Robot-assisted biopsy sampling for online Raman spectroscopy cancer confirmation in the operating room.

PURPOSE: Cancer confirmation in the operating room (OR) is crucial to improve local control in cancer therapies. Histopathological analysis remains the gold standard, but there is a lack of real-time in situ cancer confirmation to support margin confirmation or remnant tissue. Raman spectroscopy (RS), as a label-free optical technique, has proven its power in cancer detection and, when integrated into a robotic assistance system, can positively impact the efficiency of procedures and the quality of life of patients, avoiding potential recurrence. METHODS: A workflow is proposed where a 6-DOF robotic system (optical camera + MECA500 robotic arm) assists the characterization of fresh tissue samples using RS. Three calibration methods are compared for the robot, and the temporal efficiency is compared with standard hand-held analysis. For healthy/cancerous tissue discrimination, a 1D-convolutional neural network is proposed and tested on three ex vivo datasets (brain, breast, and prostate) containing processed RS and histopathology ground truth. RESULTS: The robot achieves a minimum error of 0.20 mm (0.12) on a set of 30 test landmarks and demonstrates significant time reduction in 4 of the 5 proposed tasks. The proposed classification model can identify brain, breast, and prostate cancer with an accuracy of 0.83 (0.02), 0.93 (0.01), and 0.71 (0.01), respectively. CONCLUSION: Automated RS analysis with deep learning demonstrates promising classification performance compared to commonly used support vector machines. Robotic assistance in tissue characterization can contribute to highly accurate, rapid, and robust biopsy analysis in the OR. These two elements are an important step toward real-time cancer confirmation using RS and OR integration.

Repeat CyberKnife Radiosurgery for Trigeminal Neuralgia: Outcomes and Complications.

BACKGROUND: CyberKnife radiosurgery (RS), as an initial first treatment, is recognized as an efficient and safe modality for trigeminal neuralgia (TN). However, knowledge on repeat CyberKnife RS in refractory cases is limited. The objective was to evaluate the clinical outcomes of repeat CyberKnife RS for TN. METHODS: A retrospective review of 33 patients with refractory TN treated a second time with CyberKnife RS from 2009 to 2021. The median follow-up period after the second RS was 26.0 months (range 0.3-115.8). The median dose for the repeat RS was 60 Gy (range 60.0-70.0). Pain relief after the intervention was assessed using the Barrow Neurological Institute scale for pain (I-V). Scores I to IIIb were classified as an adequate pain relief and scores IV-V were classified as a treatment failure. RESULTS: After the second RS, initial adequate pain relief was achieved in 87.9% of cases. The actuarial probabilities of maintaining an adequate pain relief at 6, 12, 24, and 36 months were 92.1%, 74.0%, 58.2%, and 58.2%, respectively. Regarding sustained pain relief, there was no significant difference between the first and the second RS. Sensory toxicity after the first RS was predictive of a better outcome following the second RS. The onset of hypesthesia rate was the same after the first or the second RS (21%). CONCLUSION: Repeat RS is an effective and safe method for the treatment of refractory TN.

A feasibility study of adaptive radiation therapy for postprostatectomy prostate cancer.

