Biomedical subjects
William R Robinson
Publications and source records attributed to William R Robinson.
A pilot study of bone density loss in menopausal women treated with chemotherapy for cancer.
GOALS OF WORK: To estimate the incidence and severity of bone loss in menopausal women diagnosed with cancer who receive treatment with chemotherapy. Also, to evaluate the use of bone loss prevention agents in this population. PATIENTS AND METHODS: A total of 25 postmenopausal women with newly diagnosed cancers who received chemotherapy for a minimum of six cycles were enrolled in this pilot study. All subjects underwent baseline bone mineral density (BMD) testing of the lumber spine (LS), left hip (LH), and femoral neck (FN). Of the 25 women, 22 also underwent follow-up BMD testing at 6 months. MAIN RESULTS: The median age of the subjects was 61 years (range 41-76 years) and the median age of menopause was 50 years (range 34-55 years). Of the 25 subjects, 9 used at least 1 g oral calcium daily, 4 used alendronate, 2 used raloxifene, and 1 used oral estrogen. The mean BMDs (g/cm2) with standard deviation above or below the mean for young adult women at baseline were: LS 0.996 (-0.5 SD), LH 0.876 (-0.5 SD), and FN 0.760 (-0.7 SD). The following values were obtained at 6 months: LS 0.965 (P<0.001), LH 0.847 (P<0.001), and FN 0.739 (P=0.009). CONCLUSIONS: Menopausal women diagnosed with cancer appear to have a high incidence of baseline bone loss, with significant additional loss during treatment. Use of agents for prevention/treatment of bone loss in this group is infrequent. A prospective, controlled analysis is indicated to determine the optimal utility of bone densitometry testing and osteoporosis prevention strategies in this population.
Cancer immunotherapy targeting Sp17: when should the laboratory findings be translated to the clinics?
Despite advances in chemotherapeutic agents, the prognosis for some cancers remains extremely poor, suggesting the need for other treatment modalities. Immunotherapy appears an ideal approach because the mechanisms of tumor cell killing induced by tumor vaccines are different from those from chemotherapy. Various investigations are ongoing to identify suitable targets for this purpose. Sperm protein 17 (Sp17) was originally identified by our group as a novel cancer-testis antigen in various malignancies, including multiple myeloma. Sp17 is a highly immunogenic protein and the observation that more than 90% of vasectomized males develop immunity against Sp17 suggests the opportunity and safety of Sp17 for tumor vaccines. Recent works by other workers suggest a low level of expression of Sp17 in some normal tissues, and investigators have questioned whether Sp17 is in fact a suitable target for immunotherapy. In this paper, we review the general principles of immunotherapy and provide evidence supporting the highly immunogenic nature of Sp17. We also address the discrepancies between the objectives of oncologists involved in treating cancer patients and their familiarity with acceptable levels of toxicity of any effective therapy and those of pure laboratory-based investigators. Finally, we present some early clinical data supporting the rationale for further investigations of Sp17 for tumor vaccines.
Detection of residual subclinical ovarian carcinoma after completion of adjuvant chemotherapy.
PURPOSE: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma. EXPERIMENTAL DESIGN: Peritoneal washings were obtained from 100 consecutive patients undergoing a second-look procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls). The washings were assayed for telomerase activity using the telomerase repeat amplification protocol. The results were compared to the histological and cytological findings. RESULTS: Among our 100 cases, 82 (82%) had either positive second-look procedures or expressed telomerase in their peritoneal washings. Fifty-three (53%) had positive second-look procedures, whereas 66 (66%) tested positive for telomerase. Twenty-nine of the 47 patients (62%) with negative second-look procedures tested positive for telomerase. Of the 53 patients with positive second-look procedures, 37 (70%) tested positive for telomerase. None of the 100 controls (0%) expressed telomerase in their peritoneal washings. CONCLUSIONS: Telomerase activity in peritoneal washings of patients treated for ovarian carcinoma and undergoing a second-look procedure may provide a means of increasing the sensitivity of such procedures for the detection of residual disease while maintaining a high level of specificity.
