Search

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle's biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultrahigh-dose-rate therapy, known as FLASH radiotherapy (RT), is an emerging cancer treatment technique that offers similar tumor control to conventional RT but with the enhanced protection of normal tissue through the FLASH-sparing effect. Preclinical studies on animals and cell lines show promising results. This is significant for patients with recurrent tumors and reirradiation cases, where conventional RT has high toxicity rates. FLASH-RT can potentially improve tumor control while reducing side effects and preserving quality of life. Among the FLASH modalities, proton therapy stands out for its superior dosimetric and delivery characteristics, making it a safe and effective option for human malignancies. Despite its potential, proton Bragg peak FLASH for HN cancer remains underexplored, and this review highlights the novel proton conformal FLASH techniques, which allow for high-quality plans while minimizing radiation exposure to critical organs at risk (OARs) for HN cancer reirradiation. Ultrahigh-dose-rate therapy, also known as FLASH radiotherapy (RT), is an emerging technique that is garnering significant interest in cancer treatment due to its potential to revolutionize therapy. This method can achieve comparable tumor control to conventional-dose-rate RT while offering the enhanced protection of normal tissue through the FLASH-sparing effect. This innovative technique has demonstrated promising results in preclinical studies involving animals and cell lines. Particularly noteworthy is its potential application in treating head and neck (HN) cancers, especially in patients with challenging recurrent tumors and reirradiation cases, where the toxicity rates with conventional radiotherapy are high. Such applications aim to enhance tumor control while minimizing side effects and preserving patients' quality of life. In comparison to electron or photon FLASH modalities, proton therapy has demonstrated superior dosimetric and delivery characteristics and is a safe and effective FLASH treatment for human malignancies. Compared to the transmission proton FLASH, single-energy Bragg peak FLASH is a novel delivery method that allows highly conformal doses to targets and minimal radiation doses to crucial OARs. Proton Bragg peak FLASH for HN cancer has still not been well studied. This review highlights the significance of proton FLASH in enhancing cancer therapy by examining the advantages and challenges of using it for HN cancer reirradiation. [ABSTRACT FROM AUTHOR]

This document is an editorial for a special topics issue of the journal Diagnostics, focusing on imaging-based diagnosis for prostate cancer. The issue includes 10 articles that describe current advances in detecting and assessing prostate tumors using imaging techniques. The editorial discusses the limitations of current diagnostic methods and suggests future trends in prostate cancer diagnostic imaging. It concludes by speculating on longer-term advances, including new biomarkers, focal proton therapy, and the combination of imaging and tumor genomics. The text also includes a table summarizing various articles on the imaging-based diagnosis of prostate cancer. The authors of the text have declared no conflicts of interest. [Extracted from the article]

Purpose: To evaluate organ at risk (OAR) auto-segmentation in the head and neck region of computed tomography images using two different commercially available deep-learning-based auto-segmentation (DLAS) tools in a single institutional clinical applications. Methods: Twenty-two OARs were manually contoured by clinicians according to published guidelines on planning computed tomography (pCT) images for 40 clinical head and neck cancer (HNC) cases. Automatic contours were generated for each patient using two deep-learning-based auto-segmentation models--Manteia AccuContour and MIM Prote'ge'AI. The accuracy and integrity of autocontours (ACs) were then compared to expert contours (ECs) using the Sørensen-Dice similarity coefficient (DSC) and Mean Distance (MD) metrics. Results: ACs were generated for 22 OARs using AccuContour and 17 OARs using Prote'ge'AI with average contour generation time of 1 min/patient and 5 min/patient respectively. EC and AC agreement was highest for the mandible (DSC 0.90 ± 0.16) and (DSC 0.91 ± 0.03), and lowest for the chiasm (DSC 0.28 ± 0.14) and (DSC 0.30 ± 0.14) for AccuContour and Prote'ge'AI respectively. Using AccuContour, the average MD was<1mm for 10 of the 22 OARs contoured, 1-2mm for 6 OARs, and 2-3mm for 6 OARs. For Prote'ge'AI, the average mean distance was<1mm for 8 out of 17 OARs, 1-2mm for 6 OARs, and 2-3mm for 3 OARs. Conclusions: Both DLAS programs were proven to be valuable tools to significantly reduce the time required to generate large amounts of OAR contours in the head and neck region, even though manual editing of ACs is likely needed prior to implementation into treatment planning. The DSCs and MDs achieved were similar to those reported in other studies that evaluated various other DLAS solutions. Still, small volume structures with nonideal contrast in CT images, such as nerves, are very challenging and will require additional solutions to achieve sufficient results. [ABSTRACT FROM AUTHOR]

