Definitive Extended-field Intensity-modulated Radiotherapy with Chemotherapy for Cervical Cancer with Para-aortic Nodal Metastasis

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1 Definitive Extended-field Intensity-modulated Radiotherapy with Chemotherapy for Cervical Cancer with Para-aortic Nodal Metastasis JINHONG JUNG 1,2, GEUMJU PARK 1 and YOUNG SEOK KIM 1 Departments of 1 Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; 2 Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, South Korea Abstract. Aim: To evaluate the efficacy and toxicity of definitive extended-field intensity-modulated radiotherapy (EF-IMRT) with chemotherapy in cervical cancer with paraaortic lymph node (PAN) metastasis. Patients and Methods: The present retrospective cohort study involved 45 consecutive patients. EF-IMRT consisted of 46 Gy to pelvic and para-aortic regions, 14 Gy-boost to gross nodes, and 30 Gy in six fractions of intracavitary brachytherapy. Platinumbased chemotherapy occurred simultaneously. Results: Twoyear overall and disease-free survival rates (median followup=30 months) were 85.4% and 61.7%, respectively. In 78%, 89%, and 89%, the primary cervical mass, pelvic metastasis, and PAN metastasis exhibited a complete response, respectively. Ten, four, and other four patients exhibited locoregional (including post-treatment residual disease), distant, and combined failure, respectively. The most common severe acute toxicity was hematological (n=36). One and two patients had severe late gastrointestinal and other toxicities, respectively. Conclusion: EF-IMRT (to 60 Gy) plus chemotherapy resulted in good locoregional control, survival rates, and acceptable toxicity. The incidence of para-aortic node (PAN) involvement in cervical cancer increases as the clinical stage of the tumor advances: 5%, 16%, and 25% of patients with stage I, II, and III cervical cancer exhibit PAN involvement, respectively (1). Correspondence to: Young Seok Kim, MD, Ph.D., Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, , Republic of Korea. Tel: , Fax: , ysk@amc.seoul.kr Key Words: Uterine cervical cancer, extended-field radiotherapy, intensity-modulated radiotherapy, chemotherapy. Although pelvic lymph node (PLN) and PAN status have been shown to be significant prognostic factors for survival in cervical cancer (2, 3), the clinical tumor stage is not influenced by the presence of lymph node (LN) involvement. Moreover, once uterine cervical cancer has spread to the PAN, clinical stage does not affect the outcome (4). Since the major pattern of recurrence in cervical cancer with PAN metastasis after extended-field radiotherapy (RT) is distant failure (4), patients with PAN metastasis usually undergo chemoradiotherapy that encompasses the pelvic and paraaortic region. This treatment associates with survival rate of approximately 40% at 2-5 years and various toxicity profiles (5-7). However, the dose delivered to the gross PAN by using conventional RT techniques has been limited by concerns about toxicity: after extended-field chemo-radiotherapy, as many as 9-50% and 12-34% of patients exhibit severe acute and late toxicity, respectively (5-7). Several recent studies on extended-field intensitymodulated radiation therapy (EF-IMRT) showed that highdose irradiation to the involved PAN and the primary cervical mass was effective and associated with acceptable toxicity (8-11). However, the total dose delivered to the PAN in these studies varied depending on the treatment aim, which ranged from definitive to elective RT of the lesions. As a result, the optimal dose and clinical outcomes of EF-IMRT for cervical cancer with PAN metastasis are not well-defined. Therefore, this retrospective cohort study was performed to evaluate the efficacy and toxicity of definitive EF-IMRT with concomitant chemotherapy in patients with cervical cancer who present with PAN metastasis. Patients and Methods Patients. Between 2008 and 2012, 88 consecutive patients with biopsy-proven, stage IB-IVA cervical cancer were treated with EF- IMRT in our hospital. Forty-five patients who presented with gross /2014 $