Postoperative prostate radiotherapy requires large planning target volume (PTV) margins to account for motion and deformation of the prostate bed. Adaptive radiation therapy (ART) can incorporate image-guidance data to personalize PTVs that maintain coverage while reducing toxicity. We present feasibility and dosimetry results of a prospective study of postprostatectomy ART. Twenty-one patients were treated with single-adaptation ART. Conventional treatments were delivered for fractions 1 to 6 and adapted plans for the remaining 27 fractions. Clinical target volumes (CTVs) and small bowel delineated on fraction 1 to 4 CBCT were used to generate adapted PTVs and planning organ-at-risk (OAR) volumes for adapted plans. PTV volume and OAR dose were compared between ART and conventional using Wilcoxon signed-rank tests. Weekly CBCT were used to assess the fraction of CTV covered by PTV, CTV D99, and small bowel D1cc. Clinical metrics were compared using a Student's t-test (p < 0.05 significant). Offline adaptive planning required 1.9 ± 0.4 days (mean ± SD). ART decreased mean adapted PTV volume 61 ± 37 cc and bladder wall D50 compared with conventional treatment (p < 0.01). The CTV was fully covered for 96% (97%) of fractions with ART (conventional). Reconstructing dose on weekly CBCT, a nonsignificant reduction in CTV D99 was observed with ART (94%) compared to conventional (96%). Reduced CTV D99 with ART was significantly correlated with large anterior-posterior rectal diameter on simulation CT. ART reduced the number of fractions exceeding our institution's small bowel D1c limit from 14% to 7%. This study has demonstrated the feasibility of offline ART for post-prostatectomy cancer. ART facilitates PTV volume reduction while maintaining reasonable CTV coverage and can reduce the dose to adjacent normal tissues.

Role of 18F-choline and 18F-fluorodeoxyglucose positron emission tomography in combination with magnetic resonance imaging in brachytherapy planning for locally advanced cervical cancer: A pilot study.

Background and purpose: This pilot study aims to describe the advantages of combining metabolic and anatomic imaging modalities in brachytherapy (BT) planning for locally advanced cervical cancer (LACC) and to evaluate the supplementary value of Fluoro(F)-Choline positron emission tomography/computed tomography (PET/CT) in comparison to 18F-fluorodeoxyglucose (FDG) in this setting. Materials and methods: A prospective cohort of six patients with LACC was included in this study. Each patient underwent BT planning CT scan, magnetic resonance imaging (MRI), and both FDG and F-Choline PET/CT scans on the same day, with BT applicators in place. Patients were treated according to the standard of care. Metabolic target volumes (TV) were generated retrospectively and compared with the anatomic volumes using Dice coefficients and absolute volume comparison. Results: The threshold at which the metabolic and anatomic volumes were the most concordant was found to be 35% maximum standardized uptake value (SUV max) for both PET/CT scans. Amongst the six patients in this cohort, three in the FDG cohort and four in the F-Choline cohort were found to have more than ten percent ratio of excess (increase) in their MRI gross tumor volumes (GTV) when incorporating the metabolic information from the PET/CT scans. However, no significant changes were needed in the high risk-clinical target volumes (CTVHR) for both PET tracers. Conclusions: FDG and F-Choline PET/CT scans can substantially modify the BT GTV on MRI, without affecting the CTVHR. F-Choline is potentially more informative than FDG in assessing residual TV, particularly in cases with significant post-radiation inflammatory changes.

Phase II multicenter trial combining nivolumab and radiosurgery for NSCLC and RCC brain metastases.

Background: Anti-PD-1 has activity in brain metastases (BM). This phase II open labeled non-randomized single arm trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with BM from non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Methods: This was a multicenter trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated BM and no prior immunotherapy were eligible. Nivolumab (240 mg or 480 mg IV) was administered for up to 2 years until progression. SRS (15-21 Gy) to all un-irradiated BM was delivered within 14 days after the first dose of nivolumab. The primary endpoint was intracranial progression free survival (iPFS). Results: Twenty-six patients (22 NSCLC and 4 RCC) were enrolled between August 2017 and January 2020. A median of 3 (1-9) BM were treated with SRS. Median follow-up was 16.0 months (0.43-25.9 months). Two patients developed nivolumab and SRS related grade 3 fatigue. One-year iPFS and OS were 45.2% (95% CI 29.3-69.6%) and 61.3% (95% CI 45.1-83.3%), respectively. Overall response (partial or complete) of SRS treated BM was attained in 14 out of the 20 patients with ≥1 evaluable follow-up MRI. Mean FACT-Br total scores were 90.2 at baseline and improved to 146.2 within 2-4 months (P = .0007). Conclusions: The adverse event profile and FACT-Br assessments suggested that SRS during nivolumab was well tolerated. Upfront SRS with the initiation of anti-PD-1 prolonged the 1-year iPFS and achieved high intracranial control. This combined approach merits validation randomized studies.

