Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response.

AIMS: A complete metabolic response (CMR) on early post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a positive prognostic factor for cervical cancer patients treated with definitive chemoradiation, but long-term outcomes of this group of patients are unknown. Patterns of failure and risk subgroups are identified. MATERIALS AND METHODS: Patients who received curative-intent chemoradiation from 1998 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IVA cervical cancer and had a CMR on post-treatment FDG-PET within 5 months of treatment completion were included. Cox proportional hazards models determined factors associated with locoregional and distant failure. Kaplan-Meier estimates of freedom from any recurrence (FFR) of patient subgroups were compared with Log-rank tests. RESULTS: There were 402 patients with a CMR after chemoradiation on FDG-PET. Initial T stage was T1 (38%)/T2 (40%)/T3 (20%)/T4 (2%); initial FDG-avid nodal status was no nodes (50%)/pelvic lymph nodes (40%)/pelvic and para-aortic lymph nodes (10%). After a median follow-up of 6 years, 109 (27%) recurred. The pattern of recurrence was locoregional (27%), distant (61%) or both (12%). No factors were associated with locoregional failure. Distant recurrence was more likely in patients with T3-4 lesions (hazard ratio = 2.4, 95% confidence interval 1.5-3.8) and involvement of pelvic (hazard ratio = 1.6, 95% confidence interval 1.0-2.7) or para-aortic lymph nodes (hazard ratio = 2.7, 95% confidence interval 1.4-5.0) at diagnosis. The 5-year FFR rates for T1-2 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 85, 76 and 62%, respectively (P = 0.04, none versus para-aortic nodes). The 5-year FFR for T3-4 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 68, 56 and 25%, respectively (P = 0.09, none versus para-aortic nodes). CONCLUSIONS: T3-4 tumours and para-aortic nodal involvement at diagnosis are poor prognostic factors, even after a CMR following chemoradiation.

Pre-operative assessment of muscle mass to predict surgical complications and prognosis in patients with endometrial cancer.

BACKGROUND: Sarcopenia or loss of skeletal muscle mass is an objective measure of frailty associated with functional impairment and disability. This study aimed to examine the impact of sarcopenia on surgical complications and survival outcomes in patients with endometrial cancer. METHODS: A retrospective review of endometrial cancer patients who underwent surgery between 2005 and 2009 was performed. Sarcopenia was assessed on preoperative computed tomography (CT) scan by measurement of the lumbar psoas muscle cross-sectional area and defined as any value below the median (<4.33 cm(2)). Sarcopenic obesity was defined as sarcopenia plus a body mass index (BMI) of 30 kg/m(2) or higher. Microsatellite instability (MSI) was analyzed using the National Cancer Institute (NCI) consensus markers and tumor from hysterectomy specimens. RESULTS: Of 122 patients, 27 (22%) met the criteria for sarcopenic obesity. Sarcopenic patients were older than patients with normal muscle mass (mean age, 69.7 vs. 62.1 years; p < 0.001), had a lower BMI (31.1 vs. 39.4 kg/m(2); p < 0.001), and had more comorbidities (p = 0.048). Sarcopenia was not associated with tumor MSI, hospital stay, 90-day readmission rate, or early/late complications. Patients with sarcopenia had a shorter recurrence-free survival than nonsarcopenic patients (median 23.5 vs. 32.1 months; log-rank p = 0.02), but did not differ in terms of overall survival (log-rank p = 0.25). After adjustment for race, BMI, lymphocyte count, and tumor histology, sarcopenia was associated with a fourfold shorter recurrence-free survival (adjusted hazard ratio [HRadj], 3.99; 95% confidence interval [CI], 1.42-11.3). CONCLUSIONS: Sarcopenia has an impact on recurrence-free survival, but does not appear to have a negative impact on surgical outcomes or overall survival among endometrial cancer patients who undergo preoperative CT scan.

The prognostic significance of lymphovascular space invasion in laparoscopic versus abdominal hysterectomy for endometrioid endometrial cancer.

