Inr. J. Radiarron Oncology Biol Ph,w. Vol. Pnnted I” the U.S.A. All rights reserved.

23, pp.

1037-1043 Copyright

036s3016/92 $5.00 + .oO Q 1992 Pergamon Press Ltd.

??Brief Communication




ALAN POLLACK, M.D., PH.D.,* RITSUKO KOMAKI, M.D.,* JAMES D. Cox, M.D.,* JAE Y. Ro, M.D.,+ MARY JANE OSWALD, B. S.,* DONG M. SHIN, M.D.* AND JOE B. PUTNAM, JR., M.D.§ The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 Thirty-six patients with pathologically confirmed thymoma were treated at M. D. Anderson Cancer Center from 1962 to 1987. The tumors were staged based on invasion and intrathoracic dissemination. Twenty-one patients had total resection, five had subtotal resection, and 10 had biopsy alone. Twenty-two patients had definitive megavoltage radiation therapy with a median dose of 50 Gy. The 5year, disease-free survival by stage was 74% for Stage I (n = ll), 71% for Stage II (n = 8), 50% for Stage III (n = lo), and 29% for Stage IVA (n = 7) (p < 0.03). The 5 year, disease-free survival by extent of surgery was 74% for total resection, 60% for subtotal resection and 20% for biopsy only (p = 0.001). There were 15 patients with recurrences: two in Stage I, two in Stage II, five in Stage III, and six in Stage IVA. The median months to relapse, for those who failed treatment, were 46, 36, 2, and 13 for Stages I, II, III, and IVA respectively. Of the patients with recurrences four had a total resection, two subtotal resection, and nine biopsy only. Only one patient had distant metastases as the first site of relapse without intrathoracic relapse. For the eight patients who relapsed following radiation therapy, four were in the radiotherapy field. All four of the in-field failures were in patients who had a partial response. There were insufficient numbers of patients to determine a dose response to radiotherapy. For patients with invasive, incompletely resected disease, a multimodality approach may be necessary for long term, disease-free survival. Thymoma, Radiotherapy,


viewed the outcome of 36 patients treated primarily at The University of Texas M. D. Anderson Cancer Center.


As more evidence concerning the clinico-pathologic pattern of thymomas is acquired, the malignant nature of these neoplasms is more clearly documented. Thymomas are rare, slow-growing, epithelial neoplasms typically classified as malignant once they evidence macroscopic invasion (4, 16,23). The histology, however, would suggest a benign behavior. Nevertheless, invasion beyond the capsule connotes a significantly poorer prognosis, even without a change in the histologic appearance of the cells. Therefore, all thymomas are potentially invasive and should be considered potentially malignant. There is still controversy concerning the staging and the optimum treatment of thymomas (4, 12, 19,28). Surgery remains the treatment of choice for noninvasive lesions, with 5-year survival rates usually above 80% (10, 21). The treatment of patients with invasive disease remains controversial. In this report we retrospectively re-




Clinical features

From 1944- 1987, 83 patients with the diagnosis of a thymic neoplasm were seen at M. D. Anderson. Of these, 47 patients were excluded from this study: two had other histologies (a lymphoma and an embryonal carcinoma), two had more than two concurrent malignancies, two died within 1 week of initial surgery, nine had thymic carcinoma, 14 were seen in consultation only, 12 received their initial treatment 6 months before referral, five were treated with radiotherapy at an outside institution, and one was treated with orthovoltage radiotherapy. The 36 patients whose treatment was primarily at M. D. Anderson and whose radiotherapy, when given, was with megavoltage,

* Dept. of Radiotherapy. +Dept. of Pathology. * Dept. of Medical Oncology. 5Dept. of Thoracic Surgery.

Acknowledgement-This investigation was supported in part by Grant CA06294, awarded by the National Cancer Institute, National lnstitutes of Health, Department of Health and Human Services. Accepted for publication 3 October 199 1.

