Mass Spectrometry-Based Tissue Imaging of Small Molecules.

Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques, and provides accurate, histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from mass spectrometry imaging laboratories around the globe.

Acute toxicity of craniospinal irradiation with volumetric-modulated arc therapy in children with solid tumors.

BACKGROUND: Craniospinal irradiation (CSI) is an important part of curative radiation therapy (RT) for many types of pediatric brain or solid tumors. After conventional CSI, long term survivors may experience sequelae due to unintended dose to normal tissue. Volumetric modulated arc therapy (VMAT) CSI reduces off-target doses at the cost of greater complexity and error risk, and we describe our initial experience in a group of pediatric patients with solid tumors presenting with disseminated or recurrent disease. PROCEDURE: Pediatric patients with brain tumors were identified at Children's Hospital Los Angeles from 2013 to 2015. Clinical characteristics, acute toxicity, and radiotherapy data were abstracted from their medical records. We identified 19 patients who received VMAT CSI. Quality assurance was performed with a cylindrical detector array and ion chamber measurements at the arc junctions. RESULTS: Patients had medulloblastoma or supratentorial primitive neuro-ectodermal tumor (n = 14, 11 high risk), germ cell tumors (two), relapsed neuroblastoma (two), and atypical teratoid/rhabdoid tumor (one). The most common acute toxicity was hematologic, including leukopenia (11% grade [Gr] 2, 26% Gr 3, and 63% Gr 4), anemia (89% Gr 2), and thrombocytopenia (16% Gr 1-2, 26% Gr 3, and 37% Gr 4). Despite leukopenia, we encountered only two Gr 3 infections (urinary tract and lung). The majority required blood products (89% red blood cells and 68% platelets). Weight loss was also common (47% Gr 1 and 26% Gr 2). CONCLUSIONS: VMAT CSI, along with chemotherapy and anesthesia, is feasible with supportive care. Daily image-guided RT improves accuracy and reduces the risk of spinal cord overdose without increasing treatment time. Further research is needed to determine whether reducing doses to organs, such as thyroid, heart, or hippocampus, offsets the risk of increased volume of low-dose irradiation.

Radiotherapy after high-dose chemotherapy with autologous hematopoietic cell rescue: Quality assessment of Head Start III.

BACKGROUND: The use of high-dose chemotherapy with autologous hematopoietic cell rescue (AuHCR) in Head Start III is a potentially curative approach for the management of young children with central nervous system neoplasms. We report the potential influence of quality and timing of radiation therapy on the survival of patients treated on the study. PROCEDURE: Between 2003 and 2009, 220 children with newly diagnosed central nervous system neoplasms were enrolled on the study. Radiation therapy was indicated following AuHCR for children between 6 and 10 years old or those younger than 6 years with residual tumor preconsolidation. Records were received for 42 patients and reviewed to determine adherence to protocol treatment volume and dose guidelines. Of these patients, seven were irradiated prior to consolidation, and additional four patients who initially avoided radiation therapy after AuHCR were subsequently treated at relapse. RESULTS: Of the 31 patients who were fully evaluable, 2 refused radiation therapy until recurrence and 4 progressed between recovery from AuHCR and radiation therapy. Of the remaining 25 patients, 8 had violations in their indication, dose, or treatment volume. All violations occurred in patients under 6 years of age. Two patients could have avoided radiation therapy. There were 6 violations in the 23 patients who received radiation therapy for guideline indications. CONCLUSION: All protocol violations occurred in patients under 6 years of age and were associated with decreased overall survival as was the time to start radiotherapy of greater than 11 weeks. When indicated, starting radiation therapy soon after neutrophil and platelet recovery may improve the outcome for these high-risk children.

Mass spectrometry-based tissue imaging of small molecules.

Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques and provides accurate histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from MSI laboratories around the globe.

Risk of Cerebrovascular Events Among Childhood and Adolescent Patients Receiving Cranial Radiation Therapy: A Pediatric Normal Tissue Effects in the Clinic Normal Tissue Outcomes Comprehensive Review.

