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  • 1
    In: Acta Radiologica, SAGE Publications, Vol. 60, No. 11 ( 2019-11), p. 1457-1464
    Type of Medium: Online Resource
    ISSN: 0284-1851 , 1600-0455
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    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
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  • 2
    In: Cancer Communications, Wiley, Vol. 39, No. 1 ( 2019-12), p. 1-10
    Abstract: The response rate and survival improvement for rituximab, a CD20‐targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single‐arm, open‐label phase II study evaluated the survival efficacy of 2 years of rituximab‐maintenance therapy in patients with stage III–IV CD20‐positive MZL who had responded to first‐line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation. Methods Prior to rituximab‐maintenance therapy, patients received 6–8 cycles of first‐line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m 2 ), cyclophosphamide (750 mg/m 2 ), and vincristine (1.4 mg/m 2 ; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3‐week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3‐week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab‐maintenance therapy which was administered intravenously at a dose of 375 mg/m 2 every 8 weeks for up to 12 cycles. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. Results 47 patients were enrolled, of whom, 45 (96%) received rituximab‐maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first‐line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow‐up of 38.2 months, their observed 3‐year PFS rate was 81%. During the rituximab‐maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS ( P = 0.003) and demonstrated a 3‐year OS rate of 90%. Rituximab‐maintenance therapy was well tolerated, and the common treatment‐emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). Conclusion Rituximab‐maintenance therapy following first‐line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov : NCT01213095
    Type of Medium: Online Resource
    ISSN: 2523-3548 , 2523-3548
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 3
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1811-1811
    Abstract: BACKGROUND: According to our prior prospective phase II trial, Rituximab in combination with chemotherapy (R-CVP) has been shown to improve response rate (RR) and progression free survival (PFS) in patients with advanced stage marginal zone lymphoma (MZL) compared with chemotherapy alone (CVP). In spite of better RR and PFS, relapses seem to continue after immunotherapeutic treatment in these patients. Thus, eventual relapse remains an important clinical issue for the majority of patients with indolent lymphoma, and defining further ways to extend the period of remission remains an essential goal. But data from clinical trials evaluating rituximab maintenance treatment in these patients are almost limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the PFS of patients with MZL. METHODS: Histologically confirmed advanced stage MZL patients who did not progress at the end of 6~8 cycles of 1st line Rituximab-CVP (cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 (maximum 2.0 mg), given intravenously on day 1, and oral prednisolone 100 mg on days 1-5) regimen were enrolled. Patients received 2 years of rituximab maintenance therapy (375 mg/m2 every 8 weeks). Primary objection was three year progression free survival. This trial is registered with ClinicalTrials.gov, number NCT012113095. RESULTS Between March 2010 and March 2013, a total of 47 patients were enrolled with informed consent at this trial from 17 institutes in Korea. Among these patients, 1 patient withdrew informed consent, 1 patient was screening failure with combined thyroid cancer. The median age of the evaluated 45 (32 males, 13 females) patients is 54 (range 33-77) years. Fifteen patients (33.3%) evidenced nodal MZL, 30 (66.7%) extranodal MZL (10 patients were lung, 6 ocular, and 5 stomach, in order of frequency). The IPI score were 1 in 13 (28.9%), 2 in 21 (46.7%), 3 in 9 (20%), and 4 in 2 (4.4%) patients. The patients received a total of 6 or 8 cycles of 1st line R-CVP chemotherapy were 10 (22.2%) and 35 (77.8%), respectively. There were 20 CR (44.4%), 22 PR (48.9%), and 3 SD (6.7%). Median treated number of rituximab maintenance followed by R-CVP was 12 (range 1-12). Thirty two patients (71.1%) patients completed planned 12 cycles of rituximab maintenance. Disease progression during rituximab maintenance was 8 patients, 2 patients stopped treatment because of side effects (1 abdominal pain, 1 recurrent pneumonia) 2 patients were follow-up loss. Four patients were expired (each 1 pneumonitis, pneumonia, sepsis, and disease progression). PFS and OS rate at 3 years were 78.9% and 90.6%, respectively. CONCLUSION: 2 years of rituximab maintenance therapy after R-CVP first-line chemotherapy for advanced stage MZL might be improve PFS with tolerable toxicities Disclosures Kim: Celltrion, Inc.: Consultancy, Honoraria. Lee:Amgen: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 4
    In: The Lancet Oncology, Elsevier BV, Vol. 17, No. 3 ( 2016-03), p. 389-400
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2049730-1
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2901-2901
    Abstract: Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease with a variety of molecular aberrations and diverse clinical outcomes. BCL2 expression has been implicated for a poor prognosis among patients with DLBCL. However, there is no consensus regarding the interpretation of BCL2 expression in DLBCL. In previous studies, the range of BCL2-positive cases, determined by immunohistochemistry (IHC), was highly variable (24 - 80%) due to subjective and semiquantitative interpretation and the absence of the established cutoff value for BCL2 expression. Consequently, the prognostic impact of BCL2 varies between studies. In addition, only the proportion of BCL2 positive tumor cells are considered in determining the BCL2 positivity. We aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. Methods We retrospectively collected formalin-fixed, paraffin-embedded (FFPE) diagnostic biopsies from 221 patients with de novo DLBCL between January 2007 and December 2012 at our institute. All patients were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line treatment. A separate validation set included 111 patients with de novo DLBCL who received first-line R-CHOP at another tertiary hospital in South Korea. BCL2 expression was analyzed using the tumor-specific Automated Quantitative Analysis (AQUA) scoring system based on multiplex immunofluorescence. The tumor-specific quantified intensity information in pixels was converted to protein expression information on a cell basis using the AQUA scoring system. The AQUA scores for BCL2 was calculated as the signal intensities of BCL2 in the target compartment divided by the pixel area of the target compartment. Cell of origin (COO) was determined according to the Hans classification using IHC. Results Ninety-eight patients (44.3%) were 〉 60 years old of age, 126 patients (57.0%) were male and 81 patients (36.7%) had an International Prognostic Index of 3-5 in the training set. With a median follow-up duration of 59 months, the 5-year event-free survival (EFS) and overall survival (OS) rate were 62.2% and 69.0%, respectively. The BCL2 AQUA score of 41.47 was determined as the optimal cutoff value in the ROC analysis. A total of 86 patients (38.9%) were classified as high BCL2 AQUA score group according to the determined cutoff value. High BCL2 AQUA score was significantly associated with worse OS and EFS (P = 0.00015; OS, P = 0.00012; EFS) (Figure 1A, B). Multivariate analysis revealed that high BCL2 AQUA score was a significant poor prognostic factor for both OS and EFS independent of the IPI, and COO (P = 0.01; OS, P = 0.015; EFS). The high BCL2 AQUA score group in the validation set was also significantly associated with worse OS and EFS (P = 0.0075; OS, P = 0.0049; EFS) (Figure 1C, D). The poor prognostic impact of BCL2 AQUA score was also in good correlation with both OS and EFS in the entire cohort (P 〈 0.0001; OS, P 〈 0.0001; EFS) (Figure 1E, F). The adverse impact of high BCL2 AQUA score was identified within both low (IPI 0-2) and high IPI (IPI 3-5) groups (Figure 2A-D). The high BCL2 AQUA score was also associated with poor prognosis within both GCB (P = 0.0077; OS, P = 0.0055; EFS) and non-GCB type DLBCL (P = 0.059; OS, P = 0.04; EFS), although a marginal statistical significance was observed regarding OS in the non-GCB type (Figure 2E-H). Conclusion Our study demonstrated that BCL2 expression analyzed by AQUA scoring system, incorporating both intensity and proportion, is an independent prognostic factor for patients with DLBCL. Given the growing clinical implications of BCL2 and the therapeutic progress in targeting BCL2 in hematologic malignancies, the concrete definition of BCL2 positivity in DLBCL holds great promise for the study of the pathophysiology of DLBCL and could be used to establish new therapeutic strategies. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 6
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3942-3942
    Abstract: Background We previously have shown that concurrent chemoradiotherapy (CCRT) followed by chemotherapy such as VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) or VIDL (etoposide, ifosfamide, dexamethasone and L-asparaginase) is an effective treatment for the management of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type. To further improve efficacy, we designed a new treatment protocol, MIDLE (methotrexate, ifosfamide, dexamethasone, L-asparaginase and etoposide), which incorporates tri-weekly administration of L-asparaginase during CCRT to reduce the probability of systemic progression and high dose methotrexate to intensify chemotherapy based on previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 36-45 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly 4,000 IU of Escherichia coli L-asparaginase was administered intravenously (IV). The chemotherapy, MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2, Ifosfamide 1000 mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000 IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days for two cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30-77 years). Twenty four patients were male while only four patients were female. Twenty-two patients had stage IE and six IIE disease. Twenty four were classified as low risk group and the other four intermediate group according to PINK-E (Kim SJ et al., EHA 2015 S110). All but two patients completed CCRT, which resulted in 85.7% of overall response rate including 16 complete responses (57.1%) and 8 partial responses (28.6%). One showed stable disease (SD) and the other one showed progressive disease (PD) with development of new distant lymph node involvement after CCRT. Grade 3 or 4 hematologic toxicity was not common. Only two patients experienced G3 neutropenia during or after CCRT. However, grade 3 non-hematologic toxicities were noted including bilirubin elevation (n = 3), mucositis (n = 1), anorexia (n=5) and nausea/vomiting (n = 11) Two could not complete CCRT according to the protocol due to G3 allergic reaction to L-asparaginase (n=1) and prolonged G3 mucositis (n=1). After the completion of CCRT, 23 out of 28 patients entered the MIDLE chemotherapy as five patients including one disease progression and four withdrawal during (n=2) or after (n=2) CCRT due to toxicities. All those who completed the planned two cycles of MIDLE chemotherapy achieved complete response after chemotherapy including those with PR (n=6) and SD (n=1) after CCRT. Three patients dropped out during or after their first cycle of MIDLE due to non-hematologic toxicities (recurrent G3 bilirubinemia (n=1), G3 increased creatinine (n=1), G5 infection (n=1)). The final complete response rate was 82% (23/28). It was associated with a significant rate of grade 3/4 neutropenia (n=21) and febrile neutropenia (n=10). Two patients experienced acute kidney injury (AKI) during the first cycle of MIDLE and one of them died of pneumonia complicated by sepsis. With a median follow-up of 46 months (95% confidence interval: 39 - 47 months), four patients progressed and five patients died with the estimated 3-year progression-free survival rate of 74.1% and overall survival rate of 81.5%. PINK-E could successfully stratify both time-to-progression (p=003) and overall survival (p=0.006) in this study. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy may be an effective treatment strategy for stage I/II extranodal NK/T-Cell lymphoma, nasal type. However, higher numbers of patients were withdrawn during or after CCRT due to toxicity or poor tolerance than previous study. MIDLE chemotherapy was associated with high rate of G3 or 4 hematologic toxicities. Thus, this approach should be reserved for selected patients such as young fit but high risk of relapse. PINK-E can be a useful prognostic index for stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 7
    In: Oncotarget, Impact Journals, LLC, Vol. 7, No. 51 ( 2016-12-20), p. 85584-85591
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2560162-3
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  • 8
    In: Cancer Medicine, Wiley, Vol. 6, No. 1 ( 2017-01), p. 100-108
    Abstract: We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone ( CTD ) or daily thalidomide, melphalan, and prednisolone ( MTP ) at 17 medical centers in Korea. Three‐hundred and seventy‐six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent ( TAS ) was second‐line chemotherapy in 142 (37.8%) patients, and third‐line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression‐free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP , but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD .
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2659751-2
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  • 9
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2844-2844
    Abstract: Introduction Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of diseases associated with poor prognosis, representing 10-15% of non-Hodgkin lymphomas. Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens are often preferred as 1st line treatment, the treatment outcome is poor with 5-year overall survival (OS) rate of 30-40%. In an effort to improve the survival outcomes of these patients, autologous hematopoietic stem cell transplantation (ASCT) as an upfront consolidative treatment has been proposed for patients achieving partial or complete remission after induction therapy. However, the role of ASCT still remains undefined since no randomized trials have demonstrated survival benefit of ASCT in this setting. To better understand the clinical characteristics, treatment patterns, and outcomes in patients with PTCL, we have conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with PTCL. Methods Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored (ClinicalTrials.gov, no. NCT02364466). All patients were pathologically diagnosed with PTCL according to the 2008 World Health Organization classification of lymphoid neoplasms. Extranodal NK/T cell lymphoma, cutaneous T cell lymphoma, Mycosis fungoides and Sezary syndrome were excluded. The target number for enrollment was 200, and an interim analysis was previously