Reprint request to: Ritsuko Komaki, M.D., Department of Radiotherapy, Box 97, The U.T. M. D. Anderson Cancer Center, 15 15 Holcombe Blvd., Houston, TX 77030. 1037


1. J. Radiation Oncology 0 Biology 0 Physics

were treated between 1962-1987; they are the subject of this report. The average follow-up was 66 months (median 63 months) with a range of 5 to 165 months. The age ranged from 8 to 78 years with a median of 53 years. The ratio of female:maIe was 1.1: 1. Twenty-five patients were white; seven were black, and four were hispanic. On presentation, 14 patients were asymptomatic, 11 had chest pain, six had dyspnea, two had hoarseness, three had superior vena cava obstruction, three had cough, two had myasthenia gravis, and one had red cell aplasia. Six patients presented with two symptoms. Pathology The diagnosis of thymoma was based on the pathologic criteria described by Rosai and Levine (23) that is, neoplasms of the thymic epithelial cells, regardless of the presence of a lymphoid component. The definition has been modified (16), such that thymic tumors containing cells with the cytologic appearance of malignancy are separately classified as thymic carcinomas. Nine patients with the pathologic diagnosis of thymic carcinoma were not included in this study because of problems identifying the primary site, the difference in histology, and the more aggressive clinical course of this disease (24, 29). Pathologic specimens from all patients were reviewed at M. D. Anderson Cancer Center on admission. Re-review of the specimens was accomplished in 29 of the 36 patients. There was good agreement between the initial histologic examination and the re-review. The tumors were classified into the four histotypes described by Berpredominant, epithelial prenatz et al. (6)-lymphocyte dominant, spindle cell, and lymphoepithelial or mixed. There were 10 patients with tumors having the lymphocyte predominant histology, seven having the epithelial predominant histology, two having the spindle cell histology, and 17 having the mixed histology.

Volume 23, Number

5, 1992

Table 1. Masaoka Stage I: Stage II:

Stage III: Stage IV:


Macroscopically completely encapsulated and no microscopic capsular invasion 1. Macroscopic invasion into surrounding fatty tissue or mediastinal pleura 2. Microscopic invasion into the capsule Macroscopic invasion into neighboring organs A. Pleural or pericardial implants B. Lymphogenous or hematogenous metastases

From Masaoka


al. (19).

had a median sternotomy and two had a thoracotomy. Of the 10 who had biopsy alone, one had a median sternotomy, six had a thoractomy, two had an anterior mediastinotomy, and one had a needle biopsy.

Staging Staging was based on the surgical and pathologic criteria described by Bergh et al. (4), as modified by Masaoka et al. ( 19). In the Bergh staging, Stage III includes all tumors confined to the thorax. In contrast, the staging system proposed by Masaoka et al. (Table 1) defines Stage IVA as tumors with intrathoracic spread, not contiguous with the primary (i.e., pleural plaques, pericardial plaques, or intraparenchymal lung metastases). Staging was accomplished retrospectively using the operative reports, pathology reports, and the pathologic specimens available.

Radiotherapy Twenty-two patients were treated at M. D. Anderson with megavoltage photon irradiation within 4 months of diagnosis. No patient had preoperative radiotherapy. Most of the patients were treated with AP:PA fields weighted 2: 1 or 3:2, at 2 Gy per fraction calculated at the midplane with the spinal cord dose limited to 45 Gy or less. Offcord oblique fields were used to boost the mediastinum to higher doses. The fields typically encompassed the tumors with about a 1.5 cm margin. The supraclavicular area(s) were treated in 10 of the 22 patients, usually in those with later stage disease. Eighty-three percent of these patients received a tumor dose of 49 Gy or higher and 64% received between 4955 Gy. The dose range was 40 Gy to 60 Gy, with a median dose of 50 Gy in 5 weeks. One patient was treated to 60 Gy in 37 fractions with the last 2 weeks given BID because of an initial poor response. This patient did not have a complete response to radiotherapy. One patient with stage IVA disease was treated with a split course consisting of 30 Gy, with a 2 week rest, followed by an additional 30 Gy (total of 60 Gy in 19 fractions). This patient recurred in the thorax after 150 months. During the 25 year span of this study, there was not a consistent treatment policy for patients with early stage tumors (I and II). In general, these patients were treated when there was an increased risk of residual disease, e.g., with extensive adherence of the capsule to the pleura or pericardium. Radiotherapy was administered to all patients with late stage tumors (III and IVA), unless the patient refused or the volume was excessive.

Surgery Twenty-one patients underwent gross total resection, five had subtotal resection (250% and ~100% resected), and 10 had biopsy alone (~50% resected). Of the 2 1 patients with total resection, 12 had a median sternotomy, eight had a thoracotomy, and one had an anterior mediastinotomy. Of the five who had subtotal resection, three

Chemotherapy Twelve patients were treated with chemotherapy within 6 months of diagnosis at thoracotomy. Two had synchronous second malignancies; one patient was treated with cyclophosphamide, Adriamycin, and vincristine for diffuse large cell lymphoma and one with 5-fluorouracil, Adriamycin, and Cytoxan for Stage II breast carcinoma.


Thymoma: Treatment and prognosis 0 A. POLLACKet al

Table 2. Stage and adjuvant treatment Number of patients





4 3 2 -

5 5 4 1

CTH* 1+ 4


Sum (S)

1’ 4 2

11 (31) 8 (22) 10 (28) 7 (19)

* XRT = Radiotherapy; CTH = Chemotherapy. + Treated with cytoxan, adriamycin and vincristine for lym-

phoma (see Methods and Materials). *Treated with 5-fluorouracil, adriamycin and cytoxan for Stage II breast cancer (see Methods and Materials).

One patient received cyclophosphamide orally for progression of myasthenia gravis. The remaining nine patients were treated for advanced stage thymoma with multiagent regimens, with five receiving cis-platinum as part of the treatment. Statistics The disease-specific survival, and overall survival were calculated from the date of surgical staging. The diseasefree survival (DFS) was calculated from the day of surgery to recurrence, or to progression (when the surgery was less than a total resection). The actuarial survival curves were calculated using the Berkson and Gage method (5) with the Lee and Desu statistic (15). RESULTS

Treatment subgroups The distribution of patients according to the stage and the type of treatment is shown in Table 2. Two of the patients with Stage I disease received chemotherapy because of second primaries. Both patients have been without evidence of disease from their second malignancies. Four patients with stage IVA disease received chemotherapy without radiation therapy because of intrathoracic implants that could not be included reasonably in a single field. The surgery for these four Stage IVA patients consisted of biopsy alone (Table 3). All of the Stage I and II patients had gross total resections, while only one patient with Stage III and one with

Fig. 1. Disease-free survival distribution

by stage.

Stage IVA had total resection. All the patients having subtotal resection had Stage III disease. One with Stage III disease had a subtotal resection and refused further treatment. He is alive with stable disease at 47 months. Another Stage III patient did not receive further treatment after total resection; he is alive and disease-free after 16 months. Twenty-two patients received definitive megavoltage radiation therapy and seven of these received chemotherapy. Suwival statistics The actuarial 5-year, disease-free survival (DFS) by stage is shown in Figure 1. The DFS was 74% for Stage I, 71% for Stage II, 50% for Stage III, and 29% for Stage IVA. Overall, there was a statistically significant difference by stage @ < 0.03). The pair-wise comparisons of Stage I versus II and stage III versus IVA were not significant. The disease-specific, 5-year survival was 88% for Stage I, 83% for Stage II, 44% for Stage III, and 57% for Stage IVA. The overall survival at 5 years was 70% for Stage I, 75% for Stage II, 58% for Stage III, and 57% for Stage IVA. When patients with noninvasive thymomas (Stage I) were compared to those with invasive thymomas (Stage II-IVA), the 5-year DFS was 74% and 49%, respectively (p < 0.05). Figure 2 shows the DFS by the extent of surgery. The 5-year, DFS was 74% for those patients who had total resection, 60% for subtotal resection, and 20% for biopsy alone (p = 0.00 1 overall). The respective, disease-specific

Table 3. Type of surgery and adjuvant treatment Number of patients Type of Surgery Biopsy Subtotal resection Total resection

None XRT* CTH* XRT + CTH 1 8

* XRT = Radiotherapy;

4 1 10

4 1

2 3 2

CTH = Chemotherapy.