INTRODUCTION: Recent reports have suggested that uterine manipulators can induce lymphovascular space involvement (LVSI) by endometrial cancer in laparoscopic hysterectomy specimens. The prognostic significance of this phenomenon known as "vascular pseudo invasion" remains elusive. MATERIALS AND METHODS: The authors conducted a retrospective, single institution study of patients who underwent initial surgery for grade 1 and grade 2 endometrioid endometrial cancers with LVSI. Cases were stratified by surgical approach (laparoscopy vs laparotomy). Clinicopathologic and procedure characteristics as well as outcome data were analyzed. Univariate and multivariate analyses were performed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier product limit method. RESULTS: A total of 104 cases (20 laparoscopic, 84 laparotomy) were analyzed. Mean age (65 vs 64 years, respectively), stage distribution, mean number of lymph nodes sampled (18 vs 21, respectively) and use of adjuvant therapy was similar for both groups (p > 0.05). Mean body mass index (BMI) was 30 vs 35 kg/m2, respectively (p = 0.002). Mean follow up was 24 months (range 0.1-102). Univariate analysis demonstrated that LVSI in the laparoscopic setting was associated with worse DFS (p = 0.002). After adjusting for grade the risk of recurrence remained higher for laparoscopic cases (HR: 15.7, 95% CI 1.7-140.0, p = 0.014). CONCLUSIONS: Adjusted risk of recurrence associated with LVSI is higher in cases approached laparoscopically arguing against the concept of "vascular pseudo invasion" associated with the use of uterine manipulators and balloons. LVSI should be regarded as a serious risk factor and taken into account for triage to adjuvant therapies, even in laparoscopically treated early-stage endometrial cancer.

The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women.

OBJECTIVE: Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN. DESIGN: Cohort study. The Women's Interagency HIV Study (WIHS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia). METHODS: HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations. RESULTS: Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression CONCLUSIONS: HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.

Evolution of cervical abnormalities among women with HIV-1: evidence from surveillance cytology in the women's interagency HIV study.

OBJECTIVE: To determine incidence, progression, and regression rates for abnormal cervical cytology and their correlates among women with HIV. METHODS: In a multicenter prospective cohort study conducted October 1, 1994, through September 30, 1999 at university, public, and private medical centers and clinics, 1639 HIV-seropositive and 452 seronegative women were evaluated every 6 months for up to 5 years using history, cervical cytology, T-cell subsets, and quantitative plasma HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by polymerase chain reaction. Cytology was read using the Bethesda system, with any smear showing at least atypia considered abnormal. Poisson regression identified factors associated with incident cytologic abnormalities whereas logistic regression identified those associated with progression and regression after an abnormality. RESULTS: At least one abnormal smear was found during all of follow-up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p <.001). Only 5.9% of seropositives ever developed high-grade lesions, and the proportion with high-grade findings did not rise over time. Incidence of atypical squamous cells of uncertain significance (ASCUS) or more severe lesions among HIV-seropositive patients and seronegative patients was 26.4 and 11.0/100 woman-years (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.9-3.0), whereas that of at least low-grade squamous intraepithelial lesions (SIL) was 8.9 and 2.2/100 (RR, 4.0; CI, 2.6-6.1). HIV status, detection of the presence of human papillomavirus (HPV), CD4 lymphocyte count, and HIV RNA level predicted incidence of abnormal cytology (p <.05); HPV detection and HIV RNA level predicted progression (p <.01); and HPV detection, CD4 lymphocyte count, and HIV RNA level predicted regression (p <.001). Rates of incidence, progression, and regression of abnormal cytology did not differ between HIV seronegative women and seropositive women with CD4 lymphocyte counts >200/mm(3) and HIV RNA levels <4000/ml of similar HPV status. CONCLUSIONS: Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immunosuppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease.

Biopsy correlates of abnormal cervical cytology classified using the Bethesda system.

