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Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Purpose Medical marijuana is often used as adjuvant therapy in cancer patients for symptom management, although limited evidence-based studies evaluating its efficacy or safety exist. Similar to over-the-counter medications, supplements, or herbal products, documentation of medical marijuana is important to monitor efficacy, potential adverse effects, or interactions. The objective of this quality improvement study was to improve the consistency of medical marijuana documentation in cancer patients by assessing current practices; educating healthcare team members about the importance of documentation and newly established documentation process; and evaluating the new documentation process. Methods This three-part quality improvement study was approved by the Institutional Review Board. In part I, a voluntary survey was sent via email to Cancer Center healthcare personnel to assess the current documentation process of medical marijuana. In part II, a best practice process for documenting medical marijuana in the electronic medical record was established. Medical marijuana was to be listed as a historical medication in the medication list. In-person and electronic education sessions were offered to Cancer Center clinical staff. The education emphasized the importance of documenting medical marijuana use and provided a detailed process for electronic medical record documentation. A pre- and post-test to assess understanding was also included. Part III was a retrospective chart review to evaluate documentation practices of certified medical marijuana users in the Cancer Center. Patients included in the study were greater than 18 years old and certified for medical marijuana use on or after 1 January 2018. Department of Corrections patients were excluded. Descriptive statistics were used for data analysis. Results The survey results in part I demonstrated a lack of consistency in the documentation of medical marijuana in the Cancer Center. The pre- and post-test scores measured in part II showed a significant improvement in understanding after education was provided. The average pre-test score was a 61 and post-test score was 88, indicating an average increase of 27 points. A larger increase in test scores was observed in those attending the in-person education than the online sessions ( p Conclusions This quality improvement study led to the implementation of medical marijuana documentation in the medication list. Education increased healthcare team members understanding of medical marijuana utilization and the importance of documentation.

Background A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. Patients and methods This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. Results Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). Conclusion In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. Clinical trial number NCT02889978.

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

BackgroundEsophageal cancer is the 11th most common cause of cancer mortality in the United States. It is aggressive in nature and has an ability to spread rapidly through direct extension, lymphatic spread, or hematogenously. With an estimated incidence of 1%, cutaneous metastases from esophageal cancer are extremely rare.Case presentationIn this case study and review, we describe a case of recurrent esophageal basaloid squamous cell carcinoma presenting as multiple, rapidly progressing and tender subcutaneous nodules. A 69-year-old male with history of basaloid squamous cell carcinoma of the esophagus treated with concurrent chemoradiation, presented to his oncologist with complaints of a large, painful nodule at the nape of his neck approximately two years after completing treatment. On further examination, he was noted to have multiple, well circumscribed, solid, tender nodules on his abdominal wall along with a painful nodule on the pulp of his index finger. Histopathology from all sites revealed skin infiltration by high-grade invasive basaloid subtype of squamous cell carcinoma, similar to patient’s prior known and treated primary esophageal cancer. Further imaging work up showed extensive metastatic disease involving lung, liver, and brain.ConclusionEsophageal squamous cell carcinoma rarely metastasize to the skin. Subcutaneous nodules can be the first presentation of recurrent disease. The lesions are commonly confused with skin infections and treated inappropriately with antibiotics, leading to delay in diagnosis of recurrent disease. Early biopsy of suspicious lesions should be performed, especially in patients with history of cancer, such that prompt diagnosis and treatment can occur to maximize patient outcomes.

Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.

