Search

PurposeTo 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.MethodsTwenty-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 ProtégéAI. 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.ResultsACs were generated for 22 OARs using AccuContour and 17 OARs using ProtégéAI 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 ProtégéAI respectively. Using AccuContour, the average MD was

This Special Topics Issue, “Imaging-based Diagnosis of Prostate Cancer—State of the Art”, of Diagnostics compiles 10 select articles [...]

IntroductionInvisible 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 materialsIn 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.ResultsOf 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

Purpose: Breath-hold (BH) technique can mitigate target motion, minimize target margins, reduce normal tissue doses, and lower the effect of interplay effects with intensity-modulated proton therapy (IMPT). This study presents dosimetric comparisons between BH and nonbreath-hold (non-BH) IMPT plans and investigates the reproducibility of BH plans using frequent quality assurance (QA) computed tomography scans (CT). Methods and Materials: Data from 77 consecutive patients with liver (n = 32), mediastinal/lung (n = 21), nonliver upper abdomen (n = 20), and malignancies in the gastroesophageal junction (n = 4), that were treated with a BH spirometry system (SDX) were evaluated. All patients underwent both BH CT and 4-dimensional CT simulations. Clinically acceptable BH and non-BH plans were generated on each scan, and dose-volume histograms of the 2 plans were compared. Reproducibility of the BH plans for 30 consecutive patients was assessed using 1 to 3 QA CTs per patient and variations in dose-volume histograms for deformed target and organs at risk (OARs) volumes were compared with the initial CT plan. Results: Use of BH scans reduced initial and boost target volumes to 72% ± 20% and 70% ± 17% of non-BH volumes, respectively. Additionally, mean dose to liver, stomach, kidney, esophagus, heart, and lung V20 were each reduced to 71% to 79% with the BH technique. Similarly, small and large bowels, heart, and spinal cord maximum doses were each lowered to 68% to 84%. Analysis of 62 QA CT scans demonstrated that mean target and OAR doses using BH scans were reproducible to within 5% of their nominal plan values. Conclusions: The BH technique reduces the irradiated volume, leading to clinically significant reductions in OAR doses. By mitigating tumor motion, the BH technique leads to reproducible target coverage and OAR doses. Its use can reduce motion-related uncertainties that are normally associated with the treatment of thoracic and abdominal tumors and, therefore, optimize IMPT delivery.

Summary: Background: Developing strategies to prevent breast cancer-related arm lymphoedema (BCRAL) is a critical unmet need because there are no effective interventions to eradicate it once it reaches a chronic state. Certain strategies such as prospective surveillance programs and prophylactic lymphatic reconstruction have been reported to be effective in clinical trials. However, a large variation exists in practice based on clinician preference, organizational standards, and local resources. Methods: A two-round international Delphi consensus process was performed from February 27, 2023 to May 25, 2023 to compile opinions of 55 experts involved in the care and research of breast cancer and lymphoedema on such interventions. Findings: Axillary lymph node dissection, use of post-operative radiotherapy, relative within-arm volume increase one month after surgery, greater number of lymph nodes dissected, and high body mass index were recommended as the most important risk factors to guide selection of patients for interventions to prevent BCRAL. The panel recommended that prospective surveillance programs should be implemented to screen for and reduce risks of BCRAL where feasible and resources allow. Prophylactic compression sleeves, axillary reverse mapping and prophylactic lymphatic reconstruction should be offered for patients who are at risk for developing BCRAL as options where expertise is available and resources allow. Recommendations on axillary management in clinical T1–2, node negative breast cancer patients with 1–2 positive sentinel lymph nodes were also provided by the expert panel. Routine axillary lymph node dissection should not be offered in these patients who receive breast conservation therapy. Axillary radiation instead of axillary lymph node dissection should be considered in the same group of patients undergoing mastectomy. Interpretation: An individualised approach based on patients' preferences, risk factors for BCRAL, availability of treatment options and expertise of the healthcare team is paramount to ensure patients at risk receive preventive interventions for BCRAL, regardless of where they are receiving care. Funding: This study was not supported by any funding. RJC received investigator grant support from the Australian National Health and Medical Research Council (APP1194051).

BackgroundSensitive and reliable biomarkers for early detection of recurrence are needed to improve post-definitive radiation risk stratification, disease management, and outcomes for patients with unresectable early-stage or locally advanced non-small cell lung cancer (NSCLC) who are treated with definitive radiation therapy (RT). This prospective, multistate single-center, cohort study investigated the association of circulating tumor DNA (ctDNA) status with recurrence in patients with unresectable stage I-III NSCLC who underwent definitive RT.MethodsA total of 70 serial plasma samples from 17 NSCLC patients were collected before, during, and after treatment. A personalized, tumor-informed ctDNA assay was used to track a set of up to 16 somatic, single nucleotide variants in the associated patient’s plasma samples.ResultsPre-treatment ctDNA detection rate was 82% (14/17) and varied based on histology and stage. ctDNA was detected in 35% (6/17) of patients at the first post-RT timepoint (median of 1.66 months following the completion of RT), all of whom subsequently developed clinical progression. At this first post-RT time point, patients with ctDNA-positivity had significantly worse progression-free survival (PFS) [hazard ratio (HR): 24.2, p=0.004], and ctDNA-positivity was the only significant prognostic factor associated with PFS (HR: 13.4, p=0.02) in a multivariate analysis. All patients who developed clinical recurrence had detectable ctDNA with an average lead time over radiographic progression of 5.4 months, and post-RT ctDNA positivity was significantly associated with poor PFS (p

Purpose: Compared with photon-based techniques, proton beam radiation therapy (PBT) may improve the therapeutic ratio of radiation therapy (RT) for locally advanced pancreatic cancer (LAPC), but available data have been limited to single-institutional experiences. This study examined the toxicity, survival, and disease control rates among patients enrolled in a multi-institutional prospective registry study and treated with PBT for LAPC. Methods and Materials: Between March 2013 and November 2019, 19 patients with inoperable disease across 7 institutions underwent PBT with definitive intent for LAPC. Patients received a median radiation dose/fractionation of 54 Gy/30 fractions (range, 50.4-60.0 Gy/19-33 fractions). Most received prior (68.4%) or concurrent (78.9%) chemotherapy. Patients were assessed prospectively for toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Kaplan-Meier analysis was used to analyze overall survival, locoregional recurrence-free survival, time to locoregional recurrence, distant metastasis-free survival, and time to new progression or metastasis for the adenocarcinoma cohort (17 patients). Results: No patients experienced grade ≥3 acute or chronic treatment-related adverse events. Grade 1 and 2 adverse events occurred in 78.7% and 21.3% of patients, respectively. Median overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and time to new progression or metastasis were 14.6, 11.0, 11.0, and 13.9 months, respectively. Freedom from locoregional recurrence at 2 years was 81.7%. All patients completed treatment with one requiring a RT break for stent placement. Conclusions: Proton beam RT for LAPC offered excellent tolerability while still maintaining disease control and survival rates comparable with dose-escalated photon-based RT. These findings are consistent with the known physical and dosimetric advantages offered by proton therapy, but the conclusions are limited owing to the patient sample size. Further clinical studies incorporating dose-escalated PBT are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.

Purpose: After adequate surgical resection, early-stage oral tongue cancer patients can harbor a low risk of local recurrence but remain at risk of regional recurrence. Oral tongue avoidance during adjuvant radiation therapy is an attractive potential treatment strategy to mitigate treatment toxicity. We sought to quantify the dosimetric advantages of this approach and hypothesized that intensity-modulated proton therapy (IMPT) may further reduce organs at risk doses compared with intensity-modulated radiation therapy (IMRT). Materials and Methods: Five patients with oral tongue cancer treated with postoperative radiation therapy from August 2020 to September 2021 were retrospectively reviewed. Novel clinical target volume contours, excluding the oral tongue, were generated while maintaining coverage of bilateral at-risk lymph nodes. Comparison IMRT (X) and IMPT (PBT) plans were generated using standard treatment volumes (control) and avoidance volumes (study) (n = 4 plans/patient). Dosimetric variables for organs at risk were compared using the paired t test. Results: The prescribed dose was 60 Gy in 30 fractions. D95% clinical target volume coverage was similar between X and PBT plans for both control and study clinical target volumes. Comparing control with study plans, both X (58.9 Gy vs 38.3 Gy, P = .007) and PBT (60.2 Gy vs 26.1 Gy, P < .001) decreased the oral cavity dosemean. The pharyngeal constrictor dosemean was also reduced (P < .003). There was no difference between control and study plans for larynx (P = .19), parotid (P = .11), or mandible dose (P = .59). For study plans, PBT significantly reduced oral cavity dosemean (38.3 Gy vs 26.1 Gy, P = .007) and parotid dosemean (23.3 Gy vs 19.3 Gy, P = .03) compared with X. For control plans, there was no difference in oral cavity dosemean using PBT compared with X, but PBT did improve the parotid dosemean (26.6 Gy vs 19.7 Gy, P = .02). Conclusion: This study quantifies the feasibility and dosimetric advantages of oral tongue avoidance while still treating the at-risk lymph nodes for oral tongue cancer. The dosimetric difference between PBT and X was most prominent with an oral tongue–avoidance strategy.

Abstract Background We investigate the impact of gender, race, and socioeconomic status on the diagnosis and management of bladder cancer in the United States. Methods We utilized the National Cancer Database to stratify cases of urothelial cell carcinoma of the bladder as early (Tis, Ta, T1), muscle invasive (T2–T3, N0), locally advanced (T4, N1–3), and metastatic. Multivariate binomial and multinomial logistic regression analyses identified demographic characteristics associated with stage at diagnosis and receipt of cancer‐directed therapies. Odds ratios (OR) are reported with 95% confidence intervals. Results After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases from 2004–2016. Relative to diagnosis at early stage, the strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included Black race (OR = 1.19 [1.15–1.23], OR = 1.49 [1.40–1.59], OR = 1.66 [1.56–1.76], respectively), female gender (OR = 1.21 [1.18–1.21], OR = 1.16 [1.12–1.20], and OR = 1.34 [1.29–1.38], respectively), and uninsured status (OR = 1.22 [1.15–1.29], OR = 2.09 [1.94–2.25], OR = 2.57 [2.39–2.75], respectively). Additional demographic factors associated with delayed diagnosis included older age, treatment at an academic center, Medicaid insurance and patients from lower income/less educated/more rural areas (all p

Purpose: Reports of proton beam therapy (PBT) utilization for cutaneous melanoma of the head and neck (HN) region is virtually non-existent. This study reports on the efficacy and acute toxicities of PBT for primary HN cutaneous melanoma. Materials and Methods: We queried the prospectively collected, multi-institutional Proton Collaborative Group registry for all consecutive patients with HN cutaneous melanoma receiving PBT from May 2010 to December 2019. Kaplan-Meier methods were used to estimate overall survival (OS), progression free survival (PFS), and local regional recurrence free survival (LRFS). Toxicity was reported per CTCAE version 4.0. Results: A total of 8 patients were identified with a median age of 69 (range, 37-88). All patients (100%) underwent surgery followed with postoperative PBT. There were 3 patients (37.5%) with T3 or T4 disease and 4 (50%) with N2 or N3 disease. The median radiation dose was 46 GyRBE (range, 27-70) and median dose per fraction was 2.4 GyRBE (range, 2.0-6.0) with the most common dose fractionation being 44 or 48 GyRBE in 20 fractions (n = 4). At a median follow-up of 40.1 months (range, 1.6-62.4) the 1 and 3 year OS rates were 85.7% and 35.7%, respectively. The median PFS was 25.40 months (95% CI, 2.53-58.70) while PFS at 1 year and 3 years was 85.7% and 35.7%, respectively. LRFS was 100% at 1 year and 85.7% at 3 years. Five of the 8 patients developed distant metastases, of which 3 received immunotherapy. Acute G2+ and G3+ toxicities occurred in 5 of 8 patients and 2 of 8 patients, respectively. G3 toxicities included radiation dermatitis (n = 1) and immunotherapy-related rash (n = 1). No G4+ toxicities were reported. Conclusion: Single modality PBT for HN melanomas in the definitive setting provides effective and durable local control rates with tolerable acute toxicity. Distant failure remains the primary pattern of failure.

