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Dose–Effect Relationship of MRI Perfusion Changes in the Pharyngeal Constrictors After Head and Neck Radiation Therapy
Poster Viewing Abstracts S475
Volume 87 Number 2S Supplement 2013 Materials/Methods: We performed a single-institution retrospective analysis of patients with locally advanced, nonmetastatic HNSCC (Stage III-IV). We conducted this analysis under the University of Illinois IRB protocol (2011-1075). From a database of 650 patients, we identified 143 patients treated with TPF or carbo-taxol induction chemotherapy followed by concurrent chemoradiation. All patients were treated between 1999 and 2012. Results: Fifty-three patients received TPF induction chemotherapy and 90 patients received carbotaxol induction chemotherapy. The median followup was 18.9 months. The two groups did not differ significantly in gender, median age, Karnofsky Performance Status (KPS), comorbidity index, stage, primary site, or tumor grade. Patients receiving carbo-taxol induction chemotherapy had improved 2y locoregional control (LRC: 78.9% vs 46.1%; p < 0.0001) and improved 2y progression-free survival (PFS: 61.1% vs 36.6%; p Z 0.015). Carbo-taxol trended to improved 2y freedom from distant metastasis (FFDM: 79.1% vs 63.1%; p Z 0.0597) and there was no difference in 2y overall survival (OS: 69.2% vs 67.2%; p Z 0.96). On multivariable analysis, carbo-taxol induction chemotherapy remained significant for LRC with a Hazard Ratio of 0.238 (95% CI 0.055-0.703, p Z 0.007) and PFS with a Hazard Ratio of 0.443 (95% CI 0.181-0.976, p Z 0.0432). TPF induction chemotherapy was associated with worse renal toxicity. TPF-based chemotherapy resulted in a greater increase in mean creatinine from baseline compared to carbo/taxol during induction (0.477, SD 1.00 vs 0.0955, SD 0.344; p Z 0.0095) and prior to radiation therapy (0.119, SD 0.582 vs 0.0867, SD 0.161; p Z 0.0148). Conclusions: Compared to TPF induction chemotherapy, carbo-taxol induction chemotherapy resulted in improved LRC and PFS while having less renal toxicity. Thus, patients with locally advanced HNSCC may benefit from carbo-taxol induction chemotherapy when they receive subsequent concurrent chemoradiation. Author Disclosure: L. Herman: None. A. Garnett: None. M. Spiotto: None.
2713 DoseeEffect Relationship of MRI Perfusion Changes in the Pharyngeal Constrictors After Head and Neck Radiation Therapy C.H. Chapman, A. Popovtzer, F.Y. Feng, A. Eisbruch, and Y. Cao; University of Michigan, Ann Arbor, MI Purpose/Objective(s): Inflammation and edema of pharyngeal constrictors after head and neck radiation are thought to be major causes of dysphagia. We conducted a prospective MRI study evaluating blood perfusion changes in the pharyngeal constrictors after radiation, to gain insight to the mechanism of their dysfunction and any dose-effect relationship. Materials/Methods: Thirteen patients with stage III-IV head and neck cancer received seven weeks of radiation therapy (RT) with concurrent chemotherapy. Patients underwent dynamic contrast-enhanced (DCE) MRI before RT, two weeks into RT, and three months post-RT. Planning CT was used to register accumulated dose at both time points to DCE images. Two indices were calculated from DCE images: blood volume (BV), an estimate of the proportion of tissue volume occupied by blood, and pseudoblood flow (BF), an estimate of blood flow density. Mean index values were measured from the pharyngeal constrictors inside 10 Gy dose bins. Dose response was determined using a linear mixed effects model for repeated measures. Results: Both BV and BF showed significant linear dose-effect relationships at two weeks into RT, with an estimated 2.5% increase in fractional blood volume per 10 Gy (p < 0.001), and 6.7 mL/min/100g increase in blood flow density per 10 Gy (p Z 0.015). Mean changes in BV and BF at three months post-RT (+308%, +90%) were greater than at two weeks into RT (+243%, +60%). At three months post-RT, BV continued to show a significant linear dose-effect relationship (p Z 0.001); however the strength of this relationship was significantly less than at two weeks into RT (p < 0.001). At three months post-RT, BF showed a near-significant trend towards linear dose-effect relationship (p Z 0.095), and the strength of this relationship was also significantly less than at two weeks into RT
