Melanoma en pacientes receptores de un trasplante de órgano sólido

In this review, we analyze the 3 clinical scenarios related to the development of melanoma in solid organ transplant recipients: melanoma in patients with a history of the tumor prior to a transplant, de novo melanoma following a transplant, and melanoma of donor origin. The main factors to consider in organ-transplant candidates with a history of melanoma are tumor stage, presence or absence of residual disease, and time from diagnosis to transplantation. Solid organ transplant recipients have a greater risk of melanoma than immunocompetent individuals. Mortality is also higher in this population, especially in patients with advanced melanoma, as treatment is especially challenging. Clinical history and physical examination provide the most useful information for preventing donor-to-recipient transmission of melanoma. Donor-derived melanoma has a very poor prognosis.     

Management of Chronic Hypotony Following Bilateral Uveitis in a Patient Treated with Pembrolizumab for Cutaneous Metastatic Melanoma

Purpose: To describe the presentation and management of severe ocular adverse events following treatment with pembrolizumab for cutaneous metastatic melanoma.

Methods: Interventional case report.

Results: A 73-year-old Caucasian man receiving pembrolizumab treatment for metastatic melanoma presented with panuveitis and subsequent profound hypotony, choroidal effusions, and optic disk swelling bilaterally. Oral prednisolone controlled intraocular inflammation. However, bilateral hypotony persisted which was managed over a 12-month period with ocular viscoelastic device injections into the anterior chamber of both eyes. There was also phacoemulsification with pars plana vitrectomy (PPV) and silicone oil (SO) tamponade performed on the left eye only. Intraocular pressure (IOP) stabilized (>6 mmHg) with best-corrected visual acuity of 6/60.

Conclusion: We report a severe adverse event from pembrolizumab therapy resulting in uveitis and persistent hypotony. Repeat injections of high viscosity OVD achieved an increase in IOP up to 12 months. This technique may be a useful adjuvant or alternative to PPV and SO.     

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy

Objective: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D?+?T; oral) and those initiated on 1?L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous).

Methods: Patients with melanoma initiated on D?+?T or N/P from Q1/2014 to Q2/2016 (defined as 1?L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D?+?T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1?L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates).

Results: Of the 445 patients included, 202 and 243 were initiated on D?+?T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1?L therapy than those initiated on D?+?T (difference?=?18.6 visits PPY [95% CI?=?16.0–21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference?=?8.1 visits PPY [95% CI?=?1.9–13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1?L therapy).

Conclusions: HRU during 1?L therapy was generally similar between patients initiated on D?+?T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.     

帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析

背景与目的:免疫检查点抑制剂(immune checkpoint inhibitor,ICI)已成为肿瘤治疗的重要手段,然而伴随其显著疗效的是药物相关不良反应。观察帕博丽珠单抗在晚期黑色素瘤治疗中的安全性;初步探讨程序性死亡[蛋白]-1(programmed death-1,PD-1)单抗不良事件发生的预测因子及与疗效的相关性。方法:收集2016年8月-2017年7月期间在北京大学肿瘤医院入组一项"帕博丽珠单抗作为二线治疗中国局部晚期或转移性黑色素瘤的Ⅰb期临床研究(Keynote-151)"的54例患者的临床资料,包括性别、年龄、疾病分期、原发部位、既往化疗史、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分及基线外周血细胞计数,以及药物治疗相关不良事件和疗效相关信息。不良事件根据通用不良事件术语标准(Common Terminology Criteria Adverse Events,CTCAE)4.03版评价,疗效根据实体肿瘤疗效评价标准(Response Evaluation Criteria in Solid Tumors,RECIST)1.1标准评估。结果:帕博丽珠单抗在晚期黑色素瘤治疗中不良事件发生率达88.9%(48/54),严重不良事件发生率为13.0%(7/54),无死亡病例;肝毒性是导致中断和终止用药的主要原因;分析严重不良事件的发生与所观察各项临床特征及实验室检查指标之间均无显著相关性;不良事件的发生与疗效相关分析提示白癜风(P=0.001)和甲状腺功能异常(P=0.007)与疗效相关。结论:帕博丽珠单抗治疗晚期黑色素瘤不良反应发生率较高,但以1~2级为主,耐受性较好;肝毒性对试验药物应用影响最大;白癜风和甲状腺功能异常均可能是疗效较好的预测因子。     

Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen,Biopsy, and Tissue Microarray

