Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy.

BACKGROUND: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown. PATIENTS AND METHODS: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions. RESULTS: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was ≥50% in 76 (25.2%), 1%-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pATB-exposed patients to have similar OS {hazard ratio (HR) = 1.42 [95% confidence interval (CI): 0.91-2.22]; P = 0.1207} and PFS [HR = 1.12 (95% CI: 0.76-1.63); P = 0.5552], compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% versus 57.4%, P = 0.1794). No differential effect was found depending on pATB exposure duration (≥7 versus <7 days) and route of administration (intravenous versus oral). Similarly, cATB was not associated with OS [HR = 1.29 (95% CI: 0.91-1.84); P = 0.149] and PFS [HR = 1.20 (95% CI: 0.89-1.63); P = 0.222] when evaluated as time-varying covariate in multivariable analysis. CONCLUSIONS: In contrast to what has been reported in patients receiving single-agent ICIs, pATB does not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinico-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.

Natural history of bone metastasis in colorectal cancer: final results of a large Italian bone metastases study.

BACKGROUND: Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. PATIENTS AND METHODS: This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. RESULTS: Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P=0.009) and produced a trend toward improved overall survival versus no zoledronic acid. CONCLUSION: This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting.

Camptocormia in Parkinson disease: an epidemiological and clinical study.

BACKGROUND: Camptocormia is an abnormal flexion of the thoracolumbar spine during standing and walking that abates in the recumbent position. METHODS: In a single-centre epidemiological and clinical study, the prevalence of camptocormia in Parkinson disease (PD) and its relationship with the clinical features of PD were investigated. A total of 275 consecutive outpatients were systematically screened for camptocormia with a clinical evaluation. Patients who screened positive for camptocormia were subsequently reassessed by formal goniometric analysis. The demographic and clinical features of the patients with and without camptocormia were then compared. RESULTS: A 6.9% (19/275, 95% CI, 4.2 to 10.6) prevalence of camptocormia was found. Camptocormia was found in patients with more severe PD, as clinically assessed by the Hoehn-Yahr (HY) staging and the motor Unified Parkinson Disease Rating Scale (UPDRS) part III, longer l-dopa treatment duration and greater l-dopa daily dose and presence of DSM-IV dementia. Camptocormia was reported to develop after the clinical onset of PD. No correlation was found between the degree of trunk flexion and age, duration of PD, UPDRS motor score, HY staging, and l-dopa treatment duration and dose. As a risk factor, the study identified previous vertebral surgery. CONCLUSIONS: Camptocormia, a relatively common sign in PD seems to be related to the clinical severity of PD.