Detection Of Recurrent Cervical Cancer Research Articles

Recurrent cervical cancer detection using DNA methylation markers in self-collected samples from home.

Early detection of recurrent cervical cancer is important to improve survival rates. The aim of this study was to explore the clinical performance of DNA methylation markers and high-risk human papillomavirus (HPV) in cervicovaginal self-samples and urine for the detection of recurrent cervical cancer. Cervical cancer patients without recurrence (n = 47) collected cervicovaginal self-samples and urine pre- and posttreatment. Additionally, 20 patients with recurrent cervical cancer collected cervicovaginal self-samples and urine at time of recurrence. All samples were self-collected at home and tested for DNA methylation and high-risk HPV DNA by PCR. In patients without recurrent cervical cancer, DNA methylation levels decreased 2-years posttreatment compared to pretreatment in cervicovaginal self-samples (p < .0001) and urine (p < .0001). DNA methylation positivity in cervicovaginal self-samples was more frequently observed in patients with recurrence (77.8%) than in patients without recurrence 2-years posttreatment (25.5%; p = .0004). Also in urine, DNA methylation positivity was more frequently observed in patients with recurrence (65%) compared to those without recurrence (35.6%; p = .038). Similarly, high-risk HPV positivity in both cervicovaginal self-samples and urine was more frequent (52.6% and 55%, respectively) in patients with recurrence compared to patients without recurrence (14.9% and 8.5%, respectively) (p = .004 and p = .0001). In conclusion, this study shows the potential of posttreatment monitoring of cervical cancer patients for recurrence by DNA methylation and high-risk HPV testing in cervicovaginal and urine samples collected at home. The highest recurrence detection rate was achieved by DNA methylation testing in cervicovaginal self-samples, detecting 77.8% of all recurrences and, specifically, 100% of the local recurrences.

Detection of Recurrent Cervical Cancer and Prediction of Its Patient Survival with Serum Squamous-Cell Carcinoma-Antigen and 2-[18F] Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography/Computed Tomography.

Aim: To evaluate the usefulness of serum squamous-cell carcinoma antigen (SCC-Ag) and 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) for the detection of recurrent squamous-cell carcinoma (SqCC) of the uterine cervix, and its prediction of patient survival. Methods: FDG-PET/CT was performed for patients with serum SCC-Ag levels elevated to ≥1.5 ng/mL (Group 1) and those with suspicious recurrences without any increase in serum SCC-Ag levels (Group 2). The results were analyzed on the basis of histological data, disease progression and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 6 months of FDG-PET/CT. The outcome was determined using medical records. Results: In total, 88 consecutive patients with cervical SqCC cancer with suspected recurrence (62 in Group 1 and 26 in Group 2) were enrolled. Recurrences were observed in 55 patients (77.4% (48/62) in Group 1 vs. 26.9% (7/26) in Group 2, p < 0.001). The overall sensitivity, specificity and accuracy of serum SCC-Ag were 87.3%, 57.6% and 76.1%, respectively, and those of FDG-PET/CT were 98.2%, 90.9% and 95.5%, respectively; the corresponding values were 97.9%, 92.9% and 96.8% for Group 1 and 100%, 89.5% and 92.3% for Group 2. Surgical resection was performed for 16 patients. At the end of the study, 40.3% (25/62) of Group 1 patients and 88.5% (23/26) of Group 2 patients were alive (p < 0.001). The survival of patients who underwent surgical resection for recurrent tumors was higher than that of patients who did not undergo resection (62.5% (10/16) vs. 17.9% (7/39), p = 0.001). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from FDG-PET/CT showed significantly different in-patient survival. Conclusions: Serum SCC-Ag could predict tumor recurrence and the survival of patients with SqCC cervical cancer. As such, the surgical resection of limited recurrent disease, as determined using FDG-PET/CT, might improve the survival of patients with cervical cancer. MTV and TLG may serve as a prognostic biomarker of survival in patients with recurrent cervical cancer.

