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.

Background: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N), which classifies patients according to the number of positive lymph nodes and extranodal extension.

Methods: Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N. Overall survival probabilities were summarised with the Kaplan-Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores.

Results: All 1,905 included patients were classified according to TNM7 and pN-N. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival.

Conclusions: The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N conveyed the best measures of prognosis and should be considered in future TNM iterations.
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http://dx.doi.org/10.1016/j.ejca.2021.03.019DOI Listing
June 2021

Microvascular reconstruction of head and neck defects in the elderly.

ANZ J Surg 2021 05 6;91(5):969-974. Epub 2021 Apr 6.

Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney Head and Neck Cancer Institute, Sydney, New South Wales, Australia.

Background: Microvascular free-flap reconstruction of the head and neck is a common technique utilized across many ages. The purpose of this study was to identify if advanced age or comorbidity was associated with worse post-operative outcomes in patients undergoing free-flap reconstruction.

Methods: A retrospective analysis was performed on 344 consecutive patients undergoing free-flap surgery of the head and neck. Demographic, clinical and pathological factors were considered along with Charlson Comorbidity Index (CCI) scores and American Society of Anesthesiologists (ASA) status. Logistic regression analysis was used to investigate the association of age, CCI or ASA with post-operative complications.

Results: Elderly patients (≥75 years) had a higher overall complication rate (odds ratio (OR) 1.7, P = 0.04) that was restricted to medical complications (OR 2.1, P = 0.05) and not surgical complications (OR 1.4, P = 0.14). Reconstructions of defects from cutaneous malignancy predominated in the elderly cohort (48% versus 29%, P < 0.01), but there was no difference in complication rate when cutaneous or mucosal subgroups were separated by age. ASA IV status was weakly associated with surgical complications (OR 3.89, P = 0.053), but CCI and elderly age were not associated with any outcome. Median length of stay was similar between age groups.

Conclusion: Free-flap reconstruction in older patients was associated with increased medical complications, and surgical complications were weakly associated with ASA status. Advanced age or comorbidity should not preclude microvascular reconstruction, but comorbid status should be optimized pre-operatively and factors predisposing to medical complications minimized where possible.
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http://dx.doi.org/10.1111/ans.16771DOI Listing
May 2021

Effect of age and gender in non-smokers with oral squamous cell carcinoma: Multi-institutional study.

Oral Oncol 2021 May 19;116:105210. Epub 2021 Feb 19.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Camperdown, NSW, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Institute of Academic Medicine, Sydney Local Health District, NSW, Australia.

Background: In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables.

Methods: Multinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes.

Results: 3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08-1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51-0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45-69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78-0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years.

Conclusions: Age, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105210DOI Listing
May 2021

Dynamic facial reanimation using active implantable prosthesis: Restoring blink.

J Plast Reconstr Aesthet Surg 2021 Jul 27;74(7):1633-1701. Epub 2021 Jan 27.

Faculty of Medicine, University of Sydney, Camperdown, NSW 2006, Australia; Department of Head and Neck Surgery, The Chris O'Brien Lifehouse, Camperdown, NSW 2050, Australia; Sydney Facial Nerve Service, The Chris O'Brien Lifehouse, Camperdown, NSW 2050, Australia.

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http://dx.doi.org/10.1016/j.bjps.2021.01.001DOI Listing
July 2021

Geographical heterogeneity in the American Joint committee on Cancer oral cancer staging and prognostic implications.

Oral Oncol 2021 02 21;113:105122. Epub 2020 Dec 21.

Fellow, Head and Neck Oncology, Chris O'Brien Lifehouse Hospital, Sydney, Australia.

Objectives: The AJCC 8th edition (AJCC 8) has introduced depth of invasion (DOI) and extranodal extension (ENE) into staging for oral squamous cell carcinoma (OSCC). Although validations have been performed on institutional datasets have shown a good performance, particularly in early OSCC, there have been no studies on diverse patient populations that determine the impact on prognostic heterogeneity.

Materials And Methods: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery +/- adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) as endpoint, the prognostic performance of AJCC 7th and 8th editions were compared using Akaike Information Criterion (AIC), Bayesian Information Criteria (BIC), Harrell's concordance index (C-index).

