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Objectives Appropriate chemotherapy and radiation near end of life is a moving target; challenged by increasing costs, evolving therapies, new reimbursement models and quality metrics. We review treatment trends and variables impacting the initiation of chemotherapy (CHT) and radiotherapy (XRT) in the final 60, 30 and 14 days of life in metastatic non-small cell lung cancer (NSCLC). Methods The Florida Cancer Data System was studied to complete a retrospective cohort analysis of 48,858 individuals with Stage IV (M1) NSCLC from 1995–2010. We evaluated the initiation of CHT and XRT after diagnosis and associations with patient demographics, insurance and socioeconomic status (SES). Results The use of CHT increased from 35% to 49%, while XRT decreased from 52% to 37% between 1995 and 2010. Initial courses of CHT occurred 8.1%, 5.0%, and 3.6% in the final 60, 30, and 14 days of life, and XRT 13.8%, 7.7%, and 5.2% of the time, respectively. Younger, married, and male patients were more likely to receive treatment. Low SES (OR 0.685, 95% CI 0.633–0.741) and uninsured individuals (OR 0.678, 95% CI 0.572–0.804) were less likely to receive CHT. SES and insurance did not impact XRT. Conclusions The initiation of late CHT and XRT treatments decreased from 1995–2010. It persisted above 3% in the last 14 days of life. Clinicians may struggle to taper treatment before death, especially in patients with limited survival. It is important to recognize the complexities of death and dying and the potential influences of palliative care in affecting treatment decisions.

To investigate the determinants of radiation therapy refusal in pediatric cancer, we used the Surveillance, Epidemiology, and End Results registry to identify 24,421 patients who met the eligibility criteria, diagnosed between 1974 and 2012. Patients had any stage of cancer, were aged 0 to 19, and received radiation therapy or refused radiation therapy when it was recommended. One hundred twenty-eight patients (0.52%) refused radiation therapy when it was recommended. Thirty-two percent of patients who refused radiation therapy ultimately died from their cancer, at a median of 7 months after diagnosis (95% confidence interval, 3-11 mo), as compared with 29.0% of patients who did not refuse radiation therapy died from their cancer, at a median of 17 months after diagnosis (95% confidence interval, 17-18 mo). On multivariable analysis, central nervous system (CNS) site, education, and race were associated with radiation refusal. The odds ratio for radiation refusal for patients with CNS disease was 1.62 (P=0.009) as compared with patients without CNS disease. For patients living in a county with ≥10% residents having less than ninth grade education, the odds ratio for radiation refusal was 1.71 (P=0.008) as compared with patients living in a county with

We hypothesized that sorafenib (BAY 43-9006), an oral multi-kinase inhibitor, used in combination with SRS will improve overall intracranial control. This Phase I study assesses the safety, tolerability, and maximal tolerated dose of sorafenib administered with SRS to treat 1-4 brain metastases. This was an open label phase I dose escalation study with an expansion cohort. Eligible adults had 1-4 brain metastases from solid malignancies. Sorafenib was begun 5-7 days prior to SRS and continued for 14 days thereafter. Dose escalation of sorafenib was conducted via a "3 + 3" dose escalation design. Dose limiting toxicities (DLT) were determined 1 month after SRS and defined as ≥grade 3 neurologic toxicities. Twenty-three patients were enrolled. There were no DLTs at dose level 1 (400 mg per day) or dose level 2 (400 mg twice per day). An expansion cohort of 17 patients was treated at dose level 2. There were six grade 3 toxicities: hypertension (n = 2), rash (n = 1), lymphopenia (n = 1), hypokalemia (n = 1), fatigue (n = 1) and hand-foot syndrome (n = 1). All of these were attributable to sorafenib and not to the combination with SRS. The median time to CNS progression was 10 months, 1 year CNS progression-free survival was 46%, the median overall survival was 11.6 months and the 1 year overall survival was 46%. The use of sorafenib concurrent with SRS for the treatment of 1-4 brain metastases is safe and well tolerated at 400 mg twice a day. Our recommended phase II dose of concurrent sorafenib with SRS would be 400 mg twice daily.

