Dirk Neuhof

Radiotherapy for Orbital Lymphoma

Purpose:To analyze the effectiveness of radiotherapy in the management of orbital non-Hodgkins lymphoma (NHL).Patients and Methods:42 patients (median age 64.5 years) were reviewed retrospectively. The median follow-up period was 58 months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive NHLs). 16 patients had advanced NHLs in stages II–IV with orbital involvement (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20–46 Gy) for indolent lymphoma and 44 Gy (20–48 Gy) for aggressive lymphoma. Patients with stage IE were treated with at least 30 Gy.Results:The 5-year local control rate for patients with stage I was 100%, the 5-year overall survival 91%. Two distant relapses were found, but no lymphoma-related death was detected. The 5-year local control rate for patients in stages II, III, and IV was 80%. Two local failures were detected. The 5-year overall survival for the advanced stages was 47%, nine patients with stages III and IV died due to systemic progression of lymphoma. Acute, radiotherapy-related complications grade 3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six patients, treated with doses of > 36 Gy, developed grade 3 complications (four cataract, two dryness).Conclusion:Radiotherapy alone yields excellent local control and overall survival rates in orbital lymphoma stage IE. Local irradiation is also well tolerated and effective in advanced NHL stages with orbital infiltration. Doses of > 36 Gy resulted in an increase of late complications.Ziel:Untersuchung der Effektivität einer Bestrahlung von orbitalen Non-Hodgkin-Lymphomen (NHL).Patienten und Methodik:42 Patienten (medianes Alter 64,5 Jahre) wurden retrospektiv untersucht. Die mediane Nachbeobachtungszeit betrug 58 Monate. 26 Patienten hatten ein orbitales NHL Stadium IE (22 indolente, vier aggressive NHL). 16 Patienten wiesen fortgeschrittene NHL der Stadien II, III und IV mit orbitaler Beteiligung auf (elf indolente, fünf aggressive NHL). Die mediane Dosis für indolente Lymphome betrug 40 Gy (20–46 Gy), für aggressive NHL 44 Gy (20–48 Gy). Patienten im Stadium IE erhielten mindestens 30 Gy.Ergebnisse:Für Patienten im Stadium IE lag die lokale Kontrollrate nach 5 Jahren bei 100%, das Gesamtüberleben bei 91%. Bei zwei dieser Patienten wurde im Verlauf eine systemische Progression diagnostiziert. Kein Patient im Stadium IE verstarb am NHL. Für die Patienten in den Stadien II, III und IV lag die lokale Kontrollrate nach 5 Jahren bei 80%. Zwei Lokalrezidive wurden diagnostiziert. Das Gesamtüberleben für die fortgeschrittenen Stadien betrug nach 5 Jahren 47%; neun Patienten in den Stadien III und IV verstarben lymphombedingt. Akute, bestrahlungsbedingte Nebenwirkungen Grad 3/4 wurden nicht gesehen. Späte Nebenwirkungen Grad 1/2 wurden bei 45% der Patienten gefunden. Sechs Patienten, die mit > 36 Gy behandelt wurden, entwickelten Grad-3-Komplikationen (viermal Katarakt, zweimal Trockenheit).Schlussfolgerung:Mit einer alleinigen Strahlentherapie können bei Orbitalymphomen im Stadium IE exzellente Kontroll- und Überlebensraten erreicht werden. Die lokale Bestrahlung ist bei fortgeschrittenen NHL-Stadien mit Orbitainfiltration gleichfalls effektiv und wird gut toleriert. Dosen von > 36 Gy führten zu einem Anstieg von Spätnebenwirkungen.

