Gabriele Reinartz

Primary Gastrointestinal Non-Hodgkin’s Lymphoma: I. Anatomic and Histologic Distribution, Clinical Features, and Survival Data of 371 Patients Registered in the German Multicenter Study GIT NHL 01/92

PURPOSE The study was initiated to obtain epidemiologic data and information on anatomic and histologic distribution, clinical features, and treatment results in patients with primary gastrointestinal non-Hodgkins lymphomas (PGI NHL). PATIENTS AND METHODS Between October 1992 and November 1996, 371 PGI NHL patients were eligible to evaluate clinical features. Radiotherapy and chemotherapy were stratified according to histologic grading, stage, and whether surgery had been carried out or not. RESULTS A total of 74.8% patients had gastric NHL (PGL). Within the intestine, the small bowel and the ileocecal region were involved in 8.6% and 7.0% of the cases, respectively. Multiple GI involvement (MGI) was 6.5%. Approximately 90% of the GI NHL were in stages IE/IIE. Aggressive NHL accounted for the majority, with a distinguishable pattern in several sites. Forty percent of PGL were of low-grade mucosa-associated lymphatic tissue type. One third of large-cell lymphomas had low-grade components. Most intestinal NHL were germinal-center lymphomas. The site of origin was prognostic. In gastric and ileocecal lymphoma, event-free (EFS) and overall survival (OS) were significantly higher as compared with the small intestine or MGI (median time of observation, 51 months). In PGL, localized disease was prognostic for EFS and OS. Histologic grade influenced only EFS significantly. Numbers in intestinal lymphomas were too small for subanalyses. CONCLUSION PGI NHL are heterogeneous diseases. The number of localized PGL allowed for detailed analyses. Larger studies are needed for stages III and IV and for intestinal NHL. A uniform reporting system for PGI NHL, in terms of definitions and histologic and staging classifications, is needed to facilitate comparison of treatment results.

Treatment Results in Localized Primary Gastric Lymphoma: Data of Patients Registered Within the German Multicenter Study (GIT NHL 02/96)

PURPOSE In the prospective study 02/96 on primary GI lymphoma, we have collected data on histology, clinical features, and treatment results. In particular, in stages I and II localized primary gastric lymphoma (PGL), our objectives were to reduce treatment intensity and to confirm our hypothesis from study 01/92, which maintained that an organ-preserving approach is not inferior to primary surgery. PATIENTS AND METHODS Patients receiving radiotherapy and/or chemotherapy were stratified for histologic grade, stage, and whether surgery had been carried out or not (as decided by each participating center). Patients with aggressive PGL received six cycles of CHOP-14 (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by involved-field radiotherapy (40 Gy). Patients with indolent PGL (including patients experiencing treatment failure with antibiotic therapy for Helicobacter pylori) were treated with extended-field radiotherapy. The volume depended on stage. The irradiation dose was 30 Gy, followed by a boost of 10 Gy (the latter omitted after complete resection) to the tumor region. RESULTS Seven hundred forty-seven patients were accrued. Of these patients, 393 with localized PGL were treated with radiotherapy and/or chemotherapy only or additional surgery between December 1996 and December 2003. The survival rate at 42 months for patients treated with surgery was 86% compared with 91.0% for patients without surgery. CONCLUSION In this nonrandomized study (02/96), we reproduced the previous results of study 01/92 showing no disadvantage for an organ-preserving treatment. Therefore, primary stomach resection should be questioned.

Operative and conservative management of primary gastric lymphoma: interim results of a German multicenter study

