Lieselot Brepoels

Breast cancer in pregnancy: recommendations of an international consensus meeting.

PURPOSE To provide guidance for clinicians about the diagnosis, staging and treatment of breast cancer occurring during an otherwise uncomplicated pregnancy. METHODS An international expert Panel convened to address a series of questions identified by a literature review and personal experience. Issues relating to the diagnosis and management of breast cancer after delivery were outside the scope. RESULTS There is a paucity of large and/or randomized studies. Based on cohort studies, case series and case reports, the recommendations represent the best available evidence, albeit of a lower grade than is optimal. RECOMMENDATIONS In most circumstances, serious consideration should be given to the option of treating breast cancer whilst continuing with the pregnancy. Each woman should ideally be referred to a centre with sufficient expertise, given a clear explanation of treatment options. Most diagnostic and staging examinations can be performed adequately and safely during pregnancy. Treatment should however be adapted to the clinical presentation and the trimester of the pregnancy: surgery can be performed during all trimesters of pregnancy; radiotherapy can be considered during the first and second trimester but should be postponed during the third trimester; and standard chemotherapies can be used during the second and third trimester. Since neonatal morbidity mainly appears to be related to prematurity, delivery should not be induced before 37 weeks, if at all possible. CONCLUSIONS The treatment of breast cancer in pregnancy should be executed by experienced specialists in a multidisciplinary setting and should adhere as closely as possible to standard protocols.

Gynaecologic cancer complicating pregnancy: An overview

Cancer complicating pregnancy endangers two lives. Any approach should look at both maternal and foetal safety. Maternal prognosis will not improve by terminating the pregnancy. Imaging for staging purposes is possible, and sonar and magnetic resonance imaging are the preferred examinations. Abdominopelvic computed tomography exposes the foetus to the highest doses radiation and should be avoided. Provided a thorough maternal monitoring to ensure a stable uteroplacental blood flow and foetal oxygenation, surgical techniques that are used in non-pregnant patients are also safe for pregnant patients. Radiotherapy of the upper part of the body is possible during pregnancy, but during the third trimester the close distance may put the foetus at risk. Chemotherapy during the second or third trimester can be administered without increasing the incidence of congenital malformations. A systematic analysis, especially on the long-term outcome of the offspring after cancer treatment during pregnancy is still lacking. Here, we present a summary of issues related to the diagnosis and treatment of gynaecological malignancies during pregnancy. Firstly, we describe general diagnostic and cancer-treatment-related problems. In the second part, organ pathology including breast, cervical, ovarian, endometrial and vulvar cancer is discussed.

Hodgkin lymphoma: Response assessment by Revised International Workshop Criteria

Until recently, response assessment in patients with Hodgkins lymphoma (HL) was primarily performed by computed tomography (CT). Based on CT, International Workshop Criteria (IWC) were developed and widely used. Fluorodeoxyglucose positron emission tomography (FDG-PET) has a higher sensitivity and specificity compared with that of CT, and Revised International Workshop Criteria (IWC + PET) were recently proposed, which combine both imaging techniques. We determined whether these integrated IWC + PET-criteria can more accurately predict outcome compared with IWC-criteria in 56 patients with HL. Of the original 56 patients, nine patients relapsed and 47 are still in remission after a median follow-up of 9 years. Based on IWC-criteria, 15 patients had a complete remission (CR) after chemotherapy, 20 had complete remission unconfirmed (CRu), 19 had partial remission (PR) and two had stable disease (SD). In comparison, by IWC + PET, 47 had CR, seven had PR and two had SD. For IWC, outcome was not significantly different in patients with CR/CRu compared to PR (P = 0.61), while for IWC + PET criteria, time-to-next-treatment was significantly shorter in patients with PR compared to CR (P = 0.01). Therefore, IWC + PET-guidelines provide a more accurate response classification compared with that of IWC-guidelines, and are the preferred method for response assessment in patients with Hodgkins lymphoma.

Positron emission tomography in mantle cell lymphoma

Mantle cell lymphoma (MCL) is a rare but aggressive non-Hodgkin lymphoma subtype with a poor prognosis; most patients relapse despite initial response to therapy. Response was traditionally evaluated by computed tomography (CT), but the introduction of [18F]Fluorine-Deoxyglucose Positron Emission Tomography (PET) changed response assessment in aggressive lymphoma. However, the value of PET-evaluation in MCL has not been studied yet. Therefore, PET- and CT-findings were investigated in 37 patients with MCL (239 scans) and categorised following standardised response criteria for CT-evaluation (IWC-criteria), PET-evaluation (EORTC-criteria) and combined PET/CT-evaluation (IWC + PET-criteria). FDG-PET showed a high sensitivity for the detection of deposits of MCL and a higher FDG-uptake was shown in patients with the more aggressive blastoid-variant of MCL versus common MCL. However, routine use of PET for end-of-treatment response assessment in MCL cannot be recommended because CT- and PET-based designation systems had equivalent prognostic value. PET-based end-of-treatment response assessment only provided additional information over CT-based response assessment in a subpopulation of patients with highly FDG-avid MCL. PET allowed early detection of preclinical relapse during post-therapy surveillance, but the therapeutic consequences of such information are currently unclear.

Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinicopathological characteristics and prognostic factors

Abstract Hematopoietic stem cell and solid organ transplant recipients diagnosed with biopsy-confirmed posttransplant lymphoproliferative disorder (PTLD) at our institution from 1989 to 2010 were identified. Patient-, transplant- and disease-related characteristics, prognostic factors and outcome were collected and analyzed. One hundred and forty biopsy-proven cases of PTLD were included. Overall incidence in the transplant population was 2.12%, with heart transplant recipients carrying the highest risk. Most PTLDs were monomorphic (82%), with diffuse large B-cell lymphoma being the most frequent subtype. The majority of cases (70.7%) occurred > 1 year posttransplant, and 66% were Epstein–Barr virus positive. Following initial therapy the overall response rate was 68.5%. Three-year relapse-free and overall survivals were 59% and 49%, respectively. At last follow-up, 44% of the patients were alive. Multivariable analysis identified several classical lymphoma-specific poor prognostic factors for the different outcome measures. The value of the International Prognostic Index was confirmed in our analysis.

18F-FDG and 18F-FLT Uptake Early After Cyclophosphamide and mTOR Inhibition in an Experimental Lymphoma Model

To be a reliable predictor of response, tracer uptake should reflect changes in the amount of active tumor cells. However, uptake of 18F-FDG, the most commonly used PET tracer, is disturbed by the inflammatory cells that appear early after cytotoxic therapy. The first aim of this study was to investigate whether 3′-18F-fluoro-3′-deoxy-l-thymidine (18F-FLT), a marker of cellular proliferation, is a better tracer for response assessment early after cytotoxic therapy. A second objective of this study was to investigate whether 18F-FDG and 18F-FLT responses were comparable early after mammalian target of rapamycin (mTOR) inhibition, as an example of proliferation-targeting therapies. Methods: Severe combined immunodeficient mice were subcutaneously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. Half the mice were treated with cyclophosphamide and the other half with mTOR inhibition. 18F-FDG and 18F-FLT uptake was evaluated by small-animal PET on day 0 (D0; before treatment), D+1, D+2, D+4, D+7, D+9, D+11, and D+14. At each time point, 2 mice of each treatment condition were sacrificed, and tumors were excised for histopathology. Results: After cyclophosphamide, 18F-FDG and 18F-FLT uptake decreased, with a maximum reduction of −29% for 18F-FDG and −25% for 18F-FLT uptake at D+2, compared with baseline. Although 18F-FDG uptake increased from D+4 on, with a maximum on D+7, 18F-FLT uptake remained virtually stable. Histology showed an increase in apoptotic or necrotic tumor fraction, followed by an influx of inflammatory cells. In mTOR-inhibited mice, 18F-FDG uptake dropped until D+2 after therapy (−43%) but increased at D+4 (−27%) to form a plateau on D+7 and D+9 (−14% and −16%, respectively). Concurrently, 18F-FLT uptake decreased to −31% on D+2, followed by an increase with a peak value of +12% on D+7, after which 18F-FLT uptake decreased again. Cyclin D1 expression dropped from D+1 until D+4 and returned to baseline at D+7. Conclusion: Because 18F-FLT uptake is not significantly influenced by the temporary rise in inflammatory cells early after cyclophosphamide, it more accurately reflects tumor response. However, a formerly unknown temporary rise in 18F-FLT uptake a few days after the administration of mTOR inhibition was defined, which makes it clear that drug-specific responses have to be considered when using PET for early treatment monitoring.

Aggressive and indolent non-Hodgkin's lymphoma: response assessment by integrated international workshop criteria.

Until recently, response assessment in patients with lymphoma was primarily performed by computed tomography (CT). Based on CT, International Workshop Criteria (IWC) were developed and widely used. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a more sensitive and specific imaging technique for the detection of residual disease in lymphoma, and Revised Integrated International Workshop Criteria (IWC + PET) were recently proposed by the members of the International Harmonization Project (IHP), which combine both imaging techniques. We determined whether these new IWC + PET-criteria, can more accurately predict outcome compared to IWC-criteria in aggressive and indolent non-Hodgkins lymphoma (NHL), and therefore correlated IWC and IWC + PET response with time-to-next-treatment (TNT) in 69 patients with NHL. We demonstrated that IWC + PET-guidelines are highly recommended over IWC-guidelines for patients with potentially-curable and routinely FDG-avid lymphoma. In contrast, no additional value of IWC + PET was demonstrated in a small group of patients with incurable histological subtypes.

