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OBJECTIVES: To determine the feasibility of incorporating a brief animated educational video shown during the radiation therapy (RT) consultation appointment for patients with breast cancer and to collect preliminary quality-of-life data. SAMPLE & SETTING: 20 participants with breast cancer were recruited from an outpatient radiation oncology facility in the southeastern United States. METHODS & VARIABLES: This single-arm, pre- and post-test feasibility study aimed to assess feasibility and preliminary outcomes of patient-reported anxiety, distress, and RT concerns. RESULTS: The video intervention demonstrated feasibility, as evidenced by meeting or exceeding benchmarks set for recruitment, retention, and feasibility measured scores. The difference in means of total patient-reported scores comparing pre- to postintervention decreased. [ABSTRACT FROM AUTHOR]

PURPOSE: To identify the unmet needs of breast cancer survivors after radiation therapy. PARTICIPANTS & SETTING: Patients who received radiation therapy for unilateral breast cancer with six months or longer of follow-up and exhibited no disease progression were eligible for selection to a study conducted at an outpatient radiation therapy academic practice in the southeastern United States. METHODOLOGIC APPROACH: A qualitative descriptive study was undertaken using semistructured interviews, framed by the five domains of the Survivor Unmet Needs Survey and analyzed using an iterative inductive and deductive process. FINDINGS: Of the 24 invited patients, 17 agreed to the interview (including one male patient). Themes emerged from the emotional, relationships, and information needs domains: (a) the struggle with adapting to body image changes; (b) living with the fear of recurrence; (c) the unexpected impact of radiation dermatitis; and (d) the need for education to prepare for radiation therapy. IMPLICATIONS FOR NURSING: Healthcare providers should perform a comprehensive needs assessment for patients with breast cancer receiving radiation therapy. Self-management assessment instruments may address patients' confidence in managing all phases of radiation therapy side effects. [ABSTRACT FROM AUTHOR]

Purpose: To determine patterns of failure, clinical outcomes, and prognostic factors among pediatric patients treated with radiation therapy for parameningeal alveolar rhabdomyosarcoma.Methods and Materials: We evaluated clinical and treatment planning records of patients aged ≤21 years with parameningeal alveolar rhabdomyosarcoma treated with definitive or adjuvant radiation therapy at our institution. The Kaplan-Meier product limit method assessed disease control and survival; the log-rank test was used to evaluate prognostic impact.Results: We identified 24 patients with a median age of 3.5 years (range, 1-20) treated between 2009 and 2016. The median follow-up was 2.4 years for all (range, 0.3-5.6) and 3.2 years for living patients (range, 0.7-5.6). Most patients had group III (96%), node-negative (67%), positive FOX fusion status (63%) disease, and intracranial extension (54%). The paranasal sinus was the most common subsite (29%). All patients were treated with concurrent chemotherapy and proton radiation therapy with a median dose of 50.4 Gy relative biological effectiveness (range, 41.4-59.4) at a median 13 weeks after induction chemotherapy (range, 3-25). The 3-year local control, regional control, disease-free survival, and overall survival rates were 66%, 94%, 40%, and 58%, respectively. Median time to any failure was 0.5 years (range, 0.2-2.1). N1 disease and intracranial extension (ICE) portended inferior overall survival (P = .002 and .02, respectively). Female sex portended better local control (P = .05). All 7 patients with distant metastases as the first site of recurrence had central nervous system metastases. Age <4 years, absence of ICE, N0 disease, and primary tumor <5 cm were associated with a statistically significant improvement in freedom from distant metastases.Conclusions: Although regional nodal failures were rare, in-field local recurrences and leptomeiningeal progression in those with ICE suggest the need for modification of local and central nervous system therapies. [ABSTRACT FROM AUTHOR]

Purpose: For infants with localized rhabdomyosarcoma who were enrolled on Children's Oncology Group ARST0331 and ARST0531, local therapy guidelines were provided, but adherence was not mandated because of toxicity concerns. We examined adherence to protocol for local therapy guidelines, treatment variations, and outcomes for these patients.Methods: Children aged ≤24 months who were enrolled on ARST0331 and ARST0531 were evaluated. Data were verified through radiologic, surgical, pathologic, and clinical records. Local therapy was assessed for adherence to protocol guidelines, with variations termed "individualized local therapy." The subdistribution hazards model assessed local failure, the Kaplan-Meier product limit method assessed event-free survival (EFS) and overall survival, and the log-rank test was used to evaluate prognostic impact.Results: The median age of the patients was 14 months, and 124 patients were eligible. Common primary sites were genitourinary (40%), parameningeal (14%), and the extremities (11%). Most patients had unresected disease (group 3, 64%) and embryonal histology (73%). Fifty-eight percent of patients received radiation therapy at a median of week 12 (weeks 1-45). The median radiation dose was 48.6 Gy (30.6-54 Gy). Forty-three percent of patients received individualized local therapy (outside protocol guidelines), typically omission or delay of radiation therapy. Delayed primary excision was performed in 28% at a median of week 14 (weeks 7-34). With a median follow-up of 5.6 years, the 5-year local failure, EFS, and overall survival rates were 24%, 68%, and 82%, respectively. Local failure was significantly higher (35%) in patients receiving individualized local therapy than in patients who received protocol-specified local therapy (16%; P = .02). The site of failure was local in 64% of patients, local and distant in 5%, and distant only in 23%. EFS was significantly higher among patients who were aged 12 to 24 months, had tumors ≤5 cm, had group 1/2 disease, and underwent protocol-specified therapy.Conclusions: Local recurrence was the predominant pattern of failure and was more common in those receiving individualized local therapy. De-escalation of effective therapies because of concerns about treatment toxicity should be considered cautiously. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the rate of and identify risk factors for vasculopathy after proton therapy in pediatric patients with central nervous system and skull base tumors.Methods and Materials: Between 2006 and 2015, 644 pediatric patients with central nervous system and skull base tumors were treated with proton therapy at a single institution. The 3 most common histologies were craniopharyngioma (n = 135), ependymoma (n = 135), and low-grade glioma (n = 131). The median age was 7.6 years (range, 0.7-21.8 years), and the median prescribed dose was 54 cobalt gray equivalent (CGE) (range, 25.2-75.6 CGE). For this analysis, vasculopathy included asymptomatic vessel narrowing identified on imaging, transient ischemic attacks, and cerebrovascular accidents. Serious vasculopathy was defined as events resulting in permanent neurologic complications or requiring revascularization surgery. Multivariate logistic regression (MVA) was used to assess predictors of toxicity. Variables examined included age, neurofibromatosis, extent of surgical resection, chemotherapy, postoperative stroke, total prescribed dose, and dose delivered to the optic nerves, chiasm, and hypothalamus.Results: With a median follow-up of 3.0 years (range, 0.1-9.6 years), the 3-year cumulative rates of any vasculopathy and serious vasculopathy were 6.4% and 2.6%, respectively. Seven children (1.2%) experienced a stroke with permanent neurologic deficits; 4 required revascularization surgery. On MVA, maximum dose to the optic chiasm ≥ 54 CGE was significantly associated with the development of any vasculopathy (13.1% vs 2.2%; P < .001); age < 5 years was also significant (8.4% vs 5.4%; P < .01). On MVA, maximum dose to the optic chiasm ≥ 54 CGE also predicted serious vasculopathy (3.8% vs 1.7%; P < .05).Conclusions: Childhood cancer survivors are at risk of vasculopathy after cranial radiation therapy. Young children and those receiving ≥54 CGE to the chiasm are at an increased risk of this toxicity. These findings suggest appropriate follow-up and screening are important in this population. [ABSTRACT FROM AUTHOR]

