The role of cytoreductive nephrectomy and systemic therapy in the management of tumour thrombus in patients with metastatic renal cell carcinoma.

BACKGROUND: Outcomes for patients with metastatic renal cell carcinoma (mRCC) and tumour thrombus remain poor. Recent data suggest limited role for cytoreductive nephrectomy (CN) and data on thrombus response to systemic therapy (ST) is scarce. Here, we describe response and survival of patients with de novo mRCC and thrombi treated with ST with or without CN. METHODS: Demographics, disease characteristics and survival of patients with de novo mRCC were collected. Progression-free survival (PFS) and overall survival (OS) in months (m) was calculated using the Kaplan-Meier method (log-rank). RESULTS: Between 2002 and 2019, 226 patients with mRCC were identified, 64 (28.3%) had tumour thrombus out of which 18 (28.1%) received only ST. Among 12 evaluable patients, thrombus response, stability and progression were seen in 3 (25%), 6 (50%) and 3 (25%) patients, respectively. Median OS was similar for patients with and without tumour thrombus treated with systemic therapy alone [OS: 12.1 m (8.8-27.7) vs. 13.9 m (7.9-21.5), p = 0.87]. CN predicted for better OS in patients with tumour thrombus [OS: 29.4 m (17.4-48.9) vs. 12.1 m (8.8-27.7), p = 0.01]. CONCLUSION: In this retrospective series of patients with mRCC and tumour thrombus, addition of CN to ST improved outcomes. Validation of these findings with contemporary regimens is needed.

Time trends for drug specific adverse events in patients on sunitinib; implications for remote monitoring.

INTRODUCTION: Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor used to treat metastatic renal cell carcinoma (mRCC). Patients on sunitinib do require regular in-person appointments to monitor for adverse events (AEs). Given the Covid-19 pandemic, regular in-person visits expose patients to an increased risk of infection in addition to potentially preventable travel costs. This study investigated the feasibility of implementing a remote monitoring strategy for patients being treated with sunitinib for mRCC by examining the time trends of AEs. MATERIALS AND METHODS: In this retrospective chart review of patients with a diagnosis of mRCC, 167 patients received sunitinib during their treatment. The time between initiation of treatment and the first AE was recorded. The AEs were categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5. Survival analysis was used to calculate the time-to-AE. RESULTS: Of the 167 patients identified, 145 experienced an AE (86.8%). Hypertension was the most common AE with 80% of AEs were ≤ Grade 2. Incidence of AE dropped by 91% after 3 months follow up and a further 36% after 6 months. The cumulative incidence of AEs were 87.8%, 94.6% and 98.0%, at 3, 6 and 9 months respectively. The severity of AEs observed were 39.3%, 38.6%, 20.7%, 1.4%,0% of Grade 1-5 events respectively. A trend of grade migration to less severe grades was also shown over time, with percentage of Grade ≥ 3 toxicity dropping from 22% between 0-3 months to 14% beyond 6 months follow up. CONCLUSIONS: The role of remote monitoring for mRCC patients on sunitinib remains relevant now with new waves of the Covid-19 pandemic, triggered by novel variants. The majority of AEs observed were of low severity ≤ Grade 2, with a trend of reduced AE frequency and severity most prevalent beyond 3 months of follow up. This data appears to support the implementation of a remote monitoring strategy 3 months after initiation of treatment.

Physician and Artificial Intelligence Chatbot Responses to Cancer Questions From Social Media.

