Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Low-dose radiotherapy for greater trochanteric pain syndrome-a single-centre analysis.

PURPOSE: To determine predictive factors associated with a good response (GR) to and efficacy of low-dose radiotherapy (LDRT) in patients with greater trochanteric pain syndrome (GTPS). METHODS: Patients with GTPS were irradiated on a linear accelerator with 0.5-1.0 Gy per fraction to a total dose of 3.0-4.0 Gy per series. The endpoint was subjective good response (GR) to treatment 2 months after completion of the last LDRT series, defined as complete pain relief or marked improvement assessed using the von Pannewitz score. A positive response to steroid injection (SI) was defined as pain relief of at least 7 days. Patient and treatment-related characteristics were evaluated with respect to LDRT outcomes. RESULTS: Outcomes were assessed for 71 peritrochanteric spaces (PTSs; 65 patients, 48 females, with mean age of 63 [44-91] years). Prior SI had been given to 55 (77%) PTSs and 40 PTSs received two series of LDRT. Two months after completion of LDRT, GR was reported in 42 PTSs (59%). Two series of LDRT provided a significantly higher rate of GR than one series (72.5 vs. 42% PTSs, p = 0.015). Temporary pain relief after prior SI predicted GR to LDRT compared with PTSs which had not responded to SI (73 vs. 28% PTSs, p = 0.001). A regional structural abnormality, present in 34 PTSs (48%), was associated with a reduction of GR to LDRT (44 vs. 73% PTSs, p = 0.017). CONCLUSION: LDRT is an effective treatment for GTPS. Administration of two LDRT series, prior response to SI, and absence of structural abnormalities may predict significantly better treatment outcomes.

Radiotherapy combined with deep regional hyperthermia in elderly and frail patients with muscle-invasive bladder cancer: quality analysis of hyperthermia and impact on clinical results.

Purpose: Radiotherapy (RT) in combination with deep regional hyperthermia (HT) after transurethral removal of bladder tumor (TURBT) can be offered to elderly and frail patients with muscle-invasive bladder cancer (MIBC).Methods: In total, 21 patients (mean age 84 years) with unifocal or multifocal MIBC received radiation to a dose of 48-50 Gy/16-20 fractions with weekly HT. The primary endpoint was the variation in temperature metrics, thermal dose expressed as cumulative equivalent minutes at 43 °C when the measured temperature is T90 (CEM43T90) and net power applied in target volume per each HT session. Secondary endpoints were three-year overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS) and toxicity.Results: The temperature metrics, CEM43T90, mean and maximum net power applied did not differ significantly among the HT sessions of the 21 patients. With a median follow-up of 65 months, 52% (95% CI 32-72%) of patients had died 3 years after treatment. The three-year DFS and LPFS rates were 62% (95%CI 41-79%) and 81% (95%CI 60-92%), respectively. The three-year bladder preservation rate was 100%. Three out of four patients with local failure received a thermal dose CEM43T90 below a median of 2.4 min. The rates of acute and late grade-3 toxicities were 10% and 14%, respectively.Conclusion: The reproducibility of HT parameters between sessions was high. A moderately high CEM43T90 (> 2.4 min) for each HT session seems to be preferable for local control. RT combined with HT is a promising organ-preservation therapy for elderly and frail MIBC patients.

Postoperative radiotherapy for meningiomas - a decision-making analysis.

BACKGROUND: The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized. METHODS: Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine. RESULTS: Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous. CONCLUSIONS: Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals.

Tetramodal therapy with transurethral resection followed by chemoradiation in combination with hyperthermia for muscle-invasive bladder cancer: early results of a multicenter phase IIB study.

BACKGROUND: Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT). METHODS: Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design. RESULTS: Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy. CONCLUSION: Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage.

State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain.

