Search

Cardiac toxicity is a well-recognized risk after radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC). However, the extent to which treatment planning optimization can reduce mean heart dose (MHD) without untoward increases in lung dose is unknown.Retrospective analysis of RT plans from 353 consecutive patients with locally advanced NSCLC treated with intensity modulated RT (IMRT) or 3-dimensional conformal RT. Commercially available machine learning-guided clinical decision support software was used to match RT plans. A leave-one-out predictive model was used to examine lung dosimetric tradeoffs necessary to achieve a MHD reduction.Of all 232 patients, 91 patients (39%) had RT plan matches showing potential MHD reductions of4 to 8 Gy without violating the upper limit of lung dose constraints (lung volume [V] receiving 20 Gy (V20 Gy)37%, V5 Gy70%, and mean lung dose [MLD]20 Gy). When switching to IMRT, 75 of 103 patients (72.8%) had plan matches demonstrating improved MHD (average 2.0 Gy reduction, P.0001) without violating lung constraints. Examining specific lung dose tradeoffs, a mean ≥3.7 Gy MHD reduction was achieved with corresponding absolute increases in lung V20 Gy, V5 Gy, and MLD of 3.3%, 5.0%, and 1.0 Gy, respectively.Nearly 40% of RT plans overall, and 73% when switched to IMRT, were predicted to have reductions in MHD4 Gy with potentially clinically acceptable tradeoffs in lung dose. These observations demonstrate that decision support software for optimizing heart-lung dosimetric tradeoffs is feasible and may identify patients who might benefit most from more advanced RT technologies.

Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR-guided radiation therapy (MRgRT) provides improved soft-tissue contrast for patient setup and real-time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR-linear accelerator (MR-Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments.A healthy volunteer was imaged on a ViewRay MRIdian MR-Linac. Organs-at-risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D-printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation.A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and computed tomography-visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2 mm). The MR-Linac was able to visualize, track, and gate larynx motion.The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR-Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR-Linac.

Figure S1. The PET/CT imaging of rabbit at 24 h post-intravenous injection of 64Cu-PLP. Figure S2. Representative H&E, pan-Cytokeratin staining and fluorescence microscopic imaging of the tumor (a) and metastatic lymph node (b) after 24 h intravenous injection of 64Cu- PLP Figure S3. The non-toxicity of PLP-PDT to healthy tissues. Figure S4. The temperature change of tumors during laser irradiation. Figure S5. The tumor size change of laser control and PLP control was monitored by CT imaging after treatment. Figure S6. Representative CT images of the regional lymph node post treatment.

Purpose: The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management.Experimental Design: Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management.Results: PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures.Conclusions: PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT. Clin Cancer Res; 22(4); 961–70. ©2015 AACR.

PET imaging of HNC with PLP

BACKGROUND/OBJECTIVE Ineffective interdisciplinary communication has negative impacts on patient outcomes. The use of regular structured interdisciplinary bedside rounds (SIBR), where each patient interaction lasts 3-5 minutes, is a model of care that improves interdisciplinary communication. We evaluated the impact of SIBR on in-hospital falls. DESIGN Prospective before-after study of older people hospitalized with acute illness. SETTING Two side-by-side aged care wards in a university hospital in Sydney, Australia. PARTICIPANTS A total of 3,673 consecutive inpatients of mean age 83.8 ± 7.7 years, with 1,703 before SIBR compared with 1,970 after SIBR. No patients were excluded from potential participation. INTERVENTION Twice-weekly SIBR. MEASUREMENTS Falls data were manually extracted from a mandatory institutional incident reporting database. Medical diagnoses were based on the Australian Refined Diagnosis Related Groups classification system. Injuries due to falls were corroborated using the institutional electronic medical record (Cerner PowerChart). Generalized estimating equations were used to evaluate the incidence rate ratio (IRR) of falls and fall-related injuries. A negative binomial distribution and a logarithmic link function were used to linearize regression equations. RESULTS After SIBR, there were 7.4 falls per 1,000 occupied bed days (OBD), compared with 10.6 falls per 1,000 OBD before SIBR (P

Purpose MR-linacs (MRLs) have enabled the use of stereotactic magnetic resonance (MR) guided online adaptive radiotherapy (SMART) across many cancers. As data emerges to support SMART, uncertainty remains regarding optimal technical parameters, such as optimal patient positioning, immobilization, image quality, and contouring protocols. Prior to clinical implementation of SMART, we conducted a prospective study in healthy volunteers (HVs) to determine optimal technical parameters and to develop and practice a multidisciplinary SMART workflow. Methods HVs 18 years or older were eligible to participate in this IRB-approved study. Using a 0.35 T MRL, simulated adaptive treatments were performed by a multi-disciplinary treatment team in HVs. For each scan, image quality parameters were assessed on a 5-point scale (5 = extremely high, 1 = extremely poor). Adaptive recontouring times were compared between HVs and subsequent clinical cases with a t-test. Results 18 simulated treatments were performed in HVs on MRL. Mean parameters for visibility of target, visibility of nearby organs, and overall image quality were 4.58, 4.62, and 4.62, respectively (range of 4–5 for all measures). In HVs, mean ART was 15.7 min (range 4–35), comparable to mean of 16.1 (range 7–33) in the clinical cases (p = 0.8963). Using HV cases, optimal simulation and contouring guidelines were developed across a range of disease sites and have since been implemented clinically. Conclusions Prior to clinical implementation of SMART, scans of HVs on an MRL resulted in acceptable image quality and target visibility across a range of organs with similar ARTs to clinical SMART. We continue to utilize HV scans prior to clinical implementation of SMART in new disease sites and to further optimize target tracking and immobilization. Further study is needed to determine the optimal duration of HV scanning prior to clinical implementation.