Introduction Local control, either with surgery, radiation (RT) or both, is essential in the management of localised Ewing sarcoma; however, the relative role of RT remains controversial. Methods Using the Surveillance, Epidemiology, and End Results database, 612 patients treated for non-metastatic skeletal Ewing sarcoma between the years 1988 and 2010 were identified. Results Median age and follow-up were 13 years (range: 0–21) and 56 months (range: 0–287), respectively. Five-year overall survival (OS) for the cohort was 74.4 ± 2.0%. Patients received surgery alone (51.3%), RT alone (21.6%) or both (27.1%). Patients with skeletal Ewing sarcoma had improved OS with surgery alone compared with other treatments. However, in subset analyses, RT was not inferior to surgery alone for appendicular (5-year OS: 80.0% vs. 79.3%), non-pelvic (84.3% vs. 79.9%) or localised disease (confined to cortex or periosteum; 79.7% vs. 80.6%). After controlling for stage and site, no increase in mortality was observed with RT versus surgery alone (hazard ratio = 0.77 (95% confidence interval: 0.49–1.19)). Conclusions In regard to survival, RT did not appear to be inferior to surgery alone for most patients, particularly those with disease at favourable sites (localised, appendicular, non-pelvic). In select patients with Ewing sarcoma, RT may be an appropriate strategy for local control that does not necessarily compromise survival outcomes.

Purpose The optimal treatment strategy following local recurrence after stereotactic radiosurgery (SRS) remains unclear. While upfront SRS has been extensively studied, few reports focus on outcomes after retreatment. Here, we report the results following a second course of SRS for local recurrence of brain metastases previously treated with SRS. Methods Using institutional database, patients who received salvage SRS (SRS2) following in-field failure of initial SRS (SRS1) for brain metastases were identified. Radionecrosis and local failure were defined radiographically by MRI following SRS2. The primary endpoint was defined as the time from SRS2 to the date of all-cause death or last follow-up [overall survival (OS)]. The secondary endpoints included local failure-free survival (LFFS) and radionecrosis-free survival, defined as the time from SRS2 to the date of local failure or radionecrosis, or last follow-up, respectively. Results Twenty-eight patients with 32 brain metastases were evaluated between years 2004 and 2015. The median interval between SRS1 and SRS2 was 9.7 months. Median OS was 22.0 months. Median LFFS time after SRS2 was 13.6 months. The overall local control rate following SRS2 was 84.4%. The 1- and 2-year local control rates are 88.3% (95% CI, 76.7–100%) and 80.3% (95% CI, 63.5–100%), respectively. The overall rate of radionecrosis following SRS2 was 18.8%. On univariate analysis, higher prescribed isodose line (p = 0.033) and higher gross tumor volume (p = 0.015) at SRS1 were associated with radionecrosis. Although not statistically significant, there was a trend toward lower risk of radionecrosis with interval surgical resection, fractionated SRS, lower total EQD2 (

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p

The development of brain metastases is a common cause of morbidity and mortality in cancer patients. Limited life expectancy is well established once a patient requires whole-brain radiotherapy (WBRT). There is emerging evidence demonstrating the value of involving palliative care services alongside traditional treatments. However, data regarding the utilization of these services in patients requiring WBRT remain unexplored.Patients with histologic or radiographic evidence of brain metastases treated with WBRT alone between July 2010 and June 2012 were reviewed retrospectively. Patient demographics, the number of hospital admissions in the last 6 months of life, survival, and referrals to palliative care services were evaluated.Ninety-eight patients were diagnosed with brain metastases and treated with WBRT alone. The median overall survival following WBRT was 80 days. Twenty-eight of the patients presented to the emergency department ≥2 times in the last 6 months of life. Sixty-eight percent of patients were referred to palliative care. Of those referrals, 57% were during an inpatient hospitalization. The median survival from palliative care referral to death was 27 days.Patients with brain metastasis requiring WBRT have a predictable dying trajectory. These patients are likely to have a high symptom burden and would benefit from palliative care. Timely palliative care referrals in this population remain inadequate and classically follow a hospital admission. Referrals continued to be late in the dying process and the recommendation for WBRT can be used as an independent marker for initiating end-of-life discussions and involving palliative care.

