Hypofractionated Radiation Therapy For Diffuse Intrinsic Pontine Glioma: A Noninferiority Randomized Study Including 253 Children.

PURPOSE: Pediatric diffuse intrinsic pontine glioma is an orphen disease. This study aimed to confirm the noninferiority of hypofractionated (HF) radiation therapy. Identification of the prognostic factors that determine the overall survival (OS) and progression-free survival (PFS) was the secondary objective. METHODS AND MATERIALS: We randomized 253 patients into 3 arms of radiation therapy regimens: HF1, receiving 39 Gy in 13 fractions; HF2, receiving 45 Gy in 15 fractions; and conventional fractionation (CF), receiving 54 Gy in 30 fractions. The OS and PFS were calculated using Kaplan-Meier methods, and the noninferiority was estimated against the CF arm. RESULTS: The median OS for the HF1, HF2, and CF were 9.6, 8.2, and 8.7 months, respectively. The 1-, 1.5-, and 2-year OS were 34.6%, 17.9%, and 10.7% for HF1; 26.2%, 13.1%, and 4.8% for HF2; and 25.3%, 12.1%, and 8.4% for CF, respectively (P = .3). The hazard ratio was 0.776 and 1.124 for HF1 and HF2, respectively. Considering the noninferiority margin (Δ) of 15% and a power of 90%, the lower inferiority confidence interval for HF1 was -14.34% and for HF2 it was 11.37% (both below Δ), confirming its noninferiority at 18-months OS. Younger patients (2-5 years of age) had better median OS in the whole cohort (11.6 months), HF1 (13.5), and CF (12.1) but not HF2 (6.2) (P = .003). Furthermore, the OS rates at 1, 1.5, and 2 years for children 2 to 5 years of age in the HF2 arm were lower than those in the HF1 and CF arms. However, similar acute and late side effects were reported in the 3 arms. CONCLUSIONS: Two hypofractionated radiation therapy proved to be noninferior to conventional fractionation. Young age (2-5 years) is the only prognostic factor determining both OS and PFS. The young age superiority was lost with a higher hypofractionated radiation therapy dose, necessitating more caution in applying 45 Gy in 15 fractions in younger children (2-5 years of age).

Favorable Outcome After Adjuvant Involved-Field Radiotherapy After Autologous Hematopoietic Stem-Cell Transplantation in Patients With High-Risk Relapsed/Refractory Lymphoma: A Single-Center Experience.

BACKGROUND: Patients with refractory or relapsed lymphoma diagnosed with bulky disease at relapse or with residual disease after salvage treatment are considered to have a dismal outcome, even after autologous hematopoietic stem-cell transplantation, as a result of disease recurrence. To minimize the risk of relapse after receipt of a transplant, involved-field radiotherapy (IFRT) to sites of either bulky or localized residual disease has been utilized; however, the ideal timing for irradiation remains controversial. The aim of this study was to assess the safety and efficacy of IFRT in the early period after transplantation. PATIENTS AND METHODS: We retrospectively evaluated the outcome of 24 autografted patients with relapsed/refractory lymphoma who presented with bulky disease at relapse or who had a persistent localized residual mass after salvage treatment and consolidated with IFRT within 4 months after autografting. RESULTS: No significant toxicity was noticed during the early postradiotherapy period, while graft function was not impaired. After a median follow-up of 3 years for survivors, 21 patients were alive, 19 of whom were event free, while 2 patients died of disease recurrence and 1 died of treatment-related myelodysplastic syndrome. The 3-year overall, lymphoma relapse-free, and event-free survival rates were 86%, 86%, and 82%, respectively. CONCLUSION: Taking into consideration the poor-risk features of the study cohort, IFRT provided early after autologous hematopoietic stem-cell transplantation showed a safe and well-tolerated toxicity profile and demonstrated long-term effective tumor control, as reflected in the promising survival rates.

Stereotactic radiotherapy as an alternative to plaque brachytherapy in retinoblastoma.

