Cancer immunotherapy in the form of immune checkpoint inhibitors has led to a dramatic increase in the survival of patients with lung cancer across all stages. Over the past decade, the field has experienced rapid maturation; however, several challenges continue to complicate patient management. This review aims to highlight the data that led to this dramatic shift in practice as well as to focus on key challenges. These include determining the optimal therapy duration, managing frail patients or those with brain metastases, addressing the challenges posed by immune-related adverse events, and defining the various patterns of clinical and radiological responses to immunotherapy.

Background: Immune checkpoint inhibitors have revolutionized cancer treatment but can induce immune-related adverse events (irAEs), which are sometimes severe, life-threatening, or refractory to corticosteroids. Current management is largely empirical and adapted from autoimmune disease protocols. Dysregulation of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway has been implicated in irAE pathogenesis, positioning JAK inhibitors (JAKi) as potential therapeutic agents. We hypothesized that JAKi may offer therapeutic benefit in treating corticosteroid-refractory or life-threatening irAEs. Methods: We conducted a prospective cohort study at the Jewish General Hospital (Montreal, Canada) within the Montreal Immune-Related Adverse Events biobank, enrolling patients who developed grade ≥3 or persistent grade 2 irAEs unresponsive to corticosteroids or life-threatening irAEs requiring urgent intervention. Results: 29 patients received JAKi; 5 were excluded due to death within 30 days of initiation, leaving 24 evaluable patients (median age 69 years; 37.5% female). The majority received anti-programmed cell death protein-1 (PD-1) monotherapy (79.2%), with some receiving combination anti-cytotoxic T-lymphocyte antigen-4/PD-1 therapy (16.7%). Indications for JAKi use included myocarditis (n=8), arthritis (n=4), colitis (n=3), hepatitis (n=3), encephalitis (n=2), pneumonitis (n=2), myasthenia gravis (n=1), and sicca syndrome (n=1). JAKi were employed as second-line therapy in 7 patients, third-line in 11, and fourth-line or later in 6. Clinical response, defined as irAE resolution to grade ≤1 while on ≤10 mg prednisone equivalent without relapse for ≥30 days, was observed in 17 patients (70.8%), with median time to resolution of 41 days. Response rates were highest for myocarditis (75%) and arthritis (100%). No opportunistic infections or JAKi-related hepatotoxicity occurred; thrombotic events were identified in three individuals (10.3%). Conclusions: These findings suggest that JAKi are a promising, well-tolerated option for managing corticosteroid-refractory or life-threatening irAEs. Further randomized studies are warranted to confirm their efficacy and safety in this setting.

Treatment with programmed cell death 1 inhibitors is associated with a wide range of cutaneous immune-related adverse events, with lichenoid eruptions representing one of the major cutaneous toxicities. We describe the case of an 81-year-old man with metastatic melanoma treated with pembrolizumab who subsequently developed a delayed-onset generalized lichenoid dermatitis. After failing multiple lines of systemic immunosuppression, narrowband ultraviolet B (NBUVB) phototherapy three times per week for 17 sessions resulted in a significant clinical response in his cutaneous eruption and was well tolerated. NBUVB is a safe, lower-cost modality that induces local, skin-specific immunosuppression without the toxicities of traditional systemic immunosuppressive agents. To date, this is the first report of use of NBUVB in immune-related lichenoid dermatitis resistant to multiple standard therapies.

In the past decade, a lot of insight was gathered into the composition of the host and tumor factors that promote oncogenesis and treatment resistance. This in turn has led to the ingenious design of multiple new classes of drugs, which have now become the new standards of care in cancer therapy. These include novel antibody-drug conjugates, chimeric antigen receptor T cell therapies (CAR-T), and bispecific T cell engagers (BitTE). Certain host factors, such as the microbiome composition, are also emerging not only as biomarkers for the response and toxicity to anti-cancer therapies but also as potentially useful tools to modulate anti-tumor responses. The field is slowly moving away from one-size-fits-all treatment options to personalized treatments tailored to the host and tumor. This commentary aims to cover the basic concepts associated with these emerging therapies and the promises and challenges to fight cancer.

Background: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. Methods: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. Results: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. Conclusions: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer after basal cell carcinoma. When squamous cell carcinomas in situ are included, nonmelanoma skin cancer incidence is nearly equal between CSCC and basal cell carcinoma. The incidence of CSCC has been increasing worldwide in recent decades, and despite the effectiveness of office-based therapies, patients with high-risk lesions associated with advanced CSCC face high rates of recurrence and mortality. This underscores the importance of accurate diagnoses and clear criteria to define high-risk lesions for prognosis and better treatment strategies. However, variability exists in CSCC registration practices internationally, and differences in pathology reporting likely contribute to an underestimate of the true burden of disease. Thus, there is a need to refine elements included in skin biopsy reports to provide a precise representation of the high-risk features of CSCC to improve patient care. In this review, a multidisciplinary group of Canadian experts discuss clinical considerations and provide key guidance and practical strategies surrounding skin biopsy techniques, completion of requisition forms, and dermatopathology reports for CSCC. This article summarizes the expert panel’s recommendations with the goal of improving diagnosis and pathological reporting of biopsy specimens to achieve better patient outcomes for CSCC.