Hyewon Ryu

Sorafenib for patients with differentiated thyroid cancer

www.thelancet.com Vol 385 January 17, 2015 227 exposure with sorafenib; sarcopenia has been associated with a larger sorafenib area under the curve on day 28 of treatment in patients with hepatocellular cancer. Patients with diff erentiated thyroid cancer receive long-term thyroxine suppressive treatment starting from the postoperative period, therefore, they are at a higher risk of sarcopenia than patients with other types of cancer starting sorafenib treatment. We propose that the mechanism for the high incidence of early toxic eff ects reported in the DECISION trial is due to reduced lean body mass in patients with diff erentiated thyroid cancer.

Just Toxicity, or Toxicity As a Biomarker of Efficacy of Ramucirumab in Breast Cancer?

TO THE EDITOR: Mackey et al reported the results of ROSE/ TRIO-012 (Ramucirumab Overall Survival Evaluation/Translational Research in Oncology 012), a randomized, placebo-controlled, phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. The study did not meet its primary end point of investigator-assessed progression-free survival (PFS), although PFS numerically favored the ramucirumab group (median PFS, 9.5 v 8.2 months; hazard ratio, 0.88; P .077). An important question was raised as to why the antiangiogenic strategy targeting vascular endothelial growth factor receptor 2 signaling in breast cancer failed to improve survival, whereas similar studies with ramucirumab in other solid tumors have shown significant survival benefits. In addition, is there any population that will benefit from this antiangiogenic treatment for breast cancer, as the authors mentioned in their Discussion section? In light of these questions, it is a critical challenge to identify relevant biomarkers, especially at the cellular or molecular level, that may help to identify molecularly defined populations with ramucirumab-sensitive disease. Alternatively, the occurrence of adverse events might act as surrogate biomarkers of drug activity, enabling the prediction of outcome during treatment, because the occurrence of treatment-related toxic effects is associated with a pharmacodynamic effect of the drug. Recently, it has been suggested that there are correlations between hypertension and outcome with ramucirumab in patients with advanced hepatocellular carcinoma. Therefore, it would be interesting to know whether the large prospective data set reported by Mackey et al shows a correlation between the development of hypertension and treatment outcome. The investigators could help to address this issue by providing survival curves related to the emergence of hypertension as an adverse event. Such data could help clinicians make better treatment decisions and could shed light on the future development of targeted therapy for breast cancer.

Nondiabetic kidney diseases in type 2 diabetic patients.

Background The aim of this study was to evaluate the clinical characteristics of nondiabetic nephropathy in type 2 diabetes mellitus patients and to find a clinical significance of renal biopsy and immunosuppressive treatment in such a patient. Methods Renal biopsy results, clinical parameters, and renal outcomes were analyzed in 75 diabetic patients who underwent kidney biopsy at Chungnam National University Hospital from January 1994 to December 2010. Results The three most common reasons for renal biopsy were nephrotic range proteinuria (44%), proteinuria without diabetic retinopathy (20%), and unexplained decline in renal function (20.0%). Ten patients (13.3%) had only diabetic nephropathy (Group I); 11 patients (14.7%) had diabetic nephropathy with superimposed nondiabetic nephropathy (Group II); and 54 patients (72%) had only nondiabetic nephropathy (Group III). Membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%) were the three most common nondiabetic nephropathies. Group III had shorter duration of diabetes and lesser diabetic retinopathy than Groups I and II (P=0.008). Group II had the lowest baseline estimated glomerular filtration rate (P=0.002), with the greatest proportion of renal deterioration during follow-up (median 38.0 months, P<0.0001). The patients who were treated with intensive method showed better renal outcomes (odds ratio 4.931; P=0.01). Absence of diabetic retinopathy was associated with favorable renal outcome in intensive treatment group (odds ratio 0.114; P=0.032). Conclusion Renal biopsy should be recommended for type 2 diabetic patients with atypical nephropathy because a considerable number of these patients may have nondiabetic nephropathies. And intensive treatment including corticosteroid or immunosuppressants could be recommended for type 2 diabetic patients with nondiabetic nephropathy, especially if the patients do not have diabetic retinopathy.

