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Purpose: To determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naïve, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods: Patients with PD-1 Ab-naïve HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly × 4 doses then every 3 weeks × 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks. Results: A total of 28 patients received 2 mg and 23 received 8 mg per injection, respectively. A total of 76% of patients had received prior systemic therapy. Combined positive score was ≥1 to < 20 in 35 patients (70%) and ≥ 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade ≥3 treatment-related adverse events (24%), and no treatment-related deaths. The objective response rate was 24% including 2 complete and 10 partial responses. The median duration of response was 7.0 [95% confidence interval (CI): 2.1–11.1] months. The response rate was higher in human papillomavirus–positive (HPV+) patients (44%, N = 16). Responses were not associated with PD-L1 expression levels or IFNγ-related gene expression at baseline. Responses were observed both in injected (32%) and in noninjected lesions (29%). Progression-free and overall survival at 9 months were 19.0% (95% CI: 9.1–31.7) and 64.7% (95% CI: 45.3–78.7), respectively. Conclusions: SD-101 combined with pembrolizumab induced objective responses, especially in HPV+ tumors, which were frequently associated with increased intratumoral inflammation and effector immune cell activity.

Purpose:To determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naïve, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).Patients and Methods:Patients with PD-1 Ab-naïve HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly × 4 doses then every 3 weeks × 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks.Results:A total of 28 patients received 2 mg and 23 received 8 mg per injection, respectively. A total of 76% of patients had received prior systemic therapy. Combined positive score was ≥1 to < 20 in 35 patients (70%) and ≥ 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade ≥3 treatment-related adverse events (24%), and no treatment-related deaths. The objective response rate was 24% including 2 complete and 10 partial responses. The median duration of response was 7.0 [95% confidence interval (CI): 2.1–11.1] months. The response rate was higher in human papillomavirus–positive (HPV+) patients (44%, N = 16). Responses were not associated with PD-L1 expression levels or IFNγ-related gene expression at baseline. Responses were observed both in injected (32%) and in noninjected lesions (29%). Progression-free and overall survival at 9 months were 19.0% (95% CI: 9.1–31.7) and 64.7% (95% CI: 45.3–78.7), respectively.Conclusions:SD-101 combined with pembrolizumab induced objective responses, especially in HPV+ tumors, which were frequently associated with increased intratumoral inflammation and effector immune cell activity.

Supplementary Figure from Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Head and Neck Squamous Cell Carcinoma: Results from a Multicenter, Phase II Trial

INTRODUCTION/BACKGROUND: This study assessed the safety and systemic (abscopal) response from the addition of local stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS/METHODS: Thirty-five patients with at least two sites of measurable disease on PET/CT received standard-of-care CPI immunotherapy alone (n=19), or in combination with 4 cycles doublet carboplatin/pemetrexed chemotherapy (n=16), and 3–5 fractions SBRT to a single extracranial target lesion between cycles 1–2 of the systemic therapy. Adverse events were assessed using CTCAE version 5.0. Best systemic objective response rate (ORR) was assessed using iRECIST criteria, excluding any irradiated lesion(s). Additional SBRT to a different target lesion was offered to patients who continued on immunotherapy with unconfirmed progressive disease or mixed response. RESULTS: Fifteen patients (44%) experienced 22 grade 1–2 toxicities potentially attributable to radiation, most commonly pneumonitis (n=9) and fatigue (n=6), and no grade 3–5 radiation-induced toxicities. Patients undergoing combined CPI-chemotherapy received a lower median biologically effective dose of SBRT than those undergoing CPI monotherapy (43.2 vs. 60Gy), but had a higher rate of radiation-induced toxcity (56% vs. 32%, p

