Search

During pregnancy, the use of radiation therapy for cancer treatment is often considered impossible due to the assumed associated fetal risks. However, suboptimal treatment of pregnant cancer patients and unjustifiable delay in radiation therapy until after delivery can be harmful for both patient and child. In non‐pregnant patients, proton‐radiation therapy is increasingly administered because of its favorable dosimetric properties compared with photon‐radiation therapy. Although data on the use of pencil beam scanning proton‐radiation therapy during pregnancy are scarce, different case reports and dosimetric studies have indicated a more than 10‐fold reduction in fetal radiation exposure compared with photon‐radiation therapy. Nonetheless, the implementation of proton‐radiation therapy during pregnancy requires complex fetal dosimetry for the neutron‐dominated out‐of‐field radiation dose and faces a lack of clinical guidelines. Further exploration and standardization of proton‐radiation therapy during pregnancy will be necessary to improve radiotherapeutic management of pregnant women with cancer and further reduce risks for their offspring. [ABSTRACT FROM AUTHOR]

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning. [ABSTRACT FROM AUTHOR]

Background and purpose Quality assurance (QA) for radiation treatment has become a priority since poorly delivered radiotherapy can negatively influence patient outcome. Within a national project we evaluated the feasibility of a central review platform and its role in improving uniformity of clinical target volume (CTV) delineation in daily practice. Material and methods All Belgian radiotherapy departments were invited to participate and were asked to upload CTVs for rectal cancer treatment onto a secured server. These were centrally reviewed and feedback was given per e-mail. For each five consecutive patients per centre, the overlap parameter dice coefficient (DC) and the volumetric parameters volumetric ratio (RV) and commonly contoured volume (VCC) were calculated. Results Twenty departments submitted 1224 eligible cases of which 909 were modified (74.3%). There was a significant increase in RV and VCC between the first ten patients per centre and the others. This was not seen for DC. Statistical analysis did not show a further significant improvement in delineation over the entire review period. Conclusion Central review was feasible and increased the uniformity in CTV delineation in the first ten rectal cancer patients per centre. The observations in this study can be used to optimize future QA initiatives. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: In head and neck cancer, diffusion weighted MRI (DWI) can predict response early during treatment. Treatment-induced changes and DWI-specific artifacts hinder an accurate registration between apparent diffusion coefficient (ADC) maps. The aim of the study was to develop a registration tool which calculates and visualizes regional changes in ADC. Methods: Twenty patients with stage IV HNC treated with primary radiotherapy received an MRI including DWI before and early during treatment. Markers were manually placed at anatomical landmarks on the different modalities at both time points. A registration method, consisting of a fully automatic rigid and nonrigid registration and two semi-automatic thin-plate spline (TPS) warps was developed and applied to the image sets. After each registration step the mean registration errors were calculated and ΔADC was compared between good and poor responders. Results: Adding the TPS warps significantly reduced the registration error (in mm, 6.3±6.2 vs 3.2±3.3mm, p <0.001). After the marker based registration the median ΔADC in poor responders was significantly lower than in good responders (7% vs. 21%; p <0.001). Conclusions: This registration method allowed for a significant reduction of the mean registration error. Furthermore the voxel-wise calculation of the ΔADC early during radiotherapy allowed for a visualization of the regional differences of ΔADC within the tumor. [Copyright &y& Elsevier]

Abstract: Background and purpose: A randomized trial was initiated to investigate whether a reduction of the dose to the elective nodal sites and the swallowing apparatus delivered by IMRT would result in a reduction of acute and late side effects without compromising tumor control. The aim of this paper is to report on dosimetrical analysis and acute toxicity. Materials & methods: Two-hundred patients were randomized. In the standard arm, elective nodal volumes (PTVelect) were irradiated up to an equivalent dose of 50Gy. In the experimental arm an equivalent dose of 40Gy was prescribed to the PTVelect. The dose to the swallowing apparatus was kept as low as possible without compromising therapeutic PTV (PTVther) coverage. Results: No significant difference was seen between both arms concerning PTVther coverage. The median D 95 of the PTVelect was significantly lower in the experimental arm (39.5 vs 49.8Gy; p <0.001). Concerning the organs at risk, the dose to swallowing structures and spinal cord was significantly reduced. There was no significant difference in acute toxicity. Three months after radiotherapy there was significantly less grade ⩾3 dysphagia in the experimental arm (2% vs 11%; p =0.03). With a median follow-up of 6months no significant differences were observed in locoregional control, disease free survival or overall survival. Conclusions: Using IMRT we were able to significantly reduce the dose to the PTVelect and several organs at risk without compromising PTVther coverage. This resulted in a significant reduction of severe dysphagia 3months after radiotherapy. Further follow-up is necessary to investigate whether these observations translate into a benefit on late treatment related dysphagia without affecting treatment outcome. [Copyright &y& Elsevier]

