Patient characteristics are given in Table 1. Mean age at initial diagnosis was 58 years (range 27–86 years). In addition to pelvic examination, all patients were staged by a CT scan of the chest and abdomen, pelvic MRI, and had biopsy-proven cervical cancer. In selected cases (21; 46%) laparoscopic paraaortic lymph node sampling was performed. FIGO stage IIA–IIIA was assigned to 24 (52%) patients, while 22 patients were classified as having FIGO stage IIIB–IVA. Squamous cell carcinoma with 39 patients (85%) was much more common than adenocarcinoma with 7 patients (15%).

Following computed tomography of the abdomen and pelvis after rectal and bladder preparation (all organs empty) using spiral CT with 3 mm reconstruction (Canon, Aquilion LB©, Neuss, Germany) and MRI of the pelvis (T2w SE, T1w-Gd enhanced data, Siemens, Altea© 1.5T or Amira© 1.5T), treatment planning was performed (Varian, Eclipse©: treatment planning, v. 15.5) and applied by IMRT using dynamic arcs (Varian, TrueBeam© v. 2.7). Dose was prescribed with single fractions of 1.8 Gy and a total dose of 50.4 Gy, specified to the D50 according to ICRU report 83. Accordingly, the median total dose was 50.4 Gy (IQR: 49.1–50.4 Gy). The median dose delivered to the primary tumor volume was 54.6 Gy (IQR: 50.4–56 Gy), for the pelvic/paraaortic lymph nodes it was 50.4 Gy (IQR 47.3–50.4 Gy). Thirteen of 46 patients received radiation to the paraaortic lymph node region given positive histologic laparoscopic sampling there.

For brachytherapy, a total dose of 28 Gy in 4 fractions was administered twice weekly (IQR: 27–28 Gy) according to the technique described by Pötter et al. [5]. After insertion of the Vienna applicator (Varian, 3D Interstitial Ring Applicator, GammaMed Plus iX©) under general and peridural anesthesia, treatment planning with CT and MRI was performed. Gross tumor volume, high-risk clinical target volume, and low-risk clinical target volume were delineated according to Pötter et al. [5]. Brachytherapy dose was intended to cover the high-risk clinical target volume and was specified to the 85% isodose. Dose constraint for organs at risk were as follows: for rectum and bladder, D2cc should not exceed a fractional dose of 3 Gy. Treatment characteristics are given in Table 1. The median D2cc for rectum was 73.8 Gy, while the bladder received a slightly higher dose with a median of 78.3 Gy.

Patients were scheduled for intravenous cisplatin chemotherapy following a sufficient urinary excretory function test with a creatinine clearance of at least 70 mL/min. A weekly dose of 40 mg/m2 was to be applied. For simultaneous cisplatin, a median total dose of 200 mg/m2 body surface area (BSA) was applied (IQR: 40–200 mg/m2 BSA). A total of 5 patients had another chemotherapeutic regimen such as carboplatin or mitomycin C together with 5‑fluoruracil (5-FU) instead of cisplatin due to hematological or nephrological limitations.

According to the medical records, a total of 27 patients (57%) complained of acute toxic effects during and after treatment and 10 (22%) of the patients complained of late toxicities. Table 2 gives an overview according to the CTC grading. In general, most symptoms could be treated in an outpatient setting and were thus staged grade 2. Pulmonary acute toxicity included a pulmonary embolism in 2 patients requiring hospitalization. Regarding late toxicities, the patients complained most about urogenital side effects, followed by gastrointestinal and musculoskeletal complaints. No toxic effects of grades 4 and 5 were seen.

Five-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively (Fig. 2a–c). A significant impact on OS was seen for FIGO stage (IIA–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), for overall treatment time (OTT; 50–65 d: 64% vs. > 65 d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. > 73 Gy: 38%, p = 0.046). Table 3 depicts the prognostic factors with impact on the OS. Figure 3a–c depict the respective survival curves. The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). Median follow-up time for surviving patients was 21 months (range 3–89 months). No impact on OS, DMFS, and PRFS was noted for histopathologic typing (adenocarcinoma vs. squamous cell carcinoma), patients age at diagnosis, total RT dose, cumulative cisplatin dose, and D2cc of the urinary bladder.

a Overall survival, b distant metastases-free survival, c pelvic tumor-free survival

a Impact of FIGO stage (IIA–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), b impact of overall treatment time (OTT; 50–65 d: 64% vs. > 65 d: 38%, p = 0.004)

a Overall quality of daily functions according to EORTC-QLQ-C30 (data are presented as mean ± standard deviation), b overall occurrence of side effects of therapy according to EORTC-QLQ-C30 (data are presented as mean ± standard deviation), c functional scale and symptom scale of EORTC-QLQ-CX24 (data are presented as mean ± standard deviation)

Global health score (overall health), general QoL score, and the cervical cancer-specific QoL score after receiving RCT and interstitial BT were assessed. The results are given on a scale of 0 to 100, where 100 is considered full functionality for the functional scales and considered with the worst outcome in symptom scales, whereas 0 is the worst possible outcome for functional scales and the best for the symptom scales. Figure 4a-c depict the QoL-parameters. The outcomes are seen in the tables below (Tables 4 and 5).

According to the evaluation of the EORTC-QLQ-C30 questionnaire, general health scored an average of 63 out of 100 (IQR: 50.0–66.6; SD ± 14.3). The least impaired was cognitive function, with a score of 84 (IQR: 66.6–100%; SD ± 18.6). Emotional functions had a mean score of 74 (IQR: 58.3–91; SD ± 18.6). The symptom limiting the patients most was insomnia, scoring 46/100 (IQR: 0–66.6%; SD ± 37.2). Thereafter, the most incisive symptoms perceived were fatigue with a mean score of 41 (IQR: 20–66.6; SD ± 26.5), dyspnea with a mean of 32 (IQR: 0–66.6; SD ± 30.7), and pain with an average score of 29 (IQR: 16.6–33.3; SD ± 18.8). Patients complained less frequently about diarrhea, constipation, and loss of appetite.

The last part of the questionnaire could be answered if one had been sexually active in the last 4 weeks. This was true for 5 female patients and showed the result that less than one third of these 5 had enjoyed sex.