(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.

BackgroundCurrent prostate cancer evaluation can be inaccurate and burdensome. To help non-invasive prostate tumor assessment, recent algorithms applied to spatially registered multi-parametric (SRMP) MRI extracted novel clinically relevant metrics, namely the tumor’s eccentricity (shape), signal-to-clutter ratio (SCR), and volume.PurposeConduct a pilot study to predict the risk of developing clinically significant prostate cancer using nomograms and employing Decision Curves Analysis (DCA) from the SRMP MRI-based features to help clinicians non-invasively manage prostate cancer.MethodsThis study retrospectively analyzed 25 prostate cancer patients. MP-MRI (T1, T2, diffusion, dynamic contrast-enhanced) were resized, translated, and stitched to form SRMP MRI. Target detection algorithm [adaptive cosine estimator (ACE)] applied to SRMP MRI determines tumor’s eccentricity, noise reduced SCR (by regularizing or eliminating principal components (PC) from the covariance matrix), and volume. Pathology assessed wholemount prostatectomy for Gleason score (GS). Tumors with GS >=4+3 (0.70) for ROC curves and p-values (

Background and purpose: Coronary calcifications are associated with coronary artery disease in patients undergoing radiotherapy (RT) for non-small cell lung cancer (NSCLC). We quantified calcifications in the coronary arteries and aorta and investigated their relationship with overall survival (OS) in patients treated with definitive RT (Def-RT) or post-operative RT (PORT). Materials and methods: We analyzed 263 NSCLC patients treated from 2004 to 2017. Calcium burden was ascertained with a Hounsfield unit (HU) cutoff of > 130 in addition to a deep learning (DL) plaque estimator. The HU cutoff volumes were defined for coronary arteries (PlaqueCoro) and coronary arteries and aorta combined (PlaqueCoro+Ao), while the DL estimator ranged from 0 (no plaque) to 3 (high plaque). Patient and treatment characteristics were explored for association with OS. Results: The median PlaqueCoro and PlaqueCoro+Ao was 0.75 cm3 and 0.87 cm3 in the Def-RT group and 0.03 cm3 and 0.52 cm3 in the PORT group. The median DL estimator was 2 in both cohorts. In Def-RT, large PlaqueCoro (HR:1.11 (95%CI:1.04–1.19); p = 0.008), and PlaqueCoro+Ao (HR:1.06 (95%CI:1.02–1.11); p = 0.03), and poor Karnofsky Performance Status (HR: 0.97 (95%CI: 0.94–0.99); p = 0.03) were associated with worse OS. No relationship was identified between the plaque volumes and OS in PORT, or between the DL plaque estimator and OS in either Def-RT or PORT. Conclusions: Coronary artery calcification assessed from RT planning CT scans was significantly associated with OS in patients who underwent Def-RT for NSCLC. This HU thresholding method can be straightforwardly implemented such that the role of calcifications can be further explored.

BackgroundEvaluating and displaying prostate cancer through non-invasive imagery such as Multi-Parametric MRI (MP-MRI) bolsters management of patients. Recent research quantitatively applied supervised target algorithms using vectoral tumor signatures to spatially registered T1, T2, Diffusion, and Dynamic Contrast Enhancement images. This is the first study to apply the Reed-Xiaoli (RX) multi-spectral anomaly detector (unsupervised target detector) to prostate cancer, which searches for voxels that depart from the background normal tissue, and detects aberrant voxels, presumably tumors.MethodsMP-MRI (T1, T2, diffusion, dynamic contrast-enhanced images, or seven components) were prospectively collected from 26 patients and then resized, translated, and stitched to form spatially registered multi-parametric cubes. The covariance matrix (CM) and mean μ were computed from background normal tissue. For RX, noise was reduced for the CM by filtering out principal components (PC), regularization, and elliptical envelope minimization. The RX images were compared to images derived from the threshold Adaptive Cosine Estimator (ACE) and quantitative color analysis. Receiver Operator Characteristic (ROC) curves were used for RX and reference images. To quantitatively assess algorithm performance, the Area Under the Curve (AUC) and the Youden Index (YI) points for the ROC curves were computed.ResultsThe patient average for the AUC and [YI] from ROC curves for RX from filtering 3 and 4 PC was 0.734[0.706] and 0.727[0.703], respectively, relative to the ACE images. The AUC[YI] for RX from modified Regularization was 0.638[0.639], Regularization 0.716[0.690], elliptical envelope minimization 0.544[0.597], and unprocessed CM 0.581[0.608] using the ACE images as Reference Image. The AUC[YI] for RX from filtering 3 and 4 PC was 0.742[0.711] and 0.740[0.708], respectively, relative to the quantitative color images. The AUC[YI] for RX from modified Regularization was 0.643[0.648], Regularization 0.722[0.695], elliptical envelope minimization 0.508[0.605], and unprocessed CM 0.569[0.615] using the color images as Reference Image. All standard errors were less than 0.020.ConclusionsThis first study of spatially registered MP-MRI applied anomaly detection using RX, an unsupervised target detection algorithm for prostate cancer. For RX, filtering out PC and applying Regularization achieved higher AUC and YI using ACE and color images as references than unprocessed CM, modified Regularization, and elliptical envelope minimization.