4529 Background: Oncology patients experience more severe disease outcomes from COVID-19 infection than the general population. BCG is a live bovine tuberculosis bacillus with immunotherapeutic effects in urothelial cancers; it is also used as vaccination against Mycobacterium tuberculosis in parts of the world. As BCG vaccination has been associated with broad protection against viral pathogens, BCG exposure through vaccination or intravesical therapy may modulate host immunity and reduce the severity of COVID-19 infection. We report the effect of BCG exposure on COVID-19 severity in oncology patients from the CCC19 registry. Methods: The CCC19 registry (NCT04354701) was used to identify patients with prior BCG exposure. Cohort A received intravesical treatment for bladder carcinoma, and cohort B received prior BCG vaccination. Each cohort was matched 3:1 to non-BCG-exposed controls by age, sex, race, primary cancer type, cancer status, ECOG performance status (PS) and calendar time of COVID-19 infection. The primary endpoint was COVID-19 severity reported on an ordinal scale (uncomplicated, hospitalized, admitted to ICU +/- ventilated, died within 30 days) of patients exposed to prior BCG compared to matched non-exposed controls. 2-sided Wilcoxon rank-sum tests were used. Results: As of 6-Feb-2021 we included 124 patients with BCG exposure, 68 patients with bladder carcinoma who had received intravesical BCG (Cohort A), and 64 cancer patients with prior BCG vaccination (Cohort B). Median age was 76 years, IQR 69-83 (Cohort A) and 67 years, IQR 62-74 (Cohort B). Bladder cancer pts were predominately male (78%) vs 55% for Cohort B. Patients with PS 2+ were uncommon, 18% in Cohort A and 16% in Cohort B. COVID-19 illness severity was no different in patients exposed to prior intravesicular BCG (p=0.87). COVID-19 illness severity was no different in patients exposed to prior intradermal BCG vaccination (p=0.60). Conclusions: Despite this being the largest such cohort reported to date, we failed to demonstrate an association of prior BCG exposure with modulation of severity of COVID-19 illness. Prospective trials evaluating the protective effect of BCG vaccination are ongoing and will add further insight into the effect of BCG on COVID-19 illness.[Table: see text]

3071 Background: Disparities in cancer screening and outcomes based on factors such as gender, socioeconomic status, and race/ethnicity are well documented.1 The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was designed to develop and validate a blood-based multi-cancer early detection (MCED) test analyzing plasma cell-free DNA (cfDNA) to detect cancer signals across multiple cancer types and simultaneously predict cancer signal origin. Findings stratified by race/ethnicity from the third and final CCGA validation sub-study are reported. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall N = 15,254). In this pre-specified exploratory analysis from the third substudy, key objectives were to evaluate test performance for cancer signal detection (specificity, overall sensitivity, and sensitivity by clinical stage) among racial/ethnic groups. Plasma cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning approach. Overall, 4077 participants comprised the independent validation set with confirmed status (cancer: n = 2823; non-cancer: n = 1254). The groups stratified by race/ethnicity were White Non-Hispanic, Black Non-Hispanic, Other Non-Hispanic (including but not limited to Asian, Native Hawaiian, Pacific Islander, American Indian, Alaska Native), Hispanic (all races), and Other/unknown. The study was not powered to detect statistical differences between groups. Results: Cancer and non-cancer groups were predominantly White (2316/2823, 82.0% and 996/1254, 79.4%, respectively). Across racial/ethnic groups, specificity for cancer signal detection was 99.6% (White Non-Hispanic: 992/996, 95% confidence interval [99.0-99.8%]), 100.0% (Black Non-Hispanic: 85/85 [95.7-100.0%]), 100.0% (Other Non-Hispanic: 33/33 [89.6-100.0%]), 98.1% (Hispanic: 101/103 [93.2-99.5%]), and 100% (Other/unknown: 37/37 [90.6-100.0%]). Despite slight differences in cancer type and staging across racial/ethnic groups, overall sensitivity for cancer signal detection among groups ranged from 43.9% to 63.0% (White Non-Hispanic: 50.5%, 1169/2316 [48.4-52.5%], Black Non-Hispanic: 53.9%, 104/193 [46.8-60.8%], Other Non-Hispanic: 43.9%, 25/57 [31.8-56.7%], Hispanic: 63.0%, 121/192 [56.0-69.5%], and Other/unknown: 52.3%, 34/65 [40.4-64.0%]). For all racial/ethnic groups, sensitivity generally increased with clinical stage (with limited exceptions at Stage IV in some groups with small sample sizes). Conclusions: The MCED test demonstrated consistent specificity and sensitivity across racial/ethnic groups, though results are limited by sample size for some groups. These findings indicate broad applicability and support clinical implementation of this MCED test on a population scale. 1. Zavela et al. Brit J Cancer 2021. Clinical trial information: NCT02889978.

