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FDG uptake correlates with recurrence and survival after treatment of unresectable stage III non-small cell lung cancer with high-dose proton therapy and chemotherapy.

ABSTRACT: We studied whether maximum standardized uptake values (SUV) from [18?F] PET/CT predict clinical outcome after concurrent proton/chemotherapy for stage III non-small cell lung cancer (NSCLC).Eighty-four patients were treated prospectively with 74?Gy(RBE) proton therapy and concurrent chemotherapy. PET/CT scans were available before (SUV1) and within 6?months after (SUV2) treatment. The predictive value of clinical and PET/CT factors were analyzed with univariate and multivariate Cox regression models.Median survival time was 29.9?months. At 3?years, the local recurrence-free survival (LRFS) rate was 34.8%; distant metastasis-free survival (DMFS), 35.4%; progression-free survival (PFS), 31.2%; and overall survival (OS), 37.2%. Patients with SUV2 ?3.6 (the median) had high rates of LR (p?=?0.021). Of 12 clinicopathologic features evaluated in univariate analysis, only KPS, SUV1, and SUV2 predicted LRFS, DMFS, PFS, and OS (p <0.05). Multivariate analysis showed that KPS (p?=?0.025) and SUV2 (p?=?0.017) were independently prognostic for LRFS and that SUV1, SUV2, and KPS were independently prognostic for DMFS, PFS, and OS (p <0.05).SUV2 predicted LRFS, and SUV1 and SUV2 predicted DMFS, PFS, and OS, in patients with stage III NSCLC treated with concurrent chemotherapy and high-dose proton therapy.

SUBMITTER: Xiang ZL

PROVIDER: S-EPMC3444399 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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FDG uptake correlates with recurrence and survival after treatment of unresectable stage III non-small cell lung cancer with high-dose proton therapy and chemotherapy.

Xiang Zuo-Lin ZL Erasmus Jeremy J Komaki Ritsuko R Cox James D JD Chang Joe Y JY

Radiation oncology (London, England) 20120828

<h4>Background</h4>We studied whether maximum standardized uptake values (SUV) from [18 F] PET/CT predict clinical outcome after concurrent proton/chemotherapy for stage III non-small cell lung cancer (NSCLC).<h4>Methods</h4>Eighty-four patients were treated prospectively with 74 Gy(RBE) proton therapy and concurrent chemotherapy. PET/CT scans were available before (SUV1) and within 6 months after (SUV2) treatment. The predictive value of clinical and PET/CT factors were analyzed with univariate ...[more]

PMID: 22929048

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Project description:ImportanceProton beam radiotherapy (PBT) has the potential to reduce toxic effects in the definitive management of locally advanced non-small cell lung cancer (NSCLC), but long-term prospective data are lacking.ObjectiveTo report the final (5-year) results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage III NSCLC.Design, setting, and participantsIn this open-label, single-group assignment study, with median follow-up of 27.3 months for all patients and 79.6 months for survivors, 64 patients were enrolled and analyzed; inclusion criteria were unresectable IIIA/IIIB histologically confirmed NSCLC, Karnofsky performance status 70 to 100, and 6-month prediagnosis weight loss of no more than 10%. Staging used positron emission tomography and/or computed tomography. Induction chemotherapy was allowed.InterventionsConcurrent chemotherapy (carboplatin-paclitaxel) and passively scattered PBT (74-Gy relative biological effectiveness) in all patients.Main outcomes and measuresKaplan-Meier analysis of overall survival (OS), progression-free survival (PFS), actuarial distant metastasis, and locoregional recurrence. Patterns of treatment failure were categorized as local/regional or distant. Acute and late toxic effects were prospectively assigned using Common Terminology Criteria for Adverse Events, v3.0.ResultsOf 64 patients (22 [34%] female; median [range] age, 70 [37-78] years; stage IIIA, 30 [47%]; IIIB, 34 [53%]), 17 (27%) were alive at last follow-up. Median OS was 26.5 months (5-year OS, 29%; 95% CI, 18%-41%). Five-year PFS was 22% (95% CI, 12%-32%); 5-year actuarial distant metastasis and locoregional recurrence were 54% (n = 36) and 28% (n = 22), respectively. Treatment failures were largely (31 [48%] patients) distant, with low rates of crude local (10 [16%]) and regional (9 [14%]) recurrences. Rates of grade 2 and 3 acute esophagitis were 18 (28%) and 5 (8%), respectively. Acute grade 2 pneumonitis occurred in 1 (2%) patient. Late toxic effects were uncommon: 1 (2%) patient developed an esophageal stricture (grade 2) and 1 (2%) grade 4 esophagitis. Late grades 2 and 3 pneumonitis occurred in 10 (16%) and 8 (12%), respectively. Two (3%) patients developed a bronchial stricture (grade 2), and 1 (2%) a grade 4 bronchial fistula. There were no acute or late grade 5 toxic effects.Conclusions and relevanceConcurrent chemotherapy and PBT to treat unresectable NSCLC afford promising clinical outcomes and rates of toxic effects compared with historical photon therapy data. Further optimization of proton therapy, particularly intensity-modulated proton therapy, is still needed.

