Start Of Radiotherapy Research Articles

The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update.

The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update.

Patient-Reported Outcome Measures and Dosimetric Correlates for Early Detection of Acute Radiation Therapy–Related Esophagitis

BackgroundWe investigate the time to and clinical factors associated with patient-reported difficulty swallowing in lung cancer patients treated with radiation therapy (RT). MethodsBetween October 2016 and October 2019, lung cancer patients treated with conventionally fractionated RT at a tertiary cancer center were identified. Weekly, patients reported difficulty swallowing (patient-reported outcome version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE] v.1: 0-none, 1-mild, 2-moderate, 3-severe, 4-very severe). Physicians graded dysphagia (CTCAE v.4: 0-none, 1-symptoms without altered intake, 2-symptomatic; altered eating/swallowing, 3-severely altered eating/swallowing, 4-life-threatening consequences, 5-death). Tumor-related difficulty swallowing was not recorded at baseline; thus, patients reporting ≥moderate symptoms ≤7 days of RT start were excluded. We evaluated the time to new patient reports of ≥moderate difficulty swallowing and CTCAE grade 2+ dysphagia and development over time using the cumulative incidence method. Multivariable logistic regression evaluated associations between clinical factors, esophageal V60, and development of esophageal symptoms. ResultsOf the 200 patients identified: median age was 69 years, 52% were male, and 89% had stage III+ disease. Patients received a median of 63 Gy with chemotherapy (91.5%). At least moderate difficulty swallowing during RT was reported by 76 of 200 patients (38%); clinicians rated dysphagia as altering oral intake or worse for 26 of 200 (13%). Median time to first report of symptoms was 21 days (interquartile ratio [IQR], 18-34.5) for the 76 patients who reported ≥moderate symptoms and 33 days (IQR, 24-42) in the 26 patients whose provider reported grade 2+ dysphagia. The 30-day incidence of patient-reported ≥moderate swallowing difficulty and provider grade 2+ dysphagia was 26% (95% CI: 20%-32%) and 6% (95% CI: 3%-9%), respectively. Esophageal V60 >7 % was the clinical factor most associated with patient-reported ≥moderate esophageal symptoms (odds ratio 6.1, 95% CI: 3.0-12.3). ConclusionsPatients report at least moderate difficulty swallowing more often and earlier than providers report grade 2+ dysphagia. Esophageal V60 ≥7% was most associated with development of moderate severity or worse patient-reported swallowing difficulty.

A Prospective Randomized Trial of the Influence of Music on Anxiety in Patients Starting Radiation Therapy for Cancer

One of the most downloaded articles in 2017 from the International Journal of Radiation Oncology, Biology, and Physics was a study suggesting that music therapy during radiation therapy (RT) simulation substantially reduces anxiety. To further evaluate the potential of music's clinical efficacy in the context of radiation therapy, we conducted a randomized trial evaluating the influence of genre-based music chosen by the study participant on anxiety during the first RT treatment session with a method that is applicable to routine clinical practice. We conducted a prospective randomized trial of music versus no music during the first RT treatment for cancer. We limited the study to women because prior studies document a higher rate of anxiety in female patients with cancer. Anxiety was evaluated before and after the first RT treatment using the State-Trait Anxiety Inventory (STAI) and Symptom Distress Thermometer (SDT). Patients randomized to music had their preferred genre of music played from a web-based application while in the treatment vault. In the study, 102 females were enrolled (51 with and 51 without music). Baseline high anxiety score before RT was recorded in 48% of patients using the STAI and 58% using the SDT. The percent decrease in mean STAI score was 16% with music versus 10% without music (P = .2197). The mean SDT percent changes were a 13% decrease with music versus a 2% increase without music (P = .3298). This study documents that high anxiety is common in women receiving RT for cancer and that music, as used in this study, does not reduce anxiety to a meaningful degree.

Identifying Variables Associated with Leave From Work in Head and Neck Cancer Patients Receiving Radiotherapy

Head and neck cancer (HNC) patients have a high rate of work discontinuation while receiving daily fractionated radiation (RT). In this analysis of HNC cancer patients treated with RT we compare baseline characteristics between working patients and not-working/not-retired patients and identify patient and treatment-related factors that can be targeted to reduce time lost from work. Number of days worked in the past week was prospectively recorded at each on treatment visit (OTV) for HNC patients receiving definitive or adjuvant (chemo)radiation from 6/2016-6/2018. Patients not working due to disability/unemployment were eligible; retired patients were excluded. Baseline characteristics were compared. Weekly patient weight (lbs), pain rating (0-10), fatigue (0-10), and ECOG status (0-5) changes were described by group. Weekly ECOG status was also analyzed dichotomously as ECOG 0 compared to ECOG ≥1. Impact of each variable on loss of working days was assessed in both univariate analysis (UVA) and multivariate analysis (MVA). A total of 69 patients were included, 29 of whom were working at the start of RT. Mean age was higher in working patients (58.8 vs 53.7 years, p = 0.004). Distance from cancer center, gender, tobacco use, alcohol use, hospitalizations during RT, presence of feeding tubes, surgery prior to RT, concurrent chemotherapy, p16 status, and location of tumor were not significantly different between working and disabled groups. Changes in weight percentages, pain, fatigue, and ECOG status between last OTV and baseline were not significantly different between the two groups. Differences in percent of patients with ECOG ≥1 in each OTV are described in the table below. In working patients, mean days worked steadily declined, starting at 4.1 days in week 1 to 1.1 in week 7. In UVA, 10% loss in weight from baseline results in 2.6 days/week lost from work (p<0.005). Pain increase by 1 unit results in 0.25 days/week lost, fatigue increase by 1 unit results in 0.28 days/week lost, and ECOG status increase by 1 unit results in 1.48 days/week lost (p<0.005 for all). In MVA, change in pain was significantly associated with days/week lost from work (p = 0.05). Changes in weight, fatigue, and ECOG status were non-significant (p = 0.08, 0.11, 0.07, respectively). The decision to work during radiation is not impacted by many baseline patient characteristics, and less than 50% of HNC patients attempt to work during radiation. In working patients, weight loss and increase in pain, fatigue, and ECOG status are significantly associated with reduction in working days per week. Of these, increase in pain has the most significant impact.Abstract 3869; TableWeek 1Week 2Week 3Week 4Week 5Week 6Week 7Working (%)10.310.317.244.848.355.671.4Not Working (%)35.045.052.555.055.075.077.8p-value0.0240.0030.0050.4690.6310.1170.741 Open table in a new tab

