Diagnosis and treatment of high-risk metastatic gestational trophoblastic neoplasia in Hungary

OBJECTIVE: To review results in treatment of high-risk metastatic gestational trophoblastic neoplasia (GTN) in Hungary. STUDY DESIGN: Between January 1, 1977, and December 31, 2006, 142 patients with high-risk metastatic GTN were treated. Patients were 14-51 years of age (average 27.9). We selected primary chemotherapy based on patient GTN stage and prognostic score. RESULTS: Methotrexate, actinomycin-D and cyclophosphamide (MAC) as a primary therapy was used in 100 cases and as second-line chemotherapy in 6 cases. Of the 100 cases, 95 achieved complete remission. Twenty-one high-risk patients were treated with etoposide, high-dose methotrexate with folinic acid rescue, actinomycin-D, cyclophosphamide and vincristine (EMA-CO). Of 17 primary therapies, 13 patients achieved complete remission. Primary cisplatin, etoposide and bleomycin (CEB) was successful in 12 of 14 high-risk cases. Hysterectomy was performed in 42 of 142 high-risk patients; metastases were resected in 26 of 142 of high-risk patients. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO and MAC and EMA-CO. CONCLUSION: Results support that patients with high-risk metastatic GTN should primarily be treated with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens.     

Analysis of treatment failure in high-risk metastatic gestational trophoblastic disease

The course of 51 patients with high-risk metastatic gestational trophoblastic tumor was reviewed. The clinical characteristics and therapy of patients who died were compared to patients who attained remission to identify parameters that are associated with treatment failure. The presence of liver, brain, or intestinal metastases and the failure of prior chemotherapy were found to portend a poor prognosis (P less than 0.001, P less than 0.05). Other high-risk factors such as markedly elevated HCG levels, time interval greater than 4 months from the antecedent pregnancy to treatment, and post-term choriocarcinoma were not independently associated with treatment failure. The mean prognostic score and the mean number of high-risk factors for patients who died were 13 and 3, as compared to 7 and 2, respectively, for patients who achieved remission (P less than 0.001, P less than 0.001). Alternative intensive chemotherapy regimens need to be developed to improve remission rates in patients with liver, brain, or intestinal metastases, failed prior chemotherapy, or a high prognostic score.     

Choriocarcinoma diagnostic score: A scoring system to differentiate choriocarcinoma from invasive mole

Okamoto T, Nomura S, Nakanishi T, Goto S, Tomoda Y, Mizutani M. Choriocarcinoma diagnostic score: A scoring system to differentiate choriocarcinoma from invasive mole. Int J Gynecol Cancer 1998; 8 : 128–132.
The histologic diagnosis of choriocarcinoma has been reported to be one of the prognostic factors for the treatment outcome of gestational trophoblastic tumors (GTT). A scoring system, called the choriocarcinoma diagnostic score (CD score), which had been devised to differentiate choriocarcinoma from invasive mole, was reevaluated in patients with GTT treated at Nagoya University Hospital from 1964 to 1996. There were 134 cases with pathologic documentation of choriocarcinoma and 155 cases of invasive mole. Sensitivity of the CD score (ie the true positive rate for the histologic diagnosis of choriocarcinoma) was 94.0%, and specificity of the score (ie true positive rate for the histologic diagnosis of invasive mole) was 97.4%. Thus, the accuracy of the score was very high (95.8%). Seventy-two (91.2%) of 79 cases with high CD scores (10 points or more) were categorized into high-risk or very high-risk groups according to the World Health Organization (WHO) prognostic index score. This unique scoring system should be included in the management of patients with GTT.     

Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy

OBJECTIVE: To evaluate the efficacy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) in the primary treatment of metastatic high-risk gestational trophoblastic neoplasia. STUDY DESIGN: Thirty women with metastatic high-risk gestational trophoblastic neoplasia were treated primarily with EMA-CO between 1986 and 2005. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing etoposide and a platinum agent with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response and factors affecting treatment success were analyzed retrospectively. RESULTS: The overall survival rate was 93.3% (28 of 30). Of the 30 patients treated with EMA-CO, 20 (66.7%) had a lasting clinical response, 8 (26.7%) developed resistance but were subsequently placed in remission with platinum-based chemotherapy, and 2 (6.7%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by human chorionic gonadotropin level (<100,000 mIU/ mL, 82%, vs. > 100,000 mIU/mL, 46%), metastatic site (lung and pelvis, 75%, vs. other, 33%) and International Federation of Gynecology and Obstetrics (FIGO) risk factor score (< 7, 92% vs. >7, 50%). Surgical procedures were performed on 12 patients, and 4 patients received brain irradiation. Eight (80%) of 10 patients who received secondary platinum-based chemotherapy or without surgery were cured. The 2 patients who died had stage IV disease (brain and/or liver metastases) with FIGO scores of 13 and 14. CONCLUSION: Over 93% of 30 patients with metastatic high-risk gestational trophoblastic neoplasia treated initially with the EMA-CO protocol, often in conjunction with brain irradiation, surgical resection of sites of persistent tumor and salvage platinum-based chemotherapy, were cured.     

"Poor prognosis" metastatic gestational trophoblastic disease: the prognostic significance of the scoring system in predicting chemotherapy failures

Twenty-eight patients with "poor prognosis" metastatic gestational trophoblastic disease were treated during a 17-year period. The primary treatment was combination chemotherapy with methotrexate, actinomycin D, and chlorambucil (MAC). Patients who failed to respond to this regimen were treated secondarily with other combinations. Adjuvant surgery and radiotherapy were used in selected cases. The overall remission rate was 89% (25 of 28): 71% for first-line treatment with MAC (20 of 28) and 62% for second-line treatment (five of eight). The response rate to MAC correlated well with the patient's score (modified World Health Organization [WHO] scoring system--1983). Seventeen patients treated with MAC had scores less than 12, and all of them achieved remission. Of 11 patients having scores of 12 or more, only three achieved remission with MAC (27%). Of the eight who did not, five achieved remission with other combinations (62%) and three died. No patient died because of chemotherapy toxicity. The WHO scoring system is a good index to select high-risk patients who need primary chemotherapy more aggressive than MAC.     

A study of the relationship between Goodwin's high-risk score and fetal outcome.

Correlation between Goodwin's high-risk score and Apgar score was studied in 266 pregnancies managed with the use of the information from clinical monitoring. The correlation coefficients between Goodwin's score and Apgar scores were -0.3178 for one-minute Apgar scores and -0.2668 for five-minute Apgar scores. Both are significant at the level of p less than 0.001. When the patients were divided into two groups by Goodwin's score, fetuses of the group with the higher score (greater than or equal to 4) were significantly more acidotic than those of the group with the lower score. Therefore, Goodwin's high-risk scoring system is simple and useful in the selection of potential risk patients.     

High-risk metastatic gestational trophoblastic disease. A new dose-intensive, multiagent chemotherapeutic regimen.

Dose-intensive, multiagent chemotherapy for the treatment of high-risk gestational trophoblastic disease has evolved as the treatment of choice for these patients. High-dose methotrexate in combination with etoposide, dactinomycin, vincristine and cyclophosphamide (EMA-CO) has now been demonstrated to be superior to the traditional methotrexate, dactinomycin, cyclophosphamide chemotherapy in patients with prognostic scores of greater than or equal to 8. An attempt was made to improve upon the EMA-CO regimen by increasing the dose intensity of etoposide and adding cisplatin to the high-dose methotrexate, etoposide and dactinomycin. That regimen was used on four patients with ultra-high-risk gestational trophoblastic disease.     

