Multicentric development and evaluation of [18F]FDG PET/CT and CT radiomic models to predict regional and/or distant recurrence in early-stage non-small cell lung cancer treated by stereotactic body radiation therapy.

PURPOSE: To develop machine learning models to predict regional and/or distant recurrence in patients with early-stage non-small cell lung cancer (ES-NSCLC) after stereotactic body radiation therapy (SBRT) using [18F]FDG PET/CT and CT radiomics combined with clinical and dosimetric parameters. METHODS: We retrospectively collected 464 patients (60% for training and 40% for testing) from University Hospital of Liège and 63 patients from University Hospital of Brest (external testing set) with ES-NSCLC treated with SBRT between 2010 and 2020 and who had undergone pretreatment [18F]FDG PET/CT and planning CT. Radiomic features were extracted using the PyRadiomics toolbox®. The ComBat harmonization method was applied to reduce the batch effect between centers. Clinical, radiomic, and combined models were trained and tested using a neural network approach to predict regional and/or distant recurrence. RESULTS: In the training (n = 273) and testing sets (n = 191 and n = 63), the clinical model achieved moderate performances to predict regional and/or distant recurrence with C-statistics from 0.53 to 0.59 (95% CI, 0.41, 0.67). The radiomic (original_firstorder_Entropy, original_gldm_LowGrayLevelEmphasis and original_glcm_DifferenceAverage) model achieved higher predictive ability in the training set and kept the same performance in the testing sets, with C-statistics from 0.70 to 0.78 (95% CI, 0.63, 0.88) while the combined model performs moderately well with C-statistics from 0.50 to 0.62 (95% CI, 0.37, 0.69). CONCLUSION: Radiomic features extracted from pre-SBRT analog and digital [18F]FDG PET/CT outperform clinical parameters in the prediction of regional and/or distant recurrence and to discuss an adjuvant systemic treatment in ES-NSCLC. Prospective validation of our models should now be carried out.

Stereotactic robotic body radiotherapy for patients with oligorecurrent pulmonary metastases.

BACKGROUND: Our aim is to report treatment efficacy and toxicity of patients treated by robotic (Cyberknife®) stereotactic body radiotherapy (SBRT) for oligorecurrent lung metastases (ORLM). Additionally we wanted to evaluate influence of tumor, patient and treatment related parameters on local control (LC), lung and distant progression free- (lung PFS/Di-PFS) and overall survival (OS). METHODS: Consecutive patients with up to 5 ORLM (confirmed by FDG PET/CT) were included in this study. Intended dose was 60Gy in 3 fractions (prescribed to the 80% isodose volume). Patients were followed at regular intervals and tumor control and toxicity was prospectively scored. Tumor, patient and treatment data were analysed using competing risk- and Cox regression. RESULTS: Between May 2010 and March 2016, 104 patients with 132 lesions were irradiated from primary lung carcinoma (47%), gastro-intestinal (34%) and mixed primary histologies (19%). The mean tumor volume was 7.9 cc. After a median follow up of 22 months, the 1, 2 and 3 year LC rate (per lesion) was 89.3, 80.0 and 77.8% respectively. The corresponding (per patient) 1, 2 and 3 years lung PFS were 66.3, 50.0, 42.6%, Di-PFS were 80.5, 64.4, 60.6% and OS rates were 92.2, 80.9 and 72.0% respectively. On univariable analysis, gastro-intestinal (GI) as primary tumor site showed a significant superior local control versus the other primary tumor sites. For OS, significant variables were primary histology and primary tumor site with a superior OS for patients with metastases of primary GI origin. LC was significantly affected by the tumor volume, physical and biologically effective dose coverage. Significant variables in multivariable analysis were BED prescription dose for LC and GI as primary site for OS. The vast majority of patients developed no toxicity or grade 1 acute and late toxicity. Acute and late grade 3 radiation pneumonitis (RP) was observed in 1 and 2 patients respectively. One patient with a centrally located lesion developed grade 4 RP and died due to possible RT-induced pulmonary hemorrhage. CONCLUSIONS: SBRT is a highly effective local therapy for oligorecurrent lung metastases and could achieve long term survival in patients with favourable prognostic features.

