Posttreatment Computed Tomography Scans Research Articles

Mucolytic treatment of chronic rhinosinusitis in a murine model of primary ciliary dyskinesia.

Background: Genetic defects in motile cilia cause primary ciliary dyskinesia (PCD), a rare disease with no specific therapeutics. Individuals with PCD often have impaired fertility and laterality defects and universally suffer from upper and lower airway diseases. Chronic rhinosinusitis is a universal feature of PCD, and mucus accumulation and subsequent infections of the sinonasal cavity cause significant morbidity in individuals with PCD. Despite this, there are no approved treatments that specifically target mucus. Objective: The goals of this study were to determine whether computed tomography (CT) imaging could be used to quantify mucus accumulation and whether the use of a mucolytic agent to reduce disulfide cross-links present in mucins would improve the effectiveness of nasal lavage at removing mucus in a murine model of PCD. Methods: Adult mice with a deletion of the axonemal dynein Dnaic1 were imaged using CT scanning to characterize mucus accumulation. The animals were then treated by nasal lavage with saline, with/without the disulfide-reducing agent tris(2-carboxyethyl)phosphine. Post-treatment CT scans were used to quantify improvement in the sinonasal cavity. Results: Mucus accumulation in the nasal cavity was readily quantified by CT. Compared to sham-treated control animals, nasal lavage with/without a mucolytic agent resulted in a significant reduction of accumulated mucus (p < 0.01). Treatment with the mucolytic agent showed a greater reduction of accumulated mucus than treatment with saline alone. Conclusion: The results suggest that inclusion of a mucolytic agent may increase the effectiveness of nasal lavage at reducing mucus burden in PCD.

Explainable machine learning model for predicting skeletal muscle loss during surgery and adjuvant chemotherapy in ovarian cancer.

Skeletal muscle loss during treatment is associated with poor survival outcomes in patients with ovarian cancer. Although changes in muscle mass can be assessed on computed tomography (CT) scans, this labour-intensive process can impair its utility in clinical practice. This study aimed to develop a machine learning (ML) model to predict muscle loss based on clinical data and to interpret the ML model by applying SHapley Additive exPlanations (SHAP) method. This study included the data of 617 patients with ovarian cancer who underwent primary debulking surgery and platinum-based chemotherapy at a tertiary centre between 2010 and 2019. The cohort data were split into training and test sets based on the treatment time. External validation was performed using 140 patients from a different tertiary centre. The skeletal muscle index (SMI) was measured from pre- and post-treatment CT scans, and a decrease in SMI≥5% was defined as muscle loss. We evaluated five ML models to predict muscle loss, and their performance was determined using the area under the receiver operating characteristic curve (AUC) and F1 score. The features for analysis included demographic and disease-specific characteristics and relative changes in body mass index (BMI), albumin, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The SHAP method was applied to determine the importance of the features and interpret the ML models. The median (inter-quartile range) age of the cohort was 52 (46-59) years. After treatment, 204 patients (33.1%) experienced muscle loss in the training and test datasets, while 44 (31.4%) patients experienced muscle loss in the external validation dataset. Among the five evaluated ML models, the random forest model achieved the highest AUC (0.856, 95% confidence interval: 0.854-0.859) and F1 score (0.726, 95% confidence interval: 0.722-0.730). In the external validation, the random forest model outperformed all ML models with an AUC of 0.874 and an F1 score of 0.741. The results of the SHAP method showed that the albumin change, BMI change, malignant ascites, NLR change, and PLR change were the most important factors in muscle loss. At the patient level, SHAP force plots demonstrated insightful interpretation of our random forest model to predict muscle loss. Explainable ML model was developed using clinical data to identify patients experiencing muscle loss after treatment and provide information of feature contribution. Using the SHAP method, clinicians may better understand the contributors to muscle loss and target interventions to counteract muscle loss.

Optimized Adaptive Radiotherapy with Individualized Plan Library for Muscle-Invasive Bladder Cancer Using Internal Target Volume Generation.