The objectives of this retrospective, observational study were to characterize the anatomical features of the cisterna chyli (CC) in a cohort of dogs diagnosed with idiopathic chylothorax that underwent CT lymphangiography (CTLa), and to evaluate the feasibility of computer-assisted design (CAD) software to quantify volumetric measurements of the CC. Twenty-three client-owned dogs with idiopathic chylothorax were included. Additionally, CTLa was performed in three canine cadavers to assess the ability of CAD software to accurately acquire volumetric measurements. Injection sites, attenuation values, anatomic location, dimensions, and aortic diameter to CC ratio (Ao:CC) were recorded. Video records of video-assisted thoracic surgery (VATS) thoracic duct ligation (TDL) were reviewed in eight out of 23 dogs to compare operative and CTLa findings. The CC was dorsal and right-sided in 18 out of 23 dogs, located between L1 and L4 in 21 dogs, and extended as far cranially as T11 in two dogs. The median measurements for length, height, and width were 150.0, 5.5, and 13.3 mm, respectively. Median total volume was 1.82 mL. Median volumes to the right and left of the aorta were 1.46 and 0.49 mL, respectively (P = .014). Median total CC volume to body weight ratio (CC:bw) was 0.07 mL/kg. The presence of an intrathoracic CC was observed intraoperatively in six out of eight cases that underwent VATS TDL. Findings supported the use of CTLa and CAD as feasible methods for characterizing the CC in dogs diagnosed with chylothorax. These methods may facilitate interventional planning involving the CC such as embolization.

The possible uses of artificial intelligence (AI) in radiation oncology are diverse and wide ranging. Herein, the authors discuss the potential applications of AI at each step of the radiation oncology workflow, which might improve the efficiency and overall quality of radiation therapy for patients with cancer. The authors also describe the associated challenges and provide their perspective on how AI platforms might change the roles of radiation oncology medical professionals. Artificial intelligence (AI) has the potential to fundamentally alter the way medicine is practised. AI platforms excel in recognizing complex patterns in medical data and provide a quantitative, rather than purely qualitative, assessment of clinical conditions. Accordingly, AI could have particularly transformative applications in radiation oncology given the multifaceted and highly technical nature of this field of medicine with a heavy reliance on digital data processing and computer software. Indeed, AI has the potential to improve the accuracy, precision, efficiency and overall quality of radiation therapy for patients with cancer. In this Perspective, we first provide a general description of AI methods, followed by a high-level overview of the radiation therapy workflow with discussion of the implications that AI is likely to have on each step of this process. Finally, we describe the challenges associated with the clinical development and implementation of AI platforms in radiation oncology and provide our perspective on how these platforms might change the roles of radiotherapy medical professionals.

Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study was to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases.We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35T magnetic resonance linear accelerator (MR linac) at a single institution from October 2019 to September 2021. Local control and overall survival were analyzed using the Kaplan-Meier method.Overall, 114 tumors were treated. The most common histology was prostate adenocarcinoma (60 tumors [53.5%]), and 65 sites (57.0%) were centered in the pelvis. Ninety-one sites (79.8%) were treated to 8 Gy × 5, and 49 (43.0%) were treated with breath-hold respiratory gating. Online adaptation resulted in a clinically significant improvement in coverage or organ sparing in 86.6% of delivered fractions. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and was higher for prostate adenocarcinoma versus other histologies (100% vs 84%; P = .009). The 12-month overall survival was 96% and was higher for prostate adenocarcinoma versus other histologies (100% vs 91%; P = .046). Three patients (3.0%) developed grade 3 toxic effects (colonic hemorrhage at 3.4 months and urinary tract obstructions at 10.1 and 18.4 months, respectively).In this study, SMART was feasible, safe, and effective for delivering ablative radiation therapy to abdominopelvic metastases. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.

PURPOSE Coronary artery calcium (CAC) quantified on computed tomography (CT) scans is a robust predictor of atherosclerotic coronary disease; however, the feasibility and relevance of quantitating CAC from lung cancer radiotherapy planning CT scans is unknown. We used a previously validated deep learning (DL) model to assess whether CAC is a predictor of all-cause mortality and major adverse cardiac events (MACEs). METHODS Retrospective analysis of non–contrast-enhanced radiotherapy planning CT scans from 428 patients with locally advanced lung cancer is performed. The DL-CAC algorithm was previously trained on 1,636 cardiac-gated CT scans and tested on four clinical trial cohorts. Plaques ≥ 1 cubic millimeter were measured to generate an Agatston-like DL-CAC score and grouped as DL-CAC = 0 (very low risk) and DL-CAC ≥ 1 (elevated risk). Cox and Fine and Gray regressions were adjusted for lung cancer and cardiovascular factors. RESULTS The median follow-up was 18.1 months. The majority (61.4%) had a DL-CAC ≥ 1. There was an increased risk of all-cause mortality with DL-CAC ≥ 1 versus DL-CAC = 0 (adjusted hazard ratio, 1.51; 95% CI, 1.01 to 2.26; P = .04), with 2-year estimates of 56.2% versus 45.4%, respectively. There was a trend toward increased risk of major adverse cardiac events with DL-CAC ≥ 1 versus DL-CAC = 0 (hazard ratio, 1.80; 95% CI, 0.87 to 3.74; P = .11), with 2-year estimates of 7.3% versus 1.2%, respectively. CONCLUSION In this proof-of-concept study, CAC was effectively measured from routinely acquired radiotherapy planning CT scans using an automated model. Elevated CAC, as predicted by the DL model, was associated with an increased risk of mortality, suggesting a potential benefit for automated cardiac risk screening before cancer therapy begins.

