Locally Advanced Esophageal Cancer Research Articles

Analysis of overall survival and self-reported fatigue in patients with locally advanced esophageal cancer: A Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus Registry Consortium study.

9057 Background: We analyzed overall survival (OS) and self-reported fatigue scores in patients with esophageal cancer (EC) enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus Registry (EABE). Methods: Patients enrolled in the EABE between September 2001 and January 2009 returned a baseline quality of life questionnaire (n=1,481) including a Linear Analog Self Assessment (LASA) fatigue score which was scored on a 0-10 scale, with 0 as the most extreme fatigue. Patients were categorized as having a clinically deficient fatigue (DF) level if they reported a score of ≤ 5 and a clinically non-deficient fatigue (nDF) level if they reported a score of >5. Kaplan-Meier methodology and Cox models explored the relationship between OS and fatigue scores in patients with EC. Results: A total of 667 patients with EC were included in the EABE, of which 659 returned a registry questionnaire with a valid LASA fatigue score recorded. Median age at the time of registry entry was 65 years (range 23-92). A total of 392 (59%) and 267 patients (41%) reported DF and nDF, respectively. On univariate analysis, patients with nDF had improved 5-year OS compared to patients with DF. In patients having esophagectomy prior to LASA, those reporting nDF had improved survival compared to patients with DF (54% vs 40%, HR=0.63, p=0.04). A similar result was seen in patients having no esophagectomy prior to LASA (28% vs 20%, HR=0.75, p=0.03). Among the 368 patients with locally advanced EC (LAEC), those reporting nDF had improved 5-year OS compared to patients with DF. This remained significant on multivariate analysis (HR=0.71, p=.015). Conclusions: Patient-reported fatigue is associated with overall survival in patients with esophageal cancer, including those with LAEC. Therefore, fatigue scores should be considered as a stratification factor in the design of future clinical trials. N (events) 5-year OS P value HR (95% CI) All EC patients DF nDF 392 (218) 267 (126) 28% (22% - 35%) 37% (30% - 46%) .006 0.74 (0.59 – 0.92) Locally advanced EC DF nDF 216 (144) 152 (84) 17% (11% - 26%) 28% (19% - 40%) .003 0.67 (0.51 – 0.87)

Patient-reported fatigue and overall survival in locally advanced esophageal cancer: A Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry Consortium study.

9 Background: We examined patient-reported fatigue scores and overall survival (OS) in patients with esophageal cancer (EC) enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry (EABE). Methods: 1,481 patients enrolled in the EABE between September 2001 and January 2009 returned a baseline quality of life questionnaire including a Linear Analog Self Assessment (LASA) fatigue score which was scored on a 0-10 scale, with 0 as the most extreme fatigue. Patients were categorized as having clinically deficient fatigue (DF) if they reported a score of ≤ 5 and clinically non-deficient fatigue (nDF) if they reported a score of > 5. Kaplan-Meier methodology and Cox models explored OS in relation to fatigue scores in patients with EC. Results: A total of 667 patients with EC were included in the EABE, of which 659 returned a registry questionnaire with a valid LASA fatigue score recorded. Median age at the time of registry entry was 65 years (range 23-92). A total of 392 (59%) and 267 patients (41%) reported DF and nDF, respectively. On univariate analysis, patients with nDF had improved 5-year survival compared to patients with DF. In patients having esophagectomy prior to LASA, those reporting nDF had improved survival compared to patients with DF. Similarly, in patients having no esophagectomy prior to LASA, those with nDF had improved survival compared to those with DF. Among the 368 patients with locally advanced EC (LAEC), those reporting nDF had improved 5-year overall survival compared to patients with DF (28% vs 17%, HR = 0.67, p = 0.003). This remained significant on multivariate analysis (HR = 0.71, p = 0.015). Conclusions: Patient-reported fatigue is associated with overall survival in patients with LAEC. As a result, fatigue scores should be considered as a stratification factor in future clinical trial design. [Table: see text] No significant financial relationships to disclose.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer

Background:Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.Methods:We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR).Results:In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD.Conclusions:Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer

Background:Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy.Methods:Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15–30 mg m−2 per week and cisplatin 15–30 mg m−2 per week in six planned dose levels (DLs) in 3–6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy.Results:A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m−2, cisplatin 15 mg m−2) and grade 3 nausea in DL2 (20 mg m−2, 15 mg m−2). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial).Conclusion:Cisplatin and docetaxel each 30 mg m−2 per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer.

