Neuropilin-1 and placental growth factor as prognostic factors in metastatic breast cancer.

BACKGROUND: Angiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF). MATERIALS AND METHODS: An analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member. RESULTS: The patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11-5.82, p = 0.02) and 3.11 (95% CI 1.30-7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97-19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02-8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19-0.98, p = 0.04)]. CONCLUSION: Especially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.

Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours.

INTRODUCTION: Gut microbiome-derived nanoparticles, known as bacterial extracellular vesicles (bEVs), have garnered interest as promising tools for studying the link between the gut microbiome and human health. The diverse composition of bEVs, including their proteins, mRNAs, metabolites, and lipids, makes them useful for investigating diseases such as cancer. However, conventional approaches for studying gut microbiome composition alone may not be accurate in deciphering host-gut microbiome communication. In clinical microbiome research, there is a gap in the knowledge on the role of bEVs in solid tumor patients. OBJECTIVES: Analyzing the functionality of bEVs using (meta)genomics and proteomics could highlight the unique aspects of host-gut microbiome interactions in solid tumor patients. Therefore, we performed a comparative analysis of the proteome and microbiota composition of gut microbiome-derived bEVs isolated from patients with solid tumors and healthy controls. METHODS: After isolating bEVs from the feces of solid tumor patients and healthy controls, we performed spectrometry analysis of their proteomes and next-generation sequencing (NGS) of the 16S gene. We also investigated the gut microbiomes of feces from patients and controls using 16S sequencing and used machine learning to classify the samples into patients and controls based on their bEVs and fecal microbiomes. RESULTS: Solid tumor patients showed decreased microbiota richness and diversity in both the bEVs and feces. However, the bEV proteomes were more diverse in patients than in the controls and were enriched with proteins associated with the metabolism of amino acids and carbohydrates, nucleotide binding, and oxidoreductase activity. Metadata classification of samples was more accurate using fecal bEVs (100%) compared with fecal samples (93%). CONCLUSION: Our findings suggest that bEVs are unique functional entities. There is a need to explore bEVs together with conventional gut microbiome analysis in functional cancer research to decipher the potential of bEVs as cancer diagnostic or therapeutic biomarkers.

Reasons for Treatment Discontinuation and Their Effect on Outcomes of Immunotherapy in Southwest Finland: A Retrospective, Real-World Cohort Study.

Immune checkpoint inhibitors (ICI) have improved survival in several cancer types. Still, most patients develop disease progression during or after treatment. We evaluated the reasons for treatment discontinuation and their effect on treatment outcomes in adult patients with advanced cancer with ICI in the first or later treatment lines in Southwest Finland between 1 January 2015 and 31 December 2021. Baseline characteristics and treatment outcomes were retrospectively obtained from the electronic medical records. There were 317 patients with 15 different cancer types, most commonly non-small cell lung cancer, melanoma, and kidney cancer, treated with ICI outside clinical trials. During follow-up, 94% of the patients had discontinued treatment. A total of 62% was due to disease progression, 17% due to immune-related adverse events (irAEs), 12% after achieving disease control or radiological response, and 9% due to poor performance status. The median progression-free survival (mPFS) was 5.4 months and the median overall survival (mOS) was 20.3 months in the whole cohort. Longer mPFS and mOS were observed in patients who discontinued ICI due to irAEs (24.3 and 49.2 months) and after disease control (49.7 months and not reached). In total, 46% of the patients who discontinued ICI after irAEs or disease control remained alive and progression-free during follow-up.

The impact of prognostic factors and comorbidities on survival in older adults with stage I - III cutaneous melanoma in Southwest Finland: A register study.

