Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery.

Department of Radiotherapy, Academic Medical Center, Amsterdam, The Netherlands.
Radiotherapy and Oncology (Impact Factor: 4.86). 02/2008; 89(2):197-204. DOI: 10.1016/j.radonc.2008.01.004
Source: PubMed

ABSTRACT Tumor recurrence after surgery for cervical carcinoma is associated with high fatality and morbidity, forming a major therapeutic challenge. This paper presents our experience with treatment of this patient group by salvage radiotherapy with curative intent.
Thirty-five patients with a pelvic recurrence after hysterectomy received high-dose radiotherapy. A retrospective analysis of long-term outcome and prognostic factors was performed.
After a median follow-up period of 12.1 years, actuarial 2-,5- and 10-year overall survival rates were 66%, 43% and 33%; disease-free survival rates were 62%, 45% and 41%, respectively. Pelvic control rates at 2-,5- and 10-years were 77%, 69% and 62%. Unfavorable prognostic factors on univariate analysis for survival were: recurrence extending to the pelvic wall versus central recurrence, early recurrence after surgery, external boost versus brachytherapy boost, low total dose and high age. Only a brachytherapy boost and a long interval between surgery and recurrence were significant on multivariate analysis. Severe complications (> or = grade 3) were seen in 6 patients (17%; actuarial after 5 years, 21%).
Salvage radiotherapy for recurrent cervical carcinoma following surgery may result in 40-50% long-term disease-free survival and an acceptable risk of severe treatment complications, even in patient with recurrences extending to the pelvic wall.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background To report outcomes in women with locally recurrent or advanced cervical cancer who received intraoperative electron beam radiotherapy (IOERT) as a component of therapy. Methods From 1983 to 2010, 86 patients with locally recurrent (n = 73, 85%) or primary advanced (n = 13, 15%) cervical cancer received IOERT following surgery. Common surgeries included pelvic exenteration (n = 26; 30%) or sidewall resection (n = 22; 26%). The median IOERT dose was 15 Gy (range, 6.25-25 Gy). Sixty-one patients (71%) received perioperative external beam radiotherapy (EBRT; median dose, 45 Gy). Forty-one patients (48%) received perioperative chemotherapy. Results Median follow-up was 2.7 years (range, 0.1-25.5 years). Resections were classified as R0 (n = 35, 41%), R1 (n = 30, 35%), or R2 (n = 21, 24%). Cumulative incidences of central (within the IOERT field) and locoregional relapse at 3 years were 23 and 38%, respectively. The 3-year cumulative incidence of distant relapse was 43%. Median survival was 15 months, and 3-year Kaplan-Meier estimates of cause-specific (CSS) and overall survival (OS) were 31 and 25%, respectively. On multivariate analysis, pelvic exenteration (p = 0.02) and perioperative EBRT (p = 0.009) were associated with improved central control in patients with recurrent disease. Recurrence within 6 months of initial therapy was associated with reduced CSS (p = 0.001). Common IOERT-related toxicities included peripheral neuropathy (n = 16), ureteral stenosis (n = 4), and bowel fistula/perforation (n = 4). Eleven of 16 patients with neuropathy required long-term pain medication. Conclusions Long-term survival is possible with combined modality therapy including IOERT for advanced cervical cancer. Distant relapse is common, yet a significant number of patients experienced local progression in spite of aggressive treatment. In addition to consideration of disease- and treatment-related morbidity, other factors to be considered when selecting patients for this approach include the time interval from initial therapy to recurrence and whether the patient is able to receive perioperative EBRT and pelvic exenteration in addition to IOERT.
    Radiation Oncology 04/2013; 8(1):80. DOI:10.1186/1748-717X-8-80 · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, the preliminary results of the first stereotactic body radiosurgery (SRS) experience with volumetric intensity modulated arc therapy (VMAT) in oligometastatic breast and recurrent gynecological tumors (OBRGT) are reported in terms of feasibility, toxicity and efficacy. Patients were treated in a head-first supine treatment position on a customized body frame immobilization shell. SRS-VMAT treatment plans were optimized using the ERGO++ treatment planning system. Response assessment was performed 8-12 weeks after treatment by morphologic imaging modalities, or if feasible, also by functional imaging. Thirty-six lesions in 24 consecutive patients (median age, 63 years; range, 40-81) were treated: 13.9% had primary or metastatic lung lesions, 30.5% had liver metastases, 36.1% had bone lesions, 16.7% had lymph node metastases and 2.8% had a primary vulvar melanoma. The median dose was 18 Gy (BED2 Gy, α/β: 10=50.4 Gy), the minimal dose was 12 Gy (BED2 Gy, α/β: 10=26.4 Gy) and the maximal dose was 28 Gy (BED2 Gy, α/β: 10=106.4 Gy). Seven patients (29.2%) experienced acute toxicity, which however was grade 2 in only 1 case. Moreover, only 3 patients (12.5%) developed late toxicity of which only 1 was grade 2. Objective response rate was 77.7% including 16 lesions achieving complete response (44.4%) and 12 lesions achieving partial response (33.3%). The median duration of follow-up was 15.5 months (range, 6-50). Recurrence/progression within the SRS-VMAT treated field was observed in 6 patients (total lesions=7) with a 2-year inside SRS-VMAT field disease control expressed on a per lesion basis of 69%. Recurrence/progression of disease outside the SRS-VMAT field was documented in 15 patients; the 2-year outside SRS-VMAT field metastasis‑free survival, expressed on a per patient basis, was 35%. Death due to disease was documented in 6 patients and the 2-year overall survival was 58%. Although the maximum tolerated dose was not reached, SRS-VMAT resulted in positive early clinical results in terms of tumor response, local control rate and toxicity.
