BackgroundCirculating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP).Methods and FindingsWe performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP.The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%–22%) compared to 0.7% (IQR 0.3%–2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28–54) compared with a median time to nadir of 84 d (IQR 42–116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07–0.67, p = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%–92%) and 88% specificity (95% CI 64%–99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort.ConclusionsIn this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was asso...

DW MR imaging has superior diagnostic accuracy in the assessment of myometrial invasion and significantly higher staging accuracy compared with DCE MR imaging.

ABSTRACT. An increasing number of breast lesions are being detected incidentally on CT. The aim of this study was to investigate the rate of referrals to the breast unit for assessment of lesions identified on CT and the resulting yield of previously undiagnosed breast malignancies from this pathway. A retrospective review was undertaken of CT examinations conducted over a period of 14 years. All patients (with no previous history of breast cancer) whose report contained the keyword ''breast'' and who were referred to a specialist breast unit for assessment were reviewed. CT lesion morphology and enhancement pattern were identified and compared with the final diagnostic outcome. 70 patients were identified by retrospective analysis, yielding 78 incidental breast lesions, of which 22 (28.2%) were malignant (category B5). This gave a positive predictive value (PPV) for malignancy of 28.2%. The best morphological predictor of malignancy was spiculation (PPV, 76%) and irregularity (PPV, 58%), whereas calcification patterns (PPV, 36%) were diagnostically unhelpful. Malignant lesions were likely to be larger (mean, 28.5 mm) than benign lesions (mean, 20.2 mm; p,0.05). In conclusion, 30% of incidental breast lesions in this large series of patients proved to be unsuspected breast cancers, particularly irregular spiculated masses. Referral for formal triple assessment of CT-diagnosed breast lesions is worthwhile, and careful examination of the breast should be a routine part of CT examinations.

Cystic disease in the female pelvis is common. The majority of cystic pelvic masses originate in the ovary, and they can range from simple, functional cysts to malignant ovarian tumors. Mimics of ovarian cystic masses include peritoneal inclusion cyst, paraovarian cyst, mucocele of the appendix, obstructed fallopian tube (eg, hydrosalpinx, pyosalpinx, and hematosalpinx), uterine leiomyoma, adenomyosis, spinal meningeal cyst, unicornuate uterus, lymphocele, cystic degeneration of lymph nodes, lymphangioleiomyomatosis, hematoma, and abscess. A cystic pelvic mass is nonovarian if it is separate from the normal ovaries. However, the different types of cystic pelvic masses may have similar imaging appearances, and radiologic evaluation may be of limited diagnostic use. It is important to understand the relationship of a mass with its anatomic location, identify normal ovaries at imaging, and relate imaging findings to the patient's clinical history to avoid misdiagnosis.