Outcome of Treatments for Infratentorial Hemangioblastomas in Children

Outcome After Surgery

• Similar outcomes for sporadic and VHL-related hemangioblastomas: Short-term outcomes are similar for sporadic and VHL-related hemangioblastomas (39). Most patients show significant clinical improvement in the immediate postoperative period. Clinical improvement occurs in more than 80% of patients with cerebellar hemangioblastomas and 30–60% of patients with brainstem hemangioblastomas. A small percentage of patients may present with new clinical symptoms/signs after surgery or exacerbation of the preexisting ones. These new symptoms are often transient and self-limiting.

• Asymptomatic at 6 months: Six months after surgery, most patients are asymptomatic and able to carry on normal activities (41).

• Morbidity is function of tumor location: Patients with brainstem hemangioblastomas commonly experience postoperative morbidity (40). Persistent hydrocephalus in posterior fossa tumors ranges between 10-15% and 40% and is more common in children with malignant tumors than in those with benign tumors such as hemangioblastoma (50). The need for ETV or permanent shunting is quite rare and arises mainly after surgery on hemangioblastomas of the fourth ventricle due to the formation of postsurgical adhesions.

• 10% mortality: At 5-year follow-up, the mortality rate that is directly due to progression of the hemangioblastoma is 2.5% in large series.  Overall mortality is 10% (15).

• 20% recurrence: The recurrence rate is approximately 20% (range 0–30%) and is higher for VHL-related hemangioblastomas than for sporadic ones (5). The risk of recurrence is also increased in the histological cellular variant (25%) compared with the reticular one (8%) (13).

• Morbidity and mortality in VHL: One of the main causes of morbidity and mortality in patients with VHL are hemangioblastomas.  Patients with VHL also suffer from other syndrome-related tumors such as renal cell carcinoma. As a consequence, the 5-year overall survival rate is 60%. Patients with VHL need life-long follow-up even in the face of long event-free periods (26).

Outcome after Nonsurgical Treatments

• Radiosurgery gives good short-term results: Moss et al. found tumor progression in only 16% of 41 irradiated hemangioblastomas after about 70 months mean follow-up, with 85% and 82% actuarial local control rates at 30 and 60 months, respectively (35). Improvement of pretreatment symptoms was noted in 88% of patients with the irradiated tumors.

• Long-term results more questionable: Radiation therapy allows the postponement of surgery for several years if used preoperatively but has poor long-term control (14). A recent prospective study on 20 patients with VHL with prolonged follow-up (average: 8.5 ± 3.2 years) showed decreased local control over time (91%, 83%, 61%, and 51% at 2, 5, 10, and 15 years after radiation therapy, respectively) (2). On these grounds, radiation therapy is advisable for non-resectable hemangioblastomas rather than as prophylaxis for multiple occurrences.

• Antiangiogenic therapy: SU5416, thalidomide, and INF-alpha have been successfully used to stabilize recurrent or disseminated hemangioblastomas in isolated adult cases and small series (36, 42, 47).

Outcome after Multimodal Therapies

• Little data available: Since surgery is the main treatment for hemangioblastomas and radiotherapy is used only as an alternative option for non-operable tumors, there is little published experienced in using multimodality treatment for these tumors. In the series of Koh and coworkers, where 16 of 18 patients received fractionated radiotherapy for recurrences or remnants after surgery, the 5-year overall survival (OS) rate was 69%, and the 10-year OS rate was 30% (21). Surprisingly, patients with VHL had a better outcome (5-year OS 100%, 10-year OS 80%) than those without VHL (5-year OS 55%, 10-year OS 48%).