SQUAMOUS CELL VERSUS ADENOCARCINOMA — There are two major histologies of esophageal cancer: squamous cell cancer (SCC) and adenocarcinoma. Although most clinical studies have not differentiated between the two histologies, an increasing amount of evidence supports the view that they differ in terms of pathogenesis, epidemiology, tumor biology, and prognosis:

• The incidence of SCC is declining in the US while that of adenocarcinoma has increased markedly over the last 20 years, suggesting underlying etiologic differences. SCC is almost always the result of tobacco and/or alcohol abuse while adenocarcinomas are associated with gastroesophageal reflux disease (GERD) and high body mass
• The precursor lesion of SCC is epithelial dysplasia, which progresses in sequence to carcinoma in situ, and finally to invasive carcinoma. In contrast, adenocarcinomas usually arise as a consequence of persistent GERD, in which the mucosa of the distal esophagus undergoes intestinal metaplasia. Carcinogenesis begins with genetic alterations which endow the metaplastic cells with a growth advantage, permitting them to hyperproliferate. As the cells progressively acquire DNA damage, they become morphologically dysplastic, and eventually, frankly malignant.
• Although SCCs tend to arise 10 years earlier, on average, than adenocarcinomas, perioperative mortality is higher for SCC than for a Barrett's adenocarcinoma, likely related to associated comorbidity and tumor location. The sequelae of GERD involve mostly the distal esophagus, and 94 percent of cancers associated with Barrett's esophagus are located below the tracheal bifurcation. In contrast, 65 percent of SCCs are located above this location. Tumors located in the upper third of the esophagus have significantly higher rates of postoperative death.

It has been proposed that the difference in tumor location also has implications for the choice of therapy. Some suggest that induction chemotherapy alone may suffice for adenocarcinomas, while results are superior with chemoradiotherapy for SCCs because of the greater need for tumor downsizing to achieve a complete radical resection. However, there are few data to support this viewpoint and little agreement as to whether histologic type should be used as a factor in selecting the treatment strategy. A major area where data are lacking is nonsurgical management for adenocarcinomas.

• Histology also influences the pattern of first recurrence after resecion. Upper or mid-thoracic SCCs tend to recur locoregionally first, while distal esophageal adenocarcinomas more commonly recur with distant dissemination.

Despite this, many (but not all contemporary series suggest that the prognosis of adenocarcinoma is better than that of SCC, particularly in early stage disease. One reason may be the lower prevalence of lymphatic spread for Barrett's-associated cancer than for SCCs

In summary, there seems little doubt that esophageal SCC and adenocarcinoma represent two different diseases with characteristic pathogenesis, epidemiology, tumor biology, and outcomes. What is less clear is whether and how histology should dictate the therapeutic approach. Future studies in esophageal cancer should analyze and report separately the results of therapeutic strategies according to histology.

GEJ adenocarcinomas — Gastroesophageal junction tumors (GEJ) are classified (and treated) as esophageal cancers if more than 50 percent of the cancer involves the esophagus, while they are classified and treated as gastric cancers if over 50 percent of the tumor is below the GEJ or there is ≥2 cm of gastric extension. Most clinicians treat adenocarcinomas that are located equally above and below the GEJ as esophageal cancers. The available data suggest that the clinical characteristics, biologic behavior, and survival after esophagectomy are similar to those of adenocarcinomas of the distal esophagus.

These distinctions appear to be blurring over time, particularly in view of data from some trials suggesting that the same approaches used for adenocarcinomas and squamous cell cancers of the esophagus (ie, neoadjuvant chemoradiotherapy) are also relevant for adenocarcinomas of the GEJ and the proximal stomach as well.

SURGERY ALONE — Although only 30 to 40 percent of patients have potentially resectable disease at presentation, surgery has been the standard treatment for early stage esophageal cancer. Its utility as monotherapy has been challenged. Data from contemporary surgical series report five-year survival rates of 15 to 20 percent for surgery alone. This poor long-term outcome has prompted an evaluation of neoadjuvant (preoperative), adjuvant (postoperative), and nonoperative strategies aimed at improving survival in patients with apparently localized disease.

