Gastric cancer: How strong can curative intent treatment be in the elderly? Caio Max S. Rocha Lima, M.D. Professor of Medicine University of Miami & Sylvester Cancer Center
Gastric cancer: epidemiology Fourth most commonly diagnosed cancer worldwide 1 Still the second most common cause of cancer-related death globally 1 Global l incidence id rates Almost 1,000,000 cases 1 Nearly 700,000000 deaths 1 1. Parkin, et al. CA Cancer J Clin 2005 2. Botterweck, et al. Int J Epidemiol 2000
Gastric Cancer and the Elderly More than 50% of the patients are diagnosed at the age of 65 or older. > 500,000 pts/year world wide More than 70% of deaths from gastric cancer occur at the 65 or older Approximately 500,000 000 deaths/year world wide
Gastric Cancer Characteristics in the Elderly Younger Elderly (70 0r 0oder) Gender ratio: M/F 1.6/1 2.45/1 Family History Presence Absence Location Proximal or GE junction Lower or Distal Third Syncronous Cancer Increased frequence Pattern metastasis Peritoneum Liver 1- Jpn J Cancer Clin 1974;20:580 93. 2-J Gastrointest Surg 2006;10:1023 32. 32. 3-Br J Surg 2007;94:737 42. 4-Cancer 1990;65:2086 90.
Surgery In the Elderly R0 resection is the only curable modality The overall 5-year survival rate after curative resection in octogenarian patients varies between 44% to 65% while disease-specific 5- year survival rates vary from 53% to 62.5%. Jpn J Clin Oncol 1998;28:112 5 Jpn J Clin Oncol 1998;28:112 5. Hepatogastroenterology 1998;45:268 75.
Surgical Risks and the Elderly Surgical risk, evaluated preoperatively with the ASA score, is higher in elderly Higher rate of concomitant diseases. Total gastrectomy and D2 lymphadenectony is less often performed in the elderly. l Howeverr 90-day postoperative mortality rate is not higher h even in octogenarian patients t with pre-existing comorbidities J S O l 2004 88 201 5 J Surg Oncol 2004;88:201 5. Gastric Cancer 2007;10:39 44.
State t of the art 5-year survival rates with surgery alone are below 25% Multimodal strategies result in 10 14% improvement of OS in stage II and III Surgical resection alone is no longer standard! Europe USA Japan D2 resection ± perioperative chemotherapy D1 or D0 resection ± adjuvant chemoradiotherapy D2 resection ± adjuvant chemotherapy
GASTRIC CANCER MAGIC CLINICAL TRIAL DESIGN Gastric and Lower Third of the Esophagus RANDOMIZE CSC Arm Preoperative ECF Surgery Postoperative ECF S Arm Surgery alone Cunningham et al NEJM, 355, 12, 2006
MAGIC Trial S arm (N=253) 95% proceed to surgery CSC arm (N=250) 20% of patients at the perioperative p chemotherapy arm were over 70 years old. 88% completed preop CT 55% began postop pct 42% (104 pts) completed all 6 cycles Postop complications (46%) and 30d mortality similar (6%) in both arms Median Duration of post-operative hospital stay = 30 days in both arms. Cunningham et al NEJM, 355, 12, 2006
MAGIC SURVIVAL 10 1.0 0.9 0.8 Events Total 149 250 170 253 CSC S S U R V I V A L 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Logrank p-value = 0.009 Hazard Ratio = 0.75 (95% CI 0.63 0.93) MS: CSC 24 monts x S 20 Months 5 year survival: CSC 36% x C23% 0.0 0 1 2 3 4 5 PATIENTS AT RISK YEARS CSC S 250 149 86 57 32 15 253 136 60 31 22 9 Cunningham et al NEJM, 355, 12, 2006
Conclusions 1 Perioperative chemotherapy + surgery improves survival compared to surgery alone. 20% of patients at the perioperative 20% of patients at the perioperative chemotherapy arm were over 70 years old.
Surgery Followed by ChemoXRT
INT-0116 RESECTED STAGE IB-IV IV (MO) GASTRIC/GE JUNCTION ADENOCARCINOMA R A N D O M OBSERVATION 5FU/LV 5- FU/LV RADIATION 4,500 cgy 5- FU/LV 5FU/LV X2 ( (Macdonald, N Engl J Med, 2001)
Adjuvant Trial:Intergroup 0116 Patient Characteristics T stage T 1/2 31,1% T 3/4 68,8% (556 pts) Nodal status Negative 14,2% Positive 85,7% Dissection D0 54% D1 (Removal all N1 Nodes) 36% D>2 perigastric, celiac, splenic 10% or splenic-hilar, hepaticartery, and cardial lymph nodes, ( (Macdonald, N Engl J Med, 2001)
INT-0116 100% 80% 60% Overall Survival by Treatment Arm Median N Events in Months RX 281 160 36 OBS 275 185 27 P=.01 40% 20% 0% 0 24 48 72 96 120 Months After Registration 3-yr survival difference: 40% vs 50%
Conclusion INT-0116 Adjuvant chemoxrt improves survival after surgery compared to observation Age as a potential covariate yielded no significant differences to the effects of treatment. ( (Macdonald, N Engl J Med, 2001)
Adjuvant Chemotherapy
Adjuvant S1 Trial 1059 Gastric Ca pts stage II and III Gastrectomy + D2 disection RANDOMIZED S1 x 1 year Observation N Engl J Med2007;357(18):1810 20.
Adjuvant S1 in Gastric Cancer S-1 adjuvant chemotherapy for 1 year led to improvement in overall and relapse-free survival chemotherapy and the trial was discontinued early. 3-year overall survival: 80% vs 70% in the S-1 and surgery-only groups, respectively. Adjuvant S-1 after curative surgery has become a standard treatment in Japan. N Engl J Med2007;357(18):1810 20.
Neo Adjuvant and Adjuvant Therapy Adjuvant chemoradiotherapy and perioperative p or chemotherapy are recommended by the ESMO Guidelines in high-risk gastric cancer. Ann Oncol 2008;19(Suppl. 2):ii23 4.
Gastric Cancer and the Elderly Conclusions Age should not dictate the patients who should be submitted to curative treatment. Performance status and organ function are paramount. T3 tumors or higher or N positive tumors that are not metastatic should be considered for surgery plus neo-adjuvant or adjuvant therapy
Strategies Surgery Your hospital standard of total or partial gastrectomy with either D1 or D2 Ln dissection. Perioperative chemotherapy (Preferred) Magic Trial (503 pts, 26% esophageal/ge Junction). Positive Adjuvant Chemotherapy alone (S1 trial) Chemotherapy and chemoradiotherapy (intergroup 0016)
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