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8510 Background: Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. Methods: Patients with stage III NSCLC or unresectable stage II NSCLC, ECOG performance status 0-1, and no contraindications to protocol-specified therapy were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) ≥ 50% underwent baseline FDG-PET/CT, received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. The primary study endpoint was one-year progression-free survival (PFS). Here we report response rates following induction pembrolizumab, PFS and overall survival (OS) rates, and adverse event rates (CTCAE v. 4.03). Results: Twenty-five subjects with PD-L1 TPS ≥ 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 71 (interquartile range [IQR] 62 to 77). One subject had stage II disease, 13 had stage IIIA disease, nine had stage IIIB disease, and two had stage IIIC disease. Median PD-L1 TPS was 75% (IQR 60 to 80%). Two subjects (8%) developed disease progression during induction pembrolizumab, and two subjects discontinued pembrolizumab after one infusion due to immune-related adverse events. Using RECIST 1.1 criteria, 12 subjects (48%) exhibited a partial (n = 11) or complete (n = 1) response following induction pembrolizumab on CT. Using PERCIST criteria, 12 subjects (48%) exhibited a partial response following induction pembrolizumab on PET. Four subjects had responses on PET but not on CT, and four had responses on CT but not on PET. With a median follow-up duration of 13 months, the actuarial 1-year PFS rate is 74%, and the actuarial 1-year OS rate is 95%. Grade 3 adverse events have been limited to single cases of anemia, arthritis, diarrhea, esophagitis, and pneumonitis, and no grade 4-5 adverse events have occurred. Exploratory analyses suggest that response to induction pembrolizumab on PET predicts efficacy of this treatment approach, with a 1-year PFS rate of 100% for responders, compared to 61% for non-responders (logrank p = 0.007). Conclusions: Treatment with pembrolizumab and risk-adapted radiotherapy is a promising treatment approach for LA-NSCLC patients with PD-L1 TPS ≥ 50%. Response on PET following induction pembrolizumab may be useful for identifying patients who can be treated successfully without chemotherapy. Clinical trial information: NCT03523702.

Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on treatment with stereotactic body radiotherapy (SBRT) for patients with early-stage non–small-cell lung cancer. ASCO has a policy and set of procedures for endorsing and/or adapting clinical practice guidelines that have been developed by other professional organizations. Methods The ASTRO Evidence-Based Guideline for Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer was reviewed for developmental rigor by methodologists. An ASCO Expert Panel updated the literature search and reviewed the guideline content and recommendations. Results The ASCO Expert Panel determined that the recommendations from the ASTRO guideline, published in 2017, are clear, thorough, and based on the most relevant scientific evidence. ASCO statements and minor modifications were added to enhance the applicability of the ASTRO guideline for the broader ASCO audience. Recommendations For standard operative risk patients with stage I NSCLC, SBRT is not recommended outside of a clinical trial. Lobectomy with systematic lymph node evaluation remains the recommended treatment, although a sublobar resection may be considered in select clinical scenarios. Recommendations are provided regarding the use of SBRT in high operative risk patients and for inoperative patients, including in challenging scenarios where tumors are: centrally located, > 5 cm in diameter, lacking tissue diagnosis, synchronous primary or multifocal, second primary after pneumonectomy, proximal to or involved with mediastinal structures, abutting the chest wall, or recurring after previous treatment. Qualifying statements are included to provide further guidance for implementation, and the importance of a discussion of treatment options among members of the multidisciplinary cancer care team is emphasized. Additional information is available at: www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .

e20525 Background: Treatment for inoperable stage II-III non-small cell lung cancer (NSCLC) involves aggressive chemo-radiotherapy (CRT). While outcomes have improved with immunotherapy, some patients transition to hospice or die early in their treatment course. To help identify these patients, we developed a predictive model for early poor outcomes in NSCLC patients treated with curative intent. Methods: In a statewide consortium involving 27 sites, information was collected prospectively on stage II-III NSCLC patients who received curative CRT from April 2012 to November 2019. We defined an early poor outcome as termination of treatment due to hospice enrollment or death within 5 months of initiating radiation therapy. Potential predictors included clinical characteristics and patient reported outcomes (PROs) from validated questionnaires. Logistic regression models were used to assess potential predictors and build predictive models. Multiple imputation was used to handle missing data. We used Lasso regularized logistic regression to build a predictive model with multiple predictor variables. Results: Of the total of 2267 included patients, 128 patients discontinued treatment early due to hospice enrollment or death. The mean age of the 128 patients was 71 years old (range 48-91) and 59% received concurrent chemotherapy. Significant uni-variable predictors of early hospice or death were advanced age, worse ECOG performance status, high PTV volume, short distance to normal tissue critical structures, high mean heart dose, uninsured status, lower scores on the Functional and Physical Well-Being scale and the Lung Cancer Symptoms sub-scale of the FACT-L quality of life instrument, as well as higher levels of patient-reported lack of energy, cough, and shortness of breath. The best predictive model included age, ECOG performance status, PTV volume, mean heart dose, patient insurance status, and patient-reported lack of energy and cough. The pooled estimate of area under the curve (AUC) for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%. Conclusions: Our models identified a combination of clinical variables and PROs that may help identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at a high risk of early hospice enrollment or death. These preliminary results are encouraging and warrant further evaluation in a larger cohort of patients.

8523 Background: In the landmark PACIFIC trial, adjuvant durvalumab after definitive chemoradiation for unresectable stage III non-small-cell lung cancer (NSCLC) produced a 11% absolute overall survival benefit at two years compared to placebo, and the US Food and Drug Administration approved durvalumab for this indication in February 2018. We investigated the real-world use of adjuvant durvalumab and other immune checkpoint inhibitors (ICI) in a contemporary cohort of patients. Methods: We identified patients with unresectable stage III (AJCC 8th edition) NSCLC treated with definitive chemoradiation from February 2018 to March 2020 from a statewide radiation oncology quality consortium, representing a mix of community (n=22 centers, 336 patients) and academic practice settings (n=5 centers, 64 patients) across the state of Michigan. Use of adjuvant durvalumab or other ICI (atezolizumab, nivolumab, or pembrolizumab) was ascertained at the time of routine three- or six-month follow-up after completion of chemoradiation. Baseline characteristics of patients treated with or without adjuvant ICI were compared with the Chi-squared test for categorical variables and a two-sided t-test for continuous variables. Results: Of 400 patients with unresectable stage III NSCLC treated with definitive chemoradiation, 268 (67%) received adjuvant ICI. Of these, the majority received durvalumab (86%) followed by pembrolizumab (7.5%) and nivolumab (6.0%). The proportion of patients receiving ICI remained stable throughout the study period with no discernable time trends. Eight-five percent of white patients received ICI compared with 77% of black patients (p=0.04), but there were no differences in gender (54.5% male in ICI vs 52.3% no ICI), current smoking (42.2% ICI vs 37.9% no ICI, p=0.68), number of comorbidities (29.5% with 3 or more comorbidities in ICI vs. 26.5% in no ICI, p=0.86), baseline oxygen use (8.9% ICI vs 10.6% no ICI, p=0.59), age (median 66.4 years [IQR 60.3-73.4] for ICI vs. 66.9 years [IQR 61.1-72.2] no ICI, p=0.89), treatment at an academic center (16.0% ICI vs 15.9% no ICI, p=0.97), or ECOG performance status (59.3% ECOG 0 in ICI vs 62.8% no ICI). Conclusions: In a broad range of academic and community-based practices across a state including 27 sites, only two-thirds of potentially eligible stage III NSCLC patients received adjuvant durvalumab or other ICI agents despite a proven overall survival benefit. Receipt of ICI was not strongly associated with baseline demographic or comorbidity variables. Further work will seek to clarify the patient-level reasons behind non-initiation of adjuvant ICI.

e21042 Background: Glycoprotein-A repetitions predominant protein (GARP), a cell surface docking and activating receptor for latent transforming growth factor β1 (LTGFβ1), has been implicated in promoting oncogenesis. We report recently that GARP-LTGFβ can be clipped by thrombin but its clinical significance remains unclear. Herein, we hypothesized that 1) the baseline plasma GARP-LTGFβ1 complex is associated with clinical stage of cancers; 2) the baseline and/or changes of plasma GARP-LTGFβ1 complex during chemo-radiotherapy is associated with overall survival (OS) in patients with NSCLC. Methods: This is a correlative study for patients with stage I-III NSCLC receiving chemo-radiotherapy. Levels of GARP-LTGFβ1 complex in platelet-poor plasma were determined by a modified ELISA at pre-RT, 2,4 weeks during-RT and post-RT. Values were calculated based on the following formula: (ODtest-ODnegative control)/ODpostive control-ODnegative control). The primary endpoint was OS, analyzed using the Kaplan-Meier method and Cox proportional hazard model. Platelet-poor plasma samples from healthy subjects were used as normal controls. Results: A total of 155 patients were included: 41 stage I-II, 111 stage III. There were 115 male, 50 female with a median age of 66 years. Compared to 13 normal controls (0.638, 95% CI:0.477-0.799), NSCLC patients had a significantly higher plasma GARP-LTGFβ1 (0.965, 95%CI: 0.881-1.048, p = 0.014). The same trend was observed for stage, higher level in more advanced stage (1.037, 95%CI: 0.930-1.145) vs for stage I-II (0.854, 95%CI: 0.720-0.988) (p = 0.0375). Univariate analysis demonstrated that age, gender, clinical stage, smoking history, histology, KPS, and radiation dose were significantly associated with OS. Post/pre RT GARP-LTGFβ1 complex (high vs. low HR = 0.384, p = 0.043) instead of pre-RT (p = 0.538), during RT (p = 0.739 for 2 weeks, p = 0.570 for 4 weeks) or post-RT (p = 0.507) plasma GARP-LTGFβ1 complex during the course of radiation therapy correlated significantly with OS under univariate analysis. On multivariate Cox regression models after adjusting for above significant clinical factors, the changes of plasma GARP-LTGFβ1 level had significance in correlating with OS (HR = 0.359, p = 0.0087). Conclusions: Baseline plasma GARP-LTGFβ1 were significantly associated with presence of cancer and advanced stages in NSCLC patients. Changes of GARP-LTGFβ1 level in plasma could be useful to predict outcomes and reflect the changes of immune status after chemoradiation.

6066 Background: Laryngeal bio-selection with induction chemotherapy (platinum + 5-FU infusion: PF) has been demonstrated to result in impressive rates of survival and organ preservation with moderate toxicities. We sought to reduce the toxicity of PF by substituting docetaxel (T) for 5-FU and improve the tumor response rate with the addition of the Bcl-xL inhibitor AT-101. Methods: Pts with advanced stage laryngeal cancer were treated with 1 cycle of T 75 mg/m2 + platinum (P) (cisplatin 100 mg/m2 or carboplatin AUC 6) and were randomized 2:1 to the addition of AT-101. Patients with a CR proceeded to chemoradiation (CRT) with concurrent weekly P. All pts with PR or NR underwent a second cycle of induction with TP + AT-101. Pts with a > 50% response (CR or PR) after the second cycle of induction chemotherapy underwent CRT. Pts with a ≤ 50% response (NR) underwent laryngectomy. PET-CT was performed 12 weeks after CRT. Pts with residual disease underwent salvage laryngectomy (SL). Results: 54 eligible pts were enrolled; 46 M, 8 F; median age 59; 26 T4; stage III 16, stage IV 38; site: 2 hypopharyngeal, 39 supraglottic, 11 glottic, 2 subglottic. After cycle 1 of induction, 2/54 (4%) died prior to assessment by DL and 2 were removed from protocol due to adverse events (AEs). 29/50 pts (58%) had ≥ 50% response, 3 of which had CR; 2 proceeded to CRT & 1 received a 2nd cycle of IC. 21/50 pts (42%) had < 50% response. A total of 48 pts received cycle 2 of IC. After the 2nd cycle, a total of 39/50 pts (78%) had ≥ 50% response & received CRT. No difference in response was seen with addition of AT-101. 11/50 pts (22%) had < 50% response- 8 had laryngectomy & 3 refused. Following CRT, 10 pts underwent SL, 2 for residual disease & 8 late SL. The organ preservation rate was 31/50 (62%). The most common grade 3/4 toxicities associated with IC were nausea 9%, neutropenia 9%, & infection 7%. 1 pt died of CNS hemorrhage unrelated to therapy & 1 from sepsis. The median follow-up time is 28 months. The 2 yr laryngectomy-free survival is 54% (95% CI:38-68) & 2 yr overall survival is 81% (95% CI: 64-90). Conclusions: AT-101 did not improve responses to P. Treatment with 2 cycles of IC with PT produced similar response rates to our institutional controls, but organ preservation was somewhat less following treatment with weekly P + RT. Toxicities were overall improved with this treatment strategy. Clinical trial information: NCT01633541.

