[Stereotactic radiation therapy for liver tumours]. / Radiothérapie stéréotaxique hépatique.

Liver lesions are common in oncology, and various focal treatments can be used, such as surgery, chemoembolization, radiofrequency, and systemic treatment. However, these treatments are often not feasible for a number of reasons, including the patient's general health or the characteristics of the lesion itself. Additionally, localized relapses may occur after focal treatments. In the past, liver radiotherapy was limited by the toxicities it caused and was mainly used in palliative situations or specific pre-transplant management. However, advancements in high-precision radiotherapy, like hypofractionated radiotherapy in stereotactic conditions, have allowed to treat the lesions with minimal margins, delivering higher doses while reducing the healthy liver's exposure. Increasingly, retrospective and prospective studies have demonstrated the effectiveness and safety of hypofractionation for both primary and secondary liver lesions. This review discusses the indications, results, and techniques of this type of treatment.

Les lésions hépatiques primitives ou secondaires sont une situation fréquente en oncologie. Plusieurs types de traitements focaux peuvent être appliqués : chirurgie, chimio-embolisation, radio-fréquence, traitement systémique. Néanmoins, les traitements focaux sont régulièrement contre-indiqués, soit par l'état général et les antécédents du patient, soit par la lésion en elle-même (volume, situation). De plus, il peut y avoir des patients qui présentent des rechutes localisées après ce type de prise en charge. Le foie est un organe très radiosensible, et la radiothérapie hépatique a longtemps été limitée par les toxicités qu'elle engendrait. La radiothérapie est le plus souvent utilisée dans les situations très palliatives (irradiation hépatique en totalité) ou dans certains schémas de prise en charge avant greffe. Pourtant, l'avènement de la radiothérapie de haute précision, telle que la radiothérapie hypofractionnée en condition stéréotaxique, permet de traiter les lésions avec des marges minimes et donc, d'augmenter la dose délivrée en diminuant le volume de foie sain irradié. On retrouve aujourd'hui un nombre de plus en plus important de séries rétrospectives et prospectives qui décrivent son efficacité et sa tolérance tant pour les lésions primitives que secondaires. Nous faisons ici un point sur les indications, les résultats et les modalités de ce type de traitement.

Pulsed electric field induces exocytosis and overexpression of MAGE antigens in melanoma.

Nanosecond pulsed electric field (nsPEF) has emerged as a promising approach for inducing cell death in melanoma, either as a standalone treatment or in combination with chemotherapeutics. However, to date, there has been a shortage of studies exploring the impact of nsPEF on the expression of cancer-specific molecules. In this investigation, we sought to assess the effects of nsPEF on melanoma-specific MAGE (Melanoma Antigen Gene Protein Family) expression. To achieve this, melanoma cells were exposed to nsPEF with parameters set at 8 kV/cm, 200 ns duration, 100 pulses, and a frequency of 10 kHz. We also aimed to comprehensively describe the consequences of this electric field on melanoma cells' invasion and proliferation potential. Our findings reveal that following exposure to nsPEF, melanoma cells release microvesicles containing MAGE antigens, leading to a simultaneous increase in the expression and mRNA content of membrane-associated antigens such as MAGE-A1. Notably, we observed an unexpected increase in the expression of PD-1 as well. While we did not observe significant differences in the cells' proliferation or invasion potential, a remarkable alteration in the cells' metabolomic and lipidomic profiles towards a less aggressive phenotype was evident. Furthermore, we validated these results using ex vivo tissue cultures and 3D melanoma culture models. Our study demonstrates that nsPEF can elevate the expression of membrane-associated proteins, including melanoma-specific antigens. The mechanism underlying the overexpression of MAGE antigens involves the initial release of microvesicles containing MAGE antigens, followed by a gradual increase in mRNA levels, ultimately resulting in elevated expression of MAGE antigens post-experiment. These findings shed light on a novel method for modulating cancer cells to overexpress cancer-specific molecules, thereby potentially enhancing their sensitivity to targeted anticancer therapy.

