The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.

Which Treatment for Which Patient: Rectal Cancer Management After PROSPECT Trial.

Determining treatment options for patients with locally advanced rectal cancer after the PROSPECT trial data readout adds an important level to the decision-making process.

Who Should Receive Immunotherapy for Advanced Gastroesophageal Cancer?

OPINION STATEMENT: This paper shines a light on the exciting progress being made in using immunotherapy to treat advanced gastroesophageal cancers. The positive results from trials using drugs like Pembrolizumab and Nivolumab are certainly encouraging and open new possibilities for treating this challenging disease. However, it is clear that we still have a lot to learn about how to predict which patients will benefit most from these treatments. The exploration of combining therapies and using machine learning to guide treatment shows promise. Moving forward, it is crucial that researchers and healthcare professionals continue to work together, sharing knowledge and findings to continue the advancements in this important area.

The risk of developing gestational diabetes mellitus in maternal subclinical hypothyroidism: a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to determine the association between maternal subclinical hypothyroidism (SCH) and gestational diabetes mellitus (GDM) risk. METHODS: This study is a systematic review and meta-analysis. Following PubMed, Medline, Scopus, Web of Science, and Google Scholar database search up to April 1 2021, a total of 4597 studies were identified. Studies published in English, with full text available, related to subclinical hypothyroidism in pregnancy, reporting or mentioning the incidence of GDM were included in the analysis. Following exclusion of studies, a total of 16 clinical trial were analyzed. For the risk of GDM, odds ratios (ORs) were calculated. Subgroup analyzes were performed according to gestational age and thyroid antibodies. RESULTS: Pregnant women with SCH were at increased risk of GDM compared to women with euthyroidism, overall (OR = 1.339, 95% CI 1.041-1.724; p = 0.023). Additionally, SCH without thyroid antibodies has no significant effect on GDM risk (OR = 1.173, 95% CI 0.88-1.56; p = 0.277) and pregnant women with SCH in the first trimester were not found to be at increased risk of GDM compared to women with euthyroidism regardless of thyroid antibodies (OR = 1.088, 95%CI 0.816-1.451; p = 0.564). CONCLUSIONS: Maternal SCH in pregnancy is related to an increased risk of GDM.

Isolated Maternal Hypothyroxinemia May be Associated with Insulin Requirement in Gestational Diabetes Mellitus.

An insulin regimen may be necessary for about 30% of the patients with gestational diabetes mellitus (GDM). We aimed to investigate the association of free T4(fT4) levels with insulin requirement in pregnant women with GDM. We included pregnant women whose TSH levels were within the normal range and who were diagnosed with GDM, and excluded patients with thyroid dysfunction, chronic illnesses, or any previous history of antithyroid medication, levothyroxine, or antidiabetic medication use. The diagnosis and treatment of GDM were based on American Diabetes Association guidelines. Demographic features, previous history of GDM and gestational hypertension were recorded. Baseline (at diagnosis of GDM) fasting blood glucose, HbA1c, TSH, fT4, and fT3 levels were analyzed. We grouped the patients according to their baseline fT4 levels: isolated maternal hypothyroxinemia (IMH) (group A) vs. in the normal range (group B). We grouped those also based on insulin requirement in 3rd trimester. Of the patients (n=223), insulin requirement was present in 56, and IMH in 11. Insulin requirement was more frequent in group A than in group B (p=0,003). HbA1c (≥47,5 mmol/mol) and fT4 level (lower than normal range) were positive predictors for insulin requirement (OR:35,35, p=0,001; and OR:6,05, p=0,008; respectively). We showed that IMH was closely associated with insulin requirement in GDM. Pregnant women with IMH and GDM should be closely observed as regards to glycemic control. If supported by future large studies, levothyroxine treatment might be questioned as an indication for patients with GDM and IMH.

The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.

To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism.

Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma.

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. METHODS: We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. RESULTS: From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. CONCLUSION: There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

Return to intended oncologic therapy after colectomy for stage III colon adenocarcinoma: Does surgical approach matter?

AIM: Return to intended oncologic treatment (RIOT) is an important paradigm for surgically resected cancers requiring multimodal treatment. Benefits of minimally invasive colectomy (MIC) may allow earlier initiation of adjuvant chemotherapy (ACT) and have associated survival benefits. We sought to determine if operative approach affects RIOT timing in resected stage III colon cancer. METHODS: NCDB identified pathological stage III colon adenocarcinoma patients who underwent resection and received ACT. Propensity score matching and kernel density estimation compared operative approaches and conversion impact on intervals to RIOT. RESULTS: A total of 15,132 open colectomies (OC) versus 14,107 MIC were included. MIC patients had two-days shorter median length of stay (LOS) (4 vs. 6 days; p < 0.001), one-week shorter median time to RIOT (6 vs. 7 weeks; p = 0.015) comparing 12,867 matched pairs. There was no difference in time interval to RIOT between the LC versus RC, converted MIC vs. OC groups. MIC was a favourable predictor of earlier RIOT (HR 1.14 [1.07-1.22]; p < 0.001). CONCLUSION: MIC in stage III colon cancer is associated with a shorter time to RIOT when compared to OC. Since timely initiation of ACT may influence cancer outcome, MIC may be oncologically preferable. Prospective studies are needed to assess RIOT and survival outcomes in stage III colon cancer.