Over the past decade there has been a call to action for researchers to explore children’s subjectivities in the context of well-being. How children understand and experience well-being in a Canadian context was examined in this study. Twenty-one children between 8 and 12 years of age participated in semi-structured interviews facilitated by the Life Story Board™. Three main themes emerged: (1) freedom and control, (2) child rights and social supports, and (3) children’s participation as social actors. Results from this study highlighted the importance of children needing to feel heard by parents and teachers; children being recognised as rights-holders with opportunities to actualise their rights; and children having meaningful opportunities to participate in matters which concerns them in everyday life as important components of subjective well-being. Results may serve to inform child-serving professionals, policymakers, and parents and guardians about how school-aged children from this Canadian context conceptualize and experience well-being.

Photoacoustic (PA) imaging has attracted much attention as a new biomedical imaging modality due to its ultrasonic spatial resolution, optical contrast resolution, and deeper imaging depth than oth...

A 10-week-old sexually intact female golden retriever was evaluated for two functional anal openings and a bipartite vulva. Examination revealed haired skin between two separate anatomically smaller anal openings. On rectal palpation, a soft tissue septum (5 cm) with a mucosal surface between the two anal openings was palpated. In addition, circumferential rectal musculature was not appreciated on the ventral aspect. Urogenital evaluation revealed duplication of the vestibule and vagina with a complete centrally located septum extending dorsoventrally. Computed tomography (CT) of the abdomen and pelvis, vaginocystourethrogram, and colonogram were performed. Complete bifurcation of the urinary bladder with duplication of the urethra, cervix, and vaginal canal was noted. Approximately 2 cm from the rectum, there was a similar bifurcation that converged the colon into two rectal portions and separate anal openings. The owner was counseled on the severity of congenital malformations and a high likelihood of aging-related developmental complications in the future. The owner elected humane euthanasia and a necropsy was performed to confirm the malformations.

PURPOSE/OBJECTIVE(S) Stereotactic body radiotherapy (SBRT) is increasingly being utilized in the management of localized prostate cancer. MR guided adaptive radiotherapy may be a valuable tool for delivery of prostate SBRT as it allows for MR based soft tissue contouring, real time MR motion management and daily plan adaptation to account for interfraction anatomic variability. The goal of the present study is to identify dosimetric gains that can be achieved with an MR guided adaptive prostate SBRT platform and describe acute clinical outcomes. MATERIALS/METHODS We reviewed our institutional experience treating patients with prostate cancer with MR guided adaptive SBRT to a dose of 36.25 Gy in 5 fractions. The adaptive workflow involves development of an "original" plan which is re-optimized daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured daily anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and organ-at-risk (OAR) metrics. Wilcoxon rank sum testing was used to compare predicted dosimetry to re-optimized dosimetry. Acute urinary and GI toxicity rates were assessed according to CTCAE v5. RESULTS A cohort of 16 patients treated was analyzed with median follow up time of 3 months. Acute G2+ GU toxicity was observed in 19% and acute G2+ GI toxicity in 6%. No G3+ events were noted. Comparison of dosimetry metrics for PTV coverage, urethra, rectum and bladder are shown in table 1; 100% of fractions required plan adaptation due to either exceeding OAR metrics (68%) or sub-optimal PTV coverage (33%). Adaptive planning increased the proportion of fractions meeting prescription metrics for PTV coverage (V34.44 from 71% to 100%), urethra (V38.78 from 58% to 100%) and rectum (V38.06 from 80% to 100%). Urethral metrics were most frequently violated in predicted plans (42% of fractions) and re-optimized to acceptable dosimetry in 100% of fractions. Re-optimization significantly improved PTV coverage, rectal metrics and urethral metrics. CONCLUSION Online adaptive re-optimization significantly improved plan dosimetry and achieved minimal acute toxicity. The clinical benefits of MR guided adaptive prostate SBRT for optimizing target coverage with urethral protection warrant further investigation.