RT ALONE — Before the era of modern chemotherapy and combined chemoradiotherapy, RT alone (60 to 66 Gy over a period of 6 to 6.6 weeks) was associated with five-year survival rates of 5 to 20 percent, depending upon tumor extent]. In a review of 49 early series involving more than 8400 patients treated with RT alone, survival rates at one, two, and five years were 18, 8, and 6 percent, respectively

Better results are reported in later studies from single institutions in well-defined patient populations using modern RT protocols. As examples:

• Three- and five-year survival rates of 27 and 21 percent, respectively, were observed in a series of 101 selected patients (11 adenocarcinomas) with clinically localized disease treated with RT alone (45 to 52.5 Gy in 15 or 16 fractions over three weeks).
• In a cohort of 17 patients with clinical stage I esophageal SCC (after endoscopic ultrasound [EUS] and CT) treated with RT alone (median 60.6 Gy), the five-year survival rate was 59 percent.

Modern techniques (eg, three-dimensional conformal RT [3D-CRT], intensity modulated RT [IMRT]) are associated with more favorable toxicity profiles than those associated with the lower energy units used in earlier years. The success of advanced radiation technology can be illustrated by a preliminary report of a Chinese trial in which surgery was compared to RT alone in 269 patients with esophageal SCC. RT was planned using 3D-CRT technique, and 69 Gy were delivered in 41 fractions over 45 days (45 Gy in 25 fractions over five weeks followed by 24 Gy in twice daily 1.5 Gy fractions for eight days using IMRT). Three- and five-year overall survival rates in the RT alone group (61 and 37 percent, respectively) were not significantly different from those in the surgery group (56 and 35 percent, respectively). These results cannot be extrapolated to patients with adenocarcinoma.

Although these data are encouraging, the role of RT alone has been supplanted by combined chemoradiotherapy in the majority of patients, despite a higher rate of treatment-related toxicity. Combined IMRT and cisplatin-based chemotherapy is under study.

CHEMORADIOTHERAPY — Concomitant chemotherapy and RT has been studied as definitive nonoperative treatment and in the preoperative (neoadjuvant) setting. The more recent strategy of using chemotherapy alone as induction therapy prior to surgery is discussed below

Definitive chemoradiotherapy — Concurrent chemoradiotherapy permits maximal tumor control because the combined local antitumor effect is more than additive (a therapeutic advantage termed radiation sensitization), and chemotherapy provides the opportunity for control of micrometastatic disease.

In randomized trials, the addition of cisplatin-based chemotherapy to RT provides a significant survival benefit over RT alone. However, the available data are almost exclusively in SCC, and none of the trials have performed adequate pretreatment staging to reliably correlate outcome with locoregional tumor extent (ie, locally advanced unresectable versus potentially operable disease). The following sections will summarize the data for patients with disease confined to the primary and regional nodes based upon radiographic imaging.

RTOG 85-01 — A landmark RTOG trial compared RT alone (64 Gy in 32 fractions over 6.5 weeks) versus concurrent chemoradiotherapy (two cycles of infusional 5-FU [1000 mg/m2 per day, days 1 to 4, weeks 1 and 5] plus cisplatin [75 mg/m2 day 1 of weeks 1 and 5] and RT [50 Gy in 25 fractions over five weeks]) in patients with locoregional thoracic esophageal cancer. Patients were required to have no evidence of spread beyond mediastinal and supraclavicular lymph nodes; 90 percent had SCC. The chemoradiotherapy group received two additional chemotherapy courses, three weeks apart, after RT. The trial was closed prematurely with 121 patients, when an interim analysis showed a significant survival advantage for chemoradiotherapy (five-year survival 27 versus 0 percent).

Analysis of failure patterns showed a significant reduction in both local-regional and distant failure for chemoradiotherapy. However, despite this benefit, 46 percent of patients in the chemoradiotherapy group had locally recurrent or persistent disease in the esophagus at 12 months. Surgery was not part of the treatment schema.

As a result of this trial, definitive chemoradiotherapy became the standard of care for patients with inoperable disease. The issue of the unacceptably high locoregional failure rate was addressed in a follow-up trial, INT 0123.

Intergroup 0123 — In the US Intergroup Study 0123 (INT 0123), 236 patients with nonmetastatic SCC or adenocarcinoma of the thoracic esophagus received concurrent cisplatin and 5-FU (as in RTOG 85-01), but they were randomly assigned to one of two different RT doses: 50.4 Gy (28 fractions of 1.8 Gy each, five fractions per week) or 64.8 Gy (36 fractions of 1.8 Gy each, five fractions per week) Higher RT doses were not associated with a higher median (13 versus 18 months) or two-year survival (31 versus 40 percent), or incidence of local-regional persistent or recurrent disease (56 versus 52 percent for the high dose and control groups, respectively). High- dose RT was associated with significantly more toxicity.