Simple SummaryThe bladder is a mobile target and is subject to filling variation. This poses a considerable challenge for effective radiotherapy (RT) delivery. We applied an internal target volume to the plan library to resolve intra-fractional errors caused by bladder filling during treatment. Adaptive radiotherapy using ITV is easy to perform and a feasible treatment approach. In this study, image-guided RT-based adaptive RT showed good survival outcomes with a high local control rate.The bladder is subject to filling variation, which poses a challenge to radiotherapy (RT) delivery. We aimed to assess feasibility and clinical outcomes in patients with bladder cancer treated with adaptive RT (ART) using individualized plan libraries. We retrospectively analyzed 19 patients who underwent RT for muscle-invasive bladder cancer (MIBC) in 2015–2021. Four planning computed tomography (CT) scans were acquired at 15-min intervals, and a library of three intensity-modulated RT plans were generated using internal target volumes (ITVs). A post-treatment cone-beam CT (CBCT) scan was acquired daily to assess intra-fraction filling and coverage. All patients completed the treatment, with 408 post-treatment CBCT scans. The bladder was out of the planning target volume (PTV) range in 12 scans. The volumes of the evaluated PTV plans were significantly smaller than those of conventional PTV. The 1-year and 2-year overall survival rates were 88.2% and 63.7%, respectively. Of eight cases that experienced recurrence, only two developed MIBC. There were no grade 3 or higher RT-related adverse events. ART using plan libraries and ITVs demonstrated good survival outcomes with a high local control rate. Irradiated normal tissue volume and treatment margins may be reduced through this approach, potentially resulting in lower toxicity rates.

Locoregional failure after postoperative flank irradiation for nephroblastoma: Results from the French cohort of the SIOP-2001 trial.

To describe locoregional failure (LRF) after postoperative flank radiotherapy (RT) among French patients with nephroblastoma included in the Société Internationale d'Oncologie Pédiatrique (SIOP)-2001 protocol. In selected SIOP-2001 patients, planning with simulation computed tomography (CT) scan and posttreatment CT scan demonstrating LRF were registered and analyzed. LRF was contoured and classified as in-field, marginal or out-of-field according to dose distribution. Total 316 French SIOP-2001 patients were treated with postoperative RT. Three patients with nephroblastoma developed LRF after flank RT. All failures were located within the retroperitoneum. In two patients, the relapse was within the RT field and in one it was classified as marginal. LRF after postoperative flank RT for nephroblastoma was rare and exclusively situated in the retroperitoneum. These results point out this region as the most at risk of local relapse. A prospective evaluation of a target volume restricted to the retroperitoneum allowing the use of modern and highly conformal radiation techniques in order to decrease dose to normal tissues shall be encouraged.

Radiation-Induced Vaginal Stenosis in Patients With Locally Advanced Cervical Cancer

Vaginal stenosis (VS) after definitive radiation therapy (RT) to the pelvis for cervical cancer is a common toxicity that can have detrimental effects on quality of life and can limit surveillance physical examinations. Quantitative measurements of VS are lacking. We investigated radiographic vaginal dimensional changes after RT for cervical cancer as a potential noninvasive marker for VS with the hypothesis that RT would be associated with reduced apical vaginal width on computed tomography (CT) imaging.We retrospectively identified 104 patients with locally advanced cervical cancer treated with definitive RT at our institution who had pre- and post-treatment CT scans available for analysis. Post-treatment scans were acquired within one year of therapy completion. We measured the transverse width at the vaginal apex, mid-canal, and introitus, as well as superior-inferior vaginal length. Changes in mean dimensional measurements were compared between pre- and post-treatment scans. We also compared mean dimensional measurements between CT and MRI where available. Nonparametric paired Wilcoxon rank sum tests were used to test for differences in measurements. Two observers made independent measurements on 15 consecutive patients and interrater reliability was assessed by calculating the intraclass correlation coefficient (ICC). Multivariable linear regression was used to identify covariables associated with change in apical width. Covariables included menopausal status, smoking history, gravida/para status, FIGO stage, tumor grade, and tumor histology. We used a backward model selection technique with stepwise removal of covariables not meeting a significance threshold of P ≤0.20.Mean transverse width at the vaginal apex was 5.87 cm on pre-treatment CT and 5.10 cm on post-treatment CT, with a mean difference of -0.77 cm (P < 0.001). There was also a statistically significant difference in width at the mid-vaginal canal although this was of smaller magnitude (pre-treatment 4.34 cm, post-treatment 4.14 cm, P < 0.001). There were no differences in width at the introitus or with respect to vaginal length. The ICC for independent apical measurements between two raters was 0.91 (95% CI 0.75, 0.97), indicating good-excellent agreement. Apical width was slightly smaller when measured on MRI compared to CT, although a small number of available paired MRI scans limited this analysis. On multivariable linear regression, menopause was correlated with less change in apical width (P = 0.001). Conversely, a smoking history was associated with increased dimensional reduction at the apex (P = 0.04). Number of deliveries and tumor stage were not significant predictors for dimensional change.Radiation-induced vaginal stenosis after definitive RT for cervical cancer treatment was demonstrable as apical and mid-vaginal constrictions on CT imaging that were more pronounced with a smoking history and less evident in post-menopausal women.C.W. Williamson: None. N.V. Kotha: None. K. Morris: None. R. Simoes-Torigoe: None. M. Kohanfars: None. J. Chen: None. B. Li: None. S. Vaitkus: None. M.T. Makale: None. F. Talke: None. J.S. Mayadev: Consultant; Astra Zeneca, NRG Oncology, GOG Foundation, Varian Medical Systems; NRG Oncology Cervix Co-Chair, GOG Foundation Board.

