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Biomedical subjects

J Rotmensch

Publications and source records attributed to J Rotmensch.

At least 37 records · Page 2Linked to original sources

Race and clinical outcome in endometrial carcinoma.

OBJECTIVE: To compare the outcomes of black and white women who have surgically staged endometrial carcinoma. METHODS: We retrospectively compared the clinicopathologic factors, socioeconomic status, treatments, and outcomes of 70 black and 302 white women who were treated for surgically staged endometrial carcinoma at our institution. RESULTS: Black women had higher-grade tumors, less favorable histologic findings, more comorbid illnesses, and lower socioeconomic indices. A nonsignificant trend was also seen toward more advanced-stage disease. The extent of surgical staging and types of adjuvant therapies were similar. On univariate analysis, black women had worse 5-year disease-free survival than white women (52.8% versus 75.2%; P = .001). Other significant factors included stage, grade, lymph node status, extension to the uterine serosa, cervical involvement, histology, adnexal involvement, lymphovascular invasion, myometrial invasion, positive peritoneal cytology, level of education, and household income. After controlling for pathologic and socioeconomic differences in multivariate analysis, race remained a significant prognostic factor (P = .008; hazard rate 2.0; 95% confidence interval 1.2, 3.5). CONCLUSION: In a large cohort of surgically staged and uniformly treated patients with endometrial carcinoma, black race was associated with significantly worse outcomes, even after controlling for clinicopathologic and socioeconomic factors.

Black or African American↗

Preoperative intracavitary brachytherapy in early-stage cervical carcinoma.

Local failure within the central pelvis is a common site of recurrence in patients with early stage cervical carcinoma who experience recurrence after radical hysterectomy and pelvic lymphadenectomy. To reduce the risk of local failure, the authors treated selected patients with early stage cervical carcinoma with a moderate dose (45 Gy) of preoperative intracavitary brachytherapy before radical hysterectomy and pelvic lymphadenectomy. Given the low risk of recurrence in patients with small (<2 cm) tumors, the authors included only patients with tumors 2 cm or more in size. Forty-three patients (37 with stage IB disease, six with stage IIA disease) were treated from 1986 through 1995. Forty-two completed intracavitary brachytherapy; intracavitary brachytherapy was stopped early in one patient secondary to a low-grade fever. Exploratory laparotomy and planned radical hysterectomy were performed 2 weeks later. Radical hysterectomy was aborted in patients found to have extrauterine disease. At a median follow-up of 45 months, only one local failure has been noted, which occurred in the patient unable to complete intracavitary brachytherapy as planned. The most significant factor correlated with poor outcome was nodal involvement (p < 0.0004). A trend to a better disease-free survival was seen in patients with no residual or only microscopically residual disease. No patients developed significant chronic bowel or bladder toxicity, including fistulae. The results suggest that preoperative intracavitary brachytherapy in selected patients with early stage cervical carcinoma is a promising approach and is associated with a high rate of local control without significant adverse sequelae. Further data is needed to determine whether this approach improves the long-term outcome of these patients.

Adult↗

Surgery and postoperative radiation therapy in stage II endometrial carcinoma.

The traditional approach to patients with stage II endometrial carcinoma is preoperative radiation therapy (RT) followed by surgery. Currently, many patients are treated with primary surgery and postoperative RT. We retrospectively reviewed the outcome of 44 stage II (32 IIA, 12 IIB) patients who underwent surgery and postoperative RT. Nine (20%) had microscopic cervical involvement noted before surgery, and 35 (80%) had occult involvement noted postoperatively. Postoperative RT consisted of whole pelvic RT (WPRT) (50%), vaginal brachytherapy (VB) (18%), or both (32%). At a median follow-up of 40 months, the 5-year actuarial disease-free survival was 72.4%. Two patients (4%) had recurrence in the pelvis (one vagina, one lateral pelvis). Eighteen stage IIA patients treated with WPRT alone and eight stage IIA patients, without deep myometrial invasion (MI), were treated with VB alone, and remained controlled in the pelvis. Extrapelvic recurrences occurred in 12 patients (25%), primarily in those with deep MI and/or grade 2-3 disease. Our results suggest that patients with stage II endometrial carcinoma with microscopic or occult cervical involvement treated with surgery and postoperative RT have a favorable outcome. A high rate of pelvic control is achieved with RT tailored to the pathologic findings.

