Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). Conclusion This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Background: The association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context. Methods: National audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data. Results: We analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis. Conclusion Annual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.

PURPOSE: ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PET(Interim)) and end-of-induction therapy PET/CT (PET(EOI)) in patients with FL.METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PET(Interim) was performed 3 or 4 cycles after chemotherapy and PET(EOI) after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (−), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test.RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CTstudies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5–72.7 months). On PET(Interim), 23 patients were negative and 10 were positive. On PET(EOI) scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PET(EOI)(−) was associated with longer PFS. PET(Interim)(+) and PET(EOI)(+) patients had a significantly shorter PFS than PET(Interim)(−) patients (39.9 months, 95%confidence interval [CI] 23.0–56.9, versus 55.5months, 95%CI 49.7–61.2, p=0.005) and PET(EOI)(−) patients (14.2 months, 95% CI 8.5–19.8, versus 60.5 months, 95% CI 52.1–69.0, p<0.001).CONCLUSION: For patients with FL, PET(Interim) and PET(EOI) response is predictive of PFS, and PET(EOI)(+) is an independent prognostic factor for progression of FL.
Disease-Free Survival ; Drug Therapy ; Electrons ; Fluorodeoxyglucose F18 ; Humans ; Kaplan-Meier Estimate ; Lymphoma ; Lymphoma, Follicular ; Multivariate Analysis ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies

OBJECTIVES: Depression is a common comorbid condition in patients with chronic obstructive pulmonary disease (COPD) and has a higher prevalence than the general population. On the other hand, studies on the incidence of depression and quality of life in COPD patients often depend on a simple self-report questionnaire rather than a psychiatrist's clinical assessment. Starting with accurately diagnosing depression, the purpose of this study was to evaluate the factors related to depression as well as how depression influences the quality of life. METHODS: The study included 30 patients diagnosed with COPD. All the patients were interviewed for a diagnosis of depression by a psychiatrist. They were divided into two groups: with and without depression. For dyspnea, the modified Medical Research Council (mMRC) scale was used to evaluate how it affected daily life. Short-Form Health Survey 36 and COPD assessment test (CAT) were used to assess the quality of life. RESULTS: The degree of COPD and respiratory symptoms were related, but the severity of COPD did not influence the quality of life. In the presence of depression, mMRC and CAT were higher, whereas PCS and MCS were lower than in those without depression. Patients with depression suffered more from dyspnea and had a lower quality of life. CONCLUSION This study suggests that the degree of COPD was not related to depression. With depression, however, it led to the aggravation of dyspnea and a deteriorated quality of life. Combined treatment is essential to improving the patients' general well-being.

BACKGROUND/AIMS: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. METHODS: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed. RESULTS: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3–4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001). CONCLUSIONS Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

PURPOSE: ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PET(Interim)) and end-of-induction therapy PET/CT (PET(EOI)) in patients with FL. METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PET(Interim) was performed 3 or 4 cycles after chemotherapy and PET(EOI) after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (−), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test. RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CTstudies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5–72.7 months). On PET(Interim), 23 patients were negative and 10 were positive. On PET(EOI) scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PET(EOI)(−) was associated with longer PFS. PET(Interim)(+) and PET(EOI)(+) patients had a significantly shorter PFS than PET(Interim)(−) patients (39.9 months, 95%confidence interval [CI] 23.0–56.9, versus 55.5months, 95%CI 49.7–61.2, p=0.005) and PET(EOI)(−) patients (14.2 months, 95% CI 8.5–19.8, versus 60.5 months, 95% CI 52.1–69.0, p<0.001). CONCLUSION For patients with FL, PET(Interim) and PET(EOI) response is predictive of PFS, and PET(EOI)(+) is an independent prognostic factor for progression of FL.

PURPOSE: The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL). MATERIALS AND METHODS: A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups. RESULTS: The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067). CONCLUSION: IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.
Ambulatory Care Facilities ; Asparaginase* ; Escherichia coli* ; Escherichia* ; Etoposide* ; Humans ; Ifosfamide* ; Length of Stay ; Lymphoma* ; Methotrexate* ; Prednisolone* ; Seoul

BACKGROUND: We developed an additional laser guidance system to improve the efficacy and safety of conventional computed tomography (CT)–guided percutaneous transthoracic needle biopsy (PTNB), and we conducted this study to evaluate the efficacy and safety of our system. METHODS: We retrospectively analyzed the medical records of 244 patients who underwent CT-guided PTNB using our additional laser guidance system from July 1, 2015, to January 20, 2016. RESULTS: There were nine false-negative results among the 238 total cases. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of our system for diagnosing malignancy were 94.4% (152/161), 100% (77/77), 100% (152/152), 89.5% (77/86), and 96.2% (229/238), respectively. The results of univariate analysis showed that the risk factors for a false-negative result were male sex (p=0.029), a final diagnosis of malignancy (p=0.033), a lesion in the lower lobe (p=0.035), shorter distance from the skin to the target lesion (p=0.003), and shorter distance from the pleura to the target lesion (p=0.006). The overall complication rate was 30.5% (74/243). Pneumothorax, hemoptysis, and hemothorax occurred in 21.8% (53/243), 9.1% (22/243), and 1.6% (4/243) of cases, respectively. CONCLUSION: The additional laser guidance system might be a highly economical and efficient method to improve the diagnostic efficacy and safety of conventional CT-guided PTNB even if performed by inexperienced pulmonologists.
Biopsy, Needle* ; Diagnosis ; Hemoptysis ; Hemothorax ; Humans ; Lung Neoplasms ; Male ; Medical Records ; Methods ; Needles* ; Pleura ; Pneumothorax ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; Skin ; Solitary Pulmonary Nodule

Successful male germ cell transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug, busulfan, is commonly used for the preparation of recipient models before transplantation, the optimal dose of this drug has not yet been defined in dogs. In this study, 1-year-old mongrel dogs were intravenously injected with three different concentrations of busulfan (10, 15, or 17.5 mg/kg). Four weeks after busulfan treatment, no fully matured spermatozoa were detected in any of the busulfan-treated groups. However, small numbers of PGP9.5-positive spermatogonia were detected in all treatment groups, although no synaptonemal complex protein-3-positive spermatocytes were detected. Of note, acrosin-positive spermatids were not detected in the dogs treated with 15 or 17.5 mg/kg busulfan, but were detected in the other group. Eight weeks after busulfan treatment, the dogs treated with 10 mg/kg busulfan fully recovered, but those in the other groups did not. PGP9.5-positive spermatogonia were detected in the 10 mg/kg group, and at a similar level as in the control group, but these cells were rarely detected in the 15 and 17.5 mg/kg groups. These results suggest that a dose of 15-17.5 mg/kg is optimal for ablative treatment with busulfan to prepare the recipient dogs for male germ cell transplantation. At least eight weeks should be allowed for recovery. The results of this study might facilitate the production of recipient dogs for male germ cell transplantation and can also contribute to studies on chemotherapy.
Animals ; Busulfan* ; Colon ; Dogs* ; Drug Therapy ; Germ Cells ; Humans ; Male ; Spermatids ; Spermatocytes ; Spermatogonia ; Spermatozoa ; Stem Cell Transplantation* ; Stem Cells* ; Synaptonemal Complex ; Testis* ; Tissue Donors