PSMA-PET/CT-Guided Intensification of Radiation Therapy for Prostate Cancer (PSMAgRT): Findings of Detection Rate, Effect on Cancer Management, and Early Toxicity From a Phase 2 Randomized Controlled Trial.

PURPOSE: Prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET) is increasingly integrated in prostate cancer management because of its diagnostic performance. We sought to evaluate the effect of PSMA-PET/computed tomography (CT)-guided intensification of radiation therapy (PSMAgRT) on patient outcomes. Here, we report secondary trial endpoints including the rate of new lesion detection, effect on prostate cancer management, and treatment-related toxicities. METHODS AND MATERIALS: In this phase 2 cohort multiple randomized controlled trial across 2 institutions, men with prostate cancer planned for RT were randomly selected for PSMAgRT across 4 strata: oligometastatic, high risk (Cancer of the Prostate Risk Assessment ≥6 or cN1), salvage post-RT, and salvage postprostatectomy (RP). Primary endpoint was failure-free survival at 5 years, with analysis pending further follow-up. Secondary endpoints included new lesion detection yield of PSMA-PET/CT, acute and delayed toxicities, effect on prostate cancer management, and health-related quality-of-life outcomes. This trial is registered with ClinicalTrials.gov, identifier NCT03525288, companion to registry NCT03378856. RESULTS: Between May 2018 and February 2021, 262 patients were enrolled and randomized. Nine patients were later excluded (5 control, 4 PSMAgRT), leaving 253 patients for analysis (23 oligometastatic, 86 high risk, 16 salvage post-RT, and 128 salvage post-RP). New lesions were detected in 45.5% of oligometastatic, 39.5% of high risk, 14.3% of salvage post-RT, and 51.6% of salvage post-RP. Overall, PSMA-PET/CT led to intensification of RT in over half of patients (52.0%), with minimal intensification of systemic therapy (4.0%). With a median follow-up of 12.9 months, this intensification was associated with 3 attributable grade 3+ events (2.5% of patients undergoing PSMAgRT) but no difference in the rate of grade 2+ events attributable to RT compared with controls (43%, both arms). CONCLUSIONS: In this randomized trial, PSMA-PET/CT led to intensification of RT in more than half of patients. Longer follow-up is required to determine whether this intensification translates to effect on cancer control and long-term toxicity and health-related quality-of-life outcomes.

Acute toxicity and health-related quality of life outcomes of localized prostate cancer patients treated with magnetic resonance imaging-guided high-dose-rate brachytherapy: A prospective phase II trial.

PURPOSE: To report acute toxicity and health-related quality of life (HRQoL) outcomes of a phase II clinical trial of magnetic resonance imaging (MRI)-guided prostate high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy. METHODS AND MATERIALS: Patients with intermediate- and high-risk prostate cancer (PCa) were eligible. Treatment consisted of a single 15 Gy MRI-guided HDR-BT followed by external beam radiotherapy (37.5-46 Gy depending on their risk category). Dosimetry, toxicity and HRQoL outcomes were collected prospectively at baseline, 1 and 3 months using Common Terminology Criteria for Adverse Events Version 4.0 and the expanded PCa index composite, respectively. General linear mixed modeling was conducted to assess the changes in expanded PCa index composite domain scores over time. A minimally important difference was defined as a deterioration of HRQoL scores at 3 months compared to baseline ≥ 0.5 standard deviation. A p value ≤ 0.05 was considered statistically significant. RESULTS: Sixty-one patients were included. Acute grade (G)2 urinary toxicity was observed in 18 (30%) patients while 1 (2%) patient had G3 toxicity, and none had G4 toxicity. Two patients had an acute urinary retention. G2 gastrointestinal toxicity was reported by 5 (8%) patients with no G3-4. Compared to baseline, urinary HRQoL scores significantly declined at 1 month (p < 0.001) but recovered at 3 months (p > 0.05). Bowel (p < 0.001) and sexual (p < 0.001) domain scores showed a significant decline over the 3-month follow-up period. At 3 months, 44%, 49% and 57% of patients reported a minimally important difference respectively in the urinary bowel and sexual domains. CONCLUSION: MRI-guided HDR-BT boost is a safe and well tolerated treatment of intermediate- and high-risk PCa in the acute setting. A longer follow-up and a comparison to ultrasound-based HDR-BT are needed to assess the potential benefit of MRI-guided prostate HDR-BT.

