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Biology-guided radiotherapy (BgRT) with fluorodeoxyglucose (FDG) signal collected via an on-board positron emission tomography (PET) system integrated in an O-ring gantry Linac was cleared by the Food and Drug Administration (FDA) for lung and bone lesions. This study aims to determine if BgRT is feasible in the liver, an organ which has a FDG signal background, and if plans are clinically acceptable for FDG-avid metastatic liver lesions. Ten patients with metastatic liver lesions were retrospectively selected from one academic institution. Diagnostic PET/CT images of these treatment sites were collected and resampled to match the CT used for planning. Diagnostic PET images were converted to mimic PET images that are acquired on a PET-Linac and would be used to guide the delivery. For BgRT planning, the planned tumor volume (PTV) was generated with 5 mm margin from gross tumor volume (GTV) and a Biology Tracking Zone was generated including the anticipated full range of target motion. BgRT plans were created to 36Gy in 4 fractions for liver lesions. BgRT plan creation was first tested to determine if the Activity Concentration (AC) and Normalized Target Signals (NTS) on converted PET images would meet BgRT AC and NTS hard constraints required for plan creation. GTV and PTV were collected. BgRT plan quality was then evaluated for PTV coverage, including V100%, D98% and mean Dose (Dmean), PTV point dose (Dmax), conformity index (CI) and Heterogeneity index (HI), and organ at risk (OAR) mean doses. Six lesions met the constraints for NTS and AC for plan creation in four patient datasets. The average GTV size was 14.9 +/- 10.4 cc, with a PTV of 35.8 +/- 21.0 cc. The diagnostic PET PTV mean AC, liver mean AC, and derived AC and NTS on converted PET images average and standard deviation were 16.6 +/- 3.2 kBq/ml, 9.6 +/-1.3 kBq/ml, 13.97 +/- 2.89 kBq/ml and 6.85 +/- 3.16, respectively. All plans met OAR dose constraints such as max dose on duodenum, ribs, skin, small bowel, and stomach. For the six plans, lesion PTV coverage, V100%, D98%, and Dmean were 91.02 +/- 5.59%, 34.8 +/- 1.5 Gy and 39.5+/- 1.3 Gy. The PTV Dmax, CI and HI were 124.8 +/-10.2%, 1.13+/- 0.04 and 1.25+/-0.10. The Dmean for Liver minus PTV, right rib, right lung, stomach, duodenum and small bowel were 7.2 +/- 2.0, 2.2 +/- 0.5, 0.5 +/-0.8, 2.4 +/-1.4, 1.4 +/- 1.4 and 0.4 +/- 0.2 Gy, respectively. This initial study demonstrates the feasibility of BgRT planning for liver lesions, indicating successful adherence to AC and NTS constraints, and satisfactory plan quality meeting clinical requirements. [ABSTRACT FROM AUTHOR]

In locally advanced rectal cancer (LARC), which is relatively radioresistant, dose escalation increases clinical and histological tumor response and improves local control 1-2. However, radiation-induced toxicity is a major limiting factor for dose-escalation. Additionally, the new 64Cu-ATSM PET-CT tracer allows for dose-painting RT since it is a potential cellular redox witness of oxidative stress, responsible for radioresistance and tumor aggressiveness 3-4. The machine is a biology-guided radiotherapy (BgRT)-capable machine that is also cleared for image-guided radiation therapy. This study compares a dose-painting and escalation IMRT plan on the X1 treatment planning system (TPS) based on a 64Cu-ATSM biological target volume (BTV), with a conventional VMAT plan for LARC. Pelvic dose distributions were retrospectively calculated for 14 patients who underwent neoadjuvant chemoradiotherapy (CRT) for LARC and had prior-CRT diagnostic 64Cu-ATSM PET-CT, 18FDG PET-CT and MRI. They were planned using two different boost definition and dose-escalation RT techniques: 64Cu-ATSM PET-CT-based BTV on the TPS and GTV based on 18FDG PET-CT and MRI for VMAT with the medical technology company's Halcyon. High-risk planning target volume (PTV HR) was defined as BTV or GTV with 10 mm isotropic margin except 7 mm laterally for both plans. Low-risk PTV (PTV LR) was defined as mesorectum and lymph node drainage area according to the recommendations of Valentini et al 5. The delineated organs at risk (OARs) were small bowel, large bowel, bladder, left and right femoral head and penile bulb or vagina. The prescribed PTV HR and PTV LR doses were 25Gy in 5 fractions and 45Gy in 25 fractions respectively, with homogeneous target dose. Dose constraints from preRADAR trial were used 6. The summed EQD2 OARs dose distributions were compared. The BTV (mean: 4.7cc [min: 0.9cc – max: 18.6cc]) was on average eleven times smaller than the GTV (mean: 52.7cc [min: 10.9cc – max: 253.7cc]). The 2 plans met the V95% requirement with slightly better coverage for IMRT plans compared to VMAT plans (98.8% and 97.6% respectively). A medical technology company's plans resulted in lower dose to OARs compared to VMAT plans. This dosimetry study is an encouraging precursor to allow clinical dose-painting and dose-escalation for LARC on the medical technology company's system. The benefit has the potential for further increase by the future incorporation of online adaptive BgRT capabilities. [ABSTRACT FROM AUTHOR]