Radiological evaluation of response to treatment in hepatobiliary fascioliasis

PurposeIn this study, we aimed to evaluate the computed tomography (CT) findings of Fasciola hepatica infestations on initial and follow-up imagings after treatment, and also to describe the role of CT during diagnosis. MethodsIn this retrospective study, patients with a diagnosis of fascioliasis by clinical and laboratory examination who underwent initial and follow-up contrast-enhanced abdominal CT scans after treatment (a single oral dose of 10mg/kg Triclabendazole) were included. The CT scans were evaluated regarding liver and spleen sizes, portal and splenic vein diameters, involved hepatic segment numbers and involvement patterns, the presence of focal perihepatic hyperdensity, gallbladder wall thickening, dilatation of the intrahepatic biliary tract, periportal-right subdiaphragmatic lymphadenopathy, hepatic subcapsular and intra-abdominal bleeding, and perihepatic/intraabdominal free fluid. Initial (pre-treatment) and post-treatment CT scans (average 25 months after the treatment) were compared with for these features. ResultsA total of 36 patients with a mean age of 39.28±14.64 [15-83] years, were included in this study. After treatment, marked improvement in liver parenchymal involvement, biliary system findings, hepatomegaly-splenomegaly, periportal-peridiaphragmatic lymphadenopathy, and hepatic subcapsular hematoma were detected and focal perihepatic hyperdensity, free intraperitoneal fluid disappeared. ConclusionContrast-enhanced abdominal CT can be used in the diagnosis and post-treatment follow-up of fascioliasis. Awareness of intrahepatic/extrahepatic lesions and all the complications of fascioliasis can greatly aid the diagnosis and also evaluation of the response to treatment.

Predictive radiomics signature for treatment response to nivolumab in patients with advanced renal cell carcinoma.

The anti-programmed cell death protein-1 (PD-1) immune checkpoint inhibitor nivolumab is currently approved for the treatment of patients with metastatic renal cell carcinoma (mRCC); approximately 25% of patients respond. We hypothesized that we could identify a biomarker of response using radiomics to train a machine learning classifier to predict nivolumab response outcomes. Patients with mRCC of different histologies treated with nivolumab in a single institution between 2013 and 2017 were retrospectively identified. Patients were labelled as responders (complete response [CR]/partial response [PR]/durable stable disease [SD]) or non-responders based on investigator tumor assessment using RECIST 1.1 criteria. For each patient, lesions were contoured from pre-treatment and first post-treatment computed tomography (CT) scans. This information was used to train a radial basis function support vector machine classifier to learn a prediction rule to distinguish responders from non-responders. The classifier was internally validated by a 10-fold nested cross-validation. Thirty-seven patients were identified; 27 (73%) met the inclusion criteria. One hundred and four lesions were contoured from these 27 patients. The median patient age was 56 years, 78% were male, 89% had clear-cell histology, 89% had prior nephrectomy, and 89% had prior systemic therapy. There were 19 responders vs. eight non-responders. The lesions selected were lymph nodes (60%), lung metastases (23%), and renal/adrenal metastases (17%). For the classifier trained on the baseline CT scans, 69% accuracy was achieved. For the classifier trained on the first post-treatment CT scans, 66% accuracy was achieved. The set of radiomic signatures was found to have limited ability to discriminate nivolumab responders from non-responders. The use of novel texture features (two-point correlation measure, two-point cluster measure, and minimum spanning tree measure) did not improve performance.