The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.

Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members.

BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer.

BACKGROUND: Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC. MATERIALS/METHODS: This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type. RESULTS: There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis. CONCLUSION: BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.

Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma.

BACKGROUND: Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. METHODS: In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. RESULTS: A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. CONCLUSION: The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. CLINICAL TRIAL REGISTRATION: NCT02935309.

Neoadjuvant rectal score is prognostic for survival: A population-based propensity-matched analysis.

INTRODUCTION: Neoadjuvant rectal (NAR) score may serve as a surrogate short-term endpoint for overall survival (OS) in clinical trials. This study aims to test the NAR score using a large, national cancer registry. METHODS: National Cancer Database patients with clinical stage II/III rectal adenocarcinoma (RAC) treated with neoadjuvant chemoradiation (CRT) followed by surgery were selected and divided into low-, intermediate-, and high-NAR subgroups. OS outcomes were analyzed using Kaplan-Meier and logistic regression models. RESULTS: A total of 12 452 patients were selected, of which 5071 (40.7%) were in clinical stage II and 7381 (59.3%) were in clinical stage III; 15.2% had pathologic complete response. The mean NAR score was 10.01 ± 10.61. Six thousand nine hundred and forty-one (55.7%) did not receive adjuvant chemotherapy (AC) and were propensity-matched across NAR subgroups (966 in each group). A significant difference in 5-year OS between low-, intermediate-, and high-NAR groups was observed (85% vs. 76% vs. 68%; p < 0.001). Five thousand five hundred and eleven (44.3%) received AC and 1045 triplets were propensity-matched per NAR groups. A significant difference was again observed for 5-year OS (93% vs. 88% vs. 75%; p < 0.001). Logistic regression confirmed NAR strata as a significant predictor of 5-year OS. CONCLUSION: NAR score, as a neoadjuvant response measure, is a strong predictor of 5-year OS, regardless of AC receipt in a heterogenous population of locally advanced RAC patients.

Minimal Residual Disease-Directed Adjuvant Therapy for Patients With Early-Stage Colon Cancer: CIRCULATE-US.

BACKGROUND: The ability to detect circulating tumor DNA (ctDNA), a novel surrogate for minimal residual disease (MRD) for patients with solid tumors, has significantly evolved over the past decade. Several studies have shown that ctDNA may provide clinical insight into the biological dynamics of MRD. The CIRCULATE-US (NRG-GI008; NCT05174169) trial will aim to address the role of ctDNA for risk stratification to intensify and deintensify adjuvant chemotherapy for patients with early-stage colon cancer. METHODS: CIRCULATE-US, a prospective phase 2/3 randomized trial, is investigating the molecular dynamics and prognostic role of ctDNA (evaluated by Natera's Signatera assay) for patients with resected colon cancer. Patients with negative postoperative ctDNA will be enrolled in cohort A and randomized to receive either immediate treatment with 5-fluorouracil and folinic acid or capecitabine plus oxaliplatin (FOLFOX6 or CAPEOX; Arm 1) or serial ctDNA surveillance with delayed adjuvant therapy (Arm 2). Patients randomized to Arm 2 with subsequent positive ctDNA results will be enrolled in cohort B for a second randomization to receive either FOLFOX6/CAPEOX (Arm 3) or 5-fluorouracil, folinic acid, oxaliplatin, and irinotecan (FOLFIRINOX; Arm 4) for 6 months. Patients with positive postoperative ctDNA results will be directly enrolled in cohort B and randomized to receive either FOLFOX6/CAPEOX (Arm 3) or FOLFIRINOX (Arm 4). Patients with stage II or stage IIIC colon cancer with positive ctDNA results (tested as standard of care with commercial testing) will be eligible for enrollment in cohort B. The primary end point for cohort A is time to positive ctDNA status for phase 2 and disease-free survival for phase 3 with a noninferiority design. The primary end point for cohort B is disease-free survival for both phase 2 and phase 3 with a superiority design. DISCUSSION: CIRCULATE-US will aim to understand postoperative ctDNA dynamics in early-stage colon cancer and will investigate escalation and de-escalation approaches by using ctDNA status as a surrogate for MRD status.

