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Organ Motion in Pediatric High-Risk Neuroblastoma (HR-NBL) Patients Using 4-Dimensional Computed Tomography (4DCT)
Volume 96 Number 2S Supplement 2016
3359 Clinical Outcomes of Pediatric Patients With Pelvic Tumors Treated With Proton Therapy A.W.J. Tann,1,2 M.F. McAleer,1 S.L. McGovern,1 D.R. Grosshans,1 W. Huh,3 A.C. Paulino,3 and A. Mahajan1; 1Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 2 Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To report toxicity and survival outcomes of pediatric patients with pelvic tumors treated with proton therapy. Materials/Methods: An IRB approved institutional prospective database to evaluate tumor control and normal tissue outcomes was queried to identify all pediatric patients who received > 36 Gy(RBE) proton therapy to a pelvic tumor between August 2006 and August 2015. Demographics, treatment characteristics, dosimetric data, and clinical outcomes were recorded and analyzed. Adverse events were graded according to CTCAE version 4.0. Local control (LC), progression free survival (PFS), and overall survival (OS) rates were estimated by Kaplan-Meier analysis. Factors associated with event outcomes were determined by Cox regression. Results: Forty-two patients (24 males, 18 females) with a median age 4.3y (range 0.4-17.3y) met study criteria. Tumor histologies included: 21 rhabdomyosarcoma, 10 Ewing sarcoma, 3 osteosarcoma, and 8 other. Thirteen tumors involved the bladder/prostate, 6 sacrum, 1 paratesticular, 2 vagina, 3 perineum, and 17 other locations of the pelvis. Thirty-five patients were treated to the primary site following initial diagnosis (9 had gross total resection, 12 subtotal resection, and 14 biopsy only prior to proton therapy). A median dose of 50.4 Gy(RBE) (range 36-70 Gy(RBE)) was delivered to the pelvic tumor volume. Forty-one patients received chemotherapy prior to proton therapy and 34 received concurrent. Seven patients had febrile neutropenia during radiation; all had chemotherapy before and during radiation therapy. The median follow up for all patients and living patients were 30.7 months (range 1.2-102.9 months) and 37.8 months (same range), respectively. At 3 years, the LC, PFS, and OS rates were 78%, 68% and 75%, respectively. Six patients received proton therapy for recurrent disease, and prior recurrence was an independent predictor of LC (HR 20.9, PZ0.009). Eight patients had local failure; 5 of whom were followed by distant relapse (4 of whom relapsed within 1 year). There were no grade 3 GI or GU acute or early late radiationassociated toxicities. Four patients had clinical or radiographic evidence of pelvic asymmetry. Their follow up ranged from 4.3 to 8.6y, and they were all younger than 10 years of age at the time of radiation treatment. These patients received 41.4 Gy(RBE) to the primary site, and the growth plate of the affected side received > 24 Gy(RBE). Conclusion: In this study of pediatric pelvic tumors treated with proton therapy, we found favorable acute and early late toxicity profiles in addition to good clinical outcomes. Continued follow up is needed to assess long term toxicity and clinical outcomes. Author Disclosure: A.W. Tann: None. M. McAleer: None. S.L. McGovern: None. D.R. Grosshans: None. W. Huh: None. A.C. Paulino: None. A. Mahajan: None.
3360 Development of Secondary Malignant Neoplasms in Pediatric Patients Diagnosed With Glioblastoma or Anaplastic Astrocytoma N.A. Madden,1 J.A. Marascio,1 D. Zaenger,1 B. Rabatic,1 C. McDonough,1 T.S. Johnson,2 F.M. Kong,3 B.G. Dasher,1 W. Martin,1 J.G. Stewart,1 J. Howington,1 E.M. Marchan,1 S. Shaaban,1 K. Huang,1 A. Al-Basheer,1 A. Amoush,1 A. Green,1 M. Pishgou,1 C.L. Ferguson,1 and W.F. Mourad1; 1 Augusta University, Augusta, GA, 2Augusta University/GRU Cancer Center, Augusta, GA, 3Department of Radiation Oncology, Augusta University, Augusta, GA Purpose/Objective(s): Glioblastoma (GBM) and anaplastic astrocytoma (AA) are rare pediatric malignancies. These tumors are often treated with
Poster Viewing E555 radiation therapy (RT), which can increase the risk for second malignant neoplasms (SMNs). These tumors can also be associated with genetic predisposition syndromes that increase the risk of secondary malignancy. The risk of second neoplasm in pediatric patients with AA or GBM has not been defined. Materials/Methods: The SEER database was queried to identify patients under age 19 at diagnosis of glioblastoma (ICD-O-3 9440/3) or anaplastic astrocytoma (ICD-O-3 9401/3). Population demographics were assessed. Cause specific (CSS) and overall survival were calculated. A MP-SIR session was utilized to determine secondary. Observed-to-expected ratios (O/E) were calculated with a 2-month latency period and with a latency period of 5 years to evaluate for early and late SMNs in comparison to incidence ratios for the population as a whole. P<0.05 was used to determine statistical significance. Results: 478 patients with anaplastic astrocytoma and 668 patients with glioblastoma were identified. A majority of patients were white (nZ885, 77.2%) and male (nZ651, 56.8%). 17.2% of patients were diagnosed before age 5; 58.1% were diagnosed after age 10. 822 patients received surgery. 69.4% of AAs and 74.5% of GBMs were treated with radiation. At 60 months, CSS and OS for AA were 40.8% and 39.0%, and for GBM were 19.6%, and 18.2%. Ninety-three percent of all deaths were attributed to primary cancer. Combined, AA and GBM had significantly increased development of SMN (O/E 10.26) and solid tumors alone (O/E 11.55). Compared to GBM, patients diagnosed with AA had higher incidences of all SMN (O/E 13.44 vs 7.97) and solid tumors (O/E 15.95 vs 8.58). The rates of CNS tumors and bone and joint tumors were all increased for the combined (O/E 56.79 and 63.83), AA (O/E 70.98 and 55.68), and GBM (O/E 40.57 and 74.79) cohorts, respectively. The combined cohort also had significantly elevated rates of leukemia and colon cancer. Patients treated with RT accounted for all of the increase risk of brain tumors, bone and joint tumors, colon cancer, and leukemia, with normal rates experienced in patients who were not treated with RT. With a latency period of 5 years, the risk of SMN (O/E 5.19), solid tumor (O/E 6.26), and brain tumors (O/E 61.17) remained elevated in those treated with RT, with normalized risk in patients not treated with RT. Conclusion: Pediatric patients with AA and GBM are at a higher risk of developing SMNs if treated with RT. Risk is higher in patients with AA, though this could be due to improved survival and more at risk years. As survival improves with novel therapies, SMNs will become more significant in patients with high grade glial tumors. Author Disclosure: N.A. Madden: None. J.A. Marascio: None. D. Zaenger: None. B. Rabatic: None. C. McDonough: None. T.S. Johnson: None. F. Kong: Honoraria; Varian Medical Systems, Zhejiang Cancer Hospital. B.G. Dasher: None. W. Martin: None. J.G. Stewart: None. J. Howington: None. E.M. Marchan: None. S. Shaaban: None. K. Huang: None. A. Al-Basheer: None. A. Amoush: None. A. Green: None. M. Pishgou: None. C.L. Ferguson: None. W.F. Mourad: None.