[Oncological and functional results of focal treatment of localized prostate cancer with HIFU]. / Résultats oncologiques et fonctionnels du traitement focal du cancer de prostate localisé par HIFU.

INTRODUCTION: In recent years, improved diagnosis of prostate cancer has allowed the development of focal therapy, in order to reduce the morbidity of treatments. Our study assesses the medium-term oncological and functional results of FocalOne® HIFU treatment in localized prostate cancer. METHODS: This is a retrospective, multicentre study including patients with low- or intermediate-risk localized prostate cancer treated with Focal one HIFU between November 2014 and December 2019. The primary endpoint was the retreatment rate and subgroup analyses were performed to identify predictive factors of retreatment. RESULTS: One hundred and thirty-seven patients were included with a median follow-up of 25.5 months. Seventy percent of patients had clinical stage T2, 64% had an ISUP score of 2 or 3 on initial biopsies and 38% were treated with hemi-ablation. Follow-up biopsies were performed in 76.6% of patients during follow-up with 21.8% having clinically significant cancers. The retreatment rate at 24 months was 37.2%, with positive biopsies being the primary criterion for retreatment. Patients with a PSA>8ng/mL had a significantly higher retreatment rate. Finally, morbidity remained acceptable with 5.8% of patients requiring reoperation for complications and 21% for de novo erectile dysfunction. CONCLUSION: Our results are in agreement with those of the literature, seeming to indicate a lower morbidity of the focal treatment by HIFU compared to the radical treatments while offering an acceptable oncological control. Prospective randomized trials are ongoing.

The SAFE Pilot Trial-SAlvage Focal Irreversible Electroporation-For Recurrent Localized Prostate Cancer: Rationale and Study Protocol.

Introduction: Currently, the majority of prostate cancer (PCa) recurrences after non-surgical first-line treatment are managed with androgen-deprivation therapy (ADT). Salvage radical prostatectomy (sRP) is a curative alternative to ADT but yields significant morbidity. Preliminary evidence from focal salvage treatments shows similar oncological control but lower morbidity compared to sRP. Among available ablative focal energies, irreversible electroporation (IRE) is a treatment modality that proved promising, especially in treating apical lesions, where PCa most often recurs. Our aim is to test the safety of salvage IRE for recurrent PCa. Methods: We performed a single-arm pilot feasibility study (IDEAL stage 2a): SAFE, SAlvage Focal irreversible Electroporation for recurrent localized PCa. Twenty patients with biopsy-proven PCa recurrence after primary non-surgical (radiation or ablation) treatment were included. All men will undergo mpMRI ± targeted biopsies, pre-operative PSMA-PET staging before inclusion and sIRE. Outcomes will be evaluated through internationally validated questionnaires and morbidity scales. All men will undergo a control biopsy at one year. Results: Primary objectives were the evaluation of the safety of sIRE (and patients' quality of life) after treatment. Secondary objectives were the evaluation of functional outcomes, namely, continence and erectile function changes and evaluation of short-term oncological efficacy. Conclusions: SAFE is the second pilot study to evaluate sIRE and the first one performed according to the most recent diagnostic and staging imaging standards. sIRE may provide a curative option for recurrent PCa together with lower comorbidities compared to sRP.

Bone metastases from differentiated thyroid carcinoma: heterogenous tumor response to radioactive Iodine therapy and overall survival.

