Christoph Rochlitz

DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer

Adjuvant chemotherapy reduces the incidence of distant metastasis and increases survival of patients with colorectal cancer. However, predictive markers are needed to define subsets of patients with stage II and III disease that may benefit from adjuvant treatment. A secreted member of the TNF receptor superfamily, the decoy receptor 3 (DcR3), was reported to be amplified in colorectal cancer as a negative regulator of Fas‐mediated apoptosis. We analyzed DcR3 gene copy number and protein expression in a large series of tumors from a randomized multicenter trial of 5‐fluorouracil/mitomycin C (FU/MMC) adjuvant chemotherapy of the Swiss Group for Clinical Cancer Research (SAKK 40/81), using real‐time quantitative PCR and immunohistochemistry on tumor microarrays. Results of gene status and protein expression of DcR3 were correlated with disease‐free and overall survival of patients. We observed amplification of the DcR3 gene in 185/294 (63%) and overexpression of the DcR3 protein in 163/223 (73%) of colorectal tumors. Multivariate analysis showed no prognostic effect of DcR3 gene amplification and protein overexpression. However, adjuvant chemotherapy was significantly more beneficial in patients with normal DcR3 gene copy number than in patients with amplification (DFS: HR 2.84, 95% CI 1.16–6.98, p = 0.02; OS: HR 3.15, 95% CI 1.19–8.32, p = 0.02), whereas DcR3 protein overexpression did not influence the effect of adjuvant chemotherapy (DFS: HR 1.02, 95% CI 0.65–1.60, p = 0.95; OS: HR 0.95, 95% CI 0.61–1.49, p = 0.83). We conclude that amplification of the 20q13 locus is a predictive marker for adjuvant chemotherapy in colorectal cancer.

Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7

Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer. Potent tumor suppressor genes located in this region encode transforming growth factor β (TGF‐β) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF‐β‐mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large‐scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD7 appears to be more frequently amplified (10%) than the three other genes (4–7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF‐β signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene.

Decision-making about fertility preservation-qualitative data on young cancer patients' attitudes and needs.

The aim of the study was to get deeper insight into the significance of fertility in cancer patients, their attitude towards fertility preservation (FP), decisional conflicts, and patient’s needs in the decision-making process. Focus groups with 12 female cancer survivors were held and revealed that the significance of fertility was high and attitude towards FP positive. Religious and ethical reservations were not negligible. Standardized decision aids were considered helpful. More support is highly in demand and specific tools would be beneficial.

Knowledge about and attitude towards fertility preservation in young female cancer patients: a cross-sectional online survey

Abstract Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. However, because of their treatment, women might be confronted with impaired fertility. The options of fertility preservation (FP) techniques are increasing. The goal of this study was to assess knowledge about, and attitudes towards, fertility preservation in young female cancer patients. A cross-sectional online survey was conducted including 155 former female cancer patients from English and German speaking countries. The survey consists of questions about attitude towards, and knowledge about, fertility preservation. Results show that knowledge about fertility preservation was limited among participants. Positive attitudes towards fertility preservation significantly outweighed negative attitudes. Knowledge and attitude did not differ according to language or different healthcare systems. Confidence of knowledge was significantly higher in women who underwent any FP procedure compared to those who did not. Greater emphasis should be placed on counselling opportunities, the provision of adequate information and supporting material. A better understanding of these issues will hopefully enhance patients’ decision-making about FP options and assist the development of strategies to improve quality of care.

Addressing decisional conflict about fertility preservation: helping young female cancer survivors’ family planning decisions

Background Health professionals are challenged by a growing number of young long-term cancer survivors with their specific needs with regard to family planning. This study aimed at assessing decisional conflict (DC) in young female cancer patients regarding fertility preservation, identifying demographic, fertility and fertility preservation related factors, which may affect DC, and assessing the helpfulness of various decision-supports. Methods A retrospective, cross-sectional, web-based survey via an online questionnaire available in three languages with specific items concerning cancer, fertility, fertility preservation and the validated Decisional Conflict Scale targeted at current or former female cancer patients aged 18–45 years, with cancer types or treatment potentially affecting reproductive function. Results The 155 participating women showed considerable DC, especially with regard to missing information and support. DC was significantly lower in patients when the risk of infertility was discussed with a health professional, when they had undergone any procedure to preserve fertility, and when they had a university education. A longer time interval since cancer diagnosis was associated with higher DC. The most helpful decision-support tools were specialised websites and leaflets. Conclusions Young female cancer patients’ DC with regard to fertility preservation is very high. Information and support seem to be deficient. More information through standardised information tools might be an effective strategy to lower their DC at the time when treatment decisions need to be taken, and to improve their reproductive health after they have overcome cancer in the future.