Clinical efficacy and safety of a highly conformal, supine, hybrid forward and inverse planned intensity modulated radiation therapy technique for craniospinal irradiation.

PURPOSE: To demonstrate the clinical efficacy and safety of a highly conformal, supine, hybrid forward and inverse planned intensity modulated radiation therapy (IMRT) technique for photon craniospinal irradiation (CSI). METHODS: Patients who received supine, hybrid IMRT CSI from 2009 to 2014 were included in this retrospective review. Clinical target volume (CTV) was defined as intracranial contents and thecal sac, including nerve roots. Dose was prescribed such that >99% of CTV received >99% of prescription and >95% of the planning target volume received >95% of prescription, with no attempt to include vertebral bodies. Lateral fields were utilized at the cranium and upper cervical spine. Spine fields were either single posterior or 2-3 obliques. Plans were generated with a hybrid of forward and inverse planned IMRT. Inferior borders of the cranium fields and superior border of the lower spine field were designed with 6-15 cm long, gradual dose gradients by sequential closing of multileaf collimator leaves using forward planned multiple static segment IMRT delivery. The sliding window upper spine IMRT field was created by the inverse planning system to match gradients of the brain and lower spine fields. The lower spine field gradient was similarly completed. RESULTS: The cohort consisted of 34 patients. Median CSI dose was 36 Gy (range: 18-39.6 Gy). With a median follow up of 59.4 months, there were no isolated recurrences or spinal myelopathies at CTV margins or field gradients. Eleven patients had recurrence, all of which were intracranial. CONCLUSIONS: Our hybrid forward and inverse planned IMRT supine CSI technique did not result in any isolated recurrences or myelopathies at CTV margins or field gradients. This suggests our target volumes and blended gradients are appropriate for highly conformal three-dimensional planning.

Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy.

PURPOSE: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). MATERIALS AND METHODS: We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014. RESULTS: Thirty-four patients received induction chemotherapy followed by radiation with or without surgery. Median follow-up was 11.1 years (0.8-23.3). Outcomes were significantly improved in these 34 patients (5-year overall survival [OS]: 88% versus 50%, P = 0.0092), so analysis is restricted to that subset. Disease-free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid-α-fetoprotein (CSF-AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P = 0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF-AFP at baseline. All three patients with ventricular relapse received local radiation therapy. CONCLUSIONS: NGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF-AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second-look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.

Adult ewing sarcoma: survival and local control outcomes in 102 patients with localized disease.

Objectives. To assess the clinical features and local control (LC) outcomes in adult patients with localized Ewing Sarcoma (ES). Methods. The records of 102 ES patients with localized disease ≥18 years of age seen from 1977 to 2007 were reviewed. Factors relevant to prognosis, survival, and LC were analyzed. Results. The 5-year overall survival (OS) and event-free survival (EFS) were 60% and 52%, respectively, for the entire cohort. Treatment era (1977-1992 versus 1993-2007) remained an independent prognostic factor for OS on multivariate analysis, with improved outcomes observed in the 1993-2007 era (P = 0.02). The 5-year OS and EFS for the 1993-2007 era were 73% and 60%, respectively. Ifosfamide and etoposide based chemotherapy and surgery were more routinely used in the 1993-2007 era (P < 0.01). The 5-year local failure rate (LFR) was 14%, with a 5-year LFR of 18% for surgery, 33% for radiation, and 0% for combined surgery and radiation in the 1993-2007 era (P = 0.17). Conclusion. Modern survival outcomes for adults with localized ES are similar to multi-institutional results in children. This improvement over time is associated with treatment intensification with chemotherapy and increased use of surgery. Aggressive LC (combined surgery and radiation) may improve outcomes in poor prognosis patients.

Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic.

OBJECT: Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. METHODS: Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. RESULTS: The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9-416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). CONCLUSIONS: This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

Comparison of trauma mortality and estimated cancer mortality from computed tomography during initial evaluation of intermediate-risk trauma patients.

BACKGROUND: Computed tomography (CT) is the primary source of nontherapeutic medical radiation exposure. Radiation exposure is associated with an increased risk of cancer mortality. Although the risk of cancer mortality is negligible in comparison with that of trauma mortality in high-risk patients, the balance of risk versus benefit in patients with less severe mechanisms of injury is unknown. METHODS: This observational cohort study using a trauma center registry included blunt trauma patients prospectively triaged to an intermediate risk group (level II). Radiation dose was calculated using average dosage for each CT scan. Age-adjusted attributable radiation risk for cancer mortality was calculated using Biological Effects of Ionizing Radiation VII data. RESULTS: Six hundred forty-two level II trauma patients were analyzed, with a mean age of 43.8 years and a median Injury Severity Score of 8. Patients received a median radiation effective dose of 24.7 mSv in the first 24 hours of medical evaluation. Higher Injury Severity Score was associated with greater total radiation dose. Of the four deaths, all were 80 years or older with intracranial injuries. The estimated risk of cancer death attributable to CT exposure was 0.1%. CONCLUSIONS: The risk of mortality from trauma is six times higher than the estimated risk of radiation-induced cancer mortality in intermediate level trauma patients. The mortality due to trauma is greatest in older patients, suggesting lower clinical suspicion is needed to warrant CT studies in this population. Efforts to reduce radiation exposure to trauma patients should focus on young patients with minor injuries.

Long-term follow-up of dose-adapted and reduced-field radiotherapy with or without chemotherapy for central nervous system germinoma.

PURPOSE: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma. METHODS AND MATERIALS: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others. RESULTS: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01). CONCLUSIONS: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used.

Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic.

The purpose of this study was to evaluate long-term survival in patients with nonpilocytic low-grade gliomas (LGGs). Records of 314 adult patients with nonpilocytic LGGs diagnosed between 1960 and 1992 at the Mayo Clinic, Rochester, Minnesota, were retrospectively reviewed. The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). Median age at diagnosis was 36 years. Median follow-up was 13.6 years. Operative pathology revealed pure astrocytoma in 181 patients (58%), oligoastrocytoma in 99 (31%), and oligodendroglioma in 34 (11%). Gross total resection (GTR) was achieved in 41 patients (13%), radical subtotal resection (rSTR) in 33 (11%), subtotal resection in 130 (41%), and biopsy only in 110 (35%). Median OS was 6.9 years (range, 1 month-38.5 years). Adverse prognostic factors for OS identified by multivariate analysis were tumor size 5 cm or larger, pure astrocytoma histology, Kernohan grade 2, undergoing less than rSTR, and presentation with sensory motor symptoms. Statistically significant adverse prognostic factors for PFS by multivariate analysis were only tumor size 5 cm or larger and undergoing less than rSTR. In patients who underwent less than rSTR, radiotherapy (RT) was associated with improved OS and PFS. A substantial proportion of patients have a good long-term prognosis after GTR and rSTR, with nearly half of patients free of recurrence 10 years after diagnosis. Postoperative RT was associated with improved OS and PFS and is recommended for patients after subtotal resection or biopsy.