Influence of Timing Between Androgen Deprivation Therapy and External Beam Radiation Therapy in Patients with Localized, High-Risk Prostate Cancer

Abstract Purpose Treatment with long-term androgen deprivation therapy (ADT) and radiation therapy (RT) is the nonsurgical standard-of-care for patients with high- or very high-risk prostate cancer (HR-PC), but the optimal timing between ADT and RT initiation is unknown. We evaluate the influence of timing between ADT and RT on outcomes in patients with HR-PC using a large national cancer database. Methods and Materials Data for patients with clinical T1-T4 N0, M0, National Cancer Comprehensive Network HR-PC who were treated with definitive external RT (≥60 Gy) and ADT starting either before or within 14 days after RT start were extracted from the National Cancer Database (2004-2015). Patients were grouped on the basis of ADT initiation: (1) >11 weeks before RT, (2) 8 to 11weeks before RT, and (3) Results With a median follow-up of 68.9 months, 37,606 patients with HR-PC were eligible for analysis: 13,346 (35.5%) with >11 weeks of neoadjuvant ADT, 11,456 (30.5%) with 8 to 11 weeks of neoadjuvant ADT; and 12,804 (34%) patients with 11 weeks, 8 to 11 weeks, and 11 weeks group. Conclusions Neoadjuvant ADT initiation 8 to 11 weeks before RT is associated with significantly improved OS compared with shorter neoadjuvant ADT duration. Although prospective validation is warranted, this analysis is the largest retrospective study suggesting an influence of timing between ADT and RT initiation in HR-PC.

Predictors of Premature Ovarian Failure (POF) in Young Women with Locally Advanced Rectal Cancer (LARC) Treated with Pelvic Radiation Therapy (RT)

Pelvic RT is standard of care for patients with LARC. POF in pre-menopausal women is a possible side effect of this treatment. The predicted rise in rectal cancer in 2030 is 124% for patients 20-34 and 6% for patients 35-49 yrs. The purpose of our study was to evaluate the clinical and dosimetric predictors of POF in women younger than 50 years, treated with pelvic RT for LARC, including those who underwent ovarian transposition (OT). We retrospectively reviewed the medical records of women younger than 50 treated with pelvic RT for LARC at our institution between 2001-2019. Clinical [date of last menstrual period], and hormonal data [FSH, LH, and estradiol levels] were used to determine ovarian function. The ovaries and uterine body/fundus were contoured on the simulation scans by a single dosimetrist, and dose volume histograms were generated. Association of factors with POF was evaluated using Cox regression and optimal dosimetry cut-offs were based on maximum log rank statistic. The study identified 76 women who were premenopausal at time of RT. Median age at RT was 43 years [range 20-49]. Fertility preservation [FP] referral was done for 53% of the women, and 34% underwent OT. Neoadjuvant, concurrent and adjuvant chemotherapy was administered in 74%, 91%, and 34% of women respectively. Median RT dose was 50Gy in 25 fractions. Intensity modulated RT was used in 61% and 39% had 3D-RT. Only 26% had preservation of ovarian function, all in the OT group, and 1 woman carried a high-risk pregnancy 15 years after end of treatments, with premature birth at 25 weeks. Ovarian function was preserved in 77% of women who underwent OT. Median time from start of RT to POF was 17 days [7-54 days], and those patients did not resume menses >1 year after competing treatments. Compared to patients who underwent OT, those who haven’t had significantly higher means of ovarian doses (p<0.001): maximum dose [Right (R): 47.1 vs. 2.7 Gy, Left (L): 46.9 vs. 5.8 Gy], minimum dose [R: 40.6 vs. 0.5 Gy, L: 30.6 vs. 0.8 Gy], and mean dose [R: 45.1 vs. 1.1 Gy, L: 43.7 vs. 1.5 Gy]. Uterine doses were similar [medians >40Gy in both groups]. On univariable analysis, OT (HR: 0.05) and age at RT (HR: 1.18) were significantly associated with POF (p <0.001). At the optimal threshold for ovarian doses, patients with mean R ovarian dose >5.322 Gy had L>4.90 and bilateral >4.12 Gy and were significantly associated with higher risk of POF (HR 16.9, p<.001). However, on multivariable analysis, only OT remained independently associated with risk of POF. RT modality and chemotherapy had no significant effect. OT significantly reduced the risk of POF in our cohort, and should be considered in premenopausal women undergoing pelvic RT. Even with OT, ovarian doses approached 6Gy in some patients. We are currently investigating the role of protons therapy in further sparing the ovaries and uterus.