Radioactive plaque brachytherapy has an established role for selected patients with retinoblastoma. Newer non-invasive radiotherapy techniques such as stereotactic conformal radiotherapy (SCR) that uses highly accurate positioning to deliver treatment with small beams may be an interesting alternative to brachytherapy. We report a case treated with SCR and compare the dosimetry with that achievable with brachytherapy. With advantages and disadvantages to both, SCR should more often be considered in the management of RB because of the more homogeneous dose within the target volume and similar or lower doses to surrounding normal tissues.

Low-grade oligodendroglioma: an indolent but incurable disease? Clinical article.

OBJECT: The authors reviewed their institutional experience with pure low-grade oligodendroglioma (LGO), correlating outcomes with several variables of possible prognostic values. METHODS: Sixty-nine patients with WHO-classified LGOs were treated between 1992 and 2006 at the McGill University Health Center. Clinical, pathological, and radiological records were carefully reviewed. Demographic characteristics; the nature and duration of presenting symptoms; baseline neurological function; extent of resection; Karnofsky Performance Scale score; preoperative radiological findings including tumor size, location, and absence/presence of enhancement; and pathological data including chromosome arms 1p/19q codeletion and O-methylguanine-DNA methyltransferase promoter gene methylation status were all compiled. The timing and dose of radio- and/or chemotherapy, date of tumor progression, pathological finding at disease progression, treatment at time of disease progression, and status at the last follow-up were also recorded. RESULTS: The median follow-up period was 6.1 years (range 1.3-16.3 years). The majority (78%) of patients presented with seizures; contrast enhancement was initially seen in 16 patients (25%). All patients had undergone an initial surgical procedure: gross-total resection in 27%, partial resection in 59%, and biopsy only in the remaining 13%. Fifteen patients received adjuvant radiotherapy. Data on O-methylguanine-DNA methyltransferase promoter gene methylation status was available in 47 patients (68%) and in all but 1 patient for 1p/19q status. Survival at 5, 10, and 15 years was 83, 63, and 29%, respectively. Multivariate analysis showed that seizures at presentation and the absence of contrast enhancement were the only independent favorable prognostic factors for survival. The 5-, 10-, and 15-year progression-free survival rates were 46, 7.7, and 0%, respectively. CONCLUSIONS: This retrospective review confirms the indolent but progressively fatal nature of LGOs. Contrast enhancement was the most evident single prognostic factor. New treatment strategies are clearly needed in the management of this disease.

Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): a randomized controlled trial.

BACKGROUND: The pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains dismal despite multiple therapeutic attempts. PURPOSE: To compare the results of treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using hypofractionated versus conventional radiotherapy. PATIENTS AND METHODS: Seventy-one newly diagnosed DIPG children were randomized into hypofractionated (HF) (39Gy/13 fractions in 2.6weeks) and conventional (CF) arm (54Gy/30 fractions in 6weeks). RESULTS: The median and one-year overall survival (OS) was 7.8months and 36.4±8.2% for the hypofractionated arm, and 9.5 and 26.2±7.4% for the conventional arm respectively. The 18-month OS difference was 2.2%. The OS hazard ratio (HR) was 1.14 (95% CI: 0.70-1.89) (p=0.59). The hypofractionated arm had a median and one-year progression-free survival (PFS) of 6.6months and 22.5±7.1%, compared to 7.3 and 17.9±7.1% for the conventional arm. The PFS HR was 1.10 (95% CI: 0.67-1.90) (p=0.71). The 18-month PFS difference was 1.1%. These differences exceed the non-inferiority margin. The immediate and delayed side effects were not different in the 2 arms. CONCLUSIONS: Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption.

Dosimetric study of current treatment options for radiotherapy in retinoblastoma.