Clinical Outcomes of 130 Patients with Primary and Secondary Lung Tumors treated with Cyberknife Robotic Stereotactic Body Radiotherapy.

BACKGROUND: Authors report clinical outcomes of patients treated with robotic stereotactic body radiotherapy (SBRT) for primary, recurrent and metastatic lung lesions. PATIENTS AND METHODS: 130 patients with 160 lesions were treated with Cyberknife SBRT, including T1-3 primary lung cancers (54%), recurrent tumors (22%) and pulmonary metastases (24%). The mean biologically equivalent dose (BED10Gy) was 151 Gy (72-180 Gy). Median prescribed dose for peripheral and central lesions was 3×20 Gy and 3×15 Gy, respectively. Local control (LC), overall survival (OS), and cause-specific survival (CSS) rates, early and late toxicities are reported. Statistical analysis was performed to identify factors influencing local tumor control. RESULTS: Median follow-up time was 21 months. In univariate analysis, higher dose was associated with better LC and a cut-off value was detected at BED10Gy ≤ 112.5 Gy, resulting in 1-, 2-, and 3-year actuarial LC rates of 93%, vs 73%, 80% vs 61%, and 63% vs 54%, for the high and low dose groups, respectively (p = 0.0061, HR = 0.384). In multivariate analysis, metastatic origin, histological confirmation and larger Planning Target Volume (PTV) were associated with higher risk of local failure. Actuarial OS and CSS rates at 1, 2, and 3 years were 85%, 74% and 62%, and 93%, 89% and 80%, respectively. Acute and late toxicities ≥ Gr 3 were observed in 3 (2%) and 6 patients (5%), respectively. CONCLUSIONS: Our favorable LC and survival rates after robotic SBRT, with low rates of severe toxicities, are coherent with the literature data in this mixed, non-selected study population.

FDG PET/CT texture analysis for predicting the outcome of lung cancer treated by stereotactic body radiation therapy.

INTRODUCTION: With (18)F-FDG PET/CT, tumor uptake intensity and heterogeneity have been associated with outcome in several cancers. This study aimed at investigating whether (18)F-FDG uptake intensity, volume or heterogeneity could predict the outcome in patients with non-small cell lung cancers (NSCLC) treated by stereotactic body radiation therapy (SBRT). METHODS: Sixty-three patients with NSCLC treated by SBRT underwent a (18)F-FDG PET/CT before treatment. Maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), as well as 13 global, local and regional textural features were analysed. The predictive value of these parameters, along with clinical features, was assessed using univariate and multivariate analysis for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Cutoff values were obtained using logistic regression analysis, and survivals were compared using Kaplan-Meier analysis. RESULTS: The median follow-up period was 27.1 months for the entire cohort and 32.1 months for the surviving patients. At the end of the study, 25 patients had local and/or distant recurrence including 12 who died because of the cancer progression. None of the clinical variables was predictive of the outcome, except age, which was associated with DFS (HR 1.1, P = 0.002). None of the (18)F-FDG PET/CT or clinical parameters, except gender, were associated with OS. The univariate analysis showed that only dissimilarity (D) was associated with DSS (HR = 0.822, P = 0.037), and that several metabolic measurements were associated with DFS. In multivariate analysis, only dissimilarity was significantly associated with DSS (HR = 0.822, P = 0.037) and with DFS (HR = 0.834, P < 0.01). CONCLUSION: The textural feature dissimilarity measured on the baseline (18)F-FDG PET/CT appears to be a strong independent predictor of the outcome in patients with NSCLC treated by SBRT. This may help selecting patients who may benefit from closer monitoring and therapeutic optimization.

Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience.

