A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases.

Purpose: Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone because of its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Methods and Materials: In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at Brigham and Women's Hospital/Dana Farber Cancer Center and Beth Israel Deaconess Medical Center between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol mandated. Local progression-free survival, progression-free survival, prostatic specific antigen progression, and overall survival were reported. Treatment-related toxicity was also reported. Results: A total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume and higher dose to the gross tumor volume. Four patients (4.1%, 4/98) experienced local progression at 1 site for each patient (3.2%, 4/126). Among the entire cohort, 2-year local progression-free survival (including death without local progression) was 84.8%, 2-year progression-free survival (including deaths as well as local, distant, and prostatic specific antigen progression) was 47.5%, and 2-year overall survival was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. Conclusions: Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

Prognostication for Patients Receiving Palliative Radiation Therapy.

Estimation of patient prognosis plays a central role in guiding decision making for the palliative management of metastatic disease, and a number of statistical models have been developed to provide survival estimates for patients in this context. In this review, we discuss several well-validated survival prediction models for patients receiving palliative radiotherapy to sites outside of the brain. Key considerations include the type of statistical model, model performance measures and validation procedures, studies' source populations, time points used for prognostication, and details of model output. We then briefly discuss underutilization of these models, the role of decision support aids, and the need to incorporate patient preference in shared decision making for patients with metastatic disease who are candidates for palliative radiotherapy.

Prognostic Understanding and Goals of Palliative Radiotherapy: A Qualitative Study.

CONTEXT: There is a paucity of data describing patients' expectations of goals of palliative radiotherapy (RT) and overall prognosis. OBJECTIVES: To explore patients' perceptions of and preferences for communication surrounding goals of palliative RT and cancer prognosis. METHODS: We conducted a qualitative study utilizing semi-structured interviews with seventeen patients with either bone or lung metastases receiving their first course of palliative RT at a comprehensive cancer center. All patient interviews were recorded, transcribed verbatim, and thematically analyzed. RESULTS: Themes of goals of palliative RT centered on either restoration, such as through improving quality of life or minimizing pain, or on a desire to combat cancer by eliminating tumor. While most patients perceived that palliative RT would palliate symptoms but not cure their cancer, some patients believed that the goal of palliative RT was to cure. Themes that emerged surrounding patients' understanding of prognosis and what lies ahead included uncertainty and apprehension about the future, a focus on additional treatment, and confronting mortality. Most patients preferred to receive information about goals of treatment and prognosis from their doctors, including radiation oncologists, rather than other members of the medical team. Patients also expressed a desire for written patient education materials on palliative RT. CONCLUSION: Unclear perceptions of goals of treatment and prognosis may motivate some patients to pursue unnecessarily aggressive cancer treatments. Patients desire prognostic information from their doctors, including radiation oncologists, who are important contributors to goals of care discussions and may improve patient understanding and well-being by using restorative rather than combat-oriented language.

Longitudinal symptoms and temporal trends in palliative care, palliative radiotherapy, and anti-cancer treatment near end of life among patients with metastatic cancer.

BACKGROUND: Early specialty palliative care (PC) integration improves oncologic outcomes. We aimed to examine longitudinal relationships between specialty PC and palliative radiotherapy (RT), temporal distribution of symptoms, and predictors of earlier specialty PC. METHODS: We retrospectively reviewed 135 patients with metastatic cancer who received palliative RT at our institution (7/2017-2/2018) and who had died by final study follow-up (6/2021). Descriptive statistics summarized frequencies of clinical visits and symptoms over relative survival time (quartiles 1-3: first 75% of life remaining from metastatic diagnosis to death versus quartile 4: last 25% of life remaining from metastatic diagnosis to death). Logistic regression analyses revealed predictors of receiving earlier (quartiles 1-3) versus later (quartile 4) specialty PC. RESULTS: There were 16.3%, 10.4%, 26.7%, and 46.7% of palliative RT consultations, compared to 4.7%, 7.6%, 14.0%, and 73.7% of specialty PC visits, that occurred in quartiles 1, 2, 3, and 4, respectively. On multivariable analysis, pain significantly predicted for receiving earlier specialty PC [odds ratios (OR) =15.34; 95% confidence interval (CI): 2.16-324.23; P=0.020], while patients with ≥2 prior chemotherapy regimens were less likely to have received earlier specialty PC (OR =0.16; 95% CI: 0.04-0.58; P=0.009). The most common reasons for first specialty PC visit were addressing pain (61.0%) and goals of care (19.5%). Overall, 73.3% (99/135) of patients were referred to hospice and 9.6% (13/135) received either palliative RT, chemotherapy, or surgery within 30 days of death. CONCLUSIONS: Nearly 47% of palliative RT visits compared with 74% of specialty PC visits occurred in the last quarter of life from metastatic diagnosis to death. Multidisciplinary efforts are needed to manage longitudinal symptoms and offer goal-concordant care.

