A proposed framework for the implementation of head and neck cancer treatment at a new cancer center from a radiation oncology perspective.

BACKGROUND: Establishing a new head and neck cancer (HNC) treatment center requires multidisciplinary team management and expertise. To our knowledge, there are no clear recommendations or guidelines in the literature for the commencement of HNC radiation therapy (RT) at a new cancer center. We propose a novel framework outlining the necessary components required to set-up a new radiation therapy HNC treatment. METHODS: We reviewed the infrastructure and methodology in the commencement of HNC radiation therapy in our cancer care center and invited several external, experienced metropolitan head and neck radiation oncologists to develop a novel consensus guideline that may be used by new RT centers to treat HNC. Recommendations were presented to our internal and external staff specialists using a survey questionnaire with ratings utilized to determine consensus using pre-defined thresholds as per the American Society of Clinical Oncology Guidelines Methodology Manual. CONCLUSION: This consensus recommendation aims to improve RT utilization whilst advocating for optimal patient outcomes by presenting a framework for new radiation therapy centers ready to step up and manage the treatment of head and neck cancer patients. We propose these evidence-based consensus guidelines endorsed by external HNC radiation oncologists.

Changes in serial multiparametric MRI and FDG-PET/CT functional imaging during radiation therapy can predict treatment response in patients with head and neck cancer.

OBJECTIVES: To test if tumour changes measured using combination of diffusion-weighted imaging (DWI) MRI and FDG-PET/CT performed serially during radiotherapy (RT) in mucosal head and neck carcinoma can predict treatment response. METHODS: Fifty-five patients from two prospective imaging biomarker studies were analysed. FDG-PET/CT was performed at baseline, during RT (week 3), and post RT (3 months). DWI was performed at baseline, during RT (weeks 2, 3, 5, 6), and post RT (1 and 3 months). The ADCmean from DWI and FDG-PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. Absolute and relative change (%∆) in DWI and PET parameters were correlated to 1-year local recurrence. Patients were categorised into favourable, mixed, and unfavourable imaging response using optimal cut-off (OC) values of DWI and FDG-PET parameters and correlated to local control. RESULTS: The 1-year local, regional, and distant recurrence rates were 18.2% (10/55), 7.3% (4/55), and 12.7% (7/55), respectively. ∆Week 3 ADCmean (AUC 0.825, p = 0.003; OC ∆ > 24.4%) and ∆MTV (AUC 0.833, p = 0.001; OC ∆ > 50.4%) were the best predictors of local recurrence. Week 3 was the optimal time point for assessing DWI imaging response. Using a combination of ∆ADCmean and ∆MTV improved the strength of correlation to local recurrence (p ≤ 0.001). In patients who underwent both week 3 MRI and FDG-PET/CT, significant differences in local recurrence rates were seen between patients with favourable (0%), mixed (17%), and unfavourable (78%) combined imaging response. CONCLUSIONS: Changes in mid-treatment DWI and FDG-PET/CT imaging can predict treatment response and could be utilised in the design of future adaptive clinical trials. CLINICAL RELEVANCE STATEMENT: Our study shows the complementary information provided by two functional imaging modalities for mid-treatment response prediction in patients with head and neck cancer. KEY POINTS: •FDG-PET/CT and DWI MRI changes in tumour during radiotherapy in head and neck cancer can predict treatment response. •Combination of FDG-PET/CT and DWI parameters improved correlation to clinical outcome. •Week 3 was the optimal time point for DWI MRI imaging response assessment.

