with Preoperative and Postoperative Radiotherapy

Transcription

1 Pancoast Tumors: Improved Survival with Preoperative and Postoperative Radiotherapy David M. Shahian, M.D., Wilford B. Neptune, M.D., and F. Henry Ellis, Jr., M.D., Ph.D. ABSTRACT Long-term survival after treatment of Pancoast tumors has been limited in most series to those patients without positive lymph nodes or residual tumor. In our series of 18 consecutive patients treated with preoperative irradiation and resection, 14 underwent supplemental postoperative radiotherapy because of positive lymph nodes, tumor at the resection margin, or both. No hospital deaths occurred. Eight patients subsequently died, 6 because of metastatic disease; only 2 deaths were secondary to local recurrence. Ten patients are alive at 6 months to 13 years after resection, and of the 10 have no evidence of tumor recurrence. The overall five-year observed survival (Kaplan-Meier) for the entire series was 56.1 & 12.7% (? standard error). Although the number of patients is small, the addition of postoperative radiotherapy for those with unfavorable operative findings resulted in long-term survival comparable to that of patients with negative nodes and margins. Despite their locally aggressive behavior, Pancoast tumors of the lung are frequently curable. Their characteristic clinical presentation, a direct result of local invasion of contiguous nerves and bones, may lead to diagnosis and treatment before lymphatic and distant metastases occur. The most effective treatment regimen for Pancoast tumor, which was originated by Shaw and associates [l], consists of low-dose preoperative radiotherapy followed by radical surgical resection. This protocol has resulted in an overall 5-year survival of more than 30% [2-61. These results have been achieved, however, primarily in patients with favorable findings at operation. Long-term survival has rarely been achieved in patients with positive lymph nodes or residual tumor, unfavorable prognostic signs that in our experience have been present in the majority of patients. In an effort to improve local control and survival in this group, we have used preoperative radiotherapy and radical resection followed by aggressive postoperative radiotherapy. From the Section of Thoracic and Cardiovascular Surgery, Lahey Clinic Medical Center, Burlington, the Division of Thoracic and Cardiovascular Surgery, New England Deaconess Hospital, Boston, the Overholt Thoracic Clinic, Boston, and Harvard Medical School, Boston, MA. Presented at the Twenty-second Annual Meeting of The Society of Thoracic Surgeons, Washington, DC, Jan 27-2, 186. Address reprint requests to Dr. Shahian, Section of Thoracic and Cardiovascular Surgery, Lahey Clinic Medical Center, Burlington, MA Material and Methods The records of all patients who underwent resection of a Pancoast tumor from June, 172, through January, 185, were reviewed. Pancoast tumors were defined as small lesions (maximum dimension of pathological specimen, less than 10 cm) located at the extreme apex of the lung and associated with one or more of the following: dense infiltration of the tumor into adjacent bone and nerve; typical pain in the shoulder, scapula, proximal arm, or axilla; neurological symptoms in the nerve distribution of C-8 to T-1; Horner s syndrome; and weakness or atrophy of the hand musculature. The demographic features, presenting symptoms, and preoperative evaluations of patients were reviewed. Operative notes, pathology reports, and radiotherapy records were obtained. Operative morbidity, mortality, and days of hospitalization were determined. Recent followup was obtained for all 18 patients by letter, chart review, or telephone conversation. Current functional status, relief of pain, and presence or absence of recurrent disease were determined for living patients. For patients who had died, the cause of death and findings at autopsy were reviewed. Survival data were analyzed using the product-limit method (Kaplan-Meier). Significance of differences in subgroup survival was determined by log rank analysis. Ninety-five percent confidence limits were calculated by the method of Rothman [71. Patient Population Our group of patients included 11 men and 7 women. Median age was 56.0 years (range, 36 to 70 years). All 18 patients had been heavy smokers. Preoperative duration of symptoms, which was ascertainable in 17 of 18 patients, averaged 5.2 months. In 17 patients (4.4%), the presenting symptom was intense pain in the shoulder or scapular area that sometimes radiated to the anterior chest, proximal arm, or axilla. Ulnar neuropathy was present in varying degrees in 7 patients (38.%), and 4 patients (22.2%) had complete or partial Horner s syndrome. The initial chest radiograph in all 18 patients showed an ill-defined apical density. Computed tomography of the chest, which has been used extensively by us in recent years, correctly identified an apical tumor in all 11 patients in whom it was performed. It was also useful in identifying destruction of contiguous bones and in determining the involvement of mediastinal nodes. Plain roentgenograms, computed tomographic scan, or bone scan suggested involvement or destruction of ribs or vertebral bodies in 8 patients (44.4%). Computed tomo- 32 Ann Thorac Surg 43:32-38, Jan 187

