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  • American Society of Clinical Oncology (ASCO)  (9)
  • Fleshner, Neil Eric  (9)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 60-60
    Abstract: 60 Background: Pre-operative radiotherapy (PreORT) improves local control in various cancer types, and has become an established oncologic treatment strategy. During 2001-2004, we conducted a phase I pilot study assessing the role of short-course PreORT for men with unfavourable intermediate- and high-risk localized prostate cancer (PCa). We present long-term follow-up toxicity and oncologic outcomes. Methods: Eligible patients had histologically proven PCa, cT1-T2N0M0, PSA 〉 15-35 ng/ml with any Gleason score, or PSA 10-15 ng/ml with Gleason score ≥7. Patients received 25 Gy in five consecutive daily fractions to the prostate, followed by radical prostatectomy (RadP) within 14 days after RT completion. Primary outcomes were intra-operative morbidity, and late genitourinary (GU) and gastrointestinal (GI) toxicities. Acute toxicity was assessed during radiotherapy treatment on daily basis using RTOG grade scoring scale. Patients were assessed post-RadP clinically and with PSA at 1 and 6 months, and every 6 months. Intra- and Post-RadP toxicity was documented prospectively and scored as per Common Terminology Criteria for Adverse Events v4.0. Biochemical failure (BF) was determined based on two consecutive post-RadP PSA 〉 0.2 ng/ml. Results: Fifteen patients were enrolled; 14 patients completed PreORT followed by RadP, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2 years (range 6.7-16.3 years). Late GU toxicity was common, with 2 patients (14.3%) experiencing G2 toxicity, and 6 patients (42.8%) G3 toxicity. There were no G4-5 late GU toxicity. Late GI toxicity was infrequent, with only 1 patient (7.1%) experiencing transient G2 proctitis. At last follow-up, 8 (57.1%) and 6 (42.8%) patients experienced BF and metastatic disease recurrence, respectively. Conclusions: The use of PreORT in men with high-risk PCa is associated with unexpected high-rates of late GU toxicity. Future studies examining the role of RT pre-RadP must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data is essential to fully determine the therapeutic index of PreORT in the management of localized PCa. Clinical trial information: NCT00252447.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 73-73
    Abstract: 73 Background: Older adults are at greater risk of cognitive decline with various oncologic therapies. Emerging data suggest cognitive effects of various therapies for mCRPC but study populations are highly selected and published data are limited and focus mostly on self-reported cognitive function. We evaluated the effects of treatment with docetaxel chemotherapy (CHEMO), abiraterone (ABI), enzalutamide (ENZA), and radium 223 (Ra223) on cognitive function in older men with mCRPC. Methods: Men age 65+ with mCRPC starting any of the 4 treatments for mCRPC were enrolled in this multicenter prospective cohort study. Three short yet reliable and sensitive measures in older adults were administered at baseline and final visit (6 months with CHEMO and Ra223, mean 14-16 months with ENZA and ABI) using the Montreal Cognitive Assessment (MoCA), Trails A, and Trails B to assess global cognition, attention, and executive function, respectively. Absolute changes in cognitive scores over time were analyzed using multivariable linear regression, and the percentage of individuals with a decline of 1.5 SD in each domain were calculated. Higher scores on MoCA are better but worse for Trails A/B. Results: A total of 51, 26, 49, and 21 men starting CHEMO, ABI, ENZA, and Ra223 with complete data were included. Mean age, education, and baseline cognition were similar between groups (Table). Most patients demonstrated stable cognition or slight reductions. Executive function was the most sensitive of the 3 cognitive domains, and declined by at least 1.5 SD in about one-fifth of each cohort. Although ABI had numerically smaller declines than ENZA, differences were generally small and clinically unimportant. Conclusions: Most older men do not experience significant cognitive decline while on treatment for mCRPC regardless of treatment used.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 250-250
    Abstract: 250 Background: Despite maximal local therapies (MLT) (radical prostatectomy followed by radiotherapy [RT]), 20-30% of men will have incurable progression of prostate cancer (PC). Most recurrences in this scenario are characterized by continuous PSA rises and failure of standard imaging (bone scan [BS] and computed tomography [CT]) to detect recurrence sites. We conducted a phase II trial for men with rising PSA after MLT using 18 F-DCFPyL PET-MR followed by targeted ablation of PET positive foci. We report the results of our pre-defined analysis. Methods: Patients with rising PSA (0.43.0 ng/mL) after MLT, negative BS/CT and no prior salvage ADT were eligible. All patients underwent 18 F-DCFPyL PET-MR followed by immediate PET-CT acquisition. Those with limited disease, where possible, underwent stereotactic ablative RT (SABR) or surgery. No ADT was used. The primary endpoint was biochemical response rate (complete [undetectable PSA] or partial [PSA decline ≥50% compared to baseline] ). A Simon’s two stage study design was employed. Stage 1 included 12 response evaluable patients, requiring 1 or more responses in the absence of grade 3+ toxicities to proceed to stage 2 (additional 25 response evaluable patients). Results: After a median of 58 months (range 29-120) post MLT, 20 patients underwent PET-MR/CT to have 12 response evaluable patients. Median PSA at enrollment was 1.3 ng/mL (range 0.4-2.8). Three patients had negative PET-MR/CT, while 17 had positive scans, of which 12 (60%) were amenable to response evaluable ablation. The median number of detected lesions in those treated was 2 (range 1-5). Ten patients underwent SABR (27-30 Gy/3 fractions) and 2 had surgery. One patient (8%) had complete and 4 (33%) had partial PSA responses at a median of 3.3 months (range 2.8-6.0) after ablation, while the remaining 7 (59%) did not have biochemical response. No grade 3+ toxicities were observed. Conclusions: 18 F-DCFPyL PET/MR has high detection rates in men with rising PSA after MLT. We observed favorable early results with SABR or surgery (41% RR). Trial completion will inform if this approach offers potential for cure in an early molecularly-defined PC oligometastatic state. Clinical trial information: NCT03160794.