Clinical Value of Combining 18F-FDG PET/CT and Routine Serum Tumor Markers in The Early Detection of Recurrence Among Follow-up Patients Treated for Cervical Squamous Cell Carcinoma.

Objective: The purpose of this retrospective study was to investigate the role of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET/CT) and evaluate if combined elevated serum tumor markers levels improve the accuracy of 18F-FDG PET/CT in detecting recurrence of cervical squamous cell carcinoma.Methods: A total number of 42 patients who were treated for cervical squamous cell carcinoma and had underwent 18F-FDG PET/CT for suspected recurrence of cervical cancer were retrospectively reviewed in this study and their clinical, pathological and serological data were collected and analyzed. The clinical value of combining 18F-FDG PET/CT with serum tumor markers was investigated.Results: Among the 42 patients, 18F-FDG PET/CT was true positive in 25 (59.5%), false positive in 5 (11.9%), true negative in 12 (28.5%) and false negative in none. The overall patient-based sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 18F-FDG PET/CT in detecting recurrent cervical cancer were 100%, 70.6, 88.1%, 83.3%, and 100%, respectively. The accuracy of 18F-FDG PET/CT with combined squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) elevation was 100% compared to only SCC Ag elevation and only CEA elevation, 90% and 33.3%, respectively. The positive predictive value of a positive 18F-FDG PET/CT with combined SCC Ag and CEA elevation was 100% for detection of recurrent cervical cancer. Also, the negative predictive value of a negative 18F-FDG PET/CT combined with normal SCC Ag and CEA levels was 100%.Conclusion: 18F-FDG PET/CT is highly sensitive in the diagnosis of recurrent cervical cancer. When 18F-FDG PET/CT is associated with both SCC Ag and CEA elevation or only SCC Ag elevation, the accuracy is increased but not when associated with only CEA elevation. Positive 18F-FDG PET/CT associated with both tumor markers elevation can precisely predict recurrence. Moreover, normal levels of both tumor markers with a negative 18F-FDG PET/CT result may clinically reassure that a recurrence is absent.

Diagnosis of recurrent uterine cervical cancer: PET versus PET/CT: a systematic review and meta-analysis.

The aim of this work was to assess and compare the overall value of stand-alone FDG PET and PET/CT in diagnosing recurrent cervical cancer with a meta-analysis. All the English published studies which addressed the use of PET whether interpreted with or without the use of CT for the diagnosis of recurrent cervical cancer were collected. Methodological quality of the included studies was evaluated. Pooled sensitivity and specificity were calculated, summary receiver operating characteristics (SROC) curve analysis was used to compare the diagnostic ability of stand-alone PET and PET/CT. A total of 18 studies were included in this meta-analysis, with a total of 762 subjects. Pooled sensitivity and specificity of PET and PET/CT were 0.91 (95% CI 0.87-0.94) and 0.94 (95% CI 0.89-0.97), and 0.92 (95% CI 0.91-0.94) and 0.84 (95% CI 0.74-0.91), respectively. The areas under the SROC curve (AUCs) of PET and PET/CT were 0.9610 and 0.9491, respectively. There was no statistical significance between the AUC of PET and PET/CT (P>0.05). Both PET and PET/CT have good performance in the detection of recurrent cervical cancer. However, interpreted CT images may have limited additional value on PET in detecting recurrent cervical cancer.

Diagnostic value of 18F-FDG-PET or PET-CT in recurrent cervical cancer

Accurate detection of recurrent cervical cancer remains a clinical difficulty. This study aims to assess the diagnostic value of PET or PET-computed tomography (PET-CT) using F-fluorodeoxyglucose (F-FDG) in recurrent cervical cancer using a meta-analysis. All published studies in English evaluating the diagnostic value of PET or PET-CT in detecting recurrent cervical cancer were collected. The methodological quality of the included studies was evaluated. Pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver-operating characteristic curves were obtained using statistical software. Twenty studies were included in the meta-analysis. The meta-analysis showed that the pooled sensitivity and specificity of PET and PET-CT to detect distant metastasis in recurrent cervical cancer were 0.87 [95% confidence interval (CI): 0.80-0.92] and 0.97 (95% CI: 0.96-0.98), respectively. The pooled sensitivity and specificity for local regional recurrence were 0.82 (95% CI: 0.72-0.90) and 0.98 (95% CI: 0.96-0.99), respectively. F-FDG-PET and PET-CT are valuable methods for the assessment of recurrent cervical cancer.

