Chemotherapy compliance in high-risk Merkel cell carcinoma treated with chemoradiotherapy.

OBJECTIVE: To evaluate chemotherapy (CT) compliance in patients treated with chemoradiotherapy (CRT) for high-risk Merkel cell cancer (MCC). METHODS: Data from three prospective clinical trials in high-risk MCC performed by the Trans-Tasman Radiation Oncology Group were included in this analysis. Patients were treated with one of two carboplatin-based CT schedules and standardised radiotherapy (RT) to the primary site and nodes to a dose of 50-60 Gy in 25-30 fractions. Patients' baseline characteristics were analysed using χ2 tests to determine compliance factors for completing CT. A Cox univariate analysis was performed to assess the impact of CT compliance on time to locoregional failure, time-to-distant failure, time-to-recurrence and time-to-death. RESULTS: A total of 88 patients were identified, with a median follow up of 38.5 months. Of these, 75 (85%) completed CT (median age 64.2 years, range 62.0-66.4), while 13 did not (median age 72 years, range 68.1-75.9), P = 0.006. Women comprised 18/75 patients who completed CT and 7/13 patients who did not complete it (P = 0.03). Performance status, site, stage, surgical margins, RT dose and toxicity did not impact on their CT compliance. At 5 years, 26% of patients had locoregional relapse, 26% had distant failure and 34% had died. CONCLUSIONS: In this small cohort of patients treated with CRT for high-risk MCC, older age and female sex were associated with failure to complete CT. Severe acute skin and haematological toxicity did not correlate with failure to complete CT.

Advances in radiotherapy technology for non-small cell lung cancer: What every general practitioner should know.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death in Australia. Radiotherapy plays an important role in the curative and palliative settings. OBJECTIVE: This article reviews recent technological advances that have expanded the radiotherapy treatment options available, and presents standard and emerging approaches to NSCLC. DISCUSSION: General practitioners play an integral role in the care and education of patients during diagnosis, treatment andfollow-up of NSCLC. Stereotactic (ablative) body radiotherapy,intensity-modulated radiotherapy, intracranial radiosurgery and hippocampal-avoidance whole-brain radiotherapy are discussed in this article.

Radiotherapy for cutaneous melanoma: current and future applications.

Cutaneous malignant melanoma remains a significant health burden worldwide despite advances in the management of locoregionally advanced and metastatic disease. Historically, the efficacy of radiation therapy (RT) has been questioned due to the perceived radioresistance of melanoma cancer cells in vitro. Nowadays, RT has limited indications for primary disease, but is used for high-risk nodal disease and in the palliative setting. This review article outlines the current role of RT for melanoma and its expanding role in oligometastatic disease scenarios as an alternative approach to surgery and highlights potential future applications to harness RT interaction with immunomodulatory targeted therapies.

Advances in radiotherapy technology for prostate cancer: What every GP should know.

BACKGROUND: One in five Australian men are diagnosed with prostate cancer. External beam radiation therapy (EBRT) is an effective treatment for men suitable for definitive therapy. OBJECTIVE: This article outlines the processes involved in EBRT for prostate cancer, with particular emphasis on recent technological advances that have had a positive impact on patient outcomes. The patient's experience is explained and comparisons are made with surgery. DISCUSSION: Patients diagnosed with localised prostate cancer may have multiple treatment options. General practitioners have an important role in helping patients navigate their way through the information needed to make this decision. Radiotherapy technologies, including image guidance, intensity-modulated radiation therapy and stereotactic (ablative) radiation therapy are discussed in this article.

Transforming cancer care in Australia: The dawn of particle therapy.

The nearing completion of the Australian Bragg Centre for Proton Therapy and Research marks a transformative leap in cancer care in Australia. Highlighting the precision and potential of particle therapy in reducing long-term side effects, particularly in paediatric and rare cancers, this editorial underscores Australia's commitment to integrating this innovative modality into national healthcare, despite challenges in accessibility and cost.

Establishing a consumer advisory group at the Australian Bragg Centre for Proton Therapy and Research.