Palliative total skin electron beam therapy (TSEBT) for advanced cutaneous T-cell lymphoma

Our aim was to analyze the effectiveness of palliative total skin electron beam therapy (TSEBT) in the management of advanced cutaneous T-cell non-Hodgkins lymphoma (CTCL). Eighteen patients (median age 59 years) with advanced and therapy-refractory CTCL in stages IIB-IV were treated with TSEBT for the first time. The most common histological subtype was Mycosis fungoides (72%). All patients suffered from lymphoma-associated symptoms. Median daily fractions of 1 Gy were administered up to a median total dose of 25 Gy. The median follow-up period was 11 months. Nine patients (50%) achieved a complete response and seven patients (39%) had a limited response. The actuarial one-year progression-free survival was 24%. Four patients (22%) had continuing remission over a median period of six months. Lymphoma associated symptoms were improved in 16 patients (89%). The median overall survival after receiving TSEBT was 12 months, resulting in an actuarial one-year overall survival of 48%. Treatment related acute effects (grade 1 or 2) were observed in all patients during radiation therapy. Transient grade 3 epitheliolyses developed in five patients (28%), late skin effects (grade 1 and 2) in 16 patients (89%), and hypohidrosis was seen in six patients (33%). We conclude that TSEBT is a very efficient and tolerable palliative treatment for patients with advanced CTCL.

Kyphoplasty in patients with multiple myeloma a retrospective comparative pilot study

This retrospective study of 73 myeloma patients with painful vertebral lesions compares clinical and radiomorphological outcomes up to 2 years after additional kyphoplasty, radiation therapy or systemic treatment only.

Radiotherapy for orbital lymphoma : outcome and late effects.

Purpose:To analyze the effectiveness of radiotherapy in the management of orbital non-Hodgkins lymphoma (NHL).Patients and Methods:42 patients (median age 64.5 years) were reviewed retrospectively. The median follow-up period was 58 months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive NHLs). 16 patients had advanced NHLs in stages II–IV with orbital involvement (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20–46 Gy) for indolent lymphoma and 44 Gy (20–48 Gy) for aggressive lymphoma. Patients with stage IE were treated with at least 30 Gy.Results:The 5-year local control rate for patients with stage I was 100%, the 5-year overall survival 91%. Two distant relapses were found, but no lymphoma-related death was detected. The 5-year local control rate for patients in stages II, III, and IV was 80%. Two local failures were detected. The 5-year overall survival for the advanced stages was 47%, nine patients with stages III and IV died due to systemic progression of lymphoma. Acute, radiotherapy-related complications grade 3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six patients, treated with doses of > 36 Gy, developed grade 3 complications (four cataract, two dryness).Conclusion:Radiotherapy alone yields excellent local control and overall survival rates in orbital lymphoma stage IE. Local irradiation is also well tolerated and effective in advanced NHL stages with orbital infiltration. Doses of > 36 Gy resulted in an increase of late complications.Ziel:Untersuchung der Effektivität einer Bestrahlung von orbitalen Non-Hodgkin-Lymphomen (NHL).Patienten und Methodik:42 Patienten (medianes Alter 64,5 Jahre) wurden retrospektiv untersucht. Die mediane Nachbeobachtungszeit betrug 58 Monate. 26 Patienten hatten ein orbitales NHL Stadium IE (22 indolente, vier aggressive NHL). 16 Patienten wiesen fortgeschrittene NHL der Stadien II, III und IV mit orbitaler Beteiligung auf (elf indolente, fünf aggressive NHL). Die mediane Dosis für indolente Lymphome betrug 40 Gy (20–46 Gy), für aggressive NHL 44 Gy (20–48 Gy). Patienten im Stadium IE erhielten mindestens 30 Gy.Ergebnisse:Für Patienten im Stadium IE lag die lokale Kontrollrate nach 5 Jahren bei 100%, das Gesamtüberleben bei 91%. Bei zwei dieser Patienten wurde im Verlauf eine systemische Progression diagnostiziert. Kein Patient im Stadium IE verstarb am NHL. Für die Patienten in den Stadien II, III und IV lag die lokale Kontrollrate nach 5 Jahren bei 80%. Zwei Lokalrezidive wurden diagnostiziert. Das Gesamtüberleben für die fortgeschrittenen Stadien betrug nach 5 Jahren 47%; neun Patienten in den Stadien III und IV verstarben lymphombedingt. Akute, bestrahlungsbedingte Nebenwirkungen Grad 3/4 wurden nicht gesehen. Späte Nebenwirkungen Grad 1/2 wurden bei 45% der Patienten gefunden. Sechs Patienten, die mit > 36 Gy behandelt wurden, entwickelten Grad-3-Komplikationen (viermal Katarakt, zweimal Trockenheit).Schlussfolgerung:Mit einer alleinigen Strahlentherapie können bei Orbitalymphomen im Stadium IE exzellente Kontroll- und Überlebensraten erreicht werden. Die lokale Bestrahlung ist bei fortgeschrittenen NHL-Stadien mit Orbitainfiltration gleichfalls effektiv und wird gut toleriert. Dosen von > 36 Gy führten zu einem Anstieg von Spätnebenwirkungen.

