T an almost uniform level in every International

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1 Stage Ib, /la, and llb Cervix Cancer, Postsurgical Staging, and Prognosis TOSHITAKA MATSUYAMA, MD, ISAO INOUE, MD, NAOKI TSUKAMOTO, MD, MASAMlCHl KASHIMURA, MD, TOSHIHARU KAMURA, MD, TOSHlAKl SAITO, MD, AND HlDEYUKl UCHINO, MD Two hundred fifty-five cases of International Federation of Gynecology and Obstetrics (FIGO) Stage Ib, IIa, and IIb cases of cervical cancer were analyzed following radical surgery with regard to the extent of invasion into vagina, parametria, and pelvic lymph nodes. Restaging was carried out based on the findings. Discrepancies were found between FIGO stages and the actual extent of the disease, particularly in Stage IIb. Among 99 cases of Stage IIb, only 42.4% were correctly staged. The 5-year disease-free survival by FIGO and postsurgical stagings were, respectively: Ib, 88.4% and 87.0%; IIa, 85.2% and 95.0%; IIb, 70.7% and 62.3%. Prognostic significance in the pathologic examination of operated materials was demonstrated when there were deep stromal invasions of cancer cell or parametrial invasions or pelvic lymph node metastases. When cancer was present in both of the parametrium and pelvic lymph nodes, the prognosis of the patient worsened (5-year survival rate, 41.4%). Cancer 54: HE SURVIVAL RATES of cervical cancer have reached T an almost uniform level in every International Federation of Gynecology and Obstetrics (FIGO) stage, thereby indicating the importance of the FIGO staging system for prediction of the prognosis of a particular patient. On the other hand, there are discrepancies between the FIGO stages and the actual extent of the cancer, because the FIGO stages are determined by pretreatment clinical evaluations. In surgical cases, the exact relationship between the actual cancer spread and the prognosis of the patient can be determined by examining the excised materials. We report our data on 255 cases of surgically treated cervical cancer with regard to the postsurgical histologic evaluations of cancer spread and prognosis. Materials and Methods From January, 1973, to December, 1977,255 Japanese women with uterine cervical cancer were surgically From the Department of Obstetrics and Gynecology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. Address for reprints: Toshitaka Matsuyama, MD, Department of Obstetrics and Gynecology, Faculty of Medicine, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812, Japan. The authors thank M. Ohara for critical readings of the manuscript. Accepted for publication October 3 I, * Stage IIb patients are treated by radiation in most hospitals around the world, however, we usually treat stage IIb cases with radical hysterectomy. This is the trend in most Japanese institutes. In 1983, The Japan Society of Obstetrics and Gynecology reported that 62.7% of stage IIb cases of cervical cancer were treated by radical hysterectomy.' treated in the Department of Obstetrics and Gynecology, Kyushu University Hospital. All of the patients were staged preoperatively, according to the FIGO staging system. Stage distributions of the cases were Stage Ib, 129 (50.6%); IIa, 27 (10.6%); and IIb,* 99 (38.8%). The patients ranged in age from 27 to 69, with a mean age of Histologic distributions were squamous cell carcinoma, 236; adenocarcinoma, 8; and adenosquamous carcinoma, 11. In 12 patients, there were lesions of the cervical stump. Radical hysterectomy with pelvic lymph node dissection (Okabayashi technique) was performed in all cases. Although para-aortic lymph node biopsy has been performed routinely in our clinic since 1977, these data are not included as the number of cases was small. Seven patients underwent cervical conization, under a diagnosis of Stage Ia or cervical intraepithelial neoplasia (CIN) 111, and were followed by subsequent radical hysterectomy under the revised diagnosis of Stage Ib-occ. Detailed postoperative macroscopic and microscopic examinations were carried out to clarify the extent of the carcinoma in the removed uterus and lymph nodes. Microscopic examination consisted of the depth of stromal invasion, vascular and/or lymphatic permeation of the cancer cells in the primary lesions, parametrial and/or vaginal involvement, and the number of pelvic lymph node metastases. Surgical margins of the parametrium and vagina were also evaluated. Concerning cases of vaginal involvement, cancer-free length from 3072