The Australian Bragg Centre for Proton Therapy and Research (ABCPTR) established the Bragg Consumer Advisory Group (BCAG) in 2023. The ABCPTR, being the first of its kind in Australia, will offer proton therapy treatment for challenging solid tumours with the potential to reduce radiation-induced side effects. With over 110 Proton Beam Therapy (PBT) centres globally, Australian patients currently can apply to access government funded treatment overseas, however, international travel for treatment presents various, significant challenges. Consumer engagement in healthcare plays a pivotal role in navigating the multifaceted journey of cancer treatment and can complement cancer control strategies by ensuring the practicalities of the cancer journey are realised. The ABCPTR aims to involve consumers in decision-making processes, especially as it prepares to open Australia's first national proton therapy centre. The aim of this commentary is to highlight the importance of involving consumers in cancer care, and to demonstrate how this was done in Australia's first proton therapy centre. To establish a consumer engagement team, ABCPTR utilised existing clinical staff. The team's formation and upskilling were integral to the project's success. The engagement framework was developed based on the five stages of commitment by the Australian Health Research Alliance and Western Australian Health Translation Network. The ABCPTR consumer engagement team successfully created a community engagement framework and upskilled in consumer engagement principles over 9-12 months. An Expression of Interest (EOI) was launched, resulting in the formation of the BCAG comprising of 10 members with diverse backgrounds and experiences. The BCAG has been actively involved in decision-making processes, with a consumer-led chair and co-chair in place. The group's feedback is expected to influence key performance indicators for the centre. The establishment of the BCAG at the ABCPTR emphasises the importance of integrating patient and community perspectives into clinical initiatives. This proactive approach ensures that processes remain patient-centred. The ongoing multi-level consumer engagement strategy aims to shape a more inclusive approach to cancer care in Australia, especially concerning PBT.

Travelling overseas for proton beam therapy: A retrospective interview study.

INTRODUCTION: Travelling for cancer treatment comes with unique challenges, particularly for a young patient and his or her family. The aims of this study were to (1) gain an understanding of the experiences of families and patients who travelled overseas (OS) from Australia for proton beam therapy (PBT) and (2) identify the supportive care needs patients and their families require when living away from home, while having PBT. METHODS: This was a retrospective, qualitative study using semi-structured interviews, conducted with participants aged under 25 years and their families who travelled OS for PBT between 2017 and 2020. Data were analysed using Microsoft Excel Software, where key themes were identified and coded based on their responses. A total of 17 participants were included in interviews from seven Australian families who travelled to America or Europe for PBT. RESULTS: The majority of participants reported a lack of coordination with travel and treatment arrangements prior to arrival OS. Families who stayed in hotel accommodation while OS reported greater feelings of isolation compared with those who stayed in share house-style accommodation. The acuity of cancer diagnosis played a significant part in patient experience, with those patients requiring the greatest amount of supportive care and availability of service provision at stand-alone centres reporting a lack of appropriate care provision. CONCLUSIONS: This study has identified services, accommodation provisions and care coordination requirements that are largely missing from the travel and treatment experience in patients travelling OS for PBT. Future use of consumer-led working groups or committees in creating models of care for families travelling for PBT treatment could be advantageous, with many families willing to share their experiences and provide support to others who are travelling for PBT.

Proton beam therapy for clival chordoma: Optimising rare cancer treatments in Australia.

With the anticipated launch of the Australian Bragg Centre for Proton Therapy and Research (ABCPTR) in Adelaide, Australia, proton therapy will become a significant addition to existing cancer treatment options for Australians. The anticipated benefits will be particularly evident in rare cancers such as clival chordomas, a challenging tumour entity due to the anatomical relationship with critical structures, and proven radio-resistance to conventional radiation therapy. The article synthesises key findings from major studies and evaluates the current evidence supporting various management strategies for clival chordomas. It also considers the influence of institutional volume and multidisciplinary team management on patient outcomes and outlines how high-quality care can be effectively delivered within the Australian healthcare system, emphasising the potential impact of proton therapy on the treatment paradigm of clival chordomas in Australia.

Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers.

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Synthetic cranial MRI from 3D optical surface scans using deep learning for radiation therapy treatment planning.

