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Single-Arm Phase 2 Study of Stereotactic Body Radiation Therapy (SBRT) Concurrent with Nelfinavir for Solid Tumor Oligometastases
ePoster Sessions S221
Volume 99 Number 2S Supplement 2017 5
Dana-Farber Cancer Institute, Boston, MA, 6McGill University Health Centre, Montreal, QC, Canada
Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose/Objective(s): As patients with advanced cancer approach end of life, ethical issues may arise. Radiation oncologists often care for these patients when they are referred for palliative radiotherapy (PRT). This study describes the frequency and types of ethical issues encountered by radiation oncologists in caring for PRT patients. Materials/Methods: A prospective, survey-based study assessed 162 consecutive consults for PRT from 5/19/14-9/26/14 at 3 Boston-area hospitals. Consulting clinicians completed a survey to assess palliative care issues encountered in care based on Domains of Palliative Care adapted from national guidelines. Assessment within the ethical domain included 5 subthemes (conflict between clinicians, conflict between patient/family and clinicians, clinician internal conflict, feeling blocked from doing what is best for the patient, and violation of personal morals), an option for unclassified issues, and open-ended responses. Univariate (UVA) and multivariate (MVA) analyses assessed potential predictors of ethical issues: gender, performance status (PS), indication for PRT, physical symptoms, and the presence of psychosocial, goals of care, care coordination, cultural, or spiritual issues. Results: Of 162 surveys, 140 were returned and analyzed (response rate Z 86%); 14 (10%) identified ethical issues relevant to the patient’s care, with 11 (78%) having more than 1 ethical issue. Half of ethical issues (n Z 7) involved conflict between clinicians; 7 (50%) involved conflict between patient/family and clinicians; 6 (43%) involved clinician distress or internal conflict; and 2 (14%) felt impeded from doing what they felt was best for the patient. Open-ended responses revealed differences in opinion between medical specialties (n Z 6; 43%) and conflict related to coordination of care among clinical caregivers (n Z 3; 21%). Ethical conflicts were more commonly associated with PRT referrals for bleeding, dyspnea, or dysphagia due to visceral metastases (30%) versus for bony metastases (7%) or for CNS indications like brain metastases or cord compression (4%), P < 0.001. Ethical issues tended to be more common among patients with psychosocial (13% vs. 4%, P Z 0.13) or spiritual issues (23% vs. 5%, P Z 0.001). PS and gender were not significant. On MVA, PRT for visceral metastases (OR 13.0, 95% CI 2.3-74.6, P < 0.001) and presence of spiritual issues (OR 4.0, 95% CI 1.1-14.5, P Z 0.04) were significantly associated with ethical issues. Conclusion: Ethical issues are frequently encountered in the care of advanced cancer patients, with 1 in 10 referrals for PRT involving ethical issues. Ethical issues are more common among patients seen for symptomatic visceral metastases (e.g., bleeding, dyspnea) and when patients have spiritual concerns. These findings suggest educational opportunities for radiation oncologists to address ethical conflicts that arise in the care of patients referred for PRT. Author Disclosure: D. Yerramilli: None. G. Parker: None. V. LeBaron: Committee Member on Advisory Board; International Society for Nurses in Cancer Care. M.S. Krishnan: None. L.M. Hertan: None. A. Spektor: None. R. Shiloh: None. S. Skamene: None. T.A. Balboni: Employee; Dana-Farber Cancer Institute. Research Grant; Templeton Foundation; ASCO Palliative Care Steering Committee Member.