A systematic review of neoadjuvant and definitive immunotherapy in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) require multi-modality treatment. Immune checkpoint inhibitors (ICIs) are now standard of care in management of recurrent/metastatic HNSCC. However, its role in the definitive and neoadjuvant setting remains unclear. METHODS: A literature search was conducted that included all articles investigating ICI in untreated locally advanced (LA) HNSCC. Data was extracted and summarised and rated for quality using the Cochrane risk of bias tool. RESULTS: Of 1086 records, 29 met the final inclusion criteria. In both concurrent and neoadjuvant settings, the addition of ICI was safe and did not delay surgery or reduce chemoradiotherapy completion. In the concurrent setting, although ICI use demonstrates objective responses in all published trials, there has not yet been published data to with PFS or OS benefit. In the neoadjuvant setting, combination ICI resulted in superior major pathological response rates compared to ICI monotherapy without a significant increase adverse event profiles, but its value in improving survival is not clear. ICI efficacy appears to be affected by tumour characteristics, in particular PD-L1 combined positive score, HPV status and the tumour microenvironment. CONCLUSIONS: There is significant heterogeneity of ICI use in untreated LA HNSCC with multiple definitive concurrent and neoadjuvant protocols used. Resultantly, conclusions regarding the survival benefits of adding ICI to standard-of-care regimens cannot be made. Further trials and translational studies are required to elucidate optimal ICI sequencing in the definitive setting as well as better define populations more suited for neoadjuvant protocols.

Rates of MRI simulator utilisation in a tertiary cancer therapy centre.

Magnetic resonance imaging (MRI) is increasingly being integrated into the radiation oncology workflow, due to its improved soft tissue contrast without additional exposure to ionising radiation. A review of MRI utilisation according to evidence based departmental guidelines was performed. Guideline utilisation rates were calculated to be 50% (true utilisation rate was 46%) of all new cancer patients treated with adjuvant or curative intent, excluding simple skin and breast cancer patients. Guideline utilisation rates were highest in the lower gastrointestinal and gynaecological subsites, with the lowest being in the upper gastrointestinal and thorax subsites. Head and neck (38% vs 45%) and CNS (46% vs 67%) cancers had the largest discrepancy between true and guideline utilisation rates due to unnamed reasons and non-contemporaneous diagnostic imaging respectively. This report outlines approximate MRI utilisation rates in a tertiary radiation oncology service and may help guide planning for future departments contemplating installation of an MRI simulator.

Low conflict and high satisfaction: Decisional outcomes after attending a combined clinic to choose between robotic prostatectomy and radiotherapy for prostate cancer.

BACKGROUND: Decisional conflict and post-treatment decisional regret have been documented in men with localised prostate cancer (LPC). However, there is limited evidence regarding decisional outcomes associated with the choice between robotic-assisted radical prostatectomy (RARP) and radiotherapy, when both treatment options are available in the public health system. There is increasing support for multidisciplinary approaches to guide men with LPC in their decision-making process. This study assessed decisional outcomes in men deciding between RARP or radiotherapy treatment before and after attending a LPC combined clinic (CC). METHODS: Quantitative longitudinal data were collected from 52 men who attended a LPC CC, where they saw both a urologist and radiation oncologist. Patients completed questionnaires assessing involvement in decision-making, decisional conflict, satisfaction and regret before and after the CC, three months, six months and 12 months post-treatment. Urologists and radiation oncologists also reported their perceptions regarding patients' suitability for, openness to, perceived preferences and appropriateness for each treatment. Data was analysed using paired/independent samples t-tests and McNemar's tests. RESULTS: Most participants (n = 37, 71%) opted for RARP over radiotherapy (n = 14, 27%); one participant deferred treatment (2%). Urologists and radiation oncologists reported low agreement (κ = 0.26) regarding the most appropriate treatment for each patient. Participants reported a desire for high levels of control over their decision-making process (77.5% patient-led, 22.5% shared) and high levels of decisional satisfaction (M = 4.4, SD = 0.47) after the CC. Decisional conflict levels were significantly reduced (baseline: M = 29.3, SD = 16.9, post-CC: M = 16.3, SD = 11.5; t = 5.37, P < 0.001) after the CC. Mean decisional regret scores were 'mild' at three-months (M = 16.0, SD = 17.5), six-months (M = 18.8, SD = 18.7) and 12-months (M = 18.2, SD = 15.1) post-treatment completion. CONCLUSION: This is the first Australian study to assess decisional outcomes when patients are offered the choice between RARP and radiotherapy in the public health system. A CC seems to support decision-making in men with LPC and positively impact some decisional outcomes. However, larger-scale controlled studies are needed to confirm these findings.

Faculty of Radiation Oncology 2018 workforce census.

