Allison Taylor

Radiation and PD-1 inhibition: Favorable outcomes after brain-directed radiation

BACKGROUND AND PURPOSE Patients with metastatic melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are increasingly treated with immune checkpoint blockade targeting the programed death (PD)-1 receptor, often with palliative radiation therapy. Outcome data are limited in this population. MATERIAL AND METHODS We retrospectively reviewed consecutive patients with metastatic NSCLC, melanoma, and RCC who received radiation and anti-PD-1 therapy at four centers. RESULTS We identified 137 patients who received radiation and PD-1 inhibition. Median survival from first PD-1 therapy was 192, 394, and 121days for NSCLC, melanoma, and RCC patients. Among 59 patients who received radiation following the start of PD-1 blockade, 25 continued to receive PD-1 inhibition for a median of 179days and survived for a median of 238 additional days. Median survival following first course of radiation for brain metastases was 634days. Melanoma patients received brain directed radiation relatively less frequently following the start of PD-1 inhibitor treatment. CONCLUSIONS Incorporation of palliative radiation does not preclude favorable outcomes in patients treated with PD-1 inhibitors; patients irradiated after the start of PD-1 inhibition can remain on therapy and demonstrate prolonged survival. Of note, patients irradiated for brain metastases demonstrate favorable outcomes compared with historical controls.

Acute pain management in radiation oncology: Quality of care and the impact of an integrated palliative oncology service.

195 Background: Radiotherapy (RT) effectively palliates bone metastases, but relief may take weeks, frequently necessitating acute pain management (APM). NCCN Guidelines for Adult Cancer Pain (V2.2015) recommend initiation/titration of analgesics for patients with pain scale value (PSV) ≥ 4. We sought to evaluate how often symptomatic patients have analgesic regimens assessed and intervened upon at radiation oncology (RO) consult for bone metastases, and the impact of a dedicated palliative RO service on APM. METHODS We reviewed consult notes for 217 bone metastases patients treated with RT at Dana Farber Cancer Institute/Brigham & Womens Hospital (DFCI/BWH) and University of California, San Francisco (UCSF) during June-July 2008, Jan-Feb 2010, Jan-Feb 2013, and June-July 2014, time periods before and after implementation in 2011 of a dedicated palliative RO service at DFCI/BWH. For symptomatic patients, rate of assessment of analgesic regimen was recorded. Among patients with PSV ≥ 4, rate of pain intervention was recorded. The impact of a palliative RO service on these rates was evaluated. RESULTS Median age was 63 and median KPS was 70. Median PSV for painful bone metastases was 5 (IQR 2-7); 51% had PSV ≥ 4. Among symptomatic patients, analgesic regimen was assessed for 44.5% (51.7% at DFCI/BWH and 28.1% at UCSF). Among patients with PSV ≥ 4, pain intervention occurred for 17.2% (20.5% for DFCI/BWH, 0% for UCSF). At DFCI/BWH, consultation by a dedicated palliative RO provider was associated with higher rate of assessment of analgesic regimen (82.4% vs 47.7%, p = 0.007). At DFCI/BWH, consultation by a palliative RO provider was associated with higher rate of pain intervention (31.2% vs 7.9%, p = 0.012). There was no difference in analgesic regimen assessment or intervention between non-dedicated palliative RO providers at DFCI/BWH and UCSF (p = 0.07 and 0.09, respectively). CONCLUSIONS At two cancer centers, half of bone metastases patients seen for RT have PSV ≥ 4, yet a minority have analgesic assessment and intervention, indicating need for APM quality improvement in RO. An integrated palliative RO service was associated with improved assessment and management of acute pain per NCCN guidelines.

