UTERINE SARCOMAS Analysis of Failures with Special Emphasis on the Use of Adjuvant Radiation Therapy

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1 UTERINE SARCOMAS Analysis of Failures with Special Emphasis on the Use of Adjuvant Radiation Therapy OMAR M. SALAZAR, MD,* THOMAS A. BONFIGLIO, MD,? STANLEY F. PATTEN, MD,$ BOWEN E. KELLER, MS, MICHAEL L. FELDSTEIN,~~ MARGARET E. DUNNE, MS,' AND JEROME H. RUDOLPH, MD' There were 47 failures among 73 verified cases of uterine sarcoma reported at the University of Rochester Tumor Registry from 1955 to 1975; they constitute the subject of this report. Of 33 patients initially treated with surgery only [S], 19 patients (58%) failed; 20 of 31 patients (65%) treated with surgery and radiation [S + R] failed; 8 of 9 patients (89%) treated by radiation alone [R] failed. According to pathology, failures occurred in 33 of 44 patients (75%) with mixed mesodermal sarcomas (MMS), 7 of 20 patients (35%) with leiomyosarcoma (LMS), 4 of 6 patients with endometrial stromal sarcomas (ESS), and 3 of 3 patients with other types of sarcoma. Once corrected by stage, there were no significant differences in failure rates, spread patterns or survival among these main histologic variants. Twenty of 41 patients (56%) with Stage I tumors failed with an average failure time of 32 months. Twentyseven of 32 patients (84%) with Stages 11, 111, and IV tumor failed; their average failure time was only 9 months. The mean failure time for both the patients treated with [S] and [S + R] was 22 months; for patients treated by [R] it was 3 months. Isolated pelvic failures constituted only 4% of all failures, failures both in the pelvis and in distant sites, 49%, and distant metastases, 47%. There was a marked decrease in pelvic failures in patients treated with [S + R] when compared to those who received [S]. Adjuvant radiation proved to increase tumor control in the pelvis but did not influence the final outcome because over 90% of all failures developed distant spread outside the pelvis. The most common distant failures were in the upper abdomen (mainly omentum and peritoneum) and in the lungs. Lung metastases alone was the only site of failure in 16% of the instances. A comprehensive treatment approach based on the spread and failure patterns will be proposed. Cancer 42: , TERINE SARCOMA IS A tumor that con- U stitutes only 1% to 3% of all uterine cancers,1*15,22,23 but represents one of the most intriguing and perhaps the most malignant of all uterine tumors. Oncologists have never Presented at the 19th Annual Meeting of the American Society of Therapeutic Radiologists, November 1-5, Denver, Colorado. From the University of Rochester Medical Center, Rochester, New York. Supported in part by NCI Grants 5 PO2 CA 11051, CA and 5 P30 CA * Assistant Professor, Division of Radiation Oncology, Cancer Center. t Associate Professor and Chief, Division of Surgical Pathology. $ Chairman and Professor, Department of Pathology. 8 Assistant Professor, Head of Physics Section, Division of Radiation Oncology, Cancer Center. II Assistant Professor, Division of Biostatistics, Cancer Center X/78/0900/1161 $ American Cancer Society 1161 been able to agree on its behavior, spread patterns and best management. Since these tumors are characterized by an overall poor prognosis, their spread and failure patterns may point toward a more effective method of treatment. There has not been much published on # Technical Associate and Research Assistant, Division of Radiation Oncology, Cancer Center. ll Clinical Associate Professor, Department of Obstetrics and Gynecology. Address for reprints: 0. M. Salazar, MD, Division of Radiation Oncology, PO Box 647, University of Rochester Cancer Center, 601 Elmwood Avenue, Rochester, NY The authors thank Elaine Tarana of the Division of Biostatistics, the Pathology Department of the Genesee Hospital, the Medical Records Department and the Tumor Registry of Strong Memorial Hospital, and E. Grecco, S. Lanzon and D. Commons for editing assistance. Accepted for publication May 5, 1978.