BACKGROUND: To evaluate efficacy and toxicity of radio-chemotherapy (RCT) and MR-guided pulsed-dose-rate (PDR) adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). MATERIAL AND METHODS: Between 2007 and 2014 85 patients with FIGO stage 1B1 N+ or ≥ 1B2 cervical cancer were treated with RCT+ IGABT. The treatment consisted of a pelvic± paraaortic external beam radiotherapy (EBRT) (45-50.4 Gy ± 10 Gy boost to primary tumor and/or to pathologic lymph nodes) with concurrent cisplatin followed by 25-35 Gy of PDR IGABT in 30-50 pulses. The ratio of 3D-CFRT/IMRT was 61/24 patients. Dose-volume parameters of high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and D2cm(3) organs at risk (OARs) were reported. Local control (LC), cancer-specific survival (CCS) and overall survival (OS) were analyzed actuarially and morbidity crude rates were scored using CTCAEv4.0. RESULTS: Mean follow-up was 36 months (range 6-94). The mean D90 and D98 for HR-CTV was 84.4 ± 9 Gy and 77 ± 8.1 Gy, while for IR-CTV was 69.1 ± 4.3 Gy and 64.8 ± 4.3 Gy, respectively. The mean D2cm(3) for OARs was the following: bladder: 77.3 ± 10.5 Gy, rectum: 65 ± 6.8 Gy, sigmoid: 63 ± 7.9 Gy and intestine: 64.0 ± 9.1 Gy. Three year LC, CSS and OS were: 94%, 85% and 81%. The three-year regional- and distant control rates were 95% and 74%. Node negative patients had significantly higher three-year CSS (100 vs. 72%, p = 0.016) and OS (92 vs. 72%, p = 0.001) compared to node positive ones. Three-year actuarial late Grade ≥ 3 morbidity was the following: GI: 8%, GU: 5%, Vaginal: 8%. The frequency of Grade ≥ 3 hematological toxicities including anemia/leukopenia/neutropenia/thrombocytopenia were 8.6%/34.7%/24.3%/24.3%, respectively. CONCLUSION: This large mono-institutional experience builds up further evidences that IGABT in conjunction with RCT should be the standard of care for patients suffering LACC.

Predictive clinical and dosimetric parameters for risk of relapse in early-stage non-small cell lung cancer treated by SBRT: A large single institution experience.

Purpose: To evaluate the impact of dosimetric parameters on efficacy of stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (ES-NSCLC), using Hypofractionated Treatment Effects in the Clinic (HyTEC) reporting standards. Methods: From April 2010 to December 2020, 497 patients who received SBRT for ES-NSCLC at the University Hospital of Liège were retrospectively enrolled. A total dose of 40 to 60 Gy in 3-5 fractions (72-180 Gy biologically effective dose with an α/ß ratio of 10 (BED10)) was prescribed to the 80 % isodose line of the PTV. Potential clinical and dosimetric predictors of recurrence, overall survival (OS) and disease specific survival (DSS) were evaluated using univariate and multivariate analyses. Results: After a median follow-up of 32 months (range 3-143 months), the local control and disease-free survival (DFS) rates at 3 years were 91 % (95 % CI: 90 %-93 %) and 75 % (95 % CI: 73 %-77 %), respectively. The median OS was 41.6 months and the median DSS was not reached. On multivariate analysis, a higher gross tumor volume (GTV) Dmax (BED10) (cut-off 198 Gy) and a larger percent of the GTV receiving ≥110 % of the prescribed dose were predictive of a better local control, only GTV volume was correlated with DSS and no parameter was correlated with OS and regional or distant recurrences. Conclusion: Lung SBRT for ES-NSCLC in 3 to 5 fractions resulted in high local control rates. A higher percent of GTV receiving ≥110 % of the prescribed dose and a higher GTV Dmax (BED10) seem to allow a better local control.

Identification of CT radiomic features robust to acquisition and segmentation variations for improved prediction of radiotherapy-treated lung cancer patient recurrence.