A Multicenter Study of Survival After Neoadjuvant Radiotherapy/Chemotherapy and Esophagectomy for ypT0N0M0R0 Esophageal Cancer

To evaluate 5-year survival of patients with locally advanced esophageal cancer (LAEC) who have undergone multimodality treatment with complete histopathologic response. Patients with LAEC may obtain excellent local-regional response to multimodality therapy. The overall benefit of a complete histopathologic response, when no viable tumor is present in the surgical specimen, is incompletely understood and existing data are limited to single-center studies with relatively few patients. The aim of this multicenter study was to define the outcome of patients with complete histopathologic response after multimodality therapy for LAEC. The study population included 299 patients (229 male, 70 female; median age: 60 years) with LAEC (cT2N1M0, T3-4N0-1M0; 181 adenocarcinomas, 118 squamous carcinomas) who underwent either neoadjuvant radiochemotherapy (n = 284) or chemotherapy (n = 15) followed by esophagectomy at 6 specialized centers: Europe (3) and United States (3). All patients in the study had stage ypT0N0M0R0 after resection. Esophagectomy with thoracotomy (n = 255) was more frequent than with a transhiatal approach (n = 44). The median number of analyzed lymph nodes in the surgical specimens was 20 (minimum-maximum: 1-77). Thirty-day mortality rate was 2.4% and 90-day mortality rate was 5.7%. Overall 5-year survival rate was 55%. The disease-specific 5-year survival rate was 68%, with a recurrence rate of 23.4% (n = 70; local vs distant recurrence: 3.3% vs 20.1%). Cox regression analysis identified age as the only independent predictor of survival, whereas gender, histology, type of esophagectomy, type of neoadjuvant therapy, and the number of resected lymph nodes had no prognostic impact. Patients with histopathologic complete response at the time of resection of LAEC achieve excellent survival.

Efficacy and side-effects of docetaxel combined with cisplatin on the treatment of local advanced esophageal cancer with concomitant radiation therapy

To investigate the therapeutical effect and side-effect of docetaxel combined with cisplatin (DDP) on the treatment of local advanced esophageal cancer with concomitant radiation therapy. Ninety patients with LOCAL advanced esophageal squamous cell carcinoma were divided into two groups: (DDP + 5-Fu) group and (docetaxel + DDP) group. Chemotherapy was carried out every 4 weeks for a total of 4 courses. The radiation dose was 50.4 Gy/28FX. The median survival time of patients in the (DDP + 5-Fu) group was 16 months and that in (docetaxel + DDP) group was 21 months (P = 0.0278). The 3-year survival rate in the (docetaxel + DDP) group was obviously higher than that in the (DDP + 5-Fu) group (23.9% vs. 12.1%). The ORR in (docetaxel + DDP) group (84.5%) was significantly higher than that in the (DDP + 5-Fu) group (71.1%) (P = 0.025). No significant differences were observed in the incidence of side-effects in the two groups. The conventional dose chemotherapy of docetaxel + DDP with concomitant radiation therapy showed a better partial remission rate and long-term survival rate for the treatment of local advanced esophageal cancer than the traditional chemotherapy (DDP + 5-Fu) with concomitant radiation therapy and the side-effects are not increased.

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

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. 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. 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. 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.