Results: When comparing AJCC 8 to AJCC 7, the heterogeneity in prediction of OS increased for T-category and N-category while remaining unchanged for TNM staging, suggesting AJCC 8 increased complexity with no improvement in predictive value. There were significant differences in median DOI and incidence of ENE between geographical regions, resulting in dissimilar rates of stage-migration when adopting AJCC 8.

Conclusion: In an attempt to improve prognostic performance, AJCC 8 introduced more variables; however heterogeneity in these results in significant geographical differences in model discrimination and performance. Caution should be applied as this may result in inaccurate and unreliable prognostic predictions that may impact treatment recommendations.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105122DOI Listing
February 2021

Survival outcomes following modern multidisciplinary management of oral squamous cell carcinoma in Australia.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Jan 5;131(1):92-98. Epub 2020 Oct 5.

Oral and Maxillofacial Surgery, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia; Faculty of Medicine, University of Queensland, Herston, Queensland, Australia.

Objective: Oral squamous cell carcinoma (SCC) has been traditionally described as a highly lethal disease. This study aims to provide updated multi-institutional data on the survival of patients with oral SCC in Australia.

Study Design: Retrospective survival analysis was performed between 2008 and 2016. All new patients with oral SCC treated with curative intent were recruited from 2 high-volume Australian head and neck oncology centers. Outcomes were measured in overall survival (OS), disease-specific survival (DSS), disease-free survival, and salvage rates for recurrences.

Results: Survival analysis included 771 patients with oral SCC. Five-year OS and DSS were 66.1% and 79.7%, respectively. Stage I and II oral SCC had significantly better survival than higher stages. Five-year OS and DSS for patients with stage I SCC were 79.7% and 93.4%, respectively, and for patients with stage IVB they were 37.9% and 54.3%, respectively. Two hundred forty-nine patients had disease recurrence (32.3%), with 66 patients (26.5% remaining disease free post salvage treatment.

Conclusion: Survival outcomes for oral SCC among Australian patients have improved, possibly due to advances in multidisciplinary care. Early detection of oral SCC leads to highly favorable prognosis; there is therefore an opportunity for routine oral cancer screening to be performed by community health practitioners with the aim of improving survival from oral SCC.
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http://dx.doi.org/10.1016/j.oooo.2020.09.012DOI Listing
January 2021

Implantable Doppler Ultrasound Monitoring in Head and Neck Free Flaps: Balancing the Pros and Cons.

Laryngoscope 2021 06 3;131(6):E1854-E1859. Epub 2020 Nov 3.

Department of Otolaryngology - Head and Neck Surgery, Western University Schulich School of Medicine and Dentistry, London, Ontario, Canada.

Objectives/hypothesis: Free flap transfer offers a versatile option for reconstruction in head and neck surgery, with success rates over 95%. There remains a substantial re-exploration rate of roughly 5% to 15%, with early recognition of compromise essential to flap survival. Monitoring techniques are highly desirable, with the gold standard being clinical monitoring. The Cook-Swartz Doppler (CSD) probe utilizes Doppler technology to inform clinicians about real-time flow. We aim to describe our adoption of this technology in 100 consecutive free flaps.

Study Design: Prospective case series.

Methods: Prospective data were collected from July 2014 to June 2015 on 100 consecutive free flaps performed at a head and neck unit in London, Ontario. All patients had a CSD inserted for arterial and venous monitoring.

Results: A total of 100 free flaps were performed on 99 patients. Sensitivity was 87.1% and specificity was 85.7%. Positive predictive value was 98.8% and negative predictive value was 33.3%. False-negative and false-positive rate were 1.0% and 12.0%, respectively. The exploration rate was 12%, with no flap loss and two partial debridements. The CSD was helpful in management in 9% of cases and was clinically unhelpful in 11% of cases, with 10 of 11 abnormal signals ignored. There were three unique CSD complications; one retained wire, one pedicle laceration during extraction, and one clot around the probe interrupting signal.

Conclusions: The CSD is a helpful adjunct to clinical monitoring but has unique complications, which were not previously described. Pros and cons must be considered for new centers adopting this technology.

Level Of Evidence: 4 Laryngoscope, 131:E1854-E1859, 2021.
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http://dx.doi.org/10.1002/lary.29247DOI Listing
June 2021

A prospective study of intraoperative assessment of mucosal squamous cell carcinoma margins in the head and neck.

