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PURPOSE Approximately 10% of patients with epidermal growth factor receptor (EGFR) mutation–positive non–small-cell lung cancer (NSCLC) harbor uncommon mutations. Here, we report the efficacy and safety of osimertinib in patients with NSCLC harboring uncommon EGFR mutations. PATIENT AND METHODS This was a multicenter, single-arm, open-label, phase II study in Korea. Patients with histologically confirmed metastatic or recurrent NSCLC harboring EGFR mutations other than the exon 19 deletion, L858R and T790M mutations, and exon 20 insertion were eligible for the study. The primary end point of objective response rate was assessed every 6 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary end points were progression-free survival, overall survival, duration of response, and safety. RESULTS Between March 2016 and October 2017, 37 patients were enrolled. All were evaluable except one patient who withdrew consent after starting treatment. Median age was 60 years, and 22 (61%) were male. Among patients, 61% received osimertinib as first-line therapy. The mutations identified were G719X (n = 19; 53%), followed by L861Q (n = 9; 25%), S768I (n = 8; 22%), and others (n = 4; 11%). Objective response rate was 50% (18 of 36 patients; 95% CI, 33% to 67%). Median progression-free survival was 8.2 months (95% CI, 5.9 to 10.5 months), and median overall survival was not reached. Median duration of response was 11.2 months (95% CI, 7.7 to 14.7 months). Adverse events of any grade were rash (n = 11; 31%), pruritus (n = 9; 25%), decreased appetite (n = 9; 25%), diarrhea (n = 8; 22%), and dyspnea (n = 8; 22%), but all adverse events were manageable. CONCLUSION Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.

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Liver transplantation (LT) is a curative modality for hepatocellular carcinoma (HCC), especially in patients with cirrhosis. However, there are still risks of recurrence. C-reactive protein (CRP), an acute-phase inflammatory reactant that is synthesized by hepatocytes, has been related to the prognosis of various malignancies, including HCC. In this study, we investigated the role of a high CRP level in predicting the posttransplant outcomes of HCC patients. We analyzed 85 patients undergoing LT between August 2000 and July 2010 whose pretransplant serum CRP levels were available. Only 2 patients underwent deceased donor LT, and the remaining patients underwent living donor LT. With 1 mg/dL used as a cutoff value, 27 patients showed high CRP levels (!1 mg/dL) at the time of LT, and 58 showed low CRP levels (<1 mg/dL). The total bilirubin level, Child-Pugh grade, Model for End-Stage Liver Disease score, maximal tumor size, and frequency of intrahepatic metastasis were significantly higher in the high-CRP group. According to multivariate analyses, HCC beyond the Milan criteria, a high CRP level, and microvascular invasion were related to tumor recurrence, and a high CRP level and microvascular invasion were related to poor overall survival. When a subgroup analysis was performed according to the Milan criteria, a high CRP level was an independent factor for predicting poor outcomes in patients with HCC beyond the Milan criteria (P ¼ 0.02 for recurrence and P < 0.001 for survival) but not in patients with HCC within the criteria. Serum CRP could be considered a useful and cost-effective biomarker for predicting outcomes after LT for HCC, particularly in patients beyond the Milan criteria.

Endothelial cell function is critical for angiogenic balance in both physiological and pathological conditions, such as wound healing and cancer, respectively. We report here that soluble heat shock protein beta-1 (HSPB1) is released primarily from endothelial cells (ECs), and plays a key role in regulating angiogenic balance via direct interaction with vascular endothelial growth factor (VEGF). VEGF-mediated phosphorylation of intracellular HSPB1 inhibited the secretion of HSPB1 and their binding activity in ECs. Interestingly, co-culture of tumor ECs with tumor cells decreased HSPB1 secretion from tumor ECs, suggesting that inhibition of HSPB1 secretion allows VEGF to promote angiogenesis. Additionally, neutralization of HSPB1 in a primary mouse sarcoma model promoted tumor growth, indicating the anti-angiogenic role of soluble HSPB1. Overexpression of HSPB1 by HSPB1 adenovirus was sufficient to suppress lung metastases of CT26 colon carcinoma in vivo, while neutralization of HSPB1 promoted in vivo wound healing. While VEGF-induced regulation of angiogenesis has been studied extensively, these findings illustrate the key contribution of HSPB1-VEGF interactions in the balance between physiological and pathological angiogenesis.

The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.

BackgroundClinical impact of the Geriatric Nutritional Risk Index (GNRI) in patients with extensive‐stage disease small cell lung cancer (ED‐SCLC) have not previously been reported.MethodsThis study analyzed 352 patients enrolled in a previous randomized phase III trial comparing the efficacy of irinotecan plus cisplatin with that of etoposide plus cisplatin as the first‐line therapy for ED‐SCLC. GNRI values were calculated using serum albumin levels and actual and ideal bodyweights. Patients with a GNRI > 98, 92–98, and <92 were grouped into no, low, and moderate/major risk groups, respectively.ResultsThe objective response rates were 63.2%, 52.6%, and 49.2% in the no, low, and moderate/major risk groups, respectively (P = 0.024). The median progression‐free survival (PFS) was shorter in patients with a lower GNRI than in those with a higher GNRI (no vs. low vs. moderate/major risk group; 6.5 vs. 5.8 vs. 5.9 months, respectively; P = 0.028). There were significant differences in median overall survival (OS) according to GNRI (no vs. low vs. moderate/major risk group; 13.2 vs. 10.3 vs. 8.4 months, respectively; P < 0.001). Multivariate analysis revealed that being in the moderate/major risk group was an independent poor prognostic factor for PFS (hazard ratio [HR]: 1.300, 95% confidence interval [CI]: 1.012–1.670; P = 0.040) and OS (HR: 1.539; 95% CI: 1.069–2.216; P = 0.020).ConclusionsThis prospective study shows that a low GNRI value was associated with a poor prognosis, and it supports the relationship between systemic inflammation, nutritional status, and clinical outcomes in patients with ED‐SCLC.Key pointsSignificant findings of the studyThe lower GNRI group had a low response rate to chemotherapy for ED‐SCLC. The HRs for PFS and OS were 1.300 and 1.539 in the patients with GNRI < 92.What this study addsLow GNRI is associated with poor prognosis in ED‐SCLC.

PurposeBreast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC.Materials and MethodsClinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively.ResultsOver a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease.ConclusionAnti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.