Characteristics and Predictors of Radiographic Local Failure in Patients With Spinal Metastases Treated With Palliative Conventional Radiation Therapy.

PURPOSE: Although local control is an important issue for longer-term survivors of spinal metastases treated with conventional external beam radiation therapy (EBRT), the literature on radiographic local failure (LF) in these patients is sparse. To inform clinical decision-making, we evaluated rates, consequences, and predictors of radiographic LF in patients with spinal metastases managed with palliative conventional EBRT alone. METHODS AND MATERIALS: We retrospectively reviewed 296 patients with spinal metastases who received palliative EBRT at a single institution (2006-2013). Radiographic LF was defined as radiologic progression within the treatment field, with death considered a competing risk. Kaplan-Meier, cumulative incidence, and Cox regression analyses determined overall survival estimates, LF rates, and predictors of LF, respectively. RESULTS: There were 182 patients with follow-up computed tomography or magnetic resonance imaging; median overall survival for these patients was 7.7 months. Patients received a median of 30 Gy in 10 fractions to a median of 4 vertebral bodies. Overall, 74 of 182 patients (40.7%) experienced LF. The 6-, 12-, and 18-month LF rates were 26.5%, 33.1%, and 36.5%, respectively, while corresponding rates of death were 24.3%, 38.1%, and 45.9%. Median time to LF was 3.8 months. Of those with LF, 51.4% had new compression fractures, 39.2% were admitted for pain control, and 35.1% received reirradiation; median time from radiation therapy (RT) to each of these events was 3.0, 5.7, and 9.2 months, respectively. Independent predictors of LF included single-fraction RT (8 Gy) (hazard ratio [HR], 2.592; 95% confidence interval [CI], 1.437-4.675; P = .002), lung histology (HR, 3.568; 95% CI, 1.532-8.309; P = .003), and kidney histology (HR, 4.937; 95% CI, 1.529-15.935; P = .008). CONCLUSIONS: Patients experienced a >30% rate of radiographic LF by 1 year after EBRT. Single-fraction RT and lung or kidney histology predicted LF. Given the high rates of LF for patients with favorable prognosis, assessing the risk of death versus LF is important for clinical decision-making.

A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer.

PURPOSE: Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC. METHODS AND MATERIALS: Eligible patients had stage II or III TNBC. Cisplatin was initiated at 10 mg/m2 intravenously once weekly during radiation and then escalated in a 3 + 3 design by 10 mg/m2 at each dose level until 40 mg/m2, or the MTD, was reached. Patients undergoing breast-conserving therapy (BCT) or mastectomy were accrued in separate parallel cohorts during dose escalation, followed by a 10-patient expansion at the MTD. RESULTS: During 2013 to 2018, 55 patients were accrued. Four patients developed dose-limiting toxicity. In the BCT cohort, 1 patient receiving 40 mg/m2 developed tinnitus resulting in a cisplatin delay; therefore, this was the BCT cohort MTD. In the mastectomy cohort, 1 patient receiving 20 mg/m2 developed a grade 3 urinary infection, and 2 additional patients had dose-limiting toxicities at 40 mg/m2 (grade 3 neutropenia and grade 2 tinnitus), both resulting in cisplatin delay. Thus, 30 mg/m2 was the mastectomy cohort MTD. Median follow-up was 48.5 months. Three-year disease-free survival was 74.7% for the BCT cohort and 64.4% for the mastectomy cohort. CONCLUSIONS: Adjuvant radiation therapy with concurrent cisplatin is feasible with a recommended phase 2 dose of 30 mg/m2 and 40 mg/m2 intravenously weekly in mastectomy and BCT cohorts, respectively.

Does hysteroscopic resection of uterine septum improve reproductive outcomes: a systematic review and meta-analysis.

