Prognostic value of radiological recurrence patterns in ovarian cancer

Objective: To study the prognostic value of CT assessed recurrence patterns on survival outcomes in women with epithelial ovarian cancer. Methods: CT scans were systematically re-evaluated on predefined anatomical sites for the presence of tumor in all 89 patients diagnosed with epithelial ovarian cancer between January 2008 and December 2013 who underwent cytoreductive surgery at our institution and developed a recurrence. A Cox proportional hazard analysis was used to test the effect of recurrence patterns on survival. Results: The median survival time for patients grouped as predominantly intraperitoneal (n = 62), hematogenous (n = 13) or lymphatic (n = 14) recurrence was 25.8 (95% CI 18.4–33.2), 27.6 (95% CI 18.5–36.6) and 52.9 months (95% CI 42.1–63.7), respectively. Univariate Cox regression analysis identified the following prognostic factors: lymphatic recurrence pattern (HR 0.42, 95% CI 0.21–0.85), ascites at diagnosis (HR 2.35, 95% CI 1.46–3.79), residual tumor at initial surgery (HR 2.16, 95% CI 1.36–3.44) and FIGO stage (I–IIIB: HR 0.59, 95% CI 0.33–1.06). The median time to recurrence was 19.5 month for patients after complete debulking surgery, 13.1 months for patients with residual disease ≤1 cm and 8.2 months for patients with residual disease >1 cm after surgery (P < 0.001). No differences in recurrence patterns between patients with complete and incomplete surgery were found. Conclusions: Prolonged survival rates were found in ovarian cancer patients with a predominantly lymphatic recurrence compared to patients with a predominantly peritoneal or hematogenous recurrence. Completeness of surgery was associated with time to recurrence. Classification of recurrence patterns can help counsel patients on their prognosis at the time of recurrence

FOXL2 and TERT promoter mutation detection in circulating tumor DNA of adult granulosa cell tumors as biomarker for disease monitoring

OBJECTIVE: Adult granulosa cell tumors (aGCTs) represent a rare, hormonally active subtype of ovarian cancer that has a tendency to relapse late and repeatedly. Current serum hormone markers are inaccurate in reflecting tumor burden in a subset of aGCT patients, indicating the need for a novel biomarker. We investigated the presence of circulating tumor DNA (ctDNA) harboring a FOXL2 or TERT promoter mutation in serial plasma samples of aGCT patients to determine its clinical value for monitoring disease. METHODS: In a national multicenter study, plasma samples (n = 110) were prospectively collected from 21 patients with primary (n = 3) or recurrent (n = 18) aGCT harboring a FOXL2 402C > G and/or TERT (C228T or C250T) promoter mutation. Circulating cell-free DNA was extracted and assessed for ctDNA containing one of either mutations using droplet digital PCR (ddPCR). Fractional abundance of FOXL2 mutant and TERT mutant ctDNA was correlated with clinical parameters. RESULTS: FOXL2 mutant ctDNA was found in plasma of 11 out of 14 patients (78.6%) with aGCT with a confirmed FOXL2 mutation. TERT C228T or TERT C250T mutant ctDNA was detected in plasma of 4 of 10 (40%) and 1 of 2 patients, respectively. Both FOXL2 mutant ctDNA and TERT promoter mutant ctDNA levels correlated with disease progression and treatment response in the majority of patients. CONCLUSIONS: FOXL2 mutant ctDNA was present in the majority of aGCT patients and TERT promoter mutant ctDNA has been identified in a smaller subset of patients. Both FOXL2 and TERT mutant ctDNA detection may have clinical value in disease monitoring

Robot-assisted laparoscopic debulking surgery for recurrent adult granulosa cell tumors

Despite an often early diagnosis and effective initial surgical management, one third of adult granulosa cell tumors (aGCTs) eventually, and often repeatedly, recurs. Debulking surgery remains the preferred treatment modality for recurrent aGCT, although the risk of intraoperative complications increases with repeated laparotomy. Minimally invasive surgery may limit the risk of complications. We aim to share our initial experience with robotic debulking surgery for recurrent aGCT. Clinical and surgical data of patients with recurrent aGCT who underwent robotic cytoreductive surgery over a three-year period at a tertiary referral center were retrospectively collected and analyzed. Between 2017 and 2020, three patients underwent robotic debulking surgery for recurrent aGCT at our institution. Complete cytoreduction was achieved in all patients. No intraoperative or postoperative complications were reported. This small pilot series at a single academic institution suggests that robot-assisted laparoscopy may be feasible and safe in selected patients with recurrent aGCT. A minimally invasive approach could reduce the complexity of successive surgeries for aGCT relapse

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for assessing tumour resectability in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer

© 2018 The Cochrane Collaboration. Background: Ovarian cancer is the leading cause of death from gynaecological cancer in developed countries. Surgery and chemotherapy are considered its mainstay of treatment and the completeness of surgery is a major prognostic factor for survival in these women. Currently, computed tomography (CT) is used to preoperatively assess tumour resectability. If considered feasible, women will be scheduled for primary debulking surgery (i.e. surgical efforts to remove the bulk of tumour with the aim of leaving no visible (macroscopic) tumour). If primary debulking is not considered feasible (i.e. the tumour load is too extensive), women will receive neoadjuvant chemotherapy to reduce tumour load and subsequently undergo (interval) surgery. However, CT is imperfect in assessing tumour resectability, so additional imaging modalities can be considered to optimise treatment selection. Objectives: To assess the diagnostic accuracy of fluorodeoxyglucose-18 (FDG) PET/CT, conventional and diffusion-weighted (DW) MRI as replacement or add-on to abdominal CT, for assessing tumour resectability at primary debulking surgery in women with stage III to IV epithelial ovarian/fallopian tube/primary peritoneal cancer. Search methods: We searched MEDLINE and Embase (OVID) for potential eligible studies (1946 to 23 February 2017). Additionally, ClinicalTrials.gov, WHO-ICTRP and the reference list of all relevant studies were searched. Selection criteria: Diagnostic accuracy studies addressing the accuracy of preoperative FDG-PET/CT, conventional or DW-MRI on assessing tumour resectability in women with advanced stage (III to IV) epithelial ovarian/fallopian tube/primary peritoneal cancer who are scheduled to undergo primary debulking surgery. Data collection and analysis: Two authors independently screened titles and abstracts for relevance and inclusion, extracted data and performed methodological quality assessment using QUADAS-2. The limited number of studies did not permit meta-analyses. Main results: Five studies (544 participants) were included in the analysis. All studies performed the index test as replacement of abdominal CT. Two studies (366 participants) addressed the accuracy of FDG-PET/CT for assessing incomplete debulking with residual disease of any size (> 0 cm) with sensitivities of 1.0 (95% CI 0.54 to 1.0) and 0.66 (95% CI 0.60 to 0.73) and specificities of 1.0 (95% CI 0.80 to 1.0) and 0.88 (95% CI 0.80 to 0.93), respectively (low- and moderate-certainty evidence). Three studies (178 participants) investigated MRI for different target conditions, of which two investigated DW-MRI and one conventional MRI. The first study showed that DW-MRI determines incomplete debulking with residual disease of any size with a sensitivity of 0.94 (95% CI 0.83 to 0.99) and a specificity of 0.98 (95% CI 0.88 to 1.00) (low- and moderate-certainty evidence). For abdominal CT, the sensitivity for assessing incomplete debulking was 0.66 (95% CI 0.52 to 0.78) and the specificity 0.77 (95% CI 0.63 to 0.87) (low- and low-certainty evidence). The second study reported a sensitivity of DW-MRI of 0.75 (95% CI 0.35 to 0.97) and a specificity of 0.96 (95% CI 0.80 to 1.00) (very low-certainty evidence) for assessing incomplete debulking with residual disease > 1 cm. In the last study, the sensitivity for assessing incomplete debulking with residual disease of > 2 cm on conventional MRI was 0.91 (95% CI 0.59 to 1.00) and the specificity 0.97 (95% CI 0.87 to 1.00) (very low-certainty evidence). Overall, the certainty of evidence was very low to moderate (according to GRADE), mainly due to small sample sizes and imprecision. Authors' conclusions: Studies suggested a high specificity and moderate sensitivity for FDG-PET/CT and MRI to assess macroscopic incomplete debulking. However, the certainty of the evidence was insufficient to advise routine addition of FDG-PET/CT or MRI to clinical practice.. In a research setting, adding an alternative imaging method could be considered for women identified as suitable for primary debulking by abdominal CT, in an attempt to filter out false-negatives (i.e. debulking, feasible based on abdominal CT, unfeasible at actual surgery)

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for assessing tumour resectability in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer

© 2018 The Cochrane Collaboration. Background: Ovarian cancer is the leading cause of death from gynaecological cancer in developed countries. Surgery and chemotherapy are considered its mainstay of treatment and the completeness of surgery is a major prognostic factor for survival in these women. Currently, computed tomography (CT) is used to preoperatively assess tumour resectability. If considered feasible, women will be scheduled for primary debulking surgery (i.e. surgical efforts to remove the bulk of tumour with the aim of leaving no visible (macroscopic) tumour). If primary debulking is not considered feasible (i.e. the tumour load is too extensive), women will receive neoadjuvant chemotherapy to reduce tumour load and subsequently undergo (interval) surgery. However, CT is imperfect in assessing tumour resectability, so additional imaging modalities can be considered to optimise treatment selection. Objectives: To assess the diagnostic accuracy of fluorodeoxyglucose-18 (FDG) PET/CT, conventional and diffusion-weighted (DW) MRI as replacement or add-on to abdominal CT, for assessing tumour resectability at primary debulking surgery in women with stage III to IV epithelial ovarian/fallopian tube/primary peritoneal cancer. Search methods: We searched MEDLINE and Embase (OVID) for potential eligible studies (1946 to 23 February 2017). Additionally, ClinicalTrials.gov, WHO-ICTRP and the reference list of all relevant studies were searched. Selection criteria: Diagnostic accuracy studies addressing the accuracy of preoperative FDG-PET/CT, conventional or DW-MRI on assessing tumour resectability in women with advanced stage (III to IV) epithelial ovarian/fallopian tube/primary peritoneal cancer who are scheduled to undergo primary debulking surgery. Data collection and analysis: Two authors independently screened titles and abstracts for relevance and inclusion, extracted data and performed methodological quality assessment using QUADAS-2. The limited number of studies did not permit meta-analyses. Main results: Five studies (544 participants) were included in the analysis. All studies performed the index test as replacement of abdominal CT. Two studies (366 participants) addressed the accuracy of FDG-PET/CT for assessing incomplete debulking with residual disease of any size (> 0 cm) with sensitivities of 1.0 (95% CI 0.54 to 1.0) and 0.66 (95% CI 0.60 to 0.73) and specificities of 1.0 (95% CI 0.80 to 1.0) and 0.88 (95% CI 0.80 to 0.93), respectively (low- and moderate-certainty evidence). Three studies (178 participants) investigated MRI for different target conditions, of which two investigated DW-MRI and one conventional MRI. The first study showed that DW-MRI determines incomplete debulking with residual disease of any size with a sensitivity of 0.94 (95% CI 0.83 to 0.99) and a specificity of 0.98 (95% CI 0.88 to 1.00) (low- and moderate-certainty evidence). For abdominal CT, the sensitivity for assessing incomplete debulking was 0.66 (95% CI 0.52 to 0.78) and the specificity 0.77 (95% CI 0.63 to 0.87) (low- and low-certainty evidence). The second study reported a sensitivity of DW-MRI of 0.75 (95% CI 0.35 to 0.97) and a specificity of 0.96 (95% CI 0.80 to 1.00) (very low-certainty evidence) for assessing incomplete debulking with residual disease > 1 cm. In the last study, the sensitivity for assessing incomplete debulking with residual disease of > 2 cm on conventional MRI was 0.91 (95% CI 0.59 to 1.00) and the specificity 0.97 (95% CI 0.87 to 1.00) (very low-certainty evidence). Overall, the certainty of evidence was very low to moderate (according to GRADE), mainly due to small sample sizes and imprecision. Authors' conclusions: Studies suggested a high specificity and moderate sensitivity for FDG-PET/CT and MRI to assess macroscopic incomplete debulking. However, the certainty of the evidence was insufficient to advise routine addition of FDG-PET/CT or MRI to clinical practice.. In a research setting, adding an alternative imaging method could be considered for women identified as suitable for primary debulking by abdominal CT, in an attempt to filter out false-negatives (i.e. debulking, feasible based on abdominal CT, unfeasible at actual surgery)

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for assessing tumour resectability in advanced epithelial ovarian, fallopian tube and/or primary peritoneal cancer

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To assess the diagnostic test accuracy of PET(-CT), conventional and diffusion-weighted MRI as an replacement or an add-on to abdominal CT, for predicting tumour resectability at primary debulking surgery in patients with stage III - IV epithelial ovarian, fallopian tube and/or primary peritoneal cancer. To investigate the year of study initiation, the annual surgical caseload and whether surgery is performed by a gynaecological oncologist as possible sources of heterogeneity. For further details, please see Investigations of heterogeneity

The role of advanced glycation end-products and their receptor on outcome in heart failure patients with preserved and reduced ejection fraction

Introduction: Advanced glycation end products (AGEs) are increased in patients with heart failure (HF). We studied the predictive value of plasma AGEs Nε-(carboxymethyl)lysine (CML), pentosidine, and the soluble form of its receptor (sRAGE) in a large HF population

18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary

Purpose: Adult granulosa cell tumors (AGCTs) of the ovary represent a rare malignancy in which timing and choice of treatment is a clinical challenge. This study investigates the value of FDG-PET/CT and FES-PET/CT in monitoring recurrent AGCTs and assessing eligibility for anti-hormonal treatment. Materials and Methods: We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG (n = 16) and FES (n = 6) uptake by qualitative and quantitative analysis. We included all consecutive patients from two tertiary hospitals between 2003-2020. Expression of ERα and ERβ and mitoses per 2 mm2 were determined by immunohistochemistry and compared to FES and FDG uptake, respectively. Results: Qualitative assessment showed low-to-moderate FDG uptake in most patients (14/16), and intense uptake in 2/16. One patient with intense tumor FDG uptake had a high mitotic rate (18 per 2 mm2) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUVmax of 2.4 (± 0.9) on FDG-PET/CT and mean SUVmax of 1.7 (± 0.5) on FES-PET/CT. Within patients, expression of ERα and ERβ varied and did not seem to correspond with FES uptake. In one FES positive patient, tumor locations with FES uptake remained stable or decreased in size during anti-hormonal treatment, while all FES negative locations progressed. Conclusions: This study shows that in AGCTs, FDG uptake is limited and therefore FDG-PET/CT is not advised. FES-PET/CT may be useful to non-invasively capture the estrogen receptor expression of separate tumor lesions and thus assess the potential eligibility for hormone treatment in AGCT patients