The aims of this study were to investigate the benefit of the Utrecht interstitial CT/MR applicator for combined intracavitary/interstitial (IC/IS) approach, using magnetic resonance imaging-guided ...brachytherapy, over the intracavitary approach alone in patients with locally advanced cervical cancer and to analyze the clinical use of needles.
This study includes the first 20 patients treated with the new applicator. Brachytherapy consisted of two pulsed dose rate applications, and the second application was performed with the IC/IS approach. The number of needles, chosen guiding holes through the ovoids, and insertion depths were based on the dose distribution and dosimetric shortcomings of the first application (IC alone). We investigated the dosimetric gain by comparing the clinical interstitial optimized plan (IC/IS(clinical)) with an additionally generated optimized plan without needle use (IC(study)). Furthermore, we studied the relation of the inserted needles and their source loading patterns with the high-risk clinical target volume (HR-CTV).
A total of 54 needles (range, 1-6 per application) were applied with an average depth of 25 mm. The chosen needle positions corresponded with the location of the HR-CTV extensions. The total and individual needle treatment times per application were on average 19% (range, 4-35%) and 7% (range, 2-14%) of the implant treatment time, respectively. The total (external-beam radiotherapy + brachytherapy) D90 HR-CTV for the IC(study) and the IC/IS(clinical) were on average 79.5 (SD 7.4) Gy(α/β10) and 83.9 (SD 6.7) Gy(α/β10), respectively, with an average gain of 4.4 (SD 2.3) Gy(α/β10) for the second application.
Needle placement was feasible in all patients and resulted in a gain in dose and better coverage of HR-CTV. Defining the location of HR-CTV protrusions and analyzing the associated needles has given us deeper understanding of the possibilities in magnetic resonance imaging-guided (pre)treatment planning with the IC/IS Utrecht applicator.
Abstract Purpose Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). Materials and ...methods Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV ⩾ 85 Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85 Gy. Results The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points ( p < 0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4 ± 4 Gy EQD2 ( p < 0.001), while doses to bladder and rectum (D2cm3 ) were reduced by 2 ± 2 Gy and 3 ± 2 Gy, respectively ( p < 0.001). Conclusions VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis.
Abstract Purpose To evaluate dosimetric parameters and clinical outcome for cervical cancer patients treated with chemo-radiation and MR-image guided adaptive brachytherapy (MR-IGABT) using ...tandem-ovoid applicators for intracavitary or combined intracavitary/interstitial approaches. Method This retrospective analysis includes 46 patients treated between 2006 and 2008. Dose–volume parameters D90 HR-CTV (high-risk clinical target volume) and D2cc OARs (organs at risk) were determined and converted into biologically equivalent doses in 2 Gy fractions (EQD2). Clinical outcome parameters (local control (LC), progression free survival (PFS) and overall survival (OS)) were analysed actuarially and late morbidity crude rates were scored using CTCAEv3.0. Results Mean D90 HR-CTV was 84 (SD9) Gy EQD2 for HR-CTV volumes of mean 57 (SD37) cm3 at time of first brachytherapy (BT). Median follow-up was 41 (range, 4–67) months. Three year LC, PFS, and OS rates were 93, 71, and 65%, respectively. Node negative patients had significantly higher 3-year survival rates compared to node positive ones (PFS 85 versus 53% ( p = 0.013), OS 77 versus 50% ( p = 0.032), respectively) with an even larger difference for patients with FIGO stages IB-IIB (PFS 87 versus 42% ( p = 0.002), OS 83 versus 46% ( p = 0.007), respectively). Late grade 3–4 mainly gastrointestinal or vaginal morbidity was observed in 4 patients (9.5%). No correlations were seen between morbidity and D2cc OAR values. Conclusion (Chemo-) radiation and MR-IGABT with tandem-ovoid applicators result in high LC and promising survival rates with reasonable morbidity.
This study relied on the theory of planned behavior (TPB) to identify the beliefs that influence young people's pro-environmental behavior. High-school students completed a questionnaire regarding ...the performance of pro-environmental behaviors early in the school year and reported on their behavior toward the end of the year. In addition to the standard TPB constructs, the initial questionnaire assessed descriptive norms, moral norms, sex, and empathic concern. Results revealed an excellent fit for the standard TPB model; attitudes, descriptive subjective norms, and perceptions of control made independent contributions to the prediction of intentions, and intentions together with perceived control predicted behavior. Behavioral, normative, and control beliefs predicted, respectively, attitudes, subjective norms, and perceived behavioral control. Empathic concern influenced intentions and behavior indirectly by its effects on behavioral, normative, and control beliefs. Examination of the effects of specific beliefs revealed important implications for designing effective behavior-change interventions.
•We tested the full TPB model applied to high school students' eco-friendly behavior.•The impact of perceived control on intentions and on future behavior is noteworthy.•Of particular importance was the behavior of the parents and the family in general.•Individual differences in empathy can influence the eco-friendly beliefs people hold.•The present study provides guidance for the design of a behavior change intervention.