Importance: Artificial intelligence (AI) chatbots pose the opportunity to draft template responses to patient questions. However, the ability of chatbots to generate responses based on domain-specific knowledge of cancer remains to be tested. Objective: To evaluate the competency of AI chatbots (GPT-3.5 [chatbot 1], GPT-4 [chatbot 2], and Claude AI [chatbot 3]) to generate high-quality, empathetic, and readable responses to patient questions about cancer. Design, Setting, and Participants: This equivalence study compared the AI chatbot responses and responses by 6 verified oncologists to 200 patient questions about cancer from a public online forum. Data were collected on May 31, 2023. Exposures: Random sample of 200 patient questions related to cancer from a public online forum (Reddit r/AskDocs) spanning from January 1, 2018, to May 31, 2023, was posed to 3 AI chatbots. Main Outcomes and Measures: The primary outcomes were pilot ratings of the quality, empathy, and readability on a Likert scale from 1 (very poor) to 5 (very good). Two teams of attending oncology specialists evaluated each response based on pilot measures of quality, empathy, and readability in triplicate. The secondary outcome was readability assessed using Flesch-Kincaid Grade Level. Results: Responses to 200 questions generated by chatbot 3, the best-performing AI chatbot, were rated consistently higher in overall measures of quality (mean, 3.56 [95% CI, 3.48-3.63] vs 3.00 [95% CI, 2.91-3.09]; P < .001), empathy (mean, 3.62 [95% CI, 3.53-3.70] vs 2.43 [95% CI, 2.32-2.53]; P < .001), and readability (mean, 3.79 [95% CI, 3.72-3.87] vs 3.07 [95% CI, 3.00-3.15]; P < .001) compared with physician responses. The mean Flesch-Kincaid Grade Level of physician responses (mean, 10.11 [95% CI, 9.21-11.03]) was not significantly different from chatbot 3 responses (mean, 10.31 [95% CI, 9.89-10.72]; P > .99) but was lower than those from chatbot 1 (mean, 12.33 [95% CI, 11.84-12.83]; P < .001) and chatbot 2 (mean, 11.32 [95% CI, 11.05-11.79]; P = .01). Conclusions and Relevance: The findings of this study suggest that chatbots can generate quality, empathetic, and readable responses to patient questions comparable to physician responses sourced from an online forum. Further research is required to assess the scope, process integration, and patient and physician outcomes of chatbot-facilitated interactions.

Association of Cabozantinib Dose Reductions for Toxicity With Clinical Effectiveness in Metastatic Renal Cell Carcinoma (mRCC): Results From the Canadian Kidney Cancer Information System (CKCis).

BACKGROUND: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC. METHODS: Employing the CKCis database, we analyzed patients treated with cabozantinib in the second line or later between 2011 to 2021. The cohort was stratified into those needing dose reductions (DR) during treatment and those not (no-DR). Outcomes, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS), were compared based on dose reduction status. The influence of the initial dose on outcomes was also explored. RESULTS: Among 319 cabozantinib-treated patients, 48.3% underwent dose reductions. Response rates exhibited no significant difference between the DR and no-DR groups (15.1% vs. 18.2%, P = .55). Patients with DR had superior median OS (26.15 vs. 15.47 months, P = .019) and TTF (12.74 vs. 6.44 months, P = .022) compared to no-DR patients. These differences retained significance following adjustment for IMDC risk group (OS HR = 0.67, P = .032; TTF HR = 0.65, P = .008). There was no association between the initial dose and ORR, OS, or TTF. CONCLUSION: This study highlights the link between cabozantinib dose reductions due to toxicity and improved survival and time to treatment failure in mRCC patients. These findings underscore the potential of using on-treatment toxicity as an indicator of adequate drug exposure to individualize dosing and optimize treatment effectiveness. Larger studies are warranted to validate these results and develop individualized strategies for cabozantinib when given alone or in combination with immunotherapy.

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma: a multicentre retrospective cohort study.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are indicated for metastatic urothelial cancer (mUC), but predictive and prognostic factors are lacking. We investigated clinical variables associated with ICI outcomes. METHODS: We performed a multicentre retrospective cohort study of 135 patients who received ICI for mUC, 2016-2021, at three Canadian centres. Clinical characteristics, body mass index (BMI), metastatic sites, neutrophil-to-lymphocyte ratio (NLR), response and survival were abstracted from chart review. RESULTS: We identified 135 patients and 62% had received ICI as a second-line or later treatment for mUC. A BMI ≥25 was significantly correlated to a higher overall response rate (ORR) (45.4% vs 16.3%, p value=0.020). Patients with BMI ≥30 experienced longer median overall survival (OS) of 24.8 vs 14.4 for 25≤BMI<30 and 8.5 months for BMI <25 (p value=0.012). The ORR was lower in the presence of bone metastases (16% vs 41%, p value=0.006) and liver metastases (16% vs 39%, p value=0.013). Metastatic lymph nodes were correlated with higher ORR (40% vs 20%, p value=0.032). The median OS for bone metastases was 7.3 versus 18 months (p value <0.001). Patients with liver metastases had a median OS of 8.6 versus 15 months (p value=0.006). No difference for lymph nodes metastases (13.5 vs 12.7 months, p value=0.175) was found. NLR ≥4 had worse OS (8.2 vs 17.7 months, p value=0.0001). In multivariate analysis, BMI ≥30, bone metastases, NLR ≥4, performance status ≥2 and line of ICI ≥2 were independent factors for OS. CONCLUSIONS: Our data identified BMI and bone metastases as novel clinical biomarkers that were independently associated with ICI outcomes in mUC. External and prospective validation are warranted.