    Oncology Reports 08/2014; 32(5). DOI:10.3892/or.2014.3412 · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cancer of the uterine cervix is a common cause of mortality in women. After initial treatment women may be symptom free, but the cancer may recur within a few years. It is uncertain whether it is more clinically effective to survey asymptomatic women for signs of recurrence or to await symptoms or signs before using imaging. This project compared the diagnostic accuracy of imaging using positron emission tomography/computerised tomography (PET-CT) with that of imaging using CT or magnetic resonance imaging (MRI) alone and evaluated the cost-effectiveness of adding PET-CT as an adjunct to standard practice. Standard systematic review methods were used to obtain and evaluate relevant test accuracy and effectiveness studies. Databases searched included MEDLINE, EMBASE, Science Citation Index and The Cochrane Library. All databases were searched from inception to May 2010. Study quality was assessed using appropriately modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. Included were any studies of PET-CT, MRI or CT compared with the reference standard of histopathological findings or clinical follow-up in symptomatic women suspected of having recurrent or persistent cervical cancer and in asymptomatic women a minimum of 3 months after completion of primary treatment. Subjective elicitation of expert opinion was used to supplement diagnostic information needed for the economic evaluation. The effectiveness of treatment with chemotherapy, radiotherapy, chemoradiotherapy, radical hysterectomy and pelvic exenteration was systematically reviewed. Meta-analysis was carried out in RevMan 5.1 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) and Stata version 11 (StataCorp LP, College Station, Texas, USA). A Markov model was developed to compare the relative cost-effectiveness using TreeAge Pro software version 2011 (TreeAge Software Inc., Evanston, IL, USA). For the diagnostic review, a total of 7524 citations were identified, of which 12 test accuracy studies were included in the review: six studies evaluated PET-CT, two evaluated MRI, three evaluated CT and one evaluated both MRI and CT. All studies were small and the majority evaluated imaging in women in whom recurrence was suspected on the basis of symptoms. The PET-CT studies evaluated local and distant recurrence and most used methods similar to current practice, whereas five of the six CT and MRI studies evaluated local recurrence only and not all employed currently used methods. Meta-analysis of PET-CT studies gave a sensitivity of 92.2% [95% confidence interval (CI) 85.1% to 96.0%] and a specificity of 88.1% (95% CI 77.9% to 93.9%). MRI sensitivities and specificities varied between 82% and 100% and between 78% and 100%, respectively, and CT sensitivities and specificities varied between 78% and 93% and between 0% and 95%, respectively. One small study directly compared PET-CT with older imaging methods and showed more true-positives and fewer false-negatives with PET-CT. The subjective elicitation from 21 clinical experts gave test accuracy results for asymptomatic and symptomatic women and the results for symptomatic women were similar to those from the published literature. Their combined opinions also suggested that the mean elicited increase in accuracy from the addition of PET-CT to MRI and/or CT was less than the elicited minimum important difference in accuracy required to justify the routine addition of PET-CT for the investigation of women after completion of primary treatment. For the effectiveness review, a total of 24,943 citations were identified, of which 62 studies were included (chemotherapy, 19 randomised controlled trials; radiotherapy or chemoradiotherapy, 16 case series; radical hysterectomy and pelvic exenteration, 27 case series). None provided the effectiveness of cisplatin monotherapy, the most commonly used chemotherapeutic agent in the NHS, compared with supportive care in a background of other treatment such as radiotherapy in recurrent and persistent cervical cancer. The model results showed that adding PET-CT to the current treatment strategy of clinical examination, MRI and/or CT scan was significantly more costly with only a minimal increase in effectiveness, with incremental cost-effectiveness ratios for all models being > £1M per quality-adjusted life-year (QALY) and the additional cost per additional case of recurrence being in the region of £600,000. There was considerable uncertainty in many of the parameters used because of a lack of good-quality evidence in recurrent or persistent cervical cancer. The evidence on diagnostic and therapeutic impact incorporated in the economic model was poor and there was little information on surveillance of asymptomatic women. Given the current evidence available, the addition of PET-CT to standard practice was not found to be cost-effective in the diagnosis of recurrent or persistent cervical cancer. However, although probabilistic sensitivity analysis showed that the main conclusion about cost-ineffectiveness of PET-CT was firm given the range of assumptions made, should more reliable information become available on accuracy, therapeutic impact and effectiveness, and the cost of PET-CT reduce, this conclusion may need revision. Current guidelines recommending imaging for diagnosis using expensive methods such as PET-CT need to be reconsidered in the light of the above. The National Institute for Health Research Health Technology Assessment programme.
    03/2013; 17(12):1-323. DOI:10.3310/hta17120