Objective Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed the efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC). Methods We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Data cut-off: July 2020. Results Twenty-nine patients (median age: 60; range: 6–80) with TRK fusion-positive TC were treated. Tumour histology was papillary (PTC) in 20 (69%) patients, follicular (FTC) in 2 (7%), and anaplastic (ATC) in 7 (24%) patients. Among 28 evaluable patients, ORR was 71% (95% CI: 51–87); best responses were complete response in 2 (7%) patients, partial response in 18 (64%), stable disease in 4 (14%), progressive disease in 3 (11%), and undetermined in 1 (4%) due to clinical progression prior to the first post-baseline assessment. ORR was 86% (95% CI: 64–97) for PTC/FTC and 29% (95% CI 4–71) for ATC. Median time to response was 1.87 months (range 1.64–3.68). The 24-month DoR, PFS, and OS rates were 81, 69, and 76%, respectively. Treatment-related adverse events were mainly grades 1–2. Conclusion In TRK fusion-positive TC, larotrectinib demonstrates rapid and durable disease control and a favourable safety profile in patients with advanced disease requiring systemic therapy. Significance statement NTRK gene fusions are known oncogenic drivers and have been identified in various histologies of thyroid carcinoma, most commonly in papillary thyroid carcinoma. This is the first publication specifically studying a TRK inhibitor in a cohort of TRK fusion-positive thyroid carcinoma patients. In the current study, the highly selective TRK inhibitor larotrectinib showed durable antitumour efficacy and a favourable safety profile in patients with TRK fusion-positive thyroid carcinoma. Our findings show that patients with advanced non-medullary thyroid carcinoma who may require systemic therapy could be considered for testing for gene fusions by next-generation sequencing.

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

e21674 Background: The purpose of this study was to assess patterns of disease progression for patients with metastatic non-small cell lung cancer (NSCLC) on checkpoint inhibitor immunotherapy in order to help guide effective use of targeted radiation therapy to sites of gross disease most likely to progress. Methods: This single center, retrospective study included all patients diagnosed with Stage IV NSCLC between June 2015 and February 2019 who received at least 2 cycles of nivolumab, pembrolizumab, or atezolizumab, with or without concurrent chemotherapy. Immune RECIST criteria were used to assess patterns of disease progression, and progression-free survival (PFS), excluding irradiated tumors. Descriptive statistics were used to report baseline patient and tumor characteristics. The Chi square and log-rank tests were used to determine whether any baseline clinical characteristics were associated with progressive disease in initial sites only (vs. new or combined sites), and PFS, respectively. Factors assessed included initial metastatic sites, tumor histology, performance status, PD-L1 expression, untreated primary tumor, history of brain metastasis, number of metastatic sites involved, and use of concurrent chemo-immunotherapy. Results: Among 143 eligible patients with a median follow-up of 11 months, 97 (68%) developed disease progression. Of these, 67 patients (69.1%) progressed only at initial disease site(s), 10 patients (10.3%) progressed only at new disease site(s), and 20 patients (20.6%) progressed in both initial and new sites. Rates of disease progression based on tumor location were higher for liver (64%) and lung metastases (61%) than for other metastatic sites (33-36%) or the primary tumor (24%). Only higher PD-L1 expression ( p= 0.002) and absence of lung metastasis ( p= 0.048) at baseline were associated with improved PFS. No baseline characteristics significantly impacted the probability of initial disease site-only progression, though a trend was observed for untreated primary tumor (72% vs. 56%, p= 0.169). Conclusions: The dominant pattern of disease progression for patients with metastatic NSCLC on checkpoint inhibitor immunotherapy is in the initial sites of disease alone, whereas only 10% of patients progressed in new disease site(s) alone, suggesting a potential role for local radiation therapy as a complementary treatment modality. Pre-treatment patient and tumor characteristics did not predict patients most likely to benefit.

Background No consensus on how to best predict for chest wall injury following SABR exists. We report our experience in chest wall dose assessment when treating peri-pleural lung lesions with stereotactic ablative radiotherapy (SABR) delivered with volumetric modulated arc therapy (VMAT). Methods 40 patients with peri-pleural peripheral lung tumors underwent SABR between July, 2012 and February, 2015. Chest wall toxicity, dose distribution, and the influence of chest wall delineation method were investigated. Results After a median follow up of 16 months, no rib fracture or skin toxicity was observed. 4 patients (10%) reported persistent chest wall pain (grade 1–2). High dose rate's association with chest wall pain trended toward statistical significance ( p =0.06). PTV exclusion and reducing chest wall expansion to 1 cm led to significant dose reduction in the chest wall dose volume parameters ( p Conclusions The risk of chest wall pain following SABR delivered with VMAT is low. High dose rate, which is 1400 MU/min with flattening filter free (FFF) beams vs. 500–600 MU/min with non-flattening filter free (non-FFF) beams, may contribute to it. Chest wall dose volume parameters may vary with PTV exclusion; while chest wall expansion of 1 cm may fail to account for some high dose regions in the chest wall.