A growing body of evidence supports the integration of palliative care with standard cancer treatments. In these situations, patients often experience a better quality of life, better quality of care, decreased cost, and, in some cases, improved survival with the addition of palliative care services to traditional treatment pathways. In this manuscript, we explore the integration of radiation oncology at palliative care. First, we discuss the impetus for change at Vanderbilt University and the inception of Vanderbilt's inpatient Palliative Radiation Oncology Service at Vanderbilt. Second, we discuss the growth of palliative care and how this invites innovative collaborative care delivery models. As you will see, this mutually beneficial relationship expands new service lines, brings radiation oncology interventions and expertise to more patients seen by palliative care specialists, and improves overall care for some of the sickest, most vulnerable patients in the health care system. As we move away from fee-for-service and toward bundled and global-based strategies, there will be further emphasis on supportive and palliative care services at the end of life. Understanding how radiation oncology can evolve is ever more relevant.

Increased use of the multimodality head and neck cancer (HNC) therapy has led to improvement in the local control, larynx preservation, and overall survival rates, leaving many HNC patients at risk for developing acute and late effects from treatment. The acute and late effects have resulted in substantial symptom burden and functional deficits in HNC population. The symptom control and functional issues associated with HNC and its aggressive treatment are complex, evolve over time, persist long term, and require frequent and ongoing assessment. In recent years, research efforts have focused on better understanding the supportive care needs in HNC patients across the trajectory of the disease treatment and recovery and developing new interventions to improve HNC patients’ overall quality of life. The aim of this chapter is to review symptom control issues in HNC, emphasizing areas in which interventions are feasible and have demonstrated improvement in patients’ outcome. Due to space limit, this chapter particularly focuses on the following areas: (1) nutrition and swallow function, (2) oral health, (3) acute and late musculoskeletal impairment (MSI), and (4) systemic effects.

Objective To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS). Study design Retrospective chart review. Setting Tertiary academic referral center. Patients Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18 months of post-treatment follow up (FU). Intervention Patients were treated with either single fraction or fractionated SRS. Main outcome measure Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression. Results Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55 years (range 35–79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15–18 Gy), and 9 (64.3%) fractionated therapy (dose 3–7 Gy × 3–15 fractions). Median tumor volume was 3.78 cm 3 (range 1.15–30.6). Median FU was 28.8 months (range 18.6–56.1), with a mean of 31.7 months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p = 0.88) or progression (p = 0.48) rates between groups (unpaired t-test). Conclusions At a median follow up of 28 months, both single fraction and fractionated SRS appear to have comparable radiographic tumor control outcomes and toxicity profiles.

The treatment design and delivery of radiation for esophageal cancer require a comprehensive understanding of the natural history of disease, patterns of failure, anatomy, and principles of radiobiology. The use of pretreatment imaging, such as computerized axial tomography (CT) scans, endoscopic ultrasonography, and positron emission tomography (PET) scans, has improved target delineation. State-of-the-art equipment and advances in radiation planning software may improve treatment-related toxicities by allowing increasing dose to tumor while minimizing dose to surrounding normal structures.

Optimal treatment of rhabdomyosarcoma (RMS) requires multidisciplinary approach, incorporating chemotherapy with local control. Although current therapies are built on cooperative group trials, a comprehensive standard of care to guide clinical decision making has been lacking, especially for relapsed patients. Therefore, we assembled a panel of pediatric and adolescent and young adult sarcoma experts to develop treatment guidelines for managing RMS and to identify areas in which further research is needed. We created algorithms incorporating evidence-based care for patients with RMS, emphasizing the importance of clinical trials and close integration of all specialties involved in the care of these patients.

Objective To date, the majority of the vestibular schwannoma (VS) literature has focused on tumor control rates, facial nerve function and hearing preservation. Other factors that have been shown to significantly affect quality-of-life (QOL), such as dizziness, remain understudied. The primary objective of the current study is to investigate the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported dizziness handicap. Materials and methods This is a prospective observational pilot study at a tertiary academic referral center including all subjects that underwent linear accelerator-based stereotactic radiotherapy (SRS) for sporadic VS and completed pre-treatment and post-treatment vestibular testing and Dizziness Handicap Inventory (DHI) questionnaires. Associations between objective vestibular test results, patient-reported DHI scores and radiation dose parameters were investigated. Results Ten patients met inclusion criteria. Tumor control was achieved in all individuals. There were no statistically significant associations or identifiable trends between radiation dose and change in vestibular function or DHI scores. Notably, the four ears receiving the highest vestibular dose had minimal changes in vestibular function tests and DHI scores. Conclusions To the best of our knowledge, no previous reports have described the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported DHI. Based on these preliminary data, radiation dose to the vestibule does not reliably predict change in objective or subjective vestibular outcome measures.

Purpose. Anaplastic thyroid carcinoma (ATC) is a rare but aggressive tumor with limited survival. To date, the ideal radiation treatment schedule, one that balances limited survival with treatment efficacy, remains undefined. In this retrospective series we investigate the effectiveness and tolerability of hypofractionated radiation therapy in the treatment of ATC.Methods. 17 patients with biopsy proven ATC treated between 2004 and 2012 were reviewed for outcomes and toxicity. All patients received short course radiation.Results. The most commonly prescribed dose was 54 Gy in 18 fractions. Median survival was 9.3 months. 47% of patients were metastatic at diagnosis and the majority of patients (88%) went on to develop metastasis. Death from local progression was seen in 3 patients (18%), 41% experienced grade 3 toxicity, and there were no grade 4 toxicities.Conclusions. Here we demonstrated the safety and feasibility of hypofractionated radiotherapy in the treatment of ATC. This approach offers shorter treatment courses (3-4 weeks) compared to traditional fractionation schedules (6-7 weeks), comparable toxicity, local control, and the ability to transition to palliative care sooner. Local control was dependent on the degree of surgical debulking, even in the metastatic setting.

Head and neck cancer (HNC) arises from the skull base to the clavicles and is the fifth most common cancer in the world by incidence. Historically, in the developed world HNC was associated with tobacco use and alcohol consumption, and the combination of the two produced a synergistic increase in risk. However, beginning in 1983, investigators have found a significant and growing proportion of HNC patients with human papillomavirus-positive (HPV) tumors who neither drank nor used tobacco. Since that time, there has been increased interest in the molecular biology of HPV-positive HNC. Multiple studies now show that HPV has shifted the epidemiological landscape and prognosis of head and neck squamous cell carcinoma (HNSCC). These studies provide strong evidence for improved survival outcomes in patients with HPV-positive HNSCC compared to those with HPV-negative HNSCC. In many reports, HPV status is the strongest predictor of locoregional control, disease specific survival and overall survival. In response to these findings, there has been significant interest in the best management of HPV-positive disease. Discussions within major cooperative groups consider new trials designed to maintain the current strong survival outcomes while reducing the long-term treatment-related toxicities. This review will highlight the epidemiological, clinical and molecular discoveries surrounding HPV-related HNSCC over the recent decades and we conclude by suggesting how these findings may guide future treatment approaches.

Background There are few published data to guide the use and timing of palliative radiation therapy (RT) in children. We aimed to determine the clinical outcomes of palliative RT in children and the relationship with palliative care and hospice referrals. Procedure A retrospective chart review was performed on all patients younger than 18 years who received palliative RT in our clinic from January 2005 to January 2015. Results In the specified time period, 50 children underwent 83 courses of palliative RT. Median survival after treatment was 124 days (range, 1–1141 days). Fifteen courses were delivered to children in the last 30 days of life (dol). Palliative RT was successful in 89% of courses delivered before the last 30 dol versus 28% of courses delivered in the last 30 dol (p < 0.0001, Fisher's exact test). At the time of data collection, 43 children were deceased. Altogether, 88% of children who received palliative RT were also referred to our institution's pediatric palliative care team or to hospice at some time in their course. Of the children who died, 74% were referred to hospice and 34% were on hospice while receiving palliative RT. For children not already on hospice, the median time to hospice referral was 96 days after the last fraction (range, 0–924 days). Conclusions Palliative RT is effective in children with advanced cancer, although less so in the last 30 dol. With careful care coordination and multidisciplinary collaboration, RT can be successfully integrated into supportive and end-of-life care for children with advanced cancer.

e21673Background: Head and neck cancer (HNC) caregivers (CG) engage in time consuming, complex and potentially distressing tasks. While the psychosocial impact of HNC CG has been studied, few repor...

6070Background: Despite IMRT technological advances, toxicity in LAHNC pts remains extreme. Different IMRT techniques have been developed, including sequential boost (SeqB) and simultaneous integra...

