Prognostic impact of the number and total tumor burden of secondary cerebral lesions in patients with resected brain metastases of non-small cell lung cancers.

OBJECTIVE: Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. METHODS: In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. RESULTS: One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. CONCLUSIONS: In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.

Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial).

BACKGROUND: Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. METHODS: In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter. RESULTS: One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients. CONCLUSION: The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM. TRIAL REGISTRATION: NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.

Target volume delineation for radiotherapy of meningiomas: an ANOCEF consensus guideline.

PURPOSE: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). MATERIALS AND METHODS: A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. RESULTS: Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. CONCLUSION: New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.

Is pre-radiotherapy metabolic heterogeneity of glioblastoma predictive of progression-free survival?

BACKGROUND AND PURPOSE: All glioblastoma subtypes share the hallmark of aggressive invasion, meaning that it is crucial to identify their different components if we are to ensure effective treatment and improve survival. Proton MR spectroscopic imaging (MRSI) is a noninvasive technique that yields metabolic information and is able to identify pathological tissue with high accuracy. The aim of the present study was to identify clusters of metabolic heterogeneity, using a large MRSI dataset, and determine which of these clusters are predictive of progression-free survival (PFS). MATERIALS AND METHODS: MRSI data of 180 patients acquired in a pre-radiotherapy examination were included in the prospective SPECTRO-GLIO trial. Eight features were extracted for each spectrum: Cho/NAA, NAA/Cr, Cho/Cr, Lac/NAA, and the ratio of each metabolite to the sum of all the metabolites. Clustering of data was performed using a mini-batch k-means algorithm. The Cox model and logrank test were used for PFS analysis. RESULTS: Five clusters were identified as sharing similar metabolic information and being predictive of PFS. Two clusters revealed metabolic abnormalities. PFS was lower when Cluster 2 was the dominant cluster in patients' MRSI data. Among the metabolites, lactate (present in this cluster and in Cluster 5) was the most statistically significant predictor of poor outcome. CONCLUSION: Results showed that pre-radiotherapy MRSI can be used to reveal tumor heterogeneity. Groups of spectra, which have the same metabolic information, reflect the different tissue components representative of tumor burden proliferation and hypoxia. Clusters with metabolic abnormalities and high lactate are predictive of PFS.

Pseudoprogression in GBM versus true progression in patients with glioblastoma: A multiapproach analysis.

BACKGROUND AND PURPOSE: To investigate the feasibility of using a multiapproach analysis combining clinical data, diffusion- and perfusion-weighted imaging, and 3D magnetic resonance spectroscopic imaging to distinguish true tumor progression (TP) from pseudoprogression (PSP) in patients with glioblastoma. MATERIALS AND METHODS: Progression was suspected within 6 months of radiotherapy in 46 of the 180 patients included in the Phase-III SpectroGlio trial (NCT01507506). Choline/creatine (Cho/Cr), choline/N-acetyl aspartate (Cho/NAA) and lactate/N-acetyl aspartate (Lac/NAA) ratios were extracted. Apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps were calculated. ADC, relative CBV values and tumor volume (TV) were collected at relapse. Differences between TP and PSP were evaluated using Mann-Whitney tests, and p values were adjusted with Bonferroni correction. RESULTS: Patients with suspected progression underwent a new MRI scan 1 month after the first one. Of these, 28 were classified as PSP, and 18 as TP. After a median follow-up of 41 months, median overall survival was higher in PSP than in TP (25.2 vs 20.3 months; p = 0.0092). Lac/NAA and Cho/Cr ratios were higher in TP than in PSP (1.2 vs 0.5; p = 0.006; and 3 vs 2.2; p = 0.021). After multivariate regression analysis, TV was the most significant predictor of TP vs PSP, and the only one retained in the model (p = 0.028). CONCLUSION: Three spectroscopic ratios could be used to differentiate PSP from TP. TV at relapse was the most predictive factor in the multivariate analysis, and overall survival was higher in PSP than in TP.

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer.

Introduction: We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT). Methods: The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis. Results: In REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58. Conclusion: Increasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.

Magnetic Resonance-Guided Reirradiation for Local Recurrence within the Prostate or in the Prostate Bed: One-Year Clinical Results of a Prospective Registry Study.

