Citations

Summary Chronic pain causes significant suffering, limitation of daily activities and reduced quality of life. Infection from COVID ‐19 is responsible for an ongoing pandemic that causes severe acute respiratory syndrome, leading to systemic complications and death. Led by the World Health Organization, healthcare systems across the world are engaged in limiting the spread of infection. As a result, all elective surgical procedures, outpatient procedures and patient visits, including pain management services, have been postponed or cancelled. This has affected the care of chronic pain patients. Most are elderly with multiple comorbidities, which puts them at risk of COVID ‐19 infection. Important considerations that need to be recognised during this pandemic for chronic pain patients include: ensuring continuity of care and pain medications, especially opioids; use of telemedicine; maintaining biopsychosocial management; use of anti‐inflammatory drugs; use of steroids; and prioritising necessary procedural visits. There are no guidelines to inform physicians and healthcare providers engaged in caring for patients with pain during this period of crisis. We assembled an expert panel of pain physicians, psychologists and researchers from North America and Europe to formulate recommendations to guide practice. As the COVID ‐19 situation continues to evolve rapidly, these recommendations are based on the best available evidence and expert opinion at this present time and may need adapting to local workplace policies.

Abstract Background The ability to accurately monitor response to treatment in patients with metastatic castration resistant prostate cancer (mCRPC) on chemotherapy has been a challenge. Conventional methods of therapy response assessment have limitations and molecular imaging has been explored as an important alternative. We set out t o determine if anti-1-amino-3-anti-1-amino-3-[18F]-fluorocyclobutane-1-carboxylic acid ([18F]fluciclovine) positron emission tomography/computed tomography (PET/CT) changes reflect response to docetaxel chemotherapy in mCRPC. Results Seven patients with mCRPC were enrolled. Each patient was scheduled to have [18F]fluciclovine PET/CT at baseline, and after 1 and 6 cycles of chemotherapy. Uptake parameters were recorded in the prostate/bed and up to 10 metastatic lesions. Decrease in uptake of ≥30% was considered response (R); appearance of new lesions or >30% increase in uptake was progressive disease (PD); and change of < 30% uptake was stable disease (SD). Prostate specific antigen (PSA) was obtained at baseline and before each cycle. Bone scintigraphy and CT were acquired at baseline and after the 6th cycle. Assessment of response was based on Prostate Cancer Clinical Trial Working Group 3 recommendations. Correlation between [18F]fluciclovine uptake and time to PSA progression was also determined. All patients completed the 1 st and 2 nd [18F]fluciclovine PET/CT, while 4/7 patients completed all 3 scans. PET response correlated with PSA response in 3/7 (42.9%) patients and 3/4 (75%) patients after 1 and 6 cycles of docetaxel, respectively. Bone scan and CT correlated with PSA response in 1/4 (25%) patients. Mean SUVmax and SUVmean were significantly higher in patients with progressive disease versus non-progressive disease after 6 cycles of docetaxel (p<0.05), but not at baseline or after 1 cycle of docetaxel. There was non-significant correlation of changes in [18F]fluciclovine uptake with changes in PSA after 1 and 6 cycles of docetaxel. There was no significant correlation between PET parameters and time to PSA progression. Conclusion [18F]fluciclovine PET/CT has better correlation than CT or bone scan with PSA response for patients with mCRPC treated with docetaxel. [18F]fluciclovine PET/CT did not predict time to PSA progression. Larger studies exploring the utility of [18F]fluciclovine PET for response assessment are recommended.

