Lieveke Ameye

Logistic Regression Model to Distinguish Between the Benign and Malignant Adnexal Mass Before Surgery: A Multicenter Study by the International Ovarian Tumor Analysis Group

PURPOSE To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery. PATIENTS AND METHODS Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign. RESULTS Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%. CONCLUSION Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.

Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

PURPOSE We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. PATIENTS AND METHODS A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC-pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. RESULTS A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC-pregnancy interval did not seem to impact the risk of relapse. CONCLUSION Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study

Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neutropenic (<500/μl) at baseline, 10 received steroids and 16 calcineurin inhibitors or sirolimus. Median duration of caspofungin treatment was 24 days. At the end of caspofungin therapy, 10 (42%) patients had complete or partial response (95% confidence interval: 22–63%); 1 (4%) and 12 (50%) had stable and progressing disease, respectively; one was not evaluable. At week 12, eight patients (33%) had complete or partial response. Survival rates at week 6 and 12 were 79 and 50%, respectively. No patient had a drug-related serious adverse event or discontinued because of toxicity. Caspofungin first-line therapy was effective and well tolerated in allogeneic hematopoietic SCT patients with mycologically documented IA.

Multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolization therapy with Yttrium-90 labeled resin microspheres

Selective internal radiotherapy (SIRT) using Yttrium-90 labeled resin microspheres is increasingly used for the radioembolization of unresectable liver metastases of colorectal cancer (CRC). The treatment can be simulated by scintigraphy with Tc(99m)-labeled macroaggregates of albumin (MAA). The aim of the study was to develop a predictive dosimetric model for SIRT and to validate it by correlating results with the metabolic treatment response. The simulation of the dosimetry was performed by mathematically converting all liver voxel MAA-SPECT uptake values to the absolute Y(90) activity. The voxel values were then converted to a simulated absorbed dose (Gy) using simple MIRD formalism. The metabolic response was defined as the change in total lesion glycolysis (TLG) on FDG-PET. A total of 39 metastatic liver lesions were studied in eight evaluable patients. The mean administered Y(90) activity was 1.69 GBq (range: 1.33-2.04 GBq). The median (95% CI) simulated absorbed dose (Gy) was 29 Gy (1–98 Gy) and 66 Gy(32–159 Gy) in the poor (<50% TLG change) and the good responders (TLG change > 50%),respectively [DOSAGE ERROR CORRECTED].Using a simple cut-off value of 1 for the MAA-tumor-to-normal uptake ratio, a significant metabolic response was predicted with a sensitivity of 89% (17/19), a specificity of 65% (13/20), a positive predictive value of 71% (17/24) and a negative predictive value of 87% (13/15). Integrated multimodality imaging allows prediction of metabolic response post radioembolization using Y(90)-resin microspheres, and should be used for patient selection.

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients

OBJECTIVES Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants. METHODS Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified intention to treat (MITT) group; secondary endpoints were response and survival at day 84 and safety. RESULTS In the MITT group (n = 61), 75% of patients had cancer not in remission (relapsing or refractory), 85% were neutropenic at enrolment and 49% had a Karnofsky score of < or =50. At end of treatment, 1 and 19 patients had complete and partial response, respectively [success rate 33% (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression. One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61) and 53% (32/60), respectively. Baseline characteristics associated with survival at day 84 were an underlying disease in remission (not relapsing or refractory) and Karnofsky score. Recovery from neutropenia at the end of treatment was also significantly associated with survival. No serious drug-related adverse events or discontinuations due to drug-related adverse events were observed. CONCLUSIONS Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of < or =35%. Underlying disease-related factors had a major impact on results.

Acute effects of tamoxifen and third-generation aromatase inhibitors on menopausal symptoms of breast cancer patients.

Endocrine treatments of breast cancer patients antagonize estrogen and may lead to consequences of estrogen deprivation including menopausal symptoms. We analyzed the changes in frequency and severity of menopausal symptoms in patients receiving tamoxifen or aromatase inhibitors and identified factors influencing these symptoms. One hundred and eighty-one consecutive postmenopausal breast cancer patients scheduled to start endocrine treatment were included in this prospective study. A menopause symptom questionnaire covering vasomotor, atrophic, psychological, cognitive and somatic symptoms was filled in at baseline, and after 1 and 3 months of therapy. Both first-line tamoxifen and aromatase inhibitors induced an increase in the occurrence and severity of hot flashes (p<0.0001 and p=0.014, respectively). Musculoskeletal pain and dyspareunia significantly increased under first-line non-steroidal aromatase inhibitors (p=0.0039 and p=0.001, respectively), while patients under tamoxifen had significant decrease in sexual interest (p≤0.0001). Younger age was associated with more hot flashes and vaginal dryness at baseline, and after 1 and 3 months of therapy (all p<0.02). We conclude that there are significant differences between the early effects of tamoxifen and aromatase inhibitors on menopausal symptoms of breast cancer patients. Our results underscore the need for safe and effective non-hormonal interventions to alleviate vasomotor and musculoskeletal symptoms which were the most prevalent and severe symptoms.