2 33 Shahian, Neptune, Ellis: Pancoast Tumors graphic scan of the liver was performed in 11 patients, and brain scan was performed in 8 patients; these findings were all normal. More recently, we have also used computed tomography to identify metastatic disease of the adrenal glands. Preoperative histological diagnosis was established in 11 of 18 patients (61.1%) by bronchoscopic brush biopsy or washing (4 patients), percutaneous needle biopsy (3 patients), rib biopsy (1 patient), mediastinoscopy (1 patient), minithoracotomy (1 patient), and a Chamberlain procedure (1 patient). In 17 of 18 patients, a preoperative radiotherapeutic dose of 3,000 to 4,000 rads delivered on an accelerated fractionation schedule was followed by operation two to four weeks later. In 1 patient, a Pancoast tumor with brain metastases had been diagnosed 4 years earlier at another hospital. The metastatic disease of the brain had been excised, and the brain (3,300 rads) and the lung (4,000 rads) were irradiated. When this patient was seen by us 4 years later, there was no evidence of disseminated metastases or recurrent disease in the brain, and the only symptom was severe pain secondary to the enlarging primary Pancoast tumor. Because 4,000 rads had previously been delivered to the lung apex, no additional preoperative radiotherapy was administered at that time. The patient received postoperative radiotherapy. Surgical Procedures The operations performed included wedge or segmental resection in patients (50%) and lobectomy in 8 patients (44.4%). One patient (5.6%) underwent pneumonectomy because of aortopulmonary nodes and involvement of the vagus and phrenic nerves. In 11 patients (61.1%), the inferior root of the brachial plexus was intentionally sacrificed. The first through third ribs were resected in 5 patients, ribs 1 through 4 in 4 patients, 1 and 2 in 3 patients, 2 through 4 in 2 patients, 2 and 3 in 1 patient, 1 through 5 in 1 patient, and the first rib alone in 1 patient. Vertebral resection was less radical and ranged from electrodesiccation of the tumor from the vertebral body in most patients to partial removal of the vertebral body in 3 patients. In some patients, definition of an uninvolved plane deep to the perivertebral ligamentous structures was possible without formal resection of bone. Pa thology Tumor histology, either of the preoperative biopsy specimen or the final surgical specimen, was identified in all 18 patients. The lesion was epidermoid carcinoma in 4 patients (22.2%), adenocarcinoma in 12 patients (66.7%), spindle cell tumor in 1 patient (5.6%), and large cell undifferentiated carcinoma in 1 patient (5.6%). In the last 2 patients (ll.l%), no viable tumor was found in the final operative specimens. The mean size of tumors in the fixed pathological specimens was 4.0 & 2.0 cm. Nine patients (50%) had positive resection margins. In 2 patients, macroscopic tumor had been left in the chest at operation because of involvement of unresectable structures and the belief that the resection was palliative only. In 7 other patients, all macrosopic evidence of tumor was removed at operation, but the resection margin was close because of involvement of vital structures. Pathological examination revealed microscopic disease at the margin. Of the patients with positive margins, 2 had undergone lobectomy and 7 had wedge or segmental resection. Residual tumor was found primarily in the chest wall margin or in the region of the brachial plexus or subclavian vessels. Conservative parenchymal resection was not responsible for the positive margins. Of these patients, 3 had negative lymph nodes and 3 had coexisting positive nodes. In the remaining 3, the lymph node status was indeterminate. Lymph nodes were examined in 13 patients; results were negative in 8 and positive in 5. Four of the latter 5 patients had adenocarcinoma. In 2 of these 5 patients, the positive nodes were hilar. One of these patients is alive and without evidence of disease at 2 years. The other patient, who also had positive chest wall margins because of involvement of unresectable structures, died of intrathoracic recurrence 7 months after operation. In 1 patient with nodes in the aortopulmonary window, phrenic and vagus nerve involvement necessitated