3361 Organ Motion in Pediatric High-Risk Neuroblastoma (HR-NBL) Patients Using 4-Dimensional Computed Tomography (4DCT) S. Kannan,1 B.K. Teo,2 T.D. Solberg,3 and C.E. Hill-Kayser2; 1Perelman School of Medicine, Philadelphia, PA, 2University of Pennsylvania, Philadelphia, PA, 3Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): Treatment of HR-NBL requires external beam radiation to the primary site following resection. Radiation therapy planning must take into account motion of the target and adjacent normal anatomy, both of which are poorly understood in the pediatric population. Materials/Methods: We examined 4DCT scans of 15 consecutive pediatric patients treated for HR-NBL, average age 4.2 years. Diaphragm and organs at risk were contoured at full inhale, full exhale, and on free-breathing scans. Maximum displacement of organs between full inhale and full exhale was measured in the anterior, posterior, superior, inferior, left, and right directions, as was displacement of centroids in the A/P, S/I, and L/R
E556
International Journal of Radiation Oncology Biology Physics
axes. Contours on free-breathing scans were compared to those on 4D scans. Results: All organs were analyzed for the maximum displacement in all directions. With the exception of the kidneys, the superior aspect of organs uniformly moved inferiorly during inhale. Overall most organs showed greater displacement of the superior edge as compared to the inferior edge. The lungs showed moderate anterior motion, which was reflected to a lesser degree in centroid-Z motion. With the exception of one spleen that reached maximum inferior position at the 87% breathing phase, the union of inhale and exhale contours encompassed the organ position extremes at all breathing phases and on all axes. No consistent and precise margin could be added to the free-breathing scans to encompass motion observed on the 4D scans; however, on positional extremes, abdominal organs differed no more than 6.3 mm between free-breathing and 4D scans and thoracic organs no more than 9.2 mm. Correlation of organ motion with diaphragmatic motion varied: In the superior direction, correlation was strong for liver (R2 Z 0.84) and spleen (R2 Z 0.51). In the inferior direction, the liver showed a strong correlation at an R2 Z0.48 but the spleen showed almost none. Correlations were weaker for kidneys in both directions. For both inhale-exhale displacement and free-breathing margins, patients were analyzed in subgroups e general anesthesia vs. no anesthesia, age < 3 vs. age 3, and abdominal surgery vs. no surgery. No significant differences between patients based on anesthesia, age, or abdominal surgery were observed. Conclusion: Maximum displacement was along the S/I axis, with the superior aspects of organs moving more than the inferior, implying organ compression with respiration. Liver and spleen exhibited the largest motion, which correlated strongly with the S/I motion of the diaphragm. Overall findings mirrored observations in adults, but with smaller magnitudes, as expected. Full inhale and exhale union volumes included all aspects of motion for all patients with the exception of one organ, underscoring the utility of 4D scanning for customized planning. Author Disclosure: S. Kannan: None. B.K. Teo: None. T.D. Solberg: None. C.E. Hill-Kayser: Employee; university of Pennsylvania Health System.
made to block the thyroid during treatment planning. Post treatment TSH was measured in 19 patients, and free T4 was measured in 18 patients. Mean values were 2.66 mlU/L (range: 0.8-9.16 mlU/L) and 1.15 ng/dl (range: 0.73-1.672 ng/dl), respectively. Reference ranges are 0.46-5 mlU/L and 0.78-2.2ng/dl, respectively. Two patients were noted to have developed hypothyroidism, managed with Synthroid. Another had abnormal thyroid function tests not requiring treatment. Outside of palpation of the thyroid gland, additional medical surveillance including thyroid ultrasound was not performed on any patients in the cohort. Conclusion: Mean dose to the thyroid gland was 6.7 Gy for this population of stage IV Wilms tumor patients. There was a low rate of thyroid dysfunction, but patients were not uniformly screened for thyroid dysfunction. Longer follow up is needed to determine ultimate risks of thyroid dysfunction and secondary thyroid malignancies in this cohort of patients. Attention to blocking the thyroid gland as much as possible when designing radiation fields can potentially mitigate the risks of long-term thyroid effects. Author Disclosure: T. Morgan: None. H. Danish: None. R.H. Nanda: None. L. Meacham: None. N. Esiashvili: None.
