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The article presents a case report of a 29-year-old male patient with BRAF V600E mutated metastatic melanoma who fathered while assuming Dabrafenib and Trametinib. It include result of an observation concluding that combined Dabrafenib and Trametinib treatment did not cause any mutagenic effect on spermatogonia or ineffective spermatogenesis.

Locked-in syndrome is a rare clinical syndrome due to basilary artery thrombosis generally associated with trauma, vascular, or cardiac malformation. It can present as various types of clinical evolution and occasionally masquerades as other pathological conditions, such as infective meningoencephalitis. These complications are the cause of diagnostic delay, if not promptly recognised, followed by patient death. We report the case of a 42-year-old female with a systemic B and cutaneous T-cell non-Hodgkin's lymphoma, with a severe neutropenia lasting over a year, who eventually developed a rapid and fatal fungal mucormycosis sepsis following a skin infection on her right arm, associated with locked-in syndrome and meningoencephalitis. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy and targeted therapy represent effective therapeutic opportunities that radically changed the available armamentarium for the treatment of melanoma. In about 50% of patients with advanced disease, long-term survival can be achieved; unfortunately, the other half of patients still have limited benefit from such innovative therapies and experience complications that affect their quality of life. Affordable, reliable and easily-to-detect biomarkers are urgently needed to facilitate the decision-making process, in order to identify patients best suited to receive immune or targeted therapy, with the aims of reducing toxicities, enhancing efficacy and preventing recurrences. Immunotherapy with Ipilimumab or antibodies against programmed death (ligand) 1 (anti-PD1/PDL1), targeted therapies with BRAF-inhibitors (anti-BRAF) and their combinations significantly changed melanoma treatment options in both primary, adjuvant and metastatic setting, allowing for a cure, or at least long-term survival, in most patients. However, up to 50% of those with advance or metastatic disease still have no significant benefit from such innovative therapies, and clinicians are not able to discriminate in advance neither who is going to respond and for how long nor who is going to develop collateral effects and which ones. However, druggable targets, as well as affordable and reliable biomarkers are needed to personalize resources at a single-patient level. In this manuscript, different molecules, genes, cells, pathways and even combinatorial algorithms or scores are included in four biomarker chapters (molecular, immunological, peripheral and gut microbiota) and reviewed in order to evaluate their role in indicating a patient's possible response to treatment or development of toxicities. [ABSTRACT FROM AUTHOR]

Liver metastases are a major management problem; since they occur in tumors of different origin, they are often multiple, difficult to visualize and can lie dormant for many years. Patients with liver metastases usually die of their disease, mostly due to liver failure, since systemic treatments are unable to eradicate micro-metastasis, and interventional loco-regional procedures cannot treat all existing ones. Cholangiocarcinoma (CCA) is the second most common primary liver tumor, showing a poor overall prognosis. When resection is not possible, treatment options include tumor-focused or local ablative therapy, organ-focused or regional therapy and systemic therapy. We reviewed available loco-regional therapeutic options, with particular focus on the CHEMOSAT® Melphalan/Hepatic Delivery System (CS-HDS), which is uniquely positioned to perform a percutaneous hepatic perfusion (PHP), in order to treat the entire liver as a standalone or as complementary therapy. This system isolates the liver circulation, delivers a high concentration of chemotherapy (melphalan), filters most chemotherapy out of the blood and is a repeatable procedure. Most CS-HDS benefits are demonstrated in liver-predominant diseases, like liver metastasis from uveal melanoma (UM), hepatocarcinoma (HCC) and CCA. More than 650 procedures have been performed in Europe to date, mostly to treat liver metastases from UM. In CCA, experience is still limited, but retrospective analyses have been reported, while phase II and III studies are closed, waiting for results or ongoing. [ABSTRACT FROM AUTHOR]

The outbreak of COVID-19 pandemia is a major health worldwide concern. Patients with cancer might have a worse outcome, because of the immunosuppression determined by the tumor itself and anti-cancer treatments, including chemotherapy and radiotherapy. The impact and course of viral infection in patients receiving immunotherapy remains unknown. We report the case of a patient with metastatic melanoma, long responder to anti PD-1 blockade who got infected with Sars CoV-2, recovering without sequelae. A critical review of literature was performed. Limited data available in literature support the possibility to continue the immunotherapy in patients with cancer under control. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium.Materials and Methods: We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations.Results: Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively).Conclusion: Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain.Key Points: • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) transformation from EGFR mutant adenocarcinoma is a rare entity that is considered to be a new phenotype of SCLC. While transformation from adenocarcinoma (ADC) with EGFR exon 19 deletions and exon 21 L858R point mutations has been described, to our knowledge, no cases of transformation to SCLC from exon-18-mutated ADC have been reported. We reported a clinical case of a patient with exon-18-EGFR-transformed SCLC, and we performed a systematic review of the literature. [ABSTRACT FROM AUTHOR]

