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The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ-preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon-derived cell-free (cf)DNA (c-cfDNA) using a tissue-specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon-specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70-0.92; P 0.0001). Baseline c-cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c-cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c-cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/mL, respectively; P = 0.013). Increased c-cfDNA after one week of therapy was also associated with disease recurrence. Methylation-based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de-escalation strategies.

Radiotherapy has an important role in the treatment of brain metastases (BrM) but carries risk of short and/or long-term toxicity, termed radiation-induced neurotoxicity (RIN). As the diagnosis of RIN is crucial for correct pa-tient management, there is an unmet need for reliable biomarkers for RIN. The aim of this proof-of concept study was to determine the utility of brain-derived circulating free DNA (BncfDNA), identified by specific methylation patterns for neurons, astrocytes, and oligodendrocytes, as RIN biomarkers. Twenty-four patients with BrM were monitored clinically and radiologically before, during and after brain radiotherapy, and blood for BncfDNA analysis (98 samples) was concurrently collected. Sixteen patients were treated with whole brain radiotherapy and eight patients with stereotactic radiosurgery. During follow-up nine RIN events were detected, and all correlated with significant increase in BncfDNA levels compared to baseline. Additionally, resolution of RIN correlated with de-crease in BncfDNA. Changes in BncfDNA were independent of tumor response. Elevated BncfDNA levels reflects brain cell injury incurred by radiotherapy, further research is needed to establish BncfDNA as a novel plasma-based biomarker for RIN.

ObjectivesStudies of depression in older Muslim Palestinians diagnosed with cancer are scarce. To gain insight into the psychological response and coping ability of this very large, globally distributed population, we collected data from older Muslim Palestinian people diagnosed with cancer concerning depression hope and perceived social support. Both hope and social support were selected because they can be manipulated through intervention and education, as shown in the geriatric literature. Data were compared to data collected from older Jewish Israeli people diagnosed with cancer. DesignThe study sample comprised 143 Muslim Palestinian and 110 Jewish Israeli people diagnosed with cancer, aged >=65. All participants were either in treatment for active disease or within six months of such treatment. Self-administered measures included depression (the Five-Item Geriatric Depression Scale), perceived social support (Cancer Perceived Agents of Social Support Questionnaire) and hope (Snyder’s Adult Hope Scale). ResultsHope and depression were both found to be significantly higher among the Muslim Palestinian patients than in the Jewish Israeli participants. In both samples, higher levels of hope were associated with lower levels of depression, with this correlation stronger in the Jewish Israeli group. ConclusionTo improve the psychological wellbeing of patients, healthcare providers must exercise cultural sensitivity in their interactions, respecting the perspectives of both the patients and their families. Incorporating the concept of hope into the therapeutic dialogue and language may improve psychological wellbeing and synchronize the needs and expectations of patients, caregivers, and healthcare professionals, resulting in more equitable, effective and value-oriented care.

Several liposome products have been approved for the treatment of cancer. In all of them, the active agents are encapsulated in the liposome water phase passively or by transmembrane ion gradients. An alternative approach in liposomal drug delivery consists of chemically modifying drugs to form lipophilic prodrugs with strong association to the liposomal bilayer. Based on this approach, we synthesized a mitomycin c-derived lipidic prodrug (MLP) which is entrapped in the bilayer of PEGylated liposomes (PL-MLP, Promitil®), and activated by thiolytic cleavage. PL-MLP is stable in plasma with thiolytic activation of MLP occurring exclusively in tissues and is more effective and less toxic than conventional chemotherapy in various tumor models. PL-MLP has completed phase I clinical development where it has shown a favorable safety profile and a 3-fold reduction in toxicity as compared to free mitomycin c. Clinical and pharmacokinetic studies in patients with advanced colo-rectal carcinoma have indicated a significant rate of disease stabilization (39%) in this chemo-refractory population and significant prolongation of median survival in patients attaining stable disease (13.9 months) versus progressive disease patients (6.35 months). The pharmacokinetics of MLP was typically stealth with long T½ (~1 day), slow clearance and small volume of distribution. Interestingly, a longer T½, and slower clearance were both correlated with disease stabilization and longer survival. This association of pharmacokinetic parameters with patient outcome suggests that arrest of tumor growth is related to the enhanced tumor localization of long-circulating liposomes and highlights the importance of personalized pharmacokinetic evaluation in the clinical use of nanomedicines. Another important area where PL-MLP may have an added value is in chemoradiotherapy, where it has shown a strong radiosensitizing effect in animal models based on a unique mechanism of enhanced prodrug activation and encouraging results in early human testing.

