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Purpose. Colorectal cancer (CRC) survivors experience cancer-related cognitive impairment and co-occurring symptoms after cancer treatments. There has been little data to inform the risk factors of complex symptom phenotypes in CRC survivors. Objectives.To determine if subgroups of CRC survivors after cancer treatments could be identified based on the cognitive impairment and common co-occurring symptoms (depression, anxiety, sleep disturbance, fatigue, and pain); and to explore risk factors (sociodemographic and clinical characteristics, perceived stress, and social support) of these subgroups. Methods. Latent class profile analysis (LCPA) was used to identify subgroups based on self-reported symptoms in 64 CRC survivors. Cognitive impairment was measured by assessing subjective cognitive function using the Patient-Reported Outcome Measurement Information System (PROMIS) measure. The Kruskal-Wallis test and regression analyses were performed. Results.Three distinct latent classes were identified (Class 1: All Low ‘28.1%’; Class 2: High Psychological Symptoms (depression/anxiety) ‘25%’; Class 3: High Somatic Symptoms (fatigue, sleep disturbance, and pain) with High Cognitive Impairment’46.9%’). Pain was the most distinguishable symptom across the latent classes. The high symptom burden group was associated with less time since cancer diagnosis, higher perceived stress levels, and poor emotional social support. Conclusion.Our study adds to the information on interindividual variability in symptom experience of CRC survivors with cognitive impairment. Findings suggest a need for increased attention to screening for co-occurring symptoms (e.g., high pain) and future interventions focused on stress management and social supports.

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

PDF file - 81K, Verification of IKKe knock down

PDF file - 233K, Viability and invasion of additional ovarian cancer cell lines

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PDF file - 23K, IKK isoform IHC scoring

PDF file - 172K, Validation of IKKe gene signature

Background: Poly-ADP ribose polymerase inhibitors (PARPi) work by impairing DNA damage repair and have demonstrated activity in patients with BRCAmt breast cancer. Their mechanism of action leads to high mutational burden and increased neoantigens suggesting tumors exposed to PARPi may have increased response to immunotherapy. Preclinical and phase I/II trials have shown evidence of antitumor effect of PARPi + PD-L1 inhibition. In this study, we assessed the efficacy of the PARPi olaparib as monotherapy vs. in combination with PD-L1 inhibitor atezolizumab in patients with BRCAmt advanced breast cancer. Methods: A multicenter, randomized, open-label, phase II study was conducted. Patients were enrolled at 20 sites in the US. Patients were allowed prior hormone or chemotherapy and randomized to receive olaparib 300 mg twice daily (O) +/- atezolizumab 1200 mg IV every 21 days (O+A) until disease progression or intolerable side effect. Patients with progression on O were allowed to crossover to O+A arm. The primary endpoint was comparison of progression free survival (PFS) between arms. Overall survival (OS) was also assessed. Safety and activity analyses were done in patients who received at least one dose of study treatment. Serial tumor biopsies were collected at baseline, 6 weeks, and progression to evaluate the effect of therapy on tumor infiltrating lymphocyte populations, whole exome DNA sequencing, and correlate with outcome to assess predictive value. Enrollment has completed and the study is ongoing. The trial is registered with ClinicalTrials.gov, NCT02849496. Results: 78 patients with BRCAmt advanced breast cancer were enrolled between 5/3/2018 and 3/17/2022 and available for analysis. Groups were generally well matched on baseline characteristics. PFS was 7.0 months (95% CI 5.5-11.5) in O arm and 7.67 months (95% CI 5.6-10) in O+A arm (p=0.92). Median OS was 26.5 months (95% CI 19.2- NR) in O arm and 22.4 months (95% CI 16.6-31.3) in O+A arm (p=0.3). In triple negative breast cancer (TNBC) subgroup (n=23), there was no significant difference in PFS (p=0.92) or OS (p=0.6). Treatment was generally well tolerated with expected side effects, with O+A group experiencing more adverse events of all grades. Analysis of tumor samples from serial biopsies will be presented separately. Conclusion: Olaparib or combination olaparib + atezolizumab resulted in clinically meaningful PFS in both treatment arms. Addition of atezolizumab did not significantly increase PFS. Treatment in both arms was generally well tolerated with expected side effects based on prior drug profiles. This is the first randomized trial to show that the addition of immunotherapy (atezolizumab) to PARPi (olaparib) in patients with advanced BRCAmt breast cancer does not add to therapeutic response but carries with it additional toxicities. Citation Format: Kristina A. Fanucci, Mary Jo Pilat, Derek Shyr, Yu Shyr, Scott A. Boerner, Diane Durecki, Anne Noonan, Vandana Abramson, Cesar Santa-Maria, Hyo Han, Rita Nanda, Elizabeth Claire Dees, Haeseong Park, Saundra Buys, Namrata Peswani, Helen Chew, Hadeel Assad, Gerburg Wulf, Angelique Richardson, Meghna S. Trivedi, Adam Brufsky, James Abbruzzese, Anosheh Afghahi, Elad Sharon, Kurt Schalper, Patricia LoRusso. Olaparib +/- atezolizumab in patients with BRCA-mutated (BRCAmt) locally advanced unresectable or metastatic (advanced) breast cancer: an open-label, multicenter, randomized phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT145.

Background: Evidence-based practice in geriatric oncology is growing, and national initiatives have focused on expanding cancer care and research to improve health outcomes of older adults. However, there are still gaps between knowledge and practice for older adults with cancer. Methods: The Cancer and Aging Resiliency (CARE) clinic is a multidisciplinary approach for implementing geriatric-driven health care for older adults with cancer. The CARE clinic was developed as a direct response to recommendations targeting key multifactorial geriatric health conditions (e.g. falls, nutritional deficits, sensory loss, cognitive impairment, frailty, multiple chronic conditions, and functional status). We review the influence of these factors across the cancer care trajectory, including at screening, diagnosis, and treatment and discuss ways in which these conditions may be targeted to improve cancer care in older adults. Results: The CARE clinic was implemented at The Ohio State University Comprehensive Cancer Center (OSUCCC) and targets modifiable risk factors affecting outcomes in older adults with cancer: weight loss, polypharmacy, physical impairments, social support, and mood symptoms. The multidisciplinary team at the CARE clinic discusses and delivers a comprehensive set of recommendations, all in one clinic visit, to minimize burden on the patient and the caregiver. The CARE clinic is part of a set of initiatives that feature education of future leaders in geriatric oncology, survivorship care for an aging population, and outcomes research. Conclusions: Older adults with cancer have a unique set of needs that need to be taken into account throughout their cancer care. The CARE clinic model is an important example of an approach that may combat these difficulties and lead to better outcomes among older adults with cancer.

In a 2012 meeting at the Centers for Disease Control and Prevention (CDC), key experts and stakeholders identified public health knowledge gaps about congenital heart defects (CHDs), namely prevalence of CHDs across the life span, long‐term outcomes of persons with CHDs, and health services