Treatment of Children With Medulloblastomas With Reduced-Dose Craniospinal Radiation Therapy and Adjuvant Chemotherapy: A Children's Cancer Group Study

1999 ◽  
Vol 17 (7) ◽  
pp. 2127-2127 ◽  
Author(s):  
Roger J. Packer ◽  
Joel Goldwein ◽  
H. Stacy Nicholson ◽  
L. Gilbert Vezina ◽  
Jeffrey C. Allen ◽  
...  

PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% ± 4% at 3 years and 79% ± 7% at 5 years. Sites of relapse for the14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.

2021 ◽  
pp. JCO.20.03128
Author(s):  
Sue S. Yom ◽  
Pedro Torres-Saavedra ◽  
Jimmy J. Caudell ◽  
John N. Waldron ◽  
Maura L. Gillison ◽  
...  

PURPOSE Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven. PATIENTS AND METHODS In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI). RESULTS Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( P = .04). For IMRT, 2-year PFS was 87.6% ( P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( P = .56). CONCLUSION The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6064-6064
Author(s):  
Zhi Hui Wang ◽  
Peijian Peng ◽  
Siyang Wang ◽  
Yumeng Liu ◽  
Zhong Lin

6064 Background: Radiation therapy is the only curative treatment modality for nonmetastatic nasopharyngeal cancer (NPC). Concurrent chemoradiation (CCRT) is the standard treatment strategy for NPC in locally advanced stages. However, the results after such treatment are suboptimal. Clearly, novel treatment strategies are needed to further improve patients’ survival rates. This trial aimed to determine the safety and efficacy of a new treatment strategy. Methods: Patients with stage III – IVa-b NPC received TP (docetaxel 75 mg/m2, cisplatin 75 mg/m2 every 3 weeks for 2-3 cycles) followed by cisplatin chemotherapy concurrently with either 3-dimentional conformal radiation therapy or intensity-modulated radiation therapy plus gemcitabine (1000mg/m2 every 2 weeks for 2 cycles) as adjuvant chemotherapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.4.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-OIC-17011464. Results: From July 2010 to July 2017, 20 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 90% (3 complete responses [CRs] and 15 partial responses [PRs]) after two or three cycles of induction chemotherapy (ICT) and 100% (17 CRs and three PRs) after CCRT plus gemcitabine adjuvant chemotherapy, respectively. With a median follow-up time of 41 months, the 3-year overall survival rates were 90% (18/20,95% confidence interval [CI], 76.9%-100%).The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 80% (16/20,95% CI, 62.5%-97.5%), 85% (17/20,95% CI, 69.4%-100%),95% (19/20,95% CI, 85,4%-100%), respectively. The most frequent grade 3–4 toxicities were neutropenia (3/20,15%) and nausea (2/20,10%) after ICT and thrombocytopenia (6/20,30%) and leukopenia (6/20,30%) after CCRT plus gemcitabine adjuvant chemotherapy. Conclusions: Neoadjuvant TP followed by concurrent chemoradiation plus gemcitabine as adjuvant chemotherapy was well tolerated and produced promising outcomes in patients with LA-NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy. Clinical trial information: ChiCTR-OIC-17011464.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jing Sun ◽  
Can Ouyang ◽  
Xiaoyun Chang ◽  
Aimin Zhang ◽  
Quan Wang ◽  
...  

