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PURPOSE: CT Hounsfield Units (HUs) are converted to electron density using a calibration curve obtained from physical measurements of an electron density phantom. HU values assigned to an MRI-derived synthetic computed tomography (sCT) may present a different relationship with electron density compared to CT HU. Correct assignment of sCT HU values is critical for accurate dose calculation and delivery. The goals of this work were to develop a sCT calibration curve using patient data acquired on a clinically commissioned CT scanner and assess for CyberKnife- and volumetric modulated arc therapy (VMAT)-based MR-only treatment planning of prostate SBRT. METHODS: Same-day CT and MRI simulation in the treatment position were performed on 10 patients treated with SBRT to the prostate. Dixon in-phase and out-of-phase MRIs were acquired on a 3T scanner using a 3D T1-weighted gradient-echo sequence to generate sCTs using a commercial sCT algorithm. CT and sCT datasets were co-registered and HU values compared using mean absolute error (MAE). An optimized HU-to-density calibration curve was created based on average HU values across an institutional patient database for each of the four sCT tissue types. Clinical CyberKnife and VMAT treatment plans were generated on each patient CT and recomputed onto corresponding sCTs. Dose distributions computed using CT and sCT were compared using gamma criteria and dose-volume-histograms. RESULTS: For the optimized calibration curve, HU values were -96, 37, 204, and 1170 and relative electron densities were 0.95, 1.04, 1.1, and 1.7 for adipose, soft tissue, inner bone, and outer bone, respectively. The proposed sCT protocol produced total MAE of 94 ± 20HU. Gamma values mean ± std (min-max) were 98.9% ± 0.9% (97.1%-100%) and 97.7% ± 1.3% (95.3%-99.3%) for VMAT and CyberKnife plans, respectively. CONCLUSION: MRI-derived sCT using the proposed approach shows excellent dosimetric agreement with conventional CT simulation, demonstrating the feasibility of MRI-derived sCT for prostate SBRT treatment planning.

PURPOSE: Having dedicated MRI scanners within radiation oncology departments may present unexpected challenges since radiation oncologists and radiation therapists are generally not trained in this modality and there are potential patient safety concerns. This study retrospectively reviews the incidental findings and safety events that were observed at a single institution during introduction of MRI sim for head and neck radiotherapy planning. METHODS: Consecutive patients from March 1, 2020, to May 31, 2022, who were scheduled for MRI sim after having completed CT simulation for head and neck radiotherapy were included for analysis. Patients first underwent a CT simulation with a thermoplastic mask and in most cases with an intraoral stent. The same setup was then reproduced in the MRI simulator. Safety events were instances where scheduled MRI sims were not completed due to the MRI technologist identifying MRI-incompatible devices or objects at the time of sim. Incidental findings were identified during weekly quality assurance rounds as a joint enterprise of head and neck radiation oncology and neuroradiology. Categorical variables between completed and not completed MRI sims were compared using the Chi-Square test and continuous variables were compared using the Mann-Whitney U test with a p-value of