2 No. 12 POSTSURGICAL STAGING AND PROGNOSIS - Matsuyama et al the distal end of the vaginal invasion to the extirpated surgical margin was measured. As the exact lesion size was not recorded in all cases, we did not analyze this factor. Indications for postoperative radiation were determined according to the above-mentioned microscopic findings. When the lesions were confined to the cervix, postoperative radiation was not given. The protocol we use for postoperative radiation is listed in Table 1. In the early part of the study, the radiation dose was 6000 rad to the whole pelvis using a telecobalt or linear accelerator. This dose was later reduced to 5000 rad because of the high incidence of radiation-related complications. Intracavitary radiation to the vaginal stump was delivered using radium or cesium 137 tubes with the dose of 2000 milligram-hour. All of the patients were followed for 5 to 9 years. This report concerns the 5-year results. Results Survival Rate According to FIGO Staging Of the 129 patients with stage Ib, 1 13 were living and free of recurrence at the end of 5 years. One patient died of cancer in other organs. In another woman, there was a recurrence in the supraclavicular lymph node 3 years after the initial treatment. She is alive after receiving radiation to the site of recurrence. Five-year disease-free survival rate of Stage Ib patients was 88.4%. Among 27 women with Stage IIa, 3 died of cancer and 1 died of radiation complication. In one patient there was a recurrence at the vaginal stump, but she is now living after effective intracavitary small-source therapy. The 5-year disease-free survival rate was 85.2%. Among 99 patients with Stage IIb, 29 died or had a recurrence of disease. Three died of radiation complications, and one died of intercurrent disease. The 5-year survival rate was 70.7%. FIGO is a clinical staging procedure determined by pretreatment clinical evaluations. There is some discrepancy between the FIGO stages and the exact spread of the cancer. Postsurgical staging based on pathologic examination will show the actual spread of the disease. We restaged all the cases according to the postoperative pathologic findings, and the 5-year results according to this staging will hereafter be discussed. Survival Rate According to Postsurgical Staging Localized primary lesion group: In 94 patients it was confirmed that the primary lesions were confined to the cervix and there was no lymph node metastases or deep stromal invasions. In these cases, we concluded that there was a complete removal of the lesions by surgery, TABLE 1. Protocol for Postoperative Radiation Findings ( 1) Lymphatic or vascular permeation of cancer cell Deep stromal invasion Parametrial invasion Lymph node metastasis (2) Positive vaginal margin Short cancer-free space in extirpated vagina (3) Presence of both (I) and (2) Treatment Whole pelvis external radiation rad with telecobalt or linear accelerator Intracavitary small sources 2000 milligram-hour using Ra or Cs tubes Whole pelvis rad and intracavitary small sources 1000 milligram-hour and no further treatments were given. Of these 94, 2 died of cancer of the stomach or colon. Three died of metastases and one had a recurrence at the vaginal stump, but is living. The 5-year survival rate was 94.7%. In another 17 patients there were localized cervical lesions. The postoperative microscopic examination revealed lymphatic or vascular permeations of the tumor cells in the primary lesions. This group of patients was given postoperative whole pelvis irradiation. Three of these 17 died, 2 with pelvic recurrences. The 5-year survival rate was 82.4%. Nineteen others had localized cervical lesions and lymph node metastases. Six of these 19 died (pelvic recurrences, 3; distant metastases, 1 ; bowel obstruction, 1; and unknown cause, 1). In one there was a recurrence in the supraclavicular lymph nodes, but she is living. The 5-year survival rate was 68.4%. This group also received postoperative radiation. The final group of localized primary lesions consisted of 16 cases in whom the stromal invasions reached the cervical serosa. Two of these 16 had lymph node metastases. Except for one who refused, postoperative radiation was prescribed for this group. Eleven patients in this group survived 5 years, the survival rate being 68.8%. The woman who refused postoperative radiation died of lung metastasis 1 year after surgery. Another three died of distant metastases, and in one other patient the cause of death was unknown. One hundred forty-six cases of the above-mentioned four groups were staged as the postsurgical Ib group. One hundred twenty-seven are living with no evidence of disease and the 5-year survival rate was 87.0%. Vaginal wall involvement group: There were two groups in this category, that is, groups with or without lymph node metastasis. Thirty-six patients were confirmed to have only vaginal wall involvements and no lymph node metastases. Positive vaginal margins were noted in 13, and in 14, there were negative margins. Here the cancer-free vaginal margins were shorter than 2 cm. These 27 received intracavitary small-source irradiation postoperatively.