TPS8571 Background: Concurrent chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC) can cause significant toxicities, and disease recurrence after treatment is common. We previously demonstrated that a dose-painted radiotherapy approach provides excellent local disease control and has a favorable toxicity profile. Consolidation immunotherapy was recently shown to improve outcomes after chemoradiotherapy for LA-NSCLC, and pembrolizumab monotherapy is now a standard of care for patients with advanced high PD-L1-positive NSCLC. We hypothesize that dose-painted thoracic radiotherapy and immunotherapy without chemotherapy will be safe and effective for the treatment of biomarker-selected patients with LA-NSCLC. Methods: Patients with a new diagnosis of unresectable stage II or stage III NSCLC and performance status 0-1 will be enrolled on this phase II trial at one of three participating institutions. Twenty-five subjects with PD-L1 Tumor Proportion Score (TPS) of at least 50% will receive three cycles of induction pembrolizumab (200 mg every 3 weeks). Subjects then receive 20 fractions of dose-painted radiotherapy, where lesions with metabolic tumor volume exceeding 20 cc on FDG-PET receive a dose of 55 Gy, while smaller lesions receive a dose of 48 Gy. Subjects then receive 12 additional cycles of pembrolizumab. The primary endpoint is progression-free survival one year following study enrollment, which we hypothesize will be achieved for at least 65% of study subjects. Other endpoints include overall survival, distant metastasis-free survival, freedom from intrathoracic disease progression, adverse events, patient-reported outcomes, and physical activity metrics captured using wearable devices. In addition, we will explore markers of immune activation as prognostic factors. Approximately 38 patients with PD-L1 TPS below 50% will receive standard chemoradiotherapy and adjuvant therapy to serve as a contemporary comparison cohort. SPRINT is an innovative biomarker-driven study that explores a paradigm shift in the local and systemic therapy used to treat LA-NSCLC. This trial opened in August of 2018, and 5 subjects have been enrolled to date. Clinical trial information: NCT03523702.

e17539 Background: University of Michigan Cancer Center (UMCC) protocol 9520 treated pts with stage III/IV LSCC with 1 cycle of cisplatin & 5-FU (PF) to select pts for definitive therapy. Pts whose tumors attained a ≥ 50% response after 1 cycle of PF underwent CRT. Those who had a < 50% response to IC were treated with total laryngectomy + RT. Correlative science from UMCC 9520 demonstrated that an increased percentage of CD4+ cells predicted response to PF & suggested improved survival. Published retrospective data also has demonstrated that lower NLR & higher LMR are associated with improved prognosis in p16- SCC of the oropharynx & pyriform sinus, while cancers with higher NLR & lower LMR have a worse prognosis. Similar to our previous correlative analysis, this study is also a secondary analysis of the predictive value of NLR & LMR in a prospective trial of bio-selective IC. Methods: NLR & LMR were calculated from pre-treatment CBC for all pts (N = 87) enrolled onto UMCC 9520. Results: All 87 pts received IC with PF. 65/87 (75%) responded to IC & received CRT. Results of response to IC compared the NLR & LMR ratios by logistic regression analysis & was used to create NLR & LMR cut points. Among pts with LMR ≥ 3, the response rate (RR) was 89% while the RR was 64% with LMR < 3 (p = 0.008). Among pts with NLR < 4.7, the RR was 79% while the RR of pts with > 4.7 was 58% (p = 0.06). Overall & disease specific survivals were greater in pts with LMR ≥ 3, (log rank p = 0.04, p = 0.03, respectively). Conclusions: Higher LMR & lower NLR are associated with favorable responses to IC & LMR ≥ 3 is associated with improved survival. This data correlates strongly with our published results from UMCC 9520, whereby elevated circulating CD4+ lymphocytes predict response to IC & survival. This important information may help direct the design of future laryngeal preservation protocols.

