Hodgkin's disease and acute leukemia: Report of eight cases and review of the literature

Eight cases of Hodgkin's disease and acute leukemia are reported. An additional 74 cases of acute myelocytic leukemia or one of its variants, 11 cases of acute lymphocytic leukemia, 12 cases of chronic myelocytic leukemia and 37 cases of chronic lymphocytic leukemia associated with Hodgkin's disease are reviewed from the literature.In 3 of the 82 patients with acute myelocytic leukemia and Hodgkin's disease, the two diseases occurred simultaneously. Of the remaining 79 patients, 76 had received radiation therapy for their Hodgkin's disease and acute myelocytic leukemia had developed 1.2 to 19 years later (mean 6.5 years). Thirty-four of these patients also received antineoplastic chemotherapy. Only three patients with Hodgkin's disease were treated with multiple chemotherapy alone; in these, Hodgkin's disease developed 1.2, 1.5 and 3.2 years later.In 4 of 11 patients with acute lymphocytic leukemia and Hodgkin's disease, the two disorders occurred simultaneously. The other seven patients were all treated with radiation for their Hodgkin's disease, and acute lymphocytic leukemia developed 2 to 8 years later (mean 4.5 years). Three of the 7 patients also received alkylating agents.It is concluded that the development of acute leukemia, mostly acute myelocytic leukemia but also acute lymphocytic leukemia, during the course of Hodgkin's disease, is most likely related to radiation therapy. There is as yet insufficient evidence to implicate intensive chemotherapy in the causation of acute leukemia since in only three patients with Hodgkin's disease treated with chemotherapy alone has the development of acute leukemia been reported. It is possible, however, that chemotherapy potentiates the effect of radiotherapy. It is also possible that acute leukemia is part of the natural history of Hodgkin's disease and is occurring with greater frequency because of improved survival in Hodgkin's disease since the introduction of better radiotherapeutic and chemotherapeutic treatment regimens.     

Staging laparotomy and splenectomy in early Hodgkin's disease: No therapeutic benefit

In a prospective randomized study of treatment for early-stage Hodgkin's disease presenting above the diaphragm, 76 patients had staging by laparotomy (Group I) and 28 had staging by closed techniques (Group II). Treatment consisted of involved-field radiotherapy alone (44 patients), involved-field radiotherapy followed by chemotherapy (38 patients), total nodal radiotherapy atone (15 patients), or total nodal radiotherapy followed by chemotherapy (seven patients). On presentation, both groups had similar clinical features and similar treatment distribution. With similar follow-up (87 months), no significant differences in remission or survival were observed between Groups I and II: remission 59 versus 68 percent; survival 74 versus 92 percent; p value 0.27 and 0.09, respectively. Multiple areas of relapse were more frequently observed in Group I (11 of 32 had relapse) as compared with Group II (none of nine had relapse, p < 0.082). In Group I, relapse in the abdomen was observed as an isolated event or as part of disseminated relapse in 12 percent of patients compared with 3 percent (one patient) in Group II with abdominal relapse alone. Seven patients in Group I and two patients in Group II died with Hodgkin's disease. Six other patients in Group I died with complete remission of non-Hodgkin's lymphoma (one patient), leukoencephalopathy (one patient), sepsis during chemotherapy (two patients), myocardial infarction (one patient), and cerebrovascular accident (one patient). Three other patients in this group had other secondary malignancies successfully controlled (histiocytic lymphoma, squamous cell carcinoma of the cervix, and malignant schwannoma). No second primary lesions or death with complete remission were observed in Group II. Staging laparotomy with splenectomy in early-stage Hodgkin's disease did not improve the duration of remission or survival or decrease the number of abdominal relapses compared with closed staging.     

