Radiation Therapy for Intracranial Germinoma: A Retrospective Study of 133 Patients

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International Journal of Radiation Oncology  Biology  Physics

patients presented with imbalance, and 12% improved after treatment. Regarding posttreatment symptoms, 43 (10%) patients reported any CNVII symptom (53% transient), and 42 (9%) reported any CNVIII symptom (50% transient). Evaluable audiograms were available in 234 patients. Median baseline and posttreatment GR scores were 2 and 3, respectively, indicating a significant trend from serviceable to nonserviceable hearing (P < .001). Among 156 patients with serviceable hearing at baseline, 52% had a decline to non-serviceable hearing at last follow-up. One possible HSRT-related secondary malignancy and two HSRT-induced brainstem injuries were noted. Eleven patients developed hydrocephalus. Conclusion: Treatment of VS with HSRT is an effective option with treatment success in 97% and an acceptable toxicity profile. Nearly 50% of patients with serviceable hearing at baseline maintain hearing function. Smaller median BTV was associated with increased risk of treatment failure, and larger median BTV is more likely to cause clinical symptoms/radiologic progression. Fifty percent of symptoms are transient and nearly 75% occur in patients with treatment success. Improved methods to differentiate treatment effect and tumor progression are needed. Author Disclosure: A.E. Marciscano: None. I. Jusue´-Torres: Research Grant; Salisbury Family Foundation. R. Garg: None. A. Rashid: None. A. Sanyal: None. H.W. Francis: None. M. Lim: None. K.J. Redmond: Research Grant; Elekta Ab Oligometastases research consortium. D. Rigamonti: Research Grant; Nicholl Family Foundation. L.R. Kleinberg: None.

Results: The median follow-up period was 57 months (range, 26e137). The 5-year overall survival, local control and disease-free survival rates were 100%, 100% and 96%, respectively. At 5 or more years after treatment, 3 patients developed local recurrence detectable by diagnostic imaging. Nine patients in total (8 silent and 1 symptomatic patient) satisfied the Cortina consensus criteria without receiving drug therapy, but the remaining 43 patients failed to satisfy the criteria. No post-SRT Grade 2 or higher visual disorder occurred. Symptomatic post-SRT hypopituitarism was observed in 1 patient. Conclusion: Hypofractionated SRT using a robotic radiosurgery system is safe for GH-PA and is rated as effective on the basis of diagnostic imaging findings; however, when SRT is applied to patients with symptomatic GHPA without combination with any other therapy, it may be difficult to satisfy the Cortina consensus criteria in most cases. Further investigations of hypofractionated SRT are warranted to define its role in the treatment of GH-PA. Author Disclosure: H. Iwata: None. K. Sato: None. R. Nomura: None. Y. Tabei: None. I. Suzuki: None. N. Yokota: None. M. Inoue: None. S. Ohta: None. S. Yamada: None. Y. Shibamoto: None.

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Purpose/Objective(s): To evaluate the outcome of radiation therapy in patients with intracranial germinoma. Materials/Methods: From January 1996-August 2013, there were 133 patients with intracranial germinoma (24 patients with pathologically verified germinoma and 109 clinically diagnosed by diagnostic radiation therapy and clinical signs) who were treated in our department. The median age at diagnosis was 15years old (range, 4e51 years old). There were 79 patients with localized germinoma and others with multifocal disease. Radiation therapy used linear accelerator 6MV-X ray, conventional RT for 109 patients, 3D-CRT for 3 patients and IMRT for 21 patients. Treatment field included local field, whole-ventricular irradiation with a boost, whole-brain radiation therapy with a boost and craniospinal irradiation (CSI) with a boost. Radiation therapy dose to the primary site ranged from 29 Gy to 52 Gy (median, 45 Gy), and the prophylactic dose to the whole-ventricular, whole-brain, and spine cord ranged from 17.8 Gy to 36 Gy (median, 25 Gy). Twelve patients were treated by chemoradiation therapy, and the RT dose to the primary site reduced to 36 Gy to 40 Gy for chemotherapy complete remission (CR) patients. Serum and/or CSF beta-human chorionic gonadotropin (bHCG) levels were elevated in most patients. All patients’ endocrine functions were assessed, and 99 patients’ neurocognitive function were evaluated. The median follow-up time was 66 months (range, 10e222 months). Results: The 5-year overall survival and relapse-free survival for 133 patients with intracranial germinoma were 92.9%  2.5% and 88.9%  3.1%. The 10-year overall survival and relapse-free survival were 89.8%  3.9% and 68.7%  8.2%. Relapse was noted in 18 patients. Of 79 patients with localized germinoma, spinal cord failure was found in 2 patients (3.3%) when using WVI and WBRT field, and in 1 of 3 patients with local field irradiation ventricular metastases occurred. In patients with multifocal disease, 4 of 22 patients (18.2%) who did not receive spinal irradiation, spinal cord failure occurred. No treatment failure happened in the chemoradiation group, 3D-CRT and IMRT groups. When the serum b-HCG 10 mIU/mL, 10e100 mIU/mL, and 100 mIU/mL, relapse patients were 2, 3 and 0 (P Z .382); when the CSF bHCG 10 mIU/mL, 10e100 mIU/mL, and 100 mIU/mL, relapse patients were 2, 1, and 1 (P Z .912). In 20 patients (20.2%), neurocognitive decline appeared after radiation therapy. There were 31 patients who needed new endocrine hormone replacement, when

Long-term Results of Hypofractionated Stereotactic Radiation Therapy With a Robotic Radiosurgery System for Growth HormoneSecreting Pituitary Adenoma: Evaluation by Cortina Consensus H. Iwata,1,2 K. Sato,3 R. Nomura,3 Y. Tabei,3 I. Suzuki,3 N. Yokota,4 M. Inoue,5 S. Ohta,5 S. Yamada,6 and Y. Shibamoto2; 1Nagoya Proton Therapy Center, Nagoya, Japan, 2Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Japanese Red Cross Medical Center, Tokyo, Japan, 4Suzukake Central Hospital, Hamamatsu, Japan, 5Yokohama CyberKnife Center, Yokohama, Japan, 6Toranomon Hospital, Tokyo, Japan Purpose/Objective(s): Favorable outcome has been reported for stereotactic radiosurgery (SRS) of growth hormone-secreting pituitary adenoma (GH-PA). Previous reports and SRS treatment, however, have several problems. First, the biochemical criteria for normalization of GH used in earlier and recent reports differ greatly. Recently, the Cortina consensus criteria have been adopted, and satisfaction of a stricter criterion has been recommended. Second, while the targeting accuracy and dose fall-off of stereotactic radiosurgery treatment are excellent, single fraction treatment may not be appropriate for tumors that are large or adjacent to optic pathways because the dose limitation for these structures is thought to be 8e10 Gy when given in a single session. The aim of this study was to evaluate the safety and feasibility of hypofractionated stereotactic radiation therapy (SRT) with a robotic radiosurgery system for GH-PA. Materials/Methods: From September 2001 to October 2012, 52 patients with GH-PA were treated with hypofractionated SRT. Fifteen patients were male and 37 were female. The patient age ranged from 14 to 67 years (median: 35 years). Eight patients had silent GH-PA, and the remaining 44 had a symptomatic type. Only 1 patient was inoperable. The other patients were recurrent cases or those receiving postoperative adjuvant SRT. All patients received pharmacotherapy: dopamine agonist, somatostatin analog and/or GH receptor antagonist. No patients had a history of previous cranial radiation therapy. The marginal doses were 17.4 to 26.8 Gy for the 3-fraction schedule and 20.0 to 32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed in accordance with the Cortina consensus criteria. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0.

