Local-regional Progression-free Survival Research Articles

A Multicentered, Randomized Phase III Study of Definitive vs. Palliative Radiotherapy to Primary Tumor for Stage IV Non-Small Cell Lung Cancer with Less than Three Metastatic Organs: CSWOG China

To investigate the local-regional progression-free survival (LPFS), overall survival (OS), progression-free survival (PFS), local control rate of primary tumor (LCRP), and toxicity of definitive radiotherapy (concurrent chemoradiotherapy of 63 Gy) compared with palliative radiotherapy (concurrent chemoradiotherapy of 45 Gy) to primary tumor in newly diagnosed stage Ⅳ non-small cell lung cancer with less than three metastatic organs. A randomized, multicentered phase Ⅲ study (ChicTR-TRC-13003749), in a 1:1 ratio, included patients with newly diagnosed stage Ⅳ NSCLC with less than three metastatic organs. The EGFR mutation was wide type or unknown mainly. The patients were divided into 63 Gy of definitive radiotherapy (D63) and 45 Gy of palliative radiotherapy (P45). The primary endpoints were LPFS, OS. Secondary endpoints included PFS, LCRP, objective response rate (ORR) and toxicity. Three hundred forty-four patients were enrolled in 14 cancer centers. The median LPFS for group D63 was 18 months (95% CI, 13.02 to 22.98) better than 13 months for group P45 (95% CI, 10.13 to 15.87). LPFS for 1, 2, and 5 years were 62.9% vs. 50.4%, 36.9% vs. 24%, 20.5% vs. 5.5%, respectively (χ2 = 9.997, P = 0.002). The 36.1% reduction in the hazard ratio for local-regional progression or death for D63. The MST for group D63 was 19 months (95% CI, 14.59 to 23.41) better than 15 months for group P45 (95% CI, 10.72 to 19.28), and the 1-, 2-, and 5-years OS were 70.2% vs. 52.2%, 41.3% vs. 30.7%, 16.2% vs. 11.3%, respectively (χ2 = 3.874, P = 0.049). PFS was 37% reduction in the hazard ratio for disease progression or death for D63 (χ2 = 12.49, P = 0.000). The 1, 2, 5-year LCRP of group D63 is better than group P45 (χ2 = 8.747, P = 0.003). The incidences of RE and grade Ⅲ-Ⅳ RP in group D63 were higher than in group P45 (P<0.05). Phase Ⅲ clinical trials achieved satisfactory results. LPFS, OS and PFS was longer with definitive than palliative radiotherapy of primary tumor for stage Ⅳ NSCLC with less than three metastatic organs. Significantly prolonged. The toxicity was accepted.

Adaptive Radiotherapy Guided by PET/CT in Patients with Locally Advanced Non–Small Cell Lung Cancer: A Phase II Randomized Study

The aim of this study was to determine whether adaptive radiotherapy guided by functional imaging with flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can improve local tumor control in patients with locally advanced non-small cell lung cancer (LA-NSCLC). This was a phase II randomized study comparing the efficacy and safety between PET-guided adaptive radiotherapy and conventional radiotherapy. The primary end point was 2-year local-regional tumor control (LRTC) rate. Secondary end points included local-regional progression-free survival (LR-PFS), progression-free survival (PFS), overall survival (OS), and radiation-related toxicities. Between November 2012 and June 2017, 72 patients were 1:1 randomized to adaptive and conventional arms. The 2- and 5-year LRTC rates were 63.2% and 58.0% versus 43.0% and 37.6% (P = 0.035) in the adaptive and conventional arms, respectively. The median LR-PFS (14.3 versus 12.0 months; P = 0.010) and PFS (12.8 versus 8.9 months; P = 0.034) were significantly longer in the adaptive arm than in the conventional arm. The median OS was 36.3 months in the adaptive arm and 28.8 months in the conventional arm (P = 0.266). The esophageal volume of receiving ≥60 Gy (V60) in the adaptive arm was lower than that in the conventional arm (P = 0.011), while the V30 for the heart in the adaptive arm was lower than that in the conventional arm (P = 0.077). Other radiological metrological parameters of tumor, organs at risk, and the incidence of ≥grade 2 radiation-related toxicities were not significantly different between the 2 arms. Compared with conventional radiotherapy, PET-guided adaptive radiotherapy significantly improved the 2-year LRTC rate, LR-PFS, and PFS without increased risks of radiation-related toxicities in patients with LA-NSCLC.

