Utilization Patterns of Single-Fraction and Short-Course Radiotherapeutic Schedules in the Management of Bone Metastases.

Purpose: Bone metastases are common, occurring in 60% to 70% of patients with advanced malignancies. Historically, bone-directed radiation therapy regimens of 30 Gy over 10 fractions were used. However, prospective randomized data suggest equivalent pain relief with shorter-course regimens. The American Society for Radiation Oncology Choosing Wisely Campaign encourages clinicians to consider shorter-course palliative regimens in patients with limited prognosis. A retrospective analysis was performed to assess patterns of short-course and single-fraction radiation therapy during the past 5 years. Methods and Materials: We queried our electronic medical record (MOSAIQ) from 2016 to 2020 for patients with bone metastases who received palliative radiation therapy. Patients receiving >10 fractions or Medicare-approved palliative courses of radiation (30 Gy/10 fractions, 24 Gy/6 fractions, 20 Gy/5 fractions, 8 Gy/1 fraction) were included. Treatment department was defined as academic (n = 2) versus community (n = 12). Short-course treatment was defined as <6 fractions, whereas long-course included patients receiving >10 fractions. Patients were subdivided based on age and disease site. Physicians were grouped according to their year of residency completion. Multivariable logistic regression analysis identified predictors of short-course and single-fraction treatment. Results: We identified 1004 patients with 1768 bony metastases meeting inclusion criteria. The spine was the most common site, followed by pelvis/hip, extremity, and other site. Use of short-course treatment increased from 40% in 2016 to 50% in 2020. Single-fraction treatment increased from 7% in 2016 to 11% in 2020. Predictors of shorter courses included treatment at academic centers, more recent treatment, patient age >76 years, and nonspine anatomic site. Predictors of single-fraction treatment included treatment at academic centers, treating physician residency completion after 2010, patient age >76 years, and treatment to extremity or other site. Conclusions: Rates of short-course and single-fraction bone-directed radiation therapy increased within our health system over time. Treatment receipt at academic centers was associated with both short-course and single-fraction regimens. Physicians completing residency after 2010 were more likely to deliver single-fraction therapy.

Interleukin 6 Signaling Blockade Exacerbates Acute and Late Injury From Focal Intestinal Irradiation.

PURPOSE: To evaluate the acute changes in leukocyte populations after focal irradiation and to assess the role of interleukin 6 (IL-6) in acute and late radiation injury. METHODS AND MATERIALS: Mice were surgically implanted with a radiopaque marker on the surface of the small intestine. Mice were then imaged with cone beam computed tomography to locate the marker and irradiated with 18 Gy of 5 × 5 mm collimated x-rays onto the marked intestine using the Small Animal Radiation Research Platform. Intestinal sections and blood were harvested 1, 3.5, 7, and 14 days and 2 months postirradiation (post-IR) for histology and complete blood count, respectively. Immune cell populations were assessed by immunofluorescence in the acute phase. Collagen deposition was assessed 2 months post-IR. IL-6-/- intestinal sections were assessed post-IR for morphology, EdU, Ki67, and TUNEL in comparison to IL-6+/+ mice. Furthermore, a set of IL-6+/+ mice were treated with anti-IL-6R to assess the role of IL-6 in late intestinal injury. RESULTS: Intestinal radiation damage peaked 14 days post-IR, and fibrosis had developed by 60 days post-IR. There was a marked infiltration of immune cells into the irradiated intestine, with increased neutrophils, macrophages, B-cells, and CD4+ T cells maintained from 3.5 to 14 days post-IR. CD8+ T cells were decreased from days 7 to 14 post-IR. Systemically, leukocytes were increased in the peripheral blood 14 days post-IR with anemia being maintained from 14 days to 2 months. IL-6 was significantly increased in the serum post-IR. IL-6-/- mice demonstrated worsened intestinal injury acutely post-IR. Moreover, anti-IL-6R-treated mice presented with worsened intestinal fibrosis 2 months post-IR. CONCLUSIONS: Focal irradiation of the intestine produced a significant increase in immune cells in the irradiated area and systemic inflammation and anemia. Blockade of IL-6 signaling was found to exacerbate acute intestinal injury and late intestinal injury after focal irradiation.

Complete Genome Sequences of 12 B1 Cluster Mycobacteriophages, Gareth, JangoPhett, Kailash, MichaelPhcott, PhenghisKhan, Phleuron, Phergie, PhrankReynolds, PhrodoBaggins, Phunky, Vaticameos, and Virapocalypse.