Abstract Purpose/Objectives Data are conflicting on the effects of time interval from neoadjuvant chemoradiation (NCRT) to surgery for locally advanced non‐small‐cell lung cancer (LA‐NSCLC). This study investigated the impact of surgical timing after NCRT and radiation dose on postoperative mortality and overall survival (OS). Materials and Methods Using the National Cancer Database, we identified 3489 LA‐NSCLC patients treated with NCRT and surgery. Multivariate Cox proportional hazards analysis (MVA) was used to examine the effects of surgery >7 weeks from NCRT completion on OS. Propensity score (PS)‐matched survival analysis for surgery ≤7 and >7 weeks was performed. Postoperative mortality was assessed. Results Median OS for surgery ≤7 weeks and >7 weeks after NCRT were 56.9 versus 45.6 months (hazard ratio, HR 1.18 [1.07–1.30]; p 7 weeks correlated with decreased OS on MVA (HR 1.15 [1.04–1.27]; p = 0.009) and PS matching (HR 1.16 [1.049–1.29]; p = 0.004). Time as a continuous variable correlated with OS on MVA (HR 1.003 [1.001–1.006]; p = 0.0056) and PS matching (HR 1.004 [1.001–1.006]; p = 0.004). Among 2902 lobectomy patients, the mortality rate for surgery ≤66 days was 5.2% versus 8.1% for >66 days (MVA HR 1.59 [1.02–2.49]; p = 0.04). Higher neoadjuvant radiotherapy dose correlated with surgery >7 weeks and lobectomy >66 days on MVA. Conclusions Increased interval >7 weeks from NCRT to surgery for LA‐NSCLC is correlated with worse OS and lobectomy ≤66 days correlated with improved OS. Surgery ≤7weeks may improve tumor control, whereas higher mortality for surgery >66 days may relate to late NCRT manifestations. Neoadjuvant doses of 44–50.4 Gy may minimize risks of radiation‐induced lung injury and surgical complications and facilitate surgery within the optimal 7‐week interval.

Summary: Background: The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality. Methods: In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy). Findings: Of 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41). Interpretation: Among head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic. Funding: National Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

Background: Current prostate cancer evaluation can be inaccurate and burdensome. Quantitative evaluation of Magnetic Resonance Imaging (MRI) sequences non-invasively helps prostate tumor assessment. However, including Dynamic Contrast Enhancement (DCE) in the examined MRI sequence set can add complications, inducing possible side effects from the IV placement or injected contrast material and prolonging scanning time. More accurate quantitative MRI without DCE and artificial intelligence approaches are needed. Purpose: Predict the risk of developing Clinically Significant (Insignificant) prostate cancer CsPCa (CiPCa) and correlate with the International Society of Urologic Pathology (ISUP) grade using processed Signal to Clutter Ratio (SCR) derived from spatially registered bi-parametric MRI (SRBP-MRI) and thereby enhance non-invasive management of prostate cancer. Methods: This pilot study retrospectively analyzed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRI (Apparent Diffusion Coefficient, High B-value, T2) were resized, translated, cropped, and stitched to form spatially registered SRBP-MRI. Efficacy of noise reduction was tested by regularizing, eliminating principal components (PC), and minimizing elliptical volume from the covariance matrix to optimize the SCR. MRI guided biopsy (MRBx), Systematic Biopsy (SysBx), combination (MRBx + SysBx), or radical prostatectomy determined the ISUP grade for each patient. ISUP grade ≥ 2 (Results: High correlation coefficients (R) (>0.55) and high AUC (=1.0) for linear and/or logistic fit from processed SCR and z-score for SRBP-MRI greatly exceed fits using prostate serum antigen, prostate volume, and patient age (R ~ 0.17). Patients assessed with combined MRBx + SysBx and from individual MRI scanners achieved higher R (DR = 0.207+/−0.118) than all patients used in the fits. Conclusions: In the first study, to date, spectral approaches for assessing tumor aggressiveness on SRBP-MRI have been applied and tested and achieved high values of R and exceptional AUC to fit the ISUP grade and CsPCA/CiPCA, respectively.

Abstract Background A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors. Methods Three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system. Results A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body. Conclusion We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB.

Radiotherapy is a common treatment modality in the management of head and neck malignancies. In select clinical scenarios of well-lateralized tumors, radiotherapy can be delivered to the primary tumor or tumor bed and the ipsilateral nodal regions, while intentional irradiation of the contralateral neck is omitted. Proton beam therapy is an advanced radiotherapy modality that allows for the elimination of exit-dose through nontarget tissues such as the oral cavity. This dosimetric advantage is apt for unilateral treatments. By eliminating excess dose to midline and contralateral organs at risk and conforming dose around complex anatomy, proton beam therapy can reduce the risk of iatrogenic toxicities. Currently, there is no level I evidence comparing proton beam therapy to conventional photon radiation modalities for unilateral head and neck cancers. However, a growing body of retrospective and prospective evidence is now available describing the dosimetric and clinical advantages of proton beam therapy. Subsequently, the intent of this clinical review is to summarize the current evidence supporting the use of proton beam therapy in unilateral irradiation of head and neck cancers, including evaluation of disease site-specific evidence, unique challenging clinical scenarios, and ongoing clinical trials.

PurposesTo evaluate the plan quality and robustness of both dose and dose rate of proton pencil beam scanning (PBS) transmission FLASH delivery in lung cancer treatment.Methods and materialsAn in-house FLASH planning platform was used to optimize 10 lung cancer patients previously consecutively treated with proton stereotactic body radiation therapy (SBRT) to receive 3 and 5 transmission beams (Trx-3fds and Trx-5fds, respectively) to 34 Gy in a single fraction. Perturbation scenarios (n=12) for setup and range uncertainties (5 mm and 3.5%) were introduced, and dose-volume histogram and dose-rate-volume histogram bands were generated. Conventional proton SBRT clinical plans were used as a reference. RTOG 0915 dose metrics and 40 Gy/s dose rate coverage (V40Gy/s) were used to assess the dose and dose rate robustness.ResultsTrx-5fds yields a comparable iCTV D2% of 105.3%, whereas Trx-3fds resulted in inferior D2% of 111.9% to the clinical SBRT plans with D2% of 105.6% (p

