Treatment and survival of rectal cancer patients over the age of 80 years: a EURECCA international comparison.

BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+. METHODS: Patients of ≥80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients. RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO. CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A EURECCA International Comparison.

BACKGROUND: Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients. SUBJECTS, MATERIALS, AND METHODS: National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001-2006 and 2007-2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame. RESULTS: Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II-IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54-0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69-0.96) compared with Belgium. CONCLUSION: There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed. IMPLICATIONS FOR PRACTICE: With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality.

Survival among clinical stage I-III rectal cancer patients treated with different preoperative treatments: A population-based comparison.

BACKGROUND: Radical resection is regarded as the cornerstone of rectal cancer treatment. Preoperative (chemo)radiotherapy and adjuvant chemotherapy are often administered. This population-based study compares the survival in clinical stage I-III rectal cancer patients who received either preoperative radiotherapy, preoperative chemoradiotherapy or no preoperative therapy. As secondary research questions, the association of type of radical resection and adjuvant chemotherapy on survival is also investigated. METHODS: Patients diagnosed between January 2006 and December 2011 with stage I-III rectal adenocarcinoma were retrieved from the Belgian Cancer Registry database. Multivariable Cox proportional hazards regression models were applied to evaluate the association of preoperative treatment, type of radical resection and use of adjuvant chemotherapy with survival, adjusting for the baseline characteristics age, gender, WHO performance status and clinical stage. RESULTS: A total of 5173 rectal cancer patients were identified. Preoperative treatment was as follows: none in 1354 (26.2%), radiotherapy in 797 (15.4%) and chemoradiotherapy in 3022 (58.4%) patients. The patient group who did not receive preoperative therapy or radiotherapy followed by radical resection had a lower observed survival compared to the patient group receiving preoperative chemoradiotherapy. The patient groups who underwent abdominoperineal excision and those receiving adjuvant chemotherapy had a worse observed survival compared to the patient group treated with sphincter-sparing surgery and no adjuvant therapy respectively. These effects were age-dependent. Multivariable analysis demonstrated similar findings for the observed survival conditional on surviving the first year since surgery. CONCLUSION: In this population-based study among clinical stage I-III rectal cancer patients treated with radical resection, a superior observed survival was noticed in the patient group receiving preoperative chemoradiotherapy compared to the patients groups receiving no or preoperative radiotherapy only, adjusting for case mix, type of radical resection and adjuvant chemotherapy. Additionally, higher adjusted observed survival was also detected for the patient groups with sphincter-sparing surgery or no adjuvant chemotherapy.

Breakage-fusion-bridge cycles leading to inv dup del occur in human cleavage stage embryos.

Recently, a high incidence of chromosome instability (CIN) was reported in human cleavage stage embryos. Based on the copy number changes that were observed in the blastomeres it was hypothesized that chromosome breakages and fusions occur frequently in cleavage stage human embryos and instigate subsequent breakage-fusion-bridge cycles. In addition, it was hypothesized that the DNA breaks present in spermatozoa could trigger this CIN. To test these hypotheses, we genotyped both parents as well as 93 blastomeres from 24 IVF embryos and developed a novel single nucleotide polymorphism (SNP) array-based algorithm to determine the parental origin of (aberrant) loci in single cells. Paternal as well as maternal alleles were commonly rearranged in the blastomeres indicating that sperm-specific DNA breaks do not explain the majority of these structural variants. The parent-of-origin analyses together with microarray-guided FISH analyses demonstrate the presence of inv dup del chromosomes as well as more complex rearrangements. These data provide unequivocal evidence for breakage-fusion-bridge cycles in those embryos and suggest that the human cleavage stage embryo is a major source of chromosomal disorders.