Search

ZusammenfassungDas follikuläre Lymphom ist das zweithäufigste Lymphom der westlichen Welt und beinhaltet im Regelfall insbesondere in den lokalisierten Stadien auch eine (18F-FDG) PET-CT im Rahmen des Stagings. Die Einteilung nach Ann-Arbor bzw. der modifizierten Lugano-Klassifikation ermöglicht eine Einschätzung über das weitere Therapievorgehen als auch über die Prognose. Der PET-CT kommt hier eine bedeutende Rolle zu, indem sie die bildgebende Sensitivität im Vergleich zur konventionellen CT weiter stark erhöhen kann. Verschiedene Parameter dienen bei der PET-CT zur Interpretation der Befunde, wobei insbesondere der SUVmax hier eine wichtige Rolle spielt. Weitere Parameter wie metabolisches Tumorvolumen (MTV) oder Total Lesion Glycolysis (TLG) sind Gegenstand der aktuellen Forschung. Für die Strahlentherapie spielt die PET-CT eine bedeutende Rolle, da sie eine noch präzisere Erfassung des metabolisch aktiven Lymphoms ermöglichen kann. Hierdurch können Zielvolumina weiter verkleinert und so umliegende Gewebe geschont werden. Zudem wird durch die PET-CT auch die initiale Stadieneinteilung präziser und damit einhergehend auch die Prognose bzw. das Therapie-Outcome besser abschätzbar. Im Bereich der Diagnostik und Therapiesteuerung der Hodgkin-Lymphomerkrankung ist die PET-CT schon länger unverzichtbar geworden. Mit der in den letzten Jahren steigenden Verfügbarkeit ist die PET-CT heute ein immer wichtiger werdender Bestandteil sowohl in der Primärdiagnostik als auch in der Rezidivsituation bei Patienten mit follikulärem Lymphom und findet zunehmend Eingang in die aktuellen Leitlinienempfehlungen für die Non-Hodgkin Lymphome (NHL).

Purpose This article reports on the long‐term impact of radiotherapy adapted to stage, histology, and previous resection in a large cohort of patients with intestinal lymphoma (iL) treated with definitive or adjuvant curative‐intent radiation therapy (RT) ± chemotherapy (CHOP, MCP, or COP). Patients and Methods In two consecutive prospective study designs, 134 patients with indolent (stage IE–IIE) or aggressive (stage IE–IVE) iL were referred to 61 radiotherapeutic institutions between 1992 and 2003. Patients with indolent iL received extended field (EF) 30 Gy (+10 Gy boost in definitive treatment); patients with aggressive iL received involved field (IF) (EF) 40 Gy by means of stage‐, histology‐, and operation‐adapted radiation fields. Results The patients had median age 58 years and were predominantly male (2:1). Histology showed aggressive prevalence (1.6:1), stage IE–to–stage IIE ratio of iL 1.04:1, and localized stages–to–advanced stages ratio of aggressive lymphoma 23:1. Median follow‐up was in total 11.7 years: 10.0 years in the first study, GIT (GastroIntestinal‐Tract) 1992, and 11.8 years in the second study, GIT 1996. Lymphoma involvement was predominantly a single intestinal lesion (82.1%). Decrease of radiation field size from EF to IF in stage I aggressive iL from GIT 1992 to GIT 1996 resulted in a nonsignificant partial reduction of chronic toxicity while maintaining comparable survival rates (5‐year overall survival 87.9 vs. 86.7%, 10‐year overall survival 77.4 vs. 71.5%) with nonsignificant difference in event‐free survival (5‐year event‐free survival 82.6 vs. 86.7%, 10‐year event‐free survival 69.7 vs. 71.5%) and lymphoma‐specific survival (5‐year lymphoma‐specific survival 90.1 vs. 91.9%, 10‐year lymphoma‐specific survival 87.6% vs. 91.9%). Comparative dose calculation of two still available indolent duodenal lymphoma computed tomography scans revealed lower radiation exposure to normal tissues from applying current standard involved site RT (ISRT) 30 Gy in both cases. Conclusion RT adapted to stage, histology, and resection in multimodal treatment of iL, despite partially decreasing field size (EF to IF), achieves excellent local tumor control and survival rates. The use of modern RT technique and target volume with ISRT offers the option of further reduction of normal tissue complication probability. Implications for Practice Although patients with intestinal lymphoma (iL) are heterogeneous according to histology and subtype, they benefit from radiotherapy. Prospective study data from 134 patients with indolent iL (stage IE–IIE) or aggressive iL (stage IE–IVE) show 100% tumor control after definitive or adjuvant curative‐intent radiation therapy ± chemotherapy. Radiation treatment was applied between 1992 and 2003. Median follow‐up in total was 11.7 years. No radiotherapy‐associated death occurred. Relapse developed in 15.7% of the entire cohort; distant failure was more frequent than local (4:1). Normal tissue complication probability can be further improved using modern involved site radiation therapy techniques., This article reports the details of radiation therapy in the therapeutic multimodality approach for treatment of patients with intestinal lymphoma.

