Assessment of bone-targeting agents use in patients with bone metastasis from breast, lung or prostate cancer using structured and unstructured electronic health records from a regional UK-based hospital

Abstract

ObjectiveTo assess use of bone-targeting agents (BTA) in patients with confirmed bone metastases (BM) from breast cancer (BC), non-small cell lung cancer (NSCLC) or prostate cancer (PC).DesignRetrospective cohort study.SettingRegional hospital-based oncology database of approximately 2 million patients in England.ParticipantsPatients aged ≥18 years with a diagnosis of BC, NSCLC or PC as well as BM between 1 January 2007 and 31 December 2018, with follow-up to 30 June 2020 or death; BM diagnosis ascertained from recorded medical codes and unstructured data using natural language processing (NLP).Main outcomes measuresInitiation or non-initiation of BTA following BM diagnosis, time from BM diagnosis to BTA initiation, time from first to last BTA, time from last BTA to death.ResultsThis study included 559 BC, 894 NSCLC and 1013 PC with BM; median age (Q1–Q3) was 65 (52–76), 69 (62–77) and 75 (62–77) years, respectively. NLP identified BM diagnosis from unstructured data for 92% patients with BC, 92% patients with NSCLC and 95% patients with PC. Among patients with BC, NSCLC and PC with BM, 47%, 87% and 88% did not receive a BTA, and 53%, 13% and 12% received at least one BTA, starting a median 65 (27–167), 60 (28–162) and 610 (295–980) days after BM, respectively. Median (Q1–Q3) duration of BTA treatment was 481 (188–816), 89 (49–195) and 115 (53–193) days for patients with BC, NSCLC and PC. For those with a death record, median time from last BTA to death was 54 (26–109) for BC, 38 (17–98) for NSCLC and 112 (44–218) days for PC.ConclusionIn this study identifying BM diagnosis from both structured and unstructured data, a high proportion of patients did not receive a BTA. Unstructured data provide new insights on the real-world use of BTA.

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy

“…Bone metastases from various cancers are a major cause of morbidity, severe pain, and mobility difficulties. The mechanisms of bone metastasis are many, and the current treatments vary. − Radionuclide treatment using Ra-223 (Xofigo) for bone pain has been approved by the FDA, providing a novel treatment to patients with castration-resistant prostate cancer with symptomatic bone metastases . It would be reasonable to assume that bone metastasis of the PSMA tumor might not be a uniform process during the progression of prostate cancer.…”

Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate

“…Solvents were dried through a molecular sieve system (Pure Solve Solvent Purification System; Innovative Technology, Inc.). 1 H NMR spectra and 13 C NMR spectra were recorded on a JEOL spectrometer at 400 and 100 MHz, respectively, and referenced to NMR solvents as indicated. Chemical shifts are reported in parts per million (δ), with coupling constants, J, in Hz.…”

“…The filtrate was concentrated, and the residue was purified by flash chromatography (DCM/MeOH/NH 4 OH = 90/10/1, v/v/v) to give compound 4 as a light yellow solid (141 mg, 0.152 mmol), yield: 41.5%. 1 H NMR (600 MHz, CD 3 OD) δ: 6.95−6.84 (m, 2H), 6.78 (dd, J = 6.2, 2.1 Hz, 2H), 6.57 (dd, J = 8.2, 1.5 Hz, 2H), 4.94 (t, J = 23.0 Hz, 1H), 4.13−3.86 (m, 9H), 3.61 (d, J = 10.2 Hz, 4H), 3.17…”

“…The solvent and volatiles were removed under vacuum, and the residue was purified by semiprep-HPLC (column: Agilent C18 250 × 9.4 mm, 5 μm, Zorbax Eclipse XDB; solvent A, 0.1% TFA in H 2 O; solvent B, 0.1% TFA in ACN; 0−20 min B 5−100%; UV = 280, t R = 6.8 min) and dried by lyophilization to give precursor P15-073 (1) as a white solid (13.8 mg, 12.2 μmol), yield: 51.7%. 1 H NMR (600 MHz, D 2 O) δ: 7.18 (t, J = 24.4 Hz, 4H), 6.87 (s, 2H), 4.54 (s, J = 24.1 Hz 1H), 4.38 (s, 4H), 3.89 (d, J = 26.9 Hz, 6H), 3.65 (d, J = 43.7 Hz, 8H), 3.17 (d, J = 16.1 Hz, 18H), 2.90−2.72 (m, 6H), 2.72−2.62 (m, 16H), 2.58 (d, J = 18.0 Hz, 2H), 2.48 (s, 2H). AMM C 45 H 69 N 9 O 21 P 2 calcd for [M + H] + 1134.4156; found 1134.4152.…”

“…The filtrate was concentrated, and the crude product was chromatographed on silica gel (DCM/ MeOH/NH 4 OH = 95/5/1, v/v/v) to give compound 8 as a white solid (30.0 mg, 22.6 μmol), yield: 56.3%. 1 H NMR (400 MHz, CD 3 OH) δ: 7.30(m, J = 13.5, 5H), 6.94 (dd, J = 13.5, 7.6 Hz, 2H), 6.80 (dd, J = 10.6, 6.9 Hz, 2H), 6.66−6.57 (m, 2H), 5.26 (dd, J = 5. 2,2′,2″- -3-oxopropyl)-2hydroxybenzyl)(carboxymethyl)amino)ethyl)(carboxymethyl)amino)methyl)-4-hydroxyphenyl)propanamido)ethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (9).…”