title: Combined modality treatment for primary gastrointestinal non-Hodgkin's lymphoma: the Milan Cancer Institute experience.
abstract: BACKGROUND
  The study analyzes clinical-pathologic features, treatment and outcome of all patients with primary lymphoma of the gastrointestinal tract (GI-NHL) seen during the past two decades at the Milan Cancer Institute.
  
  
  METHODS
  Clinical and histopathological data from 135 patients presenting with GI-NHL and disease localized within the abdomen were reviewed. Of these, 114 (84%) presented with limited disease (stage I and II), while 21 patients were found to have disease involvement of other abdominal organs (i.e., liver, pancreas, peritoneum) or more than one gastrointestinal site and were therefore classified as stage IV. Seventy-three percent presented with lymphoma in the stomach, 15% in the small intestine and 9% in the large bowel, while in 5 cases multiple localizations of the gastrointestinal tract were documented. Median age was 50 years, with one-fourth of patients older than 60 years. According to the revised Kiel classification for GI-NHL, 61% of patients presented with pure high-grade lymphoma, 9% high-grade NHL associated with residual low-grade lymphoma, and 30% had low-grade NHL. Nine percent presented with bulky disease, 5% with elevated LDH and 21% with a Karnofsky performance status (PS) < or = 80.
  
  
  RESULTS
  Laparotomy with radical (108 patients) or palliative (15 patients) intent was performed in all patients who were not deemed at high risk of complication from major surgery. Complete removal of all measurable tumor was feasible in 101 patients, with no difference relative to primary site. Surgical morbidity and mortality were 11% and 2%, respectively. Overall, 83% of patients were treated with chemotherapy. Patients who did not receive systemic chemotherapy included 12 managed with surgery alone and 10 who received only postoperative irradiation mainly because of low-grade lymphoma with superficial disease. Of patients with limited disease, 99% achieved complete tumor remission. After a median follow-up of 73 months, 13 of 113 patients have relapsed, mostly (70%) outside the gastrointestinal tract. The actuarial 10-yr. freedom from progression (FFP) and overall survival (OS) were 84% and 86%, respectively. Aside from age, no other factor revealed a statistically significant impact on outcome. There was only a trend in favor of low-grade histology (FFP 97% vs. 79%), that failed to reach statistical significance. Of patients with advanced abdominal disease, 48% achieved complete remission with chemotherapy with or without prior surgical debulking. Actuarial 10-yr. FFP and OS were 44% and 42%, respectively. In this subset, tumor burden and LDH levels represented the most important prognostic factors affecting outcome.
  
  
  CONCLUSIONS
  This retrospective study underscores the good results obtained in a wide and unselected population of patients with limited-stage primary GI-NHL following a combined-modality approach that included surgical debulking and systemic chemotherapy for most patients. Surgery alone can be considered adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the submucosa. Patients with advanced GI-NHL show a long-term outcome similar to that of patients with advanced NHL arising outside the gastrointestinal tract.
authors.affiliation: Department of Cancer Medicine, Istituto Nazionale Tumori, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tondini
authors.forename: R
authors.initials: R
authors.lastname: Giardini
authors.forename: F
authors.initials: F
authors.lastname: Bozzetti
authors.forename: P
authors.initials: P
authors.lastname: Valagussa
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: R
authors.initials: R
authors.lastname: Bertulli
authors.forename: M
authors.initials: M
authors.lastname: Balzarotti
authors.forename: A
authors.initials: A
authors.lastname: Rocca
authors.forename: F
authors.initials: F
authors.lastname: Lombardi
authors.forename: A J
authors.initials: AJ
authors.lastname: Ferreri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007813:Laparotomy; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016896:Treatment Outcome