Nivolumab and Ipilimumab Combined with Definitive Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: In-field Toxicity Analysis of a Phase I Clinical Trial

Cisplatin added to radiation therapy (RT) for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is associated with a modest improvement in survival at the cost of increased toxicity, highlighting the need for newer agents. Immune checkpoint inhibitors (ICI) have a favorable safety profile and are the standard of care in recurrent/metastatic SCCHN, but their role in the definitive setting with RT remains to be determined. We conducted a single institution clinical trial assessing the safety of combined nivolumab (Nivo), a PD-1 inhibitor, and ipilimumab (Ipi), a CTLA-4 inhibitor, with concurrent RT in patients with high risk LA-SCCHN. Newly diagnosed, chemotherapy eligible patients (pts) with stage IVA-IVB p16(-) SCC of the oral cavity, oropharynx, larynx, and hypopharynx, or T4, N2c, or N3 p16(+) SCC of the oropharynx (AJCC 7th edition) were enrolled. Nivo (3 mg/kg Q2 weeks IV x17 doses) and Ipi (1 mg/kg Q6 weeks IV x6 doses) were administered 2 weeks prior to the start of RT. RT (70 Gy in 2 Gy daily fractions) was delivered to the primary tumor using VMAT and daily cone-beam CT IGRT. The primary objective was safety of combined ICI and RT. Between July 2017 and July 2019, 24 pts were enrolled with a median follow-up of 15 months (range 7-31); median age 60 (range 48-77); 20 male; 16 oropharynx (14 HPV+), 6 larynx, and 2 hypopharynx. All pts completed RT with no treatment delays. Seventeen out of twenty-four pts (71%) experienced grade 3 acute in-field adverse events (AE) consisting of mucositis (9), dysphagia (6), dermatitis (5), odynophagia (4), and dysphonia (1) during concurrent ICI-RT; there were no grade 4/5 AEs during ICI-RT. Five pts (22%) developed soft tissue ulcers (STU) at the primary tumor site during the ICI maintenance phase, one of which was not treated and led to a fatal carotid rupture. All STUs developed at a median of 91 (range 50-107) days post RT and were negative for viable tumor. Four primary site STUs were managed with either hyperbaric oxygen (HBO) (2), lingual artery embolization (1), or surgical debridement (1). One pt treated with HBO healed after 189 days while the pt who underwent debridement healed after 285 days. Two additional pts developed areas of necrosis at adjacent sites not involved by tumor, underwent surgical debridement, and healed after an average of 18.5 days. Two other pts experienced osteoradionecrosis (ORN) at sites of prior teeth extractions and were treated with HBO. Two pts experienced persistent inflammation without ulceration (PI). Six out of eleven pts (55%) with STU, necrosis, ORN, or PI discontinued maintenance ICI. Locoregional PFS is 100%. Combined PD-1 and CTLA-4 blockade with concurrent RT is associated with excellent locoregional control in high risk LA-SCCHN, albeit at the cost of in-field complications. Patients treated with such an approach should be closely monitored for soft tissue ulceration.

Racial Disparities Among Pancreatic Adenocarcinoma Patients: A Retrospective Survival Analysis of Non-Metastatic Pancreatic Cancer Patients

It is predicted that in 2020, approximately 57,600 individuals will be diagnosed with pancreatic cancer (PaC). Based on SEER database analysis, there are conflicting opinions in literature about the overall treatment and outcomes in African-American patients with PaC. The purpose of this study was to determine if there was a racial disparity in overall survival rates between African Americans (AAs) and non-African Americans (non-AAs) diagnosed with PaC who received neoadjuvant radiation therapy (RT) in a tertiary-care cancer center with an established multi-disciplinary PaC tumor board and clinic. An IRB-approved retrospective chart analysis was completed on 100 patients who were diagnosed with pancreatic adenocarcinoma and treated with neoadjuvant RT between 2017-2019. Patients who were deemed resectable, borderline resectable (BR), or locally advanced/unresectable (LA) at initial diagnosis were included in the analysis. The following baseline characteristics were collected for each patient: staging, gender, age and ECOG score at initial diagnosis, tumor site and size, clinical T and N stage, CA19-9, and treatment variables (i.e., surgery, chemotherapy, and RT type). Overall survival was calculated from the RT start date. In order to identify any baseline differences among the AA group and the non-AA group, a two-sample t-test and Chi-square were employed. A log-rank test and Kaplan-Meier were used to determine any differences in overall survival among the two groups. Of the 100 patients included in the analysis, 25 were AA and 58 were female. There were 17 (68%) BR and 8 (32%) LA patients in the AA group. In the non-AA group, there were 2 (3%) resectable, 47 (63%) BR, and 26 (35%) LA patients. There were no statistically significant differences detected in any of the baseline characteristics except a trend for increased CA19-9 values of 399.8 U/mL for AAs and 229 U/mL for non-AAs. There was no statistically significant difference in receipt of chemotherapy and RT between the two groups. The estimated median survival rates were 11.5 months for non-AAs and 8.4 months for AAs. One-year overall survival was 45% for AAs versus 48% for non-AAs (p = 0.57). There was no difference in overall survival among AAs and non-AAs who received neoadjuvant RT+/- chemotherapy for PaC at our institution between 2017-2019. Contrary to previous publications based on large SEER database analysis, there does not appear to be any difference in overall survival based on race if patients receive treatment in a comprehensive multi-disciplinary collaborative center.