Sum (%) 10 (28) 5 (14) 21 (58) Fig. 2. Disease-free survival distribution

by extent of surgery.


I. J. Radiation Oncology 0 Biology 0 Physics

5-year survival figures were 87%, 53%, and 40%, and those for overall 5-year survival were 74%, SO%,and 40%. Since four Stage IVA patients had biopsy alone and had extensive intrathoracic disease that precluded radiotherapy, an analysis of DFS excluding these patients was done. The 5-year, DFS for the remaining six patients who had biopsy alone was 33%. The exclusion of these high risk patients did not affect the observed pattern that patients having biopsy alone had the worst prognosis. When patients who had total resection were subdivided into those having non-invasive and invasive thymoma, the 5-year DFS’s were the same (75% and 74%, respectively). A comparison of patients with invasive thymomas (Stages II-IVA) who did not have radiotherapy and those who did revealed a 5-year DFS of 18% and 62%, respectively (p = 0.22). Similar results were obtained when all patients, including those having Stage I disease, were compared. Included in these comparisons are four Stage IVA patients who had extensive intrathoracic disease that precluded radiotherapy. When these four Stage IVA patients were excluded, the 5-year DFS was 40% for the five patients with invasive thymoma who did not receive radiotherapy. There were 16 patients in Stage II-IVA who received radiotherapy. Of these, six had chemotherapy in addition to radiotherapy. A comparison of these two groups revealed a 5-year DFS of 60% for those receiving radiotherapy alone and 67% for those receiving radiotherapy and chemotherapy (p = 0.95). The numbers are too small to draw any conclusions concerning the effect of chemotherapy. The 5-year DFS by tumor histologic type was 68% for patients with lymphocyte predominant, 77% for those with epithelial predominant (including spindle cell), and 40% for those with mixed (overall a = 0.08). The trend was similar for the 5-year, disease-specific and overall survival rates; however, the differences were statistically significant (p < 0.01). Relapse patterns Table 4 shows the time to disease progression by stage, for the patients who failed treatment. Two patients with Stage I disease relapsed in the thorax. In one, postoperative radiotherapy (50 Gy) was given to the surgical bed and the recurrence was outside the radiotherapy treatment field in the form of pleural-based masses. The other patient Table 4. Months

free of disease progression by stage



Group total 2/11 218 5110 617 15136

Table 5. Months free of disease progression by extent of surgery No. relapsed


Type of surgery

Group total




Biopsy Subtotal resection Total resection

9/10 215 4121

2-150 l-9 30-61

27 5 40

5 36


did not have postoperative radiotherapy. Eleven of the 15 patients who had disease progression had Stage III or IVA disease. The median time to progression for the patients who relapsed was longer for those with early stage disease (Stages I and II), than for those with later stage disease. The median time to progression for the patients who relapsed after the tumor was totally resected was much longer than for those who had a subtotal resection or biopsy (Table 5). Moreover, 11 of the 15 patients who had subtotal resection or biopsy relapsed. Six of these patients relapsed after radiotherapy. The four patients who relapsed after total resection included two who had postoperative radiotherapy. The sites of initial relapse are shown in Table 6. In only one patient was the initial site of relapse exclusively outside of the thorax. There were eight patients who had disease progression after radiotherapy and, of these, four were within the irradiated field. All four of the in-field failures were in patients with late stage disease (Stages III & IVA) who had a partial response. The overall in-field control rate was 82% ( 1S/22). There were 1 1 patients with late stage disease treated with radiotherapy; six had a complete response and five had a partial response. Of the five patients who had a partial response, one was treated with chemotherapy after completion of radiotherapy and continued to have a residual mass that became calcified. He died of intercurrent disease at 79 months. The other four patients with a partial response died within 14 months of local disease progression. Two of the six complete responders relapsed outside of the treatment field (one with distant metastases after 1 year and one with pleural plaques after 12 years). Therefore, in-field control was obtained in all six complete responders and only one of five partial responders with late stage disease. Salvage of patients who failed initial treatment was poor. Of the 15 patients who failed, all but three have died of disease. The three patients who are alive following relapse had stable disease at the time of analysis.