Gastric marginal zone lymphoma (gMZL) of mucosa-associated lymphoid tissue (MALT) may persist even after

This retrospective study examined the role of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in stage-related therapy of follicular lymphomas (FL). Twelve patients each in stages I and II, 13 in stage III and 11 in stage IV were treated in the Department of Radiation Oncology, University Hospital of Muenster, Germany from 2004 to 2016. Radiotherapy (RT), as well as additional chemoimmunotherapy were analyzed with a median follow-up of 87.6 months. Ultrasound (US), CT and 18F-FDG-PET/CT were used to determine progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) over 5- and 10- years. 23 of 24 patients with stage I/II (95.8%) had complete remissions (CR) and 17 of 24 patients with stages III/IV FL showed CR (70.8%). 5- and 10-year PFS in stages I/II was 90.0%/78.1% vs. 44.3%/28.5% in stages III/IV. 5- and 10-year OS rates in stages I/II was 100%/93.3% vs. 53.7%/48.4% in stages III/IV. 5- and 10-year LSS of stages I/II was 100%/93.8% vs. 69.2%/62.3% in stages III/IV. FL of stages I/II, staged by 18F-FDG-PET/CT, revealed better survival rates and lower risk of recurrence compared to studies without PET/CT-staging. Especially, patients with PET/CT proven stage I disease showed significantly better survival and lower relapses rates after RT.

Long-term impact of stage-adapted field reduction in a large cohort of gastric marginal zone lymphoma (gMZL) patients treated conservatively with curative radiation therapy (RT).Prospective analysis of paper records of 290 patients with stage IE-IIE gMZL, treated in 78 radiotherapeutic institutions in Germany from 1992-2013. Stage-adapted radiation fields decreased from extended field (EF) to involved field (IF) over the course of three consecutive prospective trials of the German Study Group on Gastrointestinal Lymphoma (DSGL). Treatment results were compared between the three cohorts.Overall collective with median age of 60 years, slight male predominance (m:f = 1.1:1) and ratio of disease stage I:stage II = 2.1:1. Median follow-up 6.4 years in total: 13.0 years in the first gastrointestinal study (GIT 1992), 8.2 years in the second (GIT 1996) and 4.7 years in the third study (DSGL 01/2003). Stage-adapted radiation field decrease together with further technological development led to reduced relative frequencies of acute/chronic adverse effects and until now was accompanied by lower disease recurrence. The third study design with smallest field size (IF in stage I, locoregional EF in stage II) achieved the best survival outcome at the 5‑year follow-up (overall survival 92.7%, event-free survival 89.5% and lymphoma-specific survival 100.0%). Disease relapse observed in 10 patients. Cumulative incidence of disease-specific death was 1.7% of the followed patients. Primary disease stage associated with lymphoma-specific survival.Stage-adapted reduction towards IF in gMZL resulted in favorable adverse effects, local control and survival rates. These results support further decreases in modern RT of gMZL.ZIELSETZUNG: Langzeiteffekt der stadienadaptierten Strahlenfeldverkleinerung bei kurativer Radiotherapie (RT) in einer großen Kohorte von Patienten mit gastralem Marginalzonenlymphom (gMZL).Prospektive Analyse der Papierakten von 290 Patienten mit gMZL im Stadium IE–IIE, behandelt in 78 radiotherapeutischen Institutionen in Deutschland von 1992–2013. Stadienadaptierte Strahlenfeldreduktion vom „extended field“ (EF) zum „involved field“ (IF) im Verlauf der drei konsekutiven prospektiven Studien der Deutschen Studiengruppe Gastrointestinale Lymphome (DSGL). Behandlungsergebnisse wurden zwischen den drei Studienkohorten verglichen.Gesamtkollektiv mit medianem Alter von 60 Jahren; Geschlechterverhältnis m:w = 1,1:1 und Stadienverhältnis I:II = 2,1:1. Medianes Follow-up insgesamt 6,4 Jahre: 13,0 Jahre in der ersten gastrointestinalen Studie (GIT 1992), 8,2 Jahre in der zweiten (GIT 1996) und 4,7 Jahre in der dritten Studie (DSGL 01/2003). Die stadienadaptierte Strahlenfeldverkleinerung zusammen mit der technischen Weiterentwicklung führte zu reduzierten relativen Häufigkeiten der akuten/chronischen Nebenwirkungen und ist bislang begleitet von einer niedrigeren Rezidivrate. Das Konzept der dritten Studie mit der kleinsten Feldausdehnung (IF im Stadium I, lokoregionales EF im Stadium II) erreichte die besten Überlebensraten nach einem Follow-up von 5 Jahren (Gesamtüberleben 92,7%, ereignisfreies Überleben 89,5% und lymphomspezifisches Überleben 100,0%). Lymphomrezidive wurden bei 10 Patienten beobachtet. Die kumulative Inzidenz der krankheitsspezifischen Todesrate bei den nachbeobachteten Patienten betrug 1,7%. Das primäre Krankheitsstadium war assoziiert mit dem lymphomspezifischen Überleben.Die stadienadaptierte Feldverkleinerung zum IF bei gMZL resultiert in günstigen Nebenwirkungen, lokaler Kontrolle und Überlebensraten. Diese Ergebnisse bekräftigen die weitere Deeskalation der modernen RT von gMZL.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

