A phase Ia/Ib study of novel anti-ErbB3 monoclonal antibody, barecetamab (ISU104) in refractory solid cancers and monotherapy or in combination with cetuximab in recurrent or metastatic head and neck cancer.

We evaluated the safety, tolerability, pharmacokinetics and antitumor activity of barecetamab monotherapy and combination cetuximab therapy in patients with advanced solid cancers, especially head and neck cancer (HNC). Part 1 was a 3 + 3 dose-escalation study in which 15 patients received barecetamab at 1, 3, 5, 10 and 20 mg/kg intravenously (IV) on days 1 and 28 and weekly in patients with advanced solid cancer. Part 2 was a dose-expansion study including two patient groups with advanced HNC, including six patients receiving barecetamab at 20 mg/kg IV every 3 weeks and 12 patients receiving barecetamab and cetuximab (400 mg/m2 on day 1 followed by 250 mg/m2 every week). No dose-limiting toxicities (DLTs) were observed. Maximum serum target engagement was reached with trough levels of doses ≥3 mg/kg IV weekly. Common adverse drug reactions were diarrhea, stomatitis, dermatitis acneiform and decreased appetite. One durable complete response of more than 17 months was observed, and the overall response and disease control rates were 36.4% (4/11) and 81.1% (9/11), respectively, in the combination therapy group. In conclusion, DLT was not observed in barecetamab at 1 to 20 mg/kg. The recommended phase II dose was determined to be 20 mg/kg triweekly. Barecetamab and in cetuximab combination was well tolerated and demonstrated meaningful antitumor effects.

A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.

Mass spectrometry-based serum proteomic signature as a potential biomarker for survival in patients with non-small cell lung cancer receiving immunotherapy.

BACKGROUND: VeriStrat test is a serum assay which uses a mass spectrometry (MS)-based proteomic signature derived from machine learning. It is currently used as a prognostic marker for patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. However, little is known about its role for NSCLC patients receiving immune checkpoint inhibitors (ICIs). METHODS: This is a retrospective study that includes 47 patients with advanced stage NSCLC without an activating EGFR mutation, who underwent the VeriStrat test from 2016 to 2018. Spectra from blood samples were evaluated to assign patients into the VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) risk group. The clinical outcomes of 32 patients who received programmed cell death 1 (PD-1) inhibitors nivolumab or pembrolizumab were analyzed by VeriStrat status. RESULTS: The VS-G group demonstrated significantly higher progression-free survival (PFS) and overall survival (OS) compared to the VS-P group among overall NSCLC patients regardless of treatment (median PFS of 7.1 vs. 4.2 months, P=0.013, and median OS, not reached vs. 17.2 months, P=0.012). Among NSCLC patients treated with ICIs, VS-G classification was associated with significantly increased PFS in comparison to VS-P classification (median PFS of 6.2 vs. 3.0 months, P=0.012), while the differences in OS trended towards significance (median OS, not reached vs. 16.5 months P=0.076). Multivariate analysis showed that the VeriStrat status was significantly correlated with PFS and OS in NSCLC patients treated with ICIs (P=0.017, P=0.034, respectively). CONCLUSIONS: MS-based serum proteomic signature has potential as a biomarker for survival outcome in NSCLC patients receiving immunotherapy.

A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities.

BACKGROUND: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). MATERIALS AND METHODS: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. RESULTS: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. CONCLUSION: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.

Exceptional response to chemotherapy followed by concurrent radiotherapy and immunotherapy in a male with primary retroperitoneal serous Adenocarcinoma: a case report and literature review.

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely uncommon malignancy exclusively reported in females. Due to the rarity of the disease, it is difficult to establish a standardized treatment. CASE PRESENTATION: We describe a unique case of PRSA in a 71-year-old male who presented with right-sided lower back pain and numbness. Magnetic resonance imaging identified a mass invading the adjacent psoas muscle and twelfth rib. Tissue biopsy confirmed poorly differentiated PRSA. Patient was initially treated with neoadjuvant carboplatin and paclitaxel chemotherapy regimen. This resulted in complete radiological resolution of the tumor. However, 12 weeks later, rapid recurrence was noted on follow-up CT scan. The patient was then treated with external radiotherapy with concurrent nivolumab, an anti-PD-1 antibody. The patient displayed a positive response to treatment with reduction in primary tumor and metastases and had a sustained disease control. CONCLUSION: Treatment with radiotherapy in combination with anti-PD-1 antibody could be an effective modality of management for PRSA.