3 3074 CANCER December VOl. 54 TABLE 2. Clinical Stage versus Postsurgical Stage Postsurgical stage Clinical stage Ib IIa IIb Total Ib IIa IIb Total Another nine patients in whom the vaginal margins were sufficiently removed were not given postoperative radiation. Thirty-five of 36 in this group survived 5 years with no evidence of disease. One woman died of vesicovaginal fistula combined with bowel obstruction. There were four cases of vaginal involvement with positive pelvic lymph node metastasis. Three survived for 5 years and one died of lumbar spine metastasis. Forty were thus staged as the postsurgical IIa group and here the 5-year survival rate was 95.0%. Parametrium injiltration group: In 22 patients there were parametrial infiltrations without lymph node metastases. Eleven of these patients had parametrial infiltrations at the outer one half of the parametrium. Postoperative whole pelvis irradiation was administered to all of these 22 women. Seventeen survived for 5 years, the survival rate being 77.3%. Another I8 patients had both parametrial infiltration and vaginal involvement. Fourteen survived 5 years, the survival rate being 77.8%. Although this group was given whole pelvis radiation and additional intracavitary irradiation postoperatively, the 5-year result was almost the same as in the former group. This result indicates that it is the parametrial infiltration, not the vaginal involvement, that relates to the curability in this group. Twenty-nine patients in the parametrial infiltration group had positive lymph node metastases, and only 12 survived, even after postoperative radiation. The 5-year survival rate of 41.4% in this group was the poorest of all. The 5-year survival rate of the postsurgical Stage IIb patients, including the above-mentioned three groups, was 62.3%. Recurrence or metastasized sites in the 26 who died are listed in Table 4. To clarify the relationship between the survival rate and the site of parametrial infiltration, all cases in the postsurgical IIb group were divided into two groups according to the site of the parametrial infiltrations: the inner half side (uterine side) and the outer half side (pelvic wall side). The inner half group included 43 patients, and there were 26 in the outer half group. The mortality was 16 and 9, respectively. The 5-year results of the two groups were 62.8% and 65.4%, respectively. These figures are similar to those of the group with deep stromal invasion (68.8%). Therefore, stromal invasion extending to the cervical serosa should be considered as serious as parametrial infiltration. The site of parametrial infiltration does not seem to influence the curability. Clinical Staging versus Postsurgical Staging Table 2 correlates the clinical (FIGO) stagings and postsurgical stagings of all cases. The spread of the cancer was accurately diagnosed in 84.5% of patients in Stage Ib, 55.6% of those in Stage IIa, and 42.4% of those in Stage IIb, respectively. The accuracy was low, especially in Stages IIa and IIb. Five cases of postsurgical Stage Ib, who had been diagnosed as Stage IIa preoperatively, might be postsurgical Stage IIa, because the preoperative diagnosis must have been made by the histologically proven vaginal invasions. Our postsurgical staging was based only on the pathologic results of the removed uterus and vagina. Therefore, there is some possibility that vaginal cancerous lesions in these five cases might have been lost during preparation of the pathologic specimens. However, the accuracy of Stage IIa remains at 74% even if we include these five in the postsurgical Stage IIa group. The low accuracy of Stage IIb will be given attention later. We stress the difficulty of diagnosing the parametrial invasions by bimanual pelvic and rectal examinations. Lymph Node Metastasis and Prognosis There were 54 patients with pelvic lymph node metastases among 255 cases studied. The rates of positive lymph nodes according to FIGO stagings are 16.3% (21/129) for Stage Ib and 26.2% (24/126) for Stage 11. When calculating these rates according to the surgical stagings, the figures change to 14.4% (21/146) for Stage Ib and 30.3% (33/109) for Stage 11. These figures are almost the same for the corresponding clinical stages. The rate increases to 42.0% in Stage IIb when the postsurgical Stage I1 cases are classified into subgroups. This suggests that the risk of lymph node metastasis increases when the cancer spreads from the uterine cervix into the parametrium. The prognoses in cases of positive nodes are listed in Table 3, according to the number of metastatic nodes. The prognosis worsened when the number of metastatic nodes increased. The 5-year survival rate of those with only one node metastasis was 62.1 % and that of patients with over two positive nodes was 36.0%. Adenocarcinoma and Stump Cancer Seven of 19 patients with adenocarcinoma or adenosquamous cell carcinoma died or had a recurrence. This

