Efficacy and Factor Affecting Outcome of Induction Chemotherapy Combined Concurrent Chemoradiation Therapy in 263 Patients With Locally Advanced Nasopharyngeal Carcinoma

Efficacy and Factor Affecting Outcome of Induction Chemotherapy Combined Concurrent Chemoradiation Therapy in 263 Patients With Locally Advanced Nasopharyngeal Carcinoma

S524 International Journal of Radiation Oncology  Biology  Physics Materials/Methods: A total of 10 nasopharyngeal cancer patients (Stage T1-T4, N...

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S524

International Journal of Radiation Oncology  Biology  Physics

Materials/Methods: A total of 10 nasopharyngeal cancer patients (Stage T1-T4, N0-3) treated at our institution to 70 Gy in 33-35 fractions between 4/2011-2/2013 using fixed-jaw tomotherapy techniques without hippocampal sparing criteria underwent post facto contouring of the hippocampi. Patients were re-planned using original parameters and dose to the hippocampi/critical structures was quantified. A sub cohort of five patients was retrospectively re-planned using hippocampal sparing criteria with fixed-jaw tomotherapy planning and dynamic jaw techniques. Fixed and dynamic jaw plans were generated using a 2.5 cm field width. For consistency, the hippocampi were contoured by a single physician based on MRI fusion with CT and the re-planning was done by a single dosimetrist. Plans were optimized to meet standard criteria for PTV coverage and critical structures. Results: The mean hippocampal dose across the 10 patient cohort , without optimization to spare the hippocampi, was 20.6 Gy (range 10.141.3 Gy). With hippocampi sparing criteria in the planning process, the mean hippocampal dose was reduced by 43% on average compared to the original plan. Target coverage was not compromised by hippocampal sparing. In two cases the reduction was > 50%. Due to the sharp superior/ inferior penumbra of the dynamic jaw technique critical structure doses were decreased with dynamic jaw planning compared to fixed jaw planning. The mean hippocampal dose was additionally reduced with the dynamic jaw technique in the range of 5-35% compared to fixed jaw plans. Optic chiasm max doses were reduced by 16 Gy on average, while the mean optic nerves and temporal doses were reduced on average by 17 and 5 Gy, respectively. However, the brain stem max dose increased by 1.1 Gy on average indicating that the optimization technique prefers to deliver dose medial to the hippocampi. This was shown to be true when low-dose isodose were displayed and compared for the same cases using both techniques. Conclusions: Pilot in silico data suggest that hippocampal dose during definitive treatment of nasopharyngeal cancer may exceed dose thresholds associated with neurocognitive dysfunction for these structures. The inclusion of hippocampi in planning optimization is necessary to insure sparing of this critical structure. The use of dynamic jaw planning as opposed to fixed jaw planning can further reduce critical structure dose in the proximity of the hippocampi by several Gy. Further research needs to be conducted to establish the association between hippocampal dose and cognitive function in patients treated for nasopharyngeal cancer. Author Disclosure: R. Manon: None. P. Kelly: None. B. Chauhan: None. R. Staton: None. S. Meeks: None. N. Ramakrishna: G. Consultant; Brain Lab. H. Speakers Bureau; Brain Lab. J. Rineer: None. R. Dagan: None. O. Zeidan: None.

according to 2010 AJCC TNM) were reviewed. For all patients, the 1,3,5-year estimated overall survival (OS) rate was 96.9%,89.3%,and 81.8%, respectively. The 1,3,5-year estimated progression free survival (PFS) rate was 94.6%, 79.9%,and 76.3%, respectively. The 5-year estimated local-regional control (LRC) rate was 98.5%, 90.3%, and 87.1%, respectively. The 5-year estimated 1ocal control (LC) rate was 98.2%, 89.7%, 87.7%, respectively. The 5-year estimated distant metastasis-free survival (DMFS) rate was 95.6%,83.5%,80.5%, respectively. Induction chemotherapy plus concurrent chemotherapy with platinum was superior to concurrent with Paclitaxel in OS, PFS and DMFS (P<0.05). Major treatment related acute toxicities (grade  3) included leukopenia 33.1%, gastrointestinal reaction 11.8%, oral mucositis 26.3% and skin reaction 11.1%.26 patients died relevant to the primary disease. Thirty-six of them occurred distant metastasis, 21 with local-regional recurrence, 22 with local recurrence, while 13 of them both with local and regional recurrence. Conclusions: Paclitaxel-based induction chemotherapy followed by concurrent chemoradiation therapy for NPC yielded satisfactory survival outcomes with acceptable acute toxicity. Current chemoradiation therapy with platinum was superior to concurrent with Paclitaxel in OS, PFS and DMFS. In addition, distant metastasis and recurrence were still the most commonly seen failure pattern after treatment. Author Disclosure: F. Ma: S. Leadership; Feng Jin. F. Jin: S. Leadership; Feng Jin. F. Jin: S. Leadership; Feng Jin.