The PAIR prostate study aims to demonstrate the dosimetric feasibility of tumoral and hypoxia-guided dose escalated radiation therapy in prostate cancer on a novel ring gantry system TPS, based on conventionally fractionated and hypofractionated regimens. The GTV was delineated on MRI and the hypoxic region (biological tumor volume [BTV]) within the PTV on F-MISO PET uptake was delineated on pre-therapeutic F-MISO PET scans of 7 patients showing uptake in the tumor before undergoing external-beam RT for intermediate-risk prostate cancer. IMRT planning was performed using three different prescriptions regimen 1) Standard fractionation (SF) 77Gy/35 fractions (fx) to PTV, with a boost to 95Gy and 118Gy in 35 fx to the GTV and to the hypoxic region defined by F-MISO PET, respectively, 2) moderate hypofractionation (MH) 60 Gy/20 fx with a boost to 67Gy and 91Gy in 20 fx to the GTV and to the hypoxic region, respectively, and 3) high hypofractionation (HH) 40 Gy/5 fx with a boost to 50Gy in 5 fx to the GTV and as high as possible to the hypoxic region (SBRT). Planning was performed on a treatment planning system. The average size of the GTV and BTV was 11.4 ± 11.3 cc, and 1.30 ± 1.20 cc, respectively. For the SF regimen, the average D98% and D2% to the PTV, GTV and BTV were 71.3 ± 11.7 Gy and 105.0 ± 7.6 Gy; 90.3 ± 6.9 Gy and 113.2 ± 6.9 Gy; and 107.4 ± 5.6 Gy, and 116.0 ± 5.6 Gy, respectively. For the MH and HH techniques, the average D98% to the PTV was 54.3 ± 2.5 Gy, and 31.7 ± 5.3 Gy, and the average D2% was 83.6 ± 7.0 Gy, and 55.8 ± 2.9 Gy. In addition, the average D98%, and D2% to the GTV was 61.2 ± 6.2 Gy, and 89.8 ± 5.9 Gy using the MH treatment technique, while the average D98%, and D2% to the BTV was 85.2 ± 4.1 Gy, and 92.3 ± 3.2 Gy, respectively. Also, for the HH treatment planning method, the average D98%, and D2% to the GTV was 45.7 ± 4.9 Gy, and 59.2 ± 3.2 Gy, while the average D98%, and D2% to the BTV was 53.6 ± 4.2 Gy and 60.6 ± 2.5 Gy, respectively. The average D50% of the bladder, rectum, and femoral heads was 12.6 ± 5.4 Gy, 24.8 ± 9.9 Gy, and 9.6 ± 2.5 Gy, while the average V15Gy was 43.0 ± 11.5%, 59.4 ± 12.5 %, and 12.5 ± 14.1%, respectively. This study showed the dosimetric feasibility of dose-escalating the tumor and the hypoxic region in patients with prostate cancer using standard, moderate and high hypofractionated regimen on a treatment planning system while keeping the doses within acceptable limits for the organs at risk. [ABSTRACT FROM AUTHOR]

Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality using real-time positron emission tomography (PET) to guide radiotherapy beamlets. The present study was performed with sequential cohorts of participants to evaluate the performance and safety of BgRT. Primary endpoints were previously reported. We hereby report on one of the secondary endpoints assessing a novel treatment planning machine with integrated dual kVCT/PET imaging ("novel device") performance in comparison to a third-party diagnostic PET/CT scan. This single-arm, open-label, prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (≥2cm and ≤5cm) in the lung or bone. PET imaging data were collected on the novel device and on a third-party diagnostic PET/CT performed in sequence once at the planning timepoint in Cohort I, and immediately before the last fraction among patients undergoing stereotactic radiotherapy in Cohort II. Three central read radiation oncologists (CRRO) provided an interpretation of the novel device PET scans which were compared to an agreement standard based on 3 central radiologists' review of the paired diagnostic PET/CT scan. Positive percent agreement for localization of the target tumor within the biology-tracking zone (BTZ) was the key metric because it reflects whether advancing patients to subsequent steps in the BgRT workflow based on the novel device's imaging was ultimately appropriate. In Cohort 1, 6 image comparisons were performed. The positive (%) agreement for the aggregate radiation oncologist review was 100% (5/5), reflecting that in all 5 cases where the aggregate radiation oncologists deemed the tumor to fall within the BTZ based upon the novel device PET images, the central radiologists came to the same conclusion upon review of the paired diagnostic PET/CT images. The overall (%) agreement for the aggregate radiation oncologist review was 83.3% (5/6): localization was not established on the novel device in 1 case, even though it was established on the diagnostic PET/CT. This would not pose risk in real world practice as BgRT candidacy would be aborted for tumors not visible on the novel device. In Cohort II, among the 7 image comparisons, there was 100% positive percent agreement between the aggregate CRRO and the agreement standard as the localization criteria was met in both scans for all 7 patients. This was concordant with a 100% overall percent agreement. This investigation demonstrated a 100% positive percent agreement between central review of this novel device images by radiation oncologists and central review of the accompanying third-party PET/CT images by radiologists. There were no cases where a positive localization by the aggregate CRRO was not confirmed by the third-party PET/CT standard, providing evidence against the likelihood of falsely positive localizations on the novel device that would inappropriately advance patients in the workflow. [ABSTRACT FROM AUTHOR]