INTRODUCTION: This paper reports the key findings of the Faculty of Radiation Oncology 2018 workforce census and compares results with previous studies. METHODS: The census was conducted in mid-2018 with distribution to all radiation oncologists and trainees listed on the college database in Australia, New Zealand, Singapore and overseas. There were new questions about hours spent on multidisciplinary meetings (MDTS), leadership positions held, management of inpatients, hypofractionation, stereotactic body radiation therapy (SBRT), income type and gynae-oncology work for radiation oncologists. Trainees were asked about time spent on planning and contouring. RESULTS: The overall response rate was 69.9% with 67.7% of radiation oncologists and 77.9% of trainees responding. There were 514 radiation oncologists with 60% male and a mean age of 49 years (median = 46 years, range 31-91). The majority of respondents were Caucasian (57.7%) and from New South Wales (29.4%). Sixty-one per cent were subspecialists with breast, SBRT and urological cancers, the most popular areas of interest, and 56% held leadership positions. The majority worked in the public sector (55.7%), but 31.7% worked solely in the private sector with an average working week of 43.4 hours (h) (median = 44, range 2-110). Radiation oncologists spent an average of 3.6 h on MDTS (median = 4 h), 2.2h (median = 2 h) on simulation and 8 h (median = 5 h) on contouring per week. They averaged 245 new patients (median = 250, range 30-695) and 25 inpatients (median = 20) per year. Hypofractionation was used for radical treatment of breast (75%) and prostate cancer (49%). Radiation oncologists were mainly remunerated with a fixed income (53%) with 40% having some incentive-based income. There were 140 trainees with an equal male and female distribution. The large majority (88%) were satisfied with their career and network (83%). Most trainees worked between 36 and 55h per week with 15% having no protected time. Most trainees spent less than 5 hours on planning each week and job availability remained a major concern (90%). CONCLUSIONS: The radiation oncologist numbers have increased significantly, but unemployment remains low. Many parameters remain similar to the 2014 census, but new information has been obtained on special interest areas, leadership positions, gynae-oncology, inpatients, hypofractionation use, remuneration and contouring. Trainee numbers remain stable with an increased percentage satisfied with their career with much less concern about oversupply. Protected time remains an issue with contouring time and teaching emerging as a potential issue.

Number of nodal metastases and prognosis in metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Existing prognostic systems for metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) do not discriminate between the number of involved nodes beyond single versus multiple. This study aimed to determine if the number of metastatic lymph nodes is an independent prognostic factor in metastatic cSCCHN and whether it provides additional prognostic information to the American Joint Committee on Cancer (AJCC) staging. METHODS: We retrospectively analysed 101 patients undergoing curative intent treatment for metastatic cSCCHN to parotid and/or neck nodes by surgery +/- radiotherapy at Liverpool Hospital, Sydney, Australia. The impact of number of nodal metastases on disease-free survival (DFS) and risk of distant metastases was assessed using multivariate Cox regression. RESULTS: The mean number of nodal metastases was 2.5 (range 1-12). On multivariate analysis, increasing number of nodal metastases significantly predicted reduced DFS (hazard ratio 1.17; 95% confidence interval 1.05-1.30; P = 0.004), with a 17% increased risk of recurrence or death for each additional node. This remained significant in multivariate models adjusted for AJCC 8th edition nodal and TNM stages. Number of nodal metastases was also associated with risk of distant metastatic failure (hazard ratio 1.21; 95% confidence interval 1.05-1.39; P = 0.009). CONCLUSION: Increasing number of nodal metastases is associated with decreased DFS and increased risk of distant metastases in metastatic cSCCHN, with a cumulative risk increase with each additional node. It provides additional prognostic information to the AJCC staging, which may be improved by incorporating information on the number of nodal metastases beyond the current single versus multiple distinction.

Estimating the cost of radiotherapy for 5-year local control and overall survival benefit.