Recombinant human erythropoietin as an adjunct to radiation therapy and cisplatin for stage IIB-IVA carcinoma of the cervix: a Southwest Oncology Group study.
OBJECTIVE: The survival of cervix cancer patients is associated with their hemoglobin (Hgb) level during radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase II trial to determine whether recombinant human erythropoietin (rHuEPO) safely corrects anemia during chemoradiotherapy for cervix cancer. METHODS: Patients had stage IIB-IVA cervix cancer and a Hgb between 8.0 and 12.5 g/dl. All patients received rHuEPO thrice weekly and oral iron starting 10-15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin followed by intracavitary brachytherapy. RESULTS: Fifty-three patients from 26 institutions received the protocol treatment. The mean Hgb was 10.4 +/- 1.3 g/dl on the first day of rHuEPO administration (baseline), 11.0 +/- 1.6 g/dl on the first day of chemoradiotherapy, 11.6 +/- 1.9 g/dl at the midpoint of chemoradiotherapy, and 11.8 +/- 2.2 g/dl at the end of chemoradiotherapy. The target Hgb level of 12.5 g/dl was achieved in 40% of patients (95% CI 26-56%) by the midpoint of Chemoradiotheraphy. Change in Hgb was associated with baseline serum iron (P = 0.008) and transferrin saturation (P = 0.05) levels, but not with baseline Hgb or serum ferritin, or patient age. Seven patients developed deep vein thrombosis. Two-year progression-free survival (PFS) was 43% and overall survival (OS) was 51%. Survival was significantly associated with Hgb level at the end of chemoradiotherapy, but not with the baseline Hgb level. CONCLUSIONS: rHuEPO and iron gradually increased Hgb levels in anemic women with local advanced cervix cancer during chemoradiotherapy. There was a higher than expected incidence of deep vein thrombosis. The progression-free and overall survival rates were lower than reported for women with normal Hgb levels.
Combined real time PCR and immunohistochemical evaluation of sperm protein 17 as a cancer-testis antigen.
We previously identified sperm protein 17 (Sp17) as a normal testicular protein aberrantly expressed in a proportion of multiple myeloma (MM). However, recent studies have generated controversies on the normal tissue expression of Sp17 and whether or not it is a suitable target for immunotherapy. In this study, we have used a combination of real time polymerase chain reaction and immunohistochemistry on a large panel of normal tissues. Although Sp17 transcripts could be detected in some normal tissues, the levels of expression were <2% of those in normal testis. In contrast, Sp17+ myeloma cells expressed 3-18% of normal testis levels of Sp17 transcript. Immunohistochemistry using two Sp17 murine monoclonal antibodies, each directed at a non-overlapping B-cell epitope, showed Sp17 protein to be expressed only in testis and not any other normal tissues. Specificity of binding of the antibodies to testis was also confirmed in competitive binding assays. Our results therefore further suggest Sp17 as a cancer-testis antigen in MM and support its suitability as a target for immunotherapy.
The predictive value of cytologic testing in women with the human immunodeficiency virus who have low-grade squamous cervical lesions: a substudy of a randomized, phase III chemoprevention trial.
OBJECTIVE: The purpose of this study was to determine whether the progression of low-grade squamous intraepithelial lesions of the cervix in women with the human immunodeficiency virus can be predicted reliably by standard cytologic testing. STUDY DESIGN: As part of a previously reported trial, 288 biopsy specimens were collected from 117 women with the human immunodeficiency virus. These specimens underwent central and local interpretation, which were compared and correlated with cytologic results. Ninety-two subjects had matched cytologic/histologic pairs at study termination, which were compared to determine whether cytologic testing was predictive of progression. RESULTS: Of the central histologic interpretations, 26 of 288 interpretations (9%) differed from local results, 97 of 246 cytologic/histologic pairs (39%) were discordant, and 21 subjects had progression to high-grade squamous intraepithelial lesions by histologic evidence. Cytologic testing showed high-grade squamous intraepithelial lesions in 4 of 21 specimens (sensitivity, 19%). The remaining cytologic specimens were either low-grade squamous intraepithelial lesions or were normal. CONCLUSION: This substudy of pathologic results from a randomized clinical trial suggests that, although the risk of progression of low-grade squamous intraepithelial lesions is low, follow-up cytologic testing is unreliable. Colposcopic evaluation with directed biopsies should be continued.
Progression of cervical disease among adolescents infected with HIV with low-grade squamous intraepithelial lesions.
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Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women.
OBJECTIVE: To estimate the efficacy of isotretinoin for prevention of progression of low-grade squamous intraepithelial lesions (SIL) of the cervix to high-grade lesions or invasive cervical cancer; to estimate the regression rate of low-grade SIL with isotretinoin and the toxicity of isotretinoin in this setting; and to correlate serum CD4 levels with progression of low-grade SIL. METHODS: A randomized, phase III, observation-controlled, multicenter trial was performed in which 117 human immunodeficiency virus (HIV)-positive women with low-grade SIL of the cervix received either oral isotretinoin at 0.5 mg/kg per day for 6 months or observation. Papanicolaou smears and colposcopy/biopsy were done at regular intervals during follow-up. The primary endpoint was progression to high-grade SIL or cervical cancer. RESULTS: Twenty-one of 102 women (20.6%) completing follow-up experienced progression to high-grade SIL, 13 in the observation group and eight in the isotretinoin group. This difference was not significant (P =.29). No cases of invasive cancer were seen. Baseline CD4 levels were lower than anticipated (median 329 cells/mm(3)), but not associated with time to progression (P =.36). Most subjects (63 of 102, 61.7%) used highly active antiretroviral therapy. Subjects under age 30 were more likely to progress than those older than 30 (P =.046). CONCLUSION: Isotretinoin was not associated with longer time to progression of low-grade SIL. This appears to be a chronic condition in HIV-positive women, with a low risk of progression and significant rate of resolution. As in the general population, observation without excisional therapy may be appropriate for HIV-positive women with low-grade SIL.
Improved outcome of cervical neoplasia in HIV-infected women in the era of highly active antiretroviral therapy.
Cervical neoplasia has been associated with human immunodeficiency virus (HIV) infection. Both preinvasive disease and invasive cervical cancer have been reported to have a much poorer outcome in HIV-infected women than in the general population. The use of highly active antiretroviral therapy (HAART) has resulted in significant improvements in the treatment of HIV infection, including a decrease in the incidence and severity of several acquired immune deficiency syndrome (AIDS)-related malignancies. Two cases of cervical dysplasia in HIV-infected women are presented, one from the pre-HAART era, who subsequently developed invasive cervical cancer and died, and one in whom HAART was used with good outcome. Data from several reports of the use of HAART in HIV-infected women indicates that the prognosis for cervical neoplasia is improved. Possible reasons for this improvement include better immune function seen in HAART-treated women, as well as increased surveillance for cervical neoplasia in HIV-infected women in recent years. However, the future impact of improved HIV care, including HAART, on cervical neoplasia is unclear.
Hospice utilization by male and female cancer patients in an end-of-life transition program.
OBJECTIVE: to determine if there were sex differences in patients' use of hospice services in a regional cancer center in Texas from 1998 to 2000. METHODS: A quality-of-life program for patients with cancer that included an end-of-life component was initiated in 1998 at a regional cancer center. The records of 1057 female and 986 male cancer patients who died from 1998 to 2000 were reviewed. Data on demographics, use of hospice care, length of stay, and location at time of referral were collected and analyzed. RESULTS: Hospice utilization increased in women (47% v 64%; p<.001) and men (53% v 66%; p<.001) who died of cancer from 1998 to 2000. Length of stay (LOS) in hospice did not change for women, but decreased significantly for men over that time (31 days v 14 days, p<.001). The number of men with stays of 14 days or less increased significantly (30% v 53%, p<.001). Subjects whose LOS were less than 14 days were more likely to be hospital inpatients at time of referral. CONCLUSIONS: The institution of a targeted end-of-life program was associated with increased utilization of hospice services in women with cancer at this regional cancer center. Length of stay in hospice was longer for women than men, and more men had very short (less than 14 day) stays. Hospice referrals from outpatient settings were associated with longer LOS.