3362 Whole-Lung Irradiation for Stage IV Wilms Tumor Patients: Thyroid Dosimetry and Outcomes T. Morgan,1,2 H. Danish,2,3 R.H. Nanda,1,2 L. Meacham,1,4 and N. Esiashvili1,2; 1Emory University, Atlanta, GA, 2Department of Radiation Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, 3Emory University School of Medicine, Atlanta, GA, 4 Department of Pediatrics Divisions of Endocrinology and Hematology/ Oncology, Emory University, Atlanta, GA Purpose/Objective(s): Dysfunction of the thyroid gland has been associated with radiation therapy among childhood cancer survivors. For stage IV Wilms tumor patients, the current approach is to deliver whole lung irradiation (WLI) to residual pulmonary disease after chemotherapy; the use of WLI was previously even more ubiquitous. This treatment increases the risk of radiation dose exposure to the thyroid gland. The risk of thyroid dysfunction in this population has not been addressed before to our knowledge. The thyroid dosimetry and follow-up of patients with Wilms tumor treated with WLI is reported. Materials/Methods: Twenty-nine patients with pulmonary metastases from Wilms tumor who underwent WLI from 2000-2012 at a single institution were reviewed. The thyroid gland was contoured if not already done so, and the dose to the thyroid gland in each case was calculated. Thyroid function test results and management of thyroid function abnormalities were extracted from the medical records. Results: Median age at treatment was 5 years (range: 1-9 years), and median follow-up time was 49.9 months (range: 0-178 months). Complete dosimetry data was available for 22 of the 29 patients receiving WLI. Mean dose to the whole lung field was 12 Gy. Mean thyroid volume was 3.3 cc. Average mean dose to the thyroid was 6.7 Gy (range: 1.3-11.7 Gy), and average max dose was 12.4 Gy (range: 7.8-20.3 Gy). No effort was
3363 The Role of Local Therapy to Distant Metastatic Sites in Stage IV Rhabdomyosarcoma A.C. Mohan,1 R. Venkatramani,1 M.F. Okcu,1 J.G. Nuchtern,1 S.A. Vasudevan,1 A. Mahajan,2 N.C. Rainusso,1 W. Allen-Rhoades,1 M. Chintagumpala,1 and A.C. Paulino3; 1Baylor College of Medicine, Houston, TX, 2Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Current treatment strategies for stage IV rhabdomyosarcoma (RMS) include chemotherapy and local treatment for the primary and distant metastatic sites (DMS). Local treatments may include surgery (S), radiation therapy (RT) or both. The purpose of this study is to review the outcomes of stage IV RMS patients and determine the impact of RT and/or S on local control at DMS. Materials/Methods: A retrospective chart review was conducted on all patients diagnosed and treated for stage IV RMS at 1 institution. From 1992-2014, 35 patients with newly diagnosed stage IV RMS were identified. There were 18 males; median age at diagnosis was 6.5 years (range 1-16). Histology was embryonal in 13 (37%), alveolar in 20 (57%) and not specified in 2 (6%). DMS included the lung in 20 (57%), distant lymph nodes in 11 (31%), bone in 10 (29%), soft tissue in 9 (26%) and bone marrow in 4 (11%). Seven (20%) had isolated pulmonary metastasis. For determination of number of DMS, the lungs and bone marrow were considered 1 site each. For bone, soft tissue, and distant nodes, more than 1 site can be recorded according to degree of spread. The median number of DMS was 2 (range, 1 to 6). RT for DMS was given to bilateral lungs (nZ11), distant nodes (nZ4), bone (nZ4) and soft tissue (nZ1). Five patients had resection of DMS in lung (nZ4) and/or bone (nZ2). Median whole lung irradiation (WLI) dose was 15 Gy while median RT dose to bone, soft tissue sites was 50 Gy. All patients received chemotherapy with VAC (nZ31) as the most common regimen. Median follow up was 2 years (range: 6 months to 20 years). Results: The 5-year progression-free (PFS) and overall survival (OS) rates were 20% and 20%. Patients with lung metastasis only had better 5-year OS (43% vs. 10%, PZ 0.01) but not PFS (29% vs. 7%, PZns). None of the patients with bone marrow metastases survived. The 5-year PFS and OS were both improved in patients treated to all DMS (nZ16) compared to those who did not have all DMS treated (nZ19); PFS was 31.3% vs. 0% (PZ0.002) while OS was 37.3% vs. 0% (P<0.001) respectively. Age, gender, histology, and number of DMS did not have an effect on PFS or OS. WLI in patients with pulmonary metastasis was associated with improvement in 5-year local control to the lungs (56% vs. 10%, PZ0.03). Conclusion: Isolated pulmonary metastasis was associated with a better survival, while bone marrow involvement had an ominous prognosis. The use of WLI improved pulmonary control in patients with lung metastasis.
