Biomedical subjects

M F Mitchell

Publications and source records attributed to M F Mitchell.

At least 55 records · Page 3Linked to original sources

PubMed1995

Chemoprevention trials and surrogate end point biomarkers in the cervix.

Cervical cancer is the second most common malignancy in women worldwide and remains a significant health problem for women, especially minority and underserved women. Despite an understanding of the epidemiologic risks, the screening Papanicolaou smear, and morbid and costly treatment, overall survival remains 40%. New strategies, based on the clinical and molecular aspects of cervical carcinogenesis, are desperately needed. Chemoprevention refers to the use of chemical agents to prevent or delay the development of cancer in healthy populations. Chemoprevention studies have several unique features that distinguish them from classic chemotherapeutic trials; these features touch on several disciplines and weave knowledge of the biology of carcinogenesis into the trial design. In the design of chemoprevention trials, four factors are important: high risk cohorts must be identified; suitable medications must be selected; study designs should include Phases I, II, and III; and studies should include the use of surrogate end point biomarkers. Surrogate end point biomarkers are sought because the cancer develops over a long period of time, and studies of chemopreventives would require a huge number of subjects followed for many years. Surrogate end point biomarkers serve as alternative end points for examination of the efficacy of chemopreventives in tissue. High risk cohorts include women with cervical intraepithelial neoplasia (CIN) or squamous intraepithelial lesions (SIL). Nutritional studies have helped define micronutrients of interest (folate, carotenoids, vitamin C, vitamin E). Other medications of interest include retinoids (4-hydroxyphenylretinamide [4-HPR], retinyl acetate gel, topical all-trans-retinoic acid), polyamine synthesis inhibitors (alpha-difluoromethylornithine [DFMO]), and nonsteroidal anti-inflammatory drugs (ibuprofen). Phase I chemoprevention studies of the cervix have tested retinyl acetate gel and all-trans-retinoic acid. Phase II trials of all-trans-retinoic acid, beta-carotene, and folic acid have been and are being carried out, whereas Phase III trials of all-trans-retinoic acid have been completed and have shown significant regression of CIN 2 but not CIN 3. Phase I studies of DFMO and Phase II studies of DFMO and 4-HPR are underway. Surrogate end point biomarkers under study include (1) quantitative cytology and histopathology; (2) human papillomavirus type testing; (3) biologic measures of proliferation, regulation, differentiation, and genomic instability; and 4) fluorescence spectroscopic emission. Clinical trials with biologic end points will contribute to our understanding of the neoplastic process and hence aid us in developing new preventive and therapeutic strategies.

Aneuploidy↗

PubMed1995

Clear cell adenosquamous carcinoma of the cervix. An aggressive tumor associated with human papillomavirus-18.

BACKGROUND: It is well recognized that adenocarcinomas and adenosquamous carcinomas of the cervix are frequently associated with human papillomavirus (HPV)-16 or -18. However, few studies have investigated associations between histologic variants of these tumors and specific types of HPV. METHODS: Eleven cases of cervical adenosquamous carcinoma with an unusual histologic appearance were characterized using histochemical and immunohistochemical stains. Sections were tested for the presence of HPV DNA using the polymerase chain reaction (PCR) and type specific primers for HPV-16 and -18. Clinical outcome was determined from a chart review. RESULTS: All tumors were histologically characterized by the presence of sheets of cohesive cells with prominent cell borders and a vacuolated or clear cytoplasm containing large amounts of glycogen. All tumors had focal gland formation and stained positive with mucicarmine stain. Using PCR, HPV-18 DNA was identified in all cases. The youngest patient was 24 years old and the oldest 74 years (mean, 43 years). Eight (73%) of the 11 patients have developed recurrent disease with a mean follow-up until recurrence of 9.5 months (range, 3-22 months). Seven (64%) of the 11 patients have died of their cervical tumors. Of the five patients with Stage IB disease, three (60%) have died of their cervical tumors. CONCLUSIONS: A subset of invasive cervical adenosquamous carcinoma associated with HPV-18 that has a distinctive histologic appearance and an aggressive clinical course is described. The term "clear cell adenosquamous carcinoma" is proposed for this unique variant of invasive cervical carcinoma.

Adenocarcinoma, Clear Cell↗

PubMed1995

Inhibition of proliferation and induction of apoptosis in cervical carcinoma cells by retinoids: implications for chemoprevention.