PURPOSE: Uterine septum in women with subfertility or previous poor reproductive outcomes presents a clinical dilemma. Hysteroscopic septum resection has been previously associated with adverse reproductive outcomes but the evidence remains inconclusive. We aimed to thoroughly and systematically appraise relevant evidence on the impact of hysteroscopically resecting the uterine septum on this cohort of women. METHODS: AMED, BNI, CINAHL, EMBASE, EMCARE, Medline, PsychInfo, PubMed, Cochrane register of controlled trials, Cochrane database of systematic reviews and CINAHL were assessed to April 2020, with no language restriction. Only randomised control trials and comparative studies which evaluated outcomes in women with uterine septum and a history of subfertility and/or poor reproductive outcomes treated by hysteroscopic septum resection against control were included. The primary endpoint was live birth rate, whereas clinical pregnancy, miscarriage, preterm birth and malpresentation rates were secondary outcomes. RESULTS: Seven studies involving 407 women with hysteroscopic septum resection and 252 with conservative management were included in the meta-analysis. Hysteroscopic septum resection was associated with a lower rate of miscarriage (OR 0.25, 95% CI 0.07-0.88) compared with untreated women. No significant effect was seen on live birth, clinical pregnancy rate or preterm delivery. However, there were fewer malpresentations during labour in the treated group (OR 0.22, 95% CI 0.06-0.73). CONCLUSION: Our review found no significant effect of hysteroscopic resection on live birth. However, given the limited evidence available, high-quality randomised controlled trials are recommended before any conclusive clinical guidance can be drawn.

Patient-Provider Communication, Decision-Making, and Psychosocial Burdens in Palliative Radiotherapy: A Qualitative Study on Patients' Perspectives.

CONTEXT: Patient-provider communication impacts how patients with cancer make decisions about treatment. OBJECTIVES: To examine patient perceptions of discussions, decision-making, and psychosocial burdens related to receiving palliative radiotherapy (RT), in order to inform best practices for communication about palliative RT. METHODS: We conducted an exploratory qualitative study using oral questionnaires and semi-structured interviews. Seventeen patients receiving their first course of palliative RT for lung or bone metastases at a comprehensive cancer center were interviewed. Patient interviews were transcribed verbatim and thematically analyzed using NVivo software. RESULTS: Themes that impacted patients' decisions to initiate RT included a desire to minimize pain, optimism about what RT could provide for the future, perception of having "no other choice," disappointment about cancer progression, and unfamiliarity with RT. Most patients preferred shared decision-making regarding RT initiation and reported patient empowerment, effective communication, and team collaboration as contributing to shared decision-making. Most patients preferred their physicians to make decisions about RT treatment intensity and described trust in their physicians, institutional reputation, and RT expertise as motivators for this preference. Patients who possessed a proactive decisional mindset about initiating RT as opposed to having "no other choice" were less likely to report experiencing psychosocial burdens. CONCLUSION: Most patients prefer shared decision-making regarding RT initiation but prefer their radiation oncologists to make decisions regarding treatment intensity. Communication that empowers patients in their desired level of engagement for RT decision-making may help patients make informed decisions, contribute toward a proactive decisional mindset, and reduce their perception of psychosocial burdens.

Patterns of Specialty Palliative Care Utilization Among Patients Receiving Palliative Radiation Therapy.

CONTEXT: Palliative radiation therapy (RT) is frequently used to ameliorate cancer-associated symptoms and improve quality of life. OBJECTIVES: To examine how palliative care (PC) as a specialty is integrated at the time of RT consultation for patients with advanced cancer. METHODS: We retrospectively reviewed 162 patients with metastatic cancer who received palliative RT at our institution (7/2017-2/2018). Fisher's exact test identified differences in incidence of receiving any specialty PC. Logistic regression analyses determined predictors of receiving PC. RESULTS: Of the 74 patients (46%) who received any specialty PC, 24 (32%) initiated PC within four weeks of RT consultation. The most common reasons for specialty PC initiation were pain (64%) and goals of care/end-of-life care management (23%). Referrals to specialty PC were made by inpatient care teams (48.6%), medical oncologists (48.6%), radiation oncologists (1.4%), and self-referring patients (1.4%). Patients with pain at RT consultation had a higher incidence of receiving specialty PC (58.7% vs. 37.4%, P = 0.0097). There was a trend toward decreased PC among patients presenting with neurological symptoms (34.8% vs. 50%, P = 0.084). On multivariable analysis, receiving specialty PC significantly differed by race (non-white vs. white, odds ratio [OR] = 6.295 [95% CI 1.951-20.313], P = 0.002), cancer type (lung vs. other histology, OR = 0.174 [95% CI 0.071-0.426], P = 0.0006), and RT consultation setting (inpatient vs. outpatient, OR = 3.453 [95% CI 1.427-8.361], P = 0.006). CONCLUSION: Fewer than half of patients receiving palliative RT utilized specialty PC. Initiatives are needed to increase PC, especially for patients with lung cancer and neurological symptoms, and to empower radiation oncologists to refer patients to specialty PC.