BACKGROUND AND PURPOSE: Escalating health care costs have led to greater efforts directed at measuring the cost and benefits of medical treatments. The aim of this study was to estimate the costs of 5-year local control and overall survival benefits of radiotherapy for the cancer population in Australia. MATERIALS AND METHODS: The local control and overall survival benefits of radiotherapy at 5-years and optimal number of fractions per course have been estimated for 26 tumour sites for which radiotherapy is indicated. For this study, a hybrid approach that merges features from activity based costing (ABC) and relative value units costing (RVU) were used to provide cost estimates. ABC methodology was used to allocate costs to all radiotherapy activities associated with each patient's treatment course, while the RVUs represent the cost of each radiotherapy activity relative to the average cost of all activities and were used to achieve a weighted cost allocation. A patient's journey for the financial year was constructed by consolidating all the radiotherapy activities and their associated costs, and the average cost per activity (fraction) was determined. The cost of radiotherapy per 5-year overall survival and local control was then estimated. RESULTS: The estimated population 5-year local control and overall survival benefits of radiotherapy for all cancer were 23% and 6%, respectively. The optimal number of fractions per treatment course if guidelines were followed was 19.4 fractions. The average cost per fraction for all cancer was AU$276. The estimated cost of radiotherapy was AU$23,585 per 5-year local control and AU$86,480 per 5-year overall survival (equivalent to 5 life years) for all cancer. CONCLUSION: The cost of AU$86,480 per 5-year overall survival would translate to AU$17,296 1-year overall survival. Therefore, the cost of radiotherapy is inexpensive if delivered optimally. Policy implications from this study include knowledge about cost to deliver radiotherapy to allow one to quantify the expected benefit at a population level.

Evaluating diffusion-weighted magnetic resonance imaging for target volume delineation in head and neck radiotherapy.

INTRODUCTION: Inter-observer variability (IOV) in target volume delineation is a source of error in head and neck radiotherapy. Diffusion-weighted imaging (DWI) has been shown to be useful in detecting recurrent head and neck cancer. This study aims to determine whether DWI improves target volume delineation and IOV. METHODS: Four radiation oncologists delineated the gross tumour volume (GTV) for ten head and neck cancer patients. Delineation was performed on CT alone as well as fused image sets which incorporated fluorodeoxyglucose (FDG)-positron emission tomography (PET) and magnetic resonance imaging (MRI) in the form of CT/PET, CT/PET/T2W and CT/PET/T2W/DWI image sets. Analysis of the variability of contour volumes was completed by comparison to the simultaneous truth and performance level estimation (STAPLE) volumes. The DICE Similarity Coefficient (DSC) and other IOV metrics for each observer's contour were compared to the STAPLE for each patient and image dataset. A DWI usability scoresheet for delineation was completed. RESULTS: The CT/PET/T2W/DWI mean GTV volume of 13.37 (10.35-16.39)cm3 was shown to be different to the mean GTV of 10.92 (8.32-13.51)cm3 when using CT alone (P < 0.001). The GTV DSC amongst observers for CT alone was 0.72 (0.65-0.79), CT/PET was 0.73 (0.67-0.80), CT/PET/T2W was 0.71 (0.64-0.77) and CT/PET/T2W/DWI was 0.69 (0.61-0.75). CONCLUSION: Mean GTVs with the addition of DWI had slightly larger volumes compared to standard CT and CT/PET volumes. DWI may add supplemental visual information for GTV delineation while having a small impact on IOV, therefore potentially improving target volume delineation.

Robot or radiation? A qualitative study of the decision support needs of men with localised prostate cancer choosing between robotic prostatectomy and radiotherapy treatment.

OBJECTIVE: To understand how best to support men diagnosed with localised prostate cancer to decide which treatment option best suits their needs, when robotic prostatectomy and radiotherapy are equally appropriate to offer them. METHODS: Twenty-five men recently diagnosed with localised prostate cancer completed semi-structured interviews asking about information/decision-making needs before and/or after attending a combined clinic in which they consulted a urologist and a radiation oncologist regarding treatment options. Data was transcribed verbatim and thematically analysed. RESULTS: Most men preferred robotic prostatectomy pre-combined clinic and chose it afterwards. The thematic analysis revealed four themes: 1) trust in clinicians and the information they provide is critical for treatment choice, 2) perceived fit between treatment characteristics and personal circumstances, 3) additional considerations: specific side effects, socio-emotional and financial factors, and 4) need for tailored information delivery. Robotic prostatectomy was mistakenly believed to provide a more definitive cure than radiotherapy, which was seen as having a lesser lifestyle impact. CONCLUSIONS: Treatment choice is largely dependent on clinicians' (mainly urologists') recommendations. PRACTICE IMPLICATIONS: Patients need more balanced information about alternatives to robotic prostatectomy earlier in the treatment decision-making process. Referral to a radiation oncologist or combined clinic shortly after diagnosis is recommended.