BACKGROUND: Magnetic resonance image only (MRI-only) simulation for head and neck (H&N) radiotherapy (RT) could allow for single-image modality planning with excellent soft tissue contrast. In the MRI-only simulation workflow, synthetic computed tomography (sCT) is generated from MRI to provide electron density information for dose calculation. Bone/air regions produce little MRI signal which could lead to electron density misclassification in sCT. Establishing the dosimetric impact of this error could inform quality assurance (QA) procedures using MRI-only RT planning or compensatory methods for accurate dosimetric calculation. PURPOSE: The aim of this study was to investigate if Hounsfield unit (HU) voxel misassignments from sCT images result in dosimetric errors in clinical treatment plans. METHODS: Fourteen H&N cancer patients undergoing same-day CT and 3T MRI simulation were retrospectively identified. MRI was deformed to the CT using multimodal deformable image registration. sCTs were generated from T1w DIXON MRIs using a commercially available deep learning-based generator (MRIplanner, Spectronic Medical AB, Helsingborg, Sweden). Tissue voxel assignment was quantified by creating a CT-derived HU threshold contour. CT/sCT HU differences for anatomical/target contours and tissue classification regions including air (500 HU) were quantified. t-test was used to determine if sCT/CT HU differences were significant. The frequency of structures that had a HU difference > 80 HU (the CT window-width setting for intra-cranial structures) was computed to establish structure classification accuracy. Clinical intensity modulated radiation therapy (IMRT) treatment plans created on CT were retrospectively recalculated on sCT images and compared using the gamma metric. RESULTS: The mean ratio of sCT HUs relative to CT for air, adipose tissue, soft tissue, spongy and cortical bone were 1.7 ± 0.3, 1.1 ± 0.1, 1.0 ± 0.1, 0.9 ± 0.1 and 0.8 ± 0.1 (value of 1 indicates perfect agreement). T-tests (significance set at t = 0.05) identified differences in HU values for air, spongy and cortical bone in sCT images compared to CT. The structures with sCT/CT HU differences > 80 HU of note were the left and right (L/R) cochlea and mandible (>79% of the tested cohort), the oral cavity (for 57% of the tested cohort), the epiglottis (for 43% of the tested cohort) and the L/R TM joints (occurring > 29% of the cohort). In the case of the cochlea and TM joints, these structures contain dense bone/air interfaces. In the case of the oral cavity and mandible, these structures suffer the additional challenge of being positionally altered in CT versus MRI simulation (due to a non-MR safe immobilizing bite block requiring absence of bite block in MR). Finally, the epiglottis HU assignment suffers from its small size and unstable positionality. Plans recalculated on sCT yielded global/local gamma pass rates of 95.5% ± 2% (3 mm, 3%) and 92.7% ± 2.1% (2 mm, 2%). The largest mean differences in D95, Dmean , D50 dose volume histogram (DVH) metrics for organ-at-risk (OAR) and planning tumor volumes (PTVs) were 2.3% ± 3.0% and 0.7% ± 1.9% respectively. CONCLUSIONS: In this cohort, HU differences of CT and sCT were observed but did not translate into a reduction in gamma pass rates or differences in average PTV/OAR dose metrics greater than 3%. For sites such as the H&N where there are many tissue interfaces we did not observe large scale dose deviations but further studies using larger retrospective cohorts are merited to establish the variation in sCT dosimetric accuracy which could help to inform QA limits on clinical sCT usage.

Purpose: The purpose of this meta-analytic study was to identify clinical characteristics, defined as child factors that can be assessed by a speech-language pathologist as part of a routine speech-language evaluation that may differentiate children who persist in stuttering from children who eventually recover from stuttering. Clinical characteristics explored included sex, age at onset, family history of stuttering, stuttering frequency and severity, speech-language skills, and temperament. Method: Studies were identified through electronic databases, journals, and reference lists of relevant reports (e.g., research articles). Eligible studies followed young children who stutter (i.e., under 6 years old) for at least 24 months, assessed a potential clinical marker at study entry, and determined talker group classification (i.e., persistent or recovered) at study completion. Sex and family history differences were estimated using risk ratios; all other differences were estimated using Hedges's "g." Heterogeneity and methodological differences among studies were evaluated. Results: Eleven studies (41 reports) met eligibility criteria. Persistent children were older at stuttering onset and exhibited higher frequencies of stuttering-like disfluencies, lower speech sound accuracy, and lower expressive and receptive language skills than recovered children. Males and children with a family history of stuttering were also more likely to persist. Conclusions: Clinical characteristics were identified that are associated with increased risk for stuttering persistence. Future studies have the potential to translate these clinical characteristics into prognostic markers for stuttering persistence risk.

