Hepatic Resection Versus Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: A Cohort Study

BackgroundThe selection criteria for hepatic resection (HR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) are still controversial. We used real-world data to evaluate the overall survival (OS) in treatment with HR or transarterial chemoembolization (TACE).MethodsIn total, 942 patients with IM-HCC were categorized into the HR group and the TACE group. OS was analyzed using the Kaplan–Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analysis. Curve smoothing was performed through the generalized additive model. The interaction test was performed to evaluate the impact of HR on OS concerning risk factors. Also, we used multiple imputation to deal with missing data.ResultsIn total, 23.0% (n = 225) of patients received HR. At a median OS of 23.7 months, HR was associated with improved OS in the multivariate analysis [hazard ratio (HzR) = 0.45, 95%CI = 0.35–0.58; after PSM: HzR = 0.56, 95%CI = 0.41–0.77]. Landmark analyses limited to long-term survivors of ≥6 months, ≥1 year, and ≥2 years demonstrated better OS with HR in all subsets (all p < 0.05). After PSM analysis, however, HR increased the risk of death by 20% (HzR = 1.20, 95%CI = 0.67–2.15) in the subgroup of patients with lactate dehydrogenase (LDH) ≤192 U/L (p for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and HR with respect to the 1-, 3-, and 5-year observed survival rates (all p < 0.05).ConclusionHR was superior to TACE for intermediate-stage HCC in patients with LDH levels >192 U/L. Moreover, TACE might be suitable for patients with LDH levels ≤192 U/L.

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Hepatic resection versus transarterial chemoembolization for the intermediate stage hepatocellular carcinoma

10.1101/2020.10.18.20214833 ◽

2020 ◽

Author(s):

Linbin Lu ◽

Peichan Zheng ◽

Zhixian Wu ◽

Xiong Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Hepatic Resection ◽

Proportional Hazards ◽

Selection Criterion ◽

Smooth Curve ◽

Intermediate Stage ◽

Cox Proportional Hazards ◽

Rank Test ◽

Real World Data

AbstractBackgroundThe selection criterion for hepatic resection(HR) in intermediate-stage(IM) hepatocellular carcinoma(HCC) is still controversial. We used real-world data to evaluate the overall survival (OS) treated with HR or TACE.MethodsIn all, 946 patients with IM-HCC were categorized in HR and TACE group. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analyses. The smooth curve was performed through the generalized additive model. The interaction test was performed to evaluate the HR impact on OS concerning risk factors. Also, we used multiple imputation to deal with the missing data.ResultsTotally, 23.0% (n=225) of patients received HR. At a median overall survival of 23.7 months, HR was associated with the improved OS on multivariate analysis (hazard ratio, 0.45; 95%CI: 0.35, 0.58; after PSM: 0.56; 95%CI: 0.41, 0.77). Landmark analyses limited to long-term survivors of ≥ 6 months, ≥ 1, and ≥ 2 years demonstrated better OS with HR in all subsets (all P<0.05). After PSM analysis, however, HR increased 20% risk of survival (HR, 1.20; 95%CI: 0.67, 2.15) in the subgroup of LDH ≤192 U/L (P for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and the HR with respect to 1-, 3-, and 5-year observed survival rate (all P<0.05).ConclusionHepatic resection was superior to TACE for intermediate-stage HCC in the range of LDH level > 192 U/L. Moreover, TACE might be suitable for patients with LDH level ≤ 192 U/L.

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Impact of Early Lenvatinib Administration on Survival in Patients with Intermediate-Stage Hepatocellular Carcinoma: A Multicenter, Inverse Probability Weighting Analysis

Oncology ◽

10.1159/000515896 ◽

2021 ◽

pp. 1-10

Author(s):

Toshifumi Tada ◽

Takashi Kumada ◽

Atsushi Hiraoka ◽

Kojiro Michitaka ◽

Masanori Atsukawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Proportional Hazards ◽

Survival Rates ◽

Intermediate Stage ◽

Cox Proportional Hazards ◽

Probability Weighting ◽

Cumulative Survival ◽

Inverse Probability ◽

The Impact

Aim/Background: Transarterial chemoembolization (TACE) is recommended for patients with intermediate-stage hepatocellular carcinoma (HCC). In this study, we investigated the impact of early lenvatinib administration in patients with intermediate-stage HCC, especially those with tumors beyond the up-to-7 criteria. Materials/Methods: A total of 208 patients with intermediate-stage HCC whose initial treatment was early lenvatinib administration or TACE were enrolled. Multivariate overall survival analysis was performed in this cohort. In addition, the impact of early lenvatinib administration on survival in patients with HCC beyond the up-to-7 criteria was clarified using inverse probability weighting (IPW) analysis. Results: The overall cumulative survival rates at 6, 12, 18, and 24 months were 94.4, 79.9, 65.8, and 50.1%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that HCC treatment with lenvatinib (hazard ratio [HR], 0.199; 95% confidence interval [CI], 0.077–0.517; p < 0.001), α-fetoprotein ≥100 ng/mL (HR, 1.687), Child-Pugh class B disease (HR, 1.825), and beyond the up-to-7 criteria (HR, 2.016) were independently associated with overall survival. The 6-, 12-, 18-, and 24-month cumulative survival rates were 96.0, 90.4, 65.7, and 65.7%, respectively, in patients treated with lenvatinib, and 94.1, 78.5, 65.3, and 48.4%, respectively, in patients who received TACE (p < 0.001). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that lenvatinib therapy was significantly associated with overall survival in patients with HCC beyond the up-to-7 criteria (HR, 0.230; 95% CI, 0.059–0.904; p = 0.035). Conclusions: Lenvatinib may be a suitable first-line treatment for patients with intermediate-stage HCC beyond the up-to-7 criteria.

