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In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93-01, 2001 and UK-IMPORT databases, were included. Event-free survival (EFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT-RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE-cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5-year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%-80.6%) and 84.5% (95% CI = 77.5%-92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE-testing.

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.

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing., What's new? Pediatric renal cell carcinoma (RCC) is a rare malignancy, knowledge of which is based largely on adult RCC. Here, pediatric RCC was retrospectively studied using data from the International Society of Pediatric Oncology – Renal Tumor Study Group (SIOP‐RTSG). Pediatric RCC patients had a 5‐year overall survival rate of 84.5 percent, with notably lower survival for patients with metastatic disease. In pediatric RCC patients tested for transcription factor E3 and EB, 56.3 percent presented with translocation type. The findings highlight the importance of full registration of pediatric RCCs, with information on germline genetics and transcription factor testing.

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.

Background Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC. Methods Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT. Results There was no significant difference regarding LD and tumor volume between MRI and CT (p≥ 0.6221, respectively p≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 (r = 0.8750) and 12 months (r = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders. Conclusions DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.

Objective: To derive evidence-based recommendations for the optimal utilisation of resources during unexpected shortage of radiotherapy capacity. Methods and materials: We have undertaken a rapid review of published literature on the role of radiotherapy in the multimodality treatment of paediatric cancers governing the European practise of paediatric radiotherapy. The derived data has been discussed with expert paediatric radiation oncologists to derive a hierarchy of recommendations. Results: The general recommendations to mitigate the potential detriment of an unexpected shortage of radiotherapy facilities include: (1) maintain current standards of care as long as possible (2) refer to another specialist paediatric radiotherapy department with similar level of expertise (3) prioritise use of existing radiotherapy resources to treat patients with tumours where radiotherapy has the most effect on clinical outcome (4) use chemotherapy to defer the start of radiotherapy where timing of radiotherapy is not expected to be detrimental (5) active surveillance for low-grade tumours if appropriate and (6) consider iso-effective hypofractionated radiotherapy regimens only for selected patients with predicted poor prognosis. The effectiveness of radiotherapy and recommendations for prioritisation of its use for common and challenging paediatric tumours are discussed. Conclusion: This review provides evidence-based treatment recommendations during unexpected shortage of paediatric radiotherapy facilities. It has wider applications for the optimal utilisation of facilities, to improve clinical outcome in low- and middle-income countries, where limited resources continue to be a challenge. © 2020 Elsevier B.V.

The aim of this study was to determine the diagnostic capability of a dynamic gait analysis insole and compare its ability to detect clinical correlations to a common stationary analysis tool. Twenty-five patients with chronic plantar fasciitis were included in this prospective, blinded, diagnostic study. Conventional, stationary gait analysis on a force plate on an even surface and continuous dynamic pedobarography on a standardized course consisting of different gait tasks were performed and correlated to the disease severity. Mean patient age was 53.6 (range 41 to 68) years, with a mean pain level of 6.1 (range 4 to 10) on the Visual Analogue Scale and a calcaneodynia score of 48.7 (range 33 to 66). Significant correlations were seen between several dynamic gait values and clinical scoring: cadence (rs = 0.56, p = .004), stance time (rs =–0.6, p = .002), center-of-pressure velocity (rs = 0.44, p = .046), and double support time (rs = 0.42, p = .042). No significant correlations were seen between any force plate gait analysis values and clinical scoring. In this study setting, dynamic gait analysis was able to identify clinically relevant correlations to plantar fasciitis disease severity that standard force plate measurements could not.

In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective.A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1 Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks.The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded.Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5 Gy was not superior to the current standard dose of 6 × 1 Gy. Further trials are necessary to explore the best fractionation schedule.

Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC.Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT.There was no significant difference regarding LD and tumor volume between MRI and CT (p ≥ 0.6221, respectively p ≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 (r = 0.8750) and 12 months (r = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders.DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.

8041 Background: Primary mediastinal B-cell lymphoma (PMBCL) is a distinct entity of aggressive lymphoma, which typically presents in young patients (pts) with a bulky mediastinal mass. Therapy is based on R-CHOP or similar regimens, but the role of treatment intensification and consolidative radiotherapy (RT) is controversial, because data from randomized trials are rare. Methods: The UNFOLDER trial included 18-60 year-old pts (aaIPI = 0 with Bulk [≥7.5 cm] or aaIPI = 1) qualifying for radiotherapy to Bulk or extralymphatic involvement (E). Pts were randomized in a 2 x 2 factorial design to 6xR-CHOP-14 or 6x-R-CHOP-21 without RT or with RT (39.6 Gy) to Bulk and E. Primary endpoint was event-free survival (EFS), secondary endpoints were progression-free (PFS) and overall survival (OS). Response was evaluated by the Internat Standardized Response Criteria, Cheson 1999. Results: 131 PMBCLs were included with a median age of 34 years, 54% were female, 79% had elevated LDH > UNV and 24% had E. 82 pts (R-CHOP-21: 43; R-CHOP-14: 39) were assigned to RT and 49 (R-CHOP-21: 27, R-CHOP-14: 22) to no-RT. 96% (79/82) received RT per protocol and 5 pts in the no-RT arm received unplanned RT (4 after PR and 1 after CR/CRu). Response RT vs no-RT were CR/Cru 94% vs 84%, PR 2% vs 10%, PD 2% vs 4%. 3-year EFS was superior in pts assigned to RT (94% vs. 78%; p = 0.007), mostly due to events caused by initiation of RT (n = 5) in the no-RT arm. In an as treated analysis the difference between the RT and the no-RT arm was not significant (p = 0.136). Regarding PFS and OS no difference between the RT vs no-RT arm was detected (PFS: 95% (95% CI: 90-100) vs 90% (95% CI: 81-98), p = 0.253; OS: 98% (95% CI: 94-100) vs 96% (95% CI: 90-100), p = 0.636). Dose-densification of R-CHOP-21 by R-CHOP-14 did not improve EFS, PFS nor OS. Only 4 pts died. Conclusions: To our knowledge, this is the largest series of PMBCLs so far, which have been treated in a prospective, randomized trial in the rituximab era. The results reveal no differences between R-CHOP-14 vs R-CHOP-21. Pts assigned to RT had a superior EFS mostly due to a higher PR rate in the no-RT arm triggering RT, with no differences in PFS and OS. The results suggest a benefit of RT only for pts, who are responding to R-CHOP with PR. Testing RT in PET-positive residual tumors in a randomized trial can solve the question, while RT in PET-negative pts is studied in the ongoing randomized IELSG 37 trial. Our results indicate a very favorable 3-year OS of 96% in PMBCL pts treated with R-CHOP. Supported by Deutsche Krebshilfe, Amgen and Roche. Clinical trial information: NCT00278408 .

To further improve outcome in young high-risk patients with diffuse large B-cell lymphoma (DLBCL) the number of rituximab (R) infusions was doubled in combination with standard CHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone) chemotherapy. Seventy-seven patients (aged 18-60 years) with an age-adjusted International Prognostic Index of 2-3 received 12 × R (375 mg/m2 ) on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 99 together with eight cycles of CHOEP-14. Results were retrospectively compared to those of patients receiving 6 × R and 8 × CHOEP-14 in the standard arm of the randomized R-MegaCHOEP trial. Two-year overall survival (OS) was 82% [95% confidence interval (CI) 73%-92%]; 2-year event-free (EFS) and progression-free survival (PFS) was 69% (95% CI 59-80%) and 76% (95% CI 66%--6%), respectively. Comparing 12 to six doses of R revealed no differences (univariate/multivariate) in EFS (at 2 years: 69% vs. 71%), PFS (76% vs. 75%) and OS (82% vs. 85%), with P = 0·766, P = 0·871 and P = 0·843, respectively. Doubling the number of R infusions concomitant to CHOEP did not improve treatment outcomes. Nonetheless, OS and PFS of young high-risk patients who received only six infusions of R combined with CHOEP remain excellent and were confirmed in an independent cohort of patients.

Purpose Flattening filter-free (FFF) beams have recently become available for radiation therapy, offering much higher dose rates but complicating treatment owing to the nonflat profile. Stereotactic treatment is one of the most evident scenarios to investigate the use of FFF beams. Methods and Materials We present a planning study of a FFF 7-MV beam for the treatment of brain metastases using multiple noncoplanar arcs. Plan differences as compared with flat 6 MV photon fields are estimated using different measures of quality. Absolute dosimetry and fluence distribution are verified and the out-of-field dose is measured. Results The FFF 7-MV plans are slightly better than the flat 6-MV plans as evaluated by a number of quality indices, dose to organs at risk, and out-of-field dose, although differences may not be clinically relevant. Verification does not pose any problems. Conclusions The FFF 7-MV treatment plans are marginally superior to the flat-beam 6-MV plans in almost all cases, with greatly reduced treatment times (almost 50%).

Accurate patient positioning before radiotherapy is often verified using advanced imaging techniques such as cone-beam computed tomography (CBCT). Even for dedicated imaging beam lines, the applied dose is not necessarily negligible with respect to the treatment dose and should be considered in the treatment plan.This study presents measurements of the beam properties of the Siemens kView (Siemens AG, Munich, Germany) image beam line (IBL) and the commissioning in the Philips Pinnacle(3) treatment planning system (TPS; Philips, Amsterdam, Netherlands).The percent depth dose curve reaches its maximum at a depth of 10 mm, with a surface dose of 44 %. The IBL operates in flattening filter-free mode, showing the characteristic dose falloff from the central axis. Stability over several days to months is within less than 2 % dose deviation or 1 mm distance-to-agreement. Modelling of the IBL beam line was performed using the Pinnacle(3) automatic modelling routine, with absolute dosimetric verification and film measurements of the fluence distribution.After commissioning of the IBL beam model, the dose from the imaging IBL CBCT can be calculated. Even if the absolute dose deposited is small, repeated imaging doses may sum up to significant amounts and can shift the position of the dose maximum by several centimetres.

