Radiotherapy of the oldest old-feasibility and institutional analysis.

PURPOSE: Little is known about efficacy and toxicity of radiation therapy in the elderly, as the vast majority of prospective trials excluded patients aged over 70 years. The aim of this study was to investigate the outcome of radiation therapy in a group of so-called oldest old cancer patients (≥85 years). MATERIALS AND METHODS: We retrospectively reviewed data from patients aged ≥85 years, treated between 2010 and 2015 for any tumor histology at the University Hospital Zurich, Switzerland. Overall survival (OS), relapse-free survival (RFS), performance status (ECOG), Charlson comorbidity index (CCI) and treatment tolerance were assessed. RESULTS: We identified and included 100 patients with a mean age of 88 years (range: 85-102 years). Most patients received a curative-intent treatment (n = 64, 64%). About one third received palliative radiation therapy for symptomatic metastatic disease (n = 36, 36%). Curative treatment was well tolerated, with no high-grade acute toxicities (≥grade 4). Median OS was 52.6 and 13.1 months for the curative and palliative treated patient groups, respectively. 5­year OS for all patients was 39.5% (95% CI: 23.6-54.5%). The Charlson comorbidity index (CCI) had a predictive value for overall survival (CCI > 10, p = 0.0001) in the curative group. CONCLUSION: The number of older cancer patients will increase considerably in the next decades because of demographic changes. Our analysis supports the notion that radiation therapy for this patient group of oldest old cancer patients is feasible in general. Treatment decisions should not be based on chronological age but rather on comorbidities and functional status.

Comparison of PET and CT radiomics for prediction of local tumor control in head and neck squamous cell carcinoma.

PURPOSE: An association between radiomic features extracted from CT and local tumor control in the head and neck squamous cell carcinoma (HNSCC) has been shown. This study investigated the value of pretreatment functional imaging (18F-FDG PET) radiomics for modeling of local tumor control. MATERIAL AND METHODS: Data from HNSCC patients (n = 121) treated with definitive radiochemotherapy were used for model training. In total, 569 radiomic features were extracted from both contrast-enhanced CT and 18F-FDG PET images in the primary tumor region. CT, PET and combined PET/CT radiomic models to assess local tumor control were trained separately. Five feature selection and three classification methods were implemented. The performance of the models was quantified using concordance index (CI) in 5-fold cross validation in the training cohort. The best models, per image modality, were compared and verified in the independent validation cohort (n = 51). The difference in CI was investigated using bootstrapping. Additionally, the observed and radiomics-based estimated probabilities of local tumor control were compared between two risk groups. RESULTS: The feature selection using principal component analysis and the classification based on the multivariabale Cox regression with backward selection of the variables resulted in the best models for all image modalities (CICT = 0.72, CIPET = 0.74, CIPET/CT = 0.77). Tumors more homogenous in CT density (decreased GLSZMsize_zone_entropy) and with a focused region of high FDG uptake (higher GLSZMSZLGE) indicated better prognosis. No significant difference in the performance of the models in the validation cohort was observed (CICT = 0.73, CIPET = 0.71, CIPET/CT = 0.73). However, the CT radiomics-based model overestimated the probability of tumor control in the poor prognostic group (predicted = 68%, observed = 56%). CONCLUSIONS: Both CT and PET radiomics showed equally good discriminative power for local tumor control modeling in HNSCC. However, CT-based predictions overestimated the local control rate in the poor prognostic validation cohort, and thus, we recommend to base the local control modeling on the 18F-FDG PET.

Comprehensive summary and retrospective evaluation of prognostic scores for patients with newly diagnosed brain metastases treated with upfront radiosurgery in a modern patient collective.

BACKGROUND: Numerous prognostic scores (PS) for patients with brain metastases (BM) have been developed. Recently, PS based on laboratory parameters were introduced to better predict overall survival (OS). A comprehensive comparison of the wide range of scores in a modern patient collective is still missing. MATERIALS AND METHODS: Twelve PS considering clinical parameters only at the time of BM diagnosis were calculated for 470 patients receiving upfront SRS between January 2014 and March 2020. In a subcohort of 310 patients where a full laboratory dataset was available five additional prognostic scores were compared. Restricted mean survival time (RMST), partial likelihood and c-index were calculated as metrics for performance evaluation. Univariable and multivariable analysis were used to identify prognostic factors for OS. RESULTS: The median OS of the whole cohort was 15.8 months (95% C.I.: 13.4-20.1). All prognostic scores performed well in separating patients into different prognostic groups. RPA achieved the highest c-index, whereas GGS achieved highest partial likelihood with evaluation in the total cohort. With incorporation of the laboratory scores the recently suggested EC-GPA achieved highest c-index and highest partial likelihood. A prognostic score solely based on the assessment of performance status achieved considerable high performance as either 3- or 4-tiered score. Multivariable analysis revealed performance status, systemic disease status and laboratory parameters to be significantly associated with OS among variates included in prognostic scores. CONCLUSION: Although recent PS incorporating laboratory parameters show convincing performance in predicting overall survival, older scores relying on clinical parameters only are still valid and appealing as they are easier to calculate, and as overall performance is almost equal. Moreover, a score just based on performance status is not significantly inferior and should at least be assessed for informed decision making.

Distance to isocenter is not associated with an increased risk for local failure in LINAC-based single-isocenter SRS or SRT for multiple brain metastases.

