Prognostic factors in patients with cervical cancer treated with surgery and adjuvant radiotherapy

I. J. Radiation

318

Oncology

l Biology

l Physics

Volume 48, Number 3, Supplement,

2000

obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = I), lymphedema (n = 3), skin involvement (n = l), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in five. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA- 125 level. Forty-five percent had a partial response. Only 1 I % suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in ten patients who experienced recurrence of their symptoms between one and 21 months (median = 9 months). The one- two-, three-, and five-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33% respectively. The same survival rates calculated from the completion of radiotherapy were 39%, 278, 13%, and 10% respectively. Five percent of patients experienced grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced grade 1 or 2 diarrhea: 19% experienced grade 1 or 2 nausea and vomiting, and 11% had grade 1 or 2 myelosuppression. Conclusion: In this large series of radiation therapy for ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current salvage chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy prior to non-platinum and/or non-paclitaxel salvage chemotherapy in these patients.

2108

L oss of heterozygosity on chromosome after radiotherapy of cervical cancer

Y. Harima.

K. Nagata,

Kansai Medical

K. Harima,

Univemity,

6~212 plus 17~13.1 as a potential marker for relapse-free

survival

S. Sawada

Moriguchi,

Jqxm

Purpose: Cervical carcinomas develop as a result of multiple genetic alterations, and specitic alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p and 17p are one of those most frequently involved in a loss of heterorygosity (LOH) in patients with cervical carcinoma. Our study explored whether LOH on chromosome 6~2 12 plus 17~ 13.1 is associated with treatment outcome in patients with cervical cancer after radiotherapy. Materials and Methods: A total of 64 patients with cervical cancer (stage 1, 5 patients: stage II, 9 patients; stage III, 38 patients; and stage IV, 12 patients) who underwent definitive radiotherapy between 1995 and 1999 were included in this study. We analyzed specimens from the tumor and venous blood of all patients. Tumors and normal DNA were analyzed by polymerase chain reaction for genetic losses at six polymorphic microsatellite loci (D6S276, D6S1624, D6S1583 (6~211) and D17S796, Dl7Sl353, Dl7SlX81 (17~13. I)). Actuarial methods were used to calculate overall survival and disease-free survival. Results: A total of 26 patients (40.6%) had cancer recurrence: 8 patients had a local recurrence, six had distant metastases, and 12 had both local recurrence and distant metastases after radiotherapy. The mean tumor diameter of all patients was 5.6 cm. We divided the patients into two groups, those with tumors smaller than 5.6 cm in diameter (n = 35) and those with tumors equal to or greater than 5.6 cm in diameter (n = 29). There was a signiticant difference in overall survival (P = 0.004) and disease-free survival (P = 0.02) between these groups: the former group survived signiticantly longer than the latter group. Chromosome 6~212 and 17~13.1 is involved in the LOH in 46.9% (30 of 64), and 40.6 % (26 of 64) of the informative carcinomas. Both LOH on chromosome 6~212 and 17~13.1 are shown in 17 patients (26.6%) and no LOH on same region are revealed in 25 patients (39. I %).There was a significant difference in overall survival (P = 0.02) and disease-free survival between patients with LOH on 6p and those without (P = 0.001). The latter group survived significantly longer than the former. In addition, there was a significant difference in overall survival (P = 0.006) and disease-free survival between patients with LOH on 17~ and those without (P = 0.01). The latter group survived significantly longer than the former. The patients with LOH on chromosome 6~2 I? plus 17~13. I survived significantly shorter than the those without in overall survival (P = 0.003). Relapse-free survival were significantly worst for the patients with LOH on chromosome 6~212 plus 17~13. I as compared to those without LOH (P = 0.0004). Conclusion: The results of this study suggest that LOH on 6~212 plus 17~13. relapse-free survival in patients with cervical carcinoma after radiotherapy.