2 1162 CANCER September 1978 Vol. 42 these scarce tumors. Since there are several major histologic variants of uterine sarcomas, many authors have divided their experience and published separately on each histologic type. As a result, their observations and conclusions may have been based, with few exceptions, on a relatively small number of patients. Few reports entertain detailed accounts on the spread and failure patterns of these neoplasms, despite the fact that these constitute perhaps the best indicators for a comprehensive therapeutic approach. Forty-seven failures among 73 verified cases of uterine sarcoma constitute the subject of this report.19 A thorough follow-up in all cases and a high autopsy rate of almost 50% has allowed detailed identification of the spread and failure pathways of these tumors. This report also employs an extensive review of the literature (which documents over 200 failures) to corroborate its observations and conclusions. This dissertation will also attempt to clarify the therapeutic value of adjuvant radiation, and other forms of systemic therapy. MATERIALS AND METHODS From July 1, 1955 to June 30, 1975, there were 73 verified cases of uterine sarcoma treated in the University of Rochester's Strong Memorial Hospital (SMH).l9 Only four major histologic variants were considered: mixed mesodermal sarcoma (MMS), leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS) and a miscellaneous group consisting of other types of sarcomas. The number of patients with MMS, LMS, ESS and other sarcomas were 44, 20, 6 and 3, respectively, representing SO%, 28%, 8% and 4% of the total number of cases.19 Examples of several histologic variants and detailed histologic descriptions of each type were previously publi~hed.~ All cases were staged utilizing the FIG0 classification for endometrial carcinoma.'* Stage I was not subdivided into Stages I-A and I-B since this did not yield any statistically significant differences between substages by histolo:,ic variant or overall. A surgical staging was employed whenever possible; patients who were treated by radiation therapy alone [R] were clinically staged. Tumors were confined to the uterine corpus (Stage I) in 41 patients (56%). The number of patients with Stages 11, I11 and IV were 12, 12 and 8, respectively, representing 17%, 17% and 11% of the total number of patients.lg Stages TI, I11 and IV were grouped together since no significant difference in survival and/or failures was noticed among them. Thirty-three patients (45%) were treated with surgery only [S]. The most common surgical procedure was total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH, BSSCO), performed in 80% of all patients subjected to surgery. Thirty-one patients (43%) were treated with the combination of surgery and radiation [S + R]. In 10 of these patients, the radiation treatments were given preoperatively and in 21 patients, postoperatively. Comparison of preoperative and postoperative irradiation results was not made due to the small number of patients in each category, particularly when broken down by stage and pathology. Finally, there were nine patients (12%) who were found to be inoperable candidates and were submitted to radiation alone [R]. Radiation therapy treatments were directed at the entire pelvis. Cobalt-60 irradiation was employed utilizing two 120" lateral arcs (skipscan) which delivered 5000 rad to the central axis and 4500 rad to the pelvic sidewalls in five weeks. (The technique of external radiation delivery has been detailed in previous rep~rts.~~'~~'~ Twelve patients received, in addition to pelvic teletherapy, a vaginal obturator which delivered 4000 rad to the vaginal surface.19 The follow-up was complete for all 73 cases with uterine sarcomas. There were 45 patients who failed therapy and died; they constitute the subject of this dissertation. Of 45 deaths, 20 autopsies (44%) were obtained. All the remaining 25 patients died with disease. Statistical significance was established utilizing the Wilcoxon-Gehan test.6 RESULTS In the 20-year span of this study, 47 of 73 verified uterine sarcoma patients failed the therapy that was offered. The distribution of failures by stage and treatment appears in Table 1. Fifty-six percent of patients with Stage I tumors failed as compared to 84% with more advanced stages. This was significant (p < 0.05). There were no statistical differences in failure rates by stage among patients with [S] and [S + R]. However, there were 9 patients who were treated with [R] among whom 8 failures (89%) occurred. The distribution of failures by pathology

