Analysis of long-term mortality after total body irradiation-based and melphalan-based chemotherapy conditioning for acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for selected patients with acute myeloid leukemia. Yet, the influence of total body irradiation (TBI)-based conditioning as compared to non-TBI-based conditioning on long-term mortality is unclear. We retrospectively evaluated outcomes after TBI-based (n = 91) and non-TBI-based conditioning (melphalan-based, n = 248) for 1st allo-HSCT patients transplanted at the University Hospital Regensburg between 1999 and 2020. TBI was performed with an average dose rate of 4 cGy/min. Median follow-up was 8.3 years (interquartile range, 4.8-12.9 years). Cumulative incidence rates of 5-year non-relapse mortality (NRM) were 17% (95% confidence interval, CI, 10-25) and 33% (95% CI, 27-40) after TBI- and non-TBI-based conditioning (P < 0.001). Five-year cumulative incidences of relapse (CIR) were 42% (95% CI, 32-52) and 29% (95% CI, 23-35) after TBI- and non-TBI-based conditioning (P = 0.030). The 5-year OS was 54% (95% CI, 43-64) and 55% (95% CI, 48-62) after TBI- and non-TBI-based conditioning. Both groups had similar 100-day acute graft-versus-host disease (aGVHD, 43% vs. 40%) and 5-year chronic GVHD (34% vs. 36%). The multivariable regression models found no associations of TBI with the outcomes NRM, CIR, PFS, OS, aGVHD, and cGVHD. TBI was no risk factor for NRM, even including mortality caused by secondary malignancies. NRM was influenced by patient age, advanced disease status, and the use of female donors for male recipients. TBI- and non-TBI-based conditioning appear to be equally effective and tolerable for AML patients eligible for 1st allo-HSCT.

Three-dimensional printers applied for the production of beam blocks in total body irradiation treatment.

PURPOSE: Total body irradiation (TBI) in extended source surface distance (SSD) is a common treatment technique before hematopoietic stem cell transplant. The lungs are organs at risk, which often are treated with a lower dose than the whole body. METHODS: This can be achieved by the application of blocks. Three-dimensional (3D) printers are a modern tool to be used in the production process of these blocks. RESULTS: We demonstrate the applicability of a specific printer and printing material, describe the process, and evaluate the accuracy of the product. CONCLUSION: The blocks and apertures were found to be applicable in clinical routine.

Radiotherapy for osteoarthritis of the ankle and tarsal joints-analysis of 66 joints.

PURPOSE: Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the knee or hip, but the associated disability is at least as severe as that of the other major joints of the lower limb. The results for total arthroplasty are still not satisfactory. For this reason, arthrodesis is still the gold standard of non-joint-conserving surgery. For the reason of functionality, joint-conserving therapies play a major role in treatment of ankle and tarsal osteoarthritis. Low-dose radiotherapy has a long history of treatment of osteoarthritis. The aim of this survey was to examine the results of low-dose radiotherapy for osteoarthritis of the ankle and tarsal joints. MATERIALS AND METHODS: The analysis was performed on patients of three German radiotherapy institutions and included 66 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 68 years, with 24.5% male and 75.5% female patients. The upper ankle was treated in 37.9%, the lower ankle in 27.3% and the tarsal joints in 34.8%. RESULTS: We could find a significant response to radiotherapy. For the whole sample, the median pain was 7 on the NRS before radiotherapy, 5 after 6 and 12 weeks, and 4 after 12 months. The percentage of patients with 0 or 1 on the NRS was 19.6% 12 months after radiotherapy. An improvement of joint mobility could be detected in 56.7% of the cases. All investigated subgroups had a significant reduction in pain. CONCLUSION: Radiotherapy of ankle and tarsal osteoarthritis is an effective treatment without showing side effects. All analysed subgroups show a good response to radiotherapy for at least 24 months.

The influence of radiotherapy techniques on the plan quality and on the risk of secondary tumors in patients with pituitary adenoma.

