Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

Assessment of perineural spread in advanced cutaneous squamous cell carcinomas treated with immunotherapy.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system. METHODS: This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). RESULTS: Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT. CONCLUSIONS: PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.

AlphaBet: Combination of Radium-223 and [17 7Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol).

Background: [177Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [177Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression. Micrometastases in this area likely receive an inadequate dose of radiation, as the emitted beta-particles from 177Lu travel an average range of 0.7 mm in soft tissue, well beyond the diameter of micrometastases. Radium-223 (223Ra) is a calcium-mimetic and alpha-emitting radionuclide approved for use in men with mCRPC with bone metastases. The range of emitted alpha particles in soft tissue is much shorter (≤100 µm) with high linear energy transfer, likely more lethal for osseous micrometastases. We anticipate that combining a bone-specific alpha-emitter with [177Lu]Lu-PSMA will improve eradication of micrometastatic osseous disease, and thereby lead to higher and longer responses. Methods: This is a single-center, single-arm phase I/II trial evaluating the combination of 223Ra and [177Lu]Lu-PSMA-I&T in men with mCRPC. Thirty-six patients will receive 7.4 GBq of [177Lu]Lu-PSMA-I&T, concurrently with 223Ra in escalating doses (28 kBq/kg - 55kBq/kg), both given intravenously every six weeks for up to six cycles. Eligible patients will have at least two untreated bone metastases visible on bone scintigraphy, and PSMA-positive disease on PSMA PET scan. Patients must have adequate bone marrow and organ function and be willing to undergo tumor biopsies. Patients with discordant disease visible on FDG PET scan (defined as FDG positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other key exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than one prior line of chemotherapy for prostate cancer. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with [177Lu]Lu-PSMA-I&T and the 50% PSA response rate. Conclusion: The AlphaBet trial is a phase I/II study combining 223Ra with [177Lu]Lu-PSMA-I&T in patients with mCRPC. We aim to enroll the first patient in Q3 2022, and recruitment is anticipated to continue for 24 months. Study registration: NCT05383079.

The negative predictive value of FDG PET/CT staging in early oropharyngeal squamous cell carcinoma and implications to transoral robotic surgery patient selection.

OBJECTIVES: Our objective was to determine the negative predictive value (NPV) of preoperative FDG PET/CTfor detecting locoregional nodal disease. The aim was to help inform the decision-making process when identifying patients with early-stage OPSCC that would be suitable for transoral robotic surgery (TORS) as a single-modality treatment. MATERIALS AND METHODS: A retrospective cohort study was conducted of adults with primary stage cT1-2 OPSCC with up to one metastatic neck lymph node (cN0-1) planned for TORS. Patients with a preoperative PET/CT and who had undergone staging neck dissection (ND) were included. Clinical and pathological nodal staging was established based on PET/CT and ND, respectively. The primary outcome was the frequency of occult (not seen on PET/CT) nodal disease on ND. RESULTS: Eighty-eight patients were included (N = 88). The rate of occult nodal disease was 28.4 % (n = 25). The NPV of PET/CT in the clinically negative neck was 79 % and 66 % in cases with a single clinical node. Following staging ND, thetreatment plan changed in 27 % of cases overall, 7 % in cN0 and 36.7 % in cN1. Among these, 18 % met criteria for radiotherapy and 9 % for CRT. This represented a decrease in the number of ideal candidates for TORS as single-modality treatment from 88 to 64 (73 %). CONCLUSIONS: PET/CT is a useful tool in the workup of patients for primary TORS. However, about one third of patients with early-stage OPSCC might benefit from adjuvant therapy not predicted by preoperative PET/CT. A staging ND helps confirm candidates for single-modality treatment with TORS.

Part 1: Imaging findings of common immune checkpoint inhibitor-related adverse effects.

Over the last decade or so, immunotherapy and in particular immune checkpoint inhibitors have become common in the treatment of numerous cancers and have revolutionised oncology. The unique mechanisms of these agents has resulted in novel tumour response patterns and also new drug-related toxicities, both of which can have specific findings on imaging. The widespread and increasing use of these agents means these findings are now encountered across many radiology practices beyond just specialist oncology units. This pictorial essay aims to describe and illustrate imaging findings associated with common and important immune-related adverse events as a result of treatment with immune checkpoint inhibitors.

Part 2: Imaging findings of uncommon but important immune checkpoint inhibitor-related adverse effects.

Oncology care has significantly changed with the emergence of immunotherapy agents, in particular immune checkpoint inhibitors (ICIs). This has had an immediate effect on imaging, with different radiological tumour responses to treatment compared with conventional chemotherapies, and novel imaging findings due to complications caused by these agents (referred to as immune-related adverse effects, irAEs). Some of the more common irAEs may be familiar, but as the use of ICIs increases to a wider variety of cancers, these complications, and in particular, the less common irAEs, will be encountered more frequently on imaging. It will be increasingly important to be familiar with these uncommon irAEs, particularly since they can be difficult to recognise and distinguish from metastatic disease. The aim of this pictorial essay was to describe and illustrate imaging findings that may be encountered related to uncommon but important irAEs as a result of treatment with immune checkpoint inhibitors.