Clinical and Immunological Implications of Frameshift Mutations in Lung Cancer.

INTRODUCTION: Presently, programmed death ligand 1 is the most commonly used biomarker to predict response to immune checkpoint inhibitors (ICIs) in NSCLC. Owing to its several limitations, there is continuous search for more precise and reliable markers. Frameshift mutations by insertion or deletion (fsindels) are suggested to induce more immunogenic tumor-specific neoantigens, conferring better response to ICIs. Positive correlation of fsindels with ICI response has been studied in melanoma and renal cell carcinoma. We investigated the implication of fsindels in the clinical outcomes and immune landscape of patients with NSCLC treated with ICIs. METHODS: We utilized The Cancer Genome Atlas data set to analyze tumor mutational burden, neoantigen burden, and immune landscape in relation to fsindel status. In addition, utilizing the clinical data from 122 patients treated with ICIs, we evaluated the influence of fsindels on disease response rates and survival outcomes. RESULTS: A positive correlation between fsindel burden and tumor mutational burden and activated CD4/CD8 T-cell infiltration was shown. Presence of fsindels was also associated with significant prolongation of progression-free survival in patients treated with ICIs (median 6.2 versus 2.7 months [p = 0.01]). In addition, significant differences in the overall response rates (26% versus 12% [p = 0.04]) and disease control rates (68% versus 48% [p = 0.02]) were observed in patients with fsindels. CONCLUSION: Our findings suggest that fsindels may have a predictive role for ICI response in NSCLC.

The effects of erythropoiesis-stimulating agents on the management of chemotherapy-induced anemia and tumor growth in diffuse large B-cell lymphoma patients.

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 µg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.

Retrospective analysis of palliative chemotherapy for the patients with bladder adenocarcinoma: Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee.

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.

Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to Prevent Dexamethasone-Induced Hiccup in Cancer Patients Treated with Chemotherapy: A Randomized, Single-Blind, Crossover Phase III Trial.

BACKGROUND: To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS: Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS: No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024. CONCLUSION: Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy. IMPLICATIONS FOR PRACTICE: In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.

Intra-tumoral Metastatic Double Primary Carcinoma: Synchronous Metastatic Tumor in Lung from Breast and Thyroid Carcinoma.

Cases of phenotypic heterogeneity of cells within tumors have recently been reported. Here, we report on a patient with characteristic intra-tumor double primary metastases in the lung. This patient was a 40-year-old Korean woman who had been diagnosed with breast cancer (T1N0M0, estrogen receptor/progesterone receptor/HER2 +/+/+) and papillary thyroid cancer three years prior and underwent a complete surgical resection followed by appropriate adjuvant treatment with radiation, hormone, and radioactive iodine. She was recently admitted for newly developed pulmonary nodules. Metastasectomy through video-assisted thoracoscopic surgery revealed recurrent double primary cancer with two different components (metastatic ductal carcinomas from the breast and metastatic papillary carcinomas from the thyroid gland) in each pulmonary nodule in the right upper lobe and right middle lobe. To the best of our knowledge, this is the first report of simultaneous recurrent double metastasis in one organ from different primary origins.

The prognostic significance of elevated levels of serum ferritin before chemotherapy in patients with non-Hodgkin lymphoma.

BACKGROUND: Elevated levels of serum ferritin have been documented to be an adverse prognostic factor in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation. The purpose of this study was to estimate the correlation between elevated levels of serum ferritin and survival outcomes in patients with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: A total of 267 patients who were newly diagnosed with NHL and who received chemotherapy between September 1999 and April 2012 were retrospectively analyzed. RESULTS: In multivariate analysis, other chemotherapy regimens excluding CHOP-like chemotherapy regimens (cyclophosphamide, adriamycin, vincristine, prednisolone) and RCHOP (rituximab plus CHOP), a high level of ß2-microglobulin, a high-intermediate/high risk according to the international prognostic index (IPI), and elevated levels of serum ferritin were all significant independent prognostic factors for 5-year progression-free survival rates. RCHOP and other chemotherapy regimens, a high level of ß2-microglobulin, a high-intermediate/high IPI risk, and high levels of serum ferritin were significant independent prognostic factors for 5-year overall survival rates. CONCLUSION: Elevated levels of serum ferritin of 500 ng/mL or more as well as the use of chemotherapy regimens besides CHOP-like or RCHOP, a high-intermediate/high risk IPI, and a high level of beta2-microglobulin in NHL may be an important marker for predicting poor survival outcomes.

Comparison of therapeutic outcomes between surgical resection followed by R-CHOP and R-CHOP alone for localized primary intestinal diffuse large B-cell lymphoma.

OBJECTIVES: There is no confirmed treatment strategy for primary intestinal diffuse large B-cell lymphoma (DLBL). In this retrospective study, the purpose is to find an appropriate treatment strategy in patients with primary intestinal DLBL undergoing surgery followed by chemotherapy or chemotherapy alone. METHODS: Seventy-six patients were newly diagnosed with DLBL and received treatment between March 2004 and June 2011. Forty-seven patients were treated with surgical resection followed by rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP), and 29 patients were treated with R-CHOP chemotherapy alone. RESULTS: The characteristics of the patients were as follows: the median age was 56.5 years (range, 15 to 85 y) with a female to male ratio of 1.00:1.45. There was no significant difference in patient characteristics between the 2 groups. The estimated 3-year progression-free survival rates (PFS) and overall survival rates (OS) of surgery followed by R-CHOP (surgery/R-CHOP) and R-CHOP alone (R-CHOP) groups were 92.2% and 74.8% (P=0.009) and 94.2% and 80.7% (P=0.049), respectively. In univariate analysis, significant differences were seen in estimated PFS and OS rates when comparing Lugano stages I and II1 with II2 and IIE (P=0.006 and 0.036), low and low-intermediate risk with high-intermediate risk (P=0.004 and 0.000), and surgery/R-CHOP group with R-CHOP group (P=0.009 and 0.049), respectively. In multivariate analysis, there were no independent predictive factors for survival. CONCLUSIONS: Patients treated with surgery followed by R-CHOP seemed to have a higher survival rate than those treated with R-CHOP alone. There were no significant prognostic factors for survival, but there were possible prognostic factors such as Lugano stage, International Prognostic Index risk, and treatment modality for PFS and OS.

Predictive factors for rapid neutrophil and platelet engraftment after allogenic peripheral blood stem cell transplantation in patients with acute leukemia.

The aim of this study was to investigate predictive factors for rapid engraftment after allogeneic peripheral blood stem cell transplantation (alloPBSCT) in patients with acute leukemia. Two hundred sixty-two patients receiving alloPBSCT were analyzed. Subset analyses of donor stem cells were conducted using a flow cytometric method. The correlation between rapid engraftment of neutrophils, platelets, and donor stem cells doses, as well as other recipient and donor clinical factors, was analyzed. In univariate analysis, factors correlated with neutrophil engraftment (≥0.5 × 10(9)/L) by day 12 were achievement of complete remission (CR) after induction chemotherapy (CR1) before hematopoietic cell transplantation (HCT) and high numbers of CD34+ cells, CD3+ T cells, and CD3+/CD4+ T cells. Factors correlated with platelet engraftment (≥20 × 10(9)/L) by day 12 were achievement of CR1 before HCT, donor and recipient sex mismatch, and high numbers of mononuclear cells, CD34+ cells, CD3+ T cells, CD3+/CD4+ T cells, CD3+/CD8+ T cells, and CD56+ NK cells. In multivariate analysis, independent predictive factors for rapid neutrophil and platelet engraftment were CR1 before HCT (p < 0.001 and p = 0.002, respectively), high number of donor CD34+ cells (p = 0.005 and p < 0.001, respectively), and high number of CD3+ T cells (p = 0.005 and p = 0.001, respectively). In conclusion, achieving CR1 before HCT, as well as larger quantities of donor CD34+ and CD3+ T cells, may predict rapid neutrophil and platelet engraftment after PBSCT.

Metabolic response evaluated by 18F-FDG PET/CT as a potential screening tool in identifying a subgroup of patients with advanced non-small cell lung cancer for immediate maintenance therapy after first-line chemotherapy.

