Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

Vargas, Hebert Alberto; Burger, Irene A.; Goldman, Debra A.; Miccò, Maura; Sosa, Ramon E.; Weber, Wolfgang; S., D.; Hricak, Hedvig; Sala, Evis

doi:10.1007/s00330-015-3729-9

Cited by 43 publications

(21 citation statements)

References 25 publications

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“…Although tumour volume appears likely to be an important prognostic factor, this has not been extensively studied [40–44]. In our limited sample set, 3-D tumour volume was significantly associated with TTP in univariable analysis, but did not emerge as significantly associated with TTP in multivariable analysis including TP53MAF, TP53MAC, and other data (Tables 2 and S10).…”

Section: Discussionmentioning

confidence: 80%

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

et al. 2016

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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...

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Section: Discussionmentioning

confidence: 80%

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

et al. 2016

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“…While it is clear that BRCA gene mutation produces characteristic morphologic differences at histopathologic examination, it is unknown if the presence of BRCA gene mutation translates into distinct imaging manifestations and if these can be reliably recognized at CT. Furthermore, although several studies have shown that CT features may serve as useful predictors of cytoreductive outcome in HGSOC, it is uncertain if these CT indicators vary depending on BRCA mutation status (20)(21)(22)(23). Thus, the aims of our study were to investigate the associations between BRCA mutation status and CT phenotypes of HGSOC and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and patients with BRCA wild-type HGSOC.…”

Section: Genitourinary Imaging: High-grade Serous Ovarian Cancermentioning

confidence: 99%

High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes

et al. 2017

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Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking. Two radiologists independently reviewed the CT findings for various qualitative CT features. Associations between CT features, BRCA mutation status, cytoreductive outcome, and progression-free survival (PFS) were evaluated by using logistic regression and Cox proportional hazards regression, respectively. Results Peritoneal disease (PD) pattern, presence of PD in gastrohepatic ligament, mesenteric involvement, and supradiaphragmatic lymphadenopathy at CT were associated with BRCA mutation status (multiple regression: P < .001 for each CT feature). While clinical and CT features were not associated with cytoreductive outcome for patients with BRCA-mutant HGSOC, presence of PD in lesser sac (odds ratio [OR] = 2.40) and left upper quadrant (OR = 1.19), mesenteric involvement (OR = 7.10), and lymphadenopathy in supradiaphragmatic (OR = 2.83) and suprarenal para-aortic (OR = 4.79) regions were associated with higher odds of incomplete cytoreduction in BRCA wild-type HGSOC (multiple regression: P < .001 each CT feature). Mesenteric involvement at CT was associated with significantly shorter PFS for both patients with BRCA-mutant HGSOC (multiple regression: hazard ratio [HR] = 26.7 P < .001) and those with BRCA wild-type HGSOC (univariate analysis: reader 1, HR = 2.42, P < .001; reader 2, HR = 2.61; P < .001). Conclusion Qualitative CT features differed between patients with BRCA-mutant HGSOC and patients with BRCA wild-type HGSOC. CT indicators of cytoreductive outcome varied according to BRCA mutation status. Mesenteric involvement at CT was an indicator of significantly shorter PFS for both patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. RSNA, 2017 Online supplemental material is available for this article.

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“…In cervical cancer, PET/CT has been found to be a useful tool for detecting nodal disease, pelvic sidewall invasion and distant metastases beyond the true pelvis [1, 2, 3]. In ovarian cancer, PET/CT appears to be most valuable in detecting recurrence, tumor on the ovarian surface and extension and/or implants on the uterus [4, 5]. …”

Section: Introductionmentioning

confidence: 99%

The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer

Robertson

Hricak

Sonoda

et al. 2016

Gynecologic Oncology

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OBJECTIVES To evaluate the changes in prognostic impression and patient management following PET/CT in patients with vulvar and vaginal carcinoma; and to compare PET/CT findings with those of conventional imaging modalities. METHODS We summarized prospectively and retrospectively collected data for 50 consecutive patients from our institution that enrolled in the National Oncologic PET Registry and underwent FDG-PET/CT for a suspected or known primary or recurrent vulvar/vaginal cancer. RESULTS 54/83 (65%) studies included had a diagnosis of vulvar cancer, and the remaining 29/83 (35%), a diagnosis of vaginal cancer. Following FDG-PET/CT, the physician’s prognostic impression changed in 51% of cases. A change in patient management, defined as a change to/from a non-interventional strategy (observation or additional imaging), to/from an interventional strategy (biopsy or treatment), was documented in 36% of studies. The electronic records demonstrated that 95% of the management strategies recorded in the physician questionnaires were implemented as planned. MRI and/or CT were performed within one month of the FDG-PET/CT in 20/83 (24%) and 28/83 (34%) cases, respectively. FDG-PET/CT detected nodes suspicious for metastases on 29/83 (35%) studies performed. MRI and CT detected positive nodes on 6 and 11 studies respectively. Distant metastases were identified in 10 cases imaged with FDG-PET and 5 cases that had additional conventional CT imaging. All suspicious lesions seen on CT were positively identified on PET/CT. In 4 cases, an abnormality identified on PET/CT, was not seen on diagnostic CT. CONCLUSIONS FDG-PET/CT may play an important role in the management of vulvar and vaginal carcinoma.

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Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

Cited by 43 publications

References 25 publications

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes

The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer

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