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In patients with melanomas containing activating BRAF mutations, the combination of a BRAF inhibitor and a MEK inhibitor improved overall survival, as compared with a BRAF inhibitor alone, and was associated with many fewer second skin tumors. The treatment of metastatic melanoma is rapidly evolving. The potent and specific BRAF inhibitors vemurafenib and dabrafenib, as compared with chemotherapy, have significantly improved response rates, along with progression-free and overall survival, in patients with metastatic melanoma with BRAF V600E or V600K mutations. 1 , 2 However, acquired resistance to BRAF inhibitors frequently develops through reactivation of the mitogen-activated protein kinase (MAPK) pathway, resulting in a median progression-free survival of 6 to 8 months. 2 – 5 In addition, the use of BRAF inhibitors may result in the development of secondary skin tumors, originating from a paradoxical activation of the MAPK pathway in cells . . .

Despite newly approved treatments, metastatic melanoma remains a life-threatening condition. We aimed to evaluate the efficacy of the MAGE-A3 immunotherapeutic in patients with stage IIIB or IIIC melanoma in the adjuvant setting. DERMA was a phase 3, double-blind, randomised, placebo-controlled trial done in 31 countries and 263 centres. Eligible patients were 18 years or older and had histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1. Randomisation and treatment allocation at the investigator sites were done centrally via the internet. We randomly assigned patients (2:1) to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0·5 mL), or placebo, over a 27-month period: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals. The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) identified previously and validated here via an adaptive signature design. The final analyses included all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomised population and for safety were in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT00796445. Between Dec 1, 2008, and Sept 19, 2011, 3914 patients were screened, 1391 randomly assigned, and 1345 started treatment (n=895 for MAGE-A3 and n=450 for placebo). At final analysis (data cutoff May 23, 2013), median follow-up was 28·0 months [IQR 23·3–35·5] in the MAGE-A3 group and 28·1 months [23·7–36·9] in the placebo group. Median disease-free survival was 11·0 months (95% CI 10·0–11·9) in the MAGE-A3 group and 11·2 months (8·6–14·1) in the placebo group (hazard ratio [HR] 1·01, 0·88–1·17, p=0·86). In the GS-positive population, median disease-free survival was 9·9 months (95% CI 5·7–17·6) in the MAGE-A3 group and 11·6 months (5·6–22·3) in the placebo group (HR 1·11, 0·83–1·49, p=0·48). Within the first 31 days of treatment, adverse events of grade 3 or worse were reported by 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group, treatment-related adverse events of grade 3 or worse by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and at least one serious adverse event by 14% of patients in both groups (129 patients given MAGE-A3 and 64 patients given placebo). The most common adverse events of grade 3 or worse were neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [<1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo). No deaths were related to treatment. An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped. GlaxoSmithKline Biologicals SA.

In the COMBI-v trial, patients with previously untreated BRAF Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were treated with the combination of dabrafenib and trametinib had significantly longer overall and progression-free survival than those treated with vemurafenib alone. Here, we present the effects of treatments on health-related quality of life (HRQoL), an exploratory endpoint in the COMBI-v study. COMBI-v was an open-label, randomised phase 3 study in which 704 patients with metastatic melanoma with a BRAF Val600 mutation were randomly assigned (1:1) by an interactive voice response system to receive either a combination of dabrafenib (150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as first-line therapy. The primary endpoint was overall survival. In this pre-specified exploratory analysis, we prospectively assessed HRQoL in the intention-to-treat population with the European Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ-C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of Cancer Therapy—Melanoma (FACT-M), completed at baseline, during study treatment, at disease progression, and after progression. We used a mixed-model, repeated measures ANCOVA to assess differences in mean scores between groups with baseline score as covariate; all p-values are descriptive. The COMBI-v trial is registered with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary endpoint, but is not recruiting patients. From June 4, 2012, to Oct 7, 2013, 1645 patients at 193 centres worldwide were screened for eligibility, and 704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352). Questionnaire completion rates for both groups were high (>95% at baseline, >80% at follow-up assessments, and >70% at disease progression) with similar HRQoL and symptom scores reported at baseline in both treatment groups for all questionnaires. Differences in mean scores between treatment groups were significant and clinically meaningful in favour of the combination compared with vemurafenib monotherapy for most domains across all three questionnaires during study treatment and at disease progression, including EORTC QLQ-C30 global health (7·92, 7·62, 6·86, 7·47, 5·16, 7·56, and 7·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·005 at week 40), EORTC QLQ-C30 pain (–13·20, −8·05, −8·82, −12·69, −12·46, −11·41, and −10·57 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001), EQ-5D thermometer scores (7·96, 8·05, 6·83, 11·53, 7·41, 9·08, and 10·51 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0·001 for all assessments except p=0·006 at week 32), and FACT-M Melanoma Subscale score (3·62, 2·93, 2·45, 3·39, 2·85, 3·00, and 3·68 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; all p<0·001). From the patient's perspective, which integrates not only survival advantage but also disease-associated and adverse-event-associated symptoms, treatment with the combination of a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as standard of care in this population. GlaxoSmithKline.

Introduction Malignant neoplasms of the nail apparatus are rare tumours, often diagnosed with delay, which influences the further course. Dermoscopy improves the clinical differentiation of benign and malignant conditions of the nail apparatus, patients’ follow-up and determination of the margins during surgical intervention (intraoperative onychoscopy). Herein we present another series of Polish patients with malignant tumours of the nail apparatus analysed with dermoscopy. Objective Epidemiological, clinical and dermoscopic analysis of patients with nail apparatus melanoma and nail apparatus squamous cell carcinoma. Material and methods We retrospectively analysed clinical data of 840 patients diagnosed and treated surgically at the Department of Dermatology, Venerology and Allergology, Medical University of Gdańsk (Poland) between January 2015 and November 2017. Three cases of nail apparatus melanoma and 4 cases of nail apparatus squamous cell carcinoma were identified and included in further detailed analysis. In all cases clinical diagnosis was confirmed histopathologically. Dermoscopy was available in 5 cases. Results Nail apparatus melanoma represented 8.3% of all diagnosed melanomas and nail apparatus squamous cell carcinoma 9.2% of all squamous cell carcinomas in the analysed period of time. Conclusions According to our material, nail apparatus malignancy is not uncommon. Dermoscopy supports the clinical differentiation between benign and malignant disorders of the nail apparatus, but should always be interpreted in association with medical history and physical examination. Histopathological examination remains the gold standard in the diagnosis of malignant tumours of the nail unit.

Background: The landscape of melanoma management changed as randomized trials have launched adjuvant treatment. Materials and Methods: An analysis of data on 248 consecutive melanoma stage III and IV patients given adjuvant therapy in eight centers (February 2019 to January 2021) was conducted. Results: The analyzed cohort comprised 147 melanoma patients given anti-PD1 (33% nivolumab, 26% pembrolizumab), and 101 (41%) were given dabrafenib plus trametinib (DT). The 2-year overall survival (OS), relapse-free survival (RFS), and distant-metastases-free survival (DMFS) rates were 86.7%, 61.4%, and 70.2%, respectively. The disease stage affected only the RFS rate; for stage IV, it was 52.2% (95% CI: 33.4–81.5%) vs. 62.5% (95% CI: 52.3–74.8%) for IIIA-D, p = 0.0033. The type of lymph node surgery before adjuvant therapy did not influence the outcomes. Completion of lymph node dissection cessation after positive SLNB did not affect the results in terms of RFS or OS. Treatment-related adverse events (TRAE) were associated with longer 24-month RFS, with a rate of 68.7% (55.5–84.9%) for TRAE vs. 56.6% (45.8–70%) without TRAE, p = 0.0031. For TRAE of grade ≥ 3, a significant decline in OS to 60.6% (26.9–100%; p = 0.004) was observed. Conclusions: Melanoma adjuvant therapy with anti-PD1 or DT outside clinical trials appears to be effective and comparable with the results of registration studies. Our data support a de-escalating surgery approach in melanoma treatment.

Background: In melanoma treatment, an approach following positive sentinel lymph node biopsy (SLNB) has been recently deescalated from completion lymph node dissection (CLND) to active surveillance based on phase III trials data. In this study, we aim to evaluate treatment strategies in SLNB-positive melanoma patients in real-world practice. Methods: Five-hundred-fifty-seven melanoma SLNB-positive patients from seven comprehensive cancer centers treated between 2017 and 2021 were included. Kaplan–Meier methods and the Cox Proportional-Hazards Model were used for analysis. Results: The median follow-up was 25 months. Between 2017 and 2021, the percentage of patients undergoing CLND decreased (88–41%), while the use of adjuvant treatment increased (11–51%). The 3-year OS and RFS rates were 77.9% and 59.6%, respectively. Adjuvant therapy prolonged RFS (HR:0.69, p = 0.036)), but CLND did not (HR:1.22, p = 0.272). There were no statistically significant differences in OS for either adjuvant systemic treatment or CLND. Lower progression risk was also found, and time-dependent hazard ratios estimation in patients treated with systemic adjuvant therapy was confirmed (HR:0.20, p = 0.002 for BRAF inhibitors and HR:0.50, p = 0.015 for anti-PD-1 inhibitors). Conclusions: Treatment of SLNB-positive melanoma patients is constantly evolving, and the role of surgery is currently rather limited. Whether CLND has been performed or not, in a group of SLNB-positive patients, adjuvant systemic treatment should be offered to all eligible patients.

