BackgroundDespite progress in surgery and care, hip fracture (HF) remains a catastrophic event, burdened with high risk of mortality and disability. This study aims at identifying predictors of recovering ambulation after intensive inpatient rehabilitation within the Tuscany Region HF rehabilitation pathway.MethodsAll HF patients referred from acute care to the two Massa-Carrara Rehabilitation facilities January 2015–June 2017 were enrolled. Comorbidity Total Score (CIRS) defined high- or low-care setting referral. Recovery of ambulation, with or without aid, (assessed by SAHFE) was the primary outcome. Personal data, comorbidity, cognitive (MMSe) and pre-fracture function (mRANKIN) were recorded on admission. Outcomes included hospital readmission, length of stay (LOS) and home discharge. Urinary catheter, bedsores, disability (modified Barthel Index-mBI), communication disability (CDS), trunk control (TCT), pain (NRS), and ambulation were recorded (admission-discharge).ResultsOf 352 patients enrolled (age 83.9 ± 7.1; 80% women), 1 died and 6 were readmitted to acute-care hospital; 97% patients referred to high-care, and 64% referred to low-care, presented moderate-high comorbidity on admission. Median LOS was 22 days; 95% patients were discharged back home; daily functional gain (mBIscore/LOS) was 1.3 ± 0.7. Patients who recovered ambulation on discharge were 84%. Older age, higher comorbidity, bladder catheter, impaired trunk control, worse cognitive and functional status on admission, and pre-fracture disability were associated to poor outcome, but only higher comorbidity and impaired communication on admission predicted failure to recover ambulation on discharge.ConclusionIn HF patients entitled to intensive inpatient rehabilitation, moderate-high comorbidity and impaired communication are frequent findings and predict rehabilitation failure.

145 Background: Activity with pembro or olaparib has been observed in mCRPC pts who progressed on 2nd-generation hormonal therapy (HT) and chemotherapy. From KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study testing combinations in mCRPC, we report early results from cohort A combining pembro + olaparib. Methods: Pts with mCRPC were eligible if they progressed within 6 months prior to screening determined by either PSA progression or radiologic progression in bone or soft tissue. Pts were docetaxel-pretreated for mCRPC, may have received 1 other chemotherapy, and had ≤2 2nd-generation HT. Pts received pembro 200 mg IV Q3W + olaparib 400 mg orally twice daily. Primary end points: safety and PSA response rate (confirmed PSA decline ≥50%). Key secondary end points: ORR RECIST v1.1 (investigator review), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, composite response rate (ORR RECIST v1.1, confirmed PSA response, or confirmed decrease in circulating tumor cell count from ≥5 to <5 cells/7.5 mL blood), rPFS, and OS. Results: Median follow-up was 11 mo. 41 initiated treatment (median age 69 years; PD-L1+ 27%; visceral disease 42%; RECIST-measurable 68%; homologous recombination repair mutation [HRR] 0%). See efficacy in table below. Treatment-related AEs occurred in 39 (95%) pts. Most frequent (≥30%) were anemia (37%), fatigue (34%), and nausea (34%). Grade 3-5 treatment-related AEs were in 21 (51%) pts. There were 2 deaths; only 1 was treatment-related (cause unknown). Conclusions: Combination of pembro + olaparib has activity in pts previously treated with docetaxel and ≤2 2nd-generation HT for mCRPC and who are HRR wild type. Observed safety profile for the combination is consistent with individual profiles of pembro and olaparib. Clinical trial information: NCT02861573. [Table: see text]