Head Neck 2021 02 23;43(2):590-600. Epub 2020 Oct 23.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: In head and neck cancers, tumor margin assessment has important prognostic and therapeutic implications. Frozen section control of margins is commonly employed intraoperatively. However, this is not without limitations. The aim of this study is to determine whether intraoperative slicing of the whole specimen is feasible and what impact this may have on tumor margin assessment and the requirement for postoperative radiotherapy.

Methods: From September 2016 to August 2018, we recruited 22 patients as a pilot study looking at both the practicalities and the clinical relevance of whole margin tumor analysis intraoperatively. Our project is a prospective single arm study with historical controls.

Results: Forty-one percent of our patients required further intraoperative resection for close or involved margins. Seven of these patients who otherwise would have required adjuvant radiotherapy due to their margin status did not, after our intervention.

Conclusions: We found that although requiring resources, this process was feasible without unduly increasing operative times and with potential patient benefit including reduced incidence of adjuvant radiotherapy.
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http://dx.doi.org/10.1002/hed.26517DOI Listing
February 2021

Soft Tissue Metastases in Head and Neck Cutaneous Squamous Cell Carcinoma.

Laryngoscope 2021 04 14;131(4):E1209-E1213. Epub 2020 Sep 14.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia.

Objective: Soft tissue metastases (STM) in head and neck cutaneous squamous cell carcinoma (HNcSCC) are non-nodal based metastases to the parotid and cervical soft tissues of the head and neck. This is a unique subgroup of regional metastases amongst patients with cSCC and have been shown to be associated with poor prognosis. Detailed studies of this subgroup are lacking in the literature. A retrospective cohort analysis was performed to characterize the prognostic significance of STM in HNcSCC based on individual clinicopathological features.

Methods: Patients with HNcSCC with STM were identified from the Sydney Head and Neck Cancer Institute database. Clinicopathological characteristics were extracted from the histopathological reports. Recurrence and follow-up data were analyzed to determine disease-free and overall survival using the Kaplan-Meier method and Cox proportional hazards models.

Results: After excluding all patients with lymph node metastasis with no STM, there were 200 patients identified (161 parotid, 32 cervical, and seven with concurrent parotid and cervical STM) with a 5-year overall survival of 36%. In univariable analysis, age of patients, size of the deposits, location of the deposits, and patients that were not offered adjuvant radiotherapy have worse overall survival. However, on multivariable analysis, age and the number of STM deposits were independent factors that predict for worse survival.

Conclusion: The presence of STM in patients with HNcSCC is associated with poor prognosis. Increasing number of STM deposits, as well as involved margin of the regional excision, negatively impacted on the overall prognosis.

Level Of Evidence: Level III - retrospective cohort study. Laryngoscope, 131:E1209-E1213, 2021.
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http://dx.doi.org/10.1002/lary.29064DOI Listing
April 2021

Number of nodal metastases and the American Joint Committee on cancer staging of head and neck cutaneous squamous cell carcinoma: A multicenter study.

Oral Oncol 2020 12 21;111:104855. Epub 2020 Aug 21.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, Australia.

Objectives: We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification.

Materials And Methods: Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ± adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE.

Results: The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage.

Conclusion: Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104855DOI Listing
December 2020

Trends in parotidectomy over 30 years in an Australian tertiary care center.

Head Neck 2020 10 3;42(10):2905-2911. Epub 2020 Jul 3.

Head and Neck Oncology, Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Background: Nomenclature, classification, and management of parotid tumors are constantly evolving; this study was performed to identify temporal trends in histology and facial nerve sacrifice in parotidectomy during a 30-year period (1987-2018).

Methods: Retrospective analysis of patients treated in a single tertiary-care institution during this time period was performed with analysis of temporal trends.

Results: Two thousand eight hundred and fifty-seven parotidectomies were performed; pleomorphic adenoma was the most common histology (34.3%), followed by skin cancer metastases (32.3%). Significant trends noted were increasing age (P < .001), fewer parotidectomies for inflammatory lesions (P < .001), reduced incidence of mucoepidermoid carcinoma (P = .048), increasing incidence of parotidectomy for cutaneous malignancies (P < .001), and reduced facial nerve sacrifice (P = .034).

