A. Beaudré

Prospective Randomized Comparison of Single-Dose Versus Hyperfractionated Total-Body Irradiation in Patients With Hematologic Malignancies

PURPOSE Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. PATIENTS AND METHODS Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. RESULTS One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. CONCLUSION The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.

Involved-node radiotherapy and modern radiation treatment techniques in patients with Hodgkin lymphoma.

PURPOSE To assess the clinical outcome of the involved-node radiotherapy (INRT) concept using modern radiation treatments (intensity-modulated radiotherapy [IMRT] or deep-inspiration breath-hold radiotherapy [DIBH) in patients with localized supradiaphragmatic Hodgkin lymphoma. METHODS AND MATERIALS All but 2 patients had early-stage Hodgkin lymphoma, and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the INRT concept according to European Organization for Research and Treatment of Cancer guidelines. IMRT was performed with the patient free-breathing. For the adapted breath-hold technique, a spirometer dedicated to DIBH radiotherapy was used. Three-dimensional conformal radiotherapy was performed with those patients. RESULTS Fifty patients with Hodgkin lymphoma (48 patients with primary Hodgkin lymphoma, 1 patient with recurrent disease, and 1 patient with refractory disease) entered the study from January 2003 to August 2008. Thirty-two patients were treated with IMRT, and 18 patients were treated with the DIBH technique. The median age was 28 years (range, 17-62 years). Thirty-four (68%) patients had stage I - (I-IIA) IIA disease, and 16 (32%) patients had stage I - (I-IIB) IIB disease. All but 3 patients received three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). The median radiation doses to patients treated with IMRT and DIBH were, respectively, 40 Gy (range, 21.6-40 Gy) and 30.6 Gy (range, 19.8-40 Gy). Protection of various organs at risk was satisfactory. Median follow-up was 53.4 months (range, 19.1-93 months). The 5-year progression-free and overall survival rates for the whole population were 92% (95% confidence interval [CI], 80%-97%) and 94% (95% CI, 75%-98%), respectively. Recurrences occurred in 4 patients: 2 patients had in-field relapses, and 2 patients had visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in 1 case. CONCLUSIONS Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the INRT concept and modern radiation treatment techniques such as IMRT and DIBH.

Dosimetric Benefits of Intensity-Modulated Radiotherapy Combined With the Deep-Inspiration Breath-Hold Technique in Patients With Mediastinal Hodgkin's Lymphoma

PURPOSE To assess the additional benefits of using the deep-inspiration breath-hold (DIBH) technique with intensity-modulated radiotherapy (IMRT) in terms of the protection of organs at risk for patients with mediastinal Hodgkins disease. METHODS AND MATERIALS Patients with early-stage Hodgkins lymphoma with mediastinal involvement were entered into the study. Two simulation computed tomography scans were performed for each patient: one using the free-breathing (FB) technique and the other using the DIBH technique with a dedicated spirometer. The clinical target volume, planning target volume (PTV), and organs at risk were determined on both computed tomography scans according to the guidelines of the European Organization for Research and Treatment of Cancer. In both cases, 30 Gy in 15 fractions was prescribed. The dosimetric parameters retrieved for the statistical analysis were PTV coverage, mean heart dose, mean coronary artery dose, mean lung dose, and lung V20. RESULTS There were no significant differences in PTV coverage between the two techniques (FB vs. DIBH). The mean doses delivered to the coronary arteries, heart, and lungs were significantly reduced by 15% to 20% using DIBH compared with FB, and the lung V20 was reduced by almost one third. The dose reduction to organs at risk was greater for masses in the upper part of the mediastinum. IMRT with DIBH was partially implemented in 1 patient. This combination will be extended to other patients in the near future. CONCLUSIONS Radiation exposure of the coronary arteries, heart, and lungs in patients with mediastinal Hodgkins lymphoma was greatly reduced using DIBH with IMRT. The greatest benefit was obtained for tumors in the upper part of the mediastinum. The possibility of a wider use in clinical practice is currently under investigation in our department.

IMRT or conformal radiotherapy for adjuvant treatment of retroperitoneal sarcoma

PURPOSE To compare the dose distribution between three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) with six coplanar beams (6b-IMRT) and IMRT with nine coplanar beams (9b-IMRT) during adjuvant radiotherapy for retroperitoneal sarcoma. METHODS AND MATERIALS The 10 most recent patients who had received adjuvant radiotherapy were reviewed. Three different treatment plans were generated (3DCRT, 6b-IMRT and 9b-IMRT) to deliver 50.4 Gy in 28 fractions. The dose delivered to the organs at risk (intestinal cavity (IC), contra- and ipsilateral kidney, liver, stomach and whole body), and the conformity index (CI) were compared. RESULTS The integral dose to the intestinal cavity was similar with the three modalities but the dose distribution was different, with a change-over around 25 Gy: the V50 and the V40 were reduced five- and twofold, respectively, with IMRT compared to 3DCRT, and the V20 was increased by about 25% with IMRT. A similar integral dose was delivered to the whole body with the three modalities. The treated volume (V95 body) was approximately halved with IMRT compared to 3DCRT, and the CI was twice as good with IMRT than with 3DCRT. As expected, the V5 (body) was higher with IMRT compared to 3DCRT (p<0.0001) (a 12% increase with 6b-IMRT and a 21% increase with 9b-IMRT). Compared to 3DCRT, the mean dose delivered to the contralateral kidney increased from 1.5 to 4-4.4 Gy with IMRT. The number of monitor units was increased with IMRT, especially when nine beams were used instead of six. CONCLUSIONS As expected, IMRT greatly reduced the high-dose irradiated volume and increased the low-dose exposure of the intestinal cavity, with a change-over around 25 Gy, compared to 3DCRT. The conformity index was compellingly better with IMRT. The integral dose delivered to the whole body was conserved with both 3DCRT and IMRT. Longer follow-up is needed to assess late toxicities to the small bowel, contralateral kidney and the risk of second cancers.