Purpose/Objective(s): Patients (pts) with oligometastases (5 lesion sites) treated with SBRT have demonstrated evidence of long-term diseasefree survival despite the overall poor prognosis of metastatic disease. Nelfinavir is a HIV protease inhibitor that may potentially act as a radiosensitizer. We performed a Phase II study of nelfinavir concurrent with SBRT in pts with solid tumor oligometastases to determine 6-month (6mo) freedom from local progression (FFLP). Secondary endpoints include safety, overall survival (OS), freedom from distant metastasis (FFDM) and progression-free survival (PFS). Materials/Methods: Pts with 5 histologic confirmed metastatic lesions ( 5.0 cm or 250 cm3) of lung, liver, lymph nodes, or bone, and good performance status (ECOG 2) were eligible. Pts were given 1250 mg of nelfinavir twice daily for 7 days prior to and after a single dose of 15 Gy SBRT per lesion. Responses were evaluated based on RECIST 1.1 criteria. Results: A total of 38 pts were accrued between January 2014 and December 2015. One withdrew consent and 37 were included in the analysis, with a median follow-up of 18 months (range 5-31.5 months). The median patient age was 65 (range 35-81 years), 62% were men, and 51% and 22% had prostate and sarcoma as primary histologies, respectively. The majority of pts had 3 lesion sites (54% had 1 lesion, 22% had 2, and 16% had 3), and had recurrence sites at bone (57%) or lung (24%). The 6 mo FFLP rate was 78.4% (95% CI: 61.4-88.5%). Among the 68 treated lesions, the 6mo FFLP rate by lesion was 76.5% (95% CI: 64.584.9%). There were a total of 3 deaths due to disease progression. The 18 mo rates of OS, FFDM, and PFS were 90.7% (95% CI: 73.8-96.9), 62.4% (95% CI: 43.9-76.3), 57.6% (95% CI: 39.7-72.0), respectively. The 6 mo FFLP rate for patients with prostate cancer was 100% compared to 63% for patients with sarcoma (P < 0.0003). There were 4 grade 3 adverse events that may have been related to treatment (e.g., absolute lymphocyte decrease, anxiety, nausea, and cough). Conclusion: SBRT can be delivered safely with nelfinavir. Overall 6 mo FFLP rate for the entire cohort was not significantly higher than historical controls, although this may be secondary to tumor histology, treated site, and lesion number. Prostate cancer patients had significantly improved clinical outcomes relative to sarcoma patients and thus one may hypothesize that certain histologies may require a higher SBRT dose for local control. Further research should be conducted into the optimum patient cohort to benefit from the concurrent use of radiosensitizers with SBRT. Author Disclosure: S.A. Terezakis: Research Grant; Elekta. Honoraria; Elekta. Travel Expenses; Elekta; Red Journal. J. Herman: None. C. Hu: None. J. Yan: None. S. Di Pasquale: None. R. McIntyre: None. H. Kim: None. B.W. Loo: Research Grant; RaySearch, Varian Medical Systems Inc. Stock; TibaRay, Inc.; American College of Radiology, National Comprehensive Cancer Network, TibaRay, Inc. R.K. Hales: None. P.T. Tran: Research Grant; NIH-NCI, ACS, Kimmel Foundation, AstellasMedivation, American Lung Association, Movember-PCF, PCORI. Honoraria; Dendreon. Advisory Board; Astellas-Medivation, Dendreon. Travel Expenses; Dendreon. Patent/License Fees/Copyright; Compounds and Methods of Use in Ablative RT, Natsar Pharmaceuticals; RSNA R&E Foundation.
1115 Single-Arm Phase 2 Study of Stereotactic Body Radiation Therapy (SBRT) Concurrent with Nelfinavir for Solid Tumor Oligometastases S.A. Terezakis,1 J. Herman,2 C. Hu,3 J. Yan,4 S. Di Pasquale,5 R. McIntyre,5 H. Kim,5 B.W. Loo Jr6 R.K. Hales,7 and P.T. Tran5; 1Johns Hopkins Hospital, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, 2The University of Texas MD Anderson Cancer Center, Houston, TX, 3Johns Hopkins University School of Medicine, Division of Biostatistics and Bioinformatics, Baltimore, MD, 4 Johns Hopkins School of Medicine, Baltimore, MD, 5Johns Hopkins University School of Medicine, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, 6Stanford Cancer Institute, Stanford, CA, 7Department of Radiation Oncology and Molecular
