Boost modalities in cervical cancer: dosimetric comparison between intracavitary BT vs. intracavitary + interstitial BT vs. SBRT.

PURPOSE / OBJECTIVE: This study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses. MATERIALS AND METHODS: 24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90% (defined as the minimum dose covering 90%) of the high-risk clinical target volume (HR-CTV); (2) Normalization to the OARs. HR-CTV coverage and OARs sparing were compared. The equivalent doses in 2 Gy fractions (EQD2) of EBRT and BT for CTV-HR and OARs were calculated using the linear-quadratic model with α/ß of 10 (EQD210) and 3 (EQD23), respectively RESULTS: A total of 72 plans were investigated. In the first normalization, the mean EQD23-D2cc (defined as the minimal dose of the 2 cc) of OAR was significantly higher in the IC-BT plans, and the bladder D2cc hard constraint could not be reached. IC + IS BT leads to a 1 Gy mean absolute decrease of bladder EQD23-D2cc (relative dose: -19%), allowing to reach the hard constraint. SBRT (without PTV) delivers the lowest EQD23-D2cc to the OAR. In the second normalization, IC-BT provides a significantly lower dose to the EQD210-D90% (6.62 Gy) and cannot achieve the coverage goal. SBRT (without PTV) yields the highest dose to the D90% of HR-CTV and a significantly lower EQD210-D50% and D30%. CONCLUSION: The key dosimetric benefit of BT over SBRT without PTV is a significantly higher D50% and D30% in the HR-CTV, which increases the local and conformal dose to the target. IC + IS BT vs. IC-BT provides significantly better target coverage and a lower dose to the OARs, making it the preferred boost modality in CC.

Combination, Modulation and Interplay of Modern Radiotherapy with the Tumor Microenvironment and Targeted Therapies in Pancreatic Cancer: Which Candidates to Boost Radiotherapy?

Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly diverse disease with low tumor immunogenicity. PDAC is also one of the deadliest solid tumor and will remain a common cause of cancer death in the future. Treatment options are limited, and tumors frequently develop resistance to current treatment modalities. Since PDAC patients do not respond well to immune checkpoint inhibitors (ICIs), novel methods for overcoming resistance are being explored. Compared to other solid tumors, the PDAC's tumor microenvironment (TME) is unique and complex and prevents systemic agents from effectively penetrating and killing tumor cells. Radiotherapy (RT) has the potential to modulate the TME (e.g., by exposing tumor-specific antigens, recruiting, and infiltrating immune cells) and, therefore, enhance the effectiveness of targeted systemic therapies. Interestingly, combining ICI with RT and/or chemotherapy has yielded promising preclinical results which were not successful when translated into clinical trials. In this context, current standards of care need to be challenged and transformed with modern treatment techniques and novel therapeutic combinations. One way to reconcile these findings is to abandon the concept that the TME is a well-compartmented population with spatial, temporal, physical, and chemical elements acting independently. This review will focus on the most interesting advancements of RT and describe the main components of the TME and their known modulation after RT in PDAC. Furthermore, we will provide a summary of current clinical data for combinations of RT/targeted therapy (tRT) and give an overview of the most promising future directions.

Inter-fraction heart displacement during voluntary deep inspiration breath hold radiation therapy without visual feedback measured by daily CBCT.

Purpose/Objective: Deep Inspiration Breath Hold (DIBH) is now considered as the standard of care for many breast cancer patients. However, there are still uncertainties about the dose given to the heart, and it is unknown if patients may improve voluntary DIBH depth by gaining experience during treatment. In this study, we will examine the interfractional three-dimensional (3D) heart displacement throughout voluntary DIBH (vDIBH) radiotherapy by means of daily cone-beam computed tomography (CBCT). Material and methods: Two hundred twenty-five unique CBCTs from 15 patients treated in 15 fractions were analyzed. During CBCT, a vDIBH was conducted without any visual feedback. Patients performed their DIBH freely after receiving explanations and training. After daily CBCT matching to the chest wall (CW), surface-guided radiation therapy (SGRT) tracked DIBH depth to ensure that the CW position was the same as the daily acquired CBCT. The CBCTs were retrospectively registered to the DIBH planning-CT to calculate daily changes in heart displacement relative to the CW. Results: The mean displacement of the heart during DIBH treatment relative to the DIBH planning-CT was as follows: 1.1 mm to the right, interquartile range (IQR) 8.0; 0.5 mm superiorly, IQR 4.8; and 0 mm posteriorly, IQR 6.4. The Spearman correlation coefficients (rs) were -0.15 (p=0.025), 0.04 (p=0.549), and 0.03 (p=0.612) for the X, Y, and Z directions, respectively. The differences in median heart displacement were significant: Friedmann rank sum test p=0.031 and pairwise comparison using the Wilcoxon rank-sum test were p=0.008 for X and Y; p=0.33 for X and Z; and p=0.07 for Y and Z. The total median heart motion was δtot median= 7.26 mm, IQR= 6.86 mm. Conclusion: During DIBH, clinicians must be aware of the wide range of intra- and inter-individual heart position variations. The inter-individual heterogeneity shown in our study should be investigated further in order to avoid unexpected cardiac overexposure and to develop a more accurate heart dose-volume model.