Adult↗

Cervical cancer in the elderly treated with radiation therapy.

OBJECTIVES: The aim of this study was to evaluate the tolerance and outcome of elderly cervical carcinoma patients treated with radiation therapy (RT). METHODS: Three hundred ninety-eight patients with stage I-III cervical carcinoma treated with definitive RT were analyzed. Patients were divided into nonelderly (ages 35-69) (n = 338) and elderly (ages >/= 70) (n = 60) groups. A comparison of patient, tumor and treatment factors, morbidity, and outcome was performed. Median follow-up was 81 months. RESULTS: Elderly patients had a higher rate of comorbid conditions including diabetes (P = 0. 02), coronary artery disease (P = 0.003), and hypertension (P = 0. 001) than younger patients. Comorbid conditions in the elderly resulted in more frequent treatment breaks and less ability to undergo definitive treatment with intracavitary RT (ICRT). While the 5-year actuarial disease-free (DFS) and cause-specific (CSS) survival rates were comparable between the two groups, disease recurrence and death from cervical cancer were more common beyond 5 years in the elderly group. When patients not undergoing ICRT and those with treatment protraction were excluded, differences in the DFS and CSS curves were no longer evident. The frequency and severity of acute and chronic sequelae were similar. CONCLUSIONS: Elderly cervical carcinoma patients have an equivalent overall outcome following radiation therapy to younger patients when comparable treatment is delivered. Age per se is not associated with a higher rate of acute or chronic sequelae. Comorbid conditions adversely impacted on the quality and delivery of RT in the elderly group and help explain observed differences in outcome based on age.

Adult↗

Race and clinical outcome in patients with carcinoma of the uterine cervix treated with radiation therapy.

OBJECTIVES: The aim of this study was to examine factors underlying differences in outcome between African-American (AA) and Caucasian (C) patients undergoing radiation therapy (RT). METHODS: Patient, tumor, treatment characteristics, and the outcome of 316 AA and 94 C cervical cancer patients who underwent RT were compared. Median follow-up was 72.4 months. RESULTS: AA patients had a trend to a poorer 8-year cause-specific survival (47.9 vs 60.6%) (P = 0.10) compared to C patients with a significant difference seen in stage IIB-IVA disease (34.3 vs 59.5%) (P = 0.04). Several factors correlated with poor outcome were present in the AA group including lower mean hemoglobin levels during RT (P = 0.001), lower median income (P = 0.001), and less frequent intracavitary RT (P = 0.09). In addition, while uncommon in C patients, health problems were major reasons for treatment protraction and inability to undergo intracavitary RT in the AA patients. Multivariate analysis demonstrated that race was not an independent prognostic factor after controlling for difference in patient, tumor, and treatment factors. CONCLUSIONS: AA cervical cancer patients possess multiple factors that adversely impact upon the efficacy of RT. These findings may add further insight into the observed differences in outcome of cervical cancer patients based on race.

Adult↗

Late rectal sequelae following definitive radiation therapy for carcinoma of the uterine cervix: a dosimetric analysis.