Clarifying the Diagnosis of Clinically Suspected Recurrence of Cervical Cancer: Impact of 18F-FDG PET

Clarifying the diagnosis of clinically suspected recurrence of cervical cancer can be challenging. The aim of this study was to investigate the clinical value of (18)F-FDG PET in this context. The medical records of a cohort of 40 (18)F-FDG PET referrals in whom recurrence of cervical cancer was clinically suspected were reviewed. Two expert gynecologic oncologists assessed the level of pre-PET clinical doubt, quality of pre-PET work-up, and impact of (18)F-FDG PET on diagnostic understanding and management using questionnaires. In patients with clinically equivocal recurrence, (18)F-FDG PET had a sensitivity of 92% and a specificity of 93% (prevalence, 65%). Before (18)F-FDG PET, there was high disagreement about the adequacy of the conventional work-up (intraclass correlation coefficient [ICC], 0.25) and the presence of recurrence (ICC, 0.24). (18)F-FDG PET increased experts' confidence (median increase, 14% and 25%; P < 0.0001) and diagnostic agreement (from 68% to 98%; ICC, from 0.24 to 0.95). When (18)F-FDG PET was positive for recurrence, the median overall survival was 13 mo. For patients with negative (18)F-FDG PET findings, the median survival was not reached (log rank, 15.50, P = 0.0001). When the treatment plan was categorized as local therapy, systemic therapy, and expectative management, (18)F-FDG PET changed the treatment plan in half of all cases. The 2 experts reported that (18)F-FDG PET led to a better diagnosis and a beneficial change in management in, respectively, 60% and 65% of cases. (18)F-FDG PET can help to clarify the diagnosis of clinically suspected recurrence of cervical cancer. In this patient population, (18)F-FDG PET had significant value in diagnostic understanding and management of recurrent cervical cancer, facilitating decision making and treatment planning. Therefore, (18)F-FDG PET should be part of the diagnostic work-up in detection of recurrent cervical cancer. The high positive predictive value of (18)F-FDG PET in these patients suggests that inclusion in intervention trials might be based on a positive (18)F-FDG PET scan.

Surveillance FDG-PET detection of asymptomatic recurrences in patients with cervical cancer

Objectives To evaluate survival after detection of recurrent cervical cancer by FDG-PET in symptomatic versus asymptomatic patients. Methods This is a prospective registry study of 103 patients treated with definitive chemoradiation for advanced cervical cancer who demonstrated no abnormal FDG uptake (a complete metabolic response, CMR) on their 3-month posttherapy FDG-PET. Their median age was 48 years (range 26–84). The clinical stages were Ib in 38, IIa in 1, IIb in 39, and IIIb in 25. All patients underwent subsequent surveillance FDG-PET. Patients were grouped according to symptom status at the time of the surveillance FDG-PET. Recurrence sites and survival data were analyzed. Results The median time from the 3-month posttherapy FDG-PET to the first surveillance FDG-PET was 13 months. 25 patients (25/103; 24%) were symptomatic at the time of surveillance FDG-PET and 21 of these had FDG-PET findings indicative of recurrence. 78 patients (78/103; 76%) were asymptomatic and 9 of these had tumor recurrence detected by PET. All recurrences were confirmed by biopsy or radiologic progression. The recurrences in the 21 symptomatic patients were loco regional in 4 and distant in 17. The 9 asymptomatic patients had isolated loco regional disease in 8 and distant disease in 1. All patients received treatment for recurrence. The three-year cause-specific survival for symptomatic recurrences was 19% versus 59% for asymptomatic recurrences ( p = 0.09). Conclusions Surveillance FDG-PET can detect asymptomatic recurrent disease that is potentially amenable to salvage therapy. Prospective investigation of surveillance PET is warranted.

