Duran i Reynals Hospital

Patients enrolled in Phase I clinical trials often face substantial physical and psychological challenges. Although supportive and palliative care interventions have been previously investigated in cancer, evidence regarding their early and structured integration in Phase I populations remains limited. Multidisciplinary supportive approaches may improve symptom control and patient-centered outcomes in this context. To evaluate the impact of a structured early supportive care (ESC) program on overall quality of life, encompassing physical, psychological, and social dimensions, in patients participating in Phase I clinical trials, delivered through a systematic referral process to psycho-oncology, hospital social work, and palliative care. Participants were randomized 1:1 to receive either standard care (SC) or ESC program. The primary outcome was symptom burden, assessed with the Edmonton symptom assessment system (ESAS) which served as a proxy for overall quality of life. Secondary endpoints included psychosocial needs, assessed with the evaluation of psychosocial needs in palliative care (ENP-E) and ad hoc items on sociofamilial needs. The intervention involved multidisciplinary case discussions and referrals to appropriate supportive care services. Data were collected at baseline and at three monthly follow-ups. Longitudinal continuous outcomes were analyzed using linear mixed-effects models, and sociofamilial outcomes were analyzed using generalized estimating equations with a binomial distribution and logit link. A total of 186 patients were randomized. ESC participants improved over time, whereas SC participants worsened in both symptom burden and psychosocial needs. Linear mixed-effects models showed significantly lower ESAS scores in the ESC group (group effect β = -14.44, 95% confidence interval [95% CI] -18.13 to -10.75), with significant group × time interactions indicating attenuation of the between-group difference over time (ESC × T1: β = -14.50, 95% CI -19.21 to -9.78; ESC × T2: β = -6.75, 95% CI -10.67 to -2.83). Similar patterns were observed for psychosocial needs assessed with ENP-E (group effect: β = -3.38, 95% CI -4.52 to -2.24; ESC × T1: β = -3.61, 95% CI -5.08 to -2.14; ESC × T2: β = -1.87, 95% CI -3.14 to -0.61). Improvements in sociofamilial needs were limited to distance-related and guidance-related items. At baseline, 54% of ESC participants accessed palliative medicine, with 27% referred to psycho-oncology and social work. By T3, referrals declined to 39%, 21%, and 13%. Early integration of supportive care significantly improves symptom control and psychosocial well-being in patients enrolled in early-phase cancer trials. These findings highlight the value of early, structured multidisciplinary supportive care models specifically tailored to the needs and clinical context of Phase I cancer research.

Glucose deficiency promotes the secretion of cytokines and inflammatory factors to rewire the immune compartment and restore blood flow. Here we show that cancer cells subjected to glucose deprivation or hypoxia, but not to other metabolic stressors, secrete LIF, an interleukin-6 family cytokine implicated in the development of solid tumours. We find that mannose supplementation prevents LIF release by sustaining multiple metabolic pathways in the absence of glucose. Mechanistically, LIF release is associated with impairment of N-glycosylation and activation of PERK and MEK MAP kinases. In mouse models of non-small-cell lung cancer, reduction of LIF impairs angiogenesis and tumour growth, rewires the immune system toward an antitumour phenotype and inhibits tumour implantation in the lung. In individuals with non-small-cell lung cancer, LIF levels correlate with markers of hypoxia, glucose deprivation and angiogenesis. Overall, these findings identify LIF as a metabolic stress-induced cytokine that could be targeted to disrupt adaptive responses in cancer.

Tyrosine kinase inhibitors (TKIs) discontinuation is the standard option for patients with chronic myeloid leukaemia (CML) in deep molecular response (MR) with imatinib. This study aimed to evaluate the efficacy and safety of one year consolidation with ponatinib on treatment-free remission (TFR) rate. This was a multicenter open-label, single-arm, phase II, exploratory clinical trial including patients with CML treated ≥4 years with imatinib therapy, and MR4.0 ≥12 months. Patients entered the TFR phase after receiving ponatinib at 15 mg/day for one year. Twenty three patients received ponatinib and 19 completed consolidation. Among the patients with detectable BCR::ABL1, 70% deepened response. The 48-weeks MR4.0 rate was 68.4% (95%CI: 43.4-87.4). The 48-week TFR rate as classically defined was 73.7% (95% CI: 8 56.3-96.4). Five restarted TKIs and all regained MR. The most frequent adverse events (AEs) were constipation (34.8%), asthenia (30.4%) and myalgia (21.7%). Patients who remained relapse-free one year after ponatinib discontinuation exhibited higher levels of NK and NKT-like cells with degranulation capacity. Consolidation with ponatinib showed a high TFR rate and adequate safety, granting further research.