The effects of retinoids including all-trans-retinoic acid (ATRA), 13-CIS-RETINOIC ACID (13CRA), and N-(4-hydroxyphenyl)retinamide (4-HPR) on several cervical carcinoma cell lines in culture were investigated as a prelude to investigating the mechanisms underlying the chemopreventive potential of retinoids in cervical cancer. We found that when used at a concentration of 1 microM, 13CRA and ATRA inhibited the proliferation of three cell lines (ME-180 [HPV 68], SiHa [HPV 18], and HT-3 [HPV-]) by about 80% after a seven-day treatment. Three other cell lines (MS-751 [HPV 18], HeLa [HPV 18], C-33A [HPV-]) were moderately inhibited (30-48%), and two (C-4 II [HPV 18], CaSki [HPV 16]) responded poorly (< 25% inhibition). 4-HPR failed to inhibit the growth of any of these cell lines when used at 1 microM; however, when used at 5 or 10 microM, it induced apoptosis as evidenced by DNA fragmentation in several of the cell lines and was more potent in this effect than 10 microM ATRA. Retinoids that induce apoptosis in malignant cells may be able to exert similar effects on premalignant cells. Such retinoids would be expected to exhibit greater potency as chemopreventive agents than retinoids that exert only cytostatic effects.

Anticarcinogenic Agents↗

PubMed1995

Polyamines as biomarkers of cervical intraepithelial neoplasia.

Polyamines (putrescine, spermidine and spermine) play critical roles in cell growth and transformation. Ornithine decarboxylase (ODC), key enzyme in polyamine biosynthesis, is considered a putative protooncogene crucial to the regulation of cell growth and transformation. Cancer patients have elevated levels of polyamines in their physiological fluids compared to normal counterparts. alpha-Difluoromethylornithine (DFMO), a specific suicide inhibitor of ODC, exhibits antitumor and antimetastasis activities, and displays effectiveness in many carcinogen-induced animal chemoprevention models. Therefore, we are using DFMO in a chemoprevention trial for cervical intraepithelial neoplasia grade III (CIN III), and evaluating patients for changes in polyamine metabolism as an intermediate marker of DFMO effect. A preliminary study showed that several milligrams of abnormal cervical biopsy tissue contained detectable levels of ODC activity and polyamines. Additionally, the presence of cadaverine suggested bacterial contamination of these tissues. For this reason, normal and abnormal biopsies collected during colposcopy were rinsed prior to frozen storage. In most patients, abnormal tissue showed greater ODC activities and lower spermidine/spermine ratios than normal tissues. Patients are now being treated with de-escalating doses of DFMO (1-0.06 g/m2/day) for one month. To study the effect of DFMO in patients with CIN III, we are collecting blood and cervical tissue specimens to measure the following parameters: plasma DFMO, ornithine and arginine levels; plasma N1-acetylspermidine levels; erythrocyte (blood polyamine carrier) free polyamine levels; cervical tissue free polyamine levels; cervical tissue N1-acetylspermidine levels; and cervical tissue ODC activities. N1-acetylspermidine will be examined as this compound is known to exist primarily in tumor tissues, not in normal tissues. We therefore established a high-performance liquid chromatography method for N1-acetylspermidine. We expect to find that polyamines are effective markers in analyzing DFMO effects in this chemoprevention trial, thus functioning as pharmacodynamic parameters as well as biomarkers for transformation.

Biogenic Polyamines↗

PubMed1995

Statistical techniques for diagnosing CIN using fluorescence spectroscopy: SVD and CART.

A quantitative measure of intraepithelial neoplasia which can be made in vivo without tissue removal would be clinically significant in chemoprevention studies. Our group is working to develop such a technique based on fluorescence spectroscopy. Using empirically based algorithms, we have demonstrated that fluorescence is discriminating normal cervix from low- and high-grade cervical dysplasias with similar performance to colposcopy in expert hands. These measurements can be made in vivo, in near real time, and results can be obtained without biopsy. This paper describes a new method using automated analysis of fluorescence emission spectra to classify cervical tissue into multiple diagnostic categories. First, data is reduced using the singular value decomposition (SVD), yielding a set of orthogonal basis vectors. Each patient's emission spectrum is then fit by linear least squares regression to the basis vectors, producing a set of coefficients for each patient. Based on these coefficient values, the classification and regression tree (CART) method predicts the patient's classification. These results suggest that laser-induced fluorescence can be used to automatically recognize and differentially diagnose cervical intraepithelial neoplasia (CIN) at colposcopy. This method of analysis is general in nature, and can analyze fluorescence spectra of suspected intraepithelial neoplasms from other organ sites. As a more complete understanding of the biochemical and morphologic basis of tissue spectroscopy is developed, it may also be possible to use fluorescence spectroscopy of the cervix as a surrogate endpoint biomarker in Phase I and II chemoprevention trials.