4 No. 12 POSTSURGICAL STAGING AND PROGNOSIS - Matsuyama et al TABLE 3. Number of Lymph Node Metastases and Prognosis No. of No. of patients positive Survival nodes Alive Dead Total rate I% % 5 0 I 1 0 recurrence or death rate of 36.8% was not statistically significant compared to those with squamous cell carcinoma (17.8%). Among the 12 patients with cervical stump cancer, 3 died of cancer. Because of the small number, the survival rate of these women cannot be compared with the rate of the those with retained uterine corpus. Site of Recurrence and the Field of Postoperative Radiation Of the 49 patients who died or had a recurrence, information on the cause of death or the site of recurrence was available for 41 cases. As shown in Table 4, there were 15 cases of pelvic recurrences and 18 cases of distant metastases. Three patients died of intercurrent diseases, and five of radiation complications. Distant metastases were frequently observed when the parametria and lymph nodes were involved. To these lethal or recurrent cases, postoperative radiation did not seem to have any advantageous influence. For the locally recurrent cases, the radiation doses that were considered to be the maximum limit were not sufficient to prevent the recurrences. For the distantly recurrent cases, radiation fields could not cover the metastasized sites. There may have been some who would have benefited from postoperative radiation, but the lack of controls rules out drawing conclusions. The good results in the postsurgical Stage IIa group, even with the positive vaginal margins and the few with a vaginal stump recurrence, were attributed to the postoperative intracavitary small source irradiation. Radiation Complications Major complications of postoperative radiation are listed in Table 5. Bowel obstructions occurred in 8 of 59 cases given whole pelvis irradiation of 6000 rad. Three required surgical intervention and four died of complications. Radiation-related cystitis with a pronounced hematuria occurred in three cases, but was not severe. The incidence of major complications was 13.6% for 6000-rad cases. Among 82 patients given 5000 rad TABLE 4. Site of Recurrence and Cause of Death According to Postsurgical Stage* Postsurgical Intercurrent stage Pelvic Distant disease Complication Ib 5 I 2 1 IIa IIb * Eight cases of site unknown were excluded. to the whole pelvis, 4 had bowel obstructions, 1 died of vesicovaginal fistula combined with bowel obstruction, and 2 had radiation proctitis that necessitated blood transfusions. The incidence of complications for the 5000-rad group was 8.5%. The overall complication rate for patients given postoperative external radiation was 10.6%. One of the complications of postoperative whole pelvis radiation is hydronephroureters due to narrowing of the lower segment of ureters caused by peribladderai fibrosis. Since routine intravenous pyelogram after 6 to 12 months of initial treatment was introduced in 1975, 173 patients in this study were examined in regard to this complication. Among 83 patients who did not receive postoperative external radiation, 7 (8.4%) had hydronephroureters. On the other hand, among 90 given postoperative external radiation, 33 (36.7%) exhibited this complication, the difference being statistically significant (P = 0.005). However, we consider this change to be transient rather than permanent. In some women, the hydronephroses had resolved spontaneously, as seen on the pyelogram taken 5 years after the initial operations. Discussion Our postsurgical staging was based on findings of cancer in the uterus, vagina and, parametrium. Lymph node metastasis was not taken into consideration. We attempted to compare the clinical and postsurgical stages on the same background as the clinical stage. TABLE 5. Radiation Complications and Dose of External Radiation Dose of Ext Bowel Rectal Radiat obstruction Fistula hemorrhage Rate 5000 rad 4 (1) I* (1) 2 8.5% 6000 rad 8t (3) 13.6% Cases of operative intervention are in parentheses. * Died. t Four died. Ext: external; Radiat: radiation.

5 3076 CANCER December Vol. 54 Staging errors, thus compared, increased with the advance in clinical stage. It is relatively easy to preoperatively diagnose the localization of cancer in the cervix or invasion to the vaginal mucosa by using colposcopy. However, the parametrial invasion is usually only detectable by a well-experienced gynecologist. This is the source of staging errors, especially in Stage IIb. In this study, only 42 cases (42.4%) were correctly diagnosed as Stage IIb among 99 cases of FIGO Stage IIb. In another 57, the assessment was excessive. On the other hand, there were unexpected parametrial invasions in 27 of 156 cases with Stage Ib and IIa (17.3% of underdiagnosis). Reported staging errors ranged from 11.8% to 32.1% for Stage Ib, from 22.1% to 52.7% for Stage IIa, and from 28.6% to 75.6% for Stage IIb.24 Here, there was the same tendency of higher error rate in Stage IIb. There are several other reports concerning the misdiagnosis of parametrial infiltration in the clinical staging. Mitani er al5 found 31.5% of unexpected parametrial infiltrations in Stage Ib and IIa cases, and the absence of cancer in the parametria in 45.8% of Stage IIb. Bruntsch6 found cancer tissues in the parametria in only 31.8% of cases of Stage IIb. Burghardt and Picke17 investigated surgically obtained large cervical sections and found that only 19.3% of the cases in clinical Stage IIb had true parametrial involvements. Zander et al4 reported that parametrial invasions tended to be overdiagnosed. Care should be taken not to confuse inflammatory changes of the parametria with cancer invasion. According to the recent annual report of FIGO' concerning treatment of gynecologic cancer, the 5-year survival results of Stage I1 ranged between 21.4% and 81.5%. This is clear evidence of the unreliability of clinical stagings. Another advantage of deciding postsurgical staging without regard to the lymph node metastasis is that the lymph node metastasis rates between the two staging systems can be compared. The reported metastasis rates to the pelvic lymph nodes vaned from less than 10% to more than 30% for FIGO Stage I and from 16% to over 40% for Stage II.3,5,7,9-13 Ou r metastasis rates are averages of these figures. The metastasis rate of postsurgical Stage IIb, however, increases to 42%. The figures of Christensen and Foglmann3 on the metastasis rates according to the postsurgical staging were 11.9% for Stage Ib, 21.2% for Stage IIa, and 54.7% for Stage IIb. Mitani and coworkerss reported a 52.2% metastasis rate with parametrial infiltration, Hogan er ali4 reported a rate of 45.4%, and Burghardt and Picke17 reported a rate of 84.3%. All of these figures suggest that lymph node metastasis readily occurs when the cancer spreads to the parametria. We stress that the prognosis of the patient is poor (5-year survival rate of 41.4%) when both the parametrium and pelvic lymph nodes are involved. If the actual involvement of cancer in both the parametrium and pelvic lymph nodes can be determined preoperatively, those women should be treated with radiation. The correlation between the depth of myometrial invasion and the prognosis of endometrial cancer has been reported in detail. In cases of cervical cancer, similar prognostic value of stromal invasion has been reported. Therefore, stromal invasion of cancer cells as deep as the uterine serosa can be considered equal to parametrial invasion, when considering the prognosis of the patient. This depth corresponds to the "border zone," proposed by Burghardt and Pi~kel.~ This is the border of the uterine muscle and parametrium and has numerous branching blood vessels and a broad confluent network of lymph vessels. They stated that lymph node metastasis increased from 15.7% to 47.8% when this zone was invaded by tumor cells. Abdulhayoglu et al." reported that 80% of their patients with lymph node involvement also had outer-third myometrial invasions. Analyzing the treatment failures in Stages Ib and IIa, Chung et a1.i' found that in cases of over 70% depth invasion, the prognosis was poor in terms of the 2-year survival rate. All of these figures suggest the prognostic importance of deep stromal invasion. Lymph vessel invasion of cancer cells in the primary tumor has often been investigated in relation to pelvic lymph node metastasis.s~10~'6 In our study, lymph vessel permeation without lymph node metastasis also was of prognostic importance. In such patients, the 5-year survival rate is decreased compared with those without vessel permeation, but the results