Durable Response to PD-1 Blockade in a Patient With Metastatic Pancreatic Undifferentiated Carcinoma With Osteoclast-Like Giant Cells.

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare and potentially aggressive variant of pancreatic ductal adenocarcinoma. Data on this disease are sparse, and despite genetic similarities to pancreatic ductal adenocarcinoma, UCOGC clinical outcomes can be markedly different. We report on a female patient aged 62 years who presented with UCOGC with pulmonary metastases initially treated with 2 lines of cytotoxic chemotherapy. After rapid disease progression with both cytotoxic treatments, the patient's tissue was sent for next-generation sequencing, which revealed a high tumor mutation burden (32 mutations per megabase), as well as somatic mutations in BRAF, NF1, PIK3CA, CDKN2A, TERT, and TP53. Pancreatic cancers have previously demonstrated suboptimal responses to immunotherapeutic approaches. However, given the high tumor mutation burden and distinctiveness of the tumor class, the patient began third-line pembrolizumab monotherapy after palliative radiation to the rapidly progressing and painful abdominal mass from her primary tumor. She had a marked response in her primary UCOGC tumor and metastatic sites, and she remains on pembrolizumab monotherapy with ongoing response after 32 months of therapy. Recent evidence showing significant PD-L1 enrichment on neoplastic cells of undifferentiated carcinomas (including UCOGC) may indicate a role for immunotherapeutic approaches in these patients. Rare cancers such as UCOGC and other undifferentiated carcinomas may benefit from next-generation sequencing to inform treatment decisions when standards of care are absent, as in this report.

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.

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.

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.

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.

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.

Assessing the utility of the spinal instability neoplastic score (SINS) to predict fracture after conventional radiation therapy (RT) for spinal metastases.

PURPOSE: Assessing the stability of spinal metastases is critical for making treatment decisions. The spinal instability neoplastic score (SINS) was developed by the Spine Oncology Study Group to categorize tumor-related lesions; however, data describing its utility in predicting fractures in patients with spinal metastases are limited. The purpose of this study is to assess the validity of SINS in predicting new or worsening fracture after radiation therapy (RT) to spine metastases. METHODS AND MATERIALS: This is a retrospective analysis of patients treated with conventional RT alone (median total dose, 30 Gy; range, 8-47 Gy; median number of fractions, 10; range, 1-25) for spinal metastasis at Dana-Farber/Brigham and Women's Cancer Center from 2006 to 2013. SINS was calculated for each lesion (range, 0-18). The primary endpoint was time from RT start to radiographically documented new or worsening fracture or last disease assessment. RESULTS: A total of 203 patients and 250 lesions were included in analysis. The percentages of lesions with SINS of 0 to 6, 7 to 12, and 13 to 18 were 38.8%, 54.8%, and 6.4%, respectively. Of 250 lesions, 20.4% developed new or worsening fractures; 14.4% for SINS 0 to 6, 21.2% for SINS 7 to 12, and 50.0% for SINS 13 to 18. Multivariate analysis adjusted for sex, age, Eastern Cooperative Oncology Group, histology, and total dose indicated that, compared with stable lesions (SINS 0-6), potentially unstable lesions (SINS 7-12) demonstrated a greater likelihood of new or worsening fracture that was not statistically significant (hazard ratio, 1.66; 95% confidence interval, 0.85-3.22; P = .14), and unstable lesions (SINS 13-18) were significantly more likely to develop to new or worsening fracture (hazard ratio, HR,4.37, 95% confidence interval, 1.80-10.61; P = .001). CONCLUSIONS: In this study of patients undergoing RT for spinal metastases, 20.4% developed new or worsening vertebral fractures. SINS is demonstrated to be a useful tool to assess fracture risk after RT.

Top 10 Tips Palliative Care Clinicians Should Know About Radiation Oncology.

As palliative care (PC) moves upstream in the course of advanced illness, it is critical that PC providers have a broad understanding of curative and palliative treatments for serious diseases. Possessing a working knowledge of radiation therapy (RT), one of the three pillars of cancer care, is crucial to PC providers given RT's role in both the curative and palliative settings. This article provides PC providers with a primer on the vocabulary of RT; the team of people involved in the planning of RT; and common indications, benefits, and side effects of treatment.

Assessing the utility of a prognostication model to predict 1-year mortality in patients undergoing radiation therapy for spinal metastases.

BACKGROUND CONTEXT: Predicting survival outcomes after radiation therapy (RT) alone for metastatic disease of the spine is a challenging task that is important to guiding treatment decisions (eg, determining dose fractionation and intensity). The New England Spinal Metastasis Score (NESMS) was recently introduced and validated in independent cohorts as a tool to predict 1-year survival following surgery for spinal metastases. This metric is composed of three factors: preoperative albumin, ambulatory status, and modified Bauer score, with the total score ranging from 0 to 3. PURPOSE: The purpose of this study was to assess the applicability of the NESMS model to predict 1-year survival among patients treated with RT alone for spinal metastases. STUDY DESIGN/SETTING: This study is a retrospective analysis. PATIENT SAMPLE: This sample included 290 patients who underwent conventional RT alone for spinal metastases. OUTCOME MEASURES: Patients' NESMS (composed of ambulatory status, pretreatment serum albumin, and modified Bauer score) were assessed, as well as their 1-year overall survival rates following radiation for metastatic disease of the spine. MATERIALS AND METHODS: This study is a single-institution retrospective analysis of 290 patients treated with conventional radiation alone for spinal metastases from 2008 to 2013. The predictive value of the NESMS was assessed using multivariable logistic regression modeling, adjusted for potential confounding variables. RESULTS: This analysis indicated that patients with lower NESMSs had higher rates of 1-year mortality. Multivariable analysis demonstrated a strong association between lower NESMSs and lower rates of survival. CONCLUSIONS: The NESMS is a simple prognostic scheme that requires clinical data that are often readily available and have been validated in independent cohorts of surgical patients. This study serves to validate the utility of the NESMS composite score to predict 1-year mortality in patients treated with radiation alone for spinal metastases.