E. Neely Atkinson

Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer

Our previously reported randomized study of patients with untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer found that patients treated with perioperative chemotherapy and surgery had a significant increase in median survival compared to patients treated with surgery alone. We have now re-analyzed the results of the study with a median time from random allocation to analysis for all patients of 82 months. The increase in survival conferred by perioperative chemotherapy was maintained during the period of extended observation.

Prognosis of surgically determined complete responders in advanced ovarian cancer

From January 1971 through through December 1981, 246 patients with advanced (Stages III and IV) epithelial ovarian cancer underwent second‐look laparotomy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston. Eighty‐five of these patients had a complete response (negative second‐look laparotomy) following treatment with a variety of chemotherapeutic regimens. Three patients had also received irradiation. Patients were analyzed according to pretreatment characteristics (age, FIGO stage, ascites, pleural effusion, histologic grade, tumor type, type of surgery, residual tumor diameter, initial clinical status) and by the number of biopsy specimens taken at second‐look laparotomy. The probability of recurrence and the length of survival following a negative second‐look laparotomy are statistically related to these characteristics. Twenty of the 85 patients (24%) developed recurrent disease 5 to 32 months after laparotomy. The estimated 2‐ and 5‐year survival rates are 99% and 85%, respectively. Patients who achieve a surgically determined complete response have an excellent chance for long‐term survival.

Microscopic disease at second‐look laparotomy in advanced ovarian cancer

During the 11‐year interval from January 1971 to January 1982, 50 of 246 patients with advanced (Stage III and IV) epithelial ovarian carcinoma at second‐look laparotomy had biopsy or cytologic evidence of persistent microscopic carcinoma. The stage and grade profile include 46 Stage III and 4 Stage IV patients: 4 borderline, 9 grade 1, 20 grade 2, and 17 grade 3 patients. Following second‐look laparotomy, 4 patients received no further therapy, 45 received chemotherapy, and 1 received external radiation. No patient was lost to follow‐up, and the median interval off therapy was 24 months. Progressive or recurrent disease has manifest in 12 (24%). No recurrences have developed either in patients younger than age 40 or in patients with grade 1 tumors. Two patients died of leukemia, 1 died of heart disease, and 35 (70%) are alive with no evidence of disease. In patients developing recurrence, the median progression‐free interval was 17.5 months, with a range of 6 to 46 months. The median interval of survival following disease progression was 7 months. There was no evidence of progression at 2 years and 5 years in 81% and 70% of patients, respectively. The uncorrected 2‐ and 5‐year survival rates were 96% and 71%, respectively. The 5‐year survival rates for grades 1, 2, and 3 were 100%, 79%, and 36%, respectively. Other variables analyzed include number of positive foci, residual tumor volume at initial surgery, cytologic findings at second‐look laparotomy, type of chemotherapy, and number of courses of chemotherapy before second‐look laparotomy. In summary, patients with only microscopic evidence of disease at second‐look surgery have a good probability for extended survival.

Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo

Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy. Recent studies have identified a group of candidate tumor suppressor genes on human chromosome 3p21.3 that are frequently deleted in human lung and breast cancers. Among the various genes identified in the 3p21.3 region, we tested the antitumor activity of the FUS1 gene in two human non-small-cell lung cancer (NSCLC) xenografts in vivo. Intratumoral administration of FUS1 gene complexed to DOTAP:cholesterol (DOTAP:Chol) liposome into subcutaneous H1299 and A549 lung tumor xenograft resulted in significant (P=.02) inhibition of tumor growth. Furthermore, intravenous injections of DOTAP:Chol–FUS1 complex into mice bearing experimental A549 lung metastasis demonstrated significant (P=.001) decrease in the number of metastatic tumor nodules. Finally, lung tumor-bearing animals when treated with DOTAP:Chol–FUS1 complex demonstrate prolonged survival (median survival time: 80 days, P=.01) compared to control animals. This result demonstrates the potent tumor suppressive activity of the FUS1 gene and is a promising therapeutic agent for treatment of primary and disseminated human lung cancer.

Predictors of Breast and Cervical Screening in Vietnamese Women in Harris County, Houston, Texas

The Vietnamese are a quickly growing, important part of the Texas population. Breast cancer is known to have different biologic characteristics in Vietnamese women. In order to develop appropriate intervention and screening strategies, we conducted a study of barriers to cervical and breast screening in Vietnamese women in Harris County, Tex. Our objective was to characterize the demographic factors, beliefs, and barriers to cervical and breast cancer screening in our study population and test the effect of these on Papanicolaou test, breast self-examination (BSE), medical breast examination (MBE), and mammography use. The Health Belief Model Scales for Measuring Beliefs Related to Breast Cancer (Champion VL, Nursing Research 1993;42:139–143) was the framework used to assess attitudes regarding risk of breast cancer and to design a component assessing risk of cervical cancer. The questionnaire addressed susceptibility, seriousness, benefits, barriers, and health about screening for breast and cervical cancer. It was translated into Vietnamese and back-translated into English prior to use. The questionnaire was mailed to Harris County residents. Those returned were entered into a database. The data were analyzed for validity using Chronbachs alpha. Simple descriptive analyses and nominal logistic regression identified predictors of Papanicolaou test, BSE, MBE, and mammography use. Twelve hundred surveys were mailed out to Vietnamese women using the telephone directory and the church directories in Harris County; 209 were returned and entered into the database. Of the respondents, 67% had ever received a Papanicolaou test; of these, 89% had received a Papanicolaou test within the past year; 55% of respondents had performed a BSE, 45% of patients received an MBE, and 45% of respondents had ever received a mammogram (15% of respondents had a mammogram during the previous year). The most significant predictors of Papanicolaou test, BSE, MBE, and mammography use were marital status (being married), high educational level, lack of barriers, a family history of the cancer, older age, and increased perception of seriousness. Compared to other studies of Vietnamese women, the women in Texas are among the highest users of the Papanicolaou test, BSE, MBE, and mammography. Barriers and incentives to breast and cervical screening were similar to those in other studies.

Youth as a prognostic factor in carcinoma of the cervix: A matched analysis

A matched analysis comparing 250 patients less than 35 years old with squamous cell cancer of the cervix treated between 1971 and 1981 to a randomly selected group matched on treatment who were greater than 35 years old was performed. A chart review that focused on important prognosticators for survival and progression-free interval was performed. The groups were found to be similar for the important prognosticators. Overall survival and progression-free intervals were plotted using Kaplan-Meier curves and demonstrated that for advanced stages, younger patients were less likely to survive and more likely to recur. Cox proportional-hazard analyses were performed, looking at important prognosticators of survival and progression-free interval. Age, stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of survival, while stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of progression-free interval. The plot of relative hazard by stage of younger versus older patients showed an interaction between age and stage that merits further exploration.

Endometrioid carcinoma of the ovary : retrospective review of 145 cases

From 1967 through December 1987, 145 patients with endometrioid carcinoma of the ovary were treated at the University of Texas M. D. Anderson Cancer Center. Thirty-eight patients (26.2%) had stage I disease, 28 (19.3%) stage II, 60 (41.4%) stage III, and 11 (7.6%) stage IV; 8 patients (5.5%) were unstaged. Grade 2 or 3 histology was seen in 119 patients (82.1%). In addition to surgical therapy, 128 patients underwent chemotherapy, including single-agent therapy, noncisplatin combination therapy, and cisplatin-based therapy. No statistically significant improvement in median survival was noted among these three chemotherapy groups for stages II, III, and IV (P = 0.22). A significant improvement in median survival was noted for those patients who achieved a complete clinical response, regardless of type of chemotherapy (96 or more months for single-agent therapy, P = 0.001; 31.5 months for noncisplatin combination therapy, P = 0.016; and 85 months for cisplatin-based therapy, P = 0.0001). Synchronous ovarian and uterine malignancies were seen in 18 patients (12.4%). No difference in survival was seen for patients with endometriosis (P = 0.13) or endometrial cancer (P = 0.09) when compared with those who did not have these histologic findings.

Sexual adjustment of patients undergoing gracilis myocutaneous flap vaginal reconstruction in conjunction with pelvic exenteration.

BACKGROUND Although the technique for gracilis myocutaneous vaginal reconstruction was first described in the mid-1970s and has been used in conjunction with pelvic exenteration since that time, there is little available information regarding sexual adjustment after such a procedure. The purpose of this study was to assess the sexual adjustment of women who underwent pelvic exenteration and gracilis myocutaneous vaginal reconstruction at the study institution. METHODS In a prospective study design, 95 patients were identified who underwent pelvic exenteration and gracilis myocutaneous vaginal reconstruction at the study institution from 1977 through 1989 and a convenience sample was selected of 44 patients who completed a modified version of the Sexual Adjustment Questionnaire (SAQ) when they returned to the gynecologic oncology outpatient clinic for routine follow-up care. A vaginal assessment was also performed by the attending physician. RESULTS Twenty-one of 40 patients (52.5%) completing the questionnaire reported not resuming sexual activity after surgery; 19 patients reported sexual activity between 1.5 months to 12 years postoperatively. Of the patients who resumed sexual activity, 84% did so within 1 year of surgery. The most common problems noted by patients in adjusting to sexual activity after surgery were self-consciousness about the urostomy or colostomy and being seen in the nude by their partner, vaginal dryness, and vaginal discharge. The mean rank of preexenteration SAQ scores was 66.4, and the mean rank of postexenteration scores was 48.7 (P < 0.0001), demonstrating that sexual adjustment after exenteration was significantly poorer than before the surgery. On the basis of data gathered from a vaginal assessment form, 31 of 44 patients (70.4%) were judged to have a potentially functional neovagina. CONCLUSIONS Based on the findings of this questionnaire study, sexual adjustment is often significantly impaired in women after pelvic exenteration and gracilis myocutaneous vaginal reconstruction. Future modifications in surgical technique, more realistic patient counseling and aggressive postoperative support will hopefully minimize such problems.

Optimal excitation wavelengths for discrimination of cervical neoplasia

Fluorescence spectroscopy has shown promise for the in vivo, real-time detection of cervical neoplasia. However, selection of excitation wavelength has in the past been based on in vitro studies and the availability of light sources. The goal of this study was to determine optimal excitation wavelengths for in vivo detection of cervical neoplasia. Fluorescence excitation-emission matrices (EEMs) were measured in vivo from 351 sites in 146 patients. Data were analyzed in pairs of diagnostic classes to determine which combination of excitation wavelengths yields classification algorithms with the greatest sensitivity and specificity. We find that 330-340-, 350-380-, and 400-450-nm excitation yield the best performance. The sensitivity and specificity for discrimination of squamous normal tissue and high-grade squamous intraepithelial lesion (HGSIL) were 71 % and 77 % on cross validation using three excitation wavelengths. These results are comparable with those found in earlier in vivo studies; however, in this study we find that the proportion of samples which are HGSIL influences performance. Furthermore stratification of samples within low-grade squamous intraepithelial lesion and HGSIL also appears to influence diagnostic performance. Future diagnostic studies should be carried out at these excitation wavelengths in larger groups so that data can be stratified by diagnostic subcategory, age and menopausal status. Similarly, large studies should be done in screening populations.

Prognostic indicators for invasive carcinoma of the vulva

Three hundred sixty-five patients with invasive squamous cell carcinoma of the vulva have been treated at M.D. Anderson Cancer Center between 1944 and 1990. We undertook a rigorous review of the medical records, and a Cox proportional hazards model was applied to examine predictors of both failure to survive and recurrence. Significant predictors of both failure to survive and recurrence included tumor size, clinical stage, therapy aim, pelvic or inguinal nodal metastases, and positive margins. We then undertook an analysis of Stage I and II lesions treated with a curative aim to see if there was a difference in survival or in disease-free interval between those patients treated with radical vulvectomy and those treated with radical wide local excision. There was no survival advantage from the radical vulvectomy procedure. We conclude that careful selection may allow us to choose some patients for less radical procedures.