Impact of radiation therapy modalities on loco-regional control in inflammatory breast cancer.

INTRODUCTION: In inflammatory breast cancer (IBC), radiotherapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiotherapy modalities on the risk of loco-regional and distant relapse. METHODS: A retrospective multicenter study included patients with localized IBC treated between 2010 and 2017. Standard post-mastectomy radiotherapy consisted of daily fractions to a total dose of 50 Gy equivalent without a boost or bolus, while intensified radiotherapy referred to the use of a boost or bolus. The cumulative incidence curves of loco-regional and distant recurrence were displayed using the competing risk method. RESULTS: Of the 241 included patients, 165 were treated with standard and 76 with intensified radiotherapy. There was significantly more nodal involvement in the intensified group. With a median follow-up of 40 months post-radiotherapy, there was no difference between standard vs intensified radiotherapy regarding the cumulative incidence of loco-regional (p=0.68) or distant recurrence (p=0.29). At 5 years, the risks of loco-regional and distant recurrence were 12.1% (95% CI, 7.5; 17.7) and 29.4% (95% CI, 21.8; 37.3) for patients treated with standard radiotherapy and 10.4% (95% CI, 4.4; 19.3) and 21.4% (95% CI, 12.6; 31.9) for intensified radiotherapy. On multivariate analyses, triple-negative subtype and absence of complete pathological response (pCR) were associated with a higher risk of loco-regional recurrence. Radiotherapy intensification had no significant impact on loco-regional and distant recurrence. For non-pCR patients (n=172, 71.7%), no significant differences were observed between the two groups for loco-regional (p=0.80) and distant recurrence either (p=0.39). Severe toxicity rates were similar in both groups. CONCLUSIONS: Contrary to other important series, this large retrospective multicentric study did not show a loco-regional or distant control benefit of intensified radiotherapy. Pooled prospective studies and meta-analyses of intensified radiotherapy are warranted to endorse this approach.

Recommendations for Post-Operative Radiotherapy after complete resection of Thymoma - a French DELPHI consensus initiative.

BACKGROUND: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative Radiotherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI-method was used to question 24 national experts, with 115 questions regarding: 1/ Imaging techniques, 2/ Clinical Target Volume (CTV) and margins, 3/ Dose constraints to Organs At Risk, 4/ Dose and fractionation, 5/ Follow-up and records. Consensus was defined when opinions reached ≥ 80% agreement. RESULTS: We established the following recommendations: pre-operative contrast-enhanced CT-scan is recommended (94% agreement); optimization of radiation delivery includes either a 4D-CT based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT-imaging (81% agreement); imaging fusion based on cardiovascular structures of pre-operative and planning CT-scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/VMAT is recommended (88% agreement); total dose is 50Gy (81% agreement) with 1.8-2Gy per fraction (94% agreement); cardiac evaluation, and follow-up for patients with history of cardiovascular disease is recommended (88% agreement) with EKG and evaluation of LVEF at 5 years and 10 years. CONCLUSION: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

ExacTrac X-Ray 6D Imaging During Stereotactic Body Radiation Therapy of Spinal and Nonspinal Metastases.

The objective was to investigate the possibility of using ExacTrac X-ray (ETX) for 6D image guidance in stereotactic body radiation therapy (SBRT) of bone metastasis and to propose a patient management protocol. The analyses were first obtained from measurements on a pelvic phantom and on 19 patients treated for bone metastasis. The phantom study consisted of applying known offsets and evaluating the ETX level of accuracy, where results were compared with kV-cone beam computed tomography (kV-CBCT). Two groups of patients, 10 spinal and 9 nonspinal SBRT cases, were analyzed to evaluate ETX imaging for different bone localisations. A comparison was made between kV-CBCT and ETX prior to the treatment fractions. During treatments, two other kV-CBCT/ETX image pairs were also acquired and a total of 224 shifts were compared. A second study, using the ETX monitoring module, analyzed the intrafraction motion of 8 other patients. In the phantom study, the root mean square (RMS) of the translational and rotational discrepancies between ETX and kV-CBCT were < 0.6 mm and < 0.4°, respectively. For both groups of patients, the RMS of the discrepancies observed between the two imaging systems were greater than the phantom experiment while still remaining < 1 mm and < 0.7°. In the nonspinal group, three patients (2 scapulas and 1 humerus) did not have consistent shift values with ETX due to a lack of anatomical information. When ETX monitoring was used during irradiation, the setup errors measured were on average less than 1 mm/1°. The results obtained validated the use of ETX for 6D image guidance during bone SBRT. Real-time tracking of the target position improves the accuracy of the irradiation. This strategy allowed for faster correction of out-of-tolerance positioning errors. The registration of bone lesions with poor anatomical information is a limitation of this 2D-kV imaging system.

