Monica Maria Pagliara

BRACHYTHERAPY ALONE or with NEOADJUVANT PHOTODYNAMIC THERAPY for AMELANOTIC CHOROIDAL MELANOMA: Functional Outcomes and Local Tumor Control

Purpose: To compare visual outcomes and local tumor control between two groups of patients with amelanotic choroidal melanoma treated with brachytherapy alone, or neoadjuvant photodynamic therapy before brachytherapy. Methods: Patients diagnosed with amelanotic choroidal melanoma were recruited for the study and divided into two groups: brachytherapy alone (Group A) and photodynamic therapy preceding brachytherapy (Group B). Patients of both groups were selected to be comparable. Results: Twenty-six patients with amelanotic choroidal melanoma were enrolled in the study. Within Group B, 1 month after photodynamic therapy, ultrasonography showed reduction of tumor height in 11 patients (73.4%). The mean doses of irradiation to macula and optic nerve, at baseline were 74.37 and 52.07 Gy, whereas after photodynamic therapy there was a decrease of 17.26% (P = 0.008) and 21.22% (P = 0.025), respectively. In terms of visual acuity, a mean decrease of 14 ETDRS letters and 5 ETDRS letters was observed at 24 months follow-up, in Groups A and B, respectively (P = 0.001). Conclusion: Photodynamic therapy as neoadjuvant therapy before brachytherapy reduces tumor thickness in 73.4% of cases. As a result, a decrease of radiation toxic effects on visual function could be obtained, without compromising disease control.

Preliminary Data Analysis in Healthcare Multicentric Data Mining: a Privacy-preserving Distributed Approach

The new era of cognitive health care systems offers a large amount of patient data that can be used to develop prediction models and clinical decision support systems. In this frame, the multi-institutional approach is strongly encouraged in order to reach more numerous samples for data mining and more reliable statistics. For these purposes, shared ontologies need to be developed for data management to ensure database semantic coherence in accordance with the various centers’ ethical and legal policies. Therefore, we propose a privacy-preserving distributed approach as a preliminary data analysis tool to identify possible compliance issues and heterogeneity from the agreed multi-institutional research protocol before training a clinical prediction model. This kind of preliminary analysis appeared fast and reliable and its results corresponded to those obtained using the traditional centralized approach. A real time interactive dashboard has also been presented to show analysis results and make the workflow swifter and easier.

INTERACTS (INTErventional Radiotherapy ACtive Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) procedures

Eye plaque brachytherapy represents a safe and effective therapeutic approach for choroidal melanoma, combining clinical outcomes with an eye and visual preservation. As it represents a complex procedure, a specific quality assurance program is strongly suggested to improve patients and operators safety, and to reduce possible complications linked to surgical procedure and radiation exposure. The aim of this paper is to describe the INTERACTS (Interventional Radiotherapy Active Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) used in our institution.

Unique genomic profile associated with pediatric uveal melanoma.

Purpose To determine genetic features of a pediatric uveal melanoma in a 6-year-old girl by array-based comparative genomic hybridization (a-CGH) and assess prognosis, and to search for constitutional copy number variations (CNVs) encompassing oncosuppressor genes. Methods High-resolution a-CGH was performed on genomic DNA from cancer cells and from peripheral blood cells. Histopathology and clinical staging of the tumor were simultaneously assessed. Results Array-based CGH revealed no CNVs on tumor cells associated with poor prognosis; namely, no monosomy 3, losses of 1p, 6q, or 8p, and no gains of 8q. A unique genomic profile was observed, consisting mainly of partial terminal duplications affecting chromosomes 1, 4, 5, 9, 10, 11, 16, and 19, and complete trisomy of chromosomes 6, 7, and 20. The nonmetastatic tumor had predominantly epithelioid histology. No constitutional CNVs encompassing oncosuppressor genes were detected. Conclusions We report a very rare uveal melanoma characterized by low-risk genomic profile and poor prognostic histologic and clinical features. The child is relapse-free at 1-year follow-up. The unusual CNVs detected by a-CGH suggest specific pathogenic mechanisms.

Photodynamic Therapy in Ocular Oncology

Although introduced for the treatment of maculopathies, photodynamic therapy (PDT) is now largely used in some eye cancers treatment. The selective tissue damage with PDT is achieved by sequestration of the photosensitizer in the target tissue and focal activation of the photosensitizer by low energy directed light. In this way, it is possible to achieve the destruction of the tumor tissue by safeguarding the surrounding healthy structures. Our study describes the clinical uses and efficacy of photodynamic therapy in ocular oncology.

Cisplatin, dacarbazine and vinblastine as first line chemotherapy for liver metastatic uveal melanoma in the era of immunotherapy: a single institution phase II study

No standard therapy is established for metastatic uveal melanoma. Liver involvement in uveal melanoma may lead to organ impairment, which represents a common cause of death. Tumor shrinkage might improve survival by delaying hepatic failure. Since the combination of cisplatin, vinblastine, dacarbazine allowed a high response rate in metastatic cutaneous melanoma, we explored efficacy and safety of this regimen in unresectable liver metastases of uveal melanoma. In the present phase II study we administered intravenously cisplatin (80 mg/mq, day 1), dacarbazine (250 mg/mq/day, days 1–3), vinblastine (2 mg maximum, day 1) every 21 days as first line treatment for patients with unresectable metastases of uveal melanoma and BRAF wild type. Primary endpoint was objective response rate; overall survival (OS), progression-free survival and toxicity were secondary endpoints. Partial responses were observed in five (20%) patients, stable disease in 12 (48%) patients; disease control rate was 68%. Median OS of all the patients was 13 months, median progression free survival was 5.5 months. OS of responding patients was 21 months; OS of patients with disease control was 18 months, significantly longer than survival of progressing patients (7 months, P=0.0003). Five (20%) patients experienced grade 3–4 toxicity. Combination of cisplatin, vinblastine and dacarbazine was feasible and demonstrate both an interesting objective response rate and a survival benefit for patients achieving a disease control. This regimen could be considered for patients with good performance status and unresectable liver limited disease.

Nomogram for predicting radiation maculopathy in patients treated with Ruthenium-106 plaque brachytherapy for uveal melanoma

Purpose To develop a predictive model and nomogram for maculopathy occurrence at 3 years after 106Ru/106Rh plaque brachytherapy in uveal melanoma. Material and methods Clinical records of patients affected by choroidal melanoma and treated with 106Ru/106Rh plaque from December 2006 to December 2014 were retrospectively reviewed. Inclusion criteria were: dome-shaped melanoma, distance to the fovea > 1.5 mm, tumor thickness > 2 mm, and follow-up > 4 months. The delivered dose to the tumor apex was 100 Gy. Primary endpoint of this investigation was the occurrence of radiation maculopathy at 3 years. Analyzed factors were as follows: gender, age, diabetes, tumor size (volume, area, largest basal diameter and apical height), type of plaque, distance to the fovea, presence of exudative detachment, drusen, orange pigment, radiation dose to the fovea and sclera. Univariate and multivariate Cox proportional hazards analyses were used to define the impact of baseline patient factors on the occurrence of maculopathy. Kaplan-Meier curves were used to estimate freedom from the occurrence of the maculopathy. The model performance was evaluated through internal validation using area under the ROC curve (AUC), and calibration with Gronnesby and Borgan tests. Results One hundred ninety-seven patients were considered for the final analysis. Radiation-related maculopathy at 3 years was observed in 41 patients. The proposed nomogram can predict maculopathy at 3 years with an AUC of 0.75. Distance to fovea appeared to be the main prognostic factor of the predictive model (hazard ratio of 0.83 [0.76-0.90], p < 0.01). Diabetes (hazard radio of 2.92 [1.38-6.20], p < 0.01), and tumor volume (hazard radio of 21.6 [1.66-281.14], p = 0.02) were significantly predictive for maculopathy occurrence. The calibration showed no statistical difference between actual and predicted maculopathy (p = 1). Conclusions Our predictive model, together with its nomogram, could be a useful tool to predict the occurrence of radiation maculopathy at 3 years after the treatment.

Effect of topical antiinflammatory drugs on mechanical behavior of rabbit cornea

Background A variety of antiinflammatory therapies are employed to promote corneal wound healing. The effects of steroidal and nonsteroidal antiinflammatory drugs on the biomechanical properties of rabbit cornea were investigated over time using tensile tests. Methods Full-thickness incisions were made and used to analyze the effects of dexamethasone sodium phosphate 0.1% and diclofenac sodium 0.1% on corneal biomechanical properties during wound healing at 7, 14 and 21 days after surgery. Results The full-thickness incision deeply modified all of the mechanical properties. At 3 weeks after incision, regardless of the drug therapy, the tensile modulus was about 70% of the value for the intact cornea. Conclusions Topical treatment with dexamethasone was particularly effective during the first week after surgery; the second week after surgery, a similar result was observed in the corneas treated with diclofenac. Low doses of steroidal and nonsteroidal antiinflammatory drugs would seem to have the potential to improve biomechanical properties only during the early stage of the healing process of the cornea.