•Doses to the vaginal dose points predicts well the risk of vaginal morbidity.•Higher doses to the vaginal PIBS points are associated with vaginal stenosis.•A shorter vaginal reference length is ...associated with ≥grade 2 vaginal stenosis.
To evaluate dose–effect relationships between vaginal dose points and vaginal stenosis in patients treated for locally advanced cervical cancer with radio(chemo)therapy and image-guided adaptive brachytherapy.
Patients from six centres participating in the EMBRACE-I study were included. Information on doses to different vaginal dose points, including the Posterior-Inferior Border of Symphysis (PIBS) points and recto-vaginal reference (RV-RP) point, were retrieved from the treatment planning system. In addition, the vaginal reference length (VRL) was evaluated. Vaginal stenosis was prospectively assessed according to the CTCAEv3.0 system at baseline and follow-up. Primary endpoint was grade 2 or higher (G ≥ 2) vaginal stenosis. Impact of dose to the vaginal dose points, and impact of VRL, age, vaginal involvement and applicator on vaginal stenosis G ≥ 2 was evaluated with a Cox proportional-hazard regression model.
301 patients were included. Median follow-up was 49 months. During follow-up, the incidence of G0, G1, G2, and G3 vaginal stenosis was 25% (76), 52% (158), 20% (59) and 3% (8), respectively. Median total doses to PIBS+2 cm, PIBS, PIBS-2 cm and the RV-RP were 52.9 (IQR 49.3–64.7), 41.0 (IQR 15.4–49.0), 4.1 (IQR 2.9–7.0) and 64.6 (IQR 60.0–70.6) Gy EQD23, respectively. Higher doses to the PIBS, PIBS + 2 cm and RV-RP points were significantly associated with increased risk for vaginal stenosis G ≥ 2. Other risk factors for vaginal stenosis were: vaginal involvement at diagnosis, higher age, shorter VRL and use of a tandem-ovoid applicator.
Higher doses to the PIBS+2 cm, PIBS and RV-RP dose points are associated with vaginal stenosis G ≥ 2.
•Overlap volume histograms can be used for prediction models of D2cm3 values.•Prediction models can be used in a multi-center setting to detect suboptimal plans.•Plan quality improvement is possible ...for suboptimal plans detected by the prediction model.
Image-guided adaptive brachytherapy (IGABT) is an important modality in the cervical cancer treatment, and plan quality is sensitive to time pressure in the workflow. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) has been demonstrated to detect suboptimal plans (outliers). This analysis quantifies the possible improvement of plans detected as outliers, and investigates its suitability as a clinical QA tool in a multi-center setting.
In previous work OVH-based models were investigated for the use of QA. In this work a total of 160 plans of 68 patients treated in accordance with the current state-of-the-art IGABT protocol from Erasmus MC (EMC) were analyzed, with a model based on 120 plans (60 patients) from UMC Utrecht (UMCU). Machine-learning models were trained to define QA thresholds, and to predict dose D2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs of the EMC cohort. Plans out of set thresholds (outliers) were investigated and retrospectively replanned based on predicted D2cm3 values.
Analysis of replanned plans demonstrated a median improvement of 0.62 Gy for all Organs At Risk (OARs) combined and an improvement for 96 % of all replanned plans. Outlier status was resolved for 36 % of the replanned plans. The majority of the plans that could not be replanned were reported having implantation complications or insufficient coverage due to tumor geometry.
OVH-based QA models can detect suboptimal plans, including both unproblematic BT applications and suboptimal planning circumstances in general. OVH-based QA models demonstrate potential for clinical use in terms of performance and user-friendliness, and could be used for knowledge transfer between institutes. Further research is necessary to differentiate between (sub)optimal planning circumstances.
Abstract Background and purpose Regarding latest developments, the need of a radiotherapy ‘Patterns of Care’ survey was expressed by the Dutch National Platform Radiotherapy for Gynaecological Cancer ...(LPRGT). Therefore, this study investigated current practice for cervical cancer in all 16 radiation oncology centres in the Netherlands specialised in gynaecological oncology. Material and methods A structured ‘patterns of care’ questionnaire was completed and followed by an in-depth interview with radiation oncologists from all radiotherapy centres specialised in gynaecological oncology. Specific topics addressed were: definition of target volumes, treatment preparation, imaging for treatment planning, treatment planning, and image-guided adaptive radiotherapy for external beam radiotherapy and brachytherapy. Results Current radiotherapy practice in the Netherlands for cervical cancer appears to be in accordance with international standards. However, at the time of the survey some differences were revealed that might have relevant clinical impact. For instance: 1) Half of the centres acquired positron emission tomography combined with CT (PET-CT) for staging and target delineation for every patient, 2) The definition of upper border of the para-aortal lymph node area and dose prescription for external beam radiotherapy varied between the centres, and 3) 12 centres used a single treatment plan for delivering EBRT, and four used a plan-of-the-day strategy with a library of 3–4 treatment plans. Conclusions Most differences were found at the cutting edge of clinical evidence. However, the majority of these uncertainties are topics being addressed in current and planned (inter)national studies.
Management of Nodal Disease in Advanced Cervical Cancer Jürgenliemk-Schulz, Ina-Maria; Beriwal, Sushil; de Leeuw, Astrid A.C. ...
Seminars in radiation oncology,
April 2019, 2019-04-00, 20190401, Letnik:
29, Številka:
2
Journal Article
Recenzirano
During the last decade the adoption of image-guided adaptive brachytherapy has dramatically improved local control in patients with locally advanced cervical cancer (LACC) treated with radiotherapy ...and concomitant chemotherapy; however, nodal failure remains an obstacle. Metastatic lymph nodes can be detected by surgical and imaging approaches with different sensitivities and specificities, that improve the definition of relevant targets for macroscopic and microscopic nodal disease, and that influence our understanding of dose levels of external beam radiotherapy. Systematic use of modern radiotherapy techniques including intensity modulated radiotherapy and simultaneously integrated nodal boosts in combination with daily position verification is emerging as increasingly important for obtaining nodal control in LACC. This review summarizes published and ongoing efforts for optimizing nodal disease treatment in LACC, elaborates the state of the art approach for nodal disease detection, radiotherapy planning and delivery, and discusses future investigational efforts needed for precise optimization.
•Online RTQA with minimal data transfer is feasible and reduces manpower burden•Expert evaluation with qualitative feedback improved contouring compliance.•The Jaccard Conformity Index was not a ...reliable alternative to expert assessment.•Common delineation errors were identified which form the basis for ongoing education.•Strategies to improve engagement with educational content are needed.
EMBRACE-II is an international prospective study of IMRT and MRI-guided adaptive brachytherapy (IGABT) in locally advanced cervix cancer. An online radiotherapy quality assurance (RTQA) programme with minimal data transfer and supporting continuing medical education (CME) was implemented for IMRT contouring.
Participant contours for six volumes-of-interest (VOIs) on one benchmark case were scored (2 = excellent, 1 = fair, 0 = revision required) against a consensus reference contour. For contours receiving a 0 or 1 score, additional qualitative comments were provided. The Jaccard conformity index (JCI) was retrospectively calculated. User interaction with CME content (pre-accreditation questionnaire, contouring atlas, practice cases, quizzes, internal target volume (ITV-T) guide) was analysed.
78 clinicians submitted contours for evaluation. 41% passed at the first attempt, 44% after one revision and 6% after two or more revisions. 9% did not re-submit after failing. The lowest mean scores were for the elective nodal CTV (CTV-E) (1.01/2) and ITV-T (1.06/2). 60 different errors across the six VOIs were identified; five potentially had high impact on loco-regional control. A JCI cut-off of 0.7 would have identified 87% contours that failed expert assessment, but also excluded 54% of passing contours. 39 clinicians responded to the pre-accreditation questionnaire – 36% anticipated difficulties with the ITV-T and 13% with the CTV-E. 35% clinicians contoured on the practice cases, 17% answered a quiz, 96% used the atlas and 38% the ITV-T guide.
Expert evaluation with qualitative feedback improved contouring compliance. The JCI is not a reliable alternative to expert assessment. Moderate uptake of optional CME content limited evaluation.
•Nodal failure rate after chemo-radiation and MRI guided BT is 11%.•Nodal failure rates for the N− and N+ group were 7 and 16%•Complete remission after treatment was seen in 95% of N+ patients.•Nodes ...at diagnosis were mainly located in the pelvis, nodal failures more often in PAO.•Forty-one percent of nodal failure patients had failure outside the treated volume.
To investigate the patterns of nodal failure in patients enrolled in the international multicentre EMBRACE study.
Nodal disease at diagnosis (N−, N+) and nodal failure were analysed per region (NF) (pelvic (parametrial, common iliac, internal/external iliac), inguinal and para-aortic (PAO)) in 1338 patients. Treatment consisted of chemo-radiation and MRI guided brachytherapy. PAO radiotherapy and/or nodal boost was left to the treating centre. At time of diagnosis 52% of patients had pathologic nodes. Frequency analyses were performed in relation to patient, primary tumour and nodal disease characteristics, and treatment related factors.
Median follow up was 34 months and 83% of NF occurred within 24 months. At diagnosis 99% of the N+ patients had pathologic nodes in the pelvis and 14% in the PAO. NFpelvic and NFPAO were reported in 55% and 68% of patients with NF, respectively. Overall NF was reported in 152 patients (11%); 7 and 16% for N- and N+ patients. Of the patients with NF, 41% were located outside the elective target (39% PAO), 40% inside and 35% inside the nodal boost target. Twelve percent of N+ patients that received a nodal boost had a NF inside the nodal boost target.
Within the EMBRACE study cohort the overall number of patients developing nodal failure is low, significantly lower for N− compared to N+ patients. Pathological nodes at diagnosis are mainly located in the pelvis, whereas nodal failures are more often reported in the PAO region. About 40% of all nodal failures were reported outside the treatment targets.
PDF