e16531 Background: Among the approaches to curative-intent therapy for MIBC, neoadjuvant cisplatin-based chemotherapy (NAC) is recognized as the gold standard. The combined modality approach of concurrent chemo-radiation is also considered a standard of care. Despite guidelines recommending multidisciplinary care, studies have shown a low adoption rate of multidisciplinary approaches for MIBC. This study aimed to describe the treatment patterns for MIBC pts using real world data. Methods: Following the appropriate IRB approvals, investigators followed a common protocol under the auspices of the Rapid Case Ascertainment at the Yale Cancer Center. Manual chart review was performed on MIBC pts diagnosed in Connecticut from 2004 –2015 and treated at investigator-affiliated hospitals. Information on medical history, comorbidity, and treatment types were recorded. This data set was linked to the Surveillance, Epidemiology, and End Results (SEER) database for demographic information. The descriptive and logistic regression were used to analyze treatment patterns and predicators in each treatment lines: surgery alone, chemotherapy alone, radiation alone and standard care (NAC followed by surgery; surgery followed by adjuvant chemotherapy and concurrent chemo-radiation). Results: The number of adult MIBC pts in the cohort was 1,198. Among them, 290 (24.2%) received surgery as the only treatment; 117 (9.8%) received chemotherapy only; 100 (8.3%) received concurrent chemo-radiation; 96 (8.0%) received NAC followed by surgery. Besides age ( OR: 0.546, 95% CI: 0.289-0.986), when comparing female to male patients on the likelihood of receiving NAC to the alternative treatment types (radiation or surgery), female pts were less likely to receive NAC than males (OR: 0.421, 95% CI: 0.184-0.930). Conclusions: Regardless of demographics, the overall adoption rate of standard care was low, consisting of 236 pts (19.7%) of the population. From the logistic regression results, age was consistently shown as a predictor for receiving NAC over the alternative treatment types, and sex was identified as another strong predictor. Older and female patients were less likely to receive NAC than younger males.[Table: see text]

3072 Background: The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) previously demonstrated that a blood-based multi-cancer early detection (MCED) test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin. Cancer classes were defined within the CCGA study for sensitivity reporting. Separately, cancer types defined by the American Joint Committee on Cancer (AJCC) criteria, which outline unique staging requirements and reflect a distinct combination of anatomic site, histology and other biologic features, were assigned to each cancer participant using the same source data for primary site of origin and histologic type. Here, we report CCGA ‘cancer class’ designation and AJCC ‘cancer type’ assignment within the third and final CCGA3 validation substudy to better characterize the diversity of tumors across which a cancer signal could be detected with the MCED test that is nearing clinical availability. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall population N = 15,254). Plasma cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning approach, and test performance, including sensitivity, was assessed. For sensitivity reporting, CCGA cancer classes were assigned to cancer participants using a combination of the type of primary cancer reported by the site and tumor characteristics abstracted from the site pathology reports by GRAIL pathologists. Each cancer participant also was separately assigned an AJCC cancer type based on the same source data using AJCC staging manual (8th edition) classifications. Results: A total of 4077 participants comprised the independent validation set with confirmed status (cancer: n = 2823; non-cancer: n = 1254 with non-cancer status confirmed at year-one follow-up). Sensitivity was reported for 24 cancer classes (sample sizes ranged from 10 to 524 participants), as well as an “other” cancer class (59 participants). According to AJCC classification, the MCED test was found to detect cancer signals across 50+ AJCC cancer types, including some types not present in the training set; some cancer types had limited representation. Conclusions: This MCED test that is nearing clinical availability and was evaluated in the third CCGA substudy detected cancer signals across 50+ AJCC cancer types. Reporting CCGA cancer classes and AJCC cancer types demonstrates the ability of the MCED test to detect cancer signals across a set of diverse cancer types representing a wide range of biologic characteristics, including cancer types that the classifier has not been trained on, and supports its use on a population-wide scale. Clinical trial information: NCT02889978.