Performing this real-world analysis, we intended to see if postoperative (adjuvant) systemic treatment outcomes in a Polish melanoma patient population are comparable to the results from international trials based on which the treatment was registered worldwide. We intended to provide evidence on the efficacy and safety of postoperative melanoma treatment from everyday practice. We have shown that the type of surgical procedure on the lymph nodes prior to adjuvant treatment does not influence the outcome of that treatment. Our results support a de-escalation of surgery approach in melanoma patients. We support the value of adjuvant treatment for melanoma patients selected according to new guidelines implemented in parallel to the registration process. Analyzing the recorded side effects of adjuvant systemic treatment in our group of patients, we have noticed that severe complications worsen survival, giving us an indication not to treat by all means despite toxicity, particularly since it is a complementary to surgery treatment. Background: The landscape of melanoma management changed as randomized trials have launched adjuvant treatment. Materials and Methods: An analysis of data on 248 consecutive melanoma stage III and IV patients given adjuvant therapy in eight centers (February 2019 to January 2021) was conducted. Results: The analyzed cohort comprised 147 melanoma patients given anti-PD1 (33% nivolumab, 26% pembrolizumab), and 101 (41%) were given dabrafenib plus trametinib (DT). The 2-year overall survival (OS), relapse-free survival (RFS), and distant-metastases-free survival (DMFS) rates were 86.7%, 61.4%, and 70.2%, respectively. The disease stage affected only the RFS rate; for stage IV, it was 52.2% (95% CI: 33.4–81.5%) vs. 62.5% (95% CI: 52.3–74.8%) for IIIA-D, p = 0.0033. The type of lymph node surgery before adjuvant therapy did not influence the outcomes. Completion of lymph node dissection cessation after positive SLNB did not affect the results in terms of RFS or OS. Treatment-related adverse events (TRAE) were associated with longer 24-month RFS, with a rate of 68.7% (55.5–84.9%) for TRAE vs. 56.6% (45.8–70%) without TRAE, p = 0.0031. For TRAE of grade ≥ 3, a significant decline in OS to 60.6% (26.9–100%; p = 0.004) was observed. Conclusions: Melanoma adjuvant therapy with anti-PD1 or DT outside clinical trials appears to be effective and comparable with the results of registration studies. Our data support a de-escalating surgery approach in melanoma treatment.

In recent years the prognosis for oesophageal squamous cell carcinoma patients has improved. Together with this improvement, the occurrence of second primary carcinoma, especially gastric carcinoma, in tubes constructed from the stomach after oesophagectomy must be taken into account. We report a case of a patient who had this clinical presentation, which was revealed not in the normal follow-up, but in a consecutive operation carried out because of an anastomotic problem.

Oesophagectomy remains an acceptable treatment option for oesophageal cancer. However, it is associated with relatively high morbidity with potentially devastating complications, especially for patients who have undergone previous thoracic surgery. The majority of these complications, however, can be minimised by prevention and early recognition. In this report we present a case of a patient whose right ventricle was injured during the oesophagectomy. We try to analyse the reasons for this complication and establish an algorithm of preoperative planning for such cases.

Wprowadzenie. Czerniak aparatu paznokciowego jest rzadkim typemczerniaka o złym rokowaniu. Ocenia się, że stanowi on około 1%wszystkich czerniaków skóry w populacji kaukaskiej.Cel pracy. Ocena częstości występowania tego nowotworu w populacjipółnocnej Polski oraz jego charakterystyka kliniczna i histopatologiczna. Materiał i metody: wśród 1588 pacjentów diagnozowanych i leczonychw Klinice Dermatologii, Wenerologii i Alergologii GdańskiegoUniwersytetu Medycznego z powodu różnorodnych patologii aparatupaznokciowego do badania włączono 8 chorych (5 kobiet i 3 mężczyzn,średnia wieku 59 lat) z czerniakiem aparatu paznokciowego.Wyniki: czerniak aparatu paznokciowego stanowił 0,504% wszystkichpatologii aparatu paznokciowego. Wszyscy pacjenci cechowali się IIIlub IV fototypem skóry. Guz był zlokalizowany w większości przypadkóww obrębie palucha lub kciuka. Najczęstszym typem histopatologicznymbyłczerniak akralny. Średni naciek nowotworu według Breslowawynosił 7,2 mm (zakres 2,5–18 mm). U 37,5% badanychobserwowano przeżycie ponad 20 miesięcy. Wnioski: czerniak aparatu paznokciowego w populacji północnej Polskiwystępuje rzadko, ale jest najczęstszym nowotworem złośliwymnarządu paznokciowego.Wbadanej populacji nowotwór rozpoznawanow zaawansowanych stadiach, co wiąże się ze złym rokowaniem.