Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study

Availability of data and materials: Datasets and material analysed are available on reasonable request from the corresponding author.Supplementary Information: The online version contains supplementary material available at https://doi. org/10.1186/s40644-023-00579-2.Copyright © The Author(s) 2023. Background: In patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC). Methods: Suitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes. Results: 62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43). Conclusion: Changes in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC. Trial Registration: CICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/.John Bush Academic Fund, Mount Vernon Cancer Centre and the Cancer Treatment Research Trust

No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer

Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.</p

Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry.

Background Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted 'gold standards' of tumour biology such as immunohistochemical measures is not established.Methods A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation.Results Hypoxia-inducible factor-1α was correlated with first-order kurtosis (r = -0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness (r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis (r = -0.52, P = .047), fractal dimension (r = 0.613, P = .015), and lacunarity (r = -0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity (r = 0.547, P = .035).Conclusions The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is not appropriate for withholding surgery in high-risk patients with aortic stenosis: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a widely used risk assessment tool in patients with severe aortic stenosis to determine operability and to select patients for alternative therapies such as transcatheter aortic valve implantation. The objective of this study was to determine the accuracy of the EuroSCORE in predicting mortality following aortic valve replacement (AVR).</p> <p>Methods</p> <p>The logistic EuroSCORE was determined for all consecutive patients that underwent conventional AVR between 1995 and 2005 at our institution. Provincial Vital Statistics were used to determine all-cause mortality. The accuracy of the prognostic risk prediction provided by logistic EuroSCORE was assessed by comparing observed and expected operative mortality.</p> <p>Results</p> <p>During the study period, a total of 1,421 patients underwent AVR including 237 patients (16.7%) that had a logistic EuroSCORE > 20. Among these patients, the mean predicted operative mortality was 38.7% (SD = 18.1). The actual mortality of these patients was significantly lower than that predicted by EuroSCORE (11.4% vs. 38.7%, observed/expected ratio 0.29, 95% CI 0.15–0.52, P < 0.05). The EuroSCORE overestimated mortality within all strata of predicted risk. Although medium-term mortality is significantly higher among patients with EuroSCORE > 20 (log rank P = 0.0001), approximately 60% are alive at five years.</p> <p>Conclusion</p> <p>Actual operative mortality in patients undergoing AVR is significantly lower than that predicted by the logistic EuroSCORE. Additionally, medium-term survival following AVR is acceptable in high-risk patients with EuroSCORE > 20. More accurate risk prediction models are needed for risk-stratifying patients with severe aortic stenosis.</p

Comparison of whole-body MRI, CT, and bone scintigraphy for response evaluation of cancer therapeutics in metastatic breast cancer to bone

In participants receiving systemic anticancer therapy for bone-only metastatic breast cancer, whole-body MRI enabled identification of progressive disease earlier than whole-body CT and bone scintigraphy. Background CT and bone scintigraphy have limitations in evaluating systemic anticancer therapy (SACT) response in bone metastases from metastatic breast cancer (MBC). Purpose To evaluate whether whole-body MRI enables identification of progressive disease (PD) earlier than CT and bone scintigraphy in bone-only MBC. Materials and Methods This prospective study evaluated participants with bone-only MBC between May 2016 and January 2019 (ClinicalTrials.gov identifier: NCT03266744). Participants were enrolled at initiation of first or subsequent SACT based on standard CT and bone scintigraphy imaging. Baseline whole-body MRI was performed within 2 weeks of entry; those with extraosseous disease were excluded. CT and whole-body MRI were performed every 12 weeks until definitive PD was evident with one or both modalities. In case of PD, bone scintigraphy was used to assess for bone disease progression. Radiologists independently interpreted images from CT, whole-body MRI, or bone scintigraphy and were blinded to results with the other modalities. Systematic differences in performance between modalities were analyzed by using the McNemar test. Results Forty-five participants (mean age, 60 years ± 13 [standard deviation]; all women) were evaluated. Median time on study was 36 weeks (range, 1–120 weeks). Two participants were excluded because of unequivocal evidence of liver metastases at baseline whole-body MRI, two participants were excluded because they had clinical progression before imaging showed PD, and one participant was lost to follow-up. Of the 33 participants with PD at imaging, 67% (22 participants) had PD evident at whole-body MRI only and 33% (11 participants) had PD at CT and whole-body MRI concurrently; none had PD at CT only (P < .001, McNemar test). There was only slight agreement between whole-body MRI and CT (Cohen κ, 0.15). PD at bone scintigraphy was reported in 50% of participants (13 of 26) with bone progression at CT and/or whole-body MRI (P < .001, McNemar test). Conclusion Whole-body MRI enabled identification of progressive disease before CT in most participants with bone-only metastatic breast cancer. Progressive disease at bone scintigraphy was evident in only half of participants with bone progression at whole-body MRI

