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J S Berek

Publications and source records attributed to J S Berek.

At least 19 recordsLinked to original sources
PubMed2006

Ovarian cancer in younger vs older women: a population-based analysis.

To compare the clinico-pathologic prognostic factors and survival of younger vs older women diagnosed with epithelial ovarian cancer. Demographic, clinico-pathologic, treatment, and surgery information were obtained from patients with ovarian cancer from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001 and analysed using Kaplan-Meier estimates. Of 28 165 patients, 400 were <30 years (very young), 11 601 were 30-60 (young), and 16 164 were >60 (older) years of age. Of the very young, young, and older patients, 261 (65.3%), 4664 (40.2%), and 3643 (22.5%) had stage I-II disease, respectively (P<0.001). Across all stages, very young women had a significant survival advantage over the young and older groups with 5-year disease-specific survival estimates at 78.8% vs 58.8 and 35.3%, respectively (P<0.001). This survival difference between the age groups persists even after adjusting for race, stage, grade, and surgical treatment. Reproductive age (16-40 years) women with stage I-II epithelial ovarian cancer who received uterine-sparing procedures had similar survivals compared to those who underwent standard surgery (93.3% vs 91.5%, P=0.26). Younger women with epithelial ovarian cancer have a survival advantage compared to older patients.

Adenocarcinoma, Clear Cell↗
PubMed2001

Advances in the management of epithelial ovarian cancer.

More than 23,400 new cases of ovarian cancer and 13,900 deaths are expected in the United States this year. Epithelial ovarian cancer is the most common histologic type of ovarian malignancy. Although there have been advances in the chemotherapeutic treatment of ovarian cancer, the five year survival of women with advanced-stage disease is 25-30%. Because the disease is typically asymptomatic until the disease has metastasized and because effective screening strategies are not unavailable, 70-75% of women present with advanced-stage disease. Of ovarian cancer cases, 90-95% are sporadic and 5-10% associated with germ-line mutations, including BRCA1 and BRCA2. Known risk factors for ovarian cancer include nulliparity and a strong family history of ovarian cancer. The use of oral contraceptives is known to decrease the risk of ovarian cancer: five years of use will decrease the risk by 50%. The staging of ovarian cancer (according to the International Federation of Obstetrics and Gynecology) requires surgical exploration. Determining the extent of disease is essential to appropriate management. Survival in patients with metastatic disease is improved in those who undergo optimal primary cytoreductive surgery. Adjuvant chemotherapy is recommended in patients with high-risk, early-stage disease and all patients with advanced-stage disease. Standard chemotherapy is a combination of paclitaxel and carboplatin. Selected patients with recurrent disease can undergo secondary cytoreductive surgery. Second-line chemotherapy for patients who initially respond to paclitaxel and carboplatin and who have a prolonged disease progression-free intervals (longer than 12 months) can be re-treated with either drug or both. Those whose responses to initial therapy were less successful can be treated with other chemotherapeutic agents--e.g., liposomal doxorubicin, topotecan, etoposide, gemcitabine or taxotere.

Aged↗
PubMed2000

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Adult↗
PubMed1999

IL-2 plasmid therapy of murine ovarian carcinoma inhibits the growth of tumor ascites and alters its cytokine profile.

We have evaluated whether i.p. murine ovarian tumors could be treated with an IL-2 plasmid DNA complexed with the cationic lipid, (+/-)-N-(2-hydroxyethyl)-N,N-dimethyl-2, 3-bis(tetradecyloxy)-1-propanaminium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). Reporter gene studies were initially conducted in which mice bearing i.p. murine ovarian teratocarcinoma (MOT) were injected i.p. with reporter gene plasmid DNA (pDNA):DMRIE/DOPE. Histochemical analyses revealed that transfection occurred primarily in the tumor cells of the ascites, with only a minority of other ascitic cells or surrounding tissues transfected. IL-2 levels in the MOT ascites were determined after i. p. injection of either IL-2 pDNA:DMRIE/DOPE or recombinant IL-2 protein. IL-2 was detected in tumor ascites for up to 10 days after a single i.p. injection of IL-2 pDNA:DMRIE/DOPE, but was undetectable 24 h after a single i.p. injection of IL-2 protein. In an antitumor efficacy study, MOT tumor-bearing mice injected i.p. with IL-2 pDNA:DMRIE/DOPE on days 5, 8, and 11 after tumor cell implant had a significant inhibition of tumor ascites (p = 0.001) as well as a significant increase in survival (p = 0.008). A cytokine profile of the MOT tumor ascites revealed that mice treated with IL-2 pDNA:DMRIE/DOPE had an IL-2-specific increase in the levels of IFN-gamma and GM-CSF. Taken together, these findings indicate that i. p. treatment of ovarian tumors with IL-2 pDNA:DMRIE/DOPE can lead to an increase in local IL-2 levels, a change in the cytokine profile of the tumor ascites, and a significant antitumor effect.