The benefit of immunotherapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

Background: A systemic review of the survival benefit of immune checkpoint inhibitors (ICIs) in phase III hepatocellular carcinoma (HCC) trials was conducted. Methods: Meta-analyses were performed with the generic inverse-variance method with a fixed-effects model. Results: In 10 trials encompassing 6123 patients, ICI-based therapy (monotherapy/combination) improved overall survival (OS) compared with the control arm (hazard ratio [HR]: 0.77; 95% CI: 0.70-0.84; p < 0.001). The survival benefit was consistent across variable treatment lines, Eastern Cooperative Oncology Group performance status and AFP levels. While the OS benefit was more pronounced in hepatitis B-related HCC (HR: 0.70; 95% CI: 0.63-0.77; p < 0.001), OS was improved in hepatitis C-related (HR: 0.83; 95% CI: 0.71-0.98) and nonviral HCC (HR: 0.86; 95% CI: 0.77-0.97). Conclusion: ICI-based therapies should be the standard for all patients with advanced HCC.

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

BACKGROUND: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. AIM: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. METHODS: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. RESULTS: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). CONCLUSION: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet's disease.

PURPOSE: The molecules human interleukin (IL-18), the soluble cluster of differentiation (sCD40), platelet factor 4 variant 1 (PF4V1), and neutrophil gelatinase-associated lipocalin (NGAL) are all markers of inflammation in biological systems and are linked to prognosis in several inflammatory diseases as well. Since there is no study in which the above-mentioned molecules are studied together in ocular Behçet's disease (OBD), the aim of this study is to reveal whether these molecules are activity markers in active (OABD) and inactive (OIBD) disease. METHODS: 30 OABD and 30 OIBD and 30 healthy individuals were included in the study. IL-18, sCD40, PF4V1, and NGAL molecules were studied in blood samples by the ELISA method. RESULTS: When OABD and OIBD were compared to healthy individuals, the levels of IL-18, sCD40, PF4V1, and NGAL molecules were found to be statistically significant. These values were even more significantly higher in patients with OABD. CONCLUSION: When ROC values of IL-18, sCD40, PF4V1, and NGAL are evaluated, it is clear that these four molecules can be used as biomarkers to aid activity and diagnosis in OBD.

Mutation spectrum of hereditary myopathies in Turkish patients and novel variants.

Hereditary myopathies are a heterogeneous disorder known to be associated with more than 100 genes. Although hereditary myopathy subgroups can be partially described with traditional methods such as muscle biopsy, next-generation sequencing (NGS) is essential to reveal the disease's underlying genetic etiology and molecular mechanisms. In this study, we performed clinical exome sequencing or whole-exome sequencing (CES/WES) in 20 unrelated Turkish patients. Thirteen pathogenic or likely pathogenic variants, including five novel variantswere detected in the 16 known hereditary myopathy genes. We achieved a high rate of diagnosis (65%) compared to previous studies. The most common condition noticed was limb-girdle muscular dystrophy (LGMD), which should not be ignored in patients diagnosed with myopathy. CES or WES provides a certain molecular diagnosis from a broad perspective to demonstrate underlying genetic causes in heterogeneous disorders. Therefore, exome sequencing offers a higher and more complete diagnosis than the gene panel.

Mismatch Repair (MMR) Gene Alteration and BRAF V600E Mutation Are Potential Predictive Biomarkers of Immune Checkpoint Inhibitors in MMR-Deficient Colorectal Cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. MATERIALS AND METHODS: Patient databases at four cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and compared by the log-rank test. Twelve- and 24-month PFS rates were compared by the Z test. RESULTS: A total of 60 patients with CRC with MMR-D/microsatellite instability-high who previously received ICIs were identified. Patients with liver metastasis had a lower overall response rate as compared with other sites of metastasis (36.4% vs. 68.7%; p = .081). Patients with MLH1/PMS2 loss had worse 1-year and 2-year PFS rates compared with patients with MSH2/MSH6 loss (84.2% vs. 57.8% and 78.2% vs. 54.2%, respectively; p < .001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared with patients with BRAF V600E mutation (73.3% vs. 40%, and 73.3% vs. 26.7%; respectively; p < .001). Patients aged >65 had significantly worse PFS rates as compared with patients aged ≤65 (p < .001). CONCLUSION: BRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >65 years and liver metastasis, may be predictive of duration of ICI response in patients with MMR-D CRC. Larger cohorts are needed to confirm our findings. IMPLICATIONS FOR PRACTICE: The results of this study reveal clinically important biomarkers that potentially predict immune checkpoint inhibitor response in patients with mismatch repair-deficient colorectal cancer.

The clinical outcomes of COVID-19 infection in patients with a history of thyroid cancer: A nationwide study.

BACKGROUND: There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID-19) disease outcomes and mortality. Here, we evaluated COVID-19 infection outcomes and mortality in thyroid cancer patients with COVID-19 infection. DESIGN AND METHODS: We included a cohort of patients with thyroid cancer with PCR-confirmed COVID-19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID-19 disease. RESULTS: We evaluated 388 COVID-19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender-matched 388 COVID-19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non-cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID-19 disease in our patient group. CONCLUSIONS: Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID-19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome.