Adoptive cellular therapies have revolutionised treatment of haematological malignancies and demonstrate potential in solid tumours and autoimmune disease. Real-world implementation remains limited by biological, logistical, and manufacturing barriers, restricting global uptake despite a rapidly expanding clinical trial portfolio. Effective implementation requires national and institutional readiness, multidisciplinary collaboration, scalable manufacturing, and robust infrastructure. Efforts should prioritise decentralised and “off the shelf” platforms, integrated referral networks, and AI-assisted patient management to support safe, equitable and efficient global delivery.

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Background: Transoral robotic surgery (TORS) for the treatment of early human papillomavirusrelated oropharyngeal squamous cell carcinoma (HPVOPSCC) is a well-established treatment modality. It requires a distinctive skill set from the head and neck surgeon to achieve optimal oncological and functional outcomes. The aim of this study is to demonstrate oncological outcomes of HPVOPSCC treated with TORS and guideline indicated adjuvant therapy. Methods: A consecutive case series of adult patients with HPVOPSCC undergoing primary surgical treatment by a single fellowship trained robotic head and neck surgeon in Australia was performed. Adjuvant therapy (radiotherapy with or without chemotherapy) was delivered based on current guidelines. The primary outcomes were to determine complete resection of the primary tumour, locoregional recurrence, disease specific survival, and overall survival. The secondary outcomes were to determine complications; post-operative haemorrhage, salivary leak, and need for percutaneous gastrostomy (PEG) insertion. Results: A total of 41 patients were assessed. Adjuvant therapy was indicated in 15 (36.6%) patients (radiotherapy: 14; chemoradiotherapy: 1). The follow-up was 51 [interquartile range (IQR) 24] months. The positive margin rate on histopathology analysis was 4.9% (n=2). The locoregional recurrence rate was 4.9% (n=2). The disease-specific survival and overall survival rate was 100% at 3 years, and 95.1% at 5 years. TORS-related complications occurred in 5 patients (12.1%), of which 2 patients (4.9%) had a secondary haemorrhage, 1 patient (2.4%) had a salivary leak, and 2 patients (4.9%) required short-term PEG insertion. Conclusions: TORS for the treatment of early stage HPVOPSCC can result in complete resection, low rates of recurrence, and acceptable complication profile.