BACKGROUND Brain radiotherapy is the main therapeutic modality for brain metastases (BM), but carries short and long term toxicities, termed radiation-induced neurotoxicity (RIN), and classified to acute, early-delayed and late-delayed RIN according to its time onset. Although diagnosis of RIN is crucial for patient management, there is an unmet need for sensitive biomarkers for RIN. Here we report on a novel non-invasive biomarker for detection and monitoring RIN. As radiotherapy is known to induce brain cells apoptosis as well as BBB disruption, we hypothesized that circulating cell free DNA fragments derived from dying brain cells will be elevated in the blood of patients with RIN. Using comparative methylome analysis we identified 13 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes, and astrocytes. We searched for these brain-derived cfDNA (bncfDNA) in plasma samples of patients following brain irradiation. METHODS We followed 24 patients treated by brain radiotherapy for BM by clinical and radiological examinations before, during and after treatment. In addition, we serially collected blood samples for DNA analysis, and correlated bncfDNA levels with clinical and radiological assessment. RESULTS Patient`s median age was 60 years. Most common primary tumor sites were breast (25%), lung (20.8%) and melanoma (12.5%). RIN was detected in 10 patients (62%). BncfDNA levels increased up to 292.4 fold in acute RIN, up to 138533.1 in early-delayed RIN, and up to 58.4 fold in late-delayed RIN. Resolution of RIN correlated with decrease in bncfDNA. Changes in bncfDNA levels were independent of tumor response and suggested to reflect both symptomatic and asymptomatic RIN. CONCLUSION Increase in bncfDNA levels characterizes RIN independent of tumor response. Thus, BncfDNA may serve as a novel biomarker for brain cells death incurred by radiotherapy. Further studies are required to explore the clinical utility of bncfDNA as a RIN biomarker.

Purpose/objective(s) The benefit of radiotherapy (RT) in poor-prognosis patients with leptomeningeal disease (LMD) is not well characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT. Materials/methods Patients with breast cancer and classic radiographic LMD (36% cytology-confirmed) treated with palliative whole brain and/or partial spine RT between 2000-2020 at a single academic institution were included in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method, and differences in subgroups were determined using the log-rank test. Multivariate Cox proportional hazards models adjusting for estrogen receptor (ER), progesterone receptor (PR), HER2, ECOG performance status (ECOG), and systemic disease status assessed factors associated with OS. Domain-specific and any symptom improvement were ascertained by chart review of patient- and physician-report, and a multivariate logistic regression model developed incorporating ER/PR status, HER2 status, ECOG and steroid use to identify factors associated with symptom benefit. Results Among 64 patients of median age 50 years (IQR 31-69), the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had concurrent brain metastases, and 57% of patients had ER+ and/or PR+ tumors, 22% HER2+, and 38% triple-negative disease. Among 92% of symptomatic patients whose primary symptom domains were cranial nerve deficit (34%), sensory/motor deficits due to intracranial disease (25%) sensory/motor deficits due to spine disease (27%), and headaches/nausea (14%), 42% had > 1 reported symptom domain. Two-thirds of patients were on steroids prior to RT, and only 13% of patients received intrathecal therapy. Following a median dose of 30 Gy in 10 fractions, symptom improvement in any domain was noted in 59% of patients with symptoms pre-RT, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in > 1 symptom domain. Overall survival was only 2.1 months (95% CI 1.8-3.3) in the triple-negative subgroup, and higher among patients with HER2+ disease (5.2 months, 95% CI 3.8-NR, P = 0.003). On multivariate analysis, ER+ (HR 0.4, 95% CI 0.2-0.8, P = 0.009) and HER2+ (HR 0.4, 95% CI 0.2-0.9, P = 0.018) disease were associated with improved OS. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2-11, P = 0.029). Conclusion Even in this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yields symptomatic improvement, and may especially be of benefit among better-prognosis patients with hormone receptor-positive or HER2-positive disease. Author disclosure J. Takayesu: None. E. Sapir: Research Grant; LipoMedix, BioProtect. Consultant; AstraZeneca, MSD, Belong.Life. J. Xie: None. Y. Sun: None. A. Morikawa: Institutional research; Novartis, Lilly, Takeda, Eisai/H3b, Pfizer/National Comprehensive Cancer Network. L. Junck: Advisory Board; Orbus Therapeutics. D. Leung: None. Y. Umemura: None. J. Heth: None. W. Al-Holou: None. D.R. Wahl: Research Grant; Agios Inc, Innocrin Inc, American Cancer Society, NIH. Stock Options; Lycera Inc. Advisory Board Member; Agios Inc. T.S. Lawrence: None. C. Mayo: None. J.A. Hayman: Research Grant; Blue Cross Blue Shield of Michigan. M.M. Kim: Research Grant; Blue Earth Diagnostics.