PURPOSE: Bone metastases (BM) from differentiated thyroid carcinoma (DTC) impact negatively the quality of life and the life expectancy of patients. The aim of the study was (a) to evaluate the overall survival (OS) and prognostic factors of OS and (b) to assess predictive factors of complete BM response (C-BM-R) using radioiodine treatment (RAI) either alone or in association with focal treatment modalities. METHODS: A total of 178 consecutive DTC patients harbouring BM, treated between 1989 and 2015, were enrolled in this retrospective study conducted in two tertiary referral centers. OS analysis was performed for the whole cohort, and only the 145 considered non-RAI refractory patients at BM diagnosis were evaluated for C-BM-R following RAI. RESULTS: The median OS from BM diagnosis was 57 months (IQR: 24-93). In multivariate analysis, OS was significantly reduced in the case of T4 stage, 18FDG uptake by the BM and RAI refractory status. Among the 145 DTC considered non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a C-BM-R following RAI treatment, either alone in 32 (18%) patients or in association with focal BM treatment modalities in 14. The absence of extra-skeletal distant metastasis and of 18FDG uptake in BM were predictive for C-BM-R. CONCLUSIONS: In nearly one-third of DTC patients with RAI avid BM, RAI alone or in combination with BM focal treatment can induce C-BM-R. The presence of 18FDG uptake in BM is associated with an absence of C-BM-R and with a poor OS. 18FDG PET-CT should be performed when BM is suspected.

Focal therapy for prostate cancer: Making the punishment fit the crime.

BACKGROUND: Focal therapy is recently gaining popularity as an intermediate option between active surveillance and whole-gland treatment for localized prostate cancer. OBJECTIVE: This comprehensive review aims to present the different focal therapy technologies available to date while tackling the rationale for focal treatment, its indications, principles and outcomes of each technique. EVIDENCE ACQUISITION: A comprehensive review of the PubMed, Embase, and Web of Science was done. Keywords used for research were: "prostate cancer"; "focal therapy"; "focal treatment"; "High-Intensity Focal Ultrasound"; "cryotherapy"; "photodynamic therapy"; "focal laser ablation"; "irreversible electroporation"; "focal brachytherapy" and "gold nanoparticle directed therapy". Accepted languages were English and French. EVIDENCE SYNTHESIS: Choosing the best candidate for focal therapy is crucial (localized small to medium sized Gleason≤7 lesions). Focal high-intensity focal ultrasound has shown excellent survival rates at 5 years, while maintaining good functional outcomes (urinary continence and erectile function). Focal cryotherapy, one of the oldest focal treatments for prostate cancer, has shown good oncologic outcomes, with good continence rates and fair erectile function rates. Focal laser ablation seems a safe and feasible technique, with promising results. Irreversible electroporation has demonstrated good survival outcomes with no biochemical recurrence or disease relapse in the preliminary studies. Focal brachytherapy has a good toxicity profile, a good biochemical outcome, and gives a sustained quality of life. Finally, gold nanoparticle directed therapy is safe and is being studied in current trials. CONCLUSION: While proven to be safe in terms of continence and sexual aspects, the challenge remains to better assess oncological outcomes of these techniques in randomized longer follow-up studies.

Whole and hemi-gland cryoablation for primary localized prostate cancer: Short and medium-term oncological and functional outcomes. / Crioablación total o hemiglandular para el cáncer de próstata primario localizado: resultados oncológicos y funcionales a corto y medio plazo.

INTRODUCTION: To compare oncological, functional and post-operative outcomes of hemi (HC) vs. whole gland (WGC) cryoablation as first line treatment of localized prostate cancer. MATERIAL AND METHOD: Sixty-six consecutive patients undertaking whole-gland cryoablation (WGC=40) or hemi-cryoablation (HC=26) in a tertiary referral centre between 2010 and 2018 were included. All patients had a low-intermediate risk prostate cancer according to D'Amico risk classification. Hemi-ablation was proposed in case of biopsy and prostate MRI proven unilateral prostate cancer. Primary endpoint was Cryotherapy Failure for which 3 definitions were considered and compared: 1) biochemical failure (> PSA nadir+≥ 2 ng/mL), 2) positive prostate re-biopsy with Gleason score ≥ 7, 3) initiation of further prostate cancer treatment. RESULTS: Median patients age at treatment was 74 [42-81] vs. 76 [71-80] years in WGC vs. HC group, respectively (p=.08). Low and intermediate D'Amico risk group were 15% and 85% vs. 23% and 77% (p=.75), respectively. Median follow- up time was 41 [1.5-99.0] vs. 27 [0.9-93] months (p=.03). Four-years cryotherapy failure free survival in WGC vs. HC were 69% vs. 53% with definition 1 (p=.24), 82% vs. 80% with definition 2 (p=.95), 83% vs. 77% with definition 3 (p=.73). Early and 1-year urinary continence were 60% and 83% in WGC vs. 72% and 83% in HC (p=.26). De novo impotency after cryotherapy was 75% vs. 46% (p=.33) in WGC vs. HC. CONCLUSIONS: In our cohort of highly selected patients with unilateral low/intermediate risk PCa, hemi-cryoablation may provide similar oncological outcomes and less early complications compared to whole-gland cryoablation.