3 No. 3 UTERINE SARCOMAS * Salazar et al TABLE 1. Uterine Sarcoma: Failures by Stage and Treatment No. failureslno. patients per category (percent) Stage [SI [S + Rl [RI Overall I 10/24 (42) 7/14 (50) 3/3 (100) 20/41 (56) I1 -+ IV 919 (100) 13/17 (76) 516 (88) 27/32 (84) TOTAL 19/33 (58) (65) 819 (89) 47/73 (64) and treatment appears in Table 2. The overall failure rates for LMS, MMS and ESS were 35%, 75% and 67%, respectively. The lower failure rate of LMS is statistically significant. However, it is unclear whether or not this difference is valid since 16 of the 20 LMS in this series were Stage I tumors and were all treated by [S]. Four of these 16 Stage I LMS patients (20%) failed the surgical treatment. There were no patients with Stage I LMS treated by [S + R]. All six patients with Stage I MMS treated with [S] failed, whereas only 6 of 12 patients (50%) with Stage I MMS treated with [S + R] failed. When the average failure time for each histologic variant was determined, it was 53.0 months for LMS whereas it was 4.2 months and 5.4 months for ESS and MMS, respectively. The average failure time by stage and treatment appears in Table 3: the overall average failure time was only 18.8 months. The failure time was 3.4 months for patients treated with [R]; there were no significant differences in patients treated with [S] and [S + R]. However, for Stage I patients, the average failure time for those who had been treated with [S + R] was 41 months and for those treated with [S] only 32 months. Nevertheless, these differences are only significant at a 10% confidence level. What is striking is that patients with Stage I uterine sarcoma had an average failure time of 32 months and those with more advanced stages of only 9 months; this was significant (p < 0.05). The distribution of failure sites by treatment appear in Table 4. Isolated pelvic failures were rare; they only occurred in 2 patients with LMS treated with [S], and represented 11% of all failures with [S]. Almost 50% of all failures occurred both in the pelvis and distant sites. The remaining failures (47%) occurred in sites distant from the pelvis. There was a total of 25 pelvic failures, which represented 53% of all failures in the series. Of the total number of pelvic failures, 12 had been treated with [S], 7 with [S + R] and 6 with [R]. This represented 64%, 35% and 75% of all failures per treatment category and indicated a twofold increase in pelvic disease control by [S + R]. There were 45 patients who failed outside the pelvis. They represented 96% of all failures in the series. Of the 45 failures in distant sites, 17 had been treated with IS], 20 with [S + R] and 8 with [R], representing 90%, 100% and 100% of all failures per treatment category, and indicating the inefficiency of all these therapeutic modalities in controlling metastatic spread. The pelvic failures were analyzed independently in a purposely detailed tabulation (Table 5). Isolated vaginal failures occurred in 5 patients, failures in both the vagina and pelvis in 5 patients, and failures in the pelvis (excluding vagina) in 15 patients. This repre- TABLE 2. Uterine Sarcoma: Failures by Pathology and Treatment No. failures/no. pts per category (percent) Pathol.$ [SI [S + Rl [RI Overall MMS 12/12 (loo)* 16/26 (59)* 516 (83) 33/44 (75) LMS 5/18 (28)t 2/2t 010 7/20 (35) ESS /2 416 (67) Other 111 1/1 1/1 313 (100) * All 6 patients with Stage I MMS treated with [S] failed; only 6/12 patients with Stage I MMS treated with [S + R] failed. t 4/16 pts (20%) with Stage I LMS treated with [S] failed; there were no patients with Stage I LMS treated with [S + R]..$ The overall failure times for ESS, MMS and LMS were 4.2, 5.4 and 53.0 months, respectively.