Purpose/objective(s) Stereotactic body radiation therapy (SBRT) can be an effective method for treating metastases. However, the proximity of organs at risk (OARs) to the target can limit the safe delivery of ablative doses, particularly in the abdomen and pelvis where there can be significant interfraction and intrafraction motion. Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may allow for safer delivery of ablative radiation to abdominopelvic metastases. We report the feasibility and early outcomes of patients with abdominopelvic metastases treated with SMART using a 0.35T MR Linac in a (1) retrospective cohort and (2) a prospective phase 1 trial. Materials/methods We identified 44 patients in the retrospective cohort and enrolled 13 patients onto the phase 1 protocol, all with abdominopelvic metastases. Patients with metastases of the liver, kidneys, or adrenal glands were excluded and were enrolled on companion phase 1 trials. Patients were treated between 10/29/19-2/18/21. For the retrospective cohort, dose prescription and coverage were at the discretion of the treating physician, with 67% of sites receiving 40 Gy/5 fractions. For the phase 1 cohort, patients were treated to 40 Gy/5 fractions daily with goal PTV coverage of V40 ≥95% (ideal) and V30 ≥95% (acceptable). Results Overall, the 44 patients in the retrospective cohort were treated to 49 sites of abdominopelvic disease, and the 13 patients in the phase 1 cohort received treatment to one site of abdominopelvic disease each on protocol. The most common histology was prostate adenocarcinoma (57%). In total, 308 fractions were delivered, with 138 (45%) using a breath hold and 170 (55%) using free breathing. Online adaptation was necessary for 269/308 fractions (87%) to either satisfy critical OAR metrics (62%) or improve target coverage (38%). Additionally, there were two instances when on-board MRI allowed for the detection of bowel which had displaced the target to such a degree as to interfere with safe treatment delivery, even when utilizing adaptive planning. These two treatments were postponed to either later the same day or a subsequent day. Patients spent an average of 61 minutes in the treatment room. With median follow-up of 150 days (interquartile range 90-224 days), there were no deaths and one local failure (a patient with urothelial carcinoma who received 35 Gy/5 fractions at 102 days after start of SBRT). There was one grade ≥3 treatment-related toxicity (colonic hemorrhage in a patient with serous ovarian cancer who received 40 Gy/5 fractions at 86 days after start of SBRT in the setting of thrombocytopenia). Conclusion SMART is a feasible method for delivering ablative doses of radiation. Adaptive planning was necessary in a large portion of cases. Early data suggest a high rate of local control and low risk of significant toxicity. Longer-term results of the phase 1 protocol will be reported in the future.

Artificial intelligence (AI) has the potential to fundamentally alter the way medicine is practised. AI platforms excel in recognizing complex patterns in medical data and provide a quantitative, rather than purely qualitative, assessment of clinical conditions. Accordingly, AI could have particularly transformative applications in radiation oncology given the multifaceted and highly technical nature of this field of medicine with a heavy reliance on digital data processing and computer software. Indeed, AI has the potential to improve the accuracy, precision, efficiency and overall quality of radiation therapy for patients with cancer. In this Perspective, we first provide a general description of AI methods, followed by a high-level overview of the radiation therapy workflow with discussion of the implications that AI is likely to have on each step of this process. Finally, we describe the challenges associated with the clinical development and implementation of AI platforms in radiation oncology and provide our perspective on how these platforms might change the roles of radiotherapy medical professionals.

BACKGROUND Treatment misadministration during high dose rate (HDR) brachytherapy is mainly caused due to gross errors in incorrect manual entry of catheter length and manual connection of hardware. The probability of these errors increases with increasing complexity of a surface applicator. A simple, real-time visual verification method was developed using a scintillator to enhance quality assurance (QA) measures for HDR surface brachytherapy and thus reduce manual errors and improve patient safety. MATERIALS AND METHODS Scintillation markers were fabricated from cerium-doped lutetium yttrium orthosilicate (LYSO) embedded in a polymer compound to form 5-mm diameter markers. To verify catheter-transfer tube connections, markers were attached to each channel of a Freiburg flap and irradiated with an 192 Ir source. To determine if the source reached the edge of a target, markers were placed along the periphery. The HDR source was visually tracked by following the illumination from the markers. The response of the markers was also verified in the presence of thermoplastic material overlaid on the Freiburg applicator. RESULTS Scintillation markers emitted intense blue visible light upon irradiation when the HDR source was beneath the marker, verifying the source's presence in the correct catheter. The signal was clearly visible even when the marker was placed on top of the thermoplastic material covering the Freiburg Flap. Crosstalk from adjacent catheters was

A multinational study to understand well-being from children’s perspectives in the Children’s Worlds International Survey of Children’s Well-being (ISCWeB) recently undertook qualitative analytical research to explore children’s conceptualization of well-being in Children’s Understanding of Well-being (CUWB). This has challenged researchers to utilize methods that are meaningful and engaging, child-centred and balance children’s rights to participation and protection, and are practical and time-expedient. The paper describes the findings from a qualitative investigation of a task-oriented research tool, the Vidaview Life Story Board (LSB), used to explore school-age children’s understanding of well-being. Twenty-one children between 8 and 12 years of age from the Canadian pilot of the CUWB were interviewed using the LSB. The children and the interviewer were asked to assess their experience with the LSB. Results suggested that children found the LSB to be engaging and helpful to facilitate their articulation of subjective well-being. The main themes that emerged were: autonomy and inclusiveness; validation of children’s experiences and agency; and child-centred approach. The findings suggest that the LSB seems to be a promising participatory, child-centred, rights-based qualitative research tool.

