Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review

Abstract

Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959–2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3–14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5–9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall survival. In patients treated with radiotherapy for pituitary adenomas, the risk of secondary tumor incidence warrants a longer follow up period. Moreover, radiation and/or chemotherapy should be considered in cases of secondary glioma or sarcoma following radiotherapy to the pituitary adenomas.

Fatal high-grade skull osteosarcoma 30 years following radiotherapy for Cushing’s disease

“…Table 1 describes the characteristics of nine other cases of radiation-induced osteosarcoma following pituitary tumour irradiation. The mean age at diagnosis of secondary tumour was 50 years (16-75) with a mean latency period of 13 years (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). At 30 years, this is the longest reported duration between radiotherapy for a pituitary tumour and development of a radiationinduced osteosarcoma in the literature.…”

Fatal high-grade skull osteosarcoma 30 years following radiotherapy for Cushing’s disease

“…Table 1 describes the characteristics of nine other cases of radiation-induced osteosarcoma following pituitary tumour irradiation. The mean age at diagnosis of secondary tumour was 50 years (16-75) with a mean latency period of 13 years (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). At 30 years, this is the longest reported duration between radiotherapy for a pituitary tumour and development of a radiationinduced osteosarcoma in the literature.…”

Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma

“…Recently, Lelotte et al reported a series of 120 NFPA macroadenomas retrospectively evaluated for clinical outcomes and found 5-year recurrence of between 20 and 66 % depending on their initial proliferative and invasive status [34]. During follow-up, no secondary intracranial tumor occurred after radiotherapy, which appears to be a rare event according to a recent literature review [35]. Overall, these data suggest that a conservative approach, without radiotherapy, may be safe in a majority of patients with NFPA but justifies appropriate imaging surveillance.…”

Malignant transformation of pituitary adenoma to carcinosarcoma: illustrative case

“…The median overall survival time for sarcoma cases is approximately 6 months, with a trend toward improved median survival for patients receiving radiotherapy and/or chemotherapy. 3 Among patients who have undergone radiotherapy for PAs, the risk of secondary tumor development necessitates longer follow-up periods. 3 However, Yamada et al 17 reported that patients treated with CyberKnife for RIOS remained healthy for 24 months without neurological symptoms.…”

“… 3 Among patients who have undergone radiotherapy for PAs, the risk of secondary tumor development necessitates longer follow-up periods. 3 However, Yamada et al 17 reported that patients treated with CyberKnife for RIOS remained healthy for 24 months without neurological symptoms. The results of CyberKnife treatment indicate that this specific therapy should be considered for unresectable cranial base RIOS.…”

Fatal high-grade skull osteosarcoma 30 years following radiotherapy for Cushing’s disease

“…Table 1 describes the characteristics of nine other cases of radiation-induced osteosarcoma following pituitary tumour irradiation. The mean age at diagnosis of secondary tumour was 50 years (16-75) with a mean latency period of 13 years (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). At 30 years, this is the longest reported duration between radiotherapy for a pituitary tumour and development of a radiationinduced osteosarcoma in the literature.…”

Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma

“…Recently, Lelotte et al reported a series of 120 NFPA macroadenomas retrospectively evaluated for clinical outcomes and found 5-year recurrence of between 20 and 66 % depending on their initial proliferative and invasive status [34]. During follow-up, no secondary intracranial tumor occurred after radiotherapy, which appears to be a rare event according to a recent literature review [35]. Overall, these data suggest that a conservative approach, without radiotherapy, may be safe in a majority of patients with NFPA but justifies appropriate imaging surveillance.…”

Malignant transformation of pituitary adenoma to carcinosarcoma: illustrative case

“…The median overall survival time for sarcoma cases is approximately 6 months, with a trend toward improved median survival for patients receiving radiotherapy and/or chemotherapy. 3 Among patients who have undergone radiotherapy for PAs, the risk of secondary tumor development necessitates longer follow-up periods. 3 However, Yamada et al 17 reported that patients treated with CyberKnife for RIOS remained healthy for 24 months without neurological symptoms.…”

“… 3 Among patients who have undergone radiotherapy for PAs, the risk of secondary tumor development necessitates longer follow-up periods. 3 However, Yamada et al 17 reported that patients treated with CyberKnife for RIOS remained healthy for 24 months without neurological symptoms. The results of CyberKnife treatment indicate that this specific therapy should be considered for unresectable cranial base RIOS.…”

Fatal high-grade skull osteosarcoma 30 years following radiotherapy for Cushing’s disease

“…Table 1 describes the characteristics of nine other cases of radiation-induced osteosarcoma following pituitary tumour irradiation. The mean age at diagnosis of secondary tumour was 50 years (16-75) with a mean latency period of 13 years (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). At 30 years, this is the longest reported duration between radiotherapy for a pituitary tumour and development of a radiationinduced osteosarcoma in the literature.…”

Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma

“…Recently, Lelotte et al reported a series of 120 NFPA macroadenomas retrospectively evaluated for clinical outcomes and found 5-year recurrence of between 20 and 66 % depending on their initial proliferative and invasive status [34]. During follow-up, no secondary intracranial tumor occurred after radiotherapy, which appears to be a rare event according to a recent literature review [35]. Overall, these data suggest that a conservative approach, without radiotherapy, may be safe in a majority of patients with NFPA but justifies appropriate imaging surveillance.…”

Malignant transformation of pituitary adenoma to carcinosarcoma: illustrative case

“…The median overall survival time for sarcoma cases is approximately 6 months, with a trend toward improved median survival for patients receiving radiotherapy and/or chemotherapy. 3 Among patients who have undergone radiotherapy for PAs, the risk of secondary tumor development necessitates longer follow-up periods. 3 However, Yamada et al 17 reported that patients treated with CyberKnife for RIOS remained healthy for 24 months without neurological symptoms.…”

“… 3 Among patients who have undergone radiotherapy for PAs, the risk of secondary tumor development necessitates longer follow-up periods. 3 However, Yamada et al 17 reported that patients treated with CyberKnife for RIOS remained healthy for 24 months without neurological symptoms. The results of CyberKnife treatment indicate that this specific therapy should be considered for unresectable cranial base RIOS.…”