Stereotactic body radiotherapy of adrenal metastases-A dose-finding study.

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

Stereotactic or conformal radiotherapy for adrenal metastases: Patient characteristics and outcomes in a multicenter analysis.

To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%). Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression. Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.

Patient-related quality assurance with different combinations of treatment planning systems, techniques, and machines : A multi-institutional survey.

PURPOSE: This project compares the different patient-related quality assurance systems for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques currently used in the central Germany area with an independent measuring system. MATERIALS AND METHODS: The participating institutions generated 21 treatment plans with different combinations of treatment planning systems (TPS) and linear accelerators (LINAC) for the QUASIMODO (Quality ASsurance of Intensity MODulated radiation Oncology) patient model. The plans were exposed to the ArcCHECK measuring system (Sun Nuclear Corporation, Melbourne, FL, USA). The dose distributions were analyzed using the corresponding software and a point dose measured at the isocenter with an ionization chamber. RESULTS: According to the generally used criteria of a 10 % threshold, 3 % difference, and 3 mm distance, the majority of plans investigated showed a gamma index exceeding 95 %. Only one plan did not fulfill the criteria and three of the plans did not comply with the commonly accepted tolerance level of ±3 % in point dose measurement. CONCLUSION: Using only one of the two examined methods for patient-related quality assurance is not sufficiently significant in all cases.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

PURPOSE: The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). MATERIALS AND METHODS: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. RESULTS: In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). CONCLUSION: All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

Factors associated with overall survival, progression-free survival and toxicity in patients with small cell lung cancer and thoracic irradiation in a clinical real-world setting.

BACKGROUND: Small-cell lung cancer (SCLC) is a malignant tumor known for its poor prognosis. In addition to chemotherapy and immunotherapy irradiation plays a big role especially in inoperability. This study evaluated prognostic factors in patients with SCLC, receiving chemotherapy and thoracic irradiation, that may affect overall survival (OS), progression-free survival (PFS) and toxicity. METHODS: Patients with limited disease (LD) SCLC (n = 57) and extensive disease (ED) SCLC (n = 69) who received thoracic radiotherapy were analyzed retrospectively. The prognostic factors sex, age, Karnofsky performance status (KPS), tumor-, nodal-stage and timepoint of start of irradiation in relation to the first cycle of chemotherapy were evaluated. Start of irradiation was stratified as early ([Formula: see text] 2 cycles of chemotherapy), late (3 or 4 cycles) and very late ([Formula: see text] 5 cycles). Results were analyzed by Cox univariate and multivariate as well as logistic regression analysis. RESULTS: The median OS of LD-SCLC patients was 23.7 months in early, and 22.0 months in late start of irradiation. In very late start, median OS was not reached. PFS was 11.8, 15.2 and 47.9 months, respectively. In patients with ED-SCLC OS was 4.3 months in early, 13.0 months in late and 12.2 months in very late start of irradiation. PFS was 6.7, 13.0 and 12.2 months, respectively. Prognosis of patients with LD- or ED-SCLC receiving late or very late start of irradiation was significantly prolonged in OS and PFS compared to an early start (p < 0.05). KPS [Formula: see text] 80 shows a significant increase of OS and PFS in ED-SCLC. Female sex and smaller mean lung dose were associated with lower risk of toxicity. CONCLUSION: Late or very late start of irradiation is a prognosis-enhancing factor in LD-SCLC and ED-SCLC for OS and PFS. KPS [Formula: see text] 80 increases prognosis of OS and PFS in ED-SCLC as well. Toxicity is less common in female sex and patients with low mean lung dose in LD-SCLC.

Feasibility of a simultaneously integrated boost concept for hypofractionated stereotactic radiotherapy of unresected brain metastases.

