A recent study by Kong et al suggested an 18.9% reduction in lung cancer mortality among individuals with well-controlled HIV who receive recommended screening. At our institution, we found that persons living with HIV (PLWH) are diagnosed with lung cancer at an earlier age with more advanced stage disease than patients without HIV. One study of 143 PLWH with lung cancer revealed a mean age at diagnosis of 55.8 years, far below the average age of all lung cancer patients (68.0). Additionally, 67% of PLWH had evidence of metastatic disease at the time of diagnosis, compared to just 49% in the general population.

The landmark Lung Cancer Screening (LCS) Trial demonstrated a significant reduction in mortality. However, European LCS trials have not confirmed such benefit. We examined the impact of LCS-led diagnosis on the mortality of newly diagnosed lung cancer patients at an urban medical center. Medical records of patients diagnosed with primary lung cancer for the period 2013-2015 (n=638) were reviewed to identify those who had an established primary care provider (PCP), were LCS-eligible/ non LCS-diagnosed, and LCS-eligible/LCS-diagnosed as per the United States Preventative Services Task Force (USPSTF) guidelines. Baseline characteristics between LCS-eligible/non-diagnosed patients and LCS-eligible/diagnosed patients were analyzed using chi-squared and Wilcoxon-Mann-Whitney tests. Kaplan-Meier curves were generated, and predictors of overall survival were evaluated using Cox proportional hazards modeling. 134 primary lung cancer patients had an established PCP and were LCS-eligible; 19/134 (14%) were LCS-diagnosed. LCS-eligible/LCS-diagnosed patients were of younger age (p=0.03), English-speaking (p=0.03), of higher socioeconomic status (p=0.02), active smokers (p<0.01), and had earlier disease stages (p=0.02) than LCS-eligible/non-diagnosed patients. All-cause mortality was significantly lower in LCS-eligible/diagnosed patients compared to LCS-eligible/non-diagnosed patients (p=0.03). Disease stage was found to be the main factor associated with higher mortality by multivariate regression analysis (HR: 6.13, stage 4 vs. stage 1-2, p<0.01). To our knowledge, this is the first report of lung cancer mortality differences in LCS eligible patients as a function of them undergoing or not LCS in a single-center setting since the inception of the USPSTF guidelines. Patients with an LCS-led diagnosis had a reduced mortality, probably as a result of having an earlier disease stage, which echoes the findings of large prospective LCS trials. LCS-led diagnosis rates remain low among lung cancer patients. Fully implementing the USPSTF guidelines constitutes a great unrealized opportunity to decrease lung cancer mortality.

PD-L1 testing has been incorporated into the standard treatment paradigm given recent immunotherapy approvals for metastatic lung cancer (LC). Minority populations are notoriously under-represented in large immunotherapy clinical trials. Thus, we examined PD-L1 expression profiles in a minority-based academic cancer center. Among 989 patients with newly diagnosed LC at Montefiore Medical Center (MMC) from 2014-2015, 330 (33%) were AA and 195 (20%) were Hispanic.