No. relapsed Stage

Volume 23, Number 5. 1992




30-6 1 33-39 l-9

46 36 4

46 36 2

4-150 l-150

38 28

13 9

Complications of radiotherapy Six patients developed pericarditis after radiation therapy. In three of these patients the pericarditis was attributed to intrathoracic thymoma recurrence. Two patients who were without evidence of disease had mild chronic pericarditis and were asymptomatic. One patient died of pneumonia and was found at autopsy to have severe peri-


Thymoma: Treatment and prognosis 0 A. POLLACK etal.

Table 6. Treatment and disease status of the patients who relapsed

Pt. no.



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15


Total Total Total Total Subtotal Subtotal Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy

XRT dose (GY)

Site of first failure’

Months disease-free

50 50 60 55 45 53 60 -


30 61 33 39 9 I 7 2 2 150 19 43 4 8 5

60 -

Disease status3 DOD @ 37 mo AWD @ 74 mo AWD @ 54 mo DOD @ 74 mo DOD@ 14mo AWD @ 47 mo DOD@ 18mo DOD@5mo DOD@ 12mo DOD Q 165 mo DOD @ 43 mo DOD @ 63 mo DOD@9mo DOD@ 104mo


’Total resection, subtotal resection, or biopsy. * IT = Intrathoracic; DM = Distant metastases; Li = Liver. 3 DOD = Died of disease; AWD = Alive with disease; shown are the number of months after surgery. 4 Recurred initially outside of the radiotherapy field. 5 Eventually recurred in the thorax. 6 Eventually developed distant metastases in liver and bone. ’Eventually developed distant metastases in liver.

carditis secondary to radiotherapy. There were no other grade 3 or 4 complications from radiotherapy.


The classification and staging of thymomas has undergone considerable change in the last 15 years. With the exception of thymic carcinomas, the histologic appearance yields little information related to prognosis. The prognostic significance of the histologic type is somewhat variable because of the subjectivity of the classification into lymphocyte predominant, epithelial predominant, and mixed. In our analysis, the mixed histologic type was associated with the worst prognosis. Similar results have been reported by Bernatz et al. (6) and Maggi et al. (17). However, there are other reports that patients with epithelial predominant thymomas have the worst prognosis (20, 21). In most studies, patients with lymphocyte predominant tumors have the best prognosis (6, 17,20,2 1). The presence of myasthenia gravis at diagnosis is of less prognostic significance today ( 19,2 1,27). In this study, there were relatively few patients with myasthenia gravis, compared to other published series (19,2 1, 27, 30); however, the number is consistent with series from referral institutions where mediastinal exploration for myasthenia gravis is not routinely done (3, 25). In this report, the staging system described by Masaoka et al. (19) was used. Our data clearly indicate that early stage patients (Stages I and II) have a significantly longer DFS than late stage patients (Fig. 1). Although Stage II patients had a slightly shorter DFS than Stage I patients,

and Stage IVA patients had a slightly shorter DFS than Stage III patients, the pair-wise comparisons of these groups were not significantly different statistically. Larger numbers of patients would be needed to confirm the prognostic significance of these subdivisions. We found that patients whose tumors were totally resected had a lower risk of relapse than those whose only surgery was subtotal resection or biopsy (Fig. 2, Table 7). Moreover, when patients whose tumors were totally resected were subdivided into those with noninvasive and invasive disease, there was no difference in DFS. Several investigators have emphasized the prognostic significance of total resection (9, 17, 19, 21). Nakahara et al. (21) described a 5-year, actuarial survival rate of approximately 95% for patients treated by total resection, even with Stage III disease. Maggi et al. (17) found no significant difference in survival (- 80%) following total resection in patients who had either invasive or noninvasive thymoma. Thus, total tumor resection should be advocated in all patients, including those with Stages III and IVA disease, when possible. We also observed that patients who had a subtotal resection had a better 5-year DFS when compared to those who had biopsy alone, although the difference was not statistically different. Nakahara et al. (21) Maggi et al. (17), and Monden et al. (20) have reported a survival advantage in patients who had subtotal resection, while others (2, 27) have not observed any difference between subtotal resection and biopsy alone. Table 7 summarizes the megavoltage radiotherapy results described by other investigators. There is still controversy concerning the role of radiotherapy in patients