Background: Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations. Methods: We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian–Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes. Results: Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22, 95% CI 0.04–0.49; KDR gene, SNV rate: 0.1, 95% CI 0.05–0.16). Finally, two tumor suppressor genes were characterized by a high meta-analytic rate of CNVs: CDKN2A/B (CNV rate: 0.59, 95% CI 0.23–0.90) and PTEN (CNV rate: 0.31, 95% CI 0.02–0.95). Conclusion: MBMs harbored actionable molecular alterations that could be exploited as therapeutic targets to improve the poor prognosis of patients. [ABSTRACT FROM AUTHOR]

Proto-oncogene KIT is the gene encoding the receptor tyrosine kinase protein KIT. Activating mutations are found in 2.9% of neoplasms, with the highest prevalence in gastrointestinal stromal tumour. Exon 17 mutations typically alter the kinase activation loop and are relatively rare, representing 11.7% of all activating KIT mutations. Recently, KIT exon 17 mutants turned out to be a potential molecular target for the type 1 kinase inhibitor avapritinib (BLU-285). In this framework, we aimed at investigating the potential activity of avapritinib in mucosal melanoma and thymic carcinoma, two disease histologies with dismal prognosis, currently lacking evidence-based second line treatment options and in which KIT exon 17 activating mutations could represent a relevant therapeutic target. In this series, we report the only four cases of patients affected by exon 17 mutant mucosal melanoma and thymic carcinoma that have been treated in Italy with avapritinib within a Compassionate Use Program. Two patients harboured mucosal melanoma and the other two were diagnosed with thymic carcinoma. We describe a differential activity of avapritinib (3/4 patients responded, 1/4 did not respond), along with possible hypotheses to justify such differences and potential implications for precision oncology. Taken together, the inactivity of imatinib on KIT exon 17 mutations, the general low clinical efficacy of immunotherapy, as well as the consequent formal lack of standard available and active second line systemic treatments in both mucosal melanoma and thymic carcinoma, support the implementation of avapritinib in the therapeutic armamentarium, even though further prospective evidence is warranted. • Mucosal melanoma and thymic carcinoma are orphan diseases with dismal prognosis. • KIT exon 17 activating mutations are a relevant therapeutic target in both diseases. • Unlike imatinib, KIT exon 17 mutants are a target for kinase inhibitor avapritinib. • We describe activity of avapritinib in the only 4 patients treated within CU Program. • Hypotheses to justify different responses are provided, to serve precision oncology. [ABSTRACT FROM AUTHOR]

Background: Lymphocyte-predominant Hodgkin disease (LPHD) differs in biology and clinical behaviour from classic Hodgkin disease. Almost 100% of LPHD neoplastic cells express CD20 and thus rituximab could be effective; yet limited data are available. Patients and Methods: We performed a retrospective analysis on patients with LPHD who were treated with rituximab at our institution to determine the magnitude of benefit offered by this drug. Results: Seven patients were identified; 4 received the drug as single agent while the rest received it in combination with chemotherapy. All except 2 received the drug in the salvage setting. Response rate was 100% with 6 of 7 patients achieving complete remission. At a median follow-up of 2 years, 4 patients are still disease free while the rest relapsed at a median time of 27 months. Conclusion: Rituximab is effective in LPHD and should be considered; however, the optimal schedule remains to be determined. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We previously showed that therapy with anti-checkpoints T-lymphocyte-associated protein 4 (anti-CTLA-4) or antiprogrammed cell death protein 1 (anti-PD-1) agents was more effective for men as compared with women. However, because the sex-dimorphism of the immune system is complex, involving multiple elements of immune responses, it is possible that women could derive larger benefit than men from strategies other than therapy with immune checkpoint inhibitors (ICIs) alone. Here we investigated whether women could derive larger benefit than men from the combination of chemotherapy and anti-PD-1 or anti-PD-L1.Methods: We performed two meta-analyses. The first included all randomized controlled trials (RCTs) testing anti-PD1 and anti-PD-L1 plus chemotherapy vs chemotherapy to assess different efficacy between men and women. The second included all RCTs of first-line systemic treatment in advanced non-small cell lung cancer testing anti-PD-1/PD-L1 given either alone or combined with chemotherapy to assess the different efficacy of these two immunotherapeutic strategies according to patients' sex. For each RCT included in the two meta-analyses, first, a trial-specific ratio of hazard ratios (HRs) was calculated from the ratio of the reported hazard ratios in men and in women; second, these trial-specific ratios of hazard ratios were combined across trials using a random-effects model to obtain a pooled hazard ratios ratio. A pooled HRs ratio estimate lower than 1 indicates a greater treatment effect in men, and higher than 1 a greater effect in women.Results: Eight RCTs were included in the first meta-analysis. The pooled overall survival hazard ratios (OS-HRs) comparing anti-PD-1/PD-L1 plus chemotherapy vs chemotherapy was 0.76 (95% confidence interval [CI] = 0.66 to 0.87) for men and 0.48 (95% CI = 0.35 to 0.67) for women. The pooled ratio of the overall survival hazard ratios reported in men vs women was 1.56 (95% CI = 1.21 to 2.01), indicating a statistically significant greater effect for women. Six RCTs were included in the second meta-analysis: three tested an anti-PD-1 alone, whereas three RCTs tested anti-PD-1/PD-L1 plus chemotherapy. The pooled overall survival hazard ratios were 0.78 (95% CI = 0.60 to 1.00) in men and 0.97 (95% CI = 0.79 to 1.19) in women for anti-PD-1 alone, compared with 0.76 (95% CI = 0.64 to 0.91) in men and 0.44 (95% CI = 0.25 to 0.76) in women for anti-PD-1/PD-L1 plus chemotherapy. The pooled ratio of overall survival hazard ratios was 0.83 (95% CI = 0.65 to 1.06) for anti-PD-1 alone, indicating a greater effect in men, and 1.70 (95% CI = 1.16 to 2.49) for anti-PD-1/PD-L1 plus chemotherapy, indicating a greater effect in women.Conclusion: Women with advanced lung cancer derived a statistically significantly larger benefit from the addition of chemotherapy to anti-PD-1/PD-L1 as compared with men. [ABSTRACT FROM AUTHOR]

CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan-Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03-1.88) and 89% (OR = 0.11; 95%CL = 0.02-0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02-19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39-0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients. [ABSTRACT FROM AUTHOR]

Introduction Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). Methods We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017. We calculated summary relative risk (SRR) and 95% confidence intervals (95% CI) through random effect models to estimate the risk of skin malignancies among users of the following classes of anti-hypertensive drugs: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and β-blockers. We conducted sub-group and sensitivity analysis to explore causes of between-studies heterogeneity, and assessed publication bias using a funnel-plot based approach. Results Nineteen independent studies were included in the meta-analysis. CCB users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07–1.21), and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05–1.40), with acceptable between-studies heterogeneity (I 2  < 50%). There was no association between thiazide diuretics, ACEi or ARB use and skin cancer risk. We found no evidence of publication bias affecting the results. Conclusion Family doctors and clinicians should inform their patients about the increased risk of skin cancer associated with the use of CCB and β-blockers and instruct them to perform periodic skin self-examination. Further studies are warranted to elucidate the observed associations. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with a patient who experienced fatherhood while being treated with imatinib.

Background Elderly patients with metastatic melanoma have different disease characteristics and a poorer prognosis than younger patients. Data from clinical trials and expanded access programmes (EAPs) suggest ipilimumab confers a consistent survival benefit and has a similar safety profile across different age groups of patients with metastatic melanoma. Here we report the efficacy and safety of ipilimumab 3 mg/kg in elderly patients enrolled in an EAP in Italy. Methods Patients aged > 70 years with pretreated melanoma received ipilimumab 3 mg/kg every 3 weeks for four doses through an EAP. Tumour response was evaluated at baseline and after completion of induction therapy using immune-related response criteria and patients were monitored throughout the treatment period for adverse events (AEs), including immune-related AEs. Results The immune-related disease control rate among 188 evaluable patients was 38%, including four patients with an immune-related complete response, 24 with an immune-related partial response and 44 with immune-related stable disease. Median progression-free survival (PFS) was 4.0 months and the 1- and 2-year PFS rates were 21% and 12%, respectively. Median overall survival (OS) was 8.9 months; 1- and 2-year OS rates were 38% and 22%, respectively. The safety profile of ipilimumab was consistent with that observed in the general population of the Italian EAP and treatment-related AEs generally resolved within a median of 2 weeks with treatment as per protocol-specific guidelines. Conclusions These results suggest ipilimumab is a feasible treatment option in elderly patients with metastatic melanoma. Ipilimumab treatment was generally well tolerated and resulted in clinical benefit and extended survival in elderly patients treated at centres in Italy. [ABSTRACT FROM AUTHOR]

Simple Summary: Vitamin D has been extensively studied in relation to cancer risk at several body sites, but its relationship with non-melanoma skin cancer (NMSC), the most frequent malignancy in humans, is still unclear. Here, we performed a systematic literature search and meta-analysis of published studies and did not find convincing evidence that a causal association exists between vitamin D intake (from foods and supplements), vitamin D blood concentration, or polymorphisms of the genes coding for the vitamin D receptor and binding protein, and NMSC risk. We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation. [ABSTRACT FROM AUTHOR]