恶性滋养细胞肿瘤预后评分标准的初步评价

目的 对恶性滋养细胞肿瘤2000年国际妇产科联盟(FIGO)预后评分标准进行初步评价。方法 恶性滋养细胞肿瘤患者223例,治疗前除临床分期外,按2000年FIGO预后评分标准判定其高危因素,评价以此选择治疗方式的合理性。结果 78例绒毛膜癌患者中,43例为高危,35例为低危;145例侵蚀性葡萄胎患者中,7例为高危,138例为低危。初治化疗的原则为：低危患者以单药化疗为主,高危患者采用多药联合化疗。本组患者的1年、3年、5年生存率分别为98．60A,98．1％及97．1％。无一例因毒副反应或并发症而死亡。结论 恶性滋养细胞肿瘤患者根据2000年FIGO预后评分标准选择治疗方案,取得较满意的治疗结果。     

Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy

OBJECTIVE: The objective of the study was to evaluate the efficacy and toxicity of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy for the treatment of high-risk gestational trophoblastic neoplasia. METHODS: Forty-five patients with high-risk gestational trophoblastic tumors received 257 EMA-CO treatment cycles between 1986 and 2001. Twenty-five were treated primarily with EMA-CO because of the presence of one or more high-risk factors and 20 were treated with EMA-CO secondarily after failure of single-agent chemotherapy. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing cisplatin and etoposide with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response, and toxicity were analyzed retrospectively. RESULTS: The overall survival rates was 91% (41/45); survival rates were 92% (23/25) for primary treatment and 90% (18/20) for secondary treatment with EMA-CO. Of the 45 patients treated with EMA-CO, 32 (71%) had a complete clinical response, 9 (20%) developed resistance but were subsequently placed into remission with cisplatin-based chemotherapy, and 4 (9%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by duration of disease from antecedent pregnancy to treatment (<6 months, 84%, vs >6 months, 43%), metastatic site (lung and pelvis, 73%, vs other, 40%), and WHO score (< or =7, 96%, vs >7, 36%). The EMA-CO chemotherapy regimen produced no life-threatening toxicity, caused grade 3-4 hematologic toxicity in 1.6% of cycles, and was associated with neutropenia necessitating a 1-week delay in treatment in only 13.5% of cycles. CONCLUSION: EMA-CO chemotherapy is a well-tolerated and highly effective treatment for high-risk gestational trophoblastic neoplasia, yielding a 71% complete response rate and a 91% survival rate in this series.     

A retrospective comparison of current and proposed staging and scoring systems for persistent gestational trophoblastic disease

Abstract. Hancock BW, Welch EM, Gillespie AM, Newlands ES. A retrospective comparison of current and proposed staging and scoring systems for persistent gestational trophoblastic disease.
It is widely accepted that patients with persistent gestational trophoblastic disease (GTD) are best managed by stratifying their treatment according to recognized adverse prognostic features. We retrospectively evaluated 201 patients who had received chemotherapy for persistent low or high risk GTD at the Sheffield Center according to criteria used in established and proposed WHO scoring and FIGO staging systems to identify the numbers of patients in each risk category, the treatment they would receive, chemotherapy resistance patterns, and eventual outcome. The systems were broadly comparable and chemotherapy resistance was always greater in the high-risk groups (at least 33%), particularly when patients were divided into just two risk categories. Such a categorization led to fewer patients (less than 15%) falling into high-risk groupings, but outcome was not compromised. Mortality (3 deaths) was associated with high risk categorization in all systems evaluated. A proposal to combine revised FIGO staging and modified WHO scoring systems, with two risk groupings, is realistic and practicable.     

Guidelines for the stratification of patients recruited to trials of therapy for low-risk gestational trophoblastic tumor

OBJECTIVE: The aim of the study was to initiate a search for factors which might independently predict the need for salvage therapy in patients with low-risk gestational trophoblastic tumor. METHODS: The independent effect of six factors on the need for salvage chemotherapy was assessed in patients with low-risk gestational trophoblastic tumor who were treated with low-dose methotrexate and folinic acid. The accuracies of World Health Organization and Charing Cross Hospital scores were also compared. RESULTS: Age, pretreatment beta hCG, antecedent pregnancy-treatment interval, and the presence of chest metastases detected on chest X ray were not significantly predictive. The size of tumor (P = 0.001) and the presence of chest metastases on chest computerized tomography (P = 0. 00028) had independent, statistically significant predictive power, and a simple prognostic index was derived from these variables. The World Health Organization score was found to be significantly better than the Charing Cross Hospital score. The accuracy of the simple prognostic index was slightly greater than that of the World Health Organization score, although this was not statistically significant. CONCLUSIONS: These results confirm that patients entered into studies of different therapies for low-risk gestational trophoblastic tumor should be stratified and that a simple score, derived from the results of tumor size and chest computerized tomography, is potentially as good as the World Health Organization score for predicting the need for salvage therapy.     