Objective The benefit of radiotherapy (RT) in patients with leptomeningeal disease (LMD) is poorly characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT. Methods Patients with breast cancer-related classic radiographic LMD (36% cytology-confirmed) were treated with palliative whole brain and/or partial spine RT between 2000–2020 at a single academic institution in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method. A multivariate logistic regression model incorporating ER/PR status, HER2 status, ECOG and steroid use was developed to identify factors associated with symptom benefit, which was ascertained retrospectively by chart review. Results Among 64 patients, the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had brain metastases, and 57% of patients had ER+ and/or PR+, 22% HER2+, and 38% triple-negative disease. Of the symptomatic patients (94%), primary symptom domains included cranial nerve deficits (34%), sensory/motor deficits from intracranial disease (25%) or spinal disease (27%), and headaches/nausea (14%), with 42% of patients reporting >1 symptom domain. Two-thirds of patients were on steroids prior to RT, and 13% of patients received intrathecal therapy. OS was 3.75 months. Following a median dose of 30Gy in 10 fractions, 59% of symptomatic patients experienced symptom improvement, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in >1 symptom domain. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2–11, p=0.029). Conclusions In this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yielded symptomatic improvement, and may be particularly beneficial among better-prognosis patients with hormone receptor-positive disease.

e24118 Background: Patient-centered healthcare has focused on incorporating the values of patients (Pts) during clinical decision-making. Accordingly, assessments are often executed with patient reported outcome measurements (PROMs). In the context of tumors located in a sexual organ, life quality may be predicated on the perception of the patient’s partner when such a relational dyad exists. Therefore, we created a “partner” reported outcome measurements (pROMs). Accordingly, we sought to query the interconnection of PROMs and pROMs in the setting of early breast cancer (EBC) by using a digital health technology application. Methods: In this ongoing study, 93 EBC Pts and 18 partners, active members of Belong.life, a social engagement platform for cancer Pts and caregivers, replied anonymously and voluntarily to a targeted survey related to sexuality and intimacy parameters in the Pts and their partners. 72% of the partners were 50-69 years of age (yoa), 61% were Caucasian. 70% of the Pts were 50-69 yoa and 72% Caucasian. 72% of the Pts and 78% of the partners had college and university degrees. At diagnosis 78% of the Pts had Stages 1-2, 44% had breast conserving surgery, and most (78%) received chemotherapy. Results: We report the interim results of the first 14 patients-partner dyads. At the time of diagnosis, 86% of partners and 50% of Pts were very or extremely concerned about the patient’s health. Of note, 43% of Pts were not concerned at all or slightly concerned about their own health. With the passage of time, the concern about the patient’s health had decreased to 50% among the partners and 28% among the Pts. Regarding intimacy and sexuality issues prior to the EBC diagnosis, 64% of the Pts didn’t have any complaints but it changed dramatically after diagnosis with 50% mentioning less sex drive and 40% less intimacy. In the partners group 67% didn’t have complaints before the diagnosis but 28% voiced complaints after the diagnosis. Only half of Pts and partners felt they could speak freely about their mutual feelings. Only 23% of Pts and 11% of partners indicated they would agree to seek professional help for issues related to sexuality and intimacy. Ultimately, 71% of Pts and 79% of partners felt happy with each other. Conclusions: Partners were very concerned about the health of Pts; however, the dyad was not always synchronized. Notwithstanding it, the dyad adjusted their concerns during the course of treatment. Body changes had modest effect on the relationship. While dissatisfaction of sexual activity was evident it did not significantly affect the feelings of patients and partners towards each other. The development of pROMs could re-synchronize the dyad thereby creating a more meaningful cancer journey.

