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Background and purpose Prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) prevents brain metastases and improves survival, with the potential for neurocognitive toxicity. RTOG0933 demonstrated that hippocampal avoidance (HA) during whole brain radiotherapy preserves neurocognition. This study’s objective was to evaluate the cost-effectiveness of HA-PCI in LS-SCLC through decision analysis. Materials and methods A Markov model was developed to simulate the clinical course of LS-SCLC who received HA-PCI or conventional PCI (C-PCI). A willingness-to-pay threshold of $100,000/QALY was used. Incremental cost effectiveness ratio was calculated (ICER). Sensitivity analyses were performed to determine the parameter thresholds and to assess the robustness of the model. Results In the base case scenario, HA-PCI is more cost-effective than C-PCI, with an ICER of $47,107/QALY. HA-PCI was preferred over C-PCI provided that the risk of developing brain metastases was not increased by at least 14%, or if neurocognitive dysfunction rates were reduced by at least 40%. HA-PCI was the cost-effective strategy in 68% of tested iterations in probabilistic sensitivity analysis. Conclusion This study demonstrates that HA-PCI is more cost-effective than C-PCI in LS-SCLC. Our results support the use of HA-PCI in this patient population, should results from RTOG0933 be confirmed by the ongoing NRGCC003 trial. [ABSTRACT FROM AUTHOR]

• Details of technique, including beam angles, anatomic criteria, and image guidance. • Descriptions of target coverage and doses to OARs, and acute toxicity profiles. • Figures/images as visual guides for beam arrangements and expected dose distributions. Following mastectomy, immediate breast reconstruction often involves the use of temporary tissue expanders (TEs). TEs contain metallic ports (MPs), which complicate proton pencil-beam scanning (PBS) planning. A technique was implemented for delivering PBS post-mastectomy radiation (PMRT) to patients with TEs and MPs. A protocol utilizing a hybrid single- and multi-field optimization (SFO, MFO) technique was developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV_eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding the TE was evaluated. Organ at risk (OAR) dosimetry and acute toxicities were analyzed. Twenty-nine women were treated with this technique. A 2-field SFO technique was used superior and inferior to the MP, with a 3 or 4-field MFO technique used at the level of the MP. Virtual blocks were utilized so that beams did not travel through the MP. A port-to-CW distance of 1 cm was required. Patients underwent daily image-guidance to ensure the port remained within a 0.5 cm internal planning volume (ITV). Median RT dose to CTV_eval was 50.4 Gy (45.0–50.4). Median 95% CTV_eval coverage was 99.5% (95–100). Optically stimulated luminescent dosimeter (OSLD) readings were available for 8 patients and correlated to the dose measurements in the treatment planning system (TPS); median OSLD ratio was 0.99 (range, 0.93–1.02). Delivering PMRT with PBS for women with metal-containing TEs using a hybrid SFO/MFO technique is feasible, reproducible, and achieves excellent dose distributions. Specialized planning and image-guidance techniques are required to safely utilize this treatment in the clinic. [ABSTRACT FROM AUTHOR]

• The fluence of protons delivered to each spot is modulated in pencil beam scanning. • It has been hypothesized that heavy MU spot weighting may increase toxicity risk. • We evaluated the impact of MU spot weighting restrictions on treatment plan quality. • We found plan quality can be preserved while tightly restricting MU spot weighting. • Future work to correlate LET and RBE effects with spot weighting is critical. With reports of CNS toxicity in patients treated with proton therapy at doses lower than would be expected based on photon data, it has been proposed that heavy monitor unit (MU) weighting of pencil beam scanning (PBS) proton therapy spots may potentially increase the risk of toxicity. We evaluated the impact of maximum MU weighting per spot (maxMU/spot) restrictions on PBS plan quality, prior to implementing clinic-wide maxMU/spot restrictions. PBS plans of 11 patients, of which 3 plans included boosts, for a total of 14 PBS sample cases were included. Per sample case, a single dosimetrist created 4 test plans, gradually reducing the maxMU/spot in the plan. Test Plan 1, unrestricted in maxMU/spot, was the reference for all restricted plan comparisons (comparison sets 2 vs. 1; 3 vs. 1; and 4 vs. 1). The impact of MU/spot restrictions on plan quality metrics were analyzed with Wilcoxon signed rank test analyses. Treatment delivery time was modeled for a representative case. A total of 14 PBS sample cases, 7 (50%) single-field optimized, 7 (50%) multi-field optimized, 9 (64%) delivering > 3500 cGy, 9 (64%) with 3 beams, and 7 (50%) without a range shifter were included. There were no differences in plan quality metrics of target coverage (V95% and V100% prescription), conformality and gradient indices, hot spot volume (V105% prescription), and dose to normal brain (V10%/30%/50%/70%/90%/100% prescription) with reductions of allowable maxMU/spot across all comparison sets (p > 0.05). Max MU/spot restrictions did not increase treatment delivery time when analyzed for a representative case. MaxMU/spot restrictions within the thresholds evaluated in this study did not degrade overall plan quality metrics. Future studies should evaluate spot weighting with linear energy transfer/relative biologic effectiveness-informed planning to determine if spot weighting manipulation impacts clinical outcomes and mitigates toxicity. [ABSTRACT FROM AUTHOR]

• Hyperthermia has been shown to enhance the efficacy of RT in high grade gliomas. • A randomized study showed increased survival if combining hyperthermia and radiation. • Conventional hyperthermia had not been utilized due to the invasive procedure required. • Magnetic resonance focused ultrasound is a new non-invasive method for hyperthermia. • Studies evaluating the efficacy of new hyperthermia methods and radiation are needed. High-grade gliomas (HGGs) are aggressive primary brain tumors that confer poor prognoses. Despite aggressive combined modality treatment, HGGs invariably recur. Considerable research efforts and resources have focused on identification of novel therapies for HGGs; however, standard treatments have not changed significantly in more than 10 years, since the introduction of concurrent chemoradiation therapy with temozolomide. Hyperthermia (HT) has been shown to enhance the efficacy of radiation treatment (RT) in numerous cancer types through multiple mechanisms, including impairment of DNA repair pathways, increased perfusion/oxygenation of tumors, and immune system activation. In the 1980s and 1990s, the combination of HT with external-beam RT and interstitial brachytherapy was extensively evaluated in HGG, culminating in a randomized controlled trial that demonstrated superior survival in patients receiving combined HT and RT. However, HT was not adopted into common practice for HGG because of the need at that time for invasive implantation procedures, challenges to monitoring and maintaining a homogeneous, localized temperature elevation within the tumor tissue, as well as other technical and logistic challenges. Magnetic resonance imaging–guided focused ultrasound (MRgFUS) is a relatively new technology in clinical use that is capable of highly accurate transcranial HT and has the potential to overcome many of the limitations faced in previous trials combining HT and RT in HGG. In this review, we detail and compile the previous clinical results of combined HT and RT in HGG patients. We also introduce and discuss the potential of MRgFUS as a noninvasive method for HT to radiosensitize HGG. [ABSTRACT FROM AUTHOR]