Background: Proton therapy can reduce the low and intermediate radiation dose to uninvolved brain tissue in children with intracranial ependymomas, which may improve functional outcomes and reduce second malignancies in survivors. Accordingly, ependymoma has become the most common pediatric tumor treated with proton therapy, yet data on efficacy and toxicity are limited. Material and methods: Between June 2007 and February 2017, 179 children (≤21 years old) with nonmetastatic grade II/III intracranial ependymoma received proton therapy at our institution. Median age, 3.5 years (range, 0.7-21); 58% were male. Most (66%) tumors were in the posterior fossa and classified as WHO grade III (67%). 27% underwent multiple operations to maximize the extent of resection; ultimately 85% had a gross total or near total tumor resection before radiotherapy. 33% received preradiation chemotherapy. Median radiation dose in children ≤3 years old, 54 Gy(RBE). Most (>90%) children over 3 years old received 59.4 Gy(RBE). Patient and treatment variables were assessed for correlation with disease control. Results: Median follow-up, 3.2 years. 3-year local control, progression-free survival, and overall survival rates were 85%, 76%, and 90%, respectively. First site of progression was local, metastatic, or simultaneous in 14, 17 and 6 patients, respectively. On multivariate analysis, subtotal resection was associated with inferior local control (67% vs. 88%; p≤.01) and progression-free survival (59% vs. 79%; p<.05). Male sex was associated with inferior progression-free (67% vs. 87%; p<.05) and overall survival (84% vs. 99%; p<.01). The 3-year CTCAE grade 2+brainstem toxicity rate was 5.5% (95% CI: 2.9-10.2), including 1 grade 5 toxicity. Conclusions: This series of proton therapy for pediatric intracranial ependymoma demonstrates disease control comparable to photon series without unexpected toxicity. Subtotal resection and male sex were associated with inferior disease control. Additional follow-up to quantify the expected reductions in late toxicity with proton therapy is ongoing. [ABSTRACT FROM AUTHOR]

During the early decades of radiation therapy for breast cancer, local control of disease was documented consistently but, enigmatically, an anticipated impact on breast cancer survival was not observed, leading to confusion in our understanding of the natural history of breast cancer and radiation effects. Now, almost 90 years after its first use in breast cancer, technology developments in diagnostic imaging and radiation therapy have elucidated parts of this enigma. The data now available demonstrate a significant impact of radiation therapy on survival as well as disease control and treatment-related mortality, opening a doorway to understanding the powerful impact of radiation therapy on both breast cancer and critical organs. Efforts are focused on leveraging novel techniques to maximize the benefits of radiation for breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer.Methods and Materials: From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5.Results: Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton-photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed.Conclusion: Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity. Proton therapy simultaneously improves target coverage for the internal mammary nodes and level 2 axilla, which may positively impact long-term survival in breast cancer patients. [ABSTRACT FROM AUTHOR]

Recent advances in pediatric cancer treatment have improved disease control and survival outcomes for childhood cancers survivors, including those treated for primary central nervous system and skull base malignancies. Future research in this population will focus on identifying risk factors for infertility, novel screening techniques and recommendations, and quality-of-life outcomes improvement. The purpose of this review is to define the infertility complications observed in pediatric cancer survivors who receive cranial irradiation for central nervous system and skull base malignancies. [ABSTRACT FROM AUTHOR]

After raccoons were trapped and removed from under a house in New York, the owner and her two Papillon dogs became infested with numerous rat mites ( Ornithonyssus bacoti). Two weeks later, both dogs developed pruritus, progressively severe vesicular lesions, focal areas of skin exfoliation, swelling of the vulva or prepuce, abdominal pain, and behavioral changes. Two months after the mite infestation, the owner was hospitalized because of lethargy, fatigue, uncontrollable panic attacks, depression, headaches, chills, swollen neck lymph nodes, and vesicular lesions at the mite bite sites. Due to ongoing illness, 3 months after the mite infestation, alcohol-stored mites and blood and serum from both dogs and the owner were submitted for Bartonella serology and Bartonella alpha Proteobacteria growth medium (BAPGM) enrichment blood culture/PCR. Bartonella henselae DNA was amplified and sequenced from blood or culture specimens derived from both dogs, the owner, and pooled rat mites. Following repeated treatments with doxycycline, both dogs eventually became B. henselae seronegative and blood culture negative and clinical signs resolved. In contrast, the woman was never B. henselae seroreactive, but was again PCR positive for B. henselae 20 months after the mite infestation, despite prior treatment with doxycycline. Clinicians and vector biologists should consider the possibility that rat mites may play a role in Bartonella spp. transmission. [ABSTRACT FROM AUTHOR]