INTRODUCTION: Radiotherapy is a common treatment for brain metastases. However, it is commonly associated with central nervous system (CNS) toxicity. There are no biomarkers for early detection of radiotoxicity. Here we explore the utility of cell-free circulating DNA (cfDNA) for detection of brain cells death in the context of brain metastases. Using comparative methylome analysis we have previously identified 12 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes and astrocytes. These brain-specific methylation markers were identified in plasma of patients suffering from multiple sclerosis, as well as traumatic and ischemic brain damage. We hypothesize that brain-derived cell-free DNA (bncfDNA) can be identified in patients suffering from brain metastases receiving radiotherapy, and can potentially be used as a biomarker to help guide treatment. MATERIALS AND METHODS: We recruit oncological patients treated by brain radiotherapy for brain metastases. We serially assess each patient before, during and after treatment by neurological examination and MRI studies. In each study visit a blood sample is collected for bncfDNA measurement. RESULTS: Preliminary results on samples from 22 patients show elevation of bncfDNA in patients suffering from brain metastases (average 8501 copies/ml; range 0-112336 copies/ml) compared with an extremely low background in healthy individuals (average 6 copies/ml; range 0–33 copies/ml); p < 0.0001). We observed elevation of cfDNA derived from neurons, oligodendrocytes and astrocytes. Next, we studied bncDNA levels following brain radiotherapy. Preliminary results from a patient suffering from an acute central facial paralysis during radiotherapy show clinical correlation of bncfDNA levels with neurological impairment related to acute radiotoxicity. Other patients are still followed-up with bncfDNA measurement during and after radiotherapy. CONCLUSION: BncfDNA reflects brain cells death incurred by metastases, as well as damage associated with radiotherapy, and may serve as circulating biomarker for neurotoxicity in patients suffering from brain metastases.

Objective To identify predictive factors of severe long-term toxicity after re-irradiation of recurrent/persistent or second-primary head and neck cancer. Methods Outcomes and treatment plans of patients who underwent modern IMRT based re-irradiation to the head and neck from 2008–2015 were reviewed. Co-variables including demographic, clinical and oncologic factors, as well as interval to re-irradiation and re-irradiated planning tumor volume (PTV) were analyzed as predictors of developing severe (CTCAE grade ⩾ 3) long-term toxicity with death as a competing risk. Results A total of 66 patients who met inclusion criteria were eligible for analysis. A median re-irradiation dose of 70 Gy was delivered at a median of 37.5 months after initial radiotherapy. Re-irradiation followed surgical resection in 25 (38%) patients, and concurrent chemotherapy was delivered to 41 (62%) patients. Median follow-up after re-irradiation was 23 months and median overall survival was 22 months (predicted 2 year overall survival 49%). Of the 60 patients who survived longer than 3 months after re-irradiation, 16 (25%) patients experienced severe long-term toxicity, with the majority (12 of 16) being feeding tube -dependent dysphagia. In multivariable analysis, shorter intervals to re-irradiation ( 100 cm 3 ) were independent predictors of developing severe long-term toxicity. Patients with longer disease-free intervals and smaller PTVs had a 94% probability of being free of severe toxicity at two years. Conclusion Selection of patients with longer re-irradiation intervals and requiring smaller re-irradiated PTVs can independently predict avoidance of severe long-term toxicity.

