- Email: [email protected]
Postoperative Adjuvant Stereotactic Body Radiation Therapy (SBRT) ± Cetuximab Following Salvage Surgery in Previously Irradiated Head-and-Neck Cancer
Poster Viewing Abstracts S463
Volume 87 Number 2S Supplement 2013 Purpose/Objective(s): The prognosis for squamous cell head and neck cancer after surgical treatment and adjuvant chemo radiation is unsatisfactory in cases of close resection margins <5 mm (CM) or extracapsular extent at the lymph nodes (ECE). Therefore, we conducted a multicenter Phase II study to investigate the toxicity and efficacy of adjuvant radiation therapy in combination with concurrent cisplatin, 5-fluorouracil (5-FU), and cetuximab followed by maintenance therapy with cetuximab for 6 months. Here, we present the preliminary results on feasibility and toxicity. Materials/Methods: Patients with squamous cell cancer of the head and neck after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin (20 mg/m2 d1-5 and d29-33) and 5-FU as continuous infusion (600 mg/m2 d1-d5 + d29-33) were given concurrently to postoperative radiation therapy using an integrated boost IMRT-technique (1.8/ 2.0/2.2 Gy QD) to a total dose of 61.6 Gy. Cetuximab started 7 days prior chemoradiation therapy with a loading dose of 400 mg/m2 followed by weekly cetuximab (250 mg/m2) during chemoradiation therapy. Maintenance cetuximab started after completion of chemoradiation therapy plus cetuximab with 500 mg/m2 every 2 weeks over a 6-month period. Results: Fifty-five of 80 planned pts (46 male, 9 female, mean age 55.6, range, 29-70 years) have finished chemoradiation therapy, 50 are evaluable for toxicity. Concurrent Chemoradiation therapy plus Cetuximab was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts Cetuximab was discontinued during the last 2 weeks or at the end of chemo radiation therapy. Of those pts embarking on maintenance therapy, 80% were still on Cetuximab after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant radio chemotherapy in combination with cetuximab followed by maintenance cetuximab is feasible with toxicity in the expected range. Compliance to maintenance cetuximab was satisfactory during the first 3-5 months. Author Disclosure: C. Matuschek: None. E. Boelke: None. C. Belka: None. U. Ganswindt: None. M. Henke: None. P. Stegmaier: None. M. Bamberg: None. S. Welz: None. J. Debus: None. W. Budach: None.
2682 External Beam Radiation Therapy Is Associated With Increased Variability in Retinal Venous Oxygenation L. Stravers,1 D.S. Higginson,2 B. Chera,3 and A. Zanation4; 1University of North Carolina Chapel Hill, Chapel Hill, NC, 2Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, 3 Department of Radiation Oncology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, 4Department of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC Purpose/Objective(s): To evaluate in vivo changes in retinal oxygen saturation (SO2) via retinal oximetry after incidental radiation to the eyes. Materials/Methods: We performed in vivo measurements of arteriole and venule SO2 (SaO2 and SvO2) in patients (n Z 9, 18 retinas) who received incidental radiation to their retinas ( 45 Gy to 25% of one retina) and healthy subjects (n Z 20, 40 retinas). Retinal oximetry, a non-invasive imaging modality, was used to measure SaO2 and SvO2. The repeatability of SO2 measurements and the variability in SaO2 and SvO2 between the irradiated patient cohorts and the unirradiated volunteers were evaluated. Variability was analyzed using a random effects model using vessel type (arterioles vs venules), vessel caliber, and cohort (irradiated patients vs unirradiated subjects) as covariates. Results: Retinal oximetry measurements were highly reproducible in both irradiated patients and unirradiated subjects with standard deviations of repeated measurements of the same vessels of 1.7-2.5%. The variability of SvO2 and SaO2 measurements of different vessels in the same patient was significantly larger in the irradiated cohort than the unirradiated cohort (standard deviation 62% higher: 8.2% vs 5.1% in venules, 4.5% vs 2.8% in arterioles, p < 0.001).
