Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex. Materials and Methods: This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea. Results: A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits. Conclusion Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Objective: Few attempts have been made to investigate the prognostic value of dynamic contrast-enhanced (DCE) MRI or dynamic susceptibility contrast (DSC) MRI of non-enhancing, T2-high-signal-intensity (T2-HSI) lesions of glioblastoma multiforme (GBM) in newly diagnosed patients. This study aimed to investigate the prognostic values of DCE MRI and DSC MRI parameters from non-enhancing, T2-HSI lesions of GBM. Materials and Methods: A total of 76 patients with GBM who underwent preoperative DCE MRI and DSC MRI and standard treatment were retrospectively included. Six months after surgery, the patients were categorized into early progression (n = 15) and non-early progression (n = 61) groups. We extracted and analyzed the permeability and perfusion parameters of both modalities for the non-enhancing, T2-HSI lesions of the tumors. The optimal percentiles of the respective parameters obtained from cumulative histograms were determined using receiver operating characteristic (ROC) curve and univariable Cox regression analyses. The results were compared using multivariable Cox proportional hazards regression analysis of progression-free survival. Results: The 95th percentile value (PV) of Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, p = 0.005; AUC = 0.684, p = 0.021; and AUC = 0.670, p = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, p = 0.009; HR = 1.25, p = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, p < 0.009). Conclusion The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.

Objective: For an accurate dynamic contrast-enhanced (DCE) MRI analysis, exact baseline T1 mapping is critical. The purpose of this study was to compare the pharmacokinetic parameters of DCE MRI using synthetic MRI with those using fixed baseline T1 values. Materials and Methods: This retrospective study included 102 patients who underwent both DCE and synthetic brain MRI. Two methods were set for the baseline T1: one using the fixed value and the other using the T1 map from synthetic MRI. The volume transfer constant (Ktrans ), volume of the vascular plasma space (vp), and the volume of the extravascular extracellular space (ve) were compared between the two methods. The interclass correlation coefficients and the Bland-Altman method were used to assess the reliability. Results: In normal-appearing frontal white matter (WM), the mean values of Ktrans , ve, and vp were significantly higher in the fixed value method than in the T1 map method. In the normal-appearing occipital WM, the mean values of ve and vp were significantly higher in the fixed value method. In the putamen and head of the caudate nucleus, the mean values of Ktrans , ve, and vp were significantly lower in the fixed value method. In addition, the T1 map method showed comparable interobserver agreements with the fixed baseline T1 value method. Conclusion The T1 map method using synthetic MRI may be useful for reflecting individual differences and reliable measurements in clinical applications of DCE MRI.

Osteopetrosis refers to a group of genetic skeletal disorders characterized by osteosclerosis and fragile bones. Osteopetrosis can be classified into autosomal dominant, autosomal recessive, or X-linked forms, which might differ in clinical characteristics and disease severity. Autosomal recessive osteopetrosis, also known as malignant osteopetrosis, has an earlier onset, more serious clinical symptoms, and is usually fatal. We encountered a 1-day-old girl who was born full-term via vaginal delivery, which was complicated by meconium-stained amniotic fluid, cephalo-pelvic disproportion, and nuchal cord. Routine neonatal care was provided, in addition to blood tests and chest radiography to screen for sepsis, as well as skull radiography to rule out head injuries. Initial blood tests revealed hypocalcemia, which persisted on follow-up tests the next day. Radiographic examinations revealed diffusely increased bone density and a "space alien" appearance of the skull. Based on radiographic and laboratory findings, the infantile form of osteopetrosis was suspected and genetic testing for identification of the responsible gene. Eventually, a heterozygous mutation of the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1) gene (c.292C>T) was identified, making this the first reported case of neonatal-onset malignant osteopetrosis with TCIRG1 mutation in South Korea. Early-onset hypocalcemia is common and usually results from prematurity, fetal growth restriction, maternal diabetes, perinatal asphyxia, and physiologic hypoparathyroidism. However, if hypocalcemia persists, we recommend considering 'infantile of osteopetrosis' as a rare cause of neonatal hypocalcemia and performing radiographic examinations to establish the diagnosis.

