Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. MATERIALS AND METHODS: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. RESULTS: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). CONCLUSION: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

A Case Report of Axillary Hibernoma: US, CT, MR, and Histopathologic Findings.

Hibernoma is a rare benign tumor of brown adipose tissue. Herein, we report a case of axillary hibernoma in a 53-year-old female and discuss the various radiologic findings. The US revealed a 4.5-cm well-defined oval heterogenous hyperechoic mass in the right axilla with anterior displacement of the axillary vessels. Non-enhanced chest CT showed a 5.0-cm well defined, oval, and low-attenuated mass. MRI demonstrated a 5.5-cm mass with heterogeneous intermediate-to-high signal intensity on T1-and T2-weighted images and irregular enhancement at the peripheral portion. The patient underwent an US-guided core needle biopsy and the final diagnosis was hibernoma.

The 17-gene stemness score associates with relapse risk and long-term outcomes following allogeneic haematopoietic cell transplantation in acute myeloid leukaemia.

A 17-gene stemness (LSC17) score determines risk in acute myeloid leukaemia patients treated with standard chemotherapy regimens. The present study further analysed the impact of the LSC17 score at diagnosis on outcomes following allogeneic haematopoietic cell transplantation (HCT). Out of 452 patients with available LSC17 score, 123 patients received allogeneic HCT. Transplant outcomes, including overall (OS), leukaemia-free survival (LFS), relapse incidence (RI) and non-relapse mortality (NRM), were compared according to the LSC17 scored group. The patients with a low LSC17 score had higher OS (56.2%) and LFS (54.4%) at 2 years compared to patients with high LSC17 score (47.2%, p = 0.0237 for OS and 46.0%, p = 0.0181 for LFS). The low LSC17 score group also had a lower relapse rate at 2 years (12.7%) compared to 25.3% in the high LSC17 score group (p = 0.017), but no difference in NRM (p = 0.674). Worse outcomes in the high LSC17 score group for OS, LFS and relapse were consistently observed across all stratified sub-groups. The use of more intensive conditioning did not improve outcomes for either group. In contrast, chronic graft-versus-host-disease was associated with more favourable outcomes in both groups. The 17-gene stemness score is highly prognostic for survival and relapse risk following allogeneic HCT.

Genetic changes during leukemic transformation to secondary acute myeloid leukemia from myeloproliferative neoplasms.

Leukemic transformation (LT) is the main cause of death for patients with myeloproliferative neoplasms (MPNs). To study genetic changes associated with the LT, we performed targeted sequencing in 26 MPN patients including 21 with paired samples. We observed that, besides three driver genes, IDH2 (19%) and ASXL1 (14%) were also frequently mutated at MPN diagnosis. Although variant allele frequencies (VAFs) of mutations in DNA methylation and spliceosome did not expand during LT, they were enriched in patients with LT (the LT group). At follow-up, we also observed acquisition of mutations, mostly in the LT group. When considering dynamics of VAF from diagnosis to follow-up, VAFs in the LT group expanded (median VAF, 36.7-43.7%, p = 0.045). In contrast, mutations in patients with no clinical progression was stable (median VAF, 36.3-35.7%, p = 0.739). Overall, the present study demonstrates genetic changes during LT and provides the potential for prognostic application.

Axillary Lymphadenopathy on Ultrasound after COVID-19 Vaccination and Its Influencing Factors: A Single-Center Study.