Sehr geehrte Herausgeber, Etwa 95% der Patienten mit kutanem Plattenepithelkarzinom (cutaneous squamous cell carcinoma, cSCC) können durch Operation oder Strahlentherapie geheilt werden. Bis zu 5% der behandelten Patienten entwickeln jedoch eine inoperable oder metastasierende Erkrankung, die eine systemische Therapie erfordert.1 Als Erstlinienbehandlung für solche Patienten werden Inhibitoren des Programmed Cell Death-1 (PD-1)-Rezeptors vorgeschlagen, die objektive Ansprechraten (objective response rates, ORR) von bis zu 50% aufweisen.1 Vollständige Ansprechraten sind jedoch bei Patienten mit metastasierendem cSCC selten (5-10%), was auf einen dringenden Bedarf an Strategien zur Überwindung der Anti-PD1-Resistenz hinweist. Ein 62-jähriger hellhäutiger Mann wurde mit einer zweijährigen Vorgeschichte eines metastasierten cSCC in die onkologische Akutklinik überwiesen. Der Primärtumar, ein retroaurikuläres cSCC, war im Jahr 2020 exzidiert worden. Repräsentative histologische Bilder sind in Abbildung 1 zu sehen. Bei der Gesamtgenom-Sequenzierung (Illumina NextSeq® 500) wurden eine hohe Tumormutationslast (138 Mutationen/Megabasen), eine EGFR-Amplifikation (27 Kopien) sowie Mutationen in PTCH1 Q184, NOTCH1 S385F und TP53 H179N festgestellt. Zu den früheren Behandlungen gehörten Cemiplimab, Cisplatin plus Capecitabin, Vismodegib und mehrere Strahlentherapien (Abbildung 2). Zum Zeitpunkt der Überweisung lagen ein 30 × 20 mm großer Knoten in der rechten Parotis und ein 19 × 15 mm großer rechtsseitiger supraklavikulärer Knoten betroffen (Abbildung 3). Beide Bereiche waren zuvor strahlentherapiert worden und waren in der Folge progredient. Der Patient wurde in eine klinische Phase I-Studie aufgenommen, bei der intratumorale Injektionen mit onkolytischen Reoviren (3wöchentlich) in den supraklavikulären Knoten plus Pembrolizumab (200 mg 3wöchentlich) durchgeführt wurden. Diese Behandlung wurde gut vertragen, es traten nur leichte Schmerzen an der Injektionsstelle auf. Nach zwölf Zyklen zeigte die erneute Bildgebung ein vollständiges metabolisches Ansprechen sowohl des injizierten Knotens als auch des Parotis-Knotens (Abbildung 2). Dies ging mit Verbesserung der Leistungsfähigkeit, geringeren Schmerzen und geringerem Analgetikabedarf einher. Der Patient wurde aufgrund der Beendigung der Studie auf die Erhaltungstherapie mit Cemiplimab umgestellt, die nach drei Monaten ein vollständiges Ansprechen zeigte.2 Durch die Infektion und Abtötung von Krebszellen bewirken onkolytische Viren die Freisetzung von Neo-Antigenen, die die antitumorale Immunogenität erhöhen, was die Wirksamkeit von Immun-Checkpoint-Inhibitoren verstärken kann und die Überwindung von Resistenzen fördert.2 Dieses Phänomen wurde auch bei anderen Tumorentitäten beobachtet, darunter in einer einarmigen Phase-II-Studie mit intratumoralem Talimogen Laherparepvec (T-VEC), einem modifizierten Herpes-simplex-Virus, plus Pembrolizumab bei Anti-PD1-refraktärem Melanom. In dieser Studie wurde eine Gesamtansprechrate (ORR) von 26% bei Patienten ohne viszerale Metastasen beobachtet.3 In einer randomisierten Phase-III-Studie mit T-VEC plus Pembrolizumab bei unbehandeltem Melanom konnte jedoch keine signifikante Verbesserung der ORR oder des Gesamtüberlebens im Vergleich zu Pembrolizumab allein nachgewiesen werden.4 Daher sind zusätzliche prädiktive Biomarker erforderlich, um die Patientenpopulation und die für den Synergieeffekt der Kombination erforderliche Behandlungssequenz sowie die Suszeptibilität von Krebserkrankungen für Viren im Zusammenhang mit Anti-PD-1-Resistenz zu ermitteln. Präklinische Studien mit doppelsträngigen RNA-Viren wie Reoviridae-Spezies deuten auf eine größere onkolytische Aktivität bei Krebserkrankungen mit aktivierenden RAS-Mutationen hin,5 die bei 8–23% der cSCC vorliegen.6 Normalerweise führt eine Virusinfektion gesunder Zellen zur Freisetzung von Typ 1-Interferonen (IFN) und zur Aktivierung des JAK-STAT-Stoffwechsels, was zur Rekrutierung von Antigen-präsentierenden Zellen (APCs) und zur zytotoxischen Abtötung virusinfizierter Zellen führt.2, 5 Aktivierende RAS-Mutationen haben gezeigt, dass sie die STAT1- und STAT2-Expression reduzieren und dadurch die Transkription von mit Typ 1 IFN-assoziierten Genen wie IFN16, IFN20 und IFN/tetra1 unterdrücken.7 Neben der direkten Schädigung der DNA induziert die Strahlentherapie eine antitumorale Immunität durch die Induktion von Typ-1-IFN über den cGAS-STING-Stoffwechselweg, was zur Rekrutierung und Reifung von APCs führt.8 In ähnlicher Weise steigert die PD-1-Inhibition die IFN-γ-Produktion durch tumorinfiltrierende T-Zellen, was zu weiterer zytotoxischer T-Zell-Aktivierung und -Proliferation führt, die durch CXCL10 vermittelt wird.9 Daher wird die gestörte IFN-Signalübertragung bei Krebserkrankungen mit verminderter Wirksamkeit der Strahlentherapie und der Anti-PD1-Immuntherapie in Verbindung gebracht.8 Bemerkenswerterweise wurde bei der Tumorsequenzierung unseres Patienten eine EGFR-Amplifikation festgestellt, aber keine Mutationen im RAS selbst. Die EGFR-Amplifikation könnte die IFN-Signalwege durch die Aktivierung des nachgeschalteten RAS beeinträchtigt haben, was zu Resistenz gegen Strahlentherapie und Cemiplimab führt, während sie gleichzeitig die Suszeptibilität für onkolytische Viren erhöht, was zu seinem außergewöhnlichen Ansprechen führt. Die Wirksamkeit von Kombinationen aus onkolytischen Viren und PD-1-Inhibitoren werden derzeit bei cSCC untersucht - darunter T-VEC plus Nivolumab (NCT02978625) und RP1, ein weiteres modifiziertes Herpes-simplex-Virus, plus Cemiplimab (NCT04050436). Vorläufige Ergebnisse der letztgenannten Kombination bei Anti-PD1-naivem cSCC (n = 17) zeigten eine ORR von 64,7% (vollständiges Ansprechen 47,1%).10 Andere intratumorale Ansätze einschließlich injizierbarer Zytokine (L19IL2/L19TNF; NCT04362722) oder Checkpoint-Inhibitoren (Cemiplimab; NCT03889912) werden ebenfalls für fortgeschrittenes cSCC untersucht. Die Kombination von onkolytischen Viren und PD-1-Hemmung ist ein attraktiver Weg für künftige Krebstherapien zur Verstärkung der PD-1-Blockade bei cSCC und darüber hinaus, insbesondere bei Patienten mit begrenzten therapeutischen Möglichkeiten. Die Erforschung von Biomarkern, die eine synergistische Wirkung der Kombination von onkolytischen Viren und Anti-PD1-Therapie vorhersagen, ist von entscheidender Bedeutung. Insbesondere sollten Studien, die das Ansprechen auf diese Kombination untersuchen, auch berücksichtigen, ob eine vorherige Anti-PD1-Resistenz mit dem Ansprechen auf nachfolgende onkolytische Viren zusammenhängt, um eine effektive Behandlungsabfolge zu ermöglichen. Wir danken Dr. Dan Nguyen (Abteilung für anatomische Pathologie, St. Vincent's Hospital Sydney) für die zur Verfügung gestellten histologischen Bilder. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians. J.P.P. wird durch ein Stipendium des Australian Government Research Training Program (RTP) unterstützt. J.L. hat Honorare von MSD und Specialized Therapeutics sowie Reisekostenerstattungen von Starpharma und ImmVirX erhalten. Alle anderen Autoren haben keine Konflikte zu melden

