A quantitative analysis of craniopharyngioma cyst expansion during and after radiation therapy and surgical implications

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>When complete resection of craniopharyngioma is not achievable or the sequelae are prohibitive, limited surgery and radiation therapy have demonstrated excellent local disease control while minimizing treatment-related sequelae. When residual tissue exists, there is a propensity for further cyst development and expansion during and after radiation therapy. This can result in obstructive hydrocephalus, visual changes, and/or clinical decline. The authors present a quantitative analysis of cyst expansion during and after radiotherapy and examine how it affected subsequent management.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>The authors performed an institutional review board–approved retrospective study of patients with histologically confirmed craniopharyngioma treated between 2000 and 2015 with surgery and intensity-modulated radiation therapy (IMRT) at a single institution. Volumetric measurements of cyst contours were generated by radiation oncology treatment planning software postoperatively, during IMRT, and up to 12 months after IMRT. Patient, tumor, and treatment–related variables were collected until the last known follow-up and were analyzed.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Twenty-seven patients underwent surgery and IMRT. The median total radiation dose was 54 Gy. Of the 27 patients, 11 patients (40.7%) demonstrated cyst expansions within 1 year of IMRT. Of note, all tumors with cyst expansion were radiographically Puget Grade 2. Maximal cyst expansion peaked at 4.27 months following radiation therapy, with a median volume growth of 4.1 cm<jats:sup>3</jats:sup> (mean 9.61 cm<jats:sup>3</jats:sup>) above the postoperative cyst volume. Eight patients experienced spontaneous cyst regression without therapeutic intervention. Three patients experienced MRI-confirmed cyst enlargement during IMRT, all of whom required adaptive planning to ensure adequate coverage of the entire tumor volume. Two of these 3 patients required ventriculoperitoneal shunt placement and additional intervention. One underwent additional resection, and the other had placement of an intracystic catheter for aspiration and delivery of intracystic interferon within 12 months of completing IMRT. All 3 patients now have stable disease.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Craniopharyngioma cyst expansion occurred in approximately 40% of the patients during or after radiotherapy. In the majority of patients, cyst expansion was a self-limiting process and did not confer a worse outcome. During radiotherapy, cyst expansion may be apparent on image-guided radiation therapy. Adaptive IMRT planning may be required to ensure that the intended IMRT dose covers the entire tumor and cyst volume. The sequelae of cyst expansion include progressive hydrocephalus, which may be treated with a shunt. For patients with solitary cyst expansion, cyst aspiration and/or intracystic interferon may result in disease control.</jats:p></jats:sec>

ESTRO ACROP guideline for target volume delineation of skull base tumors

“…The GTV has historically been expanded by a margin of 10-20 mm to generate the CTV and the PTV, given less reliable immobilization and image guidance; however, margins have progressively reduced. Currently, some institutions include a 3-5 mm GTVto-CTV margin to take into account potential microscopic areas of tumor infiltration and changes of cystic components of the tumor during the treatment that may occur in up to 40% of patients [130]; as for other skull base tumors, margins can be reduced at sites where tumor invasion is unlikely, e.g. skull base bones.…”

Gliomas, germ cell tumors, and craniopharyngioma

“…Proton therapy reports support excellent outcomes with further decreased regional off‐target dose and potential for diminished late toxicity 86,87 . For conventionally fractionated radiotherapy, mid‐course volumetric imaging is recommended due to the potential for intracourse rapid cyst expansion 88 . Radiosurgical approaches commonly employ a dose appropriate for benign tumors (12‐25 Gy in 1‐5 fractions) with margins of 0‐5 mm on gross disease (GTV) as indicated by the setting (primary vs recurrence) and proximity to critical structures 89‐92 …”

Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma

“…12 In cases with residual tumor, expansion of cystic components can be problematic and may require frequent aspiration, shunting, or repeat surgical resection. 13 Craniopharyngiomas are associated with significant morbidity, including panhypopituitarism, diabetes insipidus, profound obesity, cognitive impairment, personality changes, and retarded growth and sexual maturation in children. 14 These problems often require lifelong management.…”