A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

Treatment strategy and long-term outcomes of primary intracranial rhabdomyosarcoma: a single-institution experience and systematic review.

Primary intracranial rhabdomyosarcoma (PIRMS) is rare, and the effects of the treatment strategy on overall survival (OS) are unclear. This study aimed to evaluate risk factors pertinent to OS and to propose an optimal treatment strategy. Clinical data of patients with PIRMS treated at Beijing Tiantan Hospital and from the English-language literature between 1946 and 2018 were reviewed. A literature review was performed via Ovid, MEDLINE, Embase, PubMed, Web of Science, and Cochrane databases using the terms "rhabdomyosarcoma," "intracranial," "cerebral," and "brain." Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There were 8 males (66.7%) and 4 females with PIRMS at our institution, with a mean age of 24.3 years. Gross-total resection was achieved in 4 patients (33.3%), and adjuvant radiation and chemotherapy were administered in 5 (45.5%) and 3 (27.3%) patients, respectively. After a mean follow-up period of 13.7 months, all patients developed local-regional recurrence and died of the disease. Twenty-nine cases (14 female and 15 male) were reported in the literature with a median age of 9.0 years. After a mean follow-up duration of 18.6 months, 13 patients (44.8%) developed recurrences, 7 patients (24.1%) had extracranial metastasis, and 14 patients (48.3%) died. In the pooled cases, adjuvant radiation (hazard ratio [HR] 0.089, 95% confidence interval [CI] 0.027-0.288, p < 0.001) and age < 10 years (HR 0.227, 95% CI 0.077-0.666, p = 0.007) were independent predictors of good local-regional progression-free survival (LR-PFS). Adjuvant radiation therapy (HR 0.301, 95% CI 0.110-0.828, p = 0.020) and age < 10 years (HR 0.359, 95% CI 0.131-0.983, p = 0.046) were significant predictors for favorable OS in the multivariate model. Due to the rarity of the disease, a poor outcome of PIRMS was demonstrated based on the pooled cohort. Use of radiation was associated with improved outcomes and should be considered to improve OS/LR-PFS. Further study is required to identify the optimal treatment regimen.Systematic review no.: CRD42019121249 (crd.york.ac.uk/PROSPERO/).

Tumor Mutation Load: A Novel Independent Prognostic Factor in Stage IIIA-N2 Non-Small-Cell Lung Cancer

This study is aimed at investigating the prognostic biomarkers of patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) and at analyzing the correlation between tumor mutation load (the frequency and number of tumor mutations) and prognosis. Clinical data of 35 patients with stage IIIA-N2 NSCLC were collected from Cancer Hospital, Chinese Academy of Medical Sciences. Whole blood samples from the peripheral vein were taken at different treatment periods, and the mutations of cell-free DNA (cfDNA) were detected. Multivariate analysis showed that smoking (P = 0.0308), mutation number > 2 (P = 0.0283), and max mutation frequency > 0.025 (P = 0.0450) were associated with improved progression-free survival (PFS). The overall survival (OS) of well-differentiated NSCLC patients was better than that of poorly differentiated ones (P = 0.0006). The rates of PFS, disease-free survival, local-regional recurrence-free survival, and local-regional progression-free survival were significantly higher in the group with a mutation number > 2 than in the group with a mutation number ≤ 2. The mutation number of the preoperation group was significantly higher than that of the postradiochemotherapy group (5 vs. 2.5, P = 0.023), and the max mutation frequency change was approximately significant in the postradiochemotherapy group compared with the postoperation group (2.6% vs. 1.85%, P = 0.067). The max mutation frequency is positively correlated with vascular invasion (21.13% vs. 3.62%, P = 0.04). Furthermore, Met, ALK, APC, PTEN, ERBB4, NF1, and other genes, involving multiple tumor suppressor genes and lung cancer-driven genes, did not mutate in recurrence-free patients when compared with recurrent patients. In conclusion, differentiation, smoking, mutation frequency > 0.025, and mutation number > 2 are prognostic factors. The frequency and number of gene mutations in cfDNA are expected to be prognostic predictors of NSCLC.

Increased CYFRA 21-1, CEA and NSE are Prognostic of Poor Outcome for Locally Advanced Squamous Cell Carcinoma in Lung: A Nomogram and Recursive Partitioning Risk Stratification Analysis

OBJECTIVES: This study aimed to: (1) assess the prognostic significance of serum tumor markers in locally advanced squamous cell carcinoma in lung (LA-SCCL); (2) generate a nomogram to predict the overall survival (OS) and (3) identify a prognostic stratification to assist the therapeutic decision-making. METHODS: LA-SCCL patients receiving definitive radiotherapy and baseline tumor marker measurement were eligible for this retrospective study. Cox proportional hazards regression was used to determine independent factors associated with various survival indexes and a nomogram was created to estimate the 5-year OS probability for individual patient. The identified prognostic factors were recruited into a recursive partitioning analysis (RPA) for OS to stratify patients with distinct outcome. RESULTS: A total of 224 patients were eligible for analysis. Increased cytokeratin-19 fragment (CYFRA 21-1) was independently associated with inferior OS, progression free survival (PFS) and a borderline decreased local-regional progression free survival (LRPFS). Elevated carcino-embryonic antigen (CEA) served as an unfavorable determinant for OS and increased neuron-specific enolase (NSE) was predictive of poor distant metastasis free survival (DMFS). A nomogram integrating KPS, TNM stage, CEA and CYFRA 21-1 was created, resulting in a c-index of 0.62. RPA identified 4 prognostic classifications, with median OS of 27.6, 19.9, 17.3 and 10.9 months for low, intermediate, high and very-high risk groups, respectively. CONCLUSIONS: Baseline tumor marker panel including CYFRA 21-1, CEA and NSE can be prognostic of outcome for LA-SCCL receiving definitive radiotherapy. The RPA identified four prognostic subgroups, which could assist personalized therapy and clinical trial design in LA-SCCL.

Nomograms incorporating genetic variants in BMP/Smad4/Hamp pathway to predict disease outcomes after definitive radiotherapy for non-small cell lung cancer.

Hepcidin is crucial in regulating iron metabolism, and increased serum levels were strongly linked with poor outcomes in various malignancies. Thus, we investigated if genetic variants in the BMP/Smad4/Hamp hepcidin‐regulating pathway were associated with outcomes in patients receiving definitive radiotherapy for NSCLC. Subjects were 664 NSCLC patients who received ≥60 Gy radiotherapy for NSCLC retrospectively identified from a single‐institution database. Potentially, functional and tagging single nucleotide polymorphisms (SNPs) of BMP2 (rs170986, rs1979855, rs1980499, rs235768, and rs3178250), BMP4 (rs17563, rs4898820, and rs762642), Smad4 (rs12456284), and Hamp (rs1882694, rs10402233, rs10421768, and rs12971321) were genotyped by TaqMan real‐time polymerase chain reaction. Cox proportional hazard's analyses were used to assess potential influences of SNPs on overall survival (OS), local‐regional progression‐free survival (LRPFS), progression‐free survival (PFS), and distant metastasis‐free survival (DMFS). Nomogram of each endpoint model was developed using R project. The median patient age was 66 years. Most (488 [73.2%]) had stage III NSCLC. Age, disease stage, receipt of concurrent chemotherapy, and gross tumor volume were independent factors of OS. Hamp rs1882694 AC/CC genotypes were associated with poor OS, LRPFS, PFS, and DMFS in multivariate analyses. Besides, BMP2 rs1979855, rs3178250, and rs1980499 associated with PFS; Hamp rs10402233 and BMP2 rs1979855 associated with LRPFS; BMP2 rs3178250 associated with DMFS after adjustment for clinical factors. After adding SNPs to each model, all the likelihood ratios were increased; the nomograms were improved significantly to predict LRPFS (P < 0.001) and PFS (P < 0.001), and marginally to predict OS (P = 0.056) and DM (P = 0.057). Our nomograms incorporating significant SNPs in the BMP/Smad4/Hamp hepcidin‐regulating pathway could improve the prediction of outcomes in patients given definitive radiotherapy for NSCLC. Intensified follow‐ups would be recommended for patients with unfavorable outcomes identified in nomograms. Due to the rapid developments of targeted therapies and immunotherapies for NSCLC, it is necessary to further validate our findings in patients receiving such treatments.

P2.02-003 Increased Circulating Cytokeratin-19 (Cyfra 21-1) is Predictive of Poor Outcome of Locally Advanced Squamous Cell Carcinoma in Lung

Our goal was to evaluate the prognostic significance of circulating tumor markers in locally advanced squamous cell carcinoma of lung (LA-SCCL). Eligible patients included those with histologically proven LA-SCCL, available baseline tumor marker panel analysis (carcino-embryonic antigen [CEA], carcinoma antigen 125 [CA125], squamous cell carcinoma antigen [SCC], cytokeratin-19 [Cyfra 21-1] and neuron-specific enolase [NSE]) and receiving definitive radiotherapy. Age, gender, radiation dose, baseline KPS, smoking history, weightless, TNM stage, PET staging, RT technique and treatment modality (radiotherapy alone vs. sequential chemoradiotherapy vs. concurrent chemoradiotherapy) were also retrospectively collected. To dichotomize the continuous values of tumor markers into categorical variables, ROC analysis was adopted to identify the optimal cutoff values using the progression within 2 years after diagnosis as the endpoint. Cox regression based multivariate analyses were used to select independent factors correlated with various survival endpoints. Overall survival (OS), local regional progression free survival (LRPFS) and distant metastasis free survival (DMFS) were defined as the time from diagnosis until the first occurrence of specific event: death, local-regional recurrence or distant metastasis, respectively. Progression free survival (PFS) was defined as the duration between the cancer diagnosis and the date of any progression or cancer related death. A total of 216 patients with LA-SCCL were analyzed. The optimal discriminative values for CEA, CA125, SCC, Cyfra 21-1 and NSE in predicting 2-y progression were 5.3 ng/ml, 17.0 U/ml, 2.5 ng/ml, 5.2 ng/ml and 17.8 ng/ml, respectively. Univariate analyses showed that increased Cyfra 21-1 was associated with inferior OS, LRPFS, DMFS and PFS. Increased NSE was predictive of poor OS, DMFS and PFS. CEA also presented significant correlation with OS. Under multivariate analysis involving all clinical and tumor markers, IIIA stage, better performance status, CEA ≤ 5.3 ng/ml and Cyfra 21-1 ≤ 5.2 ng/ml were independently associated with improved OS. IMRT technique, RT dose ≥ 60Gy and Cyfra 21-1 ≤ 5.2 ng/ml were correlated with better LRPFS. None-smoker, IIIA stage, NES ≤ 17.8 ng/ml were favorable predictors for DMFS. IIIA stage, KPS ≥ 80 and Cyfra 21-1 ≤ 5.2 ng/ml were advantageous factors related with favorable PFS. Baseline tumor marker panel including Cyfra 21-1, NSE and CEA can be prognostic of OS, local and distant tumor control for LA-SCCL, and should be recommended for baseline evaluation of tumor burden.