PURPOSE: This study aimed to assess the incidence of axillary lymphadenopathy on ultrasound after COVID-19 vaccination and to investigate the factors affecting lymphadenopathy. METHODS: We evaluated patients who had received a COVID-19 vaccination within 12 weeks before an ultrasound examination between August and October 2021. The incidence of vaccine-related ipsilateral axillary lymphadenopathy was evaluated using ultrasound. Age, sex, presence of axillary symptoms, injection site, vaccine type, interval from vaccination, and dose were compared between the groups with and without axillary lymphadenopathy. RESULTS: We included 413 patients, 202 (49%) of whom showed axillary lymphadenopathy on ultrasound after COVID-19 vaccination. Age, interval from vaccine, vaccine brand, vaccine type, dose, and symptom were significantly different between the lymphadenopathy and non-lymphadenopathy groups (p < 0.001), while the injection site and sex were not. Receiving an mRNA vaccine was the most important factor for axillary lymphadenopathy (p < 0.001), followed by intervals of 1-14 (p < 0.001) and 15-28 days (p < 0.001), younger age (p = 0.006), and first dose (p = 0.045). CONCLUSION: COVID-19 vaccine-related axillary lymphadenopathy on ultrasound is common. mRNA type, an interval of 4 weeks, younger age, and first dose were the important factors. Breast clinicians should be well aware of these side effects when performing imaging examinations and provide accurate information to patients.

Diagnostic efficacy, performance and safety of side-cut core needle biopsy for thyroid nodules: comparison of automated and semi-automated biopsy needles.

PURPOSE: This study was performed to compare the utility of the semi-automated and automated side-cut core biopsy needles for thyroid nodules. METHODS: Between January 2014 and March 2020, biopsy was performed for 278 thyroid nodules using the semi-automated core needle and for 225 nodules using the automated core needle. Nondiagnostic rate, inconclusive rate, diagnostic performance and complication rates were evaluated and compared between two core needle types. RESULTS: There were 1.2% (6/503) nondiagnostic results and 15.9% (80/503) inconclusive results. Nondiagnostic rate between two needle types was not significantly different. The semi-automated type (33/278, 11.9%) showed lower inconclusive rate than the automated type (47/225, 20.9%) (p = 0.006). The sensitivity, specificity, PPV, NPV and diagnostic accuracy for diagnosis of malignancy of the semi-automated type were 70.18, 100, 100, 84.96 and 88.89%, respectively; the corresponding rates of automated type were 70.45, 100, 100, 86.6, and 89.84%. There were 12 minor complications: four hematomas (4/278, 1.4%) for the semi-automated type and eight hematomas (8/225, 3.6%) for the automated type, which difference was not statistically significant. CONCLUSION: Core needle biopsy for thyroid nodules using either the semi-automated or automated needle is a safe diagnostic tool. Semi-automated needle has lower inconclusive rate than automated needle.

Case reports of shear-wave elastography (SWE) features of lymphoma involving the breast.

Breast lymphoma is a rare malignancy that is often difficult to distinguish from other breast diseases. Elastography has been proven to facilitate the diagnosis of breast lesions. However, only few reports have focused on the elastographic features of breast lymphoma. Therefore, we herein present 2 cases of breast lymphomas with a focus on the elastographic findings.

Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study.

PURPOSE: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MATERIALS AND METHODS: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). RESULTS: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). CONCLUSION: Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Rare case of contralateral supraclavicular lymphadenopathy after COVID-19 vaccination: Computed tomography and ultrasonography findings.

We present the computed tomography, ultrasonographic findings of a case of contralateral supraclavicular lymphadenopathy that occurred after AstraZeneca COVID-19 vaccination. Contralateral supraclavicular lymphadenopathy is very rare, but may be expected as an adverse reaction after COVID-19 vaccination. Radiologists as well as referring clinicians should be aware of this self-limiting process and its imaging features.

Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRDpos subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRDneg subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.

Antitumor activity and safety of sirolimus for solid tumors with PIK3CA mutations: A multicenter, open-label, prospective single-arm study (KM 02-01, KCSG UN17-16).

BACKGROUND: PIK3CA contributes to cell growth via the PI3K-AKT-mammalian target of rapamycin (mTOR) signaling pathway. Mutations in the pathway are frequently observed in solid tumors. We assessed the efficacy and safety of sirolimus, an mTOR inhibitor, in chemotherapy-refractory solid tumors with PIK3CA mutations or amplifications. METHODS: This was an open-label, single-arm, multicenter pilot study. Twenty-four patients with solid tumors harboring a PIK3CA mutation were treated with sirolimus between July 2017 and March 2019. Treatment was continued until disease progression, unacceptable adverse events, or death. The primary end points were the overall response rate (ORR), disease control rate (DCR), and safety. RESULTS: The median follow-up time was 6.1 months. Two patients with rapid disease progression-related death, one who withdrew, and one with a non-target lesion only were excluded from the analysis. Among 20 evaluable patients, 6 patients showed stable disease and 14 showed progressive disease (ORR 0%, DCR 30%). The median progression-free survival was 2.39 months (95% confidence interval, 1.97-2.81 months). The most common adverse event was abdominal pain (20.8%), followed by anemia (16.7%) and fatigue (16.7%). The adverse events were generally manageable. CONCLUSIONS: Although safe, sirolimus monotherapy did not show meaningful antitumor activity in chemotherapy-refractory solid tumors with PIK3CA mutations. Combinations of mTOR inhibitors for stabilization and other antitumor agents with beneficial effects on tumor volume may improve outcomes.

Multicenter retrospective analysis of the clinicopathologic features of monomorphic epitheliotropic intestinal T-cell lymphoma.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE-IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.

Sonographic diagnosis of thyroid metastasis from hepatocellular carcinoma.

Metastasis to the thyroid is very rare in hepatocellular carcinoma (HCC) and only a few cases have been reported. Herein, we report a rare case of metastatic HCC to the thyroid in a 63-year-old man and discuss the various radiologic findings. Computed tomography (CT) revealed a heterogeneous enhancing mass that had invaded the thyroid cartilage in the left upper thyroid, compressing the airway. Ultrasonography (US) showed a heterogeneous hypoechoic mass with increased vascularity in the peripheral portion. The mass showed focal intense uptake on positron emission tomography-computed tomography (PET-CT). The patient underwent US-guided core needle biopsy and the final diagnosis was metastatic HCC.

Breast-specific gamma imaging of invasive breast cancer: Clinicopathologic factors affecting detectability and correlation with mammographic findings.

PURPOSE: To investigate the factors affecting detectability of invasive breast cancers on BSGI. MATERIAL AND METHODS: We evaluated BSGI, mammography and pathologic reports of 89 patients with invasive breast cancers. RESULTS: 87.6% were visible on BSGI. Cancer in old or postmenopausal women were more visible on BSGI (p = 0.003, 0.046). Cancers ≥ 1.0 cm in size were significantly more visible on BSGI than those <1 cm in size (p = 0.002). Cancers in fatty breasts were more visible than those in dense breasts (p = 0.042). CONCLUSION: Invasive cancers in older, postmenopausal patients, cancers with size ≥1.0 cm, and those with fatty breast are better visualized by BSGI, than those in younger, premenopausal patients, with size <1.0 cm and dense breast.

Pazopanib maintenance after first-line etoposide and platinum chemotherapy in patients with extensive disease small-cell lung cancer: a multicentre, randomised, placebo-controlled Phase II study (KCSG-LU12-07).

BACKGROUND: We investigated whether pazopanib maintenance following first-line chemotherapy would improve survival in patients with extensive disease small-cell lung cancer (ED-SCLC). METHODS: This study is a randomised, placebo-controlled, phase II study that enroled ED-SCLC patients who had not progressed after four cycles of etoposide plus platinum therapy. Eligible patients were randomly assigned (1 : 1 ratio) to either placebo or pazopanib 800 mg per day until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). RESULTS: 97 patients were enroled and randomly assigned; 2 patients did not receive study drugs. In total, 95 patients received maintenance therapy (pazopanib, n=48; placebo, n=47) and were included in the analyses. Grade 3 toxicities for pazopanib maintenance were thrombocytopenia (10.4%, including one case with grade 4 toxicity), liver enzyme elevation (10.4%), fatigue (6.3%), and hypertension (6.3%). Median PFS was 3.7 months for pazopanib maintenance and 1.8 months for placebo (hazard ratio 0.44, 95% confidence interval: 0.29-0.69, P<0.0001). CONCLUSIONS: Pazopanib maintenance significantly prolonged PFS in patients with ED-SCLC. Given the toxicity profiles, however, relevant biomarkers to select patients for benefit from pazopanib should be further investigated.