[Vascular targeted photodynamic therapy in low-risk prostate cancer. A literature review]. / Photothérapie dynamique dans le cancer de la prostate à faible risque. Revue de la littérature.

INTRODUCTION: Currently, about 50% of newly prostate cancers are localized and low-risk according to D'Amico risk classification. Focal therapies whose objective is to treat only the index lesion appear as a new alternative being evaluated in the management of these cancers. Besides the interest in the control of the disease, focal therapies present a very low risk of morbidity. Vascular targeted photodynamic therapy (VTP) is one of these new emerging therapies. METHOD: An exhaustive review concerning VTP in prostate cancer was carried out. A search by the following keywords "low-risk prostate cancer", "focal treatment", "vascular targeted photodynamic therapy" "TOOKAD" was carried out in Pubmed and Embase. RESULTS: In phase II studies, VTP showed a rate of 80% negative biopsies at 6 months, with good clinical tolerance. The European phase III, randomized prospective study, comparing VTP to active surveillance showed a lower proportion of progression, as well as a more significant duration before progression for VTP. The adverse events are mostly moderate and transient. The quality of life of patients is preserved, with a moderate impact on erectile and urinary functions. CONCLUSION: VTP appear to be a promising new approach in localized low-risk prostate cancer.

MRI guided focal HDR brachytherapy for localized prostate cancer: Toxicity, biochemical outcome and quality of life.

PURPOSE: To describe toxicity, biochemical outcome and quality of life after MRI guided focal high dose rate brachytherapy (HDR-BT) in a single fraction of 19 Gy for localized prostate cancer. MATERIALS AND METHODS: Between May 2013 and April 2016, 30 patients were treated by MRI-guided focal HDR-BT. Patients with visible tumour on MRI were included. All patients were ≥65 years, T-stage

MR Imaging-Guided Focal Treatment of Prostate Cancer: An Update.

Focal treatment of prostate cancer has evolved from a concept to a practice in the recent few years and is projected to fill an existing need, bridging the gap between conservative and radical traditional treatment options. With its low morbidity and rapid recovery time compared with whole-gland treatment alternatives, focal therapy is poised to gain more acceptance among patients and health care providers. As our experience with focal treatment matures and evidence continues to accrue, the landscape of this practice might look quite different in the future.

Traitement focal et traitement systémique dans la prise en charge du cancer du rein métastatique : une question de complémentarité.

FOCAL TREATMENT AND SYSTEMIC THERAPY IN METASTATIC KIDNEY CANCER: COMPLEMENTARY APPROACHES: To treat metastatic renal cell carcinoma, therapies used are with an oral intake, for the vast majority, and have many side effects that may compromise observance. Strategies of drug holiday have been studied and, in case of an indolent and oligometastatic tumor, studies have shown that active surveillance is possible to delay the introduction of systemic treatment, without compromising the patient survival. A multimodal approach combining systemic and focal treatments can be done with several objectives: to delay even more introduction of systemic treatment by focally treating metastases, to allow drug holiday after partial response to medical treatment by local control of persistent metastases, and to permit drug continuation even in case of dissociated response to systemic therapy, by focal treatment of metastasis(es) in progression. Technics that can be used for focal treatment are metastasectomy, radiofrequency ablation or cryotherapy, and stereotactic radiotherapy. In literature, studies that evaluated this approach are for almost retrospective studies, but they have reported interesting results in terms of local control and low morbidity. In the era of checkpoint's inhibitors, it seems important to make prospective collections of data to validate these practices. In any case, and because international recommendations about multimodal approach are poor, discussions between the different actors of the patient care are essential to find the most beneficial treatment for him.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer.

INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients' quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging-guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with pathologically proven locally recurrent prostate cancer were treated with focal high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance imaging for treatment guidance. Primary radiotherapy consisted of external beam radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68-prostate-specific membrane antigen or F18-choline positron emission tomography in combination with multiparametric magnetic resonance imaging. All patients had a prostate-specific antigen level of less than 10 ng/mL at the time of recurrence and a prostate-specific antigen doubling time of ≥12 months. Toxicity was measured by using the Common Terminology Criteria for Adverse Events version 4. RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a median follow-up interval of 10 months (range 3-40 months), 1 patient experienced a biochemical recurrence according to the Phoenix criteria, and prostate-specific membrane antigen testing revealed that this was due to a distant nodal metastasis. One patient had a grade 3 urethral stricture at 2 years after treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients and a distant nodal metastasis in another patient. Whether this treatment option leads to cure in a subset of patients or whether it can successfully postpone androgen deprivation treatment needs further investigation.

Association of computerized texture features on MRI with early treatment response following laser ablation for neuropathic cancer pain: preliminary findings.

Laser interstitial thermal therapy (LITT) has recently emerged as a new treatment modality for cancer pain management that targets the cingulum (pain center in the brain) and has shown promise over radio frequency (RF)-based ablation, due to magnetic resonance image (MRI) guidance that allows for precise ablation. Since laser ablation for pain management is currently exploratory and is only performed at a few centers worldwide, its short- and long-term effects on the cingulum are currently unknown. Traditionally, treatment effects for neurological conditions are evaluated by monitoring changes in intensities and/or volume of the ablation zone on post-treatment Gadolinium-contrast T1-w (Gd-T1) MRI. However, LITT introduces subtle localized changes corresponding to tissues response to treatment, which may not be appreciable on visual inspection of volumetric or intensity changes. Additionally, different MRI protocols [Gd-T1, T2w, gradient echo sequence (GRE), fluid-attenuated inversion recovery (FLAIR)] are known to capture complementary diagnostic information regarding the patient's response to treatment; the utility of these MRI protocols has so far not been investigated to evaluate early and localized response to LITT treatment in the context of neuropathic cancer pain. In this work, we present the first attempt at (a) examining early treatment-related changes on a per-voxel basis via quantitative comparison of computer-extracted texture descriptors across pre- and post-LITT multiparametric (MP-MRI) (Gd-T1, T2w, GRE, FLAIR), subtle microarchitectural texture changes that may not be appreciable on original MR intensities or volumetric differences, and (b) investigating the efficacy of different MRI protocols in accurately capturing immediate post-treatment changes reflected (1) within and (2) outside the ablation zone. A retrospective cohort of four patient studies comprising pre- and immediate (24 h) post-LITT 3 Tesla Gd-T1, T2w, GRE, and FLAIR acquisitions was considered. Our quantitative approach first involved intensity standardization to allow for grayscale MR intensities acquired pre- and post-LITT to have a fixed tissue-specific meaning within the same imaging protocol, the same body region, and within the same patient. An affine registration was then performed on individual post-LITT MRI protocols to a reference MRI protocol pre-LITT. A total of 78 computerized texture features (co-occurrence matrix homogeneity, neighboring gray-level dependence matrix, Gabor) are then extracted from pre- and post-LITT MP-MRI on a per-voxel basis. Quantitative, voxelwise comparison of the changes in MRI texture features between pre- and post-LITT MRI indicate that (a) Gabor texture features at specific orientations were highly sensitive as well as specific in predicting subtle microarchitectural changes within and around the ablation zone pre- and post-LITT, (b) FLAIR was identified as the most sensitive MRI protocol in identifying early treatment changes yielding a normalized percentage change of 360% within the ablation zone relative to its pre-LITT value, and (c) GRE was identified as the most sensitive MRI protocol in quantifying changes outside the ablation zone post-LITT. Our preliminary results thus indicate potential for noninvasive computerized MP-MRI features over volumetric features in determining localized microarchitectural early focal treatment changes post-LITT for neuropathic cancer pain treatment.