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Background: The immunomodulatory receptor TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers. In preclinical models, co-inhibition of the TIGIT and PD-L1/PD-1 pathways improved anti-tumor activity compared to either agent alone. Tiragolumab (tira or MTIG7192A) is a humanized IgG1/kappa monoclonal antibody (mAb) that binds TIGIT to prevent its interaction with its ligand PVR (CD155). In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of tira as a single agent and in combination with atezolizumab (atezo) in patients with advanced solid tumors. Methods: Enrolled patients, ECOG PS 0-1, had advanced tumors for whom standard therapy did not exist or was ineffective. Patients received escalating doses of tira alone IV Q3W alone (Phase Ia) or in combination with atezo 1200 mg IV Q3W (Phase Ib) to determine the maximum tolerated dose (MTD) and continued until disease progression, intolerable toxicity, or patient/investigator decision. Study objectives included evaluation of safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of tira alone or tira + atezo. Data cut-off date was April 2019. Results: 73 patients with multiple tumor types were treated in dose-escalation (24 in Phase Ia, 49 in Ib with tira + atezo). In Phase Ia and Phase Ib, median age was 60 and 54 years, ECOG 0 for 29% and 27% of patients, and those who received ≥ 3 prior therapies were 67% and 57%, respectively. No DLTs were observed. Across doses, treatment-related AEs occurred in 67% in Phase Ia and 59% in Phase Ib (Grade ≥ 3: 4% and 4%, respectively), and most common AEs were fatigue (38%) in Phase Ia and anemia (31%) in Phase Ib. Exposure of tira increased with increasing dose, and saturation of nonlinear PK occurred at tira doses ≥ 100 mg Q3W. Complete and sustained occupancy of peripheral TIGIT receptors was observed at tira doses ≥ 30 mg Q3W. In Phase Ia, there were no objective responses, but SD of &gt; 4 months duration was observed (n=4). In Phase Ib, there were 3 responses, which all occurred in PD-L1 positive tumors (2 non-small cell lung cancer [NSCLC]: 1 CR, 1 PR; and 1 head/neck squamous cell carcinoma: PR) with two patients not receiving prior immunotherapy (CIT-naïve). Therefore, expansion cohorts were initiated in PD-L1-positive CIT-naïve indications in Phase Ib. In the metastatic NSCLC expansion cohort (n=14) ORR was 50%, with 1 CR and 6 PRs; DCR was 79%, and the safety profile was similar. Conclusions: Tira monotherapy or combined with atezo was well-tolerated and had an acceptable safety profile across all dose levels. Preliminary anti-tumor activity was observed in Phase Ib with tira + atezo in CIT-naïve PD-L1-positive tumors, including NSCLC, and enrollment is ongoing in these expansion cohorts. Citation Format: Johanna C. Bendell, Philippe Bedard, Yung-Jue Bang, Patricia LoRusso, Stephen Hodi, Michael Gordon, Sandra D'Angelo, Sandra D'Angelo, Jayesh Desai, Elena Garralda, Antoine Italiano, Myung-Ju Ahn, Andres Cervantes, Zev Wainberg, Emiliano Calvo, Marta Gil-Martin, Maria Martinez-Garcia, Rastilav Bahleda, Philippe Cassier, Jean-Pierre Delord, Amy Prawira, Ignacio Melero, Leisha Emens, Emanuela Romano, Karen Miller, Robert W. Hsieh, Cloris Xue, Kari Morrissey, Patrick Twomey, Kelly Gash, Namrata S. Patil, Jane Grogan, Raymond Meng, Byoung Cho, Tae Won Kim. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT302.

Rationale: We aimed to predict the presence of vaccine-induced hypermetabolic lymph nodes (v-HLN) on 18 F-FDG PET/CT after Coronavirus disease 2019 (COVID-19) vaccination and determine their association with lymphocyte counts. Methods: In this retrospective single-center study, we included consecutive patients who underwent 18 F-FDG PET/CT imaging after mRNA-or viral vector-based COVID-19 vaccination between early March and late April 2021. Demographic, clinical parameters and absolute lymphocyte count (ALC) were collected and their association with the presence of v-HLN in the draining territory was studied by logistic regression.Results: Two hundred and sixty patients were eligible, including 209 (80%) women and 145 (56%) with breast cancer. The median age was 50 years (range, 23-96). Two hundred thirty-three patients (90%) received the mRNA vaccine. Ninety (35%) patients had v-HLN with a median SUVmax of 3.7 [range, 2.0-26.3] and 74 (44%) displayed lymphopenia with a median ALC of 1.4 G/L [range, 0.3-18.3]. Age ≤ 50 years (odds ratio [OR] 2.2, 95%CI 1.0-4.5), the absence of lymphopenia (OR 2.2, 95%CI 1.1-4.3) and the delay from the last vaccine injection to the date of 18 F-FDG PET/CT, if < 30 days (OR 2.6, 95%CI 1.3-5.6), were independent factors for v-HLN in multivariate analysis. In breast cancer patients, the absence of lymphopenia was the only independent factor significantly associated with v-HLN (OR 2.9, 95%CI 1.2-7.4).Conclusions: Patients with normal values of ALC after COVID-19 vaccine were more likely to have v-HLN on 18 F-FDG PET/CT, which might both be associated to a stronger immune response to vaccination. KEYWORDS 18 F-FDG PET/CT; COVID-19 vaccination; absolute lymphocyte count; hypermetabolic lymph nodes; immune response. KEY-POINTSQUESTION: Could we use lymphocyte count lymphocyte for predicting the presence of vaccineinduced hypermetabolic lymph node(s) in the drainage territory on 18 F-FDG PET/CT following COVID-19 vaccination?PERTINENT FINDINGS: This retrospective and monocentric study included 260 vaccinated patients who underwent 18 F-FDG PET/CT following mRNA based-or viral vector based-COVID-19 vaccination. Patients' absolute lymphocyte count (>lower limit of normal), along with patients' age (≤ 50 years) and the timing of last injection dose (< 30 days), significantly correlated with vaccine-induced hypermetabolic lymph node(s).IMPLICATIONS FOR PATIENT CARE: Patients displaying normal count of lymphocytes after COVID-19 vaccination are more likely to present vaccine-induced hypermetabolic lymph node(s) on 18 F-FDG PET/CT and could subsequently have higher seropositivity likelihood and antibody titers.