Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment. METHODS: A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease. RESULTS: In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression. CONCLUSION: Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.

Clinicopathologic and Prognostic Differences between Three Different Age Groups (Child/Adolescent, Young Adults, and Adults) of Colorectal Cancer Patients: A Multicentre Study.

BACKGROUND: Colorectal cancer (CRC) is a rare disease amongst children and adolescents. Previous studies have reported a number of differences between children/adolescents, young adults, and adult patients with CRC. However, none of these studies compared these age groups according to their clinicopathologic and prognostic characteristics. In the current study, we compare these three age groups. METHODS: A total of 173 (1.1% of 15,654 patients) young CRC patients (≤25 years) were included in the study. As a control group, 237 adult CRC patients (>25 years) were also included. Patients were divided into three age groups: child/adolescent (10-19 years), young adult (20-25 years), and adult (>25 years). RESULTS: Statistical differences amongst the three groups in terms of gender (p = 0.446), family history (p = 0.578), symptoms of presentation (p = 0.306), and interval between initiation of symptoms and diagnosis (p = 0.710) could not be demonstrated. Whilst abdominal pain (p < 0.001) and vomiting (p = 0.002) were less common in young adults than in other groups, rectal bleeding and changes in bowel habits were relatively less common in adolescents than in other groups. Rectal localisation (p = 0.035), mucinous adenocarcinoma (p < 0.001), and a poorly differentiated histologic subtype (p < 0.001) were less common in the adult group than in other groups. The percentage of patients with metastasis and sites of metastasis (e.g., peritoneum and lung) differed between groups. The median overall survival was 32.6 months in the adolescent group, 57.8 months in the young adult group and was not reached in the adult group (p = 0.022). The median event-free survival of the adolescent, young adult, and adult groups was 29.0, 29.9, and 61.6 months, respectively (p = 0.003). CONCLUSIONS: CRC patients of different age groups present different clinicopathologic and prognostic characteristics. Clinicians should be aware of and manage the disease according to these differences.

Assessment of demodex presence in acne-like rash associated with cetuximab.

CONTEXT: Cetuximab is an epidermal growth factor receptor inhibitor. It is frequently used in the treatment of solid tumors. However, it has a high potential to cause acne-like rash. Demodex mites, which are known to increase in number in immunosuppressive circumstances, are closely related to the acneiform lesions. OBJECTIVE: The aim of this study is to evaluate the presence of demodex mites in acne-like rash that appears under the treatment of Cetuximab. METHODS: We reviewed the medical records of patients who applied to our clinic with cetuximab induced papulopustular rashes between November 2014 and March 2016. Demodex sampling was performed by standardized skin surface biopsy (SSSB) in a total of 11 patients (eight males and three females). Infestation was defined as at least 5 living parasites/cm2 of skin. RESULTS: Upon the SSSB examination in 10 out of the 11 patients, no demodex mites were detected. Demodex mites were found in only one of the patients. This patient, in whom two dead Demodex folliculorums were found through facial sampling, was also regarded as negative since his demodex density was under the threshold limit value. CONCLUSION: In this study, it has been concluded that acne-like rash that develops under the treatment of cetuximab is not related to the presence of demodex mites. Papulopustular eruptions that develop under cetuximab treatment should not be directly correlated with the presence of demodex; first SSSB and demodex presence should be evaluated.

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG).

Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.