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e16003-e16003
    Abstract: e16003 Background: Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. While radical cystectomy (RC) is currently viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) combining transurethral resection of bladder tumor, chemotherapy for radiation sensitization and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, we compared the oncological outcomes between patients managed by RC or TMT using a propensity-score matched cohort analysis. Methods: Patients seen in our multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were retrospectively reviewed. Those who received TMT for MIBC were identified and matched (for gender, cT and cN stage, ECOG status, Charlson comorbidity score, treatment date, age, CIS, hydronephrosis) using propensity scores, to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: 112 patients with MIBC were included after matching, 56 treated with TMT and 56 by RC. Median age was 68.0 years and 29.5% were cT3/cT4. At a median follow up of 4.51 years, there were 20 (35.7%) deaths (13 from BC) in the RC group and 22 (39.3%) deaths (13 from BC) in the TMT group. 5 year DSS was 73.2% and 76.6%, in the RC and TMT groups, respectively (p = 0.49). Salvage cystectomy was performed in 6/56 TMT patients (10.7%). Conclusions: In the setting of a MDBCC, TMT yielded survival outcomes similar to matched RC patients. Appropriately selected MIBC patients should be offered the opportunity to discuss various treatment options including organ-sparing TMT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 16-16
    Abstract: 16 Background: Use of ADT has been shown to adversely affect physical function and QOL within 3 months of initiation; declines persist at 12 months. Few studies have examined physical function with ongoing ADT use beyond 12 months. Methods: In this extension of our prior study, men age 50 or older with non-metastatic prostate cancer (PC) who were on continuous ADT were followed along with two control groups (PC, no ADT; healthy controls) matched on age, education, and baseline function. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test, representing endurance, upper extremity strength, and lower extremity strength, respectively. Aggregate physical and mental QOL were measured with the Medical Outcomes Study SF-36. Assessments were done at baseline and at 3, 6, 12, 18, 24, 30, and 36 months. Mixed effects regression models were used, adjusting for age, baseline function, and other covariates. Results: 87 patients on ADT, 86 PC controls, and 86 healthy controls were enrolled (mean age 69.4 y, range 50-87). At baseline, all three groups were similar in age and physical function (all ANOVA p 〉 0.05) and most subjects were otherwise quite healthy. 6MWT distance improved in both control groups but remained unchanged in ADT users (p=0.0379). Grip strength declined sharply in the ADT group by 3 months and remained stable up to 36 months (p 〈 0.001), whereas both control groups were stable over time. There was a slight worsening of TUG scores in the ADT group over 36 months (p=0.0003) but were unchanged in both control groups (p 〉 0.10). Aggregate physical QOL continued to decline in ADT users over time (p=0.0002) but remained stable in both control groups over 36 months, whereas aggregate mental QOL was stable in all groups over time. Most declines were evident within 3-6 months of ADT initiation. Conclusions: Initial declines with continuous ADT use in both physical function and aggregate physical QOL persist for 36 months but generally did not decline further beyond one year despite ongoing ADT use. Early exercise interventions and/or intermittent ADT use may improve these outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 225-225
    Abstract: 225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ 〈 6, 6-20, 〉 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received 〉 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had 〉 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs 〉 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs 〉 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA 〈 70 ug/L (HR = 0.51; p = 0.0023), LDH 〈 250 U/L (HR 0.55; p = 0.0082), Hb 〉 120 g/L(HR 0.46; p = 0.0004), ALP 〈 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p 〈 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration 〉 4 cycles of Ra-223 and baseline ALP 〈 150 U/L were associated with improved OS. Conclusions: Men who receive 〉 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 2_suppl ( 2016-01-10), p. 455-455