Weekly Chemotherapy with Cisplatin and Paclitaxel and Concurrent Radiation Therapy as Preoperative Treatment in Locally Advanced Esophageal Cancer: A Phase II Study

ABSTRACTWe evaluated the association of a weekly cisplatin (35 mg/mq) and paclitaxel (45 mg/mq) regimen with radiotherapy (46 Gy) as primary treatment in locally advanced esophageal cancer (LAEC). The main end point was the activity in terms of pathologic complete response (pathCR) rate. Thirty-three LAEC patients received chemoradiation therapy during weeks 1–6 followed by esophagectomy. A pathCR was observed in 10/33 patients; 20/33 and 3/33 patients showed PR and SD, respectively. The EUS maximal transverse cross sectional area reduction >50% significantly correlated with pathCR. Three-year survival rate was 35%. These results support the activity and mild toxicity of this regimen.

A clinical study of combination of radiotherapy and IP regimen in the treatment of patients with local advanced esophageal cancer

Objective The aim of this study was to study the clinical efficacy and toxicity of combination of the radiotherapy and IP regimen for patients with local advanced esophageal cancer.

6566 A multicenter phase II study of induction CT with Folfox-4 and Cetuximab followed by RT and Cetuximab in locally advanced esophageal cancer (LAEC)

6566 A multicenter phase II study of induction CT with Folfox-4 and Cetuximab followed by RT and Cetuximab in locally advanced esophageal cancer (LAEC)

6565 The role of PET-TC in predicting the pCR in locally-advanced esophageal cancer (LAEC) after a preoperative CT-RT treatment: data from B152 trial

6565 The role of PET-TC in predicting the pCR in locally-advanced esophageal cancer (LAEC) after a preoperative CT-RT treatment: data from B152 trial

Adjuvant sunitinib following chemoradiotherapy (CRT) and surgery for esophageal cancer: A phase II trial

e15550 Background: Locally advanced esophageal cancer (LAEC) has a 5-year survival of < 30 %. Most patients (pts) fail after curative intent tri-modality treatment with distant metastatic disease. This phase II trial aims to determine if adjuvant targeted therapy, after neoadjuvant CRT plus surgery for resectable LAEC, may impact on systemic disease without significant toxicity. Methods: Pts with LAEC of the thoracic esophagus or gastroesophageal junction, ECOG PS 0,1 and surgical candidates treated with: preoperative Irinotecan (65mg/m2 initially, ammended to 50mg/m2) + Cisplatin (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (50Gy/25 fractions) on weeks 4–8. Esophagectomy during weeks 15–18. Sunitinib 37.5mg daily (escalating to 50mg daily if tolerated) commenced 4–12 weeks post surgery, for 1 year. Primary endpoint is feasibility and efficacy of adjuvant sunitinib. Planned sample size 36pts. Results: 30pts enrolled from 11/06 to 12/08. Median age 64 yr (43–71), male: 22, adenocarcinoma: squamous 22:6; 10 pts stage IIA, 5 IIB and 13 III. 2 pts excluded with positive PET scan. 28 pts completed CRT - 18 pts (64%) received ≥80% of planned chemotherapy dose, 23 pts (82%) received full radiation dose. Grade 3/4 toxicity included: neutropenia (17/28), diarrhea (7/28), dehydration (4/28), febrile neutropenia (FN) (3/28) and nausea (2/28). 2 deaths on chemotherapy (1 bacterial meningitis, 1 FN) leading to irinotecan dose- reduction. Dysphagia improved in 14/23 pts during CRT. 18 pts have undergone esophagectomy. Complete pathological response in 4 (22%), downstaging in 3 (17%), stable disease in 11 (61%). 2 pts unresectable (metastases at laparotomy). 1 post-operative death due to pulmonary embolus. 9 pts have commenced sunitinib, 6 maintained at starting dose of 37.5mg; 2 dose reductions; 1 discontinued with poor wound healing. Grade 3 toxicity included: leukopenia (2/9), hand-foot reaction (1/9) and depression (1/9). Conclusions: In LAEC, induction Irinotecan/Cisplatin and radiotherapy followed by esophagectomy is associated with a significant but manageable toxicity profile. Early initiation of sunitinib is feasible and well-tolerated. Updated results to be presented. No significant financial relationships to disclose.