The Survival Outcomes of the Metastatic Nonclear Cell Renal Cell Carcinoma in the Immunotherapy Era: Princess Margaret Cancer Centre Experience.

Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients with metastatic clear cell renal cell carcinoma (RCC). The evidence supporting their use in metastatic nonclear cell renal cell carcinoma (nccRCC) subtypes is based on small prospective trials and retrospective analyses. Here, we report survival outcomes for patients with metastatic nccRCC treated with IO and/or TT at the Princess Margaret Cancer Centre, Toronto, ON, Canada. Demographics, disease characteristics, and survival outcomes were collected retrospectively. Overall (OS), progression-free survival (PFS), and objective response rates (ORR) were calculated. We identified 69 patients with metastatic nccRCC treated with IO and/or TT as the first-line treatment, and 36 (52.1%) patients as the second-line treatment. Median OS of the first line IO recipients (n = 12) and non-IO recipients (n = 57) was not reached (NR) and 17.2 months (95% confidence interval (95% CI): 7.3-27.0; P = 0.23), respectively. Median PFS of first-line IO recipients and non-IO recipients was NR and 4.7 months (95% CI: 3.7-5.6; P = 0.019), respectively. The ORR of IO recipients versus non-IO recipients was 50% versus 12.3% (P = 0.007). Median OS of the second-line IO recipients (n = 8) and non-IO recipients (n = 28) was NR and 6.3 months (95% CI: 3.2-9.3; P = 0.003), respectively. Median PFS of second-line IO recipients and non-IO recipients was 4.8 months (95% CI: 2.7-6.8) and 2.8 months (95% CI: 1.8-3.7; P = 0.014), respectively. ORR of IO recipients and non-IO recipients was 37.5% and 3.5%, respectively; P = 0.028. While the number of patients included in our retrospective review was small, our analysis suggested that patients with nccRCC have improved survival outcomes with IO treatment. Validation of prospective dataset is required before widespread clinical utilization.

Impact of Timing of Immunotherapy and Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: Real-World Data on Survival Outcomes from the CKCis Database.

Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN). The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST between January 2014 and June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression-free survival (PFS), after adjusting for the International Metastatic RCC Database Consortium (IMDC) risk group, age, and comorbidities. Best overall response and complications of ST and CN for these cohorts were collected. A total of 588 patients were included in this study: 331 patients received ST only, 215 patients received CN-ST, and 42 patients received ST-CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST, and metastatic sites are reported. OS analysis favored patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13-0.68) and CN-ST (HR 0.68, CI 0.47-0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26-0.77) and CN-ST (HR 0.9, CI 0.68-1.17). This study examined baseline features and outcomes associated with the use and timing of CN and ST using real-world data via a large Canadian real-world cohort. Patients selected to receive CN after ST demonstrated improved outcomes. There were no appreciable differences in perioperative complications across groups. Limitations include the small number of patients in the ST-CN group and residual confounding and selection biases that may influence the outcomes in patients undergoing CN.

Impact of the COVID-19 Pandemic on the Wellbeing of International Oncology and Hematology Fellows at the Princess Margaret Cancer Center (PMCC).

