Belgian Society of Medical Oncology

Abstract Introduction: Triple negative breast cancer (TNBC) remains a challenging disease with dismal prognosis. Platinum analogs have not yet shown to improve long term outcome in this setting, but are associated with increased pathological complete response rate (pCR) at the cost of higher toxicity. Aim: To further increase or maintain the high pCR rate with platinum containing schedules while decreasing toxicity by administering low dose weekly carboplatin instead of high-dose 3 weekly carboplatin as in CALGB 40603.(1) Patients and methods: We evaluated the tolerability and the impact of the addition of weekly carboplatin (CP) to paclitaxel (P) and dose dense epirubicin-cyclofosfamide (EC) on pCR in an open-label multicenter phase II study in stage II/III TNBC patients (pts). Sixty three pts received dose dense paclitaxel (P:80mg/m2/wk) concurrent with carboplatin (CP: AUC=2) for 12 wks, followed by two-weekly epirubicin (E:90mg/m2) and cyclophosphamide (C:600mg/m2) for 4 cycles. The primary endpoint is pCR in the breast and axilla. Additionally treatment deliveryand adverse events are recorded. A correlative assessment of germline mutations in homologous recombination (HR) genes is planned. Pts are monitored for response by magnetic resonance and mammography and also for relapse free survival and time to treatment failure. The study size sample has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of ≥47% (α= 0.05). Results: Accrual to the study is completed with 63 eligible pts with operable, noninflammatory stage II and III TNBC included. Most patients were between 40 and 60 yrs old and were clinical stageT2 tumors. Half of the pts were clinically node + and 70% were G3. Sixty six percent had breast conserving surgery. Sixteen out of 26 (61.5%) of the currently evaluable pts achieved a pCR rate in the breast and axilla. The other ongoing patients have not yet reached this endpoint. Four out of 21 evaluable pts that completed the chemotherapy missed two or more doses of CP due to neutropenia(NP) G3/4(2), general deterioration G3(1) and polyneuropathy(PNP) G3(1) and seven pts needed one dose reduction of P and/or CP due to NP G3-4 (3-2) and PNP G2(1) and one abdominal infection. Conclusion: These preliminary data suggest that the addition of weekly carboplatinum to neoadjuvant paclitaxel and EC is feasible and has a promising pCR rate in the breast and axilla as high as 61.5% in early TNBC pts. More mature toxicity and outcome data and correlation with genome analysis will be presented. (1) Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once per week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603(Alliance) Sikov WM et al. J Clin Oncol 33:13-21; 2014. Citation Format: Fontaine C, Cappoen N, Renard V, Vuylsteke P, Van Den Bulck H, Glorieux P, t'Kint de Roodenbeke D, Dopchie C, Decoster L, Vanacker L, De Grève J, Awada A, Wildiers H. Neoadjuvant weekly carboplatin and paclitaxel followed by dose dense epirubicin and cyclophosphamide in triple negative breast cancer patients: A single arm phase II study from the Belgian Society of Medical Oncology [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-06.

Bone disease is a key presenting feature of myeloma. This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone (VMP) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase (ALP), a marker for osteoblast activation, and serum Dickkopf-1 (DKK-1), an inhibitor of osteoblast differentiation, during treatment. Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2) , days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, days 1, 8, 22, 29, cycles 5-9, plus melphalan 9mg/m(2) and prednisone 60mg/m(2) , days 1-4, cycles 1-9; N=344) or MP alone (N=338). Rates of bisphosphonates use during treatment (73% vs. 82%), progression because of worsening bone disease (3% vs. 11%), and requirement for subsequent radiotherapy (3% vs. 8%) were lower with VMP vs. MP. Median maximum ALP increase was significantly higher with VMP vs. MP overall (49.7% vs. 30.3%, P=0.029), and higher by response group (complete response [CR]: 68.7% vs. 43.9%; partial response [PR]: 41.5% vs. 31.2%). Greater maximum ALP increase was strongly associated with achievement of CR (P≤0.0001) and CR/PR (P≤0.01). Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 (P=0.0069). Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients, who achieved best responses of three CR, one PR, and two stable disease. These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma.

To critically review the latest findings concerning the role of circulating tumor cells (CTCs) and other blood biomarkers in breast cancer. CTCs are epithelial tumor cells detected in the peripheral blood of patients with solid tumors using mainly cytometric/antibody-based and molecular approaches. Most technologies for CTC detection, including the FDA-approved CellSearch, are only detecting epithelial cell adhesion molecule (EpCAM)-positive CTCs and may miss clinically relevant subpopulations of CTCs. The value of CTC detection by CellSearch in metastatic breast cancer (MBC) may depend on the clinical setting and regimen used. In a retrospective analysis of 516 patients with MBC, CTC detection did not predict clinical outcome in chemo-naïve women with HER2-positive MBC treated with anti-HER2 therapy, but had prognostic value in other breast cancer subtypes. Similarly, changes in CTCs during treatment did not predict outcome in 67 women treated with first-line bevacizumab/chemotherapy. CTC detection by CellSearch before or after adjuvant chemotherapy was associated with worse disease-free survival in 1489 patients with early breast cancer. Circulating nucleic acids, microRNAs and genomic rearrangements have been suggested as promising blood biomarkers. Currently, there is no role for CTCs in clinical practice. The clinical utility of CTCs and other blood biomarkers should be prospectively tested.