3359 Clinical Outcomes of Pediatric Patients With Pelvic Tumors Treated With Proton Therapy A.W.J. Tann,1,2 M.F. McAleer,1 S.L. McGovern,1 D.R. Grosshans,1 W. Huh,3 A.C. Paulino,3 and A. Mahajan1; 1Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 2 Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To report toxicity and survival outcomes of pediatric patients with pelvic tumors treated with proton therapy. Materials/Methods: An IRB approved institutional prospective database to evaluate tumor control and normal tissue outcomes was queried to identify all pediatric patients who received > 36 Gy(RBE) proton therapy to a pelvic tumor between August 2006 and August 2015. Demographics, treatment characteristics, dosimetric data, and clinical outcomes were recorded and analyzed. Adverse events were graded according to CTCAE version 4.0. Local control (LC), progression free survival (PFS), and overall survival (OS) rates were estimated by Kaplan-Meier analysis. Factors associated with event outcomes were determined by Cox regression. Results: Forty-two patients (24 males, 18 females) with a median age 4.3y (range 0.4-17.3y) met study criteria. Tumor histologies included: 21 rhabdomyosarcoma, 10 Ewing sarcoma, 3 osteosarcoma, and 8 other. Thirteen tumors involved the bladder/prostate, 6 sacrum, 1 paratesticular, 2 vagina, 3 perineum, and 17 other locations of the pelvis. Thirty-five patients were treated to the primary site following initial diagnosis (9 had gross total resection, 12 subtotal resection, and 14 biopsy only prior to proton therapy). A median dose of 50.4 Gy(RBE) (range 36-70 Gy(RBE)) was delivered to the pelvic tumor volume. Forty-one patients received chemotherapy prior to proton therapy and 34 received concurrent. Seven patients had febrile neutropenia during radiation; all had chemotherapy before and during radiation therapy. The median follow up for all patients and living patients were 30.7 months (range 1.2-102.9 months) and 37.8 months (same range), respectively. At 3 years, the LC, PFS, and OS rates were 78%, 68% and 75%, respectively. Six patients received proton therapy for recurrent disease, and prior recurrence was an independent predictor of LC (HR 20.9, PZ0.009). Eight patients had local failure; 5 of whom were followed by distant relapse (4 of whom relapsed within 1 year). There were no grade 3 GI or GU acute or early late radiationassociated toxicities. Four patients had clinical or radiographic evidence of pelvic asymmetry. Their follow up ranged from 4.3 to 8.6y, and they were all younger than 10 years of age at the time of radiation treatment. These patients received 41.4 Gy(RBE) to the primary site, and the growth plate of the affected side received > 24 Gy(RBE). Conclusion: In this study of pediatric pelvic tumors treated with proton therapy, we found favorable acute and early late toxicity profiles in addition to good clinical outcomes. Continued follow up is needed to assess long term toxicity and clinical outcomes. Author Disclosure: A.W. Tann: None. M. McAleer: None. S.L. McGovern: None. D.R. Grosshans: None. W. Huh: None. A.C. Paulino: None. A. Mahajan: None.