Role of Radiotherapy for Adrenal Gland Metastases – A Single Institution Experience

Adrenal glands are often the metastatic site, that can be manifested as oligoprogressive or oligometastatic disease. Radiotherapy (RT) techniques such as stereotactic body radiation therapy (SBRT) and motion-management techniques (MMT) could be new promising modalities in this indication. The aim of the study was to assess the local effectiveness of RT for adrenal metastases (AM). The study group was a retrospective cohort of patients who received RT for AM in our institute between 2013-2019. The following parameters were analyzed: indication for RT, irradiated gland, pathology of primary tumor, RT technique, MMT, total dose (TD), equivalent 2-Gy dose (EQD2), dose per fraction (FD), early and late toxicity (CTCAE v4.0), local response (LR). Chi-squared test, and Fisher's exact tests were used to analyze proportions. The Spearman's rank correlation test was used to calculate correlation between EQD2 and best LR. Progression-free survival (PFS) was calculated using the Kaplan-Meier method, from the start of RT to the last follow-up (censored), disease progression or death. Totally n = 40 patients were found. Two patients were irradiated sequentially to both glands with at least two months interval, thus n = 42 RTs were analyzed. Two patients were irradiated to both glands at the same time, thus n = 31 left glands, n = 13 right glands were treated. The indications for RT were: oligometastases (n = 12), oligoprogression (n = 27), palliative (n = 3). The diagnoses were: melanoma (n = 21), lung cancer (n = 12), and others (n = 7). Data related to RT techniques and MMT were presented in the table. FD varied from 2 to 12 Gy, and TD from 20 to 50 Gy. EQD2 varied from 23 to 116 Gy. Acute grade 2 toxicities were observed in two patients. No significant late toxicity was observed. RT allowed to obtain complete response in two patients, partial response in 15 patients, stable disease in 14 patients and progressive disease in three patients. In eight patients, data regarding LR were not available. No correlation between EQD2 and the best LR was found (p = 0.31). In-field progression at any time occurred in nine patients. The occurrence of in-field progression did not differ between patients who were treated with MMT and those who did not (p = 1.00). PFS was 5.78 months. Table. Radiotherapy and motion-management techniques Modern RT allowed for high LR with good treatment tolerance in patients with AM. The MMT may be applied in selected patients, however, it might be not obligatory in RT for AM. The optimal dose/fractionation is unknown and should be limited by the tolerance of adjacent organs at risk.Abstract 2410; TableRTFusionMotion managementMRPETNoneBreath- hold4D-CT planningAbdominal compressionAbdominal compression + 4D-CT planningTrackingNone3D-conformal008001007IMRT/VMAT0010003007SBRT3318199320IMRT/VMAT - Intensity Modulated Radiation Therapy/Volumetric Modulated Arc Therapy; SBRT - Stereotactic Body Radiation Therapy Open table in a new tab

Patterns Of Failure And Prognostic Factors Of Adult Medulloblastoma Treated With Radiation Therapy

Medulloblastoma (MB) is a rare adult malignancy of the central nervous system (CNS). Treatment guidelines are not well-established, as most practice is extrapolated from experience in the pediatric population. We reviewed our single institutional experience in managing adult MB to define clinical outcomes and identify potential prognostic factors. We identified and reviewed records of all adult MB patients aged ≥18 years who received upfront postoperative radiotherapy (RT) from 1997-2017 at a single institution. A total of 50 consecutive patients (29 male) were identified with histologically proven MB, reviewed at our institution but without consistent molecular classification available, and disease confined to the craniospinal axis at presentation. A total of 33 patients were classified as standard-risk, and 17 patients were classified as high-risk; 7 patients had M+ disease by Chang staging. Gross total resection was achieved in 37 patients with subtotal resection (STR) in the remaining 13 patients. Median craniospinal irradiation (CSI) dose was 36Gy (RBE) with a median tumor bed or posterior fossa dose boosted to 54Gy (RBE). Thirty-nine patients were treated with proton beam RT, 9 with photon-based RT, and 2 with mixed proton/photon RT. Eleven patients did not receive any adjuvant chemotherapy (CHT), 25 patients received concurrent and adjuvant CHT, 8 received only adjuvant CHT (after RT), and 6 received a combination of neoadjuvant CHT with concurrent and adjuvant CHT. With a median follow up of 5.3 years, 7 patients had disease recurrence: 5 within the craniospinal axis and 2 patients with extraneural recurrence. Two patients died, both from disease progression. Overall survival (OS) at 5 years was 96.3%, and event-free survival (EFS) at 5 years was 80.7%. Twenty-nine percent (2/7) of recurrences occurred after 5 years. In the seven patients with disease recurrence, all were classified as standard risk and M0 on presentation; 86% (6/7) were treated with 36Gy to CSI and 54Gy to boost volume; 4 had anaplastic histology and 3 had desmoplastic histology. Two patients deferred adjuvant CHT, four were treated with concurrent and adjuvant CHT, and one with adjuvant CHT only. Both patients with extraneural recurrence received concurrent and adjuvant CHT. On univariate analysis, time to start of RT >35 days from diagnosis was associated with worse EFS (HR 8.46, 95% CI 1.01-70.70, p = 0.049). There was no statistically significant trend for worse EFS or OS with histology, STR, high-risk, M+ disease, RT duration, or use of adjuvant CHT. Adults with MB have survival rates similar to their pediatric counterparts, but late and distant relapses are not uncommon. RT is a major component of the treatment of adult MB, however better prognostic factors, possibly from molecular subtyping, may help to define better personalized treatments for adult MB with high risk of recurrence.

