Late toxicity following craniospinal radiation for early-stage medulloblastoma

Figures & data

Table I. Patient, tumor, and treatment characteristics.

Characteristic	Value*
Median follow-up in years (range)	15.4 (range 0.4–44.4)
Median age (range)	7.1 (range 1.2–18.5)
Male	38 (72%)
Black	5 (9%)
Age ≤ 3 years	4 (7.5%)
Hydrocephalus present at diagnosis	45 (85%)
Gross total resection/near total resection	28 (53%)
Subtotal resection/biopsy alone	25 (47%)
Desmoplastic histology	6 (11%)
Anaplastic histology	1 (2%)
Classic or unknown histology	46 (87%)
M stage
0	50 (94%)
1	3 (6%)
Chemotherapy
Preradiotherapy alone	2 (4%)
Preradiotherapy + Concurrent	1 (2%)
Preradiotherapy + Adjuvant	3 (6%)
Concurrent + Adjuvant	11 (21%)
Adjuvant alone	4 (7.5%)
None	32 (60%)
Dose in Gy (range)
Craniospinal irradiation
> 18–23.4	8 (15%)
> 23.4	45 (85%)
Total dose to posterior fossa/tumor bed
< 54	19 (36%)
≥ 54	34 (64%)
Treated twice daily	7 (13%)
Total elapsed time during radiotherapy treatment > 45 days	32 (60%)
Treated prior to 1991	31 (58%)

*The values listed in the table represent the (N) number of patients as well as the (%) of all patients, unless otherwise specified.

Figure 1. Cause-specific and overall survival rates at 15 years.

Table II. Number of registered complications by grade: N = 39 patients with > 5 years of follow-up.

	Grade 2 complication, no. of patients	Grade 3 complication, no. of patients	Grade 4 complication, no. of patients	Total no. of patients (%)
Endocrine
Hypothyroid	8	0	0	8 (21%)
Other (ACTH, cortisol, deficiency)	1	0	0	1 (3%)
Sensory
Hearing deficit or loss	7	8*	0	15 (39%)
Visual disturbance	4	0	1**	5 (13%)
Neurologic
Cognitive disturbance	12	7	0	19 (49%)
Seizures	2	1	0	3 (8%)
Other
Radionecrosis	0	0	2	2 (5%)
Secondary malignancy, non-skin	0	1	3	4 (10%)
Cerebrovascular (stroke, TIA, aneurysm)	2	1	1	4 (10%)
Other: Encephalopathy, facial nerve palsy, ataxia, serous otitis media, myocardial infarction	4	1	0	5 (13%)
Total	40	19	7	66

ACTH, adrenocorticotropic hormone; TIA, transient ischemic attack.

Note: Since many patients experienced more than 1 grade 2 + complication, the total number of complications exceeds the total number of patients.

*One patient had radiotherapy-induced serous otitis media leading to loss of hearing in the ipsilateral ear; ** This patient had radiotherapy-induced radionecrosis. Surgery for radionecrosis resulted in right-sided homonymous heminanopsia.

Table III. Fatal complications and patient and treatment characteristics.

Age at RT (years)	Stage	Gender, ethnicity	Total dose (Gy), modality	CSI dose (Gy)	Chemotherapy	Complication type	Time elapsed to death	Other
11.1	M0	Female, White	51.9, Cobalt-60	28.3	None	Radionecrosis and cerebellar degeneration	1.3 years	–
11.4	M0	Male, White	64.8, LINAC	38.4	Adjuvant cisplatin and etoposide	Serious cerebral edema and herniation	0.5 years	Patient also had surgical complications, locked-in syndrome
17.4	M0	Male, White	64.8, LINAC	28.8	Neoadjuvant cisplatin/etoposide. Concurrent vincristine and cytoxan	Secondary malignancy, glioblastoma multiforme	14 years	Patient also developed a meningioma before dying

CSI, craniospinal irradiation; LINAC, linear accelerator photons; RT, radiotherapy.

*Time elapsed to death begins from the date radiotherapy was completed.

Table IV. Time from initial surgery to occurrence of serious toxicity.

Deficit	No. of patients	Median time to occurrence from completion of treatment (years)	Range (years)
Serious edema/herniation	1	0.7	–
Radionecrosis	3	2.81	1.5–10.11
Visual disturbance	1	2.81	–
Cognitive disturbance	7	3.6	0.7–7.2
Hearing deficit	8	8.1	0.5–23
Secondary malignancy	5	12.0	6.4–13.7
Seizures	1	19.5	–
Ataxia	1	20.5	–
Stroke	1	24	–
Basilar aneurysm	1	34.5	–