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. Objective: To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. Design, Setting, and Participants: This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. Interventions: The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). Main Outcomes and Measures: The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. Results: A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. Conclusions and Relevance: This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. Trial Registration: ClinicalTrials.gov Identifier: NCT01874587.

Preoperative Radiation Therapy for Chemorefractory Localized Inflammatory Breast Cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare breast cancer subtype. Chemorefractory nonmetastatic IBC, defined by locoregional progression under neoadjuvant chemotherapy, is a rare situation with few therapeutic options. Owing to the rarity of this clinical presentation and the lack of specific data, no specific management guidelines exist. We evaluated whether preoperative radiation therapy/chemoradiotherapy could achieve locoregional control after first-line neoadjuvant chemotherapy in patients with IBC. METHODS AND MATERIALS: Patients with chemorefractory disease receiving preoperative radiation therapy were identified from a retrospective multicenter cohort of consecutive patients with IBC diagnosed between 2010 and 2017 at 7 oncology centers in France. RESULTS: Overall, 18 patients among the 364 patients (5%) treated for IBC had progressive disease during neoadjuvant chemotherapy. These patients had aggressive tumors with lymph node involvement at diagnosis (n = 17; 94.4%), triple-negative subtype (n = 11; 61.1%), Scarff Bloom and Richardson grade 3 (n = 10; 55.6%), and high Ki67 (median, 56.0%). After preoperative radiation therapy, all patients had a complete (n = 1; 5.6%) or partial (n = 17; 94.4%) locoregional response. One patient (5.6%) experienced acute grade 3 dermatitis. Twelve (66.7%) patients underwent surgery as planned. The estimated median follow-up was 31 months. The median overall survival, disease-free survival, distant metastases-free survival, and locoregional recurrence-free survival were 19 months, 4.5 months, 5 months, and 6 months, respectively. Ultimate locoregional control was obtained for 11 patients (61.1%), and 13 patients (72.2%) experienced metastatic progression. Triple-negative subtype (hazard ratio [HR], 15.54; P = .011) and surgery (HR, 0.23; P = .030) were significantly associated with overall survival in the univariate analysis. In multivariate analyses, the triple-negative subtype remained a significant prognostic factor (HR, 13.04; P = .021) for overall survival. CONCLUSIONS: Preoperative radiation therapy is a feasible approach with acceptable toxicities. It allowed surgery and ultimate locoregional control in a majority of patients. The lack of translation into better survival has been a challenge, in part owing to the metastatic propensity of patients with chemorefractory IBC, especially in the overrepresented triple-negative population in this series.

Prediction of brain tumor recurrence location based on multi-modal fusion and nonlinear correlation learning.

Brain tumor is one of the leading causes of cancer death. The high-grade brain tumors are easier to recurrent even after standard treatment. Therefore, developing a method to predict brain tumor recurrence location plays an important role in the treatment planning and it can potentially prolong patient's survival time. There is still little work to deal with this issue. In this paper, we present a deep learning-based brain tumor recurrence location prediction network. Since the dataset is usually small, we propose to use transfer learning to improve the prediction. We first train a multi-modal brain tumor segmentation network on the public dataset BraTS 2021. Then, the pre-trained encoder is transferred to our private dataset for extracting the rich semantic features. Following that, a multi-scale multi-channel feature fusion model and a nonlinear correlation learning module are developed to learn the effective features. The correlation between multi-channel features is modeled by a nonlinear equation. To measure the similarity between the distributions of original features of one modality and the estimated correlated features of another modality, we propose to use Kullback-Leibler divergence. Based on this divergence, a correlation loss function is designed to maximize the similarity between the two feature distributions. Finally, two decoders are constructed to jointly segment the present brain tumor and predict its future tumor recurrence location. To the best of our knowledge, this is the first work that can segment the present tumor and at the same time predict future tumor recurrence location, making the treatment planning more efficient and precise. The experimental results demonstrated the effectiveness of our proposed method to predict the brain tumor recurrence location from the limited dataset.