Purpose: Several works have recently focused on flattening-filter-free (FFF) beams of linear accelerators of various companies (in particular, Varian and Elekta), but no overview as yet exists for the flattening-filter free 7XU beam (Siemens Artiste). Methods: Dosimetric properties of the 7XU beam were measured in May and September 2011. We present depth dose curves and beam profiles, output factors, and MLC transmission and assess the stability of the measurements. The 7XU beam was commissioned in the Pinnacle³ treatment planning system (TPS), and modeling results including the spectrum are presented. Results: The percent depth dose curve of the 7XU beam is similar to the flat 6X beam line, with a slightly smaller surfacedose. The beam profiles show the characteristic shape of flattening-filter free beams, with deviations between measurements of generally less than 1%. The output factors of the 7XU beam decrease more slowly than for the 6X beam. The MLC transmission is comparable but slightly less for the 7XU beam. The 7XU beam can be adequately modeled by the Pinnacle³ TPS, with successful dosimetric verification. The spectrum of the 7XU beam has lower photon fluence up to approximately 2.5 MeV and higher fluence beyond, with a slightly higher mean energy. Conclusions: The 7XU beam has been commissioned for clinical use after successful modeling, stability checks, and dosimetric verification.

7574Background: The role of RT to B and E for young patients with good-prognosis DLBCL is ill-defined. Methods: 18-60 year-old patients (aaIPI = 0 with B [≥7.5 cm], aaIPI 1) qualifying for radiothe...

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14.1222 elderly patients (aged 61-80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243.3-year event-free survival was 47.2% after six cycles of CHOP-14 (95% CI 41.2-53.3), 53.0% (47.0-59.1) after eight cycles of CHOP-14, 66.5% (60.9-72.0) after six cycles of R-CHOP-14, and 63.1% (57.4-68.8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5.8% (-2.8-14.4) for eight cycles of CHOP-14, 19.3% (11.1-27.5) for six cycles of R-CHOP-14, and 15.9% (7.6-24.2) for eight cycles of R-CHOP-14. 3-year overall survival was 67.7% (62.0-73.5) for six cycles of CHOP-14, 66.0% (60.1-71.9) for eight cycles of CHOP-14, 78.1% (73.2-83.0) for six cycles of R-CHOP-14, and 72.5% (67.1-77.9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by -1.7% (-10.0-6.6) after eight cycles of CHOP-14, 10.4% (2.8-18.0) after six cycles of R-CHOP-14, and 4.8% (-3.1-12.7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR [relative risk] 0.76 [0.60-0.95], p=0.0172; six cycles of R-CHOP-14: RR 0.51 [0.40-0.65], p0.0001; eight cycles of R-CHOP-14: RR 0.54 [0.43-0.69], p0.0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0.50 [0.38-0.67], p0.0001), and eight cycles of R-CHOP-14 (RR 0.59 [0.45-0.77], p=0.0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0.63 [0.46-0.85], p=0.0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles.Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.

Background An actual clinical trial showed the effect of low dose radiotherapy in painful heel spur (plantar fasciitis) with single doses of 1.0 Gy and total doses of 6.0 Gy applied twice weekly. Furthermore, a lot of animal experimental and in vitro data reveals the effect of lower single doses of 0.5 Gy which may be superior in order to ease pain and reduce inflammation in patients with painful heel spur. Our goal is therefore to transfer this experimentally found effect into a randomized multicenter trial. Study design/methods This was a controlled, prospective, two-arm phase III-multicenter trial. The standard arm consisted of single fractions of 1.0 Gy applied two times a week, for a total dose of 6.0 Gy (total therapy time: 3 weeks). The experimental arm consisted of single fractions of 0.5 Gy applied 3 times a week, for a total dose of 6.0 Gy (total therapy time: 4 weeks). Following a statistical power calculation, there were 120 patients for each investigation arm. The main inclusion criteria were: age > = 40 years, clinical and radiologically diagnosed painful heel spur (plantar fasciitis), and current symptoms for at least 6 months. The main exclusion criteria were: former local trauma, surgery or radiotherapy of the heel; pregnant or breastfeeding women; and a pre-existing severe psychiatric or psychosomatic disorder. Methods After approving a written informed consent the patients are randomized by a statistician into one of the trial arms. After radiotherapy, the patients are seen after six weeks, after twelve weeks and then every twelve weeks up to 48 weeks. Additionally, they receive a questionnaire every six weeks after the follow-up examinations up to 48 weeks. The effect is measured using the visual analogue scale of pain (VAS), the calcaneodynia score according to Rowe and the SF-12 score. The primary endpoint is the pain relief three months after therapy. Patients of both therapy arms with an insufficient result are offered a second radiotherapy series applying the standard dose (equally in both arms). This trial protocol has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians’ chamber. Trial registration Current trial registration at German Clinical Trials Register with the number DRKS00004458

