Prognostic utility of body composition parameters based on computed tomography analysis of advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

OBJECTIVE: The purpose of this study was to evaluate the prognostic impact of body composition parameters based on computed tomography (CT) in patients with non-small cell lung cancer (NSCLC) who received ICI treatment. METHODS: This retrospective study analyzed the data from advanced NSCLC patients treated with ICI therapy between 2013 and 2019. We included patients with NSCLC who underwent baseline CT scans. The exclusion criteria included patients who received three or more lines of chemotherapy, those with insufficient clinical information, or those without treatment response evaluation. RESULTS: A total of 136 patients were enrolled. Among the volumetric body composition parameters, patients in the highest quartiles (Q2-4) of the visceral fat index (VFI) exhibited a higher response rate to ICI therapy than those in the lowest quartile (Q1) of VFI (Q1 vs. Q2-4: 18.2% vs. 43.1%, p = 0.012). Patients with a VFI in Q2-4 had significantly prolonged progression-free survival (PFS) and overall survival (OS) (PFS, Q1 vs. Q2-4: 3.0 months vs. 6.4 months, p = 0.043; OS, Q1 vs. Q2-4: 5.6 months vs. 16.3 months, p = 0.004). Kaplan-Meier analysis based on the VFI and visceral fat Hounsfield unit (HU) revealed that patients with VFI in Q1 and HU in Q2-4 had the worst prognosis. CONCLUSIONS: Visceral fat volume is significantly associated with treatment outcomes in ICI-treated patients with NSCLC. Moreover, fat quality may impact the treatment outcomes. This finding underscores the potential significance of both fat compartments and fat quality as prognostic indicators. CRITICAL RELEVANCE STATEMENT: Visceral fat volume is significantly associated with treatment outcomes in ICI-treated patients with non-small cell lung cancer. Moreover, fat quality may impact the treatment outcomes. This finding underscores the potential significance of both fat compartments and fat quality as prognostic indicators. KEY POINTS: • We found that visceral fat volume positively correlated with treatment response and survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors. • Additionally, a trend toward a negative correlation between visceral fat attenuation and survival was observed. • The findings highlight the prognostic utility of fat compartments and fat quality.

Small intestinal adenocarcinoma accompanied by lynch syndrome: A case report.

RATIONALE: Lynch syndrome is caused by germline mutations of DNA mismatch repair genes. A significant risk increase for several types of cancer is one of the characteristics of lynch syndrome. PATIENT CONCERNS: A 45-year-old female presented to the emergency department with abdominal pain that had persisted for a month. DIAGNOSES: The abdominal and pelvic computed tomography scan showed edematous and thickening of the proximal small bowel wall, as well as dilatation of the proximal bowel and stomach. INTERVENTIONS: Tumor resection of the small bowel was performed, and adenocarcinoma was confirmed pathologically. Microsatellite instability was also confirmed. OUTCOMES: Postoperative imaging revealed soft tissue lesions with potential for tumor seeding. Two months after the first surgery, a secondary surgery was performed as a result of cancer recurrence. The patient received chemotherapy with capecitabine. The latest computed tomography scan, performed 19 months after the cessation of chemotherapy, did not show any recurrence. LESSONS: In the rare incidence of small bowel cancer genetic mutation testing and detailed family history should be actively considered.

Diffuse alveolar hemorrhage from metastatic cardiac angiosarcoma of the lung successfully treated with paclitaxel chemotherapy: A case report and brief literature review.

Diffuse alveolar hemorrhage (DAH) is a life-threatening syndrome caused by various etiologies. DAH has rarely been reported to be associated with metastatic angiosarcoma. However, due to the rarity of complications, it may not be well-recognized by most clinicians. Herein, we report the case of a 70-year-old man with newly diagnosed metastatic cardiac angiosarcoma presenting with DAH. After an immediate bronchoalveolar lavage study and bronchoscopic biopsy, the patient was successfully treated with paclitaxel chemotherapy. Although most patients with this phenomenon have an extremely grave prognosis in previous literature, our experience showed that appropriate evaluation and treatment may be beneficial.

Incorporating hematopoietic stem-cell transplantation after second-line carfilzomib-lenalidomide-dexamethasone (KRd).

BACKGROUND: Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents. METHODS: A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes. RESULTS: The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression (n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd (n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) (p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039). CONCLUSIONS: In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.

L-Ascorbic Acid Inhibits Breast Cancer Growth by Inducing IRE/JNK/CHOP-Related Endoplasmic Reticulum Stress-Mediated p62/SQSTM1 Accumulation in the Nucleus.