2 PAN metastasis and treated with curative EF-IMRT and concomitant chemotherapy constituted our study population. All patients underwent exact staging, including physical examinations, complete blood counts, liver function tests, urinalysis, chest X-ray, intravenous pyelogram, cystoscopy, sigmoidoscopy, pelvic magnetic resonance imaging (MRI), and positron emission tomographycomputed tomography (PET/CT). Metastatic PAN was diagnosed on the basis of both the radiographic and the physician s interpretation of its appearance in the context of the clinical information. In two patients (4%), tissue confirmation of suspected PAN was performed. Treatment planning. Before treatment, each patient underwent CT simulation using intravenous contrast agents in the supine position (GE Light Speed RT, GE Healthcare, Buckinghamshire, UK). The gross tumor volume consisted of all areas of gross disease, including the primary tumor and the LNs. The clinical target volume (CTV) included the entire uterus, the para-cervical and parametrial regions, and the iliac, hypogastric, obturator LN and PAN area. The CTV in the para-aortic regions was contiguous with the pelvic LN stations and generously encompassed the aorta and inferior vena cava with a margin of at least 7-10 mm. The superior border of the CTV was usually set at the level of the T12-L1 interface but was adjusted based on the location of the involved PANs. The planning target volume (PTV) margin was 7 mm from the CTV. However, the anterior margin was occasionally reduced to 5 mm because of the proximity to the duodenum. Inverse treatment planning for IMRT was performed using the sliding window technique with the Helios algorithm of the Eclipse Planning System (Eclipse V8.0 or V10.0, Varian Medical System, Palo Alto, CA, USA). While planning, the authors sought to meet the following dose constraints: (i) >95% of the PTV receives >95% of the prescribed dose (PD) and <10% receives >110% of the PD; (ii) rectal Dmax <100% of the PD; (iii) bladder Dmax <110% of the PD; (iv) V20 of the kidney <30%; (v) V45 of the intestinal cavity <15% and V60 <1%; and (vi) V45 of the spinal cord <1%. No specific constraints for bone marrow were used. An external beam RT consisting of 46 Gy in 23 fractions, which comprised seven to nine coplanar fields, was delivered to the PTV once daily, five times per week, using a 15 MV X-ray from the linear accelerators (2100 C/D, 21EX, 21IX Trilogy, Varian Medical System). At the end of external beam RT, high-dose-rate (HDR) intracavitary brachytherapy (BT) was administered using Fletcher-Suit after-loading applicators. Six fractions of 5 Gy were delivered to point A twice per week using a 192 Ir brachytherapy unit (MicroSelectron, Nucletron, Veenendaal, the Netherlands). Parametrial boosts were integrated between brachytherapy sessions; after an initial treatment of 46 Gy in 23 fractions, planning CT scan was repeated to delineate the residual LNs and a boost of up to 60 Gy in 30 fractions was delivered. Platinum-based chemotherapy was administered concurrently with EF-IMRT as determined by the physicians preference, as follows: 35 patients received weekly cisplatin, eight patients received paclitaxel plus cisplatin at 3 week intervals, one patient received paclitaxel plus carboplatin at 3 week intervals, and one patient with small cell carcinoma received etoposide plus cisplatin at 4 week intervals. During treatment, all patients were evaluated weekly for toxicity and tumor response. After completing therapy, the patients were evaluated at 3 month intervals for 2 years, and every 6 months thereafter. Three months after completing chemoradiotherapy (CRT), MRI and/or PET/CT were performed to evaluate the response to treatment. A complete response (CR) was defined as the Table I. Patients characteristics. Characteristics No. of patients (%) Age (years) (9) (36) (31) (18) (7) FIGO stage IB 4 (9) IIA 5 (11) IIB 21 (47) IIIA 2 (4) IIIB 4 (9) IVA 9 (20) Primary tumor size (cm) (53) > (47) Parametrial involvement None 11 (24) Unilateral 17 (38) Bilateral 17 (38) Pre-treatment hemoglobin (g/dl) (33) <12 30 (67) Pre-treatment SCC-Ag Normal range 6 (13) Elevated 39 (87) FIGO, International Federation of Gynecology & Obstetrics; SCC-Ag, squamous cell carcinoma antigen. disappearance of gross tumor clinically and radiologically. A partial response (PR) was defined as a >50% reduction in initial tumor volume. PET/CT was performed again once a year for the first 2 years, and a CT scan was performed yearly thereafter. In cases where recurrence was suspected, additional imaging studies were performed, as appropriate. Acute toxicities (i.e., within 3 months of treatment) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Late toxicities were graded according to the Radiation Therapy Oncology Group late toxicity