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The Outcome of Reirradiation With Curative Intent: Analysis of 247 Patients in 6 Years
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Volume 93 Number 3S Supplement 2015 of patients treated with PDT, using HDR principles for planning, to review its role in cancer therapy. Materials/Methods: Between 2005 and 2009 23 patients were treated with PDT and 21 charts were retrospectively reviewed. Patients were pretreated with Porfimer Sodium, 1-2mg/kg intravenously, 48 hours prior to PDT. A Diomed 630nm light source was used in all cases. In one case an LED light source was also used. Fiber type, diffuser length, and illumination were predetermined based on lesion size and histology, according to published guidelines. Custom immobilization devices and light field defining apertures were created for skin treatments. Endobronchial fibers and cylindrical diffuser balloons were used for lung and esophageal PDT, respectively. Local control and toxicity was assessed. Results: Average age was 69 years. 27 lesions were treated in 21 patients. Sites and histologies included squamous cell carcinoma (SCC) of the face (nZ4), SCC of the extremities (nZ1), melanoma on the anterior chest (nZ1), basal cell carcinoma (BCC) of the face (nZ4), non-small cell carcinoma of a lung bronchus (nZ4), adenocarcinoma of the esophagus (nZ3), high grade dysplasia of the esophagus (nZ2), and invasive/in situ SCC of the vulva/vagina (nZ2). One patient had two BCCs treated, while another had multiple extremity SCCs. In 67% of patients PDT was used curatively, 43% for recurrent tumors. Intent was palliative in 33%. Three patients received chemotherapy prior to PDT, 7 patients had previously received external beam radiation therapy (EBRT) (EQD2 using a / bZ3, of 36-87.5Gy), brachytherapy (minimum dose 18Gy/3 for esophagus, or 14Gy/2 to bronchus), or both. Three patients underwent surgery alone prior to PDT, and 5 patients were treated with surgery and EBRT (EQD2 using a / bZ3, of 54-61.6Gy). The most common indication for PDT was prior RT dose or surgery precluding further local therapy. Median follow-up was 5.5 (range, 0- 68) months. Complete response or adequate palliation was seen in 44% of treated lesions. Acute toxicities of edema, necrosis, and pain were self-limited and managed conservatively. Chronic stricturing was seen after esophageal PDT. No significant sunburns were seen. An unexpected toxicity was seen in a patient with SCC extending from the palmar to dorsal portion of the hand who had received EBRT, surgery, and 2 PDT treatments given 70 days apart. They developed extremity swelling and subsequent infection requiring amputation 23 days post PDT. Conclusion: The use of HDR principles for PDT planning at multiple disease sites results in acceptable control and toxicity for palliative salvage therapy when prior surgery or RT preclude further treatment. Side effects must be discussed with the patient and potential benefit must be individually assessed. Author Disclosure: M. Goldberg: None. J.E. Hayward: None. R. Singh: None. R. Sur: None.
3192 Urinary Cytokines/Chemokines as Markers of Pain Flare in Patients With Painful Bone Metastases Undergoing External Beam Radiation Therapy A. Bushehri,1 M. Pasetka,2 K. Dennis,3 A. Hird,4 A. Azad,5 E. Chow,6 and C. de Angelis2; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, ON, Canada, 2Department of Pharmacy, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada, 3The Ottawa Cancer Centre, Ottawa, ON, Canada, 4Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, 6Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada Purpose/Objective(s): Pain is experienced by 50%-75% of patients with bone metastases. External beam radiation therapy (EBRT) is a mainstay for treatment of painful bone metastases. Worsening of pain (“pain flare”) within 10 days of radiation therapy to bone metastases occurs in 40% of patients. The pathophysiology of pain flare is poorly understood. In this study, we are investigating the pathophysiology of pain flare through
assessment of changes in urinary cytokines/chemokines in patients receiving EBRT for painful bone metastases. Materials/Methods: Urine samples were collected from patients receiving a single 8 Gy radiation therapy fraction for painful bone metastases pre, day 1 or 2 and on an additional day between days 3 to 5 post radiation. Patients completed a pain and analgesic use diary daily for 10 days following radiation. Patients were deemed to have pain flare if they had a two-point increase from baseline pain on 0-10 scale and no decrease in analgesic intake or a 25% increase in analgesic intake with no decrease in pain. The Millipore Milliplex 42-Plex Cytokine/Chemokine KitÔ was used to measure urinary levels of a panel of cytokines/ chemokines. Results: 28 patients were enrolled. 83/84 urine samples were collected for analysis. Pain flare was experienced by 11 patients (39%). Of the 42 possible cytokines/chemokines measured at least 50% of the patients had measurable EGF, Fractalkine, GRO, IL-4, IL-8, IP-10, MCP-1, MDC, PDGF-AA, sIL-2Ra, TGF-alpha and VEGF. Comparing patients with or without pain flare EGF, Fractalkine, GRO, IL-8, IP-10, MCP-1, MDC, sIL2Ra, and TGF-alpha increased following radiation. There was a decrease in PDGF-AA and no change in IL-4 and VEGF. Conclusion: Measurable changes in urinary cytokine/chemokine levels occurred following radiation for painful bone metastases. Patients who experience pain flare appear to have a different pattern in urinary cytokine/ chemokine levels than patients without pain flare. Author Disclosure: A. Bushehri: None. M. Pasetka: None. K. Dennis: None. A. Hird: None. A. Azad: None. E. Chow: None. C. de Angelis: None.