Corrigendum: MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2022.971344.].

CyberKnife radiosurgery for trigeminal neuralgia: a retrospective review of 168 cases.

OBJECTIVE: Gamma Knife radiosurgery is recognized as an efficient intervention for the treatment of refractory trigeminal neuralgia (TN). The CyberKnife, a more recent frameless and nonisocentric radiosurgery alternative, has not been studied as extensively for this condition. This study aims to evaluate the clinical outcomes of a first CyberKnife radiosurgery (CKRS) treatment in patients with medically refractory TN. METHODS: A retrospective cohort study of 166 patients (168 procedures) with refractory TN treated from 2009 to 2021 at the Centre Hospitalier de l'Université de Montréal was conducted. The treatment was performed using a CyberKnife (model G4, VSI, or M6). The treatment median maximum dose was 80 (range 70.0-88.9) Gy. RESULTS: Adequate pain relief, evaluated using Barrow Neurological Institute pain scale scores (I-IIIb), was achieved in 146 cases (86.9%). The median latency period before adequate pain relief was 35 (range 0-202) days. The median duration of pain relief for cases with a recurrence of pain was 8.3 (range 0.6-85.0) months. The actuarial rates of maintaining adequate pain relief at 12, 36, and 60 months from the treatment date were 77.0%, 62.5%, and 50.2%, respectively. There was new onset or aggravation of facial numbness in 44 cases (26.2%). This facial numbness was predictive of better maintenance of pain relief (p < 0.001). The maintenance of adequate pain relief was sustained longer in idiopathic cases compared with cases associated with multiple sclerosis (MS; p < 0.001). CONCLUSIONS: In the authors' experience, CKRS for refractory TN is efficient and safe. The onset or aggravation of facial hypoesthesia after treatment was predictive of a more sustained pain relief, and idiopathic cases had more sustained pain relief in comparison with MS-related cases.

Effect of magnetic resonance imaging pre-processing on the performance of model-based prostate tumor probability mapping.

Objective. Multi-parametric magnetic resonance imaging (mpMRI) has become an important tool for the detection of prostate cancer in the past two decades. Despite the high sensitivity of MRI for tissue characterization, it often suffers from a lack of specificity. Several well-established pre-processing tools are publicly available for improving image quality and removing both intra- and inter-patient variability in order to increase the diagnostic accuracy of MRI. To date, most of these pre-processing tools have largely been assessed individually. In this study we present a systematic evaluation of a multi-step mpMRI pre-processing pipeline to automate tumor localization within the prostate using a previously trained model.Approach. The study was conducted on 31 treatment-naïve prostate cancer patients with a PI-RADS-v2 compliant mpMRI examination. Multiple methods were compared for each pre-processing step: (1) bias field correction, (2) normalization, and (3) deformable multi-modal registration. Optimal parameter values were estimated for each step on the basis of relevant individual metrics. Tumor localization was then carried out via a model-based approach that takes both mpMRI and prior clinical knowledge features as input. A sequential optimization approach was adopted for determining the optimal parameters and techniques in each step of the pipeline.Main results. The application of bias field correction alone increased the accuracy of tumor localization (area under the curve (AUC) = 0.77;p-value = 0.004) over unprocessed data (AUC = 0.74). Adding normalization to the pre-processing pipeline further improved diagnostic accuracy of the model to an AUC of 0.85 (p-value = 0.000 12). Multi-modal registration of apparent diffusion coefficient images to T2-weighted images improved the alignment of tumor locations in all but one patient, resulting in a slight decrease in accuracy (AUC = 0.84;p-value = 0.30).Significance. Overall, our findings suggest that the combined effect of multiple pre-processing steps with optimal values has the ability to improve the quantitative classification of prostate cancer using mpMRI. Clinical trials: NCT03378856 and NCT03367702.