Around 33% of patients treated by EBRT or brachytherapy will present a biochemical recurrence. SBRT is a new option for the treatment of patients with local-only recurrence. MRgRT seems to be interesting for the treatment of these recurrences. This article presents the one-year late tolerance and biochemical recurrence-free survival results of a prospective registry study. Patients with intraprostatic (or in the prostate bed) recurrence were treated with 5 to 9 fractions (median dose of 30 Gy in 5 fractions) with the MRIdian® system. PSA level and toxicities were evaluated before treatment and at three, six and 12 months after treatment. Thirty-seven patients with a median age of 74.5 years old were treated between 21 October 2019 and 7 December 2020. Acute tolerance was excellent with no grade >2 toxicities. Twelve months after treatment, we observed an increase of grade 1−2 dysuria (46% vs. 13% before treatment) and grade 1 polyuria (73% vs. 7%). The six, nine and 12-months biochemical-recurrence free survival were 97.3%, 86.5% and 65.0%. Fifteen patients (40%) presented a biochemical recurrence. Nine of these 15 patients (60%) had a persistent disease within the treated volume. In conclusion, MRgRT is safe and has promising survival results.

Quality control of 3D MRSI data in glioblastoma: Can we do without the experts?

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) is a noninvasive technique for assessing tumor metabolism. Manual inspection is still the gold standard for quality control (QC) of spectra, but it is both time-consuming and subjective. The aim of the present study was to assess automatic QC of glioblastoma MRSI data using random forest analysis. METHODS: Data for 25 patients, acquired prospectively in a preradiotherapy examination, were submitted to postprocessing with syngo.MR Spectro (VB40A; Siemens) or Java-based magnetic resonance user interface (jMRUI) software. A total of 28 features were extracted from each spectrum for the automatic QC. Three spectroscopists also performed manual inspections, labeling each spectrum as good or poor quality. All statistical analyses, with addressing unbalanced data, were conducted with R 3.6.1 (R Foundation for Statistical Computing; https://www.r-project.org). RESULTS: The random forest method classified the spectra with an area under the curve of 95.5%, sensitivity of 95.8%, and specificity of 81.7%. The most important feature for the classification was Residuum_Lipids_Versus_Fit, obtained with syngo.MR Spectro. CONCLUSION: The automatic QC method was able to distinguish between good- and poor-quality spectra, and can be used by radiation oncologists who are not spectroscopy experts. This study revealed a novel set of MRSI signal features that are closely correlated with spectral quality.

Stereotactic MR-Guided Radiotherapy for Adrenal Gland Metastases: First Clinical Results.

Stereotactic MR-guided Radiotherapy (MRgRT) is an interesting treatment option for adrenal gland metastases (AGM). We reviewed data from 12 consecutive patients treated with MRgRT for an AGM in our center between 14 November 2019 and 17 August 2021. Endpoints were tolerance assessment, the impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC), and overall survival (OS). The majority of patients were oligometastatic (58.3%), with 6 right AGM, 5 left AGM and 1 left and right AGM. The prescribed dose was 35 to 50 Gy in 3 to 5 fractions. The median PTV V95% on the initial plan was 95.74%. The median V95% of the PTVoptimized (PTVopt) on the initial plan was 95.26%. Thirty-eight (69%) fractions were adapted. The PTV coverage was significantly improved for adapted plans compared to predicted plans (median PTV V95% increased from 89.85% to 91.17%, p = 0.0478). The plan adaptation also significantly reduced Dmax for the stomach and small intestine. The treatment was well tolerated with no grade > 2 toxicities. With a median follow-up of 15.5 months, the 1−year LC and OS rate were 100% and 91.7%. Six patients (50%) presented a metastatic progression, and one patient (8.3%) died of metastatic evolution during the follow-up. Adaptation of the treatment plan improved the overall dosimetric quality of MRI-guided radiotherapy. A longer follow-up is required to assess late toxicities and clinical results.

Magnetic Resonance-Guided Reirradiation for Local Recurrence Within the Prostate or in the Prostate Bed: Preliminary Results of a Prospective Registry Study.