Twelve B1 cluster mycobacteriophages were isolated from soil samples collected in Philadelphia, PA, USA, using Mycobacterium smegmatis mc2 155 as a host, and were sequenced. The genome sequences range in size from 66,887 bp to 68,953 bp in length and have between 99 and 105 putative protein-coding genes.

Assessing the Validity of Clinician Advice That Patients Avoid Use of Topical Agents Before Daily Radiotherapy Treatments.

Importance: Radiation dermatitis is common and often treated with topical therapy. Patients are typically advised to avoid topical agents for several hours before daily radiotherapy (RT) out of concern that topical agents might increase the radiation dose to the skin. With modern RT's improved skin-sparing properties, this recommendation may be irrelevant. Objective: To assess whether applying either metallic or nonmetallic topical agents before radiation treatment alters the skin dose. Design, Setting, and Participants: A 24-question online survey of patients and clinicians was conducted from January 15, 2015, to March 15, 2017, to determine current practices regarding topical therapy use. In preclinical studies, dosimetric effect of the topical agents was evaluated by delivering 200 monitor units and measuring the dose at the surface and at 2-cm depth in a tissue-equivalent phantom with or without 2 common topical agents: a petroleum-based ointment (Aquaphor, petrolatum 41%) and silver sulfadiazine cream, 1%. Skin doses associated with various photon and electron energies, topical agent thicknesses, and beam incidence were assessed. Whether topical agents altered the skin dose was also evaluated in 24 C57BL/6 mice by using phosphorylated histone (γ-H2AX) immunofluorescent staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Preclinical studies took place at the University of Pennsylvania. Main Outcomes and Measures: Patient and clinician survey responses; surface radiation dose readings in tissue-equivalent phantom; and γ-H2AX and TUNEL intensity measured in mice. Results: The 133 patients surveyed received RT for cancer and had a median (range) age of 60 (18-86) years; 117 (87.9%) were women. One hundred eight clinicians completed the survey with 105 reporting that they were involved in managing patient skin care during RT. One hundred eleven (83.4%) of the patients and 96 (91.4%) of the 105 clinicians received or gave the advice to avoid applying topical agents before RT treatments. Dosimetric measurements showed no difference in the delivered dose at either the surface or a 2-cm depth with or without a 1- to 2-mm application of either topical agent when using en face 6- or 15-megavoltage (MV) photons. The same application of topicals did not alter the surface dose as a function of beam incident angle from 15° to 60°, except for a 6% increase at 60° with the silver sulfadiazine cream. Surface dose for 6- and 15-MV beams were significantly increased with a thicker (≥3-mm) topical application. For 6 MV, the surface dose was 1.05 Gy with a thick layer of petroleum-based ointment and 1.02 Gy for silver sulfadiazine cream vs 0.88 Gy without topical agents. For 15 MV, the doses were 0.70 Gy for a thick layer of petroleum-based ointment and 0.60 Gy for silver sulfadiazine cream vs 0.52 Gy for the controls. With 6- and 9-MeV electrons, there was a 2% to 5% increase in surface dose with the use of the topical agents. There were no dose differences at 2-cm depth. Irradiated skin in mice showed no differences in γ-H2AX-positive foci or in TUNEL staining with or without topical agents of varying thickness. Conclusions and Relevance: Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence. The findings of this study suggest that applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided.

A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors.

Radiation is an important treatment modality for gastrointestinal tumors, but intestinal injury is a common side effect. Here we describe a physiologically relevant model for studying the molecular determinants of radiation-induced intestinal damage and testing novel radioprotectors. The model employs a radiopaque marker implanted into the surface of the mouse jejunum, serving as a fiducial marker for precise radiation targeting. Mice were imaged with Cone-Beam CT (CBCT) and irradiated (IR) to the marked area using the Small Animal Radiation Research Platform (SARRP). IR-induced damage was acute but reversible and largely restricted to the area of the marker, leaving the surrounding tissues intact. Although whole gut irradiation with these doses caused lethal GI syndrome, focal (5 mm) radiation of the intestine did not cause any weight loss or lethality. However, fibrosis and collagen deposition 4 months post-IR indicated chronic intestinal damage. A separate cohort of mice was treated daily with curcumin, a clinically tested radioprotector, prior to and post-IR. Curcumin-treated mice showed significant decreases in both local and systemic inflammatory cytokine levels and in fibrosis, suggesting it is an effective radioprotector of the intestine. Our results indicate that this model, which emulates clinically relevant intestinal radiation-induced injury, can be used to assess radioprotectors prior to testing in the clinic. Cancer Res; 77(4); 908-17. ©2016 AACR.