In 1999 a visionary short article by The Wall Street Journal writers Robert Langreth and Michael Waldholz popularized the new term "personalized medicine," that is to say, the targeting of drugs to each unique genetic profile. From today's perspective, targeted approaches have clearly found the widest use in the antineoplastic domain. The current review was initiated to review the progress that has been made regarding the treatment of patients with advanced cancer and brain metastases. PubMed was searched for the terms brain metastasis, brain metastases, or metastatic brain in the Title/Abstract. Selection was limited to randomized controlled trial (RCT) and publication date January 2010 to February 2022. Following visual review, 51 papers on metastatic lung cancer, 12 on metastatic breast cancer, and 9 on malignant melanoma were retained and underwent full analysis. Information was extracted from the papers giving specific numbers for intracranial response rate and/or overall survival. Since most pharmacological trials on advanced cancers excluded patients with brain metastases and since hardly any information on adjuvant radiotherapy and radiosurgery is available from the pharmacological trials, precise assessment of the effect of targeted medication for the subgroups with brain metastases is difficult. Some quantitative information regarding the success of targeted pharmacological therapy is only available for patients with breast and lung cancer and melanoma. Overall, targeted approaches approximately doubled the lifespan in the subgroups of brain metastases from tumors with targetable surface receptors such as anaplastic lymphoma kinase (ALK) fusion receptor in non-small cell lung cancer or human epidermal growth factor receptor 2 (HER2)-positive breast cancer. For these types, overall survival in the situation of brain metastases is now more than a year. For receptor-negative lung cancer and melanoma, introduction of immune checkpoint blockers brought a substantial advance, although overall survival for melanoma metastasized to the brain appears to remain in the range of 6 to 9 months. The outlook for small cell lung cancer metastasized to the brain apparently remains poor. The introduction of targeted therapy roughly doubled survival times of advanced cancers including those metastasized to the brain, but so far, targeted therapy does not differ essentially from chemotherapy, therefore also facing tumors developing escape mechanisms. With the improved perspective of patients suffering from brain metastases, it becomes important to further optimize treatment of this specific patient group within the framework of randomized trials.

Successful salvage of recurrent leptomeningeal disease in large cell neuroendocrine lung cancer with stereotactic radiotherapy.

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer.

Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature-time area under the curve (AUC).

BACKGROUND: Thermal dose in clinical hyperthermia reported as cumulative equivalent minutes (CEM) at 43 °C (CEM43) and its variants are based on direct thermal cytotoxicity assuming Arrhenius 'break' at 43 °C. An alternative method centered on the actual time-temperature plot during each hyperthermia session and its prognostic feasibility is explored. METHODS AND MATERIALS: Patients with bladder cancer treated with weekly deep hyperthermia followed by radiotherapy were evaluated. From intravesical temperature (T) recordings obtained every 10 secs, the area under the curve (AUC) was computed for each session for T > 37 °C (AUC > 37 °C) and T ≥ 39 °C (AUC ≥ 39 °C). These along with CEM43, CEM43(>37 °C), CEM43(≥39 °C), Tmean, Tmin and Tmax were evaluated for bladder tumor control. RESULTS: Seventy-four hyperthermia sessions were delivered in 18 patients (median: 4 sessions/patient). Two patients failed in the bladder. For both individual and summated hyperthermia sessions, the Tmean, CEM43, CEM43(>37 °C), CEM43(≥39 °C), AUC > 37 °C and AUC ≥ 39 °C were significantly lower in patients who had a local relapse. Individual AUC ≥ 39 °C for patients with/without local bladder failure were 105.9 ± 58.3 °C-min and 177.9 ± 58.0 °C-min, respectively (p = 0.01). Corresponding summated AUC ≥ 39 °C were 423.7 ± 27.8 °C-min vs. 734.1 ± 194.6 °C-min (p < 0.001), respectively. The median AUC ≥ 39 °C for each hyperthermia session in patients with bladder tumor control was 190 °C-min. CONCLUSION: AUC ≥ 39 °C for each hyperthermia session represents the cumulative time-temperature distribution at clinically defined moderate hyperthermia in the range of 39 °C to 45 °C. It is a simple, mathematically computable parameter without any prior assumptions and appears to predict treatment outcome as evident from this study. However, its predictive ability as a thermal dose parameter merits further evaluation in a larger patient cohort.

Clinical estimation of α/ß values for prostate cancer from isoeffective phase III randomized trials with moderately hypofractionated radiotherapy.

BACKGROUND: The α/ß values for prostate cancer (PCa) are usually assumed to be low (1.0-1.8 Gy). This study estimated the α/ß values of PCa from phase III randomized trials of conventional (CRT) versus hypofractionated (HRT) external beam radiotherapy (RT), reported as isoeffective in terms of their 5-year biochemical (BF) or biochemical and/or clinical failure (BCF) rates. MATERIAL AND METHODS: The α/ß for each trial was estimated from the equivalent biological effective doses using the linear-quadratic model for each of their HRT and CRT schedules. The cumulative outcomes of these trials were evaluated by meta-analysis for odds ratio (OR), risk ratio (RR) and risk difference (RD). RESULTS: Eight trials from seven studies, randomized 6993 patients between CRT (n = 2941) and HRT (n = 4052). RT treatment varied between the two treatment groups in terms of dose/fraction, total dose, overall treatment time and %patients on androgen deprivation therapy (ADT). Differences in OR, RR, and RD for both BF and BCF were nonsignificant. The computed α/ß ranged from 1.3 to 11.1 Gy (4.9 ± 3.9 Gy; 95% CI: 1.6-8.2). On multivariate regression, %ADT was the sole determinant of computed α/ß (model R2: 0.98, p < .001). CONCLUSIONS: Clinically estimated α/ß for PCa from isoeffective randomized trials using known variables in the linear-quadratic expression ranged between 1.3 and 11.1 Gy. The estimated α/ß values were inversely related to %ADT usage, which should be considered when planning future RT dose-fractionation schedules.