The primary objective of the present study was to identify a subset of radiomic features extracted from primary tumor imaged by computed tomography of early-stage non-small cell lung cancer patients, which remain unaffected by variations in segmentation quality and in computed tomography image acquisition protocol. The robustness of these features to segmentation variations was assessed by analyzing the correlation of feature values extracted from lesion volumes delineated by two annotators. The robustness to variations in acquisition protocol was evaluated by examining the correlation of features extracted from high-dose and low-dose computed tomography scans, both of which were acquired for each patient as part of the stereotactic body radiotherapy planning process. Among 106 radiomic features considered, 21 were identified as robust. An analysis including univariate and multivariate assessments was subsequently conducted to estimate the predictive performance of these robust features on the outcome of early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy. The univariate predictive analysis revealed that robust features demonstrated superior predictive potential compared to non-robust features. The multivariate analysis indicated that linear regression models built with robust features displayed greater generalization capabilities by outperforming other models in predicting the outcomes of an external validation dataset.

Interval From Simulation Imaging to Treatment Delivery in SABR of Lung Lesions: How Long is Too Long for the Lung?

Purpose: The purpose of this study was to evaluate the effect of delay between planning computed tomography (CT) used as a basis for treatment planning and the start of treatment (delay planning treatment [DPT]), on local control (LC) for lung lesions treated by SABR. Methods and Materials: We pooled 2 databases from 2 monocentric retrospective analysis previously published and added planning CT and positron emission tomography (PET)-CT dates. We analyzed LC outcomes based on DPT and reviewed all available cofounding factors among demographic data and treatment parameters. Results: A total of 210 patients with 257 lung lesions treated with SABR were evaluated. The median DPT was 14 days. Initial analysis revealed a discrepancy in LC as a function of DPT and a cutoff delay of 24 days (21 days for PET-CT almost systematically done 3 days after planning CT) was determined according to the Youden method. Cox model was applied to several predictors of local recurrence-free survival (LRFS). Univariate analysis showed LRFS decreasing significantly related to DPT ≥24 days (P = .0063), gross tumor volume, and clinical target volume (P = .0001 and P = .0022), but also with the presence of >1 lesion treated with the same planning CT (P = .024). LRFS increased significantly with higher biological effective dose (P < .0001). On multivariate analysis, LRFS remained significantly lower for lesions with DPT ≥24 days (hazard ratio, 2.113; 95% confidence interval, 1.097-4.795; P = .027). Conclusions: DPT to SABR treatment delivery for lung lesions appears to reduce local control. Timing from imaging acquisition to treatment delivery should be systematically reported and tested in future studies. Our experience suggests that the time from planning imaging to treatment should be <21 days.

Radiotherapy-specific quality indicators at national level: How to make it happen.

PURPOSE /OBJECTIVE: To promote best practice and quality of care, the Belgian College of Physicians for Radiotherapy Centers established a set of radiotherapy specific quality indicators for benchmarking on a national level. This paper describes the development, the collected QIs, the observed trends and the departments' evaluation of this initiative. MATERIAL AND METHODS: The Donabedian approach was used, focussing on structural, process and outcome QIs. The criteria for QI selection were availability, required for low-threshold regular collection, and applicability to guidelines and good practice. The QIs were collected yearly and individualized reports were sent out to all RT departments. In 2021, a national survey was held to evaluate the ease of data collection and submission, and the perceived importance and validity of the collected QIs. RESULTS: 18 structural QI and 37 process and outcome parameters (n = 25 patients/pathology/department) were collected. The participation rate amounted to 95 % overall. The analysis gave a national overview of RT activity, resources, clinical practice and reported acute toxicities. The individualized reports allowed departments to benchmark their performance. The 2021 survey indicated that the QIs were overall easy to collect, relevant and reliable. The collection of acute recorded toxicities was deemed a weak point due to inter-observer variabilities and lack of follow-up time. CONCLUSION: QI collection on a national level is a valuable process in steering quality improvement initiatives. The feasibility and relevance was demonstrated with a high level of participation. The national initiative will continue to evolve as a quality monitoring and improvement tool.

The COVID-19 Status of Patients Is an Essential Determinant for Decision-Making by Radiation Oncologists: A European Survey.