Quantitative MRI to Characterize Hypoxic Tumors in Comparison to FMISO PET/CT for Radiotherapy in Oropharynx Cancers.

Intratumoral hypoxia is associated with a poor prognosis and poor response to treatment in head and neck cancers. Its identification would allow for increasing the radiation dose to hypoxic tumor subvolumes. 18F-FMISO PET imaging is the gold standard; however, quantitative multiparametric MRI could show the presence of intratumoral hypoxia. Thus, 16 patients were prospectively included and underwent 18F-FDG PET/CT, 18F-FMISO PET/CT, and multiparametric quantitative MRI (DCE, diffusion and relaxometry T1 and T2 techniques) in the same position before treatment. PET and MRI sub-volumes were segmented and classified as hypoxic or non-hypoxic volumes to compare quantitative MRI parameters between normoxic and hypoxic volumes. In total, 13 patients had hypoxic lesions. The Dice, Jaccard, and overlap fraction similarity indices were 0.43, 0.28, and 0.71, respectively, between the FDG PET and MRI-measured lesion volumes, showing that the FDG PET tumor volume is partially contained within the MRI tumor volume. The results showed significant differences in the parameters of SUV in FDG and FMISO PET between patients with and without measurable hypoxic lesions. The quantitative MRI parameters of ADC, T1 max mapping and T2 max mapping were different between hypoxic and normoxic subvolumes. Quantitative MRI, based on free water diffusion and T1 and T2 mapping, seems to be able to identify intra-tumoral hypoxic sub-volumes for additional radiotherapy doses.

Advances in PET and MRI imaging of tumor hypoxia.

Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.

Different Prognostic Values of Tumour and Nodal Response to Neoadjuvant Chemotherapy Depending on Subtypes of Inflammatory Breast Cancer, a 317 Patient-Study.

Inflammatory breast cancer (IBC) is a rare entity with a poor prognosis. We analysed the survival outcomes of patients with nonmetastatic IBC and the prognostic value of tumour or nodal responses to assess their individual prognostic impact across IBC subtypes. This retrospective multicentre study included patients diagnosed with IBC between 2010 and 2017 to account for advances in neoadjuvant systemic therapies and modern radiotherapy at seven oncology centres in France. Three hundred and seventeen patients were included and analysed. After a median follow-up of 52 months, the 5-year DFS was lower for triple-negative (TN) (50.1% vs. 63.6%; p < 0.0001). After multivariate analyses, incomplete nodal response was the only significant prognostic factor in the triple-negative group (HR:6.06). The poor prognosis of TN-IBC was reversed in the case of nodal response after neoadjuvant chemotherapy. Breast response does not appear to be a decisive prognostic factor in patients with TN-IBC compared to lymph node response. Despite improvements in neoadjuvant treatments, IBC remains associated with a poor prognosis. In TN-IBC patients, lack of pathological complete node response was associated with poorer survival than any other group. Treatment intensification strategies are worth investigating.

Evaluation of a Dedicated Software "Elements™ Spine SRS, Brainlab®" for Target Volume Definition in the Treatment of Spinal Bone Metastases With Stereotactic Body Radiotherapy.