BACKGROUND: In stereotactic radiotherapy, dose is prescribed to an isodose surrounding the planning target volume (PTV). However, the desired dose inhomogeneity inside the PTV leaves the specific dose distribution to the gross tumor volume (GTV) unspecified. A simultaneously integrated boost (SIB) to the GTV could solve this shortcoming. In a retrospective planning study with 20 unresected brain metastases, a SIB approach was tested against the classical prescription. METHODS: For all metastases, the GTV was isotropically enlarged by 3 mm to a PTV. Two plans were generated, one according to the classical 80% concept with 5 times 7 Gy prescribed (on D2%) to the 80% PTV surrounding isodose (with D98%(PTV) ≥ 35 Gy), and the other one following a SIB concept with 5 times 8.5 Gy average GTV dose and with D98%(PTV) ≥ 35 Gy as additional requirement. Plan pairs were compared in terms of homogeneity inside GTV, high dose in PTV rim around GTV, and dose conformity and gradients around PTV using Wilcoxon matched pairs signed rank test. RESULTS: The SIB concept was superior to the classical 80% concept concerning dose homogeneity inside GTV: Heterogeneity index of GTV was in the SIB concept (median 0.0513, range 0.0397-0.0757) significantly (p = 0.001) lower than in the 80% concept (median 0.0894, range 0.0447-0.1872). Dose gradients around PTV were not inferior. The other examined measures were comparable. CONCLUSION: Our stereotactic SIB concept better defines the dose distribution inside PTV and can be considered for clinical use.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Liver Metastases: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE: Our purpose was to investigate whether liver stereotactic body radiation therapy treatment planning can be harmonized across different treatment planning systems, delivery techniques, and institutions by using a specific prescription method and to minimize the knowledge gap concerning intersystem and interuser differences. We provide best practice guidelines for all used techniques. METHODS AND MATERIALS: A multiparametric specification of target dose (gross target volume [GTV]D50%, GTVD0.1cc, GTVV90%, planning target volume [PTV]V70%) with a prescription dose of GTVD50% = 3 × 20 Gy and organ-at-risk (OAR) limits were distributed with computed tomography and structure sets from 3 patients with liver metastases. Thirty-five institutions provided 132 treatment plans using different irradiation techniques. These plans were first analyzed for target and OAR doses. Four different renormalization methods were performed (PTVDmin, PTVD98%, PTVD2%, PTVDmax). The resulting 660 treatments plans were evaluated regarding target doses to study the effect of dose renormalization to different prescription methods. A relative scoring system was used for comparisons. RESULTS: GTVD50% prescription can be performed in all systems. Treatment plan harmonization was overall successful, with standard deviations for Dmax, PTVD98%, GTVD98%, and PTVDmean of 1.6, 3.3, 1.9, and 1.5 Gy, respectively. Primary analysis showed 55 major deviations from clinical goals in 132 plans, whereas in only <20% of deviations GTV/PTV dose was traded for meeting OAR limits. GTVD50% prescription produced the smallest deviation from target planning objectives and between techniques, followed by the PTVDmax, PTVD98%, PTVD2%, and PTVDmin prescription. Deviations were significant for all combinations but for the PTVDmax prescription compared with GTVD50% and PTVD98%. Based on the various dose prescription methods, all systems significantly differed from each other, whereas GTVD50% and PTVD98% prescription showed the least difference between the systems. CONCLUSIONS: This study showed the feasibility of harmonizing liver stereotactic body radiation therapy treatment plans across different treatment planning systems and delivery techniques when a sufficient set of clinical goals is given.

A multi-institutional initiative on patient-related quality assurance: Independent computational dose verification of fluence-modulated treatment techniques.

PURPOSE: This multi-institutional study investigates whether computational verification of fluence-modulated treatment plans using independent software with its own Strahlerkopfmodel is an appropriate method for patient-related quality assurance (PRQA) in the context of various combinations of linear accelerators (linacs), treatment techniques and treatment planning systems (TPS). MATERIALS AND METHODS: The PRQA-software's (Mobius3D) recalculations of 9 institutions' treatment plans were analyzed for a horseshoe-shaped planning target volume (PTV) inside a phantom. The recomputed dose distributions were compared to a) the dose distributions as calculated by all TPS's and b) the measured dose distributions, which were acquired using the same independent measuring system for all institutions. Furthermore, dose volume histograms were examined. The penumbra deviations and mean gamma values were quantified using Verisoft (PTW). Additionally, workflow requirements for computational verification were discussed. RESULTS: Mobius3D is compatible with all examined TPSs, treatment techniques and linacs. The mean PTV dose differences (Mobius3D-TPS, <3.0%) and 3D gamma passing rates (>95.0%) led to a positive plan acceptance result in all cases. These results are similar to the outcome of the dosimetric measurements with one exception. The mean gamma values (<0.5) show a good agreement between Mobius3D and the TPS dose distributions. CONCLUSION: Using Mobius3D was proven to be an appropriate computational PRQA method for the tested combinations of linacs, treatment techniques and TPS's. The clinical use of Mobius3D has to be complemented with regular dosimetric measurements and thorough linac and TPS QA. Mobius3D's computational verification reduced measurement effort and personnel needs in comparison to dosimetric verifications.

Simultaneous stereotactic body radiation therapy of a primary non-small cell lung cancer and synchronous carcinoma in situ in a medically inoperable patient: case report.

The co-incidence of synchronous intraepithelial neoplasia and early stage invasive lung cancer is not a rare phenomenon. The need for curative treatment and the invasive potential of squamous cell pulmonary carcinoma in situ have been a topic of controversy. Surgical resection still remains the treatment of choice. Varieties of endoscopic techniques such as brachytherapy were developed as an alternative to surgery in selected patients. External beam radiation therapy has been used traditionally in combination with endobronchial brachytherapy in the treatment of roentgenographically occult lung cancer, and can be offered for all patients, but is handicapped, because these tumors are radiographically invisible. We report the first case of a pulmonary carcinoma in situ that was successfully treated with stereotactic body radiation therapy.