Purpose/objective(s) The use of ablative stereotactic body radiation therapy (SBRT) in pancreatic cancer is constrained by nearby radiation-sensitive organs. Magnetic resonance (MR)-guided adaptive radiation therapy (SMART) is an innovation that offers superior anatomical imaging during treatment allowing for daily plan adaptation based on the volumetric images prior to each treatment. We report results of a prospective phase 1 trial (NCT04115254) assessing feasibility of SMART and describe early outcomes of patients with pancreatic cancer. Secondary objectives included analysis of 90-day toxicity, local control, and patient-reported outcomes (PROMs) in patients undergoing SMART. Materials/methods In this prospective IRB approved study, patient eligibility criteria included: biopsy-proven diagnosis of pancreatic cancer, eligibility for SBRT, and ability to undergo and tolerate MRI imaging. Patients were ineligible if they had prior abdominal radiation, active ulcerative disease, or tumor invasion of the stomach, duodenum or bowel on endoscopy. Patients were monitored for acute and late grade ≥ 3 toxicity. PROMs included the FACT-HEP and PROMIS Physical and Mental Health batteries and were completed at baseline and during follow-up. Feasibility was defined as 1) enrolling patients and delivering SMART on the MR-Linac; 2) assessing tumor using MR guidance before, during and after MR-guided treatment and 3) generating adaptive plans. Results All 10 patients successfully completed SMART, receiving 40 Gy in 5 fractions with 48 of 50 fractions requiring adaptation to meet target or critical organ-at-risk metrics. The median follow up was 10.49 months (range 5.00 - 11.38). The median age was 72 (range 55 - 89), 60% were female, and 80% were white. Disease stages included 30% T1-T2, 10% T3, and 60% T4 disease, as well as 30% N0, 60% N1, 10% N2 disease, and 80% M0, 10% MX, and 10% M1. 90% of patients had other medical comorbidities. ECOG performance status was 0-1 in 90% of patients. There were no acute or late grade ≥ 3 treatment related toxicities. There were no local recurrences. The 6-month survival rate was 90% (95% CI 47.3-98.5) with two deaths due to progressive disease. The median change between baseline and follow-up within 6 months of treatment was -0.5 on FACT-HEP, -2.5 on PROMIS Physical, and -4.7 on PROMIS Mental Health (table 1). Conclusion We successfully demonstrated the feasibility and safety of SMART with daily adaptation in patients with pancreatic cancer. PROMs highlight that patients tolerated treatment well with minimal toxicity. Further investigation in dose escalation in pancreatic cancer is warranted.

Purpose/Objective(s) Accurate radiation therapy targeting for stomach cancer is challenging given daily variations in the stomach's size and position. We evaluated daily MR-based imaging to quantify changes in stomach volume and characterized the impact of inter-fractional variation on dosimetry for gastric cancer radiation plans. Materials/Methods We assessed inter-fraction changes in the volume and position of the stomach via MR-based imaging for 10 patients who previously underwent abdominal stereotactic body radiation therapy. All patients were simulated and treated over 5 fractions and were instructed to fast for 3 hours before each session. The stomach and regional organs-at-risk (OARs) were contoured on each fraction's MR scan according to standard RTOG guidelines. Inter-fraction variation in the size and position of the stomach was quantified by calculating the percentage volume change and dice similarity coefficient (DSC) as compared to the simulation scan. To determine the potential impact of inter-fraction stomach motion on treatment planning, we generated mock plans to recapitulate neoadjuvant or definitive stomach cancer treatments. For the purpose of this study, the stomach contour was symmetrically expanded by 1.7 cm to generate a planning treatment volume (PTV) and a prescription dose of 45 Gy in 1.8 Gy fractions was applied. Intensity-modulated radiation therapy plans were then generated to meet the following dosimetric goals: PTV V95% of 95%, liver V30 less than 30%, and bilateral kidney V20 less than 20%. Finally, the impact of gastric variation on these dose metrics was assessed. Results Despite standard daily preparation and set up procedures, we observed significant variability in the size and location of the stomach between fractions. The mean absolute daily change in gastric volume compared to the planning MRI was 19.1% (total range: -42.0% to 58.4%). The average stomach DSC was 0.69 (range: 0.40 to 0.86). Given this degree of variability, mock gastric cancer treatment plans displayed suboptimal dose metrics. The average PTV V45 was 81.5% (range: 58.8% to 99.2%. 95% CI: 78.8% to 84.2%). Average liver V30 values were 12.7% (range: 3.5% to 20.1%. 95% CI: 11.7% to 13.9%) and bilateral kidney V20 values were 12.3% (range: 0.5% to 31.3%. 95% CI: 9.2% to 15.3%). Target metrics were highly correlated with the percent change in stomach volume—a 10% increase in stomach volume was associated with a 2.4% decrease in the V45 (P Conclusion We observed significant inter-fraction variability in the dimensions of the stomach using daily MRI-based imaging, leading to dosimetrically inferior mock gastric cancer treatment plans. Our study suggests that larger PTV margins may be necessary for conventional stomach plans, which would come at the expense of greater OAR exposure. Alternatively, MRI-based image guidance and daily adaptive treatments may improve the therapeutic window of radiation therapy for gastric tumors.