2 109

I are the most important determinant

Prognostic factors in patients with cervical cancer treated with surgery and adjuvant

D. Utzig,’ J. Dunst,’ C. Richter.’

H. Methfessel,’

‘Dept. of Radiotherapy, Martin-Luther-Uni~,er.siry University Halle- Wittenberg. Halle, Germmy

H. Koelbl,’

of

radiotherapy

G. Haensgenr

H&e- Wittenberg,

Hulk,

Germmy,

‘Dept.

qf Gynecology, Martin-Luther-

Background: We have retrospectively evaluated the treatment results and prognostic factors in patients with high risk stage IB/IIB cervical cancers treated with radical hysterectomy and lymphadenectomy followed by adjuvant radiotherapy. Materials & Methods: From 198 1 through 1993, a total number of 289 patients with stage IB or IIB cervical cancers received adjuvant radiotherapy in our department. Radiotherapy was administered in surgically treated patients only in case of high risk for local failure. Indications for radiotherapy were pathologically proven lymph node involvement or unfavorable histological features for pNO-patients (G3 + histological lymphangiosis, no pelvic lymphadenectomy, involved/small vaginal margins. adenocarcinoma). Radiotherapy was administered via opposing ap/pa-portals with telecobalt or 9MV- or ISMV-photons in daily doses of I&2Gy up to a total dose of 50Gy with a parametrial boost up to 54Gy in selected cases. Additional vaginal cuff boost irradiation with HDR-brachytherapy was given if the vaginal margin was less than 1 cm. The age ranged from 25 through 81 years (mean 46 ? 12 years). All patients were followed regularly for at least 5 years in our department. Results: The overall 5.year survival was 70%. 5.year survival according to stage was 75% for IB and 58% for stage IIB. The most important single prognostic factor was lymph node involvement with a 5-year-survival of 75% for pN0 and 52% for pN + (p = 0.0003). The prognosis decreased with increasing number of involved lymph nodes (5.year survival 58% for I-2

Proceedings

319

of the 42nd Annual ASTRO Meeting

involved nodes versus 20% for 3 and more positive nodes, p = O.OOl). Survival according to stage and lymph node involvement was: IB and pN0: 72%: IIB and pN0: 6X%: IB and pN+: 63%: IIB and pN+: 43%). Grading was of marginal prognostic significance. Histology (adenocarcinoma versus squamous cell cancer) was not significant. In a Cox regression model including stage, grading. histology and lymph node status, the only significant factor was lymph node involvement (RR = 17. p = 0.000X). Grading was of marginal significance (RR = I3 for G3/4 versus Gl/2. p = 0.09). Since 1996, patients with risk factors are routinely treated with postoperative radiotherapy combined with simultaneous cisplatin/ S-FU-chemotherapy. The follow-up in this group (N = 32) is limited but the 3.year survival of X4clr compares favorably to the historical results with mdiotherapy alone. Moreover, the impact of surgery remains to be determined since our results with delinitve radiotherapy alone (S-year survival >60% for stage IIB and >SO’%for stage IIIB) favors the use of radiotherapy alone. Conclusions: For patients treated with radical hysterectomy, the amount of lymph node involvement is the most important prognostic factor. In patients with risk factors, the results of surgery and adjuvant radiotherapy in this series yielded survival figures comparable to or lower than expected with definitive radiotherapy or radiochemotherapy.

2110

A n analysis of late sequelae in patients treated with concurrent locally advanced carcinoma of the cervix

M. D. Kelly,’ C. H. Shelton.’

W. A. Anderson,’

P. T. Taylor.’

‘Urzivemir~ of Vir;qirzitr, C12trr-/ort~s~,i//r.VA, ‘Grrmhrirr Pm-pose: to analyze late toxicity

chemotherapy

and radiotherapy

for

W. C. Constable’

Vrdley Cmcrr

in a cohort of patients receiving

Cwtrr,

chemoradiation

Lcwi.hrr,y,

WV

for cervical

cancer.