Conclusions: Variation in repeated SO2 measurements using retinal oximetry was minimal. SaO2 and SvO2 varied significantly between irradiated patients and non-irradiated subjects suggesting alteration in retinal oxygenation after radiation therapy. Author Disclosure: L. Stravers: None. D.S. Higginson: None. B. Chera: None. A. Zanation: None.
2683 Postoperative Adjuvant Stereotactic Body Radiation Therapy (SBRT) ± Cetuximab Following Salvage Surgery in Previously Irradiated Head-and-Neck Cancer J. Vargo, G.J. Kubicek, R.L. Ferris, J. Grandis, U. Duvvuri, J. Johnson, J. Ohr, D.A. Clump, S. Burton, and D.E. Heron; University of Pittsburgh, Pittsburgh, PA Purpose/Objective(s): Salvage surgery represents standard of care for patients with locally-recurrent, previously-irradiated head-and-neck cancers (rHNC). Randomized multicenter phase-III data showed significant improvements in local control (LC) for the addition of post-operative conventional re-irradiation + concurrent 5-FU and hydroxyurea, at the expense of increased (28-39% grade 3) toxicity. SBRT cetuximab has emerged as a promising salvage strategy with comparable tumor control/ survival and decreased toxicity relative to conventional re-irradiation chemotherapy for unresectable rHNC. SBRT cetuximab has the potential of improving LC while reducing re-irradiation toxicity following salvage surgery for rHNC. Methods/Methods: Previously irradiated rHNC patients (n Z 35) with high-risk features following macroscopic complete (R0/R1) salvage surgery treated with adjuvant SBRT cetuximab were retrospectively reviewed as part of a prospectively maintained institutional radiosurgery database. SBRT consisted primarily of 40-44 Gy in 5 fractions administered on alternating days over 1-2 weeks with concurrent cetuximab (n Z 7) administered at 400 mg/m2 day 7 + 250 mg/m2 days 0 and +8. Acute and late toxicity were recorded above baseline using NCI CTCAE v3.0; with patient reported Quality-of-Life (QOL) prospectively assessed using the UW- QOL-R questionnaire. Results: From 2005 through 2011, 35 rNHC completed adjuvant SBRT cetuximab at a median of 62 days (range, 15-168 days) following salvage surgery. Reasons for adjuvant therapy were compromised/positive margins (n Z 28, 80%), extra-nodal extension (n Z 5, 14%), and other (n Z 2, 6%). All patients received prior radiation therapy to a median dose of 70 Gy (range, 54-99 Gy) with a median re-irradiation interval of 28 months (range, 6-168 months). At a median follow-up of 16 months (range, 2-69), the 1-year and 2-year LC, distant control (DC), and overall survival (OS) were 55/48%, 86/73%, and 66/48%, respectively. There were no significant differences in tumor control or survival by treatment volume (>25 cc), cetuximab, or reason for adjuvant therapy. Rates of acute and late severe ( grade 3) were low at 0 and 12%, respectively. At a median follow-up survey time of 6 months; 68% of patients reported improved/stable overall QOL. Conclusions: Adjuvant SBRT cetuximab following salvage surgery is well-tolerated with acceptable oncologic outcomes and little toxicity. Future prospective trials should evaluate adjuvant SBRT cetuximab vs a wait-and-see approach for rHNC patients with high-risk features following salvage surgery. Author Disclosure: J. Vargo: None. G.J. Kubicek: None. R.L. Ferris: None. J. Grandis: None. U. Duvvuri: None. J. Johnson: None. J. Ohr: None. D.A. Clump: None. S. Burton: None. D.E. Heron: None.
