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A Prospective Study on Volumetric and Dosimetric Changes during Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Patients
I. J. Radiation Oncology d Biology d Physics
S178
1045
Volume 81, Number 2, Supplement, 2011
Preliminary Result of Phase I/II Clinical Trial of Docetaxel, Cisplatin, and Fluorouracil Regimen Induction Chemotherapy for Primary Locoregionally Advanced Nasopharyngeal Carcinoma
W. Luo, Z. Yu, Q. Zhang, Q. Zhang, Q. Zhou, D. Kang, Y. Guo Sun Yat-Sen University Tumor Hospital, Guangzhou 510060, China Purpose/Objective(s): To investigate the tolerable dose and short-term efficacy of docetaxel, cisplatin and fluorouracil (TPF) regimen induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy for primary locoregionally advanced nasopharyngeal carcinoma (NPC). Materials/Methods: Na€ıve patients with locally advanced NPC were enrolled. The TPF regimen consisted of docetaxel at a dose of 60 mg/m2 and cisplatin 60 mg/m2, administered as intravenous infusion on day 1, fluorouracil as a 120-hour continuous intravenous infusion on days 1 to 5. The starting dose of fluorouracil was 450 mg/(m2$day) with a subsequent dose escalation of 50 mg/(m2$day). The maximum-tolerable dose of fluorouracil was defined as the dose at which no more than 1 of 6 patients experienced dose-limiting toxicity. Treatment was administered every 3 weeks (defined as one cycle) for three cycles, and IMRT and concomitant chemotherapy were delivered during a 6-week period within 2 to 3 weeks after the completion of chemotherapy. We delineated the primary gross tumor volume (GTV) into two parts: the post-IC primary GTV (GTVpost-IC-NP), and the region of pre-IC primary GTV minus GTVpost-IC-NP (GTVpre-post-IC-NP), which was prescribed to a total dose of 68.1-Gy and 63Gy in 2.27-Gy and 2.10-Gy daily fractions, respectively. During radiotherapy, Cisplatin at a dose of 80 mg/m2 was given every 3 weeks. The primary end point was progression-free survival, and the secondary end points were respond rate after IC and radiotherapy, overall survival, time to treatment failure, toxic effects. Results: From December 2007 to October 2010, 80 patients with Stage III – IVb (by the UICC 2002 staging system) primary NPC were treated. The maximum-tolerable dose of fluorouracil was established as 550 mg/(m2$day) by 12 patients’ treatment, and 74 patients received IC at the dose, in which, 89.2%(66/74) patients finished 3 cycles of IC. The overall and complete respond rate to IC was 99.8% (1/74) and 16.2% (12/74), respectively. During IC, Grade 3 or 4 hematologic adverse events occurred in 23.3% of patients, Grade 3 or 4 diarrhea 7.1%. Radiotherapy delay was not observed, and all patients finished concurrent chemoradiotherapy per protocol. After a median follow-up of 17.6 (3.3 – 33.9) months, 2 patients had local-regional failure, 3 distant metastasis and 1 died. The 18 months progression-free survival rate was 89.0%, overall survival 96.0%, local-regional failure-free 93.9%, and distant metastasis-free 95.1%. Conclusions: TPF regimen induction chemotherapy has excellent short-term efficacy for primary locoregionally advanced NPC. Author Disclosure: W. Luo: None. Z. Yu: None. Q. Zhang: None. Q. Zhang: None. Q. Zhou: None. D. Kang: None. Y. Guo: None.
1046
A Prospective Study on Volumetric and Dosimetric Changes during Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Patients
H. C. Cheng1,2, V. W. Wu3, R. K. Ngan1, K. Tang1, C. C. Chan1, K. Wong1, S. Au1, D. L. Kwong2 1 Queen Elizabeth Hospital, Hong Kong SAR, Hong Kong, 2The University of Hong Kong, Hong Kong SAR, Hong Kong, 3The Hong Kong Polytechnic University, Hong Kong SAR, Hong Kong
Purpose/Objective(s): Significant tumor shrinkage and/or weight loss may occur during a course of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aims to evaluate the dosimetric effect of these volumetric changes on targets volumes and organs at risk (OARs) during intra-course of IMRT, using serial reassessment of CT and MRI. Materials/Methods: Nineteen loco-regionally advanced NPC patients treated with IMRT using simultaneous integrated boost technique were recruited prospectively. The gross tumor volume (GTV) of each patient received 70 to 72 Gy in 33 fractions. Repeat planning CT and MRI were acquired at 30 and 50 Gy and they were rigidly fused to the pre-treatment planning CT. Re-contouring of target volumes and OARs was based on the fused CT-MR images. Hybrid plans at 30 (HPLAN30) and 50 Gy (HPLAN50), which were produced using the re-contoured targets and OARs, were generated for each patient by applying the same beam configurations of the original treatment plan (OPLAN). The assessment of dosimetric and volume changes was performed by comparing dosimetric and volume parameters of the hybrid plans with the original plan at the 30 and 50 Gy intervals of the treatment course. Results: There were steady volume reduction of target volumes and parotid glands over the course of IMRT (Table 1). The volume of the parotid glands decreased significantly by 14.9% (p = 0.003) and 25.1% (p = 0.001) at 30 and 50 Gy, respectively. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to the target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher mean doses to the parotid glands. Conclusions: During the course of IMRT for NPC, the dosimetric outcome was significantly altered without intra-course repeat CT and MR scans. Replanning with repeat CT and MR scans at 30 Gy is essential to keep a satisfactory dose to the target and avoid overdosing the OARs, which in turn may achieve better tumor control and reduced complications. Further adaptive radiotherapy by using deformable registration of CT and MR images is recommended. Table: Volume analysis in target volume and parotid gland of the OPLAN, HPLAN30 and HPLAN50 Mean volume (cm3) (Mean ± SD) GTV_Nasopharynx GTV_Lymph node Left parotid Right parotid Total parotid
OPLAN
HPLAN30
HPLAN50
p of OPLAN vs. HPLAN30
p of OPLAN vs. HPLAN50
42.7 ± 24.3 13.5 ± 11.2 30.0 ± 7.4 28.9 ± 8.1 58.8 ± 15.4
38.8 ± 23.8 11.5 ± 9.8 25.9 ± 6.3 24.2 ± 5.8 50.1 ± 11.8
37.1 ± 22.9 9.4 ± 8.6 22.4 ± 5.7 21.6 ± 5.3 44.1 ± 10.8
\0.001 0.003 0.010 0.007 0.003
\0.001 0.002 \0.001 0.001 0.001
Author Disclosure: H.C. Cheng: None. V.W. Wu: None. R.K. Ngan: None. K. Tang: None. C.C. Chan: None. K. Wong: None. S. Au: None. D.L. Kwong: None.
S178
1045
Volume 81, Number 2, Supplement, 2011
Preliminary Result of Phase I/II Clinical Trial of Docetaxel, Cisplatin, and Fluorouracil Regimen Induction Chemotherapy for Primary Locoregionally Advanced Nasopharyngeal Carcinoma
W. Luo, Z. Yu, Q. Zhang, Q. Zhang, Q. Zhou, D. Kang, Y. Guo Sun Yat-Sen University Tumor Hospital, Guangzhou 510060, China Purpose/Objective(s): To investigate the tolerable dose and short-term efficacy of docetaxel, cisplatin and fluorouracil (TPF) regimen induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy for primary locoregionally advanced nasopharyngeal carcinoma (NPC). Materials/Methods: Na€ıve patients with locally advanced NPC were enrolled. The TPF regimen consisted of docetaxel at a dose of 60 mg/m2 and cisplatin 60 mg/m2, administered as intravenous infusion on day 1, fluorouracil as a 120-hour continuous intravenous infusion on days 1 to 5. The starting dose of fluorouracil was 450 mg/(m2$day) with a subsequent dose escalation of 50 mg/(m2$day). The maximum-tolerable dose of fluorouracil was defined as the dose at which no more than 1 of 6 patients experienced dose-limiting toxicity. Treatment was administered every 3 weeks (defined as one cycle) for three cycles, and IMRT and concomitant chemotherapy were delivered during a 6-week period within 2 to 3 weeks after the completion of chemotherapy. We delineated the primary gross tumor volume (GTV) into two parts: the post-IC primary GTV (GTVpost-IC-NP), and the region of pre-IC primary GTV minus GTVpost-IC-NP (GTVpre-post-IC-NP), which was prescribed to a total dose of 68.1-Gy and 63Gy in 2.27-Gy and 2.10-Gy daily fractions, respectively. During radiotherapy, Cisplatin at a dose of 80 mg/m2 was given every 3 weeks. The primary end point was progression-free survival, and the secondary end points were respond rate after IC and radiotherapy, overall survival, time to treatment failure, toxic effects. Results: From December 2007 to October 2010, 80 patients with Stage III – IVb (by the UICC 2002 staging system) primary NPC were treated. The maximum-tolerable dose of fluorouracil was established as 550 mg/(m2$day) by 12 patients’ treatment, and 74 patients received IC at the dose, in which, 89.2%(66/74) patients finished 3 cycles of IC. The overall and complete respond rate to IC was 99.8% (1/74) and 16.2% (12/74), respectively. During IC, Grade 3 or 4 hematologic adverse events occurred in 23.3% of patients, Grade 3 or 4 diarrhea 7.1%. Radiotherapy delay was not observed, and all patients finished concurrent chemoradiotherapy per protocol. After a median follow-up of 17.6 (3.3 – 33.9) months, 2 patients had local-regional failure, 3 distant metastasis and 1 died. The 18 months progression-free survival rate was 89.0%, overall survival 96.0%, local-regional failure-free 93.9%, and distant metastasis-free 95.1%. Conclusions: TPF regimen induction chemotherapy has excellent short-term efficacy for primary locoregionally advanced NPC. Author Disclosure: W. Luo: None. Z. Yu: None. Q. Zhang: None. Q. Zhang: None. Q. Zhou: None. D. Kang: None. Y. Guo: None.