Purpose The coronavirus pandemic is affecting global health systems, endangering daily patient care. Hemato-oncological patients are particularly vulnerable to infection, requiring decisive recommendations on treatment and triage. The aim of this survey amongst experts on radiation therapy (RT) for lymphoma and leukemia is to delineate typical clinical scenarios and to provide counsel for high-quality care. Methods A multi-item questionnaire containing multiple-choice and free-text questions was developed in a peer-reviewed process and sent to members of the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance. Answers were assessed online and analyzed centrally. Results Omission of RT was only considered in a minority of cases if alternative treatment options were available. Hypofractionated regimens and reduced dosages may be used for indolent lymphoma and fractures due to multiple myeloma. Overall, there was a tendency to shorten RT rather than to postpone or omit it. Even in case of critical resource shortage, panelists agreed to start emergency RT for typical indications (intracranial pressure, spinal compression, superior vena cava syndrome) within 24 h. Possible criteria to consider for patient triage are the availability of (systemic) options, the underlying disease dynamic, and the treatment rationale (curative/palliative). Conclusion RT for hemato-oncological patients receives high-priority and should be maintained even in later stages of the pandemic. Hypofractionation and shortened treatment schedules are feasible options for well-defined constellations, but have to be discussed in the clinical context.

Sarcomas are rare diseases of the head and neck region, representing around 1% of all malignancies. Amongst them, ameloblastic fibrosarcoma (AFS) is of even greater rarity, with less than 100 cases reported in the literature. Consequently, no standard treatment or guidelines have been made available. Surgery is often performed as primary therapy, but may be limited due to anatomical or functional reasons. We present a case of AFS successfully treated by postoperative radiation therapy. A detailed case study is provided, followed by a review of the English-language literature focusing on the role of radiation therapy.

