Benjamin Farnia

Clinical outcomes and patterns of failure in pineoblastoma: A 30-year, single-institution retrospective review

OBJECTIVE To update outcomes and assess prognostic factors in the modern, multimodality treatment of patients with pineoblastoma. METHODS The medical records of patients with pineoblastoma evaluated at the M.D. Anderson Cancer Center between 1982 and 2012 were reviewed retrospectively. RESULTS Thirty-one patients with medical records suitable for review were identified. The majority of patients were female (67.7%) with a median age at diagnosis of 18.2 years (range, 0.3-52.8 years). Twenty-one patients underwent surgical resection, recorded as gross total (n = 9) or subtotal (n = 12) resections. Thirty patients received radiation with photon-based therapy (n = 16), proton-based therapy (n = 13), or radiosurgery (n = 1) to a median craniospinal irradiation dose of 36 Gy (range, 23.4-40 Gy) and a median focal dose of 54 Gy (range, 40-58.4 Gy). Twenty-eight patients received chemotherapy before (n = 10), during (n = 10), and after (n = 22) radiation. Median overall survival was 8.7 years for the entire cohort, with 2-, 5-, and 10- year actuarial rates of 89.5%, 69.4%, and 48.6%, respectively. Median disease-free survival was 10 years with 2-, 5-, and 10- year actuarial rates of 84.3%, 62.6%, and 55.7%, respectively. Univariate analysis failed to correlate age, sex, or extent of surgical resection with disease-free or overall survival. CONCLUSIONS Modern, multimodality treatment of pineoblastoma yields a high rate of overall survival, with acceptable short- and long-term toxicity. A greater M-stage at presentation and development of disease recurrence correlate with worse overall survival. Patients who received focal radiation initially experienced a greater rate of disease recurrence compared with those treated to the craniospinal axis.

Reirradiation of Recurrent Pediatric Brain Tumors after Initial Proton Therapy

Purpose The use of reirradiation for recurrent pediatric brain tumors has been increasing, but the effect of repeat radiation on critical cranial structures is unknown. Methods and Materials Between July 2009 and May 2013, the records of 12 pediatric patients initially treated with proton therapy and then with reirradiation for recurrent brain tumors were retrospectively reviewed for toxicity and outcomes. Initial and repeat radiation dose distributions were deformed and merged to determine the maximum dose to 0.03 cm3 of the optic chiasm, optic nerves, spinal cord, brainstem, cochleae, pituitary, and uninvolved brain, and to 1 cm3 of the brainstem and brain on individual and composite plans. These dosimetric results were compared with auditory, neurocognitive, ophthalmologic, and endocrine outcomes to identify radiation-associated toxicities. Results Median follow-up was 3.5 years from diagnosis. Median ages at initial and repeat radiation were 4.6 and 6.7 years, respectively. All patients initially received proton radiotherapy to a median tumor dose of 55.8 Gy relative biological effectiveness (RBE) (range, 45 to 60 Gy [RBE]). At progression, patients completed a second course of radiation to local fields (n = 7) or the craniospinal axis (n = 5) with a median tumor dose of 40 Gy (RBE) (range, 20 to 54 Gy [RBE]). Median progression-free survival was 22.7 months from the last day of the second radiation course. No patient developed central nervous system necrosis requiring treatment. Of evaluable patients, none developed radiation-related high-grade hearing loss (n = 11), visual pathway deficit (n = 10), or significant change in pre- and post-reirradiation full-scale intelligence quotient (n = 4). Of 11 evaluable patients, 4 (36.4%) developed secondary hypothyroidism and 1 (9.1%) developed growth hormone deficiency. Conclusion Repeat radiation for recurrent brain tumors after proton therapy may be performed in the pediatric population with acceptable short- and long-term toxicity.

Ethical Analysis as a Tool for Addressing Treatment Controversies: Radiotherapy Timing in Children With Orbital Rhabdomyosarcoma as a Case Example

PURPOSE The treatment of orbital rhabdomyosarcoma is a topic of debate between North American and European clinicians, with the utility of radiation therapy as part of initial management in question. Despite differences in philosophy, the dominant North American approach of upfront radiation and the dominant European approach of radiation only in the event of recurrence yield a similar rate of overall survival. We sought to identify the ethical arguments for each approach. METHODS Established moral principles and appeals in contemporary medical ethics were utilized to identify the ethical arguments supporting each treatment approach. The potential for technologic advances to alter the analysis was considered. RESULTS Emphasizing the principle of beneficence, the North American approach seeks to reduce recurrence rates. In contrast, the European approach seeks to avoid radiation-induced sequelae, emphasizing the principle of nonmaleficence. Both approaches are based on well-established ethical principles, evidence, and clinical experience. Thus, both approaches currently appear to have legitimacy and should be included in the informed consent process. However, if treatment-related toxicity is reduced through improvements in radiation delivery, the North American approach could emerge as ethically superior. CONCLUSIONS Ethical analysis can aid in addressing challenges that arise when professional practices and perspectives differ in the management of cancer patients.

Dosimetric and Toxicity Analyses of Reirradiation for Recurrent Pediatric Brain Tumors

Background: Reirradiation is increasingly used to treat recurrent pediatric brain tumors, but data-driven dose-volume constraints for repeat radiation are lacking. Methods: Records of 12 pediatric patients treated with reirradiation for recurrent brain tumors between July 2009 and May 2013 at MD Anderson Cancer Center were retrospectively reviewed for toxicity and outcomes. To determine dosimetric parameters, Digital Imaging and Communications in Medicine (DICOM) datasets of the initial and repeat radiation plans were deformed and merged to determine the maximum dose to 0.03 cc of the optic chiasm, optic nerves, spinal cord, brainstem, cochleae, pituitary, and normal brain and to 1 cc of the brainstem on the individual and composite plans. Results: Median follow-up was 3.5 years. Median age at initial radiation was 4.5 years and 6.7 years at repeat radiation. Patients had medulloblastoma (n = 4), primitive neuroectodermal tumor (PNET) (n = 2), anaplastic ependymoma (n = 2), or other tumors (n = 4). All patients initially received proton radiotherapy to a median dose of 55.8 cobalt grey equivalent (CGE). At recurrence, patients were treated with intensity-modulated radiation therapy (IMRT) (n = 6), proton (n = 5), or both (n = 1) to a median total dose of 42.5 CGE. All patients completed the planned second course of radiation. At last follow-up, four patients were alive with disease, five were dead, and three had no evidence of disease. No patient developed radiation necrosis. Two patients developed optic pathway defects, likely related to tumor progression. Four patients developed secondary hypothyroidism (median composite maximum dose of 36 CGE to pituitary), and one patient developed growth hormone deficiency (composite maximum dose of 39 CGE to pituitary). Conclusion: Repeat radiation for recurrent brain tumors may be performed in the pediatric population with acceptable shortand long-term toxicity. Establishment of dose-volume guidelines will facilitate treatment planning for these challenging cases.