Optimisation de l’« involved-node radiotherapy » par l’utilisation de la modulation d’intensité dans le lymphome hodgkinien localisé : expérience de l’institut Gustave-Roussy

PURPOSE To assess the clinical outcome of the involved-node radiotherapy concept with the use of intensity modulated radiotherapy (IMRT) in patients with localized supradiaphragmatic Hodgkin lymphoma. PATIENTS AND METHODS Patients with early-stage supradiaphragmatic Hodgkin lymphoma were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy (INRT) concept according to the EORTC guidelines. Intensity modulated radiotherapy was performed free-breathing. RESULTS Forty-seven patients with Hodgkin lymphoma (44 patients with primary Hodgkin lymphoma and three patients with recurrent disease) entered the study from January 2003 to December 2010. The median age was 31 years (range 17 to 62). Thirty patients had stage I-IIA, 14 had stage I-IIB disease and three had relapse. Forty-two patients received three to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The median radiation dose to patients was 36 Gy (range: 20-40). Protection of various organs at risk was satisfactory. The median follow-up was 57.4 months (range: 5.4-94.3). For patients with primary Hodgkin lymphoma, the 5-year survival and 5-year progression-free survival rates were 96% (95% confidence interval: 80-99) and 92% (95% confidence interval: 78-97), respectively. None of the three patients with recurrent disease has relapsed. Recurrences occurred in three patients: one was in-field relapse and two were visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in one case. CONCLUSION Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the involved node irradiation concept and intensity modulated irradiation.

Article originalOptimisation de l’« involved-node radiotherapy » par l’utilisation de la modulation d’intensité dans le lymphome hodgkinien localisé : expérience de l’institut Gustave-RoussyIntensity-modulated radiotherapy and involved-node concept in patients with Hodgkin lymphoma: Experience of the Gustave-Roussy Institute

PURPOSE To assess the clinical outcome of the involved-node radiotherapy concept with the use of intensity modulated radiotherapy (IMRT) in patients with localized supradiaphragmatic Hodgkin lymphoma. PATIENTS AND METHODS Patients with early-stage supradiaphragmatic Hodgkin lymphoma were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy (INRT) concept according to the EORTC guidelines. Intensity modulated radiotherapy was performed free-breathing. RESULTS Forty-seven patients with Hodgkin lymphoma (44 patients with primary Hodgkin lymphoma and three patients with recurrent disease) entered the study from January 2003 to December 2010. The median age was 31 years (range 17 to 62). Thirty patients had stage I-IIA, 14 had stage I-IIB disease and three had relapse. Forty-two patients received three to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The median radiation dose to patients was 36 Gy (range: 20-40). Protection of various organs at risk was satisfactory. The median follow-up was 57.4 months (range: 5.4-94.3). For patients with primary Hodgkin lymphoma, the 5-year survival and 5-year progression-free survival rates were 96% (95% confidence interval: 80-99) and 92% (95% confidence interval: 78-97), respectively. None of the three patients with recurrent disease has relapsed. Recurrences occurred in three patients: one was in-field relapse and two were visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in one case. CONCLUSION Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the involved node irradiation concept and intensity modulated irradiation.

Chordoma in children: Case-report and review of literature

We report an exceptional case of a very late local failure in a 9-year-old boy presenting with a chordoma of the cranio-cervical junction. The child was initially treated with a combination of surgical resection followed by high dose photon-proton radiation therapy. This aggressive therapy allowed a 9-year remission with minimal side-effects. Unfortunately, he subsequently presented with a local failure managed with a second full-dose course of protons. The child died one year later from local bleeding of unclear etiology.

Relationships between Regional Radiation Doses and Cognitive Decline in Children Treated with Cranio-Spinal Irradiation for Posterior Fossa Tumors

Pediatric posterior fossa tumor (PFT) survivors who have been treated with cranial radiation therapy often suffer from cognitive impairments that might relate to IQ decline. Radiotherapy (RT) distinctly affects brain regions involved in different cognitive functions. However, the relative contribution of regional irradiation to the different cognitive impairments still remains unclear. We investigated the relationships between the changes in different cognitive scores and radiation dose distribution in 30 children treated for a PFT. Our exploratory analysis was based on a principal component analysis (PCA) and an ordinary least square regression approach. The use of a PCA was an innovative way to cluster correlated irradiated regions due to similar radiation therapy protocols across patients. Our results suggest an association between working memory decline and a high dose (equivalent uniform dose, EUD) delivered to the orbitofrontal regions, whereas the decline of processing speed seemed more related to EUD in the temporal lobes and posterior fossa. To identify regional effects of RT on cognitive functions may help to propose a rehabilitation program adapted to the risk of cognitive impairment.

Reprint of “Chordoma in children: Case-report and review of literature” ☆

We report an exceptional case of a very late local failure in a 9-year-old boy presenting with a chordoma of the cranio-cervical junction. The child was initially treated with a combination of surgical resection followed by high dose photon-proton radiation therapy. This aggressive therapy allowed a 9-year remission with minimal side-effects. Unfortunately, he subsequently presented with a local failure managed with a second full-dose course of protons. The child died one year later from local bleeding of unclear etiology.