Algorithms↗

PubMed1995

Uterine neoplasms in patients treated with tamoxifen.

Since 1985, when Killackey originally described three cases of endometrial carcinoma in patients receiving tamoxifen, there have been several reports confirming or denying the relationship between tamoxifen and endometrial carcinoma. Our study of 15 patients treated for breast carcinoma with tamoxifen found that papillary serous carcinoma was the most common tumor in this group of patients. Several other retrospective studies reported a high incidence of high-grade endometrioid adenocarcinoma or high-risk variants of endometrial carcinoma in patients receiving tamoxifen.

Antineoplastic Agents, Hormonal↗

PubMed1995

The epidemiology of ovarian cancer.

Ovarian cancer is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancies. In 1995, 26,600 women will be diagnosed with ovarian cancer in the U.S., and 14,500 women will die from the disease. Between 1986-1900, the overall age-adjusted incidence was 14.3/100,000 women; mortality was 7.8/100,000 women. Ovarian cancer, rare before age 40, increases steeply thereafter and peaks at ages 65-75. Incidence and mortality rates are higher among white women than among African-American women. Over the last three decades, ovarian cancer incidence has remained stable in high-risk countries, while an increasing trend has been reported in low-risk countries. Despite recent advancements in treatment, the overall five-year survival rates continues to be low (39%). Over 70% of ovarian tumors are diagnosed when regional or distant involvement has already occurred, causing survival rates to remain stable. The etiology of ovarian cancer is poorly understood. Most studies have focused on the epidemiology of invasive epithelial ovarian tumors, while few have explored the epidemiology of epithelial tumors of low malignant potential and nonepithelial tumors. Factors associated with an increased risk for invasive epithelial ovarian cancer include age, race, nulliparity, family history of ovarian cancer, and history of endometrial or breast cancer. Factors associated with a reduced risk are history of one or more full-term pregnancies, use of oral contraceptives, history of breast feeding, tubal ligation, and hysterectomy. Other factors such as infertility drugs, hormone replacement therapy, age at menarche, age at menopause, dietary factors, lactose intolerance, talc use, coffee and alcohol consumption have been suggested, but their role is still inconclusive.

Female↗

PubMed1995

Staging laparotomy for endometrial carcinoma: assessment of peritoneal spread.

To evaluate surgical staging procedures in women with endometrial carcinoma, we examined the techniques used to assess the peritoneal cavity in 295 clinical stage I patients treated between 1985 and 1993. These patients were felt to be at increased risk for extrauterine disease because of significant myometrial invasion, high-grade (2 or 3), or variant histology (papillary serous, clear cell, or mixed). Patients had a mean of two intraperitoneal samples taken: 224 patients (76%) had at least an omental biopsy and peritoneal cytology. Additional peritoneal biopsy sites included pericolic gutters (50), pelvic peritoneum (45), bowel serosa/mesentery (24), diaphragm (22), appendix (11), and adhesions (7). At the time of staging laparotomy, 22 patients (7.5%) had gross evidence of peritoneal spread, which was readily confirmed by directed biopsy. In the 273 women without gross peritoneal disease, 3 (1%) had occult metastases detected by routine biopsy, 3 (1%) had microscopic metastases in palpably abnormal biopsies, and 22 had positive cytology as the only evidence of peritoneal disease. Only three operative complications were potentially attributable to peritoneal assessment: cystotomy (1), partial small bowel obstruction (1), and ileus (1). Peritoneal failures have been noted in 12 patients over a mean follow-up interval of 39 months. Seven of these patients had obvious peritoneal disease at laparotomy. Two of the remaining 5 had optimal peritoneal sampling and represent false-negative cases. A staging laparotomy that included total abdominal hysterectomy with adnexal resection, cytology, omental biopsy, and biopsy of grossly abnormal sites would have potentially identified all patients with known peritoneal disease. Routine biopsy of other grossly normal peritoneal sites is associated with extremely low yield and is not recommended.