The reason for the failure to demonstrate improved survival or local-regional control with higher RT doses is unclear. At present, 50 Gy of RT plus four courses of cisplatin and 5-FU (with the first two given concurrently as in RTOG 85-10) remains a standard approach.

Elderly patients — Few data are available on the safety and efficacy of chemoradiotherapy in the elderly. However, at least one report suggests that patients older than age 70 tolerate cisplatin-based chemoradiotherapy without a major increase in adverse events and with outcomes that seem comparable to those achieved in younger individuals.

Preoperative chemoradiotherapy — The poor long-term survival associated with surgery alone and the radiosensitizing effect of concurrent chemotherapy provided the impetus to evaluate chemoradiotherapy prior to resection. At least seven trials have directly compared preoperative chemoradiotherapy followed by surgery versus surgery alone for patients with potentially resectable esophageal carcinoma, five of which have been published. Two demonstrate a significant survival benefit from combined modality therapy, both using a concurrent rather than sequential approach.

Concurrent chemoradiotherapy — Three completed randomized trials compared preoperative concurrent chemoradiotherapy versus surgery alone, only one of which shows a statistically significant survival benefit for chemoradiotherapy.

• Irish trial — In an early trial, 113 patients with esophageal or GEJ adenocarcinoma were randomly assigned to surgery alone or preceded by chemoradiotherapy. Preoperative treatment consisted of two courses of 5-FU (15 mg/kg by bolus days 1 to 5) and cisplatin (75 mg/m2, on day 7 of each cycle), both administered during weeks 1 and 6 of concurrent RT (40 Gy in 15 fractions over three weeks). A complete pathologic response (pCR) was noted in 25 percent of the chemoradiotherapy group, and when the surgical specimens were compared, regional nodal involvement was less frequent in this group (42 versus 82 percent). Chemoradiotherapy was associated with significantly longer median (16 versus 11 months) and three-year survival (32 versus 6 percent). These results were criticized because of the lower than expected survival with surgery alone.
• Michigan study — In a second trial, 100 patients with locoregional esophageal or GEJ cancer (25 SCC, 75 adenocarcinoma) were randomly assigned to surgery with or without induction chemoradiotherapy. Neoadjuvant treatment consisted of infusional cisplatin (20 mg/m2 per day, days 1 to 5, and 17 to 21), infusional 5-FU (300 mg/m2 per day, days 1 to 4 and 17 to 20), and vinblastine (1 mg/m2 per day, on days 1 to 4, and 17 to 20) plus concurrent accelerated fraction RT (45 Gy in 1.5 Gy twice daily fractions for three weeks, using 3D-CRT treatment planning). Surgery was performed on day 42, after a three week rest.A pCR was observed in 28 percent of patients after neoadjuvant treatment. At a median follow-up of 8.2 years, the median survival was similar (16.9 versus 17.6 months for multimodality therapy and surgery respectively), but there was nearly a twofold higher, clinically relevant but nonstatistically significant, improvement in three-year survival favoring chemoradiotherapy (30 versus 16 percent).In unplanned subgroup analysis, complete responders had significantly better three-year survival compared to those with residual tumor in the resected specimen (64 versus 19 percent, respectively). Although the combined therapy group had a significantly lower locoregional recurrence rate (19 versus 42 percent), the distant metastatic rate was not lower (65 versus 60 percent).

• CALGB 9781 — CALGB 9781 was originally designed as a randomized Intergroup trial of trimodality therapy versus surgery in 500 patients with stages I-III esophageal or GEJ cancer, staged with esophagogastroduodenoscopy, barium esophagram, and CT. Staging EUS and thoracoscopy/laparoscopy were encouraged. Due to poor accrual, the study was closed prematurely with only 56 patients enrolled (42 adenocarcinomas, 14 SCC). pCR was achieved in 10 of 25 assessable patients in the trimodality arm (40 percent), and neither perioperative morbidity nor mortality were increased compared to surgery alone. Five-year survival was 39 versus 16 percent in favor of trimodality therapy, although the difference was not statistically significant.

Sequential chemoradiotherapy — In contrast to these results, three other trials comparing sequentially administered chemotherapy and RT followed by surgery to surgery alone fail to show any survival advantage to combined modality therapy.