    Abstract: 455 Background: We started in 2008 a Multidisciplinary Bladder Cancer Clinic (MDBCC), where complex bladder cancer patients are assessed concurrently by urologic and radiation oncologists, with support from medical oncologists. Patients have the opportunity to discuss various treatment options including radical cystectomy (RC) or bladder sparing trimodal therapy (TMT; endoscopic resection, radiotherapy and chemotherapy). Although reports have shown comparable outcomes of TMT to cystectomy, no direct comparison to RC has been published and no randomized studies are available. We report our long term outcomes of multidisciplinary care, comparing TMT to surgery using propensity-matched analyses. Methods: Patients seen in our MDBCC receiving TMT for MIBC from 2008 to 2012 were identified and matched, using propensity scores, to patients operated by RC. Matching occurred on age, ECOG status, Charlson comorbidity score, cT stage, cN stage and date of treatment. Overall survival (OS) and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: Between 2008 and 2012, 248 patients were assessed in the MDBCC. Of these, 162 (65%) had MIBC. Nearly half (80) opted for radiotherapy +/- concurrent cisplatin chemotherapy and 49 underwent full bladder preservation with TMT as their primary therapy. We matched 48 TMT patients with 48 RC patients with no imbalances. Median age of the cohort was 67.5 years with 29.2% cT3/cT4. With a median follow up time of 3.62 years, there were 19 (39.6%) deaths (7 from bladder cancer) in the RC group and 15 (31.3%) deaths (6 from bladder cancer) in the TMT group. 5 year DSS was 85.2% and 84.7% with TMT and surgery, respectively (p 〉 0.05). There was no statistically significant difference in DSS between the two groups (HR for TMT 1.31 (0.40-4.23), p = 0.66) or in OS (HR for TMT 0.77 (0.34-1.75), p = 0.53). Conclusions: Bladder cancer patients benefit from a multidisciplinary approach.. In selected patients with MIBC, chemo-radiation yields survival outcomes similar to matched RC patients. BC patients should be offered the possibility to discuss various treatment options.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 11510-11510
    Abstract: 11510 Background: Multiple treatment options are available for mCRPC. Being able to predict toxicity risk for different treatments in older adults can aid treatment decision-making and supportive care. The CARG tool is a promising toxicity risk prediction tool for chemotherapy, but has not been specifically validated in the mCRPC setting for either chemotherapy or androgen receptor targeted agents. We prospectively evaluated the ability of the CARG tool to predict risk of clinically relevant grade 2 and grade 3+ toxicity of treatment with chemotherapy (CHEMO) and abiraterone or enzalutamide (A/E) in older adults with mCRPC. Methods: Men age 65+ were enrolled in this prospective observational study at 3 academic centres, Princess Margaret Cancer Centre, Sunnybrook Health Sciences Centre, and Kingston Health Sciences Centre in Ontario, Canada. All grade 2 and grade 3+ toxicities were documented during cycle 1 of CHEMO or in the first 3 months of A/E via structured interviews and chart review. Lab abnormalities were documented only if resulting in emergency room visits, requiring treatment, or affecting subsequent oncologic treatment. Toxicity was rated using the Common Terminology Criteria for Adverse Events version 4. Logistic regression was performed to identify predictors of toxicity. Results: 64 men starting CHEMO (primarily docetaxel 60-75 mg/m^2, mean age 73y) and 59 men starting A/E (mean age 76y) were included. Clinically important grade 2 toxicities occurred in 86% and 70% of CHEMO and A/E patients, respectively. Grade 3+ toxicities occurred in 48% and 25% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 22%, 53%, and 71% of low, moderate, and high risk groups (p = 0.017). However, the CARG tool was not predictive of grade 2 toxicities with CHEMO, or grade 2 or 3+ toxicities with A/E (Table). Conclusions: We provide external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO. Grade 2 toxicities are very common with both CHEMO and A/E, and grade 3+ toxicity occurs in 1 in 4 older men on A/E. Additional efforts to identify men at higher risk of toxicity from various mCRPC treatments are warranted. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 193-193
    Abstract: 193 Background: Decreased BMD is a common side effect of ADT, leading to increased fracture risk. Although loss of BMD appears to be greatest within the first 12 months of starting ADT, few data on BMD changes exist beyond 12 months, and other risk factors for bone loss in men on ADT are not well-characterized. Methods: Men age 50+ with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. A matched control group of men with prostate cancer but not on ADT was also enrolled. Medication use was recorded at each visit. Multivariable regression analyses were done to examine predictors of BMD loss. Results: 80 ADT users and 80 controls were enrolled (mean age 69.4 y); 49.7% had osteopenia and 4.6% had osteoporosis at baseline. ADT was associated with significant losses in lumbar spine BMD in year 1 compared to controls (p=0.004) and trends towards greater declines at femoral neck and total hip sites. Changes in year 2 and 3 were much smaller and not statistically different from controls (Table). Vitamin D use but not calcium use was associated with improved BMD at the lumbar spine in year 1 (+5.77%, p=0.006) with positive trends at other sites (+2.19% femoral neck, +1.76% total hip) primarily in year 1. Age was not associated with changes in BMD. Conclusions: Losses in BMD with ADT use are greatest at the lumbar spine and in the first year compared to years 2 and 3 and are independent of age. Vitamin D appears to be protective particularly in the first year of ADT use. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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