scale. Locoregional failure (LRF) was defined as persistent disease or any recurrence within the radiation field, and distant failure (DF) as recurrence outside the radiation field. Disease-free survival (DFS) was calculated from the RT start date to LRF or DF or death from any cause. Overall survival (OS) was calculated from the start of treatment to death or last follow-up. Statistical analysis. The cumulative survival rate was calculated using the Kaplan-Meier method. Univariate and multivariate analysis was performed with a Cox proportional hazards model. A p-value <0.05 was considered statistical significant. Statistical analyses were performed using the Statistical Package for Social Sciences, version 18.0 (SPSS, Chicago, IL, USA). Results The patients characteristics are summarized in Table I. The median age was 50 years (range=31-75) and 21 patients (47%) had International Federation of Gynecology and Obstetrics (FIGO) stage IIB. The median primary tumor size was 5.5 cm (range= ), as determined by MRI. Most 4362

3 Jung et al: EF-IMRT Plus Chemotherapy for Cervical Cancer Table II. Radiotherapy characteristics. Characteristic Dose (Gy, EQD2) Table III. Treatment-related acute and late toxicities. Toxicity Grade 0-2 Grade 3 Grade 4 Total dose to cervical mass Median (range) 74 ( ) Total dose to PAN Median (range) 60 (26-60) BT Yes 28 (62%) No 17 (38%) Total dose of BT Median (range) 37.5 ( ) Upper PTV border T10-T11 1 (2%) T11-T12 3 (7%) T12-L1 26 (58%) L1-L2 15 (33%) RT duration (days) Median (range) 53 (31-100) RT interruption Yes 15 (33%) No 30 (67%) Durations (days) 7 (3-23) EQD2, Equivalent dose in 2 Gy fractions; PAN, para-aortic lymph node; BT, brachytherapy; PTV, planning target volume; RT, radiotherapy. of the patients (n=41, 91%) had squamous cell carcinoma. The remaining patients had adenocarcinoma (n=2), large cell neuroendocrine carcinoma (n=1), or small cell carcinoma (n=1). After 46 Gy in 23 fractions of EF-IMRT, the planned IMRT boost to the PAN and the BT to the cervical mass were administered in 41 (91%) and 28 (62%) patients, respectively (Table II). Thirteen patients received an IMRT boost to the primary mass instead of BT because of insufficient regression and unfavorable anatomy. Four patients did not complete their planned RT and stopped RT at doses of 26, 30, 42, and 44 Gy, respectively because of disease progression (n=1), refusal of additional treatment (n=1), severe hematological toxicity (n=1), and poor general condition (n=1). The median RT duration was 53 days. Fifteen (33%) experienced RT interruption that exceeded 2 days, mainly because of neutropenia. Twelve patients (27%) did not complete the scheduled chemotherapy, while 13 (29%) received adjuvant chemotherapy after CRT with paclitaxel-plus-cisplatin (n=5), paclitaxel-plus-carboplatin (n=7), or etoposide-plus-cisplatin (n=1). The most frequent acute grade 3 toxicity was hematological toxicity (80%) (Table III); however, it was usually self-limited. Four patients (9%) experienced grade 3 acute gastrointestinal (GI) toxicity (nausea, vomiting, and diarrhea), and one developed grade 3 acute genitourinary (GU) toxicity (i.e., ureteral stricture) 2 months after treatment. None of the patients died of treatment-related toxicity. In 43 patients, late toxicity could be evaluated. The remaining two patients could not be evaluated because one died of rectourethral fistula due to tumor progression during treatment and the other was lost to follow-up after treatment. One patient developed late GI toxicities of grade 3 or greater; late GU toxicities of grade 3 or greater were not observed. One patient Acute Hematological 9 (20) 22 (49) 14 (31) Gastrointestinal 41 (91) 4 (9) Genitourinary 45 (100) 1 2 (2) Late 1 Gastrointestinal 42 (98) 1 3 (2) Genitourinary 43 (100) Others 41 (95) 2 4 (5) The data are presented as numbers of patients, with the percentages in parentheses. 1 Two patients were excluded: one who died of rectourethral fistula due to tumor progression during treatment and one who was lost to follow-up. 2 This patient developed ureteral stricture 2 months after treatment completion. 3 This patient developed rectovaginal fistula with rectal bleeding 8 months after treatment due to tumor regression that invaded the rectum and bladder. 4 These two patients consisted of one patient who developed insufficiency fractures of the bilateral femur heads 8 months after treatment and one patient who developed insufficiency fracture of the sacral ala 18 months after treatment. Table IV. Treatment response according to the site as determined by MRI. Response Primary mass Pelvic LN Para-aortic LN Complete 35 (78) 40 (89) 40 (89) Partial 6 (13) 1 (2) 1 (2) Stable disease 2 (4) 2 (4) 2 (4) Not evaluated 2 (4) 2 (4) 2 (4) LN, Lymph node. The data were presented as numbers of patients, with the percentages in parentheses. developed a recto-vaginal fistula with rectal bleeding 8 months after completing treatment due to tumor regression that invaded the rectum and bladder. Two patients developed other toxicities of grade 3 or greater: one experienced insufficiency fractures of the bilateral femur heads 8 months after treatment and the other experienced insufficiency fracture of the sacral ala 18 months after treatment. The response to treatment could be evaluated in 43 patients. Three months after treatment, the CR rates of the primary cervical mass, PLN metastasis, and PAN metastasis were 78%, 89%, and 89%, respectively, as determined by MRI (Table IV). In all cases of primary cervical mass CR, the PLN and PAN metastases also exhibited CRs. The median follow-up period of all patients was 30 months. During the follow-up period, 18 patients (40%) experienced treatment failure while 25 (56%) had no evidence of disease (Table V). LRF occurred in nine women, as follows: at the vaginal 4363

4 Table V. Patterns of failure (first site of recurrence). Variables No. of patients (%) Failure 18 (40) Locoregional 1 5 (11) Distant 4 (9) Locoregional 1 + distant 4 (9) Residual disease 5 (11) No recurrence 26 (58) Not evaluated 1 (2) 1 These patients had locoregional failure at the vaginal fornix (n=1), uterus (n=1), left renal hilar LN (n=1), PAN (n=4; two were marginal), uterus + PAN (n=1; it was marginal), and perirectal space (n=1; it was marginal). fornix (n=1), the uterus (n=1), the left renal hilar LN (n=1), the PAN (n=4), the uterus plus PAN (n=1), and the perirectal space (n=1). Of the five cases with recurrence at the PAN, two were marginal failures (i.e., inside the PTV but outside the CTV) in the superior direction and one was in the radial direction. In the two cases of superior marginal failure, the upper border of the PTV was at the level of the L1-2 interspace and the recurrences were new tumors. Five patients had persistent residual disease despite CRT; they were assessed as having LRF. The 2-year OS and DFS rates of the entire 45 patient cohort were 85.4% and 61.7%, respectively (Figure 1). Univariate analysis did not detect significant prognostic factors for OS or DFS. However, an early FIGO stage (FIGO IB + IIA) seemed to associate with superior OS than advanced stages (100% vs. 82% at 2 years), although this did not achieve statistical significance (p=0.12). Discussion In the present study, we found that patients with cervical cancer and PAN metastasis who were treated with definitive EF-IMRT and concurrent chemotherapy had excellent clinical outcomes in terms of survival: the 2 year OS and DFS rates were 85% and 62%, respectively. Given that all of our patients had gross PAN metastasis, which is known to be a poor prognostic factor (2, 3), the OS and DFS rates of our study are superior to the rates reported by other studies. We speculate that there are several reasons for this. First, higher doses (60 Gy) to the PAN, which is regarded as the gateway to distant metastasis, may result in excellent locoregional control, which would, in turn, lead to less distant metastasis. Indeed, the crude rate of all distant metastases in the present study was 24%: the previous studies on prophylactic or definitive EF-IMRT reported crude rates ranging from 25% to 52%, while studies on definitive EFRT reported crude rates of 42% (7, 9, 11, 12). It should be noted that although several recent studies have evaluated the feasibility of escalated prescription doses to the PAN (8, 10, 13), our study Figure 1. Kaplan-Meier estimates of the overall survival and diseasefree survival of the 45 patients. is the largest and has the longest follow-up period of all studies showing clinical outcomes. The second possible reason for our superior survival rates may be the relatively shorter overall treatment time in the present study (median=53 days): the median treatment times of other studies were days (5, 6, 9, 11); moreover, our treatment regimen associated with minimal RT interruption and good compliance (the RT completion rate was 91%). Third, although the role of adjuvant