S1795 Incidental Finding of a MALT Lymphoma of the Rectum

INTRODUCTION: Extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) are a subtype of Non-Hodgkin lymphoma (NHL), accounting for only 5% of all NHL. MALT lymphomas can be found in different tissues of the body, the stomach being the most commonly affected gastrointestinal site. Primary colorectal MALT lymphoma is a rare entity and few cases have been reported in the literature; its presentation is often indistinguishable from that of other colonic malignancies, or it can be found incidentally during screening colonoscopies. CASE DESCRIPTION/METHODS: We report the case of an asymptomatic 51-year-old female with a family history of colorectal cancer who underwent routine screening colonoscopy. Prior colonoscopies performed since age 40 were unremarkable. Colonoscopy revealed a subepithelial nodule in the recto-sigmoid colon (Figure 1). Subsequently, a lower endoscopic ultrasound (EUS) was performed and revealed a 15 mm polypoid multi-lobulated lesion with central umbilication in the recto-sigmoid colon. Endosonographically, the lesion was hypoechoic, and it appeared to be confined to both the luminal interface/superficial mucosa and deep mucosa without evidence of extension into the submucosa or muscularis propria. The lesion was successfully removed in its entirety by endoscopic mucosal resection (EMR). The procedure was uneventful, and the patient was discharged home the same day. Pathology revealed large intestinal mucosa of the rectum with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (Figure 2). Immunohistochemistry demonstrated lymphoid cells that were positive for CD20 (Figure 3), CD23, and BCL2 but negative for CD3, CD5, CD43, CD10, and BCL6; confirming the above diagnosis. Whole-body positron emission tomography did not reveal systemic extension. Repeat colonoscopy 3 months later revealed visually prominent infiltration at post-mucosectomy scar negative for residual lymphoma on biopsy. However, due to a strong concern for submucosal spread on site, a decision was made to start radiation therapy. DISCUSSION: The treatment for patients with MALT lymphoma includes surgical resection, chemotherapy, and radiation among others. However, due to the rarity of colonic MALT lymphomas, the optimal treatment modality for them is not well defined and though its prognosis tends to be excellent, periodic surveillance colonoscopies are needed due to increased risk for other primaries and localized recurrence or transformation into higher-grade disease in some instances.Figure 1.: A subepithelial nodule is seen in recto-sigmoid colon during endoscopy.Figure 2.: Rectal mucosa with dense infiltration of lymphoid cells (H&E, 50x).Figure 3.: Diffuse expression of CD20 on immunohistochemical staining suggests lymphoid infiltrate to be composed mostly of B-cells (50x).

Outcomes with Proton and Photon Radiotherapy for Unresectable Hepatocellular Carcinoma

Emerging data suggest improved outcomes for hepatocellular carcinoma (HCC) with proton radiotherapy (RT), but the data nonetheless remain limited. Based on prior observations, we hypothesized that protons may better mitigate lymphocyte depletion and preserve liver function as compared to photon RT. We retrospectively examined liver function, lymphocyte counts, and survival outcomes for proton or photon RT for patients with HCC. We reviewed the records of 143 patients (111 male, 32 female) treated with RT for unresectable HCC from 2006-2016 at our institution. Serial absolute lymphocyte counts were graded according to CTCAE 4.0. Child-Pugh score (CPS) was calculated at RT start and at peak value within 9 months of RT completion. Univariate and multivariate logistic regressions were used to identify factors associated with change in CPS. Comparisons of distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using the log-rank test and predictors of OS were evaluated using Cox proportional-hazards models. Median age at treatment was 66 years (range, 19-90 years). Portal vein thrombus (PVT) was present in 55%. Treatment modality used was 72% photon and 28% proton; baseline characteristics between these groups were similar. The mean pre-treatment CPS for both groups was 5.8. Median biologically equivalent dose (BED) was 84Gy (range, 44-180Gy) and 97GyE (range, 39-140GyE) for patients treated with photons and protons, respectively. The mean change in CPS was +1.8 (95% confidence interval [CI], 1.3-2.2) for photon patients vs. +0.8 (95% CI, 0.3-1.2) for proton patients (p=0.0058). Grade 3+ (G3+) lymphopenia in patients treated with photons vs. protons was 76% vs. 55% (p=0.015). On univariate analysis, stage 3+, G3+ lymphopenia, pre-treatment CP Class B, and presence of PVT were associated with increased likelihood of worsening CPS. Multivariate analysis revealed that age (odds ratio [OR], 1.069, p=0.03), pre-treatment liver function (CP Class B vs. A, OR, 6.72, p=0.03) and treatment modality (proton vs. photon, OR, 0.26, p=0.03) were associated with liver decompensation. For clinical outcomes, median follow-up was 10 months (range, 1-70 months). For photon-treated patients, median DMFS was 9 months (95% CI, 6-13 months) and median OS was 13 months (95% CI, 10-24 months). For proton-treated patients, median DMFS was 22 months (95% CI, 13-28 months) and median OS was 30 months (95% CI, 15-60 months). Multivariate analysis revealed an increased risk of mortality associated independently with increase in CPS (hazard ratio [HR] 1.79, p<0.001), G3+ lymphopenia (HR 5.44, p=0.04), higher volume of PTV (HR 1.0007, p=0.04), and PVT (HR 4.35, p=0.03). Post-RT liver decompensation and G3+ lymphopenia are independently associated with reduced survival, and proton therapy may mitigate these toxicities compared to photons, especially in patients with advanced cirrhosis. Further investigation is warranted to clarify the role of protons for HCC.

