The heterogeneity of high‐grade glioma recurrences remains an ongoing challenge for the interdisciplinary neurooncology team. Response to re‐irradiation (re‐RT) is heterogeneous, and survival data depend on prognostic factors such as tumor volume, primary histology, age, the possibility of reresection, or time between primary diagnosis and initial RT and re‐RT. In the present pooled analysis, we gathered data from radiooncology centers of the DKTK Consortium and used it to validate the established prognostic score by Combs et al. and its modification by Kessel et al. Data consisted of a large independent, multicenter cohort of 565 high‐grade glioma patients treated with re‐RT from 1997 to 2016 and a median dose of 36 Gy. Primary RT was between 1986 and 2015 with a median dose of 60 Gy. Median age was 54 years; median follow‐up was 7.1 months. Median OS after re‐RT was 7.5, 9.5, and 13.8 months for WHO IV, III, and I/II gliomas, respectively. All six prognostic factors were tested for their significance on OS. Aside from the time from primary RT to re‐RT (P = 0.074) and the reresection status (P = 0.101), all factors (primary histology, age, KPS, and tumor volume) were significant. Both the original and new score showed a highly significant influence on survival with P < 0.001. Both prognostic scores successfully predict survival after re‐RT and can easily be applied in the routine clinical workflow. Now, further prognostic features need to be found to even improve treatment decisions regarding neurooncological interventions for recurrent glioma patients.

Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33–74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995–1.015), P = 0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986–1.012), P = 0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).

Purpose: A confirmatory analysis was performed to determine the prognostic value of metabolic response during induction chemotherapy followed by bimodality/trimodality treatment of patients with operable locally advanced non–small-cell lung cancer. Patients and Methods: Patients with potentially operable stage IIIA(N2) or selected stage IIIB non–small-cell lung cancer received three cycles of cisplatin/paclitaxel (induction chemotherapy) followed by neoadjuvant radiochemotherapy (RCT) to 45 Gy (1.5 Gy twice per day concurrent cisplatin/vinorelbine) within the ESPATUE (Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA[N2] and Selected IIIB Non–Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy) trial. Positron emission tomography scans were recommended before (t₀) and after (t₂) induction chemotherapy. Patients who were eligible for surgery after neoadjuvant RCT were randomly assigned to definitive RCT or surgery. The prognostic value of percentage of maximum standardized uptake value (%SUV_max) remaining in the primary tumor after induction chemotherapy—%SUV_remaining = SUV_max(t₂)/SUV_max(t₀)—was assessed by proportional hazard analysis and receiver operating characteristic analysis. Results: Overall, 161 patients were randomly assigned (155 from the Essen and Tübingen centers), and 124 of these received positron emission tomography scans at t₀ and t₂. %SUV_remaining as a continuous variable was prognostic for the three end points of overall survival, progression-free survival, and freedom from extracerebral progression in univariable and multivariable analysis (P < .016). The respective hazard ratios per 50% increase in %SUV_remaining from multivariable analysis were 2.3 (95% CI, 1.5 to 3.4; P < .001), 1.8 (95% CI, 1.3 to 2.5; P < .001), and 1.8 (95% CI, 1.2 to 2.7; P = .006) for the three end points. %SUV_remaining dichotomized at a cut point of maximum sum of sensitivity and specificity from receiver operating characteristic analysis at 36 months was also prognostic. Exploratory analysis revealed that %SUV_remaining was likewise prognostic for overall survival in both treatment arms and was more closely associated with extracerebral distant metastases (P = .016) than with isolated locoregional relapses (P = .97). Conclusion: %SUV_remaining is a predictor for survival and other end points after multimodality treatment and can serve as a parameter for treatment stratification after induction chemotherapy or for evaluation of adjuvant new systemic treatment options for high-risk patients.

Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTV${}_{entire}$). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTV${}_{entire}$ was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTV${}_{entire}$ achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.

Importance: Patients with newly diagnosed locally advanced cervical carcinomas or recurrences after surgery undergoing radiochemotherapy whose tumor is unsuited for a brachytherapy boost need high-dose percutaneous radiotherapy with small margins to compensate for clinical target volume deformations and set-up errors. Cone-beam computed tomography–based online adaptive radiotherapy (ART) has the potential to reduce planning target volume (PTV) margins below 5 mm for these tumors.Objective: To compare online ART technologies with image-guided radiotherapy (IGRT) for gynecologic tumors.Design, Setting, and Participants: This comparative effectiveness study comprised all 7 consecutive patients with gynecologic tumors who were treated with ART with artificial intelligence segmentation from January to May 2022 at the West German Cancer Center. All adapted treatment plans were reviewed for the new scenario of organs at risk and target volume. Dose distributions of adapted and scheduled plans optimized on the initial planning computed tomography scan were compared.Exposure: Online ART for gynecologic tumors.Main Outcomes and Measures: Target dose coverage with ART compared with IGRT for PTV margins of 5 mm or less in terms of the generalized equivalent uniform dose (gEUD) without increasing the gEUD for the organs at risk (bladder and rectum).Results: The first 10 treatment series among 7 patients (mean [SD] age, 65.7 [16.5] years) with gynecologic tumors from a prospective observational trial performed with ART were compared with IGRT. For a clinical PTV margin of 5 mm, IGRT was associated with a median gEUD decrease in the interfractional clinical target volume of −1.5% (90% CI, −31.8% to 2.9%) for all fractions in comparison with the planned dose distribution. Online ART was associated with a decrease of −0.02% (90% CI, −3.2% to 1.5%), which was less than the decrease with IGRT (P < .001). This was not associated with an increase in the gEUD for the bladder or rectum. For a PTV margin of 0 mm, the median gEUD deviation with IGRT was −13.1% (90% CI, −47.9% to 1.6%) compared with 0.1% (90% CI, −2.3% to 6.6%) with ART (P < .001). The benefit associated with ART was larger for a PTV margin of 0 mm than of 5 mm (P = .004) due to spreading of the cold spot at the clinical target volume margin from fraction to fraction with a median SD of 2.4 cm (90% CI, 1.9-3.4 cm) for all patients.Conclusions and Relevance: This study suggests that ART is associated with an improvement in the percentage deviation of gEUD for the interfractional clinical target volume compared with IGRT. As the gain of ART depends on fractionation and PTV margin, a strategy is proposed here to switch from IGRT to ART, if the delivered gEUD distribution becomes unfavorable in comparison with the expected distribution during the course of treatment.