Long-Term Results of Radiation Therapy Oncology Group 9903: A Randomized Phase 3 Trial to Assess the Effect of Erythropoietin on Local-Regional Control in Anemic Patients Treated With Radiation Therapy for Squamous Cell Carcinoma of the Head and Neck

This paper reports long-term results of RTOG 9903,to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5g/dL (12.5g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10days before RT was initiated in the RT+EPO arm. A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1g/dL. In the RT+EPO arm, the mean hemoglobin level at 4weeks increased by 1.66g/dL, whereas it decreased by 0.24g/dL in the RT arm. With a median follow-up of 7.95years (range: 1.66-10.08years) for surviving patients and 3.33years for all patients (range: 0.03-10.08years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT+EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Radiation dose and survival of patients with stage IV non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy: reanalysis of the findings of a single-center prospective study.

BackgroundThe objective of this study was to evaluate the radiation dose and response in terms of local-regional progression-free survival (LRPFS) and overall survival (OS) of patients with stage IV non-small cell lung cancer (NSCLC) undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy.MethodsIn all, we enrolled 201 patients with stage IV NSCLC in this study and analyzed OS in 159 patients and LRPFS in 120.ResultsThe 1-, 2-, 3-, and 5-year OS rates were 46.2%, 19.5%, 11.7%, and 5.8%, respectively, the median survival time being 12 months. The median survival times in differential treatment response of primary tumors were 19 of complete response, 13 of partial response, 8 of stable disease, and 6 months of progressive disease, respectively (P = 0.000). The 1-, 2-, 3-, and 5-year LRPFS rates of patients undergoing four to five cycles with doses ≥63 Gy and <63 Gy were 77.4% and 32.6%, 36.2% and 21.7%, 27.2% and 0, and 15.9% and 0, respectively (P = 0.002). According to multivariate analyses, four to five cycles of chemotherapy, gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score stable or increased by at least 10 units were independent prognostic factors for better OS (P = 0.035, P = 0.008, and P = 0.000, respectively). Radiation dose to the primary tumor ≥63 Gy resulted in better OS (P = 0.057) and LRPFS (P = 0.051), both findings being of borderline significance.ConclusionsTreatment of IV NSCLC with joint administration of four to five cycles of chemotherapy and three-dimensional radiotherapy may prolong survival, particularly in patients receiving ≥63 Gy radiotherapy, with gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score not lower than pretreatment values.

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

BackgroundGlutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities.MethodsThe study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation.ResultsOral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively.ConclusionIn our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.

P-0120 Prognostic Value of Gross Tumor Volume Delineated by Fdg-Pet-Ct-Based Radiotherapy Treatment Planning Locally Advanced Pancreatic cancer Treated with Chemoradiotherapy

IntroductionWe aimed to assess whether gross tumor volume (GTV) determined by fusion of contrast-enhanced computerized tomography (CT) and 18F-fluoro-deoxy-D-glucose positron emission tomography-CT (FDG-PET-CT) based radiotherapy planning could predict outcomes, namely overall survival (OS), local-regional progression-free survival (LRPFS), and progression-free survival (PFS) in cases with locally advanced pancreas cancer (LAPC) treated with definitive concurrent chemoradiotherapy. MethodsA total of 30 patients with histological proof of LAPC underwent 50.4 Gy (1.8 Gy/28 fractions) of radiotherapy concurrent with continuously infused 5-FU followed by 4 to 6 courses of maintenance gemcitabine. Target volume delineations were performed on FDG-PET-CT-based RTP. Patients were stratified into 2 groups: GTV lesser (GTVL) versus greater (GTVG) than cut off value determined by receiver operating characteristic (ROC) analysis, and compared in terms of OS, LRPFS and PFS. ResultsMedian GTV delineated according to the FDG-PET-CT data was 100.0 cm3. Cut off GTV value determined from ROC curves was 91.1cm3. At a median follow up of 11.2 months, median OS, LRPFS and PFS for the entire population were 10.3, 7.8 and 5.7 months, respectively. Median OS, LRPFS and PFS for GTVL and GTVG cohorts were 16.3 vs. 9.5 (p=0.005), 11.0 vs. 6.0 (p=0.013), and 9.0 vs. 4.8 months (p=0.008), respectively. ConclusionThe superior OS, LRPFS and PFS observed in GTV L patients over GTVG ones suggests a potential for FDG-PET-CT-defined GTV size in predicting outcomes of LAPC patients treated with definitive C-CRT, which needs to be validated by further studies with larger cohorts.