AIM: To assess the tendencies of radiation oncologists (ROs) in adjusting radiotherapy treatments (RTH) according to the coronavirus disease 2019 (COVID-19) status of patients during the early severe acute respiratory syndrome coronavirus 2 (SARS-COV2) pandemic in Europe. MATERIAL AND METHODS: An electronic survey was sent to 79 academic RTH departments across Europe. Only one respondent per institution was included. Respondents were asked how they would adjust RTH treatments based on COVID-19 status for more common cancers during the first wave of the pandemic. Respondents were also asked to report the number of external beam radiotherapy (EBRT) units and the number of new cases referred to their department. Descriptive statistical analysis was conducted focusing on different cancers. RESULTS: The overall response rate to the survey was 30.38% (24 institutions from 13 European countries). There was a wide range of different institutions regarding the number of patients, radiation oncologists, and facilities. A large proportion of respondents supported adjustment of RTH treatment (delay or switch to a shorter fractionation) for COVID-19-negative patients during the first wave of the pandemic only for early breast cancer (20% delay, 42.3% shorter), prostate cancer (53.6% delay, 21.4% shorter), and benign brain tumours (32% delay, 12% shorter). For COVID-19-negative patients with other cancers, most respondents recommended the standard RTH treatment. For COVID-19-positive patients, most respondents favoured a delay in RTH treatment or a shorter fractionation, regardless of cancer type and stage. CONCLUSION: The patient's COVID status significantly influenced the decision to undergo RTH treatment, regardless of the type and aggressiveness of cancer.

Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study.

OBJECTIVE: Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. METHODS: 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient's basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. RESULTS: Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. CONCLUSION: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. ADVANCES IN KNOWLEDGE: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.

A dosimetric selectivity intercomparison of HDR brachytherapy, IMRT and helical tomotherapy in prostate cancer radiotherapy.

BACKGROUND AND PURPOSE: Dose escalation in order to improve the biochemical control in prostate cancer requires the application of irradiation techniques with high conformality. The dosimetric selectivity of three radiation modalities is compared: high-dose-rate brachytherapy (HDR-BT), intensity-modulated radiation radiotherapy (IMRT), and helical tomotherapy (HT). PATIENTS AND METHODS: Ten patients with prostate adenocarcinoma treated by a 10-Gy HDR-BT boost after external-beam radiotherapy were investigated. For each patient, HDR-BT, IMRT and HT theoretical treatment plans were realized using common contour sets. A 10-Gy dose was prescribed to the planning target volume (PTV). The PTVs and critical organs' dose-volume histograms obtained were compared using Student's t-test. RESULTS: HDR-BT delivers spontaneously higher mean doses to the PTV with smaller cold spots compared to IMRT and HT. 33% of the rectal volume received a mean HDR-BT dose of 3.86 + or - 0.3 Gy in comparison with a mean IMRT dose of 6.57 + or - 0.68 Gy and a mean HT dose of 5.58 + or - 0.71 Gy (p < 0.0001). HDR-BT also enables to better spare the bladder. The hot spots inside the urethra are greater with HDR-BT. The volume of healthy tissue receiving 10% of the prescribed dose is reduced at least by a factor of 8 with HDR-BT (p < 0.0001). CONCLUSION: HDR-BT offers better conformality in comparison with HT and IMRT and reduces the volume of healthy tissue receiving a low dose.

The status of radiation oncology (RO) teaching to medical students in Europe.

AIM: To provide an overview of Radiation Oncology (RO) teaching to medical students around Europe. MATERIALS AND METHODS: An electronic survey was sent to European academic teachers of RO. The survey focused on the teaching of RO to medical students throughout their undergraduate education. RESULTS: A total of 87 academic RO teachers from 29 countries were invited to participate in the electronic survey. Thirty-two surveys were completed by respondents from 19 European countries (response rate: 37%). The median number of hours devoted to RO teaching was 10 h (mean 16 h, range 2-60). The number of hours assigned to RO teaching was equal or inferior compared to medical oncology. In two institutions (6%) RO was delivered as a stand-alone course with an individual knowledge assessment. In 30 institutions (94%), the RO course was taught and/or assessed in a modular curriculum with other disciplines. Radiobiology, breast, lung, gastrointestinal, gynecologic malignancies, RO adverse events and palliative RO were taught in 80% of institutions. Pediatric RO, RO for benign conditions and economic topics were taught in less than 30% of institutions. In most institutions, classical written and oral examinations were used. Computer-based examinations and/or objective structured clinical examinations (OSCE) were seldom used. E-learning methods were available in less than 10% of institutions. A clerkship in RO department was available in 28 out of 32 institutions (87%), less than 5% of medical students were involved in research in RO during their undergraduate education. Strategies to encourage medical students to consider RO as a future career were offered in 53% of institutions. CONCLUSIONS: RO teaching to medical students was not uniform in Europe. RO teaching during undergraduate education in Europe was undervalued, and its knowledge and learning tools could be broadened and updated in the core curricula of medical students.