3360 Development of Secondary Malignant Neoplasms in Pediatric Patients Diagnosed With Glioblastoma or Anaplastic Astrocytoma N.A. Madden,1 J.A. Marascio,1 D. Zaenger,1 B. Rabatic,1 C. McDonough,1 T.S. Johnson,2 F.M. Kong,3 B.G. Dasher,1 W. Martin,1 J.G. Stewart,1 J. Howington,1 E.M. Marchan,1 S. Shaaban,1 K. Huang,1 A. Al-Basheer,1 A. Amoush,1 A. Green,1 M. Pishgou,1 C.L. Ferguson,1 and W.F. Mourad1; 1 Augusta University, Augusta, GA, 2Augusta University/GRU Cancer Center, Augusta, GA, 3Department of Radiation Oncology, Augusta University, Augusta, GA Purpose/Objective(s): Glioblastoma (GBM) and anaplastic astrocytoma (AA) are rare pediatric malignancies. These tumors are often treated with
Poster Viewing E555 radiation therapy (RT), which can increase the risk for second malignant neoplasms (SMNs). These tumors can also be associated with genetic predisposition syndromes that increase the risk of secondary malignancy. The risk of second neoplasm in pediatric patients with AA or GBM has not been defined. Materials/Methods: The SEER database was queried to identify patients under age 19 at diagnosis of glioblastoma (ICD-O-3 9440/3) or anaplastic astrocytoma (ICD-O-3 9401/3). Population demographics were assessed. Cause specific (CSS) and overall survival were calculated. A MP-SIR session was utilized to determine secondary. Observed-to-expected ratios (O/E) were calculated with a 2-month latency period and with a latency period of 5 years to evaluate for early and late SMNs in comparison to incidence ratios for the population as a whole. P<0.05 was used to determine statistical significance. Results: 478 patients with anaplastic astrocytoma and 668 patients with glioblastoma were identified. A majority of patients were white (nZ885, 77.2%) and male (nZ651, 56.8%). 17.2% of patients were diagnosed before age 5; 58.1% were diagnosed after age 10. 822 patients received surgery. 69.4% of AAs and 74.5% of GBMs were treated with radiation. At 60 months, CSS and OS for AA were 40.8% and 39.0%, and for GBM were 19.6%, and 18.2%. Ninety-three percent of all deaths were attributed to primary cancer. Combined, AA and GBM had significantly increased development of SMN (O/E 10.26) and solid tumors alone (O/E 11.55). Compared to GBM, patients diagnosed with AA had higher incidences of all SMN (O/E 13.44 vs 7.97) and solid tumors (O/E 15.95 vs 8.58). The rates of CNS tumors and bone and joint tumors were all increased for the combined (O/E 56.79 and 63.83), AA (O/E 70.98 and 55.68), and GBM (O/E 40.57 and 74.79) cohorts, respectively. The combined cohort also had significantly elevated rates of leukemia and colon cancer. Patients treated with RT accounted for all of the increase risk of brain tumors, bone and joint tumors, colon cancer, and leukemia, with normal rates experienced in patients who were not treated with RT. With a latency period of 5 years, the risk of SMN (O/E 5.19), solid tumor (O/E 6.26), and brain tumors (O/E 61.17) remained elevated in those treated with RT, with normalized risk in patients not treated with RT. Conclusion: Pediatric patients with AA and GBM are at a higher risk of developing SMNs if treated with RT. Risk is higher in patients with AA, though this could be due to improved survival and more at risk years. As survival improves with novel therapies, SMNs will become more significant in patients with high grade glial tumors. Author Disclosure: N.A. Madden: None. J.A. Marascio: None. D. Zaenger: None. B. Rabatic: None. C. McDonough: None. T.S. Johnson: None. F. Kong: Honoraria; Varian Medical Systems, Zhejiang Cancer Hospital. B.G. Dasher: None. W. Martin: None. J.G. Stewart: None. J. Howington: None. E.M. Marchan: None. S. Shaaban: None. K. Huang: None. A. Al-Basheer: None. A. Amoush: None. A. Green: None. M. Pishgou: None. C.L. Ferguson: None. W.F. Mourad: None.