e17051 Background: The multidisciplinary treatment of muscle-invasive bladder cancer (MIBC) has demonstrated considerable challenges in widespread clinical adoption. Despite guidelines recommending multidisciplinary, utilization of neoadjuvant chemotherapy for bladder cancer treatment remains low in the real-world settings. This study aims to examine the real-world referral patterns from urology to medical oncology and/or radiation oncology and the factors that associated with the referral following a diagnosis of MIBC. Methods: Following approval of involved IRBs, investigators followed a common protocol under the auspices of the Rapid Case Ascertainment at the Yale Cancer Center and performed manual chart review of MIBC patients diagnosed in the state of Connecticut from 2004 – 2015 and treated at investigator-affiliated hospitals. Information on medical history, radical or partial cystectomy, chemotherapy, radiation therapy, initial treating physician, and referrals to additional providers were recorded. This data set was linked to the Surveillance, Epidemiology, and End Results (SEER) database for demographic information. Logistic regression analysis adjusted with demographics (i.e. gender, race) and medical histories (i.e. prior cancers) was conducted to identify factors associated with referral. Results: Of the 665 patients whose initial treating physician was urologist, only 291 (43.8%) were referred to a medical oncologist and/or a radiation oncologist. Independent factors associated with lack of referral included: older age (OR = 0.994 for every incremental year, P-value: 0.0055), and greater Charlson comorbidity score (OR = 1.064. P-value: 0.015). Patients with kidney diseases and diabetes were less likely to be referred. Conclusions: Lack of referral to medical oncology and/or radiation oncology is a critical barrier to the use of optimal multidisciplinary therapy. Referral decision made by urologists is impacted by a patient’s age and overall health condition. [Table: see text]

Adenosquamous carcinoma is an extremely rare and lethal subtype of prostate cancer affecting an estimated 0.03 per million men annually. It has been associated with prior hormone therapy for prostate adenocarcinoma. We present a case of de novo adenosquamous carcinoma of the prostate treated with a multimodal approach including surgery, androgen-deprivation therapy, chemotherapy, and radiation. Keywords: Neoplasms, Prostate, Carcinoma, Adenosquamous

The differential diagnosis for an adult patient presenting with an aggressive-appearing bone lesion includes metastatic disease, multiple myeloma, lymphoma, chondrosarcoma, osteosarcoma, non-neoplastic conditions such as infection, and metabolic bone diseases such as Paget disease of bone[1][1]. An

Oxaliplatin, a third-generation, platinum-based agent is widely used, most commonly in the FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) regimen, which is the first-line therapy in metastatic colorectal adenocarcinoma and adjuvant chemotherapy in stage III colorectal cancer. Platinum-based products are well known for causing hypersensitivity reactions. Fever associated with oxaliplatin-hypersensitivity reactions typically follows a specific pattern. It usually starts during the oxaliplatin infusion or immediately after (within hours instead of days) and happens after several administrations (mean 2–25) with unpredictable clinical presentations. We report a case of oxaliplatin-induced hypersensitivity reaction manifesting as fever but with unusual presentation than the aforementioned features.

481 Background: Overcoming resistance to anti-PD-1 therapy in UC patients (pts) is of major interest given the modest single agent response rates for pts with mUC. Herein we report the outcome of combined NIVO and IPI in pts who progressed on single agent NIVO. Methods: This prospective, open label, adaptive study treated platinum resistant mUC pts with NIVO monotherapy with the designated intent to add IPI at disease progression. RECIST 1.1 assessments were performed every 6 wks for 24 wks then every 12 wks. Primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS) and possible associations between clinical endpoints and tumor genomic characteristics. Next generation sequencing (NGS) was performed to assess DNA Damage Response (DDR) gene mutations and Tumor Mutation Burden (TMB). Results: To date, 21 pts who progressed after NIVO monotherapy have received IPI plus NIVO. ORRs to prior NIVO monotherapy were variable; partial response (PR = 4/21, 19%), stable disease (SD = 6/21, 29%) and progressive disease (PD = 11/21,52%). 57% (12/21) had visceral metastases. For IPI + NIVO the ORR was 19% (PR: n=4, CR: n=0) and duration of response >12 mo in a subset; 2 pts with PR remain on treatment (3+, 5+ mo), 1 pt has an ongoing PR (13+ months) after stopping treatment due to toxicity. Responding disease sites include node, liver and lung. Immune-related toxicity ≥ G3 seen in 9 pts (43%), of whom 4 (44%) had disease control (PR+SD≥3mo). No correlation detected between clinical outcome and TMB or DDR mutations. Conclusions: IPI plus NIVO responses can be seen in pts with NIVO resistance and the benefit from combined checkpoint blockade can be prolonged. Immune related toxicity frequently accompanied disease control. TMB and DDR were not associated with benefit in this small cohort; immune correlative analyses are ongoing. Clinical trial information: NCT02553642. [Table: see text]

BACKGROUND There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities. METHODS These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites. RESULTS Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved ≤ 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients). CONCLUSIONS The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease. Cancer 2013;119:1994–1998. © 2013 American Cancer Society.

Oligometastatic disease was postulated by Hellman and Weichselbaum in 1995 to be a disease state that may reflect a time point in the malignant process that may be amenable to local therapies to allow for patients to achieve a durable response or possible cure despite having advanced disease. Aggressive metastasis-directed therapy has been used in malignancies such as renal cell carcinoma, non–small-cell lung cancer, and colorectal cancer with some evidence of long-term benefit in selected patients. Recently, it has been proposed that some men with oligometastatic hormone-sensitive prostate cancer may also benefit from metastasis-directed therapy. As with most malignancies, optimal therapy for prostate cancer relies on multimodal therapy, best highlighted by the survival benefit seen in high-volume metastatic prostate cancer with the addition of docetaxel to androgen-deprivation therapy. This is becoming increasingly evident for oligometastatic prostate cancer, with emerging data sets suggesting a possible benefit of local ablative therapies for metastatic lesions combined with androgen-deprivation therapy. However, the bulk of the data is retrospective and thus subject to bias. Ongoing clinical trials are evaluating combination therapy to help elucidate the role of each therapy separately and together to determine optimal interventions for this population. This clinical review discusses the retrospective data evaluating local therapies such as radiation and surgery in men with lymph node–positive disease, as well as limited bone metastases, and outlines ongoing, prospective clinical trials designed to further investigate the role of multimodality therapy in the outcomes of men with oligometastatic hormone-sensitive prostate cancer.

Background With the introduction of oral chemotherapy, the paradigm for cancer treatment is shifting. Use of oral chemotherapy agents offers a non-invasive option for patients with metastatic castrate-resistant prostate cancer. However, these medications are not without challenges including strict adherence for optimal effects, novel toxicity profiles, frequent lab parameter monitoring, high cost, and proper handling and disposal methods. Pharmacists are positioned to play a key role in providing patients with the education required to assure an optimal treatment course is carried out. Methods Two cohorts of patients receiving abiraterone, bicalutamide, or enzalutamide for metastatic castrate-resistant prostate cancer seen in our outpatient cancer center 21 months before and 24 months after the implementation of a pharmacist-led oral chemotherapy-monitoring program in December of 2012 were retrospectively compared. Patients were evaluated for number of interventions, adherence to lab parameter monitoring, and overall time on each therapy. Results Of the 64 patients identified, 31 patients fulfilled inclusion criteria. A significant increase in the average number of interventions per patient (6.9 vs. 2.6; P = 0.004) and adherence to lab parameter monitoring (10 vs. 3; P = 0.04) in the post-program implementation cohort was found. However, no significant difference in overall time on therapy (10.3 vs. 8.1; P = 0.341) between the two groups was observed. Conclusion These results suggest a potential opportunity exists to maximize oral chemotherapy treatment outcomes with the addition of a formalized monitoring program directed by an oncology pharmacist.

OBJECTIVE To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC.

Purpose SATB1, a global genome organizer, has been shown to play a role in the development and progression of some solid tumors, but its role in bladder cancer is undetermined. Moreover, there is conflicting data about the role of SATB1 in other tumors. This study was initiated to assess a potential role for SATB1 with the hypothesis that SATB1 acts as a tumor promoter in bladder cancer. Materials and methods We evaluated SATB1 expression in bladder cancer cell lines (HTB-5, HTB-9) and compared them to a benign urothelial cell line (UROtsa). Short-hairpin RNA was used to silence SATB1 in multiple cell lines, and cell death and cell proliferation were assessed using multiple assays. Results SATB1 expression was increased significantly in all cancer cell lines compared to benign urothelial cells. SATB1 expression was knocked down by short-hairpin RNA and functional outcomes, including cell number, cell-cycle arrest, cell viability, and apoptosis after cisplatin treatment, were measured. Surprisingly, knockdown of SATB1 in 2 high-grade cancer cell lines showed opposing functional roles. Compared to the non-silencing control, HTB-5 cells, showed decreased cellular proliferation and increased sensitivity to cisplatin, whereas HTB-9 cells, showed increased cell numbers and increased resistance to cisplatin. Conclusion We conclude that our results in bladder cancer are consistent with the conflicting data reported in other cancers, and that SATB1 might have different roles in cancer dependent on genetic background and stage of the cancer.

