Clinical results of external beam radiotherapy alone with a concomitant boost program or with conventional fractionation for cervical cancer patients who did not receive intracavitary brachytherapy

摘要

The patients were treated with EBRT alone administered by a combination of whole pelvic irradiation (WPI) and local irradiation (LI) (Fig. 1). All patients underwent CT simulation, and EBRT was administered with 3DCRT. EBRT was delivered using a linear accelerator with an X-ray energy of ≥6-MV photons. The patients were instructed to void their bladder and rectum as a countermeasure to avoid uterus motion which is influenced by rectal filling and bladder filling just before both CT simulation and daily treatment. The clinical target volume (CTV) of WPI included the gross tumor volume of the primary tumor, uterine cervix, uterus corpus, vagina, parametrial tissue and regional nodes (common iliac, internal iliac, external iliac, hypogastric, obturator and presacral nodes). For primary tumor delineation, we referred to T2-weighted axial MRI images. The primary tumor, uterine cervix and uterine corpus are subject to internal motion, which is individual and unpredictable. We generally set an internal margin of 5–10 mm around the primary tumor, cervix and corpus. For contouring of the nodal areas for CTV, an 8-mm margin was set around the vessels for nodal coverage. The CTV of WPI was expanded uniformly by 1 cm in all directions to produce a planning target volume (PTV). The CTV of LI included primary tumor, parametrium invasion area and metastatic regional nodes. Additionally, the CTV was expanded uniformly by 5–10 mm in all directions to produce an internal target volume (ITV) for LI. In creating the PTV of LI, a margin of 1 cm was circumferentially added around the ITV, and a 1.5-cm margin was added both superiorly and inferiorly. A four-field technique by 3DCRT was used to irradiate the whole pelvis sparing the small bowel. For LI, multiple fields or dynamic conformal arc fields were used to reduce the total dose to the surrounding tissue, especially to the rectum and bladder. The follow-up evaluations were performed at 1-month intervals for the first year, at 3-month intervals for the second year and at 6-month intervals thereafter. At the time of the follow-up visits, we prospectively collected data regarding the locoregional and distant status and late toxicities. The follow-up evaluation routinely included a physical examination, diagnostic imaging and toxicity assessment. The median follow-up time was 40 months (range: 6–93 months) for all patients. The actuarial curves of LC and overall survival (OAS) rates were calculated using the Kaplan–Meier method, with the first day of treatment as the starting point. The Log-rank test was used to compare important treatment variables and tumor characteristics on a univariate analysis, and the results were considered to be statistically significant with P?≤?0.05. The evaluated RT variables and tumor characteristics included fractionation, OTT, FIGO stage and maximum tumor diameter (MTD). The clinical response rate was evaluated at 2 months after the completion of treatment, according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines [5]. Of 16 patients, 12 achieved complete response (CR), two achieved partial response (PR) and two had stable disease (SD). Of 12 CR patients, seven patients are alive without disease (one patient in whom para-aortic and supraclavicular recurrence occurred at 25 months and who was successfully treated by EBRT alone is included) and one patient who had stage IIB disease with 5.5 cm of MTD was alive with local recurrence. In three patients with CR, distant metastasis occurred and they died of disease without pelvic recurrence. The remaining patient with CR died of intracerebral hemorrhage. Of the four patients with PR or SD, one patient with PR was successfully locally controlled, however, she eventually died of para-aortic, supraclavicular recurrence and bone metastasis. The remaining three patients with PR or SD died of various types of recurrence (local recurrence; local recurrence; local recurrence and liver metastasis). The 3-year LC and OAS rates for all patients were 75.0% and 43.8%, respectively. The 3-year LC curves according to the RT variables and tumor characteristics are shown in Fig. 2, 3, 4 and 5. The 3-year LC of the CCB group tended to improve in comparison with the CF group (90.0% vs. 50.0%, P?=?0.0692, Fig. 2). The 3-year LC of the OTT ≤42 days group showed a significant statistical increase in comparison with the OTT ≥43 days group (100% vs. 42.9%, P?=?0.0095, Fig. 3). No significantly statistical difference was observed in the 3-year LC between the FIGO Stage IIB/IIIB group and Stage IVA (88.9% vs. 57.1%, P?=?0.1242, Fig. 4). The 3-year LC of the MTD ≤5 cm group tended to be improved in comparison with the MTD 5 cm group (100% vs. 55.6%, P?=?0.0513, Fig. 5). In the OAS there was no significant statistical difference depending on the RT variables and tumor characteristics. The acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE