ABSTRACT
OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.
Subject(s)
Adenocarcinoma/mortality , Antineoplastic Agents/therapeutic use , Pancreatectomy , Pancreatic Neoplasms/mortality , Adenocarcinoma/surgery , Adenocarcinoma/therapy , Aged , Chemotherapy, Adjuvant , Female , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/therapy , Prognosis , Proportional Hazards Models , Quality of Life , Radiotherapy, Adjuvant , Survival RateABSTRACT
AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.
Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Apoptosis/drug effects , Apoptosis/radiation effects , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Tumor Suppressor Protein p53/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/physiopathology , Adenocarcinoma/radiotherapy , Chemotherapy, Adjuvant , Humans , Mitotic Index/drug effects , Mitotic Index/radiation effects , Radiotherapy, Adjuvant , Rectal Neoplasms/drug therapy , Rectal Neoplasms/physiopathology , Rectal Neoplasms/radiotherapyABSTRACT
A patient treated for ovarian epithelial cancer by total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), total omentectomy and five courses of single agent carboplatin chemotherapy, developed retroperitoneal fibrosis. This was diagnosed at exploratory laparotomy 6 months after completing treatment. No predisposing drug history existed in this patient. We believe that there have been no previous reports of an association between retro peritoneal fibrosis and carboplatin treatment.
