Involved-Site Radiation Therapy Enables Effective Disease Control in Parenchymal Low-Grade Primary Cerebral Lymphoma.

BACKGROUND: Primary lymphoma of the central nervous system (PCNSL) encompasses a variety of lymphoma subtypes, with the majority being diffuse large B-cell lymphomas, which require aggressive systemic treatment. In contrast, low-grade lymphomas are reported infrequently and are mostly limited to dural manifestations. Very rarely, parenchymal low-grade PCNSL is diagnosed, and the cases documented in the literature show a wide variety of treatment approaches. METHODS: We screened all cases of PCNSL treated at our department (a tertiary hematooncology and neurooncology center) in the last 15 years and conducted a comprehensive literature research in the PubMed database. RESULTS: Overall, two cases of low-grade primary parenchymal PCNSL treated with irradiation were identified. The dose prescriptions ranged from 30.6 to 36 Gy for the involved site, with sparing of the hippocampal structures. Both patients had an excellent response to the treatment with a mean follow-up of 20 months. No clinical or radiological signs of treatment toxicity were detected. CONCLUSIONS: Our analysis corroborates the results from the literature and demonstrates that parenchymal low-grade PCNSL shows a good response to localized radiation treatment, enabling a favorable outcome while avoiding long-term treatment toxicity.

Impact of Modern Low Dose Involved Site Radiation Therapy on Normal Tissue Toxicity in Cervicothoracic Non-Hodgkin Lymphomas: A Biophysical Study.

This biophysical study aimed to determine fitting parameters for the Lyman-Kutcher-Burman (LKB) dose-response model for normal tissue complication probability (NTCP) calculations of acute side effects and to investigate the impact of reduced radiation doses on the probability of their occurrence in supradiaphragmatic non-Hodgkin lymphoma (NHL) irradiation. A cohort of 114 patients with NHL in the cervicothoracic region, treated between 2015 and 2021 at the University Hospitals of Münster, Hamburg, and Essen, with involved site radiation therapy (ISRT), were included. Among them, 68 patients with aggressive NHL (a-NHL) received consolidative radiation therapy with 24-54 Gy following (R-)CHOP chemotherapy. Additionally, 46 patients with indolent NHL (i-NHL) underwent radiotherapy with 22.5-45.0 Gy. Two treatment plans were prospectively created for each patient (a-NHL: 30.0/40.0 Gy; i-NHL: 24.0/30.0 Gy). NTCP were then calculated using the optimized LKB model. The adapted dose-response models properly predicted the patient's probability of developing acute side effects when receiving doses ≤ 50 Gy. In addition, it was shown that reduced radiation doses can influence the NTCP of acute side effects depending on the aggressiveness of NHL significantly. This study provided a foundation to prospectively assess the probability of adverse side effects among today's reduced radiation doses in the treatment of NHL.

Radiotherapy in Combination with Systemic Therapy for Multiple Myeloma-A Critical Toxicity Evaluation in the Modern Treatment Era.

Radiotherapy (RT) is an established treatment modality in the management of patients with multiple myeloma (MM), aiming at analgesia and stabilization of osteolytic lesions. As a multifocal disease, the combined use of RT, systemic chemotherapy, and targeted therapy (ST) is pivotal to achieve better disease control. However, adding RT to ST may lead to increased toxicity. The aim of this study was to evaluate the tolerability of ST given concurrently with RT. Overall, 82 patients treated at our hematological center with a median follow-up of 60 months from initial diagnosis and 46.5 months from the start of RT were evaluated retrospectively. Toxicities were recorded from 30 days before RT up to 90 days after RT. 54 patients (65.9%) developed at least one non-hematological toxicity, with 50 patients (61.0%) showing low-grade (grade I or II) and 14 patients (17.1%) revealing high-grade (grade III and IV) toxicities. Hematological toxicities were documented in 50 patients (61.0%) before RT, 60 patients (73.2%) during RT, and 67 patients (81.7%) following RT. After RT, patients who had received ST during RT showed a significant increase in high-grade hematological toxicities (p = 0.018). In summary, RT can be safely implemented into modern treatment regimens for MM, but stringent monitoring of potential toxicities even after completion of RT has to be ensured.

Long-Term Survival of Patients with Mantle Cell Lymphoma after Total Body Irradiation, High-Dose Chemotherapy and Stem Cell Transplantation: A Monocenter Study.