1. J. Radiation Oncology ??Biology 0 Physics


Table 7. Radiotherapy

Volume 23, Number 5. 1992 results of others No. relapsed’




Dose (GY)


Batata (3) Marks (18) Nordstrom (22) Ariaratnam (1) Chahinian (7) Aniagada (2) Cohen (8) Monden (20)

1973 1978 1979 1979 1981 1983 1984 1984

-404 35-48 21-50 30-54 36-60 25-65 32-63 >25

lnv.5 Inv. III Ii-iv. Inv. Inv. III Inv.

Verley (28) Kersh (13) Maggi (17) Krueger ( 14) Curran ( 10) Nakahara (2 1) Urgesi (27) Current report

1985 1985 1986 1988 1988 1988 1990

40-90 46-52 45-55 30-56 32-60 30-508 50-60 40-60



No. totally resected

21128 O/9 10/19 3/gh 416 17156 13/lgh 23/896

? 3 ? 0 3 6 8 7

21167 6/10h l/6 4112 O/5. 4120 ?/33, ?/48 9159, 9/ 18 8122’

2’1 0 0 1 5, 0 33, 35 33, 0 12

Overall* survival (%)

DFS3 (%)




57 86,69 92, 88 71,26 65

58, 53’


’Number of patients who relapsed locally over the total treated with XRT. ’ Overall 5 year survival. 3 5 year disease-free survival. 4 Some patients were treated with interstitial implant and some with “P, in addition to external beam. ’ Inv. = Invasive (implies stage II-IVA). ’ Includes all failures, local and distant. ’ Includes patients who did not receive XRT. * Postoperative radiotherapy in 73%, 30-40 Gy for total resection, 50 Gy for incomplete resection.

after total resection of Stage I disease. Fujimura et al. ( 12) reported no recurrences in 31 thymoma patients with Stage I disease after total surgical resection alone. There were also no recurrences reported by Cm-ran et al. ( 10) in 42 Stage I patients after total resection. In contrast, Nakahara et al. (2 1) described four thymoma patients with Stage I-II disease that relapsed after complete resection. Their policy is to administer postoperative radiation therapy in these patients to 30-40 Gy in 3-4 weeks. Thus, treatment of early stage, totally resected, patients by radiotherapy may be indicated in some circumstances, for example, extensive pericardial or pleural adhesion. We found two relapses in 11 patients with Stage I disease after total surgical excision. It should be noted that it is difficult in some cases to assess microscopic invasion into the perithymic fat and, therefore, to distinguish Stage I and Stage II, particularly in a retrospective review. An adequate microscopic examination of the capsule for sites of discontinuity, microscopic invasion into or through the capsule, and microscopic invasion into adherent pleura or pericardium is often impossible. Moreover, the capsule may be thin (in some cases < 1.Omm) and capsular integrity may be broached during handling and preparation. There is general agreement that postoperative radiotherapy should be used in the treatment of invasive thymoma (Table 7), regardless of whether the tumor was totally excised. When we compared patients with invasive thymomas that received radiation therapy to those who