A multicenter phase II study of induction CT with FOLFOX-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC)

4546 Background: Preoperative CRT improves the survival of pts with EC when compared with surgery alone. Epidermal growth factor receptor (EGFR) is overexpressed in 30–90% of EC and is associated with poor prognosis, providing the rationale for using the anti-EGFR monoclonal antibody cetuximab (C). The purpose of the study was to investigate the efficacy, toxicity and feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC in a multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus; staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions.All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. Simons two stage design was used. Primary endpoint was histopathological response rate. Results: Up to December 2008, 40 pts, 30 men, were enrolled from 4 institutions; median age 59 y (35–70y); AC 12; SCC 28; stage II 15, stage III 25 pts. At this time 32/40 pts were evaluable. The most frequent grade 3/4 toxicity of chemoradiotherapy were skin (32%),neutropenia (29%) and esophagitis (9%); 10 pts had no resection (9 progressive disease,1 patient's refusal). Of 22 operated pts, 17 pts (77%) had RO-resection, 5 pts had palliative surgery.2 pts died due to complications after surgery (1 after > 30 days). The pathological response rate was 68 %, with a complete histopathological remission recorded in 6 pts (27%);17 pts (53%) are still alive without residual or recurrent disease. Conclusions: The current findings suggest the feasibility of incorporating cetuximab into a preoperative regimen for LAEC pts and an encouraging antineoplastic activity with 68% histopathological responders. No significant financial relationships to disclose.

502 POSTER Modification of cisplatin administration schedule in FLEP preoperative chemotherapy improved response to the chemotherapy in patients with locally-advanced esophageal cancer

502 POSTER Modification of cisplatin administration schedule in FLEP preoperative chemotherapy improved response to the chemotherapy in patients with locally-advanced esophageal cancer

A Phase I Study of Concurrent Late Course Accelerated Hyper-fractionated Radiotherapy and Capecitabine and Cisplatin for Local Advanced Esophageal Cancer

A Phase I Study of Concurrent Late Course Accelerated Hyper-fractionated Radiotherapy and Capecitabine and Cisplatin for Local Advanced Esophageal Cancer

Induction primary CT with Folfox-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC): Analysis of preliminary data from B152 Trial

15524 Background: Primary CRT improves the survival of pts with EC when compared with surgery alone.However, the survival benefit conferred by CRT is modest and further improvements in the management of LAEC are required. In EC, increased EGFR expression correlates with a worse prognosis in terms of shorter DFS and OS suggesting the possibility of treatment with anti- EGFR mAb Cetuximab (C). Methods: Based on this background, we initiated a phase II trial to investigate the feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC. Pts underwent staging with EUS plus biopsies, PET and CT scans. Eligibility: untreated EC; EUS stage II-III; ECOG PS 0–2; adequate organs function; informed consent. All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. The primary end-point was the pathologic complete responses (pCR) rate. According on a two step Simon design, 31 pts have to be enrolled at the first step of the study. In case of 4 or more pCR, the study will be continued and 24 additional pts will be treated. Results: Up to December 2007, 27 pts have been enrolled: 21 men, 6 women, squamous cell carcinoma 18, adenocarcinoma 9, stage II 3 pts, stage III 24 pts. After induction treatment, the following grade 3–4 toxicities were recorded: neutropenia 7%, thrombocytopenia 4%, skin 4%. Between the 16 pts who completed RT and C, the main grade 3–4 toxicities were: esophagitis 6%, skin 12 %. After CRT 3 pts had PD; of the remaining pts, 10 underwent esophagectomy and 3 pts await surgery. All 10 pts had R0 resections:9 pts were downstaged and 1 pt had no change; a pCR was recorded in 4 pts (40%). Conclusions: The integration of CRT with C is well tolerated; the preliminary activity, indicate that this regimen is efficacy suggesting the continuation of the study until the final sample of 55 pts. No significant financial relationships to disclose.