Prognostic implications of body composition change during primary treatment in patients with ovarian cancer: A retrospective study using an artificial intelligence-based volumetric technique

ObjectiveTo investigate the impact of changes in body composition during primary treatment on survival outcomes in patients with epithelial ovarian cancer (EOC). MethodsWe retrospectively identified patients diagnosed with EOC between 2010 and 2019. Using an artificial intelligence-based tool, the volumes of skeletal muscle, visceral fat, and subcutaneous fat were measured automatically at the waist level from pre-treatment and post-treatment computed tomography scans. Associations between changes in body mass index (BMI) and volume of each body composition component and survival outcomes were evaluated. ResultsA total of 208 patients were included. A significant decrease in BMI and waist volumes of skeletal muscle and visceral fat was observed during the primary treatment. Patients with BMI loss ≥5% showed significantly worse progression-free survival (PFS) and overall survival (OS) than those with BMI loss <5%. In multivariate analyses adjusting for clinicopathologic factors, BMI loss ≥5% was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.565; 95% CI, 1.074–2.280; P = 0.020) and OS (adjusted HR, 2.754; 95% CI, 1.382–5.488; P = 0.004). Meanwhile, both muscle loss ≥10% and visceral fat loss ≥20% were associated with an increased mortality rate but did not affect disease recurrence. In multivariate analyses, muscle loss ≥10% (adjusted HR, 2.069; 95% CI, 1.055–4.058; P = 0.034) and visceral fat loss ≥20% (adjusted HR, 2.292; 95% CI, 1.023–5.133; P = 0.044) were poor prognostic factors for OS. Consistent results were observed in the advanced-stage disease subgroup (n = 173). ConclusionsChanges in BMI and waist volume of skeletal muscle and visceral fat were associated with survival outcomes in patients with EOC.

The surgical perspective in neoadjuvant immunotherapy for resectable non-small cell lung cancer.

BackgroundThe recent novel conception of neoadjuvant immunotherapy has generated interest among surgeons worldwide, especially the lack of experience involving surgical treatment for the neoadjuvant immunotherapy population.MethodsPatients with non-small cell lung cancer (NSCLC), who underwent neoadjuvant immunotherapy or chemo-immunotherapy, were retrospectively collected between September 2018 and April 2020. Demographic data, pathological and clinical features, therapeutic regimens and outcome data of all individuals were collected by retrospective chart review. Operative details, information of neoadjuvant therapy, were also abstracted.ResultsIn total, 31 patients were included in the final analysis. The patients’ median age was 61 years. In total, 29 of the patients were males, while 2 were females. Patients received a median of 3 doses before resection. The median duration from final treatment to surgery was 34 days. After neoadjuvant treatment, post-treatment computed tomography scan showed that 24 patients had partial response. In total, 12 of 31 patients had a major pathological response, 15 pathological downstaging. Three patients had no residual viable tumor. A positive surgical margin was identified in 7 cases. One or more postoperative complications occurred in 18 of all 31 patients. In total, 26 patients underwent next-generation sequencing before surgery in total. Among them, 2 patients were detected STK11 mutations, none of whom had a major pathological response by final pathological examination.ConclusionsPulmonary resection after neoadjuvant immunotherapy or chemo-immunotherapy for resectable NSCLC appears to be safe with low operative mortality and morbidity rate in the current population.

Predicting the coagulation volume induced by microwave ablation of hepatocellular carcinoma: the role of deposited energy, ex-vivo bovine liver charts and central hyperdense area on post-treatment CT

Purpose To study the correlation between the overall coagulation zone (A) attained in percutaneous microwave ablation (MWA) of hepatocellular carcinomas (HCC) and: (1) the hyperdense zone (C) visible in the central part of zone A on post-treatment unenhanced CT scans; (2) the deposited energy; (3) the coagulation zones observed on ex-vivo bovine liver. Materials and methods The post-procedural computed tomography (CT) scans of HCCs treated with a single energy deployment through the same 2450 MHz MWA system were retrospectively analyzed, retrieving the dimensions of A and C zones and the deposited energy (E). Ex-vivo bovine liver MWA with the same system were performed and analyzed to determine the same quantities by gross-pathologic examination and CT imaging. Results A total of 101 HCC treatments were analyzed. The average coagulation volumes increased linearly with deposited energy (1.11 cc/kJ, R 2 = 0.90, 4.2 kJ ≤ E ≤ 48 kJ), similarly to ex-vivo findings (1.38 cc/kJ, R 2 =0.97, 7.2 kJ ≤ E ≤ 144 kJ). The long axis (L) and short axis (D) of zones A and C held a fairly constant ratio both in-vivo (LC/LA=0.43 ± 0.13; DC/DA=0.42 ± 0.10) and ex-vivo (LC/LA = 0.49 ± 0.07; DC/DA = 0.28 ± 0.06). Conclusions The average dimensions of the ablation zone induced by the considered system on HCC increase linearly with the deposited energy and are fairly well predicted by the corresponding ex-vivo dimensions. The ratio between each linear dimension of A and C zones was found to be roughly constant over a large deposited energy span, both ex-vivo and in-vivo.