Due to the high incidence of recurrent squamous cell carcinoma of the head and neck and the toxicity profile of current salvage regimens, there is a need for tolerable and effective treatment options. We performed a retrospective matched case series to report our experience with recurrent high-risk patients who received capecitabine (CAP) therapy in the adjuvant setting after salvage therapy. The 5-year recurrence-free survival rates for the CAP and control cohorts were 54% (95% CI, 0.27%-0.75%) and 27% (95% CI, 0.09%-0.50%), respectively. Multivariable Cox modeling showed a significant improvement in recurrence-free survival in the CAP cohort (hazard ratio, 0.19; 95% CI, 0.04-0.92; P = .0392). While this was a respective analysis that could not control for all variables, these exploratory findings offer insights that may inform a prospective study to determine CAP efficacy.

BACKGROUND: Radiotherapy is a common treatment for brain metastases. However, it is commonly associated with central nervous system (CNS) toxicity, leading to functional disability. There are no biomarkers capable of detecting preclinical neurotoxicity for the purpose of early detection of radiation-induced CNS damage. Here we explore the utility of cell-free circulating DNA (cfDNA), shed from dying cells, for detection of brain cell death in the context of brain metastases. Using comparative methylome analysis we have previously identified 12 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes and astrocytes. These brain-specific methylation markers were identified in the plasma of patients suffering from multiple sclerosis, as well as traumatic and ischemic brain damage. We hypothesize that brain-derived cell-free DNA (bncfDNA) can be identified in patients suffering from brain metastases receiving radiotherapy, and can potentially be used as a biomarker to help guide treatment. MATERIAL AND METHODS: We recruit oncological patients treated by brain radiotherapy for brain metastases. We serially assess each patient before, during and after treatment by neurological examination. MRI studies are performed before and after radiotherapy in 2–3 months intervals. In each study visit a blood sample is collected for bncfDNA. We measure bncfDNA from serial blood samples of each patient, and correlate bncfDNA levels with clinical assessment. RESULTS: Preliminary results on samples from 22 patients show elevation of bncfDNA in patients suffering from brain metastases (average 8501 copies/ml; range 0-112336 copies/ml) compared with an extremely low background in healthy individuals (average 6 copies/ml; range 0–33 copies/ml); p

PurposeToconduct a large single-institution comparison of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes in similar groups of patients with hepatocellular carcinoma (HCC).Methods and materialsFrom 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed.ResultsThe TACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease, and baseline liver function. Patients treated with SBRT were older (65 vs 61years, P=.01), had smaller tumors (2.3 vs 2.9cm, P

Background: The association between sarcoidosis and malignancy is poorly defined. Sarcoidosis can precede, be diagnosed concurrently with, or follow malignancy. Objectives: We describe the clinical and radiological features of patients with sarcoidosis following malignancy to determine whether this association is causal or coincidental. Methods: We performed a search for all patients with confirmed sarcoidosis following malignancy in our institution during 2001-2015. Clinical and radiological features, bronchoscopic findings, bronchoalveolar lavage cell counts, and pulmonary function tests (PFTs) were reviewed to evaluate patterns of disease involvement. Details of the histological type of cancer, staging, treatment, and follow-up were reviewed. Results: Twenty-nine patients were identified. The most prevalent malignancies were breast cancer and lymphoma (24% each). Based on the incidence of these malignancies, we estimated the incidence of sarcoidosis was 175 times higher after lymphoma and 38 times higher after breast cancer as compared to the general population. Most patients had early stage cancer (stage I, II) (75%), and only 2 patients (7%) had recurrence of their malignancy after diagnosis of sarcoidosis. Sarcoidosis was diagnosed within 5 years of malignancy in over half the patients, 76% were asymptomatic and 69% had normal PFTs. Mediastinal lymphadenopathy was present in 81% of cases, hilar lymphadenopathy in 67%, and pulmonary parenchymal involvement in 41%. Fifty percent of patients had received Adriamycin, 38% cyclophosphamide, and 33% vincristine. Conclusions: Sarcoidosis following malignancy is indistinguishable from “idiopathic” sarcoidosis, although it is frequently asymptomatic. The high frequency of sarcoidosis after specific cancers but not others, suggests a causative association between malignancy and development of sarcoidosis.