BACKGROUND: The COVID-19 pandemic has led to significant disruptions across all levels of medical training. International fellows in subspecialty training programs are essential members of the frontline physician workforce, but may face additional and unique challenges as a result of being away from their home country. In this study, we aimed to understand the impact of the COVID-19 pandemic on the wellbeing of international fellows in the Hematology and/or Oncology fellowship program at the PMCC. METHODS: In collaboration with our staff psychiatrist, we conducted an online survey of hematology and/or oncology fellows at the PMCC from July 6 to August 10, 2020. The survey consisted of 60 questions divided into 4 sections: demographics, wellbeing assessment using the validated Short Warwick Edinburgh Mental Wellbeing Scale (SWEMWBS), fellowship specific questions (personal and professional) and coping strategies using the validated brief COPE scale. RESULTS: Overall 24/52 (46%) fellows completed the survey: 21/24 were international fellows with 48% from Asia, 3/24 were Canadian fellows but away from home; 54% were male; 48% were aged 31-35 years; 65% were married, 48% had children. Mean SWEMWBS score was 21, indicating lower overall wellbeing than the general population who had a score of 23.6. Compared to their pre-COVID status, many reported a decline in their wellbeing (63%), sense of guilt for not being with their family (45%) or helping their country (41%), stress in personal relationships (26%), fatigue (50%), sleep disorders (38%) and loss of interest in daily activities (38%). Personal events were altered by almost 80%; and 20% planned to extend their fellowship. According to the Brief-COPE scale, during the pandemic, most fellows used more adaptive coping mechanisms (mean score 39.2) as opposed to maladaptive ones (mean score 21.8). CONCLUSIONS: The ongoing COVID-19 pandemic has negatively affected the overall wellbeing of international fellows. Understanding the specific challenges and coping mechanisms used by international fellows may help institutions develop better targeted strategies to promote wellbeing, professional development and ensure high-quality patient care during unprecedented times like the COVID pandemic.

The prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma treated with first-line platinum-based chemotherapy.

Background: In metastatic urothelial cancer (mUC), bone metastasis (BM) are associated with significant morbidity and mortality, yet their role as an independent prognostic variable remains unclear. We aimed to determine the impact of BM on overall survival (OS) in patients with mUC treated with first-line platinum-based chemotherapy (PBC). Methods: mUC patients receiving PBC at the Princess Margaret Cancer Center, Tom Baker Cancer Center, or Cross Cancer Institute from January 2005 to January 2018 were identified retrospectively using central pharmacy database records. Patient disease, treatment, and response characteristics were collected. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Variables reaching significance (p < 0.05) in univariable analysis (UVA) of survival (OS) were included in multivariable analysis (MVA) (Cox). Results: Overall, 376 patients with a median follow-up of 16.8 (range: 2.2-218.3) months were included. Median age was 67 (range: 28-91) years, 76% were male, 63% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and 41% had BM. All patients received first-line PBC. Patients with BM had inferior median PFS (4.9 months (95% CI 3.6-6.2) versus 6.5 months (95% CI 5.4-7.6), p = 0.03) and median OS (8.8 months (95% CI 7.8-9.7) versus 10.8 months (95% CI 9.1-12.5), p = 0.002). In UVA, ECOG PS 2-3 (p < 0.001), presence of BM (p = 0.002), and WBC count ⩾ 11,000 cells/mm3 (p = 0.001) were associated with inferior survival. Prior cystectomy (p < 0.001) and lack of progression (stable disease, partial or complete response) on treatment was associated with improved OS (p < 0.001). These variables maintained significance in MVA. Conclusion: In this retrospective study, mUC patients with BM had worse OS suggesting that BM may be an independent negative prognostic factor and including BM as a stratification factor in future mUC clinical trial designs may be warranted. A greater focus must be placed on novel therapeutic strategies to better manage BM to reduce both morbidity and mortality.

Comprehensive genomic profiling of treatment resistant metastatic castrate sensitive prostate cancer reveals high frequency of potential therapeutic targets.

