Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy.

PURPOSE: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. METHODS AND MATERIALS: We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m(2)/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and > or =40 Gy (V(10), V(20), V(30), and V(40), respectively) was calculated. HT was graded according to the Radiation Therapy Oncology Group system. Multivariate regression models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. RESULTS: Increased pelvic BM V(10) (BM-V(10)) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V(10) > or =90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V(10) <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V(30) and V(40) were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. CONCLUSION: The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.

Quantifying the risk of cervical intraepithelial neoplasia in women with unsatisfactory colposcopy results.

OBJECTIVE: To define the risk of high-grade cervical intraepithelial neoplasia (CIN 2,3) among women with unsatisfactory colposcopy results who underwent a loop electrosurgical excision procedure. METHODS: Loop electrosurgical excision procedures were performed for clinical indications by residents supervised by attending obstetrician-gynecologists at an urban public hospital referral clinic. Specimens obtained between July 1, 1996, and April 30, 2002, were retrieved retrospectively after grading and recording in an institutional database. The endpoint of interest was high-grade cervical disease, a composite of CIN 2, CIN 3, and cancer, in excision specimens. RESULTS: Of 169 evaluable patients, five (3%) had cancer. High-grade disease was found in 6 of 21 patients (29%) without a colposcopic lesion, in 13 of 33 patients (36%) with only koilocytosis on colposcopic biopsy, in 15 of 55 patients (27%) with CIN 1, in 13 of 25 patients (54%) with CIN 2, and in 26 of 35 patients (74%) with CIN 3 (p < 0.001). High-grade disease was associated with the grade of referral cytologic results, cytologic analysis repeated at colposcopy, and colposcopic biopsy (p < 0.001 for all). Limiting excision to women with cytologic results at the time of colposcopy read as atypical squamous cells of undetermined significance or worse yielded a high-grade disease prevalence of 12%, with a sensitivity of 92%, specificity 46%, negative predictive value 88%, and positive predictive value 56%. Referral cytologic results, colposcopic biopsy, age, and endocervical curettage results did not seem to identify women at low risk for high-grade disease. CONCLUSIONS: Women with negative cytologic results at the time of colposcopy have a low risk for high-grade disease and may avoid a loop electrosurgical excision procedure despite unsatisfactory colposcopy.

Clitoral therapy device for treatment of sexual dysfunction in irradiated cervical cancer patients.

PURPOSE: The purpose of this pilot study was to evaluate the efficacy of the clitoral therapy device (Eros Therapy) in alleviating sexual dysfunction in irradiated cervical cancer patients. METHODS AND MATERIALS: Eligible patients had a history of cervical cancer treated with radiotherapy and self-reported sexual dysfunction of sexual arousal and/or orgasmic disorders. Patients used the noninvasive, nonpharmacologic clitoral therapy device using a hand-held, battery-powered vacuum to cause clitoral engorgement four times weekly for 3 months during foreplay and self-stimulation. Study instruments included the Female Sexual Function Index, Derogatis Interview for Sexual Functioning, and Dyadic Adjustment Scale. The outcome evaluation was performed at 3 months. RESULTS: Between 2001 and 2002, 15 women were enrolled and 13 completed the study. The median patient age and radiotherapy-enrollment interval was 43.5 years and 2 years, respectively. At baseline, all patients reported symptoms of sexual arousal and/or orgasmic disorders, and some also had sexual desire and pain disorders. At 3 months, statistically significant improvements were seen in all domains tested, including sexual desire, arousal, lubrication, orgasm, sexual satisfaction, and reduced pain. The median Female Sexual Function Index total score increased from 17 to 29.4 (maximal score, 36; p <0.001). The median Derogatis Interview for Sexual Functioning total raw score increased from 46 to 95 (maximal score, 118; p <0.001). At baseline, the Derogatis Interview for Sexual Functioning total T-score corresponded to the bottom 10th percentile of normal sexual functioning. At 3 months, the total T-score placed the patients at the normalcy cutoff. Gynecologic examinations revealed improved mucosal color and moisture and vaginal elasticity and decreased bleeding and ulceration. CONCLUSION: Our results from this pilot study suggest that the clitoral therapy device may alleviate sexual dysfunction in irradiated cervical cancer patients. A randomized, controlled trial is warranted to assess the full benefits of this approach.

Strength of correlations between colposcopic impression and biopsy histology.

OBJECTIVE: The aim of this study was to determine the strength of the correlation between colposcopic impression and biopsy histology. METHODS: In an urban referral clinic, colposcopy and directed biopsy were performed between July 1, 1996, and December 31, 1999, by residents supervised by board-certified attending obstetrician-gynecologists. Impression and biopsy were graded as benign, suggesting condyloma or koilocytosis, cervical intraepithelial neoplasia (CIN) grades 1-3, or cancer. The significance of association was assessed by chi(2) testing and the strength by kappa statistics. RESULTS: Colposcopies were performed on 2825 women, with colposcopic impression and biopsy grade known for 2112. Exact agreement was found in only 893 (37%) women, but results agreed within one grade in 1203 (75%). The association between impression and histology was significant (P < 0.001), but the strength of the correlation was poor (0.20). The positive predictive value of any colposcopic abnormality for any histologic abnormality was 80%. The negative predictive value of a benign colposcopic impression was 68%. The sensitivity of colposcopy with a threshold of any lesion detected was 89%, and the specificity was 52%. The sensitivity for CIN 2/3 was 56%. CONCLUSION: Colposcopy is imprecise, although useful in estimating lesion grade. Management decisions require biopsy.