Objective(s) Dysgeusia is a significant factor reducing quality of life and worsening dysphagia in patients receiving chemoradiation therapy for head and neck cancer. The factors affecting dysgeusia severity are uncertain. We investigated the effects on patient-reported dysgeusia of doses to the oral cavity, salivary output (required to dissolve food particles), and patient-reported xerostomia. Methods and Materials Seventy-three patients with stage III to IV oropharyngeal cancer (OPC) (N=73) receiving definitive intensity modulated radiation therapy concurrently with chemotherapy participated in a prospective, longitudinal study of quality of life (QOL), including assessment of patient-reported gustatory function by taste-related questions from the Head and Neck QOL instrument (HNQOL) and the University of Washington Head and Neck-related QOL instrument (UWQOL), before therapy and periodically after treatment. At these intervals, patients also completed a validated xerostomia-specific questionnaire (XQ) and underwent unstimulated and stimulated major salivary gland flow rate measurements. Results At 1, 3, 6, and 12 months after treatment, dysgeusia improved over time: severe dysgeusia was reported by 50%, 40%, 22%, and 23% of patients, respectively. Significant associations were found between patient-reported severe dysgeusia and radiation dose to the oral cavity ( P =.005) and tongue ( P =.019); normal tissue complication probability for severe dysgeusia at 3 months showed mean oral cavity D 50 doses 53 Gy and 57 Gy in the HNQOL and WUQOL questionnaires, respectively, with curve slope ( m ) of 0.41. Measured salivary output was not statistically significantly correlated with severe taste dysfunction, whereas patient-reported XQ summary scores and xerostomia while eating scores were correlated with severe dysgeusia in the UWQOL tool ( P =.04). Conclusions Taste impairment is significantly correlated with mean radiation dose to the oral cavity. Patient-reported xerostomia, but not salivary output, was correlated with severe dysgeusia in 1 of the 2 QOL questionnaires. Reduction in oral cavity doses is likely to improve dysgeusia.

Objectives Analyze patterns of failure of patients with head-and-neck cutaneous squamous cell carcinoma with perineural involvement: gross cranial nerve involvement (GCNI), microscopic focal perineural invasion (MFPNI), and microscopic extensive perineural invasion (MEPNI), managed with or without radiotherapy (RT). Materials and methods Retrospective review: 102 patients with GCNI, MFPNI and MEPNI, observed or treated with RT from 2000 through 2013. The pathology specimens were reviewed for the purpose of the study. Results 35 patients had GCNI, all irradiated definitely; 37% failed in-field, and two year disease free survival (DFS) rate was 56%. 19/30 patients (63%) with MEPNI without evidence of GCNI received adjuvant RT to the course of the nerves supplying the involved skin. Recurrence-free survival (RFS) in nerves (94% vs. 25%, P =0.01) and DFS (73% vs. 40%, P =0.05) were significantly higher in the irradiated MEPNI patients compared with the observed. 10/37 (27%) patients with MFPNI were irradiated adjuvantly. MFPNI had low rate of neural and overall failure, without significant benefit to irradiation over observation. Conclusions In patients with GCNI radiotherapy achieves a substantial chance of disease control. Radiotherapy to nerves at risk in MFPNI did not affect outcome, but in MEPNI it achieved less gross perineural recurrences and better DFS, compared with observation.

Molecular portraits of numerous tumors have flooded oncologists with vast amounts of data. In parallel, effective inhibitors of central pathways have shown great clinical benefit. Together, this promises potential clinical benefits to otherwise end-stage cancer patients. Here, we report a clinical service offering mutation detection of archived samples using the ion Ampliseq cancer panel coupled with clinical consultation. A multidisciplinary think tank consisting of oncologists, molecular-biologists, genetic counselors, and pathologists discussed 67 heavily pretreated, advanced cancer patient cases, taking into account mutations identified using ion Ampliseq cancer panel, medical history, and relevant literature. The team generated a treatment plan, targeting specific mutations, for 41 out of 64 cases. Three patients died before results were available. For 32 patients, the treating oncologists chose not to include the panel recommendation in the treatment plan for various reasons. Nine patients were treated as recommended by the panel, 5 with clinical benefit, and 4 with disease progression. This study suggests that routine use of massive parallel tumor sequencing is feasible and can judiciously affect treatment decisions when coupled with multidisciplinary team-based decision making. Administration of personalized based therapies at an earlier stage of disease, expansion of genetic alterations examined, and increased availability of targeted therapies may lead to further improvement in the clinical outcome of metastatic cancer patients.

4087Background: TACE is a standard treatment for patients (pts) with HCC. SBRT is a newer, noninvasive therapy. There have been no comparative studies to date. Thus, we examined TACE and SBRT outco...

Purpose: Observations in our clinic have suggested a trend towards increased skin-toxicity for head and neck (HN) patients treated with Volumetric Modulated Arc Therapy (VMAT) compared with Intensity Modulated Radiation Therapy (IMRT). Here, we report on these observations and quantify surface dose differences between VMAT and IMRT treatment plans for HN cancer patients. Methods: We retrospectively compared skin-toxicity scores gathered by the treating physician according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0) for head and neck squamous cell carcinoma (HNSCC) patients treated with IMRT (102) and VMAT (88) . A Cochran-Armitage test evaluated the relationship between treatment modality, chemotherapy and toxicity. Six patients with grade 3 skin-toxicities were selected from this cohort and the target/organ at risk volumes were transferred onto an anthropomorphic phantom using a deformable image registration based atlas (SmartSegmentation, Varian Medical). Two-arc VMAT and 9-field IMRT plans were optimized and delivered to the anthropomorphic phantom to produce similar, clinically-acceptable, dose distributions. Surface dose was measured using optically-stimulated luminescent dosimeters placed at 2 positions on the phantom’s neck which were identical between VMAT and IMRT deliveries. N-factor ANOVA was performed to identify statistically significant differences in surface dose. Results: Our retrospective study showed a marginally significant higher skin-toxicity (Grade≥ 2) for VMAT compared with IMRT (35%vs.20%, p=0.06) for patients treated with radiation alone. Phantom measurements showed a significant effect of treatment modality on surface dose (F=42.5,p

e17043 Background:For patients with recurrent SCCHN there are currently no evidence- based, approved adjuvant treatment options (following surgery and/or chemoradiotherapy for recurrent disease). Roughly 40-75% of these high-risk patients recur after treatment, with median survival rates up to 10 months. Capecitabine, an oral 5FU pro-drug, has documented efficacy in the treatment of metastatic and locally advanced SCCHN. In this retrospective analysis, we hypothesize that prolonged exposure to capecitabine may offer benefit to patients with recurrent/high disease when given adjunctively. Methods: We identified 17 patients with either locally advanced SCCHN with multiple high-risk features or recurrent SCCHN that were treated with adjuvant capecitabine post chemo-radiation or surgery for 1 year. The data was extracted from a database of patients treated for SCCHN at the University of Michigan Comprehensive Cancer Center from 2003 through 2015 and matched with 17 control patients by age, sex, and clinical s...

e16100 Background: , Sequential hormonal deprivation therapy incorporating old inexpensive pharmaceuticals may still have a role in the treatment of castrate resistant metastatic prostate carcinoma...