High dose craniospinal irradiation as independent risk factor of permanent alopecia in childhood medulloblastoma survivors: cohort study and literature review.

PURPOSE: Our aim was to determine the main risk factors related to the occurrence of permanent alopecia in childhood medulloblastoma (MB) survivors. METHODS: We retrospectively analyzed the clinical features of all consecutive MB survivors treated at our institute. We divided the patients into 3 groups depending on the craniospinal irradiation (CSI) dose received and defined permanent alopecia first in terms of the skin region affected (whole scalp and nape region), then on the basis of the toxicity degree (G). Any relationship between permanent alopecia and other characteristics was investigated by a univariate and multivariate analysis and Odds ratio (OR) with confidence interval (CI) was reported. RESULTS: We included 41 patients with a mean10-year follow-up. High dose CSI resulted as an independent factor leading to permanent hair loss in both groups: alopecia of the whole scalp (G1 p-value 0.030, G2 p-value 0.003) and of the nape region (G1 p-value 0.038, G2 p-value 0.006). The posterior cranial fossa (PCF) boost volume and dose were not significant factors at multivariate analysis neither in permanent hair loss of the whole scalp nor only in the nuchal region. CONCLUSION: In pediatric patients with MB, the development of permanent alopecia seems to depend only on the CSI dose ≥ 36 Gy. Acute damage to the hair follicle is dose dependent, but in terms of late side effects, constant and homogeneous daily irradiation of a large volume may have a stronger effect than a higher but focal dose of radiotherapy.

In vivo expression of the collagen-related heat shock protein HSP47, following hyperthermia or photodynamic therapy.

Heat shock protein 47 (HSP 47), a molecule expressed constitutively in cells that synthesise collagen, is involved in collagen type I biosynthesis, and after insult acts as a stress response molecule to sequester abnormal procollagen. Photodynamic therapy (PDT) is claimed not to result in extensive collagen damage, such as that which can occur after other laser treatments, e.g. hyperthermia (HT) or coagulation, thereby conferring on PDT a potential therapeutic advantage. In previous studies on mouse fibroblasts in vitro we demonstrated HSP47 elevation in the first hours after the application of conditions known to damage collagen, and an absence of HSP47 elevation following PDT with two well-established photosensitisers, haematoporphyrin ester (HpE) and meta-tetrahydroxyphenylchlorin (mTHPC). The present study examines HSP47 metabolism in murine skin following (1) HT, (2) PDT with HpE and (3) PDT with riboflavin (RB). Riboflavin was examined because of reports of collagen injury induced by its photoactivation. All three stresses were applied at grossly equitoxic, 'tolerance' doses. Three months after these doses, linear extensometry revealed the skin to have fibrotic characteristics after HT and RB PDT, but not after HpE PDT. HSP47 expression levels were analysed at transcriptional (Northern) and translational (Western) levels at early time intervals up to 24 h after the treatment application, starting immediately after the treatment for mRNA and 6 h post-treatment for protein. Highly significant upregulation of HSP47 was detected following HT, and PDT with RB. PDT mediated by HpE did not have any impact on HSP47 levels. These results were thus consistent with those from in vitro work and support the hypothesis of early elevation of HSP47 expression only by modalities affecting collagen or its precursors.

Expression of the collagen-related heat shock protein HSP47 in fibroblasts treated with hyperthermia or photodynamic therapy.

Heat shock protein (HSP) 47 is associated with collagen type I metabolism, both constitutively and after stress-inflicted injury. It has been claimed that, in contrast to hyperthermia (HT), photodynamic therapy (PDT) does not damage collagen, as measured at the level of tissue. We have studied HSP47 expression in normal murine skin fibroblasts (3T6) treated with hyperthermia or photodynamic therapy (PDT) mediated by three different photosensitizers: (1) haematoporphyrin ester (HpE), (2) meta tetra hydroxyphenyl chlorin (mTHPC) and (3) riboflavin (RB). Riboflavin is not an established photosensitizer for PDT and was chosen here because it is known to provoke collagen damage. The applied doses of the treatments were isoeffective in terms of 3T6 clonogenic cell survival. Analysis, at both transcriptional and translational levels, revealed HSP47 elevation after hyperthermia and after PDT with RB. PDT sensitized by HpE and mTHPC did not significantly alter HSP47 expression. These observations are consistent with our hypothesis that this collagen chaperone is up-regulated by laser-mediated modalities known to damage collagen (i.e. HT and RB PDT) but not by more conventional PDT treatments. Additionally, unexpected significant up-regulation of HSP47 was detected after illumination alone (no photosensitizer) of 3T6 cells at 653 nm laser light, but not at 630 nm.