3361 Organ Motion in Pediatric High-Risk Neuroblastoma (HR-NBL) Patients Using 4-Dimensional Computed Tomography (4DCT) S. Kannan,1 B.K. Teo,2 T.D. Solberg,3 and C.E. Hill-Kayser2; 1Perelman School of Medicine, Philadelphia, PA, 2University of Pennsylvania, Philadelphia, PA, 3Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): Treatment of HR-NBL requires external beam radiation to the primary site following resection. Radiation therapy planning must take into account motion of the target and adjacent normal anatomy, both of which are poorly understood in the pediatric population. Materials/Methods: We examined 4DCT scans of 15 consecutive pediatric patients treated for HR-NBL, average age 4.2 years. Diaphragm and organs at risk were contoured at full inhale, full exhale, and on free-breathing scans. Maximum displacement of organs between full inhale and full exhale was measured in the anterior, posterior, superior, inferior, left, and right directions, as was displacement of centroids in the A/P, S/I, and L/R
E556
International Journal of Radiation Oncology Biology Physics
axes. Contours on free-breathing scans were compared to those on 4D scans. Results: All organs were analyzed for the maximum displacement in all directions. With the exception of the kidneys, the superior aspect of organs uniformly moved inferiorly during inhale. Overall most organs showed greater displacement of the superior edge as compared to the inferior edge. The lungs showed moderate anterior motion, which was reflected to a lesser degree in centroid-Z motion. With the exception of one spleen that reached maximum inferior position at the 87% breathing phase, the union of inhale and exhale contours encompassed the organ position extremes at all breathing phases and on all axes. No consistent and precise margin could be added to the free-breathing scans to encompass motion observed on the 4D scans; however, on positional extremes, abdominal organs differed no more than 6.3 mm between free-breathing and 4D scans and thoracic organs no more than 9.2 mm. Correlation of organ motion with diaphragmatic motion varied: In the superior direction, correlation was strong for liver (R2 Z 0.84) and spleen (R2 Z 0.51). In the inferior direction, the liver showed a strong correlation at an R2 Z0.48 but the spleen showed almost none. Correlations were weaker for kidneys in both directions. For both inhale-exhale displacement and free-breathing margins, patients were analyzed in subgroups e general anesthesia vs. no anesthesia, age < 3 vs. age 3, and abdominal surgery vs. no surgery. No significant differences between patients based on anesthesia, age, or abdominal surgery were observed. Conclusion: Maximum displacement was along the S/I axis, with the superior aspects of organs moving more than the inferior, implying organ compression with respiration. Liver and spleen exhibited the largest motion, which correlated strongly with the S/I motion of the diaphragm. Overall findings mirrored observations in adults, but with smaller magnitudes, as expected. Full inhale and exhale union volumes included all aspects of motion for all patients with the exception of one organ, underscoring the utility of 4D scanning for customized planning. Author Disclosure: S. Kannan: None. B.K. Teo: None. T.D. Solberg: None. C.E. Hill-Kayser: Employee; university of Pennsylvania Health System.
made to block the thyroid during treatment planning. Post treatment TSH was measured in 19 patients, and free T4 was measured in 18 patients. Mean values were 2.66 mlU/L (range: 0.8-9.16 mlU/L) and 1.15 ng/dl (range: 0.73-1.672 ng/dl), respectively. Reference ranges are 0.46-5 mlU/L and 0.78-2.2ng/dl, respectively. Two patients were noted to have developed hypothyroidism, managed with Synthroid. Another had abnormal thyroid function tests not requiring treatment. Outside of palpation of the thyroid gland, additional medical surveillance including thyroid ultrasound was not performed on any patients in the cohort. Conclusion: Mean dose to the thyroid gland was 6.7 Gy for this population of stage IV Wilms tumor patients. There was a low rate of thyroid dysfunction, but patients were not uniformly screened for thyroid dysfunction. Longer follow up is needed to determine ultimate risks of thyroid dysfunction and secondary thyroid malignancies in this cohort of patients. Attention to blocking the thyroid gland as much as possible when designing radiation fields can potentially mitigate the risks of long-term thyroid effects. Author Disclosure: T. Morgan: None. H. Danish: None. R.H. Nanda: None. L. Meacham: None. N. Esiashvili: None.
