ypN0: Does It Matter How You Get There? Nodal Downstaging in Esophageal Cancer.

BACKGROUND: ypN0 following induction treatment for advanced esophageal cancer improves survival. Importance of how ypN0 is achieved is unknown. This study evaluates survival in "natural" N0 (cN0/ypN0) and "downstaged" N0 (cN+/ypN0) patients. METHODS: Among patients treated with induction treatment and surgery, 83 CT scans were retrieved in digital format and re-evaluated by a radiologist, blinded to pathological nodal status: 28 natural N0, 37 downstaged N0, and 18 ypN+. Impact of N0 classification on survival and associations with survival were identified. RESULTS: Survival varied with ypN: 3-year survival was 84 % for natural N0 patients, 59 % for downstaged N0, and 20 % for ypN+ (p < .001). Compared with natural N0 patients, risk of cancer mortality was 3.8 for downstaged N0 and 7.6 for ypN+ (p = .01). Survival was also stratified by ypT: compared with ypT0 natural N0, who had the best survival, intermediate survival was seen in ypT+ natural N0 [hazard ratio (HR), 1.3] and ypT0 downstaged N0 (HR, 1.8), and poor survival in ypT+ downstaged N0 (HR, 9.5) and ypN+ (HR, 12.0) (p = .026). CONCLUSIONS: Natural N0 and downstaged N0 patients are different clinical entities: downstaging cN+ with induction treatment producing downstaged N0 improves survival only if there is concomitant primary cancer downstaging to ypT0. Intermediate survival is seen in downstaged N0 patients with complete tumor response. Natural N0 patients experience intermediate survival with incomplete response (ypT+). Complete response in natural N0 patients produces the best survival. Means of obtaining ypN0 status matters and requires a complete response for downstaged N0 patients to benefit from induction treatment.

A phase II trial of induction epirubicin, oxaliplatin, and fluorouracil, followed by surgery and postoperative concurrent cisplatin and fluorouracil chemoradiotherapy in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction.

INTRODUCTION: Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy. METHODS: Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m/d, oxaliplatin 130 mg/m/d, and fluorouracil 200 mg/m/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) during weeks 1 and 4 of radiotherapy. RESULTS: Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control. CONCLUSIONS: Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.

The long-term efficacy of pneumatic dilatation and Heller myotomy for the treatment of achalasia.

BACKGROUND & AIMS: Studies comparing long-term success after pneumatic dilatation (PD) and laparoscopic Heller myotomy (HM) are lacking. This study compares long-term outcome of PD (single dilatation and graded approach) and laparoscopic HM and identifies risk factors for treatment failure. METHODS: A cross-sectional follow-up evaluation of an achalasia cohort treated between 1994 and 2002 was followed-up for a mean of 3.1 years. There was a total of 106 patients treated by graded PD (1-3 dilatations with progressively larger balloons) and 73 patients treated by HM (20 had failed graded PD and crossed over to HM). A symptom assessment (structured telephone interview or clinic visit) was performed and patients were given freedom from alternative therapies to determine treatment outcome. Endoscopy, manometry, and timed barium esophagram were performed to determine the cause of treatment failure. RESULTS: The success of single PD was defined as freedom from additional PDs: 62% at 6 months and 28% at 6 years (risk factors for failure: younger age, male sex, wider esophagus, and poor emptying on posttreatment timed barium esophagram). Freedom from subsequent PDs increased with each dilatation (graded PD). The success of graded PD and HM, defined as dysphagia/regurgitation less than 3 times/wk or freedom from alternative treatment, was similar: 90% vs 89% at 6 months and 44% vs 57% at 6 years (no risk factors for failure were identified). Causes of symptom recurrence were incompletely treated achalasia (96% after PD vs 64% after HM) and gastroesophageal reflux disease (4% after PD vs 36% after HM). CONCLUSIONS: No treatment cures achalasia. Short- and long-term success is similar for graded PD and laparoscopic HM. Therapeutic success decreases steadily over time. Achalasia patients need careful long-term follow-up evaluation.

Impact of induction concurrent chemoradiotherapy on pulmonary function and postoperative acute respiratory complications in esophageal cancer.

STUDY OBJECTIVE: To evaluate the effects of induction concurrent chemoradiotherapy (cCRT) on pulmonary function and postoperative acute respiratory complications (PARCs). DESIGN: A retrospective review of our patients treated with induction cCRT to determine the impact on pulmonary function and identify predictors of PARCs. Correlations were sought between patient demographics, clinical characteristics, pre-cCRT and post-cCRT pulmonary function, radiotherapy dose, chemotherapy agents, and the development of PARCs. PARTICIPANTS: One hundred fifty-five patients treated in three separate clinical trials were identified; 47 patients received 30 Gy (150 cGy bid) of radiation concurrently with a single course of cisplatin/5-fluorouracil (5FU), and 108 patients received 45 Gy (150 cGy bid in a split course) concurrent with two courses of either cisplatin/5FU (n = 69) or cisplatin/paclitaxel (n = 39). Esophagectomy was performed in 141 of these 155 patients following cCRT. RESULTS: cCRT was only associated with significant worsening of the diffusion capacity of the lung for carbon monoxide (Dlco), which decreased a median of 21.7% in the 45-Gy group (p = 0.007), and 8.6% in the 30-Gy group (p = 0.07). This Dlco decrease was statistically greater in the 45-Gy group than in the 30-Gy group (p = 0.02). PARCs developed in 18 patients. Percentage of predicted FEV(1) and FVC, both before and after cCRT, were both significantly higher in patients without PARCs than in patients with PARCs (p = 0.031 and p = 0.010, respectively). Post-cCRT Dlco was also significantly worse in patients with PARCs (p = 0.002). PARCs occurred significantly more often among those treated with 45 Gy (17 of 102 patients) compared to those treated with 30 Gy (1 of 39 patients) [p = 0.025]. In the 18 patients with PARCs, the median survival was only 2.1 months. This was significantly less than the 16.4-month median survival in the 123 patients who did not have PARCs (p = 0.001). CONCLUSIONS: In patients treated with induction cCRT, higher radiation doses result in increasing impairment of gas exchange. PARCs were more likely in those patients with lower lung volumes, lower post-cCRT Dlco, and in those receiving higher radiation doses. These acute respiratory complications were also associated with a significant reduction in patient survival.