The National Association for Proton Therapy conducted 8 surveys of all operational United States proton centers (2012-2021) and analyzed the patients treated, diagnoses, and treatment complexity to evaluate trends and diversification of patients receiving proton therapy. Detailed surveys were sent in 2015, which requested data from 2012 to 2014, and then annually thereafter to active proton centers in the United States. The numbers of patient treated at each center for the preceding calendar year(s) were collated for tumors in the following categories: central nervous system, intraocular, pituitary, skull base/skeleton, head/neck, lung, retroperitoneal/soft tissue sarcoma, pediatric (solid tumors in children of age ≤18), gastrointestinal tract, urinary tract, female pelvic, prostate, breast, and "other." Complexity levels were assessed using Current Procedural Terminology codes 77520-77525. Survey response rates were excellent (100% in 2015 to 94.9% in 2021); additional publicly available information provided near-complete information on all centers. Trend comparisons between 2012 and 2021 showed that the total annual number of patients treated with protons gradually increased from 5377 to 15,829. The largest numeric increases were for head/neck (316 to 2303; 7.3-fold), breast (93 to 1452; 15.6-fold), and gastrointestinal tumors (170 to 1259; 7.4-fold). Patient numbers also increased significantly for central nervous system (598 to 1743; 2.9-fold), pediatric (685 to 1870; 2.7-fold), and skull base tumors (179 to 514; 2.9-fold). For prostate cancer, the percentage of proton-treated patients decreased from 43.4% to 25.0% of the total. Simple compensated treatments decreased from 43% in 2012 to 7% in 2021, whereas intermediate complexity treatments increased from 45% to 73%. The number of patients treated with protons is gradually increasing, with a substantial proportionate decline in patients with prostate cancer receiving proton therapy. The number of patients treated for "commonly accepted" indications for protons (eg, pediatric, central nervous system, and skull base tumors) is gradually increasing. Greater proportional increases were observed for breast, lung, head/neck, and gastrointestinal tumors. Treatment complexity is gradually increasing over time. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: The proper management of prostate cancer requires accurate assessment of patients diagnosed with prostate cancer, a common and often lethal cancer. Current conventional prostate cancer diagnosis relies on: (1) needle biopsy, which can result in side effects such as hemorrhage or infection, as well as misplacement of needles resulting in evaluation inaccuracy, (2) prostate serum antigen detection that can lead to overdiagnosis, or (3) MRI interpretations using the Prostate Imaging-Reporting and Data System (PI-RADS), which is a subjective method that depends on the experience of the radiologist's interpretation of the images. Quantitative analysis of MRI can alleviate the limitations of conventional approaches. Artificial intelligence applied to MRI requires big training datasets, and its application is restricted to patients scanned under certain restricted conditions. More recently, spectral/statistical techniques, adapted from remote sensing, have been applied and tested in spatially registered multi-parametric MRI. The new spectral/statistical techniques require limited training, are flexible regarding patient scanning conditions, and perform well relative to other techniques. This study extends spectral/statistical techniques to make them more independent of the individual radiologist by autonomously finding the appropriate tumor signature within a prostate and, therefore, providing an objective, non-invasive, accurate means for determining prostate tumor aggressiveness. Background: Accurate, reliable, non-invasive assessment of patients diagnosed with prostate cancer is essential for proper disease management. Quantitative assessment of multi-parametric MRI, such as through artificial intelligence or spectral/statistical approaches, can provide a non-invasive objective determination of the prostate tumor aggressiveness without side effects or potential poor sampling from needle biopsy or overdiagnosis from prostate serum antigen measurements. To simplify and expedite prostate tumor evaluation, this study examined the efficacy of autonomously extracting tumor spectral signatures for spectral/statistical algorithms for spatially registered bi-parametric MRI. Methods: Spatially registered hypercubes were digitally constructed by resizing, translating, and cropping from the image sequences (Apparent Diffusion Coefficient (ADC), High B-value, T2) from 42 consecutive patients in the bi-parametric MRI PI-CAI dataset. Prostate cancer blobs exceeded a threshold applied to the registered set from normalizing the registered set into an image that maximizes High B-value, but minimizes the ADC and T2 images, appearing "green" in the color composite. Clinically significant blobs were selected based on size, average normalized green value, sliding window statistics within a blob, and position within the hypercube. The center of mass and maximized sliding window statistics within the blobs identified voxels associated with tumor signatures. We used correlation coefficients (R) and p-values, to evaluate the linear regression fits of the z-score and SCR (with processed covariance matrix) to tumor aggressiveness, as well as Area Under the Curves (AUC) for Receiver Operator Curves (ROC) from logistic probability fits to clinically significant prostate cancer. Results: The highest R (R > 0.45), AUC (>0.90), and lowest p-values (<0.01) were achieved using z-score and modified registration applied to the covariance matrix and tumor signatures selected from the "greenest" parts from the selected blob. Conclusions: The first autonomous tumor signature applied to spatially registered bi-parametric MRI shows promise for determining prostate tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is one of the most diagnosed cancers in men. While it can be successfully treated with radiotherapy (RT), patients often leave treatment with previously healthy organs affected by radiation. This work assessed a novel ultra-high dose rate FLASH proton therapy technique for the treatment of prostate cancers. We were able to generate clinically viable Bragg peak FLASH treatment plans for prostate cancer patients previously treated with conventional proton RT. Feasible prostate treatment quality was observed with all constraints for organs at risk (OARs) being met while maintaining an ultra-high dose rate. Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT. [ABSTRACT FROM AUTHOR]