Conclusion: In this contemporary series of parotid pathology, metastatic cutaneous malignancies accounted for a third of cases. Despite reducing facial nerve sacrifice in parotid disease, it is still required in approximately 15% of malignancy and needs to be discussed with all patients preoperatively.
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http://dx.doi.org/10.1002/hed.26335DOI Listing
October 2020

Squamous Cell Carcinoma of the Oral Tongue in Young Patients: Outcomes and Implications for Treatment.

Indian J Surg Oncol 2020 Jun 22;11(2):274-280. Epub 2020 Feb 22.

Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Ponekkara PO, Kochi, 682 041 India.

Squamous cell carcinoma oral tongue (SCCOT) in patients below 45 years is relatively uncommon in literature; however, there have been increasing trends in incidence. Previous studies showed conflicting data, with no conclusive evidence of differences in outcome compared with older patients. The aim of our study was to determine if younger patients with tongue cancer in India had different clinico-pathological characteristics, prognostic determinants or survival than their older counterparts. Retrospective analysis of 425 adult patients of SCCOT, with 114 patients < 45 years of age (younger group) and 311 patients ≥ 45 years of age (older group), treated with surgery and adjuvant as indicated. Clinical and pathological features were described. Survival analysis was performed using Kaplan Meier's method and multivariate analysis was performed for recurrence and survival using Cox proportional hazards ratio. Younger patients had a higher incidence of adverse pathological features (APFs) like lymphovascular invasion ( = 0.01), perineural invasion ( = 0.009), poorer differentiation ( = 0.044), nodal involvement ( = 0.021), extranodal extension ( = 0.003) and local recurrence ( = 0.008). All of these factors were noted to impact survival. However, on multivariate analysis for APFs, age was not an independent predictor of recurrence or survival. Younger patients with squamous cell carcinoma of tongue have an increased risk of APFs and local recurrence. The clinical observation that young patients have a worse outcome is likely due to the association of APFs rather than age being an independent prognostic factor. Further study is required to show if tumour biology in this cohort is distinct.
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http://dx.doi.org/10.1007/s13193-020-01049-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260305PMC
June 2020

Sydney Facial Nerve Clinic: experience of a multidisciplinary team.

ANZ J Surg 2020 05 4;90(5):856-860. Epub 2020 Mar 4.

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

Background: The Sydney Facial Nerve Clinic (SFNC) is a multidisciplinary clinic established in 2015, consisting of surgeons (otolaryngologists, head and neck and plastics/reconstructive), physiotherapists and speech pathologists.

Methods: We reviewed patients who attended the SFNC in the first 3 years and who had their symptoms recorded using the Facial Disability Index, and clinical staging recorded utilising the House-Brackmann (HB) score, Sydney Facial Nerve Score and Sunnybrook Facial Grading System (SFGS).

Results: Between May 2015 and June 2018, 145 patients attended the clinic. Mean age was 44.6 ± 17.3 years with 94 (64.8%) females. Most referrals came from general practitioners (n = 75, 54.5%). The most common aetiology was iatrogenic injury (n = 55, 37.9%), followed by Bell's palsy (n = 48, 33.1%), congenital (n = 11, 7.6%), herpes zoster oticus (n = 9, 6.2%), trauma (n = 9, 6.2%) and other (n = 13, 9.0%). The median HB was 4, the mean Sydney score 7.3/15 and the mean SFGS was 45/100. Patients with iatrogenic causes had the worse facial nerve scoring in HB, Sydney and SFGS. Patients with congenital aetiology reported the least symptoms on Facial Disability Index (P < 0.001). Most patients were recommended non-surgical management (n = 92, 64.3%); 51 (35.7%) were referred for botulinum toxin + facial physiotherapy, 25 (17.2%) for physiotherapy alone, seven (4.9%) for botulinum toxin alone and nine (6.3%) for conservative management. Fifty-one patients (35.7%) were recommended surgery, generating 75 procedures; 24 oculoprotective, 22 static, 12 gracilis transfers, 10 temporalis myoplasties and seven nerve transfers.

Conclusion: Iatrogenic injuries are the most common presentation for this clinic and have a more severe clinical presentation. Most patients presenting to the SFNC were managed non-surgically.
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http://dx.doi.org/10.1111/ans.15782DOI Listing
May 2020

Recreation of eyelid mechanics using the sling concept.

J Plast Reconstr Aesthet Surg 2020 May 9;73(5):942-950. Epub 2020 Jan 9.