4 1164 CANCER September 1978 Vol. 42 TABLE 3. Uterine Sarcoma: Failure Time by Stage and Treatment Average failure time (in months) Stage [SI [S + R] [R] Overall I II+IV TOTAL sented 20%, 20% and 60% of all pelvic failures. It is important to note that among 10 failures in Stage I tumors treated with [S], seven (70%) failed in the pelvis. On the other hand, only one (a rhabdomyosarcoma) of seven failures (14%) with Stage I tumors treated with [S + R] occurred in the pelvis. This was statistically significant (p < 0.05) and clearly demonstrated the degree of pelvic disease control achieved by adjuvant radiation therapy in Stage I disease. Furthermore, four of five isolated vaginal failures were seen in patients treated with [S]. The remaining patient who developed an isolated vaginal failure after [S + R] had Stage IV LMS with massive disease in the pelvis and lung metastases at presentation; consequently did not receive supplementary intravaginal radium. Finally, 12 of 19 failures (63%) who were initially treated with [S] failed in the pelvis whereas only 7 of 20 failures (35%) treated with [S + R] failed in that site. In the latter 7 patients, advanced disease at diagnosis had been found in 6 patients. A detailed analysis of the 45 patients who failed in distant sites appears in Table 6. The most common site of metastases was the upper abdomen (69%), followed closely by the lungs (60%). Simultaneous metastases to the upper TABLE 4. Uterine Sarcoma: Failure Site by Treatment No. failures (% total failures per Rx category) Pelvis Rx and Dis- Category No. fail. Pelvis* distant tantt [SI 19 2 (11) 10 (53) 7 (37) [S + Rl 20 0 (0) 7 (35) 13 (65) [Rl 8 0 (0) 6 (75) 2 (25) TOTAL 47 2 (4) 23 (49) 22 (47) * Overall pelvic failures: [S] = 12/19-64%; [S + Rl = 7/20-35%; [R] = 6/8-75%; All patients = 25/47 = 53%. t Overall distant metastases: [S] = 17/19-90%; [S + R] = 20/20-100%; [R] = 8/8-100%; All patients = 45/47-96%. abdomen and the lungs occurred in 16 instances (36%). Bone metastases were seen in 11 patients (24%) who failed and brain metastases in only 2 (4%). Metastases to the lungs was the sole failure pathway in 7 patients; this represents 10% of the entire series and 16% of all failures. Lung metastases as the only manifestation of distant failure were observed in 11 patients (7 MMS, 3 LMS and 1 rhabdomyosarcoma); this constituted 25% of all failures. Another 25% of all failures in distant sites occurred in the upper abdomen only and another 25% of all failures were seen in both the upper abdomen and lung. A more precise definition of the 3 1 failures in the upper abdomen appears in Table 7. The most common spread patterns were to the omentum, peritoneum and bowel, seen in over 50% of the upper abdominal failures. Curiously, involvement of the liver, spleen or para-aortic nodes occurred in only 25% of the TABLE 5. Uterine Sarcoma: Analysis of 25 Pelvic Failures No. fail. by Rx category Pelvic failure No. fail. per Percent of total no. site Stage [Sl [S + Rl [Rl pelvic site pelvic fail. Vag. only Vag + Pelvis Pelvis (excl. vag.) Overall I II+ IV I II+IV I II-+IV II+IV (20) 5 (20) 15 (60) 25 ( 100)

5 No. 3 UTERINE SARCOMAS. Salazar et al instances and usually with widespread abdominal disease. Nodal involvement occured in less than 20% of all failures. The incidence of nodal metastases in decreasing order of frequency was: para-aortic (8), pelvic (4), mesenteric (3), mediastinal (3), hilar (2), supraclavicular (2) and axillary (1). Of the 4 patients with pelvic nodal involvement, one was treated with [S] and three with [R]. DISCUSSION Uterine sarcoma is a unique tumor because it is both rare and characterized by an extremely aggressive behavior which leads to an early pattern of widespread dissemination and death. Through the years, several questions regarding these tumors have remained unanswered: What exactly are their patterns of spread? Do all the histologic variants spread in the same fashion and/or carry similar prognosis? Does radiation therapy play any role in their management? What constitutes a realistic therapeutic approach for these neoplasms? It is the purpose of this report to address most of these critical issues by analyzing 45 failures among 73 verified cases of uterine sarcoma. Once the spread and failure patterns have become firmly established in these tumors, it will perhaps become easier to diagnose and treat them properly. Incidence of Failures As mentioned in an earlier report,19 the main prognosticator for uterine sarcomas, irrespective of histology, is the tumor extent at diagnosis, a view which is shared by many investigator^.