Cutaneous malignancies in Indigenous Peoples of urban Sydney.

INTRODUCTION: Despite 3% of Australians identifying as Indigenous, cutaneous malignancies in these patients, including incidence, risk factors and outcomes have not been investigated. This is despite recognition that cancer outcomes in this population are significantly poorer. METHODS: We undertook a retrospective case series of Indigenous Peoples who presented to two urban cancer therapy centres for the management of cutaneous malignancies from 2003 to 2017. Risk factors, tumour-specific characteristics, treatments and outcomes were reviewed. RESULTS: Twenty-two patients identified as Aboriginal and/or Torres Strait Islander. The median age at presentation was 61 years and the majority were male (63.6%) and had skin phototype III (86.4%). Patients presented with basal cell carcinoma (50%), squamous cell carcinoma (31.8%), melanoma (9.1%) and cutaneous sarcomas (9.1%). The majority (68.2%) presented with stage II or higher disease, and there were high rates of immunosuppression (45.5%). At the time of reporting, 68.2% patients were alive, 18.2% had died from their skin cancers and 13.6% had died from unrelated causes. CONCLUSION: This cohort has demonstrated late-stage presentation of skin cancers, with substantial morbidity and mortality from potentially treatable cutaneous malignancies. This parallels other health conditions in Indigenous Australians and has highlighted the need for improved data collection of Indigenous status to better quantify the epidemiology of skin cancer in this population. There is an imperative to improve skin cancer awareness in this population to allow earlier detection and management to ensure better outcomes.

Differences in LC3B expression and prognostic implications in oropharyngeal and oral cavity squamous cell carcinoma patients.

BACKGROUND: This study examined the prognostic significance of microtubule-associated protein light chain 3B (LC3B) expression in oropharyngeal and oral cavity squamous cell carcinoma (SCC). The prognostic significance of LC3B expression in relation to human papillomavirus (HPV) status in oropharyngeal SCC was also examined. METHODS: Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded oropharyngeal (n = 47) and oral cavity (n = 95) SCC tissue blocks from patients with long-term recurrence and overall survival data (median = 47 months). LC3B expression on tumour was assessed by immunohistochemistry and evaluated for associations with clinicopathological variables. LC3B expression was stratified into high and low expression cohorts using ROC curves with Manhattan distance minimisation, followed by Kaplan-Meier and multivariable survival analyses. Interaction terms between HPV status and LC3B expression in oropharyngeal SCC patients were also examined by joint-effects and stratified analyses. RESULTS: Kaplan-Meier survival and univariate analyses revealed that high LC3B expression was correlated with poor overall survival in oropharyngeal SCC patients (p = 0.007 and HR = 3.18, 95% CI 1.31-7.71, p = 0.01 respectively). High LC3B expression was also an independent prognostic factor for poor overall survival in oropharyngeal SCC patients (HR = 4.02, 95% CI 1.38-11.47, p = 0.011). In contrast, in oral cavity SCC, only disease-free survival remained statistically significant after univariate analysis (HR = 2.36, 95% CI 1.19-4.67, p = 0.014), although Kaplan-Meier survival analysis showed that high LC3B expression correlated with poor overall and disease-free survival (p = 0.046 and 0.011 respectively). Furthermore, oropharyngeal SCC patients with HPV-negative/high LC3B expression were correlated with poor overall survival in both joint-effects and stratified presentations (p = 0.024 and 0.032 respectively). CONCLUSIONS: High LC3B expression correlates with poor prognosis in oropharyngeal and oral cavity SCC, which highlights the importance of autophagy in these malignancies. High LC3B expression appears to be an independent prognostic marker for oropharyngeal SCC but not for oral cavity SCC patients. The difference in the prognostic significance of LC3B between oropharyngeal and oral cavity SCCs further supports the biological differences between these malignancies. The possibility that oropharyngeal SCC patients with negative HPV status and high LC3B expression were at particular risk of a poor outcome warrants further investigation in prospective studies with larger numbers.

