BackgroundImmune checkpoint inhibitors (ICIs), targeting CTLA-4 or PD-1 molecules, have shown impressive therapeutic results. However, only 20–40% of advanced melanoma patients have durable responses to ICI, and these positive effects must be balanced against severe off-target immune toxicity and high costs. This urges the development of predictive biomarkers for ICI response to select patients with likely clinical benefit from treatment. Although many candidate biomarkers exist, a systematic overview of biomarkers and their usefulness is lacking.ObjectivesHere, we systematically review the current literature of clinical data of ICI treatment to provide an overview of candidate predictive biomarkers for ICI in melanoma patients.MethodsTo identify studies on biomarkers for clinical response or survival to ICI therapy in melanoma patients, we performed a systematic search in OVID MEDLINE and retrieved 429 publications, of which 67 met the eligibility criteria.ResultsBlood and genomic biomarkers were mainly studied for CTLA-4 ICI, while tumor tissue markers were analyzed for both CTLA-4 and PD-1 ICI. Blood cytology and soluble factors correlated more frequently to overall survival (OS) than to response, indicating their prognostic rather than predictive nature. Systemic T-cell response and regulation markers correlated to response, but progression-free survival or OS were not analyzed. Tumor tissue analyses revealed response correlations with mutational load, neoantigen load, immune-related gene expression, and CD8+ T-cell infiltration at the invasive margin. The predictive value of PD-L1 varied, possibly due to the influence of T-cell infiltration on tumor PD-L1 expression. Genomic biomarker studies addressed CTLA-4 and other immune-related genes.ConclusionThis review outlines all published biomarkers for ICI therapy and highlights potential candidate markers for future research. To date, PD-L1 is the best studied biomarker for PD-1 ICI response. The most promising candidate predictive biomarkers for ICI response have not yet been identified. Variations in outcome parameters, statistical power, and analyses hampered summary of the results. Further investigation of biomarkers in larger patient cohorts using standardized objectives and outcome measures is recommended.

Background Cancer survivorship care is traditionally performed in secondary care. Primary care is often involved in cancer management and could therefore play a more prominent role. Purpose To assess outcomes of cancer survivorship care in primary versus secondary care. Methods A systematic search of MEDLINE and EMBASE was performed. All original studies on cancer survivorship care in primary versus secondary care were included. A narrative synthesis was used for three distinctive outcomes: (1) clinical, (2) patient-reported, and (3) costs. Results Sixteen studies were included: 7 randomized trials and 9 observational studies. Meta-analyses were not feasible due to heterogeneity. Most studies reported on solid tumors, like breast (N = 7) and colorectal cancers (N = 3). Clinical outcomes were reported by 10 studies, patient-reported by 11, and costs by 4. No important differences were found on clinical and patient-reported outcomes when comparing primary- with secondary-based care. Some differences were seen relating to the content and quality of survivorship care, such as guideline adherence and follow-up tests, but there was no favorite strategy. Survivorship care in primary care was associated with lower societal costs. Conclusions Overall, cancer survivorship care in primary care had similar effects on clinical and patient-reported outcomes compared with secondary care, while resulting in lower costs. Implications for cancer survivors Survivorship care in primary care seems feasible. However, since the design and outcomes of studies differed, conclusive evidence for the equivalence of survivorship care in primary care is still lacking. Ongoing studies will help provide better insights.

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