Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients.

PURPOSE: This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. MATERIALS AND METHODS: We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. RESULTS: Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). CONCLUSION: Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase-Low Squamous Cell Lung Cancer.

PURPOSE: Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression. MATERIALS AND METHODS: In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate. RESULTS: Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2. CONCLUSION: Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome.

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning. METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG. RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, "41%, and 36%" for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not. CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Prognostic Impact of Pregnancy in Korean Patients with Breast Cancer.

BACKGROUND: Pregnancy concurrent with, shortly before, or after breast cancer poses unique challenges because hormonal changes in pregnancy potentially interact with breast cancer outcomes. MATERIALS AND METHODS: We studied a cohort of 3,687 female patients of reproductive age (<50 years) with breast cancer, linking a large institutional database and the nationwide claims database to comprehensively capture exposure status and tumor characteristics. Exposures included breast cancer during pregnancy, postpartum breast cancer (<12 months after delivery), and pregnancy after breast cancer. RESULTS: Forty-five patients with postpartum breast cancer were significantly more likely to have advanced stage, hormone receptor-negative tumor and to be younger than 35 years at diagnosis than those without postpartum breast cancer. This trend was not observed with 18 patients with breast cancer during pregnancy. The unadjusted 5-year survival rates were 77% versus 96% for patients with postpartum breast cancer versus their counterparts, 89% versus 96% for patients with breast cancer during pregnancy versus their counterparts, and 98% versus 96% for patients with pregnancy after breast cancer versus their counterparts, respectively. In the multivariable analyses, postpartum breast cancer exhibited hazard ratios for death of 1.57 (95% confidence interval [CI], 0.82-2.99), whereas those for breast cancer during pregnancy and pregnancy after breast cancer were 1.09 (95% CI, 0.15-7.91) and 0.86 (95% CI, 0.26-2.83), respectively. CONCLUSION: Postpartum breast cancer, but not breast cancer during pregnancy, was associated with advanced stage, younger age at diagnosis (<35 years), hormone receptor-negative disease, and poorer survival. Pregnancy after breast cancer did not compromise overall survival. IMPLICATIONS FOR PRACTICE: Although pregnancy around the time of diagnosis of breast cancer is expected to become increasingly common with maternal age at first childbirth on the rise, data on the prognostic impact of pregnancy have been inconsistent and rare from Asian populations. In this investigation of a Korean patient cohort with breast cancer, pregnancy-associated breast cancer was associated with advanced stage, younger age at diagnosis (<35 years), hormone receptor-negative disease, and poorer survival. This adverse impact of pregnancy on the prognosis was apparent with postpartum breast cancer but not observed with breast cancer during pregnancy. Pregnancy after breast cancer did not compromise overall survival.

Pemetrexed in the Treatment of Leptomeningeal Metastasis in Patients With EGFR-mutant Lung Cancer.

INTRODUCTION: Leptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016. Post-LM survival was evaluated as well as clinical factors. RESULTS: In our patient cohort with EGFR-mutant NSCLC (n = 631), 17.4% (n = 110) developed LM. Their median post-LM survival was 5.7 months (95% confidence interval, [CI], 0.0-12.0 months). Post-LM survival was significantly longer with pemetrexed use after LM (median, 13.7 months; 95% CI, 4.1-23.2 months) than without pemetrexed use after LM (median, 4.0 months; 95% CI, 2.2-5.7 months; P = .008). In the multivariate analyses, no pemetrexed use after LM (vs. use) and no EGFR tyrosine kinase inhibitor use after LM (vs. use) were independently associated with a poor post-LM survival with a hazard ratio of 3.1 (95% CI, 1.5-6.3; P = .002) and 3.0 (95% CI, 1.6-5.8; P = .001), respectively. CONCLUSION: Pemetrexed use after LM was independently associated with a longer post-LM survival in patients with EGFR-mutant NSCLC with LM. Prospective studies are warranted to validate this finding.

Prognostic Value of Platelet Count in Patients with Peripheral T Cell Lymphoma.

BACKGROUND: Peripheral T cell lymphoma (PTCL) is a heterogeneous entity with poor survival. We evaluated the neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and platelet count as new prognostic factors for PTCL. PATIENTS AND METHODS: We retrospectively analyzed 77 patients with PTCL initially treated with anthracycline-based chemotherapy. Survival curves were compared between groups with different initial NLR (iNLR), end-point NLR (eNLR), initial ALC, and platelet counts. Cox regression was used to analyze the risk factor for survival. RESULTS: Patients with a higher eNLR (≥3), lymphopenia (< 1,000/µL), and thrombocytopenia (< 150 K/µL) had an inferior progression-free survival (PFS) and overall survival (OS) compared to their counterparts, while a higher iNLR (≥3) was predictive of a shorter OS but not PFS. Among these, thrombocytopenia was an independent poor prognostic factor for both PFS and OS, with a hazard ratio of 2.42 (p = 0.012) for PFS and 4.21 (p = 0.006) for OS. The presence of thrombocytopenia further stratified patients with a worse prognosis within overlapping risk-groups by the prognostic index for PTCL. CONCLUSIONS: Our study showed that thrombocytopenia at diagnosis was an independent prognostic factor for survival in patients with PTCL.

Treatment patterns and outcomes in patients with metastatic gastric cancer receiving third-line chemotherapy: A population-based outcomes study.