Detection of recurrent cervical cancer by whole-body FDG PET scans

Objective To evaluate the role of whole-body {18F}fluro-2-dexoxyglucose (FDG) positron emission tomography (PET) scans in the detection of recurrent cervical cancer.

Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence

Cervical cancer is the second most frequently diagnosed cancer in women worldwide. About one-third of patients experience recurrent disease. A better chance of survival might be achieved by the early detection of recurrent cervical cancer. [(18)F]fluoro-2-deoxy-D-glucose (FDG) PET could be a promising imaging modality for this purpose, given that FDG PET has high diagnostic efficacy. Ideally, pre-selection of patients should be performed before considering FDG PET. The purpose of this study was to investigate parameters of primary cervical cancer associated with recurrence as a basis for pre-selection of patients in whom FDG PET should be performed. Thirty-eight cervical cancer patients, clinically suspected of having recurrent disease, underwent FDG PET. Tissue from primary tumours and nine histologically confirmed metastases was analysed for biomarkers possibly related to glucose metabolism and prognosis (vascular endothelial growth factor, CD31 for microvessel density, glucose transporter-1, hexokinases I, II and III, Ki67, p53, hypoxia-inducible factor 1alpha, and degree of infiltration by lymphocytes and macrophages). Based on clinical outcome, sensitivity and specificity of FDG PET were 96% and 100%, respectively. Cox regression revealed microvessel density and p53 (tumour suppressor protein) to be the two most important biomarkers for prediction of recurrence (hazard ratios 2.54 and 2.28, respectively). By combining these two biomarkers in a parallel test, sensitivity and specificity in predicting recurrence were 87% and 71%, respectively. Leave-one-out cross-validation demonstrated predictive validity of a model based on microvessel density and p53. In this first study of its kind, we have demonstrated that microvessel density and p53 profiles could be important in pre-selecting cervical cancer patients for detection of recurrence by FDG PET.

Clinical impact of FDG-PET imaging in post-therapy surveillance of uterine cervical cancer: From diagnosis to prognosis

Objectives. To evaluate the ability of whole-body 2-[ 18F]-fluoro-2-deoxy- d-glucose (FDG) positron emission tomography (PET) scan to detect recurrent cervical cancer in women during follow-up after definitive treatment. Methods. We retrospectively reviewed the whole-body FDG-PET scan of the women who had reached complete response after primary treatment for detection of recurrent cervical cancer between September 1, 2001 and October 31, 2004. Results. One hundred twenty-one consecutive patients were registered for the current study and seventy-six women were diagnosed as recurrence, twenty of which were asymptomatic. The FDG-PET scan detected 73 (96.1%) patients among 76 patients with recurrent disease and discriminated 38 (84.4%) patients among 45 patients without recurrence. The sensitivity, specificity and accuracy of the FDG-PET scan in assessment of recurrence among patients with cervical cancer were 96.1%, 84.4% and 91.7% respectively. Sixteen patients with no evidence of distant metastasis on FDG-PET scan received pelvic exenteration; complete response was achieved in 6 (37.5%) patients, and all are alive with no evidence of disease. The FDG-PET scan detected FDG-avid lesions in 17 (85.0%) of the 20 asymptomatic patients with recurrent disease, and 8 (40.0%) patients received therapy with curative intent; complete response was achieved in five (25.0%) patients and all are alive with no evidence of disease. Three-year overall survival of this study was 85.6%. Conclusions. The whole-body FDG-PET scan is a sensitive post-therapy surveillance modality for detection of recurrent cervical cancer even in asymptomatic patients and aids in deciding treatment plans and, eventually, may have favorable impact on prognosis and survival.

