Sustained Suppression of Gorlin Syndrome-Associated Basal Cell Carcinomas with Vismodegib or Sonidegib: A Case Series.

Nevoid basal-cell carcinoma syndrome (Gorlin syndrome) is characterized by numerous cutaneous basal cell carcinomas mediated by mutations in the hedgehog pathway. Vismodegib or sonidegib represent promising treatment options. We identified 10 Gorlin patients who were treated with sonidegib (n = 6) or vismodegib (n = 4) between March 2012 and March 2022. We analyzed the activity, toxicity, and duration of the response to oral hedgehog inhibitors. The number of new tumors that developed prior to treatment or after treatment as well as the time of response and durability of responses were assessed. All patients achieved a complete remission. With a 30.7 ± 48.4-month median follow-up, the drug treatment significantly reduced the number of new basal cell cancers from a mean of 28.3 ± 24.6 prior to treatment to a mean of 1.4 ± 2.0 during treatment (p = 0.0048). The median time to develop a new basal cell cancer was 47.3 months. Three patients eventually developed localized recurrences. After resection, ongoing treatment suppressed the development of additional lesions. One patient developed numerous new drug-resistant basal cell cancers and died of acute leukemia. Six patients required treatment modifications for toxicity. Sustained hedgehog inhibitor treatment can suppress the progression of both new and existing basal cell carcinomas for an extended period. Drug administration schedule adjustments improved tolerance without altering efficacy, potentially contributing to a prolonged response duration.

Neoadjuvant photodynamic therapy as a therapeutic alternative in multiple basal cell carcinoma induced by radiotherapy.

INTRODUCTION: Non-melanoma skin cancer within previously irradiated areas presents a common challenge, requiring innovative therapies. Complex scenarios, like XRT-induced basal cell carcinoma (BCC) or Gorlin's syndrome, often involve multiple synchronous tumor lesions where photodynamic therapy (PDT) offers a viable therapeutic alternative. CLINICAL CASE: We present the case of a 49-year-old male with a history of XRT for brain tumors. The patient was undergoing treatment for recurrent basal cell carcinomas (BCCs) in the right temporal irradiated area, unresponsive to conventional treatments. In the latest evaluation, the patient presented a nodular tumor and several peripheral superficial foci. Photodynamic therapy (PDT) was administered using methyl aminolevulinate 160 mg/g in cream (Metvix®) in two sessions spaced 7 days apart before surgery. The photosensitizer was applied 3 h before initiating PDT, and red light exposure was performed with the Aktilite© lamp (wavelength 630 nm, 100 mm distance, voltage 100 to 240 V, frequency 50 Hz, power 180 W) for 7 min. CONCLUSIóN: PDT with methyl aminolevulinate demonstrated efficacy as a neoadjuvant treatment in a case of multiple XRT-induced BCCs before surgery. PDT emerges as a valuable therapeutic alternative for multiple BCCs, particularly in non-responsive cases.

The use of the photodynamic method in the treatment of recurrent basal cell carcinoma on the example of Gorlin-Goltz syndrome-management algorithm.

INTRODUCTION: Conventional methods of basal cell carcinomas (BCC) treatment bring many severe side effects, especially, if they are repeated many times. The aim of this study is to present the clinical effectiveness of photodynamic method in the treatment and prevention of BCC relapses on the face and to propose a management algorithm. METHODS: In a patient with Gorlin-Goltz syndrome (NBCCS) lesions on the face were assessed clinically and with photodynamic diagnostics (PDD), initially and in follow-up every 3 months, for a total of 12 months. Detected BCCs were treated with photodynamic therapy three times every week. RESULTS: In whole follow-up period no clinical relapses were shown. However, in PDD after 6 month in one irradiated and in one initially clinically clear area red fluorescence indicating atypical foci was observed and irradiated additional one time. DISCUSSION: Photodynamic therapy is not limited by previous treatments, can be repeated without adverse events, heals multiple lesions at once and prevents new ones. Because BCC in NBCCS will occur constantly, the implementation of PDD to control the condition of the skin in long-term care should be obligatory. We indicate the validity of using the photodynamic diagnostic and therapy, as a medical procedures of choice.

5-aminolevulinic acid photodynamic therapy and excision surgery for nevoid basal cell carcinoma syndrome with multiple basal cell carcinomas and PTCH1 mutation.

This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS.

Drug holiday approach for Vismodegib treatment in patients with nevoid basal cell carcinoma syndrome: Three cases from real clinical practice.

Sonic hedgehog pathway inhibitor Vismodegib is the first systemic treatment to be approved for metastatic or locally advanced basal cell carcinoma non-subsidiary of surgical treatment, and appears to be a promising treatment option for patients with nevoid basal cell carcinoma syndrome. In these patients, where repeated or prolonged treatment may be necessary, the psychological exhaustion caused by the chronicity of less severe adverse effects appears as the main limiting factor in the persistence of the drug in the long term and in the willingness of patients to take the drug again after its suspension. We report our experience with three cases where a drug holiday approach was effective in decreasing the intensity of adverse effects or improving the patient's subjective tolerance to the drug while maintaining clinical response.

Traitement médical des carcinomes basocellulaires avancés: Medical treatment of advanced basal cell carcinoma.

Until recently, advanced BCC were only accessible to a highly morbid surgery not necessarily proving to be carcinologic, and leaving terrible dysmorphic sequelae hard to accept by the patient. Another possibility, the only one in case of metastatic BCC, was chemotherapy which efficacy has never been proven in a clinical trial. Radiotherapy is most often not accessible because of previous radiotherapy or because of the localization or the extension of the lesion. The discovery of the importance of the sonic hedgehog pathway in the physiopathology of BCC has opened a new strategy with the development of targeted anti SMO drugs inactivating the pathway. Two molecules have become available following Phase I and II studies: vismodegib (Erivedge®) the first in class indicated for locally advanced and metastatic BCC and sonidegib (Odomzo®) indicated only for locally advanced BCC. The pharmacokinetic profiles of sonidegib and vismodegib showed several differences. No head to head comparative studies are available between these two drugs. Their pivotal phase II studies had similar study designs and endpoints. The objective response rate (ORR) by central review for vismodegib was 47.6% (95% CI 35.5-60.6) at 21 months follow-up. The ORR for sonidegib according to central review at 18 months follow-up is 56.1% (95% CI 43.3-68.3). Although both treatments share a similar adverse event profile with possible numerically differences in incidence, most patients will discontinue hedgehog inhibitors treatment in the long term because of side effects. Some resistant cases to these drugs have been described but are rather rare. In case of resistance or bad tolerability to the drug future hopes rely on immunotherapy currently under investigation. © 2018. Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.

Effective anti-programmed death-1 therapy in a SUFU-mutated patient with Gorlin-Goltz syndrome.

We present the case of a 77-year-old male patient with more than 50 basal cell carcinomas on the head and upper trunk. The patient did not respond to several lines of treatment, including surgery, imiquimod, retinoids, itraconazole and therapy with the hedgehog inhibitor vismodegib. The patient responded well to off-label therapy with the anti-programmed death-1 antibody pembrolizumab after four infusions.

Blue light versus red light for photodynamic therapy of basal cell carcinoma in patients with Gorlin syndrome: A bilaterally controlled comparison study.

BACKGROUND: Photodynamic therapy (PDT) is a non-scarring alternative for treating basal cell carcinoma (BCC) in patients with Basal Cell Nevus Syndrome (BCNS), also known as Gorlin syndrome. In Europe, red light (635 nm) is the predominant source for PDT, whereas in the United States blue light (400 nm) is more widely available. The objective of this study was to conduct a head-to-head comparison of blue light and red light PDT in the same BCNS patients. METHODS: In a pilot study of three patients with 141 BCC lesions, 5-aminolevulinate (20% solution) was applied to all tumors. After 4 h, half of the tumors were illuminated with blue light and the remainder with red light. To ensure safety while treating this many tumors simultaneously, light doses were escalated gradually. Six treatments were administered in three biweekly sessions over 4 months, with a final evaluation at 6 months. Tumor status was documented with high-resolution photographs. Persistent lesions were biopsied at 6 months. RESULTS: Clearance rates after blue light (98%) were slightly better than after red light (93%), with blue light shown to be statistically non-inferior to red light. Eight suspicious lesions were biopsied, 5 after red light (5/5 were BCC) and 3 after blue light (1 was BCC). Blue light PDT was reportedly less painful. CONCLUSION: Blue light and red light PDT appear to be equally safe and perhaps equally effective for treating BCC tumors in BCNS patients. Further studies to evaluate long-term clearance after blue light PDT are needed.