Beau’s Lines of the Fingernails

A 75-year-old man with castration-resistant prostate cancer who had been treated with 4 cycles of docetaxel and prednisone chemotherapy presented with 4 distinct, transverse depressed lines, which were parallel and evenly spaced, on all of his fingernails (Figure 1A, left hand; Figure 1B, right hand). Diagnosis of transverse ridging of the nails, also known as Beau’s lines, was made. Nail changes are a common side effect of systemic chemotherapy. The clinical presentation of drug-induced nail alterations depends on duration and severity of the toxic damage and on which nail structure is affected. Transverse linear lesions in nails can result from interruption in the growth of the nail matrix or changes in the color in the nail itself and may suggest an underlying systemic illness or the effect of toxins. Beau’s lines are typical signs of acute toxicity to the nail matrix keratinocytes with transient arrest in the nail plate production. The nail shows a transverse depression that migrates distally as the nail grows. The depth of the depression represents the extent of damage, and the width indicates the duration of the insult. These nail abnormalities are not exclusive to drugs but are commonly seen after traumas or systemic conditions. A drug should be suspected when Beau’s lines affect all nails at the same level as in our case. The responsible drug should be investigated among treatments taken 2 to 3 weeks before the appearance of the nail alteration, as a fingernail takes about 40 days to emerge from the proximal nail fold. Druginduced Beau’s lines are usually dose related and reproducible with readministration of the drug. There are no preventive measures or treatments, and the changes generally resolve as the nails grow out.

Chronic kidney disease in the BCR-ABL1 -negative myeloproliferative neoplasm: a single-center retrospective study

Background/Aims Renal complications related to BCR-ABL1-negative myeloproliferative neoplasms (MPNs) have not been examined fully in Asian populations. Methods We analyzed estimated glomerular filtration rate (eGFR) and its changes with time retrospectively in patients with BCR-ABL1-negative MPN from 2005 to 2015. Results The prevalence of chronic kidney disease (CKD) was 11% (6.6% having stage 3 and 4.4% having stage 4). In a linear regression analysis of eGFR versus time (years), overall, patients showed increased eGFR (mL/min/1.73 m2) by 0.51 (95% confidence interval [CI], –0.30 to 1.33; p = 0.22). Patients with polycythemia vera (PV), and those treated with hydroxyurea, showed statistically significant increases in eGFR (1.59; 95% CI, 0.28 to 2.90; p = 0.22 in PV; and 1.55; 95% CI, 0.56 to 2.54; p = 0.22 in treatment with hydroxyurea). In total, 17 patients (20.5%) showed rapid loss of eGFR (<–3 mL/min/1.73 m2per year). This rapid loss in eGFR was associated with a higher incidence of kidney disease (23.5% vs. 6.1%, p= 0.05) and a higher percentage of patients with high neutrophil (>7.0 × 109 /L) and high monocyte (> 0.7 × 109 /L) counts (76.5% vs. 50%, p=0.05; 52.9% vs. 28.8%, p= 0.06, respectively). More patients had high serum lactate dehydrogenase (> 500 U/L) levels (52.9% vs. 25.8%, p = 0.03) at diagnosis. Conclusions CKD is prevalent in patients with BCR-ABL1-negative MPN. Active cytoreductive therapy has the potential to improve kidney function in BCR-ABL1-negative MPN.

VIP (etoposide, ifosfamide, and cisplatin) in patients with previously treated soft tissue sarcoma

