J.J.M. van der Hoeven

Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels <10 g/dl (P<0.001 and <0.05, respectively). A haemoglobin decrease <1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

Preoperative [18F] FDG–PET after chemotherapy in locally advanced breast cancer: prognostic value as compared with histopathology

BACKGROUND Established prognosis-based criteria determine the need for further treatment after primary surgery for breast cancer. Such criteria are lacking after neo-adjuvant chemotherapy. We determine the prognostic value of preoperative [(18)F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography ((18)FDG-PET) after chemotherapy in locally advanced breast cancer (LABC), both as independent indicator and as add-on to postoperative histopathology. PATIENTS AND METHODS Preoperative PET was carried out in 40 LABC patients. Two expert readers assessed residual (18)FDG uptake in the primary tumor. At histopathological examination of the surgical specimen, chemotherapy response was graded using the Honkoop criteria. Cox proportional hazards analysis was used to determine prognostic relevance of PET and histopathology. RESULTS Median follow-up was 60 months (range 15-94), during which 13 patients had recurrent disease, eight of whom died. (18)FDG uptake in the primary tumor was inversely related with disease-free survival (DFS) [hazard ratio (HR) 4.09; 95% confidence interval (CI) 1.26-13.31; P = 0.02] and this was superior to histopathology (HR 2.52; 95% CI 0.77-8.23; P = 0.13). Observer agreement of PET was excellent (intraclass correlation coefficient 0.88). Multivariate Cox regression revealed no added value of histopathology versus PET results. CONCLUSION (18)FDG uptake in the primary tumor at PET was inversely associated with DFS and may help to guide adjuvant therapy.

Quantitative assessment of lymph vascular space invasion (LVSI) provides important prognostic information in node-negative breast cancer

BACKGROUND Some studies investigating the prognostic value of lymph vascular space invasion (LVSI) have shown an association between LVSI and disease-free survival. Definitive criteria and optimal determination of this parameter remain unclear, however, especially regarding the clinical relevance of LVSI quantification. PATIENTS AND METHODS A subset of node-negative breast carcinomas from premenopausal patients from the European Organization for the Research and Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy patients with T1-T3, N0-2, and M0 breast cancer (BC) was selected and scored for LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells was determined in the largest tumor embolus within the lymph vessels. These two parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The optimal cutoff for this parameter was calculated in a test set (N = 120), tested in a validation set (N = 238), and compared with simple quantitation of the number of LVSI foci. RESULTS Tumors with a single LVSI focus are not associated with increased risk for relapse [hazard ratio (HR) 1.423, 95% confidence interval (CI) 0.762-2.656]. The LVSI TB had higher sensitivity and specificity compared with simple determination of the number of LVSI foci. LVSI TB was independently associated with disease-free survival in the validation set (HR 2.366, 95% CI 1.369-4.090, P = 0.002) in multivariate analysis and provided prognostic information in both the low- and high-risk node-negative BC groups (P < 0.001 and P = 0.007, respectively). CONCLUSION The determination of the number of LVSI foci multiplied by the number of tumor cells gives the most reliable quantitative assessment of this parameter, which can provide prognostic information in node-negative BC.

CorrespondenceRe: Sarcoid-like reaction to malignancy on whole-body integrated (18)F-FDG PET/CT: prevalence and disease pattern

SirdWe read with interest the manuscript by Chowdhury et al.1 reporting the occurrence of sarcoid-like reactions in 1.1% of cancer patients at 2[18F]-fluoro-2-deoxy-D-glucose (FDG)/computed tomography (CT) examination. We also observed FDG uptake in sarcoid-like reactions in cancer patients. In addition, we have observed two cancer patients with mediastinal and hilar biopsy-proven sarcoid-like reactions demonstrating a significant decrease in FDG uptake after anticancer treatment. Although false-positive FDG uptake in sarcoid-like reactions in cancer patients is a well-known and frequently described phenomenon in the evaluation of tumour stage and during follow-up,5–7 this decrease in FDG accumulation in sarcoid-like lesions after anticancer treatment is not. As metabolic tumour response assessment with FDG-positron-emission tomography (PET) has been accepted as a surrogate endpoint for the evaluation of anticancer treatment in oncology, and decrease in FDG uptake is considered to be a treatment-induced tumour response, we would like to bring these two cases to the attention of readers. The first patient was a 45-year-old woman with locally advanced ductal adenocarcinoma of the left breast and no history of granulomatous disease who underwent FDG-PET for distant metastatic staging. FDG-PET demonstrated pathological FDG uptake in the primary tumour in the left breast (Fig. 1a) and in the bilateral mediastinal and hilar lymph nodes (Fig. 1b). No focal axillary uptake was seen. Histological examination of the mediastinal lymph nodes excluded mediastinal metastases, but revealed non-caseating, sarcoid-like granulomas with small birefringent fragments consisting of silicium and calcium. The patient was treated with neoadjuvant chemo-immunotherapy consisting of six cycles of high-dose doxorubicin/cyclophosphamide with granulocyte-macrophage colony-stimulating factor (GM-CSF). Five months after the start of chemotherapy, FDG uptake in the primary tumour (Fig. 1c), as well as in the mediastinal and hilar lymph nodes (Fig. 1d) had decreased substantially. A left mastectomy and axillary lymph node dissection were performed. Histological specimen revealed a residual infiltrating ductal carcinoma with a diameter of 3 cm, one of the 15 axillary lymph nodes was

Patient-reported outcome assessment and objective evaluation of chemotherapy-induced alopecia

PURPOSE Alopecia is one of the most distressing side effects of chemotherapy. Evaluating and comparing the efficacy of potential therapies to prevent chemotherapy-induced alopecia (CIA) has been complicated by the lack of a standardized measurement for hair loss. In this study we investigated the correlation between patient-reported outcome assessments and quantitative measurement with the hair check to assess CIA in clinical practice. METHOD Scalp cooling efficacy was evaluated by patients by World Health Organisation (WHO) of CIA, Visual Analogue Scale (VAS) and wig use. The Hair Check was used to determine the amount of hair (in mm2) per unit of scalp skin area (in cm2) (Hair Mass Index, HMI). CIA was also evaluated by doctors, nurses and hairdressers. RESULTS Baseline HMI was not predictive for hair loss. HMI declined throughout all chemotherapy cycles, which was not reflected by patient-reported measures. HMI correlated with patient-reported hair quantity before the start of the therapy, but not with WHO and/or VAS during therapy. Patients opinion correlated moderately with the opinion of doctors and nurses (ρ = 0.50-0.56 respectively), but strongly with hair dressers (ρ = 0.70). CONCLUSIONS The Hair check is suitable to quantify the amount of hair loss and could complement research on refining outcome of scalp cooling, but the patients opinion should be considered as the best method to assess hair loss in clinical practice. TRIAL REGISTRATION Trialregister.nl NTR number 3082.