Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas

HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials

Breast MRI: guidelines from the European Society of Breast Imaging

The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)

Apoptosis in gallbladder carcinomas and dysplasias, its relation to the expression of caspases 3,6 and 8 and apoptosis regulating proteins bcl-2, mcl-l and bax

In this study we investigated apoptosis and the expression of caspases 3, 6 and 8 and bcl-2, mcl-l and bax in 39 gallbladder carcinomas and 7 epithelia1 dysplasias. The average apoptotic index was 0.68+-0.91%. The extent of apoptosis was higher in grade 11-111 than grade I tumours or epithelial dysplasias (p=0.003). Also, tumours invading beyond serosa or into other organs (T3-T4) had a higher apoptotic index than other tumours (p=0.05). Caspase 3 expression was found in 37 (95%) and caspase 6 and 8 expression each in 30 (77%) carcinomas. Their expression associated with each other and tended to increase along with the progression of the lesions. Bcl-2 expression was found in only 4 (10%) tumours. In contrast, mcl-l positivity was found in 34 (87%) and bax positivity in all cases. The results show that apoptosis is increased along with progression of the neoplastic lesion of the gallbladder epithelium. Caspases 3,6 and 8 are strongly expressed in gallbladder carcinomas suggesting that they contribute to the increased apoptosis observed in them. Of the bcl-2 family proteins, bcl-2 was expressed infrequently suggesting that it does not play any significant role in apoptosis inhibition in gallbladder tumours

Apoptosis in gallbladder carcinomas and dysplasias, its relation to the expression of caspases 3,6 and 8 and apoptosis regulating proteins bcl-2, mcl-l and bax

In this study we investigated apoptosis and the expression of caspases 3, 6 and 8 and bcl-2, mcl-l and bax in 39 gallbladder carcinomas and 7 epithelia1 dysplasias. The average apoptotic index was 0.68+0.91%. The extent of apoptosis was higher in grade 11-111 than grade I tumours or epithelial dysplasias (p=0.003). Also, tumours invading beyond serosa or into other organs (T3-T4) had a higher apoptotic index than other tumours (p=0.05). Caspase 3 expression was found in 37 (95%) and caspase 6 and 8 expression each in 30 (77%) carcinomas. Their expression associated with each other and tended to increase along with the progression of the lesions. Bcl-2 expression was found in only 4 (10%) tumours. In contrast, mcl-l positivity was found in 34 (87%) and bax positivity in all cases. The results show that apoptosis is increased along with progression of the neoplastic lesion of the gallbladder epithelium. Caspases 3,6 and 8 are strongly expressed in gallbladder carcinomas suggesting that they contribute to the increased apoptosis observed in them. Of the bcl-2 family proteins, bcl-2 was expressed infrequently suggesting that it does not play any significant role in apoptosis inhibition in gallbladder tumours