reported at the time of enrollment of 155 patients (ASH 2017). An updated analysis of 198 patients was performed. Results The median age was 59 years (range, 49-70), 122 patients (61.6%) were male and 168 (84.9%) had ECOG performance status of 0-1. PTCL, not otherwise specified was the most common pathologic subtype (n = 80, 40.4%), followed by angioimmunoblastic T cell lymphoma (n = 60, 30.3%). The most frequently administered 1st line regimen was CHOP or CHOP-like regimen (n = 165, 83.3%), followed by ICE (ifosfamide, carboplatin, and etoposide) or ICE-like regimen (n = 23, 11.6%), and others (n = 10, 5.1%). With a median follow-up duration of 28.2 months (95% CI, 25.6-30.6), 2-yr progression-free survival (PFS) rate was 44.4% (95% CI, 37.5-57.4) and 2-yr OS rate was 64.4% (95% CI, 57.4-72.1). Response evaluation for 1st line regimens were available in 175 patients. Among these patients, there was no significant difference in overall response rate (ORR) and complete response (CR) rate between patients treated with CHOP or CHOP-like vs. ICE or ICE-like regimen (ORR: 73.6 vs. 72.7%, P = 1.000; CR rate: 58.1% vs. 45.5%, P = 0.375). In addition, no significant difference was observed regarding PFS and OS between the two treatment groups (CHOP or CHOP-like vs. ICE or ICE-like; 2-yr PFS rate: 45.2 vs. 38.3%, P = 0.39; 2-year OS rate: 65.7 vs. 50.7% P = 0.43) (Figure 1A, B). Among 121 patients younger than 65 years of age who are eligible for transplantation, autologous hematopoietic stem cell transplantation (ASCT) was performed as an upfront consolidative treatment in 51 patients (42.1%). Patients who received upfront ASCT was associated with significantly better PFS and OS compared with patients who did not, with a 2-yr PFS rate of 52.3 vs. 37.0% (P = 0.032) and 2-yr OS rate of 74.2 vs. 57.1% (P = 0.028), respectively (Figure 2A, B). A total of 81 patients were treated with 2nd line chemotherapy for refractory or relapsed disease, and response evaluation for 2nd line chemotherapy was available in 63 patients. Among these patients ORR and CR rate were 49.2% and 30.2%, respectively. Conclusion Our study demonstrated that survival outcome with current treatment options for patients with PTCL remains poor. Although CHOP or CHOP-like regimens were the most commonly used 1st line regimens, no survival benefit was observed when compared with ICE or ICE-like regimens, suggesting that more efforts are needed to establish a standard 1st line treatment for PTCL. ASCT may provide survival benefit in transplant eligible patients, which warrants further evaluation in randomized controlled trials. Disclosures Yoon: Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy, Honoraria; Yuhan Pharma: Research Funding; Amgen: Consultancy, Honoraria; Genentech, Inc.: Research Funding; Kyowa Hako Kirin: Research Funding. Kim:F. Hoffmann-La Roche Ltd: Research Funding; Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15578-e15578
    Abstract: e15578 Background: Although dCRT is the standard treatment for pts who have locally advanced unresectable EC or refuse surgery, the prognosis of these pts remains dismal. There are urgent needs to develop the novel treatment strategy based on prognostic stratification after dCRT. Methods: A total of 382 pts with locoregional EC without distant metastasis except for supraclavicular lymph node who received dCRT at Asan Medical Center in South Korea from 2006 to 2015 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Risk factors were analyzed using Cox regression. Risk scores were calculated by multiplying coefficients in Cox proportional hazard model. Results: Baseline characteristics were as follows: median age = 66 yrs (range: 40-85); male = 359 pts (94.0%); squamous cell carcinoma = 375 (98.2%); cTNM stage (AJCC 8th) I = 40 (10.5%), II = 122 (31.9%), III = 128 (33.5%), IV = 92 (24.1%). During median follow-up of 52.9 mo, median PFS was 13.5 mo (95% CI, 10.9-16.1), and median OS was 26.7 mo (95% CI, 19.8-33.7). In the univariate analyses, sex (only for PFS), weight loss (≥ 5 kg) during dCRT, cT stage, cN stage, cTNM stage, clinical response after dCRT, reason for dCRT were significant prognostic factors for PFS and OS. In the multivariate analyses, clinical response after dCRT, cTNM stage, and weight loss were independent prognostic factors for PFS and OS (Table). Risk-scoring model using these factors stratified pts into four groups: for median PFS (p 〈 0.0001), group 1 = 58.2 mo (95% CI, 43.5-73.0), group 2 = 17.0 mo (95% CI, 11.9-22.1), group 3 = 9.0 mo (95% CI, 7.0-11.1), and group 4 = 3.9 mo (95% CI, 3.7-4.2); for median OS (p 〈 0.0001), group 1 = 106.2 mo (95% CI, 44.9-167.6), group 2 = 38.0 mo (95% CI, 24.4-51.5), group 3 = 13.0 mo (95% CI, 8.5-17.6), and group 4 = 8.0 mo (95% CI, 7.4-8.6). Conclusions: In dCRT-treated locoregional EC pts, survival outcome significantly varied according to baseline clinical stage, treatment response, and dynamic change in body weight. Different treatment and surveillance strategies based on the risk score might be needed in these pts.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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