BACKGROUND: This planning study compares different radiotherapy techniques for patients with pituitary adenoma, including flatness filter free mode (FFF), concerning plan quality and secondary malignancies for potentially young patients. The flatness filter has been described as main source of photon scatter. MATERIAL AND METHODS: Eleven patients with pituitary adenoma were included. An Elekta Synergy™ linac was used in the treatment planning system Oncentra® and for the measurements. 3D plans, IMRT, and VMAT plans and non-coplanar varieties were considered. The plan quality was evaluated regarding homogeneity, conformity, delivery time and dose to the organs at risk. The secondary malignancy risk was calculated from dose volume data and from measured dose to the periphery using different models for carcinoma and sarcoma risk. RESULTS: The homogeneity and conformity were nearly unchanged with and without flattening filter, neither was the delivery time found substantively different. VMAT plans were more homogenous, conformal and faster in delivery than IMRT plans. The secondary cancer risk was reduced with FFF both in the treated region and in the periphery. VMAT plans resulted in a higher secondary brain cancer risk than IMRT plans, but the risk for secondary peripheral cancer was reduced. Secondary sarcoma risk plays a minor role. No advantage was found for non-coplanar techniques. The FFF delivery times were not shortened due to additional monitor units needed and technical limitations. The risk for secondary brain cancer seems to depend on the irradiated volume. Secondary sarcoma risk is much smaller than carcinoma risk in accordance to the results of the atomic bomb survivors. The reduction of the peripheral dose and resulting secondary malignancy risk for FFF is statistically significant. However, it is negligible in comparison to the risk in the treated region. CONCLUSION: Treatments with FFF can reduce secondary malignancy risk while retaining similar quality as with flattening filter and should be preferred. VMAT plans show the best plan quality combined with lowest peripheral secondary malignancy risk, but highest level of second brain cancer risk. Taking this into account VMAT FFF seems the most advantageous technique for the treatment of pituitary adenomas with the given equipment.

Secondary malignancy risk for patients with localized prostate cancer after intensity-modulated radiotherapy with and without flattening filter.

Men treated for localized prostate cancer by radiotherapy have often a remaining life span of 10 yr or more. Therefore, the risk for secondary malignancies should be taken into account. Plans for ten patients were evaluated which had been performed on an Oncentra® treatment planning system for a treatment with an Elekta Synergy™ linac with Agility™ head. The investigated techniques involved IMRT and VMTA with and without flattening filter. Different dose response models were applied for secondary carcinoma and sarcoma risk in the treated region and also in the periphery. As organs at risk we regarded for carcinoma risk urinary bladder, rectum, colon, esophagus, thyroid, and for sarcoma risk bone and soft tissue. The excess absolute risk (EAR) was found very similar in the treated region for both techniques (IMRT and VMAT) and also for both with and without flattening filter. The secondary sarcoma risk resulted about one magnitude smaller than the secondary carcinoma risk. The EAR to the peripheral organs was statistically significant reduced by application of the flattening filter free mode concerning the flattening filter as main source of scattered dose. Application of flattening filter free mode can thus support to reduce second malignancy risk for patients with localized prostate cancer.

Volumetric-modulated arc therapy and intensity-modulated radiation therapy treatment planning for prostate cancer with flattened beam and flattening filter free linear accelerators.

This study on patients with localized prostate cancer was set up to investigate valuable differences using flattened beam (FB) and flattening filter free (FFF) mode in the application of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). For ten patients, four different plans were calculated with Oncentra planning system of Elekta, using Synergy machines: IMRT and VMAT, with and without flattening filter. Homogeneity and conformity indexes, dose to the organs at risk, and measurements of peripheral dose and dosimetric plan verification including record of the delivery times were analyzed and statistically evaluated. The indexes for homogeneity and conformity (CTV and PTV) are either advantageous or not significantly different for FFF compared to FB with one minor exception. Regarding the doses to the organs at risk and the measured peripheral dose, equivalent or lower doses were delivered for FFF than with FB. Furthermore, the delivery times were significantly shorter for FFF. VMAT compared to IMRT reveals benefits or at least equivalent values. VMAT-FFF combines the most advantageous plan quality parameters with the shortest delivery times and reduced peripheral dose and is therefore recommended for the given equipment and cancer localization.

Stereotactic radiosurgery of brain metastases: a retrospective study.

BACKGROUND: Single-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS. METHODS: Seventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6-22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis. RESULTS: Melanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17-0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4-64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40-63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4-26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699). CONCLUSIONS: Our results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases. TRIAL REGISTRATION: This study is retrospectively registered (ethics approval number 23-3451-104).

Fractionated stereotactic radiotherapy of brain metastases: results of a retrospective study.

BACKGROUND: Lasting local control of brain metastases following stereotactic radiotherapy is becoming increasingly relevant since systemic treatment constantly improves the prognosis of patients with extracranial metastases. METHODS: 73 patients with 103 brain metastases received hypofractionated stereotactic radiotherapy (FSRT) in 6 fractions of 5 Gy between January 2017 and December 2021 at the University Hospital Regensburg, Germany. The study retrospectively evaluated local progression free survival (LPFS), overall survival (OS) and distant brain progression free survival (DPFS) of patients without prior radiotherapy of the brain. Response rate and brain radiation necrosis were reported. Cox proportional hazard models evaluated prognostic factors of OS and LPFS. RESULTS: The median patient age was 61.0 years (Interquartile range, IQR 51.0, 67.5). The most common tumor types were malignant melanoma (34.2%) and non-small cell lung adenocarcinoma (26.0%). The median gross tumor volume (GTV) was 0.9 cm³ (IQR 0.4, 3.6). The median follow-up time of all patients was 36.3 months (95%CI 29.1, 43.4). The median OS was 17.4 months (95%CI 9.9, 24.9). Overall survival rates at 6-, 12-, 18-, 24-, and 30 months were 81.9%, 59.1%, 49.0%, 41.3%, and 37.2%, retrospectively. The mean LPFS was 38.1 months (95%CI 31.4, 44.9), while the median LPFS has not been reached. LPFS rates at 6-, 12-, 18-, 24- and 30 months were 78.9%, 68.7%, 64.3%, 61.6% and 58.7%, retrospectively. Median DPFS of all patients was 7.7 months (95%CI 6.1, 9.3). Six, 12-, 18-, 24- and 30 months DPFS rates were 62.1%, 36.3%, 31.1%, 24.8% and 21.7%. Five brain metastases (4.8%) developed brain radiation necrosis. In multivariate analysis, the number of brain metastases negatively affected LPFS. Non-melanoma and non-renal cell cancer was associated with a higher chance of LPFS in comparison to other cancer. A GTV > 1.5 cm³ translated into a higher risk of death compared to a GTV ≤ 1.5 cm³ and Karnofsky performance score was predictive of OS. CONCLUSIONS: FSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases although melanoma and renal cell cancer seem to have a worse local control in comparison to other cancer. TRIAL REGISTRATION: This study is retrospectively registered.

IMRT of prostate cancer: a comparison of fluence optimization with sequential segmentation and direct step-and-shoot optimization.

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its superiority to three-dimensional conformal radiotherapy in the treatment of prostate cancer. Different optimization algorithms are available: algorithms which first optimize the fluence followed by a sequencing (IM), and algorithms which involve the machine parameters directly in the optimization process (DSS). The aim of this treatment-planning study is to compare both of them regarding dose distribution and treatment time. PATIENTS AND METHODS: Ten consecutive patients with localized prostate cancer were enrolled for the planning study. The planning target volume and the rectum volume, urinary bladder and femoral heads as organs at risk were delineated. Average doses, the target dose homogeneity H, D(5), D(95), monitor units per fraction, and the number of segments were evaluated. RESULTS: While there is only a small difference in the mean doses at rectum and bladder, there is a significant advantage for the target dose homogeneity in the DSS-optimized plans compared to the IM-optimized ones. Differences in the monitor units (nearly 10% less for DSS) and the number of segments are also statistically significant and reduce the treatment time. CONCLUSION: Particularly with regard to the tumor control probability, the better homogeneity of the DSS-optimized plans is more profitable. The shorter treatment time is an improvement regarding intrafractional organ motion. The DSS optimizer results in a higher target dose homogeneity and, simultaneously, in a lower number of monitor units. Therefore, it should be preferred for IMRT of prostate cancer.

[Practical dosimetry and constancy check at introduction of intraoperative radiotherapy with Intrabeam (Zeiss)]. / Praktische Dosimetrie und Konstanzprüfung zur Einführung der intraoperativen Bestrahlung mit Intrabeam (Zeiss).

The check of dosimetry of the intraoperative radiotherapy system Intrabeam is predefined by the manufacture (Zeiss). The purpose of the study was to develop and implement a method to verify the internal dosimetry of Intrabeam (Zeiss). Additionally the long-term stability of Intrabeam was checked for dose and isotropy. For dose to water measurements an Unidos was combined with a soft jet chamber (TM 23342) which was calibrated in water absorbed dose and as a phantom the type 2962 (PTW Freiburg) was used. RW1 plates were inserted as build up material. The applicators were placed in a bag filled with water to consider the side-scattering. At the surface of the applicator there was a mean difference of 3 percent between the dose to water measurement and the internal dosimetry. The constancy of the dose rate showed a mean deviation of 0.3% at the reference point. The analysis of the dose distribution perpendicular to the applicator axis z (reference z-axis) resulted in a mean deviation of -2.7% (x-direction) and -7,1% (-x-direction) for the x-axis and, respectively -4.1% (y-direction) and -5.3% (-y-direction) for the y-axis. The proposed method is suitable to verify the absolute dose of Intrabeam. The dose values measured by this method were congruent to the dosimetry of the manufacture (Zeiss). From our point of view it is sufficient to verify the absolute dosimetry only at time of commissioning of the system or in the case of changing the applicator. For the daily routine the check of constancy specified by the manufacture is adequate, because the dose rate is checked on a daily basis. Additionally the test of constancy showed a high long-term stability in terms of dose rate and symmetry.

[Certification of an in-house manufactured translational couch unit for total body irradiation in accordance with the medical devices act]. / Zertifizierung einer Translationsliege zur Ganzkörperbestrahlung aus In-Haus-Herstellung gemäss dem Medizinproduktegesetz.

UNLABELLED: A new translational couch unit with extended potentials of dose optimization by variable velocity and a comfortable user interface with integrated patient administration was developed at the university clinic of Regensburg. MATERIALS AND METHODS: The concept and construction were elaborated in legal accordance with the in-house manufacture conditions mentioned in the German Medical Devices Act. In particular we have implemented a concept of functional safety based on a controller unit, an independent monitoring unit and self-testing procedures. Redundant safety relevant hard- and software components are continuously checked against each other. In case of any malfunction the translation movement and the linear accelerator are stopped. Gap-free continuation of the treatment will be possible after elimination of the cause of the interrupt. RESULTS AND CONCLUSION: After the testing of the implemented functional safety features including the risk assessment and management, electrical safety, electromagnetic compatibility by accredited technical experts the translational couch system complies with the requirements of the Medical Devices Act and can be operated in terms of in-house application. The presented certification procedure can motivate other radiation departments to develop own systems for in-house usage.

Clinical results of intracoronary brachytherapy (ICBT) for multiple in-stent restenosis.

BACKGROUND AND PURPOSE: Treatment of in-stent restenosis (ISR) with percutaneous coronary intervention (PCI) alone is often followed by early re-restenosis. The present study focused on the effect of intracoronary brachytherapy (ICBT) on multiple in-stent restenosis (MISR) after repeated PCI. PATIENTS AND METHODS: 40 patients (27 male, 13 female, age: 66 +/- 9 years) with MISR (two to six ISRs, median three ISRs) were retrospectively analyzed. All patients were treated by using the Novoste((R)) Beta-Cathtrade mark 3.5F System after PCI. The target vessel received 18.4-25.3 Gy of radiation at a depth of 2 mm from the center of the source. The restenosis-free survival and overall survival were calculated by Kaplan-Meier analysis (log-rank). The time interval between last PCI without ICBT and the consecutive recurrence was compared with the follow-up time after PCI with ICBT. RESULTS: The 3-year overall survival rate after ICBT was 93%. The 0.5-, 1-, 2-, and 3-year ISR-free survival rates after PCI + ICBT were 81%, 72%, 52%, and 38%, respectively. After PCI alone, the 0.5-, 1-, and 2-year ISR-free survival rates were 30%, 13%, and 0%, respectively. This difference was highly significant (p < 0.0001). Patients with more than three ISRs before ICBT had a better outcome (3-year ISR-free survival: 80%) than patients with only two or three ISRs before ICBT (3-year ISR-free survival: 25%; p < 0.05). CONCLUSION: ICBT is highly effective and safe in patients with ISR. The results of this study are in accordance with the WRIST and BETA-WRIST data. After 6 months both studies revealed an ISR-free survival rate of 86% (WRIST) and 66% (BETA-WRIST), respectively. The ISR rates in the own control group (70%) were comparable to the placebo groups in WRIST (68%) and BETA-WRIST (72%). Interestingly, patients with more than three ISRs before ICBT had the lowest ISR rate after ICBT.

Total body irradiation-an attachment free sweeping beam technique.