3193 The Outcome of Reirradiation With Curative Intent: Analysis of 247 Patients in 6 Years R. Oh,1 H. Shiomi,1 O. Suzuki,2 N. Masai,1 and D. Tatsumi1; 1Miyakojima iGRT Clinic, Osaka, Japan, 2Miyakojima iGRT Clinic, Osaka University, Osaka, Japan Purpose/Objective(s): In recent decades, the number of long-term cancer survivors has increased. This has caused increasing requests for the delivery of a second course of radiation to recurrent tumors that occurred in previous radiation therapy fields. Most radiation oncologists are reluctant to offer reirradiation due to a lack of experience and potential toxicity. We reviewed our experience during 6 years and analyzed the outcome, in terms of tumor response, survival rates, and toxicity. Materials/Methods: A total of 247 patients reirradiated with IMRT between 01/2008 and 06/2014 at Miyakojima iGRT Clinic were analyzed. The prescribed doses were corrected to the biologically effective dose (BED) using the linear-quadratic (LQ) formulation for intercomparison over a wide variety of fraction sizes. The median BED10 of the first radiation therapy was 60Gy (12-134Gy). The median interval between the first and second radiation therapy courses was 18 months (1-308 months). The median BED10 of reirradiation was 77Gy (20-107Gy). Results: The median follow-up after reirradiation was 9 months (1e66 months). All patients completed the prescribed course of reirradiation and acute toxicity was limited. A total of 23 (9.3%) patients developed grade>3 late toxicity with the reirradiated sites including head and neck, chest, and abdomen/pelvis in 56.5%, 21.7%, and 21.7% of patients, respectively. Local recurrence was observed in 31 patients (12.6%). Median overall survival and 2-year overall survival rate after reirradiation were 18.5 months and 45.0% (95% CI, 37.1-52.5%). Conclusion: The low toxicity of reirradiation by using modern techniques should allow the delivery of higher doses and, as a consequence, lead to an improvement in the reirradiation outcome. Author Disclosure: R. Oh: None. H. Shiomi: None. O. Suzuki: None. N. Masai: None. D. Tatsumi: None.
Volume 93 Number 3S Supplement 2015 of patients treated with PDT, using HDR principles for planning, to review its role in cancer therapy. Materials/Methods: Between 2005 and 2009 23 patients were treated with PDT and 21 charts were retrospectively reviewed. Patients were pretreated with Porfimer Sodium, 1-2mg/kg intravenously, 48 hours prior to PDT. A Diomed 630nm light source was used in all cases. In one case an LED light source was also used. Fiber type, diffuser length, and illumination were predetermined based on lesion size and histology, according to published guidelines. Custom immobilization devices and light field defining apertures were created for skin treatments. Endobronchial fibers and cylindrical diffuser balloons were used for lung and esophageal PDT, respectively. Local control and toxicity was assessed. Results: Average age was 69 years. 27 lesions were treated in 21 patients. Sites and histologies included squamous cell carcinoma (SCC) of the face (nZ4), SCC of the extremities (nZ1), melanoma on the anterior chest (nZ1), basal cell carcinoma (BCC) of the face (nZ4), non-small cell carcinoma of a lung bronchus (nZ4), adenocarcinoma of the esophagus (nZ3), high grade dysplasia of the esophagus (nZ2), and invasive/in situ SCC of the vulva/vagina (nZ2). One patient had two BCCs treated, while another had multiple extremity SCCs. In 67% of patients PDT was used curatively, 43% for recurrent tumors. Intent was palliative in 33%. Three patients received chemotherapy prior to PDT, 7 patients had previously received external beam radiation therapy (EBRT) (EQD2 using a / bZ3, of 36-87.5Gy), brachytherapy (minimum dose 18Gy/3 for esophagus, or 14Gy/2 to bronchus), or both. Three patients underwent surgery alone prior to PDT, and 5 patients were treated with surgery and EBRT (EQD2 using a / bZ3, of 54-61.6Gy). The most common indication for PDT was prior RT dose or surgery precluding further local therapy. Median follow-up was 5.5 (range, 0- 68) months. Complete response or adequate palliation was seen in 44% of treated lesions. Acute toxicities of edema, necrosis, and pain were self-limited and managed conservatively. Chronic stricturing was seen after esophageal PDT. No significant sunburns were seen. An unexpected toxicity was seen in a patient with SCC extending from the palmar to dorsal portion of the hand who had received EBRT, surgery, and 2 PDT treatments given 70 days apart. They developed extremity swelling and subsequent infection requiring amputation 23 days post PDT. Conclusion: The use of HDR principles for PDT planning at multiple disease sites results in acceptable control and toxicity for palliative salvage therapy when prior surgery or RT preclude further treatment. Side effects must be discussed with the patient and potential benefit must be individually assessed. Author Disclosure: M. Goldberg: None. J.E. Hayward: None. R. Singh: None. R. Sur: None.