To report on patterns of failure using detailed information from follow-up positron emission tomography-computed tomography (PET/CT) scans for patients with laryngeal squamous cell carcinoma treated with definitive radiation therapy using IMRT with simultaneous integrated boost. We identified 18 patients with laryngeal squamous cell carcinoma treated with definitive RT using IMRT with simultaneous integrated boost and with loco-regional recurrence diagnosed via follow-up PET/CT scans. These follow-up scans were then fused to the original treatment planning computed tomography (CT) scan using deformable image registration. Recurrence volumes were then delineated on the co-registered PET/CT scans. We then calculated the mathematical focal epicenter of the high-uptake region to identify the origin of recurrence for each patient. This was done using a previously published method that finds the point within the recurrence volume for which the maximum distance to the surface of the surrounding recurrence volume is smaller than for any other point. The failure pattern was then determined by whether the point of recurrence origin fell within the GTV70, CTV70, PTV70 (all receiving 70 Gy) or intermediate-risk PTV59 (receiving 59.4 Gy) or low-risk PTV54 (receiving 54.12 Gy), in the original treatment planning CT. Twenty-one primary/nodal recurrences in the 18 patients were included in the analysis. Eighty-six percent (18/21) of the recurrences originated in the high-dose treatment volume, as seen in Table 1. The 4 recurrences that originated in the high-dose (70 Gy) volume but outside the GTV70 were on average within 1.4 mm from the edge of the GTV70. There were 3 nodal failures all within low/intermediate CTV. Eighty-six percent of the recurrences for laryngeal cancer patients treated with definitive radiation therapy using IMRT with simultaneous integrated boost in this analysis originated from within the high dose region. This can have implications for reducing clinical target volume expansions to constrain dose to critical areas. In addition, a risk-adaptive treatment approach to further escalate the dose to the gross tumor might improve local control rates.Abstract 1135; Table 1Pattern of failure for the laryngeal cancer patients included in the study.Target volumeGTV70CTV70PTV70PTV59PTV54Nr. of recurrences (% of total)14 (67%)17 (81%)18 (86%)19 (90%)20 (95%) Open table in a new tab

To report clinical outcomes of patients with locally advanced hypopharyngeal squamous cell carcinoma treated with definitive radiation therapy using IMRT with adaptive planning. We identified 30 patients with locally advanced hypopharyngeal head and neck squamous cell carcinoma who were treated with definitive radiation therapy between 2004 and 2014 at a single institution. 90% (27/30 patients) received concurrent chemotherapy and 83% (25/30) had stage IVa or IVb disease. Head and neck cancer patients treated at our institution undergo planned rescans at 15th RT fraction and are replanned if there is inadequate dose to gross disease or an increased dose to organs at risk. Disease and patient characteristics, treatment information, and clinical outcomes were tabulated for each patient. The median follow-up for these patients was 15.5 (Range: 5.2-104.4) months. Of the 30 patients, 10 (33.3%) developed loco-regional recurrence with 4 of these recurrences salvaged with laryngectomy/pharyngectomy with or without neck dissection. 13 patients (43.3%) developed metastatic disease. Two-year actuarial overall survival, progression-free survival, distant metastasis-free survival, locoregional control and laryngectomy-free survival for the entire cohort were 75%, 46%, 54%, 76% and 87%, respectively. Compliance with RT trended towards improved locoregional control with a hazard ratio for locoregional recurrence of 3.69 (95% CI: 0.96-14.17, P = 0.057) in patients with >5 missed treatment days. At time of last follow up, 56.7% (17/30) of all patients and 93.8% (15/16) of patients without disease recurrence were alive without need for tracheostomy and/or PEG tube. IMRT using adaptive planning results in good locoregional control and excellent functional outcomes in patients with locally advanced hypopharyngeal squamous cell carcinoma. Development of distant metastatic disease remains a significant problem for these patients and studies investigating ways to improve outcomes for these patients are warranted.

Statistical image features from computed tomography (CT) and positron emission tomography (PET) scans are currently being explored for their potential to predict clinical outcome and thus provide indications for risk-adapted treatment strategies. Here, we analyze tumor textural features from pretreatment 18F-fluorodeoxyglucose (FDG) PET scans as related to clinical outcomes in patients treated with definitive radiation therapy (RT) for laryngeal cancer. Seventy-five consecutive patients with laryngeal squamous cell carcinoma treated with definitive RT with available pretreatment PET/CT scans at our institution were retrospectively evaluated. Disease and patient characteristics, treatment information, and clinical outcomes data were tabulated for each patient. Pretreatment PET/CT scans were used for image feature analysis on the primary tumor volume from each scan. Multiple statistical image features were computed, along with several measures related to the standard uptake value (SUV). Redundant image features were excluded based on a strong correlation with parameters commonly reported as important such as metabolic tumor volume and maximum SUV (SUVmax). The correlation between the remaining image features and local control (LC), progression-free survival (PFS), and overall survival (OS) was evaluated through univariate Cox regression, and statistically significant features were combined with clinical parameters in multivariate Cox proportional hazards regression models. Correction for multiple testing was performed using the Benjamini-Hochberg method. With a median follow-up of 31.4 months, the 3-year LC, PFS, and OS (with 95% confidence intervals) were 66% (53%-79%), 49% (36%-62%), and 75% (64%-87%), respectively. Out of the calculated image features, only SUVpeak (highest possible mean value of a 1 cm3 spherical volume within the primary tumor) corrected for lean body mass appeared to correlate with outcome. Interestingly, the SUVpeak was found to be a statistically significant parameter in the model for PFS (P=.006), but not for LC, suggesting that the SUVpeak value may hold important information about potential regional or distant spread. Dividing the patient population based on the median SUVpeak value shows a split of the Kaplan-Meier survival curves, although not statistically significant with a log-rank P value of .082. KPS>70 was the only parameter significantly related to OS (P=.0002). The SUVpeak value from pretreatment PET scans may hold important information about the risk of distant and regional spread for laryngeal cancer patients. We are currently working on gathering additional patient data to validate these findings.