FDG-PET/CT imaging for evaluating durable responses to immune check point inhibitors in patients with advanced cutaneous squamous cell carcinoma.

BACKGROUND: The role of FDG-PET/CT imaging in assessing response to immunotherapy in advanced cutaneous squamous cell carcinoma (CSCC) is unknown. This study compared complete metabolic response (CMR) rates by FDG-PET and RECIST1.1 via CT or MRI in patients on cemiplimab for > 10 months. METHODS: This was a single-centre retrospective study of 15 patients treated with cemiplimab for advanced CSCC who had CT/MRI and FDG-PET/CT at > 10 months to assess metabolic treatment response. The median age was 73 years (range 55-84) and 93% were male. RECIST1.1 and PERCIST1.0 tumor responses were evaluated by blinded readers. RESULTS: Seventy-three percent (11/15) (95%CI 44.9, 92.2%) achieved a CMR on PET. Of these 11, on RECIST1.1 there was one complete response, 9 partial responses and one stable disease. CONCLUSIONS: In patients on cemiplimab for > 10 months, there was discordance between CR rates on FDG-PET versus RECIST1.1. FDG-PET/CT may have utility for clarifying depth of response in patients treated with immunotherapy for CSCC.

Celiac Disease on FDG PET/CT.

An FDG PET with diagnostic CT was performed on a 52-year-old man for investigation of lymphocytosis and the clinical suspicion of lymphoma. The PET/CT demonstrated diffuse small bowel uptake, prominent mesenteric lymph nodes without significant FDG uptake, and other features suggestive of celiac disease. Subsequently, the patient was found to have markedly elevated celiac disease antibodies (deamidated gliadin IgG and tissue transglutaminase IgA) and to be HLA DQ2 and DQ8 allele positive on genotyping for celiac disease. Gastroscopy and duodenal biopsy also confirmed the diagnosed.

Examining Clinical Utility of Imaging for Inpatient Palliative Care.

BACKGROUND: Medicine in the final months of life is increasingly interventional, both in the manner by which life may be prolonged and symptoms may be reduced. Radiology is frequently utilized to provide diagnostic clarity and improve symptom control. As with any intervention, examining the benefit and potential harms of a procedure is required to establish its role in ongoing clinical care. METHODS: This retrospective cohort study involved patients admitted to an inpatient palliative care unit between October 2013 and September 2014. Data were collected using clinical databases manually searched by the researchers. RESULTS: Of 388 admissions, there were a total of 154 imaging events completed in 85 patients. Patients who had imaging performed had longer mean length of stays, more likely to be discharged home, and male. Very few imaging events (4%) occurred in the 3 days prior to death and none on the day of death. In total, 43% of imaging confirmed the clinical suspicion and management changed 42% of times. Limbs X-rays and computed tomography brain had low rates of confirming clinical suspicion (21% and 17%) and changing management (21% and 33%). There were a total of 7 complications resulting from imaging, the majority due to interventional procedures. CONCLUSION: The use of imaging in inpatient palliative care seems to be of substantive utility, prompting alterations in management in >40% of instances. The majority of imaging occurred prior to the terminal phase of the disease and with few complications.

Surface display of IgG Fc on baculovirus vectors enhances binding to antigen-presenting cells and cell lines expressing Fc receptors.

Recombinant baculoviruses (recBV) were constructed with dual cassettes for constitutive expression of human IgG Fc following infection of insect cells and the structural proteins of hepatitis C virus (core, E1 and E2) following transduction of mammalian cells. The IgG Fc was expressed in insect cells as a fusion protein with the signal sequence and transmembrane region of either the native baculovirus envelope protein gp64 or the human transferrin receptor as a type I or type II integral membrane protein, respectively. The IgG Fc fusion proteins formed functional homodimers on the surface of recBV-infected insect cells and were incorporated into the envelope of recBV particles during egress from the infected cell. Both pseudotyped recBV bound specifically to recombinant soluble FcgammaRIIalpha receptor and to cell lines and antigen-presenting cells expressing Fc receptors (FcRs). These novel baculoviral vectors, which target cells of the immune system that express FcRs, have potential applications for vaccination or gene therapy.

Influences on medical students' decisions to study at a rural clinical school.

OBJECTIVE: To identify factors that influenced medical students at Monash University to undertake their first year of clinical training (third year of the medical course) at a rural clinical school (RCS). DESIGN: Third-year Monash University medical students undertaking clinical placements at a RCS were surveyed in 2005. A semistructured questionnaire was used to ask students to rate the influence of a list of factors on their decision to undertake their year-long placement at a RCS. RESULTS: Under half (48%) of students studying at an RCS reported that they were of rural background. All surveyed items were identified as having had a positive influence. Greater clinical experience, learning opportunities and patient access were identified as having the greatest positive influence followed closely by free accommodation and other financial and supportive incentives. Future rural career intention was eight times more likely to be a positive influence in rural compared with urban background students. CONCLUSION: The most important positive influence on Monash third-year medical students' decision to study at an RCS is the perception of high-quality clinical experiences and education. This perception arises from rural exposure during pre-clinical years.