Animals↗
PubMed1999

Intraperitoneal alpha-interferon alternating with cisplatin in residual ovarian carcinoma: a phase II Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study was to study the combination of intraperitoneal alpha-interferon and cisplatin administered second-line in an alternating sequence in small volume residual epithelial ovarian cancer after second-look surgery and the activity of this combination based on prior response to first-line platinum compounds. METHODS: Sixty-two patients with minimal residual (<0.5 cm) epithelial ovarian cancer at reassessment laparotomy were entered into a multicenter trial of intraperitoneal alpha-interferon alternating with cisplatin given for eight cycles unless disease progression or unacceptable toxicity occurred. The patients were considered favorable if they were platinum-sensitive and/or relapsed 6 months or longer after completing treatment. Another reassessment laparotomy was performed within 12 weeks of completion of treatment in patients who were in clinical remission. RESULTS: Fifty-four patients were clinically evaluable and 18 were surgically reassessed, 5 of whom had a negative reassessment operation (20% complete response and 8% partial response). Of the 54 patients evaluable for toxicity, the most common adverse effects of more than grade 2 were gastrointestinal in 13 (47%), neutropenia in 9 (17%), and leukopenia in 6 (12%). Grade 4 toxicity was seen in 10 instances: 4 gastrointestinal, 2 neutropenia, 2 thrombocytopenia, 1 wound infection, and 1 allergic reaction. CONCLUSIONS: alpha-Interferon and cisplatin are active agents in favorable patients with minimal residual epithelial ovarian cancer at second-look. The combination of the two drugs administered in an alternating sequence appears to be associated with more side effects than when either drug is administered alone. The combination produced response rates similar to those seen when either drug is given alone.

Adult↗
PubMed1999

Intraperitoneal interferon-alpha in residual ovarian carcinoma: a phase II gynecologic oncology group study.

OBJECTIVE: The purpose of this study was to confirm the activity of interferon-alpha intraperitoneally in minimal residual epithelial ovarian cancer in a Phase II multi-institutional trial and to investigate the activity of the agent based on prior response to first-line platinum compounds. METHODS: Ninety-two patients with minimal residual (<0.5 cm) epithelial ovarian cancer at reassessment laparotomy were entered into a multicenter trial of intraperitoneal interferon-alpha given for 12 cycles unless disease progression or unacceptable toxicity occurred first. Patients were considered favorable if they were platinum sensitive and/or relapsed 6 months or longer after completing treatment and unfavorable if they were platinum insensitive and/or relapsed shorter than 6 months after completing treatment and/or had stable or progressive disease during initial therapy. A third-look laparotomy was performed within 12 weeks of completion of treatment in those patients who were in clinical remission. RESULTS: Eighty patients were clinically evaluable for toxicity only (48 favorable, 32 unfavorable) and 46 of them were evaluable for response, of whom 25 were favorable (platinum sensitive) and 21 unfavorable (platinum resistant). In the favorable group, there was a 28% surgically documented response rate (7/25 patients): 16% (4/25) had complete responses (negative reassessment operation), 12% (3/25) had partial responses, 32% (8/25) were nonresponders, and 40% (10 patients) developed progressive disease before planned reassessment operation. In the unfavorable group, there were no responding patients: 6 were nonresponders at reassessment operation and 15 developed progressive disease before planned reassessment operation. Of the 80 patients evaluable for toxicity, the most common adverse effects that were more than grade 2 were gastrointestinal (12; 15%), fever (8; 10%), neutropenia (7;9%), and leukopenia (6; 8%). Grade 4 toxicity was seen in 5 patients; each had fever and gastrointestinal toxicity, and 1 each had neutropenia and thrombocytopenia. CONCLUSIONS: Interferon-alpha is an active and generally well-tolerated agent in favorable patients with minimal residual epithelial ovarian cancer at second-look surgery. These results are comparable to those achieved with cytotoxic chemotherapy. If Phase III trials are considered in the patients with minimal residual ovarian cancer, they should be limited to the platinum-sensitive patient population.

Adult↗
PubMed1999

Advanced epithelial ovarian cancer: 1998 consensus statements.