Image-guided Raman spectroscopy navigation system to improve transperineal prostate cancer detection. Part 1: Raman spectroscopy fiber-optics system and in situ tissue characterization.

SIGNIFICANCE: The diagnosis of prostate cancer (PCa) and focal treatment by brachytherapy are limited by the lack of precise intraoperative information to target tumors during biopsy collection and radiation seed placement. Image-guidance techniques could improve the safety and diagnostic yield of biopsy collection as well as increase the efficacy of radiotherapy. AIM: To estimate the accuracy of PCa detection using in situ Raman spectroscopy (RS) in a pilot in-human clinical study and assess biochemical differences between in vivo and ex vivo measurements. APPROACH: A new miniature RS fiber-optics system equipped with an electromagnetic (EM) tracker was guided by trans-rectal ultrasound-guided imaging, fused with preoperative magnetic resonance imaging to acquire 49 spectra in situ (in vivo) from 18 PCa patients. In addition, 179 spectra were acquired ex vivo in fresh prostate samples from 14 patients who underwent radical prostatectomy. Two machine-learning models were trained to discriminate cancer from normal prostate tissue from both in situ and ex vivo datasets. RESULTS: A support vector machine (SVM) model was trained on the in situ dataset and its performance was evaluated using leave-one-patient-out cross validation from 28 normal prostate measurements and 21 in-tumor measurements. The model performed at 86% sensitivity and 72% specificity. Similarly, an SVM model was trained with the ex vivo dataset from 152 normal prostate measurements and 27 tumor measurements showing reduced cancer detection performance mostly attributable to spatial registration inaccuracies between probe measurements and histology assessment. A qualitative comparison between in situ and ex vivo measurements demonstrated a one-to-one correspondence and similar ratios between the main Raman bands (e.g., amide I-II bands, phenylalanine). CONCLUSIONS: PCa detection can be achieved using RS and machine learning models for image-guidance applications using in situ measurements during prostate biopsy procedures.

Image-guided Raman spectroscopy navigation system to improve transperineal prostate cancer detection. Part 2: in-vivo tumor-targeting using a classification model combining spectral and MRI-radiomics features.

SIGNIFICANCE: The diagnosis and treatment of prostate cancer (PCa) are limited by a lack of intraoperative information to accurately target tumors with needles for biopsy and brachytherapy. An innovative image-guidance technique using optical devices could improve the diagnostic yield of biopsy and efficacy of radiotherapy. AIM: To evaluate the performance of multimodal PCa detection using biomolecular features from in-situ Raman spectroscopy (RS) combined with image-based (radiomics) features from multiparametric magnetic resonance images (mpMRI). APPROACH: In a prospective pilot clinical study, 18 patients were recruited and underwent high-dose-rate brachytherapy. Multimodality image fusion (preoperative mpMRI with intraoperative transrectal ultrasound) combined with electromagnetic tracking was used to navigate an RS needle in the prostate prior to brachytherapy. This resulting dataset consisted of Raman spectra and co-located radiomics features from mpMRI. Feature selection was performed with the constraint that no more than 10 features were retained overall from a combination of inelastic scattering spectra and radiomics. These features were used to train support vector machine classifiers for PCa detection based on leave-one-patient-out cross-validation. RESULTS: RS along with biopsy samples were acquired from 47 sites along the insertion trajectory of the fiber-optics needle: 26 were confirmed as benign or grade group = 1, and 21 as grade group >1, according to histopathological reports. The combination of the fingerprint region of the RS and radiomics showed an accuracy of 83% (sensitivity = 81 % and a specificity = 85 % ), outperforming by more than 9% models trained with either spectroscopic or mpMRI data alone. An optimal number of features was identified between 6 and 8 features, which have good potential for discriminating grade group ≥1 / grade group <1 (accuracy = 87 % ) or grade group >1 / grade group ≤1 (accuracy = 91 % ). CONCLUSIONS: In-situ Raman spectroscopy combined with mpMRI radiomics features can lead to highly accurate PCa detection for improved in-vivo targeting of biopsy sample collection and radiotherapy seed placement.