Survivin expression in esophageal cancer: Association with histomorphological response to neoadjuvant therapy and prognosis

4536 Background: The poor prognosis associated with locally advanced esophageal cancer prompted an evaluation of combined modality treatments including neoadjuvant radiochemotherapy in combination with surgery. However, it has been well established that only patients with a complete pathological response to neoadjuvant therapy will have a significant survival benefit. Therefore, predictive markers to allow a tailored radiochemotherapy are needed. The aim of this study was to examine the association of the protein expression of survivin, an inhibitor of apoptosis, with histopathologic response to neoadjuvant radiochemotherapy and prognosis of patients with locally-advanced esophageal cancer. Methods: 59 patients with esophageal cancer (cT2–4, Nx, M0) received neoadjuvant radiochemotherapy (cisplatin, 5-FU, 36 Gy) followed by esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10 % and as minor response when resected specimens contained more than 10 % of residual vital tumor cells. Pre- and post-therapeutic intratumoral protein expression of survivin was determined and correlated with clinicopathologic parameters. Results: The pre-therapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor, including histopathologic response and prognosis. Survivin protein expression was significantly reduced during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p<0.01). Higher postoperative survivin levels were significantly associated with a higher ypT-stage (p<0.009), a poorer histopathologic response (p<0.01) and a shorter overall survival (p<0.028). Conclusions: The intratumoral protein expression of survivin was significantly down-regulated during neoadjuvant therapy, whereas a higher survivin level after pre-operative therapy was significantly associated with a worse histopathologic response and prognosis. Therapeutic strategies which are able to reduce survivin expression or to block survivin mediated pathways might increase the histopathologic response rate and prognosis in the multimodal therapy of patients with locally-advanced esophageal cancer. No significant financial relationships to disclose.

Baseline Nutritional Status Is Predictive of Response to Treatment and Survival in Patients Treated by Definitive Chemoradiotherapy for a Locally Advanced Esophageal Cancer

To assess the impact of baseline nutritional status on treatment response and survival in nonmetastatic patients with a locally advanced esophageal cancer (LAEC) treated with definitive chemoradiotherapy (CRT). One hundred five patients with LAEC treated by definitive CRT were retrospectively included. The CRT regimen was based on an external radiotherapy (RT) delivered concomitantly to a cisplatin-based chemotherapy (CT). Patients were considered to have a complete response (CR) to CRT when no residual tumor was detected on CT scan and esophagoscopy performed 2 months after the end of CRT. Multivariate analysis of predictive factors of response to CRT and survival were performed using a logistic regression and a Cox model, respectively. Mean value of baseline nutritional parameters was significantly different between nonresponder (N = 42) and responder (N = 63) patients to CRT (weight loss 10%vs 5.8%, P= 0.0047; serum albumin level 35 g/L vs 38.7 g/L, P= 0.0004; BMI 22.8 kg/m2vs 25.2 kg/m2, P= 0.01). In multivariate analysis, serum albumin level > 35 g/L was the only independent predictive factor of CR to CRT (P= 0.009). Independent prognostic factors of survival were BMI > 18 kg/m2 (P= 0.003), dysphagia Atkinson score <2 (P= 0.008), dose of RT > 50 Grays (Gy) (P < 0.0001) and CR to CRT (P < 0.0001). Survival was influenced by baseline nutritional status as well as dysphagia, dose of RT, and CR to CRT. Despite the retrospective design of the study, our results may provide the concept basis for performing a prospective nutritional intervention study in patients treated by definitive CRT for an esophageal cancer.