Purpose/objective(s) Metastases to the pancreas (MPs) are difficult to treat with radiation therapy (RT) due to respiratory and bowel motion and proximity to critical organs at risk (OARs). Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) may improve tumor coverage and OAR sparing through motion control with breath hold gating and continuous MR imaging during treatment, and the option for daily online adaptive replanning (ARP) to account for changes in tumor and/or OAR position. We evaluated the need for online adaptive MRgSBRT and its effect on target coverage, OAR metrics, and tumor control in patients with MPs. Materials/methods In this IRB-approved retrospective study, we reviewed the records of patients with MPs treated with MRgSBRT between July 2019 and January 2021. Patients were identified from a prospectively maintained database. Data were collected regarding dose to targets and OARs, use and rationale for ARP, toxicity, and outcomes. Treatment response was defined as a decrease in size of the treated MP. Local failures were defined as recurrences within the RT field. Descriptive statistics were used. Results We identified 8 MPs in 6 patients. Median age was 70 years (range, 61-88). Patients had oligoprogressive or oligometastatic renal cell carcinoma (n = 3), carcinoid (n = 1), hepatocellular carcinoma (n = 1), and lung adenocarcinoma (n = 1). The median time from diagnosis to development of metastatic disease was 17 months (range, 0-105 months) and to treatment of the MP was 36 months (range, 7-230 months). All patients received 40 Gy in 5 fractions with breath hold technique. The median GTV was 8.5 cc (range, 2.2-132.8 cc) and PTV was 27.7 cc (range, 8.3-175.7 cc). 35/40 (87%) fractions required ARP, necessary to meet stomach and duodenal metrics in 11 (27%) and 16 (40%) fractions, respectively. The mean stomach, duodenal, and PTV metrics before and after ARP are reported in Table 1. On average, ARP increased the PTV coverage by 4.9% and decreased the stomach V33, stomach V35, and duodenum V33 by 0.61 cc, 0.31 cc, and 1.10 cc, respectively. At a median follow-up of 5.0 months, 6/8 (75%) lesions had a partial response. There were no local failures. There was one distant failure 27 days after treatment. One patient developed a grade 2 pyloric ulcer which resolved with medical management. There were no other ≥ grade 2 toxicities. Conclusion In this study, ARP was necessary in most MRgSBRT treatments to MPs. Adaptive MRgSBRT improved PTV coverage and OAR metrics, and it provided high rates of tumor control with minimal toxicity. Further study in larger patient populations and in peripancreatic metastases is needed.

PURPOSE/OBJECTIVE(S) Dose escalated stereotactic body radiotherapy (SBRT) may improve both local control and overall survival for patients with pancreatic cancer. However, escalated dose cannot be routinely offered because of the risk of injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents an innovation that may achieve safer delivery of ablative doses and improve outcomes. The goal of the present study is to identify specific dosimetric gains that can be achieved with MR-guided adaptive pancreatic SBRT and describe acute clinical outcomes. MATERIALS/METHODS We performed a single institution IRB approved retrospective analysis of 37 consecutive pancreatic cancer patients treated with 40 Gy in 5 fractions with SMART on a MR-linear accelerator using a light inspiration breath hold. The adaptive workflow starts with an "original" plan which is then adapted daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured pre-treatment anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and meet critical organ-at-risk (OAR) metrics, including stomach, duodenum, large bowel and small bowel V33 < 1cc. Acute GI toxicity rates were assessed according to CTCAE v5. RESULTS The median age of our cohort was 71 (range 35-87) with 23/37 (62%) patients having locally advanced disease and 14/37 (38%) having borderline resectable disease. Adaptive planning was used in all cases with a prescription goal of 40 Gy in 5 fractions prescribed to 90% of the target volume. The median CTV was 80.5 cc (range, 10-180cc) and the PTV was a 3mm expansion. Adaptive planning was required in 156/185 fractions to meet either the stomach (63.8%), duodenum (33.5%), large bowel (12.4%) or small bowel (11.4%) V33 < 1cc metric. Of the plans adapted for OAR sparing, 90 plans required adaptation for one gastrointestinal organ, 50 plans for two, 10 plans for three and 1 plan for four. For predicted plans exceeding the V33 < 1cc metric, the median V33 for duodenum was 2.475cc (range: 1.01-10.68cc), stomach was 2.67cc (range: 1.01-8.21cc), small bowel was 2.71cc (range: 1.14-9.54cc) and large bowel was 1.93cc (range: 1.05-8.36cc). All re-optimized plans met the V33 < 1cc metric. No local failure or acute grade 3 toxicities were observed with a median follow-up of 6 months (range 3-15). CONCLUSION Online adaptive re-optimization was necessary for the majority of fractions and improved plan dosimetry was achieved specifically for duodenum, stomach, large and small bowel, achieving low rates of acute toxicity. The clinical benefits of MR-guided adaptive pancreatic SBRT for dose escalation warrant further investigation.