PURPOSE: Radiation-induced cerebrovascular toxicity is a well-documented sequelae that can be both life-altering and potentially fatal. We performed a meta-analysis of the relevant literature to create practical models for predicting the risk of cerebral vasculopathy after cranial irradiation. METHODS AND MATERIALS: A literature search was performed for studies reporting pediatric radiation therapy (RT) associated cerebral vasculopathy. When available, we used individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose. RESULTS: The search identified 766 abstracts, 5 of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack, stroke, moyamoya, or arteriopathy. For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9% to 1.3%, 1.8% to 2.7%, and 2.8% to 4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.2%-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1% to 4.2%, 4.5% to 8.6%, and 6.7% to 13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.5%-1.0%). CONCLUSIONS: Risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population.

Investigation of Radiation Oncologists' Awareness of Online Reputation Management.

BACKGROUND: Online reputation management (ORM) is an emerging practice strategy that emphasizes the systematic and proactive monitoring of online reviews relating to one's professional reputation. OBJECTIVE: We developed this survey project to assess whether radiation oncologists are aware of ORM and how it is utilized in their practices. We hypothesized that ORM is largely unknown by most practicing radiation oncologists and that little time is spent actively managing their reputations. METHODS: An online survey was submitted to 1222 radiation oncologists using the Qualtrics research platform. Physician emails were gathered from the American Society for Radiation Oncology member directory. A total of 85 physicians initiated the survey, whereas 76 physicians completed more than or equal to 94% (15/16) of the survey questions and were subsequently used in our analyses. The survey consisted of 15 questions querying practice demographics, patient satisfaction determination, ORM understanding, and activities to address ORM and 1 question for physicians to opt-in to a US $50 Amazon gift card raffle. The survey data were summarized using a frequency table, and data were analyzed using the Chi-square test, Fisher exact test, and Spearman correlation coefficients. RESULTS: We calculated a 7% (85/1222) response rate for our survey, with a completion rate of 89% (76/85). A majority of respondents (97%, 74/76) endorsed being somewhat or strongly concerned about patient satisfaction (P<.001). However, 58% (44/76) of respondents reported spending 0 hours per week reviewing or managing their online reputation and 39% (30/76) reported spending less than 1 hour per week (P<.001). A majority of physicians (58%, 44/76) endorsed no familiarity with ORM (P<.001) and 70% (53/76) did not actively manage their online reputation (P<.001). Although 83% (63/76) of respondents strongly or somewhat believed that patients read online reviews (P<.001), 57% (43/76) of respondents did not check their online reviews (P=.25) and 80% (61/76) endorsed never responding to online reviews (P<.001). Moreover, 58% (44/76) of the respondents strongly or somewhat supported the idea of managing their online reputation going forward (P=.001). In addition, 11 out of the 28 pairs of questions asked in our correlation studies reached statistical significance. Degree of concern for patient satisfaction and the notion of managing one's ORM going forward were the 2 most frequently correlated topics of statistical significance in our analyses. CONCLUSIONS: ORM is presently under-recognized in radiation oncology. Although most practitioners are concerned about patient satisfaction, little effort is directed toward the internet on this matter. ORM offers an area of practice improvement for many practicing radiation oncologists.

Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature.

Primary intracranial germ cell tumors are rare, representing less than 5% of all central nervous system tumors. Overall, the majority of germ cell tumors are germinomas and approximately one-third are non-germinomatous germ cell tumors (NGGCT), which include teratoma, embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or mixed malignant germ cell tumor. Germ cell tumors may secrete detectable levels of proteins into the blood and/or cerebrospinal fluid, and these proteins can be used for diagnostic purposes or to monitor tumor recurrence. Germinomas have long been known to be highly curable with radiation therapy alone. However, many late effects of whole brain or craniospinal irradiation have been well documented. Strategies have been developed to reduce the dose and volume of radiation therapy, often in combination with chemotherapy. In contrast, patients with NGGCT have a poorer prognosis, with about 60% cured with multimodality chemoradiation. There are no standard approaches for relapsed germ cell tumors. Options may be limited by prior treatment. Radiation therapy has been utilized alone or in combination with chemotherapy or high-dose chemotherapy and transplant. We discuss two cases and review options for frameless radiosurgery or fractionated radiotherapy.