Role of the multidisciplinary team in breast cancer management: results from a large international survey involving 39 countries

BACKGROUND The optimal management of patients with breast cancer (BC) requires the expertise of specialists from different disciplines. This has led to the evolution of multidisciplinary teams (MDTs), allowing all key professionals to jointly discuss individual patients and to contribute independently to clinical decisions. Data regarding BC MDTs in different regions and countries are scarce. METHODS The investigators of a large global phase III adjuvant BC trial being conducted by the Breast International Group were invited to respond to a questionnaire about the extent, structure, and function of BC MDTs. RESULTS One hundred and fifty-two responses from 39 countries were received, and remarkable differences were noted in different geographic regions. Sixty-five percent of the respondents from eastern Europe, 63% from western Europe, 35% from Asia, and 25% from South America declared that MDT was a mandatory part of BC care in their country. Ninety percent of the respondents from Europe stated their MDTs met weekly, compared with only half of the respondents from Asia. CONCLUSION This survey is perhaps the first large-scale effort to collect information regarding BC MDTs from different parts of the world and provides objective information of frequency, composition, function, and working mechanism of BC MDTs.

Interpregnancy weight change and risk for adverse perinatal outcome.

OBJECTIVE: To examine the association between interpregnancy weight change and the risk for adverse maternal and neonatal outcomes. METHODS: All live-born singleton births delivered at 21–42 weeks of gestation in women who had their first two consecutive births between 2009 and 2011 in Flanders (the northern part of Belgium) and who were included in the Study Center for Perinatal Epidemiology database (N=7,897) were included. Interpregnancy weight change was calculated as the difference between the prepregnancy body mass index (BMI) of the first pregnancy and the prepregnancy BMI of the second pregnancy. Multivariate logistic regression analysis to predict gestational diabetes mellitus, pregnancy-induced hypertension, cesarean delivery, macrosomia (4,000 g or greater), low birth weight (less than 2,500 g), and congenital malformations were performed. RESULTS: The adjusted odds ratio (OR) for gestational diabetes mellitus was 2.25 (95% confidence interval [CI] 1.33–3.78; P=.002) for interpregnancy weight retention of 2 or more BMI units, and the adjusted OR for pregnancy-induced hypertension was 3.76 (95% CI 2.16–6.57; P<.001) with an increase of 3 or more BMI units between pregnancies, but these associations were only present in underweight and normal-weight women. In overweight and obese women, the adjusted OR was 2.04 (95% CI 1.41–2.95; P<.001) for cesarean delivery for an interpregnancy weight retention of 2 or more BMI units. In underweight and normal-weight women, the risk for macrosomia was halved if women lost more than 1 BMI unit between pregnancies, but at the same time, the risk for low birth weight doubled. CONCLUSION: We show that weight retention between the first and second pregnancy is associated with an increased risk for perinatal complications, even in underweight and normal-weight women. Stabilizing interpregnancy weight appears an important target for reducing adverse perinatal outcomes in a second pregnancy. LEVEL OF EVIDENCE: II

Serial FDG–PET/CT for early outcome prediction in patients with metastatic colorectal cancer undergoing chemotherapy

BACKGROUND The study purpose was to assess the predictive value of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computerized tomography (CT) metabolic response after a single course of chemotherapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS FDG-PET/CT scans were carried out at baseline and on day 14 in 41 patients with unresectable mCRC treated with a biweekly regimen of chemotherapy. Metabolic nonresponse was defined by <15% decrease in FDG uptake in the dominant proportion of the patients lesions or if a lesion was found metabolically progressive. The PET-based response was correlated with radiological response (primary end point) and patients outcome (secondary end points). RESULTS RECIST response rate in metabolically responding patients was 43% (10 of 23) compared with 0% (0 of 17) in nonresponding patients (P=0.002). The metabolic assessments predictive performance for RECIST response was sensitivity 100% [95% confidence interval (CI) 69% to 100%], specificity 57% (95% CI 37% to 75%), positive predictive value 43% (95% CI 23% to 66%), and negative predictive value 100% (95% CI 80% to 100%). Comparing metabolically responding versus nonresponding patients, the hazard ratio (HR) was 0.28 (95% CI 0.10-0.76) for overall survival and 0.57 (95% CI 0.27-1.21) for progression-free survival. CONCLUSION The metabolic response measured by FDG-PET/CT after a single course of chemotherapy in mCRC is able to identify patients who will not benefit from the treatment.

Cerebral Tissue Oxygenation and Regional Oxygen Saturation Can Be Used to Study Cerebral Autoregulation in Prematurely Born Infants

The coupling of cerebral intravascular oxygenation (dHbD) with mean arterial blood pressure (MABP) was taken as a reflection of autoregulation assuming constant arterial oxygen content. However, this method is sensitive to movement artifacts. We examined whether the cerebral tissue oxygenation index (cTOI) and regional oxygen saturation (rScO2) may replace dHbD and changes in total Hb (dHbT), respectively. Correlation (COR) and coherence (COH) were used to measure the agreement of MABP with rScO2/dHbT and cTOI/dHbD. dHbD/cTOI and dHbT/rScO2 recordings of, respectively, 34 and 20 preterm infants in need for intensive care were studied during the first days of life. dHbD and cTOI were obtained with the NIRO300 and rScO2 and dHbT with the INVOS4100. Invasive MABP was measured continuously. COR and COH scores of MABP versus dHbD/dHbT were compared with the corresponding ones by replacing dHbD/dHbT by cTOI/rScO2, respectively. Generally, no significant score differences were found for dHbD/cTOI. Differences for dHbT/rScO2 were slightly larger but still within the normal variation of the parameters. Differences become insignificant when restricting calculations to epochs of larger variation in MABP (>10 mm Hg). Hence, we suggest that cTOI and rScO2 can be used to study cerebral autoregulation in newborns.