1046
A Prospective Study on Volumetric and Dosimetric Changes during Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma Patients
H. C. Cheng1,2, V. W. Wu3, R. K. Ngan1, K. Tang1, C. C. Chan1, K. Wong1, S. Au1, D. L. Kwong2 1 Queen Elizabeth Hospital, Hong Kong SAR, Hong Kong, 2The University of Hong Kong, Hong Kong SAR, Hong Kong, 3The Hong Kong Polytechnic University, Hong Kong SAR, Hong Kong
Purpose/Objective(s): Significant tumor shrinkage and/or weight loss may occur during a course of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aims to evaluate the dosimetric effect of these volumetric changes on targets volumes and organs at risk (OARs) during intra-course of IMRT, using serial reassessment of CT and MRI. Materials/Methods: Nineteen loco-regionally advanced NPC patients treated with IMRT using simultaneous integrated boost technique were recruited prospectively. The gross tumor volume (GTV) of each patient received 70 to 72 Gy in 33 fractions. Repeat planning CT and MRI were acquired at 30 and 50 Gy and they were rigidly fused to the pre-treatment planning CT. Re-contouring of target volumes and OARs was based on the fused CT-MR images. Hybrid plans at 30 (HPLAN30) and 50 Gy (HPLAN50), which were produced using the re-contoured targets and OARs, were generated for each patient by applying the same beam configurations of the original treatment plan (OPLAN). The assessment of dosimetric and volume changes was performed by comparing dosimetric and volume parameters of the hybrid plans with the original plan at the 30 and 50 Gy intervals of the treatment course. Results: There were steady volume reduction of target volumes and parotid glands over the course of IMRT (Table 1). The volume of the parotid glands decreased significantly by 14.9% (p = 0.003) and 25.1% (p = 0.001) at 30 and 50 Gy, respectively. Relative to the original plan, the hybrid plans demonstrated significantly higher dose to the target volumes with greater dose inhomogeneity, higher maximum doses to the spinal cord and brainstem, and higher mean doses to the parotid glands. Conclusions: During the course of IMRT for NPC, the dosimetric outcome was significantly altered without intra-course repeat CT and MR scans. Replanning with repeat CT and MR scans at 30 Gy is essential to keep a satisfactory dose to the target and avoid overdosing the OARs, which in turn may achieve better tumor control and reduced complications. Further adaptive radiotherapy by using deformable registration of CT and MR images is recommended. Table: Volume analysis in target volume and parotid gland of the OPLAN, HPLAN30 and HPLAN50 Mean volume (cm3) (Mean ± SD) GTV_Nasopharynx GTV_Lymph node Left parotid Right parotid Total parotid
OPLAN
HPLAN30
HPLAN50
p of OPLAN vs. HPLAN30
p of OPLAN vs. HPLAN50
42.7 ± 24.3 13.5 ± 11.2 30.0 ± 7.4 28.9 ± 8.1 58.8 ± 15.4
38.8 ± 23.8 11.5 ± 9.8 25.9 ± 6.3 24.2 ± 5.8 50.1 ± 11.8
37.1 ± 22.9 9.4 ± 8.6 22.4 ± 5.7 21.6 ± 5.3 44.1 ± 10.8
\0.001 0.003 0.010 0.007 0.003
\0.001 0.002 \0.001 0.001 0.001
Author Disclosure: H.C. Cheng: None. V.W. Wu: None. R.K. Ngan: None. K. Tang: None. C.C. Chan: None. K. Wong: None. S. Au: None. D.L. Kwong: None.