Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children

被引:45
作者
Kann, Benjamin H. [1 ]
Park, Henry S. [1 ]
Lester-Coll, Nataniel H. [1 ]
Yeboa, Debra N. [1 ]
Benitez, Viviana [2 ]
Khan, Atif J. [3 ]
Bindra, Ranjit S. [1 ]
Marks, Asher M. [1 ]
Roberts, Kenneth B. [1 ]
机构
[1] Yale Univ, Sch Med, 35 Pk St,LL509, New Haven, CT 06519 USA
[2] Boston Childrens Hosp, New Haven, CT USA
[3] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA
关键词
PROSPECTIVE RANDOMIZED-TRIAL; CRANIOSPINAL RADIATION-THERAPY; STANDARD-RISK MEDULLOBLASTOMA; NERVOUS-SYSTEM TUMORS; ADJUVANT CHEMOTHERAPY; CANCER GROUP; CHILDHOOD MEDULLOBLASTOMA; MAINTENANCE CHEMOTHERAPY; PHASE-III; STAGE;
D O I
10.1001/jamaoncol.2016.2547
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
IMPORTANCE Postoperative radiotherapy to the craniospinal axis is standard-of-care for pediatric medulloblastoma but is associated with long-term morbidity, particularly in young children. With the advent of modern adjuvant chemotherapy strategies, postoperative radiotherapy deferral has gained acceptance in children younger than 3 years, although it remains controversial in older children. OBJECTIVE To analyze recent postoperative radiotherapy national treatment patterns and implications for overall survival in patients with medulloblastoma ages 3 to 8 years. DESIGN, SETTING, AND EXPOSURES Using the National Cancer Data Base, patients ages 3 to 8 years diagnosed as having histologically confirmed medulloblastoma in 2004 to 2012, without distant metastases, who underwent surgery and adjuvant chemotherapy with or without postoperative radiotherapy at facilities nationwide accredited by the Commission on Cancer were identified. Patients were designated as having "postoperative radiotherapy upfront" if they received radiotherapy within 90 days of surgery or "postoperative radiotherapy deferred" otherwise. Factors associated with postoperative radiotherapy deferral were identified using multivariable logistic regression. Overall survival (OS) was compared using Kaplan-Meier analysis with log-rank tests and multivariable Cox regression. Statistical tests were 2-sided. MAIN OUTCOMES AND MEASURES Postoperative radiotherapy utilization and overall survival. RESULTS Among 816 patients, 123 (15.1%) had postoperative radiotherapy deferred, and 693 (84.9%) had postoperative radiotherapy upfront; 36.8% of 3-year-olds and 4.1% of 8-year-olds had postoperative radiotherapy deferred (P<.001). On multivariable logistic regression, variables associated with postoperative radiotherapy deferral were age (odds ratio [OR], 0.57 per year; 95% CI, 0.49-0.67 per year) and year of diagnosis (OR, 1.18 per year; 95% CI, 1.08-1.29 per year). On survival analysis, with median follow-up of 4.8 years, OS was improved for those receiving postoperative radiotherapy upfront vs postoperative radiotherapy deferred (5-year OS: 82.0% vs 63.4%; P<.001). On multivariable analysis, variables associated with poorer OS were postoperative radiotherapy deferral (hazards ratio [HR], 1.95; 95% CI, 1.15-3.31); stage M1-3 disease (HR, 1.86; 95% CI, 1.10-3.16), and low facility volume (HR, 1.75; 95% CI, 1.04-2.94). CONCLUSIONS AND RELEVANCE Our national database analysis reveals a higher-thanexpected and increasing rate of postoperative radiotherapy deferral in children with medulloblastoma ages 3 to 8 years. The analysis suggests that postoperative radiotherapy deferral is associated with worse survival in this age group, even in the modern era of chemotherapy.
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收藏
页码:1574 / 1581
页数:8
相关论文
共 34 条
[1]   PROSPECTIVE RANDOMIZED TRIAL OF CHEMOTHERAPY GIVEN BEFORE RADIOTHERAPY IN CHILDHOOD MEDULLOBLASTOMA - INTERNATIONAL-SOCIETY-OF-PEDIATRIC-ONCOLOGY (SIOP) AND THE (GERMAN)-SOCIETY-OF-PEDIATRIC-ONCOLOGY (GPO) - SIOP-II [J].
BAILEY, CC ;
GNEKOW, A ;
WELLEK, S ;
JONES, M ;
ROUND, C ;
BROWN, J ;
PHILLIPS, A ;
NEIDHARDT, MK .
MEDICAL AND PEDIATRIC ONCOLOGY, 1995, 25 (03) :166-178
[2]   M4 PROTOCOL FOR CEREBELLAR MEDULLOBLASTOMA - SUPRATENTORIAL RADIOTHERAPY MAY NOT BE AVOIDED [J].
BOUFFET, E ;
BERNARD, JL ;
FRAPPAZ, D ;
GENTET, JC ;
ROCHE, H ;
TRON, P ;
CARRIE, C ;
RAYBAUD, C ;
JOANNARD, A ;
LAPRAS, C ;
CHOUX, M ;
CARTON, M ;
AIMARD, L ;
PHILIP, T ;
BRUNATMENTIGNY, M .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1992, 24 (01) :79-85
[3]   Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy [J].
Camara-Costa, Hugo ;
Resch, Anika ;
Kieffer, Virginie ;
Lalande, Clemence ;
Poggi, Geraldina ;
Kennedy, Colin ;
Bull, Kim ;
Calaminus, Gabriele ;
Grill, Jacques ;
Doz, Francois ;
Rutkowski, Stefan ;
Massimino, Maura ;
Kortmann, Rolf-Dieter ;
Lannering, Birgitta ;
Dellatolas, Georges ;
Chevignard, Mathilde .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2015, 92 (05) :978-985
[4]   Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma [J].
Chi, SN ;
Gardner, SL ;
Levy, AS ;
Knapp, EA ;
Miller, DC ;
Wisoff, JH ;
Weiner, HL ;
Finlay, JL .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (24) :4881-4887
[5]   Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols [J].
Dhall, Girish ;
Grodman, Howard ;
Ji, Lingyun ;
Sands, Stephen ;
Gardner, Sharon ;
Dunkel, Ira J. ;
McCowage, Geoffrey B. ;
Diez, Blanca ;
Allen, Jeffrey C. ;
Gopalan, Anjali ;
Cornelius, Albert S. ;
Termuhlen, Amanda ;
Abromowitch, Minnie ;
Sposto, Richard ;
Finlay, Jonathan L. .
PEDIATRIC BLOOD & CANCER, 2008, 50 (06) :1169-1175
[6]   THE TREATMENT OF MEDULLOBLASTOMA - RESULTS OF A PROSPECTIVE RANDOMIZED TRIAL OF RADIATION-THERAPY WITH AND WITHOUT CCNU, VINCRISTINE, AND PREDNISONE [J].
EVANS, AE ;
JENKIN, RDT ;
SPOSTO, R ;
ORTEGA, JA ;
WILSON, CB ;
WARA, W ;
ERTEL, IJ ;
KRAMER, S ;
CHANG, CH ;
LEIKIN, SL ;
HAMMOND, GD .
JOURNAL OF NEUROSURGERY, 1990, 72 (04) :572-582
[7]   Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial [J].
Gajjar, Amar ;
Chintagumpala, Murali ;
Ashley, David ;
Kellie, Stewart ;
Kun, Larry E. ;
Merchant, Thomas E. ;
Woo, Shaio ;
Wheeler, Greg ;
Ahern, Valerie ;
Krasin, Matthew J. ;
Fouladi, Maryam ;
Broniscer, Alberto ;
Krance, Robert ;
Hale, Gregory A. ;
Stewart, Clinton F. ;
Dauser, Robert ;
Sanford, Robert A. ;
Fuller, Christine ;
Lau, Ching ;
Boyett, James M. ;
Wallace, Dana ;
Gilbertson, Richard J. .
LANCET ONCOLOGY, 2006, 7 (10) :813-820
[8]   Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: A report from the children's cancer group [J].
Geyer, JR ;
Sposto, R ;
Jennings, M ;
Boyett, JM ;
Axtell, RA ;
Breiger, D ;
Broxson, E ;
Donahue, B ;
Finlay, JL ;
Goldwein, LW ;
Heier, LA ;
Johnson, D ;
Mazewski, C ;
Miller, DC ;
Packer, R ;
Puccetti, D ;
Radcliffe, J ;
Tao, ML ;
Shiminski-Maher, T .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (30) :7621-7631
[9]   Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children [J].
Grill, J ;
Sainte-Rose, C ;
Jouvet, A ;
Gentet, JC ;
Lejars, O ;
Frappaz, D ;
Doz, F ;
Rialland, X ;
Pichon, F ;
Bertozzi, AI ;
Chastagner, P ;
Couanet, D ;
Habrand, JL ;
Raquin, MA ;
Le Deley, MC ;
Kalifa, C .
LANCET ONCOLOGY, 2005, 6 (08) :573-580
[10]  
Henrich N, 2014, PEDIATR BLOOD CANCER, V61, P1300, DOI 10.1002/pbc.24990