Histologic findings from the cervix among older women with abnormal cervical cytology.

OBJECTIVE: The aim of this study was to determine rates of cervical neoplasia among women at least 50 years of age referred for colposcopy after abnormal cytology and to compare these to younger women. METHODS: From a prospectively accrued database of 2825 women undergoing colposcopy in the gynecology clinic of an urban public hospital, women at least 50 years of age with a known cytologic abnormality were selected for retrospective analysis. Demographic and medical information collected at colposcopy and subsequent histology was reviewed. Cytology results were based on the Bethesda system, and histology was reported as grades of cervical intraepithelial neoplasia (CIN). Statistical analysis was by t test, chi(2) test, and Mann-Whitney U test. RESULTS: Among 325 women at least age 50, cervical histologic results were benign or atypical for 147 (45%), CIN1 for 28 (9%), CIN2 for 21 (6%), CIN3 for 49 (15%), cancer for 11 (3%), and ungraded dysplasia for 7 (2%), with no biopsy performed for 62 (19%) women. Symptoms were more common among women with cancer (6/11 or 55%) than those without (62/263 or 21%, P = 0.01). Negative histology (80/231 or 35%), CIN3 (49/231 or 21%), and cancer (9/231 or 4%) were more common among older than younger women (287/1403 or 20%, 199/1403 or 14%, and 11/1403 or 1%, respectively), while atypia (438/1403 or 31%), CIN1 (321/1403 or 23%), and CIN2 (147/1403 or 10%) were more common among younger than older women (53/231 or 23%, 23/231 or 10%, and 17/231 or 7%, respectively, P < 0.04). Differences in the distribution of cervical histology results remained significant among women with ASCUS (P = 0.001) but not those with LSIL (P > 0.9), HSIL (P > 0.07), or cancer (P > 0.4). CONCLUSIONS: Most older women are referred for colposcopy with lesser grades of abnormality, but cervical cancers are found across all cytologic grades and were more common in symptomatic women. Compared to younger women with abnormal cytology, women at least 50 years of age with ASCUS had higher rates of negative evaluations and high grade but not low- or mid-grade lesions.

Using history and colposcopy to select women for endocervical curettage. Results from 2,287 cases.

OBJECTIVE: To enhance the yield of endocervical curettage (ECC) by defining risks for abnormality. STUDY DESIGN: Demographic and medical information collected at colposcopy and subsequent histology were reviewed retrospectively. Statistical analysis was by t and chi 2 tests. RESULTS: Among 2,287 women undergoing ECC at colposcopy, in only 105 (5%) did positive ECC require excisional therapy that would not otherwise have been recommended. Women with positive ECC were older (mean, 39.0 vs. 33.2 years; P < .001) and of higher parity (mean, 3.0 vs. 2.0 births; P < .001), with earlier first intercourse (at 16.6 vs. 17.2 years, P = .006), more unsatisfactory colposcopy (148 [27%] of 545 women with unsatisfactory colposcopy vs. 183 [12%] of 1,523 women with satisfactory colposcopy; P < .001) and more colposcopic impressions of cervical intraepithelial neoplasia (CIN) 2-3 (163 [51%] of 323 vs. 443 [25.6%] of 1,730 women with low grade or a negative impression; P < .001). The likelihood of missed CIN 2-3 was 0.4%, with no missed cancers among women with satisfactory colposcopy and either a normal colposcopic impression (1/254) or nulliparity (2/474). CONCLUSION: ECC identifies otherwise-undetected preinvasive and invasive lesions but may be avoided in women with satisfactory colposcopy who are nulliparous or have no colposcopic lesions.

Histologic findings after a colposcopic biopsy showing CIN2.

OBJECTIVE: To determine the risk of CIN3 and cancer in subsequent specimens among women with colposcopic biopsy showing CIN2. METHODS: A retrospective review of demographic and medical information collected at colposcopy. Patient records were again reviewed 8 to 26 months later for information on procedures and histology results. RESULTS: Histologic evaluation of specimens showed no lesions in 14, atypia or koilocytosis in 21, CIN1 in 25, CIN2 in 26, CIN 3 in 27, ungraded CIN in 3, and cancer in 3. No cancers were found in women at or below the median age of 33 years or those with satisfactory colposcopy. However, cancers were found in women with negative repeat cytology and negative colposcopic impression. CONCLUSION: Observation may be an option for young women with CIN2 on colposcopic biopsy if they are reliable for follow up and the entire squamocolumnar junction is seen.