Jan Kriz

Radiotherapy for Early Mediastinal Hodgkin Lymphoma According to the German Hodgkin Study Group (GHSG): The Roles of Intensity-Modulated Radiotherapy and Involved-Node Radiotherapy

PURPOSE Cure rates of early Hodgkin lymphoma (HL) are high, and avoidance of late complications and second malignancies have become increasingly important. This comparative treatment planning study analyzes to what extent target volume reduction to involved-node (IN) and intensity-modulated (IM) radiotherapy (RT), compared with involved-field (IF) and three-dimensional (3D) RT, can reduce doses to organs at risk (OAR). METHODS AND MATERIALS Based on 20 computed tomography (CT) datasets of patients with early unfavorable mediastinal HL, we created treatment plans for 3D-RT and IMRT for both the IF and IN according to the guidelines of the German Hodgkin Study Group (GHSG). As OAR, we defined heart, lung, breasts, and spinal cord. Dose-volume histograms (DVHs) were evaluated for planning target volumes (PTVs) and OAR. RESULTS Average IF-PTV and IN-PTV were 1705 cm(3) and 1015 cm(3), respectively. Mean doses to the PTVs were almost identical for all plans. For IF-PTV/IN-PTV, conformity was better with IMRT and homogeneity was better with 3D-RT. Mean doses to the heart (17.94/9.19 Gy for 3D-RT and 13.76/7.42 Gy for IMRT) and spinal cord (23.93/13.78 Gy for 3D-RT and 19.16/11.55 Gy for IMRT) were reduced by IMRT, whereas mean doses to lung (10.62/8.57 Gy for 3D-RT and 12.77/9.64 Gy for IMRT) and breasts (left 4.37/3.42 Gy for 3D-RT and 6.04/4.59 Gy for IMRT, and right 2.30/1.63 Gy for 3D-RT and 5.37/3.53 Gy for IMRT) were increased. Volume exposed to high doses was smaller for IMRT, whereas volume exposed to low doses was smaller for 3D-RT. Pronounced benefits of IMRT were observed for patients with lymph nodes anterior to the heart. IN-RT achieved substantially better values than IF-RT for almost all OAR parameters, i.e., dose reduction of 20% to 50%, regardless of radiation technique. CONCLUSIONS Reduction of target volume to IN most effectively improves OAR sparing, but is still considered investigational. For the time being, IMRT should be considered for large PTVs especially when the anterior mediastinum is involved.

Long-Term Outcome and Prognostic Factors in Early-Stage Nodal Low-Grade Non-Hodgkin’s Lymphomas Treated with Radiation Therapy