Faculty of Medicine, University of Sydney, Camperdown, New South Wales 2006, Australia; Department of Head and Neck Surgery, The Chris O'Brien Lifehouse, Camperdown, New South Wales 2050, Australia; Sydney Facial Nerve Service, The Chris O'Brien Lifehouse, Camperdown, New South Wales 2050, Australia; Central Clinical School, University of Sydney; Sydney, Camperdown, New South Wales 2050, Australia.

Background: Paralytic lagophthalmos causes major functional, aesthetic and psychological problems in patients with facial paralysis. The Bionic Lid Implant for Natural Closure (BLINC) project aims to restore eyelid function using an implanted electromagnetic actuator combined with an eyelid sling. The authors performed a preliminary study using cadaveric heads to investigate the optimal application of an eyelid sling in various configurations around the orbit.

Methods: The sling was tested in a cadaveric sheep head using 2 medial anchor points and 4 lateral ostectomy points. An impulse was generated using gravitational force to test each combination of medial and lateral sling insertion sites using weights between 10 and 50 g. Each generated blink was recorded and analysed. The final result was validated in a human cadaveric model.

Results: The maximum amount of eye closure and closure speed displayed in sheep were 83.7 ± 9.4% of total closure and 70.6 ± 6.9 mm/s at a maximum force of 490 mN, respectively. The 2 inferior lateral attachments performed better at displacing the eyelid than the superior attachments. The position with the highest degree of eye-closure (improvement of 21.6%, p < 0.001) and speed (improvement of 30.4 mm/s, p < 0.001) was the combination of a posterior medial attachment and an inferior-posterior lateral attachment, which resulted in a near physiological closure in human cadaver.

Conclusion: Closure improved with an inferior lateral position due to increased force acting in the direction of closure. Posterior positioning increases force acting radially, towards the centre of eyelid movement. The latter directs the closure force to effectively move the eyelid around the curved globe.
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http://dx.doi.org/10.1016/j.bjps.2019.12.007DOI Listing
May 2020

Time and cost-analysis of virtual surgical planning for head and neck reconstruction: A matched pair analysis.

Oral Oncol 2020 01 30;100:104491. Epub 2019 Nov 30.

Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney, Australia; Institute of Academic Surgery at Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia; Central Clinical School, University of Sydney, Sydney, Australia.

Objectives: Virtual surgical planning (VSP) uses patient-specific modelling of the facial skeleton to provide a tailored surgical plan which may increase accuracy and reduce operating time. The aim of this study was to perform a time and cost-analysis comparing patients treated with and without VSP-technology.

Material And Methods: A retrospective analysis of 138 patients undergoing microvascular free flap mandible (76.8%) or maxillary (23.2%) reconstruction between 2010 and 2018 was performed. The cohort was divided into two groups according to reconstruction-approach: non-VSP and proprietary-VSP (P-VSP). Cost-analysis was performed comparing non-VSP and P-VSP by matching patients according to site, bone flap, indication, complexity and age.

Results: Fibula, scapula and iliac crest free flaps were used in 92 patients (66.7%), 33 patients (23.9%) and 13 patients (9.4%), respectively. Eight patients (5.8%) required revision of the microvascular anastomosis, of which four flaps were salvaged giving a 2.9% flap failure rate. P-VSP was associated with shorter median length of stay (LOS) (10.0 vs 13.0 days, p = 0.009), lower mean procedure time (507.38 vs 561.75 min, p = 0.042), and similar median total cost ($34939.00 vs $34653.00, p = 0.938), despite higher complexity (2.0 vs 1.0, p = 0.09). In the matched-series, P-VSP was associated with a similar median LOS (10.5 vs 11 days), lower mean procedure time (497 vs 555 min, p = 0.231), lower mean total cost ($35,493 v $37,345) but higher median total cost ($35504.50 vs $32391.50, p = 0.607), although not statistically different.

Conclusion: VSP-technology represents a helpful surgical tool for complex reconstructions, without adversely impacting on the overall-cost of treatment.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104491DOI Listing
January 2020

Assessment of shoulder function following scapular free flap.

Head Neck 2020 02 27;42(2):224-229. Epub 2019 Oct 27.

Department of Otolaryngology-Head and Neck Surgery, Western University, London, Ontario, Canada.

Background: The scapular system free flap has been increasing in popularity to reconstruct short segment mandibular bony defects. It is important to assess donor site morbidities systematically.