1035 Radiation Therapy for Intracranial Germinoma: A Retrospective Study of 133 Patients X. Lian, X.R. Hou, F.Q. Zhang, K. Hu, and J. Shen; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China

Volume 93  Number 3S  Supplement 2015 compared with preradiation therapy, and 26 patients who did not need hormone replacement after radiation therapy. Conclusion: Radiation therapy for intracranial germinoma resulted in excellent treatment outcome. Omitting spinal irradiation was feasible for germinoma with localized disease, but CSI was still recommended for multifocal disease. Serum and/or CSF b-HCG levels had no significant influence on treatment outcome. Author Disclosure: X. Lian: None. X. Hou: None. F. Zhang: None. K. Hu: None. J. Shen: None.

1036 Quality of Life and Locoregional Disease Control Following Stereotactic Body Radiation Therapy in Previously Irradiated Recurrent Head and Neck Cancer I. Zhang, G.S. Gill, A. Sharma, M. Marrero, J.B. Cohen, D. Paul, S. Teckie, and M. Ghaly; North Shore e Long Island Jewish Medical Center, Lake Success, NY Purpose/Objective(s): To evaluate quality of life (QOL) outcomes and disease control following stereotactic body radiation therapy (SBRT) in previously irradiated recurrent head and neck cancer (HNC). Materials/Methods: We reviewed the records of 54 patients who received SBRT for recurrent HNC in a previously irradiated field from 2010 to 2014. SBRT was delivered to protect organs at extreme risk (OARE), defined as structures that approached radiation tolerance after the first course of RT. Delineation of gross tumor volume and OAR was done with deformable image registration, integrating the images and combined dose delivered by all treatment plans. The radiation tolerances of OARE were calculated using total biologically effective doses (BED) for late toxicities. Radiation was delivered using volumetric modulated arc therapy (VMAT) SBRT with OARE as anatomic references to accurately target RT. A dose of 35 Gy to 40 Gy was delivered in 5 fractions with concurrent cetuximab. Patient-reported QOL (PR-QOL) was prospectively acquired using the MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASIHN) and Dysphagia Inventory (MDADI). Acute radiation toxicities were scored using Common Terminology Criteria for Adverse Events version 4.0 guidelines, and late complications were scored by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. Locoregional control and overall survival were measured using the Kaplan-Meier method. Results: Patients who completed the prescribed SBRT and had minimum follow-up of 6 months were included for analysis. A total of 41 patients with 48 recurrences were treated: 20 tumors (42%) in the upper aerodigestive tract, 17 (35%) in the skull base, and 11 (23%) in the neck. Median follow-up was 11.2 months. The median previously delivered RT dose was 64 Gy (range, 30e72 Gy) with a median interval of 2 years (range, 1 month to 24 years) from initial RT to tumor recurrence. SBRT dose of 40 Gy was delivered as definitive therapy in 26 recurrences, and 35 Gy was delivered as adjuvant therapy in 22. The median volume treated with SBRT was 60 mL (range, 4.5e256 mL) with median V90 of 98% and D90 of 85%. One patient developed a grade 3 or higher toxicity of hyoid chondronecrosis. Among the 25 patients who completed the MDASI-HN and MDADI questionnaires, there were no significant differences between PR-QOL before reirradiation and at first follow-up (all P values > .35). Locoregional control at 1 year was 90%. At the time of analysis, 78% of the patients were alive with a 1-year overall survival of 53%. Conclusion: OARE-sparing SBRT for reirradiation of HNC achieves a low rate of severe late toxicities and excellent locoregional control and maintains stable PR-QOL. SBRT with OARE sparing may provide a promising salvage treatment option for patients with in-field recurrence of HNC in whom reirradiation may have been avoided for concerns of intolerable side effects. Further study with longer follow-up is necessary to evaluate this approach in routine practice. Author Disclosure: I. Zhang: None. G.S. Gill: None. A. Sharma: None. M. Marrero: None. J.B. Cohen: None. D. Paul: None. S. Teckie: None. M. Ghaly: None.