Management of patients with metastatic gestational trophoblastic tumor

OBJECTIVE: This study was designed to analyze the results of treatment on patients with metastatic gestational trophoblastic tumor (metastatic GTT). METHOD: During 1996-2001, 38 cases with metastatic GTT were diagnosed and received treatment in Vali-e-Asr Hospital, Tehran, Iran. Data were gathered retrospectively and analyzed based on therapy and response rate. Sixteen patients initially labeled as low-risk, four as middle-risk and eighteen as high-risk patients according to FIGO scoring system (1992). Thirty-four (89.5%) patients responded to treatment; 13 to single-agent [methotrexate (MTX) or ACT] and 21 to multiagent chemotherapy [EMA/cisplatinum and etoposide (EMA-EP) or MTX, ACT-D and cyclophosphamide or chlorambucil (MAC)]. RESULTS: All low-risk patients, 2 middle-risk patients and 16 high-risk patients responded to treatment. Four cases failed to respond to therapy due to CNS involvement. CONCLUSIONS: Patients with low-risk metastatic GTT have a 100% chance to response to single-agent chemotherapy and those with high-risk disease have great chance to response to multiagent chemotherapy such as EMA-EP.     

浆液性卵巢癌预后评分模型的建立和预后相关基因的筛选

目的寻找与卵巢癌预后相关的临床因素和基因。方法用数学统计方法对104例浆液性卵巢癌患者进行生存分析，筛选预后相关的临床因素，建立卵巢癌预后评分模型。通过对22例浆液性卵巢癌基因表达谱芯片进行生物信息学分析，筛选卵巢癌预后相关的基因群，并进行基因调控网络分析。结果根据对预后的影响程度，卵巢癌预后相关的临床因素依次包括手术病理分期、化疗，术后残余灶，组织学分级和淋巴结转移；根据各因素及其内部分层因素对预后影响的风险系数，对各因素及其内部因素进行量化，结合生存函数对患者生存概率的估计，建立了卵巢癌预后评分模型。通过生物信息学分析，筛选得到卵巢癌预后相关的基因群，共236个基因。筛选得到调控基因数超过20个的基因共112个。结论通过该模型可以用直观的数字反映各因素对预后的影响程度和用患者各项因素总评分来判断患者的3年和5年生存概率，使综合判断患者预后的工作得以简化，对于临床工作有一定意义。利用生物学信息学分析卵巢癌基因表达谱芯片，为未来医学研究提供了从基因组水平进行研究的思路和方法学上的摸索。     

Adjuvant chemotherapy as treatment of high-risk stage I and II endometrial cancer

OBJECTIVE: This study was performed to define the subgroups of patients who benefit from postoperative adjuvant chemotherapy in stage I and II endometrial carcinoma. METHODS: A retrospective review of 170 International Federation of Gynecology and Obstetrics (FIGO) stage I and II endometrial carcinoma patients treated between 1988 and 2000 at Niigata University Hospital was performed. All patients underwent surgery, of which 41 patients underwent adjuvant chemotherapy, consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. RESULTS: The patients were divided into low-risk and high-risk groups based on the number of prognostic factors (tumor grade G3, outer half myometrial invasion, lymph-vascular space involvement (LVSI), and cervical invasion). The 5-year disease-free survival and the 5-year overall survival for the low-risk group were 97.4%, and 100%, respectively, which were significantly better than 77.4% and 88.1% for the high-risk group (P < 0.0001, P < 0.0001), respectively. Among high-risk group patients, the 5-year disease-free survival and the 5-year overall survival were 88.5% and 95.2% in 26 patients treated with adjuvant chemotherapy, and 50.0% and 62.5% in eight cases who underwent only surgery (P = 0.0150, P = 0.0226). Disease recurrence occurred in 7 (20.6%) of 34 high-risk group patients. Four of seven recurrences occurred in patients who did not receive postoperative chemotherapy, in which all four were distant failure. In the remaining three patients who were in the CAP group, two had vaginal wall recurrence and only one had pulmonary recurrence. Three recurrences were also observed in the 133 low-risk group patients. Only isolated vaginal wall recurrence occurred in three patients without adjuvant chemotherapy after the initial surgery. CONCLUSIONS: There is possibility that postoperative adjuvant CAP may be omitted in surgical stage I or II endometrial cancer patients with 0 or 1 prognostic factor. The high-risk group of patients should be treated with postoperative adjuvant CAP to decrease distant failure and improve prognosis.     

Stage III endometrial cancer: analysis of prognostic factors and failure patterns after adjuvant chemotherapy

OBJECTIVE: This study was performed to assess the prognostic factors and patterns of recurrence in stage III endometrial carcinoma treated with surgery and adjuvant chemotherapy. METHODS: A retrospective review of 61 stage III endometrial carcinoma patients treated between 1988 and 1998 at Niigata University Hospital was performed. All patients underwent surgery, followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. RESULTS: The 5-year disease-free survival was 78.6%. Multivariate analysis revealed deep myometrial invasion and lymph-vascular space involvement correlated significantly with disease-free survival. Based on these two factors, the patients could be divided into low-risk and high-risk groups. The 5-year disease-free survival for the low-risk group was 100%, which was significantly better than the 59.1% for the high-risk group. Disease recurrence occurred in 13 of 30 high-risk patients, and there was no recurrence in the 31 low-risk patients. Looking at the patterns of recurrence for the high-risk group by lymph node metastasis, 5 recurrences were locoregional, 1 was locoregional/distant, and 1 was distant in 16 node-positive high-risk patients. In 14 node-negative patients, 5 had distant and 1 had locoregional/distant recurrences. CONCLUSIONS: The locoregional failure in the node-positive high-risk group deserves further attention. For improvement of locoregional control, it may be worthwhile to consider new strategies. The role of new adjuvant chemotherapy should be investigated to control distant failure in node-negative high-risk patients.     

Diagnosis and management of gestational trophoblastic neoplasia

The FIGO Committee Report on the FIGO 2000 staging for gestational trophoblastic disease included criteria for the diagnosis of gestational trophoblastic neoplasia (GTN). It recommended investigative tools for diagnosing metastases. Anatomical and prognostic indicators were combined into a stage : risk score to stratify patients into low and high-risk groups. This is the first staging system to incorporate inclusive criteria that are likely to be adopted universally. The diagnostic evaluation of GTN is presented. The rationale of using the various investigative tools is discussed. The problem of measuring human chorionic gonadotrophin (hCG) levels using commercial kits and the phenomenon of 'phantom hCG' is explored. The use of single agent chemotherapy for low-risk disease versus multi-agent chemotherapy for high-risk disease is discussed. Controversies regarding when to stop chemotherapy are explored with a view to minimizing the short and long-term toxicity, in particular the small risk of developing a second malignancy. Recommendations for the follow up of patients after chemotherapy with particular reference to contraceptive advice and future pregnancies are discussed in the light of current evidence.     

术后化疗对有高危因素的早期子宫内膜癌患者预后的影响

目的 探讨术后化疗对有高危因素的早期(Ⅰ、Ⅱ期)子宫内膜癌患者预后的影响.方法 选择1994年1月-2007年6月间,北京大学第一医院妇产科收治的66例有高危因素的早期子宫内膜癌且术后均辅以化疗的患者(化疗组),40例相同期别及相同高危因素但术后未予化疗者作为对照组,Kaplan-Meier法计算两组患者的5年累积生存率,并进行比较;对有高危因素的早期子宫内膜癌患者的预后影响因素进行单因素及多因素分析.结果化疗组患者的5年累积生存率为94%,对照组为81%,化疗组明显高于对照组(P<0.05).单因素分析显示,化疗组中≥4个疗程患者的5年累积生存率为100%,<4个疗程患者的5年累积生存率为86%,两者比较,差异有统计学意义(P<0.05);而不同年龄、手术病理分期、病理类型、病理分化程度及术后有无放疗、术后化疗后是否联合放疗、有无孕激素治疗患者间比较,差异均无统计学意义(P>0.05).多因素分析显示,术后化疗是影响有高危因素的早期子宫内膜癌患者预后的独立因素(P<0.05).结论术后化疗可改善有高危因素的早期子宫内膜癌患者的预后,且疗程数应≥4个,但因例数较少,需通过前瞻性随机对照研究的进一步证实.     