Impact of a dedicated palliative radiation oncology service on the use of single fraction and hypofractionated radiation therapy among patients with bone metastases

BACKGROUND Radiation therapy (RT) is frequently used to palliate symptomatic bone metastases. While high quality literature has shown that for uncomplicated bone metastases, shorter radiotherapy courses are just as effective as longer courses for the treatment of pain, shorter courses remain under-utilized. We aimed to assess the impact of a dedicated palliative radiation oncology service on the frequency of single fraction RT (SF-RT) and hypofractionated radiation (hypo-RT) (≤5 fractions) among patients with bone metastases. METHODS We identified 2,086 instances of palliative radiation (RT) for complicated and uncomplicated bone metastases between April 10, 2008 and September 17, 2014. We used multivariable logistic regression analysis (MVA) to estimate the association of the Supportive and Palliative Radiation Oncology (SPRO) service with the likelihood of receiving SF-RT or hypo-RT after controlling for age, sex, tumor type, and treatment site. RESULTS Prior to SPROs implementation on July 1, 2011, the proportion of SF-RT and hypo-RT for bone metastases was 6.4% and 27.6% respectively. After SPROs implementation, the proportion of SF-RT and hypo-RT increased to 22.3% (P<0.001) and 53.5% (P<0.001) respectively. In MVA, patients were more likely to receive SF-RT [odds ratio (OR) =3.3, 95% confidence interval (CI) =2.4-4.7, P<0.001], and hypo-RT (OR =2.5, 95% CI =2.0-3.1, P<0.001) after SPROs implementation. Compared to sites without a dedicated palliative service, patients receiving care at the SPRO affiliated department were more likely to receive SF-RT (OR =1.9, 95% CI =1.1-3.2, P=0.02) and hypo-RT (OR =1.5, 95% CI =1.1-2.0, P=0.004) for bone metastases. After SPROs implementation, the average number of RT courses delivered for bone metastases increased from 17.4 to 25.6 per month, (+8.3, 95% CI =4.99-11.55, P<0.001). Despite greater SF-RT and hypo-RT, the average total fractions per month of palliative RT for bone metastases increased from 163.5 pre-SPRO to 166.8 post-SPRO, though not significantly (+3.22, P=NS). CONCLUSIONS Implementation of a dedicated palliative radiation oncology service was associated with increased use of SF and hypo-RT and with greater courses of RT delivered for bone metastases.

Development and implementation of a clinical pathway for radiation of bone metastases on a palliative radiation oncology service.

170 Background: Clinical pathways increase compliance with treatment guidelines and reduce in-hospital complications. Evidence around treatment of complicated bone metastases is increasingly nuanced and although ASTRO/ACR recommend single fraction radiation therapy for uncomplicated bone metastases, implementation is variable. We sought to determine the effects of a bone metastases-focused clinical pathway on the practice patterns of our institutions palliative radiation oncology service (SPRO), which sees 600 patients yearly and on a rotating basis, involves 23 physicians, 28 residents, 2 nurse practitioners, and 1 fellow. We hypothesized that pathway implementation would augment data-driven use of palliative radiation for bone metastases, including use of 8 Gy x 1 for uncomplicated metastases. It would also enhance physician efficiency and confidence. METHODS Using published literature, clinical guidelines, and expert input, we designed a comprehensive clinical pathway for bone metastases radiation. This was translated to a secure electronic interface as a decision support tool and integrated into daily SPRO workflows. Providers were surveyed pre and post implementation to assess expectations and elicit feedback. Rates of pathway compliance and reasons for non-compliance were assessed. Rates of 8 Gy x 1 use for uncomplicated metastases were compared pre and post implementation. Our aim was for approximately 70-80% on-pathway rates. RESULTS The final pathway, which includes twenty endpoints, integrates several validated scoring systems, including assessments of life expectancy, spinal stability, and appropriateness of surgical management. The pathway has been well received on the SPRO service, with addition of extra steps to workflows being the main cause of resistance to use. Data on rates of pathway adherence will be reported, and rates of 8 Gy x 1 use will be compared to the baseline of 22%. CONCLUSIONS Our experience suggests the utility of pathways-based decision support for bone metastases radiation on a palliation consult service. Next steps include assessing the pathways effects on guideline-concordant care and calculating associated cost savings.