Purpose:Retrospective analysis of therapy results in patients with stage I–II and limited stage III nodal low-grade non-Hodgkin’s lymphoma (NHL).Patients and Methods:The present retrospective study covers 65 patients treated between 1988 and 2006 at the Department of Radiation Oncology, University of Cologne, Germany. 50 patients were treated with radiotherapy alone (EF [extended field]: n = 35, IF/REG [involved field/regional field]: n = 9, TNI/TLI [total nodal/total lymphatic]: n = 6), 15 patients additionally received chemotherapy. Median age was 58 years. 58 patients presented with centroblastic-centrocytic or follicular lymphomas, seven patients had centrocytic lymphomas. Apart from overall and relapse-free survival, relapse patterns were examined and the impacts of patient characteristics and therapy modalities were analyzed.Results:After a median follow-up of 9.1 years, overall 5-year and 10-year survival was 86% and 55%, relapse-free survival was 55% and 37%, respectively. Relapses occurred in 28 patients during the observation period. Overall survival was favorably influenced by low patient age (p = 0.037), centroblastic-centrocytic/follicular histology (p = 0.006), and early disease stage (p = 0.045). Favorable prognostic factors for relapse-free survival were low patient age (p = 0.035) and centroblastic-centrocytic/follicular histology (p = 0.001).Conclusion:Radiotherapy of early-stage low-grade NHL is a curative therapy option, particularly in younger patients and patients with follicular histology. Relapse analysis confirmed the benefits of total nodal or total lymphatic irradiation, although the small number of patients needs to be considered.Ziel:Retrospektive Auswertung der Behandlungsergebnisse bei Patienten mit niedrigmalignen nodalen Non-Hodgkin-Lymphomen (NHL) im Stadium I–II und im limitierten Stadium III.Patienten und Methodik:Die vorliegende retrospektive Studie umfasst 65 Patienten, die zwischen 1988 und 2006 in der Klinik und Poliklinik für Strahlentherapie der Universitäat zu Köln behandelt wurden. 50 Patienten erhielten eine alleinige Radiotherapie (EF [„extended field“]: n = 35, IF/REG [„involved field“]: n = 9, TNI/TLI [„total nodal/total lymphatic“]: n = 6), 15 Patienten zusätzlich eine Chemotherapie. Das mediane Alter betrug 58 Jahre. Bei 58 Patienten handelte es sich um ein zentroblastisch-zentrozytisches bzw. follikuläres Lymphom, bei sieben Patienten um ein zentrozytisches Lymphom. Neben Gesamtüberleben und rezidivfreiem Überleben wurden das Rezidivmuster untersucht und der prognostische Einfluss von Patientencharakteristika und Therapiemodalitäten analysiert.Ergebnisse:Bei einer medianen Nachbeobachtungszeit von 9,1 Jahren betrug das 5- bzw. 10-Jahres-Gesamtüberleben aller Patienten 86% und 55%, das rezidivfreie Überleben 55% und 37%. Bei 28 Patienten kam es im Verlauf zum Auftreten eines Rezidivs. Prognostisch günstigen Einfluss auf das Gesamtüberleben hatten niedriges Patientenalter (p = 0,037), zentroblastisch-zentrozytische/follikuläre Histologie (p = 0,006) und frühes Erkrankungsstadium (p = 0,045). Fur das rezidivfreie Überleben zeigten sich ebenfalls das jungere Alter (p = 0,035) und die zentroblastisch-zentrozytische/follikuläre Histologie (p = 0,001) als günstige Prognosefaktoren.Schlussfolgerung:Die Radiotherapie niedrigmaligner NHL in frühen Stadien ist eine kurative Therapieoption, insbesondere bei jungeren Patienten und follikulärer Histologie. In der Rezidivanalyse erwies sich die totale nodale bzw. totale lymphatische Bestrahlung als vorteilhaft, zu berücksichtigen ist jedoch die geringe Patientenzahl.

Total Skin Electron Beam for Primary Cutaneous T-cell Lymphoma.

PURPOSE Recent trials with low-dose total skin electron beam (TSEB) therapy demonstrated encouraging results for treating primary cutaneous T-cell lymphoma (PCTCL). In this study, we assessed the feasibility of different radiation doses and estimated survival rates of different pathologic entities and stages. METHODS AND MATERIALS We retrospectively identified 45 patients with PCTCL undergoing TSEB therapy between 2000 and 2015. Clinical characteristics, treatment outcomes, and toxicity were assessed. RESULTS A total of 49 courses of TSEB therapy were administered to the 45 patients. There were 26 pathologically confirmed cases of mycosis fungoides (MF) lymphoma, 10 cases of Sézary syndrome (SS), and 9 non-MF/SS PCTCL patients. In the MF patients, the overall response rate (ORR) was 92% (50% complete remission [CR]), 70% ORR in SS patients (50% CR), and 89% ORR in non-MF/SS patients (78% CR). The ORR for MF/SS patients treated with conventional dose (30-36 Gy) regimens was 92% (63% CR) and 75% (25% CR) for low-dose (<30-Gy) regimens (P=.09). In MF patients, the overall survival (OS) was 77 months with conventional dose regimens versus 14 months with low-dose regimens (P=.553). In SS patients, the median OS was 48 versus 16 months (P=.219), respectively. Median event-free survival (EFS) for MF in conventional dose patients versus low-dose patients was 15 versus 8 months, respectively (P=.264) and 19 versus 3 months for SS patients (P=.457). Low-dose regimens had shorter treatment time (P=.009) and lower grade 2 adverse events (P=.043). A second TSEB course was administered in 4 MF patients with 100% ORR. There is a possible prognostic impact of supplemental/boost radiation (P<.001); adjuvant treatment (P<.001) and radiation tolerability (P=.021) were detected. CONCLUSIONS TSEB therapy is an efficacious treatment modality in the treatment of several forms of cutaneous T-cell lymphoma. There is a nonsignificant trend to higher and longer clinical benefit for MF and SS patients receiving conventional dose. Low-dose TSEB regimens are well tolerated and achieve short-term palliation.