BACKGROUND: Optical scanning technologies are increasingly being utilised to supplement treatment workflows in radiation oncology, such as surface-guided radiotherapy or 3D printing custom bolus. One limitation of optical scanning devices is the absence of internal anatomical information of the patient being scanned. As a result, conventional radiation therapy treatment planning using this imaging modality is not feasible. Deep learning is useful for automating various manual tasks in radiation oncology, most notably, organ segmentation and treatment planning. Deep learning models have also been used to transform MRI datasets into synthetic CT datasets, facilitating the development of MRI-only radiation therapy planning. AIMS: To train a pix2pix generative adversarial network to transform 3D optical scan data into estimated MRI datasets for a given patient to provide additional anatomical data for a select few radiation therapy treatment sites. The proposed network may provide useful anatomical information for treatment planning of surface mould brachytherapy, total body irradiation, and total skin electron therapy, for example, without delivering any imaging dose. METHODS: A 2D pix2pix GAN was trained on 15,000 axial MRI slices of healthy adult brains paired with corresponding external mask slices. The model was validated on a further 5000 previously unseen external mask slices. The predictions were compared with the "ground-truth" MRI slices using the multi-scale structural similarity index (MSSI) metric. A certified neuro-radiologist was subsequently consulted to provide an independent review of the model's performance in terms of anatomical accuracy and consistency. The network was then applied to a 3D photogrammetry scan of a test subject to demonstrate the feasibility of this novel technique. RESULTS: The trained pix2pix network predicted MRI slices with a mean MSSI of 0.831 ± 0.057 for the 5000 validation images indicating that it is possible to estimate a significant proportion of a patient's gross cranial anatomy from a patient's exterior contour. When independently reviewed by a certified neuro-radiologist, the model's performance was described as "quite amazing, but there are limitations in the regions where there is wide variation within the normal population." When the trained network was applied to a 3D model of a human subject acquired using optical photogrammetry, the network could estimate the corresponding MRI volume for that subject with good qualitative accuracy. However, a ground-truth MRI baseline was not available for quantitative comparison. CONCLUSIONS: A deep learning model was developed, to transform 3D optical scan data of a patient into an estimated MRI volume, potentially increasing the usefulness of optical scanning in radiation therapy planning. This work has demonstrated that much of the human cranial anatomy can be predicted from the external shape of the head and may provide an additional source of valuable imaging data. Further research is required to investigate the feasibility of this approach for use in a clinical setting and further improve the model's accuracy.

A Systematic Review of LET-Guided Treatment Plan Optimisation in Proton Therapy: Identifying the Current State and Future Needs.

The well-known clinical benefits of proton therapy are achieved through higher target-conformality and normal tissue sparing than conventional radiotherapy. However, there is an increased sensitivity to uncertainties in patient motion/setup, proton range and radiobiological effect. Although recent efforts have mitigated some uncertainties, radiobiological effect remains unresolved due to a lack of clinical data for relevant endpoints. Therefore, RBE optimisations may be currently unsuitable for clinical treatment planning. LET optimisation is a novel method that substitutes RBE with LET, shifting LET hotspots outside critical structures. This review outlines the current status of LET optimisation in proton therapy, highlighting knowledge gaps and possible future research. Following the PRISMA 2020 guidelines, a search of the MEDLINE® and Scopus databases was performed in July 2023, identifying 70 relevant articles. Generally, LET optimisation methods achieved their treatment objectives; however, clinical benefit is patient-dependent. Inconsistencies in the reported data suggest further testing is required to identify therapeutically favourable methods. We discuss the methods which are suitable for near-future clinical deployment, with fast computation times and compatibility with existing treatment protocols. Although there is some clinical evidence of a correlation between high LET and adverse effects, further developments are needed to inform future patient selection protocols for widespread application of LET optimisation in proton therapy.

If we build it, will they come? Modeling of public hospital care requirements for the Australian Bragg Centre for Proton Therapy and Research.

INTRODUCTION: The Australian Bragg Centre for Proton Therapy and Research (ABCPTR) will be Australia's first proton beam therapy (PBT) facility. A model was developed to predict associated public hospital care requirements for patients during PBT, to facilitate resource planning for pediatric, adolescent and young adult (AYA), and adult public hospitals in South Australia. METHODS: National incidence rates for specific cancer indications were obtained from the Australian Childhood Cancer Registry, Australian Institute of Health and Welfare and published data. Australian Bureau of Statistics national population projections were used to estimate new cases in 2025 and beyond. Radiation oncologists and pediatric oncologists from the Central Adelaide Local and Women's and Children's Health Network, along with international colleagues, provided guidance on chemotherapy utilization and inpatient admission estimates. RESULTS: It was estimated 180 patients (40.4%) within the adult population (≥25 years) and 265 patients (59.6%) within the pediatric/AYA population (<25 years) would be eligible for PBT in 2025. There was no indication adult cancers would require concurrent outpatient/inpatient chemotherapy, in contrast with pediatric and AYA patients (59.5% and 62.8% outpatient and 18.9% and 41.9% inpatient, respectively). It was estimated 53% and 29% of pediatric and AYA patients could require inpatient admission for toxicity related to disease, concurrent chemotherapy or PBT. CONCLUSION: Associated public hospital care requirements related to the delivery of a national PBT service were estimated. This has particular implications for planning of the new Women's and Children's hospital, co-located with the ABCPTR. True data accuracy will be determined on future data generation and analysis.

