M.S. Krishnan

Predicting Life Expectancy in Patients With Metastatic Cancer Receiving Palliative Radiotherapy: The TEACHH Model

Predicting life expectancy (LE) in patients with metastatic cancer who are receiving palliative therapies is a difficult task. The purpose of the current study was to develop a LE prediction model among patients receiving palliative radiotherapy (RT) that identifies those patients with short (< 3 months) and long (> 1 year) LEs.

Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

PURPOSE Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. METHODS AND MATERIALS At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Grays multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. RESULTS The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥ 11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. CONCLUSION In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥ 11 and SF RT were associated with a higher rate of SAEs.

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.

Postoperative radiation therapy for osseous metastasis: Outcomes and predictors of local failure

PURPOSE To evaluate patterns and predictors of local failure in patients undergoing postoperative radiation therapy (RT) for osseous metastases. METHODS AND MATERIALS Patients undergoing postoperative RT for bone metastases between June 2008 and January 2012 were retrospectively reviewed. Patterns of local failure were assessed, and Fine and Grays univariable and multivariable analyses (MVA) were used to evaluate factors associated with local progression, including dose intensity of RT (biological equivalent dose, BED, Gy10) and percent coverage of the surgical hardware by the RT fields. Additional predictors were similarly assessed, including patient (eg, age, performance status), disease (eg, tumor type, metastasis site), and treatment (eg, interval from surgery to RT) characteristics. RESULTS A total of 82 cases were followed for a median of 4.3 months (11.5 months among living patients) after treatment completion. Median BED was 39 Gy10 (range, 14-60), and RT fields covered an average of 71% (standard deviation, 26%) of the hardware. Fourteen cases (17%) experienced local progression. Although most (71%) failures occurred within the RT fields, 29% occurred marginally or out of field, but adjacent to surgical hardware. Increasing coverage of the surgical hardware by RT fields was associated with a reduced risk of local failure in MVA (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.012-0.82; P = .03), whereas a greater risk of failure was seen with increasing time between surgery and RT (HR, 1.03; 95% CI, 1.01-1.06; P = .01). Extremity rather than spinal site trended toward a greater risk of failure but did not reach significance (HR, 3.79; 95% CI, 0.96-14.89; P = .057). BED ≥39 Gy10 did not predict local failure (P = .51) in MVA. CONCLUSIONS Current strategies achieve good outcomes after postoperative RT for osseous metastases. Greater coverage of the surgical hardware with RT fields and avoiding delays between surgery and postoperative RT should be considered to reduce recurrence risk for patients with bone metastases requiring surgical stabilization.

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.

Radiation for Treatment of Painful Bone Metastases

Several variables may be considered when deciding on optimal modality of radiation therapy for each cancer patient with bone pain, including prognosis, tumor histology, location and extent of metastases, and association with cord compression. Hypofractionated external beam radiation therapy is as effective as a multiple fraction radiotherapy course in most cases, although retreatment rates are higher after a single dose of radiation. Stereotactic body radiation may be used in cases of oligometastatic disease, repeat irradiation, and radiation-resistant tumors. Radiopharmaceuticals may be used for pain from diffuse bone metastases and have an overall survival benefit in patients with castrate-resistant prostate cancer.

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.

Burden of palliative care issues encountered by radiation oncologists caring for patients with advanced cancer

PURPOSE Radiation oncologists frequently provide care for patients with advanced cancer who are in their last months or weeks of life. This study examined the previously not well-characterized types and frequencies of palliative care issues encountered in consultations for palliative radiation therapy (PRT). METHODS AND MATERIALS This prospective, survey-based study assessed consecutive consults for PRT from May 19, 2014, to September 26, 2014 at 3 Boston-area community and academic, hospital-based centers. Participating physicians and nurse practitioners completed a survey to identify and rank the relevance (5-point Likert scale, not at all to extremely) of palliative care issues. Eight domains adapted from national palliative care guidelines (physical symptoms, psychosocial issues, cultural considerations, spiritual needs, care coordination, advance care planning, goals of care, and ethical and legal issues) were evaluated. A total of 162 consecutive consultations were surveyed with 140 responses received (86% response rate). RESULTS Most (82%) consults had 2 or more palliative care domains ranked as highly (very or extremely) relevant to care. The domains of physical symptoms (91%), care coordination (70%), goals of care (59%), and psychosocial issues (52%) were the most commonly reported domains as highly relevant to care. Forty-six percent of consults involved a high palliative care burden (4 or more palliative care domains identified as highly relevant to care). Predictors of high palliative care burden in multivariable analysis were Eastern Cooperative Oncology Group performance status >2 (odds ratio, 3.57; P = .047), a plan for no further anticancer therapy after PRT (odds ratio, 3.46; P = .03), and a recommendation against PRT (odds ratio, 4.80; P = .01). CONCLUSIONS Radiation oncology clinicians encounter multiple palliative care issues when consulting on patients for PRT. Clinicians identified physical symptoms, care coordination, and goals of care as the most relevant palliative care domains. These findings can help guide palliative care development within radiation oncology, including education and structures of care delivery.

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.

Predicting life expectancy in patients with metastatic cancer receiving palliative radiotherapy

Predicting life expectancy (LE) in patients with metastatic cancer who are receiving palliative therapies is a difficult task. The purpose of the current study was to develop a LE prediction model among patients receiving palliative radiotherapy (RT) that identifies those patients with short (< 3 months) and long (> 1 year) LEs.