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

Background and purpose: Locally recurrent prostate cancer after radiotherapy merits an effective salvage strategy that mitigates the risk of adverse events. We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT). Materials and methods: Analysis of a prospective cohort of 88 patients treated across two institutions with MRI-guided salvage HDR-BT to visible local recurrence after radiotherapy (RT). Tumor target dose ranged from 22-26 Gy, using either an integrated boost (ibBT) or focal technique (fBT), delivered in two implants over a median of 7 days. Outcome metrics included cancer control and toxicity (CTCAE). Quality of life (QoL-EPIC) was analyzed in a subset. Results: At a median follow-up of 35 months (6 -134), 3 and 5-year failure-free survival (FFS) outcomes were 67% and 49%, respectively. At 5 years, fBT was associated with a 17% cumulative incidence of local failure (LF) outside the GTV (vs. 7.8% ibBT, p=0.14), while LF within the GTV occurred in 13% (vs. 16% ibBT, p=0.81). Predictors of LF outside fBT volumes included pre-salvage PSA>7 ng/mL (p=0.03) and interval since RT less than 5 years (p=0.04). No attributable grade 3 events occurred, and ibBT was associated with a higher rate of grade 2 toxicity (p<0.001), and trend towards a larger reduction in QoL sexual domain score (p=0.07), compared to fBT. Conclusion: A tumor-targeted HDR-BT salvage approach achieved favorable cancer control outcomes. While a fBT was associated with less toxicity, it may be best suited to a subgroup with lower PSA at later recurrence. Tumor targeted dose escalation may be warranted.

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC).

BACKGROUND: Management of Non-Small Cell Lung Cancer (NSCLC) patients with oligoprogression remains controversial. There is limited data to support the strategy of Stereotactic Ablative Radiotherapy (SABR) targeting the oligoprogressive disease in combination with ongoing systemic treatment. We aim to assess the benefit of this approach compared to standard of care in the treatment of oligoprogressive NSCLC. METHODS: This phase II study will enroll 68 patients with oligoprogressive NSCLC, defined as 1-5 progressive extracranial lesions ≤5 cm involving ≤3 organs. Patients on active systemic therapy (chemotherapy, immunotherapy, targeted therapy or a combination) will be randomized 1:1 to either continue their current systemic therapy in combination with SABR to all lesions or the standard of care (switch to the next line of treatment, continue same treatment or observation). The co-primary endpoints are progression-free survival (PFS) and overall survival (OS). Secondary endpoints include time to next systemic treatment, patient-reported quality of life, cost effectiveness as well as translational analysis to characterize both adaptive immunity and immunogenic cell death markers in the peripheral blood. DISCUSSION: There is an unmet need to carefully examine the efficacy, safety and quality of life impact of SABR in the context of oligoprogressive disease. The present study will provide higher level randomized evidence on the role of SABR in oligoprogressive NSCLC.

PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial.

