EFFECTIVENESS OF RADIATION THERAPY IN THE TREATMENT OF CARCINOMA OF THE ESOPHAGUS*

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1 APRIL, 1970 EFFECTIVENESS OF RADIATION THERAPY IN THE TREATMENT OF CARCINOMA OF THE ESOPHAGUS* A RETROSPECTIVE STUDY Bv A. B. l RAZIER, M.I)., S. H. LEVITT, M.D., and L. S. DEGIORGI, M.D. RICHMOND, CARCINOMA of the esophagus is one of the most discouraging diseases that the radiotherapist encounters. The 5 year survival rate had! been und!er 5 per cent, according to most ofthe early series. 37 \\Tith tile advent of megavoltage therapy and more radical therap\r regimens, there has been a slight but definite reported increase in the 5 year survival rate of between 5 per cent and 10 per cent Somewhat more encouraging is the reported increase in the average survival rate, which approaches I year in some series.4 8 This may reflect greater selectivity as we!l as improved! methods of treatment. Surgical results have been variable but generally are no better than those of radiiation therapy, and are associated! with a considerable operative mortality of from between 10 per cent and! 40 per cent.1 8 Generally, surgery is used for the more favorable lesions and for patients who are in good physical condition. Comparison of the results of surgery and! radiation tilerapy is therefore not feasible. In evaluating the results of treatment in this dhsease, it is important to consider not only the curative role, but also the palliative role. therapy has long been recognized! as a prime palliative agent in carcinoma of the esophagus. However, despite this prolonged! use, the contraindications and ind!ications for the utilization of rad!iation therapy are not well d!efined. It is the purpose of this study to evaluate the result of both curative and palliative radiation therapy and! to ascertain if possible the indications and contraindications for the use of this form of treatment. VIRGINIA MA I ERIAL AND METHOD The clinical course of 90 patients treated at the Medical College of Virginia from J anuary 1961 to December 1966 was reviewed. Included were only those patients treated by rad!iation therapy alone and/or surgery plus radiation therapy. The age of the patients ranged! from 3 years to 84 years of age. There were 68 males and 22 females. Nineteen (21 per cent) of the lesions were in the upper third of the esophagus, 47 (52 per cent) were in the middle third and 24 (26 per cent) were in the lower third. Twelve of the 7 patients having a mid!dle third lesion had! extension into the upper or lower third making it difficult to (Jetermine the point of origin of the lesion. This accounts for the increased! incidence of middle third lesions in our series when compared! with the other series. 7 therapy was given using either cobalt 6o or a 2 mev. Maxitron unit. The majority of patients were treated through opposing anterior and posterior ports. Some were treated with i anterior and! 2 posterior ports. One patient was treated with rotational therapy. In I I patients the lesions were resected; 5 patients received preoperative radiation therapy and! 6 received! postoperative radiation therapy. The over-all survival statistics included all 90 patients, but the i I who had surgery are excluded from the other categories, exdept where specified. All survivals were counted from the start of irrad!iation: 13 patients (14 per cent) survived i year; 3 patients per cent) survived 2 years; and i patient of the 90 is now surviving 5 * Presented at the Sixty-ninth Annual Meeting of the American Roentgen Ray Society, New Orleans, Louisiana, October 1-4, From the Division of, Department of Radiology, Medical College of Virginia, Richmond, Virginia. 830

2 VOL. io8, No. Carcinoma of the Esophagus 831 years after esophagectomy and postoperative irradiation (Tables i and ii). Correlation of the length of the lesion with survival is shown in Table in for both the radiation therapy and radiation therapy plus surgery groups. Measurements were taken from the roentgenographic reports, when given, and for the rest the roentgenograms were reviewed and the lesion measured. Because ofsubmucosal extension in many cases, the true extent of the lesion could! not be determined. As expected, the larger the lesion, the worse the survival. Follow-up roentgenograms were obtained in about half the cases. Interestingly, some patients who showed a marked radiographic improvement did not obtain complete symptomatic relief. The effects of the most common complication of the disease process and/or treatment on survival were evaluated. These included : ( I ) tracheoesophageal fistulae; (2) obstruction of esophagus by tumor; or (3) stricture after radiation therapy. In our series, 36 of the 90 patients (40 per cent) developed or previously had one or more complications. Ten patients developed tracheoesophageal fistulae: 3 before radiation therapy was started; 2 during radiation therapy, and 5 after completed treatment. As shown in Table Iv, when fistulae developed before starting radiation therapy, the average survival was only I.7 months and the patients could not finish the planned course of therapy. When fistulae developed during radiation therapy the patients did little better. One patient had a fistula develop during the course of rad!iation therapy, had it re- TOTAL I ATIENTS IN STUDY I Yr. 2 Yr. 5 Yr. No. of T No. Per Cent I T No. Per Cent No. Per Cent I 3.5 SURVIVAL CORRELATED WITH TYPE OF TREATMENT No.of. PatIents II Average. Mediaṇ SurVlval Total patients in Study with 79 6.i only withsurgery ii and paired and was able to finish the planned! course of therapy, but expired 2 weeks later. One patient developed! a tracheoesophageal fistula i6 months after preoperative radiation therapy and partial esophagectomy. He survived for 2 more months after developing the fistula. Sixteen patients became obstructed and! had a gastrostomy performed; 7 of these before radiation therapy was started. This later group had an extremely low average survival of2.6 months and! frequently could! not finish the full course of therapy. Even more significant was the fact that they did not obtain any relief of their symptoms of dysphagia and drooling. Likewise, those patients who became obstructed during SURVIVAL CORRELATED WITH LENGTH OF THE LESION III No.of. Averagẹ. A. 0-5 cm. in Length Surgery and 6 i6.o 6 B. 6 cm. and Above I Surgery and