Radiation therapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). Although radiation therapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination and worsening clinical outcomes in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC. In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60 to 70/1.8-2.0 Gy radiation therapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/d; cohort 2, 1000 mg/d; cohort 3, 1500 mg/d) was self-administered once daily starting 2 to 7 days before initiating concurrent chemoradiotherapy and continued until the end of radiation therapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival. Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (n = 11) were all mild to moderate in severity (grade 1, n = 9; grade 2, n = 2) and predominantly gastrointestinal (n = 7). A dose-dependent decrease in serum transforming growth factor β1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient-reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate). The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector. [ABSTRACT FROM AUTHOR]

Introduction: There are currently limited data comparing the efficacy of stereotactic body radiation therapy (SBRT) to transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). The aim of this systematic review and meta-analysis was to report on the summary effect estimate of overall survival and local control at 1-year based on available evidence. Methods: A literature search was conducted in PubMed from database inception until April 2020. Articles were independently screened by two reviewers and included if they reported on a propensity-matched study design comparing SBRT to TACE for the treatment of HCC with at least 1 year follow up. Event data of overall survival (OS) and local control (LC) at 1-year were extracted. A random-effects model was applied to generate summary odds ratio and corresponding 95% confidence intervals (CI). Results: Four studies compiling a total of 606 patients were identified and included. SBRT (73.6%) and TACE (67.0%) had similar 1-year rates of OS, with an OR of 0.87 (0.56, 1.37). SBRT (88.4%) had greater LC at 1 year compared to TACE (71.7%); OR of 0.34 (0.13, 0.86). Conclusion: SBRT is comparable to TACE in terms of 1-year survival for the treatment HCC and may provide an advantage in terms of local control. Future controlled trials are necessary to determine the clinical advantages and best indications for each treatment. [ABSTRACT FROM AUTHOR]

Stereotactic body radiation therapy (SBRT) has been used with high effectiveness in early-stage non-small cell lung cancer (NSCLC) but has not been studied extensively in locally advanced NSCLC. We conducted a phase 2 study delivering SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes for patients with node-positive locally advanced NSCLC. This manuscript serves as both a guide to planning techniques used on this trial and the subsequent phase 3 study, NRG Oncology LU-008, and to report patient dosimetry and toxicity results. We initiated a phase 2 multicenter single arm study evaluating SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by conventionally fractionated chemoradiation to 60 Gy in 2 Gy fractions with doublet chemotherapy to the involved lymph nodes for patients with stage III or unresectable stage II NSCLC. Patients eligible for adjuvant immunotherapy received up to 12 months of durvalumab. We report a detailed guide for the entire treatment process from computed tomography simulation through treatment planning and delivery. The dosimetric outcomes from the 60 patients who completed therapy on study are reported both for target coverage and normal structure doses. We also report correlation between radiation-related toxicities and dosimetric parameters. Sixty patients were enrolled between 2017 and 2022. Planning techniques used were primarily volumetric modulated arc therapy for SBRT to the primary tumor and conventionally fractionated radiation to the involved nodes, with a minority of cases using dynamic conformal arc technique or static dynamic multileaf collimator intensity modulated radiation therapy. Grade 2 or higher pneumonitis was associated with lung dose V5 Gy > 70% and grade 2 or higher pulmonary toxicity was associated with lung dose V10 Gy > 50%. Only 3 patients (5%) experienced grade 3 or higher pneumonitis. Grade 2 or higher esophagitis was associated with esophageal doses, including mean dose > 20 Gy, V60 Gy > 7%, and D1cc > 55 Gy. Only 1 patient (1.7%) experienced grade 3 esophagitis. SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes is feasible with planning techniques as described. Radiation-related toxicity on this phase 2 study was low. This manuscript serves as a guideline for the recently activated NRG Oncology LU-008 phase 3 trial evaluating this experimental regimen. [ABSTRACT FROM AUTHOR]