pneumonectomy (13-year survivor). In 1 patient a paratracheal node was positive, and the tumor was incompletely resected because of tracheal and esophageal invasion. This patient died 1 year after operation and radiotherapy. Finally, 1 patient with a positive intersegmental node is alive and well 1 year after treatment. Lymph nodes were not specifically evaluated at operation in 5 patients. Results There were no surgical or hospital deaths. Major postoperative complications included a new Horner s syndrome (4 patients), mild weakness of the arm (2 patients), severe brachial neuropathy (1 patient), dyspnea (2 patients), prolonged need for ventilatory support (1 patient), prolonged parenchymal air leak (1 patient), apical space and bronchopleural fistula (1 patient), hemorrhage from a small pulmonary venous branch (1 patient), and pulmonary embolism (1 patient). The mean duration of hospitalization was 14.7 days (range, 5 to 42 days). Fourteen patients received postoperative radiotherapy because of positive lymph nodes, positive margins, or both. This consisted of external beam irradiation (10 patients), intraoperative implantation of gold 18 seeds (2 patients), and external beam combined with gold 18 seeds (1 patient) or iridium 12 through afterloading tubes (1 patient). The dose, method of delivery, and portals of radiation varied, depending on the extent and location of residual disease, the specific fields used during preoperative irradiation, and the preferences of the radiotherapist. For isolated mediastinal node involvement, the dose ranged from 2,000 to 3,500 rads and was always ad-

3 34 The Annals of Thoracic Surgery Vol 43 No 1 January 187 ministered using external beam. Incompletely resected vertebral body tumor was treated with external beam, radioactive seeds, or afterloading tubes, either singly or in combination. Lateral vertebral body doses totaling 2,500 to 6,500 rads were employed with appropriate techniques to spare the spinal cord. Residual disease in the apex of the chest involving the brachial plexus was treated with doses ranging from 1,000 to 5,000 rads (usually 3,000 to 3,500 rads). This resulted in total doses to the chest apex and brachial plexus as high as 6,000 rads in some patients. A few patients treated with brachytherapy, either alone or in combination with external beam, received very localized supplemental irradiation to the apex or lateral vertebral body in excess of these levels. However, the potential risks of radiation injury to the spinal cord or brachial plexus must be weighed carefully when such high doses are employed. The overall 5-year survival for the entire series of 18 patients was % (* standard error). The survival curve significantly conformed to a lognormal distribution with an early peak hazard function (216 days) (Figure). Six of the 8 deaths in the series occurred at less than 18 months; 4 were secondary to metastatic disease, and 2 were secondary to local recurrence. Only 2 of the 8 deaths occurred after 18 months, 1 at 2% years and 1 at 7 years after resection. Both were secondary to metastatic disease. The Table lists the observed 5-year survival by the following subgroups: histological tumor type, size of tumor, involvement of bone, extent of resection, and status of lymph nodes and resection margins. No statistically significant differences in survival pattern were associated with these factors, but the overall numbers analyzed were small. Of the 8 patients who died, only 2 died of local recurrence in the chest. Both patients had poorly.differentiated adenocarcinoma, and both had had positive mediastinal nodes. Both patients underwent lobectomy and chest wall resection. However, they were both 0 ~~~~~~~~~~~~~~~ Ycan Survival distribution (Kuplan-Meier) with 5% confidence limits [71 for overall series of 18 patients. Vertical marks indicate withdrawal of 10 living patients ( without evident malignant disease and I with bilateral pulmonu y metastases at 4% years). Survival Analysis of Patient Subgroups' Observed 5-Year No. of Survival Subgroup Patients (%) p Value Histological typeb Adenocarcinoma Epidermoid Size 24 cm <4 cm Involvement of bone Destruction No destruction Extent of resection Wedge or segment Lobe or pneumonectorny Nodes' Negative Positive Margins Negative Positive t t t ? ? ? ? "Data are shown as the mean t the standard error. bthis excludes 2 patients, 1 with large cell tumor and 1 with spindle cell tumor. 