Quantitative-qualitative analyses of patient-reported pain response after palliative radiation therapy.

PURPOSE: While the 0-10 pain scale is often used to assess treatment response, it may not accurately reflect change in pain over time. The purpose of this study is to correlate pain improvement using the 0-10 pain scale to patients' perceived improvement in pain following palliative radiation therapy (RT), and to qualitatively characterize themes of pain assessment. METHODS: Patients age ≥ 20 receiving RT for spinal metastases were enrolled. Patients rated their pain (0-10) at the treatment site at RT start, and 1 and 4 weeks post-RT completion. At 1 and 4 weeks post-RT, patients reported their perceived percent improvement in pain (pPIP) (0-100%), which was compared to calculated percent improvement in pain (cPIP) based on the 0-10 pain scores. At 4 weeks post-RT, 20 randomly selected patients participated in a qualitative pain assessment. RESULTS: Sixty-four patients treated at 1-2 sites were analyzed. At 1 week post-RT completion, 53.7% (36/67) reported pPIP within 10 percentage points of cPIP, 32.8% (22/67) reported pPIP > 10 percentage points higher than cPIP, and 13.4% (9/67) reported pPIP > 10 percentage points lower than cPIP. Similar degrees of discordance were seen at 4 weeks post-RT. Qualitative analysis revealed five themes: pain quality (n = 19), activities (n = 9), function (n = 7), medication use (n = 2), and radiation side effects (n = 1). CONCLUSIONS: About half of patients reported a pPIP substantially disparate from their cPIP, and the change in pain measured by the 0-10 scale tended to underestimate the degree of perceived pain improvement. Multiple themes were identified in qualitative analysis of pain response.

Inter-rater reliability in performance status assessment among healthcare professionals: an updated systematic review and meta-analysis.

INTRODUCTION: Survival prediction for patients with incurable malignancies is invaluable information during end-of-life discussions, as it helps the healthcare team to appropriately recommend treatment options and consider hospice enrolment. Assessment of performance status may differ between different healthcare professionals (HCPs), which could have implications in predicting prognosis. The aim of this systematic review and meta-analysis is to update a prior systematic review with recent articles, as well as conduct a meta-analysis to quantitatively compare performance status scores. METHODS: A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, from the earliest date until the first week of August 2019. Studies were included if they reported on (1) Karnofsky Performance Status (KPS), Eastern Cooperative Oncology Group (ECOG) Performance Status, and/or Palliative Performance Scale (PPS) and (2) assessment of performance status by multiple HCPs for the same patient sets. The concordance statistics (Kappa, Krippendorff's alpha, Kendall correlation, Spearman rank correlation, Pearson correlation) were extracted into a summary table for narrative review, and Pearson correlation coefficients were calculated for each study and meta-analyzed with a random effects analysis model. Analyses were conducted using Comprehensive Meta-Analysis (Version 3) by Biostat. RESULTS: Fourteen articles were included, with a cumulative sample size of 2808 patients. The Pearson correlation coefficient was 0.787 (95% CI: 0.661, 0.870) for KPS, 0.749 (95% CI: 0.716, 0.779) for PPS, and 0.705 (95% CI: 0.536, 0.819) for ECOG. Four studies compared different tools head-to-head; KPS was favored in three studies. The quality of evidence was moderate, as determined by the GRADE tool. CONCLUSIONS: The meta-analysis's Pearson correlation coefficient ranged from 0.705 to 0.787; there is notable correlation of performance status scores, with no one tool statistically superior to others. KPS is, however, descriptively better and favored in head-to-head trials. Future studies could now examine the accuracy of KPS assessment in prognostication and focus on model-building around KPS.

Correction to: Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

The appendices were incorrectly numbered in the original article. Please see below correcct appendices.

Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

INTRODUCTION: Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time. METHODS: A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality. RESULTS: An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots. CONCLUSIONS: The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades.

Ethical issues in patients referred for palliative radiation therapy.