INTRODUCTION: Despite being diagnosed with thicker and more often ulcerated melanomas, cancer-specific survival (CSS) is not necessarily inferior in older adults with melanoma compared to younger patients. MATERIALS AND METHODS: Our aim was to evaluate the impact of baseline melanoma-specific prognostic factors and comorbidities on recurrence-free survival (RFS), CSS, and overall survival (OS) in patients aged 70-79 (n = 474) and ≥ 80 years (n = 286) with resected stage I - III cutaneous melanoma in Southwest Finland between January 1, 2000 and December 31, 2020. Patients were restaged according to the 8th edition of TNM classification, and comorbidities were assessed using the Charlson Comorbidity Index (CCI). RESULTS: Patients aged ≥80 years had thicker and more commonly ulcerated melanomas: 43.0%, 40.9%, and 16.1% of patients aged ≥80 and 56.5%, 25.3%, and 18.1% of patients aged 70-79 years were diagnosed with stage I, II, and III melanoma, respectively. Multiple comorbidities (CCI ≥2) were more common and sentinel lymph node biopsy less frequently performed in patients aged ≥80 years. RFS and CSS were similar in patients aged 70-79 years and ≥ 80 years: median RFS 13.8 years vs not reached, with the hazard ratio of melanoma recurrence or death from melanoma 1.25 (95% confidence interval [CI]: 0.91-1.71); median CSS was not reached, with the hazard ratio of death from melanoma 1.12 (95%CI: 0.81-1.75). The proportion of patients who were alive with melanoma recurrence or had died from melanoma was similar in both age groups. In multivariable analysis, higher pathological stage was the only independent risk factor for short RFS regardless of age group, sex, CCI, and tumor ulceration. Higher stage and male sex were associated with short CSS. Age ≥ 80 years, stage III disease, and CCI ≥ 2 were associated with short OS and female sex with long OS in multivariable analysis. DISCUSSION: Pathological stage was the most influential factor determining RFS and CSS in older adults with resected stage I - III melanoma. Concerning OS, age ≥ 80 years, stage III disease, and multiple comorbidities had a significant negative impact.

Smoking is an Independent Marker of Poor Prognosis in Cutaneous Melanoma.

Previous studies have suggested that persistent tobacco smoking impairs survival in cutaneous melanoma, but the effects of smoking and other prognostic factors have not been described in detail. This study examined the association of smoking (persistent, former, or never) with melanoma-specific (MSS) and overall survival (OS) in patients with cutaneous melanoma treated in Southwest Finland during 2005 to 2019. Clinical characteristics were obtained from electronic health records for 1,980 patients. Smoking status was available for 1,359 patients. Patients were restaged according to the 8th edition of the tumour-node-metastasis (TNM) classification. Smoking remained an independent prognostic factor for inferior melanoma-specific survival regardless of age, sex, stage, and comorbidities. The hazard ratio of death from melanoma was 1.81 (1.27-2.58, p = 0.001) in persistent and 1.75 (1.28-2.40, p = 0.001) in former smokers compared with never smokers. In 351 stage IV patients, smoking was associated with increased melanoma-specific and overall mortality: median MSS 10.4 (6.5-14.3), 14.6 (9.1-20.1), and 14.9 (11.4-18.4) months, p = 0.01 and median OS 10.4 (6.5-14.3), 13.9 (8.6-19.2), and 14.9 (11.7-18.1) months, p = 0.01 in persistent, former, and never smokers, respectively. In conclusion, since smoking represents an independent modifiable poor prognostic factor in patients with cutaneous melanoma, smoking habits should be proactively asked about by healthcare professionals, in order to support smoking cessation.

Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor.

BACKGROUND: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. MATERIAL AND METHODS: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. RESULTS: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. CONCLUSION: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.

Increased incidence of melanoma in children and adolescents in Finland in 1990-2014: nationwide re-evaluation of histopathological characteristics.