1116 Outcomes and Characteristics of Patients Treated with Emergent Radiotherapy S.A. Dudley,1 S. Aggarwal,2 M.M. Grade,3 K.A. Kumar Jr4 B.E. Turner,5 Y. Liu,6 R. Von Eyben,6 D.T. Chang,7 and S.J. Knox2; 1Stanford Department of Radiation Oncology, Stanford, CA, 2Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, 3Stanford School of Medicine, Stanford, CA, 4Stanford University School of Medicine, Stanford, CA, 5Stanford School of Medicine, Stanford, CA, United States, 6Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 7Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA
Volume 99 Number 2S Supplement 2017 5
Dana-Farber Cancer Institute, Boston, MA, 6McGill University Health Centre, Montreal, QC, Canada
Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose/Objective(s): As patients with advanced cancer approach end of life, ethical issues may arise. Radiation oncologists often care for these patients when they are referred for palliative radiotherapy (PRT). This study describes the frequency and types of ethical issues encountered by radiation oncologists in caring for PRT patients. Materials/Methods: A prospective, survey-based study assessed 162 consecutive consults for PRT from 5/19/14-9/26/14 at 3 Boston-area hospitals. Consulting clinicians completed a survey to assess palliative care issues encountered in care based on Domains of Palliative Care adapted from national guidelines. Assessment within the ethical domain included 5 subthemes (conflict between clinicians, conflict between patient/family and clinicians, clinician internal conflict, feeling blocked from doing what is best for the patient, and violation of personal morals), an option for unclassified issues, and open-ended responses. Univariate (UVA) and multivariate (MVA) analyses assessed potential predictors of ethical issues: gender, performance status (PS), indication for PRT, physical symptoms, and the presence of psychosocial, goals of care, care coordination, cultural, or spiritual issues. Results: Of 162 surveys, 140 were returned and analyzed (response rate Z 86%); 14 (10%) identified ethical issues relevant to the patient’s care, with 11 (78%) having more than 1 ethical issue. Half of ethical issues (n Z 7) involved conflict between clinicians; 7 (50%) involved conflict between patient/family and clinicians; 6 (43%) involved clinician distress or internal conflict; and 2 (14%) felt impeded from doing what they felt was best for the patient. Open-ended responses revealed differences in opinion between medical specialties (n Z 6; 43%) and conflict related to coordination of care among clinical caregivers (n Z 3; 21%). Ethical conflicts were more commonly associated with PRT referrals for bleeding, dyspnea, or dysphagia due to visceral metastases (30%) versus for bony metastases (7%) or for CNS indications like brain metastases or cord compression (4%), P < 0.001. Ethical issues tended to be more common among patients with psychosocial (13% vs. 4%, P Z 0.13) or spiritual issues (23% vs. 5%, P Z 0.001). PS and gender were not significant. On MVA, PRT for visceral metastases (OR 13.0, 95% CI 2.3-74.6, P < 0.001) and presence of spiritual issues (OR 4.0, 95% CI 1.1-14.5, P Z 0.04) were significantly associated with ethical issues. Conclusion: Ethical issues are frequently encountered in the care of advanced cancer patients, with 1 in 10 referrals for PRT involving ethical issues. Ethical issues are more common among patients seen for symptomatic visceral metastases (e.g., bleeding, dyspnea) and when patients have spiritual concerns. These findings suggest educational opportunities for radiation oncologists to address ethical conflicts that arise in the care of patients referred for PRT. Author Disclosure: D. Yerramilli: None. G. Parker: None. V. LeBaron: Committee Member on Advisory Board; International Society for Nurses in Cancer Care. M.S. Krishnan: None. L.M. Hertan: None. A. Spektor: None. R. Shiloh: None. S. Skamene: None. T.A. Balboni: Employee; Dana-Farber Cancer Institute. Research Grant; Templeton Foundation; ASCO Palliative Care Steering Committee Member.