^^^^^^^^^^^^^ Fifty-six percent of the patients with Stage I tumors failed as compared to 84% of the patients with Stages II- IV (Table l).639,19 It must be emphasized that Stages 11, I11 and IV were not considered individually since no significant differences in failure rates and survival among these three stages was found.19 DiSaia et al., reporting two-year survival figures for 101 patients with MMS, found that it was 53% for Stage I, 9% for Stage I1 and 0% for Stages I11 and IV.6 They also found a threefold increase in pelvic control among the patients with Stage I than in those with more advanced stages.6 In the present series there was no difference in the number of failures treated with [S] and TABLE 6. Uterine Sarcoma: Analysis of 45 Distant Failures No. failures ( % total no. failures) Over- Sole dist. Sole Distant fail. site all failure failure Upper abdomen 31 (69) 11 (25) 4 (9)* Lung 27 (60) 11 (25) 7 (16)t Upper abdm. + lung 16 (36) 11 (25) 5 (11)t: Bone 11 (24) 2 (4) 2 (4) Brain 2 (4) 0 (0) 0 (0) * All 4 patients with high-staged MMS. + 5 MMS and 2 LMS. + 3 MMS and 2 LMS. 0 2 MMS. [S + R] (Table 1). That 89% of the patients treated with [R] failed indicated that radiation therapy alone was not sufficient management for these tumor^,'^ and also that if the main prognosticator for uterine sarcomas is the tumor extent at presentation, the best way to assess true tumor extent is with an initial open surgical procedure. Whenever a retrospective analysis such as this is undertaken, certain points must be emphasized. Definitive surgery without postoperative irradiation and/or chemotherapy is reserved for a selected group of patients. The patients treated by [S] are usually younger, free of serious associated diseases, advanced local disease or distant spread which would have them rendered inoperable. On the other extreme are those patients who were considered to be inoperable for a variety of reasons and were submitted to [R]; they constitute the group of patients with the poorest prognosis for whom there is no accurate information on the true extent of their tumors at diagnosis. An intermediate group of patients were treated with [S + R] mainly because disease was more extensive than sus- TABLE 7. Uterine Sarcoma: Distant Failures in Upper Abdomen Upper abdominal fail. site No. fail. (% of U/A failures) Omentum and peritoneum 16 (52) Bowel 15 (48) Liver 8 (26) Para-aortic nodes 8 (26) Spleen 5 (16) IJ/A: Upper abdomen.

6 1166 CANCER September 1978 Vol. 42 pected clinically or a definitive surgical procedure was not performed. In the original series of 73 verified cases of uterine sarcomas, over 70% of the patients who were treated by [S] had Stage I tumors, and in nearly 50% of the instances were free of serious associated diseases. On the other hand, the majority of the patients treated with [S + R] or [R] had history of severe associated diseases or more advanced tumor^.'^ All these points must be remembered whenever treatment modalities are compared retrospectively. In our previous report,19 we mentioned that once corrected by stage, there seemed to be no apparent differences in prognosis among the three major histologic variants of uterine sarcoma, a finding which has also been reported by Badib et al. Neither was there a statistical difference in failure rates among the different histologies (Table 2). LMS seemed to have a lower percentage of failures (35%) than MMS (75%) and ESS (67%), and the same was true for survival, as reported earlier. ~ 3, 9 The differences disappeared when each histologic variant was analyzed stage by stage.ig The fact remains, however, that LMS seemed to be a slower growing tumor than MMS and ESS; consequently, it was more often confined to the corpus (Stage I) at presentati~n. ~ When the average failure time for each histologic variant was determined, it was 53.0 months for LMS and only 4.2 months and 5.4 months for ESS and MMS, respectively. These differences may also be somewhat deceiving since 16 of 18 LMS in the original population were Stage I tumors, whereas a lower incidence of Stage I disease was seen for both MMS and ESS.lS TABLE 8. Uterine Sarcoma: Review on Failure Distribution* No. fail. by site (% failures by path.) Pelvis No. fail. arid Path. by path. Pelvis distant Distant LMS (14) 49 (60) 21 (26) MMS (13) 52 (54) 38 (39) ESS 37 5 (14) 19(51) 13 (35) ALL 235t 34 (14) 125 (53) 76 (32) * Based on a review of the literature which includes the present series (see text). t Not necessarily the addition of cases by histologic type since some series lack this distinction. Uterine sarcomas are characterized by a rapid disease progression. Almost 90% of the patients who failed therapy died during the first two years after treatment.3*6*15*19 The overall average failure time was only 19 months; 32 months for patients with Stage I tumors and only 9 months for patients with more advanced stages (Table 3). Distribution of Failures Distant metastases overwhelmingly constituted the main failure pathway in these tumors; they occurred in 45 of 47 failures (96%) (Table 4). Distant metastases in this report represent disease that appeared outside the pelvis, whether in the upper abdomen or in a distant viscerae. Almost 50% of all failures occurred both in the pelvis and in distant sites; isolated distant failures without pelvic recurrences occurred in 47% of all failures (Table 4). This led us to the assumption that isolated pelvic failures are a rarity