3362 Whole-Lung Irradiation for Stage IV Wilms Tumor Patients: Thyroid Dosimetry and Outcomes T. Morgan,1,2 H. Danish,2,3 R.H. Nanda,1,2 L. Meacham,1,4 and N. Esiashvili1,2; 1Emory University, Atlanta, GA, 2Department of Radiation Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, 3Emory University School of Medicine, Atlanta, GA, 4 Department of Pediatrics Divisions of Endocrinology and Hematology/ Oncology, Emory University, Atlanta, GA Purpose/Objective(s): Dysfunction of the thyroid gland has been associated with radiation therapy among childhood cancer survivors. For stage IV Wilms tumor patients, the current approach is to deliver whole lung irradiation (WLI) to residual pulmonary disease after chemotherapy; the use of WLI was previously even more ubiquitous. This treatment increases the risk of radiation dose exposure to the thyroid gland. The risk of thyroid dysfunction in this population has not been addressed before to our knowledge. The thyroid dosimetry and follow-up of patients with Wilms tumor treated with WLI is reported. Materials/Methods: Twenty-nine patients with pulmonary metastases from Wilms tumor who underwent WLI from 2000-2012 at a single institution were reviewed. The thyroid gland was contoured if not already done so, and the dose to the thyroid gland in each case was calculated. Thyroid function test results and management of thyroid function abnormalities were extracted from the medical records. Results: Median age at treatment was 5 years (range: 1-9 years), and median follow-up time was 49.9 months (range: 0-178 months). Complete dosimetry data was available for 22 of the 29 patients receiving WLI. Mean dose to the whole lung field was 12 Gy. Mean thyroid volume was 3.3 cc. Average mean dose to the thyroid was 6.7 Gy (range: 1.3-11.7 Gy), and average max dose was 12.4 Gy (range: 7.8-20.3 Gy). No effort was
3363 The Role of Local Therapy to Distant Metastatic Sites in Stage IV Rhabdomyosarcoma A.C. Mohan,1 R. Venkatramani,1 M.F. Okcu,1 J.G. Nuchtern,1 S.A. Vasudevan,1 A. Mahajan,2 N.C. Rainusso,1 W. Allen-Rhoades,1 M. Chintagumpala,1 and A.C. Paulino3; 1Baylor College of Medicine, Houston, TX, 2Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Current treatment strategies for stage IV rhabdomyosarcoma (RMS) include chemotherapy and local treatment for the primary and distant metastatic sites (DMS). Local treatments may include surgery (S), radiation therapy (RT) or both. The purpose of this study is to review the outcomes of stage IV RMS patients and determine the impact of RT and/or S on local control at DMS. Materials/Methods: A retrospective chart review was conducted on all patients diagnosed and treated for stage IV RMS at 1 institution. From 1992-2014, 35 patients with newly diagnosed stage IV RMS were identified. There were 18 males; median age at diagnosis was 6.5 years (range 1-16). Histology was embryonal in 13 (37%), alveolar in 20 (57%) and not specified in 2 (6%). DMS included the lung in 20 (57%), distant lymph nodes in 11 (31%), bone in 10 (29%), soft tissue in 9 (26%) and bone marrow in 4 (11%). Seven (20%) had isolated pulmonary metastasis. For determination of number of DMS, the lungs and bone marrow were considered 1 site each. For bone, soft tissue, and distant nodes, more than 1 site can be recorded according to degree of spread. The median number of DMS was 2 (range, 1 to 6). RT for DMS was given to bilateral lungs (nZ11), distant nodes (nZ4), bone (nZ4) and soft tissue (nZ1). Five patients had resection of DMS in lung (nZ4) and/or bone (nZ2). Median whole lung irradiation (WLI) dose was 15 Gy while median RT dose to bone, soft tissue sites was 50 Gy. All patients received chemotherapy with VAC (nZ31) as the most common regimen. Median follow up was 2 years (range: 6 months to 20 years). Results: The 5-year progression-free (PFS) and overall survival (OS) rates were 20% and 20%. Patients with lung metastasis only had better 5-year OS (43% vs. 10%, PZ 0.01) but not PFS (29% vs. 7%, PZns). None of the patients with bone marrow metastases survived. The 5-year PFS and OS were both improved in patients treated to all DMS (nZ16) compared to those who did not have all DMS treated (nZ19); PFS was 31.3% vs. 0% (PZ0.002) while OS was 37.3% vs. 0% (P<0.001) respectively. Age, gender, histology, and number of DMS did not have an effect on PFS or OS. WLI in patients with pulmonary metastasis was associated with improvement in 5-year local control to the lungs (56% vs. 10%, PZ0.03). Conclusion: Isolated pulmonary metastasis was associated with a better survival, while bone marrow involvement had an ominous prognosis. The use of WLI improved pulmonary control in patients with lung metastasis.