(p < 0.001). Changes in both indices at two weeks into RT were significant predictors of changes at three months post-RT (BV, p < 0.001; BF, p Z 0.046). Conclusions: DCE MRI measurements of fractional blood volume and blood flow density in the pharyngeal constrictors were increased by radiation therapy in a dose-dependent manner, even before radiation therapy was complete. This suggests that these indices are sensitive early indicators of pharyngeal constrictor inflammation and edema. Future studies should examine whether mid-treatment MRI changes can predict radiationinduced dysphagia. Author Disclosure: C.H. Chapman: None. A. Popovtzer: None. F.Y. Feng: None. A. Eisbruch: E. Research Grant; NIH PO1 CA59827. Y. Cao: None.
2714 NTCP-Based Adaptive Radiation Therapy in Head-and-Neck Cancers: A New Look Into the Old Bottle B. Emami, M. Surucu, K. Shah, J. Breunig, and B. Chiappetta; Loyola University Medical Center, Maywood, IL Purpose/Objective(s): In current practice of radiation therapy, the original treatment plan (3 DCRT or IMRT) is routinely carried out to completion. During the course of radiation therapy often there is a change in tumor size, (response) or patient’s anatomy (i.e., weight loss). These changes can have profound impact on delivered doses to targets and normal tissues different from the conformity of the original plan. We investigated the potential impact of these changes of the final dosimetric and clinical outcome (NTCP and T.C.) by adaptive IGRT. Materials/Methods: Fifty-one patients with advanced head and neck cancers (naso - 6, oro - 5, oral - 9, hypo - 2, other 7) have been rescanned and 39 of them were replanned. Of this group 25 patients (naso - 3, oro 12, hypo - 2, oral cancer e 7, and occult primary - 1) with detailed information were selected for this analysis. All patients had original optimized plan to total tumor dose of 7020 cGy (in combination with cisplatin chemotherapy) and normal tissue doses at or often below tolerance. At 3800 cGy patients were rescanned, new target volumes were contoured. For this study the original plan was then superimposed on new contours and doses to target volumes and normal tissues were recalculated. Then a new best plan (composite) was constructed based on new contours for the remainder of the treatment. Results: In analyzed group with mean follow-up of 11.93 months there is two local failure (both oral cavity), one nodal failure. Continuation of original plan without replanning would have resulted in an increase in spinal cord dose in 68% of patients (mean - 8.42%, range, - 0.90%, 30.31%) and in 15 of 17 beyond the tolerance level of 50 Gy. In 32% of the patients spinal cord dose would have been decreased (mean 2.21%, range, 0.89%, 4.56%). In all patients the final composite adapted plan spinal cord dose was at or below tolerance dose. Similar disturbances and subsequent optimization were also observed in other organs (i.e., brain stem, parotid, etc). Conclusions: This study suggests that part of radiation therapy complications may be due to overdose of normal tissue as results of changes during treatment. A prospective protocol is underway to determine the appropriate criteria and timing for rescanning and replanning. Detailed results will be presented. Author Disclosure: B. Emami: None. M. Surucu: None. K. Shah: None. J. Breunig: None. B. Chiappetta: None.
2715 Outcome of Dental Implants in Patients With Previous Radiation History to the Head and Neck Area H. Han, J. Cha, and C. Lee; Yonsei Cancer Center, Seoul, Korea, Republic of Korea Purpose/Objective(s): To analyze implant outcome in patients who previously received radiation treatment for head and neck malignancies.