Photons, protons or carbon ions for stage I non-small cell lung cancer - Results of the multicentric ROCOCO in silico study.

PURPOSE: To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial. METHODS: For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions. RESULTS: The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ. CONCLUSION: On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient.

Adjuvant stereotactic permanent seed breast implant: a boost series in view of partial breast irradiation.

PURPOSE: The aim of this study was to use permanent seed implants in the breast and describe our experience with 15 cases, using iodine seed implants as a tumor bed boost. METHODS AND MATERIALS: Breasts were fixed with a thermoplastic sheet, a template bridge applied, the thorax scanned and the images rotated to be perpendicular to the implant axis. Skin, heart, and lung were delineated. A preplan was made, prescribing 50 Gy to the clinical target volume (CTV), consisting in this boost series of nearly a quadrant. Iodine (125) seeds were stereotactically implanted through the template, and results were checked with a postplan computed tomographic (CT) scan. RESULTS: The breast was immobilized reproducibly. Simulation, scanning, and implant were performed without difficulties. Preplan CTV D90% (the dose delivered to 90% of the CTV) was 66 Gy, and postoperative fluoroscopic or CT scan checks were satisfactory. Pre- and postplan dose-volume histogram showed good organ sparing: mean postplan skin, heart, and lung V30 Gy (the organ volume receiving a dose of 30 Gy) of 2 +/- 2.2 mL, 0.24 +/- 0.34 mL, and 3.5 +/- 5 mL, respectively. No short-term toxicity above Grade 1 was noted, except for transient Grade 3 neuropathy in 1 patient. CONCLUSIONS: Seeds remained in the right place, as assessed by fluoroscopy, absence of significant pre- to postplan dose-volume histogram change for critical organs, and total irradiated breast volume. The method could be proposed as a boost when high dosimetric selectivity is required (young patients after cardiotoxic chemotherapy for left-sided cancer). This boost series was a preliminary step before testing partial breast irradiation by permanent seed implant in a prospective trial.

Stereotactic Robotic Body Radiotherapy for Patients With Unresectable Hepatic Oligorecurrence.

BACKGROUND: The purpose of this study was to analyze local control (LC), liver progression-free survival (PFS), and distant PFS (DFS), overall survival (OS), and toxicity in a cohort of patients treated with stereotactic body radiotherapy (SBRT) with fiducial tracking for oligorecurrent liver lesions; and to evaluate the potential influence of lesion size, systemic treatment, physical and biologically effective dose (BED), treatment calculation algorithms and other parameters on the obtained results. PATIENTS AND METHODS: Unoperable patients with sufficient liver function had [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography and liver magnetic resonance imaging to confirm the oligorecurrent nature of the disease and to further delineate the gross tumor volume (GTV). An intended dose of 45 Gy in 3 fractions was prescribed on the 80% isodose and adapted if risk-related. Treatment was executed with the CyberKnife system (Accuray Inc) platform using fiducials tracking. Initial plans were recalculated using the Monte Carlo algorithm. Patient and treatment data were processed using the Kaplan-Meier method and log rank test for survival analysis. RESULTS: Between 2010 and 2015, 42 patients (55 lesions) were irradiated. The mean GTV and planning target volume (PTV) were 30.5 cc and 96.8 cc, respectively. Treatments were delivered 3 times per week in a median of 3 fractions to a PTV median dose of 54.6 Gy. The mean GTV and PTV D98% were 51.6 Gy and 51.2 Gy, respectively. Heterogeneity corrections did not influence dose parameters. After a median follow-up of 18.9 months, the 1- and 2-year LC/liver PFS/DFS/OS were 81.3%/55%/62.4%/86.9%, and 76.3%/42.3%/52%/78.3%, respectively. Performance status and histology had a significant effect on LC, whereas age (older than 65 years) marginally influenced liver PFS. Clinical target volume physical dose V45 Gy > 95%, generalized equivalent uniform dose (a = -30) > 45 Gy and a BED (α/ß = 10) V105 Gy > 96% showed statistically significant effect on the LC. Acute Grade 3 gastrointestinal (GI) and late Grade 2 GI and fatigue toxicity were found in 5% and 11% patients, respectively. CONCLUSION: Favorable survival and toxicity results support the potential paradigm shift in which the use of SBRT in oligorecurrent liver disease could benefit patients with unresectable or resectable liver metastases.