PURPOSE: To evaluate the impact of the distance between treatment isocenter and brain metastases on local failure in patients treated with a frameless linear-accelerator-based single-isocenter volumetric modulated arc (VMAT) SRS/SRT for multiple brain metastases. METHODS AND MATERIALS: Patients treated with SRT for brain metastases (BM) between April 2014 and May 2019 were included in this retrospective study. BM treated with a single-isocenter multiple-target (SIMT) SRT were evaluated for local recurrence-free intervals in dependency to their distance to the treatment isocenter. A Cox-regression model was used to investigate different predictor variables for local failure. Results were compared to patients treated with a single-isocenter-single-target (SIST) approach. RESULTS: In total 315 patients with a cumulative number of 1087 BM were analyzed in this study of which 140 patients and 708 BM were treated with SIMT SRS/SRT. Median follow-up after treatment was 13.9 months for SIMT approach and 11.9 months for SIST approach. One-year freedom from local recurrence was 87% and 94% in the SIST and SIMT group, respectively. Median distance to isocenter (DTI) was 4.7 cm (range 0.2-10.5) in the SIMT group. Local recurrence-free interval was not associated with the distance to the isocenter in univariable or multivariable Cox-regression analysis. Multivariable analysis revealed only volume as an independent significant predictor for local failure (p-value <0.05). CONCLUSION: SRS/SRT using single-isocenter VMAT for multiple targets achieved high local metastases control rates irrespective of distance to the isocenter, supporting efficacy of single-isocenter stereotactic radiation therapy for multiple brain metastases.

ITV, mid-ventilation, gating or couch tracking - A comparison of respiratory motion-management techniques based on 4D dose calculations.

PURPOSE: Respiratory motion-management techniques (MMT) aim to ensure tumor dose coverage while sparing lung tissue. Dynamic treatment-couch tracking of the moving tumor is a promising new MMT and was compared to the internal-target-volume (ITV) concept, the mid-ventilation (MidV) principle and the gating approach in a planning study based on 4D dose calculations. METHODS: For twenty patients with lung lesions, planning target volumes (PTV) were adapted to the MMT and stereotactic body radiotherapy treatments were prepared with the 65%-isodose enclosing the PTV. For tracking, three concepts for target volume definition were considered: Including the gross tumor volume of one phase (single-phase tracking), including deformations between phases (multi-phase tracking) and additionally including tracking latencies of a couch tracking system (reliable couch tracking). The accumulated tumor and lung doses were estimated with 4D dose calculations based on 4D-CT datasets and deformable image registration. RESULTS: Single-phase tracking showed the lowest ipsilateral lung Dmean (median: 3.3Gy), followed by multi-phase tracking, gating, reliable couch tracking, MidV and ITV concepts (3.6, 3.8, 4.1, 4.3 and 4.8Gy). The 4D dose calculations showed the MidV and single-phase tracking overestimated the target mean dose (-2.3% and -1.3%), while it was slightly underestimated by the other MMT (<+1%). CONCLUSION: The ITV concept ensures tumor coverage, but exposes the lung tissue to a higher dose. The MidV, gating and tracking concepts were shown to reduce the lung dose. Neglecting non-translational changes of the tumor in the target volume definition for tracking results in a slightly reduced target coverage. The slightly inferior dose coverage for MidV should be considered when applying this technique clinically.

Three-dimensional versus four-dimensional dose calculation for volumetric modulated arc therapy of hypofractionated treatments.

PURPOSE: Respiratory motion is a non-negligible source of uncertainty in radiotherapy. A common approach is to delineate the target volume in all respiratory phases (ITV) and to calculate a treatment plan using the average reconstruction of the four-dimensional computed tomography (4DCT) scans. In this study the extent of the interplay effect caused by interaction between dynamic dose delivery and respiratory tumor motion, as well as other motion effects were investigated. These effects are often ignored when the ITV concept is used. METHODS AND MATERIALS: Nine previously treated patients with in ten abdominal or thoracic cancer lesions (3 liver, 3 adrenal glands and 4 lung lesions) were selected for this planning study. For all patients, phase-sorted respiration-correlated 4DCT scans were taken, and volumetric modulated arc therapy (VMAT) treatments were planned using the ITV concept. Margins from ITV to planning target volume (PTV) of 3-10mm were used. Plans were optimized and dose distributions were calculated on the average reconstruction of the 4DCT. 4D dose distributions were calculated to evaluate motion effects, caused by the interference of dynamic treatment delivery with respiratory tumor motion and inhomogeneously planned target dose. These calculations were performed on the phase-sorted CT series with a respiration-correlated assignment of the treatment plan's monitor units (MU) to the respiration phases of the 4DCT. The 4D dose was accumulated with rigid as well as deformable registrations of the CT series and compared to the original 3D dose distribution. Maximum, minimum and mean doses to ITV and PTV, and maximum or mean doses to organs at risk (OAR), were compared after rigid accumulation. The dose variation in the gross tumor volume (GTV) was compared after deformable registration. RESULTS: Using rigid registrations, variations in the investigated dose parameters between 3D and 4D dose calculations were found to be within -2.1% to 1.4% for all target volumes and within -0.8% to 1.7% in OAR. Using deformable registrations, dose differences in the GTV were below 3.8% for dose accumulation of lung and adrenal gland patients. For liver patients the used deformable registrations were not considered to be robust enough. It was also shown that a major part of the dose differences originates from the Hounsfield unit differences between 3D and 4D calculations, regardless of the interplay effect. CONCLUSION: The evaluated motion effects during VMAT treatments resulted in negligible dose variability. Therefore, the approximation of calculating the dose on the average reconstruction of the 4DCT (3D dose calculation), instead of calculating on the respiration-correlated phase CTs (4D dose calculation) with assignment of the corresponding MUs, gives acceptable results.