Anticancer effects of L-ascorbic acid (Vitamin C, L-AA) have been reported in various types of cancers. L-AA intake reduces breast cancer recurrence and mortality; however, the role of L-AA in the treatment of breast cancer remains poorly understood. In this study, we investigated the effect and mechanism action of L-AA on breast cancer growth. L-AA inhibited the growth of breast cancer cells by inducing apoptotic cell death at the evaluated treatment concentrations without affecting normal cells. Moreover, L-AA induces autophagosome formation via regulation of mammalian target of rapamycin (mTOR), Beclin1, and autophagy-related genes (ATGs) and increased autophagic flux. Notably, we observed that L-AA increased p62/SQSTM1 (sequestosome 1) protein levels. Accumulation of p62 protein in cancer cells in response to stress has been reported, but its role in cancer regulation remains controversial. Here, we demonstrated that L-AA-induced p62 accumulation is related to L-AA-induced breast cancer growth inhibition. Furthermore, L-AA induced endoplasmic reticulum (ER) stress via the IRE-JNK-CHOP (inositol-requiring endonuclease-c-Jun N-terminal kinase-C/EBP homologous protein) signaling pathways, which increased the nuclear levels of p62/SQSTM1. These findings provide evidence that L-AA-induced ER stress could be crucial for p62 accumulation-dependent cell death, and L-AA can be useful in breast cancer treatment.

Daratumumab Monotherapy in Heavily Pretreated Asian Patients With Relapsed and Refractory Multiple Myeloma: A Real-world Experience.

BACKGROUND/AIM: Daratumumab is a promising novel agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its efficacy and toxicity profiles in real-world patients, especially in the Asian population. PATIENTS AND METHODS: This was a multicenter, retrospective, longitudinal cohort study set between January 2017 and April 2019. We collected and analyzed clinical and survival data of 21 patients treated with daratumumab monotherapy. All patients were previously exposed to proteasome inhibitors and immunomodulatory drugs. RESULTS: The overall response rate was 42.1%, including one complete remission (4.8%) and three very good partial responses (14.3%). The cycles of daratumumab delivered were three (range=1-10 cycles) and the median progression-free survival was 6 months, while the overall survival was not reached. Infusion reaction was observed in nine patients (42.9%), and one discontinued permanently. Fatigue was the most common adverse event (52.4%), and there were five cases of documented infection during daratumumab treatment, two of them leading to the death of the patient. CONCLUSION: Daratumumab monotherapy showed fairly promising activity with modest tolerance in heavily treated Asian RRMM patients.

Capecitabine Plus Oxaliplatin Combination Therapy for Basal Cell Carcinoma.

No effective systemic chemotherapy is well-established in basal cell carcinoma. We report a case with three simultaneous malignancies: colon cancer, basal cell carcinoma, and smoldering multiple myeloma. The patient was treated with capecitabine and oxaliplatin after surgery for colon cancer. Surprisingly, he achieved a complete response for basal cell carcinoma. This is the first report of this chemotherapy regimen in basal cell carcinoma. This finding suggests that combination capecitabine and oxaliplatin can be a treatment option for patients unable to receive local therapy.

Efficacy of Pemetrexed-based Chemotherapy in Comparison to Non-Pemetrexed-based Chemotherapy in Advanced, ALK+ Non-Small Cell Lung Cancer.

PURPOSE: Previous retrospective studies suggest that anaplastic lymphoma kinase (ALK) mutation-positive (ALK+) non-small cell lung cancer (NSCLC) patients are sensitive to pemetrexed. To determine its efficacy, we retrospectively evaluated clinical outcomes of pemetrexed-based chemotherapy in patients with ALK+ NSCLC. MATERIALS AND METHODS: We identified 126 patients with advanced, ALK+ NSCLC who received first-line cytotoxic chemotherapy. We compared response, progression-free survival (PFS), and overall survival (OS) rates according to chemotherapy regimens. Furthermore, we evaluated intracranial time to tumor progression (TTP) and proportion of ALK+ cells as prognostic factors. RESULTS: Forty-eight patients received pemetrexed-based chemotherapy, while 78 received other regimens as first-line treatment. The pemetrexed-based chemotherapy group showed superior overall response (44.7% vs. 14.3%, p<0.001) and disease control (85.1% vs. 62.3%, p=0.008) rates. The pemetrexed-based chemotherapy group also exhibited longer PFS (6.6 months vs. 3.8 months, p<0.001); OS rates were not significantly different. The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS. Intracranial TTP was similar between the treatment groups (32.7 months vs. 35.7 months, p=0.733). Patients who harbored a greater number of ALK+ tumor cells (≥70%) showed prolonged OS on univariate analysis (not reached vs. 44.8 months, p=0.041), but not on multivariate analysis (hazard ratio: 0.19, 95% confidence interval: 0.03-1.42; p=0.106). CONCLUSION: Pemetrexed-based regimens may prolong PFS in patients with ALK+ NSCLC as a first-line treatment, but are not associated with prolonged OS. Exposure to second-generation ALK inhibitors may improve OS rates in patients with ALK+ NSCLC.

Prospective Evaluation of the Clinical Implications of the Tumor Metabolism and Chemotherapy-Related Changes in Advanced Biliary Tract Cancer.