Adult↗

PubMed1995

Staging laparotomy for endometrial carcinoma: assessment of retroperitoneal lymph nodes.

The surgical staging scheme for uterine corpus cancer adopted in 1988 by the International Federation of Gynecology and Obstetrics assigns patients with tumor spread to retroperitoneal lymph nodes to stage IIIC. However, a recommended approach to the detection of lymph node metastasis is not delineated. As part of an ongoing project to assess the value of surgical staging procedures, we reviewed the techniques of lymph node evaluation in 295 at-risk patients. Cases included clinical stage I patients whose preoperative biopsies demonstrated grade 2 or 3 adenocarcinoma or papillary serous, clear cell, or mixed carcinoma. We arbitrarily divided the retroperitoneal space into 10 lymphatic zones: left and right para-aortic, common iliac, external iliac, hypogastric, and obturator. Eighty-two percent of patients had some type of node sampling that involved a mean of three zones. Thirty-three of 244 sampled cases (13.5%) had nodal metastases: 20 had gross involvement and 13 had microscopic. We stratified patients into three groups: (1) those who had no node sampling (n = 51), (2) those with some nodes biopsied (n = 193), and (3) those whose node sampling included a minimum of one para-aortic plus at least one right and left pelvic specimen (n = 51). Retroperitoneal recurrences thought to originate from lymph node sites were identified for the "node-negative" patients in each group: Group 1, 4/51 (8%); Group 2, 9/173 (5%); and Group 3, 0/38 (0%). Lymphatic site failures were seen in 8 of 33 (24%) patients with biopsy-proven metastases. We found that failure to systematically sample pelvic and para-aortic nodes results in a small, but real, risk of undetected extrauterine metastasis. A selective approach to sampling that includes biopsy from both para-aortic and bilateral pelvic lymphatic zones appears to provide an accurate estimate of true node negativity. Further evaluation of this approach is warranted.

Adult↗

PubMed1995

Studies on in vivo induction of cytotoxic T lymphocyte responses by synthetic peptides from E6 and E7 oncoproteins of human papillomavirus type 16.

Induction of cytotoxic T lymphocyte (CTL) responses is an important defense mechanism against infectious agents, specifically viruses. In the present investigation we employed a mouse assay system we previously developed, for rapid induction of CTLs by synthetic peptides from E6 and E7 oncoproteins of human papillomavirus type 16 (HPV-16). In particular, we compared the efficiency of CTL induction by HPV-16 peptides synthesized as linear monomers with those containing a dipalmitoyl-lysine-glycine-glycine (P2-KGG) moiety at the amino-terminus. Our results identified a 15-amino-acid peptide from E6(Q15L, aa 43-57) to be capable of inducing CTLs in vivo and addition of the lipid tail significantly increased CTL induction over that seen with the linear form of the peptide. Further, we identified a shorter peptide, V1OC, with 9 of 10 amino acids overlapping with Q15L peptide (aa 49-58) to be capable of inducing CTLs against both V1OC and Q15L. In case of E7 protein, our results demonstrated usefulness of P2-KGG moiety for enhanced CTL induction by previously identified CTL epitope peptides Q19D (aa 44-62) and R9F (aa 49-57). CTLs induced by both the E6 and E7 peptides were MHC class I-restricted and exhibited strict allele specificity and CD8+ phenotype. Our results showing enhanced cell-mediated immune responses with lipid-tailed forms of peptides add strength to the concept of a synthetic peptide-based vaccine for prophylaxis and therapy of HPV-associated cervical cancer.

Amino Acid Sequence↗

PubMed1995

Chemoprevention trials in the cervix: design, feasibility, and recruitment.

The cervix is an ideal organ for chemoprevention studies and the study of squamous carcinogenesis. In chemoprevention trial design, four factors are important: high-risk cohorts must be identified; suitable agents must be selected; study designs should include Phase 1, II, and III; and studies should include the use of surrogate endpoint biomarkers. High-risk cohorts can be selected for Phase I, II and III trials in the cervix, for example, patients with high grade lesions such as cervical intraepithelial neoplasia (CIN) grade 3 and carcinoma in situ (CIS). A Phase III trial might also include patients with lesions infected with oncogenic HPV types. The cervix is accessible and can be safely followed with Papanicolaou (Pap) smears and colposcopy. Suitable agents include those likely to work in squamous lesions, including retinoids, difluoromethylornithine, beta-carotene, and others. In Phase I chemopreventive studies, does are de-escalated rather than escalated, determining toxicity and optimal dose schedule. Phase II studies looking at effectiveness need placebo control groups since regression of high-risk lesions is possible. Phase III studies, now multicentric, should be carefully designed and include wide patient representation in order to evaluate the risk-benefit ratio of therapy, focusing on cancer incidence reduction. Surrogate endpoint biomarkers include quantitative histopathology, biologic measures of proliferation, regulation, differentiation, genetic instability, and fluorescence emission. Quantitative histopathologic markers include nuclear grading (i.e., shape, area, optical density, texture), nuclear pleomorphism, ploidy, and nucleolar size and position. Biomarkers under study at the present time in the cervix include proliferation markers (PCNA), regulation marker (EGFR, ras, myc, p53, retinoic acid receptors, ODC, spermidine/spermine ratios), differentiation markers (involucrin, cornifin, keratins), and markers of genetic instability (chromosome polysomy). Fluorescent spectroscopy uses light to probe the biochemical properties of tissue. This technique provides an automated diagnosis in real time with comparable sensitivity and specificity to colposcopy and can be used to monitor lesions in chemoprevention trials. Recruitment designs for cervix studies need to include a large referral population and patients with sufficiently large lesions. Clinicians involved in such studies need to stress contraception and smoking cessation, deal with language barriers, and provide compensation for child care and parking to patients in order to increase compliance.

Anticarcinogenic Agents↗

PubMed1994

In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence.

Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Cervix Uteri↗

PubMed1994

Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN).

A spectroscopic system incorporating a pulsed nitrogen laser, an optical fiber probe, and an optical multichannel analyzer was utilized to record fluorescence spectra of the intact cervix at colposcopy. Spectra were obtained from 66 colposcopically normal areas and 49 histologically abnormal areas (5 pathologic inflammation, 21 HPV infection, 9 CIN I, 10 CIN II, and 4 CIN III) in 28 patients. The resulting spectra could be used to differentiate histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92, 90, and 88%. Furthermore, CIN could be differentiated from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87, 73, and 74%. These results suggest that laser-induced fluorescence can be used in the recognition and differential diagnosis of CIN at colposcopy.

Algorithms↗

PubMed1994

A phase II study of carboplatin and cisplatin in advanced or recurrent squamous carcinoma of the uterine cervix.

Between March 1990 and July 1992, 42 women with squamous carcinoma of the uterine cervix were prospectively treated with carboplatin (260 mg/m2) on Day 1 and cisplatin (50 mg/m2) on Day 2 every 28 days. Patients had either stage IVb (FIGO) cancer (5 patients) or recurrent cancer (37 patients) and a Zubrod score < or = 2. Forty-one patients had received either radiation or surgery as primary therapy; 179 cycles of chemotherapy were delivered. The mean number of cycles administered to each patient was 4 (range, 2-8 cycles). Dose escalation was possible in 32 cycles (23.4%) and dose reduction was required in 10 cycles (7.3%). The dose-limiting toxic effect was myelosuppression, with grade 3-4 thrombocytopenia in 39 cycles (22%) and neutropenia in 19 cycles (11%). Neurotoxic effects were observed in 3 patients. Forty-two patients were evaluable for response: 1 had a complete response and 11 had a partial response (response rate 28.6%, 95% confidence interval, 14.9-42.3%). For all patients and for responders, median progression-free interval was 4.4 and 9.5 months, respectively, and median length of survival was 8.9 and 9.5 months, respectively. This regimen was well tolerated and had significant activity in the treatment of cervical cancer. Comparison to other platinum-based regimens in a Phase III trial should be considered.

Adult↗

PubMed1994

In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker.