3192 Urinary Cytokines/Chemokines as Markers of Pain Flare in Patients With Painful Bone Metastases Undergoing External Beam Radiation Therapy A. Bushehri,1 M. Pasetka,2 K. Dennis,3 A. Hird,4 A. Azad,5 E. Chow,6 and C. de Angelis2; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, ON, Canada, 2Department of Pharmacy, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada, 3The Ottawa Cancer Centre, Ottawa, ON, Canada, 4Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, 6Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada Purpose/Objective(s): Pain is experienced by 50%-75% of patients with bone metastases. External beam radiation therapy (EBRT) is a mainstay for treatment of painful bone metastases. Worsening of pain (“pain flare”) within 10 days of radiation therapy to bone metastases occurs in 40% of patients. The pathophysiology of pain flare is poorly understood. In this study, we are investigating the pathophysiology of pain flare through
assessment of changes in urinary cytokines/chemokines in patients receiving EBRT for painful bone metastases. Materials/Methods: Urine samples were collected from patients receiving a single 8 Gy radiation therapy fraction for painful bone metastases pre, day 1 or 2 and on an additional day between days 3 to 5 post radiation. Patients completed a pain and analgesic use diary daily for 10 days following radiation. Patients were deemed to have pain flare if they had a two-point increase from baseline pain on 0-10 scale and no decrease in analgesic intake or a 25% increase in analgesic intake with no decrease in pain. The Millipore Milliplex 42-Plex Cytokine/Chemokine KitÔ was used to measure urinary levels of a panel of cytokines/ chemokines. Results: 28 patients were enrolled. 83/84 urine samples were collected for analysis. Pain flare was experienced by 11 patients (39%). Of the 42 possible cytokines/chemokines measured at least 50% of the patients had measurable EGF, Fractalkine, GRO, IL-4, IL-8, IP-10, MCP-1, MDC, PDGF-AA, sIL-2Ra, TGF-alpha and VEGF. Comparing patients with or without pain flare EGF, Fractalkine, GRO, IL-8, IP-10, MCP-1, MDC, sIL2Ra, and TGF-alpha increased following radiation. There was a decrease in PDGF-AA and no change in IL-4 and VEGF. Conclusion: Measurable changes in urinary cytokine/chemokine levels occurred following radiation for painful bone metastases. Patients who experience pain flare appear to have a different pattern in urinary cytokine/ chemokine levels than patients without pain flare. Author Disclosure: A. Bushehri: None. M. Pasetka: None. K. Dennis: None. A. Hird: None. A. Azad: None. E. Chow: None. C. de Angelis: None.
3193 The Outcome of Reirradiation With Curative Intent: Analysis of 247 Patients in 6 Years R. Oh,1 H. Shiomi,1 O. Suzuki,2 N. Masai,1 and D. Tatsumi1; 1Miyakojima iGRT Clinic, Osaka, Japan, 2Miyakojima iGRT Clinic, Osaka University, Osaka, Japan Purpose/Objective(s): In recent decades, the number of long-term cancer survivors has increased. This has caused increasing requests for the delivery of a second course of radiation to recurrent tumors that occurred in previous radiation therapy fields. Most radiation oncologists are reluctant to offer reirradiation due to a lack of experience and potential toxicity. We reviewed our experience during 6 years and analyzed the outcome, in terms of tumor response, survival rates, and toxicity. Materials/Methods: A total of 247 patients reirradiated with IMRT between 01/2008 and 06/2014 at Miyakojima iGRT Clinic were analyzed. The prescribed doses were corrected to the biologically effective dose (BED) using the linear-quadratic (LQ) formulation for intercomparison over a wide variety of fraction sizes. The median BED10 of the first radiation therapy was 60Gy (12-134Gy). The median interval between the first and second radiation therapy courses was 18 months (1-308 months). The median BED10 of reirradiation was 77Gy (20-107Gy). Results: The median follow-up after reirradiation was 9 months (1e66 months). All patients completed the prescribed course of reirradiation and acute toxicity was limited. A total of 23 (9.3%) patients developed grade>3 late toxicity with the reirradiated sites including head and neck, chest, and abdomen/pelvis in 56.5%, 21.7%, and 21.7% of patients, respectively. Local recurrence was observed in 31 patients (12.6%). Median overall survival and 2-year overall survival rate after reirradiation were 18.5 months and 45.0% (95% CI, 37.1-52.5%). Conclusion: The low toxicity of reirradiation by using modern techniques should allow the delivery of higher doses and, as a consequence, lead to an improvement in the reirradiation outcome. Author Disclosure: R. Oh: None. H. Shiomi: None. O. Suzuki: None. N. Masai: None. D. Tatsumi: None.