143 Background: Advancements in the diagnosis and treatment of metastatic non-small cell lung cancer (NSCLC) have contributed to improved quality of life and survival. However, these successes are matched with rising healthcare costs and a growing debate over the appropriate utilization of medical resources near the end of life. To date, the majority of utilization studies report outcomes based on single institution or Medicare models. This may lead to significant bias due to individual physician preferences, narrow age groups or single payer systems. The purpose of this study is to analyze the broader trends and variables impacting the use of chemotherapy (CHT) and radiation (XRT) in the final months of life. Methods: The Florida Cancer Data System (FCDS) was used to evaluate patients with Stage IV (M1) NCLC from 1995 to 2010. Logistic Regression was used to determine the association between insurance types, census-based socioeconomic status (SES) and demographic variables with XRT received or CHT received. Results: 48,858 patients were identified within the FCDS and eligible for this study. The median age was 69 years. The median survival was 4.8 months. The overall use of XRT decreased between 1995 and 2010 from 52% to 37%, while the use of CHT increased from 35% to 49%. The utilization of treatment during the final 60, 30 and 14 days of death was 28%, 13% and 5% respectively for XRT, and 18%, 8% and 4% for CHT. Neither insurance status (OR, 0.852; 95% CI, 0.721 -1.174) nor poverty status (OR, 1.026; 95% CI, 0.950 -1.109) was predictive for XRT received. Those classified as low SES (OR, 0.685, 95% CI, 0.633-0.741) or not insured (OR, 0.678, 95% CI, 0.572-0.804) were less likely to receive CHT. Older-unmarried-females were less likely to receive CHT and XRT compared to their younger-married-male counterparts. Conclusions: When examining a broader demographic and insurance mix, the utilization of XRT and CHT in the final 30 and 14 days of death remain low at 13% and 5% for radiation and 8% and 4% for chemotherapy consistent with previously reported studies. Younger-married-males were more likely to receive palliative treatments. Insurance and SES did not influence the delivery of XRT while they did impact the use of CHT.

Patients with metastatic non-small cell lung cancer (NSCLC) have limited survival. Population studies have evaluated the impact of radiation refusal in the curative setting; however, no data exist concerning the prognostic impact of radiation refusal in the palliative care setting.To investigate the patterns of radiation refusal in newly diagnosed patients with metastatic NSCLC.Patients with Stage IV NSCLC diagnosed between 1988 and 2010 were identified in the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses were used to identify predictors for refusal of radiation and the impact of radiation and refusal on survival in the palliative setting.A total of 285,641 patients were initially included in the analysis. Palliative radiation was recommended in 42% and refused by 3.1% of patients. Refusal rates remained consistent across included years of study. On multivariate analysis, older, nonblack/nonwhite, unmarried females were more likely to refuse radiation (P0.001 in all cases). Median survival for patients refusing radiation was three months vs. five months for those receiving radiation and two months for those whom radiation was not recommended.Patients with metastatic NSCLC who refuse recommended palliative radiation have a poor survival. Radiation refusal or the recommendation against treatment can serve as a trigger for integrating palliative care services sooner and contributes greatly to prognostic awareness. Further investigation into this survival difference and the factors behind refusal are warranted.

Background Planning and delivery of IMRT for locally advanced head and neck cancer (LAHNC) can be performed using sequential boost or simultaneous integrated boost (SIB). Whether these techniques differ in treatment-related outcomes including survival and acute and late toxicities remain largely unexplored. Methods We performed a single institutional retrospective matched cohort analysis on patients with LAHNC treated with definitive chemoradiotherapy to 69.3 Gy in 33 fractions. Treatment was delivered via sequential boost (n = 68) or SIB (n = 141). Contours, plan evaluation, and toxicity assessment were performed by a single experienced physician. Toxicities were graded weekly during treatment and at 3-month follow up intervals. Recurrence-free survival, disease-free survival, and overall survival were estimated via Kaplan-Meier statistical method. Results At 4 years, the estimated overall survival was 69.3% in the sequential boost cohort and 76.8% in the SIB cohort (p = 0.13). Disease-free survival was 63 and 69% respectively (p = 0.27). There were no significant differences in local, regional or distant recurrence-free survival. There were no significant differences in weight loss (p = 0.291), gastrostomy tube placement (p = 0.494), or duration of gastrostomy tube dependence (p = 0.465). Rates of acute grade 3 or 4 dysphagia (82% vs 55%) and dermatitis (78% vs 58%) were significantly higher in the SIB group (p