Integration of Risk Survival Measures Estimated From Pre- and Posttreatment Computed Tomography Scans Improves Stratification of Patients With Early-Stage Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy

To predict overall survival of patients receiving stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (ES-NSCLC), we developed a radiomic model that integrates risk of death estimates and changes based on pre- and posttreatment computed tomography (CT) scans. We hypothesize this innovation will improve our ability to stratify patients into various oncologic outcomes with greater accuracy. Two cohorts of patients with ES-NSCLC uniformly treated with SBRT (a median dose of 50 Gy in 4-5 fractions) were studied. Prediction models were built on a discovery cohort of 100 patients with treatment planning CT scans, and then were applied to a separate validation cohort of 60 patients with pre- and posttreatment CT scans for evaluating their performance. Prediction models achieved a c-index up to 0.734 in predicting survival outcomes of the validation cohort. The integration of the pretreatment risk of survival measures (risk-high vs risk-low) and changes (risk-increase vs risk-decrease) in risk of survival measures between the pretreatment and posttreatment scans further stratified the patients into 4 subgroups (risk: high, increase; risk: high, decrease; risk: low, increase; risk: low, decrease) with significant difference (χ2 = 18.549, P= .0003, log-rank test). There was also a significant difference between the risk-increase and risk-decrease groups (χ2 = 6.80, P = .0091, log-rank test). In addition, a significant difference (χ2 = 7.493, P = .0062, log-rank test) was observed between the risk-high and risk-low groups obtained based on the pretreatment risk of survival measures. The integration of risk of survival measures estimated from pre- and posttreatment CT scans can help differentiate patients with good expected survival from those who will do more poorly following SBRT. The analysis of these radiomics-based longitudinal risk measures may help identify patients with early-stage NSCLC who will benefit from adjuvant treatment after lung SBRT, such as immunotherapy.

Dosimetric evaluation of image-guided radiation therapy for prostate cancer

The aim of this study was to investigate the dosimetric accuracy of imaged-guided radiation therapy for prostate patients using the in-room computed tomography (CT) target localization technique. A Siemens CT-on-rails system was used for patient setup and target localization for intensity-modulated radiation therapy (IMRT) of prostate cancer. Fifteen previously treated prostate patients were included in this retrospective study. CT-on-Rails scans were performed before and after the IMRT treatment under local IRB approval. A total of 15 original simulation CT scans and 98 post-treatment CT scans were contoured by the same oncologist to delineate the prostate target, bladder, and rectum. IMRT plans were generated on the original simulation CTs and the same MUs and leaf sequences were used to compute the dose distributions using post-treatment CTs. Varian Velocity deformable registration was used for the summation of the fractional doses and the cumulative doses were compared with the planned doses. For the 15 patients investigated, the mean isocenter shift was up to 4.0 mm in the left-right direction, 5.9 mm in the anterior-posterior direction and 5.6 mm in the superior-inferior direction due to interfractional organ motion. The mean rectal volume varied from 0.6 to 1.73 times and the mean bladder volume varied from 0.59 to 3.65 times between simulation and the end of treatment. The prescription dose to 95% of the PTV, Dp, was set to 76 Gy for all treatment plans. The dose to 95% of the clinical treatment volume (CTV), D95, was 74.0 to 77.6 Gy and the minimum CTV dose, Dmin, was 61.0 to 71.6 Gy, respectively, in the cumulative dose distributions. Detailed analyses showed that 7.1% of the treatment fractions had cold spots (< 85% of Dp) in the peripheral CTV, leading to Dmin < 64 Gy in the cumulative dose distributions for 4 patients. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions while the bladder dose was much improved in 82.7% of the treatment fractions. The current IGRT procedure for patient setup and target localization using rigid-body registration based on contour/anatomy matching is effective for population-based PTV margins. For a small group of patients, specific PTV margins and/or real-time target monitoring/tracking will be necessary due to significant prostate deformation/rotation caused by inter- and intrafractional bladder and rectal volume variation.