Methods: Prospective cohort study using objective measures of range of motion (ROM) and shoulder strength were measured. Subjective disability was evaluated with validated questionnaires-Neck Disability Impairment Index and Shoulder Pain and Disability Index.

Results: Twenty-six patients were recruited-19 with scapular tip and 7 with lateral border scapular free flap. Decreased ROM on the operated side was noted for shoulder abduction, shoulder flexion, and external rotation. No significant difference was noted for shoulder extension. Strength was reduced for shoulder flexion, shoulder abduction, and external rotation. Subjective measurements did not indicate significant shoulder function disruption.

Conclusion: Patients with scapular free flap reconstruction did not experience significant shoulder morbidity. Measures of shoulder ROM and power were objectively affected; however, subjective measures of shoulder disability were not significantly affected.
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http://dx.doi.org/10.1002/hed.25992DOI Listing
February 2020

Tumour mismatch repair protein loss is associated with advanced stage in oral cavity squamous cell carcinoma.

Pathology 2019 Dec 18;51(7):688-695. Epub 2019 Oct 18.

Central Clinical School, University of Sydney, Sydney, NSW, Australia; Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, NSW, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

An unexplained increase in the incidence of oral cavity squamous cell carcinoma (oSCC) has been observed despite decreasing smoking rates, particularly in younger patients. Links to defects in the DNA mismatch repair (MMR) system are well established in early onset colorectal, urothelial and gynaecological malignancies. MMR deficient patients treated with immune checkpoint inhibitors have demonstrated improved response rates. Studies exploring MMR status in head and neck squamous cell carcinoma (HNSCC) demonstrate conflicting results. This study explores the incidence of MMR protein loss and its association with clinicopathological features and outcome in oSCC. Immunohistochemical staining using tissue microarrays to assess the expression of MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed on 285 consecutive oSCC cases between 2000 and 2016. Data on smoking, alcohol and metachronous malignancies were retrospectively collected. Proportional hazards regression models were used to compare survival in MMR intact and deficient patients. MMR deficiency was seen in 21 patients (7.4%). MMR deficient tumours were associated with bone invasion (52% vs 32%, p=0.05), higher pT stage (pT4 in 57% vs 35%, p<0.001) and a higher number of metachronous malignancies (p=0.05). MMR deficiency was not associated with younger age at presentation or absence of smoking or alcohol. There was no significant association between MMR status and survival (overall survival hazard ratio 1.36; p=0.32). The incidence of MMR loss in oSCC is low and is not associated with young age at presentation. MMR deficiency in oSCC is associated with an increase in the number of metachronous malignancies and more advanced primary tumours.
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http://dx.doi.org/10.1016/j.pathol.2019.08.005DOI Listing
December 2019

Multifocal perineural invasion is a better prognosticator than depth of invasion in oral squamous cell carcinoma.

Head Neck 2019 11 5;41(11):3992-3999. Epub 2019 Sep 5.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Objectives: Prognostic significance of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) characterized as unifocal and multifocal was compared to depth of invasion (DOI) and extranodal extension (ENE).

Materials And Methods: Univariable and multivariable analyses of 861 consecutive patients with OSCC undergoing treatment between 1995 and 2018 were performed, with local failure (LF) and disease-specific mortality (DSS) as the primary endpoints.

Results: After adjusting for other adverse histopathological factors and adjuvant therapy, multifocal PNI was associated with a greater risk of LF (P = .01) and DSS (P = 0.02) compared to DOI. The effect of multifocal PNI was comparable to the effect of nodal metastases without ENE (P = 0.02). LF and DSS were not improved by the administration of adjuvant radiotherapy within unifocal or multifocal PNI groups.

Conclusion: Multifocal PNI is associated with a greater risk of death in OSCC than DOI. Its effect is comparable to that of nodal metastases (without ENE).
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http://dx.doi.org/10.1002/hed.25940DOI Listing
November 2019

Treatment for oral squamous cell carcinoma: Impact of surgeon volume on survival.

Oral Oncol 2019 09 10;96:60-65. Epub 2019 Jul 10.

Oral and Maxillofacial Surgery, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia; School of Medicine, University of Queensland, St Lucia, Queensland, Australia.

