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To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. Retrospective observational study; review of patient records in fifteen Australian institutions. All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 – 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression‐free survival. A total of 286 people with advanced CSCC received ICI therapy during May 2017 – May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3–97.5 years) and 232 were men (81%); median follow‐up time was 12.2 months (interquartile range, 5.5–20.5 months). Eighty‐eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve‐month overall survival was 78% (95% confidence interval [CI], 72–83%); progression‐free survival was 65% (95% CI, 58–70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0–4.3) and progression‐free survival (aHR, 2.4; 95% CI, 1.8–3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1–3.0; progression‐free: aHR, 1.8; 95% CI, 1.2–2.7). Fifty‐five people (19%) reported immune‐related adverse events of grade 2 or higher; there were no treatment‐related deaths. In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.

Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common cancer and represent a global health burden. Immune checkpoint inhibitors (ICIs) have shown promise in treating recurrent/metastatic disease with durable benefit in ∼30% of patients. Current biomarkers for HNSCC are limited in their dynamic ability to capture tumor microenvironment (TME) features with an increasing need for deeper tissue characterization. Therefore, new biomarkers are needed to accurately stratify patients and predict responses to therapy. Here, we have optimized and applied an ultra-high plex, single-cell spatial protein analysis in HNSCC. Tissues were analyzed with a panel of 101 antibodies that targeted biomarkers related to tumor immune, metabolic and stress microenvironments. Our data uncovered a high degree of intra-tumoral heterogeneity intrinsic to HNSCC and provided unique insights into the biology of the disease. In particular, a cellular neighborhood analysis revealed the presence of six unique spatial neighborhoods enriched in functionally specialized immune subsets. In addition, functional phenotyping based on key metabolic and stress markers identified four distinct tumor regions with differential protein signatures. One region was marked by infiltration of CD8+ cytotoxic T cells and overexpression of BAK, a proapoptotic regulator, suggesting strong immune activation and stress. Another adjacent region within the same tumor had high expression of G6PD and MMP9, known drivers of tumor resistance and invasion, respectively. This dichotomy of immune activation-induced death and tumor progression in the same sample demonstrates the heterogenous niches and competing microenvironments that may underpin variable clinical responses. Our data integrate single-cell ultra-high plex spatial information with the functional state of the TME to provide insights into HNSCC biology and differential responses to ICI therapy. We believe that the approach outlined in this study will pave the way toward a new understanding of TME features associated with response and sensitivity to ICI therapies.

Sarcopenia is a known independent prognostic factor for decreased survival in patients with head and neck cancer; yet, its importance for the growing number of younger patients diagnosed with human papillomavirus (HPV)–positive oropharyngeal carcinoma (OPC+) has not been established. This systematic literature review aimed to determine the prevalence and impact of computed tomography (CT)–defined sarcopenia on survival outcomes for adult OPC+ patients (>18 y) undergoing any treatment modality. Prospective studies were searched using PubMed, Embase, CENTRAL, CINAHL, and Web of Science up until and including February 2022. Bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. In total, 9 studies (total pooled OPC+ patients, n= 744) were identified and included in this review; 2 at low, 6 at moderate, and 1 at high risk of bias. All studies varied in sarcopenia assessment methods and skeletal muscle index threshold cutoff values. These studies demonstrated the cumulative prevalence of sarcopenia for OPC+ patients to be 42.9% (95% CI: 37.8%, 47.9%). While overall survival (3 studies, n= 253) and progression-free survival (1 study, n= 117) was lower in sarcopenic OPC+ patients, this was not statistically significant. GRADE certainty of evidence for impact of pretreatment sarcopenia on overall survival was low and progression-free survival was very low. Although these studies showed there to be a high prevalence of pretreatment sarcopenia in patients with OPC+, which may decrease survival, the impact on progression-free survival is very uncertain. Further, high-quality research utilizing consistent sarcopenia definitions and assessment methods that are conducted specifically in OPC+ is required to strengthen evidence certainty and determine if sarcopenia is an independent prognostic factor for this population.

First-line therapy for patients with metastatic NSCLC includes checkpoint inhibitor monotherapy, dual checkpoint inhibition, or combination with chemotherapy. We compared outcomes with combination chemoimmunotherapy versus dual checkpoint inhibition as first-line treatment for patients with metastatic NSCLC.

Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.

The JAVELIN Lung 101 phase 1b/2 trial evaluated avelumab (immune checkpoint inhibitor) combined with lorlatinib or crizotinib (tyrosine kinase inhibitors) in ALK-positive or ALK-negative advanced non-small cell lung cancer (NSCLC), respectively.

There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1).

Over the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with ALK-positive (ALK+) lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival.

Distal-to-proximal technique has been recommended for anticancer therapy administration. There is no evidence to suggest that a 24-hour delay of treatment is necessary for patients with a previous venous puncture proximal to the administration site.

Unexpected focal colorectal fluorodeoxyglucose (FDG) uptake is becoming a common clinical dilemma with the increasing utilization of positron emission tomography (PET). These findings may subsequently reveal malignant or premalignant pathology.

OBJECTIVE: To describe a case of severe accidental cyanide poisoning following a single ingestion of amygdalin with therapeutic intent.CASE SUMMARY: A 68-year-old patient with cancer presented to the emergency department shortly after her first dose (3 g) of amygdalin with a reduced Glasgow Coma Score, seizures, and severe lactic acidosis requiring intubation and ventilation. The patient also ingested 4800 mg of vitamin C per day. She responded rapidly to hydroxocobalamin treatment. The adverse drug reaction was rated probable on the Naranjo probability scale.DISCUSSION: Amygdalin and laetrile (a synthetic form of amygdalin) are commonly used as complementary or alternative medicine (CAM) for the treatment of cancer. Vitamin C is known to increase the in vitro conversion of amygdalin to cyanide and reduce body stores of cysteine, which is used to detoxify cyanide. Amygdalin has been used for decades by patients with cancer who are seeking alternative therapies, and severe reactions have not been reported with this dose. An interaction with vitamin C is a plausible explanation for this life-threatening response.CONCLUSIONS: This case highlights the fact that CAMs can produce life-threatening toxicity. This case also adds a further note of caution, namely, the potential for serious interactions between CAMs, particularly where there is no tradition of concomitant use.

Purpose:Visual field assessment is extremely important in glaucoma management, but interpretation is affected by the quality of the patient's performance. The authors have investigated the reliability of visual field performance by a randomly selected sample of the chronic glaucoma population at an urban tertiary care practice.