Prognostic factors for survival in stage I epithelial ovarian carcinoma

In a retrospective analysis prognostic factors were studied in 204 patients with primary Stage I epithelial ovarian carcinoma (borderline tumors were excluded) treated between 1975 and 1987. Only histologic grade (P = 0.01) and kind of surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy +/- omentectomy versus unilateral salpingo-oophorectomy, P = 0.02) were found to have a significant influence on survival prognosis (Cox model). All other factors (age, the International Federation of Gynecology and Obstetrics [FIGO] stage, integrity of the capsule, unilaterality versus bilaterality, and histology) were of no prognostic importance. Unilateral salpingo-oophorectomy without any additional staging reduces five-year survival probability (62% versus 84%). Therefore this kind of operation should be abandoned. Furthermore, histologic grade should be a stratification criterion in studies, which will be necessary for proving the value of adjuvant therapy in Stage I epithelial ovarian carcinoma.     

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.     

Stage I epithelial ovarian tumors of low malignant potential

Clinical and pathological details of 10 patients with stage I low malignant potential tumors of the ovary, between September, 1969, and February, 1988, have been reviewed. The mean age of the patients was 46.6 years. Six patients had serous and four had mucinous tumors. Of the 10 patients, five had a unilateral salpingo-oophorectomy, one had a bilateral salpingo-oophorectomy and four a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The mean duration of follow-up was 12.8 years. All patients have remained alive and disease-free. A recurrence occurred in one patient who has been managed well by additional surgery. Stage I ovarian tumor of low malignant potential appears to carry a favorable prognosis.     

Treatment Outcomes of Epithelial Ovarian Cancers Following Maximum Cytoreduction and Adjuvant Paclitaxel-Carboplatin Chemotherapy: Egyptian NCI Experience

Background: Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximumsurgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of caretreatments. Aims: To study treatment outcomes of EOC patients that were maximally cyto-reduced and receivedadjuvant paclitaxel-carboplatin (PC) chemotherapy. Materials and Methods: This retrospective cohort studyincluded 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. Forinclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy.MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingooophorectomy[USO] plus comprehensive staging. Results: The median age was 50 years. Most patients weremarried (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic painand swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I(55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles.Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. Therespective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associatedwith poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression,stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS.     

Transitional cell carcinoma in high-grade high-stage ovarian carcinoma. An indicator of favorable response to chemotherapy

We reviewed 53 high-grade carcinomas of the ovary in order to define pathologic features that correlate with prognosis. All tumors were Stage III with comparable amounts of residual tumor left after the primary resection. Similar postoperative chemotherapeutic regimens were given to each patient, and there was a clinical followup of at least four years in each case. The tumors were classified according to their predominant (greater than 50%) histology as transitional cell carcinoma (TCC) (18 tumors), papillary serous (18), undifferentiated (8), or endometrioid (3). There were six mixed carcinomas without predominant histology. In 17 of 18 patients, TCC predominant tumors responded completely to chemotherapy and 15 of 18 patients (83%) are alive without disease 4 to 10 years after presentation (average 6.8 years). In comparison, tumor progression/recurrence developed in 31 of 35 non-TCC tumors (18 serous, eight undifferentiated, one endometrioid predominant, and four mixed carcinomas). Of these 35 patients, 27 (77%) died of disease from 6 months to 7 years after presentation (average 2.5 yrs.). Flow cytometric determination of DNA content and immunoperoxidase studies did not allow discrimination between the histologic types of high-grade ovarian carcinomas. We conclude that TCC should be recognized as a distinct histologic type of ovarian carcinoma because of the favorable response to chemotherapy and improved patient survival.     

Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide in the treatment of small cell carcinoma of the ovary

This report presents five adolescent girls and adult women with small cell carcinoma of the ovary (SCCO) who were treated with a polychemotherapy regimen consisting of vinblastine, cisplatin, cyclophosphamide, bleomycin, Adriamycin (doxorubicin), and etoposide (VPCBAE). Two patients had Stage IA, one Stage IIC, and two Stage IIIA disease. Initial therapy consisted of unilateral salpingo-oophorectomy in two cases and total abdominal hysterectomy and bilateral salpingo-oophorectomy in three cases. Three patients remained clinically free of disease after six courses of VPCBAE and the two patients who had measurable pelvic disease before the administration of chemotherapy had objective responses. Four patients died of disease from 11 to 18 months after initial laparotomy. One patient is alive and disease-free at 29 months. The VPCBAE combination appears to be effective in select cases of SCCO. A study of the efficacy of VPCBAE in a larger group of patients with SCCO seems to be indicated.     