PURPOSE: This prospective registry study evaluated the feasibility of stereotactic magnetic resonance imaging (MRI)-guided radiation therapy for the local treatment of isolated prostate cancer recurrence within the gland or prostate bed after primary radiation therapy. METHODS AND MATERIALS: Patients with isolated recurrence without any regional or distant extension after treatment by external radiation therapy of the prostate gland/bed or by prostate brachytherapy were included. A 173-second Fast Imaging with Steady state Precession (TrueFISP) sequence was used for MRI simulation, and the gross tumor volume was delineated using multimodal images. The initial treatment plan varied from 27.5 Gy in 5 fractions to 38.7 Gy in 9 fractions and was adapted at each session, if necessary. The primary endpoint was acute toxicities (according to the Common Terminology Criteria for Adverse Events v5.0 criteria). Secondary endpoints were the effects of the adaptive treatment on target volume coverage, late toxicities, and oncologic events. RESULTS: Twenty patients were included. After a minimum follow-up of 6 months, grade 2 dysuria (from grade 1 at baseline; n = 1), grade 2 polyuria (n = 1), grade 1 urinary incontinence (n = 1), grade 1 urinary pain (n = 2), and grade 1 diarrhea (n = 1) were reported.All initial treatment plans met the tumor coverage objectives, with a mean 95% planning target volume value of 95.7%. No plan exceeded the bladder and rectum dose constraints, but 8 exceeded the urethra dose constraints because of urethra proximity to the planning target volume. The initial plan was adapted in 7 patients (35%). The tumor coverage improved by 3.7% compared with the predicted plan (P = .0001) without increase in the dose to organs at risk. The biochemical control rate for the whole cohort was 75% (15/20 patients) including the 4 patients who received androgen-deprivation therapy. CONCLUSIONS: MRI-guided reirradiation for isolated recurrence within the prostate or in the prostate bed appears to be safe with excellent dosimetric results.

Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging.

BACKGROUND: Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival. METHODS/DESIGN: In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status. DISCUSSION: This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging. TRIAL REGISTRATION: NCT01507506 , registration date December 20, 2011.

Low- vs. Middle-dose Total Skin Electron Beam Therapy for Mycosis Fungoides: An Efficiency-based Retrospective Survey of Skin Response.

Optimal doses of total skin electron beam therapy for mycosis fungoides remain to be established. Clinical efficiency and adverse effects of middle-dose (25 Gy) vs. low-dose (10-12 Gy) total skin electron beam therapy were retrospectively compared in a series of 14 and 12 mycosis fungoides, respectively. Overall skin response rate was 96.2% (92.9% middle-dose and 100% low-dose; not significant (NS)). Overall complete and partial skin response rates were 57.7% (42.9% middle-dose and 75% low-dose; NS) and 38.5% (50% middle-dose and 25% low-dose; NS), respectively. All responding patients relapsed after an overall median time of 5 months (7 months middle-dose vs. 4 months low-dose; p = 0.164, NS). Tolerance was equally fair in both groups, with only grade 1 and 2 adverse events observed in 100% vs. 66.7% of patients in middle-dose and low-dose groups (NS). Although no significant difference was observed, middle-dose protocol may be recommended owing to a longer relapse-free survival for a similar tolerance.

Association of patterns of care, prognostic factors, and use of radiotherapy-temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study.

BACKGROUND: Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. OBJECTIVES: To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. METHODS: Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. RESULTS: Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7-11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6-2.1), 27% received treatment without the combination of radiotherapy (RT)-temozolomide (MS = 5.9, 95% CI 5.5-6.6), 60% received treatment including the initiation of the concomitant phase of RT-temozolomide (MS = 16.4, 95% CI 15.2-17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0-19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0-28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2-1.9). CONCLUSION: In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS.

Do perfusion and diffusion MRI predict glioblastoma relapse sites following chemoradiation?

To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy (60 Gy) and concomitant temozolomide for glioblastoma, who were included in the reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed and their imaging data were analyzed. All patients underwent anatomical MRI, DSC-MRI and DWI before radiotherapy and every 2 months thereafter until relapse. Voxels within the sites of relapse were correlated with their perfusion and/or diffusion abnormality (PDA) pretreatment status after rigid co-registration. The relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels using a 1.75 fixed rCBV threshold (HPt); hypoperfused (hPg) and hyperperfused (HPg) voxels using a histogram-based Gaussian method; diffusion-restricted voxels (DRg); and HPg voxels with diffusion restriction (HPg&DRg). Two sets of voxels (2,459,483 and 2,073,880) were analyzed according to these thresholding methods. Positive predictive values (PPV) of PDA voxels were low (between 9.5 and 31.9 %). The best PPV was obtained with HPg&DRg voxels within the FLAIR hyperintensity, as 18.3 % of voxels without initial PDA were within relapse sites, versus 31.9 % with initial PDA (p < 0.0001). This prospective study suggests that DSC and/or DWI-MRI do not predict the glioblastoma relapse sites. However, further investigations with new methodological approaches are needed to better understand the role of these modalities in the prediction of glioblastoma relapse sites.