Background: The volume-outcome relationship is a well-known phenomenon in surgical oncology. The aim of this study was to quantify the impact of surgeon volume on the treatment outcome of oral squamous cell carcinoma (OSCC) patients.

Methods: All new OSCC cases treated with curative intent between 2008 and 2013 were included. A heterogeneous set of predictor variables was collected, including patient, tumour and treatment factors. The outcomes of interest were recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). To investigate the cut-off in surgeon volume, the number of OSCC resections was analysed in multiplies of 5 cases per annum according to DSS, using univariable regression analysis.

Results: 534 cases were recruited. Independently, the negative predictors for patient survival were age, perineural invasion, worsening tumour staging, and extracapsular spread. High-volume surgeon was determined to be most significant at 20 cases per annum and significantly associated with improved RFS (HR: 0.67), OS (HR: 0.44), and DSS (HR: 0.39).

Conclusions: Results from this study support the rationalisation of OSCC management at high-volume centres and in the hands of experienced surgeons for better patient survival. Head and neck surgeons should perform a minimum of 20 OSCC cases per year to maintain competency in OSCC ablation.
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http://dx.doi.org/10.1016/j.oraloncology.2019.06.030DOI Listing
September 2019

Positive survival trend in metastatic head and neck cutaneous squamous cell carcinoma over four-decades: Multicenter study.

Head Neck 2019 11 12;41(11):3826-3832. Epub 2019 Aug 12.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: This study assessed changes over time of survival of head and neck cutaneous squamous cell carcinoma (HNcSCC) with lymph node metastases.

Methods: A multicenter analysis of 1301 patients with metastatic HNcSCC treated between 1980 and 2017. Differences in disease-specific survival (DSS) and overall survival (OS) by decade were assessed using multivariate Cox regression.

Results: Over the study period, we noted an increase in the proportion of patients aged over 80 years (3.9%-31.7%; P < .001) and immunosuppression (1.9%-9.9%; P = .03). After adjusting for number and size of metastatic nodes, extranodal extension, perineural invasion, immunosuppression, treatment, and institution, there was a reduction in risk of cancer-related mortality from 0.47 in 1990-1999 (P = .04) to 0.30 in 2000-2009 (P < .001) when compared to 1980-1989. This remained stable at 0.30 in 2010-2017 (P = .001). OS remained stable after 1990.

Conclusion: Despite an aging and more frequently immunosuppressed population, fewer patients are dying from metastatic HNcSCC.
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http://dx.doi.org/10.1002/hed.25912DOI Listing
November 2019

Is high-risk cutaneous squamous cell carcinoma of the head and neck a suitable candidate for current targeted therapies?

J Clin Pathol 2020 Jan 12;73(1):17-22. Epub 2019 Jul 12.

Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

Objective: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management.

Methods: Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed.

Results: High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance ( S821F, T670I, mutations at codons 12 and 13).

Conclusion: We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.
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http://dx.doi.org/10.1136/jclinpath-2019-206038DOI Listing
January 2020

The Milan System for Reporting Salivary Gland Cytopathology-Proposed modifications to improve clinical utility.

Head Neck 2019 08 5;41(8):2566-2573. Epub 2019 Mar 5.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia.

Background: Fine-needle aspiration of a salivary gland lesion is a well-established diagnostic procedure that aids management decisions. Recently, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) classification has been proposed in order to improve the reproducibility and communication in the management of salivary gland lesions.

Methods: A total of 375 patient's cytological reports collected between January 2010 and December 2017 were reviewed and reclassified according to MSRSGC and a risk of malignancy was calculated for each of the category.

Results: The rate of malignancy in MSRSGC classification was 19.0%, 11.8%, 25.0%, 5.5%, 50.0%, 71.4%, and 94.6% for each of the category (I, II, III, IVa, IVb, V, and VI), respectively.

Conclusion: The MSRSGC classification is a valuable tool in everyday practice. The modified version of MSRSGC aims to improve the surgical relevance and facilitate uniform management.
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http://dx.doi.org/10.1002/hed.25732DOI Listing
August 2019

Validation of the eighth edition AJCC staging system in early T1 to T2 oral squamous cell carcinoma.

J Surg Oncol 2019 Mar 21;119(4):449-454. Epub 2018 Dec 21.

Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, India.

Background: To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control.

Methods: Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems.

Results: The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively (P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively.

