Circulating immune cell dynamics as outcome predictors for immunotherapy in non-small cell lung cancer.

The use of immune checkpoint inhibitors (ICIs) continues to transform the therapeutic landscape of non-small cell lung cancer (NSCLC), with these drugs now being evaluated at every stage of the disease. In contrast to these advances, little progress has been made with respect to reliable predictive biomarkers that can inform clinicians on therapeutic efficacy. All current biomarkers for outcome prediction, including PD-L1, tumor mutational burden or complex immune gene expression signatures, require access to tumor tissue. Besides the invasive nature of the sampling procedure, other disadvantages of tumor tissue biopsies are the inability to capture the complete spatial heterogeneity of the tumor and the difficulty to perform longitudinal follow-up on treatment. A concept emerges in which systemic immune events developing at a distance from the tumor reflect local response or resistance to immunotherapy. The importance of this cancer 'macroenvironment', which can be deciphered by comprehensive analysis of peripheral blood immune cell subsets, has been demonstrated in several cutting-edge preclinical reports, and is corroborated by intriguing data emerging from ICI-treated patients. In this review, we will provide the biological rationale underlying the potential of blood immune cell-based biomarkers in guiding treatment decision in immunotherapy-eligible NSCLC patients. Finally, we will describe new techniques that will facilitate the discovery of more immune cell subpopulations with potential to become predictive biomarkers, and reflect on ways and the remaining challenges to bring this type of analysis to the routine clinical care in the near future.

Complete remission for 4 years with crizotinib in advanced ALK-positive non-small cell lung cancer after thoracostomy for empyema.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) gene translocation occurs in 3%-5% of patients with non-small cell lung cancer (NSCLC), typically in younger patients. Crizotinib (tyrosine kinase inhibitor) has been considered as the standard of care for advanced ALK-positive lung cancer but it only gives a median progression-free survival of 7.7-11 months. CASE: A 41-year-old old man, former smoker, was diagnosed with NSCLC in the right lung with manifest pleural effusion. This case was complicated by a pleural empyema and because of a trapped lung, there was an indication for the construction of a thoracostomy. After confirmation of the ALK translocation, therapy with crizotinib was started. After 8 weeks, there was excellent response, and 6 months later, all lesions were undetectable on CT scan. There was also complete healing of the thoracostomy wound. CONCLUSION: This case describes a relatively young patient with a poor prognosis but with a remarkable and long-term response to crizotinib monotherapy.

Durability of pulmonary homografts for reconstruction of the right ventricular outflow tract: how relevant are donor-related factors?

OBJECTIVES: Our goal was to evaluate the influence of donor-related factors on the durability of pulmonary homografts (PHGs) for right ventricular outflow tract reconstruction of congenital heart defects. METHODS: Between 1990 and 2016, 223 PHGs were used in 197 patients for right ventricular outflow tract reconstruction. Long-term durability was investigated in relation to patient- and disease-specific as well as to donor-related factors, based on the PHG replacement rate. To minimize the effect of outgrowth, a subgroup analysis was performed on patients with PHG size >22 mm, as the discriminant cut-off identified by the classification tree method. RESULTS: During a median follow-up of 8.5 years [interquartile range (IQR) 12.3], 47 (21%) PHGs were explanted within a mean interval of 9.5 ± 5.3 years, resulting in a freedom from PHG replacement of 82 ± 6% at 10 years. The risk factors for PHG explantation determined by univariable analysis were predominantly patient-related, including younger age (P = 0.003), extra-anatomic implantation (P = 0.006), bicuspidalization (P = 0.002) and younger donor age (P = 0.032). PHG size [hazard ratio (HR) 0.80, 95% confidence interval 0.73-0.88; P < 0.001] was the only independent determinant in multivariable analysis. The subgroup analysis comprised 119 PHG >22 mm, implanted at a median age of 15 years (IQR 7). A significant beneficial effect of ABO matching on the explantation rate was only identified with univariable analysis (HR 0.24, 95% confidence interval 0.12-4.68; P = 0.010). CONCLUSIONS: Cryopreserved PHGs provide a durable substitute for right ventricular outflow tract reconstruction in congenital heart disease. PHG size at the time of implantation remains the principal determinant of PHG explantation during late follow-up. However, once an adult-sized homograft is required, matching for ABO blood group compatibility between host and donor might help to improve homograft durability.