Multimodality therapy for adenocarcinoma of the esophagus

doi:10.1016/0003-4975(95)00119-6

The Annals of Thoracic Surgery

Volume 59, Issue 5, May 1995, Pages 1085-1091

https://doi.org/10.1016/0003-4975(95)00119-6 Get rights and content

Few reports exist detailing results of multimodality treatment for adenocarcinoma of the esophagus. We have treated 28 such patients using a preoperative regimen consisting of two courses of cisplatin and 5-fluorouracil with radiation (either 3,000 or 3,600 cGy). There were 25 men and 3 women (mean age, 62.9 years; range, 35 to 86 years), and 16 patients were known to have Barrett's esophagus. Dysphagia was present for a mean of 2.7 months, and the average weight loss was 6.5 kg. Tumors ranged from 2 to 10 cm in length (mean, 5.2 ± 1.8 cm) with American Joint Committee on Cancer clinical stage I in 2 patients, stage II in 19 patients, and stage III in 7. Dysphagia improved in 23 patients (82%), and in 8 (29%) no tumor was detected during radiologic and endoscopic staging after neoadjuvant therapy. Four patients refused operation. Esophagectomy via standard Ivor Lewis approach was accomplished in 20 of 24 patients (87%) undergoing operation. There were no operative deaths, and mean hospital stay was 15.5 ± 11.6 days. Four patients (17%) were complete responders with no tumor in the resected specimen. Actuarial survival in the 28 patients at 1, 2, and 3 years is 71%, 28%, and 20% respectively. Of the 20 esophagectomy patients, 6 are alive with no evidence of disease at 10, 50, 54, 70, 77, and 84 months. Three of these were complete responders. Only 1 of the 8 patients not undergoing resection is alive at 16 months with no evidence of disease after further radiotherapy and chemotherapy. These data suggest that preoperative combined modality therapy for adenocarcinoma of the esophagus is safe and effective treatment. It results in excellent symptomatic improvement, a complete response rate of 17%, and a significant chance for long-term survival.

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Cited by (45)

Oesophagus side effects related to the treatment of oesophageal cancer or radiotherapy of other thoracic malignancies
2016, Best Practice and Research: Clinical Gastroenterology
Citation Excerpt :
In this review we put the main focus on oesophageal side effects derived from treatment of oesophageal cancer and in a second part shortly provide an overview on oesophageal toxicity from conventional, respectively stereotactic fractionated radiotherapy to the thoracic area in general, where target organ and the organ at risk are not identical. In the neoadjuvant approach total doses that typically range between 30 and 50 Gy have been applied [7–9]. Despite absence of a threshold dose for oesophagitis the volume of the oesophagus receiving 40 or 50 Gy (V40,V50) is commonly accepted as a guidance level to estimate the risk of oesophagitis [10].
The oesophagus as a serial organ located in the central chest is frequent subject to “incidental” dose application in radiotherapy for several thoracic malignancies including oesophageal cancer itself. Especially due to the radiosensitive mucosa severe radiotherapy induced sequelae can occur, acute oesophagitis and strictures as late toxicity being the most frequent side-effects. In this review we focus on oesophageal side effects derived from treatment of gastrointestinal cancer and secondly provide an overview on oesophageal toxicity from conventional and stereotactic fractionated radiotherapy to the thoracic area in general. Available data on pathogenesis, frequency, onset, and severity of oesophageal side effects are summarized. Whereas for conventional radiotherapy the associations of applied doses to certain volumes of the oesophagus are well described, the tolerance dose to the mediastinal structures for hypofractionated therapy is unknown. The review provides available attempts to predict the risk of oesophageal side effects from dosimetric parameters of SBRT.
Positron Emission Tomographic Scanning Predicts Survival After Induction Chemotherapy for Esophageal Carcinoma
2007, Annals of Thoracic Surgery
The ability to accurately predict clinical and pathological response and survival in patients undergoing preoperative chemotherapy may have a significant impact on treatment strategy for esophageal carcinoma. This study assessed the predictive accuracy of clinical response (CR) and positron emission tomography (PET) scanning in determining pathological downstaging and disease free survival (DFS) after chemotherapy.
This is a retrospective review of patients who underwent chemotherapy prior to complete surgical resection for esophageal carcinoma between 1999 and 2005. Clinical response was correlated with pathological downstaging and survival. For PET scanning, the percent reduction in maxSUV after induction therapy was determined and we identified the optimal threshold of percent reduction in maxSUV for predicting clinical response and pathological downstaging.
Sixty-two patients (52 men, median age 62.3) were evaluated. Thirty-nine patients (62.9%) had either a partial (n = 32) or complete clinical response (n = 7) to induction therapy. The sensitivity, specificity, positive, and negative predictive value of an objective clinical response in predicting downstaging in T and (or) N were 85.7%, 55.9%, 61.5%, and 82.6%, respectively. There was no difference in DFS between responders and nonresponders. The PET sensitivity, specificity, positive, and negative predictive values for predicting pathologic downstaging were 77.8%, 52.9%, 56.8%, and 75%, respectively. Thirty-seven patients (59.7%) had a 50% or greater reduction in the maxSUV of their primary tumor and had a significant improvement in DFS compared with patients with a less than 50% reduction in maxSUV (median DFS time: 35.5 months vs 17.9 months, respectively, p = 0.03). Significantly, 11 patients had a 100% reduction in maxSUV despite the presence of residual tumor.
Complete response and PET appear equivalent in predicting pathological downstaging. However, a 50% reduction in the maxSUV after induction therapy is more significantly associated with improved DFS than CR or pathological downstaging. Additionally, a complete absence of PET signal cannot be equated with a complete pathological response.
Downstaging of T or N Predicts Long-Term Survival After Preoperative Chemotherapy and Radical Resection for Esophageal Carcinoma
2006, Annals of Thoracic Surgery
The purposes of this study were to determine the frequency of downstaging of T or N after neoadjuvant chemotherapy and radical resection in patients with carcinoma of the esophagus, and to evaluate the effect of tumor downstaging on survival.
A cohort of patients who underwent neoadjuvant chemotherapy followed by radical surgical resection for carcinoma of the esophagus was identified from a large, prospectively maintained, single-institution database of esophageal cancer patients. Patients were included if they had an accurate pretreatment clinical stage determined by the authors. Data collected included demographic data, the type of staging regimen, the chemotherapy agents used, clinical and pathologic data and stages, and survival data. Downstaging of T or N was determined by comparing the pretreatment, clinical stage to the postresection, pathologic stage. Downstaging was then evaluated in the context of survival.
Seventy-seven patients were identified who had an accurate clinical stage assigned and underwent neoadjuvant chemotherapy followed by radical resection. Patients were clinically staged before treatment using computed tomography, positron emission tomography, and endoscopic ultrasonography. Thirty-seven patients (48%) experienced downstaging of T or N, and this group of patients had a 5-year overall actuarial survival of 63%, compared with 23% for those who were not downstaged (p = 0.002). Three patients had a complete pathologic response to neoadjuvant chemotherapy (3.9%).
Patients who experience downstaging of T or N after neoadjuvant chemotherapy and radical surgical resection for esophageal carcinoma have a significantly higher survival rate compared with those who do not experience downstaging. This enhanced survival is comparable to survival rates reported in complete pathologic responders after neoadjuvant chemoradiation.
Differential response to preoperative chemoradiation and surgery in esophageal adenocarcinomas based on presence of Barrett's esophagus and symptomatic gastroesophageal reflux
2005, Annals of Thoracic Surgery
Barrett's esophagus and gastroesophageal reflux disease (GERD) are recognized to predispose to esophageal adenocarcinoma. Abdel-Latif and colleagues recently suggested that esophageal adenocarcinoma patients with GERD might be resistant to multimodality treatment. In this study, we investigated potential differences in clinical outcomes in esophageal adenocarcinoma patients based on the presence of identifiable Barrett's mucosa and/or history of symptomatic GERD.
Eighty-four patients with resectable esophageal adenocarcinoma, who completed the planned preoperative chemoradiation and underwent a potentially curative esophageal resection were retrospectively evaluated. Postoperative survival was compared between patients with or without underlying Barrett's esophagus and history of symptomatic GERD. Patients with pathologic complete response (path CR) and those with partial or no response (path PR) were compared to determine if presence of Barrett's esophagus and history of symptomatic GERD influence the path CR rates.
We found significantly lower postoperative survival in patients with Barrett's associated adenocarcinoma (vs adenocarcinoma arising de novo, p = 0.031) and patients with symptomatic GERD (vs patients without symptomatic GERD, p = 0.019). Furthermore, the subset of patients with path PR (vs path CR) after chemoradiation have a significantly higher proportion of patients with Barrett's esophagus (HR = 4.38, confidence interval [CI] = 1.39 to 13.83, p = 0.012) and patients with GERD (HR = 2.71, CI = 1.13 to 6.50, p = 0.026).
Patients with esophageal adenocarcinoma may have differences in response to preoperative chemoradiation based on the presence of Barrett's esophagus and history of symptomatic GERD.
Effects of neoadjuvant radio-chemotherapy on <sup>18</sup>F-FDG-PET in esophageal carcinoma
2004, European Journal of Surgical Oncology
Citation Excerpt :
The therapy of choice in non-metastatic esophageal carcinoma (EC) is surgical resection of the primary tumour. Preoperative radio-chemotherapy is not generally established but is increasingly applied for local downstaging and systemic disease control.1–3 A pathologic complete response to neoadjuvant therapy is the strongest predictor of long-term survival.4
Aim. To investigate whether results of [F-18]-fluorodeoxy-d-glucose (FDG) positron emission tomography (PET) of esophageal cancer (EC) before and after neoadjuvant radio-chemotherapy correlate with histopathology after esophageal resection.
Methods. Twenty consecutive patients with EC without distant metastases were examined twice with ¹⁸F-FDG-PET during primary staging and after neoadjuvant radio-chemotherapy. FDG standardised uptake values (SUV) were correlated with the histopathological findings (percentage of viable tumour cells, tumour regression grade 1–5).
Results. Regression analysis revealed a slight (not significant) positive correlation between SUV_pre (R=0.41, p=0.08) and SUV_post (R=0.37, p=0.11) and the percentage of viable tumour cells in the resectate. Although all patients showed a significant decrease in SUV after radio-chemotherapy (p<0.01), the percentual decrease of the SUV after therapy (ΔSUV_%) did not significantly differ between the TRG-groups. In 12 of 20 patients (60%), therapy-induced esophagitis was detected in post-therapeutic PET images.
Conclusion. In EC, a higher pre-therapeutic SUV might be correlated with a higher fraction of vital tumour cells remaining after radio-chemotherapy. Applying the neoadjuvant therapy protocol and the study design used in this examination, there is no correlation between decrease in SUV and histopathology.
Preoperative chemoradiation therapy does not improve early survival after esophagectomy for patients with clinical stage III adenocarcinoma of the esophagus
2004, Annals of Thoracic Surgery
Citation Excerpt :
All major series report a consistent patient group that varies from 17%–40% who do not have evidence of residual tumor in their resected specimens [16, 17–25]. Five-year survival in this subgroup of patients has been reported as high as 60% [22]. Unfortunately, no pretreatment characteristics have been identified that indicate which patients are more likely to respond to therapy [10, 26].
The optimal treatment for locally advanced esophageal cancer remains controversial. The objective of this study was to determine if preoperative chemoradiation therapy (P-CRT) followed by esophagectomy for patients with clinical stage III adenocarcinoma of the esophagus offered any survival advantage as compared with esophagectomy alone.
Between January 1998 and June 2001, 75 nonrandomized patients with clinical stage III adenocarcinoma of the esophagus underwent either P-CRT and esophagectomy or esophagectomy alone. All patients were staged before initiation of treatment with computed tomography and endoscopic ultrasound.
P-CRT followed by esophagectomy was performed in 47 patients (63%) and esophagectomy alone in 28 patients (37%). Although the P-CRT group was younger (median age, 61 years versus 67 years), the two groups were otherwise similar for gender, comorbidities, and symptoms. Overall operative mortality was 4%. Follow-up was complete in all patients and ranged from 5 to 40 months (median, 20 months). Overall, one-, two-, and three-year survivals were 72%, 44%, and 42%, respectively. Three-year survival was identical (42%) for both the P-CRT and surgery alone patients (p = 0.70). Three-year disease-free survival for the P-CRT group was 29% as compared with 33% for the surgery only group (p = 0.51).
Patients with clinical stage III adenocarcinoma of the esophagus do not appear to gain an early overall or disease-free survival advantage when treated with P-CRT followed by surgery as compared with surgery alone. However, long-term follow-up is needed. A large, prospective, randomized trial is warranted to address the question of whether P-CRT offers any survival benefit or impact on pattern of recurrence in patients undergoing esophagectomy for locally advanced disease.

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: Presented at the Forty-first Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 10–12, 1994.

View full text

Multimodality therapy for adenocarcinoma of the esophagus

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Rising incidence of adenocarcinoma of the esophagus and gastric cardia

JAMA

Esophagogastrectomy for adenocarcinoma of the cardia

Ten years' experience and current approach

Ann Surg

Surgical management of adenocarcinoma at the gastroesophageal junction

Esophageal carcinoma: surgery without preoperative adjuvant chemotherapy

Ann Thorac Surg

Cancer of the esophagus: the Cleveland Clinic experience

Ann Surg

A pilot study of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and postoperative radiation therapy and/or chemotherapy in adenocarcinoma of the esophagus

Cancer