Identifying Quantitative In Vivo Multi-Parametric MRI Features For Treatment Related Changes after Laser Interstitial Thermal Therapy of Prostate Cancer.

Laser interstitial thermal therapy (LITT) is a new therapeutic strategy being explored in prostate cancer (CaP), which involves focal ablation of organlocalized tumor via an interstitial laser fiber. While little is known about treatment-related changes following LITT, studying post-LITT changes via imaging is extremely significant for enabling early image-guided intervention and follow-up. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis via quantitative comparison of MRI features pre- and post-LITT, and hence identifying computerized MRI features that are highly sensitive as well as specific to post-LITT changes within the ablation zone in the prostate. A retrospective cohort of 5 patient datasets comprising both pre- and post-LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. Our scheme involved (1) inter-protocol registration of T2w and ADC MRI, as well as inter-acquisition registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters by correcting for intensity drift in order to examine tissuespecific response, and (3) quantification of the information captured by T2w MRI and ADC maps via texture and intensity features. Correction of parameter drift resulted in visually discernible improvements in highlighting tissue-specific response in different MRI features. Quantitative, voxel-wise comparison of the changes in different MRI features indicated that steerable and non-steerable gradient texture features, rather than the original T2w intensity and ADC values, were highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. The highest ranked texture feature yielded a normalized percentage change of 186% within the ablation zone and 43% in a spatially distinct normal region, relative to its pre-LITT value. By comparison, both the original T2w intensity and ADC value demonstrated a markedly less sensitive and specific response to changes within the ablation zone. Qualitative as well as quantitative evaluation of co-occurrence texture features indicated the presence of LITT-related effects such as edema adjacent to the ablation zone, which were indiscernible on the original T2w and ADC images. Our preliminary results thus indicate great potential for non-invasive computerized MRI imaging features for determining focal treatment related changes, informing image-guided interventions, as well as predicting long- and short-term patient outcome.

Identifying MRI markers to evaluate early treatment related changes post laser ablation for cancer pain management.

Laser interstitial thermal therapy (LITT) has recently emerged as a new treatment modality for cancer pain management that targets the cingulum (pain center in the brain), and has shown promise over radio-frequency (RF) based ablation which is reported to provide temporary relief. One of the major advantages enjoyed by LITT is its compatibility with magnetic resonance imaging (MRI), allowing for high resolution in vivo imaging to be used in LITT procedures. Since laser ablation for pain management is currently exploratory and is only performed at a few centers worldwide, its short-, and long-term effects on the cingulum are currently unknown. Traditionally treatment effects are evaluated by monitoring changes in volume of the ablation zone post-treatment. However, this is sub-optimal since it involves evaluating a single global parameter (volume) to detect changes pre-, and post-MRI. Additionally, the qualitative observations of LITT-related changes on multi-parametric MRI (MP-MRI) do not specifically address differentiation between the appearance of treatment related changes (edema, necrosis) from recurrence of the disease (pain recurrence). In this work, we explore the utility of computer extracted texture descriptors on MP-MRI to capture early treatment related changes on a per-voxel basis by extracting quantitative relationships that may allow for an in-depth understanding of tissue response to LITT on MRI, subtle changes that may not be appreciable on original MR intensities. The second objective of this work is to investigate the efficacy of different MRI protocols in accurately capturing treatment related changes within and outside the ablation zone post-LITT. A retrospective cohort of studies comprising pre- and 24-hour post-LITT 3 Tesla T1-weighted (T1w), T2w, T2-GRE, and T2-FLAIR acquisitions was considered. Our scheme involved (1) inter-protocol as well as inter-acquisition affine registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters by correcting for intensity drift in order to examine tissue-specific response, and (3) quantification of MRI maps via texture and intensity features to evaluate changes in MR markers pre- and post-LITT. A total of 78 texture features comprising of non-steerable and steerable gradient and second order statistical features were extracted from pre- and post-LITT MP-MRI on a per-voxel basis. Quantitative, voxel-wise comparison of the changes in MRI texture features between pre-, and post-LITT MRI indicate that (a) steerable and non-steerable gradient texture features were highly sensitive as well as specific in predicting subtle micro-architectural changes within and around the ablation zone pre- and post-LITT, (b) FLAIR was identified as the most sensitive MRI protocol in identifying early treatment changes yielding a normalized percentage change of 360% within the ablation zone relative to its pre-LITT value, and (c) GRE was identified as the most sensitive MRI protocol in quantifying changes outside the ablation zone post-LITT. Our preliminary results thus indicate great potential for non-invasive computerized MRI features in determining localized micro-architectural focal treatment related changes post-LITT.