Purpose/Objective(s): Monte Carlo (MC) dose calculation has appeared in primary commercial treatment-planning systems and various in-house platforms. Dual-energy computed tomography (DECT) and metal artifact reduction (MAR) techniques complement MC capabilities. However, no publications have yet reported how proton therapy centers implement these new technologies, and a national survey is required to determine the feasibility of including MC and companion techniques in cooperative group clinical trials. Materials/Methods: A 9-question survey was designed to query key clinical parameters: scope of MC utilization, validation methods for heterogeneities, clinical site-specific imaging guidance, proton range uncertainties, and how implants are handled. A national survey was distributed to all 29 operational US proton therapy centers on 13 May 2019. Results: We received responses from 25 centers (86% participation). Commercial MC was most commonly used for primary plan optimization (16 centers) or primary dose evaluation (18 centers), while in-house MC was used more frequently for secondary dose evaluation (7 centers). Based on the survey, MC was used infrequently for gastrointestinal, genitourinary, gynecology and extremity compared with other more heterogeneous disease sites (P < .007). Although many centers had published DECT research, only 3/25 centers had implemented DECT clinically, either in the treatment-planning system or to override implant materials. Most centers (64%) treated patients with metal implants on a case-by-case basis, with a variety of methods reported. Twenty-four centers (96%) used MAR images and overrode the surrounding tissue artifacts; however, there was no consensus on how to determine metal dimension, materials density, or stopping powers. Conclusion: The use of MC for primary dose calculation and optimization was prevalent and, therefore, likely feasible for clinical trials. There was consensus to use MAR and override tissues surrounding metals but no consensus about how to use DECT and MAR for human tissues and implants. Development and standardization of these advanced technologies are strongly encouraged for vendors and clinical physicists.

Introduction: High-risk prostate cancer is associated with poorer overall survival (OS) and biochemical control compared to more favorable risk groups. External beam radiation therapy (EBRT) is widely used; however, outcomes data are limited with respect to time elapsed between diagnosis and initiation of EBRT. Methods: The National Cancer Database was queried from 2004 to 2015 for patients diagnosed with high-risk adenocarcinoma of the prostate who received androgen deprivation therapy (ADT) and definitive EBRT. Logistic regression was utilized to determine covariates associated with missing EBRT treatments. OS was analyzed using multivariate cox proportional hazards models and propensity score matching. Results: 9,610 patients met inclusion criteria with median follow-up of 40.6 months and median age of 72 years. Median PSA was 8.7 and median EBRT dose was 78 Gy. ADT was initiated at a median of 36 days and EBRT at a median of 63 days post-diagnosis. Median number of prolonged treatment days was 2.2. Black race (OR: 1.40; p 74 days (HR: 1.20; p = 0.01) and prolonged treatment>3 days of EBRT (HR: 1.26; p = 0.005) were associated with an increased hazard of death. The 5-year OS was 79.6% and 82.9% for patients with prolonged treatment of 3 days or more of EBRT and those missing 3 days or less, respectively (p = 0.0006). Conclusion: In this hypothesis-generating study, prolonged treatment delays and missing three or more EBRT treatments was associated with poorer OS in patients with high-risk adenocarcinoma of the prostate.

Purpose: Spatially fractionated radiation therapy (SFRT), which delivers highly nonuniform dose distributions instead of conventionally practiced homogeneous tumor dose, has shown high rates of clinical response with minimal toxicities in large-volume primary or metastatic malignancies. However, prospective multi-institutional clinical trials in SFRT are lacking, and SFRT techniques and dose parameters remain variable. Agreement on dose prescription, technical administration, and clinical and translational design parameters for SFRT trials is essential to enable broad participation and successful accrual to rigorously test the SFRT approach. We aimed to develop a consensus for the design of multi-institutional clinical trials in SFRT, tailored to specific primary tumor sites, to help facilitate development and enhance the feasibility of such trials. Methods and Materials: Primary tumor sites with sufficient pilot experience in SFRT were identified, and fundamental trial design questions were determined. For each tumor site, a comprehensive consensus effort was established through disease-specific expert panels. Clinical trial design criteria included eligibility, SFRT technology and technique, dose and fractionation, target- and normal-tissue dose parameters, systemic therapies, clinical trial endpoints, and translational science considerations. Iterative appropriateness rank voting, expert panel consensus reviews and discussions, and public comment posting were used for consensus development. Results: Clinical trial criteria were developed for head and neck cancer and soft-tissue sarcoma. Final consensus among the 22 trial design categories each (a total of 163 criteria) was high to moderate overall. Uniform patient cohorts of advanced bulky disease, standardization of SFRT technologies and dosimetry and physics parameters, and collection of translational correlates were considered essential to trial design. Final guideline recommendations and the degree of agreement are presented and discussed. Conclusions: This consensus provides design guidelines for the development of prospective multi-institutional clinical trials testing SFRT in advanced head and neck cancer and soft-tissue sarcoma through in-advance harmonization of the fundamental clinical trial design among SFRT experts, potential investigators, and the SFRT community.

Purpose: Phantosmia, an underreported toxicity of brain radiation therapy (RT), is defined as an olfactory disorder resulting in a malodorous phantom smell. This study aimed to characterize the incidence of phantosmia in patients treated with intensity modulated proton therapy (IMPT). Methods and Materials: In this institutional review board–approved retrospective study, the electronic medical record of a pencil beam scanning-only proton center was queried for patients ≤39 years of age who received IMPT for primary intracranial, metastatic intracranial, skull base, nasopharyngeal or sinonasal neoplasms between August 2019 and December 2020. Patient, clinical, and phantosmia-related characteristics were collected. The olfactory region was defined to include the olfactory bulb and tract. Phantosmia severity was graded by intervention use (mild, no intervention; moderate, supportive treatment; severe, RT discontinuation). Results: Ninety-nine patients met the inclusion criteria. Twelve patients (12.1%) reported phantosmia. Patients described perceiving a “chlorine,” “broccoli,” “stale water,” “metallic,” or “noxious” smell. Of the patients who reported phantosmia, median age was 17 (12-33) years, 66.7% were male, and 91.7% had intracranial tumors. None of the patients had prior RT. Chemoradiotherapy treatment did not correlate with phantosmia development (odds ratio, 1.09; 95% confidence interval, 0.32-3.70; P = .90). Ten patients experienced accompanying toxicities, including taste changes (n = 3), vision disturbances (n = 5), and nausea/emesis (n = 7). Phantosmia was mild (n = 7) or moderate (n = 5). All patients completed their RT course. Sixty-seven percent received craniospinal irradiation (CSI) while 33% received focal brain RT, with the olfactory region receiving doses as low as 0.5 Gy. Notably, 8 of 27 patients who received CSI (30%) reported phantosmia (odds ratio, 7.66; 95% confidence interval, 2.07-28.34; P = .002). Conclusions: In the first-ever study examining radiation-induced phantosmia among children and young adults treated with IMPT, all affected patients received irradiation dose to the olfactory region. Physician awareness of phantosmia, especially in the context of CSI, may improve the patient experience and treatment compliance. A prospective study is needed to elucidate frequency, severity, and phantosmia mechanism.