OBJECTIVE:To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment. METHODS:A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis. RESULTS:The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease. CONCLUSION:The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated.

BackgroundEstablishing 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. MethodsWe 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. ConclusionThis 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.

BackgroundPatients 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. MethodsA 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. ResultsOf 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. ConclusionsThere 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.

Journal of the European Academy of Dermatology and VenereologyVolume 37, Issue 3 p. e363-e365 LETTER TO THE EDITOR Safety of cemiplimab for advanced cutaneous squamous cell carcinoma in a patient with p-ANCA-associated vasculitis James P. Pham, James P. Pham orcid.org/0000-0002-9263-3889 The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, AustraliaSearch for more papers by this authorVanathi Sivasubramaniam, Vanathi Sivasubramaniam Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia Sydpath, St Vincent's Pathology, Sydney, New South Wales, AustraliaSearch for more papers by this authorRichard Gallagher, Richard Gallagher The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, AustraliaSearch for more papers by this authorDion Forstner, Dion Forstner The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia Genesis Care Radiation Oncology, St Vincent's Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this authorMuh Wong, Muh Wong Department of Renal Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this authorJia Liu, Corresponding Author Jia Liu [email protected] orcid.org/0000-0003-4442-6516 The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales, Australia Correspondence Dr Jia Liu, The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, 370 Victoria St, Darlinghurst, NSW 2010, Australia. Email: [email protected]Search for more papers by this author James P. Pham, James P. Pham orcid.org/0000-0002-9263-3889 The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, AustraliaSearch for more papers by this authorVanathi Sivasubramaniam, Vanathi Sivasubramaniam Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia Sydpath, St Vincent's Pathology, Sydney, New South Wales, AustraliaSearch for more papers by this authorRichard Gallagher, Richard Gallagher The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, AustraliaSearch for more papers by this authorDion Forstner, Dion Forstner The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia Genesis Care Radiation Oncology, St Vincent's Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this authorMuh Wong, Muh Wong Department of Renal Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this authorJia Liu, Corresponding Author Jia Liu [email protected] orcid.org/0000-0003-4442-6516 The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia Faculty of Medicine and Health, the University of Sydney, Sydney, New South Wales, Australia Correspondence Dr Jia Liu, The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, 370 Victoria St, Darlinghurst, NSW 2010, Australia. Email: [email protected]Search for more papers by this author First published: 13 October 2022 https://doi.org/10.1111/jdv.18649Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume37, Issue3March 2023Pages e363-e365 RelatedInformation

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 ADC mean from DWI and FDG-PET parameters SUV max , SUV mean , 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 ADC mean (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 ∆ADC mean 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 .

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.

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.