Abstract Under the auspices of the Belgian Society of Medical Oncology (BSMO).Background: New drugs are generally tested in patients with metastatic disease where bulky tumor mass is present. However, antiangiogenic compounds are probably more beneficial in the prevention of regrowth from tumors with small tumor load than in bulky tumors. This study wants to test the hypothesis that antiangiogenic compounds such as sunitinib are able to delay tumor progression after tumor mass reduction by taxanes, i.e. an objective response (PR or CR).Materials and methods: This is a dual-arm open-label randomized multicenter phase II clinical trial with 2:1 randomization evaluating the efficacy of sunitinib (study arm) versus no therapy (control arm, only for descriptive purposes) in patients with metastatic breast cancer after objective response to taxane chemotherapy. Eligible patients had metastatic HER2 negative breast cancer, had received 10 to 20 weeks of first- or second line taxane containing chemotherapy resulting in an objective response (RECIST). Patients received sunitinib (arm A) 50 mg/d po 4w/6 (amended to 37.5 mg continuously in 1-2008) or no therapy (arm B). Patients were stratified for disease free interval and dominant site of disease. Patients randomized to arm B were offered the opportunity to receive open-label sunitinib treatment upon development of disease progression. Treatment was pursued until disease progression or major intolerance or patients refusal. All patients who received at least day 1 of study treatment were evaluated for efficacy, toxicity and safety. The duration of response after taxane treatment in previous studies with metastatic breast cancer is around 7 months. Based on this, the median time interval between the end of chemotherapy and tumor progression was expected to be about 5 months in our study population. The primary endpoint was to determine the proportion of patients alive and without disease progression (PFS) at 5 months after study entry in arm A. If ≤ 18/36 patients are progression-free and alive at 5 months, sunitinib will be declared insufficiently active (beta 0.05); if ≥ 22 patients are progression-free and alive at 5 months, sunitinib will be declared active (alpha 0.05) and it will be recommended to continue the trial as a phase III design.Results: 10/36 patients (28%) reached 5 months PFS in arm A and 4/19 in arm B (21%). Median PFS was 3.4 months in Arm A and 3.1 months in Arm B. Toxicity and overall survival data will be reported at the meeting.Discussion: This study does not confirm the hypothesis that sunitinib can lead to a significant proportion of patients with PFS of ≥ 5 months after objective response to taxanes. This proof-of-principle study suggests that also the role of consolidation therapy with other (already approved) antiangiogenic treatments should be evaluated carefully in prospective clinical trials (high economic cost). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 203.

Modern missiles cause important damage in the tissues. In case of bone injury, apart from the presence of foreign bodies and soil dirt in the foyer, the lesion is characterized by a certain instability caused by the smashing and resulting in the comminutive fractures, as well as severe lesions of the soft tissues. If primary treatment includes the necessity of a large wound excision, of which the modalities have been described for centuries, it also includes a rigorous immobilization of the foyer as precaution against shock and infection. All techniques proposed during former conflicts proved that they are little adapted to the final goal. Their inadequacy may lead to amputation, at any rate to severe sequelae. In war traumatology, opposed to the shortcomings of nonoperative methods and opposed to the prohibitions of intrafocal synthesis, external fixation is considered to be the best among compromises: it stabilizes fractures efficiently without risk, retains the distance between bone fragments, and prevents contracture of the muscles. External fixators promote debridement of the wounds, permit vascular repairs and control of the wounds, allow mobilization of the limbs, improve the injured's comfort, and facilitate evacuation . All types of external fixators can be used, but a number of military imperatives must be taken into account. Fixing of the device must be easy to every user, even with little training. A minimal number of parts must allow a maximal number of assemblies. Easy use implies simplicity, but the assembled set must be stable. It must reduce the reprise of reductions, its compression, and its distraction to a minimal number of acts. Moreover, it must be relatively cheap. In theory, all open war fractures should be treated by means of an external fixator. The problem, however of mass surgery under uncertain circumstances, the limited equipment, and a precarious supplying must be considered. Rwanda was involved in a war from October 1, 1990 to August 1, 1993 (Arusha's agreement). A Belgian medical team from the Military Cooperation had to cope with 4,646 different casualties. We treated 1,129 fractures, and among them 115 fractures of the arm, 122 fractures of the forearm, 80 fractures of the femur (including the neck and the condylae), and 148 fractures of the leg. We had to cope with 315 fractures of the hand, of which 220 fractures were of the metacarpal bone. "Strangely," there were always more lesions of the left hand (9.5%) than the right hand (5.8%), sometimes up to five times (the only exception was met in August 1993). We placed 209 external fixators (of which 20 bridging the joint in case of important impairment), including those used for an arthrodesis. In the majority fo the cases (93.3%), we used the French device Fixateur Externe du Service de Sante des Armees (FESSA). Until March 1993, we had no "orthopedic table." Since March 1988, we had an Image Intensifier, but not very appropriate to an operating room (no mobile C-arm). A more accurate one was lent by the Belgian Medical Service and set up in September 1992. The average time to place an external fixator was about 30 minutes. General practitioners were also trained to handle external fixators. According to the importance of mass casualties, an external fixator was used immediately upon arrival of the wounded or at revision day (5th day after debridement). The only exception were femoral fractures that were at first time-treated by traction for 10 days. Sometimes we had precarious supplying because the supplies had to be ordered in Europe. Sometimes one patient had to wait until material became available from another patient. External fixation was also used for reconstructive surgery, mainly for ankle arthrodesis. In conclusion, it was possible for a very small surgical team, on its own for 18 months, to cope with a lot of difficulties caused by lack of readiness of the Rwandan Armed Forces, lack of organization, and lack of discipline of the R