To evaluate clinical, histopathologic, and radiation (RT) dose parameters in patients with extranodal low-grade (ENLG) non-Hodgkin lymphoma (NHL) and their possible impact on local control (LC) and survival. The medical records of 159 patients with 181 histologically confirmed ENLG-NHL lesions treated at our institution were reviewed retrospectively. The predominant histological subtype (73%) was marginal zone lymphoma (MZL). Common lesion sites were the gastrointestinal tract (GIT; 33%), skin (26%), and orbit (21%). The majority of patients (88%) presented with stage I/II disease. Thirty-three (20%) lesions were treated with reduced-dose RT (≤30.6 Gy) and 148 lesions (80%) with conventional-dose RT (>30.6 Gy), with an overall median dose of 39.6 Gy (range 4–63). The median follow-up period was 72 months. The 10-year local control (LC), Progression-free survival (PFS), and overall survival (OS) rates were 96, 65, and 82%, respectively. Higher overall response rate (ORR; 98% vs. 94%, p = 0.001) and complete response rate (CRR; 95% vs. 73%, p = 0.001) were observed in patients treated with conventional-dose regimens than in those treated with reduced-dose regimens. Ten-year PFS (p = 0.90) and OS (p = 0.40) was similar between the two dose groups. RT was well tolerated in both dose groups, with no grade 4/5 toxicities. In the multivariate analysis, RT dose and timing (upfront or salvage) were related to LC, whereas age, histology, and complete response (CR) to RT were associated with PFS. Patient age and radiation field size impacted OS. RT is an effective and curative local treatment for early-stage FL and MZL at conventional and reduced radiation doses. Conventional-doses seems to be associated with local response improvement, without significant differences in PFS rates. Age, histology, and response to RT may influence the PFS.

Purpose: We previously reported that ∼30% of patients with localized follicular lymphoma (FL)staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT)will relapse within 5 years. We sought to report outcomes for those who relapsed. Methods and Materials: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose ( 18F-FDG)positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS)and freedom from progression (FFP)were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. Results: Of 512 patients with median follow-up of 52 months, 149 (29.1%)developed recurrent lymphoma at a median of 23 months (range, 1-143)after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others—88.7% versus 97.6%, respectively (P =.01)—and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index–adjusted hazard ratio, 3.61; P =.009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74)or had presumed (n = 23)indolent recurrence, 58 patients (59.8%)were observed, 19 (19.6%)had systemic therapy, 16 (16.5%)had RT, and 4 (4.1%)had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed)3-year FFP was 73.9%. Conclusions: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (

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 Sezary 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 ( 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 P 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 (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As

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.

To summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign symptomatic functional disorders with low-dose radiotherapy.This overview reports on the role of low-dose radiotherapy in the treatment of functional disorders in cases of heterotopic ossification (HO) and Graves orbitopathy (GO). The most relevant aspects of the DEGRO S2e Consensus Guideline "Radiation Therapy of Benign Diseases 2014" regarding diagnostics, treatment decision, dose prescription, as well as performance of radiotherapy and results are summarized.For both indications (HO, GO), retrospective and some prospective analyses have shown remarkable effects in terms of symptom relief. Nevertheless, the level of evidence (LoE) and the grade of recommendation (GR) vary: LoE 1-2 and GR A-B (HO), LoE 2 and GR B (GO).Low-dose radiotherapy for benign symptomatic functional disorders has proven to be effective, according to different authors, for 25-100 % of the patients studied and therefore it may be a reasonable prophylactic and therapeutic option if noninvasive or invasive methods have been used without persistent success. For HO, a single-fraction dose of 7-8 Gy or fractionated radiation with five fractions of 3.5 Gy is recommended. For GO, single-fraction doses of 0.3-2.0 Gy, and total doses of 2.4-20 Gy/series, applied in one daily fraction are recommended.

Background Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. Patients and methods In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival. Results Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively. Conclusion Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach.

The MabThera and Involved field Radiotherapy study investigated efficacy and safety of involved field (IF) radiotherapy in combination with the anti-CD20 antibody Rituximab for early-stage follicular lymphoma (FL) in a prospective, single-arm multicenter phase 2 design. Eighty-five stage I-II FL patients received 8 cycles of Rituximab (375 mg/m2) and IF irradiation (30/40 Gy). The primary endpoint was progression-free survival (PFS) 2 years from treatment start. Secondary endpoints were overall survival (OS), complete response rates, toxicity, quality of life, and minimal residual disease (MRD) response with protocol defined visits up to month 30. For the primary endpoint, PFS at 2 years was 85% for the intention-to-treat set. Long-term data were captured in selected sites and evaluated as post hoc analysis in the per protocol (PP) set: PFS and OS were 78% and 96% at 5 years with a median follow-up of 66 or 78 months, respectively. There were 17/76 recurrences in the PP set, of which 14 were outside the radiation volume only. MRD analyses revealed a clonal marker in 36% of patients at diagnosis. All but 1 marker positive patients experienced a molecular treatment response. There were 13 serious adverse events (4 related to the therapy) during the first 30 months. IF radiotherapy combined with Rituximab is well tolerated and highly efficient with low rates of recurrence in the first years in early-stage FL. The efficacy is comparable with more aggressive therapy approaches without compromising the quality of life and maintains for an extended follow-up of more than 5 years.