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1037 Changes in Lymphocyte-to-Monocyte Ratio During Definitive Chemoradiation Therapy for Locally Advanced Cancers of the Head and Neck Are Prognostic for Survival J. Molitoris,1 J. Hyder,1 A. Engelman,1 N. D’Emic,1 A. Hanlon,2 D.P. Zandberg,3 K.J. Cullen,3 M. Suntharalingam,3 and M.D. Chuong3; 1 University of Maryland Medical Center, Baltimore, MD, 2University of Pennsylvania, Philadelphia, PA, 3University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): Increased systemic inflammation, as measured by increased neutrophil-to-lymphocyte ratio (NLR) and increased platelet-tolymphocyte ratio (PLR), are negative prognostic factors in multiple cancer types. Lymphocyte-to-monocyte ratio (LMR), while not as commonly reported, also appears to correlate with clinical outcomes. Recent studies report that higher pretreatment LMR is associated with improved overall survival (OS). However, the significance of LMR has not been reported for cancers of the Head and Neck (H&N). Materials/Methods: We retrospectively identified patients treated with definitive chemoradiation therapy (CRT) for H&N cancer at our institution between 2000 and 2014 who had complete blood counts with differential (CBCd) performed through treatment. Of over 600 patients identified, 100 patients had available CBCd information from within 2 weeks prior to treatment and 2 weeks after the conclusion of treatment. Of these, 93 patients had CBCd data from weeks 2 to 3 during CRT. We evaluated pre(TP1), mid- (TP2), and posttreatment (TP3) values for absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR for each patient. We also evaluated changes (TP1 minus TP2; TP1 minus TP3) in ALC, AMC, and LMR. Univariate analysis (UVA) was performed for the values tabulated along with age, gender, subsite involvement, T stage, N stage, AJCC stage, grade, and chemotherapy use. Factors found to be significant on UVA were analyzed in multivariate analysis (MVA). Cutoff values were determined for inflammatory variables that were significant on MVA. The Kaplan-Meier method was used to determine OS. Results: Median OS was 46.5 months and median follow-up was 94 months. Median age at diagnosis was 56.9 years. Median ALC decreased during treatment from 1.7 (kcells/mL-all) at TP1 to 0.5 at TP2 and 0.6 at TP3. On the other hand, median AMC did not significantly change during treatment: 0.6 (TP1), 0.4 (TP2), and 0.5 (TP3). Median LMR decreased from 2.69 (TP1) to 1.29 (TP2) and 1.15 (TP3). On UVA, a decrease in LMR between TP1 and TP2 was significant for improved OS. On MVA, a decrease in LMR between TP1 and TP2 was associated with a decreased risk of death (hazard ratio [HR] Z 0.506, 95% CI: Z 0.408e0.909, P Z .0245). An LMR decrease of greater than 1.31 between TP1 and TP2 was associated with improved median survival (11.9 vs 4.1 years; P Z .035). Conclusion: This is the first study of LMR in H&N cancer patients who received definitive CRT. While higher pretreatment LMR values have been shown to confer a better prognosis in other disease sites, this study is the first to evaluate LMR changes during definitive CRT for H&N cancer. We observed changes in LMR within the first several weeks of CRT, and our data suggest that LMR increase early in treatment is associated with a statistically significantly worse prognosis. We are now studying what treatment-related factors may have affected the LMR. Author Disclosure: J. Molitoris: None. J. Hyder: None. A. Engelman: None. N. D’Emic: None. A. Hanlon: Consultant; University of Maryland. D.P. Zandberg: None. K.J. Cullen: None. M. Suntharalingam: None. M.D. Chuong: None.

1038 Exploratory Assessment of Swallowing Muscle Dose Volume Parameters With Chronic Dysphagia in Patients Receiving Head and Neck Chemoradiation Therapy T.M. Dale,1,2 K.A. Hutcheson,2 A.S.R. Mohamed,3 G.B. Gunn,2 D.I. Rosenthal,2 and C.D. Fuller3; 1Baylor College of Medicine, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Houston, TX, 3 MD Anderson Cancer Center, Houston, TX