Phase II trial of preoperative (POP) irinotecan (I) + cisplatin (C) and radiotherapy for esophageal cancer

4056 Background: Esophagectomy (E) for locally advanced esophageal cancer (LAEC) yields limited survival; this phase II trial assess feasibility and efficacy of induction chemo-radiotherapy followed by E. Methods: Patients (pts) with LAEC of the thoracic esophagus (TE) or gastroesophageal junction (GEJ), ECOG PS ≤ 2 and surgical candidates underwent POP I (65mg/m2) + C (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (40Gy/20 fractions (F) during wk 4–7) and external beam boost (10Gy/5F on wk 8); E was performed on wk 12–16 after restaging. Pts receiving 75% of POP chemotherapy were eligible for pathologic (p) evaluation; planned sample size 36 nonM1A pts. Results: 52 pts enrolled from 11/02 to 12/05, mean age 60 yr (33–79), male:40, GEJ:TE/15:37; 37 adenocarcinoma, 13 SCC, 2 other; 13 pts were stage IIA, 7 IIB, 22 III, and 10 IVA. Toxicity during POP treatment included ANC (G3/4:36%), febrile neutropenia (9%), diarrhea (G3:9%), nausea (G3:6%), esophagitis (G3:2%) and anorexia (G3/4:15%); 3 pts stopped treatment due to toxicity, 2 withdrew, 2 progressed becoming non-operable, 1 died of a stroke and 1 from central line sepsis. Clinical response by RECIST was CR:2%, PR:30%, SD:62% and PD in 6%. Dysphagia improved or resolved in 34/47 pts (72%) during POP treatment. Of 43 evaluable pts, 41 underwent E, achieving R0 resection in 98% (1 refused E, 1 pending). Perioperative complications included anastomotic leak (23%), Afib (21%), pneumonia (21%), delirium (10%) and aspiration (10%); 1 pt died from aspiration. 7 pts (17%) achieved pCR, 2 of whom were pretreatment clinical stage IIA, 1 IIb and 4 III; downstaging occurred in 3/7 pts; 15 pts (36.6%) achieved minimal residual disease, 15 (36.6%) pPR, and 4 (9.8%) pSD. At a median (med) follow-up of 15.2 months (1.3–34.5m), 16/52 patients died (med &amp; 2yr overall survival (OS) of 29 m &amp; 66%). Of 41 resected pts, 17 recurred (med &amp; 2yr disease free survival (DFS) of 20m &amp; 46%) of whom 10 died of progression (med &amp; 2-yr OS of 29m &amp; 68.4%). 2yr DFS &amp; OS was 83% &amp; 86% in pCR vs 41% &amp; 76% in non-pCR. Conclusion: In LAEC, induction I/C and radiotherapy followed by E is associated with 72% dysphagia improvement, a significant but manageable toxicity profile, and encouraging survival compared to historical controls. [Table: see text]

Pathologic Complete Response May Not Represent the Optimal Surrogate for Survival After Preoperative Therapy for Esophageal Cancer

We designed a phase II trial to examine the benefit of preoperative hyperfractionated radiation therapy (XRT) and concurrent chemotherapy for patients with locally advanced esophageal cancer (LAEC). The pathologic complete response (pCR) was the primary endpoint to estimate efficacy. Twenty-three patients with LAEC received twice-daily XRT during wk 1 and 5 and once-daily XRT during wk 2-4 (59 Gy). Cisplatin (100 mg/m(2)) was given on d 1, while 5-fluorouracil (1000 mg/m(2)) was given by continuous infusion the first and fifth weeks of the XRT. The pCR for the 19 patients undergoing esophagectomy was 16%. The study was closed at the interim analysis having not met the required minimum pCR rate of 20%. Hematologic toxicities consisted of grades III and IV neutropenia observed in 33% and 14% of patients, respectively. Grade III nausea and vomiting was seen in 38% of patients. One grade V pulmonary toxicity occurred. The median survival was 44.6 mo with 65% of patients alive at 2 yr. The pCR rate in this trial did not meet the predetermined statistical minimum. With the encouraging 2-yr survival, it is not clear that pCR is a reliable surrogate endpoint to discern treatment efficacy.