OBJECTIVE: The goal of this study was to determine the colposcopic findings underlying cytologic abnormalities classified according to the Bethesda system. METHODS: Women undergoing colposcopy for abnormal cytology at an urban teaching hospital between July 1, 1996 and December 31, 1999 had Papanicolaou smears repeated. Results were compared both with biopsy histology and with the worst histology reported after 8-26 months of follow-up. kappa statistics and Spearman's rho were calculated to determine the degree of agreement. RESULTS: Colposcopy was performed for 2263 (94%) women. Referral and repeat Pap smears were reported identically in 493 (25%) of the 1962 women with results for both. No AGUS (atypical glandular cells of uncertain significance) smears were confirmed on repeat smear, and after excluding AGUS, agreement within one grade was found in 1305 of 1854 (70%). Among the 1842 women with squamous cytologic abnormalities, biopsy revealed a lesion more severe than that suggested by referral cytology in 577 (31%) and a less severe lesion in 648 (35%); exact correspondence was found in only 646 (35%). Of 317 women with ASCUS (atypical squamous cells of uncertain significance) on referral Pap smear, a negative repeat smear, and a specific biopsy result, 95 (30%) had true negative histology, while 148 (47%) had condyloma, 56 (18%) had cervical intraepithelial neoplasia (CIN) 1, 8 (3%) had CIN 2, 10 (3%) had CIN 3, and none had cancer. Comparison of repeat smear and colposcopic biopsy yielded a kappa statistic of 0.16. CONCLUSIONS: Cytology classified according to the Bethesda system does not accurately predict histologic diagnosis.

Characteristics and survival of cervical cancer patients managed at adjacent urban public and university medical centers.

OBJECTIVE: The goal of this work was to compare characteristics and survival of cervical cancer patients at adjacent public and university hospitals to define the effects of poverty and ethnicity on disease. METHODS: A retrospective chart review was conducted of cervical cancer patients managed by gynecologic oncologists at two adjacent urban hospitals between 1992 and 1998. Continuous variables were compared by t test, categorical variables by chi(2), and survival by the Kaplan-Meier and log-rank methods. RESULTS: In all, 372 patients were identified, with 209 (56%) at the public hospital and 163 (44%) at the adjacent university hospital. Ethnic distribution differed between the two hospitals: 100 (52%) versus 46 (28%) African-American, 56 (29%) versus 13 (8%) Hispanic, 31 (16%) versus 96 (60%) Caucasian, and 5 (3%) versus 6 (4%) other (P < 0.001). In addition, public hospital patients presented with more advanced cancers (stages II--IV) than those managed at the university hospital, 96 (48%) versus 53 (34%) (P = 0.008), and squamous cancers were more common at the public hospital, 154 (89%) versus 120 (76%) (P = 0.03). However, with a median follow-up of 17 months, stage-adjusted survival did not differ between the two institutions. CONCLUSIONS: The higher proportions of advanced and squamous cervical cancers encountered at the public hospital likely reflect suboptimal screening. Equal access to gynecologic oncologists eliminated disparities in stage-adjusted survival. Efforts at earlier diagnosis should be directed at indigent, especially minority women.

Compliance with and acute hematologic toxic effects of chemoradiation in indigent women with cervical cancer.

OBJECTIVES: The goals of this work were to describe the compliance with and acute hematologic toxic effects of chemoradiation for cervical cancer in indigent women and to explore the likelihood that chemoradiation is effective outside research settings. We hypothesized that if compliance and toxicity are not limiting in this high-risk group of patients, the effectiveness of chemoradiation for cervical cancer in community settings is likely to mirror the efficacy demonstrated in clinical trials. METHODS: This study is a retrospective review of prospectively maintained data on women with newly diagnosed cervical cancer treated with chemoradiation between August 1998 and August 2000. Cisplatin was given weekly at 40 mg/m(2) to a maximum of six courses. A WBC count <3000/mm(3) resulted in cancellation of cisplatin but not radiation, and patients were transfused for hemoglobin <9 g/dl. Statistical analysis was performed using the t test, chi(2) test, and Fisher's exact test. RESULTS: In all, 19 of 65 patients treated (29.2%) missed at least one chemotherapy cycle, with 10 (15.4%) due to missed appointments, 8 (12.3%) due to a low WBC count, and 1 due to increased creatinine. Nineteen patients (29.2%) received RBC transfusion during chemoradiation, and two (3%) had platelets <75,000/mm(3). Noncompliant patients had a lower mean total point A dose (7986 cGy vs 8413 cGy, P = 0.04) and longer overall treatment duration (79 days vs 51 days, P < 0.001). No patient had a fatal hematologic complication. CONCLUSION: Nearly a third of the indigent women treated with chemoradiation for cervical cancer do not complete the prescribed treatment, and a similar number require blood transfusions. In indigent and minority women, the effectiveness of chemoradiation protocols may not mirror the efficacy obtained in clinical trials.

Correlating Papanicolaou Smear, Colposcopic Impression, and Biopsy: Results from the Women's Interagency HIV Study.

OBJECTIVE: To determine associations among cervical cytology, colposcopy, and biopsy in HIV-seropositive women. MATERIALS AND METHODS: HIV-seropositive women and uninfected comparison women in a multicenter prospective cohort study underwent colposcopy for protocol indications. Women were eligible if they had a cervix, satisfactory cytology, and colposcopy between October 1994 and September 1999. Cytology, colposcopic impression, and biopsy were compared using equivalent categorizations. Kappa statistics with bootstrap sampling assessed strength of associations. RESULTS: Colposcopy was performed in 978/1370 HIV-seropositive women and in 154/224 seronegative women. Biopsies were performed on 603 (44%) seropositive women at least once during 1015 colposcopy visits and on 82 (37%) seronegative women at 116 visits. The positive predictive value of cytology was 72% for seropositive women and 60% for seronegative women. The positive predictive value of colposcopy was 71% for seropositive women and 55% for seronegative women. CONCLUSION: The correlation between either cervical cytology or colposcopic impression and colposcopic biopsy was poor.

Poor compliance with postmolar surveillance and treatment protocols by indigent women.

OBJECTIVE: To estimate compliance by indigent women with surveillance protocols after molar pregnancy. METHODS: Women whose molar pregnancies were evacuated at an urban, public hospital were advised to return weekly either until hCG levels decreased below 5 mIU/mL, then monthly for 6 months, or until diagnosis and treatment of gestational trophoblastic disease, then monthly for 12 months. Hormone testing was by enzyme-linked immunosorbent assay. Statistical analysis was by chi(2) tests. RESULTS: Of 51 women identified, 11 (22%) developed trophoblastic disease. All achieved remission after chemotherapy. Five (45%) of these 11 missed at least one treatment, seven (64%) missed at least one postremission visit, and none was fully compliant with protocols. Five (13%) of the 40 remaining women were lost to follow-up before remission. Seven (18%) of the 40 women who did not receive chemotherapy complied fully with protocols, whereas five (13%) were lost to follow-up before remission, and 16 (40%) were lost before completing 6 months of follow-up. Only 15 (29%) of the 51 women completed surveillance without gestational trophoblastic disease or pregnancy. Six women conceived, and injectable medroxyprogesterone acetate was associated with a lower pregnancy rate (zero of 25 compared with six of 26 (23%), P <.01). CONCLUSION: Most indigent women failed to comply with postmolar surveillance, although most achieved remission. Injectable medroxyprogesterone acetate is recommended for postmolar contraception in this population.

Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women.

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/L). Analysis of Papanicolaou smears showed SILs in 216 (16.4%) of 1314 women. Cervical SILs were found to be associated with retinol concentrations <1.05 micromol/L (multivariate odds ratio [OR], 1.63; P=.04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n=774), a multivariate analysis again revealed a significant independent association between retinol <1.05 micromol/L and cervical SILs (multivariate OR, 1.75; P=.02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.

Assessing disease extent in women with bulky or clinically evident metastatic cervical cancer: yield of pretreatment studies.

OBJECTIVE: The objective of this study was to determine the impact of pretreatment tests on staging and management for women with bulky or clinically evident metastatic cervical cancer. METHODS: Demographics and findings of clinic pelvic examination (PE), examination under anesthesia (EUA), chest x ray (CXR), abdominopelvic computed tomography (CT), and intravenous urography (IVU) were reviewed for women with primary, untreated cervical cancers either > or =4 cm or with extracervical disease apparent on PE or CXR evaluated between July 1, 1994, and March 31, 1999. Stage was assigned according to standards of the International Federation of Gynecology and Obstetrics. RESULTS: In 133 women studied, tumor diameter averaged 4. 9 cm on PE and 5.7 cm at EUA (P = 0.0005). Of 92 women undergoing both PE and EUA, 30 (33%) had size discrepancies of more than 1 cm. Compared with EUA, PE had sensitivity, specificity, and positive and negative predictive values, respectively, of 65, 89, 79, and 81% for vaginal disease, 74, 91, 95, and 63% for parametrial disease, and 57, 90, 60, and 89% for sidewall fixation. CXR was abnormal in 5 (4%). IVU showed ureteral dilation in 20 (22%) of 90 women, while CT showed dilation in 34 (28%) of 123 women. CT also showed pelvic lymphadenopathy in 22 (18%) women and paraaortic lymphadenopathy in 12 (10%). Bladder biopsies showed malignancy in 8 (8%), including one transitional cell carcinoma of the bladder. Proctoscopy failed to reveal metastatic cervical cancer. CONCLUSIONS: CXR and EUA with cystoscopy are important to the accurate staging and treatment of bulky or clinically metastatic cervical cancers, while proctoscopy is rarely useful. CT predicts ureteral obstruction well, and its greater information yield may justify its higher cost compared with IVU.

Topotecan for recurrent cervical cancer after platinum-based therapy.

The activity and toxicity of topotecan in women with recurrent cervical cancer are described from a case series of women with recurrent cervical cancer who had measurable disease and were not amenable to cure by surgery or radiation. All patients had prior platinum-based chemotherapy and developed progressive disease. Topotecan was given as 1 mg/m2/day over 30 min for 5 days every 3 weeks until progression of disease or prohibitive toxicity. Between July 1998 and July 1999, 12 patients received a total of 20 cycles of topotecan. Median age was 41 years (range 21-62), and 11 (92%) patients had prior whole pelvic radiation. The mean number of topotecan cycles was 1.5 (median 1, range 1-3). There were two partial responses (16.7%; 95% CI, 2% to 48%), both in prior radiation fields. Five patients required red blood cell transfusions, four had grade II nausea and vomiting, two developed sepsis (one with neutropenia), one developed fever, and one reported hyperpigmentation. There were no treatment-related mortalities. Although topotecan appears to exhibit modest activity in recurrent cervical cancer after radiation and platinum-based therapy, bone marrow toxicity may limit the utility of this regimen without hematopoietic growth factor support.

Multimodality therapy for carcinoma of the Bartholin gland.

OBJECTIVE: The aim of this study was to report the value of chemoradiation in the management of cancers of the Bartholin gland. METHODS: Primary treatment consisting of 45-46 Gy teletherapy radiation to the vulva, pelvis, and groins in combination with 50 mg/m(2) of cisplatin and 1000 mg/m(2)/day of 5-fluorouracil for 5 days during the first and fifth weeks of irradiation was delivered, followed by interstitial implant or excision. RESULTS: Two patients were free of disease at 30 and 59 months following therapy. Both patients required myocutaneous flap closure, one after excision of tumor after radiation and one after radionecrosis at the implant site. CONCLUSIONS: Primary chemoradiation may allow continence-sparing therapy for women with primary carcinoma of the Bartholin gland.

Predicting compliance with follow-up recommendations after colposcopy among indigent urban women.

OBJECTIVE: To determine correlates of compliance with follow-up recommendations after colposcopy. METHODS: Between October 1, 1992, and June 30, 1997, management recommendations were made to 451 consecutive women who attended a resident colposcopy clinic. Compliance was determined after 8-12 months. Correlates of compliance were assessed by univariate and multivariate analyses. RESULTS: Recommendations included repeat cytology in 6 months for 252 women, loop excision for 114, conization for 27, repeat colposcopy for 51, other for three, and not recorded for four. Rates of ever complying were 81% for loop excision, 85% for conization, 62% for repeat colposcopy, and 36% for repeat cytology. In multivariate analysis, the only significant predictors of compliance were history of genital herpes simplex infection (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.05, 0.86, P = .03) and the nature of the recommendation (OR 4.73; CI 2.51, 8.92 for loop excision; OR 8.72; CI 2.57, 29.6 for conization; and OR 2.53; CI 1.30, 4.93 for repeat colposcopy, all against observation, P<.001). CONCLUSION: After colposcopy, women were more likely to comply with earlier, more intensive interventions, although the relative effect of follow-up interval and intervention could not be distinguished.