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.

Pulmonary Leukocytoclastic Vasculitis as an Initial Presentation of Myelodysplastic Syndrome.

Systemic vasculitis involving the lung is a rare manifestation of myelodysplastic syndrome (MDS), and secondary vasculitis is considered to have poor prognosis. A 44-year-old man presented with fever and dyspnea of 1 month duration. A chest radiograph revealed bilateral multiple wedge shaped consolidations. In addition, the results of a percutaneous needle biopsy for non-resolving pneumonia were compatible with pulmonary vasculitis. Bone marrow biopsy was performed due to the persistence of unexplained anemia and the patient was diagnosed with MDS. We reported a case of secondary vasculitis presenting as non-resolving pneumonia, later diagnosed as paraneoplastic syndrome of undiagnosed MDS. The cytopenia and vasculitis improved after a short course of glucocorticoid treatment, and there was no recurrence despite the progression of underlying MDS.

Prognostic Model to Predict Survival Outcome for Curatively Resected Liposarcoma: A Multi-Institutional Experience.

PURPOSE: We performed this study to analyze the clinical features and prognosis of Korean patients with liposarcoma. PATIENTS & METHODS: Between October 1986 and April 2013, 231 patients who were diagnosed with liposarcoma by histologic examination were enrolled in this study. RESULTS: The distribution of histologic subtypes was well-differentiated (n = 97, 42%), myxoid (n = 74, 32%), dedifferentiated (n = 32, 13.9%), pleomorphic (n = 15, 6.5%), and round-cell liposarcoma (n = 13, 5.6%). The majority of liposarcomas were located in the lower extremities (35.5%) and retroperitoneum (34.2%). Prognosis was worse for the trunk group compared with the extremity group (median disease-free survival [DFS] 3.3 vs. 9.9 years, respectively, P <0.001). Median DFS was significantly worse in patients with high grade histology compared to those with low grade histology (16.9% vs. 65.7%, P <0.001). The independent prognostic factors associated with survival were histology (hazard ratio [HR] 3.01; 95% confidence interval [CI], 1.82-4.97; P <0.001) and primary site (HR 1.80; 95% CI, 1.12-2.89; P = 0.015). Three risk groups with different survival outcomes were identified: group 1 (n = 98), no risk factors; group 2 (n = 92), one risk factor; and group 3 (n = 41), two risk factors. CONCLUSIONS: Histologic subtype and primary site were independent prognostic factors for curatively resected liposarcoma. A prognostic model for patients with liposarcoma clarified distinct groups of patients with good prognostic discrimination.

Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010-2012 Korea National Health and Nutrition Examination Survey.

PURPOSE: Little is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population. METHODS: In total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90-104; 75-89; Group 4, 60-74; and Group 5, <60 mL/min/1.73m2. RESULTS: The weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60-89 mL/min/1.73m2 and decreased thereafter at an eGFR of <60 mL/min/1.73m2 (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75-89 mL/min/1.73m2 and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60-104 mL/min/1.73m2 was significantly lower than that with an eGFR of ≥105 mL/min/1.73m2 (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5). CONCLUSIONS: We noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m2) prior to a marked decrease in hemoglobin level with severe renal dysfunction.

Prognostic implications of PIK3CA amplification in curatively resected liposarcoma.

BACKGROUND: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma. PATIENTS AND METHODS: A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH). RESULTS: Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival. CONCLUSIONS: We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.