Employment for radiation oncologists in Australia and New Zealand: Recent graduates survey of experiences and perspectives.

INTRODUCTION: This paper reports the key findings of the first survey of recent Radiation Oncology graduates in Australia, New Zealand (ANZ) and Singapore. It explores their experiences in entering the workforce, challenges and perspectives. METHODS: The survey was conducted in April and May 2016 focusing on graduates from 2013 to 2015. The questions related to relocation, current employment, experiences in finding a job, intentions regarding rural work, job satisfaction and perceptions of the job market. RESULTS: The response rate was 80% (66/83). Most respondents (72.7%) commenced and completed their training in the same location. The large majority of respondents (91%) were employed with 51% as consultants, 20% as fellows and 15% as locums. Sixty-four percent of respondents spent more than twelve weeks looking for a consultant position, but this was expected by 80% of respondents. Seventy-three percent of respondents spent more than four weeks looking for a fellowship position, but this was expected by 90%. Twenty seven percent of respondents lived and worked in a rural area with nearly half of respondents who did not work in a rural area, indicating they would consider so if certain conditions were met. The large majority (75%) were satisfied with their current employment with only seven percent reporting dissatisfaction. Respondents felt that the job market was very competitive because of the large number of trainees and better workforce planning was required to ensure a reasonable balance between workforce supply and demand. Some career guidance and mentorship for readiness for the job market was thought to be beneficial. CONCLUSIONS: This initial survey of recent Radiation Oncology graduates in ANZ and Singapore has revealed the large majority are employed as consultants or fellows, although there is apprehension about a competitive job market. The survey should be repeated on a regular basis to monitor future trends.

Prostatectomy versus radiotherapy for early-stage prostate cancer (PREPaRE) study: protocol for a mixed-methods study of treatment decision-making in men with localised prostate cancer.

BACKGROUND: Men diagnosed with localised prostate cancer (LPC) wanting curative treatment face a highly preference-sensitive choice between prostatectomy and radiotherapy, which offer similar cure rates but different side effects. This study aims to determine the information, decision-making needs and preferences of men with LPC choosing between robotic prostatectomy and standard external beam or stereotactic radiotherapy. METHODS AND ANALYSIS: This study will be conducted at a large public teaching hospital in Australia offering the choice between robotic prostatectomy and radiotherapy from early 2017. Men (20-30) diagnosed with LPC who want curative treatment and meet criteria for either treatment will be invited to participate. In this mixed-methods study, patients will complete semistructured interviews before and after attending a combined clinic in which they consult a urologist and a radiation oncologist regarding treatment and four questionnaires (one before treatment decision-making and three after) assessing demographic and clinical characteristics, involvement in decision-making, decisional conflict, satisfaction and regret. Combined clinic consultations will also be audio-recorded and clinicians will report their perceptions regarding patients' suitability for, openness to and preferences for each treatment. Qualitative data will be transcribed verbatim and thematically analysed and descriptive statistical analyses will explore quantitative decision-making outcomes, with comparison according to treatment choice. DISCUSSION: Results from this study will inform how to best support men diagnosed with LPC deciding which curative treatment option best suits their needs and may identify the need for and content required in a decision aid to support these men. ETHICS AND DISSEMINATION: All participants will provide written informed consent. Data will be rigorously managed in accordance with national legislation. Results will be disseminated via presentations to both scientific and layperson audiences and publications in peer-reviewed scientific journals.

Multiparametric magnetic resonance imaging in mucosal primary head and neck cancer: a prospective imaging biomarker study.