Prognostic value of gross tumor volume delineated by FDG-PET-CT based radiotherapy treatment planning in patients with locally advanced pancreatic cancer treated with chemoradiotherapy

BackgroundWe aimed to assess whether gross tumor volume (GTV) determined by fusion of contrast-enhanced computerized tomography (CT) and 18F-fluoro-deoxy-D-glucose positron emission tomography-CT (FDG-PET-CT) based radiotherapy planning could predict outcomes, namely overall survival (OS), local-regional progression-free survival (LRPFS), and progression-free survival (PFS) in cases with locally advanced pancreas cancer (LAPC) treated with definitive concurrent chemoradiotherapy.MethodsA total of 30 patients with histological proof of LAPC underwent 50.4 Gy (1.8 Gy/28 fractions) of radiotherapy concurrent with continuously infused 5-FU followed by 4 to 6 courses of maintenance gemcitabine. Target volume delineations were performed on FDG-PET-CT-based RTP. Patients were stratified into 2 groups: GTV lesser (GTVL) versus greater (GTVG) than cut off value determined by receiver operating characteristic (ROC) analysis, and compared in terms of OS, LRPFS and PFS.ResultsMedian GTV delineated according to the FDG-PET-CT data was 100.0 cm3. Cut off GTV value determined from ROC curves was 91.1 cm3. At a median follow up of 11.2 months, median OS, LRPFS and PFS for the entire population were 10.3, 7.8 and 5.7 months, respectively. Median OS, LRPFS and PFS for GTVL and GTVG cohorts were 16.3 vs. 9.5 (p = 0.005), 11.0 vs. 6.0 (p = 0.013), and 9.0 vs. 4.8 months (p = 0.008), respectively.ConclusionsThe superior OS, LRPFS and PFS observed in GTVL patients over GTVG ones suggests a potential for FDG-PET-CT-defined GTV size in predicting outcomes of LAPC patients treated with definitive C-CRT, which needs to be validated by further studies with larger cohorts.

Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy.

BackgroundWe aimed to study the predictive value of combined 18F-fluoro-deoxy-D-glucose positron emission tomography and computerized tomography (FDG-PET-CT), on outcomes in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT).MethodsThirty-two unresectable LAPC patients received 50.4 Gy (1.8 Gy/fr) of RT and concurrent 5-FU followed by 4 to 6 cycles of gemcitabine consolidation. Response was evaluated by FDG-PET-CT at post-C-CRT 12-week. Patients were stratified into two groups according to the median difference between pre- and post-treatment maximum standard uptake values (SUVmax) as an indicator of response for comparative analysis.ResultsAt a median follow-up of 16.1 months, 16 (50.0%) patients experienced local/regional failures, 6 of which were detected on the first follow-up FDG-PET-CT. There were no marginal or isolated regional failures. Median pre- and post-treatment SUVmax and median difference were 14.5, 3.9, and -63.7%, respectively. Median overall survival (OS), progression-free survival (PFS), and local-regional progression-free survival (LRPFS) were 14.5, 7.3, and 10.3 months, respectively. Median OS, PFS, and LRPFS for those with greater (N = 16) versus lesser (N = 16) SUVmax change were 17.0 versus 9.8 (p = 0.001), 8.4 versus 3.8 (p = 0.005), and 12.3 versus 6.9 months (p = 0.02), respectively. On multivariate analysis, SUVmax difference was predictive of OS, PFS, and LRPFS, independent of existing covariates.ConclusionsSignificantly higher OS, PFS, and LRPFS in patients with greater SUVmax difference suggest that FDG-PET-CT-based metabolic response assessment is an independent predictor of clinical outcomes in LAPC patients treated with definitive C-CRT.