Abstract Background: The combination of cediranib (ced) and olaparib (olap) improves progression-free survival and overall response rates (ORR) in women with recurrent plat sensitive high-grade serous (HGS) ovarian cancer compared to olap alone. In this Phase 2 study of ced/olap in women with relapsed ovarian cancer (NCT02345265), we observed an ORR of 74% with ced/olap in plat sensitive relapsed patients (pts) and an ORR of 20% in plat resistant pts. BROCA-HR was performed to characterize tumor HRD status and to correlate this with the activity of ced/olap in the plat sensitive and resistant settings. Methods: Pts with relapsed ovarian cancer across 11 centers were enrolled to 2 cohorts, either plat sensitive or resistant. All pts received ced 30mg daily and olap tablets 200mg BID. Archival, pre-treatment, and on-treatment biopsies were collected on all pts where safely feasible; pts also had the option of undergoing a post-progression biopsy. A baseline blood sample was collected for germline testing and matched control. Available samples were sequenced with BROCA-HR, and HRD status was determined by (1) presence of an HR-related mutation or (2) an increase in loss of heterozygosity (LOH) score. Results: 72 pts were enrolled, with 70 pts receiving study treatment (35 plat sensitive and 35 plat resistant). BROCA-HR analysis is complete on 60 samples, with 10 samples in final analysis. The concordance of HRD status by presence of an HR-related mutation or by LOH score was relatively low (agreement=36/60=60%, Cohen's Kappa=0.28). In 19 pts with a germline BRCA mutation, 16 were HRD+ by LOH (LOH high), 2 were HRD- by LOH (LOH low), and 1 not quantifiable. 3 pts had a somatic BRCA mutation; 1 was LOH high, 1 LOH low, and 1 not quantifiable. 4 pts had non-BRCA somatic HR-related mutations (3 CDK12; 1 ATR); 3 were LOH high and 1 LOH low. Of the 34 pts without HR-related mutations, 15 were LOH high, 16 were LOH low, and 3 not quantifiable. In 29 plat sensitive pts with BROCA-HR results, 18 were HRD+ by mutation (12 germline BRCA, 3 somatic BRCA, 3 somatic other), and 16 were HRD+ by LOH (LOH high). The ORR in plat sensitive pts by HRD status with available HRD results was: 22/29=75.9% (13/18=72% HRDmut+; 9/11=82% HRDmut-); (12/16=75% LOH high; 6/9= 67% LOH low). In 31 plat resistant pts with BROCA-HR results, 8 were HRD+ by mutation (7 germline BRCA, 0 somatic BRCA, 1 somatic other), and 19 were HRD+ by LOH. The ORR in plat resistant pts by HRD status with available HRD results was: 7/31=22.6% (4/8=50% HRDmut+; 3/23=13% HRDmut-, P=0.05); (7/19=37% LOH high; 0/11= 0% LOH low, P=0.03). Updated results with the full data set are pending. Conclusion: Ced/olap has clinical activity in women with relapsed ovarian cancer, both in the plat sensitive and plat resistant settings. In women with plat sensitive disease, where response rates are high, HRD status by presence of an HR-related mutation or LOH status does not appear to provide significant additional information regarding likelihood of response. In women with plat resistant disease, the presence of HRD by an HR-related mutation or LOH status is correlated with a higher likelihood of response. Citation Format: Joyce F Liu, Su-Chun Cheng, Robert M Wenham, Andrea E Wahner Hendrickson, Deborah K Armstrong, Nancy Chan, David E Cohn, Jung-Min Lee, Richard T Penson, Mihaela Cristea, James Abbruzzese, Koji Matsuo, Alexander B Olawaiye, Jennifer Curtis, Geoffrey Shapiro, Ursula A Matulonis, Elise Kohn, Percy Ivy, Elizabeth M Swisher. Correlation of homologous recombination deficiency (HRD) status by BROCA-HR sequencing with response to combination cediranib and olaparib in relapsed ovarian cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A074. doi:10.1158/1535-7163.TARG-19-A074

Objective: Anemia is common during critical illness and often persists after hospital discharge; however, its potential association with physical outcomes after critical illness is unclear. Our objective was to assess the associations between hemoglobin at intensive care unit (ICU) and hospital discharge with physical status at 3-month follow-up in acute respiratory distress syndrome (ARDS) survivors. Methods: This is a secondary analysis of a multisite prospective cohort study of 195 mechanically ventilated ARDS survivors from 13 ICUs at 4 teaching hospitals in Baltimore, Maryland. Multivariable regression was utilized to assess the relationships between ICU and hospital discharge hemoglobin concentrations with measures of physical status at 3 months, including muscle strength (Medical Research Council sumscore), exercise capacity (6-minute walk distance [6MWD]), and self-reported physical functioning (36-Item Short-Form Health Survey [SF-36v2] Physical Function score and Activities of Daily Living [ADL] dependencies). Results: Median (interquartile range) hemoglobin concentrations at ICU and hospital discharge were 9.5 (8.5-10.7) and 10.0 (9.0-11.2) g/dL, respectively. In multivariable regression analyses, higher ICU discharge hemoglobin concentrations (per 1 g/dL) were associated with greater 3-month 6MWD mean percent of predicted (3.7% [95% confidence interval 0.8%-6.5%]; P = .01) and fewer ADL dependencies (−0.2 [−0.4 to −0.1]; P = .02), but not with percentage of maximal muscle strength (0.7% [−0.9 to 2.3]; P = .37) or SF-36v2 normalized Physical Function scores (0.8 [−0.3 to 1.9]; P = .15). The associations of physical outcomes and hospital discharge hemoglobin concentrations were qualitatively similar, but none were statistically significant. Conclusions: In ARDS survivors, higher hemoglobin concentrations at ICU discharge, but not hospital discharge, were significantly associated with improved exercise capacity and fewer ADL dependencies. Future studies are warranted to further assess these relationships.