PURPOSE/OBJECTIVE Biology and appropriate management of gastrointestinal (GI lymphomas are matters of an ongoing controversial debate. To evaluate histological features, sites of involvement and management of primary GI-lymphomas, a prospective multicentric study was initiated in 10/1992. Aim of study was the further standardization of operative and conservative treatment modalities. MATERIALS AND METHODS Study started 10/1992 and was closed 11/1996. A total of 381 evaluable patients had been accrued then. Standardized diagnostic workup included endoscopic and radiological evaluation of the complete GI-tract as well as a central histological review. Diagnosis was established after Lewin, stage classification was made after Musshoff, and histological classification was made after Isaacson. Treatment decision concerning operative or conservative management was due to the initially acting physician. Patients with resection of low grade lymphoma received total abdominal irradiation 30 Gy + 10 Gy boost to incompletely resected areas. After resection of high grade lymphoma CHOP chemotherapy (4 cycles for stage IE, 6 cycles for higher stages) after McKelvy was followed by total abdominal irradiation 30 Gy for stage IE respectively involved field irradiation 30 Gy for higher stages with 10 Gy boost to incompletely resected areas. Primary conservative- treatment consisted of six cycles COP chemotherapy after Bagley for low grade lymphomas stage > IE and total abdominal irradiation 30 Gy + 10 Gy boost to involved areas for all stages. Patients with high grade lymphomas received 4 x CHOP followed by total abdominal irradiation 30 Gy + 10 Gy boost to involved areas or 6 x CHOP plus involved field radiation therapy with 40 Gy. 257 patients are considered for analysis due to exclusion criteria of the study, 190 of them were suffered from gastric lymphoma. Their median observation time is 29 months, maximum observation time is 68 months. RESULTS Sites of involvement were stomach in 73.4%, small bowel 9.6%, ileocoecal region 6.9%, and other sites 3.2% More than one GI site was involved in 6.9%. Gastric lymphomas achieved a survival probability of 89% after 3 years. Though surgical and conservative treatment was not randomized, outcome was analyzed in gastric NHL stages I and II (histologic subtype not considered showing no significant influence). At 3 and 5 years survival is 88% in resected cases vs. 94% and 86% in conservatively treated patients (p = 0.350). Analyzing only stages I + II(1) surgery also seems of no advantage even considering only RO-resections. There was one acute gastrointestinal bleeding under primary chemotherapy for a high grade lymphoma. Toxicities of grade III and IV WHO were rarely seen during treatment. All other acute toxicities were not more than grade II WHO. CONCLUSION Conservative treatment in this setting is feasible. The operative approach seems not to be advantageous compared to conservative treatment and should be critically reconsidered.

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.

Analysis of Failures after Whole Abdominal Irradiation in Gastrointestinal Lympomas Is Prophylactic Irradiation of Inguinal Lymph Nodes Required

Background: To evaluate failures and to investigate the need for prophylactic inclusion of the inguinal lymph nodes in case of whole abdominal irradiation in gastrointestinal lymphoma. Patients and Method: In October 1992 a prospective study on primary gastrointestinal lymphoma was initiated to evaluate management strategies. Treatment consisted either of conservative management comprehending radiotherapy ± chemotherapy or radio-/chemotherapy sequential to primary surgery, depending on the physicians decision. Until November 1996, 382 patients were enrolled. Out of them we analyzed 92 patients who received a whole abdominal irradiation, in 21 cases with prophylactic inclusion, in 71 cases without inclusion of the inguinal lymph nodes. Results: After a median follow-up time of 36 months in 92 patients with whole abdominal irradiation 9 patients developed relapse of gastrointestinal lymphoma (8 local failures, 1 distant failure). In these cases the analysis of radiation therapy shows low tumor doses or small field sizes. No significant difference in the relapse rates is shown between the 21 patients with inclusion of the inguinal lymph nodes in the abdominal radiation fields (3 recurrences≅14,3%) and the 71 patients without enclosure of the inguinal lymph nodes (6 recurrences ≅8,5%). Conclusion: General prophylactic enclosure of the inguinal lymph nodes in the case of whole abdominal irradiation in gastrointestinal lymphoma seems to be unnecessary.Hintergrund: Analyse der Therapieversager und der Notwendigkeit der prophylaktischen Miterfassung der inguinalen Lymphknoten im Rahmen der Ganzabdomenbestrahlung von gastrointestinalen Lymphonen. Patienten und Methode: Im Oktober 1992 wurde eine prospektive Studie über gastrointestinale Lymphome initiiert, um Therapiestrategien zu evaluieren. Das Therapiekonzept umfaßte entweder ein konservatives Regime, bestehend aus Radiotherapie ± Chemotherapie, oder ein primär operatives Vorgehen mit sequentieller Radio-/Chemotherapie; konservatives oder operatives Vorgehen wurde den teilnehmenden Zentren freigestellt. Bis November 1996 wurden 382 Patienten rekrutiert. Von diesen untersuchten wir 92 Patienten (Tabelle 1), die eine Ganzabdomenbestrahlung erhielten, in 21 Fällen unter prophylaktischem Einschluß, in 71 Fällen ohne Miterfassung der inguinalen Lymphknoten. Ergebnisse: Nach einer medianen Nachbeobachtungszeit von 36 Monaten entwickelten von 92 Patienten mit Ganzabdomenbestrahlung neun ein Rezidiv (acht Lokalrezidive, eine Fernmetastase) (Tabelle 3). Die Analyse der Bestrahlung in diesen Fällen ergab niedrige Tumordosen oder kleine Feldgrößen. Es zeigte sich kein signifikanter Unterschied zwischen den Rezidivraten (Tabelle 4) der 21 Patienten, deren Ganzabdomenbestrahlung unter Einschluß der inguinalen Lymphknoten erfolgte (drei Rezidive≅14,3%), und den 71 ohne Leistenlymphknoten bestrahlten Patienten (sechs Rezidive≅8,5%). Schlußfolgerung: Die generelle prophylaktische Miterfassung der Leistenlymphknoten im Rahmen der Ganzabdomenbestrahlung bei gastrointestinalen Lymphomen scheint überflüssig zu sein.