Pre-treatment CT imaging in stage IIIA lung cancer: Can we predict local recurrence after definitive chemoradiotherapy?

ObjectivesThe aim of this study was to delineate computed tomography (CT) features of stage IIIA non-small cell lung cancers on pre-treatment staging studies and identify features that could predict local recurrence after definitive concurrent chemoradiotherapy. Materials and methodsWe retrospectively reviewed pre- and post-treatment CT scans for 91 patients with Stage IIIA non-small cell lung cancer undergoing definitive concurrent chemoradiotherapy. Pre-treatment CT qualitative features were evaluated by consensus. The primary endpoint was local recurrence as determined on post-treatment CT scans along with the radiotherapy fields. Local recurrence was defined as intrathoracic in-field and marginal as opposed to out-of-field failures. Competing risk regressions were used to examine associations between CT features and recurrence. ResultsThe median follow-up was 51.5 months (range 2.4–111.2). Median overall survival was 25.6 months (95% CI: 20.4–30). At last follow-up, 72 (79.1%) patients had died, 48 (52.7%) had in-field recurrence, and 30 (32.9%) presented with out-of-field recurrence. On pre-treatment CT scans, tumors presenting as pulmonary consolidations (hazard ratio = 2.34, 95% CI: 1.05–5.22; p 0.038) were more likely to have in-field failure. Tumors with 50–100% necrosis (hazard ratio = 0.15, 95% CI: 0.02–1.06) were associated with decreased out-of-field failure (overall p = 0.038). However, these were rare features in our sample which limit the ability of these features to be associated with such outcomes. ConclusionsPre-treatment CT features alone are limited in predicting locoregional recurrence. Larger studies using quantitative tools are needed to predict such outcomes.

Radiographic and Serologic Predictors of Pathologic Major Response to Preoperative Therapy for Pancreatic Cancer.

We sought to identify potential radiologic and serologic markers of pancreatic tumor response to therapy, using pathologic major response (pMR) as the objective endpoint. We previously demonstrated that a pMR to preoperative therapy, defined as detection of <5% viable cancer cells in the surgical specimen on histopathological analysis, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC). Pretreatment and posttreatment computed tomography scans of consecutive patients who received preoperative chemotherapy and/or (chemo)radiation before pancreatectomy for PDAC between January 2010 and December 2018 were rereviewed. Response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, other radiographic changes in tumor size and anatomic extent, and posttreatment CA 19-9 levels were compared between patients who did and did not have a pMR on final histopathologic analysis of their surgical specimens. A total of 290 patients with localized PDAC underwent pancreatectomy between 2010 and 2018 after receiving preoperative chemotherapy (n = 36; 12%), (chemo)radiation (n = 87; 30%), or both (n = 167; 58%). Among them, 28 (10%) experienced pMR, including 9 (3.1%) who experienced pathologic complete response. On multivariable logistic regression, low posttreatment CA 19-9 level, RECIST partial response, and reduction in tumor volume were confirmed to be independently associated with pMR (P < 0.01). We identified serologic and radiographic indicators of pMR that could help inform the delivery of preoperative therapy to patients with PDAC.

Asymptomatic Late-phase Radiographic Changes Among Chest-Wall Patients Are Associated With a Proton RBE Exceeding 1.1

Clinical practice assumes a fixed proton relative biological effectiveness (RBE) of 1.1, but invitro experiments demonstrate higher RBEs at the distal edge of the proton spread-out Bragg peak, that is, in a region that falls within the lung for chest-wall patients. We performed retrospective qualitative and quantitative analyses of lung-density changes-indicative of asymptomatic fibrosis-for chest-wall patients treated with protons or photons. Our null hypothesis was that, assuming a fixed RBE of 1.1, these changes would be the same for the 2 cohorts, supporting current RBE practice. Our alternative hypothesis was that radiographic abnormalities would be greater for the proton cohort, suggesting an RBE > 1.1. We analyzed follow-up computed tomography (CT) scans for 20 proton and photon patients. All were prescribed 50.4Gy (RBE) in 28 fractions, assuming a fixed RBE of 1.1 for protons and 1 for photons. Deformable registrations enabled us to calculate density changes in the normal lung, specifically (1) median Hounsfield unit (HU) values among posttreatment CT scans and (2) changes in median HU values between pretreatment and posttreatment CT scans, both as a function of grays (RBE). In addition, qualitative abnormality grading was performed by a radiologist. Proton patients exhibited higher values of HU/Gy (RBE) (endpoint 1) and ΔHU/Gy (RBE) (endpoint 2): P=.049 and P=.00019, respectively, were obtained (likelihood ratio tests of full linear mixed-effects models against models without "modality"). Furthermore, qualitative radiologic scoring indicated a significant difference between the cohorts (Wilcoxon P=.018; median score, 3 of 9 for protons and 1.5 of 9 for photons). Our data support the hypothesis that the proton RBE for lung-density changes exceeds 1.1. This RBE elevation could be attributable to (1) the late, normal tissue endpoint that we consider or (2) end-of-range proton linear energy transfer elevation-or a combination of the two. Regardless, our results suggest that variations in proton RBE prove important invivo as well as invitro.

Early morphological change for predicting outcome in metastatic colorectal cancer after regorafenib.

Background and ObjectiveIt is unclear whether early morphological change (EMC) is a predictive marker for regorafenib in metastatic colorectal cancer (mCRC). Therefore, the present study investigated whether EMC can predict the outcome of mCRC patients receiving regorafenib.ResultsThis study evaluated 68 patients. Among 52 patients with lung metastasis, 16 (31%) had cavity formation (CF). The median progression-free survival (PFS) and overall survival (OS) in patients with/without CF were 4.2/2.4 months (p<0.01) and 9.2/6.5 months (p=0.09), respectively. Among 45 patients with liver metastasis, 14 (31%) had active morphological response (MR). The median PFS and OS in patients with/without active MR were 5.3/2.4 months (p<0.01) and 13.6/6.9 months (p=0.02), respectively. Overall, 25 patients (37%) had EMC. The median PFS and OS in patients with/without EMC were 5.3/2.1 months (p<0.01) and 13.3/6.1 months (p<0.01), respectively.Materials and MethodsThis retrospective study included mCRC patients with lung and/or liver metastases receiving regorafenib. CF in lung metastasis and MR in liver metastasis were evaluated at the first post-treatment computed tomography scan. EMC was determined as CF and/or active MR. We compared PFS and OS between patients with and those without EMC.ConclusionsEMC could be a useful predictive marker for regorafenib in mCRC.

Sequential CT Findings in Patients With Non–small-cell Lung Cancer Receiving Nivolumab

BackgroundNivolumab is a novel immunotherapy that was recently approved for treatment of advanced non–small-cell lung cancer (NSCLC). Patients treated with checkpoint inhibitors may show variable computed tomography (CT) features on follow-up imaging, and it is unclear how reliable conventional response criteria are to determine patient management and outcomes. We report the spectrum of sequential CT findings in patients with advanced stage lung cancer who received nivolumab in an effort to better inform appropriate imaging strategies. Materials and MethodsWe identified all patients at our institution with advanced NSCLC who received nivolumab. Pre- and posttreatment CT scans were reviewed and categorized based on radiographic response to therapy. Demographic data as well as survival data were recorded. ResultsThere were 34 patients with advanced NSCLC who received nivolumab with sufficient follow-up data. Nineteen patients were classified as responders to treatment; 6 (32%) of 19 showed improvement on their initial follow-up CT and had an average survival of 11.2 months, whereas 13 (68%) of 19 responders initially had stable or progressive disease on CT with an average survival of 11.6 months. Fifteen patients were classified as nonresponders to treatment with an average survival of 3.4 months. ConclusionNovel immunotherapies such as nivolumab mechanistically differ from conventional chemotherapy. Some patients have improved survival despite initial radiographic progression of disease. Our findings underscore the heterogeneous radiographic appearance at follow-up CT in patients with lung cancer who ultimately respond to nivolumab.

Prediction of Blood-Brain Barrier Disruption and Intracerebral Hemorrhagic Infarction Using Arterial Spin-Labeling Magnetic Resonance Imaging.