2684 Stereotactic Radiosurgery for Head and Neck Malignancies D. Owen,1 F. Iqbal,2 B. Pollock,1 M. Link,1 K. Stien,1 Y. Garces,1 P. Brown,3 and R. Foote1; 1Mayo Clinic, Rochester, MN, 2Durham Regional Cancer Centre, Oshawa, ON, Canada, 3The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Stereotactic radiosurgery (SRS) is a highly targeted technique that allows for delivering additional dose to head and neck
Volume 87 Number 2S Supplement 2013 Purpose/Objective(s): The prognosis for squamous cell head and neck cancer after surgical treatment and adjuvant chemo radiation is unsatisfactory in cases of close resection margins <5 mm (CM) or extracapsular extent at the lymph nodes (ECE). Therefore, we conducted a multicenter Phase II study to investigate the toxicity and efficacy of adjuvant radiation therapy in combination with concurrent cisplatin, 5-fluorouracil (5-FU), and cetuximab followed by maintenance therapy with cetuximab for 6 months. Here, we present the preliminary results on feasibility and toxicity. Materials/Methods: Patients with squamous cell cancer of the head and neck after primary surgery were eligible for the study, if a CM or ECE was detected. Cisplatin (20 mg/m2 d1-5 and d29-33) and 5-FU as continuous infusion (600 mg/m2 d1-d5 + d29-33) were given concurrently to postoperative radiation therapy using an integrated boost IMRT-technique (1.8/ 2.0/2.2 Gy QD) to a total dose of 61.6 Gy. Cetuximab started 7 days prior chemoradiation therapy with a loading dose of 400 mg/m2 followed by weekly cetuximab (250 mg/m2) during chemoradiation therapy. Maintenance cetuximab started after completion of chemoradiation therapy plus cetuximab with 500 mg/m2 every 2 weeks over a 6-month period. Results: Fifty-five of 80 planned pts (46 male, 9 female, mean age 55.6, range, 29-70 years) have finished chemoradiation therapy, 50 are evaluable for toxicity. Concurrent Chemoradiation therapy plus Cetuximab was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts Cetuximab was discontinued during the last 2 weeks or at the end of chemo radiation therapy. Of those pts embarking on maintenance therapy, 80% were still on Cetuximab after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant radio chemotherapy in combination with cetuximab followed by maintenance cetuximab is feasible with toxicity in the expected range. Compliance to maintenance cetuximab was satisfactory during the first 3-5 months. Author Disclosure: C. Matuschek: None. E. Boelke: None. C. Belka: None. U. Ganswindt: None. M. Henke: None. P. Stegmaier: None. M. Bamberg: None. S. Welz: None. J. Debus: None. W. Budach: None.
2682 External Beam Radiation Therapy Is Associated With Increased Variability in Retinal Venous Oxygenation L. Stravers,1 D.S. Higginson,2 B. Chera,3 and A. Zanation4; 1University of North Carolina Chapel Hill, Chapel Hill, NC, 2Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, 3 Department of Radiation Oncology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, 4Department of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC Purpose/Objective(s): To evaluate in vivo changes in retinal oxygen saturation (SO2) via retinal oximetry after incidental radiation to the eyes. Materials/Methods: We performed in vivo measurements of arteriole and venule SO2 (SaO2 and SvO2) in patients (n Z 9, 18 retinas) who received incidental radiation to their retinas ( 45 Gy to 25% of one retina) and healthy subjects (n Z 20, 40 retinas). Retinal oximetry, a non-invasive imaging modality, was used to measure SaO2 and SvO2. The repeatability of SO2 measurements and the variability in SaO2 and SvO2 between the irradiated patient cohorts and the unirradiated volunteers were evaluated. Variability was analyzed using a random effects model using vessel type (arterioles vs venules), vessel caliber, and cohort (irradiated patients vs unirradiated subjects) as covariates. Results: Retinal oximetry measurements were highly reproducible in both irradiated patients and unirradiated subjects with standard deviations of repeated measurements of the same vessels of 1.7-2.5%. The variability of SvO2 and SaO2 measurements of different vessels in the same patient was significantly larger in the irradiated cohort than the unirradiated cohort (standard deviation 62% higher: 8.2% vs 5.1% in venules, 4.5% vs 2.8% in arterioles, p < 0.001).