Purpose Different doses and techniques used in high-dose-rate (HDR) prostate brachytherapy make it difficult to define universal quality parameters. The aim of this study was to develop individual, objective parameters for the evaluation of an HDR brachytherapy plan for prostate radiation. Methods Fifty-three patients who received an HDR brachytherapy boost after external radiation were analyzed in this study. Brachytherapy was performed with a 192Ir source after ultrasound-guided, transperineal metal needle application followed by removal of the ultrasound probe to reduce organ dose levels at the anterior rectum wall. The rectum and prostate locations as well as the dose at the anterior rectum wall were estimated under the anatomical conditions of HDR prostate brachytherapy. The doses at the organs at risk (rectum and urethra) were analyzed for several parameters, which were compared to values of former patients before the start of treatment. In cases of major deviations, modifications of the treatment plan were performed before starting the treatment. Results Deflating of the water balloon led to an increase of the space between the anterior rectal wall and the dorsal margin of the prostate (mean, 6 mm; 1–10 mm). The dose of the introduced “virtual rectum,” represented by the ventral surface of the ultrasound probe, in the treatment plan correlated to dose measurements in the rectum. Pretreatment evaluation and comparison of the established individual quality parameters led in two cases to a treatment plan modification. Conclusions This method allows a fast and objective individual brachytherapy treatment plan evaluation and improvement.

New imaging protocols for radiotherapy in localized gastric lymphoma were evaluated to optimize planning target volume (PTV) margin and determine intra-/interfractional variation of the stomach. Imaging of 6 patients was explored prospectively. Intensity-modulated radiotherapy (IMRT) planning was based on 4D/3D imaging of computed tomography (CT) and positron-emission tomography (PET)-CT. Static and motion gross tumor volume (sGTV and mGTV, respectively) were distinguished by defining GTV (empty stomach), clinical target volume (CTV = GTV + 5 mm margin), PTV (GTV + 10/15/20/25 mm margins) plus paraaortic lymph nodes and proximal duodenum. Overlap of 4D-Listmode-PET-based mCTV with 3D-CT-based PTV (increasing margins) and V95/D95 of mCTV were evaluated. Gastric shifts were determined using online cone-beam CT. Dose contribution to organs at risk was assessed. The 4D data demonstrate considerable intra-/interfractional variation of the stomach, especially along the vertical axis. Conventional 3D-CT planning utilizing advancing PTV margins of 10/15/20/25 mm resulted in rising dose coverage of mCTV (4D-Listmode-PET-Summation-CT) and rising D95 and V95 of mCTV. A PTV margin of 15 mm was adequate in 3 of 6 patients, a PTV margin of 20 mm was adequate in 4 of 6 patients, and a PTV margin of 25 mm was adequate in 5 of 6 patients. IMRT planning based on 4D-PET-CT/4D-CT together with online cone-beam CT is advisable to individualize the PTV margin and optimize target coverage in gastric lymphoma.

The present study addresses the role of intensity-modulated radiotherapy (IMRT) in contrast to standard RT (APPA) for patients with Hodgkin’s lymphoma (HL) with a focus on deep inspiration breath-hold (DIBH) technique and a comparison between the International Lymphoma Radiation Oncology Group (ILROG) Involved Site Radiotherapy (IS-RT) versus the German Hodgkin Study Group (GHSG) Involved Field Radiotherapy (IF-RT). APPA treatment and 2 IMRT plans were compared for 11 patients with HL. Furthermore, treatment with DIBH versus free breathing (FB) and two different treatment volumes, i.e. IF-RT versus IS-RT, were compared. IMRT was planned as a sliding-window technique with 5 and 7 beam angles. For each patient 12 different treatment plans were calculated (132 plans). Following organs at risk (OAR) were analysed: lung, heart, spinal cord, oesophagus, female breast and skin. Comparisons of the different values with regard to dose–volume histograms (DVH), conformity and homogeneity indices were made. IS-RT reduces treatment volumes. With respect to the planning target volume (PTV), IMRT achieves better conformity but the same homogeneity. Regarding the Dmean for the lung, IMRT shows increased doses, while RT in DIBH reduces doses. The IMRT shows improved values for Dmax concerning the spinal cord, whereas the APPA shows an improved Dmean of the lung and the female breast. IS-RT reduces treatment volumes. Intensity-modulated radiotherapy shows advantages in the conformity. Treatment in DIBH also reduces the dose applied to the lungs and the heart.