Arterial spin-labeling magnetic resonance imaging is sensitive for detecting hyperemic lesions (HLs) in patients with acute ischemic stroke. We evaluated whether HLs could predict blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) in acute ischemic stroke patients. In a retrospective study, arterial spin-labeling was performed within 6 hours of symptom onset before revascularization treatment in 25 patients with anterior circulation large vessel occlusion on baseline magnetic resonance angiography. All patients underwent angiographic procedures intended for endovascular therapy and a noncontrast computed tomography scan immediately after treatment. BBB disruption was defined as a hyperdense lesion present on the posttreatment computed tomography scan. A subacute magnetic resonance imaging or computed tomography scan was performed during the subacute phase to assess HTs. The relationship between HLs and BBB disruption and HT was examined using the Alberta Stroke Program Early Computed Tomography Score locations in the symptomatic hemispheres. A HL was defined as a region where CBFrelative≥1.4 (CBFrelative=CBFHL/CBFcontralateral). HLs, BBB disruption, and HT were found in 9, 15, and 15 patients, respectively. Compared with the patients without HLs, the patients with HLs had a higher incidence of both BBB disruption (100% versus 37.5%; P=0.003) and HT (100% versus 37.5%; P=0.003). Based on the Alberta Stroke Program Early Computed Tomography Score locations, 21 regions of interests displayed HLs. Compared with the regions of interests without HLs, the regions of interests with HLs had a higher incidence of both BBB disruption (42.8% versus 3.9%; P<0.001) and HT (85.7% versus 7.8%; P<0.001). HLs detected on pretreatment arterial spin-labeling maps may enable the prediction and localization of subsequent BBB disruption and HT.

Computed Tomography Evaluation of Density Following Stereotactic Body Radiation Therapy of Nonspine Bone Metastases.

Stereotactic body radiation therapy allows for the precise delivery of high-dose radiation to disease sites and is becoming increasingly used to treat nonspine bone metastases. Previous studies have shown that remineralization of lytic bone metastases follows after conventional radiotherapy. The objective of this study was to investigate changes in bone density in nonspine bone metastases following stereotactic body radiation therapy. A retrospective review was conducted for all patients treated with stereotactic body radiation therapy to nonspine bone metastases between May 2011 and April 2014. A minimum of 1 pretreatment and 1 posttreatment computed tomography scan was required. An independent musculoskeletal radiologist contoured the lesions on the most representative computed tomography slices. Density was measured in Hounsfield units and analyzed using pretreatment and posttreatment ratios. Forty sites were treated (55% lytic, 30% sclerotic, and 15% mixed). The median follow-up duration was 7 months. Lytic osseous metastases from renal cell carcinoma progressed during initial follow-up imaging and then returned to baseline. Of 9 lytic lesions not from renal cell carcinoma, 6 showed an immediate increase in density and 2 remained stable. Six of 7 sclerotic lesions from prostate cancer showed decreased density throughout all follow-ups. Stereotactic body radiation therapy is efficacious in the remineralization of lytic and demineralization of sclerotic nonspine bone metastases.

A Feasibility Study of a Tilted Head Position in Helical Tomotherapy for Fractionated Stereotactic Radiotherapy of Intracranial Malignancies.

Herein, we evaluated the feasibility of placing patients in a tilted head position as part of routine clinical practice for fractionated stereotactic radiotherapy (FSRT) of intracranial tumors using helical tomotherapy (HT), by assessing its dosimetric benefit and setup accuracy. We reviewed treatment plans of four cases that were to receive FSRT for brain lesions in normal and head-tilted positions. These patients underwent two computed tomography (CT) scans: first in the normal supine position and then in the supine position with the head tilted at a 458 angle. Two separate HT plans for each position were generated in these four patients, using the same planning parameters. Plans were compared for target conformity and dose homogeneity. Maximum and average doses to critical organs, including normal brain, brain stem, optic chiasm, optic nerves, and the eyes, were considered. To evaluate setup accuracy, patient movement during treatment was assessed by post-treatment megavoltage CT scans. Both HT plans achieved similar conformal and homogeneous dose coverage to the target. Head-tilted HT delivered lower average and maximum doses to critical organs in the cases where the tumor was located on the same plane with critical organs, particularly when they were not directly attached. Placement in the head-tilted position without a mouthpiece allowed for increased patient movement during treatment, while use of a mouthpiece reduced patient movement to even less than that observed for normal setup in the supine position. This pilot study showed that placement in a tilted head position for FSRT of intracranial tumors using HT may be of clinical use, but depends on the tumor location.