Introduction: To date, no studies examining the effect of treatment interruptions (TI) with proton beam therapy (PBT) have been published. The goal of our study was to determine the predictors of TI amongst patients with prostate cancer (PCa) treated with PBT and to determine whether TI are associated with biochemical failure (BF). We hypothesized that any correlation between TI and biochemical control would be more pronounced in high risk groups. Methods: Data for 4278 patients with PCa was obtained from the prospectively collected Proton Collaborative Group (PCG) data registry. Univariate and multivariate logistic regression analysis (MVA) was used to model possible predictors of BF. A subset analysis was performed for high risk patients treated with ADT and PBT. Finally, propensity score (PS) analysis was performed to account for any indication bias caused by lack of randomization. Results: Total treatment duration (OR, 1.05 [1.04–1.06]; p

Purpose: The novel coronavirus (COVID-19) forced radiation oncology clinics to overhaul operational policies, but the effect on employee safety has not, to our knowledge, been reported. The New York Proton Center (NYPC), a large freestanding clinic in New York City, New York, presents a 1-month experience of employee-reported health outcomes after the infiltration of COVID-19 and enforcement of policies designed to mitigate its impact. Materials and Methods: In March 2020, new operational policies were implemented, including rigorous and frequent sanitation, visitor and treatment restrictions, distribution of personal protective equipment, work-from-home orders, and isolated nursing and radiation therapy teams. Employees of NYPC were prospectively monitored for exposure and symptoms of COVID-19. Work hours lost because of illness or quarantines were quantified from March 1, 2020, to March 31, 2020. Results: Among 95 total employees, 23 (24%) were quarantined because of symptoms (n = 15; 65%), high-risk exposure (n = 5; 22%), or self-quarantined with personal concern (n = 3; 13%). Of 44 full-time, on-site employees, 39% (n = 17, including 6 therapists and 5 nurses) missed significant work time, including 6 (14%) with confirmed COVID-19. At full capacity, NYPC would have used 7260 work hours during March 2020 from the full-time, on-site staff, which was reduced by 18.8% overall (25.2% of nursing and 13.3% of therapy work hours), all in the latter half of the month. Among the therapist lost work hours, 92% were from 2 of 7 distinct, isolated therapy teams (29%). Without isolation, the exposure was modeled to have been 100%. Conclusion: Despite losing significant staff hours in our department because of COVID- 19, early and aggressive adoption of current, recommended policy guidelines outlined in this manuscript allowed NYPC to continue patient operations at full capacity.

Abstract Introduction Durvalumab after concurrent chemoradiation (cCRT) is now standard of care for unresected stage III non–small cell lung cancer (NSCLC). However, there is limited data on radiation pneumonitis (RP) with this regimen. Therefore, we assessed RP and evaluated previously validated toxicity models in predicting for RP in patients treated with cCRT and durvalumab. Methods Patients treated with cCRT and ≥ 1 dose of durvalumab were evaluated to identify cases of ≥ grade 2 RP. The validity of previously published RP models was assessed in this cohort as well a reference cohort treated with cCRT alone. The timing and incidence of RP was compared between cohorts. Results In total, 11 (18%) of the 62 patients who received cCRT and durvalumab developed ≥ grade 2 RP a median of 3.4 months after cCRT. The onset of RP among patients treated with cCRT and durvalumab was significantly longer vs the reference cohort (3.4 vs 2.1 months; P = .01). Numerically more patients treated with cCRT and durvalumab developed RP than patients in the reference cohort (18% vs 9%, P = .09). Among patients treated with cCRT and durvalumab, 82% (n = 9) were responsive to treatment with high‐dose glucocorticoids. Previously published RP models widely underestimated the rate of RP in patients treated with cCRT and durvalumab [AUC ~ 0.50; p(Hosmer‐Lemeshow): 0.98‐1.00]. Conclusions Our data suggest a delayed onset of RP in patients treated with cCRT and durvalumab vs cCRT alone, and for RP to develop in a greater number of patients treated with cCRT and durvalumab. Previously published RP models significantly underestimate the rate of symptomatic RP among patients treated with cCRT and durvalumab.

Background and Purpose: Radiation esophagitis is a clinically important toxicity seen with treatment for locally-advanced non-small cell lung cancer. There is considerable disagreement among prior studies in identifying predictors of radiation esophagitis. We apply machine learning algorithms to identify factors contributing to the development of radiation esophagitis to uncover previously unidentified criteria and more robust dosimetric factors. Materials and Methods: We used machine learning approaches to identify predictors of grade ≥ 3 radiation esophagitis in a cohort of 202 consecutive locally-advanced non-small cell lung cancer patients treated with definitive chemoradiation from 2008 to 2016. We evaluated 35 clinical features per patient grouped into risk factors, comorbidities, imaging, stage, histology, radiotherapy, chemotherapy and dosimetry. Univariate and multivariate analyses were performed using a panel of 11 machine learning algorithms combined with predictive power assessments. Results: All patients were treated to a median dose of 66.6 Gy at 1.8 Gy per fraction using photon (89.6%) and proton (10.4%) beam therapy, most often with concurrent chemotherapy (86.6%). 11.4% of patients developed grade ≥ 3 radiation esophagitis. On univariate analysis, no individual feature was found to predict radiation esophagitis (AUC range 0.45–0.55, p ≥ 0.07). In multivariate analysis, all machine learning algorithms exhibited poor predictive performance (AUC range 0.46–0.56, p ≥ 0.07). Conclusions: Contemporary machine learning algorithms applied to our modern, relatively large institutional cohort could not identify any reliable predictors of grade ≥ 3 radiation esophagitis. Additional patients are needed, and novel patient-specific and treatment characteristics should be investigated to develop clinically meaningful methods to mitigate this survival altering toxicity. Keywords: Radiation esophagitis, Machine learning, Non-small cell lung cancer, Chemoradiation, Radiation-induced toxicity, Intensity-modulated radiation therapy, Proton beam therapy