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Sorafenib versus transarterial chemoembolization as adjuvant therapies for patients with hepatocellular carcinoma and microvascular invasion.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.244 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 244-244 ◽

Cited By ~ 1

Author(s):

Xinyu Bi ◽

Jie Gao ◽

Jianqiang Cai

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Resection ◽

Transarterial Chemoembolization ◽

Standard Of Care ◽

Intermediate Stage ◽

Microvascular Invasion ◽

Rank Test ◽

Control Group ◽

Adjuvant Therapies ◽

Sorafenib Group

244 Background: Microvascular invasion (MVI) is a risk factor for poor prognosis following curative resection in hepatocellular carcinoma (HCC). Currently, there is no standard of care for patients with HCC and MVI. The present study compared the effectiveness of sorafenib and transarterial chemoembolization (TACE) as adjuvant therapies following hepatic resection in patients with early and intermediate-stage HCC and MVI. Methods: This bi-center retrospective study examined 70 patients with HCC and MVI treated by hepatic resection between June 2009 and March 2018. Twenty-four patients received no postoperative adjuvant therapy (control), 19 received TACE and 27 received sorafenib. Recurrence-free survival (RFS) and overall survival (OS) were compared by the log-rank test. Results: Subjects consisted of 62 males and 8 females, with a median age of 53.5 (range, 28-82) years. The median follow-up was 26.0 (range, 4.1-103.1) months. RFS in the sorafenib group was significantly improved compared with the TACE group (P=0.048), but not with the control group. OS in the sorafenib group was significantly improved compared with both TACE (P=0.015; 2-year OS: 100% vs. 78.6%) and control (P=0.023; 2-year OS: 100% vs. 80.0%) groups. Conclusions: Adjuvant sorafenib following hepatic resection improved OS in patients with HCC and MVI and might be a better choice than adjuvant TACE.

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The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank p = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, p = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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A Proposal of a Personalized Surveillance Strategy for Gastric Cancer: A Retrospective Analysis of 9191 Patients

Gastroenterology Research and Practice ◽

10.1155/2019/3248727 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Si-wei Pan ◽

Peng-liang Wang ◽

Han-wei Huang ◽

Lei Luo ◽

Xin Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Rank Test ◽

Surveillance Strategy ◽

Risk Of Death ◽

Kaplan Meier ◽

Advanced Stages ◽

Personalized Cancer

Background. In gastric cancer, various surveillance strategies are suggested in international guidelines. The current study is intended to evaluate the current strategies and provide more personalized proposals for personalized cancer medicine. Materials and Methods. In the aggregate, 9191 patients with gastric cancer after gastrectomy from 1998 to 2009 were selected from the Surveillance, Epidemiology, and End Results database. Disease-specific survival was analyzed by Kaplan-Meier method and the log-rank test. Cox proportional hazards regression analyses were used to confirm the independent prognostic factors. As well, hazard ratio (HR) curves were used to compare the risk of death over time. Conditional survival (CS) was applied to dynamically assess the prognosis after each follow-up. Results. Comparisons from HR curves on different stages showed that earlier stages had distinctly lower HR than advanced stages. The curve of stage IIA was flat and more likely the same as that of stage I while that of stage IIB is like that of stage III with an obvious peak. After estimating CS at intervals of three months, six months, and 12 months in different periods, stages I and IIA had high levels of CS all along, while there were visible differences among CS levels of stages IIB and III. Conclusions. The frequency of follow-up for early stages, like stages I and IIA, could be every six months or longer in the first three years and annually thereafter. And those with unfavorable conditions, such as stages IIB and III, could be followed up much more frequently and sufficiently than usual.

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Impact of Hydroxyurea on Survival and Risk of Thrombosis Among Older Patients With Essential Thrombocythemia

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7095 ◽

2019 ◽

Vol 17 (3) ◽

pp. 211-219 ◽

Cited By ~ 1

Author(s):

Nikolai A. Podoltsev ◽

Mengxin Zhu ◽

Amer M. Zeidan ◽

Rong Wang ◽

Xiaoyi Wang ◽

...