5525Background: DNA immunotherapies targeting HPV oncogenes, E6 and E7, have demonstrated clinical efficacy in pre-invasive cervical lesions. Here, we assessed the feasibility of chemoradiation and...

6071Background: We designed a single arm phase II trial to determine the efficacy and toxicity of concurrent cetuximab (C) radiotherapy (RT) in patients non-eligible for standard chemotherapy. Non-...

87 Background: Following radiation therapy (RT), gynecologic oncology patients report high rates of sexual dysfunction. However, little is known regarding communication of sexual health among these patients and their healthcare providers. The aim of this study was to assess the beliefs/attitudes of patients regarding sexual history taking. Methods: Survey results were obtained from 75 women who presented for follow up care for gynecologic cancers in the radiation oncology department. The surveys assessed patient beliefs about sexual health and its impact on overall quality of life, the role practitioners should play in obtaining an accurate sexual history, and preferences and level of embarrassment regarding sexual history collection. Overall level of sexual functioning was assessed using the Female Sexual Function Index (FSFI). Chi-squared tests were used to analyze categorical variables and logistic regression modeling was used to predict agreement with survey statements. Results: Most subjects were white and married with a mean FSFI score of 9.9 [(SD = 10.3) sexual dysfunction is defined as < 26.5]. 78.7% agreed that sexual function is an important component of overall health, and only 12.0% reported embarrassment about discussing their sexual health with healthcare providers. 62.79% agreed that medical providers should take a sexual history on a regular basis. However, 58.7% and 22.7% of women report never or almost never being asked about their sexual health by their primary care physician or Ob/Gyn, respectively. Approximately two-thirds of women expressed a preference to have a female provider obtain their sexual health history. Conclusions: Gynecologic cancer patients s/p RT report low sexual function scores. A majority agree that sexual function is essential to overall health. They report little embarrassment regarding discussions of sexual health, yet, note limited discussion about the topic with their healthcare providers. This work highlights the need for improvements in communication about sexual health. We suggest that healthcare providers caring for women with gynecologic cancers should more regularly inquire about their patients’ sexual health and function.

e20606 Background: Concurrent chemotherapy and radiation (CCRT) to treat head and neck cancer (HNCa) is associated with significant reductions of weight, mobility and quality of life (QoL). Support...

55 Background: Palliative care services enhance quality of life in patients with advanced malignancies and are an integral component of multidisciplinary cancer care. They provide symptom control and psychosocial support for patients and family members. A survey in non-VHA cancer centers showed that despite availability of palliative care programs, there was wide variability in the use of these services (Hui et al, JAMA 2010). Palliative care services are a component of the VHA medical benefits package. We sought to determine the ease of access to palliative care services and provider satisfaction among VHA Radiation Oncologists. Methods: VHA-based Radiation Oncologists were identified using the National VHA Radiation Oncology list serve group. All practicing Radiation Oncologists were surveyed to determine the extent of Palliative Care Services available to them and to measure their level of satisfaction with these services. Eighty two surveys were electronically mailed to practitioners at the 38 active VHA Radiation Oncology sites, followed by a reminder phone call.This survey was conducted over a four week period in May of 2014. Results: Sixty four of the 82 surveys distributed over the 4 week period, or 78% were completed. They represent 89% (34/38) of VHA Radiation Oncology Services. All respondents had Palliative Care Services available to them and 98% were happy with the services rendered by the Palliative Care teams. Conclusions: All VHA-based Radiation Oncologists who responded to this survey have access to local VHA based Palliative Care Services. This represented 82% of VHA Radiation Oncology practitioners and 98% were satisfied with the services rendered. Further studies should explore the scope and extent of palliative care involvement including when these services are integrated into the management of patients with advanced malignancies, availability of outpatient palliative care services and variations in care delivery. Radiation therapy is utilized in over 50% of patients with malignancy, often in advanced disease for symptom management and standard guidelines integrating radiotherapy and palliative care should be developed.

52 Background: The rapid evolution of technology in the treatment of cancer has paralleled other technological advancements in modern society. Intensity Modulated Radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Brachytherapy (BT), Cone Beam Computed Tomography (CBCT), Stereotactic Radiosurgery (SRS), and Stereotactic Body Radiotherapy (SBRT) facilitate treatment with higher, more conformal radiation doses, potentially improving cancer control while reducing normal tissue toxicity. Recent Surveillance, Epidemiology and End Results (SEER) program data and physician surveys indicate prostate BT is declining and the integration of SRS and SBRT is slower compared to IMRT. As utilization of technology increases, an understanding of its availability within the VHA is necessary to ensure quality and patient safety. Methods: An electronic survey was sent to 82 Radiation Oncologists (ROs)at 38 active VHA Radiation Oncology Centers with subsequent follow-up phone calls. The survey occurred from May-June 2014. ROs were queried on the availability of advanced RT technologies including IMRT, IGRT, BT, CBCT, SRS and SBRT at their facility. Practitioner specific details: years in practice, academic appointment and VHA employment status were collected. Results: Responses were obtained from 62 ROs representing 75% of VHA ROs and 34 or 89% of facilities. Full time VHA employees made up 60% of respondents with 35% in practice for 20 years; 71% held an academic appointment. The Table shows on site availability of advanced RT technologies within the 34 VHA sites that responded. Conclusions: For veterans receiving cancer treatment, VHA ROs are able to routinely use IMRT and IGRT with CBCT capabilities. However, stereotactic (SRS and SBRT) and BT services are less available, and may require referrals externally or to other VHA facilities. Limited availability of SRS and SBRT parallels the community experience. Likewise the decreasing utilization of BT is common to the VHA and private sector. SBRT, SRS and BT require significant expertise and technology. [Table: see text]

e20632 Background: Population studies indicate that 40% of cancer patients use CAM. Most are not well informed of their chosen CAM and do not discuss it with their healthcare providers. However, no...

9607 Background: Head and neck cancer (HNCa) treatment results in unfavorable changes in physical function, body composition and quality of life. The ability of these patients to perform physical activity after cancer treatment has not been previously evaluated. To develop clinical models that will guide the care of HNCa survivors, it is important to characterize these physical activity changes. Methods: From 2008 to 2011, as part of an institutional Head and Neck SPORE longitudinal epidemiology project, health survey data including the Physical Activity Scale in the Elderly (PASE) was collected at baseline, 6 months and annually thereafter. The PASE score assesses the hours doing leisure time physical activity, walking, occupational, and household chores over a typical 7-day period. During follow up, subjects deceased, were lost to follow-up, or refused survey completion. Paired t-test was used to compare the mean PASE score at various endpoints from baseline. Results: 294 HNCa patients completed the survey at baseline. Following a mean follow-up of 25.7 (+/-11.9) months, 66%(n=193), 73%(n=215) and 42%(n=124) of patients completed the assessment at 6-months, 1-year and 2-years respectively. Majority (97%) of the HNCa patients had oropharynx, oral cavity or larynx cancer, which were treated by chemoradiation (36%), surgery followed by chemoradiation (23%) or surgery alone (20%). Results of the PASE score revealed the lowest levels of physical activity at baseline with steady statistically significant improvement at each subsequent timepoint (p