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Purpose: Noncoplanar plans (NCPs) are commonly used for proton treatment of bilateral head and neck (HN) malignancies. NCP requires additional verification setup imaging between beams to correct residual errors of robotic couch motion, which increases imaging dose and total treatment time. This study compared the quality and robustness of NCPs with those of coplanar plans (CPs). Methods and Materials: Under an IRB‐approved study, CPs were created retrospectively for 10 bilateral HN patients previously treated with NCPs maintaining identical beam geometry of the original plan but excluding couch rotations. Plan robustness to the inter‐fractional variation (IV) of both plans was evaluated through the Dose Volume Histograms (DVH) of weekly quality assurance CT (QACT) sets (39 total). In addition, delivery efficiency for both plans was compared using total treatment time (TTT) and beam‐on time (BOT). Results: No significant differences in plan quality were observed in terms of clinical target volume (CTV) coverage (D95) or organ‐at‐risk (OAR) doses (p > 0.4 for all CTVs and OARs). No significant advantage of NCPs in the robustness to IV was found over CP, either. Changes in D95 of QA plans showed a linear correlation (slope = 1.006, R2 > 0.99) between NCP and CP for three CTV data points (CTV1, CTV2, and CTV3) in each QA plan (117 data points for 39 QA plans). NCPs showed significantly higher beam delivery time than CPs for TTT (539 ± 50 vs. 897 ± 142 s; p < 0.001); however, no significant differences were observed for BOT. Conclusion: NCPs are not more robust to IV than CPs when treating bilateral HN tumors with pencil‐beam scanning proton beams. CPs showed plan quality and robustness similar to NCPs while reduced treatment time (∼6 min). This suggests that CPs may be a more efficient planning technique for bilateral HN cancer proton therapy. [ABSTRACT FROM AUTHOR]

Background: Proton beam therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation and useful for Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We present a single center experience in HCC and iCCA treated with Pencil Beam Scanning (PBS) PBT. Methods: Forty-four consecutive patients (22 patients in each group) receiving PBT were included and reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy (SBRT) using PBS. Tumor size was approximated by clinical target volume (CTV). Outcomes were evaluated with Kaplan-Meier and liver toxicity was determined by MELD-Na and albumin-bilirubin (ALBI) grade. Results: Median follow up was 38.7 months, fourteen (35%) had multifocal disease and median CTV was 232.5cc. Four (9%) and 40 (91%) patients received SBRT and hypofractionated radiation, respectively. Two year overall survival was statistically higher for HCC (entire group: 68.9% months [95% CI: 61.3 - 76.3%]; iCCA: 49.8% [95% CI: 38.5% - 61.1%]; HCC: 89.4% [95% CI: 82.3 - 96.5%]; P <0.005). There was no statistical difference in progression-free survival or freedom from local failure. Biologically Equivalent Dose (BED) was greater than or equal to 80.5Gy in 37 (84%) patients. All iCCA patients had stable or improved ALBI grade following treatment. ALBI effecgrade was stable in 83% of HCC patients and average MELD-Na score remained stable. Tumor size, pretreatment liver function, and total radiation dose were not associated with liver toxicity. Conclusions: PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis in this advanced population with large tumors. [ABSTRACT FROM AUTHOR]

Background: While prostate specific membrane antigen (PSMA) is overexpressed in high-grade prostate cancers, it is also expressed in tumor neovasculature and other malignancies, including hepatocellular carcinoma (HCC). Importantly, no functional imaging for HCC is clinically available, making diagnosis and surveillance following local therapies particularly challenging. 18F-DCFPyL binds with high affinity to PSMA yet clears rapidly from the blood pool. PET imaging with 18F-DCFPyL may represent a new tool for staging, surveillance and assessment of treatment response in HCC. The purpose of this Functional Imaging Liver Cancer (FLIC) trial is to assess the ability of 18F-DCFPyL-PET/CT to detect sites of HCC. Methods: This is a phase II multi-site prospective imaging trial with a plan to enroll 50 subjects with suspected HCC on standard of care CT or MRI and eligible for standard local treatment. Participants will undergo a baseline 18F-DCFPyL-PET/CT, prior to therapy. Subjects will also be scanned with 18F-FDG-PET/CT within 2 weeks of 18F-DCFPyL-PET/CT. Participants will undergo histopathologic assessment and standard of care local treatment for HCC within a multidisciplinary team context. Participants with histopathologic confirmation of HCC and a positive baseline 18F-DCFPyL-PET/CT will undergo a post-treatment 18F-DCFPyL-PET/CT during the first routine follow-up, typically within 4–8 weeks. Subjects with negative baseline 18F-DCFPyL-PET/CT will not be re-scanned after treatment but will remain in follow-up. Participants will be followed for 5-years to assess for progression-free-survival. The primary endpoint is the positive predictive value of 18F-DCFPyL-PET for HCC as confirmed by histopathology. Secondary endpoints include comparison of 18F-DCFPyL-PET/CT with CT, MRI, and 18F-FDG-PET/CT, and evaluation of the value of 18F-DCFPyL-PET/CT in assessing treatment response following local treatment. Exploratory endpoints include next generation sequencing of tumors, and analysis of extracellular vesicles to identify biomarkers associated with response to therapy. Discussion: This is a prospective imaging trial designed to evaluate whether PSMA-PET/CT imaging with 18F-DCFPyL can detect tumor sites, assess local treatment response in HCC patients, and to eventually determine whether PSMA-PET/CT could improve outcomes of patients with HCC receiving standard of care local therapy. Importantly, this trial may help determine whether PSMA-selective radiopharmaceutical therapies may be beneficial for patients with HCC. Clinical trial registration: NIH IND#133631. Submission date: 04-07-2021. Safe-to-proceed letter issued by FDA: 05.07.2021. NIH IRB #00080. ClinicalTrials.gov Identifier NCT05009979. Date of Registry: 08-18-2021. Protocol version date: 01-07-2022. [ABSTRACT FROM AUTHOR]