Keyword(s):

Overall Survival ◽

Essential Thrombocythemia ◽

Lower Risk ◽

Older Patients ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Competing Risk Models ◽

Medicare Database ◽

The Impact

ABSTRACTBackground: Current guidelines recommend hydroxyurea (HU) as frontline therapy for patients with high-risk essential thrombocythemia (ET) to prevent thrombosis. However, little is known about the impact of HU on thrombosis or survival among these patients in the real-world setting. Patients and Methods: A retrospective cohort study was conducted of older adults (aged ≥66 years) diagnosed with ET from 2007 through 2013 using the linked SEER-Medicare database. Multivariable Cox proportional hazards regression models were used to assess the effect of HU on overall survival, and multivariable competing risk models were used to assess the effect of HU on the occurrence of thrombotic events. Results: Of 1,010 patients, 745 (73.8%) received HU. Treatment with HU was associated with a significantly lower risk of death (hazard ratio [HR], 0.52; 95% CI, 0.43–0.64; P<.01). Every 10% increase in HU proportion of days covered was associated with a 12% decreased risk of death (HR, 0.88; 95% CI, 0.86–0.91; P<.01). Compared with nonusers, HU users also had a significantly lower risk of thrombotic events (HR, 0.51; 95% CI, 0.41–0.64; P<.01). Conclusions: Although underused in our study population, HU was associated with a reduced incidence of thrombotic events and improved overall survival in older patients with ET.

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The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size

Liver Cancer ◽

10.1159/000517992 ◽

2021 ◽

pp. 1-12

Author(s):

Hiroji Shinkawa ◽

Shogo Tanaka ◽

Daijiro Kabata ◽

Shigekazu Takemura ◽

Ryosuke Amano ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Resection ◽

Tumor Size ◽

Proportional Hazards ◽

Treatment Strategies ◽

Early Recurrence ◽

Cox Proportional Hazards ◽

Prognostic Impact ◽

Tumor Differentiation ◽

Negative Effects

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

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Transarterial Chemoembolization Combined with Radiofrequency Ablation in the Treatment of Stage B1 Intermediate Hepatocellular Carcinoma

Journal of Oncology ◽

10.1155/2019/6298502 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Furong Liu ◽

Minshan Chen ◽

Jie Mei ◽

Li Xu ◽

Rongping Guo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Transarterial Chemoembolization ◽

Progression Free Survival ◽

Intermediate Stage ◽

Multivariate Regression Analysis ◽

Rank Test ◽

Free Survival ◽

Kaplan Meier ◽

Tace Group

Background. Due to the heterogeneity of patients with Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC), Bolondi criteria were proposed and patients were divided into four substages. The purpose of this study was to compare the survival of substage B1 patients who were initially treated with a combination of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (TACE-RFA) or TACE alone. Methods. 404 patients with stage B1 HCC were retrospectively analyzed from January 2005 to December 2012. 209 patients received TACE-RFA, and 195 received TACE alone as initial treatment. The overall survival (OS) and progression-free survival (PFS) rates were estimated by the Kaplan–Meier method and compared by the log-rank test. Results. 1-, 3-, and 5-year OS rates were 83.7%, 45.8%, and 24.8% in the TACE-RFA group and 80.7%, 26.4%, and 16.7% in the TACE group, respectively (P=0.003). The corresponding PFS rates were 71.8%, 26.6%, and 13.0% and 59.1%, 11.0%, and 2.2% in the TACE-RFA group and TACE group, respectively (P<0.001). Multivariate regression analysis indicated that tumor size (OS: hazard ratio (HR) = 0.683, P=0.001; PFS: HR = 0.761, P=0.013), along with treatment allocation (OS: HR = 0.701, P=0.003; PFS: HR = 0.620, P<0.001), was the independent prognostic factor for both OS and PFS. Conclusions. Combination TACE and RFA treatment yielded better survival than TACE alone for patients with stage B1 HCC according to the Bolondi criteria.

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Survival of Patients with Hepatocellular Carcinoma in Renal Insufficiency: Prognostic Role of Albumin-Bilirubin Grade

Cancers ◽

10.3390/cancers12051130 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1130

Author(s):

Shu-Yein Ho ◽

Chia-Yang Hsu ◽

Po-Hong Liu ◽

Chih-Chieh Ko ◽

Yi-Hsiang Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Renal Insufficiency ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Performance Status ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Prognostic Role ◽

The Impact

Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade in this special setting is unclear. We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan–Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors. Of all patients, RI was an independent predictor associated with decreased survival. In multivariate Cox analysis for patients with RI, α-fetoprotein level ≥20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence of ascites, performance status 1–2, performance status 3–4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival (p < 0.001). In summary, HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.

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Impact of radiotherapy duration on outcomes in patients with esophageal cancer treated with definitive concurrent radiotherapy and chemotherapy on RTOG trials 8501 and 9405.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.119 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 119-119

Author(s):

Christopher Leigh Hallemeier ◽

Jennifer Moughan ◽

Michael G. Haddock ◽

Arnold M. Herskovic ◽

Bruce D. Minsky ◽

...

Keyword(s):

Esophageal Cancer ◽

Proportional Hazards ◽

Negative Impact ◽

Standard Dose ◽

Cox Proportional Hazards ◽

High Dose ◽

Risk Of Death ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

The Impact

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (< vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose < 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose < 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]

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