Introduction: Stereotactic body radiotherapy (SBRT) is a treatment option for spine metastases. The International Spine Radiosurgery Consortium (ISRC) has published consensus guidelines for target delineation in spine SBRT. A new software called Elements™ Spine SRS by Brainlab® that includes the module Elements SmartBrush Spine (v3.0, Munich, Germany) has been developed specifically for SBRT treatment of spine metastases, and the latter provides the ability to perform semiautomatic clinical target volume (CTV) generation based on gross tumor volume (GTV) localization and guidelines. The aims of our study were to evaluate this software by studying differences in volumes between semiautomatic CTV contours compared to manual contouring performed by an expert radiation oncologist and to determine the dosimetric impact of these differences on treatment plans. Methods: A total of 35 volumes ("Expert GTV" and "Expert CTV") from 30 patients were defined by a single expert. A semiautomatic definition of these 35 CTVs based on the location of "Expert GTV" and following ISRC guidelines was also performed in Elements SmartBrush Spine ("Brainlab CTV"). The spatial overlap between "Brainlab" and "Expert" CTVs was calculated using the Dice similarity coefficient (DSC). We considered a threshold of 0.80 or above to indicate that Elements SmartBrush Spine performed very well with adequate contours for clinical use. Two dosimetric treatment plans, each corresponding to a specific planning target volume (PTV; Expert PTV, Brainlab PTV), were created for 11 patients. Results: We showed that "Brainlab CTV" and "Expert CTV" mean volumes were 29.8 ± 16.1 and 28.7 ± 15.7 cm3, respectively (p = 0.23). We also showed that the mean DSC for semiautomatic contouring relative to expert manual contouring was 0.85 ± 0.08 and less than 0.80 in five cases. For metastases involving the vertebral body only (n = 13,37%), the mean DSC was 0.90 ± 0.03, and for ones involving other or several vertebral regions (n = 22.63%), the mean DSC was 0.81 ± 0.08 (p < 0.001). The comparison of dosimetric treatment plans was performed for equivalent PTV coverage. There were no differences between doses received by organs at risk (spinal cord and esophagus) for Expert and Brainlab PTVs, respectively. Conclusion: The results showed that the semiautomatic method had quite good accuracy and can be used in clinical routine even for complex lesions.

Synthetic MRI for Radiotherapy Planning for Brain and Prostate Cancers: Phantom Validation and Patient Evaluation.

Purpose: We aimed to evaluate the accuracy of T 1 and T 2 mappings derived from a multispectral pulse sequence (magnetic resonance image compilation, MAGiC®) on 1.5-T MRI and with conventional sequences [gradient echo with variable flip angle (GRE-VFA) and multi-echo spin echo (ME-SE)] compared to the reference values for the purpose of radiotherapy treatment planning. Methods: The accuracy of T 1 and T 2 measurements was evaluated with 2 coils [head and neck unit (HNU) and BODY coils] on phantoms using descriptive statistics and Bland-Altman analysis. The reproducibility and repeatability of T 1 and T 2 measurements were performed on 15 sessions with the HNU coil. The T 1 and T 2 synthetic sequences obtained by both methods were evaluated according to quality assurance (QA) requirements for radiotherapy. T 1 and T 2 in vivo measurements of the brain or prostate tissues of two groups of five subjects were also compared. Results: The phantom results showed good agreement (mean bias, 8.4%) between the two measurement methods for T 1 values between 490 and 2,385 ms and T 2 values between 25 and 400 ms. MAGiC® gave discordant results for T 1 values below 220 ms (bias with the reference values, from 38% to 1,620%). T 2 measurements were accurately estimated below 400 ms (mean bias, 8.5%) by both methods. The QA assessments are in agreement with the recommendations of imaging for contouring purposes for radiotherapy planning. On patient data of the brain and prostate, the measurements of T 1 and T 2 by the two quantitative MRI (qMRI) methods were comparable (max difference, <7%). Conclusion: This study shows that the accuracy, reproducibility, and repeatability of the multispectral pulse sequence (MAGiC®) were compatible with its use for radiotherapy treatment planning in a range of values corresponding to soft tissues. Even validated for brain imaging, MAGiC® could potentially be used for prostate qMRI.

Correction: Brochet et al. A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction. Entropy 2022, 24, 436.

Alexandre Huat, Sébastien Thureau, David Pasquier, Isabelle Gardin, Romain Modzelewski, David Gibon, Juliette Thariat and Vincent Grégoire were not included as authors in the original publication [...].

Characterization of positioning uncertainties in PET-CT-MR trimodality solutions for radiotherapy.