(1) Background: Non-invasive prostate cancer assessments using multi-parametric MRI are essential to the reliable detection of lesions and proper management of patients. While current guidelines call for the administration of Gadolinium-containing intravenous contrast injections, eliminating such injections would simplify scanning and reduce patient risk and costs. However, augmented image analysis is necessary to extract important diagnostic information from MRIs. Purpose: This study aims to extend previous work on the signal to clutter ratio and test whether prostate tumor eccentricity and volume are indicators of tumor aggressiveness using bi-parametric (BP)-MRI. (2) Methods: This study retrospectively processed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRIs (apparent diffusion coefficient, high b-value, and T2 images) were resized, translated, cropped, and stitched to form spatially registered BP-MRIs. The International Society of Urological Pathology (ISUP) grade was used to judge cases of prostate cancer as either clinically significant prostate cancer (CsPCa) (ISUP ≥ 2) or clinically insignificant prostate cancer (CiPCa) (ISUP < 2). The Adaptive Cosine Estimator (ACE) algorithm was applied to the BP-MRIs, followed by thresholding, and then eccentricity and volume computations, from the labeled and blobbed detection maps. Then, univariate and multivariate linear regression fittings of eccentricity and volume were applied to the ISUP grade. The fits were quantitatively evaluated by computing correlation coefficients (R) and p-values. Area under the curve (AUC) and receiver operator characteristic (ROC) curve scores were used to assess the logistic fitting to CsPCa/CiPCa. (3) Results: Modest correlation coefficients (R) (>0.35) and AUC scores (0.70) for the linear and/or logistic fits from the processed prostate tumor eccentricity and volume computations for the spatially registered BP-MRIs exceeded fits using the parameters of prostate serum antigen, prostate volume, and patient age (R~0.17). (4) Conclusions: This is the first study that applied spectral approaches to BP-MRIs to generate tumor eccentricity and volume metrics to assess tumor aggressiveness. This study found significant values of R and AUC (albeit below those from multi-parametric MRI) to fit and relate the metrics to the ISUP grade and CsPCA/CiPCA, respectively. [ABSTRACT FROM AUTHOR]

Simple Summary: For proton therapy, verification CT (vCT) scans are routinely acquired to ensure the accuracy and precision of treatment delivery, as this approach allows clinicians to monitor and adapt treatment plans based on potential changes to the patient's anatomy and tumor. This study investigates synthetic CT's (sCT) potential as an alternative to vCT scans, focusing on its reliability across various treatment sites. Synthetic CT could offer a more efficient approach and possibly enhance patient experience by reducing the necessity for frequent vCT scans. The consistency between sCT and vCT in terms of image quality and dosimetric impact is crucial. It will allow clinicians to monitor and adjust treatment plans promptly and more accurately based on patients' anatomical changes, potentially optimizing treatment processes and outcomes. The insights from this study are pivotal for refining clinical practices and fostering advancements in treatment strategies, ultimately aiming at precision and accuracy in adaptive treatment. Purpose: The study evaluates the efficacy of cone-beam computed tomography (CBCT)-based synthetic CTs (sCT) as a potential alternative to verification CT (vCT) for enhanced treatment monitoring and early adaptation in proton therapy. Methods: Seven common treatment sites were studied. Two sets of sCT per case were generated: direct-deformed (DD) sCT and image-correction (IC) sCT. The image qualities and dosimetric impact of the sCT were compared to the same-day vCT. Results: The sCT agreed with vCT in regions of homogeneous tissues such as the brain and breast; however, notable discrepancies were observed in the thorax and abdomen. The sCT outliers existed for DD sCT when there was an anatomy change and for IC sCT in low-density regions. The target coverage exhibited less than a 5% variance in most DD and IC sCT cases when compared to vCT. The Dmax of serial organ-at-risk (OAR) in sCT plans shows greater deviation from vCT than small-volume dose metrics (D0.1cc). The parallel OAR volumetric and mean doses remained consistent, with average deviations below 1.5%. Conclusion: The use of sCT enables precise treatment and prompt early adaptation for proton therapy. The quality assurance of sCT is mandatory in the early stage of clinical implementation. [ABSTRACT FROM AUTHOR]