Meta-analysis — A meta-analysis of randomized trials comparing preoperative chemoradiation versus surgery alone included 1116 patients enrolled on nine trials. When compared to surgery alone, there was only a nonsignificant trend towards improved survival with chemoradiotherapy (odds ratio [OR] 0.79, 0.77, and 0.66 for one-, two-, and three-year mortality, respectively). The improvement in three-year survival was statistically significant when the analysis was restricted to trials of concurrent chemoradiotherapy (OR for mortality 0.45, 95 % CI 0.26 to 0.79).

A second meta-analysis of 10 randomized comparisons of preoperative chemoradiotherapy plus surgery versus surgery alone (1209 patients, six restricted to SCC, the rest mixed) came to the same conclusion. Compared to surgery alone, preoperative chemoradiotherapy was associated with significantly better two-year all-cause mortality (hazard ratio [HR] 0.81, 95 % CI 0.70-0.93). This corresponded to a 13 percent absolute difference in survival at two years. The results were similar for SCC and adenocarcinoma.

In the absence of a single definitive trial but with three small trials and at least two meta-analyses demonstrating better survival with neoadjuvant concurrent chemoradiation, the majority of patients now undergo some form of combined modality therapy rather than local therapy alone. However, the optimal management of localized cancer of the thoracic esophagus and GEJ remains controversial.

In summary, early results from many of these trials are encouraging but whether the added toxicity of any of these intensified approaches is counterbalanced by substantial survival gains is unclear. Phase III trials are needed to confirm the benefit of these more toxic approaches over concurrent cisplatin/5-FU.

Necessity for surgery — The necessity of resection in patients undergoing chemoradiotherapy is controversial. A survival benefit for postchemoradiotherapy esophagectomy has been suggested in national surveys of patients with thoracic adenocarcinoma or squamous cell cancer (SCC) who were treated in the 1990s However, others have questioned the necessity of surgery.

In contemporary series, definitive chemoradiotherapy provides long-term survival in up to 27 percent of patients with SCC, a result that is not dissimilar to that achieved with preoperative chemoradiotherapy followed by surgery, neoadjuvant chemotherapy and surgery, and surgery alone Nearly all reports note a higher rate of locally persistent/recurrent disease when surgery is not a component of treatment. In general, there is a lack of data on nonsurgical management for patients with adenocarcinoma.

At least two randomized trials directly comparing chemoradiotherapy alone to chemoradiotherapy followed by surgery have failed to demonstrate better survival, although both show better locoregional control and a lesser need for palliative procedures when surgery is a component of multimodality treatment. The patient populations in both were either exclusively or predominantly SCC. Taken together, these data suggest that patients who undergo surgery after chemoradiotherapy appear to have better locoregional control and similar quality of life. Thus, inclusion of surgery remains the preferred treatment approach for clinically resectable esophageal cancer, particularly for adenocarcinoma since there are few data on nonsurgical management, and the rate of pathologic complete response is relatively low as compared to SCC.

NEOADJUVANT CHEMOTHERAPY — Multiple randomized trials have evaluated the benefit of chemotherapy administered prior to resection in patients with esophageal cancer limited to the primary and regional nodes by clinical assessment. Four are negative while three others, one of which has been reported in preliminary form only, demonstrate a survival benefit compared to surgery alone

Meta-analyses — A survival benefit for neoadjuvant chemotherapy relative to surgery alone was also suggested in a review of eight randomized trials of surgery alone or chemotherapy followed by surgery for esophageal cancer (n = 1724 patients, any histology, excluding cervical esophageal cancers) The hazard ratio for all-cause survival at two years favored chemotherapy followed by surgery (hazard ratio [HR] for all-cause mortality 0.90, 95% CI 0.81 to 1.0), a difference which translated into a two-year absolute survival benefit of 7 percent. There was no significant benefit for chemotherapy among patients with SCC, while there was a significant benefit for those with adenocarcinoma, which was based only on data from the United Kingdom MRC trial [81] (HR 0.78, 95% CI 0.64-0.95).

These data support the view that chemoradiotherapy is a preferred strategy rather than induction chemotherapy alone for patients with esophageal or GE junction cancers.

TECHNIQUE FOR PREOPERATIVE RT — The degree of response of a tumor and normal tissues/organs to radiation depends upon several radiotherapeutic factors

• Fraction size (standard fraction size, 1.8 Gy to 2.0 Gy) and interfractional intervals (standard interval, 24 hours)
• Total dose (standard preoperative dose in once daily schedule, 45 to 50.4 Gy)
• Duration of treatment (5 to 5.6 weeks for standard fractionation, without a rest during treatment)
• The arrangement of radiation portals in a manner that achieves the maximum dose differential between tumor and adjacent vital organs

Significant deviations from standard techniques should be avoided in a potentially curative setting. Fraction sizes that are larger than 2.5 Gy, treatment breaks of longer than one week, split-course fractionation schedules, and suboptimal radiation plans with a potential for increased risk of injury to the lung, heart and spinal cord should be avoided.

3D conformal RT — Three-dimensional conformal RT (3D-CRT) is recommended for the best possible coverage of the target volume while protecting the surrounding normal organs from excess RT dose.

Target volume — The target volume consists of gross tumor volume (GTV) with a margin of clinically uninvolved tissue (clinical target volume, or CTV). The CTV should include 4 to 5 cm margins beyond the radiographic tumor extent (GTV) in the cephalad-caudad direction and 2 to 2.5 cm beyond the radial border of GTV (defined by barium esophagogram or CT scan). For lesions of the lower third of the esophagus and gastroesophageal junction (GEJ), the caudal extension CTV beyond GTV includes a 3 to 4 cm margin of gastric cardia below the lower border of GTV. CTV for regional lymph nodes includes the celiac, gastric, and gastrohepatic Iymph node groups for primary tumors at the GE junction. For primary tumors involving the upper two-thirds of the thoracic or the cervical esophagus, CTV includes both supraclavicular regions. It is necessary to add another 0.7 cm beyond CTV as the PTV (planning target volume) in order to compensate for daily set-up error and respiratory tumor motion.

Esophageal cancers that are located at the GE junction can have a significant degree of tumor motion associated with respiration. We reported peak-to-peak motion of the primary tumor in 10 patients (nine near the GE junction with their involved lymph nodes at the celiac region). The peak-to-peak tumor motion in craniocaudal directions ranged from 0.6 cm to 4.8 cm for the primary tumor and from 1.2 cm to 4.4 cm for the involved lymph nodes. In order to avoid geographic miss in some of these patients when using 3D CRT, four-dimensional (4D) CT treatment planning and delivery of 3D CRT according to the tumor characteristics of individual patients has a significant advantage for optimum coverage of the target volume over 3D-CRT planned with the conventional helical CT.

Optimal dose and fractionation schedules — Tumor size and radiation dose are important considerations for local-regional tumor control. Radiation therapy with curative intent requires a total dose of 60 to 66.6 Gy in 30 to 37 daily fractions using 1.8 to 2.0 Gy daily fractions, five fractions per week. Small daily fractions (ie, 1.8 to 2.0 Gy instead of 2.5 to 3.0 Gy) reduce the likelihood of late toxicity.

The optimal radiation dose for preoperative chemoradiotherapy regimens is not defined, although a total dose of 45 to 50.4 Gy administered in daily 1.8 Gy fractions, five days per week, produces reasonable results with acceptable toxicity

Altered fractionation schedules such as accelerated schedules (45 Gy in 30 fractions over three weeks using twice daily 1.5 Gy fractions) or hybrid schedules using twice daily radiation during chemotherapy and once daily treatment between chemotherapy cycles (45 Gy in 25 fractions over five weeks to CTV, and 58.5 Gy in 34 fractions over five weeks to GTV, respectively) are tolerable, with encouraging tumor response, high pathologic CR rates, and survival

Patients judged inoperable because of either poor general condition or the presence of distant metastases can be treated by rapid fractionation schedules. A total dose of 40 to 45 Gy at 2.5 Gy daily fractions five days a week is a reasonable schedule for patients who require palliation of esophageal obstruction.

3D CRT uses four to six beams to conform the distribution of radiation dose to the GTV and PTV, while the surrounding normal structures are spared from excessive radiation dose, to the greatest extent possible. 3D CRT plan provides a dose-volume-histogram for GTV and PTV as well as for normal organs at risk for complications. Thus, it is feasible to formulate a radiation dose schedule for the desired level of tumor control probability that is balanced with an acceptable level of toxicities.

Intensity-modulated radiation therapy (IMRT) is an advanced form of 3D CRT. IMRT uses inverse treatment planning to generate optimum treatment plan. IMRT uses dynamic multileaf collimators to conform the radiation beam to the shape of the tumor from any angle, while protecting normal adjacent tissue as much as possible. It may be expected (though not yet proven) that treatment with IMRT will result in fewer side effects.

CERVICAL ESOPHAGUS TUMORS — Squamous cell cancer (SCC) of the cervical esophagus presents a unique management situation. If surgery is performed, it usually requires removal of portions of the pharynx, the larynx, the thyroid gland, and portions of the proximal esophagus. In addition, radical neck dissections are usually carried out; as such, the management is more closely related to SCC of the head and neck than for malignancies involving the more distal portions of the esophagus. In general, radiation therapy combined with chemotherapy is preferred over surgery for these patients since survival appears to be the same, and major morbidity is avoided in most.

SUMMARY AND RECOMMENDATIONS — The management of local-regional esophageal and gastroesophageal junction (GEJ) cancer has undergone a major evolution over the past 15 years. The majority of patients now undergo some form of combined modality therapy rather than local therapy alone. However, the optimal management of these patients remains controversial.

There are two major histologies of esophageal cancer: squamous cell cancer (SCC) and adenocarcinoma. Although most clinical studies have not differentiated between these two tumor entities, an increasing amount of evidence supports the view that they differ in terms of their pathogenesis, epidemiology, tumor biology, and prognosis. Largely due to the lack of data on the impact of histology on treatment outcomes, the approach is similar for both histologies

The following conclusions regarding therapy can be derived from phase III studies comparing definitive chemoradiotherapy to radiotherapy alone, and preoperative chemoradiotherapy or preoperative chemotherapy to surgery alone for patients with esophageal or GEJ cancer that is localized to the primary site and regional nodes:

• While definitive chemoradiotherapy is a potentially curative option for SCC, there remains a high rate of locally persistent/recurrent disease after chemoradiotherapy alone and a lack of data for nonsurgical management of patients with adenocarcinoma. Thus, inclusion of surgery is preferred for clinically resectable esophageal cancer regardless of histology.
• Contemporary series suggest that a concurrent trimodality approach (concomitant chemoradiotherapy followed by surgery) provides a survival benefit compared to surgery alone. This conclusion is supported by three small randomized studies and at least two meta-analyses. Further, local control appears to be better with preoperative chemoradiotherapy compared to surgery alone
• Induction chemotherapy without RT also provides a significant survival benefit over surgery alone, and this approach has been adopted in the United Kingdom based upon the MRC and MAGIC trials. However, a preliminary report of at least one randomized trial comparing preoperative chemotherapy to preoperative chemoradiotherapy in patients with gastroesophageal junction (GEJ) adenocarcinoma suggests that the likelihood of a complete pathologic response (pCR) is higher with chemoradiotherapy and that survival might also be superior. Whether these results can be extrapolated to the setting of distal esophageal adenocarcinomas or SCCs is uncertain.

Furthermore, local failure rates may be lower in patients treated with chemoradiotherapy followed by surgery compared to those receiving either chemotherapy followed by surgery or surgery alone.  As a result of these issues, we suggest combined modality therapy using preoperative chemoradiotherapy followed by surgery rather than either surgery alone or definitive chemoradiotherapy for patients with stages IIA, IIB, and III esophageal SCC or adenocarcinoma of the distal esophagus or GEJ  We also suggest induction chemoradiotherapy instead of chemotherapy alone followed by surgery

The benefit of preoperative chemoradiotherapy for patients with stage I esophageal or GEJ adenocarcinoma or SCC is less clear. We recommend surgery alone in these patien. However, combined modality therapy is a reasonable approach for patients who are not surgical candidates.

• Although the optimal type, dose, combination, and schedule of drugs is unclear, we suggest multiagent chemotherapy rather than single agent cisplatin. We use concurrent treatment with two courses of cisplatin and 5-FU plus radiation therapy (50 Gy), as per the RTOG 85-01 trial

We suggest not administering concurrent chemoradiotherapy with a taxane or irinotecan-containing regimen outside of the context of a clinical trial. Results published thus far do not consistently indicate a superior toxicity profile or higher response rates compared to standard 5-FU and cisplatin.

• The optimal dose-fractionation RT schedule for concurrent chemoradiotherapy regimens remains to be determined. However, 3-D conformal techniques should be used for modern treatment planning to minimize toxicities to adjacent vital organs (ie, heart, lung, spinal cord, or liver). A standard dose of radiation for patients treated with concurrent 5-FU and cisplatin is 50.4 Gy.
• Management of carcinoma arising in the cervical esophagus is more closely related to SCC of the head and neck than for malignancies involving the more distal portions of the esophagus. In general, radiation combined with chemotherapy is preferred over surgery for these patients since survival appears to be the same, and major morbidity is avoided in most.