The purpose of this study was to evaluate the positioning uncertainties of two PET/CT-MR imaging setups, C1 and C2. Because the PET/CT data were acquired on the same hybrid device with automatic image registration, experiments were conducted using CT-MRI data. In C1, a transfer table was used, which allowed the patient to move from one imager to another while maintaining the same position. In C2, the patient stood up and was positioned in the same radiotherapy treatment position on each imager. The two setups provided a set of PET/CT and MR images. The accuracy of the registration software was evaluated on the CT-MRI data of one patient using known translations and rotations of MRI data. The uncertainties on the two setups were estimated using a phantom and a cohort of 30 patients. The accuracy of the positioning uncertainties was evaluated using descriptive statistics and a t-test to determine whether the mean shift significantly deviated from zero (p < 0.05) for each setup. The maximum registration errors were less than 0.97 mm and 0.6° for CT-MRI registration. On the phantom, the mean total uncertainties were less than 2.74 mm and 1.68° for C1 and 1.53 mm and 0.33° for C2. For C1, the t-test showed that the displacements along the z-axis did not significantly deviate from zero (p = 0.093). For C2, significant deviations from zero were present for anterior-posterior and superior-inferior displacements. The mean total uncertainties were less than 4 mm and 0.42° for C1 and less than 1.39 mm and 0.27° for C2 in the patients. Furthermore, the t-test showed significant deviations from zero for C1 on the anterior-posterior and roll sides. For C2, there was a significant deviation from zero for the left-right displacements.This study shows that transfer tables require careful evaluation before use in radiotherapy.

A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction.

In this paper, we propose to quantitatively compare loss functions based on parameterized Tsallis-Havrda-Charvat entropy and classical Shannon entropy for the training of a deep network in the case of small datasets which are usually encountered in medical applications. Shannon cross-entropy is widely used as a loss function for most neural networks applied to the segmentation, classification and detection of images. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy. In this work, we compare these two entropies through a medical application for predicting recurrence in patients with head-neck and lung cancers after treatment. Based on both CT images and patient information, a multitask deep neural network is proposed to perform a recurrence prediction task using cross-entropy as a loss function and an image reconstruction task. Tsallis-Havrda-Charvat cross-entropy is a parameterized cross-entropy with the parameter α. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy for α=1. The influence of this parameter on the final prediction results is studied. In this paper, the experiments are conducted on two datasets including in total 580 patients, of whom 434 suffered from head-neck cancers and 146 from lung cancers. The results show that Tsallis-Havrda-Charvat entropy can achieve better performance in terms of prediction accuracy with some values of α.

Respiratory gated multistatic PET reconstructions to delineate radiotherapy target volume in patients with mobile lung tumors.

BACKGROUND: PET-CT with 18F-FDG or other radiopharmaceuticals is a recommended tool to help the delineation of lung cancers candidate to radiotherapy. The motion artifacts caused by respiratory movements are reduced by 4D acquisitions. We introduced an extended reconstruction algorithm (multiple reconstruct register and average [multi-RRA]) which requires much shorter acquisition times than standard 4D PET-CT. Our aim was to evaluate the interest on multi-RRA images as an alternative of 3D and 4D PET-CT for the delineation of lung lesion. METHODS: PET acquisitions synchronized to the respiratory signal were obtained in 18 patients with mobile lung tumors. We compared the tumor volumes delineated on Multi-RRA images to 3D and 4D PET-CT, considering the 4D CT as a reference. The tumor volumes were delineated and compared with topologic similarity indexes (Dice, Jaccard and overlap). RESULTS: Twenty tumors were delineated. The volumes delineated with multi-RRA and 4D PET were not significantly different (mean difference of 0.2±0.7 mL). Comparison by pairs (Tukey-Kramer test) showed that 3D-PET volumes were significantly smaller than 4D-PET and multi-RRA volumes (P<0.001). Topologic similarity indexes with 4D-PET were slightly statistically higher with multi-RRA than with 3D-PET (Dice and Jaccard) or 4D-CT (Dice, Jaccard and Overlap). CONCLUSIONS: The tumor volumes delineated on multi-RRA are similar to the volumes obtained with 4D PET, with shorter acquisition time.