BACKGROUND: During an international workshop held in September 1998, a group of specialists in the field of ovarian cancer reached consensus on a number of issues with implications for standard practice and for research of advanced epithelial ovarian cancer. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, initial chemotherapy, second-line treatment, the use of CA 125, investigational drugs, intra-peritoneal treatment and high-dose chemotherapy. The group attempted to arrive at answers to questions such as: Are there prognostic factors, which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? These issues were discussed in a plenary meeting. RESULTS: One of the major conclusions drawn by the consensus committee was that in previously untreated advanced ovarian cancer, cisplatin plus paclitaxel has been shown to be superior to previous standard therapy with cisplatin plus cyclophosphamide (level I evidence). However, for many patients, carboplatin plus paclitaxel is a reasonable alternative because of toxicity and convenience considerations. Most participants felt that the benefits in terms of toxicity for the paclitaxel-carboplatin are such that its widespread adoption at this stage is justified. Until mature survival data are available a minority of investigators would recommend continued use of cisplatin plus paclitaxel, specifically for those patients with advanced disease with the best prognostic characteristics. For future clinical research in this area, new end points for randomised clinical trials, together with a new Trials Network, are proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Surgery during chemotherapy and at relapse of ovarian cancer.

During chemotherapy and after relapse several types of operations are used in ovarian cancer: secondary cytoreductive surgery, interval cytoreductive surgery, second-look surgery, and palliative secondary surgery. The role of these operations has been difficult to define because there is considerable variation in the patterns of behaviour of tumours among those with persistent or recurrent disease. The definitions, indications and impact of these procedures are reviewed.

Female↗
PubMed1999

Basic research: how much do we know, and what are we likely to learn about ovarian cancer in the near future?

The scientific community, which studies ovarian cancer in the laboratory, is making progress in understanding many aspects of the disease. At present there is evidence that the cancer prone ovary has a preneoplastic phenotype. These genetic changes may constitute a surrogate intermediate end-point biomarker of cancer risk, which might be altered by preventive measures. Studies that aim at understanding the genetic basis of the disease are reviewed. Many of these studies use clinical ovarian cancer samples. To augment study of clinical specimens, an experimental system has been developed where malignancy is induced in the rat ovarian surface epithelium (ROSE). This system markedly facilitates examination of how genes fit into the ovarian cancer puzzle. The problem of drug resistance in ovarian cancer has received considerable attention. Although the functional changes responsible for resistance have been identified there has been little progress in identifying the actual genes capable of conferring the substantial resistance seen in cell lines.

Animals↗
PubMed1999

Endometrial cancer: recent developments in evaluation and treatment.

Endometrial carcinoma is the most common gynecologic malignancy in the United States. Most cases are diagnosed at an early stage. However, the outcome for women diagnosed with advanced-stage disease remains poor. The etiology of most endometrial carcinomas stems from the effects of excess estrogen, whether this comes from exogenous or endogenous sources. Differences in epidemiology and presentation suggest the existence of two forms of endometrial cancer: those related to and those unrelated to hormonal stimulation. Most women with endometrial cancer present with abnormal uterine bleeding; endometrial sampling is essential to exclude endometrial carcinoma in such patients. Endometrial cancer is surgically staged, and staging usually includes a hysterectomy and bilateral salpingooophorectomy. Lymphadenectomy also should be performed in selective cases to better assess disease spread and to evaluate the need for adjuvant therapy. Adjuvant treatment may include the use of radiation, progestins, or cytotoxic chemotherapeutic agents. Several clinical trials are underway to compare these treatment modalities, as well as to determine the optimal combination of active chemotherapeutic agents, such as doxorubicin, platinum agents, and paclitaxel (Taxol).

Endometrial Neoplasms↗
PubMed1998

Combination of transforming growth factor beta antisense and interleukin-2 gene therapy in the murine ovarian teratoma model.

The immunosuppressive protein transforming growth factor beta (TGF-beta) inhibits the activation of various immune effector cells including cytotoxic T lymphocytes and may therefore inhibit the efficacy of immunostimulatory interleukin-2 (IL-2) gene therapy. In this study, we investigated the effect of TGF-beta downregulation on IL-2 gene therapy in the intraperitoneal model of murine ovarian teratoma (MOT). MOT cells, like many human ovarian carcinomas, were found to produce TGF-beta. Production of TGF-beta by MOT cells was suppressed using a TGF-beta antisense plasmid vector (pCEP4/TGF-beta antisense). Subcutaneous immunization of C3H mice with a mixture of IL-2 gene-transduced fibroblasts and TGF-beta antisense-modified MOT cells induced significantly better protection against a subsequent intraperitoneal tumor challenge compared with immunization with unmodified MOT cells alone [11/16 (69%) vs 4/21 (19%) tumor-free animals, P < 0.01]. Immunization with either a mixture of IL-2 gene modified fibroblasts and unmodified MOT cells [2/12 (17%) tumor-free animals] or TGF-beta antisense-modified MOT cells alone (0/13 tumor free animals) failed to induce significant protection compared with immunization with unmodified MOT cells. These data show that combined TGF-beta antisense and IL-2 gene therapy is required to generate effective antitumor responses in the MOT model. Our findings suggest that tumor cell expression of immunosuppressive factors may inhibit cytokine immunogene therapy and may have potential implications for the development of future clinical immunogene therapy protocols.

3T3 Cells↗
PubMed1998

A phase II study of intraperitoneal cisplatin and thiotepa in residual ovarian carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: Patients with advanced epithelial ovarian cancer treated with salvage therapy using new combinations of systemic chemotherapy, radiation therapy, and systemic immunotherapy have had limited success. Since the most common site of relapse or failure to conventional systemic chemotherapy has been the peritoneal cavity, intraperitoneal (IP) chemotherapy was selected to treat small-volume residual disease. METHODS: Sixty-five patients were entered on a protocol using intraperitoneal cisplatin and thiotepa following a response to intravenous cisplatin-based chemotherapy. Patients had surgically documented residual disease (0.5 cm or less maximum tumor diameter) at completion of preprotocol surgery and had no clinical, radiologic, or histologic evidence of extraperitoneal disease. Cisplatin (100 mg/m2) and thiotepa 30 mg/m2 was delivered intraperitoneally every 4 weeks for a maximum of six cycles. The dose of thiotepa was reduced to 12 mg/m2 due to unexpected severe myelosuppression. RESULTS: Of the 52 evaluable patients, grade 4 neutropenia, thrombocytopenia, neurotoxicity, and nephrotoxicity were observed in 31, 19, 13, and 6% of patients, respectively. For all evaluable patients, the complete response rate was 19% and the partial response rate was 2% for a total response rate of 21%. Of 16 patients who had a reassessment laparotomy, 10 patients achieved a surgically documented complete response and 1 patient had a partial response. Four patients are still in response for 67+, 70+, 70+, and 73+ months after third-look surgery. Three patients who did not undergo third-look surgery after chemotherapy are alive and clinically free of disease at 49+, 69+, and 85+ months. CONCLUSION: Thiotepa, when used with cisplatin for IP salvage therapy in patients with advanced or recurrent ovarian cancer, may produce significant myelosuppression and doses must be adjusted accordingly. In cisplatin-sensitive patients with small-volume residual ovarian cancer, IP cisplatin and thiotepa appears to have activity. Determining the utility of this approach will require a randomized trial.

Adult↗
PubMed1998

Diagnostic and therapeutic advances in gynecologic oncology: screening for gynecologic cancer.

Endometrial carcinoma is associated with a good prognosis because patients tend to present with early disease. Mass screening is therefore unlikely to be of benefit. High-risk populations may benefit from screening, but no prospective studies have demonstrated a benefit in any population. The most promising modality for screening appears to be TVS, and a normal TVS may also preclude the need for further evaluation of symptomatic patients. The appropriate use of TVS in patients on tamoxifen is currently unknown. Hysteroscopy and endometrial biopsy may have a role in the evaluation of symptomatic patients but do not appear promising as screening modalities.

Biomarkers, Tumor↗
PubMed1998

Psammocarcinoma with an aggressive course.

BACKGROUND: Psammocarcinoma is an unusual variant of serous cystadenocarcinoma characterized by heavy deposits of psammoma bodies. This disease has been suggested to be similar to carcinomas of low malignant potential in its indolent clinical course. We present this case report of an aggressive course of this disease to alert others that psammocarcinoma may not always follow a benign course. CASE: A 66-year-old woman underwent staging laparotomy for bilateral ovarian cystadenofibromata with rare foci of borderline serous tumors and several small bowel peritoneal surface nodules showing infiltrating psammocarcinoma. She was not recommended for adjuvant therapy because of the previously reported indolent course of this disease. Eighteen months later she represented with small bowel obstruction and underwent an exploratory laparotomy that demonstrated diffuse recurrence of the psammocarcinoma. CONCLUSION: Psammocarcinoma may have a more aggressive course than has been suggested. Patients with this disease should have optimal tumor debulking. There may be a role for adjuvant therapy in its treatment.

Aged↗