INTRODUCTION: In patients with mantle cell lymphoma (MCL), long-term remissions can be achieved by stem cell transplantation (SCT). Different conditioning treatment protocols exist with or without total body irradiation (TBI). There are few data published on the role of TBI before autologous stem cell transplantation (autoSCT) or allogenic stem cell transplantation (alloSCT). We report on the long-term survival data of patients treated by TBI prior to autologous or allogenic SCT at our center. PATIENTS: In a retrospective analysis, the data of patients treated at the University Hospital of Muenster from May 2004 to February 2015 were collected and evaluated. For the analysis, all data of patients who were histopathologically diagnosed with MCL and underwent TBI prior to stem cell transplantation (SCT) were evaluated. RESULTS: A total of 22 patients (19 men and 3 women) were treated with a TBI-based conditioning prior to SCT. The median age at initial diagnosis was 57.5 years (38-65 years). Seventeen patients had Ann Arbor stage IV, two patients had Ann Arbor stage III, and three patients Ann Arbor stage II disease. AutoSCT was performed in 19 patients and alloSCT was performed in 3 patients. In 18 patients, autoSCT was applied as part of first-line therapy, and in one patient after relapse. Two patients received alloSCT after relapse of MCL, and one patient received alloSCT during first-line therapy after an inadequate treatment response. TBI was performed in 12 patients with 10 Gy and in 6 patients with 12 Gy, these patients subsequently received autoSCT. In the group of four patients who received TBI with four Gy, four patients subsequently received alloSCT and one patient received autoSCT. Median overall survival after autoSCT and previous TBI was 11.4 years (142 months). In total, 11 out of 19 patients treated with autoSCT lived longer than 6.8 years (82-202 months). After alloSCT and previous TBI, the median overall survival was 3.25 years (14-59 months). CONCLUSIONS: A large proportion of patients with advanced MCL survived remarkably longer than 11.4 years after high-dose chemotherapy, TBI, and SCT. The present results of multimodal treatment support the published reports that TBI-based high-dose therapy followed by autoSCT is highly effective in this prognostically unfavorable disease situation.

Efficacy and Tolerance of IMRT Boost Compared to IORT Boost in Early Breast Cancer: A German Monocenter Study.

The aim of this retrospective study is to compare the two boost subgroups, IORT or IMRT, in terms of overall survival (OS), progression-free survival (PFS), cosmesis, and acute and late toxicity. It shall be shown whether and which of the boost techniques offers better results with respect to the facial points, since there are already many studies on applying boost to the tumor bed after/during breast conserving surgery, and there are few which compare the different techniques. For this comparison, two subgroups of 76 patients each (n = 152), treated between 2002 and 2015, were enrolled in the study. In one subgroup, the 9 Gy boost was intraoperatively administered after complete removal of the primary tumor, while the other subgroup received the boost of 8.4 Gy percutaneously and simultaneously integrated into the tumor bed after breast conserving surgery. Both subgroups have subsequently undergone whole breast irradiation (WBI) of 50.4/50 Gy in 1.8−2 Gy per fraction. OS and the incidence of late toxicity did not differ between the two subgroups and no risk factor was found regarding PFS. Acute toxicities initially occurred significantly less (p < 0.001) in the IORT subgroup; however, after WBI took place, this difference vanished. Therefore, boost application by means of IORT or IMRT can be considered equivalent.

Development of Organ-Preserving Radiation Therapy in Gastric Marginal Zone Lymphoma.

Gastric marginal zone lymphoma (gMZL) of mucosa-associated lymphoid tissue (MALT) may persist even after H. pylori eradication, or it can be primarily Helicobacter pylori (H. pylori) independent. For patients without the successful eradication of lymphoma, or with progressive disease, treatment options have historically included partial or total gastrectomy. Presently, in these instances, curative radiation therapy (RT) is the current standard of care. This review emphasizes the historically changing role of radiation therapy in gMZL, progressing from large-volume RT without surgery, to localized RT, on its own, as a curative organ-preserving treatment. This overview shows the substantial progress in radiation therapy during the recent two to three decades, from high-dose, large-field techniques to low-dose, localized target volumes based on advanced imaging, three-dimensional treatment planning, and advanced treatment delivery techniques. RT has evolved from very large extended field techniques (EF) with prophylactic treatment of the whole abdomen and the supradiaphragmatic lymph nodes, applying doses between 30 and 50 Gy, to involved-field RT (IF), to the current internationally recommended involved site radiation therapy (ISRT) with a radiation dose of 24-30 Gy in gMZL. Stage-adapted RT is a highly effective and safe treatment with excellent overall survival rates and very rare acute or late treatment-related toxicities, as shown not only in retrospective studies, but also in large prospective multicenter studies, such as those conducted by the German Study Group on Gastrointestinal Lymphoma (DSGL). Further de-escalation of the radiation treatments with low-dose 20 Gy, as well as ultra-low-dose 4 Gy radiation therapy, is under investigation within ongoing prospective clinical trials of the International Lymphoma Radiation Oncology Group (ILROG) and of the German Lymphoma Alliance (GLA).

Radiotherapy in Follicular Lymphoma Staged by 18F-FDG-PET/CT: A German Monocenter Study.

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.

Biophysical Analysis of Acute and Late Toxicity of Radiotherapy in Gastric Marginal Zone Lymphoma-Impact of Radiation Dose and Planning Target Volume.

