United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) Randomized Controlled Trial Comparing Targeted Nodal Assessment and Ultrastaging With Standard Pathological Evaluation for Colon Cancer

OBJECTIVE:: Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. METHODS:: In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. RESULTS:: Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. CONCLUSIONS:: TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.     

Arm morbidity following sentinel lymph node biopsy or axillary lymph node dissection: a study from the Danish Breast Cancer Cooperative Group

BACKGROUND: Sentinel lymph node biopsy was implemented in the treatment of early breast cancer with the aim of reducing shoulder and arm morbidity. Relatively few prospective studies have been published where the morbidity was assessed by clinical examination. Very few studies have examined the impact on shoulder mobility of node positive patients having a secondary axillary dissection because of the findings of metastases postoperatively. AIM: We aimed to investigate the objective and subjective arm morbidity in node negative and node positive patients. METHODS AND MATERIALS: In a prospective study, 395 patients with tumors less than 4 cm, were included. Patients were recruited from seven Danish breast cancer clinics. Both subjective and objective arm and shoulder morbidity were measured before, 6 and 18 months after the operation. RESULTS: Comparing node negative patients having a sentinel lymph node biopsy with node negative patients having a lymph node dissection of levels I and II of the axilla, we found significant increase in arm volume among the patients who had an axillary dissection. Only minor, but significant, differences in shoulder mobility were observed comparing the two groups of node negative patients. Highly significant difference was found comparing sensibility. Comparing the morbidity in node positive patients who had a one-step axillary dissection with patients having a two-step procedure (sentinel lymph node biopsy followed by delayed axillary dissection) revealed no difference in objective or subjective arm morbidity. CONCLUSION: Node negative patients operated with sentinel lymph node biopsy have less arm morbidity compared with node negative patients operated with axillary lymph node dissection. Node positive patients who had a secondary axillary lymph node dissection after sentinel lymph node biopsy had no difference in either objective or subjective morbidity compared with node positive patients having a one-step axillary dissection.     

Multicenter prospective randomized trial comparing standard esophagectomy with chemoradiotherapy for treatment of squamous esophageal cancer: Early results from the Chinese University Research Group for Esophageal Cancer (CURE)

We conducted a prospective randomized trial to compare the efficacy and survival outcome by chemoradiation with that by esophagectomy as a curative treatment. From July 2000 to December 2004, 80 patients with potentially resectable squamous cell carcinoma of the mid or lower thoracic esophagus were randomized to esophagectomy or chemoradiotherapy. A two- or three-stage esophagectomy with two-field dissection was performed. Patients treated with chemoradiotherapy received continuous 5-fluorouracil infusion (200 mg/m2/day) from day 1 to 42 and cisplatin (60 mg/m2) on days 1 and 22. The tumor and regional lymphatics were concomitantly irradiated to a total of 50-60 Gy. Tumor response was assessed by endoscopy, endoscopic ultrasonography, and computed tomography scan. Salvage esophagectomy was performed for incomplete response or recurrence. Forty-four patients received standard esophagectomy, whereas 36 were treated with chemoradiotherapy. Median follow-up was 16.9 months. The operative mortality was 6.8%. The incidence of postoperative complications was 38.6%. No difference in the early cumulative survival was found between the two groups (RR = 0.89; 95% confidence interval, 0.37-2.17; log-rank test P = 0.45). There was no difference in the disease-free survival. Patients treated with surgery had a slightly higher proportion of recurrence in the mediastinum, whereas those treated with chemoradiation sustained a higher proportion of recurrence in the cervical or abdominal regions. Standard esophagectomy or chemoradiotherapy offered similar early clinical outcome and survival for patients with squamous cell carcinoma of the esophagus. The challenge lies in the detection of residue disease after chemoradiotherapy.     

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.