192Ir or 125I prostate brachytherapy as a boost to external beam radiotherapy in locally advanced prostatic cancer: a dosimetric point of view.

PURPOSE: This work aims at comparing the dosimetric possibilities of 125I or 192Ir prostate brachytherapy (Bt) as a boost to external beam radiotherapy in the treatment of locally advanced adenocarcinoma. METHODS AND MATERIALS: From 1/1997 to 12/2002, 260 patients were treated. Until 12/2001 a low dose rate (LDR) treatment with 192Ir wires was used, later replaced by a high dose rate (HDR) delivered with an 192Ir stepping source technology. For the present work, we selected 40 patients including the last 20 treated, respectively, by LDR and HDR. The planning CT Scans of all these 40 patients were transferred into the 3D Prowess system for 125I permanent implants design according to the Seattle method. The reference data for dosimetric comparisons were the V100 and the prescribed dose for 192Ir as well as the dose delivered with 125I techniques to the 192Ir V100. We compared V100-150 data as well as doses to the organs at risks (OR) and cold spots (CS). RESULTS: The V100 is 85.3+/-8% for 192Ir LDR and 96+/-2% for HDR techniques (P < 0.0001). In comparison with 125I, the 192Ir LDR mode induces higher hyperdosage volumes inside the CTV but also more CS, while maximal doses to urethra and rectum are, respectively, 17 and 39% less with 125I (P < 0.0001). In comparison with the 192Ir HDR mode, 125I Bt induces higher hyperdosage volumes and slightly more CS deliberately planned around the bladder neck. If delivered doses to urethra are identical, those to the 20% anterior part of the rectum are 33% less with 125I (P < 0,0001). The 125I Bt technique was only possible in 24 out of the 40 patients studied due to pelvic bone arch interference. CONCLUSIONS: At the present time, there is no evident dosimetric superiority of one Bt method when all the criteria are taken into account. However, improving Bt techniques to implant any prostatic size could found the superiority of the 125I or permanent implants. 125I indeed allows large hyperdosage volumes inside the CTV in comparison with 192Ir HDR techniques while lowering doses to OR and minimizing CS.

192Ir low dose rate brachytherapy for boosting locally advanced prostate cancers after external beam radiotherapy: a phase II trial.

BACKGROUND AND PURPOSE: To evaluate on 201 locally advanced prostatic cancers prospectively treated in a phase II trial, the efficacy of a combination of external beam radiotherapy (39.6 Gy) and (192)Ir low dose rate brachytherapy (Bt) (40-45 Gy). PATIENTS AND METHODS: Sixty-four patients were included in the intermediate prognosis group with only one of the following adverse factors (PSA > 10 ng/ml, Gleason score > or = 7 or clinical stage > or =T2b) and 137 in the unfavourable group when at least two of these factors were present. RESULTS: The actuarial 4 years biochemical no evidence of disease is 82.8% for the entire population. It is, respectively, 97 and 76% in the intermediate and unfavourable prognosis groups (P < 0.0001). Grade > or =3 late urinary complications occurred in 13 patients (6.5%). Eight patients (4%) presented late grade 2 rectal complications but no grades 3-5 was observed. CONCLUSIONS: Even if an alpha/beta of 1.5-3 Gy theoretically favours the use of a high dose rate mode of irradiation, the early results presented here are as good as those reported for similar groups of patients with high dose rate treatments. Late toxicity is identical but our urinary toxicity is within the less favourable and rectal toxicity within the most favourable results. We can postulate that while inducing very high hyperdosage regions (V150) mainly focused on the peripheral zone, most of the Bt techniques consist of a more ablative treatment. Many of the radiobiological studies on Bt did not in fact take into account the heterogeneity of irradiation inside the CTV. This study highlights the need to explore pulsed dose rate therapies, permanent implant and new available radioisotopes such as (169)Ytterbium that will offer the safety of low and lower dose rates. The actual late toxicity of the different Bt techniques is not yet inexistent indeed.