6016 Background: Concurrent CRT with 70.6 Gy is the standard treatment for locally advanced head and neck cancer (LA-SCCHN). There exist no prospective data on safety and efficacy of a reduced radiation (RT) dose. Methods: Pts with stage III-IVB LA-SCCHN were randomized 1:1 to receive 70.6 Gy with concurrent cisplatinum (20mg/m²/d IV on days 1-5 and 29-33) and fluorouracil (600 mg/m²/d CIV on days 1-5 and 29-33) (standard arm A) versus 63,6 Gy with intensified chemotherapy using concurrent cisplatinum (20mg/m²/d IV on days 1-4 and 29-32) and paclitaxel (20mg/m²/d IV on days 2, 5, 8, 11 and 25, 30, 33, 36) (experimental arm B). After a planned interim analysis recruitment was stopped due to statistical reasons. Results: Between 06/2010 and 02/2015 a total of 221 pts were randomized with 105 pts receiving treatment in arm A and 112 in arm B (4 pts dropped out). Median follow-up was 38 months. Pts’ characteristics: Oral cavity (15%), oropharynx (54%), hypopharynx (28%), larynx (14%); 17 pts had more than one primary site; tumor stage: III (14%), IV (86%); HPV-status (p16) was positive in 20%, negative in 38%, currently pending in 42%. A total of 96 PFS-related events occurred. 3-year PFS (ITT) was 58% in the standard arm A and 48% in experimental arm B (p = 0.454). 3-year OS (ITT) was 64% in arm A and 59% in arm B (p = 0.688). 3-year rates of distant metastases, loco-regional recurrences and death were 10% vs 12%, 17% vs 21% and 15% vs 19% for pts in arm A and B, respectively. As for the p16-positive subgroup, 3-year PFS/OS were 77%/76% in arm A (n = 21) and 69%/80% in arm B (n = 22), respectively. Grade 3+ hematologic adverse events during therapy (arm A/arm B): Anemia 11%/4% (p = 0.038); neutropenia 40%/16% (p < 0.001); thrombocytopenia 8%/3% (p = 0.130). Conclusions: These preliminary results indicate that pts receiving concurrent CRT for LA-SCCHN did not benefit from a lower total RT dose of 63.6Gy despite intensified chemotherapy. However, in the subgroup of p16-positive pts a reduced RT dose may be sufficiently effective. Clinical trial information: NCT01126216.

7506 Background: RT to bulky sites improves outcome of elderly DLBCL patients [Lancet Oncol 2008; 9: 105-116; J Clin Oncol 2014; 32:112-1118]. Whether RT can be spared in PET-negative pts. after R-CHOP was prospectively addressed in OPTIMAL >60. Methods: 61 to 80 y-old pts. were randomized in a 2x2 factorial design to 6xCHOP-14 or 6xCHLIP-14 (liposomal instead of conventional vincristine) plus 8 x rituximab 375 mg/m2(R) q 2 wks. or 12xR (days -4,-1,1,4,14,28,42,56,91,126,175, 238). Pts. with bulk (>=7.5 cm) PET-positive after 6 cycles chemotherapy were assigned to RT (39.6 Gy), while PET-negative bulks were observed. Results: 187/505 (37%) had bulky disease and were compared to 117/306 (38%) RICOVER-60 pts. (38%) who had received 6xCHOP-14+8R. OPTIMAL>60 pts. were older (70 vs. 68 years) and had more IPI=3 (33% vs. 29%) and IPI=4,5 (34% vs. 23%) compared to RICOVER-60. PET was performed in 166/187 OPTIMAL>60 bulk pts. (reasons for no PET: early death: 5; excessive toxicity: 3; protocol violation: 1, non-compliance: 4, change of diagnosis: 6, others: 2). 80/166 (48%) bulks remained PET-positive after 6 cycles of chemotherapy and 62/80 (78%) were irradiated (reasons for no RT: progression: 8; medical reasons: 9; negative biopsy: 1), reducing RT from 67/117 (57%) in RICOVER-60 by 42% to 62/187 (33%) in OPTIMAL>60. Despite the unfavorable demographics, outcome of the 187 bulk pts. in OPTIMAL>60 was non-inferior to RICOVER-60, not even in the least intensive of the 4 OPTIMAL>60 treatment arms consisting of 47 pts. who received 6xCHOP-14+8R as in RICOVER-60. 2-year PFS and OS in OPTIMAL>60 was 79% and 88%, respectively, compared to 75% and 78% of the 117 RICOVER-60 pts. In a multivariable analysis adjusting for the IPI risk factors, the hazard ratio of the OPTIMAL>60 compared to the RICOVER-60 bulk pts. was 0.7 (95% CI: 03.; 1.5; p=0.345) for PFS and 0.5 (95% CI: 02.; 1.3; p=0.154) for OS. Conclusions: RT can be spared in bulky disease PET-negative after chemotherapy. This strategy results in a 42% reduction of RT without compromising the outcome of these patients. Supported by Amgen, Roche, Spectrum. Clinical trial information: NCT01478542.

Background The modulated arc (mARC) technique has recently been introduced by Siemens as an analogue to VMAT treatment. However, up to now only one certified treatment planning system supports mARC planning. We therefore present a conversion algorithm capable of converting IMRT plans created by any treatment planning system into mARC plans, with the hope of expanding the availability of mARC to a larger range of clinical users and researchers. As additional advantages, our implementation offers improved functionality for planning hybrid arcs and provides an equivalent step-and-shoot plan for each mARC plan, which can be used as a back-up concept in institutions where only one linac is equipped with mARC. Methods We present a feasibility study to outline a practical implementation of mARC plan conversion using Philips Pinnacle and Prowess Panther. We present examples for three different kinds of prostate and head-and-neck plans, for 6 MV and flattening-filter-free (FFF) 7 MV photon energies, which are dosimetrically verified. Results It is generally more difficult to create good quality IMRT plans in Pinnacle using a large number of beams and few segments. We present different ways of optimization as examples. By careful choosing the beam and segment arrangement and inversion objectives, we achieve plan qualities similar to our usual IMRT plans. The conversion of the plans to mARC format yields functional plans, which can be irradiated without incidences. Absolute dosimetric verification of both the step-and-shoot and mARC plans by point dose measurements showed deviations below 5% local dose, mARC plans deviated from step-and-shoot plans by no more than 1%. The agreement between GafChromic film measurements of planar dose before and after mARC conversion is excellent. The comparison of the 3D dose distribution measured by PTW Octavius 729 2D-Array with the step-and-shoot plans and with the TPS is well above the pass criteria of 90% of the points falling within 5% local dose and 3 mm distance to agreement. For all plans, the treatment time was noticeably reduced by conversion to mARC. Conclusions We present the feasibility test for converting IMRT step-and-shoot plans from the RTP-output of any treatment planning system (Philips Pinnacle and Prowess Panther, in our case) into mARC plans. The feasibility and dosimetric equivalence is demonstrated for the examples of a prostate and a head-and-neck patient.