BACKGROUND: As patients with advanced cancer approach end of life, ethical issues may arise. We describe ethical issues encountered by radiation oncologists in this setting. METHODS: A prospective, survey-based study assessed 162 consecutive consults for palliative radiation therapy (PRT) over 4 months at 3 hospitals. Consulting radiation clinicians completed a survey assessing palliative care issues encountered, based on national guidelines. Ethical issues included 5 subthemes (conflict between clinicians, caregiver-clinician conflict, internal conflict, feeling unable to do what was best for the patient, and violation of personal morals), an option for unclassified issues, and open-ended responses. Multivariate analyses (MVA) assessed potential patient-related predictors of ethical issues: gender, performance status (PS), PRT indication, physical symptoms, and presence of psychosocial, goals of care, care coordination, cultural, or spiritual issues. RESULTS: Of 162 surveys, 140 were completed (response rate =86%). Overall, 14 (10%) surveys identified ethical issues relevant to care; 11 of 14 (78%) identified more than 1 ethical issue. Half (7; 50%) involved conflict between clinicians and clinician-caregiver conflict; 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=6, 43%), and conflict related to coordination of care among clinicians (n=3, 21%). On UVA, ethical issues were associated with PRT referrals for bleeding, dyspnea, or dysphagia due to visceral metastases (30%) versus CNS indications such as brain metastases or cord compression (7%) or for bony metastases (4%) P<0.001. On MVA, ethical issues were associated with 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=0.04). CONCLUSIONS: At least 1 in 10 referrals for PRT involve ethical issues. Further studies are warranted to assess the ability of radiation oncologists to manage ethical issues.

Efficiency of using a vaginal drain after hysterectomy: A systematic review.

Objective Hysterectomy is the second most frequently performed surgical procedure for women of reproductive age topped only by caesarean section. Hysterectomies may be associated with a significant risk of ultrasonographically detected vault haematomas in up to 59% with consequent postoperative morbidity. The aim of this systematic review was to compare women who had a vaginal drain placed intraoperatively after a hysterectomy and the impact on peri and postoperative outcomes related to vault haematomas. Study Design Electronic searches of AMED, BNI, CINAHL, EMBASE, HBE, HMIC, Medline, PsycINFO and PubMed, Cochrane register of controlled trials (CCTR), Cochrane database of systematic reviews (CDSR) CINAHL and Google scholar were performed. A systematic review and meta-analysis of studies comparing women with and without a vaginal drain after a hysterectomy and the impact on different outcomes was carried out. Results Ten studies involving 1778 women, 811 with a vaginal drain and 967 without a drain, were included in the meta-analysis. This suggests that the use of a vaginal drain after hysterectomy may significantly reduce the incidence of vault haematoma (OR 0.22, 95% CI 0.08 - 0.57) and febrile morbidity (OR 0.54, 95% CI 0.40 to 0.73), non- significantly reduce the rate of usage of antibiotics (OR 0.80, 95% CI 0.46-1.42) and makes no difference to the length of hospital stay (MD 0.12, 95% CI -0.14 to 0.38). Conclusion The use of a vaginal drain after hysterectomy could reduce the incidence of vault haematoma and febrile morbidity.

Palliative Radiation Therapy for Vertebral Metastases and Metastatic Cord Compression in Patients Treated With Anti-PD-1 Therapy.

Background: There is increasing use of immune checkpoint blockade (ICB) across multiple cancer types, including in patients at risk for vertebral metastases and cord compression. These patients are often treated with palliative radiotherapy (PRT); however, data evaluating the combination of PRT and ICB in patients with vertebral metastases is limited. Furthermore, patients with cord compression are generally excluded from prospective clinical trials. Therefore, we retrospectively evaluated outcomes following PRT and PD-1 inhibition in patients with vertebral metastases. Methods: We performed a retrospective chart review of 37 consecutive patients (total 57 lesions) treated with radiation for vertebral metastases who also received PD-1 inhibition. Patient, treatment and outcomes data were abstracted from the medical records. Results: Histologies included non-small cell lung cancer (n = 21), renal cell carcinoma (n = 9) and melanoma (n = 7). Out of 57 lesions,18 involved >1 segments of the vertebral column. There were isolated lesions in thoracic (16), lumbar (9), cervical (6), and sacral (8) vertebrae. Presenting symptoms included pain (19), numbness (10), and weakness (3). Eleven patients were asymptomatic. Radiologic cord compression was present in 12, epidural extension in 28 and compression fracture in 14. Eleven patients underwent surgical decompression prior to the onset of RT. Median radiation dose was 24 Gy (range 8-30 Gy). Stereotactic radiation was delivered in 4 patients; 33 patients received conformal RT. 21 patients received PD-1 inhibition after RT, 9 before RT and 7 with RT. Seven patients received concurrent CTLA-4 inhibitors with anti-PD-1 therapy. Treatment was in general well-tolerated. Toxicities included fatigue (6), transient pain flare (1), nausea/vomiting (1) and G1 skin changes (1). All patients reported some degree of pain relief. Numbness/weakness was improved in 6 of 13 patients with baseline symptoms (46%) and this was more likely in patients that received vertebral radiation after starting PD-1 inhibitors (71 vs. 17%, p = 0.04). Most patients (22 of 33 evaluable patients, 67%) had stability of irradiated lesions on subsequent follow up imaging performed at median of 30 days from RT, whereas 3 had a complete local response and 4 had a partial local response. Conclusions: We demonstrate that PRT administered to vertebral metastases was well-tolerated and effective in patients treated with PD-1 inhibitors. There was an encouraging rate of pain reduction and neurological improvement.