PET and PET/CT for response evaluation in lymphoma: Current practice and developments

Positron emission tomography (PET) using the radiolabelled glucose analog 2-[18F]fluoro-2-deoxy-d-glucose (FDG) is increasingly used for response assessment in patients with Hodgkins disease (HD) and non-Hodgkins lymphoma (NHL). These patients often present with a residual mass after therapy, but only a minority will relapse as most of these masses consist of inactive fibrosis. However, some patients have residual disease after first-line treatment and they can benefit from additional or early salvage therapy. Special interest for early, but accurate, assessment of response is growing accordingly. Conventional radiological techniques cannot differentiate between active tumoural tissue and fibrosis in these masses. In contrast, FDG-PET has the ability to differentiate between viable tumour and fibrosis and has been evaluated as an initial staging tool, for response assessment after completion of therapy and as a prognostic marker early during treatment. In this review, we will focus especially on the value of PET for response assessment.

Fdg positron emission tomography/computed tomography scan may identify mantle cell lymphoma patients with unusually favorable outcome

ObjectivePatients diagnosed with mantle cell lymphoma (MCL) have generally poor prognosis, but a minority have a longer survival. There are no markers to identify this group and no generally established prognostic index for MCL. Our objective was to assess the prognostic value of the staging FDG PET/computed tomography (CT) scan. MethodsWe retrospectively analyzed initial scans performed at three institutions on biopsy-proven, cyclin D (+) MCL patients. The association of the SUVmax of the ‘hottest focus’ with overall survival (OS) and failure-free survival (FFS) was evaluated. Receiver operating characteristic analysis of SUVmax versus survival was used to establish a cut-off point of 4.83. In addition, PET findings were compared with contrast-enhanced CT performed within 3 weeks in patients from one institution. ResultsBoth the OS and FFS for patients with SUVmax greater than 5 were significantly decreased (P<0.01 and <0.001, respectively) as compared with the patients with SUV ≤5. The 5-year OS for group with SUVmax ≤5 was 87.7% and for SUVmax greater than 5 it was 34%. For SUVmax ≤5, the median FFS was 45.3 months as compared with 10.6 months for SUVmax greater than 5. PET changed the stage as compared with CT alone in 45% of patients. ConclusionStaging FDG PET/CT is superior to CT and may be used in the future for identification of a subset of MCL patients with a better outcome than otherwise expected.

The accuracy of positron emission tomography in the detection of posttransplant lymphoproliferative disorder

We investigated sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-fluorodeoxyglucose-positron emission tomography in 170 cases with suspected or biopsy-proven posttransplant lymphoproliferative disorder. All solid organ and hematopoietic stem cell transplant recipients who underwent an 18F-fluorodeoxyglucose-positron emission tomography scan between 2003 and 2010 in our center for the indication posttransplant lymphoproliferative disorder, were retrospectively reviewed and results were compared with tissue biopsy whenever possible. One hundred and seventy positron emission tomography scans in 150 patients were eligible for evaluation. In 45 cases, the patient had a biopsy-confirmed posttransplant lymphoproliferative disorder before positron emission tomography scanning and positron emission tomography was performed for staging purposes. In the remaining 125 cases, positron emission tomography was performed to differentiate between posttransplant lymphoproliferative disorder and other diseases. 18F-fluorodeoxyglucose-uptake was quantitatively expressed by calculation of maximum and mean standardized uptake value in the most intense lesion or, in the absence of attenuation corrected positron emission tomography scans, by comparing uptake in target lesion to liver and mediastinal uptake. We found an overall sensitivity of 89%, specificity of 89%, positive predictive value of 91% and negative predictive value of 87% for posttransplant lymphoproliferative disorder detection by 18F-fluorodeoxyglucose-positron emission tomography. In a subanalysis of the 125 scans performed for differentiating posttransplant lymphoproliferative disorder from other diseases, sensitivity, specificity, positive predictive value and negative predictive value were 90%, 89%, 85% and 93%, respectively. 18F-fluorodeoxyglucose-uptake in posttransplant lymphoproliferative disorder was generally high with a median mean and maximum standardized uptake value of 9.0 (range 2.0–18.6) and 17.4 (range 2.6–26.4). Posttransplant lymphoproliferative disorder often had an atypical presentation on positron emission tomography with high incidence of extranodal involvement. In conclusion, from these data, we can conclude that 18F-fluorodeoxyglucose-positron emission tomography is highly sensitive for detecting posttransplant lymphoproliferative disorder and has an excellent ability to differentiate posttransplant lymphoproliferative disorder from non-malignant diseases.