Respiratory Motion, Anterior Heart Displacement and Heart Dosimetry: Comparison Between Prone (Pr) and Supine (Su) Whole Breast Irradiation.

To analyze respiratory motion of surgical clips, chest wall (CW) and the anterior displacement of the heart and its impact on heart dosimetry between prone (Pr) and supine (Su) positions during whole breast radiotherapy after breast conserving surgery. Sixteen patients underwent 4D-CT for radiotherapy planning in Pr and Su positions. Maximum inhale and maximum exhale phases were analyzed. Mean 3D vectorial displacements ± standard deviations (SD) of the surgical clips were measured. Volumetric changes of the CW were recorded and compared. Cardiac displacement was assessed by a volume between the inner surface of CW and the myocardium of the heart (CW/H-V). For left-sided cases, comparative dosimetry was performed in each position simulating no- (Pr-noC, Su-noC) versus daily correction protocols (Pr-C, Su-C). The movements of 81 surgical clips were analyzed. Prone positioning significantly reduced both the mean 3D vectorial displacements (1.1 ± 0.6 (Pr) vs. 2.0 ± 0.9 mm (Su), p < 0.01) and their variability (0.3 ± 0.2 vs. 0.5 ± 0.3 mm, p = 0.01). Respiration-induced volumetric changes of CW were also significantly lower in Pr (2.3 ± 4.9 vs. 9.6 ± 7.1 cm(3), p < 0.01). The CW/H-V was significantly smaller in Pr than in Su (39.9 ± 14.6 vs. 64.3 ± 28.2 cm(3), p < 0.01). Besides identical target coverage heart, left-anterior-descending coronary artery (LADCA) and ipsilateral lung dose parameters were lowered with Pr-C compared to Pr-noC, Su-C and Su-noC. Prone position significantly reduced respiration-related surgical clip movements, their variability as well as CW movements. Significant anterior heart displacement was observed in Pr. Prone position with daily online correction could maximize the heart and LADCA protection.

First study of oral Artenimol-R in advanced cervical cancer: clinical benefit, tolerability and tumor markers.

BACKGROUND/AIM: Artenimol-R is cytotoxic in transformed cervical cells and safety in humans is yet to be established. The present study investigates the clinical benefits, safety and the tumor marker effect of orally administered Artenimol-R in patients with advanced cervix carcinoma. PATIENTS AND METHODS: Ten patients were treated with Artenimol-R for 28 days. Clinical symptoms, vaginal discharge and pain were followed-up. Adverse events were recorded. Biopsy samples were analyzed by immunohistochemistry for the expression of relevant tumor markers. RESULTS: Artenimol-R treatment induced clinical remission with a median time for the disappearance of the symptoms being 7 days. No adverse events of grade 3 or 4 occurred. The expression of p53, Epidermal growth factor receptor (EGFR), and antigen Ki-67 as a cellular marker of proliferation, as well as the number of blood vessels stained by the CD31 antibody decreased, whereas the expression of transferrin receptor protein 1 (CD71) increased. CONCLUSION: The current pilot study provides evidence on the improvement of the clinical symptoms and the good tolerability of Artenimol-R in patients with advanced carcinoma of the cervix uteri. A survival trial with Artenimol-R in advanced patients is warranted.