No abstract

Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor.

The purpose of this study was to examine the uptake and metabolism of 5-fluorouracil (5-FU) in human liver metastases. Patients with liver metastases of colorectal cancer were treated with 5-FU (500/600 mg/m)+folinic acid with or without trimetrexate. The clinical application of F-magnetic resonance spectroscopy (MRS) of 5-FU in a random group of patients (n=17) was investigated. MR spectra of all patients showed 5-FU and catabolite resonances, and fluoronucleotides were also seen in seven patients. A correlation was found between maximum levels of 5-FU catabolites as measured by F-MRS and response in a group with larger metastases. However, such correlation was not observed in a group with smaller metastases, probably because of a significant contribution of normal liver tissue to the MR spectra.

ObjectiveTo test the psychometric properties of the Dutch 45-item Supportive Care Needs Survey—Partners and Caregivers (SCNS-P&C45-D) among partners of women with breast cancer living in the Netherlands.MethodsIn this cross-sectional validation study, partners of patients with breast cancer were invited to complete a survey on the patient’s cancer and the caregiver’s level of unmet needs (SCNS-P&C45-D), psychological distress (HADS) and burden (EDIZ).Results43% of the invited informal caregivers responded (n = 302). Flooring effects were identified for three items of the SCNS-P&C45-D,which were then deleted from further analysis. The original factor structure and loading pattern of the SCNS-P&C45-D was not replicated. Internal consistency of the SCNS-P&C45-D and all subscales’ (emotional and relational needs, health care and illness related needs, practical needs, work and social needs) Cronbach’s alpha coefficients exceeded 0.80, the entire measure’s Cronbach’s alpha is 0.98. Most SCNS-P&C45-D subscales showed moderate correlations with distress and burden from informal care which was in line with expectations based on validity. The domain ‘Work and Social needs’ showed a high correlation with burden from informal care. Participants reported significantly more or higher unmet needs if they were younger (25.5% vs. 20.3% in older patients, p = 0.004), if diagnosis was less than 1 year ago in one subscale (Health Care and Illness related needs; 19.5% and 18%, p = 0.029, and the total SCNS-P&C45-D; 23.2% vs. 22.4%, p = 0.018).ConclusionsThe SCNS-P&C45-D is able to identify those partners of patients with breast cancer in need and those who are not.Electronic supplementary materialThe online version of this article (10.1186/s41687-019-0092-7) contains supplementary material, which is available to authorized users.

Although the rate of false-positive MRI results is high, the impact on the choice for prophylactic mastectomy is limited and is determined by the woman's preference before the establishment of a BRCA mutation.

Following an i.p. dose of 150 mg kg À1 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo 19 F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n ¼ 11) and C26-10 (5-FUsensitive; n ¼ 15) implanted s.c. in Balb/C mice. Time courses for tumour growth, intracellular levels of FdUMP, thymidylate synthase (TS) activity, and 5-FU in RNA were also determined, and the effects of a 9.5-min period of carbogen breathing, starting 1 min before drug administration, on MRS-detected 5-FU metabolism and tumour growth curves were examined. Both tumour variants generated MRS-detectable 5-FU nucleotides and showed similar initial growth inhibition after treatment. However, the growth rate of C26-B tumours returned to normal, while the sensitive C26-10 tumours, which produced larger fluoronucleotide pools, still showed moderate growth inhibition. Carbogen breathing did not significantly influence 5-FU uptake or fluoronucleotide production but did significantly enhance growth inhibition in C26-10 tumours. While both tumour variants exhibited incorporation of 5-FU into RNA and inhibition of TS via FdUMP, clearance of 5-FU from RNA and recovery of TS activity were greater for the insensitive C26-B line, indicating that these processes, in addition to 5-FU uptake and metabolism, may be important determinants of drug sensitivity and treatment response.

No abstract

Chemotherapy in non-responding cancer patients leads to unnecessary toxicity. A marker is therefore required that can predict the sensitivity of a specific tumour to chemotherapy, which would enable individualisation of therapy. 19F MR spectroscopy (19F MRS) can be used to monitor the metabolism of fluorinated drugs. The aim of this study was to develop a method for quantified localised detection of fluorinated compounds in human liver. For this purpose, sensitivity-optimised localised 19F MRS methods at 3 T were used to detect MR signals from capecitabine, 5'DFUR, 5'DFCR and FBAL after oral intake of capecitabine. As the radio-frequency (rf) coil is made tuneable to 19F and 1H, the same localisation method is applied to obtain 1H MR signals of water and of the 19F metabolites. In addition, T1 measurements have been performed to correct for measurement-induced saturation effects. Finally, absolute tissue concentrations of capecitabine metabolites were obtained in vivo, which revealed a substantial spatial heterogeneity of these metabolites in human liver after chemotherapy.