Purpose: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). Methods and Materials: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10–15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0–1000 s/mm2) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (∆ADC), and volume change (∆V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0–2 vs. ypT3–4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, ∆ADC, and ∆V for the detection of pCR was compared with receiver operating characteristics analysis. Results: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm2/s: 0.94 ± 0.12 × 10−3 vs. 1.19 ± 0.22 × 10−3, p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: ΔVduring: −62 ± 16 vs. −33 ± 16, respectively, p = 0.015; and ΔVpost: −86 ± 12 vs. −60 ± 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the ΔVduring and, respectively, 83% and 86% for the ΔVpost. The ∆ADC during (ΔADCduring) and after RCT (ΔADCpost) showed a significantly higher value in patients with pCR compared with patients without (in %: ΔADCduring: 72 ± 14 vs. 16 ± 12, p = 0.0006; and ΔADCpost: 88 ± 35 vs. 26 ± 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the ΔADCduring and, respectively, 100% and 93% for the ΔADCpost. Conclusions: These initial findings indicate that DWI, using pretreatment ADC, ΔADCduring, and ΔADCpost may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements. [ABSTRACT FROM AUTHOR]

Abstract: A large number of histological and anatomically distinct malignancies originate from the gastro-intestinal (GI) tract. Radiotherapy (RT) plays an increasing role in the multimodal treatment of most of these malignancies. The proximity of different organs at risk such as the kidneys, the spinal cord and the small bowel and the potential toxicity associated with combined treatment modalities make accurate target volume delineation imperative. The ability of positron emission tomography (PET) imaging to visualize a so-called ‘biological target volume’ (BTV) may be helpful in this respect. Currently the most widely used tracer for diagnosis, staging, restaging and response assessment is [18F]Fluoro-deoxyglucose (FDG). Promising preliminary results in esophageal, pancreatic and anorectal cancers and colorectal liver metastasis suggest that FDG-PET might provide us with additional information useful in target volume delineation. Poor image resolution and a low sensitivity for lymph node detection currently obstructs its widespread implementation. Moreover, validation in large prospective trials and the pathological validation of the correct tumor volume is still lacking. In hepatocellular carcinoma (HCC) and gastric adenocarcinoma there is currently little evidence for the use of FDG-PET in target delineation. However more extensive research is warranted before the true value of FDG-PET in these sites can be assessed. Also other tracers are constantly being developed and investigated. Up to now however none of these tracers has found its way into the daily practice of target volume delineation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the incidence and localization of regional recurrences after definitive (chemo-) radiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods: From May 1987 to March 2008, 368 patients with advanced HNSCC were irradiated to 66–80.5 Gray in 6–7weeks, with (37%) or without (63%) concomitant chemotherapy (Cisplatinum 100mg/m2) every 3weeks. No planned neck dissections were performed. Data on clinical outcome were retrospectively reviewed, location of the original nodal disease and the regional recurrence was indicated on imaging and correlated with radiation dose. Results: Mean follow-up was 34months (range: 50days–216months). Three-year overall survival and disease-specific survival were 55% and 62%, respectively. Loco-regional, local and regional controls were 58%, 65%, and 80%, respectively. Forty-one patients (11.1%) relapsed in the neck, but only 11 patients (2.99%) developed a true isolated regional recurrence, 6 of whom could be successfully salvaged by surgery. Only 2 patients (0.54%) developed an isolated recurrence in the electively treated nodal levels. Conclusion: Isolated nodal recurrences are uncommon and recurrences in the electively treated neck are extremely uncommon. [Copyright &y& Elsevier]

• Nodal definition and delineation for lung cancer is variable in clinical practice. • Knowledge of anatomy and strict guidelines are crucial for high contouring quality. • A qualitative review is essential to understanding interobserver variability. • Quantitative evaluations are more robust if performed after a qualitative review. • Standardization and peer review of clinical practice at country level is feasible. The Quality Assurance project for stage III non-small cell lung cancer radiotherapy ProCaLung performed a multicentric two-step exercise evaluating mediastinal nodal Target Volume Definition and Delineation (TVD) variability and the opportunity for standardization. The TVD variability before and after providing detailed guidelines and the value of qualitative contour reviewing before applying quantitative measures were investigated. The case of a patient with stage III NSCLC and involved mediastinal lymph nodes was used as a basis for this study. Twenty-two radiation oncologists from nineteen centers in Belgium and Luxembourg participated in at least one of two phases of the project (before and after introduction of ProCaLung contouring guidelines). The resulting thirty-three mediastinal nodal GTV and CTV contours were then evaluated using a qualitative-before-quantitative (QBQ) approach. First, a qualitative analysis was performed, evaluating adherence to most recent guidelines. From this, a list of observed deviations was created and these were used to evaluate contour conformity. The second analysis was quantitative, using overlap and surface distance measures to compare contours within qualitative groups and between phases. A 'most robust' reference volume for these analyses was created using the STAPLE-algorithm and an averaging method. Five GTV and seven CTV qualitative groups were identified. Second step contours were more often in higher-conformity groups (p = 0.012 for GTV and p = 0.024 for CTV). Median Residual Mean Square Distances improved from 2.34 mm to 1.36 mm for GTV (p = 0.01) and from 4.53 mm to 1.58 mm for CTV (p < 0.0001). Median Dice coefficients increased from 0.81 to 0.84 for GTV (p = 0.07) and from 0.82 to 0.89 for CTV (p ≤ 0.001). Using HC-contours only to generate references translated in more robust quantitative evaluations. Variability of mediastinal nodal TVD was reduced after providing the ProCaLung consensus guidelines. A qualitative review was essential for providing meaningful quantitative measures. [ABSTRACT FROM AUTHOR]