We propose here that cigarette smoke (CS), in addition to its established genotoxic effects, elicits chronic albeit sub-clinical immune suppression, which is a major contributor to cancer progression. This hypothesis, presented here primarily in the context of bladder cancers (BCs), is applicable to other cancers, including those without a confirmed link to smoking.

Objectives To create physician awareness of complementary and alternative medicine therapy use in patients with prostate cancer so that physicians can monitor for adverse events. Approximately one fourth to one third of patients diagnosed with prostate cancer reported complementary and alternative medicine use, and many of these patients are taking a supplement called "Dr. Donsbach's Prostasol." Methods We discuss the cases of 2 patients with prostate cancer who were taking Dr. Donsbach's Prostasol and developed venous thromboembolic events while taking this supplement, in the absence of other obvious risk factors. We review these 2 cases and the time-line for the development of the venous thromboembolic events and use of Dr. Donsbach's Prostasol. We compared Prostasol with PC-SPES, a similar supplement that was associated with thrombosis and was ultimately taken off the market because of patient safety concerns. Results Prostasol contains phytoestrogens that could result in both the suppression of testosterone and the predisposition to thrombosis. Both patients had suppression of their testosterone to castrate levels with an associated decrease in prostate-specific antigen at the time of their thrombotic event. Conclusions These cases are suggestive of an association between Prostasol use and venous thromboembolic events. Physicians should be aware of the use of this agent in their patients, although it is not known whether it would be appropriate to prescribe prophylactic low-dose warfarin therapy. If possible, additional study of complementary and alternative medicine therapies for safety and efficacy are indicated.

384 Background: Programmed cell death –1 (PD-1) and its ligand (PD-L1) serve as checkpoints that regulate the interaction between the immune system and tumors. Antibodies blocking PD-1 or PD-L1 enhance antitumor activity in pts with UC. NIVO, a PD-1 blocking antibody, has clinical activity in UC as a single agent. IPI, an antibody blocking the checkpoint molecule CTLA-4, has demonstrated biologic activity in UC. Dual checkpoint blockade with both NIVO and IPI also has clinical activity in UC, but has not been systematically studied in NIVO-refractory UC. We sought to evaluate whether the addition of IPI to NIVO is feasible and clinically beneficial in pts whose UC is refractory to single agent NIVO. Methods: Forty pts with advanced or metastatic UC were treated with NIVO (3 mg/kg every 2 weeks) as part of a single arm, IRB-approved, investigator initiated study (NCT02553642). The study offered the option of treatment with the combination of IPI (1 mg/kg) and NIVO (3 mg/kg) for pts who had confirmed progression after treatment with NIVO monotherapy. The combination was dosed once every 3 weeks for 4 doses and followed by NIVO monotherapy. Pts were monitored for response and toxicity. Results: Ten pts who were refractory to NIVO monotherapy were treated with the combination of IPI and NIVO. There was a modest increase in the frequency of toxicities associated with the combination, compared to NIVO alone. One pt developed grade 3 diarrhea after treatment with the combination. No grade 3/4 toxicities were observed in pts treated with NIVO monotherapy. One pt achieved a confirmed partial response. Three additional pts achieved stable disease after documented progression. Pharmacodynamic changes in peripheral blood immune cells were monitored during treatment with NIVO monotherapy and combination therapy. Conclusions: The combination of IPI and NIVO is well tolerated and may have clinical activity in pts with UC who fail to respond to PD-1 blockade. Further studies to evaluate the magnitude of clinical activity and predictors of response for this combination are needed. Clinical trial information: NCT02553642.