BackgroundTrimodality therapy (TMT) with preoperative chemoradiation followed by surgical resection is used for locally-advanced non-small-cell lung cancer (LA-NSCLC). Traditionally, preoperative radiation doses ≤54 Gy are used due to concerns regarding excess morbidity, but little is known about outcomes and toxicities after TMT with intensity-modulated radiotherapy (IMRT) to higher doses.MethodsA retrospective analysis of patients who received planned TMT with IMRT for LA-NSCLC at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2008 and 2017 was performed. Clinical and treatment characteristics, pathologic response, and surgical toxicity were assessed. Kaplan-Meier method and log-rank test was used for survival outcomes. Cox proportional-hazards regression was used for multivariable analysis.ResultsForty-six patients received less than definitive doses of 7 days were associated with OS.ConclusionsWith IMRT, there was no increased rate of surgical complications in patients receiving higher doses of radiation. Survival outcomes or LOS did not differ based on radiation dose, but increased LOS was associated with worse OS. Larger prospective studies are needed to further examine outcomes after IMRT in patients with LA-NSCLC receiving TMT.

BackgroundA significant proportion of patients with advanced cancer undergo palliative radiotherapy (RT) within their last 30 days of life. This study characterizes palliative RT at our institution and aims to identify patients who may experience limited benefit from RT due to imminent mortality.MethodsFive hundred and-eighteen patients treated with external beam RT to a site of metastatic disease between 2012 and 2016 were included. Mann-Whitney U and chi-squared tests were used to identify factors associated with RT within 30 days of death (D30RT).ResultsMedian age at RT was 63 years (IQR 54-71). Median time from RT to death was 74 days (IQR 33-174). One hundred and twenty-five patients (24%) died within 30 days of RT. D30RT was associated with older age at RT (64 vs. 62 years, p = 0.04), shorter interval since diagnosis (14 vs. 31 months, p

Although the role of cancer-activated stroma in malignant progression has been well investigated, the influence of an activated stroma in therapy response is not well understood. Using retrospective pilot cohorts, we previously observed that MRI detected stromal contrast enhancement was associated with proximity to the tumor and was predictive for relapse-free survival in patients with breast cancer receiving neoadjuvant chemotherapy. Here, to evaluate the association of stromal contrast enhancement to therapy, we applied an advanced tissue mapping technique to evaluate stromal enhancement patterns within 71 patients enrolled in the I-SPY 1 neoadjuvant breast cancer trial. We correlated MR stromal measurements with stromal protein levels involved in tumor progression processes. We found that stromal percent enhancement values decrease with distance from the tumor edge with the estimated mean change ranging [Formula: see text] to [Formula: see text] ([Formula: see text]) for time points T2 through T4. While not statistically significant, we found a decreasing trend in global stromal signal enhancement ratio values with the use of chemotherapy. There were no statistically significant differences between MR enhancement measurements and stromal protein levels. Findings from this study indicate that stromal features characterized by MRI are impacted by chemotherapy and may have predictive value in a larger study.

BackgroundHead and neck cancer is often managed with a combination of surgery, radiation therapy, and chemotherapy, and skin toxicity is not uncommon. Xanthogranuloma is a pathological finding resulting from an inflammatory reaction that has not been previously reported following head and neck radiation therapy.Case presentationA patient with squamous cell carcinoma of the oropharynx, treated with definitive chemoradiation and hyperthermia, presented at eight-month follow-up with an in-field cutaneous lesion in the low neck, initially concerning for recurrent tumor. Biopsy showed xanthogranuloma and the patient underwent complete resection with congruent surgical pathology. The patient remained free of malignancy but continued to experience wound healing difficulties at the resection site which resolved with specialized wound care and hyperbaric oxygen.ConclusionsSkin toxicity is not uncommon in patients with head and neck cancer treated with radiation therapy. Awareness of unusual pathologic sequelae, such as xanthogranuloma, is needed to provide patient counseling while continuing appropriate surveillance for recurrent malignancy.

Despite the use of systemic therapy and prophylactic cranial irradiation (PCI), outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC) remain poor. Consolidative radiation therapy (RT) to the chest may improve outcomes by improving local control. In a recently completed multi-institutional phase III clinical trial, investigators randomized patients with ES-SCLC and response to chemotherapy to PCI with or without consolidative RT. Two-year overall survival (OS) and 6-month progression-free survival (PFS) were improved with the use of consolidative RT; however, the prognosis for ES-SCLC in the experimental arm was still poor and there was no statistically significantly difference in 1-year OS, the trial's primary endpoint. In this editorial, the results of this trial are discussed and the methods are compared to those used in other trials of consolidative RT in ES-SCLC. More research is needed to identify the optimal RT dose and fractionation and to clarify the role of consolidative RT in ES-SCLC.

Molecular types of the Cryptococcus neoformans/Cryptococcus gattii species complex that infect dogs and cats differ regionally and with host species. Antifungal drug susceptibility can vary with molecular type, but the susceptibility of Cryptococcus isolates from dogs and cats is largely unknown. Cryptococcus isolates from 15 dogs and 27 cats were typed using URA5 restriction fragment length polymorphism analysis (RFLP), PCR fingerprinting, and multilocus sequence typing (MLST). Susceptibility was determined using a microdilution assay (Sensititre YeastOne; Trek Diagnostic Systems). MICs were compared among groups. The 42 isolates studied comprised molecular types VGI (7%), VGIIa (7%), VGIIb (5%), VGIIc (5%), VGIII (38%), VGIV (2%), VNI (33%), and VNII (2%), as determined by URA5 RFLP. The VGIV isolate was more closely related to VGIII according to MLST. All VGIII isolates were from cats. All sequence types identified from veterinary isolates clustered with isolates from humans. VGIII isolates showed considerable genetic diversity compared with other Cryptococcus molecular types and could be divided into two major subgroups. Compared with C. neoformans MICs, C. gattii MICs were lower for flucytosine, and VGIII MICs were lower for flucytosine and itraconazole. For all drugs except itraconazole, C. gattii isolates exhibited a wider range of MICs than C. neoformans. MICs varied with Cryptococcus species and molecular type in dogs and cats, and MICs of VGIII isolates were most variable and may reflect phylogenetic diversity in this group. Because sequence types of dogs and cats reflect those infecting humans, these observations may also have implications for treatment of human cryptococcosis.

Rationale and objectivesThe aim of this work was to compare a high-resolution diffusion-weighted imaging (HR-DWI) acquisition (voxel size = 4.8 mm(3)) to a standard diffusion-weighted imaging (STD-DWI) acquisition (voxel size = 29.3 mm(3)) for monitoring neoadjuvant therapy-induced changes in breast tumors.Materials and methodsNine women with locally advanced breast cancer were imaged with both HR-DWI and STD-DWI before and after 3 weeks (early treatment) of neoadjuvant taxane-based treatment. Tumor apparent diffusion coefficient (ADC) metrics (mean and histogram percentiles) from both DWI methods were calculated, and their relationship to tumor volume change after 12 weeks of treatment (posttreatment) measured by dynamic contrast enhanced magnetic resonance imaging was evaluated with a Spearman's rank correlation.ResultsThe HR-DWI pretreatment 15th percentile tumor ADC (P = .03) and early treatment 15th, 25th, and 50th percentile tumor ADCs (P = .008, .010, .04, respectively) were significantly lower than the corresponding STD-DWI percentile ADCs. The mean tumor HR-ADC was significantly lower than STD-ADC at the early treatment time point (P = .02), but not at the pretreatment time point (P = .07). A significant early treatment increase in tumor ADC was found with both methods (P < .05). Correlations between HR-DWI tumor ADC and posttreatment tumor volume change were higher than the STD-DWI correlations at both time points and the lower percentile ADCs had the strongest correlations.ConclusionThese initial results suggest that the HR-DWI technique has potential for improving characterization of low tumor ADC values over STD-DWI and that HR-DWI may be of value in evaluating tumor change with treatment.