Avascular necrosis of bone complicating treatment of malignant lymphoma

Over a 15-year period, 12 patients were seen at the Ontario Cancer Institute in whom avascular necrosis of bone developed after or during treatment for malignant lymphoma. All but one were treated with systemic chemotherapy that included high-dose intermittent corticosteroids. The average time to onset of symptoms was 34 months (range, eight to 72 months) after an average of 9.0 g of prednisone (range, 1.4 to 18.75 g). The one exception was a patient with Hodgkin's disease treated by pelvic radiation alone who had development of avascular necrosis of the femoral head within one month of irradiation. More than one joint was involved in 58 percent of patients. Six patients required surgery (usually hip replacement) but two patients had no evidence of deterioration over many years (average, seven years) and three patients had minimal symptoms easily controlled by mild analgesics up to six years after diagnosis. The evidence implicating corticosteroids in the development of avascular necrosis is presented and the various hypotheses of pathogenesis are reviewed, The predominance of Hodgkin's disease over non-Hodgkin's lymphomas (5:1) in this and other series and the identification of one patient with Hodgkin's disease with development of avascular necrosis within one month of radiotherapy treatment suggests that Hodgkin's disease itself may predispose to this condition.     

Radiation-related pericarditis

To determine the incidence of pericardial effusion in patients undergoing upper mantle radiation therapy, 81 patients with Hodgkin's disease, stages I to IIIB, were selected from a protocol series of 98 patients. Twenty-four patients (29.6 percent) met X-ray criteria for the presence of pericardial effusion. Eleven of the 24 also underwent right heart catheterization to confirm the presence of pericardial effusion and to define any hemodynamic abnormality. Fourteen patients were found to have transient effusion. Five of the 11 patients have had partial pericardiectomy for symptoms and signs of cardiac tamponade. There has been no evidence of recurrent Hodgkin's disease in these surgically treated patients. Ninety-two percent of the pericardial effusions occurred in the first 12 months after the end of radiation therapy. Therapeutic implications depend on elucidation of the natural history of this process. At present close follow-up is necessary with surgical intervention for signs or symptoms of cardiac tamponade.     

Graft-versus-host reaction following blood product transfusion

The observation of graft-versus-host (GVH) reaction after platelet transfusion in a patient with Hodgkin's disease led us to analyze 38 reported cases in the literature, to outline prognostic factors and to characterize patients at risk. Overall mortality was 68 percent. It was higher among children (76 percent) than among adults (62 percent), and among patients with Hodgkin's disease and immune deficiency syndromes (88 percent) than among those with leukemias (23 percent, p < 0.005). Following blood transfusions from normal donors, mortality was higher (88 percent) than after transfusions from donors with chronic myelocytic leukemia (25 percent, p < 0.05). Minimal lymphocyte doses necessary to cause GVH reaction are in excess of 10⁷/kg. Adults seem more resistant to homografts than do children, and the host's cellular immune status is of major prognostic importance. Lymphocytes from donors with chronic myelocytic leukemia may be deficient, and after a threshold dose, the number of lymphocytes transfused does not correlate with clinical outcome. Effective prophylactic measures do exist for this complication but satisfactory therapy does not.     

Acquired Gaucher's cells in Hodgkin's disease

A patient with Hodgkin's disease associated with low glucocerebrosidase levels in the peripheral leukocytes, and Gaucher's cells in the bone marrow and lymph nodes, is described. After MOPP therapy, complete remission of Hodgkin's disease was accompanied by normalization of the glucocerebrosidase level and disappearance of Gaucher's cells. This observation appears unique when compared with the four cases of combined Hodgkin's and Gaucher's disease reported in earlier literature in which Gaucher's disease remained unchanged after chemotherapy. We conclude that our patient had Hodgkin's disease and acquired Gaucher's cells with diminished glucocerebrosidase levels, rather than a combination of Hodgkin's disease and Gaucher's disease.     