BACKGROUND: Radical radiotherapy, with or without concomitant chemotherapy forms the mainstay of organ preservation approaches in mucosal primary head and neck cancer. Despite technical advances in cancer imaging and radiotherapy administration, a significant proportion of patients fail to achieve a complete response to treatment. For those patients who do achieve a complete response, acute and late toxicities remain a cause of morbidity. A critical need therefore exists for imaging biomarkers which are capable of informing patient selection for both treatment intensification and de-escalation strategies. METHODS/DESIGN: A prospective imaging study has been initiated, aiming to recruit patients undergoing radical radiotherapy (RT) or chemoradiotherapy (CRT) for mucosal primary head and neck cancer (MPHNC). Eligible patients are imaged using FDG-PET/CT before treatment, at the end of week 3 of treatment and 12 weeks after treatment completion according to local imaging policy. Functional MRI using diffusion weighted (DWI), blood oxygen level-dependent (BOLD) and dynamic contrast enhanced (DCE) sequences is carried out prior to, during and following treatment. Information regarding treatment outcomes will be collected, as well as physician-scored and patient-reported toxicity. DISCUSSION: The primary objective is to determine the correlation of functional MRI sequences with tumour response as determined by FDG-PET/CT and clinical findings at 12 weeks post-treatment and with local control at 12 months post-treatment. Secondary objectives include prospective correlation of functional MRI and PET imaging with disease-free survival and overall survival, defining the optimal time points for functional MRI assessment of treatment response, and determining the sensitivity and specificity of functional MRI sequences for assessment of potential residual disease following treatment. If the study is able to successfully characterise tumours based on their functional MRI scan characteristics, this would pave the way for further studies refining treatment approaches based on prognostic and predictive imaging data. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616000534482 (26 April 2016).

A review of the predictive role of functional imaging in patients with mucosal primary head and neck cancer treated with radiation therapy.

Advanced radiotherapy techniques, such as intensity-modulated radiotherapy, have been reported to reduce toxicities by improving the dose conformity in mucosal primary head and neck cancer (MPHNC). However, to further optimize the therapeutic ratio, details on individual patient and disease characteristics may be necessary to tailor treatments. This is likely to include identifying poor responders for treatment intensification and good responders for de-escalation strategies. Non-invasive, repeatable imaging biomarkers are attractive modalities in both pre-treatment and intra-treatment response prediction with a view to individualized treatment options. This review has assessed the current literature on the prognostic/predictive role of widely available functional imaging (FI) studies such as fMRI(functional magnetic resonance imaging), functional computed tomography (fCT) and positron-emission-tomography(PET). A literature search was carried out using Medline, Embase and PubMed. Studies were included if imaging was undertaken pre and/or during radiotherapy (with or without the addition of chemotherapy and/or surgery). A total of 99 relevant studies were identified: 14 fMRI, 10 fCT, 59 FDG-PET and 16 non-FDG-PET studies. These articles were reviewed to identify imaging parameters demonstrating a correlation with patient outcome or a factor considered to impact on patient outcome and thus likely to be of potential predictive value in MPHNC and associated future radiotherapy treatment directions. Several studies have demonstrated that both pre-treatment and mid-treatment FDG-PET is predictive of outcomes. However, further studies are required to confirm the role of other imaging studies including fMRI and PET using other tracers. There is large heterogeneity within and between published studies, including tumour sites, treatment options, outcome endpoints and parameters assessed. We propose a minimum set of factors that should be reported and make recommendations for studies evaluating the predictive utility in MPHNC.

Differences in survival outcome between oropharyngeal and oral cavity squamous cell carcinoma in relation to HPV status.

BACKGROUND: This study examined the prognostic significance of human papillomavirus (HPV) in patients with oropharyngeal and oral cavity squamous cell carcinoma (SCC). METHODS: Tissue microarrays were constructed from oropharyngeal and oral cavity SCC (n = 143). The presence of functional HPV in tumour was determined by combined assessments of p16 immunohistochemistry and HPV in situ hybridisation. RESULTS: Oropharyngeal SCC patients presented with more advanced disease in comparison with oral cavity SCC patients (P = 0.001). HPV is present in 60% and 61% of oropharyngeal and oral cavity SCC patients, respectively. HPV-positive oropharyngeal SCC patients with advanced TNM stages displayed better overall and disease-free survival outcomes than HPV-negative patients (P = 0.022 and 0.046, respectively). Such survival differences were not observed in oral cavity SCC. CONCLUSIONS: HPV is common in both oropharyngeal and oral cavity SCC and is associated with better survival outcome in oropharyngeal SCC but not in oral cavity SCC patients.