To evaluate whether biomarkers derived from FDG-PET-CT performed prior to (prePET) and during the third week (iPET) of radiotherapy can predict treatment outcomes in oropharyngeal squamous-cell-carcinoma (OPC). Seventy-nine consecutive patients with newly diagnosed OPC from 2009 to 2015 treated with radical radiotherapy and underwent pre-PET and iPET were included in the study. This analysis included fifty-eight patients with available tissue blocks that have been independently prepared and P16 immunohistochemistry re-validated to ensure standardization. The median follow-up was 42.5 months. HPV status was positive (HPV+OPC) in 46 patients based on p16 status. The maximum-standardized-uptake-value (SUV), metabolic-tumor-volume (MTV) and total-lesional-glycolysis (TLG) of primary tumor, index-node (IN) (node with highest TLG) and "total-lymph-nodes" (TN), and their median % (≥50%) reductions in iPET were analyzed, and correlated with 5-year Kaplan–Meier and multivariable analyses including local-failure-free, regional-failure-free, loco-regional-failure-free, distant-metastatic-failure-free, disease-free, and overall-survival (LFFS, RFFS, LRFFS, DMFFS, DFS and OS). At the time of analysis, 22 patients (38%) had treatment failure. Seventeen patients had loco-regional failures (local failure: 6, regional failure: 14, and combined: 3), and eleven patients had distant failure, of which 5 had distant failure only and 6 had concurrent loco-regional failure There was no association of outcomes with pre-PET parameters, except for IN-TLG and DMFFS in HPV+OPC patients: 94.4% vs. 57.8%, (p=0.04, HR=6.81, CI 0.82-56.78). Complete metabolic response of primary tumor was seen in 13 HPV+OPC patients, and negative-predictive-value for local failure was 100%. More than 50% reduction in TN-MTV provided the best predictor of favorable outcomes in HPV+OPC patients, including LRFFS (88% vs. 47.1%, p=0.006, HR=0.153, CI 0.033-0.711) and DFS (78.2% vs. 41.2%, p=0.01, HR=0.234, CI 0.07-0.782). More than 50% reduction in IN-TLG predicted better DMFFS outcome in HPV-negative-OPC (83.3% vs. 33.3%, p=0.017), but was inversely related to DMFFS (66.7% vs. 100%, p=0.005, HR 3.0, CI 1.32-6.83) in HPV+OPC patients. Our research suggests that volumetric nodal metabolic response during the week 3 of radiotherapy can potentially identify a subgroup of HPV+OPC patients at low risk of loco-regional-failure but inversely at higher risk of distant-metastatic-failure, and may have a role in individualized adaptive radiotherapy and systemic immunotherapy. This clinical finding can be consistent with the current radiobiology understanding that Abscopal responses are not induced by high dose radiation, and are dependent on the critical balance between Trex1 induction and systolic DNA accumulations that were induced by fractionated radiation doses between 12-18 Gy.

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. (C) 2019 Elsevier B.V. All rights reserved.

BackgroundExisting 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.MethodsWe 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.ResultsThe 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).ConclusionIncreasing 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.

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.

multivariable prognostic model PREDICT Prostate -derived from high quality survival data and validated in 3 PCa cohorts (including >80,000 men).We then reviewed current treatment practices, and assessed what impact PREDICT Prostate would have on these.METHODS: Study materials were managed using Qualtrics research software (Utah, USA).Participation of PCa specialists was requested predominantly through professional mailing lists.Respondents were randomised into group A or B and presented with opposing hypothetical vignettes: 6 with clinical diagnostic information only and 6 with these details plus PREDICT Prostate estimates.Comparisons were made between groups for clinician-estimated and model-predicted 15-year outcomes.Data analyses were performed using Stata 14 (Texas, USA).RESULTS: 190 responses were received.63.7% and 16.8% of respondents were urologists and oncologists respectively.59.5% work in specialist cancer centres and 81.6% counsel men with PCa at least weekly.Only 19.3% reported using any survival prediction tool in their current routine practice.Clinician estimates of 15-year prostate cancer mortality (PCM) exceeded PREDICT Prostate estimates in 92% of the case vignettes; clinicians estimated 1.9-fold greater disease lethality than PREDICT.Clinician perceptions of overall survival benefit from radical treatment at 15 years were over-optimistic in every vignette, with mean clinician estimates 5.4-fold greater than PREDICT.Concomitantly viewing data from PREDICT Prostate led to reductions in likelihood of recommending radical treatment in 9/12 (75%) vignettes, with reductions most evident in intermediate-risk cases.For example, in a fit 75-year old man with PSA 5.1, Gleason 3þ4 PCa in 2/12 biopsy cores: likelihood of recommending treatment dropped from 32.5% to 19.1% when PREDICT estimates were also shown (p[0.009).CONCLUSIONS: Our study suggests clinicians consistently overestimate PCM and the survival benefits of radical treatment.PREDICT Prostate can provide individualised and contextualised prognostic information to help standardise therapy recommendations.

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.