Minimum data elements for the Australian Particle Therapy Clinical Quality Registry.

INTRODUCTION: Construction of the first Australian particle therapy (PT) centre is underway. Establishment of a national registry, to be known as the Australian Particle Therapy Clinical Quality Registry (ASPIRE), has been identified as a mandatory requirement for PT treatment to be reimbursed by the Australian Medicare Benefits Schedule. This study aimed to determine a consensus set of Minimum Data Elements (MDEs) for ASPIRE. METHODS: A modified Delphi and expert consensus process was completed. Stage 1 compiled currently operational English-language international PT registries. Stage 2 listed the MDEs included in each of these four registries. Those included in three or four registries were automatically included as a potential MDE for ASPIRE. Stage 3 interrogated the remaining data items, and involved three rounds - an online survey to a panel of experts, followed by a live poll session of PT-interested participants, and finally a virtual discussion forum of the original expert panel. RESULTS: One hundred and twenty-three different MDEs were identified across the four international registries. The multi-staged Delphi and expert consensus process resulted in a total of 27 essential MDEs for ASPIRE; 14 patient factors, four tumour factors and nine treatment factors. CONCLUSIONS: The MDEs provide the core mandatory data items for the national PT registry. Registry data collection for PT is paramount in the ongoing global effort to accumulate more robust clinical evidence regarding PT patient and tumour outcomes, quantifying the magnitude of clinical benefit and justifying the relatively higher costs of PT investment.

Proton-to-photon comparative treatment planning guidelines for the Australian context.

Proton-to-photon comparative treatment planning is a current requirement of Australian Government funding for patients to receive proton beam therapy (PBT) overseas, and a future requirement for Medicare funding of PBT in Australia. Because of the fundamental differences in treatment plan creation and evaluation between PBT and conventional radiation therapy with x-rays (XRT), there is the potential for a lack of consistency in the process of comparing PBT and XRT treatment plans. This may have an impact on patient eligibility assessment for PBT. The objective of these guidelines is to provide a practical reference document for centres performing proton-to-photon comparative planning and thereby facilitate national uniformity.

Proton beam therapy in paediatric cancer: Anticipating the opening of the Australian Bragg Centre for Proton Therapy and Research.

Proton Beam Therapy (PBT) has the potential to improve paediatric cancer care by reducing radiation exposure and thus long-term toxicities. Ethical concerns and debates surrounding the treatment, such as eligibility and accessibility, are ongoing in Australia. The Australian Bragg Centre for Proton Therapy and Research (ABCPTR) (named after Sir William Henry Bragg who described the Bragg peak in his laboratory at the University of Adelaide in 1903) aims to increase access to PBT in Australasia and offer a patient-centred care approach. Research is underway to assess PBT's safety and cost-effectiveness, using tools including Normal Tissue Complication Probability (NTCP) models. Collaborative efforts are focused on developing tailored survivorship clinics to enhance patient follow-up and quality of life. With the anticipated opening of the ABCPTR, Australia is preparing to take a significant step in radiation oncology, offering new research opportunities and creating a publicly funded treatment centre. The initiative aims to balance treatment efficacy with patient care, setting the stage for a future in which radiation therapy will reduce long-term side effects compared to the current standard of care. The implementation of PBT in Australia represents a complex and promising approach to paediatric oncology. This article provides an overview of the current landscape, highlighting the potential benefits and challenges of a treatment that could redefine the quality of survivorship and contribute to global research and best clinical practice.

The Role of Hypofractionation in Proton Therapy.

Hypofractionated radiotherapy is an attractive approach for minimizing patient burden and treatment cost. Technological advancements in external beam radiotherapy (EBRT) delivery and image guidance have resulted in improved targeting and conformality of the absorbed dose to the disease and a reduction in dose to healthy tissue. These advances in EBRT have led to an increasing adoption and interest in hypofractionation. Furthermore, for many treatment sites, proton beam therapy (PBT) provides an improved absorbed dose distribution compared to X-ray (photon) EBRT. In the past 10 years there has been a notable increase in reported clinical data involving hypofractionation with PBT, reflecting the interest in this treatment approach. This review will discuss the reported clinical data and radiobiology of hypofractionated PBT. Over 50 published manuscripts reporting clinical results involving hypofractionation and PBT were included in this review, ~90% of which were published since 2010. The most common treatment regions reported were prostate, lung and liver, making over 70% of the reported results. Many of the reported clinical data indicate that hypofractionated PBT can be well tolerated, however future clinical trials are still needed to determine the optimal fractionation regime.