Most patients with p16-positive oropharynx cancer (p16+OPC) receive elective nodal radiation therapy that improves regional control but increases acute and long-term toxicity. We evaluated the efficacy and toxicity profile of a reduced contralateral elective nodal volume in patients with p16+OPC receiving definitive or adjuvant radiation therapy. Patients with newly diagnosed p16+OPC without contralateral nodal involvement treated with primary proton or photon-based (chemo)radiation therapy or adjuvant (chemo)radiation therapy following transoral robotic surgery (TORS) were eligible for enrollment. The reduced contralateral nodal volume included high-risk regions of levels II and III1. The primary endpoint was elective out-of-field contralateral nodal failure. Dosimetric studies comparing standard versus reduced elective nodal volumes were analyzed with the t-test. Acute toxicity was collected using CTCAE v4.0. Fifty-two patients were enrolled of which 36 (69.2%) received definitive (chemo)radiation therapy. Sixteen (30.8%) patients underwent adjuvant radiation therapy following TORS of which 5 (31.2%) received concurrent chemotherapy. Proton therapy was used in 38 (73.1%) of patients. There were no elective nodal failures at a median follow up of 15 months (range 1-24 months). For the first 20 patients enrolled, dosimetric comparison of the reduced contralateral elective nodal volume to a consensus elective nodal volume demonstrated a decrease in mean dose (14.1 Gy to 18.5 Gy [p<0.05]) and V30 Gy (11.6% to 21.3% [p<0.01]) of the contralateral parotid gland. Significant differences were independent of radiation modality or technology. Acute grade 3 toxicity was observed in 13 (25%) patients including 6 (11.5%) who received a gastrostomy tube during treatment. There were no grade 4-5 acute toxicities, and no patients with 6 months of follow up retained gastrostomy tube. Precise delivery of radiation therapy to high-risk areas for contralateral nodal disease results in excellent regional control regardless of treatment approach. Dose to contralateral organs at risk and toxicity profile were favorable. Longer follow-up is needed to further support this de-intensification strategy. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on head and neck oncologic care at a tertiary care facility. Study Design: This was a cross-sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period. Secondary outcome measures were tumor conference volume, operative volume, and outpatient patient procedure and clinic volumes. Setting: This single-center study was conducted at a tertiary care academic hospital in a large metropolitan area. Methods: The study included a consecutive sample of adult subjects who were presented at a head and neck interdepartmental tumor conference during the study period. Patients were compared to historical controls based on review of operative data, outpatient procedures, and clinic volumes. Results: In total, 117 patients were presented during the review period in 2020, compared to 69 in 2019. There was an 8.4% treatment modification rate among cases presented at the tumor conference. There was a 61.3% (347 from 898) reduction in outpatient clinic visits and a 63.4% (84 from 230) reduction in procedural volume compared to the prior year. Similarly, the operative volume decreased by 27.0% (224 from 307) compared to the previous year. Conclusion: Restrictions related to the COVID-19 pandemic resulted in limited treatment modifications. Transition to virtual tumor board format observed an increase in case presentations. While there were reductions in operative volume, there was a larger proportion of surgical cases for malignancy, reflecting the prioritization of oncologic care during the pandemic. [ABSTRACT FROM AUTHOR]

Purpose: Pencil-beam scanning proton therapy has been considered as a potential modality for the 3D form of spatially-fractionated-radiation-therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans., Methods: Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using two-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross-target-volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in treatment of two patients and their dosimetric parameters are reported., Results: The RPL strategy was able to achieve the clinical planning goals. Compared to previously-treated photon plans, the average number of vertices increased by 30%, average vertex volume by 49% (18.2±25.9cc vs. 12.2±14.5cc, P=0.21), and higher PVDR (10.5±4.8 vs. 2.5±0.9, P<0.005) was achieved. In addition, RPL plans show more conformal dose with less low-dose to GTV (V30%: 60.9±7.2% vs. 81.6±13.9% and V10%: 88.3±4.5% vs. 98.6±3.6% [P<0.01]). The RPL plan for two treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively., Conclusion: A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation, with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts., Methods and Materials: To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation ( n = 4) were compared to photon radiation ( n = 4). Additional control groups included healthy age- and sex-matched controls ( n = 5), head and neck cancer patients who never received radiation therapy ( n = 8), and patients with oral inflammatory disease ( n = 3)., Results: Photon therapy patients presented with lower microbial alpha diversity at all timepoints, and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy, in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. The bacterial de novo pyrimidine biosynthesis pathway and the nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for the proliferation of pathogenic bacteria., Conclusion: Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status., Competing Interests: The author(s) declare(s) that there is no conflict of interest., (Copyright: © 2024 Meiller T, et al.)