The potential of integrating stereotactic ablative radiotherapy techniques with hyperfractionation for lung cancer.

BACKGROUND: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. METHODS: We utilized the linear-quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal-tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early-stage lung cancer. Mean lung BED, Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed-rank test. RESULTS: The transition point occurs when the tumor-to-normal tissue ratio (TNR) of the physical dose equals the TNR of α/ß in the BED dose-volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). CONCLUSIONS: The hyperfractionated regimen has an advantage in the high-dose region of the lung but a disadvantage in the low-dose region. Further research is needed to determine the superiority between hypo- and hyperfractionation.

Developing an AI-assisted planning pipeline for hippocampal avoidance whole brain radiotherapy.

BACKGROUND AND PURPOSE: Hippocampal avoidance whole brain radiotherapy (HA-WBRT) is effective for controlling disease and preserving neuro-cognitive function for brain metastases. However, contouring and planning of HA-WBRT is complex and time-consuming. We designed and evaluated a pipeline using deep learning tools for a fully automated treatment planning workflow to generate HA-WBRT radiotherapy plans. MATERIALS AND METHODS: We retrospectively collected 50 adult patients who received HA-WBRT. Using RTOG- 0933 clinical trial protocol guidelines, all organs-at-risk (OARs) and the clinical target volume (CTV) were contoured by experienced radiation oncologists. A deep-learning segmentation model was designed and trained. Next, we developed a volumetric-modulated arc therapy (VMAT) auto-planning algorithm for 30 Gy in 10 fractions. Automated segmentations were evaluated using the Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95 % HD). Auto-plans were evaluated by the percentage of PTV volume that receives 30 Gy (V30Gy), conformity index (CI), and homogeneity index (HI) of planning target volume (PTV) and the minimum dose (D100%) and maximum dose (Dmax) for the hippocampus, Dmax for the lens, eyes, optic nerve, brain stem, and chiasm. RESULTS: We developed a deep-learning segmentation model and an auto-planning script. For the 10 cases in the independent test set, the overall average DSC and 95 % HD of contours were greater than 0.8 and less than 7 mm, respectively. All auto-plans met the RTOG- 0933 criteria. The HA-WBRT plan automatically created time was about 10 min. CONCLUSIONS: An artificial intelligence (AI)-assisted pipeline using deep learning tools can rapidly and accurately generate clinically acceptable HA-WBRT plans with minimal manual intervention and increase efficiency of this treatment for brain metastases.

Monitoring Tumor Response After Histone Deacetylase Inhibitor Treatment Using 3'-Deoxy-3'-[18F]-fluorothymidine PET.

PURPOSE: This study employed 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) microPET scanning to assess the treatment response of histone deacetylase inhibitors (HDACi), e.g., N1-hydroxy-N8-phenyloctanediamide (SAHA) and its iodinated derivative ISAHA, in a hepatoma mouse model. PROCEDURES: The in vitro cytotoxicity of HDACi in various hepatoma cell lines was determined by MTT assay and flow cytometry. ISAHA and SAHA were used to treat HepG2 hepatoma xenograft-bearing mice. The treatment responses were characterized in terms of tumor burden, microPET imaging, and immunohistochemical staining of tumor sections. RESULTS: ISAHA effectively inhibited HepG2 hepatoma cell survival and tumor growth. A significantly reduced tumor uptake during HDACi treatment was noticed in [(18)F]FLT microPET imaging, which was consistent with the findings in immunohistochemical staining. CONCLUSIONS: ISAHA can suppress tumor cell proliferation both in vitro and in vivo. [(18)F]FLT PET is a promising modality for evaluating the in vivo therapeutic efficacy of HDACi at the early stage of treatment.

Pulsed-focused ultrasound enhances boron drug accumulation in a human head and neck cancer xenograft-bearing mouse model.

PURPOSE: This study aims to demonstrate that pulsed high-intensity focused ultrasound (pulsed-HIFU) may enhance the fructose-conjugated 4-borono-L-phenylalanine (BPA-Fr) accumulation in tumor lesion using (18)F-FBPA-Fr microPET scans. PROCEDURES: To the mice bearing orthotopic SASC03 human tongue squamous carcinoma xenograft, a 2-min pulsed-HIFU was applied to tumor. Immediately after pulsed-HIFU treatment, (18)F-FBPA-Fr was intravenously injected, and biological characterizations including microPET imaging and biodistribution were conducted. RESULTS: Both biodistribution studies and microPET imaging performed after intravenous injection of (18)F-FBPA-Fr revealed higher tumor uptake in HIFU-treated mice than that of the control. CD31 and Ki-67 histochemical staining of tumor sections and H&E staining of nearby normal tissues revealed no significant difference between the pulsed-HIFU-treated mice and the control. CONCLUSION: This study demonstrated that pulsed-HIFU was beneficial to the accumulation of boron drug in the head and neck tumor lesion and may enhance the therapeutic efficacy of clinical BNCT.

Monitoring tumor response with radiolabeled nucleoside analogs in a hepatoma-bearing mouse model early after doxisome(®) treatment.

PURPOSE: This study aims to demonstrate that 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) positron emission tomography (PET) is a promising modality for noninvasively monitoring the therapeutic efficacy of Doxisome(®) in a subcutaneous hepatoma mouse model. PROCEDURES: Male BALB/c nu/nu mice were inoculated with HepG2 hepatoma xenograft in the right flank. Doxisome(®) (5 mg/kg, three times a week for 2 weeks) was intravenously administrated for treatment. (18)F-FLT-microPET, biodistribution studies, and immunohistochemistry of Ki-67 were performed. RESULTS: A significant difference (p < 0.05) in tumor volume was observed on day 5 between treated and control groups. The tumor-to-muscle ratio derived from (18)F-FLT-PET and (123)I-ICdR-microSPECT images of Doxisome(®)-treated mice dropped from 12.55 ± 0.76 to 3.81 ± 0.31 and from 2.48 ± 0.42 to 1.59 ± 0.08 after a three-dose treatment, respectively, while that of the control group remained steady. The retarded proliferation rate of treated xenograft was confirmed by Ki-67 immunohistochemistry staining. CONCLUSIONS: This study clearly demonstrated that Doxisome(®) is an effective anti-cancer drug against the growth of HepG2 hepatoma and that (18)F-FLT-PET could provide early information of tumor response during treatment.