BACKGROUND: Positron emission tomography targeting the prostate specific membrane antigen (PSMA PET/CT) has demonstrated unparalleled performance as a staging examination for prostate cancer resulting in substantial changes in management. However, the impact of altered management on patient outcomes is largely unknown. This study aims to assess the impact of intensified radiotherapy or surgery guided by PSMA PET/CT in patients at risk of advanced prostate cancer. METHODS: This pan-Canadian phase III randomized controlled trial will enroll 776 men with either untreated high risk prostate cancer (CAPRA score 6-10 or stage cN1) or biochemically recurrent prostate cancer post radical prostatectomy (PSA > 0.1 ng/mL). Patients will be randomized 1:1 to either receive conventional imaging or conventional plus PSMA PET imaging, with intensification of radiotherapy or surgery to newly identified disease sites. The primary endpoint is failure free survival at 5 years. Secondary endpoints include rates of adverse events, time to next-line therapy, as well as impact on health-related quality of life and cost effectiveness as measured by incremental cost per Quality Adjusted Life Years gained. DISCUSSION: This study will help create level 1 evidence needed to demonstrate whether or not intensification of radiotherapy or surgery based on PSMA PET findings improves outcomes of patients at risk of advanced prostate cancer in a manner that is cost-effective. TRIAL REGISTRATION: This trial was prospectively registered in ClinicalTrials.gov as NCT04557501 on September 21, 2020.

Performance of an integrated multimodality image guidance and dose-planning system supporting tumor-targeted HDR brachytherapy for prostate cancer.

BACKGROUND AND PURPOSE: Advances in high-dose-rate brachytherapy to treat prostate cancer hinge on improved accuracy in navigation and targeting while optimizing a streamlined workflow. Multimodal image registration and electromagnetic (EM) tracking are two technologies integrated into a prototype system in the early phase of clinical evaluation. We aim to report on the system's accuracy and workflow performance in support of tumor-targeted procedures. MATERIALS AND METHODS: In a prospective study, we evaluated the system in 43 consecutive procedures after clinical deployment. We measured workflow efficiency and EM catheter reconstruction accuracy. We also evaluated the system's MRI-TRUS registration accuracy with/without deformation, and with/without y-axis rotation for urethral alignment at initialization. RESULTS: The cohort included 32 focal brachytherapy and 11 integrated boost whole-gland implants. Mean procedure time excluding dose delivery was 38 min (range: 21-83) for focal, and 56 min (range: 38-89) for whole-gland implants; stable over time. EM catheter reconstructions achieved a mean difference between computed and measured free-length of 0.8 mm (SD 0.8, no corrections performed), and mean axial manual corrections 1.3 mm (SD 0.7). EM also enabled the clinical use of a non or partially visible catheter in 21% of procedures. Registration accuracy improved with y-axis rotation for urethral alignment at initialization and with the elastic registration (mTRE 3.42 mm, SD 1.49). CONCLUSION: The system supported tumor-targeting and was implemented with no demonstrable learning curve. EM reconstruction errors were small, correctable, and improved with calibration and control of external distortion sources; increasing confidence in the use of partially visible catheters. Image registration errors remained despite rotational alignment and deformation, and should be carefully considered.

Probabilistic target definition and planning in patients with prostate cancer.

Intro.Current radiation therapy (RT) planning guidelines handle uncertainties in RT using geometric margins. This approach is simple to use but oversimplifies complex underlying processes and is cumbersome for non-homogeneous dose prescriptions. In this work, we characterize the performance of a novel probabilistic target definition and planning (PTP) approach, which uses voxel-level tumor likelihood information in treatment plan optimization.Methods.We expanded a treatment planning system with probabilistic therapy planning functionality that utilizes non-binary target maps (TM) as voxel-level input to dose plan optimization. Different dose plans were calculated and compared for twelve prostate cancer patients with multiparametric magnetic resonance imaging derived TMs. Dose plans were created using both classical and PTP approaches for uniform and integrated dose boost prescriptions. Dose performance between the different approaches was compared using dose benchmarks on target and organ-at-risk (OAR) volumes.Results.Over all dose metrics, PTP was shown to be comparable to classical planning. For plans of uniform dose prescription, the PTP approach created plans within 1 Gy of the classical planning approach across all dose metrics, with no significant differences (p > 0.2). For plans with the integrated dose boost, PTP plans exhibited higher dose heterogeneity, but still showed target doses comparable to the classical approach, without increasing doses to OAR.Conclusion.In this work we introduce direct incorporation of probabilistic target definition into treatment planning. This treatment planning approach can produce both uniform dose plans and plans with integrated dose boosts that are comparable to ones created using classical dose planning. PTP is a flexible way to optimize external beam radiotherapy, as it is not limited by the use of margins. PTP can produce dose plans equivalent to classical planning, while also allows for greater versatility in dose prescription and direct incorporation of patient target definition uncertainty into treatment planning.