PURPOSE: Among patients with advanced non-small cell lung cancer (NSCLC), identification of a subgroup of patients for immediate maintenance treatment after first-line chemotherapy has great importance in improving survival. The purpose of this study was to investigate whether the metabolic responses evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be a potential screening tool for identifying patients with early disease progression who may benefit from immediate maintenance treatment. METHODS: A total of 52 patients with advanced NSCLC (36 men and 16 women, mean age 57.2 ± 10.6 years) who underwent baseline and follow-up (18)F-FDG PET/CT after four cycles of first-line chemotherapy were enrolled. Maximum standardized uptake value (SUV(max)), SUV(peak), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the tumour lesions were measured and percentage decrease of the parameters was calculated. The prognostic significance of percentage decrease of these parameters and other clinical variables related to progression-free survival (PFS) and overall survival (OS) were assessed by Cox proportional hazards regression analysis. Receiver-operating characteristic (ROC) curve analysis was used to define the optimal cut-off value of percentage decrease of the parameters that could distinguish between early (PFS < 6 months) and late (PFS ≥ 6 months) disease progression groups. RESULTS: Multivariate analysis showed that percentage decrease of TLG [hazard ratio per 10% decrease = 1.030, 95% confidence interval (CI) = 1.012-1.048, p = 0.001) was a significant predictor of PFS and OS. ROC curves identified a 50.0% decrease in TLG as the optimal cut-off value to distinguish disease progression groups. Positive and negative predictive values of the optimal TLG value for selecting patients with late disease progression were 36.4 and 100.0%, respectively. CONCLUSION: The percentage decrease in TLG of measurable tumour lesions may be a potential parameter to appropriately identify a subgroup of patients for immediate maintenance treatment after first-line chemotherapy in patients with advanced NSCLC.

Unique perception of clinical trials by Korean cancer patients.

BACKGROUND: In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied. METHODS: Between July 1st and November 30th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC) were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS) score. RESULTS: In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trials was substantially higher in patients who had a higher level of education (p<0.001), were married (p=0.004), and had a higher economic status (p=0.001). However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%). Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p<0.001). CONCLUSIONS: This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.

Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma NSCLC patients with EGFR mutation.

PURPOSE: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) gefitinib and erlotinib have shown dramatic response rate (RR) and significant prolongation of progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation. Since only a few patients with non-adenocarcinoma histology have been enrolled in clinical trials, the efficacy of EGFR TKIs in non-adenocarcinoma NSCLC patients with EGFR mutation has not yet been fully determined. METHODS: We retrospectively analyzed clinical outcomes, including RR, PFS, and OS, in patients who were treated with the EGFR TKIs gefitinib or erlotinib and compared the results with those of adenocarcinoma patients with EGFR mutation and non-adenocarcinoma patients with wild-type EGFR. RESULTS: Among 250 patients with non-adenocarcinoma of the lung who underwent EGFR mutation genotyping, 21 were found to have an EGFR mutation (8.4 %). Twelve of the 21 patients were treated with the EGFR TKIs gefitinib (n = 6) or erlotinib (n = 6). The most common mutation was exon 19 deletion (n = 7). The RR and disease control rate for 12 patients receiving EGFR TKIs were 50 and 75 %, respectively. The median PFS was 3.67 months (95 % CI: 1.34-5.99), which was significantly lower than that of 269 adenocarcinoma patients with EGFR mutation (13.53 months) but better than that of 32 non-adenocarcinoma patients with wild-type EGFR (1.83 months) who were treated with EGFR TKIs. CONCLUSIONS: The results of this study show that the EGFR mutation rate in Korean patients with non-adenocarcinoma of the lung is relatively high and that the clinical outcomes of EGFR TKIs are modest.

The impact of baseline and interim PET/CT parameters on clinical outcome in patients with diffuse large B cell lymphoma.