Conclusion: The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers.
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http://dx.doi.org/10.1002/jso.25348DOI Listing
March 2019

Role of adverse pathological features in surgically treated early oral cavity carcinomas with adequate margins and the development of a scoring system to predict local control.

Head Neck 2018 11 1;40(11):2329-2333. Epub 2018 Nov 1.

Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Kerala, India.

Background: The purpose of this study was to determine the factors affecting local control in patients with T1N0 squamous cell carcinoma (SCC) of the tongue.

Methods: We conducted a retrospective analysis of 144 patients with pT1N0 SCC of the tongue who underwent wide excision and neck dissection without adjuvant therapy.

Results: The adverse pathological features associated with local control were least margin 5 mm (P = .004), infiltrative margin (P = .403), depth >4 mm (P = .136), lymphovascular invasion (P = .301), and perineural invasion (P = .342). We derived a scoring system of 10 points based on the hazard ratio for local failure; those with scores >5 points had a 5-year local control of <60%.

Conclusion: This study suggests patients having a margin of 5 mm need revision, however, if they do not have additional adverse pathological features (score ≤4), local control is 88% at 5 years, and they may be observed. Those who have margins over 5 mm with a total score >5 may still benefit from adjuvant therapy. Those with margins over 5 mm have improved local control (P = .029).
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http://dx.doi.org/10.1002/hed.25163DOI Listing
November 2018

Prognostic implications of the 8th edition American Joint Committee on Cancer (AJCC) staging system in oral cavity squamous cell carcinoma.

Oral Oncol 2018 10 4;85:82-86. Epub 2018 Sep 4.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia; Central Clinical School, University of Sydney, Sydney, Australia; South West Clinical School, University of New South Wales, Sydney, Australia.

Background: The American Joint Committee on Cancer (AJCC) has changed the staging system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging manual to include depth of invasion (DOI) of the primary tumor as a modifier to the T category and extranodal extension (ENE) to upstage node positive OSCC. This study aims to evaluate the performance of the AJCC 8 pathologic staging system in OSCC and compare it to its predecessor (AJCC 7).

Methods: Analysis of 663 patients with OSCC from a prospective database was performed using the Cox proportional hazards competing risk model. The prognostic performance of the pathologic staging system was assessed using the Akaike Information Criterion (AIC) and Harrell's concordance index (C-index).

Results: AJCC 8 led to upstaging of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited monotonicity and poor stratification between stage groups I to III. The estimates for model performance reveal that AJCC 8 has modest predictive capacity for overall survival (OS) and disease specific survival (DSS) (Harrell's C of 0.70 and 0.74, respectively) but is superior to AJCC 7 (Harrell's C of 0.65 and 0.69, respectively).

Conclusions: The AJCC 8 staging system is more complex than its former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it performs better in stratifying survival of OSCC patients by stage.
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http://dx.doi.org/10.1016/j.oraloncology.2018.08.013DOI Listing
October 2018

Adverse pathologic features in T1/2 oral squamous cell carcinoma classified by the American Joint Committee on Cancer eighth edition and implications for treatment.

Head Neck 2018 10 13;40(10):2123-2128. Epub 2018 Aug 13.

Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Tamilnadu, India.

Background: The American Joint Committee on Cancer (AJCC) eighth edition has incorporated depth of invasion into TNM classification of oral cavity squamous cell carcinoma (SCC) due to the prognostic impact on recurrence and survival. After reclassifying our patients with T1 to T2 oral cavity SCC according to these recommendations, we intended to study the effect of adverse pathological features (perineural invasion [PNI], lymphovascular invasion, and differentiation) on overall survival (OS).

Methods: We conducted a retrospective analysis of 442 patients with T1 to T2 oral cavity SCC. Univariate and multivariate analysis was performed for impact of adverse pathological features on OS.

Results: For the newly reclassified T1 to T2 oral cavity tumors, on multivariate analysis, the prognostically relevant parameters were PNI (P = .032) and differentiation (P = .009). Increasing adverse pathological features resulted in worse survival (P = .005).

Conclusion: Incorporation of PNI and differentiation better reflect prognostic outcome in oral cavity tumors classified as T1 to T2 as per the new AJCC eighth edition. Increasing adverse pathological features resulted in worse survival.
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http://dx.doi.org/10.1002/hed.25168DOI Listing
October 2018