Comparison of volumetric-modulated arc therapy and dynamic conformal arc treatment planning for cranial stereotactic radiosurgery.

The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10° table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 ± 0.05) compared with DCA procedure (0.27± 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 ± 0.04) compared with those obtained with the DCA technique (0.77 ± 0.05). DCA improved healthy brain protection (8.35 ± 5.61 cc vs. 10.52 ± 6.40 cc for RANC) and reduced monitor unit numbers (3046 ± 374 MU vs. 4651 ± 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 ± 0.07). The CI was improved with RAT (0.8 ± 0.08 for RAT vs. 0.71 ± 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 ± 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 ± 0.03 vs. 0.53 ± 0.2 for DCA) and conformity (0.72± 0.06vs. 0.56 ± 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 ± 1.05Gyvs. 14.12 ± 0.59 Gy for DCA, and Dmean = 3.96 ± 3.57Gyvs. 4.72 ± 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 ± 190 MUvs. 3438 ± 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA provide better plan considering low doses to healthy brain even if quality indexes are better for the others techniques. For multiple lesions, RANC seems to be the best compromise, due to the ability to deliver a good conformity and homogeneity plan while sparing healthy brain tissue. For a single lesion close to organs at risk, RAT is the most appropriate technique.

Feasibility of accelerated partial breast irradiation with volumetric-modulated arc therapy in elderly and frail patients.

BACKGROUND: Accelerated partial breast irradiation (APBI) is an option for adjuvant radiotherapy according to ASTRO and ESTRO recommendations. Among the available techniques, volumetric-modulated arc therapy (VMAT) is attractive but has not been extensively studied for APBI. This study assessed its feasibility, tolerance and early oncological outcomes. METHODS: We analysed the data of nine patients (median age 74 years) with ten lesions (one bilateral cancer) treated from May 2011 to July 2012 with APBI using VMAT. The radiation oncologist delineated the surgical tumour bed, and added an 18 mm isotropic margin to obtain the planning target volume (PTV). The dose was 40 Gy prescribed in 4 Gy fractions given twice a day over five days. Patients were regularly followed for toxicities and oncological outcomes. RESULTS: Mean PTV was 100.0 cm(3) and 95 % of the PTV received a mean dose of 99.7 % of the prescribed dose. Hot spots represented 0.3 % of the PTV. 6.2 %, 1.6 % and 0.3 % of the ipsilateral lung volume received 5 Gy (V5Gy), 10 Gy (V10Gy) and 20 Gy (V20Gy), respectively. Regarding the contralateral lung, V5Gy was 0.3 %, and V10Gy and V20Gy were nil. V5Gy accounted for 3.1 % of the heart. An average 580 monitor units were delivered. No acute or late grade ≥ 2 toxicities were observed. With a median follow-up of 26 months, no relapses occurred. CONCLUSION: In our study, VMAT allowed optimal dosimetry with consequential high therapeutic ratio in elderly and frail patients.

Spinal metastases in breast cancer: single center experience.

OBJECTIVE: Metastases to the spine are a common manifestation of breast cancer leading to considerable reduction in the patient's quality of life. Physicians must consider the different treatments available to decrease pain, reduce tumor burden, and ensure spinal stability to prevent neurological compromises. The first objective of this study is to analyze the epidemiology and outcomes of patients with spinal metastases from breast cancer and describe changes over time in these lesions. The second objective is to establish the current treatment of spinal metastases in this type of cancer. METHODS: A total of 140 patients with breast cancer and spinal metastasis involvement were studied retrospectively. Demographic, clinical, and radiologic parameters were assessed, and the effects of systemic and local treatments on spinal metastasis were analyzed. RESULTS: Median patient age at diagnosis of breast cancer was 50 years (19-86 years) and average follow-up was 100 months (4-384 months). Median overall survival after diagnosis of spinal metastasis was 18.6 months. Fractures were present in 24 patients (19.3%) at diagnosis and in up to 60 cases (48.6%) by the end of the study period. CONCLUSIONS: The survival rate was better in patients with spinal metastases who received specific treatment. The evolution from lytic spinal metastasis to mixed and blastic subtypes is observed with adjunctive therapy for spinal metastases (bisphosphonates, radiotherapy). Increased attention must be given for high-grade breast cancer, as spinal metastases declare faster for these stages. This study provides evidence that a multidisciplinary tumor board specifically focusing on bone metastasis is essential to effectively manage patients with breast cancer and spinal metastasis.