PURPOSE: To determine the best treatment technique for patients with retinoblastoma requiring radiotherapy to the whole eye. METHODS AND MATERIALS: Treatment plans for 3 patients with retinoblastoma were developed using 10 radiotherapy techniques including electron beams, photon beam wedge pair (WP), photon beam three-dimensional conformal radiotherapy (3D-CRT), fixed gantry intensity-modulated radiotherapy (IMRT), photon volumetric arc therapy (VMAT), fractionated stereotactic radiotherapy, and helical tomotherapy (HT). Dose-volume analyses were carried out for each technique. RESULTS: All techniques provided similar target coverage; conformity was highest for VMAT, nine-field (9F) IMRT, and HT (conformity index [CI] = 1.3) and lowest for the WP and two electron techniques (CI = 1.8). The electron techniques had the highest planning target volume dose gradient (131% of maximum dose received [D(max)]), and the CRT techniques had the lowest (103% D(max)) gradient. The volume receiving at least 20 Gy (V(20Gy)) for the ipsilateral bony orbit was lowest for the VMAT and HT techniques (56%) and highest for the CRT techniques (90%). Generally, the electron beam techniques were superior in terms of brain sparing and delivered approximately one-third of the integral dose of the photon techniques. CONCLUSIONS: Inverse planned image-guided radiotherapy delivered using HT or VMAT gives better conformity index, improved orbital bone and brain sparing, and a lower integral dose than other techniques.

Geometrical uncertainty margins in 3D conformal radiotherapy in the pediatric age group.

PURPOSE: To evaluate set-up variation of pediatric patients undergoing 3D conformal radiotherapy (3DCRT) using electronic portal image device (EPID), in an effort to evaluate the adequacy of the planning target volume (PTV) margin employed for the 3DCRT treatment of pediatric patients. MATERIALS AND METHODS: Set-up data was collected from 48 pediatric patients treated with 3DCRTfor head and neck (31 patients), abdomino-pelvic (9 patients) and chest (8 patients) sites during the period between September 2008 and February 2009. A total of 358 images obtained by EPID were analyzed. The mean (M) and standard deviation (SD) for systematic and random errors were calculated and the results were analyzed. RESULTS: All images were studied in anterior and lateral portals. The systematic errors along longitudinal, lateral and vertical directions in all patients showed an M equal to 1.9, 1.6, and 1.6mm with SD of 1.8, 1.4, and 1.8mm, respectively; (head and neck cases: M equal to 1.5, 1.2, and 1.6mm with SD 1.4, 1.2, and 1.8mm; chest cases: M equal to 2.5, 1.8, and 0.8mm with SD 2.7, 1.7, and 1.2mm, abdomino-pelvic cases: M equal to 2.9, 2.8 and 2.3mm with SD 1.6, 1.2, and 2.3mm). Similarly, the random errors for all patients showed SD of 1.9, 1.6, and 1.8mm, respectively (head and neck cases: SD 1.7, 1.3, and 1.5mm; chest cases: SD 1.2, 1.9, and 2.5mm; abdomino-pelvic cases SD 2.5, 2, and 2.4mm, respectively). Using Van Herk's formula the suggested (PTV) margin around the clinical target volume (CTV) of 5.5mm appears to be adequate. CONCLUSION: The ranges of set-up errors are site specific and depends on many factors.

Stereotactic radiosurgery and radiotherapy in benign intracranial meningioma.

PURPOSE: To investigate the role of stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) in treatment of benign intracranial meningioma. PATIENTS AND METHODS: Between 2003 and 2010, 32 patients with a median age of 44 years (range 21-67 years) were treated with SRS (n=19), and hypo-fractionated SRT (n=13) for intracranial meningioma. Fourteen patients underwent SRS or SRT as their primary treatment, while 18 patients underwent post operative SRS or SRT (PORT). Cumulative progression free survival, overall cumulative survival, toxicity and symptomatology were evaluated. RESULTS: The median follow up period was 39 months (range 6-72 months). The 5 year overall survival and progression free survival were 90 ± 5% and 94 ± 4% after SRT or SRS respectively. Symptoms were improved or stable in 94% of patients. Acute toxicity was mild, and was seen in 41% of patients. Clinically significant late morbidity or new cranial nerve palsies did not occur. CONCLUSION: Stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) are effective and safe treatment modality for local control of meningioma with low risk of significant late toxicity. In case of large tumor size and adjacent critical structures, hypo-fractionated SRT is highly recommended.