Abstract We retrospectively reviewed outcomes of treatment with VIP (combination of etoposide, ifosfamide, and cisplatin) in patients with previously treated soft tissue sarcoma (STS). We analyzed the medical records of patients with advanced or relapsed STS who had undergone VIP treatment as second-line or more chemotherapy between January 2000 and December 2015. The patients were treated with a combination of etoposide (100 mg/m2 for 5 days), ifosfamide (2000 mg/m2 for 2 days), and cisplatin (20 mg/m2 for 5 days) once every 4 weeks. Treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed in all patients and between responder and nonresponder groups (responders showed a tumor response to any prior systemic chemotherapy before VIP). Twenty-four patients with a median age of 50 years (range: 20–68 years) were treated with VIP. Eleven (45.8%) patients were male and 7 (29.2%) received 2 or more chemotherapy regimens before VIP. Median PFS was 3.7 months (95% confidence interval [CI], 1.3–6.1 months) and median OS was 10.0 months (95% CI, 6.6–13.5). The overall response rate was 37.5%, and the disease control rate was 50%. The responder group showed better PFS (7.7 months vs 3.0 months; P = 0.101) and significantly improved OS (11.0 months vs 8.8 months; P = 0.039) compared to those of nonresponders. All patients reported some grade of hematological toxicity. The most frequently encountered hematological toxicity was neutropenia (any grade, 77.7%; grade 3 or 4, 74.0%). VIP might be effective in patients with previously treated STS.

Abstract 3947: Atypical chemokine receptor ACKR3 expression is associated with aggressive behavior and poor prognosis in gastric cancer

Chemokine and their receptors are key mediators of normal physiology and a large number of pathologic conditions such as cancer, and this family of receptors is the emerging therapeutic target in the field of cancer treatment. ACKR3 is an atypical chemokine receptor first cloned from a dog cDNA library as the orphan receptor and was initially named Receptor Dog cDNA 1 (RDC1). Shortly after demonstrating that RDC1 binds with its ligand, stromal cell-derived factor-1α (SDF-1α) and interferon-inducible T-cell α chemoattractant (I-TAC), RDC1 was officially deorphanized. Accumulating evidence of recent studies have suggested that expression of ACKR3 is augmented in most of tumor cells as compared to their normal counterparts and is involved in cell proliferation, survival, migration, invasion during the initiation and progression of cancer. However, there is little information regarding their expression and clinical relevance in gastric cancer. The expression status of ACKR3 was investigated in 221 specimens of primary gastric cancer using immunohistochemistry. The correlation of ACKR3 expression with the clinicopathological features and survival outcomes was analyzed as well. Immunohistochemical staining of gastric cancer tissue sections revealed diverse cytoplasmic and membrane staining patterns for ACKR3. One hundred-fourteen cases (51.6%) showed low ACKR3 expression according to an arbitrary scoring system (grade 0-1; grade 0, n = 26; grade 1, n = 88), and one hundred-seven cases (48.4%) showed high expression (grade 2-3; grade 2, n = 58; grade 3, n = 49). There were no significant differences in age, gender, histology, tumor location, lymphatic and venous invasion among the two groups. However, high CXCR7 expression in cancer cells tended to be associated with proportion of tumor size greater than 5 cm (P = 0.055) and was significantly correlated with depth of tumor invasion (P Citation Format: Nayoung Kim, Seung-Woo Baek, Hyewon Ryu, Yoon Seok Choi, Ik Chan Song, Hwan Jung Yun, Deog Yeon Jo, Samyong Kim, Hyo Jin Lee. Atypical chemokine receptor ACKR3 expression is associated with aggressive behavior and poor prognosis in gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3947.

Solitary pulmonary plasmacytoma

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. A 79-year-old woman presented with a pulmonary nodule, which was incidentally found during regular health examination. Chest computed tomography revealed a solitary nodule of 1.4 cm in diameter located in the upper lobe of the right lung (A). Percutaneous needle biopsy of the nodule revealed extensive infiltration of plasma cells (B, C). Immunohistochemically, the cells were positive for CD138 and were restricted to kappa light chain (D). Complete blood count, routine chemistry (including BUN, creatinine and calcium) and urine analysis were nonspecific. Serum and urine protein electrophoresis and immunofixation did not show the presence of paraprotein, and serum kappa and lambda free light chains were within normal limits. Bone marrow plasma cells were less than 1%. Skeletal X-ray survey was negative. She was diagnosed with solitary pulmonary plasmacytoma and was placed on curative radiotherapy (36 Gy over 4 weeks). This case illustrates that plasmacytoma can be presented as a solitary pulmonary nodule.