Microscopic Residual Disease Is a Risk Factor in the Primary Treatment of Breast Cancer

Objectives: In the primary treatment of breast cancer, postoperative radiotherapy is performed in high-risk patients after mastectomy and in patients who received breast conserving surgery. In a retrospective analysis, our mono-institutional results of postoperative irradiation have been evaluated. Patients and Methods: Between 1992 and 1996, 500 patients have been irradiated after surgery for primary breast cancer. Of these, 489 patients had no initial metastases. 89 patients with loco-regional disease had a mastectomy, 400 patients were irradiated after breast conserving surgery. Radiotherapy at the chest wall was performed with 50 Gy and 2 Gy fractions. After microscopically incomplete resection, an electron boost of 10 Gy was given. The ipsilateral lymph nodes were irradiated with 50 Gy when there was extensive lymph node involvement or invasion of tumor in the axillary fat tissue. Results: The 5-year local control rate after mastectomy was 97.4% and 91.2% after breast conserving surgery. The only statistically significant risk factor for local failure was microscopically incomplete resection. The corresponding 5-year local control rates for microscopically incomplete and complete resections were 76.4% and 92.7% (p = 0.01). The risk of local relapse was increased with both marginal invasive and marginal DCIS-tissue. 86.6% of local relapses were in the same quadrant. Conclusions: High-risk patients after mastectomy and patients with breast conserving surgery achieve a high local control rate with postoperative irradiation. After microscopically incomplete resection, there is an increased risk for local relapse.Hintergrund: In der Primärtherapie des Mammakarzinoms wird nach Mastektomie bei Hochrisikopatientinnen sowie nach brusterhaltender Operation eine postoperative Strahlentherapie durchgeführt. In einer retrospektiven Analyse wurden die Ergebnisse der postoperativen Strahlentherapie von Patientinen unserer Klinik evaluiert. Patientinnen und Methode: Zwischen 1992 und 1996 wurden 500 Patientinnen postoperativ am Mammakarzinom bestrahlt, davon hatten 489 Patientinnen einen M0-Status. Bei 89 dieser Patientinnen erfolgte die Radiatio nach Mastektomie, bei 400 Patientinnen nach brusterhaltener Operation. Die Radiotherapie an der Brustwand wurde mit 50 Gy CT-gestützt rechnergeplant mit 5 × 2 Gy/Woche durchgeführt. R1-resezierte Patientinnen erhielten einen lokalen Elektronen-Boost von 10 Gy. Die ipsilateralen Lymphabflusswege wurden bei ausgedehntem Lymphknotenbefall oder kapselüberschreitendem Wachstum ebenfalls mit 50 Gy bestrahlt. Ergebnisse: Die lokale Kontrollrate nach 5 Jahren betrug bei radikal operierten Patientinnen 97,4%, nach brusterhaltender Operation 91,2%. Der einzige statistisch signifikante Risikofaktor für ein Lokalrezidiv war der Resektionsstatus (R1 vs. R0); dabei war das Rezidivrisiko sowohl bei randständigen invasiven als auch bei DCIS-Anteilen erhöht. Nach brusterhaltender Operation betrugen die entsprechenden lokalen 5-Jahres-Kontrollraten 76,4% (R1) bzw. 92,7% (R0), p = 0,01. Bei 86,6% der Patientinnen traten Rezidive nach brusterhaltender Operation im gleichen Quadranten auf. Schlussfolgerung: Hochrisikopatientinnen nach Mastektomie sowie Patientinnen mit brusterhaltender Operation haben nach postoperativer Bestrahlung eine hohe lokale Kontrollrate. Nach R1-Resektion besteht ein erhöhtes lokales Rezidivrisiko.

Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

PURPOSE To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. METHODS AND MATERIALS All patients with residual disease of ≥ 2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluated all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. RESULTS A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. CONCLUSIONS The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses.