- Email: [email protected]
Perioperative chemotherapy for gastro-oesophageal cancer
Newsdesk
Predictive model for hereditary colorectal cancer
For predictive model, see: http://www1.hgu.mrc.ac.uk/ Softdata/MMRpredict.php
Researchers have been able to predict a patient’s risk of carrying mutations in DNA mismatch repair genes at the diagnosis of colon cancer, without the need to assess their familial gene status (N Engl J Med 2006; 354: 2751–63). Hereditary non-polyposis colorectal cancer (also known as Lynch syndrome) occurs in 3–4% of colon-cancer cases, and is caused by mutations that inactivate mismatch repair genes (mainly MLH1, MSH2, and MSH6). Carriers are at high risk of developing colorectal cancer and other cancers. Malcolm Dunlop and colleagues (University of Edinburgh, UK) did a comprehensive mutation analysis of 870 patients, diagnosed with colorectal cancer at age 54 years or younger. Germline DNA was analysed for MLH1, MSH2, and MSH6, and tumour DNA analysed for microsatellite instability. The mismatch repair genes also underwent immunohistochemical analysis,
and researchers recorded patients’ age and sex, location of the cancer, and familial cancer history. These data were used to develop a multivariate logistic regression model that could predict presence of mutations, and 38 patients were identified as carriers. The validity of the model was then assessed in a retrospective series of 155 patients. “We see the model being useful for both prospective patient surgical management at the time of diagnosis, and also for retrospective assessment of risk in helping clinical genetics departments decide who should have a gene test when there is an affected person in the family”, explains Dunlop. Although studies have suggested that the prognosis of colorectal cancer for patients with Lynch syndrome is better than for those with sporadic cases, Dunlop and co-workers did not find a significant difference between groups. Henry T Lynch (Creighton
University School of Medicine, Omaha, NE, USA), after whom the syndrome is named, says “this contradiction may be a consequence of the relatively small number of carriers, but certainly it conflicts with any retrospective analysis of families with the Lynch syndrome. This subject is a prime candidate for further study, given the extreme importance of identifying evidence for survival advantage in this disorder”. Christoph Engel (University of Leipzig, Germany) notes that this work is important in the trade-off between sensitivity and specificity depending on the probability cutoff of the model. However, “for clinical decision-making on whether a patient should undergo mutational analysis or not, the model alone does not provide enough information on the optimal decision threshold”, he warns.
Stephanie Bartlett
Perioperative chemotherapy for gastro-oesophageal cancer
Sheila Terry/Science Photo Library
Perioperative chemotherapy for patients with operable gastric or lower oesophageal adenocarcinomas reduces tumour size and stage, and significantly improves progression-free and overall survival compared with surgery alone.
Perioperative chemotherapy checkmates surgery in gastro-oesophageal cancer
624
“Our findings are the first demonstration that perioperative chemotherapy significantly improves survival in gastro-oesophageal cancer”, says David Cunningham, Royal Marsden Hospital, Surrey, UK. Until now, the standard of care in the UK and most of Europe has been surgery alone. In North America, patients have been given postoperative chemoradiation, but nothing before surgery. Researchers randomly assigned patients with resectable adenocarcinoma of the stomach, oesophagogastric junction, or lower oesophagus to either perioperative chemotherapy and surgery (n=250) or to surgery alone (n=253). Three cycles of epirubicin, cisplatin, and infused fluorouracil were given both before and after surgery. Resected tumours were significantly smaller and less advanced in the chemotherapy group. After 4 years’
median follow-up, fewer patients in the chemotherapy group had died than in the surgery-only group (149 vs 170). 5-year survival was greater in the group assigned perioperative chemotherapy compared with the group assigned surgery alone (36% vs 23%; N Engl J Med 2006; 355: 11–20). “This is a very important study because it shows both the benefit and the tolerability of the chemotherapy programme…the effectiveness of the strategy of giving preoperative treatment, and most importantly…that stomach cancer death can be reduced”, says Robert Mayer, Dana-Farber Cancer Institute, Boston, USA. “Whether this [study] will improve the likelihood that surgeons in the USA and other parts of the world will refer their patients to a cancer specialist before they operate remains to be seen”, he adds.
Rosie Taylor http://oncology.thelancet.com Vol 7 August 2006
Predictive model for hereditary colorectal cancer
For predictive model, see: http://www1.hgu.mrc.ac.uk/ Softdata/MMRpredict.php
Researchers have been able to predict a patient’s risk of carrying mutations in DNA mismatch repair genes at the diagnosis of colon cancer, without the need to assess their familial gene status (N Engl J Med 2006; 354: 2751–63). Hereditary non-polyposis colorectal cancer (also known as Lynch syndrome) occurs in 3–4% of colon-cancer cases, and is caused by mutations that inactivate mismatch repair genes (mainly MLH1, MSH2, and MSH6). Carriers are at high risk of developing colorectal cancer and other cancers. Malcolm Dunlop and colleagues (University of Edinburgh, UK) did a comprehensive mutation analysis of 870 patients, diagnosed with colorectal cancer at age 54 years or younger. Germline DNA was analysed for MLH1, MSH2, and MSH6, and tumour DNA analysed for microsatellite instability. The mismatch repair genes also underwent immunohistochemical analysis,
and researchers recorded patients’ age and sex, location of the cancer, and familial cancer history. These data were used to develop a multivariate logistic regression model that could predict presence of mutations, and 38 patients were identified as carriers. The validity of the model was then assessed in a retrospective series of 155 patients. “We see the model being useful for both prospective patient surgical management at the time of diagnosis, and also for retrospective assessment of risk in helping clinical genetics departments decide who should have a gene test when there is an affected person in the family”, explains Dunlop. Although studies have suggested that the prognosis of colorectal cancer for patients with Lynch syndrome is better than for those with sporadic cases, Dunlop and co-workers did not find a significant difference between groups. Henry T Lynch (Creighton
University School of Medicine, Omaha, NE, USA), after whom the syndrome is named, says “this contradiction may be a consequence of the relatively small number of carriers, but certainly it conflicts with any retrospective analysis of families with the Lynch syndrome. This subject is a prime candidate for further study, given the extreme importance of identifying evidence for survival advantage in this disorder”. Christoph Engel (University of Leipzig, Germany) notes that this work is important in the trade-off between sensitivity and specificity depending on the probability cutoff of the model. However, “for clinical decision-making on whether a patient should undergo mutational analysis or not, the model alone does not provide enough information on the optimal decision threshold”, he warns.
Stephanie Bartlett
Perioperative chemotherapy for gastro-oesophageal cancer
Sheila Terry/Science Photo Library
Perioperative chemotherapy for patients with operable gastric or lower oesophageal adenocarcinomas reduces tumour size and stage, and significantly improves progression-free and overall survival compared with surgery alone.
Perioperative chemotherapy checkmates surgery in gastro-oesophageal cancer
624
“Our findings are the first demonstration that perioperative chemotherapy significantly improves survival in gastro-oesophageal cancer”, says David Cunningham, Royal Marsden Hospital, Surrey, UK. Until now, the standard of care in the UK and most of Europe has been surgery alone. In North America, patients have been given postoperative chemoradiation, but nothing before surgery. Researchers randomly assigned patients with resectable adenocarcinoma of the stomach, oesophagogastric junction, or lower oesophagus to either perioperative chemotherapy and surgery (n=250) or to surgery alone (n=253). Three cycles of epirubicin, cisplatin, and infused fluorouracil were given both before and after surgery. Resected tumours were significantly smaller and less advanced in the chemotherapy group. After 4 years’
median follow-up, fewer patients in the chemotherapy group had died than in the surgery-only group (149 vs 170). 5-year survival was greater in the group assigned perioperative chemotherapy compared with the group assigned surgery alone (36% vs 23%; N Engl J Med 2006; 355: 11–20). “This is a very important study because it shows both the benefit and the tolerability of the chemotherapy programme…the effectiveness of the strategy of giving preoperative treatment, and most importantly…that stomach cancer death can be reduced”, says Robert Mayer, Dana-Farber Cancer Institute, Boston, USA. “Whether this [study] will improve the likelihood that surgeons in the USA and other parts of the world will refer their patients to a cancer specialist before they operate remains to be seen”, he adds.
Rosie Taylor http://oncology.thelancet.com Vol 7 August 2006