How to improve loco-regional control in stages IIIa–b NSCLC?

Nyman, Jan; Friesland, Signe; Hallqvist, Andreas; Seke, Mihalj; Bergström, Stefan; Thaning, Lars; Lödén, Britta; Sederholm, Christer; Wagenius, Gunnar

doi:10.1016/j.lungcan.2008.10.021

Cited by 21 publications

(6 citation statements)

References 30 publications

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“…The studies are as mentioned published previously but in short patients in the Satellite trial had a median survival of 17 months with a toxicity profile inferior to what usually is seen in concurrent chemoradiation. The RAKET trial had a median survival of 17.8 months, with all arms showing acceptable side effects, however there was no difference between the arms regarding local control or survival [ 5 , 6 ].…”

Section: Resultsmentioning

confidence: 99%

“…The statistics for the main studies have been previously described [ 5 , 6 ]. The OS survival analyses are done according to the Kaplan Meier method and possible univariate differences between groups are estimated with log-rank test.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we analysed tumour tissue samples regarding KRAS mutations, EGFR mutations, and EGFR positivity by FISH—high polysomy and amplification as defined by Cappuzzo et al [ 4 ]—in patients with NSCLC stage III disease. The study population is represented by patients from two prospective trials who have received combined radiochemotherapy with curative intent: The RAKET study, a randomized three-armed phase II study where patients were treated with two cycles of induction chemotherapy (carboplatin/paclitaxel) followed by either hyperfractionated accelerated radiotherapy concurrent with a third cycle chemotherapy, conventional radiotherapy concurrent with daily paclitaxel or conventional radiotherapy concurrent with weekly paclitaxel [ 5 ]. Secondly the recently finished Satellite trial, a one-armed phase II study, where the treatment consisted of two cycles of induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent with the EGFR-directed antibody cetuximab [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy

Hallqvist

Enlund

Andersson

et al. 2012

Lung Cancer International

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Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy

Hallqvist

Enlund

Andersson

et al. 2012

Lung Cancer International

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“…Data were collected retrospectively from two different phase II studies evaluating radiotherapy in stage III NSCLC conducted between the years 2002-2007 in Sweden. The first study, the RAKET trial [22], was a three-armed randomized trial of 151 patients with NSCLC stage IIIA/IIIB treated with induction chemotherapy (carboplatin AUC 6/paclitaxel 200 mg/m 2 ) followed by either A, hyperfractionated accelerated radiotherapy 1.7 Gy twice-a-day to 64.6 Gy concurrent with a third cycle chemotherapy, B, radiotherapy with 2 Gy daily to 60 Gy concurrent with daily paclitaxel 12 mg/m 2 , or C, radiotherapy with 2 Gy daily to 60 Gy concurrent with weekly paclitaxel 60 mg/m 2 . The second study, the Satellite trial [23], was a one-armed phase II trial of 71 patients with NSCLC stage IIIA/IIIB treated with two cycles of induction chemotherapy (cisplatin 75 mg/m 2 /docetaxel 75 mg/m 2 ) followed by radiotherapy, 2 Gy daily, to 68 Gy concurrent with weekly cetuximab (initial dose of 400 mg/m 2 followed by 250 mg/m 2 ).…”

Section: Methodsmentioning

confidence: 99%

The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy

Holgersson¹,

Bergström²,

Hallqvist³

et al. 2017

neo

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Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.

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“…This resulted in an improvement in overall survival of 4.5% at 5 years (15.1 vs. 10.6%, p = 0.004) and as suggested by the authors of this study, survival may be directly related to loco-regional control. The risk of regional failure, i.e., in the mediastinum, is relatively low after chemo-radiation to a dose of approximately 60 Gy with conventional fractionation (5, 7); in contrast, the rate of local failure remains relatively high. As such, it seems reasonable to propose that techniques to improve primary tumor control through dose escalation may be one strategy to improve treatment outcome in locally advanced NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Strategies of Dose Escalation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer: Image Guidance and Beyond

Chi

Nguyen²,

Welsh

et al. 2014

Front. Oncol.

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Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG–positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

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How to improve loco-regional control in stages IIIa–b NSCLC?

Cited by 21 publications

References 30 publications

Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy

Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy

The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy

Strategies of Dose Escalation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer: Image Guidance and Beyond

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