Çocukluk Çağı Medülloblastom Hastalarında "Collins Risk Periyodu"

Abstract

ABSTRACT

Shirinova, Sh., “Collins Risk Period” in Pediatric Medulloblastoma Patients, Hacettepe University Faculty of Medicine, Pediatrics Specialty Thesis, Ankara, 2019. In 1955, the period of risk for tumor recurrence in embryonal tumors was proposed as “the age of the child at diagnosis plus 9 months of gestation” (V.P. Collins; Collins Risk Period, CRP). Many studies (especially with medulloblastoma) reported the validity of this hypothesis in the following years, although there are also publications showing exceptions to this concept. The purpose of our study was to evaluate the validity of the concept of “CRP” for recurrence in medulloblastoma patients followed in the Pediatric Oncology Department of Hacettepe University. Of 240 medulloblastoma patients diagnosed between 1995 and 2016, 145 were eligible for the study. The demographic, clinical, pathological features, follow-up periods, events and recurrences in the follow-up and overall outcome data were examined. Correlations with the “CRP” were analyzed. The mean age at diagnosis was 7.9 years (± 4.1) (median 8.4; 0.5-17.9), and the male / female ratio was 1.9. At the time of diagnosis, 82.8% of the patients had primary tumor located only in the posterior fossa; 82.7% of the patients had complete or near-complete resection of the tumor. In 61.4% of the patients postoperative tumor residues were not detected. Four patients did not receive radiotherapy because of their young age and all patients received chemotherapy. At a median follow-up of 98 months (11-281), 98/145 cases were alive, 12/145 were lost to follow-up and 35/145 were dead. Five-year event-free and overall survival rates were higher in females (p< 0.03). The 5-year event-free and overall survival rates were significantly lower in patients with metastasis at the time of diagnosis (p< 0.001). There was no difference in survival rates according to age groups (age< 5 years X ≥5 years) (p= 0.76). Recurrences in the follow-up were observed in 37 (25.5%) patients. The incidence of recurrence was significantly higher in male patients than in females (p= 0.01). There was no difference in recurrence rates in patients with age <5 and ≥5 years at the time of diagnosis (p= 0.6). Significantly higher recurrence was observed in patients with metastasis at the time of diagnosis (p= 0.005). Eight recurrences (21%) occurred in the posterior fossa and the recurrence of 11/37 patients was histopathologically confirmed. In 37 patients, recurrences occurred at a mean of 25.9 months (2.1 years) after diagnosis (in 97% of patients in the first 5 years), and only in one patient beyond 5 years (65 months). Three patients with recurrences were alive and under follow-up at the time of our study; one of these patients had the longest overall follow-up (207 months) in our study. The median “CRP” was 104 months (8.7 years; 15-223) for all patients. Recurrences occurred in the “CRP” in 36/37 cases; only one occurred after the “CRP”. The patient who experienced disease recurrence after the “CRP” was 25-month-old at initial diagnosis and recurrence occurred at 51 months of follow-up (17 months after end of the “CRP”). Of the 65 patients who completed “CRP” without recurrence, 58 were alive and the median overall survival / median “CRP” ratio was 2.1. The use of “CRP” concept (Collins Law) as a ‘definitive indicator of cure from disease’ for medulloblastoma cases was not justified in our study. However, our results support the hypothesis that the risk for recurrence is highest in the “CRP” and minimum after the “CRP”. In childhood embryonal cancers, including medulloblastomas, the risk period for recurrence should be assessed individually for each patient taking into account the “CRP”. The regular long-term follow-up is important in all patients for possible late recurrences, as well as secondary cancers and the late complications of treatments even after decades.

Key words: medulloblastoma, recurrence, survival, “Collins Risk Period”