First Comparison between [18f]-FMISO and [18f]-Faza for Preoperative Pet Imaging of Hypoxia in Lung Cancer.

Hypoxic areas are typically resistant to treatment. However, the fluorine-18-fluoroazomycin-arabinoside (FAZA) and fluorine 18 misonidazole (FMISO) tracers have never been compared in non small cell lung cancer (NSCLC). This study compares the capability of 18F-FAZA PET/CT with that of 18F-FMISO PET/CT for detecting hypoxic tumour regions in early and locally advanced NSCLC patients. We prospectively evaluated patients who underwent preoperative PET scans before surgery for localised NSCLC (i.e., fluorodeoxyglucose (FDG)-PET, FMISO-PET, and FAZA-PET). The PET data of the three tracers were compared with each other and then compared to immunohistochemical analysis (GLUT-1, CAIX, LDH-5, and HIF1-Alpha) after tumour resection. Overall, 19 patients with a mean age of 68.2 ± 8 years were included. There were 18 lesions with significant uptake (i.e., SUVmax >1.4) for the F-MISO and 17 for FAZA. The mean SUVmax was 3 (±1.4) with a mean volume of 25.8 cc (±25.8) for FMISO and 2.2 (±0.7) with a mean volume of 13.06 cc (±13.76) for FAZA. The SUVmax of F-MISO was greater than that of FAZA (p = 0.0003). The SUVmax of F-MISO shows a good correlation with that of FAZA at 0.86 (0.66-0.94). Immunohistochemical results are not correlated to hypoxia PET regardless of the staining. The two tracers show a good correlation with hypoxia, with FMISO being superior to FAZA. FMISO, therefore, remains the reference tracer for defining hypoxic volumes.

Evaluation of inter- and intra-fraction 6D motion for stereotactic body radiation therapy of spinal metastases: influence of treatment time.

BACKGROUND: The objective of this study was to analyze the amplitude of translational and rotational movements occurring during stereotactic body radiotherapy (SBRT) of spinal metastases in two different positioning devices. The relevance of intra-fractional imaging and the influence of treatment time were evaluated. METHODS: Twenty patients were treated in the supine position either (1) on a body vacuum cushion with arms raised and resting on a clegecel or (2) on an integrated SBRT solution consisting of a SBRT table top, an Orfit™ AIO system, and a vacuum cushion. Alignments between the cone beam computed tomography (CBCT) and the planning computed tomography allowed corrections of inter- and intra-fraction positional shifts using a 6D table. The absolute values of the translational and rotational setup errors obtained for 329 CBCT were recorded. The translational 3D vector, the maximum angle, and the characteristic times of the treatment fractions were calculated. RESULTS: An improvement in the mean (SD) inter-fraction 3D vector (mm) from 7.8 (5.9) to 5.9 (3.8) was obtained by changing the fixation devices from (1) to (2) (p < 0.038). The maximum angles were less than 2° for a total of 87% for (1) and 96% for (2). The mean (SD) of the intra-fraction 3D vectors (mm) was lower for the new 1.1 (0.8) positioning fixation (2) compared to the old one (1) 1.7 (1.7) (p = 0.004). The angular corrections applied in the intra-fraction were on average very low (0.4°) and similar between the two systems. A strong correlation was found between the 3D displacement vector and the fraction time for (1) and (2) with regression coefficients of 0.408 (0.262-0.555, 95% CI) and 0.069 (0.010-0.128, 95% CI), respectively. An accuracy of 1 mm would require intra-fraction imaging every 5 min for both systems. If the expected accuracy was 2 mm, then only system (2) could avoid intra-fractional imaging. CONCLUSIONS: This study allowed us to evaluate setup errors of two immobilization devices for spine SBRT. The association of inter- and intra-fraction imaging with 6D repositioning of a patient is inevitable. The correlation between treatment time and corrections to be applied encourages us to move toward imaging modalities which allow a reduction in fraction time.

Angiogenesis imaging study using interim [18F] RGD-K5 PET/CT in patients with lymphoma undergoing chemotherapy: preliminary evidence.