Background. A single-institution review of long-term outcomes and factors affecting local control (LC) following radiotherapy for non-metastatic medulloblastoma. Material and methods. From 1963 to 2008, 50 children (median age, 7.3 years; range 1.2-18.5) with stage M0 medulloblastoma were treated with radiotherapy; half underwent a gross total resection (no visible residual tumor) or near-total resection (< 1.5 cm3 of gross disease remaining after resection). Median craniospinal dose was 28.8 Gy (range 21.8-38.4 Gy). Median total dose to the posterior fossa was 54.3 Gy (range 42.4-64.8 Gy). Eighteen patients (36%) received chemotherapy as part of multimodality management, including 11 who received concurrent chemotherapy. Results. Median follow-up was 15.7 years (range 0.3-44.4 years) for all patients and 26.6 years (range 7.3-44.4 years) for living patients. The 10-year overall survival, cancer-specific survival, and progression-free survival rates were 65%, 65%, and 69%. The 10-year LC rate was 84% and did not significantly change across eras. Four percent of patients experienced local progression five years after treatment. On univariate analysis, chemotherapy and overall duration of radiotherapy ≤ 45 days were associated with improved LC. Patients receiving chemotherapy had a 10-year 100% LC rate versus 76% in patients not receiving chemotherapy (p = 0.0454). When overall radiotherapy treatment lasted ≤ 45 days, patients experienced a superior 95% 10-year LC rate (vs. 73% in patients treated > 45 days; p = 0.0419). Three patients (6%) died from treatment complications, including radionecrosis/cerebellar degeneration, severe cerebral edema leading to herniation, and secondary malignancy. Conclusions. While we cannot draw definitive conclusions given the retrospective nature of our study, our long-term data suggest that reductions in craniospinal dose and boost target volume to reduce toxicity have not compromised disease control in the modern era. Our data also support analyses that implicate duration of radiotherapy, rather than interval between surgery and radiotherapy, as a factor in LC. Chemotherapy in multimodality management of medulloblastoma may have an underappreciated role in improving LC rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma among infants. The clinical characteristics and biology of RMS among infants are distinct from those of older children with RMS. The management of infants with RMS follows a parallel approach of risk-stratification and treatment with multimodality chemotherapy in combination with surgery and/or radiation. but with a few caveats. Modification of chemotherapy regimens is often needed to reduce the risk of excessive treatment-related morbidity due to developmentally immature organs. Adequate surgical resection is more challenging due to the technical difficulties associated with large tumors arising from critical structures in small-sized patients. Similarly, irradiating developing organs can impair long-term function or form and increase the risk of secondary malignant neoplasms. A few clinical trials conducted by international cooperative groups have addressed the challenges of managing infants with RMS and their outcomes. RMS most commonly presents in children and adolescents, however a subset of tumors are diagnosed in infants under one year of age. Due to the rarity of infant RMS, utilization of different treatment approaches and goals, and small sample sizes, the published studies of infants with RMS have yielded heterogeneous results. In this review, we discuss the outcomes of infants with RMS treated in various clinical trials and the strategies that various international cooperative groups have employed to reduce the morbidity and mortality related to treatment without compromising the overall survival of this population. This review discusses the unique scenarios of diagnosing and managing congenitals or neonatal RMS, spindle cell RMS and relapsed RMS. This review concludes by exploring novel approaches to diagnosis and management of infants with RMS that are currently being studied by various international cooperative groups. [ABSTRACT FROM AUTHOR]

Purpose: Intensity-modulated radiation therapy (IMRT) is a promising treatment modality for patients with head and neck cancer (HNC). The dose distributions from IMRT are static and, thus, are unable to account for variations and/or uncertainties in the relationship between the patient (region being treated) and the beam. Organ motion comprises one such source of this uncertainty, introduced by physiological variation in the position, size, and shape of organs during treatment. In the head and neck, the predominant source of this variation arises from deglutition (swallowing). The purpose of this study was to investigate whether cinematographic MRI (cine MRI) could be used to determine asymmetric (nonuniform) internal margin (IM) components of tumor planning target volumes based on the actual deglutition-induced tumor displacement. Methods: Five head and neck cancer patients were set up in treatment position on a 3 T MRI scanner. Two time series of single-slice, sagittal, cine images were acquired using a 2D FLASH sequence. The first time series was a 12.8 min scan designed to capture the frequency and duration of deglutition in the treatment position. The second time series was a short, 15 s scan designed to capture the displacement of deglutition in the treatment position. Deglutition frequency and mean swallow duration were estimated from the long time series acquisition. Swallowing and resting (nonswallowing) events were identified on the short time series acquisition and displacement was estimated based on contours of gross tumor volume (GTV) generated at each time point of a particular event. A simple linear relationship was derived to estimate 1D asymmetric IMs in the presence of resting- and deglutition-induced displacement. Results: Deglutition was nonperiodic, with frequency and duration ranging from 2.89-24.18 mHz and from 3.86 to 6.10 s, respectively. The deglutition frequency and mean duration were found to vary among patients. Deglutition-induced maximal GTV displacements ranged from 0.00 to 28.36 mm with mean and standard deviation of 4.72±3.18, 3.70±2.81, 2.75±5.24, and 10.40±10.76 mm in the A, P, I, and S directions, respectively. Resting-induced maximal GTV displacement ranged from 0.00 to 5.59 mm with mean and standard deviation of 3.01±1.80, 1.25±1.10, 3.23+2.20, and 2.47±1.11 mm in the A, P, I, and S directions, respectively. For both resting and swallowing states, displacement along the S-I direction dominated displacement along the A-P direction. The calculated IMs were dependent on deglutition frequency, ranging from 3.28-4.37 mm for the lowest deglutition frequency patient to 3.76-6.43 mm for the highest deglutition frequency patient. A statistically significant difference was detected between IMs calculated for P and S directions (p=0.0018). Conclusions: Cine MRI is able to capture tumor motion during deglutition. Swallowing events can be demarcated by MR signal intensity changes caused by anatomy containing fully relaxed spins that move medially into the imaging plane during deglutition. Deglutition is nonperiodic and results in dynamic changes in the tumor position. Deglutition-induced displacements are larger and more variable than resting displacements. The nonzero mean maximum resting displacement indicates that some tumor motion occurs even when the patient is not swallowing. Asymmetric IMs, derived from deglutition frequency, duration, and directional displacement, should be employed to account for tumor motion in HNC RT. [ABSTRACT FROM AUTHOR]

The article discusses the films which have resisted the master of globalization but still managed to break through to audiences globally which include "Ermo," "Goodbye, Lenin," and "Secret Ballot." It notes that the said films have captured the audience's attention by changing the point of view of globalization from global to local through small stories. It cites how the films examine how globalization brought changes that impacted the means and judgments of protagonists and their communities.

We identified the gene carrying the juvenile spermatogonial depletion mutation (jsd), a recessive spermatogenic defect mapped to mouse chromosome 1 (refs. 1,2). We localized jsd to a 272-kb region and resequenced this area to identify the underlying mutation: a frameshift that severely truncates the predicted protein product of a 2.3-kb genomic open reading frame. This gene, Utp14b, evidently arose through reverse transcription of an mRNA from an X-linked gene and integration of the resulting cDNA into an intron of an autosomal gene, whose promoter and 5' untranslated exons are shared with Utp14b. To our knowledge, Utp14b is the first protein-coding retrogene to be linked to a recessive mammalian phenotype. The X-linked progenitor of Utp14b is the mammalian ortholog of yeast Utp14, which encodes a protein required for processing of pre-rRNA and hence for ribosome assembly. Our findings substantiate the hypothesis that mammalian spermatogenesis is supported by autosomal retrogenes that evolved from X-linked housekeeping genes to compensate for silencing of the X chromosome during male meiosis. We find that Utp14b-like retrogenes arose independently and were conserved during evolution in at least four mammalian lineages. This recurrence implies a strong selective pressure, perhaps to enable ribosome assembly in male meiotic cells. [ABSTRACT FROM AUTHOR]

• High conformality of proton therapy doesn't compromise expected favorable outcomes. • Induction chemotherapy with low dose proton therapy is an efficacious treatment. • Majority of serious and permanent side effects could be attributed to chemotherapy. Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG. We enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 – September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5. Median follow-up was 6.2 years (range, 0.9–––15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed. When utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation. [ABSTRACT FROM AUTHOR]

A pediatric normal tissue effects in the clinic (PENTEC) comprehensive review of patients with childhood cancer who received radiation therapy (RT) to the liver was performed to develop models that may inform RT dose constraints for the liver and improve risk forecasting of toxicities. A systematic literature search was performed to identify published data on hepatic toxicities in children. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. Complications from both whole and partial liver irradiation were considered. For whole liver irradiation, total body irradiation and non–total body irradiation treatments were considered, but it was assumed that the entire liver received the prescribed dose. For partial liver irradiation, only Wilms tumor flank field RT could be analyzed. However, a prescribed dose assumption could not be applied, and there was a paucity of analyzable liver dosimetry data. To associate the dose-volume exposures with the partial volume complication data from flank irradiation, liver dose-volume metrics were reconstructed for Wilms tumor flank RT using age-specific computational phantoms as a function of field laterality and superior extent of the field. The literature search identified 2103 investigations pertaining to hepatic sinusoidal obstructive syndrome (SOS) and liver failure in pediatric patients. All abstracts were screened, and 241 articles were reviewed in full by the study team. A model was developed to calculate the risk of developing SOS after whole liver RT. RT dose (P =.006) and receipt of nonalkylating chemotherapy (P =.01) were significant. Age <20 years at time of RT was borderline significant (P =.058). The model predicted a 2% risk of SOS with zero RT dose, 6.1% following 10 Gy, and 14.5% following 20 Gy to the whole liver (modeled as the linear-quadratic equivalent dose in 2-Gy fractions [α/β = 3 Gy]). Patients with Wilms tumor treated with right flank RT had a higher observed rate of SOS than patients receiving left flank RT, but data were insufficient to generate an NTCP model for partial liver irradiation. From the phantom-based dose reconstructions, mean liver dose was estimated to be 2.16 ± 1.15 Gy and 6.54 ± 2.50 Gy for left and right flank RT, respectively, using T10-T11 as the superior field border and a prescription dose of 10.8 Gy (based on dose reconstruction). Data were sparse regarding rates of late liver injury after RT, which suggests low rates of severe toxicity after treatment for common pediatric malignancies. This pediatric normal tissue effects in the clinic (PENTEC) review provides an NTCP model to estimate the risk of hepatic SOS as a function of RT dose following whole liver RT and quantifies the range of mean liver doses from typical Wilms tumor flank irradiation fields. Patients treated with right flank RT had higher rates of SOS than patients treated with left flank RT, but data were insufficient to develop a model for partial liver irradiation. Risk of SOS was estimated to be approximately ≤6% in pediatric patients receiving whole liver doses of <10 Gy. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted on the use of intraoperative radiation therapy (IORT) in the patients of breast cancer, discussing its current states and challenges. It reports that the American Society for Radiation Oncology (ASTRO) has updated and released its guidelines for the use of accelerated partial breast irradiation. The guideline includes the topics of prospective registry of IORT before its use, whole breast irradiation (WBI) and its use in clinical trials.

Purpose: To report the long-term efficacy and toxicity of proton therapy for pediatric ependymoma.Methods and Materials: Between 2000 and 2019, 386 children with nonmetastatic grade 2/3 intracranial ependymoma received proton therapy at 1 of 2 academic institutions. Median age at treatment was 3.8 years (range, 0.7-21.3); 56% were male. Most (72%) tumors were in the posterior fossa and classified as World Health Organization grade 3 (65%). Eighty-five percent had a gross total or near total tumor resection before radiation therapy; 30% received chemotherapy. Median radiation dose was 55.8 Gy relative biologic effectiveness (RBE) (range, 50.4-59.4).Results: Median follow-up was 5.0 years (range, 0.4-16.7). The 7-year local control, progression-free survival, and overall survival rates were 77.0% (95% confidence interval [CI], 71.9%-81.5%), 63.8% (95% CI, 58.0%-68.8%), and 82.2% (95% CI, 77.2%-86.3%), respectively. Subtotal resection was associated with inferior local control (59% vs 80%; P < .005), progression-free survival (48% vs 66%; P < .001), and overall survival (70% vs 84%; P < .05). Male sex was associated with inferior progression-free (60% vs 69%; P < .05) and overall survival (76% vs 89%; P < .05). Posterior fossa tumor site was also associated with inferior progression-free (59% vs 74%; P < .05) and overall survival (79% vs 89%; P < .01). Twenty-one patients (5.4%) required hearing aids; of these, 13 received cisplatin, including the 3 with bilateral hearing loss. Forty-five patients (11.7%) required hormone replacement, typically growth hormone (38/45). The cumulative incidence of grade 2+ brain stem toxicity was 4% and occurred more often in patients who received >54 GyRBE. Two patients (0.5%) died of brain stem necrosis. The second-malignancy rate was 0.8%.Conclusion: Proton therapy offers disease control commensurate with modern photon therapy without unexpected toxicity. The high rate of long-term survival justifies efforts to reduce radiation exposure in this young population. Independent of radiation modality, this large series confirms extent of resection as the most important modifiable factor for survival. [ABSTRACT FROM AUTHOR]

To evaluate the LETd-weighted biological dose to OARs in proton therapy for breast cancer and to study the relationship of the LETd-weighted biological dose relative to the standard dose (RBE = 1.1) and thereby to provide estimations of the biological dose uncertainties with the standard dose calculations (RBE = 1.1) commonly used in clinical practice. This study included 20 patients who received IMPT treatment to the whole breast/chest wall and regional lymph nodes. The LETd distributions were calculated along with the physical dose using an open-source Monte Carlo simulation package, MCsquare. Using the McMahon linear model, the LETd-weighted biological dose was computed from the physical dose and LETd. OAR doses were compared between the Dose (RBE = 1.1) and the LETd-weighted biological dose, on brachial plexus, rib, heart, esophagus, and Ipsilateral lung. On average, the LETd-weighted biological dose compared to the Dose (RBE = 1.1) was higher by 8% for the brachial plexus D0.1 cc, 13% for the ribs D0.5 cc, 24% for mean heart dose, and 10% for the esophagus D0.1 cc, respectively. The LETd-weighted doses to the Ipsilateral lung V5, V10, and V20 were comparable to the Dose (RBE = 1.1). No statistically significant difference in biological dose enhancement to OARs was observed between the intact breast group and the CW group, with the exception of the ribs: the CW group experienced slightly greater biological dose enhancement (13% vs. 12%, p = 0.04) to the ribs than the intact breast group. Enhanced biological dose was observed compared to standard dose with assumed RBE of 1.1 for the heart, ribs, esophagus, and brachial plexus in breast/CW and regional nodal IMPT plans. Variable RBE models should be considered in the evaluation of the IMPT breast plans, especially for OARs located near the end of range of a proton beam. Clinical outcome studies are needed to validate model predictions for clinical toxicities. [ABSTRACT FROM AUTHOR]

Background: To identify prognostic factors for grade 3 radiation dermatitis following passive-scattering proton therapy for breast cancer.Methods: This retrospective study included data on 23 (11 post-mastectomy and 12 post-lumpectomy) breast cancer patients who underwent proton therapy with the passive scattering technique in our institute from 2012 to 2016. Each patient received 50-50.4 cobalt Gy equivalent (CGE) at 1.8 or 2 CGE per daily fraction. Logistic regression analysis was performed to identify prognostic factors for grade 3 skin toxicity. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models.Results: 43% of the studied patients developed grade 3 radiation dermatitis. The dose-volume histogram (DVH) parameters of V52.5CGE and D10cm3 to skin5mm were correlated with grade 3 radiation dermatitis in both univariate and multivariate logistic regression analyses. Univariate logistic regression analysis suggested that D10cm3 to skin5mm (AUC = 0.69) and V52.5CGE to skin5mm (AUC = 0.70) were prognostic for grade 3 skin toxicity. The models using the combination of D10cm3 to skin5mm or V52.5CGE to skin5mm with breast volume marginally increased the AUC to 0.72 and 0.73, respectively. Models using the combination of D10cm3 to skin5mm or V52.5CGE to skin5mm with history of smoking increased the AUC to 0.75 and 0.83, respectively.Conclusion: In the current study, we identified prognostic factors for grade 3 radiation dermatitis in patients treated with passive-scattering proton therapy for breast cancer. This study provides promising tool for identifying high risk patients for whom treatment plan adjustment could be done to reduce the risk of radiation-induced grade 3 skin toxicity. [ABSTRACT FROM AUTHOR]

Hemangiosarcoma (HSA), a locally invasive and highly metastatic endothelial cell neoplasm, accounts for two-thirds of all cardiac and splenic neoplasms in dogs. Bartonella spp. infection has been reported in association with neoplastic and non-neoplastic vasoproliferative lesions in animals and humans. The objective of this study was to determine the prevalence of Bartonella spp. in conjunction with two other hemotropic pathogens, Babesia spp. and hemotropic Mycoplasma spp., in tissues and blood samples from 110 dogs with histopathologically diagnosed HSA from throughout the United States. This was a retrospective, observational study using clinical specimens from 110 dogs with HSA banked by the biospecimen repository of the Canine Comparative Oncology and Genomics Consortium. Samples provided for this study from each dog included: fresh frozen HSA tumor tissue (available from n = 100 of the 110 dogs), fresh frozen non-tumor tissue (n = 104), and whole blood and serum samples (n = 108 and 107 respectively). Blood and tissues were tested by qPCR for Bartonella, hemotropic Mycoplasma, and Babesia spp. DNA; serum was tested for Bartonella spp. antibodies. Bartonella spp. DNA was amplified and sequenced from 73% of dogs with HSA (80/110). In contrast, hemotropic Mycoplasma spp. DNA was amplified from a significantly smaller proportion (5%, p<0.0001) and Babesia spp. DNA was not amplified from any dog. Of the 100 HSA tumor samples submitted, 34% were Bartonella PCR positive (32% of splenic tumors, 57% of cardiac tumors, and 17% of other tumor locations). Of 104 non-tumor tissues, 63% were Bartonella PCR positive (56% of spleen samples, 93% of cardiac samples, and 63% of skin/subcutaneous samples). Of dogs with Bartonella positive HSA tumor, 76% were also positive in non-tumor tissue. Bartonella spp. DNA was not PCR amplified from whole blood. This study documented a high prevalence of Bartonella spp. DNA in dogs with HSA from geographically diverse regions of the United States. While 73% of all tissue samples from these dogs were PCR positive for Bartonella DNA, none of the blood samples were, indicating that whole blood samples do not reflect tissue presence of this pathogen. Future studies are needed to further investigate the role of Bartonella spp. in the development of HSA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Survivorship care plans are tools for long-term cancer care management; however, little is known regarding radiation therapy providers' perspectives on survivorship care and education. OBJECTIVES: This study was designed to identify priorities for improvement in radiation therapy-- specific cancer survivorship education. METHODS: An investigator-developed online survey of healthcare provider communication with patients regarding cancer survivorship was administered within an academic radiation therapy oncology practice. Seventeen survivorship categories were evaluated for each provider, including when and how often survivorship issues were addressed, perceived priority of issues, and provider knowledge of survivorship resources. FINDINGS: 23 providers responded. Providers reported that the five most important patient concerns were fear of recurrence, radiation therapy side effects, surveillance, preventive measures and nutrition, and stress management. The most time was spent discussing side effects and recurrence risk. [ABSTRACT FROM AUTHOR]

Background: Orbital rhabdomyosarcoma (ORMS) commonly presents as low‐risk disease (stage 1, group I–III, embryonal RMS) with excellent outcome. Long‐term follow‐up of patients with low‐risk ORMS and outcomes of less common subgroups of ORMS treated on recent Children's Oncology Group (COG) trials have not been reported. Methods: Patients with ORMS enrolled on COG trials from 1997 to 2013 were identified. Demographic information and disease characteristics were collected. Outcomes were determined for the following subgroups: 1) low‐risk ORMS, 2) resected (group I/II) low‐risk ORMS, 3) non–low‐risk ORMS, and 4) recurrent ORMS. Event‐free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method. ResultsThe authors identified 218 patients with ORMS. Most tumors were embryonal/botryoid (n = 169; 77.5%), <5 cm (n = 213; 97.7%), group III (n = 170; 78.0%), and without lymph node involvement (N0; n = 215; 98.6%). For 192 patients with low‐risk ORMS, the 10‐year EFS and OS rates were 85.5% (95% confidence interval [CI], 77.0%–94.0%) and 95.6% (95% CI, 90.8%–100.0%), respectively. Those with group I/II low‐risk ORMS (n = 5 in group I; n = 39 in group IIA) had 10‐year EFS and OS rates of 88.0% (95% CI, 72.6%–100.0%) and 97.6% (95% CI, 90.0%–100.0%), respectively. Twenty‐six patients with non–low‐risk ORMS had 5‐year EFS and OS rates of 88.5% (95% CI, 75.6%–100.0%) and 95.8% (95% CI, 87.7%–100.0%), respectively. For patients with recurrent ORMS, the 10‐year OS rate from the time of recurrence was 69.4% (95% CI, 50.0%–88.8%). Conclusions: Patients with ORMS had favorable long‐term survival outcomes on COG studies from 1997 to 2013, including those who had both low‐risk and non–low‐risk disease. A significant proportion of patients with recurrent ORMS may achieve long‐term survival. The authors analyzed the long‐term survival outcomes for orbital rhabdomyosarcoma on Children's Oncology Group trials. The results indicated that long‐term survival outcomes were comparable to those reported at 3 years and 5 years, and a significant portion of recurrent orbital rhabdomyosarcomas appeared to be salvageable. [ABSTRACT FROM AUTHOR]

Purpose: To report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy.Patients and Methods: Between February 2007 and November 2013, 66 children with a median age of 4.1 years (range, 0.6-15.3 years) diagnosed with nonmetastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 was defined as the prechemotherapy tumor plus a 1-cm anatomically constrained margin. Clinical target volume 2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5-cm anatomically constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis.Results: Of the 66 children, 11 developed locally progressive disease at a median of 16 months (range, 14-32 months), for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7 years (range, 0.6-16 years) and 6 cm (range, 2-8 cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3, and all 11 were group III. Of the relapses, 100% (11 of 11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field.Conclusion: Early data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm clinical target volume 1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features. [ABSTRACT FROM AUTHOR]

Purpose: To quantify swallowing frequency and tumor and normal structure displacements during deglutition using dynamic magnetic resonance imaging (MRI) and to determine planning target volume (PTV) margins to account for resting and deglutition-induced displacements in patients with head-and-neck cancer (HNC). Methods and Materials: Twenty-two patients with HNC were imaged in the treatment position using dynamic MRI. Sagittal images were acquired. Two-dimensional displacement was analyzed using contours of normal structures and GTV drawn for one swallowing event. Deglutition-induced displacements were quantified based on position change during deglutition relative to preswallow structure location for anterior (A), posterior (P), superior (S), and inferior (I) directions. Additional long-time MRI series were obtained from a subset of 11 patients while they were resting in order to determine swallowing frequency and duration. PTV margins to account for setup error, frequency and duration of deglutition, and resting and deglutition-induced GTV motion were calculated. Results: Mean maximum resting displacements ranged from 1.5 to 3.1 mm for combined GTV subsites. Mean maximum swallowing GTV displacement for combined subsites ranged from 4.0 to 11.6 mm. Swallowing was nonperiodic, with a frequency ranging from 0 to 19 swallows over 12.8 min and mean swallow duration of 3.5 s. Based on the average swallowing characteristics in this cohort, the average PTV margins to account for setup error and tumor motion are estimated to be 4.7 mm anteriorly, 4.2 mm posteriorly, 4.7 mm inferiorly, and 6.0 mm superiorly. Conclusions: The measurable mean maximum resting displacement for the GTV indicates that tumor motion occurs even when the patient is not swallowing. Nonuniform margins should be used as a standard PTV margin that accounts for setup error and tumor motion in radiotherapy of HNC unless adaptive radiotherapy with respect to intrafraction tumor motion is performed. The PTV margin can be individualized to a single patient’s swallowing characteristics or calculated as an average based on the swallowing data from the cohort. [Copyright &y& Elsevier]

Purpose: There is a lack of level I evidence to guide radiation therapy recommendations for patients receiving neoadjuvant chemotherapy for breast cancer. We used 4 neoadjuvant chemotherapy trials to determine which patients benefit from regional nodal irradiation (RNI).Methods and Materials: We obtained data from the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-18, B-27, B-40, and B-41 clinical trials. B-40 and B-41 allowed RNI at physician's discretion. We evaluated locoregional recurrence (LRR), distant recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier, Peto-Peto, χ2, Fisher exact, and Wilcoxon rank-sum tests were used for survival estimates and comparison.Results: Median follow-up for B-18, B-27, B-40, and B-41 was 13.7, 9.7, 4.5, and 5.1 years, respectively, including 742, 2254, 1154, and 504 patients for analysis. On multivariable analysis, factors significantly associated with RNI included tumor size, ypN status, and tumor subtype; Hispanic patients were less likely to receive RNI. Patients with ypN+HER2+ disease who received RNI had improved OS. B-40 patients with ypN+HR+ disease had improved LRR. On multivariable analysis for the B-40 and B-41 study population, RNI was not associated with significantly improved OS, disease-free survival, distant recurrence, or LRR.Conclusions: RNI was associated with a clinical benefit for patients with ypN+HER2+ and ypN+HR+ disease. RNI was not significantly associated with a clinically beneficial outcome for the entire cohort. Prospective phase 3 clinical trials are needed to establish guidelines for patients who should receive RNI after neoadjuvant treatment, and action is necessary to eliminate the disparity in care delivery shown for Hispanic women. [ABSTRACT FROM AUTHOR]

Purpose: Owing to adjacent critical organs, the aggressive multimodality local therapy necessary for Ewing sarcoma of the chest wall is a challenge. Our previous review of historical outcomes at our institution revealed suboptimal disease control and a high incidence of grade ≥3 toxic effects in patients treated before 2006. The purpose of this study was to evaluate changes during the past decade since the introduction of proton therapy.Methods and Materials: Thirty-nine consecutive pediatric patients with a chest wall Ewing sarcoma treated between 2006 and 2020 at the University of Florida were identified. The median maximum tumor diameter was 10 cm (range, 4-28 cm). At diagnosis, 19 patients had local disease and the others had a pleural effusion (11), pleural nodules (5), or pulmonary metastases (4). Patients were treated with chemotherapy regimens according to contemporary North American and European protocols: 7 were treated with preoperative, 18 with postoperative, and 14 with definitive radiation. Preceding primary site treatment, 15 patients required hemithorax radiation and 4 patients underwent whole-lung irradiation using photon techniques. The total median radiation dose to the primary tumor was 52.8 GyRBE [relative biological effectiveness] (range, 44.4-55.8 GyRBE).Results: With a median follow-up of 4 years (range, 0.7-14.7 years), the 5-year local control, progression-free survival, and overall survival rates were 97.2%, 74.4%, and 81.6%, respectively, for the whole cohort. For the 19 patients with nonmetastatic disease, the 5-year local control, progression-free survival, and overall survival rates were 100%, 78.9%, and 78.9%, respectively. No patients developed grade ≥4 toxic effects. Two patients (5%) experienced grade 3 toxic effects related to multimodality treatment; both were patients who required surgery to correct scoliosis. Two patients (5%) developed grade 2 pneumonitis.Conclusions: Compared with our prior published institutional experience, our data suggest improvements in disease control and multimodality toxic effects since the introduction of proton therapy. This should be confirmed with a larger sample size and longer follow-up. [ABSTRACT FROM AUTHOR]

Radiation treatment is widely used to address unresectable intracranial tumors. Owing to the nature of therapy, healthy tissue and diseased regions will be affected. New insights have shown that not only does this impact brain parenchyma but it causes changes in fluid status, myelination, and the integrity of the blood-brain barrier. This alters how peripheral and central immune systems interact, perpetuating neuroinflammation. Rare case reports in the adult literature have described multifocal, multiphasic demyelinating lesions after radiation. Here we describe 2 pediatric cases of relapsing demyelination after and in conjunction with radiation therapy for ependymoma, consistent with a multiple sclerosis phenotype. Insights into the underpinnings of multiple sclerosis show peripheral inflammation, blood-brain barrier disruption, and antigenic mimicry stimulating neuroinflammation. Here we investigate the role that radiation, tumor burden, and systemic inflammation may play in creating demyelinating disorders. We strive to elucidate common pathophysiology between radiation-induced brain injury and multiple sclerosis. [ABSTRACT FROM AUTHOR]

Introduction Effective and safe cardiac arrest care in the hospital setting is reliant on the immediate availability of emergency equipment. The patient safety literature highlights deficiencies in current approaches to resuscitation equipment provision, highlighting the need for innovative solutions to this problem. Methods We conducted a before–after study at a large NHS trust to evaluate the effect of a sealed tray system and database on resuscitation equipment provision. The system was evaluated by a series of unannounced inspections to assess resuscitation trolley compliance with local policy prior to and following system implementation. The time taken to check trolleys was assessed by timing clinicians checking both types of trolley in a simulation setting. Results The sealed tray system was implemented in 2010, and led to a significant increase in the number of resuscitation trolleys without missing, surplus, or expired items (2009: n = 1 (4.76%) vs 2011: n = 37 (100%), p < 0.001). It also significantly reduced the time required to check each resuscitation trolley in the simulation setting (12.86 (95% CI: 10.02–15.71) vs 3.15 (95% CI: 1.19–4.51) min, p < 0.001), but had no effect on the number of resuscitation trolleys checked every day over the previous month (2009: n = 8 (38.10%) vs 2011: n = 11 (29.73%), p = 0.514). Conclusion The implementation of a sealed tray system led to a significant and sustained improvement in resuscitation equipment provision, but had no effect on resuscitation trolley checking frequency. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study is to review late toxicity following craniospinal radiation for early-stage medulloblastoma. Material and methods. Between 1963 and 2008, 53 children with stage M0 (n = 50) or M1 (n = 3) medulloblastoma were treated at our institution. The median age at diagnosis was 7.1 years (range 1.2-18.5). The median craniospinal irradiation (CSI) dose was 28.8 Gy (range 21.8-38.4). The median total dose, including boost, was 54 Gy (range 42.4-64.8 Gy). Since 1963, the CSI dose has been incrementally lowered and the high-risk boost volume reduced. Twenty-one patients (40%) received chemotherapy in their initial management, including 12 who received concurrent chemotherapy. Late sequelae were evaluated by analyzing medical records and conducting phone interviews with surviving patients and/or care-takers. Complications were graded using the NCI Common Terminology Criteria for Adverse Events, version 4.0. Results. The median follow-up for all patients was 15.4 years (range 0.4-44.4) and for living patients it was 24 years (range 5.6-44.4). The overall survival, cause-specific survival, and progression-free survival rates at 10 years were 67%, 67%, and 71%, respectively. Sixteen patients (41% of patients who survived five years or more) developed grade 3 + toxicity; 15 of these 16 patients received a CSI dose > 23.4 Gy. The most common grade 3 + toxicities for long-term survivors are hearing impairment requiring intervention (20.5%) and cognitive impairment (18%) prohibiting independent living. Four patients developed secondary (non-skin) malignancies, including three meningiomas, one rhabdomyosarcoma, and one glioblastoma multiforme. Three patients (5.6%) died from treatment complications, including radionecrosis, severe cerebral edema, and fatal secondary malignancy. Conclusion. Ongoing institutional and cooperative group efforts to minimize radiation exposure are justified given the high rate of serious toxicity observed in our long-term survivors. Follow-up through long-term multidisciplinary clinics is important and warranted for all patients exposed to radiotherapy in childhood. [ABSTRACT FROM AUTHOR]

Purpose: In 2010, we published a comprehensive review of our institutional outcomes about treating children with spinal and paraspinal Ewing sarcoma using photon therapy. Multimodality therapy was associated with fair disease control but also with serious toxicity, including a 37% rate of grade 3 or greater toxicity. We therefore sought to assess our more recent experience about treating children with more modern technology and treatment regimens.Methods and Materials: Between 2010 and 2021, 32 pediatric patients with nonmetastatic spinal and paraspinal Ewing sarcoma were treated at University of Florida and enrolled in a retrospective outcome study. Median age at diagnosis was 9.8 years (range, 2.1-21.8 years). Within the cervical, thoracic, and lumbar spine regions, 3, 22, and 7 tumors arose, respectively. Median maximum tumor diameter was 5 cm (range, 3-19 cm). At diagnosis, 28 of 32 patients had motor, bowel, or bladder deficits. Chemotherapy was delivered according to contemporary North American and European interval-compressed regimens. Before radiation therapy, 14 patients underwent gross total resection, whereas 18 underwent a biopsy or subtotal resection with cord decompression. All patients were treated with proton therapy; 6 with hardware stabilization also received a component of intensity modulated photon therapy. Median prescription dose was 50.4 gray relative biological effectiveness (GyRBE; range, 45-55.8 GyRBE). Median maximum dose to the spinal cord was 50.2 GyRBE (range, 0-54.9 GyRBE).Results: With a median follow-up of 4.1 years (range, 0.7-9.4 years), the 5-year local control, progression-free survival, and overall survival rates were 92%, 79%, and 85%, respectively. Ten of 30 living patients have residual motor, bowel, or bladder deficits. Overall, 22% of patients experienced Common Terminology Criteria for Adverse Events grade 3 late toxicity related to multimodality treatment: kyphosis (n = 4), esophagitis (n = 2), and chronic kidney disease (n = 1). No patients developed grade 4 or greater toxicity, new neurologic deficits, or second malignancy.Conclusions: Modern treatment advances may offer an improved therapeutic ratio for pediatric patients with spinal and paraspinal Ewing sarcoma. With appropriate management, most patients can be cured with recovery of long-term neurologic function and modest side effects. [ABSTRACT FROM AUTHOR]

Purpose: Few studies report outcomes in children treated with radiation for nonmyxopapillary ependymoma of the spinal cord, and little evidence exists to inform decisions regarding target volume and prescription dose. Moreover, virtually no mature outcome data exist on proton therapy for this tumor. We describe our combined institutional experience treating pediatric classical/anaplastic ependymoma of the spinal cord with proton therapy.Methods and Materials: Between 2008 and 2019, 14 pediatric patients with nonmetastatic nonmyxopapillary grade II (n = 6) and grade III (n = 8) spinal ependymoma received proton therapy. The median age at radiation was 14 years (range, 1.5-18 years). Five tumors arose within the cervical cord, 3 within the thoracic cord, and 6 within the lumbosacral cord. Before radiation therapy, 3 patients underwent subtotal resection, and 11 underwent gross-total or near total resection. Two patients received chemotherapy. For radiation, the clinical target volume received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter receiving a boost to the gross tumor volume after the initial 50.4 Gy, modified to respect spinal cord tolerance.Results: With a median follow-up of 6.3 years (range, 1.5-14.8 years), no tumors progressed. Although most patients experienced neurologic sequela after surgery, only 1 developed additional neurologic deficits after radiation: An 18-year-old male who received 54 Gy after gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of musculoskeletal toxicity attributable to surgery and radiation. At analysis, no patient had developed cardiac, pulmonary, or other visceral organ complications or a second malignancy.Conclusion: Radiation to a total dose of 50 to 54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with nonmyxopapillary spinal cord ependymoma. Proton therapy may reduce late radiation effects and is not associated with unexpected spinal cord toxicity. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to develop and preliminarily test a radiotherapy system for patient posture correction and alignment using mixed reality (MixR) visualization. The write‐up of this work also provides an opportunity to introduce the concepts and technology of MixR for a medical physics audience who may be unfamiliar with the topic. Methods: A MixR application was developed for on optical‐see‐through head‐mounted display (HoloLens 2) allowing a user to simultaneously and directly view a patient and a reference hologram derived from their simulation CT scan. The hologram provides a visual reference for the exact posture needed during treatment and is initialized in relation to the origin of a radiotherapy device using marker‐based tracking. The system further provides marker‐less tracking that allows the user tofreely navigate the room as they view and align the patient from various angles. The system was preliminarily tested using both a rigid (pelvis) and nonrigid (female mannequin) anthropomorphic phantom. Each phantom was aligned via hologram and accuracy quantified using CBCT and CT. Results: A fully realized system was developed. Rigid registration accuracy was on the order of 3.0 ± 1.5 mm based on the performance of three users repeating alignment five times each. The lateral direction showed the most variability among users and was associated with the largest off‐sets (approximately 2.0 mm). For nonrigid alignment, the MixR setup outperformed a setup based on three‐point alignment and setup photos, the latter of which showed a difference in arm position of 2 cm and a torso roll of 6–7°. Conclusions: MixR visualization is a rapidly emerging domain that has the potential to significantly impact the field of medicine. The current application is an illustration of this and highlights the advantages of MixR for patient setup in radiation oncology. The key feature of the system is the way in which it transforms nonrigid registration into rigid registration by providing an efficient, portable, and cost‐effective mechanism for reproducing patient posture without the use of ionizing radiation. Preliminary estimates of registration accuracy indicate clinical viability and form the foundation for further development and clinical testing. [ABSTRACT FROM AUTHOR]

The article discusses a study which hypothesized that magnetic resonance imaging (MRI) would alter eligibility of partial breast irradiation (PBI) by identifying cancers outside the PBI volume compared to mammography alone. It reveals that MRI discovered frequent secondary cancers that would not be removed routinely by surgery or could not be targeted in the radiation field through PBI. It suggests that MRI should be considered to assess the eligibility of PBI to lessen local failures.

A naturally occurring infection of Ehrlichia chaffeensis in lemurs is described. DNA of Ehrlichia chaffeensis was identified by polymerase chain reaction in peripheral blood from six of eight clinically ill lemurs. Organisms were cultured from the blood of one lemur exhibiting clinical and hematologic abnormalities similar to those of humans infected with E. chaffeensis. [ABSTRACT FROM AUTHOR]

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. [ABSTRACT FROM AUTHOR]

• Infants treated with proton therapy have similar disease control to their older counterparts. • Young age may not be an adverse prognostic factor if patients receive standard radiation doses. • Rhabdomyosarcoma of the nasal ala in infants may signify a distinctly poor prognosis. • Toxicity data suggest evidence of hypoplasia among survivors. In infants with rhabdomyosarcoma, young age is considered an adverse prognostic factor and treatment is often attenuated to reduce side effects. Proton therapy may improve the therapeutic ratio in these patients. We report outcomes in infants with rhabdomyosarcoma treated with proton therapy. Between 2009 and 2019, 37 infants <24 months old with non-metastatic rhabdomyosarcoma received proton therapy. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan–Meier product limit. The log-rank test assessed significance between selected prognostic factors. Toxicity was graded per CTCAEv5.0. Median follow-up was 5.1 years. Overall, 76% of patients had an unfavorable primary site. Median dose was 50.4GyRBE. At 5 years, LC, PFS, and OS rates were 83%, 78%, and 83%. On univariate analysis, 5-year LC and OS were inferior for favorable versus unfavorable disease sites (67% vs 89%, 67% vs 89%, respectively; p <.05) and 5-year OS was superior in stage 3 versus stage 1–2 disease (91% vs 69%; p =.05), owing to inclusion of nasal ala patients among stage 1. Of 9 recurrences, 7 were in-field, 4 occurring in infants with nasal ala primaries. Recategorizing nasal ala as an unfavorable site resulted in 100% 5-year LC and OS for favorable sites. Six infants experienced late grade 3 toxicity. None developed grade 4 or 5 late toxicity. Young age alone may not be an adverse prognostic factor provided infants receive local therapy similar to older children. Consideration should be given to classifying nasal ala primaries as an unfavorable site. [ABSTRACT FROM AUTHOR]

Recently, infections with emerging zoonotic bacteria of the genus Bartonella have been reported in association with a range of central nervous system (CNS) symptoms. Currently, it remains unknown if Bartonella spp. infection is associated with symptoms of schizophrenia/schizoaffective disorder (SCZ/SAD). The objective of this study was to determine if there is an association between Bartonella species infection and SCZ/SAD. A secondary objective was to determine if SCZ/SAD symptoms were more severe among participants with documented Bartonella spp. infection. Using a case-control study design, 17 cases and 13 controls were evaluated with a series of clinical and cognitive assessments. Blood samples were collected and tested for Bartonella spp. infection using serological, microbiological, and molecular techniques. People with SCZ/SAD were more likely than healthy volunteers to have Bartonella spp. DNA in their bloodstream, with 11 of 17 cases (65%) positive by Bartonella spp. droplet digital PCR (ddPCR). In comparison, only one healthy volunteer was Bartonella spp. ddPCR positive (8%, p = 0.0024). Based on serology, Bartonella spp. exposure was common among people with SCZ/SAD (12 of 17) as well as among healthy volunteers (12 of 13), with no significant difference between the groups (p = 0.196). Within the case group of people with SCZ/SAD, there was no significant difference in SCZ/SAD severity scores between people with and without ddPCR evidence of Bartonella spp. infection. This pilot study provides preliminary evidence in support of future investigations that should examine a potential contribution of Bartonella spp. infection to SCZ/SAD. [ABSTRACT FROM AUTHOR]