PET/CT-Based Salvage Radiotherapy for Recurrent Prostate Cancer After Radical Prostatectomy: Impact on Treatment Management and Future Directions.

Biochemical recurrence is a clinical situation experienced by 20 to 40% of prostate cancer patients treated with radical prostatectomy (RP). Prostate bed (PB) radiation therapy (RT) remains the mainstay salvage treatment, although it remains non-curative for up to 30% of patients developing further recurrence. Positron emission tomography with computed tomography (PET/CT) using prostate cancer-targeting radiotracers has emerged in the last decade as a new-generation imaging technique characterized by a better restaging accuracy compared to conventional imaging. By adapting targeting of recurrence sites and modulating treatment management, implementation in clinical practice of restaging PET/CT is challenging the established therapeutic standards born from randomized controlled trials. This article reviews the potential impact of restaging PET/CT on changes in the management of recurrent prostate cancer after RP. Based on PET/CT findings, it addresses potential adaptation of RT target volumes and doses, as well as use of androgen-deprivation therapy (ADT). However, the impact of such management changes on the oncological outcomes of PET/CT-based salvage RT strategies is as yet unknown.

Adult Medulloblastoma Demographic, Tumor and Treatment Impact since 2006: A Canadian University Experience.

Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults; therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006-2012 and 2013-2017. In our adult population, median follow up was 26 months and SHH-activated MB comprised 39% of tumors. Adult 5yOS was 80% and first-line therapy led to a 5yPFS of 77%. The absence of radiosensitizing chemotherapy (100% vs. 50%; p = 0.033) negatively influenced 5yPFS. 96% of adult patients received radiotherapy and 48% of them received concomitant radiosensitizing chemotherapy. Complete surgical resection was performed on 85% of adults, but the extent of resection did not have a discernable impact on survival and did not change with time. Adjuvant chemotherapy did not clearly affect prognosis (5yOS 80% vs. 67%, p = 0.155; 5yPFS 78% vs. 67%, p = 0.114). From 2006-2012, the most common chemotherapy regimen (69%) was Cisplatinum, Lomustine and Vincristine, which was replaced in 2013 by Cisplatinum, Etoposide and Cyclophosphamide (77%) with a trend for worse survival. Nine patients recurred and seven of these (78%) were treated with palliative chemotherapy. In conclusion, we did not identify prognostic demographic or tumor factors in our adult MB population. The presence of radiosensitizing chemotherapy was associated with a more favorable PFS. Cisplatinum, Lomustine and Vincristine regimen might be a better adjuvant chemotherapy regimen.

Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is increasingly being used worldwide as part of the clinical workup for men with prostate cancer. With high overall accuracy for the detection of prostate cancer, PSMA-targeted PET has an increasingly established role in the setting of biochemical failure after primary therapy and an evolving role in the setting of initial disease staging; its utility for guiding management in the setting of metastatic disease is less clear. Although the specificity is high, familiarization with potential pitfalls in the interpretation of PSMA-targeted PET, including knowledge of the causes for false-positive and negative examinations, is critical. The aim of this best practice report is to provide an illustrative discussion of the current and evolving clinical indications for PSMA-targeted PET, as well as a review of physiological radiopharmaceutical biodistribution and potential imaging pitfalls.