Detection of radiation cardiomyopathy by gated radionuclide angiography

Twenty-one asymptomatic adults underwent rest and exercise gated radionuclide angiography seven to 20 years after having received mediastinal radiation (2,000 to 7,600 rads) for Hodgkin's disease. None of these patients received cytotoxic chemotherapy. Twelve patients (57 percent) had abnormal left (less than 53 percent at rest and/or greater than 5 percent decrease at peak exercise) and/or right (less than 27 percent at rest and/or greater than 5 percent decrease at peak exercise) ventricular ejection fractions. Previous reports have described myocardial fibrosis occurring late after therapeutic mediastinal radiation; however, the incidence of this occurrence based on clinical follow-up has been low. Rest and exercise radionuclide angiography is a sensitive method for assessing systolic ventricular function and reveals a high prevalence of cardiomyopathy that can be linked to previous radiotherapy.     

High-dose gallium imaging in lymphoma

The role of gallium-67 imaging in the management of patients with lymphoma, traditionally assessed using low tracer doses and the rectilinear scanner, was assessed when using larger doses (7 to 10 mCi) and a triple-peak Anger camera. Gallium scan results in 51 patients with non-Hodgkin's lymphoma and 21 patients with Hodgkin's disease were compared with simultaneous radiologic, clinical, and histopathologic reports. Subsequent disease course was also evaluated in light of radionuclide findings. Sensitivity and specificity of the scans were 0.90 or greater for both non-Hodgkin's lymphoma and Hodgkin's disease, and overall accuracy by site was 96 percent. Although there are insufficient numbers of pretreatment scans to allow any conclusions, our data suggest that newer approaches to gallium scanning in treated patients are (1) highly specific in all lymphomas and most sensitive in high-grade non-Hodgkin's lymphoma and Hodgkin's disease; (2) valuable in assessing the mediastinum in both non-Hodgkin's lymphoma and Hodgkin's disease; and (3) helpful adjuncts to computed tomographic scanning and ultrasonography in assessing abdominal node disease.     

Pancytopenia and Leukemia in Hodgkin's Disease: Report of Three Cases

Three patients with Hodgkin’s disease whodeveloped severe pancytopenia terminating in acute leukemia (two patients) orpreleukemia (one patient) are presented.Prior treatment consisted of radiationtherapy alone in two patients, and radiation plus chemotherapy in the third. Theonly patient in whom chromosomal analysis was performed showed an abnormalchromosome. Therapeutic radiation exposure is thought to contribute to thedevelopment of leukemia in such patients.Leukemia is an uncommon complicationof Hodgkin’s disease, but is being reportedwith increasing frequency. The rapid evolution of more aggressive modes of therapymakes it imperative that we seek more information regarding the incidence of thiscomplication in order to achieve maximumtherapeutic benefit for patients withHodgkin’s disease.

Submitted on February 5, 1973 Revised on March 28, 1973 Accepted on April 2, 1973     

The decision between single- and combined-modality therapy in Hodgkin's disease

Using the technique of decision analysis to evaluate data on single-modality and combined-modality therapy in Hodgkin's disease, we have been able to determine which treatment gives the best chance for prolonged disease-free survival in given settings. Both the potential of combined-modality therapy for inducing secondary hematologic malignancies and the rate of salvage with MOPP following relapse after radiotherapy have been studied to observe the effect of different rates of these variables on the therapeutic decision. An analysis of patients with known pathologic stage endorsed the continued use of extended-mantle radiotherapy for Stages IA and IIA disease; under most of the conditions analyzed, combined-modality therapy appeared the best option for Stage IIIA disease. The results for Stages IB and IIB disease showed neither combined-modality therapy nor total nodal irradiation to have a conclusive advantage. We also analyzed management decisions for patients who had not had pathologic staging. For this, probabilities of each pathologic stage were derived from a large patient data base and were incorporated into the decision analysis. The results of this analysis indicated that, despite the mortality of laparotomy, treatment designated according to pathologic stage was more effective than immediate combined-modality therapy for most types of patients. For certain patients in whom the clinical features could be used to predict a high probability of advanced disease, the most effective management was immediate MOPP chemotherapy without staging laparotomy.     