Purpose/Objective(s): Patients (pts) with oligometastases (5 lesion sites) treated with SBRT have demonstrated evidence of long-term diseasefree survival despite the overall poor prognosis of metastatic disease. Nelfinavir is a HIV protease inhibitor that may potentially act as a radiosensitizer. We performed a Phase II study of nelfinavir concurrent with SBRT in pts with solid tumor oligometastases to determine 6-month (6mo) freedom from local progression (FFLP). Secondary endpoints include safety, overall survival (OS), freedom from distant metastasis (FFDM) and progression-free survival (PFS). Materials/Methods: Pts with 5 histologic confirmed metastatic lesions ( 5.0 cm or 250 cm3) of lung, liver, lymph nodes, or bone, and good performance status (ECOG 2) were eligible. Pts were given 1250 mg of nelfinavir twice daily for 7 days prior to and after a single dose of 15 Gy SBRT per lesion. Responses were evaluated based on RECIST 1.1 criteria. Results: A total of 38 pts were accrued between January 2014 and December 2015. One withdrew consent and 37 were included in the analysis, with a median follow-up of 18 months (range 5-31.5 months). The median patient age was 65 (range 35-81 years), 62% were men, and 51% and 22% had prostate and sarcoma as primary histologies, respectively. The majority of pts had 3 lesion sites (54% had 1 lesion, 22% had 2, and 16% had 3), and had recurrence sites at bone (57%) or lung (24%). The 6 mo FFLP rate was 78.4% (95% CI: 61.4-88.5%). Among the 68 treated lesions, the 6mo FFLP rate by lesion was 76.5% (95% CI: 64.584.9%). There were a total of 3 deaths due to disease progression. The 18 mo rates of OS, FFDM, and PFS were 90.7% (95% CI: 73.8-96.9), 62.4% (95% CI: 43.9-76.3), 57.6% (95% CI: 39.7-72.0), respectively. The 6 mo FFLP rate for patients with prostate cancer was 100% compared to 63% for patients with sarcoma (P < 0.0003). There were 4 grade 3 adverse events that may have been related to treatment (e.g., absolute lymphocyte decrease, anxiety, nausea, and cough). Conclusion: SBRT can be delivered safely with nelfinavir. Overall 6 mo FFLP rate for the entire cohort was not significantly higher than historical controls, although this may be secondary to tumor histology, treated site, and lesion number. Prostate cancer patients had significantly improved clinical outcomes relative to sarcoma patients and thus one may hypothesize that certain histologies may require a higher SBRT dose for local control. Further research should be conducted into the optimum patient cohort to benefit from the concurrent use of radiosensitizers with SBRT. Author Disclosure: S.A. Terezakis: Research Grant; Elekta. Honoraria; Elekta. Travel Expenses; Elekta; Red Journal. J. Herman: None. C. Hu: None. J. Yan: None. S. Di Pasquale: None. R. McIntyre: None. H. Kim: None. B.W. Loo: Research Grant; RaySearch, Varian Medical Systems Inc. Stock; TibaRay, Inc.; American College of Radiology, National Comprehensive Cancer Network, TibaRay, Inc. R.K. Hales: None. P.T. Tran: Research Grant; NIH-NCI, ACS, Kimmel Foundation, AstellasMedivation, American Lung Association, Movember-PCF, PCORI. Honoraria; Dendreon. Advisory Board; Astellas-Medivation, Dendreon. Travel Expenses; Dendreon. Patent/License Fees/Copyright; Compounds and Methods of Use in Ablative RT, Natsar Pharmaceuticals; RSNA R&E Foundation.
1115 Single-Arm Phase 2 Study of Stereotactic Body Radiation Therapy (SBRT) Concurrent with Nelfinavir for Solid Tumor Oligometastases S.A. Terezakis,1 J. Herman,2 C. Hu,3 J. Yan,4 S. Di Pasquale,5 R. McIntyre,5 H. Kim,5 B.W. Loo Jr6 R.K. Hales,7 and P.T. Tran5; 1Johns Hopkins Hospital, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, 2The University of Texas MD Anderson Cancer Center, Houston, TX, 3Johns Hopkins University School of Medicine, Division of Biostatistics and Bioinformatics, Baltimore, MD, 4 Johns Hopkins School of Medicine, Baltimore, MD, 5Johns Hopkins University School of Medicine, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, 6Stanford Cancer Institute, Stanford, CA, 7Department of Radiation Oncology and Molecular
1116 Outcomes and Characteristics of Patients Treated with Emergent Radiotherapy S.A. Dudley,1 S. Aggarwal,2 M.M. Grade,3 K.A. Kumar Jr4 B.E. Turner,5 Y. Liu,6 R. Von Eyben,6 D.T. Chang,7 and S.J. Knox2; 1Stanford Department of Radiation Oncology, Stanford, CA, 2Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, 3Stanford School of Medicine, Stanford, CA, 4Stanford University School of Medicine, Stanford, CA, 5Stanford School of Medicine, Stanford, CA, United States, 6Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 7Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA