Abstract Purpose Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This ...is the first comprehensive report on clinical outcome in a large multi-institutional cohort. Patients and methods From twelve centres 731 patients, treated with definitive EBRT ± concurrent chemotherapy followed by IGBT, were analysed. Kaplan–Meier estimates at 3/5 years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3–4 late toxicity (CTCAEv3.0) was reported. Results Median follow up was 43 months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA–IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46 ± 2.5 Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87 ± 15 Gy (EQD210 ), mean D2cc was: bladder 81 ± 22 Gy, rectum 64 ± 9 Gy, sigmoid 66 ± 10 Gy and bowel 64 ± 9 Gy (all EQD23 ). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5 years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5 years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3–G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. Conclusion IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Purpose To establish dose volume–effect relationships predicting late rectal morbidity in cervix cancer patients treated with concomitant chemoradiation and MRI-guided adaptive brachytherapy ...(IBABT) within the prospective EMBRACE study. Material and method All patients were treated with curative intent according to institutional protocols with chemoradiation and IGABT. Reporting followed the GEC-ESTRO recommendations ( D 0.1 cm 3 , D 2 cm 3 ), applying bioeffect modeling (linear quadratic model) with equieffective doses (EQD23 ). Morbidity was scored according to the CTC-AE 3.0. Dose–effect relationships were assessed using comparisons of mean doses, the probit model and log rank tests on event-free periods. Results 960 patients were included. The median follow-up was 25.4 months. Twenty point one percent of the patients had grade 1 events, 6.0% grade 2, 1.6% grade 3 and 0.1%, grade 4. The mean DICRU , D 0.1 cm 3 , and D 2 cm 3 were respectively: 66.2 ± 9.1 Gy, 72.9 ± 11.9 Gy, and 62.8 ± 7.6 Gy. Increase of dose was associated with increase in severity of single endpoints and overall rectal morbidity (grade 1–4) ( p < 0.001–0.026), except for stenosis ( p = 0.24–0.31). The probit model showed significant relationships between the D 2 cm 3 , D 0.1 cm 3 , and DICRU and the probability of grade 1–4, 2–4, and 3–4 rectal events. The equieffective D 2 cm 3 for a 10% probability for overall rectal grade ⩾ 2 morbidity was 69.5 Gy ( p < 0.0001). After sorting patients according to 6 D 2 cm 3 levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A D 2 cm 3 ⩾ 75 Gy was associated with a 12.5% risk of fistula at 3 years versus 0–2.7% for lower doses ( p > 0.001). A D 2 cm 3 < 65 Gy was associated with a two times lower risk of proctitis than D 2 cm 3 ⩾ 65 Gy. Conclusions Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose–volume ( D 2 cm 3 , D 0.1 cm 3 ) and dose-point (DICRU ) parameters. A D 2 cm 3 ⩽ 65 Gy is associated with more minor and less frequent rectal morbidity, whereas a D 2 cm 3 ⩾ 75 Gy is associated with more major and more frequent rectal morbidity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To evaluate the clinical use of 3D printing technology for the modelling of individual applicators for advanced gynecological tumors in magnetic resonance imaging (MRI)-based brachytherapy (BT).
We ...tested individually designed 3D-printed applicators in nine patients with advanced gynecological cancer. Before BT was performed, all patients were treated with external beam radiotherapy (EBRT). The most common indication for individualized BT was advanced gynecological tumors where the use of standard BT applicators was not feasible. Other indications were suboptimal dose-volume histogram (DVH) parameters for high-risk clinical target volume (CTV-T
) at the first BT (V
≤ 90% of CTV-T
volume and D
≤ 80%, D
≤ 100%, and D
≤ 60% of dose aim). The EQD
dose aim to the target volume D
CTV-T
per one BT fraction was 20 Gy for cervical or recurrent endometrial cancer and 16 Gy for vaginal cancer patient. The first BT with the standard applicator
was used as the virtual plan for designing a 3D-printed applicator. The next BT was performed with a 3D-printed applicator
. The primary endpoint was to improve CTV-T
DVH parameters without exceeding the dose to the organs at risk (OARs).
All DVH parameters for CTV-T
were significantly higher with the use of an individually designed applicator. Mean D
CTV-T
improved from 14.1 ±5.4 Gy to 22.0 ±2.5 Gy and from 7.1 Gy to 16.2 Gy for cervical/recurrent endometrial and vaginal cancer, respectively (
< 0.001). The mean D
bladder, rectum, sigmoid, and bowel dose was within institutional dose constraints, and increased from 13.0 ±1.5 Gy to 13.6 ±1.5 Gy (
= 0.045), 10.8 ±1.2 Gy to 11.7 ±1.3 Gy (
= 0.004), 8.9 ±3.2 Gy to 10.3 ±3.3 Gy (
= 0.008), and 8.7 ±3.8 Gy to 9.2 ±3.1 Gy (
= 0.2).
With the use of individual 3D-printed applicators, all DVH parameters for CTV-T
significantly improved without compromising the dose constraints for the OARs.
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IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UL, UM, UPUK
To compare 4 Gy × 5 (1 week) to 3 Gy × 10 (2 weeks) in relieving pain and distress in patients with metastatic epidural spinal cord compression (MESCC).
The randomized SCORE-2 trial compared 4 Gy × 5 ...(n = 101) to 3 Gy × 10 (n = 102) for MESCC. In this additional analysis, these regimens were compared for their effect in relieving pain and distress. Distress was evaluated with the distress-thermometer (0 = no distress, 10 = extreme distress) and pain on a linear scale (0 = no pain, 10 = worst pain). Relief of distress was defined as decrease of ≥2 points; complete and partial pain relief were defined as achieving a score of 0 points and a decrease ≥2 points, respectively, without increase of analgesic use. This prospective secondary analysis of the SCORE-2 trial aimed to show that 4 Gy × 5 was not inferior to 3 Gy × 10 regarding distress and pain relief. Analyses were performed using the unconditional test of noninferiority for binomial differences based on restricted maximum likelihood estimates (noninferiority margin: -20%). Evaluations were performed before, directly after, and 1, 3, and 6 months after radiation therapy. (ClinicalTrials.gov: NCT02189473).
At baseline, median distress scores were 8 (2-10) points in the 4 Gy × 5 group and 8 (2-10) points in the 3 Gy × 10 group. At 1 month, distress relief rates were 58.1% (43/74) and 62.7% (47/75) (difference: -4.6%; 95% confidence interval, -20.0% to +11.1%; P = .025). At baseline, median pain scores were 7 (2-10) and 7 (2-10) points, respectively. At 1 month, complete pain relief rates were 23.5% (16/68) versus 20.0% (14/70) (difference, +3.5%; 95% confidence interval, -10.4% to +17.5%; P < .001), and overall pain relief rates were 52.9% (36/68) versus 57.1% (40/70) (difference, -4.2%; 95% confidence interval, -20.5% to +12.3%; P = .029). Distress and pain relief rates after 4 Gy × 5 were largely comparable to 3 Gy × 10 at all time points. Associated 95% confidence intervals did not point toward any relevant differences.
In patients with MESCC and poor to intermediate survival prognoses, 4 Gy × 5 appeared noninferior to 3 Gy × 10 regarding pain and distress relief.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Abstract Background and purpose In planning to meet evidence based needs for radiotherapy, guidelines for the provision of capital and human resources are central if access, quality and safety are ...not to be compromised. A component of the ESTRO-HERO (Health Economics in Radiation Oncology) project is to document the current availability and content of guidelines for radiotherapy in Europe. Materials and methods An 84 part questionnaire was distributed to the European countries through their national scientific and professional radiotherapy societies with 30 items relating to the availability of guidelines for equipment and staffing and selected operational issues. Twenty-nine countries provided full or partial evaluable responses. Results The availability of guidelines across Europe is far from uniform. The metrics used for capital and human resources are variable. There seem to have been no major changes in the availability or specifics of guidelines over the ten-year period since the QUARTS study with the exception of the recent expansion of RTT staffing models. Where comparison is possible it appears that staffing for radiation oncologists, medical physicists and particularly RTTs tend to exceed guidelines suggesting developments in clinical radiotherapy are moving faster than guideline updating. Conclusion The efficient provision of safe, high quality radiotherapy services would benefit from the availability of well-structured guidelines for capital and human resources, based on agreed upon metrics, which could be linked to detailed estimates of need.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this ...background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT.
Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology.
The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1-2 LVSI-negative disease. For 74-84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT.
There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1-2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Malignant spinal cord compression (SCC) is treated with radiotherapy (RT). Additional neurosurgery has become more widely used since a trial showed a benefit for selected patients. Although lymphomas ...were excluded from that trial, neurosurgery is also increasingly being performed in these patients. This study investigated whether neurosurgery is actually required for this group.
Twenty-nine patients receiving RT alone for SCC from vertebral lymphoma were analyzed for motor function, walking ability, in-field recurrence and survival.
Overall response was 100% (72% improvement, 28% stable). At 1, 6 and 12 months after RT, 83%, 100% and 100% of patients were able to walk; 64%, 100%, and 100% of non-ambulatory patients regained their walking ability. Freedom from in-field recurrence was 100% at 6 and 12 months. Survival rates at 6 and 12 months were 79% and 75%.
RT alone resulted in excellent outcomes for SCC from lymphoma. These patients may not require surgery.
According to our randomized trial, 5×4Gy was comparable to 10×3Gy for metastatic spinal cord compression. Since it remained unclear whether findings applied to poor and intermediate prognoses ...patients, subgroup analyses were performed.
In patients with poor prognoses, 58 received 5×4Gy, 53 received 10×3Gy. In intermediate-prognoses patients, numbers were 43 and 49.
In patients with poor prognoses, 1-month overall response (OR) was 85% after 5×4Gy and 10×3Gy (p=0.99), improvement 38% vs. 42%, ambulatory status 60% vs. 64% (p=0.83), 6-month local progression-free survival (LPFS) 75% vs. 69% (p=0.74) and 6-month overall survival (OS) 26% vs. 19% (p=0.43). In patients with intermediate prognoses, 1-month OR was 89% after 5×4Gy and 93% after 10×3Gy (p=0.85), improvement 39% vs. 45%, ambulatory status 84% vs. 82% (p=0.90), 6-month LPFS 79% vs. 92% (p=0.17) and 6-months OS 65% vs. 58% (p=0.65).
5×4Gy was not significantly inferior to 10x3Gy in both subgroups.
Abstract Background and purpose Survival scores for patients with brain metastasis exist. However, the treatment regimens used to create these scores were heterogeneous. This study aimed to develop ...and validate a survival score in homogeneously treated patients. Materials and methods Eight-hundred-and-eighty-two patients receiving 10 × 3 Gy of WBRT alone were randomly assigned to a test group ( N = 441) or a validation group ( N = 441). In the multivariate analysis of the test group, age, performance status, extracranial metastasis, and systemic treatment prior to WBRT were independent predictors of survival. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. Scores were summed and total scores ranged from 6 to 19 points. Patients were divided into four prognostic groups. Results The 6-month survival rates were 4% for 6–9 points, 29% for 10–14 points, 62% for 15–17 points, and 93% for 17–18 points ( p < 0.001) in the test group. The survival rates were 3%, 28%, 54% and 96%, respectively ( p < 0.001) in the validation group. Conclusions Since the 6-month survival rates in the validation group were very similar to the test group, this new score (WBRT-30) appears valid and reproducible. It can help making treatment choices and stratifying patients in future trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To investigate the prognostic role of the number of involved extracranial organs in patients with brain metastasis from small-cell lung cancer (SCLC).
Data of 155 patients receiving whole-brain ...radiotherapy (WBRT) alone for brain metastasis from SCLC were retrospectively evaluated. In addition to the number of involved extracranial organs, six potential prognostic factors were analyzed including WBRT regimen, age, gender, Karnofsky performance score (KPS), number of brain metastases, and interval from diagnosis of SCLC to WBRT.
Six-month survival rates of patients with involvement of 0, 1, 2, and ≥3 extracranial organs were 52%, 29%, 9%, and 0%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (p=0.003). Older age (p=0.005), lower KPS (p<0.001), and greater number of brain metastases (p=0.005) were also significantly associated with poorer survival.
The number of involved extracranial organs is an independent prognostic factor of survival in SCLC patients with brain metastasis.
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