Summary Background High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities. Methods We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18–60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00129090. Findings 136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29–59), 3-year event-free survival was 69·5% (95% CI 61·3–77·7) in the R-CHOEP-14 group and 61·4% (52·8–70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9–2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3–4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14. Interpretation In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy. Funding Deutsche Krebshilfe.

Several works have recently focused on flattening-filter-free (FFF) beams of linear accelerators of various companies (in particular, Varian and Elekta), but no overview as yet exists for the flattening-filter free 7XU beam (Siemens Artiste).Dosimetric properties of the 7XU beam were measured in May and September 2011. We present depth dose curves and beam profiles, output factors, and MLC transmission and assess the stability of the measurements. The 7XU beam was commissioned in the Pinnacle[superscript three] treatment planning system (TPS), and modeling results including the spectrum are presented.The percent depth dose curve of the 7XU beam is similar to the flat 6X beam line, with a slightly smaller surface dose. The beam profiles show the characteristic shape of flattening-filter free beams, with deviations between measurements of generally less than 1%. The output factors of the 7XU beam decrease more slowly than for the 6X beam. The MLC transmission is comparable but slightly less for the 7XU beam. The 7XU beam can be adequately modeled by the Pinnacle[superscript three] TPS, with successful dosimetric verification. The spectrum of the 7XU beam has lower photon fluence up to approximately 2.5 MeV and higher fluence beyond, with a slightly higher mean energy.The 7XU beam has been commissioned for clinical use after successful modeling, stability checks, and dosimetric verification.

Purpose To conduct a randomized trial of radiation therapy for painful heel spur, comparing a standard dose with a very low dose. Methods and Materials Sixty-six patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with a total dose of 0.6 Gy applied in 6 fractions of 0.1 Gy twice weekly (low dose). In all patients lateral opposing 4- to 6-MV photon beams were used. The results were measured using a visual analogue scale, the Calcaneodynia score, and the SF12 health survey. The fundamental phase of the study ended after 3 months, and the follow-up was continued up to 1 year. Patients with insufficient pain relief after 3 months were offered reirradiation with the standard dosage at any time afterward. Results Of 66 patients, 4 were excluded because of withdrawal of consent or screening failures. After 3 months the results in the standard arm were highly significantly superior compared with those in the low-dose arm (visual analogue scale, P =.001; Calcaneodynia score, P =.027; SF12, P =.045). The accrual of patients was stopped at this point. Further evaluation after 12 months' follow-up showed the following results: ( 1 ) highly significant fewer patients were reirradiated in the standard arm compared with the low-dose arm ( P 2 ) the results of patients in the low-dose arm who were reirradiated were identical to those in the standard arm not reirradiated (reirradiation as a salvage therapy if the lower dose was ineffective); ( 3 ) patients experiencing a favorable result after 3 months showed this even after 12 months, and some results even improved further between 3 and 12 months. Conclusions This study confirms the superior analgesic effect of radiation therapy with 6-Gy doses on painful heel spur even for a longer time period of at least 1 year.

Purpose To retrospectively evaluate the results after a regimen of surgery, IORT (intraoperative radiotherapy), and EBRT (external beam radiotherapy) for soft-tissue sarcomas Methods 38 consecutive patients underwent IORT for soft-tissue sarcoma; 29 were treated for primary tumours, 9 for recurrences. There were 14 cases with liposarcomas, 8 with leiomyosarcomas, 7 with malignant fibrous histiocytomas. 27/38 tumours were located in the extremities, the remaining ones in the retroperitoneum or the chest. Radical resection was attempted in all patients; a R0-resection was achieved in 15/38 patients, R1 in 12/38 pats and R2 in 4/38 pats. IORT was performed using a J-125 source and a HDR (high dose rate) afterloading machine after suturing silicone flaps to the tumour bed. The total dose applied ranged from 8–15 Gy/0.5 cm tissue depth measured from the flap surface. After wound healing external beam radiotherapy (EBRT) was applied in 31/38 patients with total doses of 23–56 Gy dependent on resection status and wound situation. The mean duration of follow-up was 2.3 years. Results A local recurrence was found in 10/36 patients, lymph node metastases in 2/35, and distant metastases in 6/35 patients. The actuarial local control rate was 63%/5 years. The overall survival rate was 57%/5 years. There was no statistically significant difference between the results after treatment for primaries or for recurrences. Late toxicity to the skin was found in 13/31 patients, wound healing problems in 5/31 patients. A neuropathy was never seen. Conclusion The combination of surgery, IORT, and EBRT yields favourable local control and survival data which are well within the range of the results reported in the literature. The complication rates, however, are considerable although the complications are not severe, they should be taken into account when therapy decisions are made.

Background To evaluate retrospectively the results of radiotherapy for periarthritis of the shoulder Methods In 1983–2004, 141 patients were treated, all had attended at least one follow-up examination. 19% had had pain for several weeks, 66% for months and 14% for years. Shoulder motility was impaired in 137/140 patients. Nearly all patients had taken oral analgesics, 81% had undergone physiotherapy, five patients had been operated on, and six had been irradiated. Radiotherapy was applied using regular anterior-posterior opposing portals and Co-60 gamma rays or 4 MV photons. 89% of the patients received a total dose of 6 Gy (dose/fraction of 1 Gy twice weekly, the others had total doses ranging from 4 to 8 Gy. The patients and the referring doctors were given written questionnaires in order to obtain long-term results. The mean duration of follow-up was 6.9 years [0–20 years]. Results During the first follow-up examination at the end of radiotherapy 56% of the patients reported pain relief and improvement of motility. After in median 4.5 months the values were 69 and 89%, after 3.9 years 73% and 73%, respectively. There were virtually no side effects. In the questionnaires, 69% of the patients reported pain relief directly after radiotherapy, 31% up to 12 weeks after radiotherapy. 56% of the patients stated that pain relief had lasted for "years", in further 12% at least for "months". Conclusion Low-dose radiotherapy for periarthropathy of the shoulder was highly effective and yielded long-lasting improvement of pain and motility without side effects.

Purpose In the Society of Pediatric Oncology (SIOP) 93-01 study, 30 patients older than 16 years were found to have Wilms' tumor. They were treated according to the pediatric protocol and were analyzed for clinical presentation, stage distribution, and prognosis. Patients and Methods Patient age ranged from 16 to 62 years (median, 25.4 years). Tumor stages were defined according to SIOP, and treatment was risk-adapted according to SIOP 93-01/Society for Pediatric Oncology and Hematology (GPOH) protocol. The patients were evaluated with regard to response, toxicity, and prognosis. Specimens of all tumors were centrally reviewed. Results Ten patients (33%) had metastatic disease at the time of diagnosis (liver, four patients; lung, three patients; liver and lung, three patients). The local stage distribution showed a predominance of higher stages (stage I, eight patients; stage IIN−, three patients; stage IIN+, four patients; stage III, 15 patients). Histologic studies revealed intermediate-risk in 23 of 30 tumors; two tumors were classified as high-risk; and three tumors were clear-cell sarcomas. Two of 30 patients showed a nephroblastoma and a renal cell carcinoma simultaneously in the same kidney. A complete remission was achieved in 24 patients; four patients relapsed after complete remission; and three of them reached a second remission with further treatment. Event-free survival was 57%, with an overall survival of 83% (median observation time, 4 years). Conclusion Adults can be cured in a high percentage by a multimodal treatment according to pediatric protocols. Toxicity is higher than in children, but acceptable in view of the high remission rate.

8566 Background: The role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement of aggressive B-cell lymphoma remains to be determined in the rituximab era. Methods: In a retrospective subgroup analysis of 9 consecutive prospective DSHNHL trials covering all DLBCL risk groups from 18 to 60 years of age, patients with and without craniofacial involvement were compared with respect to clinical presentation, event-free and overall survival. Results: 336 sites of extralymphatic craniofacial involvement were observed in 284/3840 (7.4%) patients (orbita: 30, paranasal sinuses: 90; main nasal cavity: 38, tongue: 26, remaining oral cavity: 99, salivary glands: 53). In a multivariable analysis adjusting for IPI risk factors the addition of rituximab improved EFS and OS in both patients with and without craniofacial involvement. The 141 responding patients who received radiotherapy to sites of craniofacial involvement had a similar 3-year event-free (79% vs 79%; p=0.835) and 3-year overall survival (88% vs. 85%; p=0.311) when compared with the 56 patients who did not receive radiotherapy. Without rituximab, the 2-year-rate of cumulative risk of CNS disease was increased in 205 patients with compared to 2586 patients without craniofacial involvement (4.2% vs. 2.8%; p=0.038), while this difference disappeared in patients who received CHOP(like) chemotherapy in combination with rituximab (1.7% in 77 patients with compared to 2.9% in 946 patients without craniofacial involvement; p=0.868). Of 85 patients with craniofacial involvement who received intrathecal prophylaxis with methotrexate, the 2-year-rate of cumulative risk of CNS disease was 4.3% compared to 2.3% in 189 patients who did not (p=0.995). Conclusions: Rituximab eliminates the increased risk for CNS disease in patients with craniofacial involvement. As a practical consequence intrathecal prophylaxis and radiotherapy to sites of craniofacial involvement should not be given any more.

Respiratory motion during percutaneous radiotherapy can be considered based on respiration-correlated computed tomography (4DCT). However, most treatment planning systems perform the dose calculation based on a single primary CT data set, even though cine mode displays may allow for a visualisation of the complete breathing cycle. This might create the mistaken impression that the dose distribution were independent of tumour motion. We present a movie visualisation technique with the aim to direct attention to the fact that the dose distribution migrates to some degree with the tumour and discuss consequences for gated treatment, IMRT plans and flattening-filter-free beams. This is a feasibility test for a visualisation of tumour and isodose motion. Ten respiratory phases are distinguished on the CT, and the dose distribution from a stationary IMRT plan is calculated on each phase, to be integrated into a movie of tumour and dose motion during breathing. For one example patient out of the sample of five lesions, the plan is compared with a gated treatment plan with respect to tumour coverage and lung sparing. The interplay-effect for small segments in the IMRT plan is estimated. While the high dose rate, together with the cone-shaped beam profile, makes the use of flattening-filter-free beams more problematic for conformal and IMRT treatment, it can be the option of choice if gated treatment is preferred. The different effects of respiratory motion, dose build-up and beam properties (segments and flatness) for gated vs. un-gated treatment can best be considered if planning is performed on the full 4DCT data set, which may be an incentive for future developments of treatment planning systems.

Abstract 690 Background: There is limited information on the role of skeletal involvement in DLBCL patients treated with rituximab. Methods: In a retrospective subgroup analysis patients with aggressive B-cell lymphomas with and without skeletal involvement were compared with respect to clinical presentation, event-free and overall survival. Results: Of 3840 patients 292 (7.6%) had skeletal involvement. In a multivariable analysis of patients treated within the randomized MInT and RICOVER-60 trials, the two largest randomized trials addressing the role of rituximab in DLBCL to date, skeletal involvement was associated with a reduced hazard ratio (HR) of 0.8 (p=0.181) for event-free survival and 0.7 (p=0.083) for overall survival for patients treated without, but with an increased HR (1.5; p=0.048) for event-free and (1.1; p=0.828) for overall survival in patients treated with rituximab. This was due to the failure of rituximab to improve the outcome of patients with skeletal involvement. In the MInT trial, the 3-year EFS rates were 64% without and 63% with rituximab (p=0.680) and the 3-year OS rates were 83% without and 90% with rituximab (p=0.542). similarly, in the RICOVER-60 trial, the 3-year EFS rates were 45% without and 50% with rituximab (p=0.593) and the 3-year OS rates were 68% without and 68% with rituximab. In a Cox regression model for event-free survival adjusted for the IPI risk factors a relevant interaction (HR 1.5; p=0.056) term between rituximab and skeletal involvement was observed. In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a better outcome: 3-year EFS rates were 40% without and 75% with radiotherapy (p Conclusion: Addition of rituximab failed, but radiotherapy to sites of skeletal involvement did improve the outcome of DLBCL patients with skeletal involvement. Radiotherapy to sites of skeletal involvement, though abandoned by many cooperative groups world-wide, is recommended in the rituximab era, unless prospective trials demonstrate that it might be omitted in cases with a negative PET after immunochemotherapy. Disclosures: Dreyling: Roche: Membership on an entity's Board of Directors or advisory committees. Hallek:Roche: Membership on an entity's Board of Directors or advisory committees. Schmitz:Chugai: Membership on an entity's Board of Directors or advisory committees. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy.

8022 Background: 117/306 (38%) of the total of 1,222 elderly (61-80 y) DLBCL pts. treated in RICOVER-60 with 6xR-CHOP-14+2R were assigned to receive additional radiotherapy (Rx) to bulky disease (Pfreundschuh et al., Lancet Oncol. 2008). To study the relevance of Rx to bulky disease (Bx), 166 pts. were prospectively treated without Rx in the R-CHOP-14-noRx amendment of RICOVER-60. Methods: The outcome of 166 R-CHOP-14-noRx patients was compared with the 306 patients who had received 6xR-CHOP-14+2R plus radiotherapy to Bx (≥7.5 cm) in RICOVER-60. Methods: The outcome of 166 R-CHOP-14-noRx patients was compared with the 306 patients who had received 6xR-CHOP-14+2R plus radiotherapy to Bx (≥7.5 cm) in RICOVER-60. Results: 164/166 R-CHOP-noRx patients are evaluable (median observation: 39 mos). Patients in R-CHOP-noRx were older (71 vs. 69 y.; median; p=0.018), more frequently in advanced stages (60% vs. 50%; p=0.037), and with extranodal involvement (63% vs. 53%; p=0.024), while Bx was more frequent in R-CHOP-14-Rx (38% vs. 29%; p=0.038). Overall response to therapy, EFS and OS were similar in the two studies adjusting for the prognostic imbalances between the cohorts. Patients with Bx who received received additional radiotherapy to Bx in R-CHOP-14-Rx had a better 3-year EFS (80% vs. 54%; p=0.001), a better PFS (88% vs. 62%; p