PURPOSE/OBJECTIVE(S) Recent work has challenged emphasis of chronologic age in cancer treatment decision-making. For patients with non-small cell lung cancer (NSCLC), cardiopulmonary risk histories widely vary, possibly impacting "biologic age." We aimed to apply an externally-derived deep learning model to estimate chest imaging age (ChIA) from digitally reconstructed radiographs (DRRs) created from simulation computed tomography (CT) scans of patients with locally advanced NSCLC (LA-NSCLC). We hypothesized ChIA could serve as a prognostic imaging biomarker in this population. MATERIALS/METHODS We previously pretrained a Resnet34 convolutional neural network (CNN) to predict chronologic age using normal chest radiographs (CXRs) from public cohorts (CheXpert, NIH, and PadCHEST, n = 24,934). We fine-tuned the CNN to predict ChIA based on time to death using CXRs from 13,657 (25%) patients of the Prostate, Lung, Colorectal and Ovarian Cancer Trial, testing in the remaining 75% (n = 40,967) and the National Lung Screening Trial (n = 5,414). We applied the model to simulation CT DRRs in an institutional cohort of patients with LA-NSCLC receiving lung radiation (Lung-RT, n = 847). Recursive partitioning analysis (RPA) identified a cut point associated with overall survival (OS) in Lung-RT, above which patients were classified ChIA-high. We evaluated association between ChIA and OS using Kaplan-Meier calculations and Cox regression analyses and then validated in the multi-institutional RTOG 0617 trial (n = 460). RESULTS In Lung-RT, median age was 67 (Range 21-90) years and median ChIA was 67 (Range 57-80) years. In RTOG 0617, median age was 64 (37-83) years, and median ChIA was 66 (52-77) years. Age/ChIA correlation coefficients were 0.29 (95% CI 0.23-0.35, P < 0.001) and 0.32 (95% CI 0.23-0.40, P < 0.001), respectively. Table 1 shows OS after median follow-up in Lung-RT of 56 (95% CI 53-58) months, and in RTOG 0617 of 36 (95% CI 32-37) months. In Lung-RT, adjusting for age, race, and sex, ChIA-high patients had HR 1.22 (95% CI 1.00-1.49, P = 0.049) for OS. In RTOG 0617, adjusting for trial arm, age, gender, race, ethnicity, performance status, histology, and stage, ChIA-high patients had HR 1.41 (95% CI 1.02-1.91, P = 0.037) for OS. CONCLUSION Our work validates use of a deep learning CXR-based model to predict ChIA using DRRs created from routine simulation CTs of patients with LA-NSCLC. In an institutional and multi-institutional trial cohort, ChIA-high patients had worse survival than ChIA-low patients, suggesting potential use of ChIA as a prognostic imaging biomarker enabling de-emphasis of chronologic age in treatment decision-making.

Background Although childhood cancer mortality rates are decreasing, intensive treatment modalities and missed school days may leave childhood cancer patients psychologically and socially vulnerable. Children with cancer often have increased anxiety, lower levels of self-esteem, and higher rates of depression, all of which may impair their psychosocial wellbeing. Specialized camps for children with cancer are becoming increasingly popular, as they provide a stress-free, outdoor environment in which children are able to interact with individuals similar to themselves, while experiencing the joys of a “normal childhood.“ Objective The aim of this review was to explore how camp participation impacts the psychosocial wellbeing of childhood cancer patients and survivors. Methods Six databases (MEDLINE, PsychINFO, EMBASE, CINHAL, Sociological Abstracts, Social Sciences Citation Index) were systematically searched for English literature published between 2007 and 2018. The search generated 1707 titles, and after being evaluated for relevance, 18 articles met the inclusion criteria. A thematic analysis was conducted. Results A variety of camp programs and methodologies were employed among the studies. Camp participation led to improved social health, followed by enhanced constructions of the self, quality of life, sense of normalcy, and attitude. Conclusion This review demonstrates the potential ability of camp to buffer psychosocial losses for children affected by cancer. Addressing limitations, such as the lack of child-centered methodologies employed in camp settings, may not only help to guide future research on therapeutic recreation experiences for children with cancer, but also expand the evidence base for children living with other chronic illnesses and disabilities.

Purpose: The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management. Experimental Design: Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management. Results: PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures. Conclusions: PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT. Clin Cancer Res; 22(4); 961–70. ©2015 AACR.

BackgroundValues used in economic evaluation are typically obtained from the general public, which is problematic when measures are to be used with people experiencing a life-course stage such as the end of life.ObjectiveTo assess the feasibility of obtaining values for the ICECAP-Supportive Care Measure (SCM) from patients receiving advanced supportive care through a hospice.MethodsParticipants completed eight best-worst scaling questions in a think-aloud interview to explain choices in different hypothetical end-of-life scenarios. Three independent raters identified errors in completion of the best-worst scaling task, and thematic analysis of associated qualitative data was undertaken to explore task difficulty and choices.ResultsTwelve hospice patients were recruited. Most were able to complete the task and prioritise aspects of supportive care with either no difficulty (n=50%) or difficulty in just one of the eight scenarios (n=25%). Two patients (n=17%) were unable to comprehend the hypothetical nature of the task. The qualitative data confirmed there was good engagement with the task and identified the importance the respondents attached to maintaining dignity.ConclusionThe findings suggest that people at the end of life will be able to complete a short, interviewer-administered, best-worst scaling task. To maximise engagement, it is recommended that the task is short and initiated with an example. Scenarios are best presented on show-cards in large print. A full evaluation of the ICECAP-SCM with those at the end of life is feasible.