Quantitative evaluation of multi-parametric MR imaging marker changes post-laser interstitial ablation therapy (LITT) for epilepsy.

Laser-induced interstitial thermal therapy (LITT) has recently emerged as a new, less invasive alternative to craniotomy for treating epilepsy; which allows for focussed delivery of laser energy monitored in real time by MRI, for precise removal of the epileptogenic foci. Despite being minimally invasive, the effects of laser ablation on the epileptogenic foci (reflected by changes in MR imaging markers post-LITT) are currently unknown. In this work, we present a quantitative framework for evaluating LITT-related changes by quantifying per-voxel changes in MR imaging markers which may be more reflective of local treatment related changes (TRC) that occur post-LITT, as compared to the standard volumetric analysis which involves monitoring a more global volume change across pre-, and post-LITT MRI. Our framework focuses on three objectives: (a) development of temporal MRI signatures that characterize TRC corresponding to patients with seizure freedom by comparing differences in MR imaging markers and monitoring them over time, (b) identification of the optimal time point when early LITT induced effects (such as edema and mass effect) subside by monitoring TRC at subsequent time-points post-LITT, and (c) identification of contributions of individual MRI protocols towards characterizing LITT-TRC for epilepsy by identifying MR markers that change most dramatically over time and employ individual contributions to create a more optimal weighted MP-MRI temporal profile that can better characterize TRC compared to any individual imaging marker. A cohort of patients were monitored at different time points post-LITT via MP-MRI involving T1-w, T2-w, T2-GRE, T2-FLAIR, and apparent diffusion coefficient (ADC) protocols. Post affine registration of individual MRI protocols to a reference MRI protocol pre-LITT, differences in individual MR markers are computed on a per-voxel basis, at different time-points with respect to baseline (pre-LITT) MRI as well as across subsequent time-points. A time-dependent MRI profile corresponding to successful (seizure-free) is then created that captures changes in individual MR imaging markers over time. Our preliminary analysis on two patient studies suggests that (a) LITT related changes (attributed to swelling and edema) appear to subside within 4-weeks post-LITT, (b) ADC may be more sensitive for evaluating early TRC (upto 3-months), and T1-w may be more sensitive in evaluating early delayed TRC (1-month, 3-months), while T2-w and T2-FLAIR appeared to be more sensitive in identifying late TRC (around 6-months post-LITT) compared to the other MRI protocols under evaluation. T2-GRE was found to be only nominally sensitive in identifying TRC at any follow-up time-point post-LITT. The framework presented in this work thus serves as an important precursor to a comprehensive treatment evaluation framework that can be used to identify sensitive MR markers corresponding to patient response (seizure-freedom or seizure recurrence), with an ultimate objective of making prognostic predictions about patient outcome post-LITT.

Quantitative Evaluation of Treatment Related Changes on Multi-Parametric MRI after Laser Interstitial Thermal Therapy of Prostate Cancer.

