Citations

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.

Purpose Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. Methods Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH ‐, AAPM ‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format ( DICOM ‐ CT ‐ PD ). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic ( JAFROC ) figure of merit, which was used for breaking ties. Results 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data ( CTDI vol = 3.0 ± 1.8 mG y, SSDE = 3.5 ± 1.3 mG y). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. Conclusion Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.

OBJECTIVE: The aim of this study was to compare the accuracy of CT colonography versus optical colonoscopy for neoplastic involvement at the surgical anastomosis 1 year after curative-intent colorectal cancer resection. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Two hundred one patients (mean age, 58.6 years; 117 men, 84 women) underwent same-day contrast-enhanced CT colonography and colonoscopy approximately 1 year (mean, 12.1 months; median, 11.9 months) after colorectal cancer resection as part of a prospective, multicenter trial. All patients enrolled were without clinical evidence of disease and considered low risk for recurrence (stage I–III). MAIN OUTCOME MEASURES: Suspected neoplastic lesions within 5 cm of the colonic anastomosis were recorded at CT colonography, with subsequent colonoscopy performed for the same, with segmental unblinding of colonography findings. Anastomotic region biopsy or polypectomy was performed at the endoscopist’s discretion. RESULTS: None of the 201 patients had intraluminal anastomotic cancer recurrence or advanced neoplasia (or metachronous cancers). CT colonography detected extramural perianastomotic recurrence in 2 patients (1.0%); neither was detected at colonoscopy. Only 2 patients (1.0%; 2/201) were called positive at CT colonography for intraluminal anastomotic nondiminutive lesions (7- to 8-mm polyps), which were confirmed at colonoscopy but nonneoplastic at histopathology. At optical colonoscopy, the anastomosis was deemed abnormal and/or biopsied in 10.0% (20/201), yielding only 1 nondiminutive benign neoplasm (7-mm tubular adenoma). LIMITATIONS: The lack of luminal cancer recurrence in our lower-risk cohort precludes assessment of sensitivity for detection, rendering the study underpowered in this regard. Potential cost savings of combined CT/CT colonography over the standard CT/colonoscopy approach were not assessed. CONCLUSIONS: Relevant intraluminal anastomotic pathology appears to be very uncommon 1 year after colorectal cancer resection in lower-risk cohorts. Unlike colonoscopy, diagnostic contrast-enhanced CT colonography effectively evaluates both the intra- and extraluminal aspects of the anastomosis. See Video Abstract at http://links.lww.com/DCR/A471.

Abstract Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients. Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes. Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced). Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival. Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470–3. ©2017 AACR.

Abstract Significant endocrine therapy–resistant tumor proliferation is present in ≥20% of estrogen receptor–positive (ER+) primary breast cancers and is associated with disease recurrence and death. Here, we uncover a link between intrinsic endocrine therapy resistance and dysregulation of the MutL mismatch repair (MMR) complex (MLH1/3, PMS1/2), and demonstrate a direct role for MutL complex loss in resistance to all classes of endocrine therapy. We find that MutL deficiency in ER+ breast cancer abrogates CHK2-mediated inhibition of CDK4, a prerequisite for endocrine therapy responsiveness. Consequently, CDK4/6 inhibitors (CDK4/6i) remain effective in MutL-defective ER+ breast cancer cells. These observations are supported by data from a clinical trial where a CDK4/6i was found to strongly inhibit aromatase inhibitor–resistant proliferation of MutL-defective tumors. These data suggest that diagnostic markers of MutL deficiency could be used to direct adjuvant CDK4/6i to a population of patients with breast cancer who exhibit marked resistance to the current standard of care. Significance: MutL deficiency in a subset of ER+ primary tumors explains why CDK4/6 inhibition is effective against some de novo endocrine therapy–resistant tumors. Therefore, markers of MutL dysregulation could guide CDK4/6 inhibitor use in the adjuvant setting, where the risk benefit ratio for untargeted therapeutic intervention is narrow. Cancer Discov; 7(10); 1168–83. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047