FDG-PET for management of cervical and ovarian cancer

Objective To assess the diagnostic performance of Positron Emission Tomography using fluorodeoxyglucose (FDG-PET) in comparison to conventional imaging modalities in the assessment of patients with cervical and ovarian cancer. Methods Studies published between 1966 and 2003 were identified using an OVID search of the MEDLINE database. Inclusion criteria were use of a dedicated scanner, resolution specified, ≥12 human subjects, clinical follow-up ≥6 months or histopathology as reference standard, and sufficient data provided to construct a two-by-two table. Two reviewers independently abstracted data regarding sensitivity and specificity of PET. Results 25 studies (15 cervical cancer, 10 ovarian cancer) met inclusion criteria for full text review. For cervical cancer, pooled sensitivity and specificity of PET for aortic node metastasis are 0.84 (95% CI 0.68–0.94) and 0.95 (0.89–0.98). Pooled sensitivity and specificity for detection of pelvic node metastasis are: PET, 0.79 (0.65–0.90) and 0.99 (0.96–0.99); MRI, 0.72 (0.53–0.87) and 0.96 (0.92–0.98). Pooled sensitivity for CT is 0.47 (0.21–0.73) (pooled specificity not available). Pooled sensitivity and specificity of PET for recurrent cervical cancer with clinical suspicion are 0.96 (0.87–0.99) and 0.81 (0.58–0.94). For ovarian cancer, pooled sensitivity and specificity to detect recurrence with clinical suspicion are: PET, 0.90 (0.82–0.95) and 0.86 (0.67–0.96); conventional imaging, 0.68 (0.49–0.83) and 0.58 (0.33–0.80); CA-125, 0.81 (0.62–0.92) and 0.83 (0.58–0.96). When conventional imaging and CA-125 are negative, pooled sensitivity and specificity of PET are 0.54 (0.39–0.69) and 0.73 (0.56–0.87), respectively. When CA-125 is rising and conventional imaging is negative, the pooled sensitivity and specificity of PET are 0.96 (0.88–0.99) and 0.80 (0.44–0.97). Conclusions There is good evidence that PET is useful for the pre-treatment detection of retroperitoneal nodal metastasis in cervical cancer. There is fair evidence that PET is useful for the detection of recurrent cervical cancer. PET is less useful for the detection of microscopic residual ovarian cancer but has fair sensitivity to detect recurrence in the setting of a rising CA-125 and negative conventional imaging studies. Available studies are limited by low numbers of patients and wide confidence intervals.

Detection of Recurrent Cervical Cancer by Whole-Body FDG PET Scan in Asymptomatic and Symptomatic Women

The authors reviewed the medical records of 44 patients who had been previously treated for cervical carcinoma. In these women, a total of 47 examinations with whole-body [18F]fluoro-2-deoxyglucose (FDG) positron emissiontomography (PET) scans were performed to detect recurrent disease. Twenty-one PET scans were performed in women who had symptoms of recurrence and 26 were in asymptomatic women. In the surveillance group, the time to posttreatment PET scans ranged from 2 to 40 months. In symptomatic women, posttreatment scans were performed from 3 to 80 months after treatment (P = 0.02 for difference). Recurrent disease was detected in 8 (30.8%) asymptomatic and 14 (66.7%) symptomatic patients (P = 0.01). Two asymptomatic women had false-negative PET scans. One patient, whose scan was negative for the presence of disease 3 months after treatment, had persistent disease detected in a cervical biopsy taken at the same time. Another developed a recurrence 4 months after a negative PET scan. A diagnosis of recurrent disease 13 months after a negative scan was not considered a false-negative. The sensitivity of PET scan for detection of recurrent disease among asymptomatic patients was 80.0%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 88.9%. There were 15 positive PET scans reported among symptomatic women. Fourteen of these were confirmed by biopsy or computed tomography (CT), but no disease was found in 1 patient whose PET scan indicated vaginal recurrence. Repeat PET scan at 4 months was negative for disease. Another patient had a pelvic mass detected by PET scan and CT, but because it did not appear to exceed surrounding areas in the FDG uptake, she was not considered positive for recurrence. She was found to have adherent bowel at laparotomy and had no evidence of recurrent disease. All negative findings by PET scan in symptomatic women were confirmed by clinical examination, biopsy, or CT. The sensitivity of PET scan for detection of recurrent disease in symptomatic patients was 100%, specificity was 85.7%, positive predictive value was 93.3%, and negative predictive value was 100%.

Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic and symptomatic women

Objective. To determine the ability of whole-body [ 18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) scan to detect recurrent cervical carcinoma in both symptomatic and asymptomatic women. Materials and methods. We retrospectively reviewed the records of 44 women previously treated for cervical cancer who underwent 47 posttreatment whole-body FDG PET scans in an attempt to detect recurrent disease. Twenty-six scans were performed in asymptomatic women, whereas 21 scans were performed in women with symptoms suggestive of recurrence. Results. About 30.8% of asymptomatic women had recurrent disease detected by PET scan compared to 66.7% of women in the symptomatic group. The sensitivity of PET scan for recurrent disease in asymptomatic women was 80.0%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 88.9%. For symptomatic women, the sensitivity of PET was 100%, specificity of 85.7%, a positive predictive value of 93.3%, and a negative predictive value of 100%. Conclusions. The whole-body FDG PET scan is a sensitive imaging modality for the detection of recurrent cervical carcinoma in both symptomatic and asymptomatic women.

Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic and symptomatic women

Objective. To determine the ability of whole-body [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) scan to detect recurrent cervical carcinoma in both symptomatic and asymptomatic women. Materials and methods. We retrospectively reviewed the records of 44 women previously treated for cervical cancer who underwent 47 posttreatment whole-body FDG PET scans in an attempt to detect recurrent disease. Twenty-six scans were performed in asymptomatic women, whereas 21 scans were performed in women with symptoms suggestive of recurrence. Results. About 30.8% of asymptomatic women had recurrent disease detected by PET scan compared to 66.7% of women in the symptomatic group. The sensitivity of PET scan for recurrent disease in asymptomatic women was 80.0%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 88.9%. For symptomatic women, the sensitivity of PET was 100%, specificity of 85.7%, a positive predictive value of 93.3%, and a negative predictive value of 100%. Conclusions. The whole-body FDG PET scan is a sensitive imaging modality for the detection of recurrent cervical carcinoma in both symptomatic and asymptomatic women.

The role of PET scanning in the detection of recurrent cervical cancer

Objectives [ 18F] Fluoro-2-deoxyglucose positron emission tomography (FDG PET) has recently been established as a sensitive and specific method of detecting lymph node metastases in newly diagnosed cervical cancer. Little is known about the efficacy of PET for detecting recurrent disease. We evaluated the potential role of FDG PET in the context of suspected recurrent cervical cancer. Methods The records of patients undergoing PET scan to evaluate for cervical cancer recurrence between July 1998 and February 2002 were reviewed. Radiographic findings were classified as negative, suspicious, or equivocal. PET scan findings were compared to available clinical data to classify each PET result as a true positive, true negative, false positive, or false negative. Clinical proof of recurrence consisted of a tissue biopsy revealing recurrent cancer within 3 months of the PET scan. Clinical proof of no evidence of disease consisted of a negative tissue biopsy within 3 months or no clinical evidence of recurrence within 6 months after the PET scan. Results Twenty-eight patients underwent 37 PET scans. Twenty-nine cases among 22 patients were clinically evaluable for recurrence status. Median age was 42, and stage distribution was IB 1 ( n = 3), IB2 ( n = 4), IIA ( n = 1), IIB ( n = 10), IIIB ( n = 9), IVB ( n = 1). Histologic types included squamous ( n = 23) adenocarcinoma ( n = 4) and unknown ( n = 1). There were 12 true positive PET scans, 13 true negatives, 2 false positives, and 2 false negatives. The sensitivity and specificity of FDG PET for detecting recurrent cervical cancer were 85.7 and 86.7%, respectively. The positive and negative predictive values were 85.7 and 86.7%, respectively. Conclusions Whole-body FDG PET is a sensitive and specific tool for the detection of recurrent cervical cancer in patients who have clinical findings suspicious for recurrence. A larger prospective trial will determine whether this modality should be used routinely in conjunction with, or in lieu of, other imaging studies to detect recurrent disease in a broader population of cervical cancer patients.