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.     

Changing role of chemotherapy in treatment of head and neck cancer

The role of chemotherapy in the management of head and neck cancer includes treatment for recurrent disease and as an adjunct to conventional therapy with radiation and/or surgery in the primary treatment program. The best single agents, methotrexate and cisplatin, used for recurrent disease give response rates of 20 to 50 percent but of short duration. Results may be improved with combination chemotherapy, but often with increased toxicity. Prognostic factors that influence response are discussed. A newer role of chemotherapy in this disease is in the initial treatment program. Pretreatment chemotherapy can debulk these lesions prior to surgery and/or irradiation in up to 80 percent of patients. Controlled trials are in progress to determine the effect on cure rates. Chemotherapy utilized during radiotherapy has resulted in survival benefit in several studies. Post-treatment adjuvant chemotherapy still needs to be evaluated. The potential advantages and disadvantages of chemotherapy used in the initial treatment are discussed. Major strides have been made in the last decade in the treatment of head and neck cancer, and chemotherapy is assuming an increasingly important role.     

Long-term follow-up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease

Twenty-seven women previously treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone) chemotherapy were evaluated to determine the status of ovarian function. All patients had completed therapy a median of nine years earlier and had a median age of 30 years at the time of evaluation. Persistent amenorrhea has occurred in 11 of 24 patients (46 percent) treated with MOPP alone or MOPP plus radiation excluding the pelvis. Of patients with amenorrhea, 89 percent were older than age 25 at the time of treatment. In contrast, 80 percent of patients younger than age 25 at treatment continue to menstruate regularly. The time from diagnosis to amenorrhea was significantly shorter in the older patients (p = 0.001). Evaluation of serum gonadotropin and estradiol levels confirms ovarian failure as the cause of amenorrhea in all patients. Overall, these 27 patients have borne 13 normal children subsequent to chemotherapy. This long-term follow-up study demonstrates that chemotherapy-induced ovarian failure is age-related, that ovarian failure is often gradual in onset following the completion of chemotherapy and that, to date, the children born of women treated with this chemotherapy regimen appear to be entirely normal.     

Circulating immune complexes in Hodgkin's disease

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 μg/ml ± 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (< 15 μg/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific Raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.     

Curability of relapsed childhood B-cell non-Hodgkin's lymphoma after intensive first line therapy: a report from the Societe Francaise d'Oncologie Pediatrique

The very high cure rate in advanced B-cell non-Hodgkin's lymphoma in children using intensive multiagent therapy has been previously reported by the French Societe Francaise d'Oncologie Pediatrique lymphoma Malin B type (LMB) group. To address the issue of salvageability in an unselected group of patients who had all received the same front-line therapy, the outcome of relapses following the LMB 84 (216 patients) protocol have been reviewed. Fourteen percent of patients achieving complete remission (CR) relapsed, ie, 27 of 195. Relapse sites comprised the central nervous system (CNS) alone (6 cases), lung or mediastinum (2 cases), abdomen (8 cases), head and neck (2 cases), or multifocal (9 cases). There were three early deaths due to disease. Twenty-four patients received rescue chemotherapy regimens and 15 were treated with high-dose chemotherapy and bone marrow rescue (1 allogeneic). Of these, 9 were in second CR, 4 in second partial remission, and 2 treated during progressive disease. One died in CR from treatment-related toxicity. Ten relapsed postbone marrow transplant and 4 are alive disease free and probably cured. Two of the long-term survivors had some delay during initial chemotherapy due to toxicity and two were isolated CNS relapses. Twelve of 27 patients did not proceed to megatherapy (12 of 12 died).     

