Biomarkers of prognosis and toxicity for metastatic melanoma patients treated with ipilimumab.

Background Metastatic melanoma has a dismal prognosis, as a consequence of its intrinsic aggressiveness and the lack of effective treatment options: in fact, until recently, systemic therapies were numbered. Ipilimumab is a fully humanized monoclonal anti-Cytotoxic T-Lymphocyte Antigen 4 antibody that demonstrated a significant improvement of metastatic melanoma patient survival, however toxicity may be severe and life threatening. Clinicians lack reliable prognostic factors for prognosis and toxicity and this makes treatment decisions difficult. Methods An observational prospective study was performed at the Veneto Institute of Oncology (IOV), the main inclusion criteria being the administration of ipilimumab 3mg/kg every 3 weeks for metastatic melanoma. A total of 140 patients were included, clinical features and circulating biomarkers were evaluated for an association with prognosis or adverse events. Out of 140 patients, 113 were evaluated for prognostic factors, and the full cohort was included in a toxicity study. A prognostic model was derived and data from 97 patients from two other Italian Institutes were used to validate this prognostic model. Results Baseline serum lactic dehydrogenase (LDH) concentration and neutrophil count were significantly associated with prognosis. In particular, patients with higher circulating levels of LDH and higher neutrophils before treatment had a shorter survival and increased HR of death (HR=1.36, 95% CI 1.16-1.58, P<.001 and HR=1.76, 95% CI 1.41-2.10, P<.001, respectively). Data were validated on the external cohort and the prognostic model was confirmed. Female patients and patients with lower baseline serum levels of interleukin-6 (IL6) had a higher risk of developing severe toxicity (OR=1.5, 95% CI 1.06-2.16 and OR=2.84 for 1ng/L variation, 95% CI 1.34-6.03, respectively). Conclusions We demonstrated that baseline levels of neutrophils and serum LDH could help clinicians to predict the outcome of melanoma patients treated with ipilimumab and that ipilimumab may not be the best treatment in patients with higher neutrophil count and LDH. Only comparative and translational studies could define if patients with high LDH and neutrophil are refractory to immunotherapy or have a more aggressive variant of melanoma independent from the treatment. Serum baseline IL6 could help in identifying patients with a greater risk of toxicity from ipilimumab and in planning a more specific monitoring during and after the treatment, with the purpose of increasing its safety. In particular, females with low IL6 serum levels should be carefully monitored for AEs

Basal cell carcinoma: 10-year experience with electrochemotherapy

BACKGROUND: Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. METHODS: In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. RESULTS: Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age 6469 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p 64 0.001). CONCLUSIONS: One or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation. Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-02Publication status: PublishedFunder: Wellcome Trust; Grant(s): 100282/Z/12/ZFunder: Cancer Research UK; Grant(s): A22902, A27412Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy

Recommendations for improving the quality of reporting clinical electrochemotherapy studies based on qualitative systematic review

Background: Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on electrochemotherapy. Methods: The quality of reporting in published studies on electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria. Results: A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on electrochemotherapy were prepared and summarized into a checklist. Conclusions: There is an increasing body of published clinical data on electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice

Immune senescence and cancer in elderly patients: Results from an exploratory study

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Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis.

The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC

Depression in Cancer: the many biobehavioural pathways driving tumor progression

Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote: (1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic-pituitary-adrenal axis. Consequently, the prompt recognition of depression among patients with cancer who may benefit of treatment strategies targeting depressive symptoms, cognitive dysfunction, fatigue and sleep disturbances, is a public health priority. Moreover, behavioral strategies aiming at reducing psychological distress and depressive symptoms, including addressing unhealthy diet and life-style choices, as well as physical inactivity and sleep dysfunction, may represent important strategies not only to treat depression, but also to improve wider cancer-related outcomes. Herein, we provide a comprehensive review of the intertwined biobehavioural pathways linking depression to cancer progression. In addition, the clinical implications of these findings are critically reviewed