are better than in those with lymph node metastasis. The unreliability of the clinical staging, especially in Stage IIb was discussed, and some risk factors concerning spread of the cancer were outlined. Accordingly, the prognosis can be estimated by the postsurgical histologic evaluations. REFERENCES I. Annual report from cancer registry committee of Japan Society of Obstetrics and Gynecology. Acta Obstet Gynecol Jpn 1983; 35: Averette HE, Dudan RC, Ford JH. Exploratory celiotomy for surgical staging of cervical cancer. Am J Obstet Gynecoll972; 1 13: Christensen A, Foglmann R. Cervical carcinoma stage I and I1 treated by primary radical hysterectomy and pelvic lymphadenectomy. Acla Obstet Gynecol Scund 1976; (Suppl) 58:l Zander J, Baltzer J, Lohe KJ, Ober KG, Kaufmann C. Carcinoma of the cervix: An attempt to individualize treatment. Results of a 20-year cooperative study. Am J Obstet Gynecol 1981; 139:

6 No. 12 POSTSURGICAL STAGING AND PROGNOSIS MUtSUyUmU et a/ Mitani Y, Fujii J, Miyamura M, Ishizu S, Matsukado M. Lymph node metastases of carcinoma of the uterine cervix. Am J Obstet Gynecol 1962; Bruntsch KH. Die Wertung der histologischen Untersuchung der Parametrien beim operierten Kollumcarzinom im Hinblick auf die Feststellung des Ausbreitungsgrades. Geburtschilfe Frauenheilkd 1957; 17: Burghardt E, Pickel H. Local spread and lymph node involvement in cervical cancer. Obstet Gynecol 1978; 52: Kottmeier HL, ed. Annual Redort on the Results of Treatment in Gynecological Cancer, vol. 18. Stockholm: International Federation of Gynecology and Obstetrics, Ballon SC, Berman ML, Lagassq LD, Petrilli ES, Castaldo TW. Survival after extraperitoneal pelvic and paraaortic lymphadenectomy and radiation therapy in cervical carcinoma. Obstet Gynecol 1981; 57 : Chung CK, Nahhas WA, Stryker JA, Curry SL, Abt AB, Mortel R. Analysis of factors contributing to treatment failures in stages Ib and IIa carcinoma of the cervix. Am J Obstet Gynecol 1980; 138: I I. Martimbeau PW, Kjorstad KE, Iversen T. Stage Ib carcinoma of the cervix, The Norwegian Radium Hospital: 11. Results when pelvic nodes are involved. Obstet Gynecol 1982; 60: Piver MS, Chung WS. Prognostic significance of cervical lesion size and pelvic node metastases in cervical carcinoma. Obstet Gynecol 1975; Sall S, Pineda AA, Calanog A, Heller P, Greenberg H. Surgical treatment of stages IB and IIA invasive carcinoma of the cervix by radical abdominal hysterectomy. Am J Obstet Gynecol 1979; 135: Hogan WM, Littman P, Griner L, Miller CL, Mikuta JJ. Results of radiation therapy given after radical hysterectomy. Cancer 1982; 49: Abdulhayoglu G, Rich WM, Reynolds J, DiSaia PJ. Selective radiation therapy in stage Ib uterine cervical carcinoma following radical pelvic surgery. Gynecol Oncol 1980; 10: Van Nagell JR, Donaldson ES, Wood EG, Parker JC Jr. The significance of vascular invasion and lymphocytic inliltration in invasive cervical cancer. Cancer 1978; 41: STATEMENT OF OWNERSHIP, MANAGEMENT AND CIRCULATION (Required by 39 U.S.C. 3685) Average No. Copies Each Issue during preceding I2 Months Actual No. of Copies of Single Irsues Published Nearest to Filing Date Date of Filing--October I, 1984 Title of Publication-Cancer Publication No Frequency of Issue-Twice Subscription Price-$60.00 monthly Location of Known Ofice of Publication-2350 Virginia Ave., Hagerstown, MD Location of the Headquarters of General Business Ofices of the Publisherr-East Washinglon Square, Philadelphia, PA Publisher-American Cancer Society, East Washington Square, Philadelphia, PA Editor-Jonathan E. Rhoads, MD, 3400 Spruce St., Philadelphia, PA Managing Editor-Deborah G. Huey, East Washington Square, Philadelphia, PA Owner-American Cancer Society, 777 Third Ave., New York, NY Known Bondholders, Mortgagees and other security holders owning or holding I Per Ent or more of total amount of bonds, mortgages or other securities-none A. Total no. copies printed (nel press run) B. Paid circulation I. Sales through dealers and carriers, street vendors and counter sales 2. Mail subscriptions C. Total paid circulation D. Free distribution by mail, carrier or other means. Samples, complimentary. and other free copies E. Total distribution (sum ofc and D) F. Copies not distributed 1. Ofice use, leftover, unaccounted, spoiled after printing 2. Returns from news agents G. Total (sum of E & F-should equal net press run shown in A) 25, , ,944 3, ,409 21,618 21, ,479 24,409 I certify that the statements made by me above are correa and complete. Joseph W. Lippincott 111, Assmiale Publisher