A simple clinical model for planning transfusion quantities in heart surgery

<p>Abstract</p> <p>Background</p> <p>Patients undergoing heart surgery continue to be the largest demand on blood transfusions. The need for transfusion is based on the risk of complications due to poor cell oxygenation, however large transfusions are associated with increased morbidity and risk of mortality in heart surgery patients. The aim of this study was to identify preoperative and intraoperative risk factors for transfusion and create a reliable model for planning transfusion quantities in heart surgery procedures.</p> <p>Methods</p> <p>We performed an observational study on 3315 consecutive patients who underwent cardiac surgery between January 2000 and December 2007. To estimate the number of packs of red blood cells (PRBC) transfused during heart surgery, we developed a multivariate regression model with discrete coefficients by selecting dummy variables as regressors in a stepwise manner. Model performance was assessed statistically by splitting cases into training and testing sets of the same size, and clinically by investigating the clinical course details of about one quarter of the patients in whom the difference between model estimates and actual number of PRBC transfused was higher than the root mean squared error.</p> <p>Results</p> <p>Ten preoperative and intraoperative dichotomous variables were entered in the model. Approximating the regression coefficients to the nearest half unit, each dummy regressor equal to one gave a number of half PRBC. The model assigned 4 units for kidney failure requiring preoperative dialysis, 2.5 units for cardiogenic shock, 2 units for minimum hematocrit at cardiopulmonary bypass less than or equal to 20%, 1.5 units for emergency operation, 1 unit for preoperative hematocrit less than or equal to 40%, cardiopulmonary bypass time greater than 130 minutes and type of surgery different from isolated artery bypass grafting, and 0.5 units for urgent operation, age over 70 years and systemic arterial hypertension.</p> <p>Conclusions</p> <p>The regression model proved reliable for quantitative planning of number of PRBC in patients undergoing heart surgery. Besides enabling more rational resource allocation of costly blood-conservation strategies and blood bank resources, the results indicated a strong association between some essential postoperative variables and differences between the model estimate and the actual number of packs transfused.</p

Patient preferences for whole-body MRI or conventional staging pathways in lung and colorectal cancer:a discrete choice experiment