in this disease; they constituted only 4% of all failures in this series, an observation which has also been made by Gilbert et al9 Nevertheless, the overall incidence of pelvic failures was 53% and thus deserves important consideration (Table 4). To corroborate the findings in the present report, a thorough search of the literature was performed looking for series which divided their failures into pelvic or distant metas- tases or both.2*7* 4-6,21-23 Almost 200 cases were found to whom 47 failures in this series were added; the results appear in Table 8. It was clearly seen that there were no significant differences in failure sites among the major histologic types; for years this has been a major point of controversy. In Table 8, one could also appreciate that, although isolated pelvic failures are seen in less than 15% of the instances and that almost 90% of the patients who fail do so in sites outside the pelvis, over 60% of all failures actually occurred in the pelvis. This constitutes the solid grounds for the possible benefit derived in adding adjuvant pelvic radiation. Pelvic failures: The general idea that the combination of [S + R] decreases the number of pelvic failures than when either modality is employed independently can be appreciated in Table 4. Disregarding the high incidence of failures seen among patients treated with [R], of a total of 25 pelvic failures in this series, 12 had been treated with [S] and

7 No. 3 UTERINE SARCOMAS. Snlazar et al FIG. 1A. Vaginal metastases in a Stage I (MMS) appearing 4 months after TAH, BS&O. Appearance of the lesion prior to radiation therapy treatment. 7 with [S + R]. The latter represented 64% of all failures with [S] and only 35% of all failures with [S + R], a twofold increase in pelvic control. DiSaia et al. also found a higher degree of pelvic control by a combined ap- proach.6 Other investigators have reached similar conclusions as ~ell. ~3 ~ There are, however, individuals who maintain that radiation has not been shown to sterilize any of these sarcomas due to their so-called radioresistance, and therefore, do not favor its As mentioned in a previous report,lg sterilization of uterine sarcomas with preoperative intracavitary radium has been reported in the literature7 and 3 of 10 patients who received preoperative external irradiation in the present series showed no evidence of tumor at the time of hysterectomy. The story pertaining to the value of adjuvant radiation in augmenting pelvic tumor control, particularly vaginal metastases, unfolds in Table 5. The value of external and/or internal radiation therapy in significantly decreasing isolated vaginal failures in endometrial carcinoma is a well-established point.17, * For those who believe that uterine sarcomas are radioresistant and that salvage by radiation therapy has never been proven, Fig. l is quite illustrative. This represents a patient with Stage I MMS who developed vaginal metastasis 4 months after treatment by [S]. A complex therapy by external, intracavitary and radiation was employed with total tumor resolution in the vagina. The patient died 8 months later of lung metastases. 1B. Vaginal metastases in a Stage I (MMS) appearing 4 nionths after TAH, BS&O. The patient received 5000 rad to the pelvic axis with C0.60 teletherapy. This was the appearance of the lesion after this treat- nient.

8 1168 CANCER September 1978 Vol. 42 FIG. 1C. Vaginal metastases in a Stage I (MMS) appearing 4 months after TAH, BS&O. A combined intravaginal obturator and external curitherapy delivered an additional 4000 rad to the lesion. At autopsy, she had disease in the lungs and the upper abdomen (liver and para-aortic nodes), but the pelvis, specifically the vagina, was free of tumor. Distant Failures: Overall, this is the main failure pathway, making adjuvant local pelvic ra- diation ineffective in overall s~rvival.'~ Table 6 demonstrates that most common sites for distant failures are the upper abdomen, the lungs and both. Metastases to the lungs by uterine sarcoma constitute an interesting topic; they occur more commonly than thought. The reported incidence of lung metastases with these tumors ranges between 15% and 26%.6j22 Of the original population of 73 uter- ine sarcoma patients, lung metastases occurred in 27 (37%); in 7 of these patients (10%) this represented the only failure site (Table 6). Lung metastases constituted 60% of all failures. Of the original population of patients, the upper abdomen constituted the only site of failure in 4 patients (10%). However, upper abdominal spread was the sole manifestation of distant failure in one fourth of all patients who failed and was seen in almost 70% of all failures. It is for this reason that they deserved special consideration in Table 7. It must be mentioned that peritoneal and omentum implants with bowel involvement, re- FIG. 1D. Vaginal metastases in a Stage I (MMS) appearing 4 months after TAH, BS&O. Appearance of the lesion a month after all radiation therapy had ended. There was total tumor resolution.

