Outcomes of patients with squamous cell carcinoma of esophagus who did not receive surgical resection after neoadjuvant radiochemotherapy.

AIMS AND BACKGROUND: The primary objective was to assess the different reasons for refusal of surgical resection (SR) in patients with esophageal squamous cell cancer (ESCC), who were initially planned for neoadjuvant radiochemotherapy (N-RCT) + SR, but SR was not performed after N-RCT. METHODS AND STUDY DESIGN: From 1988 to 2011, 311 patients with ESCC were treated with N-RCT in a tertiary referral center for esophageal diseases. Fifty-three patients were analyzed who received RCT with 40-45 Gy and concomitant chemotherapy in neoadjuvant intention, but in whom the treatment was stopped or switched to definitive RCT due to progression, patient decision, or new findings. RESULTS: The reasons for refusal of SR for these 53 patients were as follows: (1) patients' or physicians' preference for the planned treatment was changed during the N-RCT, such that RCT was continued to a curative dose without a break (group 1, n = 23, 44%); (2) patients were restaged after 4 weeks, and the tumor board decided to continue RCT because R0 resection was unlikely and/or patients were medically unfit (group 2, n = 15, 28%); (3) patients refused continuation of any treatment (group 3, n = 15, 28%). Refusal of SR was significantly more likely in patients with longitudinal tumor dimension >8 cm and those with an Eastern Cooperative Oncology Group performance status score of 2. Median follow-up time from the start of N-RCT was 57 months (range 1-137 months). The survival rates at 2 and 5 years were 36 ± 7% and 27 ± 7%, respectively. Group 1 had significantly longer survival. CONCLUSIONS: The planned N-RCT+SR could not be completed in a considerable number of patients in a tertiary referral center. More strict selection criteria for multimodality treatment including SR could spare some of these patients an incomplete treatment and probably lead to increased utilization of definitive RCT.

Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus: long-term outcome.

PURPOSE: The purpose of this work is to report the long-term outcomes of three-dimensional conformal radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A retrospective analysis of patients treated with radio(chemo)therapy between 1988 and 2011 at Klinikum rechts der Isar, Technische Universität München was performed. In all, 168 patients received radio(chemo)therapy for ESCC in curative intention. The median follow-up time was 91 months (range 1-212 months). There were 128 men and 40 women with a median age of 63 years. Selection criteria for radio(chemo)therapy were unfit for surgery and/or unresectable primary tumor (n = 146, 87 %) or patients' choice (n = 22, 13 %). The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 54 Gy in 30 fractions of radiotherapy. RESULTS: The median overall survival (OS) was 20 months (95 % confidence interval 17-23 months). The OS at 2 and 5 years for the whole cohort was 41 ± 4 % and 22 ± 3 %, respectively. Forty patients (24 %) suffered an in-field recurrence. The most common acute nonhematologic toxicity >grade 2 was dysphagia in 35 % of the patients. Acute hematologic toxicity > grade 2 was recorded in 14 % of the patients. There was no grade 5 toxicity observed during the study. Poor ECOG performance status (0-1 vs. 2-3, HR = 1.70, p = 0.002) and weight loss ≥ 10 % before the start of therapy (HR = 1.99, p = 0.001) were among the factors significantly associated with poor OS in multivariate analysis. CONCLUSION: Three-dimensional conformal definitive radio(chemo)therapy is well tolerated and leads to long-term survival in more than 20 % of patients with advanced disease and/or contraindication to surgery. However, 24 % in-field recurrence remains a major concern. Prospective trials are warranted to assess if a well-tailored conformal radiochemotherapy can improve the local control and obviate the need for surgical resection in patients with good general condition and potentially resectable tumors.

Association between radiation dose and pathological complete response after preoperative radiochemotherapy in esophageal squamous cell cancer.

AIM: This study was undertaken to examine the impact of radiation dose on pathological complete response (pCR) rates following neoadjuvant radiochemotherapy (N-RCT) for squamous cell esophageal cancer (ESCC). PATIENTS AND METHODS: From 1988 to 2011, 218 patients were treated with 30-30.6 Gy (1.8-2 Gy per fraction), 39.6-40 Gy (1.8-2 Gy per fraction) or 44-45 Gy (1.8-2 Gy per fraction) and concomitant cisplatin ± 5-fluorouracil (5-FU), oxaliplatin + 5-FU or 5-FU alone. The most commonly used concomitant chemotherapy was continuous infusion of 5-FU-alone with a dose of 300 mg/m(2)/day during the whole course of treatment (n=111). To eliminate the dispersing effect of potentially different efficacy levels of these drug regimens on pCR, we excluded patients with regimens other than 5-FU-alone. RESULTS: Histomorphological regression grade 1a (0% residual tumor), 1b (<10% residual tumor), 2 (10-50% residual tumor) and 3 (>50% residual tumor) was observed in 26 (23%), 24 (22%), 36 (32%) and 25 (23%) patients, respectively. pCR was observed in 9 out of 71 (13%) patients treated with 30 Gy-30.6 Gy, 13 of 34 (38%) patients treated with 39.6-40 Gy and 4 of 6 (67%) patients treated with 44-45 Gy (p=0.001). Median follow-up time from the start of N-RCT was 191 months (range=2-262 months). The estimated 5-year overall survival (OS) was 33% for the whole cohort. OS at 5 years was 58% for patients with pCR compared to 25% for patients with less favorable response to N-RCT (p=0.009), respectively. CONCLUSION: The dose of radiation correlates significantly with the likelihood of achieving a pCR in stage II/III squamous cell esophageal cancer patients. Prospective randomized trials are required to definitively evaluate the impact of application of higher radiation doses on efficacy and safety/tolerability in the context of N-RCT on the clinical outcomes.

Long-term outcomes of trimodality treatment for squamous cell carcinoma of the esophagus with cisplatin and/or 5-FU: more than 20 years' experience at a single institution.

PURPOSE: The purpose of this article is to report the outcome of neoadjuvant radiochemotherapy (N-RCT) + surgery in patients with squamous cell carcinoma of the esophagus at a single institution. METHODS: We retrospectively reviewed data from patients who were referred to our department for N-RCT. From 1988­2011, 103 patients were treated with N-RCT with cisplatin and/or 5-fluorouracil (5-FU). Group 1: (n = 55) from 1988­2006 with 39.6­40 Gy and 5-FU with (n = 17) or without cisplatin (n = 38). Group 2: from 2003­2010 with 44­45 Gy and 5-FU with (n = 40) or without cisplatin (n = 8). All patients underwent radical resection with reconstruction according to tumor location and 2-field lymph node dissection. The degree of histomorphologic regression was defined as grade 1a (pCR, 0 % residual tumor), grade 1b (pSTR, < 10 % residual tumor), grade 2 (10­50 % residual tumor), and grade 3 (> 50 % residual tumor). RESULTS: Median follow-up time from the start of N-RCT was 100 months (range 2­213 months). The median overall survival (OS) for the whole cohort was 42 months and the 5-year OS was 45 ± 5 %. In the multivariate analysis, worse ECOG performance status (p < 0.001), weight loss > 10 % before the start of the N-RCT (p = 0.025), higher pT category (p = 0.001), and grade 2/3 pathologic remission (p < 0.001) were significantly associated with a poor OS. PCR and pSTR rates for group 1 were 36 % and 18 % compared to 53 % and 22 % for group 2 (p = 0.011). There was a tendency for a better outcome in group 2 patients without statistical significance. The 5-year OS, disease-free survival and recurrent-free survival were 36 ± 7 %, 35 ± 6, and 36 ± 7 % for group 1 and 55 ± 7, 49 ± 7, and 53 ± 7 in group 2 (p = 0.117, p = 0.124, and p = 0.087). There was no significant difference between the two groups considering the postoperative morbidity and mortality. CONCLUSION: Higher radiation doses and more use of simultaneous cisplatin lead to higher pathologic response rates to N-RCT and may be associated with better survival outcomes. Prospective controlled trials are needed to assess the true value of intensified N-RCT regimens.