PURPOSE: There is limited data on third-line chemotherapy in patients with metastatic gastric cancer (MGC). This study was conducted to assess third-line treatment patterns, outcomes, and clinical parameters related to survival outcomes in patients with MGC. METHODS: Using the Korean Health Insurance Review and Assessment Service (HIRA) database, a nationwide population-based outcomes study was conducted. From the HIRA database, patients newly diagnosed in 2010 with MGC were identified (N = 1,871), and of these, 229 patients who had received third-line chemotherapy were finally selected for this study. RESULTS: Prior to third-line chemotherapy, more than 90% of patients received fluoropyrimidine and platinum, and 43.7% and 40.6% received taxane and irinotecan, respectively. Various third-line chemotherapy regimens containing taxane (docetaxel or paclitaxel), irinotecan, or oxaliplatin were prescribed. The median overall survival (OS) of all patients receiving third-line chemotherapy was 4.4 months. The median time from the start date of first-line chemotherapy to the start date of third-line chemotherapy (TF1T3) was 9.5 months, and a longer TF1T3 was the only factor that was significantly associated with an increased OS. The median OS of patients who had received fluoropyrimidine, platinum, and taxane followed by third-line irinotecan-based therapy was similar to that of patients who had received fluoropyrimidine, platinum, and irinotecan followed by third-line taxane-based therapy (p = 0.894). CONCLUSION: In patients with MGC receiving third-line chemotherapy, TF1T3 was the only significant factor associated with OS. The sequence of using taxane and irinotecan as subsequent therapy after first-line failure was not shown to impact survival outcome.

Prognostic role of the neutrophil-to-lymphocyte ratio in patients with primary central nervous system lymphoma.

Neutrophil-to-lymphocyte ratio (NLR) is one of the parameters of a complete blood cell count (CBC) test and has been reported to be an easily accessible prognostic marker in aggressive cancer, including non-Hodgkin lymphoma (NHL). Primary central nervous system lymphoma (PCNSL) is an extranodal NHL with highly aggressive features. However, the importance of the NLR has never been assessed in PCNSL. This retrospective study enrolled 62 biopsy-proven patients whose baseline NLR was available, and reviewed their medical records to compare both high (≥2.0) and low NLR (<2.0) groups, in terms of clinical characteristics and outcomes. The low NLR group showed significantly better response rates to induction chemotherapy compared to the high NLR group (p=0.041). At a median follow-up of 41.5 months, the high NLR group revealed a significantly worse 3-year overall survival (OS) (42.5 vs. 71.2%; p=0.031) and a worse 3-year progression-free survival (PFS) (37.3 vs. 60.1%; p=0.028). Univariable Cox analysis results showed that a high NLR at diagnosis was a poor prognostic factor for both 3-year OS (HR 2.64, 95% CI 1.06-6.60; p=0.038) and 3-year PFS (HR 2.41, 95% CI 1.07-5.42; p=0.034). However, multivariable analyses adjusting for International Extranodal Lymphoma Study Group (IELSG) score and induction chemotherapy regimen with rituximab, which were strongly prognostic in this study, showed no statistical significance even with the high NLR group's tendency towards a worse 3-year OS (HR 2.36, 95% CI 0.84-6.62, p=0.102) and a worse 3-year PFS (HR 2.28, 95% CI 0.93-5.63, p=0.073). In conclusion, given that NLR is simple and easily obtainable, it might play a potentially prognostic role in PCNSL from early disease onset.

Effect of Accurate Staging Using Positron Emission Tomography on the Outcomes of Prophylactic Cranial Irradiation in Patients With Limited Stage Small-Cell Lung Cancer.

BACKGROUND: Prophylactic cranial irradiation (PCI) was reported to offer survival benefits in patients with limited stage small-cell lung cancer (LS-SCLC). However, earlier studies did not routinely use positron emission tomography (PET) as part of the initial evaluation, thereby reducing the accuracy of tumor staging. We examined the effect of more accurate staging with PET on the role of PCI in patients with LS-SCLC. PATIENTS AND METHODS: We retrospectively collected data from 280 patients with LS-SCLC who had objective responses after combined chemoradiotherapy between 2001 and 2013. The outcomes of PCI were analyzed after stratifying the patients according to whether or not the initial staging included PET imaging. RESULTS: The risk of brain metastasis as the first site of relapse was lower in patients who received PCI than in those who did not, only in patients without initial PET imaging (13.3% vs. 37.0%; P = .020), but not in patients with initial PET imaging (34.3% vs. 41.1%; P = .243). There was no survival difference between subgroups who received PCI or not (5-year survival rates, 34.8% vs. 34.1%; P = .938). Patients who had initial staging evaluation with PET achieved long-term survival even without PCI (5-year survival rates, 38.3% with PCI, 38.6% without PCI). CONCLUSION: The role of PCI needs to be critically reassessed in LS-SCLC patients whose initial staging evaluation included PET because the benefit of PCI was not apparent for them.

Recurrent hypoglycemia triggered by sorafenib therapy in a patient with hemangiopericytoma.

Targeted therapy has been proven to be one of the most effective cancer treatments. However, some endocrine disorders can occur during treatment with targeted agents. We report the case of a patient who exhibited a wax and wane pattern of hypoglycemia that was attributed to sorafenib therapy. A 32-year-old woman with metastatic hemangiopericytoma visited the emergency department in a stuporous state. Nonhyperinsulinemic hypoglycemia was diagnosed, was exacerbated shortly after sorafenib therapy, and was improved by the cessation of sorafenib with additional glucocorticoid therapy. Patients with metastatic hemangiopericytoma should be carefully monitored with particular attention to hypoglycemia when sorafenib therapy is initiated.

Systemic Nocardiosis Mimicking Disease Flare-up after Discontinuation of Gefitinib in a Patient with EGFR-Mutant Lung Cancer.

Disease flare-up after discontinuing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been considered as a critical issue in lung cancer patients who have experienced radiologic progression after showing initial durable response. This is a case of systemic nocardiosis that occurred after chronic steroid use for radionecrosis from stereotactic radiosurgery. It was initially thought as a disease flare-up after stopping EGFR-TKI.