Objective: Few attempts have been made to investigate the prognostic value of dynamic contrast-enhanced (DCE) MRI or dynamic susceptibility contrast (DSC) MRI of non-enhancing, T2-high-signal-intensity (T2-HSI) lesions of glioblastoma multiforme (GBM) in newly diagnosed patients. This study aimed to investigate the prognostic values of DCE MRI and DSC MRI parameters from non-enhancing, T2-HSI lesions of GBM. Materials and Methods: A total of 76 patients with GBM who underwent preoperative DCE MRI and DSC MRI and standard treatment were retrospectively included. Six months after surgery, the patients were categorized into early progression (n = 15) and non-early progression (n = 61) groups. We extracted and analyzed the permeability and perfusion parameters of both modalities for the non-enhancing, T2-HSI lesions of the tumors. The optimal percentiles of the respective parameters obtained from cumulative histograms were determined using receiver operating characteristic (ROC) curve and univariable Cox regression analyses. The results were compared using multivariable Cox proportional hazards regression analysis of progression-free survival. Results: The 95th percentile value (PV) of Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, p = 0.005; AUC = 0.684, p = 0.021; and AUC = 0.670, p = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, p = 0.009; HR = 1.25, p = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, p < 0.009). Conclusion The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.

Objective: For an accurate dynamic contrast-enhanced (DCE) MRI analysis, exact baseline T1 mapping is critical. The purpose of this study was to compare the pharmacokinetic parameters of DCE MRI using synthetic MRI with those using fixed baseline T1 values. Materials and Methods: This retrospective study included 102 patients who underwent both DCE and synthetic brain MRI. Two methods were set for the baseline T1: one using the fixed value and the other using the T1 map from synthetic MRI. The volume transfer constant (Ktrans ), volume of the vascular plasma space (vp), and the volume of the extravascular extracellular space (ve) were compared between the two methods. The interclass correlation coefficients and the Bland-Altman method were used to assess the reliability. Results: In normal-appearing frontal white matter (WM), the mean values of Ktrans , ve, and vp were significantly higher in the fixed value method than in the T1 map method. In the normal-appearing occipital WM, the mean values of ve and vp were significantly higher in the fixed value method. In the putamen and head of the caudate nucleus, the mean values of Ktrans , ve, and vp were significantly lower in the fixed value method. In addition, the T1 map method showed comparable interobserver agreements with the fixed baseline T1 value method. Conclusion The T1 map method using synthetic MRI may be useful for reflecting individual differences and reliable measurements in clinical applications of DCE MRI.

Osteopetrosis refers to a group of genetic skeletal disorders characterized by osteosclerosis and fragile bones. Osteopetrosis can be classified into autosomal dominant, autosomal recessive, or X-linked forms, which might differ in clinical characteristics and disease severity. Autosomal recessive osteopetrosis, also known as malignant osteopetrosis, has an earlier onset, more serious clinical symptoms, and is usually fatal. We encountered a 1-day-old girl who was born full-term via vaginal delivery, which was complicated by meconium-stained amniotic fluid, cephalo-pelvic disproportion, and nuchal cord. Routine neonatal care was provided, in addition to blood tests and chest radiography to screen for sepsis, as well as skull radiography to rule out head injuries. Initial blood tests revealed hypocalcemia, which persisted on follow-up tests the next day. Radiographic examinations revealed diffusely increased bone density and a "space alien" appearance of the skull. Based on radiographic and laboratory findings, the infantile form of osteopetrosis was suspected and genetic testing for identification of the responsible gene. Eventually, a heterozygous mutation of the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1) gene (c.292C>T) was identified, making this the first reported case of neonatal-onset malignant osteopetrosis with TCIRG1 mutation in South Korea. Early-onset hypocalcemia is common and usually results from prematurity, fetal growth restriction, maternal diabetes, perinatal asphyxia, and physiologic hypoparathyroidism. However, if hypocalcemia persists, we recommend considering 'infantile of osteopetrosis' as a rare cause of neonatal hypocalcemia and performing radiographic examinations to establish the diagnosis.