Treatment outcomes in retinoblastoma and the effect of tumor topography.

BACKGROUND: Retinoblastoma, the most common intraocular malignancy in children, has high fatality rates if untreated. It is crucial to monitor treatment effectiveness and explore factors influencing favorable outcomes. Our study aims to examine how tumor location impacts the response to standard treatments and the achievement of favorable outcomes among retinoblastoma patients, while controlling for other tumor-related factors. METHODS: This retrospective study analyzed medical records of retinoblastoma patients from November 2012 to December 2022 enrolled in the retinoblastoma program at the Children's Cancer Center of Lebanon (established in collaboration with St.y Jude Children's Research Hospital, Memphis, TN). Data were extracted from the electronic chart reviews and operative reports of examinations under anesthesia (EUAs), and included patient's demographics, tumor characteristics (size, location), and treatment parameters (treatment type, resolution, recurrence). RESULTS: The study included 42 patients with retinoblastoma, with a total of 57 eyes and 115 tumors/lesions. The median age at diagnosis was 12 months (range: 2-36 months). Among the patients, 26 (61.9%) were males and 16 (38.1%) were females. A minority of patients (21.4%) presented with unilateral involvement, whereas the majority (78.6%) had bilateral involvement. The locations of retinoblastoma lesions were distributed as follows: optic nerve (4.4%), macula (19.1%), superior (16.5%), inferior (17.4%), nasal (27.8%), and temporal (14.8%). Resolution rate tended to be highest for tumors close to optic nerve and temporal lesions, but no statistical significance was attained (p = .45). Macular lesions tended to have the fastest resolution, but again not significantly (p = .5). Multiple logistic regression revealed that the odds for resolution of tumor was not significantly associated with tumor size (p = .57) or location (p = .52). CONCLUSION: Location of retinoblastoma lesions was not directly associated with recurrence-free resolution in our cohort. Further research in large retinoblastoma databases is needed to explore the association of tumor characteristics with recurrence and the need for secondary therapeutic interventions.

Distinction of papillary and adamantinomatous craniopharyngioma: Clinical features, surgical nuances and hypothalamic outcomes.

OBJECTIVE: Understanding the differences of suprasellar papillary and adamantinomatous craniopharyngiomas (PCPs/ACPs) is pivotal for target therapy, surgical strategy or postoperative management. Here, the clinical features, surgical nuances and postoperative hypothalamic outcomes of PCPs were systematically recapitulated. METHODS: 24 PCPs and 52 ACPs underwent initial surgery were retrospectively reviewed. Clinical data, quantified third ventricle (3rd V) occupation and optic chiasm distortion were compared, as well as intra-operative findings, operating notes and prognosis. Moreover, analysis of tumor/3rd V relationship and hypothalamic outcomes were also performed. RESULTS: Tumors were more likely to occupies the 3rd V cavity in PCPs. Chiasm distortion of "compressed forward" was the most common pattern (45.8 %) in PCPs, whereas "stretched forward" pattern accounted the highest (42.5 %) in ACPs. Besides, round-shaped with less calcification, duct-like recess, solid consistency, rare subdiaphragmatic invasion, visible lower stalk and improved postoperative visual outcome were more frequently observed in PCPs. The basal membranes of the tumor epithelium and the reactive gliosis were separated by a layer of collagen fibers in most PCPs, which differs from ACPs in the morphological examination of tumor/3rd V floor interface. In daytime sleepiness and memory difficulty, the PCPs showed significantly better outcomes than the ACPs groups, and PCPs suffered less postoperative weight gain (p < 0.05) than ACPs among adult-onset cases. CONCLUSION: PCPs are different from ACPs regards the clinical features, operative techniques and outcomes. If necessary, PCPs are suggested more amenable to total removal since its less invasiveness to the 3rd V floor and better hypothalamic outcomes.

An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFß blockade therapy.

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGFß activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFß pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGFß pathway activation, together with elevated TGFß signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between "cold" tumor-immune phenotypes and TGFß signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFß blockade.