The Impact of Radiation Therapy on Lymphocyte Count and Survival in Metastatic Cancer Patients Receiving PD-1 Immune Checkpoint Inhibitors.

PURPOSE: Therapeutic radiation has conflicting immune effects: radiation therapy (RT)-induced immunogenic cell death can contribute to immune response, but lymphocytes are also sensitive to RT. It is unknown whether palliative RT leads to lymphopenia in patients treated with immune checkpoint inhibitors (ICIs) and whether this affects outcomes. As such, we sought to assess the impact of palliative RT on circulating lymphocyte count and neutrophil-to-lymphocyte ratio in patients being treated with PD-1-directed ICI and associations with survival. METHODS AND MATERIALS: We identified patients from 5 radiation oncology centers, treated with palliative RT and either pembrolizumab or nivolumab with non-small cell lung cancer, metastatic melanoma, and renal cell carcinoma. Patients who received intervening cytotoxic chemotherapy were excluded. We recorded absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio before and after palliative RT and at the start of ICI. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: One hundred ten patients received 225 courses of palliative RT. Median change in ALC after RT was -161 cells/mL. Decreases in ALC were greater with RT to the spine, lung/mediastinum, and chest wall compared with the brain, extremity, or abdomen/pelvis (P = .002) and after courses >5 fractions (P = .003). Extracranial and >5-fraction RT was associated with increased odds of severe lymphopenia (ALC <500) at the end of RT (odds ratio [OR], 3.7; P = .001; and OR, 3.9; P = .001, respectively). Patients who developed RT-induced severe lymphopenia were more likely to have severe lymphopenia when ICI was initiated (OR, 6.4; P = .0001), particularly when RT was administered in the previous 3 months (OR, 189; P < .0001). Severe lymphopenia at onset of ICI therapy was associated with increased mortality on multivariable analysis (hazard ratio, 2.1; P = .03). CONCLUSIONS: Extracranial or prolonged courses of RT increase the risk of severe lymphopenia, which is associated with poorer survival in patients treated with ICI.

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 clinical pathway tool on appropriate palliative radiation therapy for bone metastases.

PURPOSE: Clinical pathways increase compliance with treatment guidelines, improve outcomes, and reduce costs. Guidelines recommend single fraction radiation therapy (SFRT) for palliation of uncomplicated bone metastases, but implementation is variable. We examined the effects of a pathway tool on SFRT rates in an academic radiation oncology practice. METHODS AND MATERIALS: Using published literature, clinical guidelines, and expert input, we designed a clinical pathway for bone metastases radiation therapy displayed on a Web-based electronic interface. In March 2016, the pathway launched on a palliative radiation service at the Dana Farber/Brigham and Women's Cancer Center main campus and at affiliated community sites. Providers were surveyed pre- and postimplementation to assess expectations and elicit feedback. Rates of pathway utilization, compliance with SFRT recommendations, and reasons for noncompliance were assessed. RESULTS: The final pathway includes 20 endpoints and several validated prognostic scoring systems. It was used in 38% of 723 bone metastases radiation prescriptions, with appropriate SFRT rates rising from 18% before implementation to 48% after launch (P < .01). Major reasons for rejecting recommendations included disagreement with life expectancy prognostication and patient convenience. The pathway increased physicians' confidence regarding compliance with treatment guidelines and made it easier to find well-supported treatment recommendations. Workflow disruptions and the inability to handle nuanced situations emerged as limitations. CONCLUSIONS: Our experience demonstrates the utility of clinical pathway decision support for bone metastases radiation in complex academic settings. Next steps include increasing the pathway's ease of use, refining the pathway's prognostic abilities, and measuring cost savings related to the pathway.