Malnutrition is a common problem for head and neck cancer patients. Loss of skeletal muscle mass, or sarcopenia, has been associated with malnutrition, poor tolerance of cancer therapy, and poorer outcomes in a number of malignancies. At our institution, we initiated a nutritional program where patients treated with definitive radiation therapy (RT) are evaluated and closely followed by a registered oncologic dietitian. In this report, we analyze nutritional factors and compliance with dietary recommendations for associations with overall survival (OS) and progression-free survival (PFS) in patients receiving definitive RT for laryngeal and oropharyngeal cancers. We identified 352 patients with non-metastatic oropharyngeal (146) and laryngeal (206) cancer who were treated with definitive RT between 2004 and 2013. Disease and patient characteristics, treatment information, compliance with nutritional program, and clinical outcomes data were tabulated. Adherence to the nutritional program was scored weekly and patients were deemed non-compliant with nutritional program if they cancelled >25% of their appointments with the dietitian, refused nutritional counseling or did not follow recommendations. Of the 352 patients, 158 patients had a pretreatment CT including the abdomen within 30 days of RT start date to assess sarcopenia. Sarcopenia was defined based on muscle areas at the level of L3 using cutoffs established by Prado et al. Descriptive statistics, Kaplan Meier survival analysis, and log rank tests were performed, and Cox regression models were used to examine predictors of OS and PFS. The median follow-up for the entire cohort was 22.86 (0.56-116) months. The actuarial rates for OS were 91%, 86% and 73% at years 1, 2, and 5, respectively. 70.9% (112/158) of patient with abdominal CT prior to starting RT were sarcopenic with a median muscle mass index of 48.2 (range: 30.4-70.9) for males and 35.9 (range: 24.6-53.2) for females. 85.8% (302/352) of patients met with a dietitian during their course of RT and 62.5% of patients who met with dietitian were compliant with the nutritional program. Compliance with the nutritional program resulted in 27% (HR: 0.73, 95% CI: 0.43, 1.26) and 31% (HR: 0.69, 95% CI: 0.50, 0.94) protection from death and disease progression. Lower pretreatment BMI was associated with a higher risk for death (HR: 0.94, 95%CI: 0.90, 0.99) and disease progression (HR: 0.96, 95% CI: 0.93, 0.99). Sarcopenia was not independently predictive for increased risk for overall death and disease progression. Laryngeal and oropharyngeal cancer patients treated with definitive RT who are compliant with an aggressive nutritional program appear to have improved outcomes. Sarcopenia is very common in this patient population and further studies exploring ways to increase compliance with nutritional programs are warranted.