10521 Background: Sarcomas are rare cancers, with > 50 subtypes, and require multi-disciplinary care. Their management benefits from multi-institutional input due to the paucity of concentrated experience with each subtype. However, sarcoma tumor boards, wherein a patient-specific, consensus treatment approach is determined, are predominantly conducted in isolation at individual centers. Methods: Since March 2010, we have conducted a weekly multi-institutional, multi-disciplinary sarcoma tumor board to combine knowledge and experience in the management of our most challenging patients. The Mayo Clinic bridge links sites by interactive videofeed. Each site may contribute cases. De-identified history, radiology and pathology are reviewed. A didactic series reviews a rotation of seminal papers, newly published research, or our own data. An “Expert Guest" series allows outside experts to connect to one conference. A yearly participant survey assesses quality. Conference is free to sites and is CME accredited. Results: Currently, 8 sarcoma programs connect Mondays from 8-9am ET. Median attendance is 20 (range: 8-27). In 2012, 342 cases were reviewed over 43 conferences (median: 8 cases/conference; range: 4-12 cases/conference). The 2012 survey revealed 96% (25/26) agreed HIPAA rules are followed; 93% (25/27) agreed conference is educational; 93% (25/27) agreed recommendations are evidenced-based or reasonable; 100% (27/27) agreed participants are respectful; and 86% (18/21) agreed input from other sites has changed their management. Staff attendance (quantity) rated as meets/exceeds needs was 100% (25/25) for medical oncology; 96% (26/27) for pathology; 93% (25/27) for orthopedic oncology; 92% (23/25) for radiation oncology, surgical oncology and radiology; and 61% (17/23) for thoracic oncology. Conclusions: To our knowledge, this is the only weekly multi-institutional sarcoma tumor board in existence. It permits consistent oncology care across a wide geographic area, and is a model for providing consensus recommendations regardless of the remoteness of the patient and care team. Future plans for this group include prospective collection of outcomes data.

TPS2621 Background: TKM-080301 is a lipid nanoparticle formulation of a small interfering RNA (siRNA) directed against PLK1, a serine/threonine kinase that regulates multiple critical aspects of cell cycle progression and mitosis. Anti-tumor activity, RNA interference and pharmacodynamic effects of PLK1 inhibition have been conclusively demonstrated in preclinical models. Demonstration of pharmacodynamic effects of PLK1 inhibition in patient biopsy samples is an exploratory objective of this first-in-human study. Methods: TKME080301 is being evaluated in an open-label, non-randomized, dose-escalation study in patients with advanced solid tumors or lymphoma. Sequential cohorts of 3 to 6 patients receive TKME080301 as a 30-minute intravenous infusion on Days 1, 8 and 15 of a 28-day cycle. Treatment can continue until disease progression, based on overall clinical benefit. Tumor response is determined according to RECIST criteria. Primary study objectives include determination of safety, maximum tolerated dose and dose limiting toxicities. Secondary objectives include characterization of pharmacokinetics and the preliminary assessment of anti-tumor activity. Five cohorts have been enrolled and a tentative Phase 2 dose has been identified. An expansion cohort of 10 patients began enrolling in February, 2013. The focus of the expansion cohort will be to collect additional safety and pharmacokinetic data at the tentative Phase 2 dose, as well as pharmacodynamic data from mandatory biopsy samples. Pre- and post-dose biopsy samples will be evaluated for potential evidence of PLK1 inhibition using 5’ RACE (rapid amplification of cDNA ends) polymerase chain reaction (to identify the predicted PLK1 mRNA cleavage product), histology (to assess for the presence of aberrant mitotic figures) and immunohistochemistry. An update on enrollment and pharmacodynamic evaluations will be presented. Clinical trial information: NCT01262235.

8053 Background: Lenalidomide (LEN) is an immunomodulatory agent that has shown significant single-agent anti-lymphoma activity in patients with relapsed disease and in combination may enhance the efficacy of rituximab by various mechanisms. There is limited data on the role of LEN in combination regimens for treatment-naïve patients. This phase II single arm trial was designed to evaluate tumor response, toxicity (AE) and survival with a combination of LEN, rituximab, cyclophosphamide (CTX) and dexamethasone (DEX) (LR-CD) in symptomatic untreated patients with low grade B-cell non-Hodgkin lymphoma. Methods: Eligibility required age ≥18, ECOG PS ≤2, confirmed diagnosis of low-grade B-cell lymphoma (FL1-2, SLL, MZL or LPL/WM), measurable nodes ≥2cm or IgM ≥400mg/dL(LPL/WM), ANC ≥1400/mm3, platelets ≥100,000/mm3, creatinine ≤2mg/dL, signed informed consent and in need of therapy. Treatment consisted of IV rituximab 375mg/m2 D1, oral LEN 20mg D1-21, CTX 250mg/m2 D1, 8, 15, DEX 40mg D1, 8, 15, 22 and ASA 325 mg daily in a 28 day cycle. Treatment continued 2 cycles beyond best response (max 12). Toxicity was assessed by NCI CTCAE v3.0. Results: 28 patients have enrolled at Mayo Clinic with 25 evaluable for toxicity and 21 for response: Median age 65(43-83), 72% male, FL 24%, MZL 28%, LPL/WM 38%, and SLL 4%. Median number of cycles given was 5. Overall response in 21 patients with response data is 95% (95% CI 76-100%) with 19% CR (95% CI 5-42%), and 76% PR (confirmed and unconfirmed, 95% CI 53-92%). The ORR in 8 patients with LPL/WM with response data was 88%, all PR (95% CI 47-100%). At a median f/u of 14.7 months 96% are alive without progression. 1 death (unrelated) occurred 7.7 months after completing 12 cycles of treatment. The most common grade ≥3 AEs were neutropenia (37.5%), leukopenia (16.7%), anemia (12.5%) and fatigue (12.5%). Conclusions: The combination LR-CD with the novel agent LEN is feasible, well tolerated and produces high response rates in symptomatic patients with low grade B-cell NHL. Toxicities are manageable and similar to reported data of single agent LEN.

3060 Background: EP-100 is a synthetic 28 amino acid LHRH peptide conjugated to an 18 aa cytolytic peptide. Selective targeting in LHRH-R expressing cells occurs via direct binding to the extracellular membrane receptor followed by disruption of the membrane by the cytolytic peptide portion. A first in human, phase I study was performed. Methods: Eligible pts had adequate organ function and LHRH-R tumor expression, as determined by IHC. EP-100 was given IV (30-60 min) weekly x 3 for cohorts 1- 6 (n=20 at 0.6 - 5.2 mg/m2) and then twice weekly x 3 for cohorts 7- 11 (n=18 at 7.8 - 40 mg/m2) with a week break. The pharmacokinetic profile of EP-100 and antibody production against EP-100 was determined by a validated HPLC/MS and ELISA respectively. Potential activity of EP-100 on the pituitary gonadotropes was determined by plasma LH and FSH. Results: We screened 97 pts, archival tumor tissue obtained from 81 pts; 53 (65%) were positive for LHRH-R, of which 37 were enrolled (female 76%) and treated. The LHRH-R expression rate in breast was 81% (N=21) and in ovarian cancer 56% (n=18). Most pts had breast (n= 16, 42%) ovary (n=7,18%), colon (n=4, 11%) or uterine (n=3, 8%) cancer. Pts were treated in a 3 + 3 standard dose escalation scheme. Doses were escalated 100% in the absence of a grade 2 drug related toxicity. MTD was not reached at the highest dose level of 40 mg/m2. Only one DLT occurred, a grade 2 increase in ALT/AST. The only other drug-related toxicity was a self limited infusion-related skin reaction (grade 1-2) in 10 pts. EP-100 was rapidly cleared from circulation, mean half life ranged from 7.1 ± 3.8 min to 15.9 ± 3.6 min. Best response was stable disease for >12 weeks in 5 pts. In 3 pts rapid, sustained decreases in LH/FSH levels were noted. Antibody production against EP-100 was absent in all pts. Conclusions: The study has completed accrual, the phase II dose is 30-40 mg/m2 twice a week x 3 weeks.EP-100is safe, well tolerated and not antigenic/immunogenic. Preclinical studies indicated synergy with paclitaxel and doxorubicin. A phase II study of EP-100 plus paclitaxel in ovarian cancer is planned.

16018 Background: Second opinions (SO) are common in medical practice. Aside from case series, little evidence exists to demonstrate a clinical benefit associated with SO. Lack of relevant data limits knowledge of numbers of patients, diseases, and motivations of SO seekers. Within the field of medical hematology/oncology (H/O), no specific demographic data are available to characterize patients seeking SO in the United States. Methods: To typify such patients at Mayo Clinic in Arizona (MCA), we recorded demographic and disease-related information for patients seeking these evaluations over a six month period from 1/1 through 6/30/05. Results: A total of 683 patients contacted MCA for medical H/O SO over the 6 month study period. A complete set of demographic and disease-related information was obtained from 655 patients; the remainder were excluded from the data set. Demographically, the majority of patients were female (53%), married (66%), and lived nearby (i.e., from Arizona-58%, or bordering state-22%). Average age was 62.3 years. Among oncologic diagnoses, the majority of patients (60% of 374 reported oncologic diagnoses) stated a diagnosis of breast, lung, colorectal, pancreatic or prostate cancer. Approximately 1/3 of patients had metastatic disease at the time they sought evaluation at MCA. There were 278 patients seeking evaluation for hematologic abnormalities, with the majority (160 patients, 58%) seeking evaluation for non-malignant conditions. Of those with malignancies, lymphoma (including Hodgkin and non-Hodgkin) was the most common (45%), followed by multiple myeloma (21%) and chronic lymphocytic leukemia (15%). Conclusions: This study provides insight into demographics and disease processes of patients seeking medical H/O SO at a tertiary care center in the United States. Although no definite conclusions can be drawn about motivations for seeking H/O SO, future research should examine patient motivation to better understand factors leading to this behavior. Given a lack of evidence for clinical benefit associated with SO seeking, and its potential costliness, better knowledge of demographic and motivational factors may allow for a more constructive approach to be taken toward the needs of SO seekers. No significant financial relationships to disclose.

Objective: The purpose of this study is to assess the outcomes of symptomatic and asymptomatic solitary dilated ducts detected on mammography, ultrasound, and MRI. Methods: All cases of isolated solitary dilated ducts between January 1, 2009 and December 31, 2016 in non-lactating females were reviewed. Clinical data, including patient’s age, breast cancer history, and pathology results were collected. Imaging was reviewed, and indication for the exam, breast density, maximum diameter of the dilated duct on ultrasound, presence of an intraductal mass, presence of intraductal vascularity, presence of intraductal echogenicity, and subareolar or peripheral location of the dilated duct were recorded. Results: 87 cases of solitary dilated ducts were assessed in this study, of which 3 were malignant, resulting in a positive predictive value of 3.5% (3/87). No malignancy was identified in asymptomatic screening patients. The three malignant cases were seen in patients presenting with a palpable lump (n = 1) or bloody nipple discharge (n = 2). There was a statistically significant association observed between the dilated duct diameter (p = 0.049) and presence of intraductal vascularity (p = 0.0005) with presence of malignancy. Conclusion: Rate of malignancy is low in solitary dilated ducts, especially among asymptomatic patients. Patient’s presenting with clinical symptoms, larger dilated duct diameters, and/or intraductal vascularity may require additional evaluation including biopsy to exclude malignancy. Advances in knowledge: Clinical and imaging factors can assist in better identifying patients with solitary dilated ducts who should undergo biopsy.