Successful studies on radiation therapy for gastric lymphoma led to a decrease in planning target volume (PTV) and radiation dose with low toxicities, maintaining excellent survival rates. It remains unclear as to which effects are to be expected concerning dose burden on organs at risk (OAR) by decrease in PTV vs. dose and whether a direct impact on toxicity might be expected. We evaluated 72 radiation plans, generated prospectively for a cohort of 18 patients who were treated for indolent gastric lymphoma in our department. As a prospective work, four radiation plans with different radiation doses and target volumes (40 Gy-involved field, 40 Gy-involved site, 30 Gy-involved field, 30 Gy-involved site) were generated for each patient. Mean dose burden on adjacent organs was compared between the planning groups. Cohort toxicity data served to estimate parameters for the Lyman-Kutcher-Burman (LKB) model for normal tissue complication probability (NTCP). These were used to anticipate adverse events for OAR. Literature parameters were used to estimate high-grade toxicities of OAR. Decrease of dose and/or PTV led to median dose reductions between 0.13 and 5.2 Gy, with a significant dose reduction on neighboring organs. Estimated model parameters for liver, spleen, and bowel toxicity were feasible to predict cohort toxicities. NTCP for the endpoints elevated liver enzymes, low platelet count, and diarrhea ranged between 15.9 and 22.8%, 27.6 and 32.4%, and 21.8 and 26.4% for the respective four plan variations. Field and dose reduction highly impact dose burden and NTCP for OAR during stomach radiation. Our estimated LKB model parameters offer a good approximation for low-grade toxicities in abdominal organs with modern radiation techniques.

Renaissance of Radiotherapy in Intestinal Lymphoma? 10-Year Efficacy and Tolerance in Multimodal Treatment of 134 Patients: Follow-up of Two German Multicenter Consecutive Prospective Phase II Trials.

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.

Radiotherapy of extranodal low-grade follicular and marginal zone lymphomas: long-term follow-up of 159 patients.

OBJECTIVE: 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. MATERIALS AND METHODS: The medical records of 159 patients with 181 histologically confirmed ENLG-NHL lesions treated at our institution were reviewed retrospectively. RESULTS: 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. CONCLUSION: 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.

Salvage Treatment and Survival for Relapsed Follicular Lymphoma Following Primary Radiation Therapy: A Collaborative Study on Behalf of ILROG.

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 (<12 months) have inferior survival compared with those with longer disease-free interval.

Favorable radiation field decrease in gastric marginal zone lymphoma : Experience of the German Study Group on Gastrointestinal Lymphoma (DSGL).

PURPOSE: 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). PATIENTS AND METHODS: 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. RESULTS: 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 5­year 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. CONCLUSION: 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.

Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG.

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 95.7%. 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.

Rituximab With Involved Field Irradiation for Early-stage Nodal Follicular Lymphoma: Results of the MIR Study.

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.

Successful treatment of a rare case of ameloblastic fibrosarcoma with radiation therapy.

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.

4D-Listmode-PET-CT and 4D-CT for optimizing PTV margins in gastric lymphoma : Determination of intra- and interfractional gastric motion.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cone-beam CT-guided radiotherapy in the management of lung cancer: Diagnostic and therapeutic value.

BACKGROUND: Recent studies have demonstrated an increase in the necessity of adaptive planning over the course of lung cancer radiation therapy (RT) treatment. In this study, we evaluated intrathoracic changes detected by cone-beam CT (CBCT) in lung cancer patients during RT. METHODS AND MATERIALS: A total of 71 lung cancer patients treated with fractionated CBCT-guided RT were evaluated. Intrathoracic changes and plan adaptation priority (AP) scores were compared between small cell lung cancer (SCLC, n = 13) and non-small cell lung cancer (NSCLC, n = 58) patients. RESULTS: The median cumulative radiation dose administered was 54 Gy (range 30-72 Gy) and the median fraction dose was 1.8 Gy (range 1.8-3.0 Gy). All patients were subjected to a CBCT scan at least weekly (range 1-5/week). We observed intrathoracic changes in 83 % of the patients over the course of RT [58 % (41/71) regression, 17 % (12/71) progression, 20 % (14/71) atelectasis, 25 % (18/71) pleural effusion, 13 % (9/71) infiltrative changes, and 10 % (7/71) anatomical shift]. Nearly half, 45 % (32/71), of the patients had one intrathoracic soft tissue change, 22.5 % (16/71) had two, and three or more changes were observed in 15.5 % (11/71) of the patients. Plan modifications were performed in 60 % (43/71) of the patients. Visual volume reduction did correlate with the number of CBCT scans acquired (r = 0.313, p = 0.046) and with the timing of chemotherapy administration (r = 0.385, p = 0.013). CONCLUSION: Weekly CBCT monitoring provides an adaptation advantage in patients with lung cancer. In this study, the monitoring allowed for plan adaptations due to tumor volume changes and to other anatomical changes.

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.

Breath-hold technique in conventional APPA or intensity-modulated radiotherapy for Hodgkin's lymphoma: Comparison of ILROG IS-RT and the GHSG IF-RT.

INTRODUCTION: 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). METHODS: 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. RESULTS: IS-RT reduces treatment volumes. With respect to the planning target volume (PTV), IMRT achieves better conformity but the same homogeneity. Regarding the D mean 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 D mean of the lung and the female breast. CONCLUSION: 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.

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.