[en] Purpose: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors < 100 cm³), or vincristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-risk tumors (central tumors and extremity tumors ≥ 100 cm³). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for conventional fractionation). For quality assurance in radiotherapy, a central treatment planning program was part of the protocol. Results: Forty-four patients (25%) received definitive radiotherapy; 39 (22%) had surgery, and 93 (53%) had resection plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiotherapy, 26% after radical surgery, and 34% after combined local treatment. The better local control after radical surgery (100%) and resection plus radiotherapy (95%) as compared to definitive radiotherapy (86%) was not associated with an improvement in relapse-free or overall survival because of a higher frequency of distant metastases after surgery (26% vs. 29% vs. 16%). In irradiated patients, hyperfractionated split-course irradiation and conventional fractionation yielded the same results (5-year overall survival of definitively irradiated patients 63% after conventional fractionation and 65% after hyperfractionation; relapse-free survival 53% vs. 58%; local control 76% vs. 86%, not significant). The six local failures after radiotherapy did not correlate with tumor size or response to chemotherapy. Radiation treatment quality (target volume, technique, dosage) was evaluated retrospectively and was scored as unacceptable in only 1 out of 44 patients (2%) with definitive radiotherapy. Grade 3-4 complications developed in 4 out of 44 (9%) patients after definitive radiotherapy. Conclusions: Under the given selection criteria for local therapy, radiation therapy yielded relapse-free and overall survival figures comparable to radical surgery. Hyperfractionated split-course irradiation simultaneously with multidrug chemotherapy did not significantly improve local control or survival

[en] Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated patients seem to be at low risk for solid tumors within the first ten years after treatment but have a 5%-risk of developing any solid tumor after 15 years. However, there have been no deaths due to secondary sarcomas up to now

[en] Purpose: To evaluate the functional effects of ionizing radiation in patients with unresectable pancreatic cancer in the early period after accelerated radiochemotherapy (ART). Methods and Materials: To analyze the exocrine component, the amino acid consumption test and fecal elastase 1 were performed in 13 patients immediately before and 4-8 weeks after ART. Pancreatic duct morphology was evaluated before therapy. Weight loss and clinical steatorrhea were recorded. Endocrine parameters were examined according to standardized criteria. Results: The relative change of the amino acid consumption test results and the median elastase concentration was 41.2% and 56.4%, respectively. Five patients still had normal test results after ART and 5 patients developed pathologic values. The median relative weight loss of the total body weight was 7.7% ± 4.5%. No steatorrhea occurred. Of the 5 patients with normal values, 3 had a mean organ dose of <40 Gy. Of the 5 patients with pathologic values, 4 had a mean organ dose of >41 Gy. The endocrine function measurements remained unchanged. Conclusion: Although a nominal reduction of exocrine function parameters occurred in most patients, ART was not necessarily related to a pathologic level in the early period. Diabetes was not established. The functional impairment that was existent in the patient population presumably contributed to the weight loss. Pancreatic enzyme preparations may also play a role in maintaining an anabolic state during and after radiochemotherapy

[en] Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. Results: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clincal remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1% (3/328) of all deaths in the CESS-studies. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5% after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible

[en] The mARC technique is a hybrid rotational IMRT modality operating in ''burst mode''. While it is generally assumed that it will be slower than VMAT, the real limits of operation have not been defined so far. We here present the first systematic study of the technical limits on mARC treatment. The following scenarios are considered: 18, 30, 36 or 45 arclets per rotation (spacing between 20 and 8 ), flat and flattening-filter-free (FFF) energy, arclet width 4 or 2 , from 1 MU/arclet to 1000 MU/plan. All scenarios are irradiated, treatment times are measured and treatment parameters reported. Dose linearity was assessed by point dose measurements of the 18 arclet plans with 1-30 MU per arclet. Minimum treatment times (no MLC movement, few MUs) depend strongly on the number of arclets per rotation (1 minute for 18 arclets to 1:50 min for 45 arclets), and rise linearly with MU/arclets after a given cut-off value depending on scenario, arclet width and available maximum dose rate. MLC movement adds up to 2 minutes of treatment time, but generally less (ca. 45 seconds in realistic plans). The rules by which irradiation parameters are selected by the firmware can be partly discovered. The choice of dose rate is most clearly defined. For the flat 6 MV energy, the highest available dose rate (300 MU/min) is always applied. For FFF 7 MV dose rate is reduced for arclets with few MUs, so that an arclet is irradiated in no less than 0.3 s. Only for the case of 1 MU/arclet can this constraint not be met (the technical limit on the dose rate if 500 MU/min for FFF 7 MV). In this case, dosimetric linearity is reduced. In all other instances, deviations from linearity at low MU remain below 2%. Treatment times of down to 90 seconds are technically achievable for treatment with FFF beams using up to 36 arclets per rotation (arclet spacing every 10 ) for up to 900 MU/plan, comparable to VMAT treatment times. The values provided here are meant to serve as a reference for the design of mARC plans (choice of arclets spacing etc.) and as minimum times against which the performance of different treatment planning systems can be evaluated.

[en] To evaluate retrospectively the results of radiotherapy for periarthritis of the shoulder 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]. 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'. Low-dose radiotherapy for periarthropathy of the shoulder was highly effective and yielded long-lasting improvement of pain and motility without side effects

[en] 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 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 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.

[en] Linac-based patient imaging is possible with a variety of techniques using different photon energies. The purpose of this work is to compare three imaging systems operating at 6 MV, flattening free filter (FFF) 1 MV, and 121 kV. The dose distributions of all pretreatment set-up images (over 1,000) were retrospectively calculated on the planning computed tomography (CT) images for all patients with prostate and head-and-neck cancer treated at our institution in 2013. We analyzed the dose distribution and the dose to organs at risk. For head-and-neck cancer patients, the imaging dose from 6-MV cone beam CT (CBCT) reached maximum values at around 8 cGy. The 1-MV CBCT dose was about 63-79 % of the 6-MV CBCT dose for all organs at risk. Planar imaging reduced the imaging dose from CBCT to 30-40 % for both megavoltage modalities. The dose from the kilovoltage CBCT was 4-10 % of the 6-MV CBCT dose. For prostate cancer patients, the maximum dose from 6-MV CBCT reached 13-15 cGy, and was reduced to 66-73 % for 1 MV. Planar imaging reduces the MV CBCT dose to 10-20 %. The kV CBCT dose is 15-20 % of the 6-MV CBCT dose, slightly higher than the dose from MV axes. The dose distributions differ markedly in response to the different beam profiles and dose-depth characteristics. (orig.)

[en] The potential of intensity-modulated radiation therapy (IMRT) as opposed to three-dimensional conformal radiotherapy (3D-CRT) is analyzed for two different concepts of fluorodeoxyglucose positron emission tomography (FDG PET)-based target volume delineation in locally advanced non-small cell lung cancer (LA-NSCLC): involved-field radiotherapy (IF-RT) vs. elective nodal irradiation (ENI). Treatment planning was performed for 41 patients with LA-NSCLC, using four different planning approaches (3D-CRT-IF, 3D-CRT-ENI, IMRT-IF, IMRT-ENI). ENI included a boost irradiation after 50 Gy. For each plan, maximum dose escalation was calculated based on prespecified normal tissue constraints. The maximum prescription dose (PD), tumor control probability (TCP), conformal indices (CI), and normal tissue complication probabilities (NTCP) were analyzed. IMRT resulted in statistically significant higher prescription doses for both target volume concepts as compared with 3D-CRT (ENI: 68.4 vs. 60.9 Gy, p < 0.001; IF: 74.3 vs. 70.1 Gy, p < 0.03). With IMRT-IF, a PD of at least 66 Gy was achieved for 95 % of all plans. For IF as compared with ENI, there was a considerable theoretical increase in TCP (IMRT: 27.3 vs. 17.7 %, p < 0.00001; 3D-CRT: 20.2 vs. 9.9 %, p < 0.00001). The esophageal NTCP showed a particularly good sparing with IMRT vs. 3D-CRT (ENI: 12.3 vs. 30.9 % p < 0.0001; IF: 15.9 vs. 24.1 %; p < 0.001). The IMRT technique and IF target volume delineation allow a significant dose escalation and an increase in TCP. IMRT results in an improved sparing of OARs as compared with 3D-CRT at equivalent dose levels. (orig.)

[en] 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. 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. 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. 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