2793 Efficacy and Factor Affecting Outcome of Induction Chemotherapy Combined Concurrent Chemoradiation Therapy in 263 Patients With Locally Advanced Nasopharyngeal Carcinoma F. Ma,1 F. Jin,1 and F. Jin2; 1Guiyang Medicine College, Guiyang City, China, 2NO.4 Beijing Road, Guiyang, Guizhou, China, Guiyang Medical College, Guizhou Guiyang, China Purpose/Objective(s): To evaluate the effects of Paclitaxel-based induction chemotherapy followed by Concurrent Chemoradiation Therapy in patients with non-metastatic locally advanced nasopharyngeal carcinoma. Materials/Methods: From August December 2008 to December August 2012, previously untreated 263 patients with histologically diagnosed locally advanced nasopharyngeal carcinoma were reviewed. All were treated with two or three cycles of Paclitaxel-based induction chemotherapy, followed by cisplatin 100 mg/m2 or Paclitaxel 135 mg/m2 day 1, 22, concurrent with radiation. Similar dosage and fractionation of RT was administered in both arms. The prescribed dose was 69.96-73.92 Gy to the primary nasopharyngeal gross tumor volume, 69.96 Gy to the involved cervical lymph nodes , 66 Gy to high-risk cervical draining lymph node, and 50.96 Gy to low-risk cervical draining lymph node. Results: 236 patients (196 M, 67 F, M:F 2.93:1; median age: 46 yrs, median follow-up period: 29 months; 85 pts stage III and 179 pts IVa/b

2794 A Single Physician Experience of Intensity Modulated Radiation Therapy for Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Concurrent Chemoradiation C. Wee and H. Wu; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea, Republic of Korea Purpose/Objective(s): Intensity Modulated Radiation therapy (IMRT) provides a dose distribution that conforms more accurately to the target volume. The role of neoadjuvant chemotherapy remains yet to be defined and various radiation therapy fractionation schemes are utilized in locoregionally advanced stage III-IV nasopharyngeal carcinoma (NPC). This study reviewed the outcomes of NPC patients treated with a homogenous concurrent chemoradiation (CCRT) schedule with or without neoadjuvant chemotherapy. Materials/Methods: Eighty-six stage III-IV NPC patients who underwent neoadjuvant chemotherapy followed by CCRT (49%) or CCRT with/ without adjuvant chemotherapy (51%) using IMRT between January 2004 and September 2012 were reviewed. The target volumes for radiation therapy were delineated by a single radiation oncologist using a uniform dose prescription of 67.5 Gy in 30 fractions to the gross tumor volume (except 1 patient), 54-60 Gy to the high risk area, and 48-54 Gy to the clinically negative neck. Intravenous weekly cisplatin (35 mg/m2/week) was delivered to all patients during CCRT and the most commonly used neoadjuvant chemotherapy regimen was a combination of docetaxel, cisplatin, and 5-fluorouracil. There were 59 males and 27 females, with a median age of 48 (range 14-77). The disease was Stage III in thirty-eight (44%) and Stage IV in forty-eight (56%) patients. Results: With a median follow-up of 41.2 months, the 5 year overall survival (OS), progression-free survival (PFS), locoregional control rate (LRCR), and distant metastasis-free rate (DMFR) were 80.7%, 62.1%, 86.5%, 76.5%, respectively. The use of neoadjuvant chemotherapy showed no benefit in any of the four endpoints. In univariate analysis, no significant prognostic factor for OS was found and N3b disease was a negative factor for PFS. In multivariate analysis, N3b disease was a negative factor for both OS and PFS. Conclusions: Comparable survival outcomes for stage III-IV NPC were achieved by CCRT using IMRT (2.25 Gy/fraction) with concurrent weekly cisplatin and N3b disease was a negative factor. With the potential of increased toxicity, overtreatment, and delay of local treatment, neoadjuvant chemotherapy should not be routinely recommended for locoregionally advanced NPC in lack of evidence. Author Disclosure: C. Wee: None. H. Wu: None.