Granulosa cell tumor of the ovary: A study of 18 cases

In a study of 18 patients diagnosed with ovarian granulosa cell tumor between 1961 and 1992, clinical and pathologic findings were evaluated. Of the 18 patients, 15 (83.3%) were diagnosed in Stage I and three (16.7%) in Stage III or IV. Six patients (33.3%) underwent conservative surgery and in 12 (66.7%) total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. At follow-up three patients (16.6%) had died of disease, three, 16 and 288 months, respectively, after initial surgery. The actuarial 5-year survival rate for Stage I was 100%, while that for Stages III and IV combined was 33.3% (P < 0.05). It is concluded that for patients with Stage IA, unilateral oophorectomy seems to be adequate treatment and for those with more than Stage IA, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy. Postoperative adjuvant chemotherapy is advocated for patients in whom spread of tumor beyond the ovaries has occurred. © Wiley-Liss, Inc.     

Ovarian Sertoli-Leydig cell tumor (androblastoma) with retiform pattern. A clinicopathologic study

The clinicopathologic findings in nine patients with ovarian Sertoli-Leydig cell tumor with retiform pattern are described. The patients ranged in age from 11 months to 23 years; and seven patients were 12 years of age or younger. The most frequent presenting sign was the finding of an abdominal mass. This was associated with pain in five patients. In three patients the pain was severe due to torsion, causing an acute abdominal emergency. Slight virilization was observed in one patient only. Two patients had elevated serum alphafetoprotein (AFP), which correlated well with disease activity. The remaining patients had normal serum AFP. All the tumors were unilateral. At laparotomy the tumor was intact in six patients and ruptured in three. The tumors ranged from 8 to 22 cm, were round or oval, and cystic or solid and cystic. Eight tumors were in FIGO Stage I, and one was associated with abdominal metastases and was Stage III. Histologically, the retiform component varied from moderate to predominant in eight of the nine cases. In two tumors a heterologous component composed of striated muscle was also present. Three patients developed metastases. Two of the patients died 11 months and 2 years after diagnosis and the third patient was lost to follow-up with evidence of disease 2 years after diagnosis. The remaining six patients were well and disease-free for periods of 8 months to 6 years. The majority of these tumors were misinterpreted as serous papillary cystadenocarcinoma or endodermal sinus tumor, which are more malignant neoplasms requiring different therapy. This further underlines the importance of recognizing this histopathologic entity.     

Borderline epithelial ovarian tumors: a review of 81 cases with an assessment of the impact of treatment.

Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.     

Ovarian epithelial tumors of borderline malignancy. A clinical and pathologic study of 109 cases

One hundred nine cases of ovarian tumors of low malignant potential (borderline tumors) diagnosed at Stanford University Medical Center from 1958 to 1982 were reviewed. The patients ranged in age from 10 to 79 years (mean, 40.5 years). The histologic types and corresponding stages of these neoplasms were 73 serous (Stage IA: 35 patients; Stage IB+C: 16 patients; stage II: 8 patients; Stage III: 14 patients), 30 mucinous (Stage IA: 27 patients; Stage IB+C: 3 patients), and 6 mixed seromucinous (all Stage IA). Borderline endometrioid, clear cell, and Brenner tumors were excluded. Follow-up information from 3 to 27 years from the time of initial diagnosis (mean, 7.6 years; median, 7.1 years) revealed that 89 patients are alive without further evidence of neoplasm, and three patients died of unrelated disease without recurrent tumor. Seventeen patients have developed persistent or recurrent neoplasms in the contralateral ovary (six patients) and/or elsewhere within the peritoneal cavity (15 patients) at 5 to 226 months (mean, 61 months) after the initial excision. All of the second neoplasms were borderline serous or seromucinous tumors histologically identical to the original tumor; none of the borderline mucinous tumors recurred. Patients who initially had Stage III borderline serous tumors developed persistent or recurrent neoplasms more commonly (64%) than did patients with lower stage tumors (12%). No correlation was found between the development of a subsequent serous neoplasm and patient age, the primary tumor size, or any single histologic feature. Following treatment of the subsequent neoplasms, 13 patients are free of neoplasm, one patient is alive with tumor, one patient has died of intercurrent disease with tumor, and two patients have died with widespread abdominal tumor 53 and 232 months after their initial diagnosis. These findings confirm the excellent prognosis for patients with borderline serous tumors, despite involvement of the peritoneal cavity and the development of recrudescent tumor, although long-term follow-up is indicated. Mucinous borderline tumors, as defined by published criteria, almost invariably present as localized (low-stage) tumors and, in our experience, do not recur when confined to the ovary.     

Small carcinoma of the pancreas. Clinical and pathologic evaluation of 17 patients

The clinical and pathologic characteristics of 17 small carcinomas (less than 2 cm in diameter) of the pancreas are reviewed in this article. All the tumors were located in the head of the pancreas, and the clue to the diagnosis was jaundice in ten patients and abdominal pain in seven. Carcinoembryonic antigen (CEA) and CA 19-9 were not reliable markers for detecting small carcinomas of the pancreas. Ultrasonography (US), computerized tomography (CT), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP) were useful diagnostic tools. Lymph node metastases were found in 41% of affected patients, capsular invasion in 24%, retroperitoneal invasion in 24%, and portal system involvement in 29%. In five patients the carcinoma was Stage I; in eight patients, Stage II; in two patients, Stage III, and in two patients, Stage IV. Fifteen patients with Stages I to III and one patient with Stage IV underwent curative pancreaticoduodenectomy or total pancreatectomy, and one patient with liver metastasis and Stage IV underwent noncurative pancreaticoduodenectomy. The cumulative 4-year survival rate was 37%. Although four patients with Stage I disease lived for more than 48 months, the survival period of the 12 patients with Stages II to IV disease was less than 25 months. Thus, small carcinoma of the pancreas is not always curable; however, a small, localized lesion without any extratumoral extension can be resected with a chance of cure.     

Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vincristine, dactinomycin, and cyclophosphamide

Eighty patients with malignant nondysgerminomatous germ cell tumors of the ovary were treated with the combination of vincristine, dactinomycin, and cyclophosphamide (VAC) at The University of Texas M.D. Anderson Hospital and Tumor Institute. All patients underwent initial surgery: biopsy alone in 3 patients, unilateral salpingo-oophorectomy in 48 patients, and bilateral salpingo-oophorectomy with or without hysterectomy in 29 patients. Sixty-six patients received VAC as primary postoperative therapy; 46 patients (70%) achieved a sustained remission. VAC produced sustained remission in 86% of patients with Stage I, 57% of patients with Stage II, 50% of patients with Stage III, and no patients with Stage IV disease. For patients with Stage I disease, survival rates did not differ among histologic groups, but in advanced disease, patients with immature teratoma did significantly better than the others. Four of the 20 patients who failed primary VAC therapy were salvaged with other therapies, and 8 of 14 treated with VAC after relapse or failure of other treatments were salvaged. Although VAC produces excellent results with very acceptable toxicity in patients with Stage I disease and advanced immature teratoma, survival of patients with other advanced histologic types has been disappointing. The authors are therefore treating this latter group with alternative therapy such as vinblastine, bleomycin, and cisplatin with the goal of achieving improved efficacy.     

Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases.

The clinical and pathologic features of 71 endodermal sinus tumors of the ovary were studied in an effort to delineate the histogenesis and biologic behavior of this neoplasm and to evaluate the efficacy of different forms of treatment. Alpha-fetoprotein (AFP) was identified in hyaline droplets, cell cytoplasm, and intercellular spaces of all 15 tumors examined by an immunoperoxidase technique; this supports the view that the neoplasm simulates yolk sac endoderm. There were only nine survivors among 65 patients on whom follow-up information was available; the actuarial survival was 13% at 3 years. Of the neoplasms that recurred, 93% did so within 1 year, and of those patients who died, 93% did so within 2 years. The size and stage of the tumor had prognostic significance, but the patient's age, the mitotic activity, and histologic pattern did not. Although 71% of the patients had Stage I tumors at the time of diagnosis, subclinical metastasis was present in 84% of Stage I patients. Triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide (VAC)) employed after unilateral salpingo-oophorectomy in four patients with Stage I tumors resultivors among 12 Stage I patients treated with combined surgery and radiation. The finding of AFP in all tumors in which this was evaluated suggests that serum radioimmunoassay might be useful to monitor response to therapy.     

Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases

BACKGROUND: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy. RESULTS: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring.     

A randomized study of two doses of abdominopelvic radiation therapy for patients with optimally debulked stage I,II, and III ovarian cancer

Purpose: To determine whether an increased dose of abdominal radiation therapy results in improved disease control and survival in patients with early ovarian cancer.Methods and Patients: Between 1981 and 1990, 125 patients with optimally debulked Stage I, II, and III ovarian cancer were entered into a prospective randomized clinical trial of abdominopelvic radiation therapy. Patients were stratified and randomized to either the control arm, treated with an abdominal dose of 22.5 Gy in 22 fractions, or the experimental arm of 27.5 Gy in 27 fractions. A pelvic boost dose of 22.5 Gy was used in both arms. There were 43 patients with Stage I tumors, 71 Stage II tumors, and 11 Stage III tumors. Nineteen patients had grade 1 histology, 77 grade 2, and 29 grade 3. Three patients had small-volume residual disease (<2 cm) in the pelvis alone and the remainder had no gross tumor following surgery. Median follow-up was 6.6 years (range 1.4–9.9).Results: Overall survival (OS) at 5 years was 83% in the low-dose arm and 72% in the high-dose arm (p = 0.3). Disease-free survival (DFS) at 5 years was 74% and 67% in the low-dose and high-dose arms, respectively (p = 0.5). The difference in OS between the two arms was −11%, with 95% confidence intervals of −26% (favoring low-dose treatment) to 4% (in favor of high dose). The difference in DFS was −7% (95% confidence interval, −23 to 9%). Failure in the pelvis alone predominated (n = 15); six patients had abdominal and pelvic failure and seven patients failed in the abdomen alone. There were no differences in patterns of relapse, hematologic toxicity, or late complications between the two arms. Serious bowel toxicity was seen in three patients: two in the low-dose and one in the high-dose arm. A Cox proportional hazards model was used to assess the effect of treatment when adjusting for other prognostic variables. Ascites (p = 0.03, relative risk 2.05) was the only significant covariate in predicting disease-free survival, but was not prognostic for overall survival.Conclusions: There was no difference in survival, tumor control, or toxicity between high-dose and low-dose abdominopelvic radiation therapy. High-dose abdominopelvic radiation therapy is unlikely to be associated with an increase in OS of more than 4% or DFS of more than 9%.     

Clinicopathological Features and Prognosis of Thai Women with Endometrioisis-Associated Ovarian Carcinoma

This study was undertaken to evaluate the clinical features and survival outcomes of ovarian cancer patients whohad associated pelvic endometrioisis. The medical records of 1076 patients with ovarian cancer treated at ChiangMai University Hospital between 1995 and 2005 were reviewed. Among of these patients, 37 (3.4%) had associatedpelvic endometriosis. The mean age of the patients was 44 years (25-62 years). The most common presenting signand symptom was an abdominal mass (12), followed by abdominal pain (10), abdominal distension (7), abnormaluterine bleeding (2). Twenty-one (56.8%) patients were nulliparous and 14 (37.8%) were single. The stage distributionwas stage I (24), stage II (4), stage III (4), and stage IV (1). Four patients had 2 primary carcinomas. The mostcommon histology of the 37 patients was clear cell carcinoma (17) followed by endometrioid carcinoma (11). Theestimated 5-year disease - free survival was 55.4%. In conclusion, most patients associated with endometriosisassociatedovarian carcinoma present with abdominal masses and pain. Clear cell CA is the most common histologyin ovarian cancer patients who have associated endometriosis. Three fourths of the patients are in stage I and havefavorable prognosis.     

Behaviour of ovarian tumors of low malignant potential treated with conservative surgery

Objective

Fertility-sparing surgery has been proposed for the treatment of borderline ovarian tumors. The aim of this study was to evaluate the outcome of patients submitted to cystectomy (CYS) compared with patients treated by unilateral salpingo-oophorectomy (USO) or bilateral salpingo-oophorectomy with/without total hysterectomy (radical surgery, RS).

Methods

We reviewed retrospectively the data of patients treated in 3 institutions for borderline ovarian tumors. One hundred and sixty-eight patients underwent laparoscopic or laparotomic surgical treatment from 1985 to 2006. Tumor recurrence rate, disease-free survival and site of recurrences were evaluated. Specific prognostic factors, such as stage, histology, micropapillary subtype, exophytic tumor growth, intraoperative spillage, endosalpingiosis, staging procedures, and route of surgery were analysed.

Results

Thirty-five patients underwent cystectomy, 50 unilateral salpingo-oopohorectomy, and 83 radical surgery. Twelve patients in the CYS group (34.3%), 10 in the USO group (20.0%), and 5 (6.0%) in RS group relapsed. Five-year progression-free survival (PFS) was 59.6%, 78.4%, and 93.5% in CYS, USO and RS groups, respectively. None of the relapsed patients died of disease.

Conclusions

Cystectomy is an effective surgical strategy for patients with borderline ovarian tumor. The higher risk of local relapses is not associated with a reduction in the overall survival. The procedure should be offered to young patients with bilateral tumors and to very young ones, considering the higher risk of local relapse.     

Survival analysis of clinical, pathologic, and genetic features in neuroblastoma presenting as locoregional disease

BACKGROUND: Locoregional neuroblastoma is a clinical subgroup characterized by the absence of distant metastasis (International Neuroblastoma Staging System Stages 1, 2, and 3). Although these patients generally have an excellent survival with minimal therapy, some do experience recurrence with lethal consequences. METHODS: To identify risk factors for disease progression, the authors performed a retrospective analysis of clinical (age and stage) and tumor biologic markers (histology, MYCN, DNA index, and allelic analysis of chromosomes 1p, 11q12-qter, and 14q12-q32) in 44 patients (10 Stage 1, 18 Stage 2, and 16 Stage 3). Allelic analysis was performed using polymorphic polymerase chain reaction markers in a semiautomated, fluorescent detection system. RESULTS: Sixteen patients (38%) were younger than 365 days at diagnosis. Seventeen of 39 tumors (43%) had unfavorable histology, 6 (13%) were MYCN amplified, 14 (31%) were diploid, 17 (38%) had 1p36 loss of heterozygosity (LOH), 11 (25%) had 1p22 LOH, 10 (22%) had 11q LOH, and 13 (29%) had 14q LOH. Seventeen patients (38%) progressed, including 6 who progressed to Stage 4 disease (13%). Sixteen patients with progressive disease received cytotoxic therapy. Thirty-seven patients are alive (84%) with a median follow-up of 51 months. By permutation log rank test, both MYCN amplification and diploidy were associated with overall survival (OS), but only diploidy was associated with progression free survival (PFS) and progression to Stage 4 disease. LOH of 1p36, 1p22, 11q, or 14q did not show correlation with either OS or PFS. CONCLUSIONS: Locoregional neuroblastoma tumors with diploid DNA index, regardless of other biologic features, have increased risk of local recurrence and Stage 4 progression.     

Incidence trends and survival of penile squamous cell carcinoma in the Netherlands

We examined trends in the incidence and mortality, and described the survival of patients with penile squamous cell carcinoma in the Netherlands between 1989 and 2006. On the basis of nationwide population‐based data, 3‐year moving average European age‐standardized incidence and 10‐year relative survival estimates were calculated. Penile squamous cell carcinomas were categorized according to stage grouping based on the TNM classification. In the 17‐year study period, 2000 primary penile cancers were diagnosed in the Netherlands of which 1883 (94%) were squamous cell carcinomas. Median age at diagnosis was 68 years. The majority of patients (57%) were diagnosed with localized tumors (Stage 0 or I). The percentage of missing disease characteristics increased with increasing age. The 3‐year moving average incidence rate of patients with penile squamous cell carcinoma increased significantly from 1.4 per 100,000 person‐years in 1989 to 1.5 in 2006 with an estimated annual percentage of change of 1.3%. Ten‐year relative survival of patients according to the different stage groups was 93% for Stage 0, 89% for Stage I, 81% for Stage II, the 9‐year survival was 50% for patients with Stage III disease and a 2‐year survival of 21% for patients was found for Stage IV disease. Our study shows that the incidence rate of penile squamous cell carcinoma in the Netherlands has increased slightly, especially the incidence of carcinomas in situ. Patients with Stage III and IV tumors have poor survival.     

Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988.

BACKGROUND. The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH). METHODS. Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation). RESULTS. The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases. CONCLUSIONS. For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.