3 832 A. B. Frazier, S. H. Levitt and L. S. DeGiorgi APRIL, 1970 IV COMPLICATIONS RELATED TO SURVIVAL (All ) Tracheoesophageal fistulae io A. Before Started! I B. During C. After. 7. S 7.0 Obstruction requiring gastrostomy A. Before Started! B. After 9 1 I therapy and required a gastrostomy had! a very low average survival of 4.2 months. Stricture requiring dilatation developed in 10 patients following rad!iation therapy. The average survival for this group was 5.75 months. related to tumor dose is shown in Table v. Of the patients receiving less than 3,000 rads, 5 were preoperative patients who received 2,000 rads, 2 had recurrent lesions, and io were patients who did not finish their course of therapy, due to debility or death. The 3 patients receiving more than 6,ooo rad!s tumor!ose had an average survival of i6.6 months. The relation between the type of therapy and survival is noted in Table vi. Although there is an apparent difference in average survival, the median survival in all groups is similar. Pain, dysphagia, weight loss, and! weak- SURVIVAL CORRELATED WITH RADIATION DOSE Dose No. of Total 79 V Average Under3,ooorads ,Iooto4,000rads ,Iooto5,000rads ,Iooto6,000rads o 6,iooradsandabove 3 i6.6 8.o No. of Per Cent of Average Total ness were tile symptoms evaluated!. Almost 50 per cent ofour patients failed to achieve significant relief of their symptoms and! all of these had a very low over-all average survival of about 3.2 months (Table vii). Likewise, those patients requiring more than weeks to adllieve relief of symptoms had a lower average survival than those patients receiving relief in a shorter period. Other factors which were found! to be present in those patients not palliated were: ( i) demonstrable metastases at the start of radiation therapy; (2) the presence of tracheoesophageal fistulae ; (,) gastrostom y prior to or development of a stricture during radiation therapy; and! (.) poor general condition prior to starting rad!iation therapy. Preoperative Postoperative Only DISCUSSION The effectiveness of any therapeutic VI SURVIVAL AFTER RADIATION THERAI Y COMI ARED WITH SURGERY No. of Average

4 VOL. io8, No. Carcinoma of the Esophagus 833 agent is measured by the ability of this agent to cure the disease, arrest the disease process and/or offer symptomatic relief. This study was initiated to evaluate the effectiveness of radiation therapy as an agent in the treatment of carcinoma of the esophagus and to ascertain the indications, contraindications and complications of this agent. The over-all survival of our group of patients is fairly low when compared to more recent series with more radical therapy.3 8 This may partially be explained! on the basis that little or no selection of patients for treatment was attempted!. Almost all patients, regardless of extent of disease or physical condition, were treated!. The average survival in months for all patients was 5.77 months, but when onl those who finished their planned! course of radiation therapy were considered!, it was increased! to 7.3 months. Most recent series have an average survival ofabout 12 months. Factors that affected survival in this series were: (i) length of the lesion when diagnosed; (2) presence or absence of metastases; (3) complications before or (luring radiation therapy; (4) response to rad!iation therapy as gauged by symptomatic relief; and () radiation dosage. Although there appeared to be improved survival in the surgically treated group, there was no difference in median survival. This apparent difference in survival could be explained by the fact that the patients receiving the combination treatment were generally patients with less advanced d!isease than those receiving radliation therapy alone (Table iii). From the small group, one cannot draw any conclusions concerning the effectiveness of combination of stirgery and radiation therapy when compared! to radiation therapy alone. However, one cannot help but wonder if an actual advantage to the patient is obtained by the use of surgery when the operative mortality and postoperative morbidity and questionable improvement in survival are considered!. Symptomatic relief was adversely affected by: (i) complications; (2) metas- Relief in I -4 Weeks Relief in 4 or More Weeks No Significant Relief VII SURVIVAL AND RELIEF OF SYMPTOMS ( Only) No. of Average 30 (38%) II 7 10(12.7%) (.%)._). - tases; and () the general condition of the patient. The length of the lesion did not correlate too well with symptom relief. The general condition of the patient, individual tumor responsiveness to radiation therapy, and! biologic differences between patients may account for this apparent inconsisten cv. A significant factor in this series was the poor survival and poor symptomatic response of those patients with major cornplications before radiation therapy was started, or who developed them during radiation therapy. with obstruction requiring gastrostomy prior to irradiation had an average survival of 2.6 months. Besid!es the poor survival, these patients did not obtain symptomatic relief of their distressing cornplaints of d sphagia and excessive drooling. requiring gastrostomv during treatment had a survival of4.2 months and! also no relief of symptoms of d!rooling and! pain after the gastrostomy was performed!. For these reasons it is felt that radiation therapy is not indicated after a patient has had a gastrostomy and should be stopped if a gastrostorny is required! during the course of treatment. developing tracheoesophageal fistulae before or during therapy also had! a low average survival. Those patients who had fistulae before treatment had an average survival of 1.7 months, and no relief of symptoms. developing fistulae during treatment also had a short sur-