PURPOSE: This study attempted to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients treated with radiation therapy (RT) for cervical carcinoma. METHODS AND MATERIALS: A total of 183 patients with cervical carcinoma (67 Stage I, 93 Stage II, and 23 Stage III) treated with definitive RT with a minimum of 2 years follow-up were evaluated. Treatment consisted of external beam pelvic RT (EBRT) followed by intracavitary RT (ICRT) consisting of one or two insertions. Complications were scored and analyzed as a function of 25 patient and treatment factors. Conventional total rectal doses were obtained by adding together the EBRT and ICRT rectal doses. To account for differences in dose rate between the ICRT and EBRT, and variations in EBRT fractionation schemes, biologically equivalent rectal doses (BED) were calculated using a linear quadratic model. In addition, the influence of the varying proportions of EBRT and ICRT rectal doses were evaluated. RESULTS: Twenty-eight patients (15.3%) developed late rectal sequelae (13 Grade 1, 3 Grade 2, and 12 Grade 3). Diabetes (p = 0.03), Point A dose (p = 0.04), and conventional EBRT dose (p = 0.03) were the most significant factors on multivariate analysis. Logistic regression analysis demonstrated a low risk (<10%) of late rectal sequelae below conventional and biological rectal doses of 75 Gy and 135 BED, respectively. The percentage of rectal dose delivered by the EBRT significantly influenced the dose-response relationship. A defined threshold percentage above which rectal sequelae were more common was identified over the range of doses evaluated. This threshold was 87% at a total rectal dose of 60 Gy and decreased to 60% at 80 Gy. CONCLUSION: Diabetes, Point A, and EBRT doses are the most significant factors associated with the risk of late rectal sequelae in patients treated with RT for cervical carcinoma. The percentage of rectal dose delivered by the EBRT significantly affects the conventional and biological dose-response relationship. This suggests that the volume of rectum irradiated is an important and independent parameter in the development of late rectal sequelae.

Adult↗

Phase II study of 96-hr continuous-infusion etoposide and doxorubicin with bolus cyclophosphamide in refractory epithelial ovarian cancer.

Effective salvage chemotherapy for patients with ovarian cancer who have failed platinum- and taxane-based regimens has not been identified. It has been reported that prolonged infusions of chemotherapy may be active in some malignancies which have become refractory to bolus treatments. We evaluated a regimen of 96-hr continuous-infusion doxorubicin (10 mg/m2/24 hr), etoposide (50 mg/m2/24 hr), and bolus cyclophosphamide (750 mg/m2) administered every 21 days to patients with ovarian cancer who had previously been treated with paclitaxel and a platinum compound. Nineteen women were treated, 15 of whom had platinum-refractory cancer. Six of the first 9 experienced a neutropenic fever after the first treatment cycle, and therefore all subsequent patients received prophylactic granulocyte-colony-stimulating factor. Other significant toxicities included hand and foot syndrome (1 patient) and mucositis (4 patients). There was one partial response in a patient with platinum-sensitive disease. We conclude that this regimen causes significant myelosuppression and does not have major activity in heavily pretreated patients with ovarian cancer.

Adult↗

In vitro and in vivo studies on the development of the alpha-emitting radionuclide bismuth 212 for intraperitoneal use against microscopic ovarian carcinoma.

OBJECTIVE: Our objective was to develop the alpha-emitting radionuclide bismuth 212 for possible intraperitoneal use against microscopic ovarian cancer. STUDY DESIGN: The radiobiologic effectiveness of bismuth 212 was compared in vitro to x rays and chromic phosphate phosphorus 32). The distribution, toxicity, and maximum tolerated dose of bismuth 212 were determined after intraperitoneal administration in animal models. Dose estimates in animals and humans were made. RESULTS: In in vitro studies bismuth 212 was three times more effective in eradicating tumor cells grown in monolayers and in 800 microm spheroids. In in vivo studies bismuth 212 was distributed uniformly after intraperitoneal administration. The maximum tolerated dose in rabbits was 60 mCi. There was reversible hematologic toxicity with minimal organ damage. Bismuth 212 prolonged survival and cured up to 40% of animals inoculated with Ehrlich carcinoma cells. Dose estimates made from these studies indicated that dosages administered were effective in eradicating tumor cells and were within the radiotolerance of normal human tissue. CONCLUSION: Bismuth 212 appears to be a suitable candidate for intraperitoneal use against microscopic ovarian cancer.

Adenocarcinoma↗

Monosomy 22 in two ovarian granulosa cell tumors.

Cytogenetic studies of ovarian sex cord stromal cell tumors, although limited in number, have found trisomy 12 to be a recurring abnormality, especially in fibromas and granulosa cell tumors (GCTs). However, recent fluorescence in situ hybridization (FISH) studies have failed to confirm a high prevalence of trisomy 12 in GCTs. We describe the karyotypic findings in one adult and one juvenile GCT. Only the juvenile GCT had an extra, abnormal chromosome 12, but both the adult and juvenile GCT had monosomy 22. In light of these findings and the data in the literature, we suggest that monosomy 22 may be important in the genesis of these relatively rare tumors.

Adult↗

Ultrasound guidance for placement of difficult intracavitary implants.

Placement of a radiation implant in patients with cervical cancer may be difficult because of distortion of the canal by tumor or fibrosis from previous radiation. The objective of this study was to determine whether ultrasound may be useful in recognizing or preventing complications associated with placement of an intracavitary implant. Transabdominal ultrasound was used during and after 20 intracavitary implants in patients with cervical cancers. In placing 20 implants, there were 9 placed in less than satisfactory relation to the anatomy of the uterus. In 6 patients, occult perforations occurred, with two-thirds not detected by the operator. Increased difficulty was seen at the time of placement of a second implant after external radiation. By using ultrasound, correction of the misplaced tandem could be made immediately without resorting to more invasive surgical approaches.

Female↗

Comparison of sensitivities of cells to X-ray therapy, chemotherapy, and isotope therapy using a tumor spheroid model.

Numerous treatment modalities have been used in treating microscopic carcinoma confined to the peritoneal cavity. However, there is little information at the cellular level regarding which modality is most effective in eradicating small nests of tumor cells. In order to determine whether chemotherapy, X rays, or isotope therapy is most effective, we have compared in a three-dimensional spheroid model the survival of cells after treatment with cis-platinum, X ray, or the investigational high-energy isotope 212-bismuth (Bi-212). In this study, V-79 cells were grown to 100-microns diameter spheroids. In killing spheroids, high-energy isotopes were at least six times more effective than X rays at fractionated doses of up to 1300 cGy. High-energy isotopes appear also to be as efficient as cis-platinum. Regardless of exposure time to treatment, Bi-212 was more toxic to spheroids than the other treatment modalities. From this study we conclude that high-energy isotope therapy biologically is very effective in eradicating microscopic nests of cells.

Animals↗

Multiplex polymerase chain reaction-based deletion analysis of spontaneous, gamma ray- and alpha-induced hprt mutants of CHO-K1 cells.

Independent Chinese hamster ovary (CHO)-K1 cell mutants at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus were isolated from untreated, 60Co gamma ray- and 212Bi alpha-exposed cells and the genetic changes underlying the mutation determined by multiplex polymerase chain reaction (PCR)-based exon deletion analysis. In the 71 spontaneous mutants analyzed, 77.5% of the clones showed no change in exon number or size, 15.5% showed a loss of a single exon, 4.2% showed a loss of 2-8 exons, and 2.8% showed loss of all nine hprt exons (total gene deletion). Exposure to 6 Gy of gamma rays, which reduced survival levels to 10%, produced a significantly different deletion spectrum that was shifted toward deletions with 45% of the 20 mutants analyzed showing a loss of a single exon and 30% showing a loss of all nine exons. Exposure to 2 Gy alpha radiation from 212Bi, a 220Rn daughter, a dose which also reduced survival levels to about 10%, resulted in a deletion spectrum similar to the gamma-ray spectrum in that more than 75% of the 49 mutants analyzed were deletions. The alpha spectrum, however, was significantly different from both the spontaneous and gamma spectra with 55.1% of the alpha mutants showing a loss of all nine exons, 10.2% showing loss of a single exon, and 14.3% showing loss of 2-8 exons. Thus, alpha-radiation appears to produce larger intragenic deletions than gamma radiation. The results suggest that intragenic deletion size should be considered when low- and high linear energy transfer (LET) mutation spectra are compared.

Alpha Particles↗

CA-125 in peritoneal fluid from patients with nonmalignant gynecologic disorders.

To assess the diagnostic value of measuring CA-125 levels in peritoneal fluid from women with nonmalignant gynecologic disorders, we determined CA-125 levels in peritoneal fluid and in serum collected simultaneously from 46 women undergoing gynecologic surgery. Patients with benign ovarian disease, non-ovarian gynecologic pathology and severe endometriosis had, on average, higher CA-125 levels in peritoneal fluid than did patients with a normal pelvis and those with mild endometriosis. There was no obvious correlation between peritoneal fluid and serum levels of CA-125. Our data show that (1) measurement of serum CA-125 levels is not useful for distinguishing between different benign gynecologic disorders, and (2) levels of CA-125 in peritoneal fluid in benign gynecologic disorders are comparable to the reported lower range of levels observed in women with intraperitoneal malignancies.

Aftercare↗

Analysis of ascites from patients with ovarian carcinoma by cell flow cytometry.

Cell flow cytometry offers the opportunity to analyze cytopathological samples with regards to DNA content and proliferative activity. To investigate whether this modality can quantitate certain aspects of ovarian carcinoma by analyzing ascites, 43 samples from patients with advanced papillary serous adenocarcinoma of the ovary were studied. In 28 samples (65%) ploidy and the percentage of cells in S phase (%S phase) could be analyzed. Fifteen samples could not be analyzed because of overlapping cell populations distorting distinct cell cycle phases. Of the 28 samples studied, 8 (29%) were diploid and 20 (71%) were aneuploid. The DNA in aneuploid samples ranged from 1.23 to 2.65. The %S phase for aneuploid was greater than that for diploid samples. Patients with diploid samples survived longer. Cytometric analysis of cells from ascites in 4 patients in whom disease progressed after they received chemotherapy showed that the percentage of cells in S phase increased. Cells from ascites established in vitro showed that ploidy and proliferative activity changed as cells were passed in culture. In conclusion, the analysis of ascites by cell flow cytometry may be a prognosticator in patients with advanced ovarian carcinoma. In addition, conclusions extrapolated from in vitro data to the in vivo situation should be done cautiously since late-passaged cells may not always be representative of the initial tumor sample.

Aneuploidy↗

Interlaboratory comparison of different alpha-particle and radon sources: cell survival and relative biological effectiveness.

Alpha radiation-induced cell killing was determined in four different laboratories in order to: 1) measure interlaboratory variability and 2) compare the effects of radon and radon daughter exposures with the effects of 238Pu (an often-used model for radon exposure). The results suggest that differences in handling from laboratory to laboratory can affect both low and high linear energy transfer responses and should be considered when comparing results from different laboratories.

Alpha Particles↗

The effects of radon daughter alpha-particle irradiation in K1 and xrs-5 CHO cell lines.

We investigated the radiobiological effects of the radon daughter bismuth-212 (212Bi) in Chinese hamster ovary (CHO) K1 cells and in xrs-5 cells, which are X-ray sensitive and deficient in the ability to rejoin DNA double-strand breaks. The cells were exposed to 250 kVp X-rays or to 212Bi chelated to diethylene triamine pentaacetic acid (DTPA); chelation of 212Bi to DTPA prevented its attachment to or entry into the cells. Cytotoxic, clastogenic, and mutagenic responses of the cells were measured and RBEs (D10, 2 chromatid aberrations/cell and 10 induced 6-thioguanine-resistant mutants) were calculated to be 3.8, 3.5, and 3.9, respectively for K1, and 1.4, 0.8, and 5.1, respectively, for xrs-5. With the exception of the RBE of less than 1 for alpha-induced aberrations in xrs-5, the results are consistent with the following conclusions: (1) alpha-particles are in general more effective cytotoxic, clastogenic and mutagenic agents than X-rays; (2) the primary lethal and clastogenic lesion induced by both X-rays and alpha-particles is probably a DNA double-strand break; (3) DNA double-strand breaks induced by alpha-radiation are less well repaired than those induced by X-rays, although a portion of alpha-induced damage is repairable; and (4) deficiencies in rejoining DNA double-strand breaks affect the clastogenic and cytotoxic effects of X-rays and alpha-radiation, not their mutagenic effects. The RBE of 0.8 for aberration induction in xrs-5 cells could reflect a deficiency in the ability of these cells to convert alpha-induced damage to chromosome aberrations. Alternatively, the RBE of less than 1 might reflect an unusual sensitivity of xrs-5 cells to alpha-induced G2 delays.

Alpha Particles↗