Phase 2 trial of preoperative irinotecan plus cisplatin and conformal radiotherapy, followed by surgery for esophageal cancer.

BACKGROUND: Esophagectomy for locally advanced esophageal cancer (LAEC) is associated with limited survival. Trimodality therapy yields a small survival advantage, with cisplatin and 5-fluorouracil regimens most frequently studied. Newer regimens may impact these poor outcomes. This phase 2 trial assessed the feasibility and efficacy of induction chemoradiotherapy with cisplatin and irinotecan followed by esophagectomy. METHODS: Patients with LAEC of the thoracic esophagus or gastroesophageal junction underwent chemotherapy with preoperative irinotecan (65 mg/m(2)) plus cisplatin (30 mg/m(2)) on Weeks 1, 2, 4, 5, 7, and 8 with concurrent conformal radiotherapy (40 grays [Gy]/20 fractions during Weeks 4-7) and external beam boost (10 Gy/5 fractions at Week 8). Esophagectomy was performed between Weeks 12 and 16. Pathologic response was the primary endpoint with follow-up data on progression, survival, and toxicity as secondary endpoints. RESULTS: Fifty-two patients were enrolled from November 2002 to October 2005. Nineteen patients had American Joint Committee on Cancer stage II, 22 had stage III, and 11 had stage IVA disease. Grade 3 to 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria 2.0) during induction included neutropenia (36%), febrile neutropenia (8%), diarrhea (10%), and esophagitis (4%). Three patients withdrew from treatment due to toxicity. There was 1 treatment-related death. Clinical responses included complete response in 2%, partial response in 30%, stable disease in 62%, and progressive disease in 6% of patients. Dysphagia improved/resolved in 72% of patients during induction. Forty-three patients underwent esophagectomy and 7 (16%) achieved pathologic complete responses. Median and 3-year overall survival for patients receiving trimodality therapy was 36 months and 51%, respectively. CONCLUSIONS: In LAEC, concurrent irinotecan/cisplatin and radiotherapy followed by esophagectomy is reported to be associated with dysphagia improvement in 72% of patients, a significant but manageable toxicity profile, and encouraging survival compared with historic controls.

PET CT thresholds for radiotherapy target definition in non-small-cell lung cancer: how close are we to the pathologic findings?

PURPOSE: Optimal target delineation threshold values for positron emission tomography (PET) and computed tomography (CT) radiotherapy planning is controversial. In this present study, different PET CT threshold values were used for target delineation and then compared pathologically. METHODS AND MATERIALS: A total of 31 non-small-cell lung cancer patients underwent PET CT before surgery. The maximal diameter (MD) of the pathologic primary tumor was obtained. The CT-based gross tumor volumes (GTV(CT)) were delineated for CT window-level thresholds at 1,600 and -300 Hounsfield units (HU) (GTV(CT1)); 1,600 and -400 (GTV(CT2)); 1,600 and -450 HU (GTV(CT3)); 1,600 and -600 HU (GTV(CT4)); 1,200 and -700 HU (GTV(CT5)); 900 and -450 HU (GTV(CT6)); and 700 and -450 HU (GTV(CT7)). The PET-based GTVs (GTV(PET)) were autocontoured at 20% (GTV(20)), 30% (GTV(30)), 40% (GTV(40)), 45% (GTV(45)), 50% (GTV(50)), and 55% (GTV(55)) of the maximal intensity level. The MD of each image-based GTV in three-dimensional orientation was determined. The MD of the GTV(PET) and GTV(CT) were compared with the pathologically determined MD. RESULTS: The median MD of the GTV(CT) changed from 2.89 (GTV(CT2)) to 4.46 (GTV(CT7)) as the CT thresholds were varied. The correlation coefficient of the GTV(CT) compared with the pathologically determined MD ranged from 0.76 to 0.87. The correlation coefficient of the GTV(CT1) was the best (r=0.87). The median MD of GTV(PET) changed from 5.72 cm to 2.67 cm as the PET thresholds increased. The correlation coefficient of the GTV(PET) compared with the pathologic finding ranged from 0.51 to 0.77. The correlation coefficient of GTV(50) was the best (r=0.77). CONCLUSION: Compared with the MD of GTV(PET), the MD of GTV(CT) had better correlation with the pathologic MD. The GTV(CT1) and GTV(50) had the best correlation with the pathologic results.

Health-related quality of life in esophageal cancer: effect of neoadjuvant chemoradiotherapy followed by surgical intervention.

OBJECTIVE: We sought to determine the effect of neoadjuvant chemoradiotherapy followed by surgical intervention on health-related quality of life in patients with esophageal cancer. METHODS: Health-related quality of life was evaluated in a prospective phase II study of neoadjuvant chemoradiotherapy followed by esophagectomy in 52 patients with carcinoma of the esophagus. Esophagectomy was performed 6 weeks after completion of induction. Functional Assessment of Cancer Therapy-Esophageal scoring was performed before treatment, 7 weeks after initiation of neoadjuvant therapy, before resection, and at 1, 3, and 6 months and 1 year after resection. RESULTS: Forty-three patients completed the entire treatment protocol. Functional Assessment of Cancer Therapy-Esophageal scores decreased significantly after chemoradiation at week 7 (120 vs 127 at baseline, P = .04) but returned to baseline levels before surgical intervention (127). Similarly, scores decreased significantly after surgical intervention (115 at 1 month, P = .02) but returned to baseline levels by 3 months postoperatively (127). At 1 year postoperatively, there was a statistically significant improvement in scores compared with those at baseline (139, P = .003). Functional Assessment of Cancer Therapy-Esophageal scores continued to increase over time for patients who were alive at least 1 year after the operation with or without disease but were observed to significantly decrease in those who died within 1 year after the operation (P = .0001). An increase in quality of life was associated with a significantly lower risk of death (P = .04). CONCLUSION: Neoadjuvant therapy has a significant effect on health-related quality of life, but this is transient, with recovery to baseline within 5 to 7 weeks after completion of induction therapy. Health-related quality of life decreases again after surgical intervention but returns to baseline levels within 3 months.