Tumor metabolism measured by 18F-FDG PET has a diagnostic and prognostic role in several cancers. The clinical implication of tumor metabolism in biliary tract cancer (BTC) has not been studied well. Therefore, we evaluated the prognostic value of tumor metabolism and chemotherapy-related changes in advanced BTC patients. Methods: We prospectively enrolled advanced BTC patients before the initiation of palliative chemotherapy. Using 18F-FDG PET, we assessed the baseline SUVmax and monitored the changes in SUVmax during chemotherapy. We analyzed the associations between SUVmax, and clinicopathologic factors and clinical outcomes. Results: Seventy-five patients were enrolled. All patients received gemcitabine/cisplatin as first-line chemotherapy. Primary tumor site, histologic differentiation, molecular characteristics, laboratory findings, and disease extent were associated with the metabolic characteristics. The high-metabolism group showed worse survival outcome (hazard ratio [HR] = 4.09, P = 0.001 for progression-free survival; HR = 2.61, P = 0.019 for overall survival [OS]) than the low-metabolism group. The lesser reduction of SUVmax was also associated with worse outcome (HR = 3.35, P = 0.002 for progression-free survival; HR = 1.96, P = 0.082 for OS). When both baseline tumor metabolism and its chemotherapy-related changes were considered, patients with a low metabolism and more reduction in metabolism obtained the best OS (20.7 vs. 6.2 mo, P = 0.013). Conclusion: Tumor metabolic activity and the chemotherapy-related changes in the metabolism are associated with prognosis in advanced BTC patients.

[Clinical Efficacy of Dynamic Contrast-enhanced Multidetector-row Computed Tomography in Patients with Obscure Gastrointestinal Bleeding].

BACKGROUND/AIMS: Obscure gastrointestinal bleeding (OGIB) accounts for 5% of all gastrointestinal (GI) bleeding cases. Dynamic contrast-enhanced multidetector-row CT (DCE-MDCT) is not generally recommended in OGIB patients due to its low sensitivity. However, it can be used to quickly and simply diagnose OGIB according to some guidelines. The aim of this study was to evaluate the clinical efficacy of DCE-MDCT in OGIB patients. METHODS: We retrospectively analyzed the medical records of 362 patients who underwent DCE-MDCT between March 2009 and January 2014. A total of 45 patients diagnosed with OGIB were included in this study. Their baseline characteristics and treatment procedure were analyzed retrospectively. The positive rates of DCE-MDCT for the detection of bleeding and associated factors were assessed. RESULTS: The mean age of the patients was 59 years, and males represented 51.1%. Melena was the most common symptom (44.4%). Positive rate of DCE-MDCT findings was 20.0% (9/45). Among these patients, intraluminal contrast extravasation was found in 5 patients (55.6%) and intraluminal hematoma or mass lesions were found in 2 patients each (22.2%). Thirty nine patients (86.7%) underwent conservative management, and 6 patients (13.3%) underwent specific treatment, such as endoscopic treatment, embolization, or surgery. Patients who showed positivity in DCE-MDCT more frequently received specific treatment compared with those who were negative (44.4% vs. 5.6%, p=0.010). CONCLUSIONS: Although DCE-MDCT showed a low positive rate (20.0%), positive findings of DCE-MDCT could lead to specific treatment. Positive DCE-MDCT findings play a useful role in the management of patients with OGIB.

Pazopanib for Non-small Cell Lung Cancer: The First Case Report in Korea.

Pazopanib is a potent multitargeted tyrosine kinase inhibitor that has been shown to have good efficacy in patients with renal cell carcinoma. A previous phase II trial demonstrated that short-term pazopanib administration was generally well tolerated and showed antitumor activity in patients with early-stage non-small cell lung cancer. Herein, we report on the case of a 66-year-old man with simultaneous metastatic squamous cell carcinoma of the lung and renal cell carcinoma who was treated with pazopanib. The patient showed an unexpected partial response and experienced a 10-month progression-free survival without significant toxicity. To the best of the authors' knowledge, this is the first report of pazopanib treatment in a non-small cell lung cancer patient in Korea. The results in this patient suggest that pazopanib may be a valid treatment option for advanced non-small cell lung cancer.

Small cell carcinoma of the liver and biliary tract without jaundice.

An 80-year-old woman presenting with chest pain was found to have a large, lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography (CT). The tumor had invaded the common hepatic artery and main portal vein. Jaundice developed 4 wk later, at which point, a pancreas and biliary CT scan revealed a large mass in the right lobe of the liver and a hilar duct obstruction, which was found to be a small cell carcinoma. Despite its rarity, liver and bile duct small cell carcinoma should be considered in the differential diagnosis of atypical chest pain without jaundice.

Secondary Syphilis with Nodular Vasculitis Mimicking Behçet's Disease.

Although, erythema nodosum is a common skin manifestation associated with syphilis, nodular vasculitis is a rare feature. Here, we describe a case of a 22-year-old, human immunedeficiency virus negative, non-immunocompromised man who developed recurrent oral and scrotal ulcers with nodular lesions of the lower extremitie. Behçet's disease was initially suspected, however, his serologic test for syphilis was positive, and he was thus diagnosed with secondary syphilis, with a skin biopsy showing nodular vasculitis. The patient was treated with benzathine penicillin, and the skin lesions disappeared after treatment.