'This excludes 5 patients in whom nodal status was not evaluated. = not significant. found to have extensive and incompletely resectable vertebral body and brachial plexus involvement. One patient also had invasion of the trachea and esophagus. The other patient had a separate small focus of adenocarcinoma in the middle lobe, either a second primary or a synchronous parenchymal metastasis. Both patients received postoperative external beam irradiation. They died at 7 months and 13 months, respectively, after operation. The manifestations of local recurrence were superior vena cava obstruction, brachial neuropathy, and local adenopathy. Six patients died of metastatic disease to the brain, liver, or adrenal glands at 6 months to 7 years after operation. Nine patients are alive and disease free at 6 months (1 patient), 1 year (2 patients), 2 years (1 patient), 3% years (1 patient), 4% years (1 patient), 5% years (1 patient), 7 years (1 patient), and 13 years (1 patient) after resection. One patient is alive 4% years after operation but has bilateral pulmonary parenchymal metastases. In retrospect, we believe that at least one of these was present but unrecognized at the time of operation. The functional results in 10 long-term survivors were graded with respect to relief of pain, shoulder mobility, and neurological dysfunction secondary to a partial resection of the brachial plexus. The grading system was excellent, good, fair, and poor, and the following results were achieved. The status in terms of pain relief was excellent in 80%, good in lo%, and poor in 10%; for

4 35 Shahian, Neptune, Ellis: Pancoast Tumors shoulder mobility, it was excellent in 70%, good in lo%, and fair in 20%; and for neurological function, functional status was excellent in 30%, good in 60%, and fair in 10%. Pain relief and shoulder mobility have been excellent although the latter is dependent on aggressive physical therapy after operation and radiotherapy. Brachial plexus neurological dysfunction is present to some extent in 70% of the current survivors. None are completely incapacitated. Comment Apical lung tumors associated with local pain, ulnar neuropathy, Horner's syndrome, and vertebral invasion were reported by Hare [8] in One-half century ago, Dr. H. K. Pancoast [, 101, then chairman of the Section on Radiology of the American Medical Association, reported the first extensive series of patients with this lesion and characterized its radiographic features. He [] defined the lesion as "a small, homogeneous shadow at the extreme apex, always more or less local rib destruction and often vertebral infiltration. Death occurred as a result of what seemed to be a comparatively trivial growth without detectable metastases roentgenologically." He noted: "The tumors in question seemed to occur at a definite location at the thoracic inlet, were characterized clinically by pain around the shoulder and down the arm, Horner's syndrome, and atrophy of the muscles of the hand... '"1. The commonest presentation today is an apical lung mass associated with severe shoulder or scapular pain, which often radiates down the arm and which may be associated with ulnar neuropathy. Horner's syndrome is found in about onefourth of patients, and atrophy or weakness of the hand musculature is uncommon. A proper definition of Pancoast tumor is critical in any evaluation of therapeutic regimens or comparison among institutions. The original characterization by Pancoast [], which has been elaborated on by Paulson [ll], excludes more common lung cancers of the upper lobe, which in their advanced stages might encroach on the same apical structures as a true Pancoast tumor. True Pancoast tumors start in the apex as an almost imperceptible pleural thickening. Local invasion of nerves and bone produces symptoms at a comparatively early stage of growth before the mass is prominent radiographically. Such symptoms as cough, dyspnea, and hemoptysis, which are associated with the more common carcinomas of the upper lobe, are usually absent, as are signs of advanced mediastinal invasion (e.g., superior vena caval syndrome, recurrent or phrenic nerve paralysis). These distinctions are crucial and help to explain the great disparity in survival statistics (0 to 4.7%) reported for this lesion [2-6, 12-16]. The early treatment of Pancoast tumors lacked consistent success. Surgeons were usually unwilling to attempt resection of these lesions because of their dense infiltration into surrounding structures at the thoracic inlet. Before the operation performed by Chardack and MacCallum [17] in 150, there had been no successful surgical resections. Radiotherapy alone was for many years the preferred treatment for Pancoast lesions, but it too achieved little success, in part because of inadequate doses and fields of radiation. Even in modern series [ , overall 5-year survival with radiotherapy alone remains only 18 to 23%. Currently, the most successful treatment regimen for Pancoast tumor is low-dose preoperative radiotherapy and radical resection [l]. Shaw and co-workers [l] originally observed that 3,000 rads administered to a patient with an apparently unresectable Pancoast tumor had reduced the lesion to one-half its previous size and had rendered the patient free from pain. Radical resection followed, and the patient lived more than 27 years. Subsequent application of this regimen has resulted in 5- year survival of 30 to 34%, as reported by Miller and associates [2], Ginsberg [5], Martini [6], Hilaris and colleagues [12], and Paulson and co-workers [13, 141. In patients with negative lymph nodes, Paulson [3] achieved a 5-year survival of 44%, and Stanford and associates [4] reported a survival of 4.7%. Conversely, patients with positive lymph nodes or residual tumor have rarely achieved long-term survival. In our series of 18 patients, 14 had positive lymph nodes, tumor at the resection margin, or both. In an attempt to improve the expected dismal prognosis for these patients, we added postoperative radiotherapy. Low-dose preoperative radiotherapy may shrink a bulky tumor and sterilize local lymphatics, but in our experience, the dose is often insufficient to destroy all viable tumor (only 2 of 18 patients in our series). It does not encompass mediastinal lymphatics, and it cannot be delivered precisely in high doses to the extreme margins of the tumor where residual disease may be found. Postoperative radiotherapy, although not indicated for routine use in bronchogenic carcinoma, appears to be of value for tumors that extend beyond the visceral pleura to involve the chest wall or regional lymph nodes It may be delivered precisely and at relatively high doses, either by external beam or brachytherapy, to areas of residual disease. Our current approach combines radical resection with the distinct and complementary advantages of both preoperative and postoperative irradiation. After they are screened for distant metastases, all patients receive low-dose preoperative radiotherapy. This is followed by exploration, conservative pulmonary resection, and radical resection of the chest wall, including the inferior root of the brachial plexus, the sympathetic chain, and the vertebral bodies as necessary. Although not uniformly performed early in our experience, sampling of lymph nodes is now routine. When findings at operation are unfavorable (e.g., positive lymph nodes, tumor at the resection margins), supplemental postoperative irradiation is delivered using external beam, afterloading catheters, or implantation of radioactive seeds, either singly or in combination. This is specifically directed at areas of residual disease in lymphatics and at the resection margin. Such areas are carefully marked with radiopaque

5 36 The Annals of Thoracic Surgery Vol 43 No 1 January 187 clips to allow precise planning of radiation portals, taking into consideration the preoperative irradiation dose and fields and adjacent critical structures, such as the spinal cord. With such a program, overall 5-year survival of 56.1% has been achieved in a consecutive series of patients, three-fourths of whom had unfavorable findings at operation. Although the number of patients in this series is small, our data suggest that postoperative radiotherapy may ameliorate the adverse impact on survival of positive nodes or residual tumor at the resection margin in patients with Pancoast tumors. Long-term local control should be possible in most of these patients. Reluctance to resect Pancoast tumors solely because of the presence of positive lymph nodes seems unwarranted. Death of patients with Pancoast tumors usually results from distant metastatic disease that is present at the time of operation although undetected by conventional screening methods. Improved detection of occult distant metastases and, perhaps, adjunctive chemotherapy may be the next steps toward improving survival. We acknowledge the statistical evaluation performed by Gerald J. Heatley, M.S., of the Sias Surgical Research Unit. Preoperative and postoperative therapy was performed in most patients by the Department of Radiotherapy, Lahey Clinic Medical Center, Burlington, and the Joint Center for Radiation Therapy, Boston, MA. References 1. Shaw RR, Paulson DL, Kee JL Jr: Treatment of the superior sulcus tumor by irradiation followed by resection. Ann Surg 154:20, Miller JI, Mansour KA, Hatcher CR Jr: Carcinoma of the superior pulmonary sulcus. Ann Thorac Surg 28:44, Paulson DL: Superior sulcus tumors. In Glenn WL, Baue AE, Geha AS, et al (eds): Thoracic and Cardiovascular Surgery. Fourth edition. East Norwalk, CT, Appleton- Century-Crofts, 183, pp Stanford W, Barnes RP, Tucker AR: Influence of staging in superor sulcus (Pancoast) tumors of the lung. Ann Thorac Surg 2:406, Ginsberg R: Discussion of Attar et al [I61 6. Martini N: Discussion of Attar et al [ Rothman KJ: Estimation of confidence limits for the cumulative probability of survival in life table analysis. J Chronic Dis 31:557, Hare ES: Tumor involving certain nerves. Lond Med Gazette 1:16, Pancoast HK: Superior pulmonary sulcus tumor: tumor characterized by pain, Horner s syndrome, destruction of bone and atrophy of hand muscles. JAMA :131, Pancoast HK: Importance of careful roentgen-ray investigations of apical chest tumors. JAMA 83:1407, Paulson DL: The importance of defining location and staging of superior pulmonary sulcus tumors. Ann Thorac Surg 15:54, Hilaris BS, Luomanen RK, Beattir EJ Jr: Integrated irradiation and surgery in the treatment of apical lung cancer. Cancer 27:136, Paulson DL, Shaw RR, Kee JL, et al: Combined preoperative irradiation and resection for bronchogenic carcinoma. J Thorac Cardiovasc Surg 44:281, 162 Paulson DL: Carcinomas in the superior pulmonary sulcus. J Thorac Cardiovasc Surg 70:105, 175 Kirsh MM, Dickerman R, Fayos J, et al: The value of chest wall resection in the treatment of superior sulcus tumors of the lung. Ann Thorac Surg 15:33, 173 Attar S, Miller JE, Satterfield J, et al: Pancoast s turnor: irradiation or surgery? Ann Thorac Surg 28:578, 17 Chardack WM, MacCallum JD: Pancoast tumor: 5-year survival without recurrence or metastases following radical resection and postoperative irradiation. J Thorac Surg 31:535, 156 Mantell BS: Superior sulcus (Pancoast) tumors: results of radiotherapy. Br J Dis Chest 67:315, 173 Morris RW, Abadir R: Pancoast tumor: the value of high dose radiation therapy. Radiology 132:717, 17 Komaki R, Roh J, Cox JD, Lopes da Conceicao A: Superior sulcus tumors: results of irradiation of 36 patients. Cancer 48:1563, 181 Van Houtte P, MacLennan I, Poulter C, Rubin P: External radiation in the management of superior sulcus turnor. Cancer 54:223, 184 Byfield JE: Radiation therapy, local tumor control, and prognosis in bronchogenic carcinoma: current status and future prospects. Am J Surg 143: 675, 182 Eisert DR, Hazra TA: The role of radiation therapy in carcinoma of the lung. JAMA 247:338, 182 Choi NC, Grillo HC, Gardiello M, et al: Basis for new strategies in postoperative radiotherapy of bronchogenic carcinoma. Int J Radiat Oncol Biol Phys 6:31, 180 Discussion DR. DONALD L. PAULSON (Dallas, TX): Dr. Shahian has brought a very interesting message to you. He suggests that patients who have an incomplete extended resection of Pancoast tumors after preoperative irradiation would benefit by the addition of postoperative radiotherapy, although I do not believe that this conclusion is necessarily justified on the basis of the small number of patients and the patient selection. Our own experience indicates the stage of nodal involvement, the extent of the carcinoma, and the pathological effects of irradiation of the chest wall are the important factors in the prognosis. In 74 patients seen from 156 to 180, squamous cell and large cell undifferentiated carcinomas predominated. There was no difference in survival among patients with squarnous cell carcinoma, large cell undifferentiated, and adenocarcinoma. In contrast, 12 of 18 tumors in the present study were adenocarcinomas. Of 74 patients, only 3 of 17 patients with involvement of hilar or mediastinal lymph nodes, T3 N1 or T3 N2 lesions, survived 1 year and none of them survived 3 years. In contrast, 25 of 57 patients with either no nodes involved or an intersegmental node involved (1 patient) survived 3 years, and 22 survived over 5 years. As is true for any location in the lung, patients with T3 N2 lesions do not survive more than 2 years because of distant metastases. We used external beam radiotherapy postoperatively in an attempt to control residual or locally recurrent tumor for 10 patients with neither relief of pain nor control of the lesion. Those patients in whom viable tumor was found at the chest wall level or the margin of the resection in the perineural lymphatics or of the nerve roots at the intervertebral foramen did

6 37 Shahian, Neptune, Ellis: Pancoast Tumors poorly regardless of treatment and died in less than 2 years, mainly of distant metastases but also with local recurrence of carcinoma. There is clinical and experimental evidence that surgical interference by alteration of the vascular bed of a tumor and its lymphatics decreases oxygen tension and diminishes radiosensitivity of the tumor. Our experience suggests that once a tumor has been disturbed by extended resection-and we do a really extended resection-irradiation is ineffective in checking the advance of the residual neoplasm. A further consideration is that if to a 3,000-rad preoperative radiotherapeutic dose in 10 fractions, which is biologically equivalent to 4,000 rads in 20 fractions, we add 3,000 rads in 15 fractions postoperatively, we arrive at a biologically equivalent dose of close to 6,000 rads in 30 fractions of continuous, uninterrupted therapy. My questions to the authors concern the specific dosage used and the late development of new brachial plexus neurological findings in the absence of recurrence of tumor which may be secondary to radiation fibrosis and nerve entrapment. I congratulate Dr. Shahian on a very well presented paper that represents an attempt to improve the management of this difficult and painful lesion. DR. JOSEPH I. MILLER (Atlanta, GA): 1 congratulate Dr. Shahian on his presentation. My colleagues and I agree with the majority of things he has said. I will just briefly explain why. Between 170 and 185, on the thoracic surgical service of Emory University Affiliated Hospitals, we operated on 36 patients who were considered to meet criteria for an attempted curative resection following the Paulson criteria of preoperative irradiation and surgical resection. Of this group, 25 of the 36 patients survived longer than 2 years and 11 have survived more than 5 years, an actuarial survival of 31%. In an initial retrospective review of this group in 178, we noted that there were two problems, the high incidence of persistent postoperative pain in at least 50% of patients even though no residual disease was noted and the two areas of recurrence included brain metastasis and local recurrence. Beginning in 178 in all patients, we routinely added postoperative irradiation as part of our protocol following completion of surgical resection regardless or irrespective of the positivity of the margin or the absence of nodes. The majority of this group of patients did not have positive nodes or positive margins. In the group of 18 patients operated on since that time, we have been very pleased with the outcome. There has been evidence of only one instance of local recurrence in patients who have survived more than 2 years following the initiation of routine postoperative radiation therapy. We have also noted that we have had no survivors among patients who have had invasion of the vertebral body, the prevertebral fascia, or subclavian artery longer than 2 years. At least 50% of our patients still have substantial pain postoperatively. This has continued to be a problem, and I cannot explain why. The main area of recurrence that we see now is in the brain, and as part of the protocol, we routinely advocate utilization of postoperative irradiation to completion of the dose. DR. MARTIN MC KNEALLY (Albany, NY): The experience of our group in Albany with a similar series lends support to the hypothesis advanced by Dr. Shahian and his colleagues. Among 25 patients with Pancoast tumors treated surgically in the past decade, there were 10 with residual disease: 6 had positive surgical margins, and 4 had positive mediastinal nodes. These patients with incomplete resection were treated with postoperative radiotherapy, some received BCG, and 2 received chemotherapy. Based on other evidence, we believe that the last two methods did not contribute importantly to patient survival. We had better results than expected, particularly in the pa. tients with incomplete resection, and we think that the addition of postoperative radiation therapy made an important contribution to survival. Of 10 patients followed more than 5 years, 6 are alive. The 5-year actuarial survival was 51% overall and 42% for patients with incomplete resections. We compliment Dr. Shahian on his presentation and have three questions. How do you prove from your data or any of the data presented that operation and not irradiation alone was the definitive treatment? Is the quality of life in the survivors worth the morbidity of treatment? What would you do next to study this question? DR. SAFUH ATTAR (Baltimore, MD): My associates and I have reviewed our experience with Pancoast tumors at the University of Maryland over the past 10 years. It comprises less than 100 patients. They were divided into four groups. The first one, a small group, was treated by operation alone because of early detection and the localization of the lesion. It did not involve the apex of the chest extensively or the brachial plexus. The second group was treated by Dr. Paulson s recommended therapy, that is, preoperative irradiation followed by operation within two to three weeks. The third group was treated by irradiation alone because of extensive involvement of the mediastinum or distant metastases. The fourth group was treated by operation followed by radiation therapy because the operation was an incomplete resection as a result of the extent of the disease. The survival was not significantly affected by the addition of postsurgical radiation therapy to irradiation alone for the reasons given by Dr. Paulson. We noticed that although there appeared to be a big difference between the group having operation alone versus the group having operation and preoperative irradiation, the difference was nut statistically significant. I have two points to raise with Dr. Shahian. I noticed that the extent of the resection was very small in 50% of the patients. The lesions were resected by wedge resection, which is really very limited. In our group, there may have been only one tumor that was resected by wedge resection. This indicates to me a very incomplete resection, and I believe that probably there was a positive margin. Dr. Shahian, were the margins positive in the 50% of patients who had incomplete resection? 1 think we can get better survival by early detection and more extensive resection rather than by the addition of radiotherapy to the treatment. The results that we are seeing are not an indication of the modes of therapy but represent the extent of the disease. DR. SHAHIAN: I thank the discussants for their comments. It is a particular honor to have had this paper discussed by Dr. Paulson, who, along with Dr. Shaw, revolutionized the treatment of this lesion. 1 will take the questions in order. First, Dr. Paulson, it is difficult to precisely determine the total delivered dose to areas of residual tumor when a combination of brachytherapy and external beam are employed. However, the total delivered dose for most of our patients was approximately 6,000 rads. 1 think you must administer approximately that dose with any radiotherapeutic program to achieve local control and survival.

7 38 The Annals of Thoracic Surgery Vol 43 No 1 January 187 A few radiation-related complications did occur. A superior vena caval syndrome developed in 1 patient which resolved spontaneously after several months and was clearly not due to tumor but rather to sclerosis. Benign brachial neuropathy developed in several other patients, which in 1 seems to be resolving. It is important to note that after radical surgical intervention and perioperative irradiation, symptoms such as these do not necessarily indicate tumor recurrence. Dr. McKneally asked three questions. First, how do we prove that it was irradiation postoperatively and not the operation itself that cured these patients? There are in the literature many series demonstrating the results in patients who did not receive aggressive postoperative radiotherapy. All of them show substantially lower survival than those whom we presented and those whom Dr. McKneally's own group has presented. I think we must conclude it is probably postoperative irradiation that accounts for this difference. There have been few adverse systemic or functional sequelae. I have already suggested what the next steps might be in improving survival for these patients, Dr. McKneally. The combination of treatments 1 have outlined is very effective in dealing with the local problem. We must find, however, a way to better identify and treat distant disease. Dr. Attar, you commented on the extent of resection. This disease occurs at the very periphery of the lung, and extended resections of lung are usually not indicated. It is not the pulmonary parenchymal margin that is typically involved; it is the chest wall margin. I think if one has a series in which many extended pulmonary resections were done, I would question whether tumors were really Pancoast tumors to begin with or whether in fact they were non-pancoast upper lobe lesions that in their advanced stages encroached on the apex. BOOKS RECEIVED Manual of Cardiac Arrhythmias E. K. Chung New York, Yorke, pp, illustrated, $30.00 Cardiac Arrhythmias: Self-Learning Text E. K. Chung New York, Yorke, pp, illustrated, $30.00 Manual of Exercise ECG Testing E. K. Chung New York, Yorke, pp, illustrated, $30.00 These three books are practically designed for easy reading and interpretation by the relatively uninitiated. Clinical Doppler Echocardiography 1. Missri New York, Yorke, pp, illustrated This is a short text on the use of Doppler in evaluation of heart disease. A Guide to Cardiac Pacemakers: Supplement D. Morse, R. M. Steiner, and V. Parsonnet Philadelphia, Davis, pp, illustrated, $50.00 This manual of various pacemakers and their characteristics updates the edition published in 183. This could be a reference book wherever a lot of pacemaker implantation is carried out. Color Atlas of Anatomy. A Photographic Study of the Human Body 1. W. Rohen and C. Yokochi New York, lgaku-shoin, pp, illustrated, $42.50 Two professors of anatomy-one Japanese, the other German -have collaborated with an American professor of anatomy to produce a unique English language atlas of anatomy. All of the illustrations are excellent photographs of dissections which usefully illustrate the anatomy as the student would actually see it in the laboratory.