Background Traditionally, benign blood disorders are being evaluated and managed by hematologists who are also trained in oncology. Many of these physicians have their clinics located in Cancer Centers. Based on our clinical observations, the term “Cancer Center” is misleading to many benign hematology patients and it may affect their perception of their disease and/or reason for referral. There are currently no studies investigating patient understanding of benign hematology, the impact of a referral to a cancer center on a patients' well being or their understanding of a referral- therefore we designed this survey to explore those issues. Methods At West Virginia University/Mary Babb Randolph Cancer Center we drafted a survey. This IRB approved, anonymous and voluntary survey included twenty-eight questions that abstracted patient data that included: age, gender, race, level of education, understanding of reason for referral, knowledge of basic training aspects of hematologists, and multiple questions on stress and the impact of emotional well-being of a referral to the cancer center. Multiple-choice questions were drafted with 4-6 answer choices with no option for unknown. Surveys were collected from exclusively new patient benign hematology visits from May 2013-July 2013. Patients were surveyed at outpatient appointments after a verbal consent was obtained prior to their first contact with a hematologist. Results A total of 55 patients consented and received the questionnaire. Of the 55 questionnaires, 4 were incomplete and thus were excluded. 41.2% (21) responders were males, 58.8% (30) were females, 76.4% (39) were >40 yrs, 98% (50) were Caucasian, and 56.8% (29) had at least some college education or above. 60.7% (31) of patients surveyed stated that they were surprised when they found that their appointment was at the Cancer Center and 39.2% (20) stated that they received no explanation as to why they were referred to the cancer center prior to the visit. 70.5% (36) of patients did not know what benign hematology was and only 54.9% (28) patients knew that cancer doctors are also frequently trained to see benign hematology patients. 49% (25) of patients stated that their primary care physician's office did not explain that their referral to the cancer center was for a benign hematologic problem. 45% (23) and 41.1% (21) of patients expressed an increase in their anxiety and stress levels, respectively, when they found out their referral was to a Cancer Center. 27.4% (14) of patients said they were afraid they might have cancer during the process of referral and 37.3% (19) actually thought that the reason for their referral to the Cancer Center was an evaluation for cancer. Only 11.7% (6) patients expressed that they would prefer to be referred at a benign hematology clinic that is not located in a Cancer Center. Conclusion Referral to Cancer Center for benign hematologic diseases appears to increase stress and anxiety of patients and patients may perceive that they are referred for evaluation of a cancer diagnosis. Careful explanation by the entire team including referring physicians, hematologists, and office staff as to the reason for evaluation of a benign hematologic disorder may decrease stress and increase understanding of this subset of patients. Disclosures: No relevant conflicts of interest to declare.

9534 Background: SD-101 is a synthetic CpG TLR9 agonist. Pembrolizumab is a PD-1 inhibitor. SYNERGY-001/KEYNOTE-184 assesses the safety and preliminary efficacy of the combination of SD-101 and pembrolizumab in patients naïve to anti-PD-1/L1 therapy with unresectable stage IIIC-IV melanoma. Methods: SD-101 was evaluated as 2 mg/lesion injected into 1 to 4 lesions and 8 mg/lesion in 1 lesion as 4 weekly doses followed by 7 doses Q3W. Pembrolizumab was administered as 200 mg IV Q3W. CT scans were performed every 9 weeks. Responses were assessed per investigator using RECIST v1.1. Responses and post-hoc Kaplan-Meier analyses of PFS in the ITT population were compared for patients who received 2 mg/lesion with 8 mg/lesion. Results: 86 patients (2 mg: N = 45; 8 mg: N = 41) have been enrolled with similar baseline characteristics: median age = 66 years; male = 67%; ECOG stage 0 = 67%; disease stage: IIIC = 21%; IVM1a/b = 50%; IVM1c = 28%; LDH ≤ ULN = 71%; treatment naïve = 73%. Median follow up to date is 8.1 months in 2 mg group and 8.3 months in 8 mg group. SD-101 safety profile comprises flu-like symptoms with most frequent grade ≥3 SD-101-related AEs of headache (7%), fatigue (7%), malaise (5%), myalgia (4%), and chills (4%). Immune-related AEs were reported in 19%. ORR in 2 mg group = 71% (95% CI: 57, 82) (CR: 13%) and in 8 mg group = 49% (95% CI: 33, 65) (CR: 7%) with responses in both injected and non-injected lesions, including visceral. DOR = not reached (NR) in either group. ORR by baseline PD-L1 expression in 62 patients, 53% of whom were PD-L1 positive: 2 mg = 80%/79% (PD-L1 positive/negative); 8 mg = 62%/40% (PD-L1 positive/negative). PFS was higher in 2 mg group with median PFS in 2 mg = NR (95% CI: Not estimable [NE], NE) and in 8 mg = 10.4 months (95% CI: 4.2, NE), HR = 0.45 (95% CI: 0.21, 0.98), p = 0.036. 6 month PFS rate in 2 mg = 81% and in 8 mg = 60%. 6 month OS rate in 2 mg = 98% and in 8 mg = 92%. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab has been well-tolerated, and is showing promising high response rates and PFS, regardless of PD-L1 expression, particularly in patients who received 2 mg SD-101. Clinical trial information: NCT02521870.