Local antibiotic decontamination to prevent anastomotic leakage short-term outcome in rectal cancer surgery.

PURPOSE: Anastomotic leakage still presents an issue in rectal cancer surgery with rates of about 11%. As bacteria play a critical role, there is the concept of perioperative local decontamination to prevent anastomotic leakage. METHODS: To ascertain the effectiveness of this treatment, we performed a retrospective analysis on 206 rectal resections with primary anastomosis and routine use of a selective decontamination of the digestive tract (SDD) regimen for local decontamination. SDD medication was administered every 8 h from the day before surgery to the seventh postoperative day. All patients were treated according to the fast-track protocol without mechanical bowel preparation; instead, a laxative was used. RESULTS: Overall morbidity was 30%, overall mortality 0.5%. In our data, overall rate of anastomotic leakage (AL) was 5.8%, with 3.9% in anterior rectal resection and 6.5% in low anterior rectal resection group. In 75% of cases, anastomotic leakage was grade "C" and needed re-laparotomy. Surgical site infection rate was 19.9%. No serious adverse events were related to decontamination. CONCLUSION: Local antibiotic decontamination appears to be safe and effective to decrease the rate of anastomotic leakage in rectal cancer surgery. Further focus should be on perioperative management including bowel preparation and choice of antimicrobial agents for local decontamination.

Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: A systematic review and meta-analysis.

The efficacy of concurrent chemoradiotherapy (CTRT) in locally advanced cervix cancer (LACC, stages IIB-IVA) is contentious. This is due to the variable extent of therapeutic benefit reported in different randomized clinical trials and meta-analyses that usually include all stages of cervix cancer. A systematic review and meta-analysis was therefore conducted to evaluate the efficacy of concurrent CTRT over radiotherapy (RT) alone, predominantly in LACC for the key endpoints; complete response (CR), long-term loco-regional control (LRC), overall survival (OS), grade III/IV acute and late toxicities. Six databases namely - PubMed, EMBASE, SCOPUS, Web of Science, Google Scholar and Cochrane library were explored and supplemented by hand-searching. Only prospective randomized trials conducted in LACC between concurrent CTRT and RT alone with no surgical interventions were included. Fourteen English language articles from 1788 citations were shortlisted for the final analysis. Of the 2445 patients evaluated (CTRT: n=1217; RT: n=1228), 95.7% had LACC and 96% had a squamous cell histology. Eight studies used cisplatin alone, 4 had cisplatin-based combination chemotherapy (CT) while 2 used mitomycin-C, either alone or in combination. CTRT improved the CR (+10.2%, p=0.027), LRC (+8.4%, p<0.001) and OS (+7.5%, p<0.001) over RT alone. However a 10.4% higher incidence of grade III/IV acute toxicities (p<0.001) was also evident with CTRT. Late toxicities in both groups were equivalent. Subgroup analysis and meta-regression did not reveal any significant advantage in outcomes between the 3 CTRT regimens. Thus, although concurrent CTRT provides conclusive therapeutic benefit over RT alone in LACC, the choice of CT agents should be based on their cost-effectiveness and the anticipated expenses for the management of any associated acute toxicities. This assumes importance particularly in resource-constrained low-middle-income countries with the highest burden of LACC, where majority of the patients meet the treatment costs as out-of-pocket expenses.

Hyperthermia and radiotherapy with or without chemotherapy in locally advanced cervical cancer: a systematic review with conventional and network meta-analyses.