BACKGROUND: Changes in the incidence of melanoma in children and adolescents have been reported in Europe and in the USA in the recent decades. AIMS: The aim of this study was to examine the incidence of paediatric and adolescent melanomas in Finland in 1990-2014, and the associated clinical and histopathological characteristics to reveal temporal trends, such as changes in diagnostic sensitivity of Spitzoid melanomas. METHODS: Information on 122 patients diagnosed with cutaneous melanoma at 0-19 years of age in Finland in 1990-2014 were retrieved from the Finnish Cancer Registry. 73 primary melanoma archival samples were re-evaluated by two dermatopathologists to allow comparability over time. RESULTS: A 5.6% annual increase was observed in the incidence of melanoma among children and adolescents during the study period. Fifty-six tumours were confirmed as malignant melanomas in the re-evaluation. After correction for tumour misclassification in the Cancer Registry, the age-adjusted annual incidence was estimated to have increased from 1.4/1 000 000 in 1990-1994 to 5.8/1 000 000 in 2010-2014. The change in incidence was most prominent among adolescents and in Spitzoid melanoma subtype. Melanomas diagnosed 1990-2002 and 2003-2014 did not differ in terms of their clinicopathological characteristics or prognosis (hazard ratio for melanoma-related death 1.53, 95% CI 0.30 to 7.88). Spitzoid melanomas were diagnosed at a younger age, were of higher stage and had higher Clark level than other melanomas, yet the hazard ratio for death was 0.52 (95% CI 0.10 to 2.58) for Spitzoid versus other melanomas. CONCLUSIONS: The incidence of cutaneous melanoma has clearly increased among the young in Finland, especially among adolescents. No evidence for overdiagnosis of Spitzoid melanomas as the underlying cause of the increased incidence was observed.Key messageA nationwide retrospective re-evaluation of the cutaneous melanomas recorded in the Finnish Cancer Registry among patients aged 0-19 years in Finland in 1990-2014 revealed an approximately 4-fold increase in the incidence. The increase in the incidence was most prominent among adolescents and in the Spitzoid melanoma subtype. Our results contrast those reported in other countries, where the incidence of melanoma among adolescents has declined.

Survival of Women Previously Diagnosed of Melanoma with Subsequent Pregnancy: A Systematic Review and Meta-Analysis and a Single-Center Experience.

Melanoma incidence has increased over the last few decades. How the prognosis of a previously diagnosed melanoma may be affected by a woman's subsequent pregnancy has been debated in the literature since the 1950s, and the outcomes are essential to women who are melanoma survivors in their childbearing years. The main objective of this systematic review is to improve the understanding of whether the course of melanoma in a woman may be altered by a subsequent pregnancy and to help clinicians' diagnosis. Eligible studies for the systematic review were clinical trials, observational cohort studies and case-control studies that compared prognosis outcomes for non-pregnant patients with melanoma, or pregnant before melanoma diagnosis, versus pregnant patients after a diagnosis of melanoma. The search strategy yielded 1101 articles, of which 4 met the inclusion criteria for the systematic review. All the studies were retrospective non-randomised cohorts with patients with melanomas diagnosed before pregnancy. According to our findings, a subsequent pregnancy was not a significant influence on the outcome of a previous melanoma. However, given the small number of identified studies and the heterogeneous data included, it is recommended to approach these patients with caution, and counselling should be given by known prognostic factors. We also reviewed the medical records of 84 patients of childbearing age (35.8 ± 6.3 years, range 21-45 years) who were diagnosed with cutaneous invasive melanoma in our hospital between 2008 and 2018 (N = 724). Of these, 11 (13.1%) had a pregnancy after melanoma diagnosis (age at pregnancy: 35.6 ± 6.3 years). No statistical differences in outcome were detected.

Different expression of BRAFV600E, ALK and PD-L1 in melanoma in children and adolescents: a nationwide retrospective study in Finland in 1990-2014.

