Deep learning for high-resolution dose prediction in high dose rate brachytherapy for breast cancer treatment.

Objective.Monte Carlo (MC) simulations are the benchmark for accurate radiotherapy dose calculations, notably in patient-specific high dose rate brachytherapy (HDR BT), in cases where considering tissue heterogeneities is critical. However, the lengthy computational time limits the practical application of MC simulations. Prior research used deep learning (DL) for dose prediction as an alternative to MC simulations. While accurate dose predictions akin to MC were attained, graphics processing unit limitations constrained these predictions to large voxels of 3 mm × 3 mm × 3 mm. This study aimed to enable dose predictions as accurate as MC simulations in 1 mm × 1 mm × 1 mm voxels within a clinically acceptable timeframe.Approach.Computed tomography scans of 98 breast cancer patients treated with Iridium-192-based HDR BT were used: 70 for training, 14 for validation, and 14 for testing. A new cropping strategy based on the distance to the seed was devised to reduce the volume size, enabling efficient training of 3D DL models using 1 mm × 1 mm × 1 mm dose grids. Additionally, novel DL architecture with layer-level fusion were proposed to predict MC simulated dose to medium-in-medium (Dm,m). These architectures fuse information from TG-43 dose to water-in-water (Dw,w) with patient tissue composition at the layer-level. Different inputs describing patient body composition were investigated.Main results.The proposed approach demonstrated state-of-the-art performance, on par with the MCDm,mmaps, but 300 times faster. The mean absolute percent error for dosimetric indices between the MC and DL-predicted complete treatment plans was 0.17% ± 0.15% for the planning target volumeV100, 0.30% ± 0.32% for the skinD2cc, 0.82% ± 0.79% for the lungD2cc, 0.34% ± 0.29% for the chest wallD2ccand 1.08% ± 0.98% for the heartD2cc.Significance.Unlike the time-consuming MC simulations, the proposed novel strategy efficiently converts TG-43Dw,wmaps into preciseDm,mmaps at high resolution, enabling clinical integration.

Testosterone recovery after androgen deprivation therapy in localised prostate cancer: Long-term data from two randomised trials.

BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.

Salvage Whole-Pelvic Radiation and Long-Term Androgen-Deprivation Therapy in the Management of High-Risk Prostate Cancer: Long-Term Update of the McGill 0913 Study.

PURPOSE: To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT (LT-ADT). MATERIALS AND METHODS: From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. RESULTS: At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 µg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. CONCLUSIONS: Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.

Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature.

BACKGROUND: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. METHODS: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. FINDINGS: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. INTERPRETATION: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.

Prophylactic A-Blockers for Radiotherapy-Induced Lower Urinary Tract Symptoms in Men with Prostate Cancer: A Phase III Randomized Trial.

PURPOSE: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). METHODS: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin on day one of EBRT or the occurrence of RI-LUTSs. LUTSs were quantified using the international prostate symptom score (IPSS) at regular intervals during the study. The primary endpoint was the change in the IPSS from baseline to the last day of radiotherapy (RT). Secondary endpoints included changes in IPSS from baseline to 4 weeks and 12 weeks after the start of RT. RESULTS: Patient demographics, baseline IPSS, and prescribed radiation doses were balanced between arms. On the last day of RT, the mean IPSS was 14.8 (SD 7.6) in the experimental arm and 15.7 (SD 8.5) in the control arm (p = 0.40). There were no significant differences in IPSSs between the study arms in the intention-to-treat (ITT) analysis at baseline, the last day of RT, and 4 and 12 weeks post-RT. CONCLUSION: Prophylactic α-blockers were not effective at significantly reducing RI-LUTSs in prostate cancer patients treated with EBRT. Treating patients with α-blockers at the onset of RI-LUTSs will avoid unnecessary drug exposure and toxicity.

Advances in PARP Inhibitors for Prostate Cancer.

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.

Comparing digital to analog prostate-specific membrane antigen-targeted piflufolastat 18 F PET/CT in prostate cancer patients in early biochemical failure.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT) in prostate cancer patients with biochemical failure(BCF) showslimited sensitivity when the prostate-specific antigen(PSA) <0.5 ng/mL. The development of digital PET/CT has greatly improved smaller lesion detection. This study's goal was to compare the performance and clinical value of PSMA-targeted piflufolastat PET/CT for prostate cancer BCF with digital versus analog PET/CT. METHODS: In this retrospective study, all piflufolastat PET/CT scans in subjects with PSA ≤ 3.0 ng/mL who were referred for prostate cancer BCF were included. The performance characteristics of 171 analog PET/CT studies in 155 subjects from May 2017 to January 2020 and 106 digital PET/CT studies in 103 subjects from February 2020 to December 2020 were compared. Lesions were considered malignant if they did not match the known physiological distribution of piflufolastat and did not represent uptake in benign lesions. PSMA PET/CT studies were considered positive if at least one malignant lesion was detected and negative if none were detected. RESULTS: Digital piflufolastat PET/CT outperformed analog piflufolastat PET/CT in subjects with PSA < 0.5 ng/mL with a positivity rate of 69% versus 37%, respectively. In patients with PSA ≥ 0.5 ng/mL, both technologies performed similarly. There was no statistically significant difference between the number or size of piflufolastat-avid lesions detected per PET/CT study. CONCLUSION: In prostate cancer patients with BCF and PSA < 0.5 ng/mL, digital piflufolastat PET/CT has a higher detection rate of malignant lesions than analog piflufolastat PET/CT.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience.

Purpose/objectives: High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. Materials/methods: We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. Results: From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. Conclusions: To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

Optimizing Treatment in Intermediate-Risk Prostate Cancer: Secondary Analysis of a Randomized Phase 3 Trial.

PURPOSE: To identify patients with intermediate-risk prostate cancer (IRPC) benefiting from de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiation therapy (DERT), we performed a secondary analysis of a phase 3 trial by measuring biochemical failure (BF), distant metastases, prostate cancer-specific mortality, overall survival (OS), and distant metastases-free survival (DMFS) rates according to prognostic intermediate risk factors (IRF). METHODS AND MATERIALS: The initial trial randomized 600 patients with IRPC to a 3-arm trial with 200 patients per arm, consisting of 6 months of ADT plus 70 Gy radiation therapy (ADT + RT70) versus ADT plus a DERT of 76 Gy (ADT + DERT76) versus DERT of 76 Gy alone (DERT76). We performed an analysis based on IRF: clinical stage, prostate-specific antigen level, Gleason score, percentage of positive biopsy cores (PBC) ≥50%, and Gleason pattern. Patients were allocated to 2 groups: favorable intermediate risk (FIR), defined as patients with only 1 IRF without Gleason pattern 4 + 3 or PBC ≥50%; and unfavorable intermediate risk (UIR), defined as all other patients. BF, distant metastases, prostate cancer-specific mortality, OS, and DMFS were compared between FIR and UIR. RESULTS: The median follow-up was 11.3 years (interquartile range, 10.9-11.7). In the FIR cohort, BF and OS were not significantly different between arms. UIR patients had significantly worse DMFS (hazard ratio [95% confidence interval], 1.61 [1.20-2.15]; P = .026) and OS (1.51 [1.12-2.04]; P = .0495) and a nonsignificant higher cumulative incidence of BF rate (1.55 [0.98-2.47]; P = .08). In UIR patients, a significant improvement in BF was seen in the arms receiving ADT compared to DERT76 alone. On multivariable analysis, Gleason pattern 4 + 3 and prostate-specific antigen >10 ng/mL independently affected BF and OS, regardless of the treatment arm. CONCLUSIONS: In IRPC, therapeutic optimization appears possible. To avoid ADT side effects, DERT76 alone appears sufficient in patients harboring only 1 risk factor without Gleason pattern 4 + 3 and PBC ≥50% (FIR). All other UIR patients seem to benefit from ADT + DERT76.

Magnetic Resonance Imaging Based Radiomic Models of Prostate Cancer: A Narrative Review.

The management of prostate cancer (PCa) is dependent on biomarkers of biological aggression. This includes an invasive biopsy to facilitate a histopathological assessment of the tumor's grade. This review explores the technical processes of applying magnetic resonance imaging based radiomic models to the evaluation of PCa. By exploring how a deep radiomics approach further optimizes the prediction of a PCa's grade group, it will be clear how this integration of artificial intelligence mitigates existing major technological challenges faced by a traditional radiomic model: image acquisition, small data sets, image processing, labeling/segmentation, informative features, predicting molecular features and incorporating predictive models. Other potential impacts of artificial intelligence on the personalized treatment of PCa will also be discussed. The role of deep radiomics analysis-a deep texture analysis, which extracts features from convolutional neural networks layers, will be highlighted. Existing clinical work and upcoming clinical trials will be reviewed, directing investigators to pertinent future directions in the field. For future progress to result in clinical translation, the field will likely require multi-institutional collaboration in producing prospectively populated and expertly labeled imaging libraries.

The Clinical Significance of Bone Mineral Density Changes Following Long-Term Androgen Deprivation Therapy in Localized Prostate Cancer Patients.

PURPOSE: Long-term androgen deprivation therapy has been associated with decreased bone mineral density in men with prostate cancer. Some evidence suggests that there is no impact on fracture risk despite this bone mineral density loss. Our study aimed to quantify changes in bone mineral density in men with high risk prostate cancer on long-term androgen deprivation therapy and calcium and vitamin D supplementation. MATERIALS AND METHODS: Bone mineral density analysis was conducted for localized high risk prostate cancer patients enrolled in the phase III randomized trial PCS-V (Prostate Cancer Study 5), comparing conventional and hypofractionated radiation therapy. Patients received 28 months of luteinizing hormone-releasing hormone agonist and calcium and vitamin D supplementation (500 mg calcium BID+400 IU vitamin D3 BID). The areal density and T-scores (spine, femoral neck and total femur) at baseline and 30 months of followup were extracted, and the absolute change was calculated. Clinical bone density status (normal, osteopenia, osteoporosis) was monitored. RESULTS: The lumbar spine, femoral neck and total femoral bone mineral density were measured for 226, 231, and 173 patients, respectively. The mean percent change in bone mineral density was -2.65%, -2.76% and -4.27% for these respective sites (p <0.001 for all). The average decrease in bone mineral density across all sites was -3.2%, with no decline in bone mineral density category in most patients (83%). Eight patients (4%) became osteoporotic. CONCLUSIONS: Despite a mild decline in bone mineral density, the change in clinical bone mineral density category remained low with long-term androgen deprivation therapy. Consequently, calcium and vitamin D supplementation alone may suffice for most localized prostate cancer patients on long-term androgen deprivation therapy.

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial.

BACKGROUND: The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone. METHODS: From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. FINDINGS: With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity. INTERPRETATION: In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.

The role of brachytherapy for margin control in oral tongue squamous cell carcinoma.

BACKGROUND: The aim of this study is to assess the feasibility and effectiveness of using peri-operative brachytherapy (BRTx) for positive/narrow margins present post primary surgical resection of oral tongue squamous cell carcinoma (OTSCC). METHODS: Prospective single-centre study of patients with OTSCC (T1-3, N0-3, M0) treated with resection of primary tumour ± regional nodal resection and intra-operative insertion of BRTx catheters. BRTx was administered twice daily at 40.8Gy/12Fr for 'Positive' (≤2 mm) margins, at 34Gy/10Fr for 'Narrow' (2.1-5 mm) margins, and not given for 'Clear' (> 5 mm) margins over the course of 5-6 days, 3-5 days post operatively. RESULTS: Out of 55 patients recruited 41 patients (74.6%) were treated with BRTx, as 12 patients had clear margins and 2 patients had unfavourable tumour anatomy for catheter insertion. EBRTx was avoided in 64.3% of patients. Overall Survival (OS) at 3 and 5 years was 75.6 and 59.1% respectively, while Disease Specific Survival (DSS) was 82.3 and 68.6% at 3 and 5 years respectively. Recurrence and survival outcomes were not associated with margin status or the use of or specific dose of BRTx on Cox regression analysis. Acute and late toxicity secondary to BRTx was minimal. CONCLUSIONS: The use of BRTx after primary OTSCC resection with positive/narrow margins ± EBRTx to the neck ± CTx achieves outcomes comparable to traditional treatment of surgery followed by re-resection or EBRTx ± CTx. Morbidity associated with oral cavity EBRTx or secondary resection and reconstruction is thus avoided. Both acute and late toxicity rates are low and compare favourably with other BRTx OTSCC studies. TRIAL REGISTRATION: Retrospectively registered. https://www.mcgill.ca/rcr-rcn/files/rcr-rcn/2017.06.05_rcn_hn.pdf . LEVEL OF EVIDENCE: 4.

Combined Long-Term Androgen Deprivation and Pelvic Radiotherapy in the Post-operative Management of Pathologically Defined High-Risk Prostate Cancer Patients: Results of the Prospective Phase II McGill 0913 Study.

Purpose: Following radical prostatectomy, prostate bed radiotherapy (PBRT) has been combined with either long-term androgen deprivation therapy (LT-ADT) or short-term ADT with pelvic lymph node radiotherapy (PLNRT) to provide an oncological benefit in randomized trials. McGill 0913 was designed to characterize the efficacy of combining PBRT, PLNRT, and LT-ADT. It is the first study to do so prospectively. Methods: In a single arm phase II trial conduced from 2010 to 2016, 46 post-prostatectomy prostate cancer patients at a high-risk for relapse (pathological Gleason 8+ or T3) were assessed for treatment with combined LT-ADT (24 months), PBRT, and PLNRT. Patients received PLNRT and PBRT (44 Gy in 22 fractions) followed by a PBRT boost (22 Gy in 11 fractions). The primary endpoint was progression-free survival (PFS). Toxicity and quality of life (QoL) were evaluated using CTCAE V3.0 and EQ-5D-3L questionnaires, respectively. Results: Among the 43 patients were treated as per protocol, median PSA was 0.30 µg/L. On surgical pathology, 51% had positive margins, 40% had Gleason 8+ disease, 42% had seminal vesicle involvement, and 19% had lymph node involvement. At a median follow-up of 5.2 years, there were no deaths or clinical progression. At 5 years, PFS was 78.0% (95% Confidence Interval 63.7-95.5%). Not including erectile dysfunction, patients experienced: 14% grade 2 endocrine toxicity while on ADT, one incident of long-term gynecomastia, 5% grade 2 acute urinary toxicity, 5% grade 2 late Urinary toxicity, and 24% long-term hypogonadism. No comparison between the average or minimum self-reported QoL at baseline, during ADT, nor after ADT demonstrated a statistically significant difference. Conclusions: Combining PBRT, PLNRT, and LT-ADT had an acceptable PFS in patients with significant post-operative risk factors for recurrence. While therapy was well-tolerated, long-term hypogonadism was a substantial risk. Further investigations are needed to determine if this combination is beneficial. Trial registration: NCT01255891.

Does Interfraction Cone Beam Computed Tomography Improve Target Localization in Prostate Bed Radiotherapy?

PURPOSE: In this prospective phase II study, we investigated whether cone beam computed tomography scan was a superior method of image-guided radiotherapy relative to 2D orthogonal kilovoltage images in the post-radical prostatectomy setting. METHODS: A total of 419 treatment fractions were included in this analysis. The shifts required to align the patient for each treatment were performed using 3D matching between cone beam computed tomography scans and the corresponding computed tomography images used for planning. This was compared with the shifts obtained from 2D orthogonal kilovoltage images, matching with the corresponding digitally reconstructed radiographs. Patients did not have fiducials inserted to assist with localization. Interfractional changes in the bladder and rectal volumes were subsequently measured on the cone beam computed tomography images for each fraction and compared to the shift differences between orthogonal kilovoltage and cone beam computed tomography scans. The proportion of treatment fractions with a shift difference exceeding the planning target volume of 7 mm, between orthogonal kilovoltage and cone beam computed tomography scans, was calculated. RESULTS: The mean vertical, lateral, and longitudinal shifts resulted from 2D match between orthogonal kilovoltage images and corresponding digitally reconstructed radiographs were 0.353 cm (interquartile range: 0.1-0.5), 0.346 cm (interquartile range: 0.1-0.5), and 0.289 cm (interquartile range: 0.1-0.4), compared to 0.388 cm (interquartile range: 0.1-0.5), 0.342 cm (interquartile range: 0.1-0.5), and 0.291 cm (interquartile range: 0.1-0.4) obtained from 3D match between cone beam computed tomography and planning computed tomography scan, respectively. Our results show a significant difference between the kilovoltage and cone beam computed tomography shifts in the anterior-posterior direction ( P = .01). The proportion of treatment fractions in which the differences in kilovoltage and cone beam computed tomography shifts between exceeded the 7 mm planning target volume margin was 6%, 2%, and 3% in the anterior-posterior, lateral, and superior-inferior directions, respectively. CONCLUSION: We prospectively demonstrated that the daily use of volumetric cone beam computed tomography for treatment localization in post-radical prostatectomy patients demonstrated an increased need for a shift in patient position. This suggests that in post-radical prostatectomy patients the daily cone beam computed tomography imaging improved localization of the prostate bed and may have prevented a limited number of geographic misses, compared to daily kilovoltage imaging that was not assisted with fiducials.

No 370 - Prise en charge du cancer spinocellulaire de la vulve.

OBJECTIF: Cette directive clinique porte sur l'évaluation clinique et la prise en charge du cancer spinocellulaire (CSC) de la vulve, plus particulièrement sur son diagnostic, sa prise en charge primaire au moyen de la chirurgie, de la radiothérapie ou de la chimiothérapie et la nécessité d'une chimiothérapie et/ou d'une radiothérapie adjuvante. Cette directive clinique ne traite pas des autres diagnostics pathologiques de cancer de la vulve. UTILISATEURS CIBLES: La première partie de ce document, qui comprend les recommandations 1 à 3, s'adresse aux gynécologues, aux obstétriciens, aux médecins de famille, aux infirmières autorisées, aux infirmières praticiennes, aux résidents et aux fournisseurs de soins généralistes; elle est axée sur la présentation et le diagnostic de la maladie, et fournit des renseignements à jour sur les chirurgies effectuées par les professionnels surspécialisés. La partie sur la prise en charge chirurgicale et le traitement des cancers avancés de la vulve s'adresse aux gynécologues oncologues, aux radio-oncologues et aux oncologues médicaux appelés à traiter les patientes aux besoins complexes. Cette directive clinique a pour but de renseigner les intervenants qui pourraient suivre ces patientes après leur traitement. POPULATION CIBLE: Femmes adultes (18 ans et plus) présentant un CSC de la vulve. Les femmes atteintes d'un cancer préinvasif ne sont pas visées par cette directive clinique. OPTIONS: Les femmes ayant reçu un diagnostic de CSC de la vulve devraient être dirigées vers un gynécologue oncologue, qui effectuera une évaluation initiale et déterminera si une chirurgie primaire, une évaluation des ganglions lymphatiques inguinaux et une radiothérapie ou une chimiothérapie adjuvante sont nécessaires. Ces femmes devraient également faire l'objet d'une discussion tenue dans le cadre d'une conférence de cas multidisciplinaire. La radiothérapie et la chimiothérapie primaires peuvent être envisagées chez les femmes qui pourraient avoir besoin d'une exentération ou d'une chirurgie radicale, comme une résection abdomino-périnéale. ÉVIDENCE: Des études pertinentes rédigées en anglais ont été repérées dans PubMed, Medline, et la Cochrane Database of Systematic Reviews à l'aide des termes suivants, seuls ou combinés : « vulva ¼, « vulvar cancer ¼, « inguinofemoral lymph node dissection ¼, « sentinel nodes ¼, « systemic chemotherapy ¼, « radiotherapy ¼, « neoadjuvant ¼, « adjuvant ¼, « primary ¼, « exenteration ¼, « survival ¼, « follow up ¼. La recherche initiale a été menée en septembre 2016, et une dernière recherche a été effectuée en mai 2017. Dans l'ordre, les données probantes pertinentes pour la sélection ont été tirées de méta-analyses, de revues systématiques, de directives cliniques, d'essais cliniques randomisés, d'études de cohortes prospectives, d'études observationnelles, de revues non systématiques, d'études de série de cas et de rapports. D'autres articles pertinents ont été ciblés au moyen d'une vérification des références des revues de la littérature retenues. Au total, 286 études ont été repérées, et 78 ont été retenues pour la présente directive. VALEURS: Le contenu et les recommandations ont été rédigés et acceptés par les auteurs principaux. La direction et le conseil de la Société de gynéco-oncologie du Canada ont examiné le contenu et soumis des commentaires, puis le Conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version finale avant publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) [tableau 1]. L'interprétation des recommandations fortes et faibles est décrite dans le tableau 2. Le résumé des conclusions peut être fourni sur demande. AVANTAGES, INCONVéNIENTS ET COûTS: La présente directive clinique vise à guider les médecins vers une utilisation appropriée de l'évaluation du ganglion sentinelle inguinal en cas de CSC de la vulve. Le comité encourage également la centralisation du traitement des cancers de la vulve dans des centres de traitement spécialisés. MIS-à-JOUR: Une revue des données probantes sera menée cinq ans après la publication de la présente directive clinique afin de déterminer si une mise à jour complète ou partielle s'impose. Cependant, si de nouvelles données probantes importantes sont publiées avant la fin du cycle de cinq ans, le processus pourrait être accéléré afin que certaines recommandations soient mises à jour rapidement. COMMANDITAIRES: Cette directive Clinique a été développée avec les ressources de la Société de gynécologie oncologique du Canada et de la Société des obstétriciens et gynécologues du Canada. DéCLARATIONS SOMMAIRES: RECOMMENDATIONS.

No. 370-Management of Squamous Cell Cancer of the Vulva.

OBJECTIVE: This guideline reviews the clinical evaluation and management of squamous cell cancer (SCC) of the vulva with respect to diagnosis, primary surgical, radiation, or chemotherapy management and need for adjuvant treatment with chemotherapy and/or radiation therapy. Other vulvar cancer pathologic diagnoses are not included in the guideline. INTENDED USERS: The first part of this document which includes recommendations 1 through 3 is for general gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers with a focus on the presentation, diagnosis, and updated information about surgical procedures performed by subspecialists. The surgical management and treatment of advanced vulvar cancer are intended for gynaecologic oncologists, radiation oncologists, and medical oncologists who treat these complex patients. This guideline is intended to provide information for interested parties who may follow these patients once treatment is complete. TARGET POPULATION: Adult women (18 years and older) with SCC of the vulva. Excluded from these guidelines are women with preinvasive disease. OPTIONS: Women diagnosed with SCC of the vulva should be referred to a gynaecologic oncologist for initial evaluation, consideration for primary surgery and inguinal lymph node assessment, and potentially adjuvant radiation and/or chemotherapy. All cases of vulvar cancer should have access to discussion at a multidisciplinary cancer case conference. Women who would otherwise require radical surgery such as abdominal-perineal resection or exenterative procedures may be considered for primary treatment with radiation and/or chemotherapy. EVIDENCE: For this guideline, relevant studies were searched in PubMed, Medline, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials: vulva, vulvar cancer, inguinofemoral lymph node dissection, sentinel nodes, systemic chemotherapy, radiotherapy, neoadjuvant, adjuvant, primary, exenteration, survival, follow up. The initial search was performed in September 2016 with a final literature search in May 2017. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 286, and 78 studies were included in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the principal authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework (Table 1). The interpretation of strong and weak recommendations is described in Table 2. The Summary of Findings is available upon request. BENEFITS, HARMS, AND/OR COSTS: These guidelines are to encourage physicians in the appropriate use of sentinel inguinal lymph node assessment for SCC of the vulva. The committee also promotes the centralization of treatment of vulvar cancer in specialized treatment centres. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. SPONSORS: This guideline was developed with resources funded by the Society of Gynecologic Oncology of Canada and the Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: RECOMMENDATIONS.

Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III Trial.

BACKGROUND: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with localized high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. OBJECTIVE: The aim of this superiority randomized trial was to compare outcomes of RT combined with either 36 or 18 mo of ADT. DESIGN, SETTING AND PARTICIPANTS: From October 2000 to January 2008, 630 patients with HRPC were randomized, 310 to pelvic and prostate RT combined with 36 mo (long arm) and 320 to the same RT with 18 mo (short arm) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. RESULTS AND LIMITATIONS: With a median follow-up of 9.4 yr, 290 patients had died (147 long arm vs 143 short arm). The 5-yr OS rates (95% confidence interval) were 91% for long arm (88-95%) and 86% for short arm (83-90%), p=0.07. QoL analysis showed a significant difference (p<0.001) in six scales and 13 items favoring 18 mo ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. CONCLUSIONS: In localized HRPC, our results support that 36 mo is not superior to 18 mo of ADT. ADT combined with RT can potentially be reduced to 18 mo in selected men without compromising survival or QoL. Thus, 18 mo of ADT appears to represent a valid option in HRPC. PATIENT SUMMARY: In this study, we report outcomes from high-risk prostate cancer patients treated with radiotherapy and either 36 or 18 mo of androgen deprivation therapy. There was no difference in survival between the two groups, with the 18-mo group experiencing a better quality of life.