The Association of the Sequence of Immunotherapy With the Survival of Unresectable Pancreatic Adenocarcinoma Patients: A Retrospective Analysis of the National Cancer Database

Background: Immunotherapy has shown great success in various malignancies. However, its efficacy in pancreatic ductal adenocarcinoma (PDAC) remains a challenge, and the lack of understanding about the appropriate timing of immunotherapy with other standard-of-care cancer treatments may be one of the causes. The objective of the current study is to investigate the impact of the timing of immunotherapy with chemotherapy and radiation therapy (RT) on the overall survival (OS) of PDAC patients who did not receive surgical resection of the pancreatic tumor.Materials and Methods: Patients with pancreatic adenocarcinoma who did not receive surgical resection of the pancreatic tumor were identified from the National Cancer Database (NCDB). Cox proportional hazard models were employed to compare the OS between patients who received immunotherapy with chemotherapy or RT with a different sequence of treatment. The multivariable analysis was adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, and year of diagnosis.Results: In total, 705 patients received chemotherapy and immunotherapy, while 226 received radiation therapy and immunotherapy. In the multivariable analysis, there was no significant difference in the OS of patients who started immunotherapy 31–90 days before the start of chemotherapy with a hazard ratio (HR) of [HR:1.057 (CI: 0.716–1.56; p < 0.781)] and patients who started immunotherapy 91–180 days before the start of chemotherapy [HR: 0.900 (CI: 0.584–1.388; p < 0.635)] compared to patients who started chemotherapy and immunotherapy within 30 days of each other. There was also no significant difference in the OS of patients who started RT> 30 days before the start of immunotherapy [HR: 0.636 (CI: 0.346–1.171; p < 0.146)] and patients who started immunotherapy > 30 days before the start of RT [HR: 0.660 (CI: 0.328–1.329; p < 0.246)] compared to patients who started RT and immunotherapy within 30 days of each other.Conclusion: The sequence of immunotherapy with chemotherapy or RT was not associated with improved OS. Future studies with a larger subgroup sample size investigating the impact of the timing of immunotherapy with chemotherapy and RT on the OS of PDAC patients who do not receive surgical resection of the pancreatic tumor are needed.

1182P Baseline neutrophil-lymphocyte ratio and its variations after adjuvant radiotherapy predict clinical survival outcomes in locally advanced Merkel cell carcinoma (MCC)

High baseline neutrophil-lymphocyte ratio (NLR) ≥ 3.5 was shown to be a negative prognostic factor in several solid cancers including MCC. The present study explores the prognostic and predictive role of basal NLR and its variations after adjuvant radiotherapy (RT) in stage II-III MCC patients (pts). We retrospectively identified 95 stage II-III MCC pts referred to our Institution from 2004 to 2019. All pts had Eastern Cooperative Oncology Group Performance Status 0 or 1 and were negative for active infections and autoimmune disease. No pts received concomitant immunosuppressive/immunostimulating drugs. We collected NLR values at the following timepoints: baseline at diagnosis, within one month before RT start and within one month after RT completion. Hazard ratios (HRs) were calculated using Cox’s proportional hazards regression model. Overall DFS and OS were 17,9 and 42.1 months (mos) respectively. All pts underwent radical surgery, followed by RT treatment (28.5%, 27 pts) or follow up (FU) alone (71,5%, 68 pts). Median FU was 42.6 (4.6 - 235.5) mos. Baseline NLR was significantly associated with DFS (HR 1.71 95%CI 1.43-2.05, p<0.001) and OS (HR 1.40 95%CI 1.11-1.77 p=0.004). In 11 out 27 (40.7%) pts who underwent RT, a decrease of post-RT NRL values was observed in comparison to pre-RT NLR values. There was a trend towards worse mDFS in pts whose NLR increased after RT compared to those whose NLR decreased after RT (mPFS 13.1 vs 52 mos, 95%CI 0.86- 8.62; HR 2.73; p= 0.087). In the multivariate model, older age and baseline NLR were both strongly associated with worse DFS (HR_NLR 1.63; 95%CI 1.34-1.99 p<0.001) and OS (HR_NLR 1.44; 95%CI 1.10-1.90 p=0.008). Despite being a retrospective study design, RT seems to be able to modulate the frequencies of peripheral immune subsets and correlates with the shift to a more favorable peripheral immune profile. Further studies are needed to determine the role of NLR as potential prognostic and predictive biomarkers to consider when selecting MCC pts for adjuvant treatment.