OBJECTIVES: To determine the importance placed by patients on attributes associated with whole-body MRI (WB-MRI) and standard cancer staging pathways and ascertain drivers of preference.METHODS: Patients recruited to two multi-centre diagnostic accuracy trials comparing WB-MRI with standard staging pathways in lung and colorectal cancer were invited to complete a discrete choice experiment (DCE), choosing between a series of alternate pathways in which 6 attributes (accuracy, time to diagnosis, scan duration, whole-body enclosure, radiation exposure, total scan number) were varied systematically. Data were analysed using a conditional logit regression model and marginal rates of substitution computed. The relative importance of each attribute and probabilities of choosing WB-MRI-based pathways were estimated.RESULTS: A total of 138 patients (mean age 65, 61% male, lung n = 72, colorectal n = 66) participated (May 2015 to September 2016). Lung cancer patients valued time to diagnosis most highly, followed by accuracy, radiation exposure, number of scans, and time in the scanner. Colorectal cancer patients valued accuracy most highly, followed by time to diagnosis, radiation exposure, and number of scans. Patients were willing to wait 0.29 (lung) and 0.45 (colorectal) weeks for a 1% increase in pathway accuracy. Patients preferred WB-MRI-based pathways (probability 0.64 [lung], 0.66 [colorectal]) if they were equivalent in accuracy, total scan number, and time to diagnosis compared with a standard staging pathway.CONCLUSIONS: Staging pathways based on first-line WB-MRI are preferred by the majority of patients if they at least match standard pathways for diagnostic accuracy, time to diagnosis, and total scan number.KEY POINTS: • WB-MRI staging pathways are preferred to standard pathways by the majority of patients provided they at least match standard staging pathways for accuracy, total scan number, and time to diagnosis. • For patients with lung cancer, time to diagnosis was the attribute valued most highly, followed by accuracy, radiation dose, number of additional scans, and time in a scanner. Preference for patients with colorectal cancer was similar. • Most (63%) patients were willing to trade attributes, such as faster diagnosis, for improvements in pathway accuracy and reduced radiation exposure.</p

Bony metastases: assessing response to therapy with whole-body diffusion MRI

There are no universally accepted methods for assessing tumour response in skeletal sites with metastatic disease; response is assessed by a combination of imaging tests, serum and urine biochemical markers and symptoms assessments. Whole-body diffusion magnetic resonance imaging excels at bone marrow assessments at diagnosis and for therapy evaluations. It can potentially address unmet clinical and pharmaceutical needs for a reliable measure of tumour response. Signal intensity on high b-value images and apparent diffusion coefficient values can be related to underlying biophysical properties of skeletal metastases. Four patterns of change in response to therapy are described this review. Therapy response criteria need to be tested in prospective clinical studies that incorporate conventional measures of patient benefit

Germ cell cancer in pregnancy – Successfully treated with chemotherapy and surgery

A 31-year-old primigravida, with spontaneous singleton pregnancy, presented in 21 weeks of gestation with abdominal pain. Abdominal ultrasound (USS) and Magnetic Resonance Imaging (MRI) showed a 12 × 14cm large complex lesion arising from the right ovary suspicious for an ovarian malignancy. The radiological staging demonstrated no further metastatic disease; however, it also revealed a 6 cm lesion in the contralateral ovary, consistent with a dermoid cyst. After tumour board discussion the patient underwent a mid-line laparotomy with right oophorectomy, cytology, and peritoneal and omental staging, under oral tocolysis with indomethacin. The left presumed ovarian dermoid was left in situ to avoid additional surgical and obstetrical morbidity. Histology confirmed a grade 3 immature teratoma with primitive neuroepithelium focally present on the capsular surface and atypical cells in the cytology amounting to a stage 1 C2 disease at least. Due to high-risk disease, she was offered adjuvant treatment. The patient received one cycle of intravenous paclitaxel, etoposide, and cisplatin chemotherapy, in an adjuvant setting. She underwent an elective caesarean section at 36 weeks, with the safe delivery of a healthy baby girl. After 6 weeks of her delivery, she received three further cycles of etoposide, and cisplatin to complete her course of adjuvant chemotherapy. Three months after the last chemotherapy cycle, she underwent a laparoscopic removal of the left ovarian dermoid that had increased in size to 8 cm. Final histology revealed no immature elements. To this point, 2 years after initial diagnosis, both mother and child are healthy with no long-term complications. The patient has resumed her normal menstrual cycle and being in remission, she wishes soon to try for a second child. To our knowledge, this is the only reported case of ovarian immature teratoma in pregnancy treated successfully with surgery and adjuvant iv paclitaxel, etoposide, and cisplatin chemotherapy regime