A quantitative measure of intraepithelial neoplasia which can be made in vivo without the need for tissue removal would be of clinical significance. Our group is working to develop such a technique based on fluorescence spectroscopy. This paper reviews the use of fluorescence spectroscopy for tissue diagnosis, describes our work to apply this technique to the diagnosis of cervical intraepithelial neoplasia (CIN), and discusses the potential utility of fluorescence spectroscopy as a surrogate endpoint biomarker (SEB). The development and performance of a spectroscopic diagnostic algorithm for CIN is described in detail. Fluorescence excitation-emission matrices (EEMs) were obtained in vitro for 18 cervical biopsies from 10 patients. At all excitation emission maxima, but especially at 330 nm excitation, 385 nm emission, the average normalized fluorescence intensity of histologically normal tissue is greater than that of histologically abnormal tissue. A diagnostic algorithm based on the relative intensity at 330 nm excitation, 385 nm emission can differentiate histologically normal and abnormal biopsies with a higher sensitivity, but a lower positive predictive value and specificity than colposcopy. However, paired comparison of histologically normal and abnormal biopsies from the same patient results in a sensitivity of 75%, positive predictive value of 86%, and specificity of 88% for spectroscopic identification of histological abnormality--similar to that of colposcopy. Based on these results, in vivo studies of cervical tissue fluorescence were conducted. A spectroscopic system incorporating a pulsed nitrogen laser, an optical fiber probe, and an optical multi-channel analyzer was used to record fluorescence spectra of the intact cervix at colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Automation↗

PubMed1994

Epidemiology and screening of ovarian cancer.

Ovarian cancer is the second most common neoplasm of the female reproductive system and the leading cause of death from gynecologic cancer in the United States. The overall 5-year survival rate continues to be low. Risk factors associated with ovarian cancer are age, race, nulliparity, infertility, history of endometrial or breast cancer, and family history of ovarian cancer. The diagnosis of ovarian cancer could benefit from screening. Screening methods for ovarian cancer include pelvic examination, abdominal and transvaginal sonography, color flow Doppler, and serum CA-125 levels. Sonography and CA-125 are the most promising and most extensively studied.

Adult↗

PubMed1993

Age contrasts in patients with advanced epithelial ovarian cancer. The M.D. Anderson Cancer Center experience.

BACKGROUND: This study reviews the experience at the University of Texas M.D. Anderson Cancer Center with elderly patients treated for advanced epithelial ovarian cancer with cisplatin-based combination chemotherapy. METHODS: From 1978 through 1988, 215 patients with Stage III or IV, Grade 2 or 3 epithelial ovarian cancer were entered onto one of three consecutive trials involving cisplatin-based combination chemotherapy. The treatment plans were as follows: Trial 1: 12 cycles of cisplatin-melphalan (75 patients); Trial 2: 12 cycles of cisplatin-cyclophosphamide (49 patients); and Trial 3: 6 cycles of cisplatin-cyclophosphamide (91 patients). End-points of analysis included the effect of age on other prognostic factors, clinical response rate, surgical response rate, toxicity, progression-free survival, and survival. RESULTS: Of the entire study group, 57 patients (27%) were 65 years of age and older at diagnosis. There was no effect of age on FIGO stage or histologic grade distribution, but 61% of patients younger than 65 years of age had residual tumors less than or equal to 2 cm compared with only 33% of patients 65 years of age and older (P = 0.00027). There were no differences between the two age groups with respect to response rates, recurrence rate after negative second-look surgery, toxicity, or progression-free survival. Patients in the younger than 65 years of age group, however, had a significantly longer median survival time than those 65 years of age and older (30 versus 19 months, respectively) (P = 0.0038). CONCLUSIONS: This analysis suggests that elderly patients are more likely to begin chemotherapy with bulky residual disease and to have a significantly shorter survival time than their younger counterparts.

Adult↗

PubMed1993

Study of the fluorescence properties of normal and neoplastic human cervical tissue.

Fluorescence excitation-emission matrices (EEMs) were obtained in vitro for 18 cervical biopsies from 10 patients. At all excitation emission maxima, but especially at 330 nm excitation, 385 nm emission, the average normalized fluorescence intensity of histologically normal tissue is greater statistically than that of histologically abnormal tissue. A diagnostic algorithm based on the relative intensity at 330 nm excitation, 385 nm emission can differentiate histologically normal and abnormal biopsies with a higher sensitivity (89%), but a lower positive predictive value (67%) and specificity (44%) than colposcopy (78%, 88%, 89%, respectively). However, paired comparison of histologically normal and abnormal biopsies from the same patient results in a sensitivity of 75%, positive predictive value of 86% and specificity of 88% for spectroscopic identification of histologic abnormality similar to that of colposcopy. This pilot study indicates that fluorescence spectroscopy may be useful in differentiating normal and abnormal tissue; based on these results, a strategy for in vivo studies is discussed.

Algorithms↗