Background: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose–positron emission tomography (FDG–PET) for early assessment of chemotherapy response in patients ...with advanced colorectal cancer. Methods: Dynamic FDG–PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis metabolic rate of glucose (MRGlu) and a simplified method to measure glucose metabolism standardized uptake value (SUV) were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier estimates. Results: There was an increase in the rates of death (P = 0.049 for ΔMRGlu PET1–2; P = 0.017 for ΔSUV PET1–2; P = 0.032 for ΔMRGlu PET1–3; P = 0.048 for ΔSUV PET1–3) and progression (P = 0.026 for ΔMRGlu PET1–2; P = 0.035 for ΔSUV PET1–2; P = 0.041 for ΔMRGlu PET1–3; P = 0.081 for ΔSUV PET1–3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of ΔMRGlu and ΔSUV cut-off levels. Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG–PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.
Purpose: To assess the false-positive rate of breast cancer surveillance by magnetic resonance imaging (MRI) in BRCA mutation carriers and the impact of an abnormal mammography or breast MRI on the ...patients’ decision for prophylactic mastectomy. Patients and methods: A total of 196 BRCA mutation carriers were included with a median follow-up of 2 years (range 1–9) with annual mammography and MRI. Preference for prophylactic mastectomy was registered at first surveillance after the mutation carriership was revealed. Results: In all, 41% (81 of 196) of the women had at least one positive MRI or mammography. Malignancy was detected in 17 women: 11 at surveillance, 4 at an intended prophylactic mastectomy and 2 had an interval cancer. Imaging by mammography and MRI had a sensitivity of 71% and a specificity of 90%. The probability that a positive MRI result is false positive was 83%. In the group with a prior preference for mastectomy with and without a false–positive imaging, prophylactic mastectomy was carried out in 89% and 66%, respectively (P = 0.06), in the group with prior preference for surveillance these percentages were 15% and 11%, respectively (P = 0.47). Conclusion: 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.
Objective
To 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.
Methods
In 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).
Results
43% 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).
Conclusions
The SCNS-P&C45-D is able to identify those partners of patients with breast cancer in need and those who are not.
Abstract Purpose Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus ...breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients. Methods 89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength. Results 23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue. Conclusions The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients.
Following an i.p. dose of 150 mg x kg(-1) 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=11) and C26-10 (5-FU-sensitive; n=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.
Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. ...The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.
Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.
Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.
Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.
To determine whether carbogen breathing has an effect on 5-fluorouracil (5-FU) uptake, retention and metabolism in C38 murine colon tumours grown in C57Bl/6 mice, we used
in vivo
19F nuclear magnetic ...resonance (NMR) spectroscopy. Eleven tumour-bearing mice were treated with 150 mg/kg of 5-FU given intraperitoneally (i.p.). Five mice received carbogen gas (95% O
2 and 5% CO
2) for 9.5 min, starting 1 min before 5-FU administration. We found increased levels of 5-FU and its anabolites and catabolites by sequential
19F NMR spectroscopy in the group treated with 5-FU in combination with carbogen compared with the group treated with 5-FU alone. The maximum of normalised values of 5-FU and its metabolites, reached after carbogen breathing, was almost 2-fold higher than after treatment with 5-FU alone. Despite these increased concentrations no significant effect of carbogen on growth inhibition of the tumour by 5-FU was observed, which may be related to the size as well as the well vascularised and perfused conditions of the tumours studied.
In this phase IB study, 24 patients with advanced colorectal cancer were treated with escalating doses of weekly chronomodulated 48 h infusions of 5-fluorouracil (5-FU) biochemically modulated by ...methotrexate 40 mg/m2 and (6S)-leucovorin 8 x 45 mg orally. Two daily peak delivery periods (PDP), during which 65% of the daily dose was administered, were investigated: from 18.00 to 0.30 h and from 0.00 to 06.30 h. The maximal tolerated dose of 5-FU was 2800 mg/m2/48 h, with a PDP from 18.00 to 0.30 h.
High‐resolution 19F NMR spectroscopy at 9.4 T was used to study the difference in the metabolite pattern of 5‐fluorouracil (5‐FU) between viable and necrotic tissues of C38 murine colon tumors grown ...in C57BI/6 mice. Studies were performed on perchloric acid extracts of these tumor fractions after 5‐FU treatment. The 19F nuclear magnetic resonance spectra exhibited resonances representing 5‐FU, the catabolites α‐fluoro‐β‐ureidopropionic acid and α‐fluoro‐β‐alanine, as well as several fluoronucleotide anabolites. The absolute concentrations of anabolites and catabolites and the anabolite‐to‐catabolite ratio were significantly lower in the necrotic fraction than in the viable tumor fraction 50 min after administration of 5‐FU, whereas the absolute concentration of 5‐FU was the same. Therefore, in 5‐FU metabolism studies with NMR spectroscopy, it is important to consider the necrotic contribution to the tumor volume.
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