chemotherapy is not yet established, it could have reduced the distant metastasis rate in the present study. To determine whether adding adjuvant chemotherapy to standard cisplatin-based chemoradiation does indeed improve OS, the phase III OUTBACK trial is currently underway. It should be noted that when Kang et al. developed a model to predict the risk of distant recurrence in patients with locally-advanced cervical cancer, they found that PET-positive PAN associated particularly strongly with the subsequent development of distant metastasis (14). Since distant metastasis is a frequent pattern of failure in cervical cancer (particularly in patients with PAN metastasis), this means that the role of adjuvant chemotherapy should be investigated in a prospective manner. In the present study, 13 (29%) of the patients received adjuvant chemotherapy, but this did not improve OS or DFS: the 2 year OS rates of patients with and without adjuvant chemotherapy were 91% and 83%, respectively (p=0.55) while the 2 year DFS rates of patients with and without adjuvant chemotherapy were 57% and 64%, respectively (p=0.47). Last but not least, all 4364

5 Jung et al: EF-IMRT Plus Chemotherapy for Cervical Cancer patients underwent PET/CT, which prevented under-staging. However, the excellent clinical outcomes of the current study in terms of OS and DFS should be interpreted with some caution because the PANs were evaluated radiologically, not surgically. Despite the excellent accuracy of MRI and PET/CT in terms of PAN metastasis diagnosis (as described further below), it remains possible that some patients of the present cohort did not truly have PAN metastasis. In the present study, only a few patients developed severe acute GI or GU toxicity (9% and 2%, respectively) but 80% experienced grade 3 or greater acute hematological toxicity. A bone marrow-sparing IMRT technique was not adopted in the present study: instead, we sought to reduce the dose to the intestinal cavity; thus, our IMRT plan resulted in high hematological toxicity. Nevertheless, almost all patients completed the RT with minimal non-hematological toxicity or treatment breaks. By contrast, in the RTOG study, which involved planned radiation doses of Gy (twicedaily radiation doses of 1.2 Gy) to the PAN, 40% of the patients exhibited grade 3 or more radiation toxicity; the grade 4 late toxicity rate was also unacceptably high (17%) (5); thus, overall, we achieved an encouraging response rate (an 89% CR rate and a 2% PR rate) with minimal nonhematological toxicity and tolerable hematological toxicity. Therefore, an irradiation dose of 60 Gy for definitive EF- IMRT to PAN metastases may be optimal. However, there were two cases of marginal failure in the superior direction, with the upper border being at the level of the L1-2 interspace; thus, the L1 level should be included, at least. This study has some limitations. First, the PAN metastases were diagnosed radiologically by using PET-CT and MRI, not pathologically. However, MRI has a high positive predictive value (97%) and high specificity (91-99%), in terms of detecting positive LNs (15-18). PET also diagnoses PAN metastasis with a positive predictive value of 75% and a specificity of 92-98% (17-19). In addition, a recent survey showed that CT was the most common method of evaluating the LNs: only 9.7% underwent surgical evaluation (nodal biopsy) (20). In our Institution, PET-CT scanning has been performed as a routine baseline study since 2002 and was offered to all patients in the present study. Second, the present study had a retrospective design and a relatively small number of patients, which associate with inherent study weaknesses such as selection bias. Nevertheless, the current study has several unique strengths. First, the study cohort was homogeneous: all had radiologically-positive PAN metastasis, second, the RT protocol was uniform with regard to the prescription dose and fraction size, and third, the possibility of distant metastasis was excluded in all patients by PET-CT. In conclusion, in patients with cervical cancer and PAN metastasis, high-dose EF-IMRT to the PAN metastasis plus concurrent chemotherapy resulted in good locoregional control and encouraging survival rates with acceptable toxicities, albeit at the expense of acute hematological toxicity. Further studies that seek to reduce the acute hematological toxicity and evaluate the role of adjuvant chemotherapy are warranted. Conflicts of Interest None to declare. Acknowledgements This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (grant no. NRF-2012R1A1A ). References 1 Berman ML, Keys H, Creasman W, DiSaia P, Bundy B and Blessing J: Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study). Gynecol Oncol 19: 8-16, Stehman FB, Bundy BN, DiSaia PJ, Keys HM, Larson JE and Fowler WC: Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 67: , Toita T, Nakano M, Higashi M, Sakumoto K and Kanazawa K: Prognostic value of cervical size and pelvic lymph node status assessed by computed tomography for patients with uterine cervical cancer treated by radical radiation therapy. Int J Radiat Oncol Biol Phys 33: , Grigsby PW, Perez CA, Chao KS, Herzog T, Mutch DG and Rader J: Radiation therapy for carcinoma of the cervix with biopsy-proven positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys 49: , Grigsby PW, Heydon K, Mutch DG, Kim RY and Eifel P: Longterm follow-up of RTOG 92-10: cervical cancer with positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys 51: , Kim YS, Kim JH, Ahn SD, Lee SW, Shin SS, Nam JH, Kim YT, Kim YM and Choi EK: High-dose extended-field irradiation and high-dose-rate brachytherapy with concurrent chemotherapy for cervical cancer with positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys 74: , Varia MA, Bundy BN, Deppe G, Mannel R, Averette HE, Rose PG and Connelly P: Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5- fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 42: , Ahmed RS, Kim RY, Duan J, Meleth S, De Los Santos JF and Fiveash JB: IMRT dose escalation for positive para-aortic lymph nodes in patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. Int J Radiat Oncol Biol Phys 60: , Beriwal S, Gan GN, Heron DE, Selvaraj RN, Kim H, Lalonde R, Kelley JL and Edwards RP: Early clinical outcome with concurrent chemotherapy and extended-field, intensitymodulated radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys 68: ,

6 10 Esthappan J, Chaudhari S, Santanam L, Mutic S, Olsen J, Macdonald DM, Low DA, Singh AK and Grigsby PW: Prospective clinical trial of positron emission tomography/ computed tomography image-guided intensity-modulated radiation therapy for cervical carcinoma with positive para-aortic lymph nodes. Int J Radiat Oncol Biol Phys 72: , Jensen LG, Hasselle MD, Rose BS, Nath SK, Hasan Y, Scanderbeg DJ, Yashar CM, Mundt AJ and Mell LK: Outcomes for patients with cervical cancer treated with extended-field intensity-modulated radiation therapy and concurrent cisplatin. Int J Gynecol Cancer 23: , Salama JK, Mundt AJ, Roeske J and Mehta N: Preliminary outcome and toxicity report of extended-field, intensitymodulated radiation therapy for gynecologic malignancies. Int J Radiat Oncol Biol Phys 65: , Mutic S, Malyapa RS, Grigsby PW, Dehdashti F, Miller TR, Zoberi I, Bosch WR, Esthappan J and Low DA: PET-guided IMRT for cervical carcinoma with positive para-aortic lymph nodes-a dose-escalation treatment planning study. Int J Radiat Oncol Biol Phys 55: 28-35, Kang S, Nam BH, Park JY, Seo SS, Ryu SY, Kim JW, Kim SC, Park SY and Nam JH: Risk assessment tool for distant recurrence after platinum-based concurrent chemoradiation in patients with locally advanced cervical cancer: a Korean gynecologic oncology group study. J Clin Oncol 30: , Kim SH, Kim SC, Choi BI and Han MC: Uterine cervical carcinoma: evaluation of pelvic lymph node metastasis with MR imaging. Radiology 190: , Choi HJ, Kim SH, Seo SS, Kang S, Lee S, Kim JY, Kim YH, Lee JS, Chung HH, Lee JH and Park SY: MRI for pretreatment lymph node staging in uterine cervical cancer. Am J Roentgenol 187: W , Selman TJ, Mann C, Zamora J, Appleyard TL and Khan K: Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis. Can Med Assoc J 178: , Choi HJ, Ju W, Myung SK and Kim Y: Diagnostic performance of computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/ computer tomography for detection of metastatic lymph nodes in patients with cervical cancer: meta-analysis. Cancer Sci 101: , Rose PG, Adler LP, Rodriguez M, Faulhaber PF, Abdul-Karim FW and Miraldi F: Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study. J Clin Oncol 17: 41-45, Eifel PJ, Ho A, Khalid N, Erickson B and Owen J: Patterns of Radiation Therapy Practice for Patients Treated for Intact Cervical Cancer in 2005 to 2007: A Quality Research in Radiation Oncology Study. Int J Radiat Oncol Biol Phys 89(2): , Received April 30, 2014 Revised June 17, 2014 Accepted June 18,