BACKGROUND: Pediatric melanoma may have a different biological background and more favorable prognosis compared with melanoma in adults. The aim of this study was to investigate melanoma in children and adolescents in the Finnish population in terms of incidence, clinical course, treatment, prognosis and BRAFV600E-, ALK- and PD-L1-positivity of the primary tumors. MATERIALS AND METHODS: Primary tumor samples and clinical records of all patients aged 0-19 years diagnosed with cutaneous melanoma in Finland in 1990-2014 were collected using the Finnish Cancer Registry database, Finnish hospitals and private pathology laboratories. BRAFV600E, ALK and PD-L1 were analyzed from 54 primary tumors and BRAFV600E from six metastasis samples. RESULTS: A total of 122 patients diagnosed with cutaneous melanoma were retrieved from the Cancer Registry database. The primary tumor samples of 73 patients were obtained for the review, and 56 cases were included in the study. The incidence of pediatric melanoma increased from 0.02 to 0.1/100 000 during the period 1990-2014. Spitzoid melanoma was the most common subtype (66%). The 10-year cancer-specific survival (CSS) was 88.7% in all patients. The 10-year-CSS did not differ in SLNB-positive or -negative groups. BRAFV600E was positive in 48%, ALK in 9% and PD-L1 in 2% of the tumors. BRAFV600E mutation was associated with 83% of melanoma deaths. CONCLUSIONS: Young melanoma patients had more favorable prognosis and a different staining profile for BRAFV600E, ALK, and PD-L1 in primary tumor than reported in adults. SLNB status was not an indicator for survival. BRAFV600E-positive patients have worse prognosis and could benefit from surveillance and treatment similarly to adults.

Follow-Up of Cancer Patients Receiving Anti-PD-(L)1 Therapy Using an Electronic Patient-Reported Outcomes Tool (KISS): Prospective Feasibility Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy. OBJECTIVE: This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance. METHODS: In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)- ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression. RESULTS: A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain. CONCLUSIONS: According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated. TRIAL REGISTRATION: Clinical Trials Register, NCT3928938; https://clinicaltrials.gov/ct2/show/NCT03928938.

High baseline Tie1 level predicts poor survival in metastatic breast cancer.

BACKGROUND: Angiopoietin growth factors (Angs) regulate angiogenesis and lymphangiogenesis by binding to the endothelial Tie2 receptor. Ang2 expression is elevated in tissue hypoxia and inflammation, which also induce cleavage of the extracellular domain of the orphan Tie1 receptor. Here we have examined if the concentrations of Ang2 and the soluble extracellular domain of Tie1 in patient plasma are associated with the prognosis of patients with metastatic breast cancer. METHODS: Plasma Tie1 and Ang2 levels were measured in metastatic breast cancer patients treated in a phase II trial with a taxane-bevacizumab combination chemotherapy in the first-line treatment setting. They were analyzed before treatment, after 6 weeks and 6 months of treatment, and at the final study visit. Using the median concentrations as cutoffs, Tie1 and Ang2 data were dichotomized into low and high concentration groups. Additionally, we analyzed Tie1 concentrations in plasma from 10 healthy women participating in a breast cancer primary prevention study. RESULTS: Plasma samples were available from 58 (89%) of the 65 patients treated in the trial. The baseline Tie1 levels of the healthy controls were significantly lower than those of the metastatic patients (p < 0.001). The overall survival of the patients with a high baseline Tie1 level was significantly shorter (multivariate HR 3.07, 95% CI 1.39-6.79, p = 0.005). Additionally, the progression-free survival was shorter for patients with a high baseline Tie1 level (multivariate HR 3.78, 95% CI 1.57-9.09, p = 0.003). In contrast, the baseline Ang2 levels had no prognostic impact in a multivariate Cox proportional hazard regression analysis. The combined analysis of baseline Tie1 and Ang2 levels revealed that patients with both high Tie1 and high Ang2 baseline levels had a significantly shorter overall survival than the patients with low baseline levels of both markers (multivariate HR for overall survival 4.32, 95% CI 1.44-12.94, p = 0.009). CONCLUSIONS: This is the first study to demonstrate the prognostic value of baseline Tie1 plasma concentration in patients with metastatic breast cancer. Combined with the results of the Ang2 analyses, the patients with both high Tie1 and Ang2 levels before treatment had the poorest survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00979641, registration date 19-DEC-2008. The regional Ethics Committee: R08142M, registration date 18-NOV-2008.

Uveal Melanoma: A European Network to Face the Many Challenges of a Rare Cancer.