were candidates for but did not receive radiotherapy, the 5-year DFS was 62% and 40%, respectively. Cm-ran, et al. ( 10) and Monden et al. (20) have reported similar trends. Our current policy is to administer postoperative radiation therapy to all patients with invasive thymomas, regardless of the extent of surgery. A dose response in the treatment of thymomas has not been clearly established, although pooled data (9) suggest better local control with doses at or above 60 Gy. We found 50-60 Gy to be inadequate for many of the unresectable Stage III or IVA tumors. Of the 11 late stage patients treated with radiotherapy, there were six with a complete response. All six of the complete responders were controlled within the radiotherapy field, compared to only one of the five partial responders. A higher radiation therapy dose and/or the addition of chemotherapy is indicated in patients who do not obtain a radiographic complete response. When there is residual disease following definitive treatment an attempt at excision is usually indicated. We have previously described a limited experience with cyclophosphamide, Adriamycin, and Cisplatin, with or without prednisone (CAP + PR) in five patients with unresectable thymoma before surgery (26). There were two complete and two partial responses. The responses were encouraging, however, the number of patients was too small to make any meaningful conclusion. Fomasiero et al. (11) recently described a 43% complete response rate in 37 late stage thymoma patients using a regimen containing CAP with vincristine. Recently, a Radiation

Thymoma: Treatment and prognosis 0 A. POLLACK etal.

Therapy Oncology Group protocol was approved for treatment of patients with locally advanced, unresectable, thymoma. The objective is to improve resectability with CAP f PR prior to radiotherapy. In summary, our current approach to treatment of thymoma is: ( 1) total resection whenever feasible, (2) postoperative radiation therapy to approximately 50 Gy for


completely resected noninvasive thymomas when the tumor is large and adherent to pleura or pericardium, (3) postoperative radiation therapy to 50 Gy for completely resected invasive thymomas, and (4) multimodality treatment for locally-advanced, unresectable tumors including preoperative chemotherapy and radiotherapy to approximately 60 Gy.

REFERENCES 1. Ariaratnam, L. S.; Kalnicki, S.; Mincer, F.; Botstein, C. The management of malignant thymoma with radiation therapy. lnt. J. Radiat. Oncol. Biol. Phys. 5: 77-80; 1979. 2. Aniagada, R.; Bretel, J. J.; Caillaud, J. M.; et al. Invasive carcinoma of the thymus. A multicenter retrospective review of 56 cases. Eur. J. Clin. Oncol. 20: 69-74; 1984. 3. Batata, M. A.; Martini, N.; Huvos, A. G.; Aguilar, R. I.; Beattie, E. J. Thymomas: clinicopathologic features, therapy, and prognosis. Cancer 34: 389-396; 1974. 4. Bergh, N. P.; Gatzinsky, P.; Larsson, S.; Lundin, P.; Rindell, B. Tumors of the thymus and thymic region. I. Clinicopathologic studies on thymoma. Ann. Thorac. Surg. 25: 9 l98; 1978. 5. Berkson, J.; Gage, R. Calculation of survival rates for cancer. Proc. Mayo Clin. 25: 270-286; 1950. 6. Bematz, P. E.; Khonsari, S.; Harrison, E. J.; Taylor W. F. Thymoma: Factors influencing prognosis. Surg. Clin. North Am. 53: 885-892; 1973. 7. Chahinian, A. P.; Bhardwaj, S.; Meyer, R. J.; Jaffrey, I. S.; Kirschner, P. A.; Holland, J. F. Treatment of invasive or metastatic thymoma. Cancer 47: 1752- 176 1; 198 1. 8. Cohen, D.; Ronnigen, L.; Graeber, G.; et al. Management of patients with malignant thymoma. J. Thorac. Cardiovasc. Surg. 87: 389-396; 1984. 9. Cox, J. D. The lung and thymus, In: Moss, W. T., Cox, J. D., eds. Radiation oncology rationale, technique, and results. St. Louis: C. V. Mosby Company; 1989: 305-308. 10. Curran, W. J.; Komstein, M. J.; Brooks, J. J.; Turrisi III, A. T. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J. Clin. Oncol. 6: 1722-1727; 1988. 11. Fomasiero, A.; Daniele, 0.; Ghiotto, C.; Piazza, M.; FioreDonati, L.; Calabro, F.; Rea, F.; Fiorentino, M. V. Chemotherapy for invasive thymoma: a 13 year experience. Cancer 68: 30-33, 199 1. 12. Fujimura, S.; Kondo- T.; Honda, M.; Shiraishi, Y.; Tamahashi, N.; Nakada, T. Results of surgical treatment of thymoma based on 66 patients. J. Thorac. Cardiovasc. Surg. 93: 708-7 14; 1987. 13. Kersh, C. R.; Eisert, D. R.; Hazra, T. A. Malignant thymoma: role of radiation therapy in management. Radiol. 156: 207-209; 1985. 14. Krueger, J. B.; Sager-man, R. H.; King, G. A. Stage Ill thymoma: results of postoperative radiation therapy. Radiology 168: 855-858; 1988. 15. Lee, E.; Desu, M. A computer program for comparing K samples with right-censored data. Comp. Prog. Biomed. 2: 315-321; 1972.

