Light-activated, photosensitizer-based therapies have been established as safe modalities of tumour ablation for numerous cancer indications. Two main approaches are available: photodynamic therapy, which results in localized chemical damage in the target lesions, and photothermal therapy, which results in localized thermal damage. Whereas the administration of photosensitizers is a key component of photodynamic therapy, exogenous photothermal contrast agents are not required for photothermal therapy but can enhance the efficiency and efficacy of treatment. Over the past decades, great strides have been made in the development of phototherapeutic drugs and devices as cancer treatments, but key challenges have restricted their widespread clinical use outside of certain dermatological indications. Improvements in the tumour specificity of photosensitizers, achieved through targeting or localized activation, could provide better outcomes with fewer adverse effects, as could combinations with chemotherapies or immunotherapies. In this Review, we provide an overview of the current clinical progress of phototherapies for cancer and discuss the emerging preclinical bioengineering approaches that have the potential to overcome challenges in this area and thus improve the efficiency and utility of such treatments.

Clinical development and potential of photothermal and photodynamic therapies for cancer

Background Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1805453

Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain.

Light and optical techniques have made profound impacts on modern medicine, with numerous lasers and optical devices being currently used in clinical practice to assess health and treat disease. Recent advances in biomedical optics have enabled increasingly sophisticated technologies - in particular those that integrate photonics with nanotechnology, biomaterials and genetic engineering. In this Review, we revisit the fundamentals of light-matter interactions, describe the applications of light in imaging, diagnosis, therapy and surgery, overview their clinical use, and discuss the promise of emerging light-based technologies.

/pdf/light-in-diagnosis-therapy-and-surgery-1cqacib341.pdf

Light in diagnosis, therapy and surgery.

Cancer immunotherapy utilizing blockade of the PD-1/PD-L1 checkpoint has revolutionized the treatment of a wide variety of malignancies, leading to durable therapeutic responses not typically seen with traditional cytotoxic anticancer agents. However, these therapies are ineffective in a significant percentage of patients, and some initial responders eventually develop resistance to these therapies with relapsed disease. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and can be both multifactorial and overlapping in an individual patient. As the mechanisms of resistance to PD-1/PD-L1 blockade continue to be further characterized, new strategies are being developed to prevent or reverse resistance to therapy, leading to improved patient outcomes.

/pdf/mechanisms-of-resistance-to-pd-1-and-pd-l1-blockade-53ba1v4aod.pdf

Mechanisms of Resistance to PD-1 and PD-L1 Blockade.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities

In photodynamic therapy (PDT) a photosensitizer - a molecule that is activated by light - is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancer- ous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT.

/pdf/current-evidence-and-applications-of-photodynamic-therapy-in-242sgtt6xs.pdf

Current evidence and applications of photodynamic therapy in dermatology

Background Data evaluating the impact of objectively measured psoriasis severity on type 2 diabetes mellitus (T2DM) risk are lacking. Objective To determine the risk for T2DM in patients with psoriasis compared with that in adults without psoriasis, stratified by categories of directly assessed body surface area (BSA) affected by psoriasis. Methods A prospective, population-based, cohort study from the United Kingdom in which 8124 adults with psoriasis and 76,599 adults without psoriasis were followed prospectively for approximately 4 years. Results There were 280 incident cases of diabetes in the psoriasis group (3.44%) and 1867 incident cases of diabetes in those without psoriasis (2.44%). After adjustment for age, sex and body mass index, the hazard ratios for development of incident diabetes were 1.21 (95% confidence interval [CI], 1.01-1.44), 1.01 (95% CI, 0.81-1.26), and 1.64 (95% CI, 1.23-2.18) in the groups with 2% or less of their BSA affected, 3% to 10% of their BSA affected, and 10% or more of their BSA affected compared with in the groups without psoriasis, respectively ( P  = .004 for trend). Worldwide, we estimate an additional 125,650 new diagnoses of T2DM per year in patients with psoriasis as compared with in those without psoriasis. Limitations Relatively short-term follow-up and exclusion of prevalence cases, which may have masked associations in patients with less extensive psoriasis. Conclusion Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with psoriasis.

Psoriasis and the risk of diabetes: A prospective population-based cohort study.

Objective Measures of Psoriasis Severity Predict Mortality: A Prospective Population-Based Cohort Study.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The risk of respiratory tract infections and symptoms in psoriasis patients treated with interleukin 17 pathway-inhibiting biologics: A meta-estimate of pivotal trials relevant to decision making during the COVID-19 pandemic.

AIM To show whether either nivolumab in combination with ipilimumab or nivolumab monotherapy vs. ipilimumab monotherapy extends overall survival (OS) or progression-free survival (PFS) in adults with previously untreated, advanced melanoma. SETTING AND DESIGN The trial was conducted at 137 sites in 21 countries. Randomization (n = 945; 1 : 1 : 1 ratio) was stratified according to metastasis stage, BRAF mutation status and programmed death ligand 1 status. STUDY EXPOSURE Adults were randomized to one of the following: nivolumab plus ipilimumab every 3 weeks for four doses, followed by nivolumab every 2 weeks; nivolumab every 2 weeks plus placebo; or ipilimumab every 3 weeks for four doses plus placebo. Treatment was continued until progression, unacceptable toxicity or withdrawal. OUTCOMES OS, PFS and objective response rate were determined. Patients were also assessed for adverse events. The primary end points of interest were OS and PFS, comparing either the nivolumab plus ipilimumab group or the nivolumab-only group with the patients treated with ipilimumab only. RESULTS At 3 years, the OS rates were 58%, 52% and 34% for the nivolumab plus ipilimumab, the nivolumab monotherapy and the ipilimumab monotherapy groups, respectively. For the nivolumab plus ipilimumab group, the median OS was not reached at the time of analysis. For the nivolumab-only group, the median OS was 37·6 months, and the ipilimumab-only group had a median OS of 19·9 months. The hazard ratio for death was 0·55 [95% confidence interval (CI) 0·45-0·69; P < 0·001] comparing nivolumab plus ipilimumab with ipilimumab, and 0·65 (95% CI 0·53-0·80; P < 0·001) comparing nivolumab with ipilimumab. The PFS rates at 3 years were 39% for the nivolumab plus ipilimumab group, 32% for the nivolumab monotherapy group and 10% for the ipilimumab monotherapy group, with 95% CIs for the two nivolumab groups that did not overlap with that for ipilimumab alone. CONCLUSIONS Among patients with advanced melanoma, significantly longer OS and PFS occurred with the combination of nivolumab plus ipilimumab or with nivolumab alone compared with ipilimumab alone. Furthermore, survival outcomes favoured the nivolumab-containing groups over the ipilimumab group in subgroup analyses.

Nivolumab versus ipilimumab in the treatment of advanced melanoma: a critical appraisal: ORIGINAL ARTICLE: Wolchok JD, Chiarion-Sileni V, Gonzalez R et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2017; 377:1345-56.

Marilyn T. Wan

Papers

Current evidence and applications of photodynamic therapy in dermatology

Psoriasis and the risk of diabetes: A prospective population-based cohort study.

Objective Measures of Psoriasis Severity Predict Mortality: A Prospective Population-Based Cohort Study.

The risk of respiratory tract infections and symptoms in psoriasis patients treated with interleukin 17 pathway-inhibiting biologics: A meta-estimate of pivotal trials relevant to decision making during the COVID-19 pandemic.

Nivolumab versus ipilimumab in the treatment of advanced melanoma: a critical appraisal: ORIGINAL ARTICLE: Wolchok JD, Chiarion-Sileni V, Gonzalez R et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2017; 377:1345-56.