INTRODUCTION: A sweeping beam technique for total body irradiation in standard treatment rooms and for standard linear accelerators (linacs) is introduced, which does not require any accessory attached to the linac. Lung shielding is facilitated to reduce the risk of pulmonary toxicity. Additionally, the applicability of a commercial radiotherapy planning system (RTPS) is examined. MATERIAL AND METHODS: The patient is positioned on a low couch on the floor, the longitudinal axis of the body in the rotational plane of the linac. Eight arc fields and five additional fixed beams are applied to the patient in supine and prone position respectively. The dose distributions were measured in a solid water phantom and in an Alderson phantom. Diode detectors were calibrated for in-vivo dosimetry. The RTPS Oncentra was employed for calculations of the dose distribution. RESULTS: For the cranial 120 cm the longitudinal dose profile in a slab phantom measured with ionization chamber varies between 94 and 107 % of the prescription dose. These values were confirmed by film measurements and RTPS calculations. The transmittance of the lung shields has been determined as a function of the thickness of the absorber material. Measurements in an Alderson phantom and in-vivo dosimetry of the first patients match the calculated dose. DISCUSSION AND CONCLUSION: A treatment technique with clinically good dose distributions has been introduced, which can be applied with each standard linac and in standard treatment rooms. Dose calculations were performed with a commercial RTPS and should enable individual dose optimization.

Searching standard parameters for volumetric modulated arc therapy (VMAT) of prostate cancer.

BACKGROUND: Since December 2009 a new VMAT planning system tool is available in Oncentra MasterPlan v3.3 (Nucletron B.V.). The purpose of this study was to work out standard parameters for the optimization of prostate cancer. METHODS: For ten patients with localized prostate cancer plans for simultaneous integrated boost were optimized, varying systematically the number of arcs, collimator angle, the maximum delivery time, and the gantry spacing. Homogeneity in clinical target volume, minimum dose in planning target volume, median dose in the organs at risk, maximum dose in the posterior part of the rectum, and number of monitor units were evaluated using student's test for statistical analysis. Measurements were performed with a 2D-array, taking the delivery time, and compared to the calculation by the gamma method. RESULTS: Plans with collimator 45° were superior to plans with collimator 0°. Single arc resulted in higher minimum dose in the planning target volume, but also higher dose values to the organs at risk, requiring less monitor units per fraction dose than dual arc. Single arc needs a higher value (per arc) for the maximum delivery time parameter than dual arc, but as only one arc is needed, the measured delivery time was shorter and stayed below 2.5 min versus 3 to 5 min. Balancing plan quality, dosimetric results and calculation time, a gantry spacing of 4° led to optimal results. CONCLUSION: A set of parameters has been found which can be used as standard for volumetric modulated arc therapy planning of prostate cancer.

Monte Carlo simulations to replace film dosimetry in IMRT verification.

Patient-specific verification of intensity-modulated radiation therapy (IMRT) plans can be done by dosimetric measurements or by independent dose or monitor unit calculations. The aim of this study was the clinical evaluation of IMRT verification based on a fast Monte Carlo (MC) program with regard to possible benefits compared to commonly used film dosimetry. 25 head-and-neck IMRT plans were recalculated by a pencil beam based treatment planning system (TPS) using an appropriate quality assurance (QA) phantom. All plans were verified both by film and diode dosimetry and compared to MC simulations. The irradiated films, the results of diode measurements and the computed dose distributions were evaluated, and the data were compared on the basis of gamma maps and dose-difference histograms. Average deviations in the high-dose region between diode measurements and point dose calculations performed with the TPS and MC program were 0.7 ± 2.7% and 1.2 ± 3.1%, respectively. For film measurements, the mean gamma values with 3% dose difference and 3mm distance-to-agreement were 0.74 ± 0.28 (TPS as reference) with dose deviations up to 10%. Corresponding values were significantly reduced to 0.34 ± 0.09 for MC dose calculation. The total time needed for both verification procedures is comparable, however, by far less labor intensive in the case of MC simulations. The presented study showed that independent dose calculation verification of IMRT plans with a fast MC program has the potential to eclipse film dosimetry more and more in the near future. Thus, the linac-specific QA part will necessarily become more important. In combination with MC simulations and due to the simple set-up, point-dose measurements for dosimetric plausibility checks are recommended at least in the IMRT introduction phase.

Commissioning of volumetric modulated arc therapy (VMAT) in a dual-vendor environment.

Methods and results for commissioning of the complete VMAT delivery chain are presented for the combination of Nucletron's Oncentra MasterPlan® v3.3 with Elekta's Mosaiq® v1.6 and SynergyS® linac. VMAT specific linac commissioning included determination of the size of the minimal dynamic leaf gap. Dosimetric validation of the complete treatment chain was performed using a 2D-ionization-chamber-array and showed excellent dosimetric results.