Background: The RICOVER60 trial has shown that 6 cycles of CHOP-14 with 8 applications of rituximab (6xR-CHOP-14) was superior to 8xR-CHOP-14, 6xCHOP-14 and 8xCHOP-14 in elderly patients with CD20-positive aggressive lymphoma. In that trial 117/306 (36%) of the patients in the 6xR-CHOP-14 arm were assigned to receive additional radiotherapy (Rx) to bulky disease (Pfreundschuh et al., Lancet Oncol. 2008). To study the relevance of additional Rx to bulky disease we subsequently initiated a prospective study in which no Rx was planned after 6 × R-CHOP-14. Methods: 166 elderly patients - subjected to the same inclusion and exclusion criteria as in the RICOVER-60 (R-CHOP-Rx) trial - were recruited for this study to receive 6xR-CHOP-14 without any radiotherapy (R-CHOP-noRx). The outcome of these patients was compared with the 306 patients assigned to receive 6xR-CHOP-14 and radiotherapy to bulky disease (³7.5 cm) in the R-CHOP-Rx trial. Results: 164/166 R-CHOP-noRx patients are evaluable with a median observation time of 17 months. Patients from both studies were well balanced for many known prognostic factors, but patients in R-CHOP-noRx were older (71 vs. 69 years; p=0.018), more frequently in advanced stages (60% vs. 50%; p=0.037), and with extranodal involvement (63% vs. 53%; p=0.024), while bulky disease was more frequent in the R-CHOP-Rx study (38% vs. 29%; p=0.038). Adherence to the immuno-chemotherapy protocol was excellent in both studies with median relative rituximab and cytotoxic drug doses of 99%. Overall response to therapy was similar in the two studies: CR/CRu: 76% vs. 78%; progressions 5.5% vs. 6.5%; relapses after CR/CRu 8% vs.10%; therapy-associated deaths 7% vs. 6% in R-CHOP-noRx and R-CHOP-Rx, respectively. Similarly, there were no significant differences between the two studies with respect to EFS, PFS and OS. This also holds in multivariate models adjusting for the prognostic imbalances between the cohorts. However, the patients with bulky disease in the R-CHOP-Rx trial assigned to receive additional radiotherapy to bulky disease had a 25% better 18-month EFS (68% [95%-CI: 59–76] vs. 43% [29–58]; p=0.002), a 10% better PFS (77% [70–85] vs. 67% [52–82]; p=0.123), and a 4% better OS (80% [72–87] vs. 76% [63–90]; p=0.509) compared with R-CHOP-noRx. The lower EFS rate in the R-CHOP-noRx study was due to patients with bulky disease not achieving CR or CRu after 6xRCHOP, while patients with bulky disease in CR or CRu after 6xR-CHOP-14 fared equally well with and without additional radiotherapy (18-month-EFS: 84% vs. 86%; p=0.512). Conclusion: In the rituximab era additional radiotherapy to bulky disease has no role for elderly patients in CR/CRu after completion of 6xR-CHOP-14 immunochemotherapy, but (unlike 2 additional chemotherapy cycles in the 8xR-CHOP-14 arm of R-CHOP-Rx) appears to be beneficial for patients with bulky disease achieving a PR.

5060 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. Results of an EORTC-phase-III- study (with unknown PSA-status after RP) suggested a 20% better biochemical control (bNED) after 5 years for RT. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3A+B vs. C). When the undetectable PSA-level after RP was not achieved, the pts. were stated as progressive disease and left arm A/B and were irradiated. PSA-progression for pts. with undetectable PSA was stated after two consecutive increasing PSA out of the undetectable range. Primary endpoint was bNED. Study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 53.6 months for arm A and 53.7 months for arm B. BNED at 5 years increased to 72% for arm A (RT) compared with 54% for arm B (WS) (p=0.0015, hazard ratio 0.53). Pts. with a preop. PSA > 10 ng/ml, tumor stage =pT3b, Gleason score =8 as well as positive margins profited significantly from adjuvant RT. The rate of late grade II side effects for the rectum was 1%. Conclusions: Adjuvant radiotherapy for pT3 prostate cancer significantly reduces the risk of biochemical progression after radical prostatectomy. The rate of side effects is very low. No significant financial relationships to disclose.

Background Our first trial on radiotherapy for painful heel spur published in 2012 comparing the analgesic effect of a standard dose (6 × 1.0Gy within three weeks) to that of a very low one (6 × 0.1Gy within three weeks) resulted in a highly significant superiority of the standard dose arm. In the meantime, experimental data have shown that lower single doses in the range of 0.5 – 0.7Gy might be even more effective than the current standard dose of 1.0 Gy. Therefore, we conducted a second trial comparing the analgesic effect of standard single doses of 1.0Gy to that of low single doses of 0.5Gy using uniform total doses of 6Gy. Patients and methods One hundred twenty-seven patients were randomized to receive radiation therapy either with a total dose of 6.0Gy applied in 6 fractions of 1.0Gy twice weekly (standard dose) or with the same total dose applied in 12 fractions of 0.5Gy three times weekly (experimental dose). In all patients lateral opposing 6MV photon beams were used. The results were measured using Visual analogue scale (VAS), Calcaneodynia score (CS) and SF-12 health survey. The first phase of this trial ended after a three months’ follow-up; it will be continued up to 48 weeks. Results Nine patients had to be excluded after randomization either due to the withdrawal of informed consent to radiotherapy by the patients or radiotherapy with an incorrect dosage. The groups were comparable concerning biographical and disease data. The mean calcaneodynia score (CS) was higher in the experimental group (p = 0.002). After three months’ follow-up, we saw a very favorable pain relief in both arms (decline of VAS score: standard arm 42 points, experimental arm 44 points (n.s.), but we did not notice any statistically significant difference between the arms neither concerning the pain parameters nor the quality of life parameters. No relevant acute side effects were recorded. Conclusions Favorable laboratory results could not be translated into an enhanced pain relief in our patients. This trial was terminated after the interim analysis (127 patients randomized). Further trials will be necessary to explore the best fractionation schedule. This trial has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians’ chamber. Trial registration Current trial registration at German Clinical Trials Register with the number DRKS00004458