BACKGROUND: Our aim was to measure the impact of two cycles of standard chemotherapy on tumoural neoangiogenesis by [18F] fluorine arginine-glycine-aspartic (RGD-K5) positron emission tomography-computed tomography (PET) on patients presenting with lymphoma. Nineteen patients at Rouen's Henri Becquerel Cancer Centre were prospectively included. Fluorodeoxyglucose (FDG) and RGD-K5 PET were performed before (C0) and after (C2) two cycles of chemotherapy. End-of-treatment FDG PET was performed for final evaluation. Maximum standardised uptake value (SUVmax), SUVmean, Metabolic Tumour Volume (MTV) and Angiogenic Tumour Volume (ATV) were measured for all lesions. RGD SUVmax and SUVmean were also analysed in 13 normal organs at C0 and C2. The patient's treatment response was considered using the Deauville score (DS) at the end of FDG PET treatment (DS 1-3 were considered responders, and 4 and 5 non-responders). RESULTS: Eighteen patients had both C0 FDG and RGD PET. Twelve patients had both C2 FDG and RGD, completed the treatment protocol and were included in end-of-treatment analysis. No statistical difference was found in RGD uptake of normal organs before and after chemotherapy for SUVmax and SUVmean. On C0 RGD, apart from classical Hodgkin lymphoma (cHL; n = 5) and grey zone lymphoma (GZL; n = 1), other lymphoma sub-types (n = 12) had low RGD uptake (p < 0.001). Regarding FDG, there was no significant difference for SUVmax, SUVmean and MTV at C0 and C2 between patients with cHL and non-Hodgkin lymphoma (NHL). At C2 RGD, non-responders had higher SUVmax and SUVmean compared to responders (p < 0.001). There was no significant difference in RGD ATV between responders and non-responders. CONCLUSIONS: Our study showed significant higher initial RGD uptake in patients presenting with cHL and GZL compared to NHL. Non-responder also had higher post-chemotherapy RGD uptake compared to responders. Issues raised by RGD uptake, particularly in cHL, are yet to be explored and need to be confirmed in a larger population.

Prospective Evaluation of Sarcopenia in Head and Neck Cancer Patients Treated with Radiotherapy or Radiochemotherapy.

Highlights: Sarcopenia is frequent in patients treated with radiation therapy (RT) or radiochemotherapy (RTCT) for head and neck squamous cell carcinomas. Sarcopenia is associated with poor disease-free survival and overall survival outcomes. Sarcopenia is not associated with a higher rate of treatment-related toxicity. Background: Sarcopenia occurs frequently with the diagnosis of head and neck squamous cell carcinoma (HNSCC). We aimed to assess the impact of sarcopenia on survival among HNSCC patients treated with radiotherapy (RT) or radiochemotherapy (RTCT). Methods: Patients treated between 2014 and 2018 by RT or RTCT with curative intent were prospectively included (NCT02900963). Optimal nutritional support follow-up, including weekly consultation with a dietician and an oncologist and daily weight monitoring, was performed. Sarcopenia was determined by measuring the skeletal muscles at the L3 vertebra on the planning CT scan for radiotherapy. For each treatment group (RT or RTCT), we assessed the prognostic value of sarcopenia for disease-free survival (DFS) and overall survival (OS) and its impact on treatment-related toxicity. Results: Two hundred forty-three HNSCC patients were included: 116 were treated by RT and 127 were treated by RTCT. Before radiotherapy, eight (3.3%) patients were considered malnourished according to albumin, whereas 88 (36.7%) patients were sarcopenic. Overall, sarcopenia was associated with OS and DFS in a multivariate analysis (HR 1.9 [1.1-3.25] and 1.7 [1.06-2.71], respectively). It was similar for patients treated with RT (HR 2.49 [1.26-4.9] for DFS and 2.24 [1.03-4.86] for OS), whereas for patients treated with RTCT sarcopenia was significantly associated with OS and DFS in univariate analysis only. Sarcopenia was not related to higher treatment-related toxicity. Conclusions: Pretherapeutic sarcopenia remains frequent and predicts OS and DFS for non-frail patients treated with curative intent and adequate nutritional support.