For patients with metastatic renal cell carcinoma (RCC), the prognosis is poor. Despite the recent approval of drugs such as sorafenib, sunitinib, and temsirolimus, durable remissions of metastatic disease are rare. This is largely due to the fact that these drugs, while effective, do not result in the eradication of disease. In 1992, the FDA approved the use of high-dose interleukin-2 (IL-2) for the treatment of patients with metastatic RCC because of a small number of patients that achieved durable responses. However, IL-2 has not become a mainstay of treatment because of the expense and toxicity associated with this therapy. This review article discusses a phase II trial that investigates predictive biomarkers that might help clinicians identify the patient population with metastatic RCC that would benefit from IL-2 therapy and therefore limit patients who receive this toxic therapy to those most likely to benefit.

e15524 Background: Bladder cancer is strongly associated with smoking, with close to a 50% case attribution. There is ample evidence to support the direct genotoxic effect of cigarette smoke on the...

4546 Background: There is evidence suggesting that PZD use may be a risk factor for BC, yet these reports are controversial. The aim of this meta-analysis is to review available data and evaluate the association between PZD and BC. Methods: Two independent reviewers conducted a systematic search of the Cochrane Library, OvidSP and PubMed for articles published January 1970 to April 2012. MeSH search terms included PZD, Actos, thiazolidinediones, diabetes mellitus (DM), and BC. Only studies reporting an effect measure for the association between PZD and BC were included. Subgroup analyses by study design and country were performed. Analysis was done using a random effect model after a preliminary review showed evidence of study heterogeneity. This was then assessed using the Cochrane’s Q and I2 statistics. Publication bias was evaluated using the Begg’s and Egger’s tests, and funnel plots. All analyses were performed using REVMAN 5.1. Results: A total of 6 studies (3 cohort and 3 case control) met the inclusion criteria. The overall pooled risk ratio (RR) for the association between PZD and BC was 1.12 (95% CI 1.09, 1.15; P 12 month). Conclusions: Our study analyzed 1,214,071 patients, demonstrating a weak association between PZD and BC. The results were significant with increase in treatment duration, which corresponds to previous studies. This meta-analysis has limitations. Not all studies reported known variables associated with BC, such as smoking or occupational exposure. They did not address patient BMI, time from DM diagnosis or previous drug therapy. These parameters reflect severity of disease and level of insulin-resistance. Future studies should evaluate markers of insulin-resistance with PZD use and correlate with BC. Understanding the link between PZD and BC in the context of DM may allow physicians to determine a more accurate risk of PZD use.

e16067 Background: Tumor Carbonic Anhydrase IX (CAIX) expression and histologic features can predict outcome in patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy. We sought to investigate the prognostic and predictive utility of such features in patients receiving VEGF-targeted therapy. Methods: We identified 118 patients with mRCC initiating first- line VEGF-targeted therapy including 94 with clinical data, clear cell histology and available tissue. Tumors were evaluated for specific histologic features and for CAIX expression by immunohistochemistry using the MN75 antibody. The relationship between these pathology findings and tumor shrinkage and other treatment outcomes was assessed. Results: Higher tumor clear cell component was independently associated with greater tumor shrinkage (p=0.02), response (p=0.02) and treatment duration (p=0.02). Patients with high vs. low tumor CAIX expression had mean tumor shrinkages of -12% vs. -5%, respectively (p=.38). There was heterogeneity in tumor responsiveness to sunitinib or sorafenib according to CAIX status (p=0.055 for interaction): mean shrinkage was -17% vs. -25% (mean difference +8%, 95% CI -14% to +31%) for sunitinib-treated patients with high vs. low tumor CAIX expression compared to -13% vs. +9% (mean difference -22%, 95% CI -42% to -1%) for sorafenib-treated patients. Conclusions: Patients with higher clear cell component in their tumors are likely to experience superior clinical benefit from VEGF-targeted therapy. Although CAIX expression was not found to be of prognostic value in patients with clear cell mRCC treated with VEGF-targeted therapy, it may be a predictive biomarker for response to sorafenib treatment. [Table: see text]

16071 Background: Sunitinib and other antiangiogenesis inhibitors have emerged from clinical trials as promising therapies for mRCC. However, patients in “real-world” clinical practice may differ f...

16042 Background: Expression of CAIX (a hypoxia induced protein and potential surrogate for VHL inactivation) and previously defined pathologic features (presence of alveolar features/absence of pa...

14636 Background: Sunitinib, sorafenib, and bevacizumab are angiogenesis inhibitors that have emerged as active therapies in the treatment of mRCC, however little is known about treatment modificat...