Volume 87 Number 2S Supplement 2013 Materials/Methods: We performed a single-institution retrospective analysis of patients with locally advanced, nonmetastatic HNSCC (Stage III-IV). We conducted this analysis under the University of Illinois IRB protocol (2011-1075). From a database of 650 patients, we identified 143 patients treated with TPF or carbo-taxol induction chemotherapy followed by concurrent chemoradiation. All patients were treated between 1999 and 2012. Results: Fifty-three patients received TPF induction chemotherapy and 90 patients received carbotaxol induction chemotherapy. The median followup was 18.9 months. The two groups did not differ significantly in gender, median age, Karnofsky Performance Status (KPS), comorbidity index, stage, primary site, or tumor grade. Patients receiving carbo-taxol induction chemotherapy had improved 2y locoregional control (LRC: 78.9% vs 46.1%; p < 0.0001) and improved 2y progression-free survival (PFS: 61.1% vs 36.6%; p Z 0.015). Carbo-taxol trended to improved 2y freedom from distant metastasis (FFDM: 79.1% vs 63.1%; p Z 0.0597) and there was no difference in 2y overall survival (OS: 69.2% vs 67.2%; p Z 0.96). On multivariable analysis, carbo-taxol induction chemotherapy remained significant for LRC with a Hazard Ratio of 0.238 (95% CI 0.055-0.703, p Z 0.007) and PFS with a Hazard Ratio of 0.443 (95% CI 0.181-0.976, p Z 0.0432). TPF induction chemotherapy was associated with worse renal toxicity. TPF-based chemotherapy resulted in a greater increase in mean creatinine from baseline compared to carbo/taxol during induction (0.477, SD 1.00 vs 0.0955, SD 0.344; p Z 0.0095) and prior to radiation therapy (0.119, SD 0.582 vs 0.0867, SD 0.161; p Z 0.0148). Conclusions: Compared to TPF induction chemotherapy, carbo-taxol induction chemotherapy resulted in improved LRC and PFS while having less renal toxicity. Thus, patients with locally advanced HNSCC may benefit from carbo-taxol induction chemotherapy when they receive subsequent concurrent chemoradiation. Author Disclosure: L. Herman: None. A. Garnett: None. M. Spiotto: None.
2713 DoseeEffect Relationship of MRI Perfusion Changes in the Pharyngeal Constrictors After Head and Neck Radiation Therapy C.H. Chapman, A. Popovtzer, F.Y. Feng, A. Eisbruch, and Y. Cao; University of Michigan, Ann Arbor, MI Purpose/Objective(s): Inflammation and edema of pharyngeal constrictors after head and neck radiation are thought to be major causes of dysphagia. We conducted a prospective MRI study evaluating blood perfusion changes in the pharyngeal constrictors after radiation, to gain insight to the mechanism of their dysfunction and any dose-effect relationship. Materials/Methods: Thirteen patients with stage III-IV head and neck cancer received seven weeks of radiation therapy (RT) with concurrent chemotherapy. Patients underwent dynamic contrast-enhanced (DCE) MRI before RT, two weeks into RT, and three months post-RT. Planning CT was used to register accumulated dose at both time points to DCE images. Two indices were calculated from DCE images: blood volume (BV), an estimate of the proportion of tissue volume occupied by blood, and pseudoblood flow (BF), an estimate of blood flow density. Mean index values were measured from the pharyngeal constrictors inside 10 Gy dose bins. Dose response was determined using a linear mixed effects model for repeated measures. Results: Both BV and BF showed significant linear dose-effect relationships at two weeks into RT, with an estimated 2.5% increase in fractional blood volume per 10 Gy (p < 0.001), and 6.7 mL/min/100g increase in blood flow density per 10 Gy (p Z 0.015). Mean changes in BV and BF at three months post-RT (+308%, +90%) were greater than at two weeks into RT (+243%, +60%). At three months post-RT, BV continued to show a significant linear dose-effect relationship (p Z 0.001); however the strength of this relationship was significantly less than at two weeks into RT (p < 0.001). At three months post-RT, BF showed a near-significant trend towards linear dose-effect relationship (p Z 0.095), and the strength of this relationship was also significantly less than at two weeks into RT
(p < 0.001). Changes in both indices at two weeks into RT were significant predictors of changes at three months post-RT (BV, p < 0.001; BF, p Z 0.046). Conclusions: DCE MRI measurements of fractional blood volume and blood flow density in the pharyngeal constrictors were increased by radiation therapy in a dose-dependent manner, even before radiation therapy was complete. This suggests that these indices are sensitive early indicators of pharyngeal constrictor inflammation and edema. Future studies should examine whether mid-treatment MRI changes can predict radiationinduced dysphagia. Author Disclosure: C.H. Chapman: None. A. Popovtzer: None. F.Y. Feng: None. A. Eisbruch: E. Research Grant; NIH PO1 CA59827. Y. Cao: None.
