Mithra Ghalibafian

The conundrum of hodgkin lymphoma nodes: To be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines

PURPOSE To develop easily applicable guidelines for the determination of initially involved lymph nodes to be included in the radiation fields. PATIENTS AND METHODS Patients with supra-diaphragmatic Hodgkin lymphoma. All the imaging procedures were carried out with patients in the treatment position. The prechemotherapy PET/CT was coregistered with the postchemotherapy CT simulation for planning purposes. Initially involved lymph nodes were determined on fused prechemotherapy CT and FDG-PET imaging data. The initial assessment was verified with the postchemotherapy CT scan. RESULTS The classic guidelines for determining the involvement of lymph nodes were not easily applicable and did not seem to reflect the exact extent of Hodgkin lymphoma. Three simple steps were used to pinpoint involved lymph nodes. First, FDG-PET scans were meticulously analysed to detect lymph nodes that were overlooked on CT imaging. Second, any morphological and/or functional asymmetry was sought on CT and FDG-PET scans. Third, a decrease in size or the disappearance of initially visible lymph nodes on the prechemotherapy CT scan as compared to the postchemotherapy CT scan was considered as surrogate proof of initial involvement. CONCLUSIONS All the radiological procedures should be performed on patients in the treatment position for proper coregistration. It is highly advisable that all CT and/or CT/PET scans be performed with IV contrast. Using the above-mentioned three simple guidelines, initially involved lymph nodes can be detected with very satisfactory accuracy. It is also emphasized that the classic guidelines (2, 3, 4) can always be used when deemed necessary.

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.

Prospective Coronary Heart Disease Screening in Asymptomatic Hodgkin Lymphoma Patients Using Coronary Computed Tomography Angiography: Results and Risk Factor Analysis

PURPOSE To prospectively investigate the coronary artery status using coronary CT angiography (CCTA) in patients with Hodgkin lymphoma treated with combined modalities and mediastinal irradiation. METHODS AND MATERIALS All consecutive asymptomatic patients with Hodgkin lymphoma entered the study during follow-up, from August 2007 to May 2012. Coronary CT angiography was performed, and risk factors were recorded along with leukocyte telomere length (LTL) measurements. RESULTS One hundred seventy-nine patients entered the 5-year study. The median follow-up was 11.6 years (range, 2.1-40.2 years), and the median interval between treatment and the CCTA was 9.5 years (range, 0.5-40 years). Coronary artery abnormalities were demonstrated in 46 patients (26%). Coronary CT angiography abnormalities were detected in nearly 15% of the patients within the first 5 years after treatment. A significant increase (34%) occurred 10 years after treatment (P=.05). Stenoses were mostly nonostial. Severe stenoses were observed in 12 (6.7%) of the patients, entailing surgery with either angioplasty with stent placement or bypass grafting in 10 of them (5.5%). A multivariate analysis demonstrated that age at treatment, hypertension, and hypercholesterolemia, as well as radiation dose to the coronary artery origins, were prognostic factors. In the group of patients with LTL measurements, hypertension and LTL were the only independent risk factors. CONCLUSIONS The findings suggest that CCTA can identify asymptomatic individuals at risk of acute coronary artery disease who might require either preventive or curative measures. Conventional risk factors and the radiation dose to coronary artery origins were independent prognostic factors. The prognostic value of LTL needs further investigation.

The efficacy and toxicity of EGFR in the settings of radiotherapy: Focus on published clinical trials.

Basic research in solid malignant tumours has led to a wealth of knowledge about this disease process and about novel ways to more effectively target our therapies. Laboratory research continues to identify novel therapeutic targets and moreover, clinical research is identifying effective new treatment regimens. Many preclinical studies in this area have targeted the epidermal growth factor receptor (EGFR) signalling pathway to increase radiosensitivity. The in vitro rationale for targeting EGFR and concurrent ionising radiation is well established, but to date, rare clinical data could provide proof-of-principle. Here we report all the different published clinical trials focusing on efficacy and toxicity in order to clarify and to summarise the present state-of-the-art of this particularly promising combination in solid tumour management.

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.

Low-Dose Radiation Treatment in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Plausible Approach? A Single-Institution Experience in 10 Patients

PURPOSE To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 × 2 Gy) delivered exclusively to tumor sites. METHODS AND MATERIALS Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. RESULTS Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). CONCLUSIONS Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.

Radiothérapie conformationnelle avec modulation d’intensité pour les tumeurs thoraciques : une liaison dangereuse ? Expérience de l’institut Gustave-Roussy dans le traitement des lymphomes hodgkiniens médiastinaux

IMRT is a seducing treatment option in patients with Hodgkin lymphoma mediastinal masses due to the complex form of the tumour masses and their proximity to organs at risk such as the heart and the coronary arteries. This treatment delivery technique remains risky owing to respiratory movements and heart beats. The concomitant use of IMRT and respiratory gating is enticing, but a number of theoretical and practical hurdles remain to be resolved before it can be used in clinical daily practice.

Un cas rare de lymphome B diffus primitif de la prostate et revue de la littérature

Primary malignant non-hodgkin lymphoma involving the prostate is rare. Most of the time, it is associated with extraprostatic disease. We report a case of a 72-year-old patient presenting with acute lower urinary tract irritative symptoms, due to large B-cell lymphoma limited to the prostate. Combination of chemotherapy with extern beam radiotherapy provided long-term local control.