Conclusions: Variation in repeated SO2 measurements using retinal oximetry was minimal. SaO2 and SvO2 varied significantly between irradiated patients and non-irradiated subjects suggesting alteration in retinal oxygenation after radiation therapy. Author Disclosure: L. Stravers: None. D.S. Higginson: None. B. Chera: None. A. Zanation: None.
2683 Postoperative Adjuvant Stereotactic Body Radiation Therapy (SBRT) ± Cetuximab Following Salvage Surgery in Previously Irradiated Head-and-Neck Cancer J. Vargo, G.J. Kubicek, R.L. Ferris, J. Grandis, U. Duvvuri, J. Johnson, J. Ohr, D.A. Clump, S. Burton, and D.E. Heron; University of Pittsburgh, Pittsburgh, PA Purpose/Objective(s): Salvage surgery represents standard of care for patients with locally-recurrent, previously-irradiated head-and-neck cancers (rHNC). Randomized multicenter phase-III data showed significant improvements in local control (LC) for the addition of post-operative conventional re-irradiation + concurrent 5-FU and hydroxyurea, at the expense of increased (28-39% grade 3) toxicity. SBRT cetuximab has emerged as a promising salvage strategy with comparable tumor control/ survival and decreased toxicity relative to conventional re-irradiation chemotherapy for unresectable rHNC. SBRT cetuximab has the potential of improving LC while reducing re-irradiation toxicity following salvage surgery for rHNC. Methods/Methods: Previously irradiated rHNC patients (n Z 35) with high-risk features following macroscopic complete (R0/R1) salvage surgery treated with adjuvant SBRT cetuximab were retrospectively reviewed as part of a prospectively maintained institutional radiosurgery database. SBRT consisted primarily of 40-44 Gy in 5 fractions administered on alternating days over 1-2 weeks with concurrent cetuximab (n Z 7) administered at 400 mg/m2 day 7 + 250 mg/m2 days 0 and +8. Acute and late toxicity were recorded above baseline using NCI CTCAE v3.0; with patient reported Quality-of-Life (QOL) prospectively assessed using the UW- QOL-R questionnaire. Results: From 2005 through 2011, 35 rNHC completed adjuvant SBRT cetuximab at a median of 62 days (range, 15-168 days) following salvage surgery. Reasons for adjuvant therapy were compromised/positive margins (n Z 28, 80%), extra-nodal extension (n Z 5, 14%), and other (n Z 2, 6%). All patients received prior radiation therapy to a median dose of 70 Gy (range, 54-99 Gy) with a median re-irradiation interval of 28 months (range, 6-168 months). At a median follow-up of 16 months (range, 2-69), the 1-year and 2-year LC, distant control (DC), and overall survival (OS) were 55/48%, 86/73%, and 66/48%, respectively. There were no significant differences in tumor control or survival by treatment volume (>25 cc), cetuximab, or reason for adjuvant therapy. Rates of acute and late severe ( grade 3) were low at 0 and 12%, respectively. At a median follow-up survey time of 6 months; 68% of patients reported improved/stable overall QOL. Conclusions: Adjuvant SBRT cetuximab following salvage surgery is well-tolerated with acceptable oncologic outcomes and little toxicity. Future prospective trials should evaluate adjuvant SBRT cetuximab vs a wait-and-see approach for rHNC patients with high-risk features following salvage surgery. Author Disclosure: J. Vargo: None. G.J. Kubicek: None. R.L. Ferris: None. J. Grandis: None. U. Duvvuri: None. J. Johnson: None. J. Ohr: None. D.A. Clump: None. S. Burton: None. D.E. Heron: None.
2684 Stereotactic Radiosurgery for Head and Neck Malignancies D. Owen,1 F. Iqbal,2 B. Pollock,1 M. Link,1 K. Stien,1 Y. Garces,1 P. Brown,3 and R. Foote1; 1Mayo Clinic, Rochester, MN, 2Durham Regional Cancer Centre, Oshawa, ON, Canada, 3The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Stereotactic radiosurgery (SRS) is a highly targeted technique that allows for delivering additional dose to head and neck