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
.
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.
We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG (
= 16) and FES (
= 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 mm
were determined by immunohistochemistry and compared to FES and FDG uptake, respectively.
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 mm
) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUV
of 2.4 (± 0.9) on FDG-PET/CT and mean SUV
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.
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.
Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard ...to establish. We present a protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.
To compare preoperative sentinel node (SN) mapping with planar lymphoscintigraphy (LSG) to single photon emission computed tomography with computed tomography (SPECT-CT) for differences in ...intraoperative SN retrieval time in surgically treated cervical cancer patients.
In cervical cancer patients planned for radical surgery, one day preoperatively, 220-290 MBq technetium-99m-nanocolloid was injected intracervically in four quadrants. Subsequent SN mapping was performed by either LSG (09.2009-03.2011) or SPECT-CT (03.2011-10.2012). The SN resection, by four armed robot assisted laparoscopy, was based on blue dye and technetium-99m and followed by pelvic lymph node dissection. Timing of perioperative care, including SN procedure times, was prospectively registered.
Out of the 62 subjects included, 33 (53.2%) underwent LSG and 29 (46.8%) SPECT-CT. No significant differences in baseline characteristics were observed. Bi- and unilateral SN visualization rates were 75.8% and 15.2% for LSG versus 86.2% and 6.9% for SPECT-CT (p=0.299 and p=0.305, respectively). Intraoperative bi/unilateral SN detection occurred in 84.8% and 9.1% of LSG subjects versus 89.7% and 3.4% for SPECT-CT (p=0.573 and p=0.616). Correlation in SN location between mapping and surgery was low for LSG (Spearman ρ=0.098; p=0.449) but high for SPECT-CT (ρ=0.798; p<0.001). Bilateral intraoperative SN retrieval times for LSG and SPECT-CT were 75.4±33.5 and 50.1±15.6 min, resulting in an average difference of 25.4 min (p=0.003).
SPECT-CT significantly reduces intraoperative SN retrieval with a clinically relevant time compared to LSG. The trend towards better bilateral visualization rates and significantly higher anatomical concordance may partly explain the observed difference in SN retrieval time.
Objectives
We studied the feasibility of high-resolution T
2
-weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of ...4.7-mm thickness.
Methods
A feasibility study on 20 stage IB1–IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B
1
+
shimming, T
2
-weighted turbo spin echo sequences were completed.
Results
Patients had stage IB1 (
n
= 9), IB2 (
n
= 4), IIA1 (
n
= 1) or IIB (
n
= 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0–5) and 0 (range, 0–2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T
2
-weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B
1
interference, excessive B
1
under the external antennae and SENSE reconstruction.
Conclusions
High-resolution T
2
-weighted 7.0-T MRI of stage IB1–IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients.
Key Points
•
High resolution T
2
-
weighted 7.0
-
T MRI of the inner female pelvis is challenging
•
We demonstrate a feasible approach for T
2
-
weighted 7.0
-
T MRI of cervical cancer
•
An endorectal monopole receive antenna is well tolerated by participants
•
The endorectal antenna did not lead to adverse events or session discontinuation
We studied the feasibility of high-resolution T
-weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness.
...A feasibility study on 20 stage IB1-IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B
shimming, T
-weighted turbo spin echo sequences were completed.
Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0-5) and 0 (range, 0-2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T
-weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B
interference, excessive B
under the external antennae and SENSE reconstruction.
High-resolution T
-weighted 7.0-T MRI of stage IB1-IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients.
• High resolution T
-weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T
-weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation.
Objectives
Imaging is increasingly used to assess lymph node involvement in clinically early-stage cervical cancer. This retrospective study aimed to evaluate the diagnostic accuracy of MRI, CT, and
...18
FFDG-PET-CT.
Methods
Women with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IA2-IIA cervical cancer and pretreatment imaging between 2009 and 2017 were selected from the Netherlands Cancer Registry. Patient-based and region-based (i.e. pelvic and common iliac) nodal status was extracted from radiology reports. Pathology results were considered the reference standard for calculating accuracy indices. Multiple imputation was used for missing pathology to limit verification bias risk.
Results
Nodal assessment was performed in 1676 patients with MRI, 926 with CT, and 379 with
18
FFDG-PET-CT, with suspicious nodes detected in 17%, 16%, and 48%, respectively.
18
FFDG-PET-CT was used to confirm MRI/CT results in 95% of patients. Pathology results were imputed for 30% of patients.