Can We Compare the Health-Related Quality of Life of Childhood Cancer Survivors Following Photon and Proton Radiation Therapy? A Systematic Review.

Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life (HRQoL) in children. This systematic review aimed to identify the evidence of HRQoL outcomes in childhood cancer survivors following XRT and PRT. Medline, Embase, and Scopus were systematically searched. Thirty studies were analysed, which described outcomes of 1986 childhood cancer survivors. Most studies (n = 24) described outcomes for children with a central nervous system (CNS) tumour, four studies reported outcomes for children with a non-CNS tumour, and two studies combined CNS and non-CNS diagnoses within a single cohort. No studies analysed routine HRQoL collection during paediatric radiation oncology clinical practice. There is insufficient quality evidence to compare HRQoL outcomes between XRT and PRT. Therefore, the current state of the literature does not conclude that PRT produces superior HRQoL outcomes for childhood cancer survivors. Standardised clinical implementation of HRQoL assessment using patient-reported outcomes is recommended to contribute to improvements in clinical care whilst assisting the progression of knowledge comparing XRT and PRT.

LINAC stereotactic radiosurgery for brain arteriovenous malformations: An updated single centre analysis of outcomes.

Arteriovenous malformations (AVM) of the brain are congenital, high pressure vascular malformations, which are at risk of haemorrhage. Stereotactic radiosurgery (SRS) can obliterate the nidus by delivering a precise high dose of ionising radiation in a single fraction. This paper updates long term AVM obliteration rates, time to obliteration and retreatment outcomes in LINAC delivered SRS treatment at the Royal Adelaide Hospital. A retrospective review of a prospectively maintained AVM SRS database supplemented by clinical case notes, patient correspondence and electronic medical records was performed. 89 AVMs received primary SRS treatment for which the crude obliteration rate was 61% (68% for 79 patients with adequate follow up). Higher marginal dose, smaller nidus size and lower Pollock-Flickinger (PF) score were significantly associated with AVM obliteration. The crude obliteration rates for patients with adequate follow-up and AVM diameter < 3 cm vs ≥ 3 cm were 76% vs 48%, respectively, and 93% with PF score < 1.0. Median time to obliteration was 36 months. Higher dose and lower PF score were associated with earlier obliteration. The crude obliteration rate after second SRS was 56% (9/16 patients) and no significant associations were found. These obliteration rates after primary and retreatment LINAC SRS are comparable to other studies. Marginal dose and PF score were the main predictors of obliteration overall as well as early (<36 months) obliteration.

Complete clinical response of a neglected cutaneous melanoma with combined radiotherapy and immunotherapy: A case report.

The treatment of patients with advanced melanoma has undergone a dramatic change over the past decade. Apart from refining the radiotherapy techniques, the repertoire of systemic treatments expanded from largely futile cytotoxic chemotherapy to substantially more effective MAP kinase and immune checkpoint inhibitors (Immunotargets Ther, 7, 2018)1 . We report a case which exemplifies the improved efficacy as well as increased complexity of therapeutic decision-making. A 71-year-old man presented with neglected fungating and bleeding malignant melanoma, which resulted in severe anaemia with consequent cardiac dysfunction. There was limited distant spread. Patient was treated with combined radiotherapy and immunotherapy: 55 Gray in 20 fractions over four weeks using 3D-conformal technique followed by an anti-PD1 antibody (pembrolizumab, Keytruda® Merck/MSD, Kenilworth N.J.; 2 mg/kg 3-weekly). A surgical approach to provide haemostasis and cosmesis was considered, but would be associated with significant morbidity, prolonged recovery and functional impairment and would not have altered patient survival. The sequential radioimmunotherapy resulted in a complete response. Radiotherapy was completed with only mild skin toxicity. Immunotherapy was complicated by diarrhoea, which necessitated withdrawal of the medication but was controlled with steroids. The non-operative treatment resulted in excellent oncological, functional and cosmetic outcome, with acceptable toxicity. Due to increasing complexity of melanoma therapy, a multidisciplinary approach is of paramount importance.