Purpose/Objective(s)To determine the toxicity and efficacy of concurrent sunitinib and image-guided radiotherapy (IGRT) in patients with oligometastases. Based on preclinical evidence that sunitinib reverses immune suppression (Ozao-Choy, Cancer Research 2009;69:2514), we investigated its effect on myeloid cells in treated patients.Materials/MethodsEligible patients had 1 to 5 sites of metastatic cancer measuring ≤6 cm. The most common treatment sites were bone, liver, and lung. Patients were treated with concurrent sunitinib (Days 1–28) and IGRT (40–50 Gy in 10 fractions starting on Day 8). This was followed by maintenance sunitinib (50 mg daily, 4 weeks on/2 weeks off starting on Day 43) in 10 patients. The starting dose was sunitinib 25 mg and IGRT 40 Gy and doses were escalated in a ping-pong design with incremental increases in either sunitinib or IGRT. The Phase II dose is sunitinib 37.5 mg and IGRT 50 Gy.ResultsBetween February 2007 and November 2008, 29 patients with 51 metastatic lesions were enrolled, with a median follow-up of 11 months. Dose limiting toxicity consisting of neutropenia and thrombocytopenia was noted at a dose level 4 (sunitinib 50 mg, IGRT 50 Gy), particularly in patients with large liver tumors. At last follow-up, 11 patients (38%) are alive without evidence of progression. The 1-year local, event-free, and overall survival were 84%, 42%, and 66%, respectively. Among leukocyte subtypes, sunitinib causes a rapid decrease in monocytes (mean 43%). A decrease in monocytes within 7 days of sunitinib is associated with significantly increased 1-year progression-free survival (67% vs. 0%; p = 0.003). Flow cytometric analysis suggests that the observed effect of sunitinib on monocytes are primarily due to decreased Lin-CD33+CD11b+ myeloid derived suppressor cells (MDSC) and plasmacytoid dendritic cells. Functional assays suggested reversion of MDSC-mediated immune suppression in treated patients.ConclusionsThese data demonstrating major antitumor responses suggest that adding sunitinib to radiotherapy can achieve clinically significant radiosensitization without potentiating radiation toxicity. The prognostic value of an early decline in monocytes, which appears attributable to myeloid derived suppressor cells, suggests that reversion of immune suppression may contribute to better response to therapy. Purpose/Objective(s)To determine the toxicity and efficacy of concurrent sunitinib and image-guided radiotherapy (IGRT) in patients with oligometastases. Based on preclinical evidence that sunitinib reverses immune suppression (Ozao-Choy, Cancer Research 2009;69:2514), we investigated its effect on myeloid cells in treated patients. To determine the toxicity and efficacy of concurrent sunitinib and image-guided radiotherapy (IGRT) in patients with oligometastases. Based on preclinical evidence that sunitinib reverses immune suppression (Ozao-Choy, Cancer Research 2009;69:2514), we investigated its effect on myeloid cells in treated patients. Materials/MethodsEligible patients had 1 to 5 sites of metastatic cancer measuring ≤6 cm. The most common treatment sites were bone, liver, and lung. Patients were treated with concurrent sunitinib (Days 1–28) and IGRT (40–50 Gy in 10 fractions starting on Day 8). This was followed by maintenance sunitinib (50 mg daily, 4 weeks on/2 weeks off starting on Day 43) in 10 patients. The starting dose was sunitinib 25 mg and IGRT 40 Gy and doses were escalated in a ping-pong design with incremental increases in either sunitinib or IGRT. The Phase II dose is sunitinib 37.5 mg and IGRT 50 Gy. Eligible patients had 1 to 5 sites of metastatic cancer measuring ≤6 cm. The most common treatment sites were bone, liver, and lung. Patients were treated with concurrent sunitinib (Days 1–28) and IGRT (40–50 Gy in 10 fractions starting on Day 8). This was followed by maintenance sunitinib (50 mg daily, 4 weeks on/2 weeks off starting on Day 43) in 10 patients. The starting dose was sunitinib 25 mg and IGRT 40 Gy and doses were escalated in a ping-pong design with incremental increases in either sunitinib or IGRT. The Phase II dose is sunitinib 37.5 mg and IGRT 50 Gy. ResultsBetween February 2007 and November 2008, 29 patients with 51 metastatic lesions were enrolled, with a median follow-up of 11 months. Dose limiting toxicity consisting of neutropenia and thrombocytopenia was noted at a dose level 4 (sunitinib 50 mg, IGRT 50 Gy), particularly in patients with large liver tumors. At last follow-up, 11 patients (38%) are alive without evidence of progression. The 1-year local, event-free, and overall survival were 84%, 42%, and 66%, respectively. Among leukocyte subtypes, sunitinib causes a rapid decrease in monocytes (mean 43%). A decrease in monocytes within 7 days of sunitinib is associated with significantly increased 1-year progression-free survival (67% vs. 0%; p = 0.003). Flow cytometric analysis suggests that the observed effect of sunitinib on monocytes are primarily due to decreased Lin-CD33+CD11b+ myeloid derived suppressor cells (MDSC) and plasmacytoid dendritic cells. Functional assays suggested reversion of MDSC-mediated immune suppression in treated patients. Between February 2007 and November 2008, 29 patients with 51 metastatic lesions were enrolled, with a median follow-up of 11 months. Dose limiting toxicity consisting of neutropenia and thrombocytopenia was noted at a dose level 4 (sunitinib 50 mg, IGRT 50 Gy), particularly in patients with large liver tumors. At last follow-up, 11 patients (38%) are alive without evidence of progression. The 1-year local, event-free, and overall survival were 84%, 42%, and 66%, respectively. Among leukocyte subtypes, sunitinib causes a rapid decrease in monocytes (mean 43%). A decrease in monocytes within 7 days of sunitinib is associated with significantly increased 1-year progression-free survival (67% vs. 0%; p = 0.003). Flow cytometric analysis suggests that the observed effect of sunitinib on monocytes are primarily due to decreased Lin-CD33+CD11b+ myeloid derived suppressor cells (MDSC) and plasmacytoid dendritic cells. Functional assays suggested reversion of MDSC-mediated immune suppression in treated patients. ConclusionsThese data demonstrating major antitumor responses suggest that adding sunitinib to radiotherapy can achieve clinically significant radiosensitization without potentiating radiation toxicity. The prognostic value of an early decline in monocytes, which appears attributable to myeloid derived suppressor cells, suggests that reversion of immune suppression may contribute to better response to therapy. These data demonstrating major antitumor responses suggest that adding sunitinib to radiotherapy can achieve clinically significant radiosensitization without potentiating radiation toxicity. The prognostic value of an early decline in monocytes, which appears attributable to myeloid derived suppressor cells, suggests that reversion of immune suppression may contribute to better response to therapy.

As locoregional therapy becomes more effective for head and neck squamous cell carcinoma (HNSCC), appreciating competing risks of mortality becomes increasingly important. Prior studies suggested an increase in strokes among patients with HNSCC treated with radiation therapy (RT), but lacked an appropriate control group. We investigated the impact of head and neck RT on long-term risk of stroke. The rate of inpatient hospitalization for stroke and stroke-specific mortality was analyzed in patients with stage I-IVB HNSCC diagnosed between 1988 and 2000 by querying the SEER database and Medicare claims records. Analysis was limited to ≥5 years of follow-up because strokes occurring within 5 years are unlikely to be radiation-induced. Time-to-event curves were generated using the Kaplan-Meier method and univariable analysis was made using the chi-square and log-rank tests. A multivariable Cox model was calculated using significant covariates on univariable analysis. Of the 9738 patients meeting selection criteria, 6164 (63.3%) received RT. Median follow-up was 8.5 years (range 5.0-17.4). Pairwise comparisons were made depending on whether patients received RT. Patients with RT were older and had more advanced primary and nodal disease (p < 0.01). The 10-year freedom from stroke was 90.0% (RT) and 92.5% (no RT) (p = 0.01). The incidence of stroke was 8.3/1000 person-years with RT vs. 7.6/1000 person-years without RT. However, there was no significant difference in 10-year stroke-specific mortality (1.9% w/ RT vs. 2.0% w/o RT, p = 0.57). On Cox multivariable analysis, we found that RT (HR 1.38, CI 1.17-1.64, p < 0.01), year of diagnosis (HR 1.13, CI 1.10-1.16, p < 0.01), age (HR 1.06, CI 1.06-1.07, p < 0.01), and race (HR 1.50, CI 1.19-1.89) were predicative of increased risk of hospitalization for strokes. The increased risk for stroke associated with RT was greatest in patients age ≤60 (HR 2.18, CI 1.43-3.35, p < 0.01) and with negative nodes (HR, 1.44, CI 1.20-1.72, p < 0.01). There is a small but statistically significant increase in long-term stroke incidence in the cohort treated with RT. However, RT was not associated with an increase in stroke-related mortality. With recent improvements in RT-based therapies and changes in demographics for HNSCC, strategies to decrease the risk of stroke are worthy of consideration.

306 Background: Preclinical data suggest that SU enhances the efficacy of radiotherapy. We tested the combination of SU and hypofractionated IGRT in a cohort of patients with historically incurable distant metastases. Methods: Eligible patients had 1 to 5 sites of metastatic solid tumors measuring ≤ 6 cm. The most common tumor types treated were head and neck, liver, lung, kidney, and prostate cancers. Patients were treated with concurrent SU (25 to 50 qd d 1–28) and IGRT (40 to 50 Gy in 10 fractions d 8–19). Following IGRT, patients could either receive maintenance SU (50 mg daily, 4 weeks on/2 weeks off starting on d 43) or alternate forms of systemic therapy. Most patients were treated with the recommended phase II dose of SU 37.5 mg and IGRT 50 Gy. Maintenance SU was used in 40% of patients. Results: Between 2/07 and 6/08, 43 patients with 81 metastatic lesions were enrolled with a median follow up for surviving patients was 20.1 months (range, 5–37 months). The incidence of acute grade ≥ 3 toxicities was 33%, most commonly myelosuppression, bleeding and abnormal liver function tests. The 2-year estimates for local control and distant control were 74% and 43%, respectively. The 2-year estimates for progression- free survival and overall survival were 39% and 46%, respectively. To date, 15 (35%) patients were alive without evidence of disease, 6 (14%) were alive with distant metastases, 13 (30%) were dead from distant metastases, 1 (2%) was dead from local progression, 6 (14%) were dead from comorbid illness, and 2 (5%) were dead from treatment-related toxicities. Predictors of improved progression-free survival were genitourinary primary tumor (HR 0.18; p=0.04), IGRT dose > 40 Gy (HR 0.21; p=0.005), number of metastases (HR 2.22; p=0.006) and maintenance SU (HR 0.31; p=0.06). Flow cytometry demonstrates a significant reduction in immune suppressive myeloid derived suppressor cells and T regulatory cells in SU treated patients. Conclusions: Concurrent SU and IGRT achieves durable local and distant control in a significant subset of patients with oligometastases, particularly patients with genitourinary primary tumors with ≤ 2 distant metastases. [Table: see text]

6087 Background: Although adjuvant RT is often recommended for locally advanced HNSCC, its effect on OS or cancer-specific survival (CSS) has not been clearly demonstrated. Methods: Within the Surveillance, Epidemiology, and End Results (SEER) Database, we selected patients with locally invasive but node negative (SEER stage 2) or node positive HNSCC (SEER stage 3–4) treated either with surgery alone (S) or surgery and radiation (S+RT). This analysis included 13,145 patients from the SEER 17 database diagnosed between 1988 and 2001. Exclusion criteria included distant metastases, no RT records or death within 3 months of surgery. The median follow-up was 4.7 years. Results: Adjuvant RT was utilized in 55% of patients with stage 2 and 84% of stage 3–4 HNSCC. For Stage 2 HNSCC, adjuvant RT was associated with lower 5 year OS on univariate analysis (46.32% for S+RT vs. 49.76% for S, p=0.016) but not on multivariate analysis (HR 1.00, p=0.93). For Stage 3 HNSCC, RT improved 5 year OS associated with RT on univariate analysis (52% for S + RT vs. 41% for S, p<0.001) and multivariate analysis (HR 0.80, p=0.002). For Stage 4 HNSCC, RT significantly improved 5 year OS on univariate analysis (35% for S + RT vs. 25% for S, p<0.001) and multivariate analysis (HR 0.75, p<0.001). The addition of RT improved 5 year CSS for both stage 3 (59.7% vs. 51.4%) and stage 4 HNSCC (42.1% vs. 32.8%). Conclusions: In the largest reported analysis of adjuvant RT in locally advanced HNSCC, adjuvant RT results in an approximately 10% absolute increase in 5-year CSS and OS for node-positive HNSCC compared to S alone. The absolute benefit of RT is underestimated on univariate analysis because patients with poor prognostic factors are more frequently selected for adjuvant RT. Outcomes in this high-risk population remain suboptimal, emphasizing the need for continued investigation of innovative treatment approaches. No significant financial relationships to disclose.