INTRODUCTION: While comprehensive genomic profiling (CGP) data is becoming increasingly important in the management of prostate cancer, it remains under-utilized in the setting of metastatic castrate sensitive prostate cancer (mCSPC). We aimed to explore the feasibility and potential utility of CGP in mCSPC. PATIENTS AND METHODS: Patients with mCSPC were prospectively recruited at the Princess Margaret Cancer Centre to the OCTANE trial (NCT02906943). The objective was to assess the feasibility of profiling archival standard diagnostic tumor tissue using next generation sequencing with a custom hybridization capture DNA-based or a targeted DNA/RNA amplicon-based panel. Clinical data were extracted from electronic health records. RESULTS: Among 39 mCSPC patients enrolled, 21 (54%) had sufficient archival tissue for CGP. Most had high volume (71%) or de novo (71%) mCSPC, with the majority being androgen deprivation therapy (ADT) naïve. In total, 62% of patients had a pathogenic and/or a likely pathogenic variant, many of which involved DNA damage repair (DDR, 19%), cell cycle (24%), and Androgen Receptor (AR, 10%) pathways. After median follow-up of 32.1 months, 18 of 21 patients progressed, with median time to mCRPC of 14.3 months (95% CI 10.2-21.0). Patients with AR and DDR variants seemed to have shorter median time to mCRPC; 10.2 (95% CI 9.50-NR) and 10.3 months (95% CI 6.6-14.3) respectively. CONCLUSION: In this cohort of highly treatment resistant mCSPC, most of which were ADT-naïve, CGP using archival tumor tissue was feasible for over half of patients, and 62% of patients profiled had a pathogenic and/or a likely pathogenic variant. The presence of de novo variants provides biological basis for evaluating intensification strategies of systemic therapy. This highlights the potential role of routine CGP in biomarker development and clinical trial design in the setting of mCSPC.

Significantly Minimizing Drug Wastage and the Cost of Cabazitaxel Used to Treat Metastatic Castration-Resistant Prostate Cancer.

Cabazitaxel is used to treat patients with metastatic castration-resistant prostate cancer progressing after docetaxel. It is prepackaged in 60 mg single-dose vials, a quantity much higher than the average prescribed dose, which leads to, substantial drug wastage (DW) and associated costs. To minimize DW we implemented a cost-saving, cohorting strategy where multiple patients scheduled to receive cabazitaxel (at a dose of 20mg/m2 every 3 wks) were cohorted and treated on a single weekday whenever possible. Excess drug from each vial was then saved and used for subsequent patients treated on the same day. The drug cost with cohorting was calculated from the actual number of vials used, and the drug cost without cohorting was estimated by assumingthat one vial was used per treatment. The cost of DW was determined based on the amount of drug that was discarded. All cost calculations also accounted for the discount incentives offered by Sanofi-Aventis. Over a 3-yr period, 74 patients received 402 treatments of cabazitaxel. Multiple patients were treated on 67.4% of the treatment days, and grouping of three patients on one day saved one vial. The estimated total drug cost saved was $394 536 CAD (21.1%). Pending further studies on safety and efficacy, this strategy could potentially be adopted to mitigate DW for cabazitaxel and similarly for other oncology drugs. This would significantly decrease the overall financial burden on patients, institutions, and stakeholders. PATIENT SUMMARY: Cabazitaxel chemotherapy is associated with substantial drug wastage and associated costs. By cohorting patients scheduled to receive cabazitaxel on a single weekday, the total drug cost was decreased by $394 536 CAD (21.1%) over a 3-yr period. Similar strategies could be considered to overcome the prohibitory costs associated with drug wastage for cabazitaxel and other cancer drugs.

Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study.

BACKGROUND: Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide additional insight into the molecular underpinnings of this rare entity. METHODS: NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS). RESULTS: Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45-86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7-17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR. CONCLUSIONS: NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies.

Clinicopathologic factors that influence prognosis and survival outcomes in men with metastatic castration-resistant prostate cancer treated with Radium-223.