Abstract Background To explore the survival and side effects of repeated CyberKnife stereotactic body radiation therapy (CK-SBRT) on hepatocellular carcinoma patients. Methods 24 HCC patients were collected at The Fifth Medical Center of PLA General Hospital from November 2011 to July 2016. They received second-course CK-SBRT with a prescribed dose of 50(48–55) Gy/5-8fx, and a single dose of 10 (7–11) Gy/fx. Cumulative overall survival rates (OS), progression-free survival rates (PFS) and local control rates (LC) were calculated by Kaplan-Meier method. Results All patients finished their radiotherapy plans. The 1-,2- and 3-year cumulative OS rate were 95.8,81.1 and 60.8%. The 1-,2- and 3-year LC rate were 95.5,90.7 and 90.7%, respectively. The 1-, 2- and 3-year PFS were 74.8, 49.2 and 39.4%, respectively. 16 patients complained of fatigue during second-course therapy, 2 patients showed Grade 2 gastrointestinal reaction, 1 patient was diagnosed radiation-induced liver disease and none died. PFS was significantly higher in the interval time < 12 months group than in the interval time ≥ 12 months group (p = 0.030). Conclusions It is preliminarily believed that re-CK-SBRT is an effective and safe treatment for HCC patients, but the treatment criteria should be strictly controlled.


2016 ◽  
Vol 32 (2) ◽  
pp. 194-203 ◽  
Author(s):  
Santhosh A. Upadhyaya ◽  
Carl Koschmann ◽  
Karin Muraszko ◽  
Sriram Venneti ◽  
Hugh J. Garton ◽  
...  

Safe maximal surgical resection is the initial treatment of choice for pediatric brainstem low-grade gliomas. Optimal therapy for incompletely resected tumors or that progress after surgery is uncertain. We reviewed the clinical characteristics, therapy, and outcomes of all children with nontectal brainstem low-grade gliomas treated at the University of Michigan between 1993 and 2013. Median age at diagnosis was 6 years; histology was confirmed in 23 of 25 tumors, 64% were pilocytic astrocytoma. Nineteen patients underwent initial tumor resection; 14/19 received no upfront adjuvant therapy. Eight patients in the study had progressive disease; 5 initially resected tumors received chemotherapy at tumor relapse, all with partial or complete radiographic responses. Ten-year progression-free survival is 71% and overall survival, 100%. This single-institution retrospective study demonstrates excellent survival rates for children with brainstem low-grade gliomas. The efficacy of the well-tolerated chemotherapy in this series supports its role in the treatment of unresectable or progressive brainstem low-grade gliomas.


1995 ◽  
Vol 13 (6) ◽  
pp. 1377-1383 ◽  
Author(s):  
R I Jakacki ◽  
P M Zeltzer ◽  
J M Boyett ◽  
A L Albright ◽  
J C Allen ◽  
...  

PURPOSE To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of radiation therapy (RT) and/or chemotherapy. PATIENTS AND METHODS Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen. RESULTS Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease. CONCLUSION (1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure.


Neurosurgery ◽  
2010 ◽  
Vol 66 (4) ◽  
pp. 688-695 ◽  
Author(s):  
Toshinori Hasegawa ◽  
Tatsuya Kobayashi ◽  
Yoshihisa Kida

Abstract OBJECTIVE To determine the limiting dose to the optic apparatus in single-fraction irradiation in patients with craniopharyngioma treated with gamma knife radiosurgery (GKRS). METHODS One hundred patients with 109 craniopharyngiomas treated with GKRS were evaluated with a median follow-up period of 68 months. Tumor volume varied from 0.1 to 36.0 (median, 3.3) cm3. Marginal doses varied from 10 to 18 (median, 11.4) Gy. Maximum dose to any part of the optic apparatus varied from 2 to 18 (median, 10) Gy. RESULTS The actuarial 5- and 10-year overall rates of survival of tumor progression after GKRS were 93% and 88%, respectively. Similarly, the actuarial 5- and 10-year progression-free survival rates were 62% and 52%, respectively. Among 94 patients in whom visual function was evaluable after GKRS, only 3 patients developed radiation-induced optic neuropathy, indicating an overall Kaplan-Meier radiation-induced optic neuropathy rate of 5%. Of these patients, 2 received 15 Gy or greater to the optic apparatus. Another patient who received 8 Gy or less had undergone previous fractionated radiation therapy with a biologically effective dose of 60 Gy. CONCLUSION The optic apparatus seems to be more tolerant of irradiation than previously thought. Careful dose planning is essential, particularly in patients who underwent prior external beam radiation therapy.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi226-vi227
Author(s):  
Katherine Kunigelis ◽  
Bette Kleinschmidt-DeMasters ◽  
D Ryan Ormond

Abstract Pineal parenchymal tumors of intermediate differentiation (PPTID) are rare. Even in the most recent WHO 2016, definitive histological criteria to distinguish grade II from III lesions remain to be defined. While no single institution has large numbers of cases, our experience has been that the clinical course is more varied and complicated than reported. The University of Colorado Health pathology database was queried for cases diagnosed as PPTID, 2006 – 2019, inclusive. Twelve adult patients were identified. Mean age at diagnosis was 40 years (range 26–78). There were 9 female and 3 male patients. Seven patients had well-documented clinical courses at our primary institution. At initial diagnosis, all were treated with surgery and 3/6 documented a gross total resection (GTR). Adjuvant radiation therapy to the resection bed in was administered in 5 of 7 (71%) of patients (4 IMRT, 1 SRS). Mean follow-up time was 71 months (range 13–195); 5/7 (71%) of patients developed a recurrence. Median progression free survival was 37 months (range 13- 73 months), with tendency to be longer for male gender (57.5 versus 17 months in females, p=0.17), and GTR (40 months versus 16 months in subtotal resection, p=0.49). Eighty percent of first recurrent disease had leptomeningeal dissemination. First recurrences were treated with radiation alone in 3 (60%) patients (1 SRS, 1 IMRT), craniospinal radiation with multi-agent chemotherapy in 1 (20%) patient, and surgery with radiation therapy in 1 (20%). At last follow-up, 2 patients (28.5%) had died, with median OS of 168.5 months. Although PPTIDs have a known potential for local recurrence and craniospinal dissemination (quoted as 22% and 10%, respectively in WHO 2016), our data show a more dismal experience with 71% recurrence and 80% dissemination at first recurrence. Lack of standardized therapies results in challenges in individual patient management.


1998 ◽  
Vol 16 (9) ◽  
pp. 3000-3006 ◽  
Author(s):  
V Sandor ◽  
V Stark-Vancs ◽  
D Pearson ◽  
R Nussenblat ◽  
S M Whitcup ◽  
...  

PURPOSE Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.


1994 ◽  
Vol 80 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Brian J. Goldsmith ◽  
William M. Wara ◽  
Charles B. Wilson ◽  
David A. Larson

✓ The authors retrospectively analyzed 140 patients treated at the University of California, San Francisco, from 1967 to 1990 to evaluate the results of radiation therapy (median 5400 cGy) given as an adjuvant to subtotal resection of intracranial meningioma. Of the 140 meningiomas, 117 were benign and 23 were malignant. The median follow-up period was 40 months. The overall survival rate at 5 years was 85% for the benign and 58% for the malignant tumor groups (p = 0.02); the 5-year progression-free survival rates were 89% and 48%, respectively (p = 0.001). For patients with benign meningioma, the 10-year overall and progression-free survival rates were 77%. An improved progression-free survival rate in that group was not related to tumor size but was associated with a younger age (p = 0.01) and treatment after 1980 with innovative technologies (p = 0.002); none of those variables affected the progression-free survival rate in the patients with malignant meningioma. Increased progression-free survival in the benign tumor group was also significantly associated with increasing the minimum radiation dose (p = 0.04). The 5-year progression-free survival rate for patients with benign meningioma treated after 1980 (when computerized tomography or magnetic resonance imaging was used for planning therapy) was 98%, as compared with 77% for patients treated before 1980 (p = 0.002). There were no second central nervous system tumors. Morbidity (3.6%) included sudden blindness or cerebral necrosis and death. When total resection of benign meningioma is not feasible, subtotal resection combined with precise treatment planning techniques and adjuvant radiation therapy can achieve results comparable to those of total resection.


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