I read with great interest the paper by John-Paul Kilday et al.1
I congratulate the authors for retrospectively studying 56 patients with craniopharyngiomas from different continents and aged <18 years, a study supported by 2 reputed medical societies in oncology and pediatric neurosurgery, SIOPE and ISPN.
However, the results raise some questions and concerns. First, of the 56 enrolled patients treated with intracystic interferon-alpha, 43 had already received other therapies. In our opinion, this affects the overall assessment of these patients. These 43 patients had already failed the primary treatment of choice and were therefore being treated with a second therapeutic modality (interferon-alpha). This calls into question the combined analysis of this group with treatment-naïve patients.
In addition, I question why the authors called this treatment modality the “Toronto Protocol,” as this treatment protocol is not substantially different from the protocol that was originally published by Cavalheiro et al2 in 2005 and used to treat patients in São Paulo, Brazil.2,3 The São Paulo team was the first to use and report this treatment, subjecting patients to this new therapeutic modality. They also analyzed and published the cellular changes occurring during and after treatment4 and performed the first multicenter study involving 60 patients.3
I also believe that the authors could have harnessed the collaborative nature of their study and analyzed differences in subgroups of patients with craniopharyngioma that respond differently to distinct treatment modalities. They could also have investigated why the craniopharyngiomas that were not cured with radical surgery, radiotherapy, and/or other intracystic chemotherapy agents also respond poorly to intracystic interferon, as these patients constituted 77% of the total number of patients analyzed. Because some lesions disappeared after only one treatment cycle, the genetic hallmarks of these tumors should have been evaluated.
The authors also did not clarify the criteria for new treatment cycles. It was unclear whether they evaluated only the increase in volume or also considered changes in the radiological characteristics of the cystic component. Because previous studies have not determined when interferon treatment should be halted and patients switched to another therapeutic modality, switching hastily may cause false-negative findings of drug efficacy. Because this was a retrospective study involving 21 different centers, the criteria for switching therapy were likely non-uniform.
Furthermore, craniopharyngioma surgery after treatment with interferon is no more difficult than after radiotherapy or even after treatment with bleomycin. Following treatment with interferon, the capsule of the craniopharyngioma becomes much more evident, allowing its complete exeresis. A prospective study in treatment-naïve patients, with genomic and proteomic analyses of the fluid removed during the injections, and analyses of radiological modifications before and after interferon treatment, would be very welcome.
References
- 1. Kilday JP, Caldarelli M, Massimi L. et al. Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN. Neuro Oncol. 2017;19(10)1398–1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Cavalheiro S, Dastoli PA, Silva NS, Toledo S, Lederman H, da Silva MC. Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma. Childs Nerv Syst. 2005;21(8–9):719–724. [DOI] [PubMed] [Google Scholar]
- 3. Cavalheiro S, Di Rocco C, Valenzuela S et al. Craniopharyngiomas: intratumoral chemotherapy with interferon-alpha: a multicenter preliminary study with 60 cases. Neurosurg Focus. 2010;28(4):E12. [DOI] [PubMed] [Google Scholar]
- 4. Ierardi DF, Fernandes MJ, Silva IR et al. Apoptosis in alpha interferon (IFN-alpha) intratumoral chemotherapy for cystic craniopharyngiomas. Childs Nerv Syst. 2007;23(9):1041–1046. [DOI] [PubMed] [Google Scholar]