David Basic,1 Elizabeth Huynh,2 Rinaldo Gonzales,1 Chris Shanley3 1Department of Geriatric Medicine, Aged Care Research Unit, Liverpool Hospital, Liverpool BC, NSW 1871, Australia; 2Department of Geriatric Medicine, Aged Care Research Unit, Liverpool Hospital, University of NSW, Liverpool BC, NSW 1871, Australia; 3Department of Geriatric Medicine, Centre for Applied Nursing Research, Western Sydney University and Ingham Institute of Applied Medical Research, Aged Care Research Unit, Liverpool Hospital, Liverpool BC, NSW 1871,Australia Purpose: Ineffective interdisciplinary communication is linked to many adverse consequences of hospitalization. This study evaluated the effect of SIBR, a model of care that encourages interdisciplinary communication and patient and family participations, on in-hospital deaths and new nursing home (NH) placements.Materials and methods: This before-after study included 3,673 consecutive inpatients of mean age 83.8 years, of whom 93.2% were admitted through the emergency department. After each twice-weekly SIBR session, an interdisciplinary care plan was implemented and recorded on a datasheet attached to the bedside record. Staff unable to participate in SIBR were asked to view the datasheet and to follow the care plan. Logistic regression models were computed for in-hospital deaths and new NH placements.Results: Although SIBR implementation had no effect on in-hospital deaths (OR, 1.00; 95% CI, 0.77–1.29), SIBR increased NH placements among those who survived the hospitalization (n=3,346) in both unadjusted (14.6% vs 9.1%; P

An 8-year-old, spayed female, domestic short haired cat, with diabetes mellitus, was presented to the University of Florida Veterinary Medical Center for an acute onset of vomiting and inappetence. Abdominal radiographs showed mild retroperitoneal effusion and asymmetric left-sided renomegaly. Subsequently, on abdominal ultrasound, a hypoechoic left ureteral mass with left hydronephrosis and hydroureter was identified. An abdominal computed tomography revealed a heterogeneously contrast-enhancing mass circumferentially surrounding the mid to distal left ureter, mild retroperitoneal effusion, left-sided hydronephrosis and hydroureter, and a distally located ureteral calculus at the level of the ureterovesicular junction. The patient was diagnosed with left-sided pyogranulomatous ureteritis via surgical biopsy and histopathology.

Head and neck cancer is the fifth most common type of cancer worldwide and remains challenging for effective treatment due to the proximity to critical anatomical structures in the head and neck region, which increases the probability of toxicity from surgery and radiotherapy, and therefore emphasizes the importance of maximizing the targeted ablation. We have assessed the effectiveness of porphysome nanoparticles to enhance fluorescence and photoacoustic imaging of head and neck tumors in rabbit and hamster models. In addition, we evaluated the effectiveness of this agent for localized photothermal ablative therapy of head and neck tumors. We have demonstrated that porphysomes not only enabled fluorescence and photoacoustic imaging of buccal and tongue carcinomas, but also allowed for complete targeted ablation of these tumors. The supremacy of porphysome-enabled photothermal therapy over surgery to completely eradicate primary tumors and metastatic regional lymph node while sparing the adjacent critical structures' function has been demonstrated for the first time. This study represents a novel breakthrough that has the potential to revolutionize our approach to tumor diagnosis and treatment in head and neck cancer and beyond.

Converting nanoparticles or monomeric compounds into larger supramolecular structures by endogenous or external stimuli is increasingly popular because these materials are useful for imaging and treating diseases. However, conversion of microstructures to nanostructures is less common. Here, we show the conversion of microbubbles to nanoparticles using low-frequency ultrasound. The microbubble consists of a bacteriochlorophyll-lipid shell around a perfluoropropane gas. The encapsulated gas provides ultrasound imaging contrast and the porphyrins in the shell confer photoacoustic and fluorescent properties. On exposure to ultrasound, the microbubbles burst and form smaller nanoparticles that possess the same optical properties as the original microbubble. We show that this conversion is possible in tumour-bearing mice and could be validated using photoacoustic imaging. With this conversion, our microbubble can potentially be used to bypass the enhanced permeability and retention effect when delivering drugs to tumours.

Objectives The clinical management of meningioma is guided by tumor grade and biological behavior. Currently, the assessment of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor grade may enhance clinical decision-making. Methods A total of 175 meningioma patients (103 low-grade and 72 high-grade) with pre-operative contrast-enhanced T1-MRI were included. Fifteen radiomic (quantitative) and 10 semantic (qualitative) features were applied to quantify the imaging phenotype. Area under the curve (AUC) and odd ratios (OR) were computed with multiple-hypothesis correction. Random-forest classifiers were developed and validated on an independent dataset (n = 44). Results Twelve radiographic features (eight radiomic and four semantic) were significantly associated with meningioma grade. High-grade tumors exhibited necrosis/hemorrhage (ORsem = 6.6, AUCrad = 0.62–0.68), intratumoral heterogeneity (ORsem = 7.9, AUCrad = 0.65), non-spherical shape (AUCrad = 0.61), and larger volumes (AUCrad = 0.69) compared to low-grade tumors. Radiomic and sematic classifiers could significantly predict meningioma grade (AUCsem = 0.76 and AUCrad = 0.78). Furthermore, combining them increased the classification power (AUCradio = 0.86). Clinical variables alone did not effectively predict tumor grade (AUCclin = 0.65) or show complementary value with imaging data (AUCcomb = 0.84). Conclusions We found a strong association between imaging features of meningioma and histopathologic grade, with ready application to clinical management. Combining qualitative and quantitative radiographic features significantly improved classification power.