BackgroundThe immunohistochemical analysis of programmed cell death ligand 1 (PD-L1) expression in tumor tissue of non–small-cell lung cancer patients has now been integrated in the diagnostic workup. Analysis is commonly done on small tissue biopsy samples representing a minimal fraction of the whole tumor. The aim of the study was to evaluate the correlation of PD-L1 expression on biopsy specimens with corresponding resection specimens.Materials and MethodsIn total, 58 consecutive cases with preoperative biopsy and resected tumor specimens were selected. From each resection specimen 2 tumor cores were compiled into a tissue microarray (TMA). Immunohistochemical staining with the antibody SP263 was performed on biopsy specimens, resection specimens (whole sections), as well as on the TMA.ResultsThe proportion of PD–L1-positive stainings were comparable between the resection specimens (48% and 19%), the biopsies (43% and 17%), and the TMAs (47% and 14%), using cutoffs of 1% and 50%, respectively (P > .39 all comparisons). When the resection specimens were considered as reference, PD-L1 status differed in 16%/5% for biopsies and in 9%/9% for TMAs (1%/50% cutoff). The sensitivity of the biopsy analysis was 79%/82% and the specificity was 90%/98% at the 1%/50% cutoff. The Cohens κ value for the agreement between biopsy and tumor. was 0.70 at the 1% cutoff and 0.83 at the 50% cutoff.ConclusionThe results indicate a moderate concordance between the analysis of biopsy and whole tumor tissue, resulting in misclassification of samples in particular when the lower 1% cutoff was used. Clinicians should be aware of this uncertainty when interpreting PD-L1 reports for treatment decisions.     

Association Between Early Immune-related Adverse Events and Clinical Outcomes in Patients With Non–Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

IntroductionPrevious studies have described an association between immune-related adverse events (irAEs) and better outcomes in patients administered nivolumab for advanced non–small-cell lung cancer. However, the patients in previous studies were not stratified by potential predictive factors, such as programmed cell death ligand 1 status and treatment lines. Additionally, little is known of whether the timing and type of irAEs can inform the prediction of outcomes.Patients and MethodsWe prospectively investigated the association between irAEs and outcomes in the single-center cohort that included patients administered nivolumab in the second or later line of therapy. Subsequently, we confirmed these findings in a retrospective multicenter cohort that included patients with programmed cell death ligand 1 tumor proportion score of ≥ 50% who had received first-line pembrolizumab. The primary outcome was progression-free survival (PFS).ResultsIn the prospective cohort (n = 76), the median PFS was significantly longer for the patients experiencing irAEs within 2 weeks of beginning nivolumab compared with the PFS for those who did not (median, 5.0 months [95% confidence interval (CI), 2.1-8.6 months] vs. median, 2.0 months [95% CI, 1.9-2.5 months]; P = .046). The association was stronger with earlier (within 2 weeks) than with later (within 6 weeks) irAEs. In the retrospective cohort (n = 148), the median PFS was significantly longer for the patients with early irAEs (within 3 weeks) than for those without (median, not reached [95% CI, 5.9 months to not reached] vs. median, 6.9 months [95% CI, 4.2-9.7 months]; P = .04). Rash was common and a better predictor of outcomes in both cohorts.ConclusionOur results have provided firmer evidence of the association between the occurrence of irAEs and outcomes and suggest that early irAEs (especially rash) might better predict outcomes.     

Artificial Neural Networks as a Way to Predict Future Kidney Cancer Incidence in the United States

IntroductionThe incidence of kidney cancer is increasing; it could be counteracted with new ways to predict and detect it. We aimed to implement an artificial neural network in order to predict new cases of renal-cell carcinoma (RCC) in the population using population rate, obesity, smoking incidence, uncontrolled hypertension, and life expectancy data in the United States.Patients and MethodsStatistics were collected on US population numbers, life expectancy, obesity, smoking, and hypertension. We used MATLAB R2018 (MathWorks) software to implement an artificial neural network. Data were repeatedly and randomly divided into training (70%) and validation (30%) subsets.ResultsThe number of new RCC cases will grow from 44,400 (2020) to 55,400 (2050), an increase of +24.7%. Our data show that preventing hypertension would have the greatest impact on reduction of the incidence, estimated at ?775 and ?575 cases per year in 2020 and in 2030, respectively. The prevention of obesity and smoking would have a more limited impact, estimated at ?64 and ?180 cases per year in 2020 and in 2030, respectively, for obesity, and ?173 and ?21 cases per year in 2020 and in 2030, respectively, for smoking.ConclusionsOur predictions underline the need for accurate studies on RCC-related risk factors to reduce the incidence.