18
FFDG-PET-CT outperformed MRI and CT in detecting patient-based nodal metastases with sensitivities of 80%, 48%, and 40%, and AUCs of 0.814, 0.706, and 0.667, respectively, but not in specificity: 79%, 92%, and 92%. Region-based analyses showed similar indices in the pelvic region, but worse performance in the common iliac region with AUCs of 0.575, 0.554, and 0.517, respectively.
Conclusions
18
FFDG-PET-CT outperformed MRI and CT in detecting nodal metastases, which may be related to its use as a verification modality. However, MRI and CT had the highest specificity. As MRI is generally performed routinely to assess local and regional spread of cervical cancer,
18
FFDG-PET-CT can be used to confirm suspicious nodes.
Critical relevance statement
Accurate assessment of the nodal status in clinically early-stage cervical cancer is essential for tumour staging, treatment decision making and prognosis.
Key points
• The accuracy of MRI, CT or
18
FFDG-PET-CT for nodal staging in early cervical cancer is a subject of discussion.
• Overall,
18
FFDG-PET-CT outperformed MRI, followed by CT, when used as a verification modality.
• Staging with MRI and the addition of
18
FFDG-PET-CT to verify high-risk cases seems to be a good approach.
Graphical Abstract
To evaluate consecutive vaginal radical trachelectomies (VRTs) in early-stage cervical cancer in the 2 main referral centers for fertility-preserving surgery in the Netherlands.
Oncology, fertility, ...and obstetrical data were recorded in a regional database of all VRTs without neoadjuvant chemotherapy performed in 2 major referral centers between 2000 and 2015.
Most of the patients (91.7%) had stage IB1 disease. In 72.0%, squamous cell carcinoma was the histologic diagnosis; in 24.2%, adenocarcinoma; and in 3.8%, adenosquamous carcinoma. The median follow-up was 51 months.Nine (6.8%) recurrences occurred, 4 resulting in death of disease (death rate, 3.0%). Recurrence rates were 12.5% for adenocarcinoma, 20% for adenosquamous carcinoma, and 4.2% for squamous cell carcinoma (P < 0.01).From 117 women, data about fertility and obstetrical outcome were obtained. Almost 60% of women attempted to conceive after a VRT. Of these women, 40% needed fertility treatment. A total of 47 pregnancies were established, and a total of 37 children were born of which 30 (81.1%) were delivered after 32 weeks of gestational age.
Nonsquamous cell histology and high-grade disease are associated with a significantly higher risk of recurrence in the univariate and multivariate analyses. Women with both these histology features should be counseled reticently for VRT.Pregnancies after VRT must be regarded as high-risk pregnancies with a high prematurity rate.
Recent guidelines recommend genetic counselling and DNA testing (GCT) for patients with ovarian cancer and survivors of ovarian cancer. Finding survivors of ovarian cancer is challenging. Detecting ...and referring them for GCT via primary care, to allow proper screening recommendations for patients and their family, may be a solution.
To compare the effectiveness and acceptance of two pilot strategies directed at case finding women with a history of ovarian cancer for referral for GCT by their GP.
Non-randomised comparison of the pilot implementation of two case-finding strategies for women with a history of ovarian cancer in Dutch primary care from May 2016 to April 2017.
Strategy A (unsupported) asked GPs to identify and refer eligible patients with a history of ovarian cancer. Strategy B (ICT-supported) provided GPs with information and communication technology (ICT) support to identify patients with a history of ovarian cancer electronically. The effectiveness of each strategy was assessed as the proportion of patients who were approached, referred for GCT, and seen by the clinical geneticist. Acceptance of each strategy was assessed by the intervention uptake of GP practices and GP and patient questionnaires.
Nineteen out of 30 (63%) patients identified with a history of ovarian cancer were deemed eligible for referral for strategy A, and 39 out of 94 (41%) for strategy B. For each strategy, eight patients were referred and five (63%) were seen for GCT. The intervention uptake by GP practices was 31% (11 out of 36) for strategy A and 46% (21 out of 46) for strategy B. GPs considered 'relevance' and 'workability' as facilitators across both strategies whereas, for strategy B, technical barriers hindered implementation.
The effectiveness and acceptance of both strategies for case finding of survivors of ovarian cancer in primary care for GCT is promising, but larger studies are required before wide-scale implementation is warranted.
It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.
We included 386 ...BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.
BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR
) 1.47; 95% confidence interval (CI) 1.03-2.08 and HR
1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HR
1.15; 95% CI 0.84-1.57) and OCSS (HR
1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR
1.99; 95% CI 1.21-3.31).
Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.