• Clinically significant radiotherapy toxicity can affect a number of breast cancer patients. • This genome-wide association study of 1,640 European-ancestry patients in the REQUITE cohort explored the relationship between common genetic variants (SNPs) and late radiotherapy toxicity. • Toxicity endpoints at 2-year follow-up included arm lymphoedema, breast atrophy, induration, nipple retraction, breast oedema and telangiectasia. • Eight SNPs reached genome-wide significance. • This study provides further evidence for significant association of common SNPs with distinct toxicity endpoints. Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure. Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10-5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ≥ 2 was associated with the rs188287402 variant (p = 2.80 × 10-8), breast oedema grade ≥ 2 with rs12657177 (p = 1.12 × 10-10), rs75912034 (p = 1.12 × 10-10), rs145328458 (p = 1.06 × 10-9) and rs61966612 (p = 1.23 × 10-9), induration grade ≥ 2 with rs77311050 (p = 2.54 × 10-8) and rs34063419 (p = 1.21 × 10-8), and arm lymphoedema grade ≥ 1 with rs643644 (p = 3.54 × 10-8). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level. This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints. [ABSTRACT FROM AUTHOR]

In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in head and neck squamous cell carcinoma (HNSCC) three weeks after the end of chemoradiotherapy (CRT). Methods and Materials: Twenty-nine patients with HNSCC underwent magnetic resonance imaging (MRI) prior to and 3 weeks after CRT, including T2-weighted and pre- and postcontrast T1-weighted sequences and an echo-planar DWI sequence with six b values (0 to 1,000 s/mm2), from which the apparent diffusion coefficient (ADC) was calculated. ADC changes 3 weeks posttreatment compared to baseline (∆ADC) between responding and nonresponding primary lesions and adenopathies were correlated with 2 years locoregional control and compared with a Mann-Whitney test. In a blinded manner, the ∆ADC was compared to conventional MRI 3 weeks post-CRT and the routinely implemented CT, on average 3 months post-CRT, which used size-related and morphological criteria. Positive and negative predictive values (PPV and NPV, respectively) were compared between the ∆ADC and anatomical imaging. Results: The ∆ADC of lesions with later tumor recurrence was significantly lower than lesions with complete remission for both primary lesions (−2.3% ± 0.3% vs. 80% ± 41%; p < 0.0001) and adenopathies (19.9% ± 32% vs. 63% ± 36%; p = 0.003). The ∆ADC showed a PPV of 89% and an NPV of 100% for primary lesions and a PPV of 70% and an NPV of 96% for adenopathies per neck side. DWI improved PPV and NPV compared to anatomical imaging. Conclusion: DWI with the ∆ADC 3 weeks after concluding CRT for HNSCC allows for early assessment of treatment response. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To develop and validate an accurate predictive model and a nomogram for pathologic complete response (pCR) after chemoradiotherapy (CRT) for rectal cancer based on clinical and sequential PET-CT data. Accurate prediction could enable more individualised surgical approaches, including less extensive resection or even a wait-and-see policy. Methods and materials: Population based databases from 953 patients were collected from four different institutes and divided into three groups: clinical factors (training: 677 patients, validation: 85 patients), pre-CRT PET-CT (training: 114 patients, validation: 37 patients) and post-CRT PET-CT (training: 107 patients, validation: 55 patients). A pCR was defined as ypT0N0 reported by pathology after surgery. The data were analysed using a linear multivariate classification model (support vector machine), and the model’s performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: The occurrence rate of pCR in the datasets was between 15% and 31%. The model based on clinical variables (AUCtrain =0.61±0.03, AUCvalidation =0.69±0.08) resulted in the following predictors: cT- and cN-stage and tumour length. Addition of pre-CRT PET data did not result in a significantly higher performance (AUCtrain =0.68±0.08, AUCvalidation =0.68±0.10) and revealed maximal radioactive isotope uptake (SUVmax) and tumour location as extra predictors. The best model achieved was based on the addition of post-CRT PET-data (AUCtrain =0.83±0.05, AUCvalidation =0.86±0.05) and included the following predictors: tumour length, post-CRT SUVmax and relative change of SUVmax. This model performed significantly better than the clinical model (p train <0.001, p validation =0.056). Conclusions: The model and the nomogram developed based on clinical and sequential PET-CT data can accurately predict pCR, and can be used as a decision support tool for surgery after prospective validation. [Copyright &y& Elsevier]