Weight Gain in Advanced Non–Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer

Tumour hypoxia increases tumour invasiveness and has a negative impact on response to therapy. Hypoxic tumours are also associated with severely anaemic individuals. It has therefore been hypothesised that correcting anaemia, by increasing haemoglobin levels using erythropoietin, improves tumour oxygenation and consequently the patient's prognosis. To assess whether combined treatment with radiotherapy and erythropoietin (RT plus EPO) is better than standard radiotherapy (RT alone) for the treatment of head and neck cancer patients. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 24 February 2009. Two independent authors assessed identified studies according to the eligibility criteria: RCTs which delivered radiotherapy combined with or without erythropoietin, in patients of any age with head and neck cancer of any stage or type. In addition, trials administering concomitant iron therapy among one or both arms were also eligible. For statistical analysis of survival data, we computed a weighted estimate of the typical treatment effect across studies. We used Chi(2) heterogeneity tests to test for statistical heterogeneity among trials and performed the statistical analyses using Review Manager 5.0. Five RCTs with a total of 1397 patients were included. Pooled data yielded a significantly worse overall survival (OS) for RT plus EPO as compared to RT alone (Peto odds ratio 0.73; 95% confidence interval (CI) 0.58 to 0.91; P = 0.005, five trials). For local regional tumour control (LRTC) analyses resulted in a small but non-significant difference between the RT alone group and the RT plus EPO group (RR 0.92; 95% CI 0.81 to 1.03; P = 0.15, four trials). In addition, the local regional progression free survival (LRPFS) measured in four studies was significantly different between groups (Peto odds ratio 0.63; 95% CI 0.49 to 0.80; P = 0.0002, four trials), in favour of the RT alone group. Two studies used supplemental iron in the RT plus EPO group and not in the RT alone group. When excluding these studies from the analyses, the statistically (non-) significant differences in OS, LRTC and LRPFS are maintained. There are strong suggestions that RT plus EPO has a negative influence on outcome as opposed to RT alone. However, the target haemoglobin concentration, which was higher than recommended in four of the five included RCTs, may have had a significant role. Nevertheless, based on these findings EPO should not be administered as an addition to RT outside the experimental setting for patients with head and neck cancer.

Radiotherapy With or Without Erythropoietin for Anemic Patients With Head and Neck Cancer: A Randomized Trial of the Radiation Therapy Oncology Group (RTOG 99-03)

To determine whether the addition of recombinant human erythropoietin (Epo) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Eligible patients had SCCHN, with a plan for continuous-course definitive radiotherapy (66-72 Gy) with or without chemotherapy. Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and/or accelerated fractionation radiotherapy. Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL (12.5 g/dL for women). Patients randomized to Epo received 40,000 U once weekly, starting 7-10 days before start of radiotherapy. A total of 148 patients were enrolled; 141 were evaluable. Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm, compared with an average 0.24 g/dL decrease in the control arm (p = 0.0001). Median follow-up was 2.5 years (3.1 years for surviving patients). There was no statistically significant difference in the primary endpoint of local-regional failure (LRF) rate between the treatment arms. The 3-year LRF rate was 36% for control and 44% for Epo (p = 0.56). There were also no significant differences in local-regional progression-free survival (LRPFS), patterns of failure, overall survival, or toxicity. The 3-year LRPFS rate was 52% for control and 47% for Epo. The overall survival rate was 57% and 56%, respectively. The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes. The study was not specifically designed to detect a potential negative association between Epo and tumor progression/survival.

