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.

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.

Delayed Response After Confirmed Progression (DR) and Other Unique Immunotherapy-Related Treatment Concepts in Cutaneous Squamous Cell Carcinoma.

Non-melanoma skin cancers are one of the most common cancers diagnosed worldwide, with the highest incidence in Australia and New Zealand. Systemic treatment of locally advanced and metastatic cutaneous squamous cell carcinomas has been revolutionized by immune checkpoint inhibition with PD-1 blockade. We highlight treatment issues distinct to the management of the disease including expansion of the traditional concept of pseudoprogression and describe delayed responses after immune-specific response criteria confirmed progressive disease with and without clinical deterioration. We term this phenomenon "delayed response after confirmed progression (DR)". We also discuss the common development of second primary tumors, heterogeneous disease responses, and expanding clinical boundaries for immunotherapy use.

Contralateral neck failure in oral tongue cancer: Outcomes from two centers using predefined treatment criteria.

BACKGROUND: The objective was to determine the incidence of, and factors associated with contralateral neck failure (CNF) in oral tongue squamous cell carcinoma (OTSCC). METHODS: Consecutive patients with OTSCC between 2007 and 2016 were included. The predefined policy of the contralateral neck included neck dissection (ND) where the primary tumor extended/crossed midline or the contralateral neck was involved; and elective nodal irradiation (ENI) where the primary tumor was ≤1 cm from midline/2 cm from tip. RESULTS: This study included 258 patients. ND was ipsilateral 169 (66%) and bilateral 33 (13%). Fifty-five patients (21%) received ENI to the undissected contralateral neck. CNF occurred in 19 patients (7%) and was similar by treatment received. Utilizing this approach, we observed higher rates of CNF with increasing N classification, perineural invasion, extracapsular extension, and depth of invasion ≥6 mm. CONCLUSIONS: Using our institutional policy of treatment to the contralateral neck, a low rate of CNF (≤10%) was observed.

Immunotherapy to Avoid Orbital Exenteration in Patients With Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) of the head and neck can require complex and disfiguring surgery in order to achieve cure, which can be morbid and negatively impact patient quality of life. The management of advanced CSCC has been revolutionized by immunotherapy with current clinical trials also exploring its role in the neoadjuvant and adjuvant settings. Patients may decline morbid curative surgery, such as orbital exenteration, and the outcomes of immunotherapy use in this unique group of patients require further investigation. METHODS: We reviewed the records of 119 patients treated at a major Australian quaternary oncology centre with immunotherapy (either cemiplimab or pembrolizumab) for advanced CSCC. RESULTS: We identified 7 patients recommended curative surgery involving orbital exenteration after multidisciplinary discussion, who declined surgery due to concerns about morbidity and/or disfigurement. All 7 patients demonstrated a response to treatment, and six avoided orbital exenteration. Two patients experienced pseudoprogression. CONCLUSIONS: The management of CSCC can be complex and requires the input of a multidisciplinary team. Immunotherapy to avoid or reduce the extent of morbid definitive surgery is an emerging treatment option.

A role of PSMA PET/CT in multimodality imaging approach in adenoid cystic carcinoma.

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Impact of histological Oral Tongue Cancer margins on locoregional recurrence: A multi-centre retrospective analysis.

OBJECTIVES: To assess the effect of the histological margins (HM) upon locoregional failure (LRF) and overall survival (OS) for oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: We undertook a retrospective review of 258 patients, across two institutions, treated for OTSCC between 2007 and 2016. A Cox-proportional hazards model was used to compare the relative hazard ratio of HM to the accepted standard of 5 mm margins for LRF and OS. RESULTS: The median follow up period was 4.8 years. The 5 year OS and freedom from LRF were 69% and 75% respectively. The Cox-proportional hazards model adjusted for age, DOI and LVI showed increasing risk of mortality and LRF with decreasing HM widths of <5 mm. CONCLUSION: HM >5 mm were associated with a risk reduction of both LRF and mortality in OTSCC. This study supports >5 mm HM being the oncologic goal of surgery.

Setting the stage: Contemporary staging of non-melanomatous skin cancer and implementation of the new American Joint Committee on cancer eighth edition staging manual.

Non-melanomatous skin cancer (NMSC) generally refers to basal cell and squamous cell carcinoma of the skin. The majority of patients are curatively treated with simple excision. Only few present with locally advanced disease or have evidence of high-risk features, placing them at an elevated risk of relapse. In such cases, further investigations may guide the multidisciplinary management plan. There are no universally agreed on indications for recommending additional staging investigations, due to a lack of prospective data reporting their impact on patient outcomes. Some generally agreed upon indications are discussed in this review article. Most commonly, computed tomography (CT) and magnetic resonance imaging (MR) are used in cases of locally advanced NMSC for staging purposes and surgical planning. While Positron Emission Tomography (PET)/CT and sentinel lymph node biopsy have shown utility, data is lacking to establish their roles in the staging algorithm. An updated NMSC system was included in The American Joint Committee for Cancer eighth edition staging manual (AJCC8). Under AJCC8 the majority of patients with regional disease are upstaged by the presence of extranodal extension, however, this updated system appears to provide limited prognostic discrimination between the nodal categories and the overall TNM stages. This review article will explore the contemporary role of staging investigations, including evolving technologies, and review the changes implemented in AJCC8. It will also discuss the implications of the AJCC8 decision to assign patients with p16-positive cervical nodal SCC with an unknown primary to the oropharyngeal staging system, with particular relevance to clinicians working in areas of high NMSC incidence.

Variant treatment for gastric varices with polidocanol foam using balloon-occluded retrograde transvenous obliteration: a pilot study.

INTRODUCTION: Treatment of gastric variceal rupture remains difficult with current options including transjugular intrahepatic portosystemic shunt and endoscopic therapies having significant side effects or reduced efficacy. We report five cases of gastric varices that were successfully treated with balloon-occluded retrograde transvenous obliteration of varices (BRTO) using Polidocanol foam as an alternative sclerosant to ethanolamine oleate. METHODS: Patients were recruited with cirrhotic liver disease, a history of upper gastrointestinal bleeding, and large gastric fundal varices confirmed on gastroscopy and CT venogram. BRTO was performed as a same-day procedure using a balloon catheter inserted via a gastro-renal shunt with Polidocanol foam injected and a balloon inflated for 2 h. Follow-up was with repeat CT portovenogram, gastroscopy at 6 weeks post-procedure, and in a gastroenterology liver clinic at 1- to 3-month intervals. RESULTS: Between January and December 2009, five patients safely underwent BRTO therapy of gastric varices without complication. At 6 weeks following the procedure, upper gastrointestinal endoscopy showed complete resolution of varices in 5 out of 5 patients, while CT portovenography showed resolution of varices in 4 out of 5 patients, with results in the last patient inconclusive. Clinical follow-up at 1, 3 and 6 months indicated no further episodes of bleeding. CONCLUSIONS: Our study further supports the use of foam sclerosants including Polidocanol in BRTO, showing it is a safe and effective minimally-invasive procedure to treat gastric fundal varices in the short term.

Uterine artery embolisation - a treatment alternative for women with fibroids.

BACKGROUND: Fibroids are a common benign tumour of the female reproductive tract. Uterine artery embolisation is a minimally invasive catheter based technique that compares favourably with surgical treatments. OBJECTIVE: Uterine artery embolisation is an intervention that is especially suited to women who wish to preserve their uterus. This article briefly outlines the medical and surgical treatment options for fibroids with an in depth focus on fibroid embolisation. DISCUSSION: Australian interventional radiologists have been performing uterine artery embolisation for fibroid disease successfully for a number of years. This procedure - like any intervention - is not without complication, but it does enable women a valid alternative treatment pathway for fibroids. General practitioners can discuss the procedure with their local interventional radiologist and can foster a broader understanding of the process with their female patients when considering treatment options.

Elective procedures--preparing patients with diabetic, renal and hypertensive disease.

Providing high quality pre- and peri-operative care to patients with diabetes, renal disease and hypertension requires forethought and planning. General practitioners can play a vital role in this process. A preoperative assessment provides an opportunity to support the patient, communicate accurate and relevant clinical information to the procedural team, and make therapeutic adjustments that aid a successful recovery.

What's in the doctor's bag?

BACKGROUND: A doctor's bag is invaluable when you need to take part of the practice to the patient, or in the case of an emergency. OBJECTIVE: This article aims to help new general practice registrars and experienced general practitioners consider what they may need in their doctor's bag. DISCUSSION: The doctor's bag needs to be personalised to the requirements of each GP and their patient population. Decisions need to be made about the type of bag, stationery, equipment and medications carried. Some possible additions for a rural doctor's bag are included, as well as some general tips.