Outcome and late complications of radiotherapy in patients with unicentric Castleman disease

Castleman disease is a rare lymphoproliferative disorder. Surgery is considered standard therapy for the unicentric type. However, case reports have documented favorable responses to radiotherapy. The aim of this study was to analyse the clinical outcomes of five patients with unicentric Castleman disease treated with radiotherapy between 1991 and 2005. Mediastinal lymph nodes were the most common site of disease (four patients). Three patients were treated with radiotherapy alone, two patients with surgery and radiotherapy. Patients were treated with radiotherapy doses ranging from 40 Gy to 50 Gy. The median follow-up was 12 months (range, 3–175 months). During follow-up only one patient had progressive disease and died of Castleman disease. At the time of last follow-up two patients were in complete remission, one patient in partial remission, and one patient had stable disease. One patient showed serious acute and late toxicities. At the end of radiotherapy a paraneoplastic pemphigus vulgaris occurred, and eight to 11 months after radiotherapy a stenosis of the esophagus, of the left bronchus, and of the trachea due to scars. The study shows that unicentric Castleman disease is successfully treated with radiotherapy. However, for detection of possible complications as pemphigus vulgaris or stenosis of the esophagus or trachea an accurate follow-up is necessary.

Indolent Stage IE Non-Hodgkin’s Lymphoma of the Orbit: Results after Primary Radiotherapy

Aims: Primary non-Hodgkin’s lymphoma (NHL) of the orbit is uncommon, representing approximately 8% of extranodal NHLs. Twenty-two patients with indolent stage IE NHL were reviewed retrospectively to analyze the outcome and late effects of primary local radiotherapy. Materials and Methods: The median age at first diagnosis was 63.5 years (range 24–82 years). Extranodal mucosa-associated lymphoid tissue lymphoma (n = 15) was the most common histological subtype of NHL, followed by follicular (n = 6) and lymphoplasmacytic lymphoma (n = 1). Radiotherapy was performed using a linear accelerator. The median radiation dose was 40 Gy (range 30–46 Gy). None of the patients received chemotherapy before irradiation. The follow-up period was 62 months (range 8–136 months). Results:A complete response was achieved in all patients. The 5-year local control rate was 100%. Distant relapse occurred in 2 patients, resulting in a 5-year distant relapse-free survival rate of 88%. The 5-year overall survival rate was 89%; there were no lymphoma-related deaths. No serious acute complications (grade 3/4) were observed. Grade 1/2 late effects were documented in 44% of patients. Grade 3 complications (cataract: 2, dryness: 2) were observed in 4 patients (18%). Conclusions: Indolent early stage orbital NHL can be controlled with local radiotherapy. Morbidity is low. Regular follow-up examinations are necessary to detect rare cases of distant relapse.

