A. Paumier

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.

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.

Radiotherapy in small-cell lung cancer: Where should it go?

Small-cell lung carcinomas (SCLC) represent less than 20% of all lung cancers. As it is an aggressive tumour, on account of its high and early risk of dissemination, only a third of patients have limited-stage disease at diagnosis. For these patients, the current state-of-the-art treatment involves cisplatin-etoposide chemotherapy combined with chest radiotherapy. Because of the high risk of brain metastases, prophylactic cranial irradiation (PCI) is indicated in good responders and should be part of the standard management of these patients on the basis of a PCI meta-analysis showing a 5% increase in survival at 3 years. The 5-year survival rate reaches 25% in the best series. This progress is subsequent to a better combination of polychemotherapy and both thoracic and cerebral irradiation. In extensive disease, radiotherapy has also a place in the management of SCLC: PCI reduces the risk of brain metastases and significantly improves overall survival, so that cisplatin (or carboplatin)-etoposide followed by PCI in responding patients has become the standard treatment. Many issues are subject for further clinical research concerning timing, volume and schedule of thoracic radiotherapy to be used in combination with chemotherapy regimen. Progress in thoracic radiotherapy can only be achieved by including patients in prospective studies.

Prophylactic cranial irradiation in lung cancer

As multi-modality treatments are now able to ensure better local control and a lower rate of extra cranial metastases, brain relapse has become a major concern in lung cancer. As survival is poor after development of brain metastases in spite of specific treatment, prophylactic cranial irradiation (PCI) has been introduced in the 70s. PCI has been evaluated in randomized trials in both small-cell (SCLC) and non-small-cell (NSCLC) lung cancers to reduce the incidence of brain metastases and possibly increase survival. PCI reduces significantly the BM rate in both limited disease (LD) and extensive disease (ED) SCLC and in non-metastatic NSCLC. Considering SCLC, PCI significantly improves overall survival in LD (from 15% to 20% at 3 years) and ED (from 13% to 27% at 1 year) in patients who respond to first-line treatment; it should thus be part of the standard treatment in all responders in ED and in good responders in LD. No dose-effect relationship for PCI was demonstrated in LD SCLC patients so that the recommended dose is 25Gy in 10 fractions. In NSCLC, even if the risk of brain dissemination is lower than in SCLC, it has become a challenging issue. Studies have identified subgroups at higher risk of brain failure. There are more local treatment possibilities for NSCLC patients with BM, but most of them will eventually recur so that PCI should be reconsidered. Few randomized trials have been performed and they were not able to show an effect on survival as they were underpowered. New trials are needed.

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.

Post-operative radiation therapy.

In completely resected non-small-cell lung cancer (NSCLC) patients with pathologically involved mediastinal lymph nodes (N2), administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of post-operative radiotherapy (PORT) in this group of patients remains controversial. In the PORT meta-analysis published in 1998, the conclusions were that if adjuvant radiotherapy was detrimental to patients with early-stage completely resected NSCLC, the role of PORT in the treatment of tumours with N2 involvement was unclear and further research was warranted. Recent retrospective and non-randomized studies as well as subgroup analyses of recent randomized trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The question of PORT indication is also valid for those patients with proven N2 disease who undergo neo-adjuvant chemotherapy followed by surgery. The risk of local recurrence for N2 patients varies between 20% and 60%. Based on currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, within a multidisciplinary setting, preferably after completion of adjuvant chemotherapy or after surgery if patients have had neo-adjuvant chemotherapy. There is need for new randomized evidence to reassess PORT using modern three-dimensional conformal radiation technique, with attention to normal organ sparing, particularly lung and heart, to reduce the possible additional toxicity. Randomized evidence is needed. A new large international multi-institutional randomized trial Lung ART evaluating PORT in this patient population is now underway, as well as a Chinese study comparing postoperative sequential chemotherapy followed by radiotherapy versus adjuvant chemotherapy alone.