2425: Induction Chemotherapy followed by Chemoradiotherapy in the Treatment of Locally Advanced Tonsillar Squamous Cell Carcinoma

2425: Induction Chemotherapy followed by Chemoradiotherapy in the Treatment of Locally Advanced Tonsillar Squamous Cell Carcinoma

Initial experience of using intensity modulated radiation therapy (IMRT) for recurrent nasopharyngeal carcinoma

Purpose/Objective: To report initial experience using intensity modulated radiation therapy (IMRT)(feasibility, toxicity and tumor control) for re-treatment recurrent nasopharyngeal carcinoma. Materials/Methods: 49 patients (KPS≥80) with local-regional recurrence in nasopharynx were treated with IMRT from Jan. 2001 to Feb. 2002 at Cancer Center, Zhongshan University, Guangzhou, China. The average time for local-regional in recurrence nasopharynx was 30.16 months after initial conventional radiotherapy. The isocenter dose on nasopharynx had medean dose 70Gy (60.88-78Gy) in 49 patients initial conventional radiotherapy. The number of patients with stage II, III and IV disease were 4, 9, 10 and 26 respectively. T1, T2, T3 and T4 disease were 4, 9, 11 and 25 cases respectively. N0, N1 and N3 disease were 46, 2 and 1 cases respectively. Of them, the invasion of nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, cavernous sinus and the erosion of base skull were found in 8, 1, 3, 8, 15 and 20 cases respectively. The GTV were contoured according to ICRU 62 guideline. Two CTV (CTV1 and CTV2) were set-up for the subclinical disease in nasopharynx. The CTV1 was defined 0.5-1cm away from the border of GTV. The CTV2 was defined 1-1.5cm away from the border of CTV1. The critical structures were contoured and the doses to critical structures were constrined according to ICRU 50 guideline. The inverse planning IMRT were created with CORVUS 3.0 planning system (Peacock,NOMOS) and treated with segmental tomotherapy techniques (MIMiC).The gantry rotation arc was 105 to 255 degree and beamlet changed every 5 degree. The GTV in nasopharynx and the lymph nodes in the neck received prescription dose of 68-70Gy and 60Gy respectively. All patients received full course IMRT. Three patients who had positive the lymph nodes were treated with 5-6 courses of chemotherapy(Cisplatin + 5-FU) after IMRT. Results: The plans showed that the dose of PTV covering GTV D95 in nasopharynx was 68.09Gy, and the volume of GTV V95 was 98.46%. The mean dose of GTV, CTV1 and CTV2 were delivered by IMRT in 49 patients (Table 1). At a median follow-up of 7 months (range 1 to 13 months), the local-regional progression-free survival was 100%. 3 cases (6.1%) of local-regional residual diseases were seen in 49 patients by the end of IMRT. 14 patients (28.6%) were complicated by radio-necrosis of varying degree in the nasopharynx. Three patients have developed metastases at a distant site: 2 in the bone, 1 in the liver and lung at 13 months follow-up. Acute toxicity in 49 patients was evaluated according to the RTOG radiation morbidity scoring criteria by the end of IMRT treatment. 19, 19 and 1 patients had grade 0, 1 and 2 skin toxicity respectively. Grade 0, 1, 2 and 3 toxicity in oral mucosa were 16, 10, 21 and 2 patients respectively. 26, 18 and 5 patients had grade 1, 2 and 3 xerostomia respectively. Conclusions: The improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a re-treatment option for recurrent NPC after initial radiotherapy. However, high dose IMRT for re-treatment can result in radio-necrosis of nasopharynx. We recommend that the prescription dose of GTV to be decreased and concurrent chemotherapy to be used in this setting. Tabled 1Critical StructuresMean Dose (Gy)Mean Volume (cc)Brain Stem28.5123.04Spinal Cord20.195.44Optical Chiasm21.560.87Pituitary32.590.21Len(L)3.910.20(R)4.100.20Optical Nerves(L)19.560.60(R)19.200.62Temporal Lobes(L)20.9840.46(R)22.1439.22Parotids(L)20.9710.98(R)18.4414.24T-M Joints(L)27.891.77(R)28.841.85Mandible bone(L)20.1936.30(R)19.7135.79 Open table in a new tab