9 No. 3 UTERINE SARCOMAS. Salazar et a UTERINE SARCOMA V 47 PTS. FAILED R, V /I DISTR. OF 47 FAILURES X DSTR. OF 25 PELVIC FAILURES DISTANT [ 96 X ) Z DISTR. OF 45 DISTANT FAILURES FIG. 2. Detailed representation of 47 failures occurring among 73 cases of verified uterine sarcoma. All figures are given as percentages for each particular set of diagrams. sembling the spread of ovarian carcinoma, was the rule rather than the exception; they occurred in almost 50% of the instances. Nodal Failures: Nodal involvement occurred in less than 25% of all failures. The most commonly involved were the para-aortic (8 patients) followed by pelvic, mesenteric, mediastinal, hilar and supraclavicular. This indicates a continuity in lymphatic spread. CONCLUSIONS In the literature, MMS is reported to have a tendency to spread as endometrial carcinomas to adjacent pelvic organs and nodes and to the para-aortic lymphatics; they are also thought to have a decreased propensity for blood borne meta~tases.~,'~~'~ LMS on the other hand, has been reported to have a higher propensity for distant metastases than MMS and ESS.22 The present series fails to detect any significant differences in the spread patterns of LMS and MMS. Both of these tumor variants have been observed to spread similarly. Just as it was mentioned earlier that, once analyzed by stage, all variants exhibited similar failures and survival, it must be added that the same is true of their spread patterns. As a rksume, Fig. 2 offers a diagramatic representation of the spread and failure patterns in uterine sarcoma. There should be no doubt that adjuvant radiation has proven to increase controllability of disease in the pelvis. Nevertheless, it probably exerts little influence on the final outcome since metastases outside the pelvis are seen in almost 90% of all patients who fail. In trying to detect early failures in distant sites the oncologist must concentrate all efforts in the upper abdomen and the lungs. In attempting to get ahead of the disease, these sites should be prophylactically treated by a systemic agent. The latter could be a combination of cytotoxic agents (particularly with adriamycin) as it is being investigated at the present time.l0 It could also consist of low-dose prophylactic irradiation to the upper abdomen and the lungs or high single doses in a modified half-body type of technique. What becomes certain is that although the combination of surgery and radiation has its very important role in the management of this disease, it is not sufficient therapy to encompass the spread and failure patterns even for the very early tumors confined to the corpus. 1. Aaro, L. A,, Symmonds, R. E., and Dockerty, M. D.: Sarcoma of the Uterus. A Clinical and pathologic study of 177 cases. Am. J. Obstet. Gynecol. 94:lOl-109, Badib, A Vongtamas '., Kurohara, s. and Webster, J. H.: Radiotherapy in the treatment of Sarcomas of the corpus uteri. Cancer 24: , Bartsich, E. G., Bowe, E. T., and Moore, J. (3.: Leiomyosarcoma Of the uterus. A 50-Year review Of 42 cases. Obstet. Gynecol. 32:lOl-106, Bartsich, E. G., O'Leary, J. A,, and Moore, J. G.: carcinosarcoma of the uterus, A 50-year review of 32 ( ). Obstet, Gynecol, 30: , 1967, 5. Belgrad, R., Elbadawi, N., and Rubin, P.: Uterine sarcoma. Radiology 114: , REFERENCES 6. DiSaia, P. J., Castro, J. R., and Rutledge, F. N.: Mixed mesodermal sarcoma of the uterus. Am. J. Roentgenol. 117: , Edwards, C. L.: Undifferentiated tumors.zn Cancer of the Uterus and Ovary. A Collection of papers presented at the 11th Annual Clinical conference on Cancer at the M.D. Anderson Hospital and Tumor Institute, Houston, Texas. Chicago, Year Book Medical Publishers, Inc., 1969; pp Gehan, E. A.: A generalized Wilcoxon test for comparing arbitrarily singly-censored samples. Biometrika 52: , 9. Gilbert, H. A,, Kagan, A. R., Lagasse, L., Jacobs,

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