Radiotherapy Is Effective for Desmoid Tumors (Aggressive Fibromatosis) - Long-Term Results of a German Multicenter Study

Background: Desmoids (aggressive fibromatosis) are defined as benign neoplasms of the connective tissue that arise from the deep muscle fascia, aponeurosis, tendons, and scar tissue. Recurrence rates between 40 and 80% were reported after surgery alone. We addressed the impact of radiation therapy (RT) in the management of aggressive fibromatosis. Patients and Methods: A large literature review was performed, and the data was compared with the results of a multicenter study of the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD). Results: This analysis included 52 patients treated with RT. 37 patients received postoperative RT (20 patients after R2 resection and 17 patients after R1 resection). 15 patients received RT alone (6 patients with inoperable primary tumor and 9 patients with inoperable recurrent tumor). In the case of postoperative RT, a median dose of 50 Gy (range 50-60 Gy) was used; for definitive RT, a median dose of 55 Gy (range 55-65 Gy) was used. The local control rate was 79% for the whole group. The median follow-up was 44 month (range 8-62 months). Conclusion: Given the large number of patients, these data show that RT is highly effective in the treatment of desmoid tumors. RT is an attractive alternative to mutilating surgery.

Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease.

IntroductionLangerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as “Histiocytosis X”, “Type II Histiocytosis” or “Langerhans Cell Granulomatosis”. Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described.Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis.Methods and materialEight closely cooperating centres collected patients’ data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined.ResultsA total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9–134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen.Radiation treatment was carried out with a median total dose of 15 Gy (range 3–50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed.ConclusionIn the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.

Radiotherapy of splenomegaly

Purpose:Since the 20th century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT.Material and Methods: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects.Results:From 1989–2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with 60Co gamma rays or 5–15MV photons. The fraction size ranged from 10–200 cGy and the total dose per treatment course from 30–1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°.Conclusion:The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.Einleitung:Seit Beginn des 20. Jahrhunderts hat die Radiotherapie (RT) ihren festen Stellenwert in der Behandlung einer symptomatischen Splenomegalie (SM). Die SM tritt bei hämatologischen Erkrankungen auf. Klinisch stehen Kapselschmerz sowie eine Zytopenie im Vordergrund. Die vorliegende Analyse untersucht Indikation, RT-Konzepte und die Effektivität der RT.Material und Methode:Patientendaten der letzten 20 Jahre wurden hinsichtlich klinischer Angaben, RT-Konzepte und Ergebnisse evaluiert. Endpunkte waren Schmerzfreiheit, hämatologisches Ansprechen nach RT sowie therapieassoziierte Nebenwirkungen.Ergebnisse:Zwischen 1989 und 2009 wurden 122 Patienten (79 Männer und 43 Frauen) mit insgesamt 246 RT-Serien behandelt. Folgende Grunderkrankungen waren Ursache für die Splenomegalie: CML (31), CLL (37), Osteomyelofibrose, (23), Polycyt haemia vera (17), AML (5), idiopathische Thrombozytopenie (4), Non-Hodgkin-Lymphom (3) und Plasmozytom (2) (Tabelle1). Die Behandlung erfolgte am Telekobalttherapiegerät oder am Linearbeschleuniger (5–15 MeV Photonen). Es wurden Einzelreferenzdosen zwischen 0,1–2 Gy und Gesamtreferenzdosen zwischen 3–16 Gy appliziert (Tabelle 2). Bei 74,8% der RT-Serien (74,8%), die aufgrund einer schmerzhaften Splenomegalie durchgeführt wurden, konnte eine Schmerzlinderung erzielt werden. Bei 77% der RT-Serien kam es zu einer Verkleinerung der Milz um bis zu 50% (Abbildung 1). 36 Patienten verstarben weniger als 2 Monaten nach Abschluss der RT im Rahmen der infausten Prognose ihrer Grunderkrankung. Bei 73,6% der RT-Serien kam es zu einer Verbesserung hinsichtlich Thrombozytopenien und die Transfusionsfrequenz nahm ab (Tabelle 3). Es wurden lediglich hämatologische Toxizitäten < II° (EORTC/RTOG) beobachtet.Schlussfolgerung:Die vorliegende Analyse belegt die hohe Effektivität der RT bei geringem Nebenwirkungsspektrum. Die RT der symptomatischen Splenomegalie sollte als wirksame palliative Option nicht in Vergessenheit geraten.

The role of PET in Hodgkin's lymphoma and its impact on radiation oncology

A high negative-predictive value of 18F-fluorodeoxyglucose (FDG) PET in early and late response assessment of Hodgkin’s lymphoma patients has been observed in numerous trials. The consequent substantial reduction in the number of chemotherapy cycles and radiotherapy in many current trials seems to be very promising. The criteria used to describe 18F-FDG accumulation are widely standardized, but PET interpretation in a dedicated clinical algorithm is being discussed among study groups and will be evaluated in the ongoing trials. The integration of 18F-FDG PET into radiation treatment planning could have a substantial impact on treatment volumes within the new target definition ‘involved-node radiotherapy’. Involved-node radiotherapy has been proposed as a means to further improve the therapeutic ratio by reducing the risk of acute radiation-induced toxicity and potentially lowering the rate of long-term complications, including secondary malignancies.

Primary Cardiac Angiosarcoma Treated With Positron Emission Tomography/Magnetic Resonance Imaging–Guided Adaptive Radiotherapy

Radiotherapy (RT) for inoperable patients with primary cardiac sarcomas or residual tumor is often limited by the sensitivity of the heart and lung to radiation injury. We describe a novel treatment modality with adaptive radiotherapy (ART) using tumor volume tracking in a 37-year-old woman who presented with unresectable primary cardiac angiosarcoma. The patient was treated using positron emission tomography/magnetic resonance imaging-guided ART with 55.8 Gy concomitant with paclitaxel chemotherapy. In conclusion, the treatment was well tolerated, and a significant tumor volume reduction of ∼ 57% was achieved during radiotherapy, suggesting the effectiveness and tolerability of ART in combination with paclitaxel-based chemotherapy.

Impact of centralized diagnostic review on quality of initial staging in Hodgkin lymphoma: experience of the German Hodgkin Study Group.

Accurate clinical staging is crucial for adequate risk‐adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under‐ or over‐treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re‐evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first‐line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte‐predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk‐adapted first‐line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice.

Advances in Image-Guided Radiation Therapy for Primary Cardiac Angiosarcoma: The Role of PET-CT and MRI

Background: With advances in modern diagnostic and therapeutic modalities, the main goal of intrathoracic radiation treatment is to reduce treatment-related toxicities. Here, we describe a series of cases that involved positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI)-based radiation therapy (RT) for the treatment of primary cardiac angiosarcoma (PCA). Patients and Methods: The medical records of 3 patients who underwent image-guided RT at our department between 2012 and 2015 were analyzed. Results: 3 patients with PCA underwent pre-therapeutic imaging with fluorodeoxyglucose (FDG)-PET/CT (n = 3), as well as PET/MRI (n = 2) or MRI alone (n = 1). 2 patients underwent primary tumor resection (cases 1 and 2). The tumor in case 3 was unresectable and the patient underwent definitive chemoradiation. Intensity-modulated RT was applied with a median RT dose of 50.4 Gy. At the end of the study, 2 of the patients had survived for 35 and 16 months post-treatment (cases 1 and 3, respectively), and no evidence of tumor progression has since been detected. Conclusion: For the cases examined, RT was a feasible and tolerable treatment for PCA, and FDG-PET-MRI successfully characterized each PCA for therapy planning.