High serum LDH and liver metastases are the dominant predictors of primary cancer resistance to anti-PD(L)1 immunotherapy.

AIM: Anti-PD-(L)1 immunotherapies improve survival in multiple cancers but remain ineffective for most patients. We applied machine-learning algorithms and multivariate analyses on baseline medical data to estimate their relative impact on overall survival (OS) upon anti-PD-(L)1 monotherapies. METHOD: This prognostic/predictive study retrospectively analysed 33 baseline routine medical variables derived from computed tomography (CT) images, clinical and biological meta-data. 695 patients with a diagnosis of advanced cancer were treated in prospective clinical trials in a single tertiary cancer centre in 3 cohorts including systemic anti-PD-(L)1 (251, 235 patients) versus other systemic therapies (209 patients). A random forest model combined variables to identify the combination (signature) which best estimated OS in patients treated with immunotherapy. The performance for estimating OS [95%CI] was measured using Kaplan-Meier Analysis and Log-Rank test. RESULTS: Elevated serum lactate dehydrogenase (LDHhi) and presence of liver metastases (LM+) were dominant and independent predictors of short OS in independent cohorts of melanoma and non-melanoma solid tumours. Overall, LDHhiLM+ patients treated with anti-PD-(L)1 monotherapy had a poorer outcome (median OS: 3.1[2.4-7.8] months]) compared to LDHlowLM-patients (median OS: 15.3[8.9-NA] months; P < 0.0001). The OS of LDHlowLM-patients treated with immunotherapy was 28.8[17.9-NA] months (vs 13.1[10.8-18.5], P = 0.02) in the overall population and 30.3[19.93-NA] months (vs 14.1[8.69-NA], P = 0.0013) in patients with melanoma. CONCLUSION: LDHhiLM+ status identifies patients who shall not benefit from anti-PD-(L)1 monotherapy. It could be used in clinical trials to stratify patients and eventually address this specific medical need.

Influence of Magnetic Field Strength on Magnetic Resonance Imaging Radiomics Features in Brain Imaging, an In Vitro and In Vivo Study.

BACKGROUND: The development and clinical adoption of quantitative imaging biomarkers (radiomics) has established the need for the identification of parameters altering radiomics reproducibility. The aim of this study was to assess the impact of magnetic field strength on magnetic resonance imaging (MRI) radiomics features in neuroradiology clinical practice. METHODS: T1 3D SPGR sequence was acquired on two phantoms and 10 healthy volunteers with two clinical MR devices from the same manufacturer using two different magnetic fields (1.5 and 3T). Phantoms varied in terms of gadolinium concentrations and textural heterogeneity. 27 regions of interest were segmented (phantom: 21, volunteers: 6) using the LIFEX software. 34 features were analyzed. RESULTS: In the phantom dataset, 10 (67%) out of 15 radiomics features were significantly different when measured at 1.5T or 3T (student's t-test, p < 0.05). Gray levels resampling, and pixel size also influence part of texture features. These findings were validated in healthy volunteers. CONCLUSIONS: According to daily used protocols for clinical examinations, radiomic features extracted on 1.5T should not be used interchangeably with 3T when evaluating texture features. Such confounding factor should be adjusted when adapting the results of a study to a different platform, or when designing a multicentric trial.

Life threatening bleeding from an osteonecrosis of the jaw: Are bisphosphonates safe in irradiated head and neck cancer patients?

Osteonecrosis of the jaw is a significant complication secondary to radiation therapy or drug therapy, most commonly bisphosphonates. Safety data regarding the administration of bisphosphonates in bone metastatic head and neck cancer patients with history of jaw irradiation are almost non-existent. In this paper, we report the case of a Head and Neck (HNC) patient, with history of radiation therapy to the mandible region, treated with intravenous bisphosphonates for bone metastases that resulted in gross, life threatening mouth hemorrhage secondary to advanced, locally invasive ONJ.

Bisphosphonate-related osteonecrosis of the jaw: awareness and level of knowledge of Lebanese physicians.

PURPOSE: Bisphosphonate-induced osteonecrosis of the jaw (ONJ) is a potentially destructive complication, particularly encountered in oncology. It is supposed that awareness and good knowledge of this disease by physicians are important factors of its early detection and management. This study aims to evaluate the level of knowledge among a sample of Lebanese physicians with regard to this complication. METHODS: An observational cross-sectional study was conducted at Hôtel-Dieu de France hospital between March and June 2013. Data were collected through a self-administered questionnaire distributed to 190 eligible physicians in the departments involved in prescribing bisphosphonates and managing the ONJ. RESULTS: A total of 136 valid responses were obtained (response rate 71.6 %). Eighty-six (63.2 %) physicians were treating patients with bisphosphonates: the most prescribed form being the weekly oral bisphosphonates for osteoporosis followed by zoledronate several times yearly for bone malignancies. Fifty-one (37.5 %) participants were unaware of bisphosphonate-related ONJ. Furthermore, the level of knowledge was relatively poor: the mean score of all participants was 12.42 ± 10.08, while 77 (56.6 %) had a global score more than 16 over 30. There were statistically significant associations between the level of knowledge and physicians' specialty (p value <0.0001), whether or not they prescribe bisphosphonates (p value = 0.039), the most frequently form prescribed (p value = 0.048), whether or not they attend patients already on bisphosphonate (p value = 0.047), whether or not they have observed (p value = 0.004) and treated (p value = 0.002) exposed necrotic bone of the jaw. CONCLUSIONS: Our study revealed a deficient knowledge regarding bisphosphonate-related ONJ among Lebanese physicians. Appropriate training strategies to increase their awareness are required.