It has been well documented from the early days of the 2019 novel coronavirus (COVID19) pandemic that patients with a diagnosis of cancer are not only at higher risks of contracting a COVID-19 infection but also at higher risks of suffering severe, and possibly fatal, outcomes from the infection. Given that the United States has the greatest number of positive coronavirus cases, it is likely that many, if not all, radiation oncology clinics will be faced with the challenge of safely balancing a patient‘s risk of contracting COVID-19, while under active radiation treatment, against their risk of cancer progression if treatment is delayed. To address this challenge, the New York Proton Center established an internal algorithm that considers treatment-related, tumor-related, and patient-related characteristics. Despite having suffered staff shortages due to illness, this algorithm has allowed the center to maintain patient treatment volumes while keeping the rate of COVID-19 infection low.

PurposeThis work aims to study the dose and ultra-high-dose rate characteristics of transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) for hypofractionation liver cancer based on the parameters of a commercially available proton system operating under FLASH mode.Methods and MaterialsAn in-house treatment planning software (TPS) was developed to perform intensity-modulated proton therapy (IMPT) FLASH-RT planning. Single-energy transmission proton PBS plans of 4.5 Gy × 15 fractions were optimized for seven consecutive hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the minimum MU/spot chosen between 100 and 400, and minimum spot time (MST) of 2 ms, and 2) the minimum MU/spot of 100, and MST of 0.5 ms, based upon considerations in target uniformities, OAR dose constraints, and OAR FLASH dose rate coverage. Then, the 3D average dose rate distribution was calculated. The dose metrics for the mean dose of Liver-GTV and other major OARs were characterized to evaluate the dose quality for the different combinations of field numbers and minimum spot times compared to that of conventional IMPT plans. Dose rate quality was evaluated using 40 Gy/s volume coverage (V40Gy/s).ResultsAll plans achieved favorable and comparable target uniformities, and target uniformity improved as the number of fields increased. For OARs, no significant dose differences were observed between plans of different field numbers and the same MST. For plans using shorter MST and the same field numbers, better sparing was generally observed in most OARs and was statistically significant for the chest wall. However, the FLASH dose rate coverage V40Gy/s was increased by 20% for 2-field plans compared to 5-field plans in most OARs with 2-ms MST, which was less evident in the 0.5-ms cases. For 2-field plans, dose metrics and V40Gy/s of select OARs have large variations due to the beam angle selection and variable distances to the targets. The transmission plans generally yielded inferior dosimetric quality to the conventional IMPT plans.ConclusionThis is the first attempt to assess liver FLASH treatment planning and demonstrates that it is challenging for hypofractionation with smaller fractional doses (4.5 Gy/fraction). Using fewer fields can allow higher minimum MU/spot, resulting in higher OAR FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can result in better plan quality and comparable or even better FLASH dose rate coverage.

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC.

Introduction: Given the concern for cardiopulmonary toxicity in patients with NSCLC undergoing postoperative radiation therapy (PORT), the purpose of this study was to evaluate the association between heart dose and overall survival (OS) in patients undergoing PORT with modern techniques. Methods: This is a retrospective study of consecutive patients with NSCLC treated with PORT between May 2004 and January 2017. Clinical records were reviewed and radiation dose distributions were analyzed for association with OS. Results: A total of 284 patients were analyzed. At the time of surgery, most patients had pathologic American Joint Committee on Cancer seventh edition stage III disease (91.2 %) and received either preoperative or adjuvant chemotherapy (92.3 %). Most patients underwent a lobectomy (81.3 %) and had R0 (80.6 %) or R1 (19.4 %) resection. PORT was delivered with a median radiation dose of 54 Gy, and 70.4 % of patients were treated with intensity-modulated radiation therapy. Dosimetric variables across a large range of doses to the heart were highly significant (p < 0.05) for OS. The volume of the heart receiving 8 Gy (HV8) was the most significant dosimetric variable (p < 0.001), and the median HV8 was 35.5 %. The median OS was 33.2 versus 53.6 months (p < 0.005) for patients with HV8 above or below 35.5 %, respectively. On multivariable analysis accounting for other potential prognostic confounders, HV8 remained highly significant (p < 0.001). Conclusions: The data reveal a strong correlation between increasing heart dose and OS in patients with NSCLC undergoing PORT. Taken together with the recently presented LungART trial, lowering heart dose in PORT patients may help to decrease the risk of morbidity and mortality and improve the therapeutic ratio of PORT.

Purpose: To report the outcomes of sinonasal tumors treated with proton beam therapy (PBT) on the Proton Collaborative Group registry study. Methods and Materials: Sixty-nine patients with sinonasal tumors underwent curative intent PBT between 2010 and 2016. Patients who received de novo irradiation (42 patients) were analyzed separately from those who received reirradiation (27 patients) (re-RT). Median age was 53.1 years (range, 15.7-82.1; de novo) and 57.4 years (range, 31.3-88.0; re-RT). The most common histology was squamous cell carcinoma in both groups. Median PBT dose was 58.5 Gy (RBE) (range, 12-78.3; de novo) and 60.0 Gy (RBE) (range 18.2-72.3; re-RT), and median dose per fraction was 2.0 Gy (RBE) for both cohorts. Survival estimates for patients who received de novo irradiation and those who received re-RT were calculated using the Kaplan-Meier method. Results: Median follow-up for surviving patients was 26.4 months (range, 3.5-220.5). The 3-year overall survival (OS), freedom from distant metastasis, freedom from disease progression, and freedom from locoregional recurrence (FFLR) for de novo irradiation were 100%, 84.0%, 77.3%, and 92.9%, respectively. With re-RT, the 3-year OS, freedom from distant metastasis, FFDP, and FFLR were 76.2%, 47.4%, 32.1%, and 33.8%, respectively. In addition, 12 patients (17.4%) experienced recurrent disease. Re-RT was associated with inferior FFLR (P = .04). On univariate analysis, squamous cell carcinoma was associated with inferior OS (P

Purpose: The emergence of the coronavirus disease (COVID-19) global pandemic has led to a significant shift in the delivery of health care, including an explosive growth of telemedicine services. This reverberated in the field of radiation oncology, with a recent American Society for Radiation Oncology (ASTRO) nationwide survey reporting 89% of surveyed clinics began to offer telemedicine programs to patients because of the pandemic. However, this survey did not study the perceptions and experiences of those clinicians delivering telemedicine services. Methods and Materials: We investigated through a national physician survey the merits and limitations of radiation oncology tele-consultations. An anonymous web-based survey was distributed using SurveyMonkey (www.surveymonkey.com) via email. Results: Seventy six respondents (16.1% overall response rate) completed the survey, with broad representation from both academic and community-based practices. Many respondents agreed that transitioning to tele-consultations was a needed step given the emergence of the pandemic, despite most having never previously offered this service. Despite many radiation oncologists having little prior experience with tele-consultations, a majority were satisfied in being able to explain the details of a medical diagnosis, provide results of imaging and bloodwork, and discuss recommendations around radiation treatments through this format. Nearly half of the respondents agreed that tele-consultations felt impersonal, with the inability to complete physical examinations noted as a contributor to the impersonality. Nevertheless, respondents still agreed that telemedicine will play an important role going forward, and almost 90% agreed that they would offer tele-consultations even after the pandemic has resolved.

Abstract Background Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed. Methods PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (n = 3), lung (n = 5), genitourinary (n = 4), and melanoma (n = 8) malignancies treated with ICIs were evaluated. The reference willingness-to-pay (WTP) threshold was $100,000/QALY. Results Nivolumab was not cost-effective over chemotherapy for recurrent/metastatic head/neck cancers (HNCs). For non-small cell lung cancer (NSCLC), nivolumab was not cost-effective for a general cohort, but increased PD-L1 cutoffs resulted in CE. Pembrolizumab was cost-effective for both previously treated and newly-diagnosed metastatic NSCLC. For genitourinary cancers (GUCs, renal cell and bladder cancers), nivolumab and pembrolizumab were not cost-effective options. Regarding metastatic/unresected melanoma, ipilimumab monotherapy is less cost-effective than nivolumab, nivolumab/ipilimumab, and pembrolizumab. The addition of ipilimumab to nivolumab monotherapy was not adequately cost-effective. Pembrolizumab or nivolumab monotherapy offered comparable CE profiles. Conclusions With limited data and from the reference WTP, nivolumab was not cost-effective for HNCs. Pembrolizumab was cost-effective for NSCLC; although not the case for nivolumab, applying PD-L1 cutoffs resulted in adequate CE. Most data for nivolumab and pembrolizumab in GUCs did not point towards adequate CE. Contrary to ipilimumab, either nivolumab or pembrolizumab is cost-effective for melanoma. Despite these conclusions, it cannot be overstated that careful patient selection is critical for CE. Future publication of CE investigations and clinical trials (along with longer follow-up of existing data) could substantially alter conclusions from this analysis.

Abstract Older patients are at increased risk of toxicities from aggressive oncologic therapy and of nononcologic death. A meta‐analysis of non‐nasopharyngeal head and neck cancers showed no statistical benefit in adding chemotherapy to radiotherapy (RT) in older patients; another meta‐analysis of RT versus chemoradiotherapy (CRT) in NPC found advantages to CRT, but vastly under‐represented patients ≥70 years old. This is the largest study to date evaluating outcomes of CRT versus RT alone in this population. The National Cancer Data Base (NCDB) was queried for primary nasopharyngeal cancer cases (2004–2013) in patients ≥70 years old receiving RT alone or CRT. Patients with unknown RT/chemotherapy and T1N0 or M1 disease were excluded. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan–Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. In total, 930 patients were analyzed (n = 713 (77%) CRT, n = 217 (23%) RT). Groups were relatively balanced; CRT was less frequently delivered in patients with advancing age, lower nodal burden, and females (P

Purpose: Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. Methods and materials: We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. Results: Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. Conclusions: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

Lung cancer remains the leading cause of cancer deaths in the United States (US) and worldwide. Radiation therapy is a mainstay in the treatment of locally advanced non-small cell lung cancer (NSCLC) and serves as an excellent alternative for early stage patients who are medically inoperable or who decline surgery. Proton therapy has been shown to offer a significant dosimetric advantage in NSCLC patients over photon therapy, with a decrease in dose to vital organs at risk (OARs) including the heart, lungs and esophagus. This in turn, can lead to a decrease in acute and late toxicities in a population already predisposed to lung and cardiac injury. Here, we present a review on proton treatment techniques, studies, clinical outcomes and toxicities associated with treating both early stage and locally advanced NSCLC.

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with close to half of all patients presenting with metastatic disease. A proportion of these patients with limited metastatic disease, termed oligometastatic disease, have been shown to benefit from a definitive treatment approach. Synchronous and metachronous presentation of oligometastatic disease have prognostic significance, with current belief that metachronous disease is more favorable. Surgical excision of intracranial and extracranial oligometastatic disease has been shown to improve survival, especially in patients with lymph node-negative disease, adenocarcinoma histology and smaller thoracic tumors. Definitive radiation to sites of oligometastatic disease and initial thoracic disease has also been shown to have a similar impact on survival for both intracranial and extracranial disease. Recent studies have reported on the use of targeted agents combined with ablative doses of radiation in the oligometastatic setting with promising outcomes. In this review, we present the historical and current literature describing surgical and radiation treatment options for patients with oligometastatic NSCLC.

Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties.

Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

This review article provides a systematic overview of the currently available evidence on the clinical effectiveness of particle therapy for the treatment of NSCLC and summarizes findings of in silico comparative planning studies. Furthermore, technical issues and dosimetric uncertainties with respect to thoracic particle therapy are discussed.