Immune-Related Thyroid Adverse Events Predict Response to PD-1 Blockade in Patients with Melanoma.

Antibodies against programmed cell death protein-1 or its ligand (PD-(L)1) are a standard of care in melanoma; however, this treatment may cause immune-related adverse events. The aim of this study was to evaluate the immune-related thyroid adverse events (irTAEs) during anti-PD-1 therapy and analyze their influence on the overall survival rates in melanoma. We included 249 patients with metastatic melanoma treated in our institution between 2014 and 2021; the median age was 62 years (range: 17-90); 58% were males, and 37% of patients had the BRAF mutation. We included patients with a normal TSH at baseline and followed up with measurement of TSH levels during immunotherapy. In our group, 95 patients had a TSH outside the normal range: 63 not clinically significant and 32 with clinical symptoms of hypothyroidism. The 3-year overall survival rate was related to the irTAEs of clinical hypothyroidism, abnormal clinically not significant TSH, and euthyreosis at 56%, 43%, and 32%, respectively (p = 0.002). After adjusting the Cox model for potential confounding variables, clinically significant hypothyroidism was an independent prognostic factor with HR 0.51 (95% CI 0.29-0.87). In conclusion, the patients who developed clinically significant hypothyroidism requiring replacement therapy with L-thyroxin were the group who benefitted most from anti-PD-1 treatment.

Colorectal cancer and Blastocystis sp. infection.

BACKGROUND: Blastocystis sp. is a common intestinal protozoan found worldwide. Based on gene analysis, 17 subtypes (STs, ST1-ST17) have been identified, 9 of which have been isolated from humans. Differences in clinical consequences may depend on differences among the STs. Here, we evaluated the prevalence of Blastocystis sp. in patients with colorectal cancer (CRC) compared to a control group and assessed the relationships between Blastocystis sp. infection and sex; age; and CRC grade, stage, and location. METHODS: The study included 107 CRC patients (41 women and 66 men, median age 65 years); 124 subjects without colorectal cancer or a history of oncological disease comprised the control group (55 women and 69 men, median age 63). Stool samples were collected from patients before oncological treatment and examined using light microscopy (iodine-stained smear). Additionally, PCR-based identification of Blastocystis sp. was performed in 95 stool samples from CRC patients and 76 stool samples from the control group. RESULTS: Light microscopy showed that the prevalence of Blastocystis sp. was significantly higher in CRC patients than in the control group (12.15% and 2.42%, respectively; p = 0.0041). Multivariate analysis showed that the odds of Blastocystis sp. infection were fivefold higher in the CRC group than in the control group. PCR-based molecular examinations demonstrated that the proportion of patients infected with Blastocystis sp. was significantly higher in the CRC group than in the control group (12.63% and 2.63%, respectively; p = 0.023). The predominant ST in the CRC group was ST3, detected in nine patients (75%), followed by ST1 (2 patients, 16.7%) and ST2 (1 patient, 8.3%). No association was found between Blastocystis sp. infection and age, sex, or CRC stage, grade, or location. CONCLUSIONS: The results showed that CRC was associated with an increased risk of opportunistic Blastocystis sp. infection, even before oncological treatment. To the best of our knowledge, this is the first report estimating the prevalence of Blastocystis sp. infection in CRC patients before oncological treatment in Europe.

Colorectal cancer and Cryptosporidium spp. infection.

Transient or constant impaired immunity is often associated with neoplastic disease or oncological treatment. Among the most common pathogens found in patients with HIV or patients undergoing chemotherapy are protozoans of the Cryptosporidium genus, which cause diarrhea in humans and animals. The present study determined the frequency of Cryptosporidium spp. infections in patients with colorectal cancer (N = 108; 42 women; 66 men; median age, 65 years), before beginning oncological treatment, compared to a control group (N = 125; 56 women, 69 men; median age, 63 years) without colorectal cancer or a history of oncological disease. We also assessed whether Cryptosporidium spp. infections were associated with age, gender, cancer stage (based on Astler-Coller or TNM classification), histological grade, or cancer location. Patients were treated at the Pomeranian Medical University, in 2009-2014. The presence of Cryptosporidium spp. antigen was determined in stool samples, analyzed with a commercial immunoenzymatic test. Cryptosporidium spp. infections occurred significantly more often (p = 0.015) in patients (13%) compared to controls (4%). The patient group showed no significant relationship between Cryptosporidium spp. infection and sex, age, tumor location, cancer grade, or stage. A multivariate logistic regression analysis adjusted for age and sex that included all subjects (patient + control groups, n = 233) showed that the odds of a Cryptosporidium spp. infection were more than three-fold higher in patients than in controls, and more than six-fold higher among men than among women. CONCLUSIONS: 1) Cryptosporidium spp. infections occurred significantly more frequently in patients with colorectal cancer (before oncological treatment) compared to controls, independent of age and sex. 2) Cryptosporidium spp. infections were not associated with the colorectal cancer stage, grade, or location or with patient age. 3) Male gender was significantly related to the frequency of Cryptosporidium spp. infections, independent of age and the presence of colorectal cancer.

Prevalence of Cryptosporidium sp. in patients with colorectal cancer.

UNLABELLED: Parasitic protozoans of the Cryptosporidium genus are intracellular intestinal parasites of mammals, causing cryptosporidiosis. Clinically, cryptosporidiosis manifests as chronic diarrhoea. Individuals with immune disorders, including those with neoplasms, are at risk of symptomatic invasion. THE AIM OF THE STUDY: Was the evaluation of Cryptosporidium sp. prevalence in patients with diagnosed colorectal cancer. MATERIAL AND METHODS: The studied group encompassed 87 patients with diagnosed colorectal cancer, undergoing surgery at the Department of General and Oncological Surgery, Pomeranian Medical University, in the years 2009-2010. Immunoenzymatic tests for Cryptosporidium sp. on faeces samples were performed with the use of commercial test kit, ProSpecT(®)Cryptosporidium Microplate Assay (Remel Inc). RESULTS: The presence of Cryptosporidium sp. was found in 12.6% of studied patients with colorectal cancer. The performed statistical analysis did not reveal any correlation between Cryptosporidium sp. infection and gender, age, neoplasm advancement stage as per Astler-Coller scale, neoplasm differentiation grade, or neoplastic tumour localisation in relation to the splenic flexure. CONCLUSIONS: There was found high prevalence of Cryptosporidium sp. in patients with colorectal cancer. It was comparable to the prevalence reported for patients with immune deficiency.