Quality of life and treatment-related burden during ocular proton therapy: a prospective trial of 131 patients with uveal melanoma

Background: Proton beam therapy is a well-established treatment option for patients with uveal melanoma (UM). The treatment procedure, in general, includes placing radiopaque clips to ensure exact eye-positioning during radiotherapy, followed by the delivery of proton irradiation. The short-term burden associated with proton therapy in patients with UM has rarely been addressed. In this prospective study, we investigated the physiological and psychological aspects of proton therapy that might affect the well-being of patients during the different stages of treatment. Methods: During the treatment procedure, we conducted longitudinal assessments of the Quality of life (QOL), organ-specific symptoms, and psychological aspects in patients with UM with three questionnaires (EORTC QLQ-C30, EORTC QLQ-OPT30, and GAD-7). Patients completed questionnaires before clip surgery (T0), before proton therapy (T1), after completing treatment (T2), and three months after treatment completion (T3). We also collected data on tumor characteristics and socio-demographics to identify potential risk factors associated with high treatment burdens. Results: We prospectively included 131 consecutive patients. Questionnaire data showed a significant, temporary decline in global QOL and an increase in eye-related symptoms, as a result of the clip surgery (T0-T1). After treatment completion (T2), global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy. The global QOL returned to baseline levels three months after treatment (T3). We identified baseline anxiety as an independent risk factor for experiencing an acute treatment-related burden. Furthermore, we found interactions between GAD7 and patient sex showing that anxiety had a more pronounced effect on QOL outcome in female patients. Conclusion: The short-term treatment-related burden of ocular proton therapy appeared to be largely associated with the preceding clip surgery, rather than the irradiation procedure. We found that anxiety was strongly associated with experiencing QOL issues during the treatment procedure. Our findings could contribute to the development of future strategies for improving the treatment process and psycho-oncologic patient care

Risikofaktoren und Therapieoptionen zur Behandlung des Sekundärglaukoms nach Radiatio uvealer Melanome mittels Protonentherapie

Das uveale Melanom ist eine sowohl visus- als auch lebensbedrohende Erkrankung. Erfreulicherweise hat sich in den letzten zehn Jahren unser Verständnis, insbesondere bezüglich der Genetik der uvealen Melanome, deutlich entwickelt und es bleibt zu hoffen, dass basierend auf diesen Erkenntnissen neue therapeutische Verfahren zur Behandlung des metastasierten uvealen Melanoms entstehen werden. Bei der Behandlung des Primärtumors sind wir derzeit in der Lage Tumore in einer Größenordnung zu bestrahlen, die früher eine sichere Indikation zur Enukleation dargestellt hätten. Hierzu sind zum Teil aufwändige Operationen und insbesondere während der ersten Jahre engmaschige Kontrollen notwendig, um etwaige Spätfolgen einer Radiatio rechtzeitig zu erkennen und zu behandeln. Die lokale Tumorkontrollrate mittels Protonentherapie ist mit 95-98 % so hoch, dass der häufigste Grund für eine sekundäre Enukleation meist nicht das Lokalrezidiv darstellt, sondern bestrahlungsbedingte Komplikationen, allen voran das Sekundärglaukom. In dieser Arbeit sollen daher die Risikofaktoren, die zur Entwicklung der Sekundärglaukome führen können, sowie mögliche prophylaktische Interventionen und Behandlungsoptionen erörtert werden

The Genetics of Uveal Melanoma: Overview and Clinical Relevance

Over the last ten years, much has been learnt about the genetic characteristics and genetic evolution of uveal melanoma. It has been shown that uveal melanoma differs fundamentally from non-uveal melanoma and is an independent genetic subtype. Compared to other tumours, uveal melanoma has a low mutational burden. There are recurring chromosomal aberrations with losses of 1p, 6q, 8p and 16q, gains of 6p and 8q, and the presence of monosomy 3. GNAQ, GNA11, PLCB4, CYSLTR2, MAPKAPK5, as well as mutations in BAP1, SF3B1, SRSF2 and EIF1AX, the latter being linked to a higher risk of metastasis, have been identified as significantly mutated genes. In rare cases, a BAP1 germline mutation may also be present. In addition to higher risk of uveal melanoma, this variant is also linked with other tumours. In this case, additional work-up, genetic counselling and screening of family members should be offered. While the knowledge about the genetic characteristics of uveal melanoma is already routinely used for diagnostic and prognostic purposes, targeted genotype-dependent therapy of uveal melanoma is currently still missing