2714 NTCP-Based Adaptive Radiation Therapy in Head-and-Neck Cancers: A New Look Into the Old Bottle B. Emami, M. Surucu, K. Shah, J. Breunig, and B. Chiappetta; Loyola University Medical Center, Maywood, IL Purpose/Objective(s): In current practice of radiation therapy, the original treatment plan (3 DCRT or IMRT) is routinely carried out to completion. During the course of radiation therapy often there is a change in tumor size, (response) or patient’s anatomy (i.e., weight loss). These changes can have profound impact on delivered doses to targets and normal tissues different from the conformity of the original plan. We investigated the potential impact of these changes of the final dosimetric and clinical outcome (NTCP and T.C.) by adaptive IGRT. Materials/Methods: Fifty-one patients with advanced head and neck cancers (naso - 6, oro - 5, oral - 9, hypo - 2, other 7) have been rescanned and 39 of them were replanned. Of this group 25 patients (naso - 3, oro 12, hypo - 2, oral cancer e 7, and occult primary - 1) with detailed information were selected for this analysis. All patients had original optimized plan to total tumor dose of 7020 cGy (in combination with cisplatin chemotherapy) and normal tissue doses at or often below tolerance. At 3800 cGy patients were rescanned, new target volumes were contoured. For this study the original plan was then superimposed on new contours and doses to target volumes and normal tissues were recalculated. Then a new best plan (composite) was constructed based on new contours for the remainder of the treatment. Results: In analyzed group with mean follow-up of 11.93 months there is two local failure (both oral cavity), one nodal failure. Continuation of original plan without replanning would have resulted in an increase in spinal cord dose in 68% of patients (mean - 8.42%, range, - 0.90%, 30.31%) and in 15 of 17 beyond the tolerance level of 50 Gy. In 32% of the patients spinal cord dose would have been decreased (mean 2.21%, range, 0.89%, 4.56%). In all patients the final composite adapted plan spinal cord dose was at or below tolerance dose. Similar disturbances and subsequent optimization were also observed in other organs (i.e., brain stem, parotid, etc). Conclusions: This study suggests that part of radiation therapy complications may be due to overdose of normal tissue as results of changes during treatment. A prospective protocol is underway to determine the appropriate criteria and timing for rescanning and replanning. Detailed results will be presented. Author Disclosure: B. Emami: None. M. Surucu: None. K. Shah: None. J. Breunig: None. B. Chiappetta: None.
2715 Outcome of Dental Implants in Patients With Previous Radiation History to the Head and Neck Area H. Han, J. Cha, and C. Lee; Yonsei Cancer Center, Seoul, Korea, Republic of Korea Purpose/Objective(s): To analyze implant outcome in patients who previously received radiation treatment for head and neck malignancies.