Renal remodeling after abdominal radiation therapy: parenchymal and functional changes.

OBJECTIVE: The purpose of this study was to quantify changes in renal length, volume, and function over time after upper abdominal radiation therapy. MATERIALS AND METHODS: Imaging and clinical data were retrospectively reviewed for 27 adults with abdominal radiation therapy between 2001 and 2012. All had two kidneys, radiation exposure to one kidney, and survival of at least 1 year after therapy. Mean prescribed dose was 52 ± 9 Gy to extrarenal targets. Length and volume of exposed and unexposed kidneys were measured on CT scans before treatment (baseline) and at intervals 0-3, 3-6, 6-12, 12-24, 24-36, and more than 36 months after completion of radiotherapy. Serum creatinine was correlated at each interval. Mixed-models ANOVA was used to test renal length and volume, serum creatinine, and time against multiple models to assess for temporal effects; specific time intervals were compared in pairwise manner. RESULTS: Mean follow-up duration was 35 months (range, 5-94 months). Exposed kidney length and volume progressively decreased from baseline throughout follow-up, with mean loss of 23% (p < 0.001) and 47% (p < 0.001), respectively. Slight increase in unexposed kidney length was not significant. Mean serum creatinine increased from 0.86 ± 0.18 mg/dL at baseline to 1.12 ± 0.27 mg/dL at 12-24 months (p < 0.001), then stabilized. CONCLUSION: Kidneys exposed to radiation during therapy of adjacent malignancies exhibited continuous progressive atrophy for the entire follow-up period, nearly 8 years. Volume changes were twice as great as length changes. Renal function also declined. To accurately interpret follow-up studies in cancer survivors, radiologists should be aware of the potential for progressive renal atrophy, even many years after radiation therapy.

Imaging effects of radiation therapy in the abdomen and pelvis: evaluating "innocent bystander" tissues.

Accurate interpretation of posttherapeutic images obtained in radiation oncology patients requires familiarity with modern radiation therapy techniques and their expected effects on normal tissues. Three-dimensional conformal external-beam radiation therapy techniques (eg, intensity-modulated radiation therapy, stereotactic body radiation therapy), although they are designed to reduce the amount of normal tissue exposed to high-dose radiation, inevitably increase the amount of normal tissue that is exposed to low-dose radiation, with the potential for resultant changes that may evolve over time. Currently available internal radiation therapy techniques (eg, arterial radioembolization for hepatic malignancies, brachytherapy for prostate cancer and gynecologic cancers) also carry risks of possible injury to adjacent nontargeted tissues. The sensitivity of tissues to radiation exposure varies according to the tissue type but is generally proportional to the rate of cellular division, with rapidly regenerating tissues such as intestinal mucosa being the most radiosensitive. The characteristic response to radiation-induced injury likewise varies according to tissue type, with atrophy predominating in epithelial tissue whereas fibrosis predominates in stromal tissue. Moreover, changes in irradiated tissues evolve over time: In the liver, decreased attenuation at computed tomography and increased signal intensity at T2-weighted magnetic resonance imaging reflect hyperemia and edema in the early posttherapeutic period; later, veno-occlusive changes alter the hepatic enhancement pattern; and finally, fibrosis develops in some patients. In the small bowel, wall thickening and mucosal hyperenhancement predominate initially, whereas luminal narrowing is the most prominent feature of chronic enteropathy. Correlation of posttherapeutic images with images used for treatment planning may be helpful when interpreting complex cases.

Operational Ontology for Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical and Research Use of Real-World Data From Patients Treated for Cancer.

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships. METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- and intra-institutional databases from EHRs. The Big Data Science Committee adopted an iterative, cyclical approach to engaging stakeholders beyond its membership to optimize the integration of diverse perspectives from the community. RESULTS: We developed the Operational Ontology for Oncology (O3), which identified 42 key elements, 359 attributes, 144 value sets, and 155 relationships ranked in relative importance of clinical significance, likelihood of availability in EHRs, and the ability to modify routine clinical processes to permit aggregation. Recommendations are provided for best use and development of the O3 to 4 constituencies: device manufacturers, centers of clinical care, researchers, and professional societies. CONCLUSIONS: O3 is designed to extend and interoperate with existing global infrastructure and data science standards. The implementation of these recommendations will lower the barriers for aggregation of information that could be used to create large, representative, findable, accessible, interoperable, and reusable data sets to support the scientific objectives of grant programs. The construction of comprehensive "real-world" data sets and application of advanced analytical techniques, including artificial intelligence, holds the potential to revolutionize patient management and improve outcomes by leveraging increased access to information derived from larger, more representative data sets.

Low dose rate radiosensitization of hepatocellular carcinoma in vitro and in patients.

Transarterial radioembolization (TARE) with (90)Y microspheres delivers low dose rate radiation (LDR) to intrahepatic tumors. In the current study, we examined clonogenic survival, DNA damage, and cell cycle distribution in hepatocellular carcinoma (HCC) cell lines treated with LDR in combination with varying doses and schedules of 5-fluorouracil (5-FU), gemcitabine, and sorafenib. Radiosensitization was seen with 1 to 3 µM 5-FU (enhancement ratio 2.2-13.9) and 30 to 100 nM gemcitabine (enhancement ratio 1.9-2.9) administered 24 hours before LDR (0.26 Gy/h to 4.2 Gy). Sorafenib radiosensitized only at high concentrations (3-10 µM) when administered after LDR. For a given radiation dose, greater enhancement was seen with LDR compared to standard dose rate therapy. Summarizing our clinical experience with low dose rate radiosensitization, 13 patients (5 with HCC, 8 with liver metastases) were treated a total of 16 times with TARE and concurrent gemcitabine. Six partial responses and one complete response were observed with a median time to local failure of 7.1 months for all patients and 9.9 months for patients with HCC. In summary, HCC is sensitized to LDR with clinically achievable concentrations of gemcitabine and 5-FU in vitro. Encouraging responses were seen in a small cohort of patients treated with TARE and concurrent gemcitabine. Future studies are needed to validate the safety and efficacy of this approach.

Interobserver variability in target definition for hepatocellular carcinoma with and without portal vein thrombus: radiation therapy oncology group consensus guidelines.

PURPOSE: Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. METHODS AND MATERIALS: Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. RESULTS: Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). CONCLUSIONS: In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning, especially if differential dosing is contemplated. Guidelines for HCC GTV contouring are recommended.

A pilot study of diffusion-weighted MRI in patients undergoing neoadjuvant chemoradiation for pancreatic cancer.

PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (> 90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (> 90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1 months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10(- 5) mm(2)/s (n = 3) in responding patients (> 90% tumor cell destruction) compared to 125 × 10(- 5) mm(2)/s (n = 4) in non-responding patients (> 10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.