6039 Background: SD-101, a synthetic CpG-ODN agonist of TLR9, stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in HNSCC. Study DV3-MEL-01 (NCT02521870) assesses safety and efficacy of SD-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC. We have previously reported a 27.3% ORR in 22 patients receiving 8 mg SD-101/injection in the modified ITT after at least 2 CT scans due to late responses (Abstract 3560, ESMO 2018). Higher efficacy at a lower SD-101 dose, 2 mg/injection, has been reported in advanced melanoma patients (LBA 45, ESMO 2018). Consequently, this dose is now being assessed in HNSCC. We report preliminary data with the 2 mg/injection dose in 23 patients in mITT at the first CT scan. Methods: Anti-PD-1/PD-L1 naïve patients received 2 mg SD-101 intratumorally in 1 - 4 lesions (weekly x 4 doses then Q3W x 7 doses). Pembrolizumab is was administered IV at 200 mg Q3W. Responses were assessed per RECIST v1.1. Results: 28 patients enrolled: median age 63 y/o, male 68%; ECOG PS 0-1 (18%/82%); mean prior lines of systemic therapy 1 (0-3); mean treatment duration 70 days (1-253). Primary tumors: 19 (68%) oropharyngeal; 3 (10%) laryngeal; 2 (7%) hypopharyngeal; 4 (14%) unknown. Mean number of target lesions: 1.82 (1 to 5). HPV status: 7 (25%) +, 9 (32%) -, 12 (43%) unknown. 18 (64 %) discontinued treatment: 12 (42%) due to PD, 4 (16%) deaths, 1 (3%) consent withdrawn, 1 (3%) went to hospice. Mean follow up 2.70 months. Safety: 16 non-treatment-related SAEs in 9 patients. 2 treatment-related Grade ≥3 AEs: sepsis (4%) and lymphopenia (4% ). No treatment-related deaths. Efficacy: 23 patients in the mITT population with first CT scan at day 64: ORR: CR: 2, PR: 3 (22%); SD: 6 (26%), PD: 7 (30%), non-evaluable: 5 (22%). Disease control rate (48%). 5 patients on study have not had a CT scan. Conclusions: SD-101 with Pembrolizumab shows early promising data and is well tolerated. Additional follow-up scans from both dose cohorts are being evaluated and will be presented. Clinical trial information: NCT02521870.

Background Image-guided (IG) intensity-modulated radiotherapy (IMRT) enables maximal tumor margin reduction for the sparing of organs at risk (OARs) when used to treat locally advanced non-small cell lung cancer (NSCLC) with definitive chemo-radiation. It also allows for the incorporation of stereotactic ablative radiotherapy (SABR) into the treatment regimen. Here, we describe our initial experience in combining definitive upfront SABR to the primary lesion with chemo-radiation delivered with conventionally fractionated IG-IMRT to the remaining regional disease; along with clinical outcome following chemo-radiation with conventionally fractionated IG-IMRT alone in the treatment of locally advanced NSCLC. Methods The clinical outcome of 29 patients with locally advanced NSCLC who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both) was retrospectively reviewed. Results After a median follow up of 23.7 months, the median overall survival (OS) and progression-free survival (PFS) were 19.8 and 11.3 months, respectively. The 2 year local, regional, and distant control was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT alone. SABR + IG-IMRT was well tolerated. No ≥ grade 3 radiation-related toxicity was observed. Conclusion Definitive upfront SABR followed by IG-IMRT in selected patients with locally advanced NSCLC warrants further investigation in future clinical trials, while chemo-radiation with IG-IMRT alone was well tolerated.

Background Hematologists/Oncologists spend years of training in a fellowship program. At academic centers, patients receiving treatment are often seen by fellows. it has not been established what patients understand about fellowship training, therefore the purpose of this study was to explore their understanding and whether they are content with fellows taking part in their care. Methods At West Virginia University/Mary Babb Randolph cancer center, the authors drafted a survey. This anonymous and voluntary survey abstracted basic patient demographic data and experience being cared for by fellows and basic knowledge of a Hematology/Oncology fellowship. Multiple-choice questions were drafted with 4 to 6 answer choices with no option for unknown. Surveys were collected over a 3-week period in July 2012. Patients were surveyed at outpatient appointments, infusion center visits, and laboratory draws. Results Two hundred twenty- six surveys were collected. Statistical analysis was performed and a binomial regression was fit to the data. There is evidence that higher levels of education are more likely to give correct answers ( P = 0.035). Patients who stated that they had not seen a fellow or were unsure whether they had seen a fellow were more likely to select incorrect answers ( P = 0.001). There is no statistical significance differentiating between cancer types in likelihood of getting answers correct. Of those surveyed, 1.77% felt that they completely understand the role of a fellow in their care, whereas 80.45% desired further information about fellows. Only 2.2% disliked having a fellow involved in their care. Conclusions Patients at academic centers being seen by Hematology/Oncology fellows appear to have a lack of knowledge of a fellow's role and background but have a desire to be educated. Educational initiatives can be introduced to teaching institutions to help patients better understand the role of a fellow.

Molecular testing of non-small cell lung carcinomas (NSCLCC) with adenocarcinoma features has become commonplace with the development and use of targeted treatments for these malignancies. Prior to treating these tumors with targeted drug regimens, testing for specific mutations is usually required to determine the potential response of the tumor to the therapeutic agents. This case review describes a patient with lung cancer showing a specific gene mutation who benefitted from targeted treatment. Also reviewed are the current standards of care and trends in the molecular testing of NSCLC with adenocarcinoma features and possible future molecular targets.

Problem-based learning (PBL) is a common instructional format used at many medical schools. It promotes active, self-directed learning, connecting medical students to their future real-world experience as well as enhancing training and problem-solving skills, teamwork, and interdisciplinary interactions. The PBL small-group format provides a unique opportunity over both semesters for first-year medical students to study clinical cases in a self-directed fashion and develop professional skills at various levels. The advantages of the presented lung cancer case are numerous. Clinical presentation is typically late since symptoms are not obvious and initial diagnosis is frequently misleading. A considerable number of tests are required to arrive at the final diagnosis, providing a variety of learning opportunities, as do the initially successful treatment options, including an example of personalized medicine. The follow-up and typical relapse provide additional learning opportunities, including the inevitable failure of therapy and the psychosocial issues surrounding end-of-life care. This case was implemented in the spring semester in February 2014 over three 90-minute sessions. One hundred twelve first-year medical students divided into groups of eight took the course. The lead author served as a facilitator for one of the 14 groups and received direct feedback about all aspects of the case from the students' perspective. In addition, feedback was received from other facilitators in informal discussions. Finally, the case was evaluated by each group of students on a standard form after it had been concluded. The critique received was overall very favorable and helped optimize the case for this resource. Most points were minor, but comments led to rebalancing of the material between sessions to aim at a similar amount of new material introduced between Sessions 1 and 2. Since students have formal opportunities to research learning issues only after Sessions 1 and 2, the new material introduced in Session 3 is kept to a minimum. It is planned to continue to update the case based on future student feedback and new developments.

In the United States (US), the elderly carry a disproportionate burden of lung cancer. Although evidence-based guidelines for lung cancer care have been published, lack of high quality care still remains a concern among the elderly. This study comprehensively evaluates the variations in guideline-concordant lung cancer care among elderly in the US.Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2002-2007), we identified elderly patients (aged ≥65 years) with lung cancer (n = 42,323) and categorized them by receipt of guideline-concordant care, using evidence-based guidelines from the American College of Chest Physicians. A hierarchical generalized logistic model was constructed to identify variables associated with receipt of guideline-concordant care. Kaplan-Meier analysis and Log Rank test were used for estimation and comparison of the three-year survival. Multivariate Cox proportional hazards model was constructed to estimate lung cancer mortality risk associated with receipt of guideline-discordant care.Only less than half of all patients (44.7%) received guideline-concordant care in the study population. The likelihood of receiving guideline-concordant care significantly decreased with increasing age, non-white race, higher comorbidity score, and lower income. Three-year median survival time significantly increased (exceeded 487 days) in patients receiving guideline-concordant care. Adjusted lung cancer mortality risk significantly increased by 91% (HR = 1.91, 95% CI: 1.82-2.00) among patients receiving guideline-discordant care.This study highlights the critical need to address disparities in receipt of guideline-concordant lung cancer care among elderly. Although lung cancer diagnostic and management services are covered under the Medicare program, underutilization of these services is a concern.

Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG–positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

e21630Background: Cancer patients with undiagnosed depression have poorer quality of life and can negatively impact overall survival. Studies have shown that non adherence was three times higher in...

Placement of carmustine-impregnated wafers has become a common practice after surgical resection of malignant gliomas. Bevacizumab is used as a second-line agent for the treatment of malignant gliomas and is sometimes used in patients who have had recent wafer implantation. We describe two cases of fatal cerebrospinal fluid (CSF) leak in patients treated with bevacizumab and irinotecan after 4 weeks of carmustine wafer implantation. Possible mechanisms for the CSF leak in these patients are discussed. We recommend waiting for a longer period of time before starting bevacizumab in patients who had implantation of carmustine wafers.

Positron-emission tomography (PET) scan is a widely used imaging modality in the management of various malignancies. There is considerable controversy regarding its use in breast cancer diagnosis and treatment. In this review, we discuss published data on the use of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-PET) in the staging workup of locally advanced breast cancer, and management of locally recurrent and metastatic breast cancer. FDG-PET is a useful tool in staging advanced breast cancer and assessing the extent of disease involvement when metastasis is suspected. It might also aid in assessing early response to therapy. Future goals of improving PET scan accuracy in the management of breast cancer will be achieved through utilizing radiotracers, based on a better understanding of tumor biology and improvement in breast-specific PET scans.

PURPOSE Positron emission tomography (PET) is widely used for the staging evaluation of non–small-cell lung cancer; however, its use in small-cell lung cancer (SCLC) remains investigational. PATIENTS AND METHODS We did a retrospective study of 137 patients to evaluate the role of PET in SCLC. Fifty-one of 137 patients had computed tomography (CT) and PET scans during initial evaluation of a lung mass. RESULTS All 51 patients had PET-positive results for malignancy (100% sensitivity). In 40 of 51 cases (78%), the PET staging correlated with that on CT. Two of 51 patients (4%) had disease that was accurately upstaged by PET. Positron emission tomography accurately downstaged disease in 6 of 51 patients (12%). Positron emission tomography detected additional sites of disease in 13 of 42 patients (32%). Of the 13 additional sites of disease, PET detected supraclavicular nodes in 4 of 13 patients (30%) and bone lesions in 4 of 13 patients (30%). The sensitivity to detect brain lesions was 5 of 11 patients (45%) in this series. In this series, the PET results from 8 of 51 patients (16%) resulted in a change in disease management. Because of PET results, 6 of 51 patients (12%) who otherwise would not have been treated, were treated with radiation. CONCLUSION Positron emission tomography is potentially useful for accurate initial staging of SCLC and can ensure that a patient's disease is not overstaged by CT scan, which might result in denied potentially curative treatment for limited-stage SCLC. It can identify the occult adrenal metastasis and metastasis to supraclavicular lymph nodes that are missed by CT; however, brain lesions are difficult to assess by PET.

Glioblastoma multiforme (GBM) carries a dismal prognosis despite the current standard of multimodality treatments. Recent studies showed promising results to a regimen consisting of a VEGF inhibitor, (bevacizumab) and a topoisomerase I inhibitor (irinotecan) [BI] in recurrent GBM. However, those patients with GBM who progress on BI will succumb to their disease generally in a very short period of time. We report a case of a 56-year-old male patient with GBM who declined surgical resection and received chemoradiation with temozolomide. This treatment was withheld secondary to significant thrombocytopenia. Subsequently, he achieved stable disease for 10 months with a regimen consisting of thalidomide and tamoxifen before progressing. This was followed by bevacizumab with irinotecan [BI], for which he had a significant partial response for 8 months with subsequent progression. Reinducing the patient with bevacizumab in combination with a pegylated liposomal doxorubicin [PLD] (a topoisomerase II inhibitor) demonstrated antitumor activity with significant shrinkage of contrast enhancing mass and peritumoral edema.

6634 Background: The American Society of Clinical Oncology (ASCO) has stated that consent to treatment with chemotherapy is an important part of the delivery of quality cancer care. Best practices ...

e17037 Background: Acneform rash is associated with cetuximab, can be treatment limiting and has been shown to correlate with tumor response. The rash is thought to have an inflammatory component t...