Materials and Methods: This retrospective study examines 72 patients with locally advanced cancer of the cervix (IB2-IVA) treated at a single institution from 1983 to 1990. All patients were treated using radiotherapy with concurrent S-FU and Mitomycin-C. The endpoint analyses of survival. local control and toxicity are reported with a minimum of 5 year follow-up to specifically examine the incidence of delayed toxicity. Results: 72 patients were followed for a minimum of 5 years or until death. S-year determinate survival was available in 60 patients. Survival was 42% for all stages collectively. with local control achieved in 68% with chemoradiation. Delayed toxicity was observed in 22 patients with gastrointestinal, urologic and vascular sequelae accounting for the majority of observed effects. As an absolute rate. 38% of patients were observed to have significant late sequelae, and as an actuarial rate the figure was 42%. Actuarial rates of severe late toxicity for gastrointestinal, urological and vascular sequelae were 29%. 38%. and 33% respectively at 5 years. Conclusion: An unusually high rate of late sequelae is seen in longterm survivors of locally advanced cervical cancer treated with S-FU. Mitomycin-C and radiotherapy concurrently. Whether this occurs in the settin g of current ciaplatin-based chemoradiation remains to be seen.

2 111

A study of relationship between the Ieve1 of serum squamous treatment of uterine cervix cancer

cell antigen and recurrence

patterns after

D. Choi. E. Kim. K. Nam

Purpose: Serum squamous cell carcinoma (SCC) antigen levels were examined in uterine cervix cancer undergoing therapy. and authors analyzed the relationship between SCC antigen levels and treatment results.

radiation

Materials and Results: This is a retrospective study of 181 cervical carcinoma patients who received radiotherapy and examined aerial serum SCC antigen from 199 I to I907 at Soonchunhyang University Hospital. One hundred and eighteen patients underwent SCC antigen evaluation at diagnosis. The relation between the serum tumor marker levels and disease free survival. recurrence patterns and other prognostic factors were analyzed accoring to various statistical methods. Results: The positivity rate (initial serum velue above 2.Sng/ml) was increased with FIG0 stage (IB-IIA 57% to IV Y IQ) and more discriminative than cutoff value of lSng/ml. Five year disease free survival rate\ for the stage IB-IIA, IIB. III and IV were 79.2%, 68.7%. 33.4% and 0%. respectively. The S-year disease free \urvi\al rate for patients serum SCC antigen levels above 5.0ng/ml was only 34% versus SS-62% for patients with normal range (< lSng/ml) or mildly elevated levels( IS-S.Ong/ml). Ri\ing SCC levels pl-eceded the clinical detection of disease by a mean of 4.X months (range l-13 months). Negative linear correlation was observed between initial SCC antigen levels and relapse free survival (r = ~ 0.226). and by multivariate analysis. initial SCC antigen level had a large impact on the relapse free survi\,al. Conclusions: SCC antigen assay is a useful aid to predict the prognosis to detect recurrence earlier than clinical or radiological study.

2112

of squamous

cell carcinoma

R esu Its f rom a randomized trial comparing alternating chemoradiotherapy radiotherapy in advanced squamous cell carcinoma of the head and neck

R. Corvh, M. Benasso. G. Sanguineti, Nrrtionnl Imtitute ,fiw Cmc~er Resecmh.

G. Margarine,

A. Bacigalupo,

I. Ricci, R. Lionetto.

of the uterine cervix and

versus partly accelerated

R. Rosso. V. Vitale

Germs, Italy

Purpose: We carried out a prospective controlled Phase 111 trial to compare partly accelerated chernoradiothempy in the treatment of patients affected by locally advanced HN-SCC.

radiotherapy

with alternating

Materials and Methods: One hundred and thirty-six consecutive patients with unfavournble Stage II or Stage III-IV SCC of oral cavity. pharynx and larynx were enrolled between 1992 and 1998. Patients were randomly a\\igned to receive chemo-