Vinblastine, cisplatin and bleomycin as salvage therapy for refractory high-risk metastatic gestational trophoblastic disease

Vinblastine, cisplatin and bleomycin (VPB) were utilized as salvage therapy in seven women with high-risk metastatic gestational trophoblastic tumors resistant to prior treatment with triple therapy (methotrexate, actinomycin D and cyclophosphamide) or the modified Bagshawe protocol. While four patients (57%) achieved sustained remission with VPB, surgery was performed on two of them to remove sites of resistant disease. The mean prognostic score for the patients who achieved remission was 10 versus 17 for those who died (P less than .05). Although severe hematologic toxicity occurred in five patients (71%), no deaths were attributable to toxicity. Since VPB has limited activity when used as salvage therapy, alternate chemotherapy protocols need to be developed for patients with refractory gestational trophoblastic disease.     

The lack of significance of Ca125 response in epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking

OBJECTIVES: To examine the prognostic significance of Ca125 response to neoadjuvant chemotherapy and delayed primary surgical debulking in epithelial ovarian cancer patients. METHODS: Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Ca125 response was defined as being a decrease of at least 50% from baseline assessment. Ca125 response was assessed in two phases: prior to surgical debulking to reflect the response to neoadjuvant chemotherapy and at the end of primary chemotherapy to assess the response to debulking surgery and further chemotherapy. Cox proportional hazard models were built to model progression-free intervals using predictor variables of: age, cancer stage, tumour grade, residual disease, and Ca125 response. RESULTS: Ninety-one patients were included. About 83% had a positive Ca125 response following three cycles of neoadjuvant chemotherapy preoperatively. Cox regressions revealed two significant predictive variables of prolonged time to first progression: younger age (p=0.002) and microscopic residual disease compared to suboptimal residual disease (p=0.003). Ca125 response to neoadjuvant chemotherapy was not significantly predictive of progression-free survivals. The estimated median survival was 71.42 months (95% CI: 44.34-78.50) in patients with >50% Ca125 decrease from surgery and further chemotherapy whereas in those with no response, the corresponding survival estimate was 44.02 months (95% CI: 33.26-54.79). CONCLUSION: The lack of Ca125 response from neoadjuvant chemotherapy is not an independent prognostic factor. All patients treated with neoadjuvant chemotherapy should undergo radical debulking surgery.     

Changes in the histocytological grading of epithelial ovarian carcinoma following treatment

Although the microscopic grade of epithelial ovarian carcinoma is recognized as an important prognostic factor, the grading systems are still controversial. A cytohistological grading system is described using the sum of the scores (from 1 to 4) of eight histological and cytological features. This grading is applied to the initial surgical specimens of 37 patients seen at UCLA Center for the Health Sciences; it is also used for evaluation of pathologic specimens obtained at subsequent laparotomies. The evolution of the score at subsequent laparotomies (stable, increasing, or decreasing) is correlated with the type of therapy, response to treatment, and prognosis. An increasing score at the second-look laparotomy is a poor prognostic factor with a significantly shorter patient survival (p less than 0.05). The tumor score at second-look laparotomy is significantly increased in cases of macroscopically positive operation (p less than 0.05) and tumor progression (p less than 0.001). The type of therapy has no significant effect on the tumor score. A multivariate analysis shows that a decreasing score is related to a lower mitotic activity. Conversely, an increasing score is related to a change in tumor pattern. This study demonstrates the prognostic value of our grading system, which needs to be further validated by prospective studies.