9 Background: Hematologists/oncologists spend years training in a fellowship program. At academic centers, patients receiving treatment are often seen by fellows. It has not been established what patients understand about fellowship training, therefore our purpose was to explore their understanding and if they are content with fellows taking part in their care. Methods: At West Virginia University/Mary Babb Randolph Cancer Center we drafted a survey. This anonymous and voluntary survey abstracted patient data that included: age, sex, race, level of education, type of cancer diagnosis, amount of time being treated for cancer, experience being cared for by fellows and basic knowledge of a hematology/oncology fellowship. Multiple-choice questions were drafted with 4 to 6 answer choices with no option for unknown. Surveys were collected over a three-week period from July 3, 2012 through July 24, 2012. Patients were surveyed at outpatient appointments, infusion center visits, and laboratory draws. Results: 226 surveys were collected. Statistical analysis was performed and a binomial regression was fit to the data. There is evidence that higher levels of education are more likely to give correct answers (p value 0.035). Patients who stated they had not seen a fellow or were unsure they had seen a fellow were more likely to select incorrect answers (p value 0.001). There is no statistical significance differentiating between cancer types in likelihood of getting answers correct (Table). 1.77% of those surveyed felt they completely understand the role of a fellow in their care, while 84.51% desired further information about fellows. Only 2.21% disliked having a fellow involved in their care. Conclusions: Patients at academic centers being seen by hematology/oncology fellows appear to have a lack of knowledge of a fellow’s role and background but have a desire to be educated. Educational initiatives can be introduced to teaching institutions to help patients better understand the role of a fellow. [Table: see text]

e18071 Background: NSCLC accounts for approximately 85% of lung cancers. It is subdivided into adenocarcinoma (including bronchoalveolar), squamous cell carcinoma (SCC), and large cell histologies....

e18116 Background: Up to one-third of small cell lung cancer (SCLC) patients are diagnosed with brain metastases. Our study aims to evaluate the role of staging PET/CT in detecting asymptomatic bra...

e11611 Background: Fluorine-18-FDG positron emission tomography (FDG-PET) role in the follow up care of non-metastatic breast cancer is not defined. Methods: We retrospectively analyzed 177 patients with stage I-III breast cancer between November 2004 and June 2006. IRB approval was obtained for this study. Patients were divided into two groups. Group A consisted of patients who had one or more FDG-PET scans as part of their clinical follow up (N=68), and Group B consisted of patients who did not (N=109). Clinical, radiological and pathology data were obtained from patients’ records. Results: Median follow-up is 35 months. Mean age 53 years for group A and 57 years for group B. Group A patients were more likely to have had higher stages (29% stage I, 53% stage II, and 18% stage III) compared with group B (64 % stage I, 31% stage II and 4% stage III). The two groups did not differ significantly in ER+ status (69% vs. 78% p=0.21), or Her2neu status (19% vs. 17%; p=0.6). Group A patients had more clinic visits (18 vs. 11; p=0.009), their tumor marker was checked more often (13 vs. 9 times; p=0.0001), had more radiological studies (10 studies vs. 5; p=0.0001), and had more biopsies (0.88 vs. 0.48 biopsy per patient; p=0.05). These differences were significant even after controlling for stage and chemotherapy. 9/68 patients in group A had tumor recurrence compared to 1/109 in group B (p=0.0003). PET scan indications were as follows: 29 (43%) for asymptomatic follow up evaluation [2 recurred]; 18 (26%) concerning symptoms [0 recurred]; 10 (15%) elevated tumor marker [2 recurred]; 7 (10%) other abnormal imaging studies [1 recurred]; 4 (6%) metastatic workup. Conclusions: While FDG-PET might aid in detecting recurrence in some patients with non-metastatic breast cancer, its use was associated with more clinic visits, blood tests, biopsies, and radiological tests. No significant financial relationships to disclose.

