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

Advances in radiation therapy

Radiation therapy (or radiotherapy) and surgery are the two main treatments available for curing solid tumour malignancies. Radiation therapy uses high-energy ionising radiation to destroy the DNA of cancer cells, and can be used to cure cancers, either alone or in conjunction with surgery or chemotherapy. According to the available evidence, one in two patients with cancer in Australia would benefit from receiving radiation therapy as part of their treatment. In cases of incurable disease, radiotherapy relieves distressing symptoms, such as pain, in two of three patients. Radiation therapy is an effective, safe cancer treatment that is also cost-efficient. Data analysis by Medicare and the federal Department of Health indicate that less than 9 cents of each dollar spent on cancer care in Australia is for radiation therapy. In the past decade, major technological advances have transformed the field, allowing patients to be treated with greater precision than ever before

How important is dosimetrist experience for intensity modulated radiation therapy? A comparative analysis of a head and neck case

Purpose: Treatment planning for IMRT is a complex process that requires additional training and expertise. The aim of this study was to compare and analyze IMRT plans generated by dosimetrists with varying levels of IMRT planning experience. Methods and Materials: The computed tomography (CT) data of a patient previously treated with IMRT for left tonsillar carcinoma were used. The patient\u27s preexisting planning target volumes (PTVs) and all organs at risk were provided with the CT data set. Six dosimetrists with variable IMRT planning experience generated IMRT plans according to the department\u27s protocol. Plan analysis included visual inspection and comparison of dose-volume histogram, conformity indices, treatment delivery efficiency, and dose delivery accuracy. Results: Visual review of the dose distribution showed that the 6 plans were comparable. However, only the 2 most experienced dosimetrists were able to meet the strict PTV aims and critical structure constraints. The least experienced dosimetrist had the worst planning outcome. Comparison of delivery efficiency showed that the number of segments, total monitor units, and treatment time increased as the IMRT planning experience decreased. Conclusions: Dosimetrists with higher levels of IMRT planning experience produced a better quality head and neck IMRT plan. Different planning experience may need to be considered when organizing appropriate departmental resources

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

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

Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes : SUVmean and response rate are useful imaging biomarkers

Purpose: To evaluate the prognostic utility of nodal metabolic parameters derived from FDG PET/CT performed before radiotherapy (prePET) and during the third week of radiotherapy (iPET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC). Methods: This analysis included 75 patients with newly diagnosed locally advanced node-positive MPHNSCC treated with radical radiotherapy and concurrent systemic therapy who underwent prePET and iPET: N1 11 patients, N2a 38, N2b 12, N2c 9, N3 5. The median follow-up was 28 months (9 – 70 months). The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of the index lymph node (node with the highest TLG) and the combined total lymph nodes, and their percentage reductions on iPET were determined, and the results were correlated with 3-year Kaplan-Meier locoregional, regional and distant metastatic failure-free survival (FFS), disease-free survival (DFS) and overall survival (OS). Optimal cut-off values were derived from receiver operating characteristic curves. Cox regression univariate and multivariate analyses with clinical covariates were performed. Results: Based on assessment of residual nodal metabolic burden during treatment, the iPET index node SUVmean (optimal cut-off value 2.95 g/ml) and the total node SUVmean (optimal cut-off value 3.25) were the best independent predictors of outcome in the multivariate analysis: index node SUVmean for DFS and OS p = 0.033 and 0.003, respectively, and the total node SUVmean for locoregional FFS, DFS and OS p = 0.028, 0.025 and 0.014, respectively. Based on the assessment of response rates during treatment, a reduction of more than 50 % in the total node TLG was the best biomarker for locoregional and regional FFS, DFS and OS in the multivariate analysis (p = 0.001, 0.016, 0.001 and 0.004, respectively), and reduction in the total node MTV for locoregional FFS, DFS and OS (p = 0.026, 0.003 and 0.014, respectively). There were no significant correlations between oncological outcomes and prePET nodal parameters. Conclusion: We demonstrated that the index node and total node SUVmean on iPET and a reduction of more than 50 % in MTV and TLG are useful imaging biomarkers, and can potentially identify those patients with MPHNSCC who have a high risk of locoregional metastatic failure and death

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

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

Prognostic utility of 18F-FDG PET-CT performed prior to and during primary radiotherapy for nasopharyngeal carcinoma : index node is a useful prognostic imaging biomarker site

Purpose: To evaluate the prognostic value of 18F-FDG-PET-CT performed prior to (prePET) and during the third week (iPET) of radiation therapy (RT) in nasopharyngeal carcinoma (NPC). Materials and methods: Thirty-patients with newly diagnosed loco-regionally advanced NPC treated with radical RT underwent prePET and iPET. The median follow-up was 26 months (8–66.9). The maximum standardised-uptake-value (SUVmax), metabolic-tumour-volume (MTV) and total-lesional-glycolysis (TLG) of the primary tumour (PT), index-node (IN) (lymph node with highest TLG), total-lymph-nodes (TN) and combined primary-tumour and nodal (PTN), and their % reductions in iPET were analysed, and results were correlated with 2-year Kaplan–Meier loco-recurrence-free-survival (LRFS), regional failure-free-survival (RFFS), distant-metastatic-failure-free-survival (DMFFS), disease-free-survival (DFS), and overall-survival (OS). Optimal-cut offs (OC) were derived from Receiver-Operating-Characteristic curves. Results: For LRFS, the only predictor was reduction in PT MTV by >50%: 95.2% vs. 75.0%, p = 0.024. Results: For other treatment outcomes, only nodal or PTN predicted outcomes. The IN SUVmax (pre-PET-OC = 10.45 g/mL and iPET-OC = 8.15) and TLG (prePET-OC = 90 g and iPET-OC = 33.4) were the best predictors of outcome: RFFS (iPET SUVmax/TLG): 100% vs. 50%, p < 0.001 and 100% vs. 44%, p = 0.032; DMFFS (prePET SUVmax/TLG); 100% vs. 51.9%, p = 0.004 and 100% vs. 47.6%, p = 0.002; DFS (prePET TLG and iPET SUVmax): 87.5% vs. 33%, p = 0.045 and 78.7% vs. 20%, p = 0.01; and OS (prePET TLG): 100% vs 66.3%, p = 0.036. Conclusions: We have demonstrated IN of prePET and iPET to be a feasible and potentially useful novel imaging biomarker to predict for patients with NPC who have a high risk of regional or distant metastatic failure. Future work is required to validate our findings in a well-powered, prospective study with a standardised treatment protocol, and their potential use to guide individualised therapy for NPC

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