Uveal melanoma (UM) is the most frequent primary ocular cancer in adults, accounting for 5% of all melanomas. Despite effective treatments for the primary tumour, up to 50% of UM patients will develop metastasis, leading to a very poor prognosis and a median overall survival of 6 to 12 months, with no major improvements in the last 30 years. There is no standard oncological treatment available for metastatic UM patients, and BRAF/MEK and immune checkpoint inhibitors show disappointing results when compared to cutaneous melanoma (CM). Recent advances in biology, however, identified specific gene and chromosome alterations, potentially permitting an actively tailored surveillance strategy, and dedicated clinical studies. Being a rare cancer, UM patients have to overcome issues such as identifying referral centres, having access to information, and partnering with oncologists for specific management strategies and research priorities. Here, we describe how the EUropean Rare Adult solid CAacer Network (EURACAN) will help in addressing these challenges and accelerating international collaborations to enhance the development of innovative treatments in UM.

Low Plasma IL-8 Levels During Chemotherapy Are Predictive of Excellent Long-Term Survival in Metastatic Breast Cancer.

BACKGROUND: Interleukin (IL)-8 is a proinflammatory cytokine, and high levels of IL-8 are associated with poor prognosis in many malignancies. The objective of this study was to explore the clinical benefit of monitoring plasma IL-8 levels during breast cancer chemotherapy. PATIENTS AND METHODS: We conducted an exploratory analysis of several circulating proteins, including IL-8, in the plasma. Plasma samples were obtained from 58 metastatic breast cancer patients who took part in a prospective phase 2 first-line bevacizumab chemotherapy trial. Samples were analyzed before therapy, after 6 weeks and 6 months of treatment, and at the final study visit. On the basis of a trajectory analysis of the plasma IL-8 levels, the patients were divided into 3 trajectory groups. RESULTS: Plasma IL-8, IL-6, IL-18, matrix metalloproteinase (MMP)-2, MMP-9, YKL-40, resistin, and high-mobility group box 1 (HMGB1) concentrations were measured, and the most pronounced predictor of patient survival was IL-8. On the basis of the trajectory analysis of the IL-8 levels, the majority of patients (n = 35, 60%) belonged to trajectory group 1, and these patients had significantly lower IL-8 levels before and during the entire chemotherapy treatment period than did the patients in the other groups. Trajectory group 1 patients had significantly better overall survival compared to patients in trajectory group 2 (n = 17; age-adjusted HR = 2.45; 95% confidence interval, 1.21-5.97; P = .012) and 3 (n = 6; age-adjusted HR = 8.65; 95% confidence interval, 3.16-23.7; P < .001). CONCLUSION: Low IL-8 levels during chemotherapy treatment might help identify patients with prolonged survival.

Long-term Survival of Stage IV Melanoma Patients Treated with BOLD Combination Chemotherapy and Intermediate-dose Subcutaneous Interferon-alpha.

BACKGROUND: Immune checkpoint and serine/threonine-protein kinase inhibitors have become a standard of care for advanced cutaneous melanoma, but dacarbazine-based chemotherapies are occasionally used. This study assessed the long-term efficacy of chemoimmunotherapy (bleomycin, vincristine, lomustine and dacarbazine with/without subcutaneous interferon-alpha: BOLD-INF-α) as real-world data in patients with metastatic melanoma not eligible for clinical trials. PATIENTS AND METHODS: Medical data of 146 patients with stage IV melanoma who had received BOLD/BOLD-INFα regimen during 1991-2010 were analyzed. RESULTS: The median overall survival was 8.9 months (95% confidence intervaI=7.5-10.4 months). The 1-year survival rate was 36%, 2-year 18%, and 5-year 13%. The 5-year survival rates in the M1a, M1b and M1c subgroups were 28%, 10% and 6%, respectively. Overall, 7% (n=11) of the patients were alive at the end of the follow-up. CONCLUSION: Our study showed similar overall survival among patients with stage IV cutaneous melanoma treated with BOLD/BOLD-INFα as noted previously with chemotherapy.

Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience.

BACKGROUND: In Finland, selective internal radiation therapy (SIRT) is at present the preferred first-line loco-regional therapy for uveal melanoma patients with hepatic metastases not suitable for surgery. We retrospectively evaluate the outcome and safety of SIRT in this group of patients. MATERIAL AND METHODS: Yttrium-90 microspheres were delivered via the hepatic artery into the circulation of metastases from uveal melanoma in 18 patients with a predicted life expectancy of more than three months in three Finnish tertiary referral centers between November 2010 and December 2015. Progression-free survival (PFS), toxicity and overall survival (OS) were evaluated. Patients with historical uveal melanoma without extrahepatic metastases, who had received systemic chemotherapy as first-line treatment for their hepatic metastases at the Helsinki University Hospital between January 2006 and May 2010, were used as a historical control group. RESULTS: Partial response and stable disease were observed in three (17%) and eight (44%) patients, respectively; one patient was not evaluable for response. Median PFS after SIRT was 5.6 (range, 1.3-40.8) months. Median OS after SIRT was 13.5 (range, 3.6-44.8) months compared with 10.5 (range, 3.0-16.5; p = .047) months for the historical chemotherapy group. Among patients who received SIRT as first-line treatment, the median OS was 18.7 (range, 8.2-44.8) months, significantly longer than that of the chemotherapy group (10.5 months, p = .017). There were no treatment-related deaths. Toxicity was mainly WHO grade 1-2 and self-limited. CONCLUSION: SIRT is a feasible and safe treatment for liver metastases in patients with uveal melanoma.

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer.

AIM: The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer. PATIENTS AND METHODS: In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m2 docetaxel (days 1 and 15, q4w) or 90 mg/m2 paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i.v. (q3w) alone, or with endocrine therapy. (NCT00979641). RESULTS: Progression-free survival was 11.3 months (95% confidence interval=9.7-16.0 months) and overall survival was 35.1 months (95% confidence interval=22.2-50.3 months). More than half of the patients (62%) responded at least partially. Bevacizumab-related serious adverse events occurred in 10.8% patients and one patient died because of gastrointestinal perforation. CONCLUSION: Treating advanced breast cancer with a bevacizumab-containing regimen as the first-line cytotoxic treatment resulted in excellent response rates and long survival.

[Adverse effects of new immunologic drugs for melanoma and their management in adult patients]. / Uusien immunologisten melanoomalääkkeiden haittavaikutukset ja niiden hallinta.

Conventional anticancer drugs, cytotoxic agents, function by killing all rapidly dividing cells without distinguishing between cancer cells and normal cells of the body. Understanding of the regulatory mechanisms of the immune system has enabled the development of immunotherapeutic drugs and, through them, liberation of the immune response for the management of cancer. In Finland, interferons and antibody therapies represent the clinically applied immunotherapy of melanoma. While most antibody therapies are fairly harmless, the new drugs enhancing T cell defense are associated with a significant risk of autoimmune adverse effects. Immediate recognition and treatment of adverse effects are essential for the survival of the patients.

One-cm Versus 2-cm Excision Margins for Patients With Intermediate Thickness Melanoma: A Matched-Pair Analysis.

BACKGROUND: Optimum excision margins used in the removal of intermediate thickness melanomas remain unclear. OBJECTIVE: This study's aim was to compare the clinical outcomes of 1-cm margins with 2-cm margins in patients with a tumor thickness of 1.1- to 4.0-mm. MATERIALS AND METHODS: This was a retrospective study, which was based on a matched-pairs design. Equal patient cohorts were constructed in terms of gender, age, Breslow thickness, and the anatomic location of the primary lesion. There were 80 patients whom underwent an excision with a 1-cm margin and 80 patients with a 2-cm margin. Follow-up data were analyzed by the Kaplan-Meier method and a Cox regression model. RESULTS: After a median follow-up time of 41 months, there were no differences in relapse-free survival or melanoma-specific survival between study groups. The wound was closed directly in 62 patients (78%) in the 1-cm group and in 36 patients (45%) in the 2-cm group (p < .001). CONCLUSION: A 1-cm excision margin may be sufficient in melanomas of 1.1 to 2.0 mm in Breslow thickness based on these findings of low recurrence. With thicker tumors (2.1-4.0 mm), this recommendation cannot be given due to inherent study limitations.