Harnessing ctDNA in Advanced Melanoma: A Promising Tool for Informed Clinical Decisions.

Cutaneous melanoma, an aggressive malignancy, has undergone significant transformation in clinical management with the introduction of immune checkpoint inhibitors (ICIs) and targeted therapies. Current monitoring methods, such as imaging scans, present limitations, prompting exploration of alternative biomarkers. This review comprehensively explores the role of circulating tumor DNA (ctDNA) in advanced melanoma, covering technical aspects, detection methods, and its prognostic and predictive value. Recent findings underscore ctDNA's potential applications and implications in clinical practice. This review emphasizes the need for precise and dynamic biomarkers in melanoma care, positioning ctDNA as a promising blood-based tool for prognosis, treatment response, and resistance mechanisms. The technical nuances of ctDNA detection, association with melanoma mutations, and its role in guiding therapeutic decisions for immunotherapy and targeted therapy underscore its multifaceted utility, marking a paradigm shift in clinical decision-making and offering a promising trajectory for personalized and informed care in advanced melanoma.

Sequential treatment of metastatic renal cell carcinoma patients after first-line vascular endothelial growth factor targeted therapy in a real-world setting: epidemiologic, noninterventional, retrospective-prospective cohort multicentre study.

PURPOSE: The purpose of our study was to determine whether data on the clinical effectiveness of second-line therapy collected in a real-world setting provide additional valuable information on the optimal sequence of metastatic renal cell carcinoma (mRCC) treatment. METHODS: Patients diagnosed with mRCC who were treated with at least one dose of first-line vascular endothelial growth factor (VEGF)-targeted therapy with either sunitinib or pazopanib and with at least one dose of second-line everolimus, axitinib, nivolumab, or cabozantinib were included. The efficacy of different treatment sequences was analyzed based on the time to the second objective disease progression (PFS2) and the time to the first objective disease progression (PFS). RESULTS: Data from 172 subjects were available for analysis. PFS2 was 23.29 months. The 1-year PFS2 rate was 85.3%, and the 3-year PFS2 rate was 25.9%. The 1-year overall survival rate was 97.0%, and the 3-year overall survival rate was 78.6%. Patients with a lower IMDC prognostic risk group had a significantly (p < 0.001) longer PFS2. Patients with metastases in the liver had a shorter PFS2 than patients with metastases in the other sites (p = 0.024). Patients with metastases in the lungs and lymph nodes (p = 0.045) and patients with metastases in the liver and bones (p = 0.030) had lower PFS2 rates than patients with metastases in other sites. CONCLUSIONS: Patients with a better IMDC prognosis have a longer PFS2. Metastases in the liver lead to a shorter PFS2 than metastases in other sites. One metastasis site means a longer PFS2 than 3 or more metastasis sites. Nephrectomy performed in an earlier stage of disease or metastatic setting means higher PFS and higher PFS2. No PFS2 difference was found between different treatment sequences of TKI-TKI or TKI-immune therapy.

European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment.

BACKGROUND: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent. METHODS: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting. RESULTS: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)-39% (C) routinely discuss medication options, and only 18% (P)-31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings. CONCLUSION: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.

Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II).

In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n = 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES).

BACKGROUND: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]). PATIENTS AND METHODS: Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period. RESULTS: A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300). CONCLUSION: Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.

Guidelines for diagnostics and treatment of aromatase inhibitor-induced bone loss in women with breast cancer: a consensus of Lithuanian medical oncologists, radiation oncologists, endocrinologists, and family medicine physicians.

The aim of this article is to inform about cancer treatment-induced bone loss, to identify patients at risk and those that can benefit from bone targeted treatment as well as highlight the importance of the multidisciplinary approach in the bone health in cancer care. Patients with breast cancer treated or intended to be treated with aromatase inhibitors belong to a high-risk group because their fracture risk increases up to 30% due to a significant decrease in bone mineral density within 6-12 months after the start of hormonal treatment. To evaluate bone status and predict risk for fractures, lateral thoracic and lumbar spine X-ray imaging, bone mineral density measurement by dual energy X-ray absorptiometry at the lumbar spine L1-L4 vertebrae and/or hip and fracture risk factors assessment are mandatory tests prior to hormonal treatment. Morbidity and mortality associated with bone loss can be prevented with appropriate screening, lifestyle interventions, and therapy. Algorithm for the management of bone health in breast cancer patients was established in Lithuania to screen patients with increased risk for bone loss and to provide adequate specific osteoporosis treatment.

Current standards in the treatment of metastatic breast cancer with focus on Lapatinib: a review by a Central European Consensus Panel.

In breast cancer, early detection as well as new developments in therapeutic options has resulted in less patients presenting with metastatic disease. However, about one-third of women with early stage breast cancer will eventually develop metastatic disease. Furthermore, approximately 20-30% of patients with breast cancer have tumors that overexpress human epidermal growth factor receptor (HER-2), which is associated with an aggressive tumor phenotype and poor prognosis. The identification of the HER-2 protein led to the development of highly effective therapeutics directed at this receptor. Trastuzumab, a recombinant, humanized, monoclonal antibody that binds to the extracellular domain of the HER-2 protein, has shown significant clinical benefit in metastatic and early-stage HER-2-positive breast cancer. Since the cancer recurs after adjuvant therapy in some women, and metastatic breast cancer eventually develops resistance to trastuzumab, there is a need for alternative treatment modalities to block HER-2 signaling. One of these treatment options is lapatinib, an orally active small molecule that inhibits the tyrosine kinases of HER-2 and the epidermal growth factor receptor type 1 (EGFR). In this consensus statement current treatment options in metastatic and locally advanced disease are discussed with a special focus on lapatinib.

[Combined treatment of esophageal cancer: a review]. / Stemples vezio kompleksinis gydymas (apzvalga).

While still relatively uncommon in many countries, esophageal cancer is fatal in the vast majority of cases. In the USA, estimated 13,100 of new cases were diagnosed in 2002. In Lithuania, 163 new cases were diagnosed in 2001. Evidence for an association between environment, diet and esophageal cancer comes from the profound differences in incidence observed in different parts of the world. While the overall outlook for patients diagnosed with esophageal cancer has improved in the last 30 years, most patients are still present with advanced disease and their survival remains poor. Commonly etiology and risk factors of esophageal cancer are: cigarettes and alcohol, diet and other genetics factors. Only in 50% of patients with esophageal cancer clinically localized disease is present. National Comprehensice Cancer Network (NCCN) guidelines state that patients with clinically localized disease may be treated with resection or chemotherapy plus radiation. The overall survival rates for either surgery alone or combined chemotherapy and radiation appear equivalent. Chemoradiation as primary management of localized esophageal cancer has been shown to be superior in radiation alone. A series of randomized trials have demonstrated that adjuvant postoperative chemoradiation does not offer a survival advantage to patients with esophageal cancer. The superiority of preoperative chemoradiation over surgery alone in esophageal cancer has been demonstrated in a prospective trials. Recently published phase I and II studies have demonstrated moderate response rates to taxanes in esophageal cancer. Taxanes and irinotecan in combinations with platinum compounds and fluoropyrimidines are being tested in regimes with radiation.