Taking a step forward from the IPI, attention is focused on the role of 18F-FDG PET/CT as a tool for guidance in risk stratification in patients with aggressive non-Hodgkin's lymphoma (NHL). Here, we analyzed the predictive value of various PET/CT parameters in patients with DLBCL. Particularly, we were interested in patients with an IPI score of 1, 2, or 3, whose prognosis are confusing. Between Jul 2008 and Feb 2010, a total of 100 patients (including 57 patients with an IPI score of 1-3) who were treated with R-CHOP for DLBCL, and had assessable PET/CT parameters were analyzed in this study. Absolute value of SUVmax, SUVsum(sum of SUVmax) and TLGsum(SUVmean x Volumemeta) from baseline and interim PET/CT, and ΔSUVsum, ΔSUVmax, and ΔTLGsum between baseline and interim PET/CT were selected as PET/CT parameters. The median number of R-CHOP cycles was 6, and interim PET/CT was performed after 2 or 3 cycles. None of the parameters which showed percentile change between initial and interim PET/CT were associated with prognosis. Instead, absolute value of SUVsum from baseline PET/CT, and SUVmax and SUVsum from interim PET/CT were significantly relevant to PFS in all patients, and in patients with an IPI score of 1­3.

Incidence, risk factors and clinical features of venous thromboembolism in newly diagnosed lymphoma patients: results from a prospective cohort study with Asian population.

INTRODUCTION: Venous thromboembolism (VTE) may be associated with treatment failure rate and quality of life deterioration in lymphoma patients. However, the majority of data regarding VTE has come from retrospective studies done in Western countries. MATERIALS AND METHODS: We analyzed VTE, including pulmonary embolism and deep vein thrombosis, from Asian patients enrolled a prospective cohort study. All patients were newly diagnosed Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). RESULTS: A total of 686 patients were analyzed, and the median follow-up duration was 21.8 months. There were 54 cases of VTE including deep vein thrombosis alone (33/54, 61.1%) and pulmonary embolism (21/54, 38.9%). The median time to VTE was 1.97 months, and the one-year actuarial incidence was 7.9%. The global incidence of VTE was higher in patients with NHL (51/641, 8.0%) than HL (3/45, 6.7%). All cases of VTE occurred in patients receiving chemotherapy whereas no VTE in patients without chemotherapy. VTE was also independently associated with age older than 60 years and primary central nervous system (CNS) lymphoma. No VTE-related deaths were reported among all cases of VTE. Thus, overall survival was not different between patients with and without VTE. The subgroup analysis of patients with diffuse large B-cell lymphoma showed 8.9% of one-year actuarial incidence, but the occurrence of VTE did not influence its overall survival, either. CONCLUSIONS: The incidence of VTE in our study population was comparable to that of Western countries, and VTE was associated with chemotherapy, brain involvement and old age.

Implications of different CA 15-3 levels according to breast cancer subtype at initial diagnosis of recurrent or metastatic breast cancer.

BACKGROUND: CA 15-3 is derived from proteolytic shedding of the extracellular domain of mucin 1 (MUC1) glycoprotein. Luminal subtype breast cancer shows a higher expression in MUC1 genes, and a positive relationship between MUC1 expression and estrogen receptor (ER) expression has been reported. In this study, we attempted to determine the difference of CA 15-3 level according to the subtype of breast cancer. METHODS: From January 2000 to December 2009, a total of 707 patients who were diagnosed with metastatic or recurrent breast cancer at Samsung Medical Center were included in this study. Among these, 536 patients with available clinical data including pretreatment CA 15-3 and immunohistochemistry for ER, progesterone receptor (PgR) and hormone receptor 2 (HER2) were analyzed in this study. Patients were classified into 3 groups according to their receptor status: ER-positive (ER+) and/or PgR+ irrespective of HER2 (HR+), ER-/PgR-/HER2+ (HER2-enriched) and ER-/PgR-/HER2- (triple negative, TN). RESULTS: The supranormal values of CA 15-3 were frequently observed in HR+ breast cancer compared to other types (45.6% for HR+, 24.4% for HER2-enriched and 28.8% for TN; p < 0.001). The increase of marker levels differed significantly among the 3 groups (24 U/ml for HR+, 13 U/ml for HER2-enriched and 18 U/ml for TN; p < 0.001). CONCLUSIONS: The increase of both marker levels and the frequency of supranormal values of CA 15-3 were more frequently observed in HR+ breast cancer, which is positively associated with MUC1 expression. These results could potentially serve as a basis for expanding the clinical implications of CA 15-3 in the field of clinical trials for novel targeted therapies in breast cancer.