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.

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-Hodgkin’s 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.

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.

Purpose: Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy. Material and methods: Until 10/2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10 Gy was applied (90% reference isodose), preceding WBI with 50– 54 Gy (single doses 1.7–2 Gy). Results: At a median follow up of 72.4 months (0.8–239), only 16 in-breast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5–151 months after primary treatment. In multivariate analysis only grade 3 reached significance (p = 0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients

Impairment of glucose tolerance and muscle wasting indicating a disorder of glucose metabolism are characteristic features of Cushing's syndrome. We have examined glucose and amino acid metabolism in eleven patients with pituitary dependent Cushing's disease in comparison to nine healthy controls. Furthermore, the therapeutic effect of selective pituitary microsurgery was studied by repeated stable isotope measurements of hepatic glucose production and leucine turnover rates. Eight patients remitted after surgery and 3 had persistent disease. All patients were investigated prior to surgery and again 1 week and 3 months after the operation with (6,6-2H2)-glucose and (5,5,5-2H3)-leucine by means of a primed (4 mg/kg.min and 0.27 mg/kg.min), continuous (0.05 mg/kg.min and 0.005 mg/kg.min) infusion. In Cushing's disease, both the preoperatively elevated mean glucose production rate (2.34 +/- 0.63 mg/kg.min) and the reduced mean leucine turnover (0.213 +/- 0.025 mg/kg.min) were found to be linked with hepatic insulin resistance and an insulin-induced reduction in protein breakdown combined with a reduced protein synthesis. Mean glucose production and leucine flux both normalized after surgery in the remitting patients (2.18 +/- 0.15 mg/kg.min and 0.244 +/- 0.047 mg/kg.min 3 months after the operation). The metabolic disorders thus were reversible following successful correction of hormonal oversecretion by transsphenoidal surgery.

Purpose/Objective(s): Subtypes defined by primary sites have not been well studied in extranodal nasal-type NK/T-cell lymphoma (NKTCL). This study aimed to determine the clinical diversity and treatment outcome of NKTCL arising in the upper aerodigestive tract (UADT-NKTCL) in a large cohort of multicenter study from an endemic area. Materials/Methods: A nationwide survey was performed. A total of 1147 patients with a newly diagnosed UADT-NKTCL from 9 large centers in China between 2000 and 2010 were retrospectively reviewed. The primary sites of UADT-NKTCL were localized in the nasal cavity and paranasal sinus (n Z 860), nasopharynx (n Z 156), tonsil (n Z 55), oropharynx (n Z 22), and larynx (n Z 14). The hard and soft palate (n Z 9), oral cavity (n Z 7), base of the tongue (n Z 6) and hypopharynx (n Z 1) are rarely involved (< 1%). In total, 860 patients (75%) had primary nasal-UADTNKTCL, and 287 patients (25.0%) had primary extranasal-UADTNKTCL. Among the latter 287 patients, 256 patients (22.3%) had primary Waldeyer’s ring NKTCL (nasopharynx, tonsil, oropharynx and base of the tongue, WR-NKTCL) and 156 patients (13.5%) had nasopharyngealNKTCL. Results: Compared with patients with nasal-UADT-NKTCL, patients with extranasal-UADT-NKTCL had more adverse clinical features including stage II-IV disease (61.3% vs. 22.9%, p < 0.001), regional lymph node involvement (57.8% vs. 20.0%, p < 0.001), B symptoms (45.6% vs. 38.5%, p Z 0.032), poor performance status (ECOG 1, 75.3% vs. 64.3%, p Z 0.007), and high risk scores of the international prognostic index (IPI 2, 17.4% vs. 9.2%, p Z 0.001) or Korean prognostic index (KPI 2, 48.4% vs. 27.0%, p < 0.001). Patients with extranasal-UADTNKTCL showed a similar overall survival (5-year OS, 56.9% vs. 62.2%, P Z 0.183), but worse progression-free survival (5-year PFS, 42.5% vs. 55.2%, P Z 0.003) than those with nasal-UADT-NKTCL. The prognosis for extranasal-UADT-NKTCL was similar or superior to that of nasalUADT-NKTCL, when stratified by stage I disease (5-year OS, 64.1% vs. 67.9%, P Z 0.429), stage II disease (63.9% vs. 45.9%, P Z 0.002), and stage III/IV disease (22.1% vs. 13.0%, P Z 0.019). Similarly, clinical and prognostic differences were also observed between nasal-UADT-NKTCL and extranasal-UADT-NKTCL, nasopharyngeal-NKTCL or WR-NKTCL. For early stage disease, primary radiation therapy with or without chemotherapy showed better OS for entire group of UADT-NKTCL (67.9% vs. 34.4%, p < 0.001), and even for nasal-UADT-NKTCL (67.8% vs. 28.1%, p < 0.001), or extranasal-UADT-NKTCL (67.7% vs. 45.4%, p Z 0.001) than chemotherapy alone. Conclusions: Patients with nasal and extranasal UADT-NKTCL present with significantly different clinical features and prognosis. Author Disclosure:Q. Liu: None. Y. Zhu: None. Y. Zhang: None. J. Cao: None. Z. Yuan: None. J. Wu: None. T. Wu: None. L. Qian: None. F. Zhang: None. Y. Li: None.

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.

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 × CHOP followed by total abdominal irradiation 30 Gy + 10 Gy boost to involved areas or 6 × 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 R0-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.

breast cancer. In this patient cohort, the LYL due to late side effects appeared to be dominated by lung cancer, followed by cardiovascular disease. The combined LYL was lowest with DIBH (p < 0.0001) and the additional benefit of IMRT was not significant. Conclusions: DIBH significantly decreases the estimated risk of cardiovascular disease and lung cancer after radiation therapy for mediastinal Hodgkin lymphoma. Combined risk estimates were lowest with DIBH combined with IMRT and the results should be confirmed in a larger patient cohort. Author Disclosure: M.C. Aznar: None. M.V. Maraldo: None. P. Brodin: None. I.S. Vogelius: None. M. Josipovic: None. P.M. Petersen: None. S.M. Damkjaer: None. D. Schut: None. A.K. Berthelsen: None. L. Specht: None.

Introduction: In 2001 (Koch et al.,JCO) we published the treatment results of 185 patients (pts) with localized primary gastric lymphoma (PGL) registered within the GIT NHL 01/92 German multicenter study. After a median time of observation of 130 months we present clinical and pathological features of relapsed patients. Methods: We compared treatment results in PGL after combined surgery and conservative (S/CM) versus conservative management (CM). Radiotherapy (Rx) and chemotherapy were stratified according to histological grading, stage, and the inclusion or omission of surgery as follows: PGL pts with indolent lymphomas in stage I received an extended field (EF) Rx with total abdominal irradiation and in stage II additionally a T-field preceded by 6 cycles of COP. The dose was 30 Gy for EF followed by a boost of 10 Gy on sites of tumor. All pts with aggressive PGL were treated with four (stage I) or six (stage II) cycles of CHOP-14 followed by EF Rx (stage I) or involved field Rx (stage II), dosage of Rx corresponded to Rx for indolent NHL. Results: Between the years 1992 and 1996, a total of 185 pts were registered. Recurrence of NHL occurred in 17 cases during follow-up. Analysis revealed no specific features of relapsed pts with respect to initial symptoms, clinical features (except stage II2 - more than regional lymph nodes involved) and initial treatment. DLBCL was the most common histological subtype seen in relapsed pts (58.8%). Indolent lymphoma relapsed in 41.2% pts. Interestingly 70% of the DLBCL initially had an additional small-cell component, and 56% relapsed as marginal zone B-cell lymphoma, particularly at primary site independent of the initial treatment. Conclusion: In this non-randomized study there was no disadvantage for a stomach preserving approach in the context of tumor recurrence. Patients with distant nodal involvement (Stage II2) and DLBCL relapsed more often than pts. with localized stages (Stage I/II1) and indolent lymphomas. Interestingly, aggressive lymphomas, with an initial small-cell component, predominantly relapsed as marginal zone B-cell lymphomas at primary site, while indolent lymphomas relapsed also generalized.