5 834 A. B. Frazier, S. H. Levitt and L. S. DeGiorgi APRIL, 1970 vival and no relief of symptoms. For these reasons and because of the dangers of producing a mediastinitis, it is felt that initiaflon or continuation of radiation therapy is not indicated in these patients. Our findings and recommendations in these patients appear to be in contrast to those of Marcial et al.,5 who felt that development of fistulae was not a contraindication to radiation therapy and indeed fails to treat only when the patient s general physical condition has deteriorated to such a state that he cannot be transported to the Radiotherapy Departrnent. After careful analysis of our series, we feel that selectivity should be shown in treating carcinoma of the esophagus. Gastrostomy and tracheoesophageal fistulae before starting treatment are contraindications to radiation therapy. Also, if gastrostomy is required or tracheoesophageal fistulae (ievelop during the course of radiation therapy, then treatment should be stopped, as little or no symptom relief is obtained and there is such a low survival. with obvious metastases should have only a supportive therapy. SUMMARY A review of 90 patients with carcinoma of the esophagus, treated! at the Medical College of Virginia from January, 1961 through December, 1966, is presented. Factors affecting survival and symptomatic relief are discussed!. The following points are stressed: (I) obstruction requiring gastrostomy before or during radiation therapy is a contraindication to starting or continuing rad!iation therapy (lue to the poor survival and lack of symptomatic relie1; (2) the development of a tracheoesophageal fistula before or during the course of radiation therapy is a contraindication to further irradiation; () a tumor dose of at least 5,000 to 6,ooo rads or above should be our goal whenever there are no contraindications; (4) palliative radiation therapy should be attempted to prevent esophageal obstruction when more radical therapy is not indicated; (5) in this series the addition of radiation therapy to surgery whether pre- or postoperatively did not significantly alter the cure or survival statistics. S. H. Levitt, M.D. Division of and Oncology Medical College of Virginia Richmond, Virginia REFERENCES I. ACKERMAN, L. V. and DEL REGATO, J. A. Cancer Diagnosis, Treatment and Prognosis. C. V. Mosby Company, St. Louis, CHRI5TIAN5EN, K. H., PINCH, L. W., and STAIN- BACHN, \V. Carcinoma of esophagus. Am. 7. Surg., 1966,3, H0L5TI, L. Split-course megavoltage radiotherapy: one-year follow-up. Brit. 7. Radiol., 1966, 39, LEDERMAN, M. Carcinoma of oesophagus with special reference to upper third. Brit. 7. Radiol., 1966,39, MARCIAL, V. A., BOSCH, A., CORREA, J. N., and TOME, J. II. Role of radiation therapy in esophageal cancer. Radiology, 1966, 87, MERENDINO, K. A., and MARK, V. H. Analysis of one hundred cases of squamous cell carcinoma of esophagus. Surg., Gynec. & Obst., 1952, 94, II0-II4. 7. Moss, W. T. Definitive radiation therapy for carcinoma of breast. Radiology, I965, 83, I. 8. PEARSON, J. G. Radiotherapy of carcinoma of oesophagus and post cricoid region in South East Scotland. C/in. Radiol., 1966, 7,

6 This article has been cited by: 1. J. Sule-Suso, A.M. Brunt, R. Lindup, J.E. Scoble Hyperfractionated accelerated radiotherapy for carcinoma of the oesophagus. Clinical Oncology 3:4, [CrossRef] 2. Richard Belgrad, Galen L. Wampler A pilot study with ethyl bis (2,2-dimethyl-1-aziridinyl) phosphinate (AB-163) and radiation therapy. International Journal of Oncology*Biology*Physics 8:7, [CrossRef] 3. V.A. Piccone, N. Ahmed, S. Grosberg, H.H. LeVeen Esophagogastrectomy for Carcinoma of the Middle Third of the Esophagus. The Annals of Thoracic Surgery 28:4, [CrossRef] 4. V.A. Piccone, H.H. LeVeen, N. Ahmed, S. Grosberg Reappraisal of esophagogastrectomy for esophageal malignancy. The American Journal of Surgery 137:1, [CrossRef]

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