PURPOSE: A systematic review with conventional and network meta-analyses (NMA) was conducted to examine the outcomes of loco-regional hyperthermia (HT) with radiotherapy (RT) and/or chemotherapy (CT) in locally advanced cervix cancer, IIB-IVA (LACC). METHODS AND MATERIALS: A total of 217 abstracts were screened from five databases and reported as per PRISMA guidelines. Only randomised trials with HT and RT ± CT were considered. The outcomes evaluated were complete response (CR), long-term loco-regional control (LRC), patients alive, acute and late grade III/IV toxicities. RESULTS: Eight articles were finally retained. Six randomised trials with HTRT (n = 215) vs. RT (n = 212) were subjected to meta-analysis. The risk difference for achieving CR and LRC was greater by 22% (p < .001) and 23% (p < .001), respectively, with HTRT compared to RT. A non-significant survival advantage of 8.4% with HTRT was noted with no differences in acute or late toxicities. The only HTCTRT vs. RT trial documented a CR of 83.3% vs. 46.7% (risk difference: 36.7%, p = .001). No other end points were reported. Bayesian NMA, incorporating 13 studies (n = 1000 patients) for CR and 12 studies for patients alive (n = 807 patients), comparing HTCTRT, HTRT, CTRT and RT alone, was conducted. The pairwise comparison of various groups showed that HTRTCT was the best option for both CR and patient survival. This was also evident on ranking treatment modalities based on the "surface under cumulative ranking" values. CONCLUSIONS: In LACC, HTRT demonstrates a therapeutic advantage over RT without significant acute or late morbidities. On NMA, HTCTRT appears promising, but needs further confirmation through prospective randomised trials.

Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone. MATERIAL AND METHODS: A total of 498 abstracts were screened from four databases and hand searched as per the PRISMA guidelines. Only two-arm studies treating HNCs with either radiotherapy alone, or hyperthermia and radiotherapy without concurrent chemotherapy or surgery were considered. The evaluated end point was complete response (CR). RESULTS: Following a detailed screening of the titles, abstracts and full text papers, six articles fulfilling the above eligibility criteria were considered. In total 451 clinical cases from six studies were included in the meta-analysis. Five of six trials were randomised. The overall CR with radiotherapy alone was 39.6% (92/232) and varied between 31.3% and 46.9% across the six trials. With thermoradiotherapy, the overall CR reported was 62.5% (137/219), (range 33.9-83.3%). The odds ratio was 2.92 (95% CI: 1.58-5.42, p = 0.001); the risk ratio was 1.61 (95% CI: 1.32-1.97, p < 0.0001) and the risk difference was 0.25 (95% CI: 0.12-0.39, p < 0.0001), all in favour of combined treatment with hyperthermia and radiotherapy over radiotherapy alone. Acute and late grade III/IV toxicities were reported to be similar in both the groups. CONCLUSIONS: Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

Diffusion tensor imaging for target volume definition in glioblastoma multiforme.

INTRODUCTION: Diffusion tensor imaging (DTI) is an MR-based technique that may better detect the peritumoural region than MRI. Our aim was to explore the feasibility of using DTI for target volume delineation in glioblastoma patients. MATERIALS AND METHODS: MR tensor tracts and maps of the isotropic (p) and anisotropic (q) components of water diffusion were coregistered with CT in 13 glioblastoma patients. An in-house image processing program was used to analyse water diffusion in each voxel of interest in the region of the tumour. Tumour infiltration was mapped according to validated criteria and contralateral normal brain was used as an internal control. A clinical target volume (CTV) was generated based on the T1-weighted image obtained using contrast agent (T1Gd), tractography and the infiltration map. This was compared to a conventional T2-weighted CTV (T2-w CTV). RESULTS: Definition of a diffusion-based CTV that included the adjacent white matter tracts proved highly feasible. A statistically significant difference was detected between the DTI-CTV and T2-w CTV volumes (p < 0.005, t = 3.480). As the DTI-CTVs were smaller than the T2-w CTVs (tumour plus peritumoural oedema), the pq maps were not simply detecting oedema. Compared to the clinical planning target volume (PTV), the DTI-PTV showed a trend towards volume reduction. These diffusion-based volumes were smaller than conventional volumes, yet still included sites of tumour recurrence. CONCLUSION: Extending the CTV along the abnormal tensor tracts in order to preserve coverage of the likely routes of dissemination, whilst sparing uninvolved brain, is a rational approach to individualising radiotherapy planning for glioblastoma patients.

Differentiation between calcification and hemorrhage in brain tumors using susceptibility-weighted imaging: a pilot study.

OBJECTIVE: Our aim was to develop a robust method to differentiate calcification from hemorrhage in gliomas. Histopathologic examination was performed to validate hemorrhage and calcification. CONCLUSION: Phase images from eleven patients with glioma yielded statistically significant phase-shift values for calcification and hemorrhage compared with normal brain, whereas CT showed substantial overlap of Hounsfield units. Phase image analysis correctly differentiated between intratumoral calcification and hemorrhage in 86% of cases.

Could hyperthermia with proton therapy mimic carbon ion therapy? Exploring a thermo-radiobiological rationale.

Hyperthermia has been conventionally used in conjunction with photon beam irradiation. With a gradual increase in particle therapy facilities worldwide, this paper explores the physical, thermal and radiobiological implications of using a combination of hyperthermia with proton beam therapy. Hyperthermia is known to exhibit radiobiological features similar to those of high linear energy transfer radiation. Protons have many of the physical dose distribution properties of (12)C ion therapy. Thus, the thermo-radiobiological advantages of hyperthermia coupled with the physical dose distribution advantages of proton beams could possibly mimic (12)C ion therapy.

Retrospective reconstruction of four-dimensional magnetic resonance from interleaved cine imaging - A comparative study with four-dimensional computed tomography in the lung.

Background and purpose: Imaging of respiration-induced anatomical changes is essential to ensure high accuracy in radiotherapy of lung cancer. We expanded here on methods for retrospective reconstruction of time-resolved volumetric magnetic resonance (4DMR) of the thoracic region and benchmarked the results against 4D computed tomography (4DCT). Materials and method: MR data of six lung cancer patients were collected by interleaving cine-navigator images with 2D data frame images, acquired across the thorax. The data frame images have been stacked in volumes based on a similarity metric that considers the anatomical deformation of lungs, while addressing ambiguities in respiratory phase detection and interpolation of missing data. The resulting images were validated against cine-navigator images and compared to paired 4DCTs in terms of amplitude and period of motion, assessing differences in internal target volume (ITV) margin definition. Results: 4DMR-based motion amplitude was on average within 1.8 mm of that measured in the corresponding 2D cine-navigator images. In our dataset, the 4DCT motion and the 4DMR median amplitude were always within 3.8 mm. The median period was generally close to CT references, although deviations up to 24 % have been observed. These changes were reflected in the ITV, which was generally larger for MRI than for 4DCT (up to 39.7 %). Conclusions: The proposed algorithm for retrospective reconstruction of time-resolved volumetric MR provided quality anatomical images with high temporal resolution for motion modelling and treatment planning. The potential for imaging organ motion variability makes 4DMR a valuable complement to standard 4DCT imaging.

Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy.

BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

Anisotropic phantom measurements for quality assured use of diffusion tensor imaging in clinical practice.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (MRI) is being increasingly applied in clinical practice, for example in neuronavigation and in modern radiation treatment planning. Quality assurance (QA) is therefore important to avoid clinical errors. PURPOSE: To compare four analytical programs and a neuronavigation tool to evaluate our in-house diffusion-weighted imaging protocol in order to be able to implement diffusion tensor imaging (DTI) into clinical practice. MATERIAL AND METHODS: A phantom containing crossing fibers was used for the QA. Fiber tracking and fractional anisotropy (FA) analyses were performed, and the geometrical resolution was verified using the phantom. RESULTS: FA results were reproducible within each program and no significant differences between programs were observed. Also, no significant differences in FA values were found when comparing the results between the four software programs. Geometrical resolution of the anatomical data-set was satisfactory; however the crossing of the fibers was not accurately represented by three of the four programs. CONCLUSION: Phantom QA is necessary before using DTI for novel procedures to identify the uncertainties associated with DTI data. It is important to remember that the results are software-dependent and that representation of the tracts may vary between software products. We therefore recommend caution with regard to the application of fiber tracking results intraoperatively when dealing with abnormal fiber tract anatomy.

Real World Analysis of Quality of Life and Toxicity in Cancer Patients Treated with Hyperthermia Combined with Radio(chemo)therapy.

Hyperthermia (HT) in combination with radio(chemo)therapy (RCT) is a well-established cancer treatment strategy. This report analyses the quality of life (QoL), toxicity and survival outcomes in patients with different tumor entities who received HT in combination with RCT. The primary endpoint of this study was the assessment of QoL scale items 3 and 12 months after treatment in patients who were treated with palliative intent and curative intent, respectively. The secondary endpoints of this study were acute toxicities, 1-year overall survival (OS), and local progression-free survival (LPFS). Patients treated with curative intent experienced significant improvement in emotional functioning (EF), social functioning (SF), financial difficulties (FI) and insomnia (SL) 12 months after treatment. Patients had significantly improved FI and pain (PA) three months after palliative treatment. Acute toxicity of grade 3 or more was 26% during treatment and 4% after three months. The 1-year OS rates were 90% (95% CI: 79-96%) and 44% (95% CI: 31-59%) for patients treated with curative and palliative RCT combined with HT, respectively. Moreover, the 1-year LPFS rates were 94% (95% CI: 84-98%) for patients treated with curative intent and 64% (95% CI: 50-77%) for palliative patients. In summary, combined RCT and HT stabilized or improved QoL scale items for both curative and palliative indications.