Abrogation of Radiation-Inducible Telomerase Upregulation in HPV16 E6 Transfectants of Human Lymphoblasts

Background:Telomerase activity in a human lymphoblastoid cell line with wild-type p53 status (TK6) was previously shown to be rapidly induced by ionizing radiation doses as low as 10 cGy. Since this low-dose response was absent in a closely related cell line overexpressing a mutant form of p53 (WTK1), the putative involvement of p53 was further investigated using stable human papillomavirus 16 (HPV16) E6 transfectants of these cell lines. The E6 product mediates rapid degradation of wild-type p53, but has also been found to upregulate telomerase.Material and Methods:Telomerase activity in HPV16 E6 transfectants of the human lymphoblastoid cell lines TK6 and WTK1 was measured by PCR/ELISA and was quantified using internal standards (titration by cell number) run within each separate assay. Mean telomere length was determined by Southern hybridization of terminal restriction fragments with a biotin-labeled telomeric DNA probe.Results:The TK6E6 and the WTK1E6 cells exhibited higher baseline telomerase activities than the parental cells. This was also accompanied by increased telomere lengths. Radiation exposure (up to 10 Gy) was unable to significantly further enhance telomerase activities, although the dynamic range of the assay would have allowed to record higher signals.Conclusion:The lacking radiation induction of telomerase activities in the E6 transfectants could reflect saturation, if E6 and radiation would share a common pathway of telomerase upregulation. Present evidence from the literature, however, suggests that E6 mediates telomerase reverse transcriptase (TERT) subunit transcriptional activation, whereas radiation signals to posttranscriptional/posttranslational control of telomerase activity. Therefore, the present data enforce the previous hypothesis of a p53 dependence of telomerase upregulation by low doses of radiation and its abrogation, likely due to p53 degradation, in E6-expressing cells.Hintergrund:Eine vorhergehende Studie an humanen Lymphoblasten mit Wildtyp-p53-Status (TK6) zeigte eine rasche Induktion der Telomeraseaktivität bereits durch kleine Strahlendosen (10 cGy). Da dieser Effekt in einer eng verwandten Zelllinie mit mutiertem p53 (WTK1) nicht auftrat, sollte die vermutete Rolle von p53 durch Verwendung der mit HPV16 (humanes Papillomavirus 16) E6 stabil transfizierten Zelllinien weiter untersucht werden. Das E6-Produkt vermittelt die rasche Degradation von p53, ist aber auch als Aktivator der Telomerase bekannt.Material und Methodik:Die Telomeraseaktivität in mit HPV16 E6 transfizierten Zelllinien (TK6E6 und WTK1E6) wurde mittels PCR/ELISA gemessen und anhand interner Standards in jedem separaten Assay quantifiziert. Zur Bestimmung der mittleren Telomerlängen diente die Southern-Hybridisierung terminaler Restriktionsfragmente mit einer biotinylierten Telomersonde.Ergebnisse:Die TK6E6- und WTK1E6-Zellen zeigten eine gegenüber den parentalen Zellen deutlich erhöhte Telomeraseaktivität und verlängerte Telomere. Bestrahlung (bis 10 Gy) konnte diese Telomeraseaktivität nicht signifikant steigern, obwohl der dynamische Bereich des verwendeten Assays eine Detektion höherer Werte erlaubt hätte.Schlussfolgerung:Die fehlende Induktion der Telomeraseaktivität nach Bestrahlung in E6-transfizierten Zellen könnte als ein Sättigungsphänomen interpretiert werden, wenn ein gemeinsamer Pfad der E6- und der strahleninduzierten Regulation der Telomerase unterstellt wird. Dies widerspricht aber aktuellen Ergebnissen aus der Literatur, wonach E6 Transaktivierung der Telomerase-Reverse-Transkriptase-(TERT-)Untereinheit vermittelt, während Bestrahlung die Telomeraseaktivität offenbar über posttranskriptionelle/posttranslationale Mechanismen reguliert. Die vorliegenden Daten unterstreichen daher die frühere Vermutung einer p53-Abhängigkeit der bei kleinen Strahlendosen gemessenen Telomeraseinduktion, die in E6 exprimierenden Zellen, vermutlich durch die p53-Degradation, supprimiert ist.