A number of clinical studies have demonstrated the prognostic significance of angiogenesis and angiogenic growth factors in solid tumours; however, very little is known about the relevance of these parameters in haematological malignancies. We evaluated circulating levels of angiogenic growth factors and endostatin in 36 non-Hodgkin's lymphoma (NHL) patients. Baseline vascular endothelial growth factor (VEGF) levels of patients in complete remission (CR) after a median follow-up of 21 months were significantly lower than those of patients with progressive disease (P = 0.016). Event-free survival (EFS) rate was significantly higher in patients who had baseline VEGF and basic-fibroblast growth factor (b.FGF) levels below the median values of 147 and 19.5 pg/ml (P = 0.018 and 0.039 by log-rank test, respectively). Conversely, the levels of endostatin, angiogenin and leptin were not different in CR patients compared to relapsed patients and did not correlate with EFS. Our data suggest that b-FGF and, particularly, VEGF might be considered prognostic factors in NHL staging and management. [ABSTRACT FROM AUTHOR]

Simple Summary: Talimogene laherparepvec (T-VEC; IMLYGIC®, Amgen Inc.) is the first oncolytic viral immunotherapy to be approved for the local treatment of unresectable metastatic stage IIIB/C–IVM1a melanoma. Its direct intratumoral injection aim to trigger local and systemic immunologic responses leading to tumor cell lysis, followed by release of tumor-derived antigens and subsequent activation of tumor-specific effector T-cells. Its approval has fueled the interest to study its possible sinergy with other immunotherapeutics in preclinical models as well as in clinical contextes. In fact, it has been shown that intratumoral administration of this immunostimulatory agent successfully synergizes with immune checkpoint inhibitors. The objectives of this review are to resume the current state of the art of T-VEC treatment when used in monotherapy or in combination with immune checkpoint inhibitors, describing the strong rationale of its development, the adverse events of interest and the clinical outcome in selected patient's populations. Direct intralesional injection of specific or even generic agents, has been proposed over the years as cancer immunotherapy, in order to treat cutaneous or subcutaneous metastasis. Such treatments usually induce an effective control of disease in injected lesions, but only occasionally were able to demonstrate a systemic abscopal effect on distant metastases. The usual availability of tissue for basic and translational research is a plus in utilizing this approach, which has been used in primis for the treatment of locally advanced melanoma. Melanoma is an immunogenic tumor that could often spread superficially causing in-transit metastasis and involving draining lymph nodes, being an interesting model to study new drugs with different modality of administration from normal available routes. Talimogene laherperepvec (T-VEC) is an injectable modified oncolytic herpes virus being developed for intratumoral injection, that produces granulocyte-macrophage colony-stimulating factor (GM-CSF) and enhances local and systemic antitumor immune responses. After infection, selected viral replication happens in tumor cells leading to tumor cell lysis and activating a specific T-cell driven immune response. For this reason, a probable synergistic effect with immune checkpoints inhibition have been described. Pre-clinical studies in melanoma confirmed that T-VEC preferentially infects melanoma cells and exerts its antitumor activity through directly mediating cell death and by augmenting local and even distant immune responses. T-VEC has been assessed in monotherapy in Phase II and III clinical trials demonstrating a tolerable side-effect profile, a promising efficacy in both injected and uninjected lesions, but a mild effect at a systemic level. In fact, despite improved local disease control and a trend toward superior overall survival in respect to the comparator GM-CSF (which was injected subcutaneously daily for two weeks), responses as a single agent therapy have been uncommon in patients with visceral metastases. For this reason, T-VEC is currently being evaluated in combinations with other immune checkpoint inhibitors such as ipilimumab and pembrolizumab, with interesting confirmation of activity even systemically. [ABSTRACT FROM AUTHOR]

We reviewed and meta-analysed the available evidence (until December 2019) about circulating tumour DNA (ctDNA) levels and melanoma patients survival. We included twenty-six studies (>2000 patients overall), which included mostly stage III-IV cutaneous melanoma patients and differed widely in terms of systemic therapy received and somatic mutations that were searched. Patients with detectable ctDNA before treatment had worse progression-free survival (PFS) (summary hazard ratio (SHR) 2.47, 95 % confidence intervals (CI) 1.85–3.29) and overall survival (OS) (SHR 2.98, 95 % CI 2.26–3.92), with no difference by tumour stage. ctDNA detectability during follow-up was associated with poorer PFS (SHR 4.27, 95 %CI 2.75–6.63) and OS (SHR 3.91, 95 %CI 1.97–7.78); in the latter case, the association was stronger (p = 0.01) for stage IV vs. III melanomas. Between-estimates heterogeneity was low for all pooled estimates. ctDNA is a strong prognostic biomarker for advanced-stage melanoma patients, robust across tumour (e.g. genomic profile) and patients (e.g. systemic therapy) characteristics. [ABSTRACT FROM AUTHOR]

Background:Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort. Methods:A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival. Results:Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results. [ABSTRACT FROM AUTHOR]