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Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy.

Thieke C, Nicolay NH, Sterzing F, Hoffmann H, Roeder F, Safi S, Debus J, Huber PE - Radiat Oncol (2015)

Bottom Line: Rates were compared using the logrank test.Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.Mature clinical results of trimodal treatment for MPM were presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. christian.thieke@med.uni-muenchen.de.

ABSTRACT

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT).

Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC), distant control (DC) and overall survival (OS), measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used.

Results: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-, 2-, 3-year OS rates were 63, 42, 28 %, the LRC rates were 81, 60, 40 %, and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.

Conclusions: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier curves separated for type of radiation treatment. Step&shoot-IMRT (“IMRT”) vs. helical tomotherapy-IMRT (“Tomo”) shows no significant difference regarding a overall survival, b locoregional control and c distant control
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Fig3: Kaplan-Meier curves separated for type of radiation treatment. Step&shoot-IMRT (“IMRT”) vs. helical tomotherapy-IMRT (“Tomo”) shows no significant difference regarding a overall survival, b locoregional control and c distant control

Mentions: Multivariate analysis showed that with respect to OS among all the variables tested, the male gender tended to result in worse prognosis although not reaching significance (Hazard Ratio (HR) 1.7; 95 % Confidence Interval (CI95) 0.7–4.9; p = 0.2). The only two significant variables were the postoperative resection status R (per higher status HR 3.9; CI95 1.3–12.2; p = 0.01 and biphasic histology (HR 2.2; CI95 1.2–5. 4; p = 0.03). With respect to locoregional control, no variable tested reached significance in multivariate analysis. However higher R status (HR 3.2; CI95 0.45–23.5; p = 0.2) and biphasic histology (HR = 3.4; CI95 0.77–14. 9; p = 0.1) tended to result in reduced local control. With respect to distant control, both higher R Status (HR 10.9; CI95 1.3–76. 2; p = 0.02) and biphasic histology (HR 7.4; CI95 2.2–25.4; p = 0.003) were significantly associated with worse outcome. Other variables including the IMRT technique (step&shoot vs. helical tomotherapy), dose distributions such as target mean dose, target coverage, lung dose, clinical factors such as lymph node involvement (N status), and patient factors such as age had no influence on OS, LRC and DC. Kaplan-Meier curves illustrating the equivalence of irradiation techniques are depicted in Fig. 3 and the influence of the histology is depicted in Fig. 4.Fig. 3


Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy.

Thieke C, Nicolay NH, Sterzing F, Hoffmann H, Roeder F, Safi S, Debus J, Huber PE - Radiat Oncol (2015)

Kaplan-Meier curves separated for type of radiation treatment. Step&shoot-IMRT (“IMRT”) vs. helical tomotherapy-IMRT (“Tomo”) shows no significant difference regarding a overall survival, b locoregional control and c distant control
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4696301&req=5

Fig3: Kaplan-Meier curves separated for type of radiation treatment. Step&shoot-IMRT (“IMRT”) vs. helical tomotherapy-IMRT (“Tomo”) shows no significant difference regarding a overall survival, b locoregional control and c distant control
Mentions: Multivariate analysis showed that with respect to OS among all the variables tested, the male gender tended to result in worse prognosis although not reaching significance (Hazard Ratio (HR) 1.7; 95 % Confidence Interval (CI95) 0.7–4.9; p = 0.2). The only two significant variables were the postoperative resection status R (per higher status HR 3.9; CI95 1.3–12.2; p = 0.01 and biphasic histology (HR 2.2; CI95 1.2–5. 4; p = 0.03). With respect to locoregional control, no variable tested reached significance in multivariate analysis. However higher R status (HR 3.2; CI95 0.45–23.5; p = 0.2) and biphasic histology (HR = 3.4; CI95 0.77–14. 9; p = 0.1) tended to result in reduced local control. With respect to distant control, both higher R Status (HR 10.9; CI95 1.3–76. 2; p = 0.02) and biphasic histology (HR 7.4; CI95 2.2–25.4; p = 0.003) were significantly associated with worse outcome. Other variables including the IMRT technique (step&shoot vs. helical tomotherapy), dose distributions such as target mean dose, target coverage, lung dose, clinical factors such as lymph node involvement (N status), and patient factors such as age had no influence on OS, LRC and DC. Kaplan-Meier curves illustrating the equivalence of irradiation techniques are depicted in Fig. 3 and the influence of the histology is depicted in Fig. 4.Fig. 3

Bottom Line: Rates were compared using the logrank test.Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.Mature clinical results of trimodal treatment for MPM were presented.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. christian.thieke@med.uni-muenchen.de.

ABSTRACT

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT).

Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC), distant control (DC) and overall survival (OS), measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used.

Results: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-, 2-, 3-year OS rates were 63, 42, 28 %, the LRC rates were 81, 60, 40 %, and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.

Conclusions: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM.

No MeSH data available.


Related in: MedlinePlus