Laser interstitial thermal therapy (LITT) has recently shown great promise as a treatment strategy for localized, focal, low-grade, organ-confined prostate cancer (CaP). Additionally, LITT is compatible with multi-parametric magnetic resonance imaging (MP-MRI) which in turn enables (1) high resolution, accurate localization of ablation zones on in vivo MP-MRI prior to LITT, and (2) real-time monitoring of temperature changes in vivo via MR thermometry during LITT. In spite of rapidly increasing interest in the use of LITT for treating low grade, focal CaP, very little is known about treatment-related changes following LITT. There is thus a clear need for studying post-LITT changes via MP-MRI and consequently to attempt to (1) quantitatively identify MP-MRI markers predictive of favorable treatment response and longer term patient outcome, and (2) identify which MP-MRI markers are most sensitive to post-LITT changes in the prostate. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis (high resolution) via quantitative evaluation of MR parameters pre- and post-LITT. A retrospective cohort of MP-MRI data comprising both pre- and post-LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. A spatially constrained affine registration scheme was implemented to first bring T2w and ADC images into alignment within each of the pre- and post-LITT acquisitions, following which the pre- and post-LITT acquisitions were aligned. Pre- and post-LITT MR parameters (T2w intensity, ADC value) were then standardized to a uniform scale (to correct for intensity drift) and then quantified via the raw intensity values as well as via texture features derived from T2w MRI. In order to quantify imaging changes as a result of LITT, absolute differences were calculated between the normalized pre- and post-LITT MRI parameters. Quantitatively combining the ADC and T2w MRI parameters enabled construction of an integrated MP-MRI difference map that was highly indicative of changes specific to the LITT ablation zone. Preliminary quantitative comparison of the changes in different MR parameters indicated that T2w texture may be highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. Visual evaluation of the differences in T2w texture features pre- and post-LITT also appeared to provide an indication of LITT-related effects such as edema. Our preliminary results thus indicate great potential for non-invasive MP-MRI imaging markers for determining focal treatment related changes, and hence long- and short-term patient outcome.

Procedimiento para evaluar procesos en los grupos de control de vectores / Procedure to assess the processes in vector control groups

La investigación evaluativa en los servicios es considerada un proceso de indagación sobre avances y obstáculos en una institución, cuyo resultado será un juicio de valor, una decisión. OBJETIVO: Mostrar el proceso de trabajo seguido en la construcción de un procedimiento para evaluar procesos en los grupos de control de vectores. MÉTODOS: Se siguió un algoritmo que se resume en los pasos siguientes: caracterización del trabajo de los grupos de control de vectores, definición de un enfoque y selección de procesos para la evaluación, construcción de criterios y de instrumentos para la obtención de información. En cada uno se apuntaron los elementos teóricos y metodológicos que fundamentaron el resultado mostrado. La revisión documental, las entrevistas a informantes claves, los talleres con expertos y la ejecución de estudios observacionales fueron las fuentes utilizadas en la caracterización. RESULTADOS. Se identificó y se argumentó la conveniencia de un enfoque para la evaluación basado en procesos, a partir de la selección de un proceso operativo y "trazador" del desempeño de los grupos (proceso operativo focal) y de procesos de soporte a este. Se refirieron aspectos sobre la construcción de los criterios evaluativos y los instrumentos para la obtención de información: un cuestionario de clima organizacional con el que se evalúan elementos del ambiente de trabajo y una guía para observar procesos.

Evaluative research in services is considered as an inquiry process on the advances and obstacles in a institution whose result will be value judgment, a decision. OBJECTIVE: To show the working process followed in the creation of a procedure to assess processes in vector control groups. METHODS: Authors followed an algorithm summarized in: working characterization of the vectors control groups, definition of an approach and selection of assessment processes criteria and tools construction to obtain information. In each are signaled the theoretical and methodological elements supported the result showed. RESULTS: The documentary review, interviews to key informants, the workshops with experts and execution of observational studies were sources used in characterization. Authors identified and argued the usefulness of an approach to assessment based on processes, from the selection of a functional process and «tracer¼ of performance of groups (focal operative process) and its supportive processes. Features on the construction of evaluation criteria and the tools to obtain information: a questionnaire of the organizational climate used to assess the elements of the working environment and a guide to observe the processes.