Combined-modality therapy in locally advanced primary rectal cancer

PURPOSE: Patients with unresectable, locally advanced rectal cancer are reported to have a dismal prognosis. The aim of this study was to analyze the effect of combined-modality therapy on clinical outcome. METHODS: From March 1990 to December 1997, 43 patients (28 males; median age, 62 years; median follow-up, 74 months) with locally advanced (T4 and/or N3) nonmetastatic rectal cancer received external-beam radiation (23.6 plus 23.6 Gy (split course), 8 patients; 45 Gy, 35 patients) plus 5-fluorouracil (96-hour continuous infusion, Days 1–4, at 1,000 mg/m2/day) and mitomycin C (10 mg/m2, intravenous bolus, Day 1). Concomitant chemotherapy was repeated at the beginning of the second course (split-course group) or in the last week of radiotherapy (continuous-course group). After 6 to 8 weeks, patients were evaluated for surgical resection and intraoperative radiation therapy (10 to 15 Gy). Thereafter, adjuvant chemotherapy (5-fluorouracil plus leucovorin, 6–9 courses) was prescribed. RESULTS: During chemoradiation, 5 patients (11.6 percent) developed Grade 3 to 4 hematologic toxicity. After chemoradiation, 29 patients (67.4 percent) had an objective clinical response (complete response, 2.3 percent; partial response, 65.1 percent). Thirty-eight patients underwent radical surgery (anterior resection, 24 patients; abdominoperineal resection, 14 patients; intraoperative radiation therapy boost on the tumor bed, 19 patients), and 2 patients had partial tumor resection. No perioperative deaths occurred in the patient group. Five-year survival and local control rates were 59.9 and 69.1 percent, respectively. Distant metastasis occurred in 44.2 percent of patients. Statistically significant relationships between intraoperative radiation therapy and local control (P = 0.0104), radical surgery and survival (P = 0.0120), and adjuvant chemotherapy and disease-free survival (P = 0.0112) were observed. CONCLUSIONS: Our data suggest that combined-modality therapy was relatively well tolerated and resulted in good local control and survival. With regard to the impact of surgical resection on survival, additional studies aimed at improving the local response rate are necessary, whereas the positive impact of intraoperative radiotherapy on local control appears to justify the inclusion of this therapeutic modality in prospective multi-institutional trials.     

Treatment of small cell lung cancer

The incidence of small cell lung cancer (SCLC) is declining in the United States (US). SCLC is nearly universally smoking-related and is very sensitive to both chemotherapy and radiation therapy. In contrast to non-small cell lung cancer (NSCLC), SCLC is staged as either limited-stage disease (LD) or extensive-stage disease (ED). Chemotherapy remains the essential component for treatment of all patients with SCLC, regardless of stage or performance status. In LD, the addition of radiation therapy improves survival over chemotherapy alone. However, the dose, timing and schedule of radiation are not well defined. Prophylactic cranial irradiation (PCI) reduces brain relapse rates, and modestly improves survival in patients in a clinical remission. Many chemotherapy agents and combinations result in high response rates in ED SCLC; however, median survival time remains 8-10 months. Cisplatin (or carboplatin) and etoposide is the standard doublet used in the United States. One study has shown cisplatin plus irinotecan to have a survival benefit over cisplatin plus etoposide, but confirmatory studies are needed. Patients with ED frequently relapse, and relapsed/refractory SCLC has a poor prognosis. The challenge remains to identify novel therapies and molecular targets to improve survival in SCLC.     

Combination chemotherapy for osteosarcoma.

Because of the great risk for development of pulmonary metastases following amputation for osteosarcoma, 24 consecutive patients with "clinically localized" osteosarcoma of an extremity were given adjuvant combination chemotherapy with adriamycin-cyclophosphamide-high-dose methotrexate-citrovorum factor. Thirteen of these patients remain free of tumor from 11 to 48 months following amputation. The median disease-free survival is estimated to be 18 months and the median survival 27 months. No relapses have been observed in any patients surviving free of disease beyond 23 months. Combination chemotherapy was also given to 16 patients whose disease was not localized; eight with pulmonary metastases at or following diagnosis, one with nodal metastases at diagnosis, two with osteosarcoma following radiation therapy for other malignant tumors, three with osteosarcoma of flat bones, one with parosteal osteosarcoma, and one with multifocal osteosarcoma. Three of this latter group of patients are surviving free of tumor at 8, 17, and 19 months from diagnosis. Two young patients died from complications of methotrexate and adriamycin toxicity.     

Critical value of laparotomy with splenectomy in stage III Hodgkin's disease as restaging procedure after chemotherapy

38 patients with stage III Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first line chemotherapy which included MOPP, ABVD, or both. 28 patients were judged to be in clinical complete remission (CR) and 10 were resistant or had relapsed. Among patients in CR, 27 (96%) were confirmed to be in pathological CR; among patients resistant or relapsed, 9 (90%) were confirmed to have disease in the abdomen or retroperitoneum. The therapy for patients in clinical remission before laparotomy consisted of TNI or sTNI in 19 patients, mediastinal radiation in 6 patients and no further therapy in the remaining 3 patients. No significant differences were seen in survival and relapse-free survival between those patients treated by extensive and those treated by local radiotherapy or no further therapy. Instead, among those patients who received extensive radiotherapy 3 developed acute non-lymphoid leukemia (ANLL). The therapy for this group of patients consisted of further chemotherapy in 7 who had concomitant liver involvement and TNI in the remaining 3 who had the disease confined to the spleen and/or lymph nodes. Among these patients, only 3 obtained CR; 2 with radiation and 1 who was resistant to MOPP, with ABVD. This study leads us to re-consider the role of laparotomy in stage III HD which should be used as non-routine procedure only in selected patients without poor prognostic factors who may be cured by radiotherapy alone. In patients resistant to chemotherapy, an early evaluation of disease in the abdomen may be useful for a better salvage treatment.     

The role of radiation therapy in the treatment of esophagus cancer

Historical series of external beam radiation therapy alone report 5-year survival rates of 0%–10%. In general, radiation therapy alone should be reserved for palliation or for patients who are medically unable to receive chemotherapy. In the RTOG 85-01 randomized trial, patients with T1–4 primarily squamous cell cancers received 5-FU, cisplatin, and concurrent 50Gy. The control arm was radiation therapy alone (64Gy). Patients who received combined modality therapy (CMT) had a significant improvement in both median (14 months vs 9 months), and 5-year survival (27% vs 0%). With a minimum follow-up of 5 years, the 8-year survival was 22%. The incidence of local failure and/or persistence was also lower in the CMT arm (47% vs 65%). INT 0123 was the follow-up trial to RTOG 85-01 to test if higher doses of radiation were helpful. Patients were randomized to a slightly modified RTOG 85-01 CMT regimen with 50.4Gy versus the same chemotherapy with a higher dose of radiation (64.8Gy). For the 218 eligible patients, there was no significant difference in median survival (13.0 vs 18.1 months), 2-year survival (31% vs 40%), or local/regional failure and/or local/regional persistence of disease (56% vs 52%) between the high-dose and standard-dose arms. Recent trials have used more novel agents such as paclitaxel, docetaxel, or irinotecan-based chemotherapy. Brachytherapy alone is as a palliative modality and results in a local control rate of 25%–35% and a median survival of approximately 5 months. In the RTOG 92-07 trial, 75 patients received the RTOG 85-01 CMT regimen followed by a intraluminal boost. Local failure was 27%, the cumulative incidence of fistula was 18%/year, and the crude incidence was 14%. Therefore, the additional benefit of adding intraluminal brachytherapy to radiation or combined modality therapy, although reasonable, remains unclear. In the adjuvant setting, one randomized trial reveals a survival advantage with postoperative CMT. A meta-analysis from the Oesphageal Cancer Collaborative Group also showed no clear evidence of a survival advantage with preoperative radiation. There are four randomized trials comparing preoperative CMT with surgery alone in patients with clinically resectable disease; the results are conflicting. Although this approach is reasonable, it remains investigational.