BACKGROUND: In men with metastatic castration-resistant prostate cancer (mCRPC) with primarily bone metastases, radium-223 (223 Ra) improves overall survival (OS). However, the selection of 223 Ra is not guided by specific validated clinicopathologic factors, and thus outcomes are heterogeneous. PATIENTS AND METHODS: This retrospective survival analysis was performed in men with mCRPC treated with 223 Ra at our cancer center. Demographics and disease characteristics were collected. OS was calculated using the Kaplan-Meier method (log-rank). The potential prognostic factors were determined using both univariable (UVA) and multivariable analysis (MVA) (Cox-regression) methods. RESULTS: In total, 150 patients with a median age of 74 years (52-93) received 223 Ra between May 2015 and July 2018, and 58% had 6-20 bone metastases. Ninety-four (63%) patients received >4 223 Ra doses, and 56 (37%) received ≤4. The following pre-treatment factors were analyzed (median [range]): eastern cooperative oncology group performance status (ECOG PS), (1 [0-3]); Albumin (ALB), (39 g/L [24-47]); alkaline phosphatase (ALP), (110 U/L [35-1633]); and prostate-specific antigen (PSA), (49 µg/L [0.83-7238]). The median OS for all patients was 14.5 months (95% CI: 11.2-18). These factors were associated with poor survival outcomes in UVA and MVA: ALB <35 g/L, ALP >150 U/L, ECOG PS 2-3, and PSA >80 µg/L. By assigning one point for each of these factors, a prognostic model was developed, wherein three distinct risk groups were identified: good, 0-1 (n = 103); intermediate, 2 (n = 30); and poor risk, 3-4 points (n = 17). The median OS was 19.4, 10.0, and 3.1 months, respectively (p < 0.001). CONCLUSIONS: Pre-treatment ALB, ALP, ECOG, and PSA, were significantly correlated with OS and could guide treatment selection for men with mCRPC by identifying those who are most or least likely to benefit from 223 Ra. Validation in an independent dataset is required prior to widespread clinical utilization.

The utility of dobutamine stress echocardiography for the diagnosis of coronary artery disease in the HIV population.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has increased human immunodeficiency virus (HIV) patient longevity by 10-15 years. This increased longevity has habituated new cardiovascular complications, in particular, accelerated coronary artery disease (CAD). Although dobutamine stress echocardiography (DSE) is a highly sensitive and specific test for the noninvasive detection of underlying CAD in the general population, its utility in the HIV population remains unknown. OBJECTIVE: The objective of the current study was to assess the validity of DSE for the noninvasive detection of underlying symptomatic CAD in the HIV population using cardiac catheterization as the gold standard. METHODS AND RESULTS: A total of 40 HIV positive patients (mean 49 ± 8 years; 31 males) between 2006 and 2009 inclusively underwent routine DSE and coronary angiography. A positive stress echo with new wall motion abnormalities was detected in 9 (23%) individuals. Coronary angiography, following DSE, detected obstructive CAD in 12 (30%) individuals. For the diagnosis of obstructive CAD, DSE has a sensitivity of 67%, specificity of 97%, positive predictive value (PPV) of 89%, and negative predictive value (NPV) of 87%. CONCLUSION: In this select HIV population, DSE was highly specific for the noninvasive detection of obstructive CAD.

Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study.

Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 +/- 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 +/- 5% vs. 51 +/- 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.

Development of pulmonary endovascular metastases following vertebroplasty: case report.

A 69-year-old man developed pulmonary metastases following vertebroplasties for pathological fractures of vertebrae T12-L4. The fractures developed due to spinal metastases from castrate-resistant prostate cancer. A CT scan performed 1 month prior indicated no evidence of pulmonary malignancy. However, CT scans performed 2 months after the vertebroplasties demonstrated intravascular pulmonary metastases distributed similarly to embolized polymethylmethacrylate. Vertebroplasty is a well-established procedure for symptomatic management of vertebral compression fractures. However, studies have demonstrated an increase in circulating tumor cells following vertebroplasties, theoretically increasing the risk of distant metastases. In this case, the chronicity and radiological findings suggest that the pulmonary intravascular metastases may have resulted from the vertebroplasties.

Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy.

BACKGROUND: Trastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10-15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR) in the assessment of trastuzumab mediated cardiomyopathy. METHODS AND RESULTS: Between 2005-2006 inclusive, 160 breast cancer patients were identified at a single tertiary care oncology centre. Of the total population, 10 patients (mean age 40 +/- 8 years) were identified with trastuzumab induced cardiomyopathy, based on a LVEF less than 40% on serial MUGA or echocardiography. CMR was performed in all patients to determine LV volumes, systolic function and evidence of late gadolinium enhancement (LGE). At the time of diagnosis of trastuzumab induced cardiomyopathy, the mean LVEF was 29 +/- 4%. Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients. CONCLUSION: LGE-CMR is a novel way of detecting early changes in the myocardium due to trastuzumab induced cardiotoxicity.