e19038 Background: Up to one-third of non-small cell lung cancer (NSCLC) patients are diagnosed with brain metastasis. Our study aims to evaluate the role of whole body and brain FDG-PET/CT in detecting asymptomatic brain metastasis in this population. Methods: We performed a retrospective chart review of 282 consecutive non-small cell lung cancer patients between February of 2005 and June of 2008. 60 patients with brain metastasis were identified. Information regarding tumor histology and presence of neurological symptoms at the time of discovery of brain metastasis was collected. In addition, data was acquired from brain MRI and PET/CT (with IV contrast) reports including: study date, findings and any change in staging secondary to the study. Results: The median age was 63 years (47 % women). 39 (65%) of the patients had neurological symptoms at the time of discovery of brain metastasis. PET/CT scan with IV contrast was performed in 53 patients with brain metastasis. For patients who had a PET/CT scan, the histological types were: adenocarcinoma (58.4%), unclassified (22.6%), squamous (13.2%), large cell (3.8%) and other (1.8%). PET/CT scan had a sensitivity of 97.8% in detecting CNS metastasis seen on brain MRI. 19/53 patients were found to have asymptomatic brain metastasis on PET/CT scan (2 stage I, 1 stage II, 2 stage III and 13 stage IV). Overall, PET/CT scan resulted in upstaging of 5 asymptomatic and 6 symptomatic patients or 11/53 (20.7%). Conclusions: PET/CT scan with IV contrast has a high sensitivity in detecting brain metastasis in patients with NSCLC when compared to brain MRI. It is effective in detecting asymptomatic brain metastasis in this population. Those patients, who initially were thought to have non-metastatic disease, are spared inappropriate aggressive surgery or radiation. No significant financial relationships to disclose.

Purpose: Peripheral allogeneic SCT is used to treat different types of hematologic malignancies. The target CD34 stem cell dose is 2 -5 x 106/Kg. The dose of CD3+ cells in the infusate is not taken into account except in T-depleted transplant. T-cell dose in peripheral blood stem cell collections is at least 10-fold more than that in a bone marrow harvest. Regulatory T cells (CD4+, CD25+), which comprises 5–10% of CD4 + T cells have been correlated with less incidence of aGVHD. In our study we are trying to determine the impact of T-cell dosing on the overall survival and incidence of aGVHD after peripheral allogeneic SCT in a group of patients with hematological malignancy. Methods: A retrospective study of 66 consecutive patients who underwent peripheral allogeneic SCT for hematological malignancy in our institution between January 2003 and April 2006. The median duration of follow up after SCT was 12.6 months (range 0.2–53). Duration of follow up was compromised only in a subset of patients who had early mortality following SCT. Proportional hazard model was used to define the cutoff value of CD3, CD4, and CD8 cell dose that separate 2 groups of patients with highest statistically significant difference in terms of incidence of aGVHD. Kaplan-Meier Survival Analysis was used for correlate the overall survival (calculated from date of transplant) among these groups subdivided in terms of CD3, CD4, and CD8 cell doses. Results: The 66 patients (6 females, and 60 males) with median age of 48 years (range: 19–63 years) had different malignancies; 6 ALL, 34 AML, 1 biphenotypic leukemia, 1 CLL, 11 CML, 5 Hodgkin lymphoma, 8 NHL. The SCT was from matched related donors in 39 patients, and from matched unrelated donors in 27 patients. The incidence of aGVHD (grade 2–4) was statistically significantly less among those who received CD3 dose < 33.5 × 107/kg IBW (P value: 0.04), tended to be less among those who received CD4 dose < 32.6 × 107/kg IBW (P value: 0.06), and was statistically significantly less among those who received CD8 dose < 6.2 × 107/kg IBW (P value: 0.04). Survival analysis showed no statistically significantly difference in the overall survival (OS) among all patients groups. Median OS was 10.5 months for those who received CD3 dose ≤ 33.5 ×107/kg IBW and 17 months for those who received > 33.5 ×107/kg IBW (P value: 0.35). Median OS was 12 months for those who received CD4 dose ≤ 32.6 ×107/kg IBW and 16.3 months for those who received > 32.6 ×107/kg IBW (P value: 0.8). Median OS was 6 months for those who received CD8 dose ≤ 6.2 ×107/kg IBW and 14.4 months for those who received > 6.2 ×107/kg IBW (P value: 0.13). Conclusions: In our series, CD3 dose less than 33.5 ×107/kg IBW and CD8 dose less than 6.2 ×107/kg IBW were associated with statistically significant reduced risk of grade 2–4 acute GVHD following peripheral allogeneic SCT. Overall survival was not statistically different among these groups of patients. These data suggest that, in addition to considering CD34 dose required for engraftment in allogeneic transplant, the CD3 dose and its subsets CD8 and CD4 may need to be considered to try to minimize the risk of acute GVHD without compromising survival after transplant.