Cannabis and Radiation Therapy: A Scoping Review of Human Clinical Trials

Abstract Introduction It is estimated that at least 20% of Canadian patients with cancer use cannabis to alleviate symptoms of their disease and/or cope with the side effects of their treatment. Most patients want to learn more about cannabis from their healthcare team, but most oncology professionals feel too uninformed to make recommendations. The purpose of this scoping review was to address this oncology professionals’ knowledge gap, by summarizing the literature on evaluations of the benefits and harms of cannabis use before, during, or after radiation therapy (RT). Methods and Materials A literature search was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines, using multiple electronic databases and combinations of key terms. To be included, studies must address the use of cannabis in patients undergoing RT. In vitro and in vivo evaluations, reviews, and editorials were excluded. Eligible full text manuscripts were then subjected to a formal risk of bias assessment using the Cochrane RoB 2.0 or ROBINS-I frameworks. Results A total of 48 records were identified, and 8 articles were included after vetting. These 8 studies suggest that the use of cannabinoids may calm anxious patients about to start RT, reduce nausea and vomiting consistent with the contemporary standard of care, reduce the symptoms of relapse for patients with glioma, and provide symptom relief >3 years after head and neck RT but not during or immediately. Six of these studies contained a high risk of bias (eg lack of randomization, poor blinding, and subjective outcome assessments). Most studies reported mild episodes of drowsiness and dry mouth with Δ9tetrahydrocannabinol, but substantial rates of dizziness, fatigue, and disorientation were also seen. It is important to note that these studies did not measure the impact of long-term cannabis consumption. Conclusions The existing body of literature evaluating the use of cannabinoids by patients undergoing RT is very limited. Well-designed randomized controlled trials are urgently needed, which address the significant design flaws of previous studies and evaluate the impact of phytocannabinoids in patients undergoing RT.

Effects of N-acetylcysteine inhalation therapy on the quality of life of patients with head and neck cancer who are receiving radiation therapy: a prospective non-randomized controlled multi-center study.

Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients. We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400mg daily) for 8weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35. N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019). N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect.

The Role of Palliative Radiotherapy in the Treatment of Spinal Bone Metastases from Head and Neck Tumors-A Multicenter Analysis of a Rare Event.

This retrospective multi-center analysis aimed to assess the clinical response and stabilizing effects of palliative radiotherapy (RT) for spinal bone metastases (SBM) in head and neck cancer (HNC), and to establish potential predictive factors for stability and overall survival (OS). Patients included in this analysis were treated at the University Hospitals of Mainz, Freiburg, and Heidelberg between 2001 and 2019. Clinical information was taken from the medical records. The stability of affected vertebral bodies was assessed according to the validated spine instability neoplastic score (SINS) based on CT-imaging before RT, as well as 3 and 6 months after RT. OS was quantified as the time between the start of palliative RT and death from any cause or last follow-up. Potential predictive factors for stability and OS were analyzed using generalized estimating equations and Cox regression for time-varying covariates to take into account multiple observations per patient. The mean follow-up time of 66 included patients after the first palliative RT was 8.1 months (range 0.3–85.0 months). The majority of patients (70%; n = 46) had squamous cell carcinomas (SCC) originating from the pharynx, larynx and oral cavity, while most of the remaining patients (26%; n = 17) suffered from salivary glands tumors. A total of 95 target volumes including 178 SBM were evaluated that received a total of 81 irradiation series. In patients with more than one metastasis per irradiated region, only the most critical bone metastasis was analyzed according to the SINS system. Prior to RT, pain and neurologic deficits were present in 76% (n = 72) and 22% (n = 21) of irradiated lesions, respectively, and 68% of the irradiated lesions (n = 65) were assessed as unstable or potentially unstable prior to RT. SBM-related pain symptoms and neurologic deficits responded to RT in 63% and 47% of the treated lesions, respectively. Among patients still alive at 3 and 6 months after RT with potentially unstable or unstable SBM, a shift to a better stability class according to the SINS was observed in 20% and 33% of the irradiated SBM, respectively. Pathological fractures of SBM were frequently detected before the start of irradiation (43%; n = 41), but after RT, new fractures or increasing vertebral body sintering within the irradiated region occurred rarely (8%; n = 8). A pathological fracture before RT was negatively associated with stabilization 6 months after RT (OR 0.1, 95% CI 0.02–0.49, p = 0.004), while a Karnofsky performance score (KPS) ≥ 70% was associated positively with a stabilization effect through irradiation (OR 6.09, 95% CI 1.68–22.05, p = 0.006). Mean OS following first palliative RT was 10.7 months, and the KPS (≥70% vs. <70%) was shown to be a strong predictive factor for OS after RT (HR 0.197, 95% CI 0.11–0.35, p < 0.001). There was no significant difference in OS between patients with SCC and non-SCC. Palliative RT in symptomatic SBM of HNC provides sufficient symptom relief in the majority of patients, while only about one third of initially unstable SBM show re-stabilization after RT. Since patients in our multi-center cohort exhibited very limited OS, fractionation schemes should be determined depending on the patients’ performance status.

Rapid Adaptation of Breast Radiation Therapy Use During the Coronavirus Disease 2019 Pandemic at a Large Academic Cancer Center in Canada

PurposeMitigation strategies to balance the risk of coronavirus disease 2019 (COVID-19) infection against oncologic risk in patients with breast cancer undergoing radiation therapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiation therapy by oncologic risk and omission or deferral of radiation therapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers and preserves resources. Herein, we present our early response and adaptation of breast radiation therapy utilization during the COVID-19 pandemic at a large academic cancer center in Canada. Methods and MaterialsA state of emergency was announced in Ontario on March 17, 2020, owing to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast radiation therapy starts, type of breast radiation therapy, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. ResultsAfter the declaration of emergency in Ontario, there was a decrease of 39% in radiation therapy starts in 2020 compared with 2019 (79 vs 129, P < .001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared with 2019 (46% vs 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiation therapy were aged >50 years in 2020, 66% (78 of 118) versus 83% (132 of 160) in 2019, P = .0027. ConclusionsA significant reduction in breast radiation therapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiation therapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical and is of particular importance for higher volume cancer sites where the potential effect on resources is greater.

Factors Associated With Fatigue in Patients with Breast Cancer Undergoing External Beam Radiation Therapy

PurposeCancer-related fatigue (CRF), a prevalent symptom among cancer patients, is a side effect of external beam radiation therapy (EBRT). Even when targeting organs unrelated to caloric intake or the central nervous system, radiation therapy can increase CRF, a poorly understood toxicity resulting from patient-specific, systemic therapy-related, and radiation-specific factors. We sought to determine factors associated with fatigue among patients receiving EBRT for breast cancer. Methods and MaterialsTo determine the variables associated with fatigue among patients with nonmetastatic breast cancer, we retrospectively analyzed prospectively collected toxicity data for a cohort of 1286 adult females with breast cancer who began curative-intent EBRT between April 4, 2010, and October 10, 2017. We hypothesized certain variables are associated with provider-reported Common Terminology Criteria for Adverse Events version 4 fatigue, graded 0 to 3, at baseline and over the course of radiation treatment. ResultsAll patients were women, with a median age of 57 (range, 24-90). Mean fatigue was low (0.35 [95% confidence interval, 0.32-0.38]) at the start of radiation, increasing weekly and peaking at week 6 (0.85 [0.81-0.90]). Baseline fatigue was associated with higher American Joint Committee on Cancer stage (P < .001), N-stage (P < .001), anxiolytics (P < .001), anticonvulsants (P = .002), antidepressants (P = .006), antihistamines (P < .001), and antipsychotics (P < .001). Chemotherapy was not associated with baseline fatigue. Over the course of treatment, on multivariable analysis, only lower dose per fraction (P < .001) was significantly associated with increasing fatigue. In a subgroup analysis, heart and lung mean, V5, and V20 doses were not found to be associated with increasing fatigue. ConclusionsThis work informs clinicians which factors are associated with CRF at the start of radiation therapy (more advanced disease and prescription of anxiolytics, anticonvulsants, antidepressants, antihistamines, and antipsychotics) and increase CRF over the course of radiation (smaller fraction size). This extensive analysis of factors associated with fatigue provides further evidence that hypofractionated radiation therapy for breast cancer is associated with less acute toxicity than conventionally fractionated treatment.

Abstract A133: Comparison of radiation therapy initiation timelines among varied referral streams to identify sources of delay

Abstract Purpose/Objective(s): Tertiary radiation oncology centers receive referrals from diverse care settings, including private facilities, Veteran’s Affair (VA) hospitals, and county hospitals. An exploratory study of county patients treated at our institution identified that each missed consult or simulation (sim) appointment was associated with a greater than three-week delay from referral to radiation (RT) start. We sought to validate this in a larger sample and compared RT referral-to-start timelines for a variety of referral streams. Materials and Methods: Up to 60 consecutively referred patients from each facility (internal health system, VA, county hospital, and external private facilities) between June to December 2018 were included. Primary disease site, interpreter requirements, and dates of referral, consultation, sim, and RT start were recorded. Linear regression and analysis of variance models were developed to identify variables associated with delays in RT. Results: Of 214 patients were included; 55 (26%) internal, 53 (25%) from the VA, 60 (29%) from the county hospital, and 46 (22%) from other facilities. Among the 33 patients requiring interpreters, 28 (85%) were county patients. The most common referrals were for genitourinary (GU) cancers (n = 63, 29%), followed by breast (n = 29, 14%), lung (n = 26, 12%), and head and neck (n = 21, 10%) cancers. The median days from referral to consult was 16 (IQR 7-28), with the shortest time to consult for bone (1.5 days, IQR 1-5) and central nervous system sites (5 days, IQR 3-9) and the longest for gynecologic cancers (21.5 days, IQR 8.5-44). Excluding GU patients, who often require two months of neoadjuvant hormone therapy prior to RT, the median days from consult to sim was 13 (IQR 6-20) with no significant differences in referral to consult or consult to sim by referring facility. In all patients, the median days from sim to RT start was 8 (IQR 6-14) with no significant differences by referral facility. In univariate analysis among non-GU patients, referring facility and requirement of an interpreter were not associated with referral-to-start delays; only missing one or more consult/sim appointments was significant (p &amp;lt; 0.001). Each missed appointment was associated with a 37-day delay (95% CI 26 – 48) in referral-to-start. Conclusion: In a patient cohort with heterogeneous cancer diagnoses, no facility-specific delays were identified despite county hospital patients having known socioeconomic vulnerability. Efforts to decrease RT delays may require department-wide, as opposed to interfacility, interventions. Future goals involve using site-specific referral-to-start benchmarks (e.g. one week for palliation and 10 weeks for GU) to further discriminate differences. Citation Format: Melody J Xu, Sumi Sinha, Sunny Wang, Terence Friedlander, Steve E Braunstein. Comparison of radiation therapy initiation timelines among varied referral streams to identify sources of delay [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A133.