Project description:PurposeTo quantify the post-radiotherapy 2-[(18)F]-fluoro-2-deoxyglucose (FDG) pulmonary uptake dose-response in lung cancer patients and determine its relationship with radiation pneumonitis symptoms.Methods and materialsThe data from 24 patients treated for lung cancer with thoracic radiotherapy who received restaging PET/CT imaging between 4 and 12 weeks after radiotherapy completion were evaluated. Their radiation dose distribution was registered with the post-treatment restaging PET/CT. Using histogram analysis, the voxel average FDG-PET uptake vs. radiation dose was obtained for each case and linear regression was performed. The resulting slope, the pulmonary metabolic radiation response (PMRR), was used to characterize the dose-response. The Common Toxicity Criteria version 3 was used to score clinical pulmonary toxicity symptoms. Receiver operating characteristic (ROC) curves were used to determine the level of FDG uptake vs. dose, MLD, V(5), V(10), V(20), and V(30) that can best predict symptomatic and asymptomatic patients.ResultsThe median time between radiotherapy completion and FDG-PET imaging was 59 days (range, 26-70 days). The median of the mean SUV from lung that received 0-5 Gy was 1.00 (range, 0.37-1.48), 5-10 Gy was 1.01 (range, 0.37-1.77), 10-20 Gy was 1.04 (0.42-1.53), and >20 Gy was 1.29 (range, 0.41-8.01). Using the dose range of 0 Gy to the maximum dose minus 10 Gy, hierarchical linear regression model of the radiation dose and normalized FDG uptake per case found an adequate fit with the linear model. Pneumonitis scores were: Grade 0 for 13, Grade 1 for 5, Grade 2 for 6, and Grade 3, 4 or 5 for none. Using a PMRR threshold of 0.017 yields an associated true positive rate of 0.67 and false positive rate of 0.15 with average error of 30%. A V(5) threshold of 57.6 gives an associated true positive rate of 0.67 and false positive rate of 0.05 with a 20% average error.ConclusionThe metabolic radiation pneumonitis dose-response was evaluated from post-treatment FDG-PET/CT imaging. Statistical modeling found a linear relationship. The FDG uptake dose-response and V(5) correlated with symptomatic radiation pneumonitis.

Project description:BackgroundMethylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients.Materials and methods129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes.ResultsThe LINE-1 methylation of all 129 patients was measured on a 0-100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (?6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7.57, p=0.041).ConclusionThere was a significantly greater risk of early postoperative recurrence and a shorter period of disease-free survival in Stage III colon cancer patients exhibiting LINE-1 hypomethylation status after being treated with radical resection and FOLFOX chemotherapy.

Project description:BackgroundThe benefit of chemotherapy in colon cancer patients is well documented but depends largely on whether patients complete the planned treatment regimen. We evaluated predictors of early discontinuation (EDChemo) and dose reduction of chemotherapy, especially the role of adverse treatment effects, in stage III patients who received adjuvant chemotherapy.MethodsStage III colon cancer patients who were diagnosed in 2003-2014 and recruited into a population-based study in Germany and received FOLFOX [5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin], capecitabine monotherapy (CapMono), or 5-FU/LV were included. We assessed determinants of EDChemo and dose reduction using multivariable logistic regression. Also, we estimated proportions of EDChemo and dose reduction that are attributable to adverse effects using attributable fractions.ResultsEDChemo and dose reduction rates were 52% and 17% for FOLFOX, 28% and 9% for CapMono, and 45% and 6% for 5-FU/LV, respectively. Predictors of EDChemo were low-grade tumor and treatment in a medium-volume hospital (for FOLFOX), obesity (for CapMono), and increasing age, T4 stage, and treatment in a medium-volume hospital (for 5-FU/LV). Adverse effects were particularly strongly associated with EDChemo and contributed to about 63%, 51%, and 32% of EDChemo of FOLFOX, CapMono, and 5-FU/LV, respectively. Of the various adverse effects, gastrointestinal events showed the strongest associations with EDChemo and accounted for about 7%, 26%, and 20% of EDChemo of FOLFOX, CapMono, and 5-FU/LV, respectively. Adverse effects were, moreover, a strong determinant of dose reduction and accounted for about 82% of all cases.ConclusionsEDChemo is common in stage III colon cancer patients receiving chemotherapy and more than half of the cases of EDChemo and dose reduction are due to adverse treatment effects. Further research should address the potential for reducing EDChemo and dose reduction rates by close monitoring of patients for early signs and enhanced management of adverse effects, especially gastrointestinal events.

Dataset Information

FDG uptake correlates with recurrence and survival after treatment of unresectable stage III non-small cell lung cancer with high-dose proton therapy and chemotherapy.

Publications

FDG uptake correlates with recurrence and survival after treatment of unresectable stage III non-small cell lung cancer with high-dose proton therapy and chemotherapy.

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