16. Levine, G. D.; Rosai, J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum. Pathol. 9: 495-515; 1978. 17. Maggi, G. M.; Giaccone, G.; Donadio, M.; et al. Thymomas: A review of 169 cases with particular reference to results of surgical treatment. Cancer 58: 765-776; 1986. 18. Marks, R. D.; Wallace, K. M.; Pettit, H. S. Radiation therapy control of nine patients with malignant thymoma. Cancer 41: 117-l 19; 1978. 19. Masaoka, A.; Monden, Y.; Nakahara, K.; Tanioka, T. Follow-up study of thymomas with special reference to their clinical stage. Cancer 48: 2485-2492; 198 1. 20. Monden, Y.; Nakahara, K.; lioka, S.; et al. Recurrence of thymoma: clinicopathologic features, therapy, and prognosis. Ann. Thorac. Surg. 39: 165-169; 1985. 21. Nakahara, K.; Ohno, K.; Hashimoto, J.; et al. Thymoma: Results with complete resection and adjuvant post-operative irradiation in 141 consecutive patients. J. Thorac. Cardiovasc. Surg. 95: 1041-1047; 1988. 22. Nordstrom, D. G.; Tewfik, H. H.; Latourette, H. B. Thymoma: therapy and prognosis as related to operative staging. lnt. J. Radiat. Oncol. Biol. Phys. 5: 2059-2062; 1979. 23. Rosai, J.; Levine, G. D. Tumors of the thymus. In: Atlas of tumor pathology, Series 2, Fascicle 13. Washington, DC: Armed Forces Institute of Pathology; 1976: 55-99. 24. Snover, D. C.; Levine, G. D.; Rosai, J. Thymic carcinoma: Five distinctive histological variants. Am. J. Surg. Pathol. 6: 451-470; 1982. 25. Soudajian, J. V.; Enriquez, P.; Silverstein, M.; Pepin, J-M. The spectrum of diseases associated with thymoma. Arch. Intern. Med. 34: 274-279; 1974. 26. Umswasdi, T.; Chiuten, D. F.; Holoye, P. Cytoxan, Adriamycin, Cisplatin with or without prednisone (CAP f PR) in treatment of malignant thymic tumors. Proc. Amer. Sot. Clin. Oncol. 4: 149; 1985. 27. Urgesi, A.; Monetti, U.; Rossi, G.; Ricardi, U.; Casadio, C. Role of radiation therapy in locally advanced thymoma. Radiother. Oncol. 19: 275-280, 1990. 28. Verley, J. M.; Hollman, K. H. Thymoma: A comparative study of clinical stages, histologic features and survival in 200 cases. Cancer 55: 1074-1086; 1985. 29. Wick, M. R.; Scheithauer, B. D.; Weiland, L. H.; Bematz, P. E. Primary thymic carcinomas. Am. J. Surg. Pathol. 6: 6 13-630; 1982. 30. Wilkins, E. W.; Castleman, B. Thymoma: a continuing survey at Massachusetts General Hospital. Ann. Thorac. Surg. 28: 252-256; 1979.

Thymoma: treatment and prognosis.

Thirty-six patients with pathologically confirmed thymoma were treated at M.D. Anderson Cancer Center from 1962 to 1987. The tumors were staged based ...
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