Months Of Radiation Therapy Research Articles

Safety of Pelvic and Abdominal Radiation Therapy for Patients With Inflammatory Bowel Disease: A Dosimetric Analysis of Acute Bowel Toxicity

ObjectivesInflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities. This study aims to assess acute toxicity outcomes in patients with IBD treated with abdominal/pelvic RT. MethodsAfter institutional review board approval, patients with IBD who received RT to the abdomen/pelvis were identified from an institutional research repository and their electronic medical records were reviewed. The IBD cohort was matched 1:1 with controls according to all of the following: radiotherapy, gender, disease site, age, and year of RT. Acute toxicity was defined as toxicity occurring within 3 months of RT. Primary outcomes were assessed via univariable logistic regression models and predicted probability of acute toxicity and acute gastrointestinal (GI) toxicity were plotted for the most significant covariates. IBD and control control cohorts were compared on demographic and toxicity variables using chi-square/Fisher's exact tests and Kruskal-Wallis tests where appropriate. ResultsWe identified 62 patients with median age of 64 years (interquartile range [IQR] 54-70) who received RT from 2006-2022. Patients were treated with intensity-modulated RT (38; 61.3%), 3-dimensional conformal RT (12; 19.4%), and stereotactic body RT/brachytherapy (12; 19.4%). After RT, 28 (45.2%) and 23 (37.1%) patients experienced grade ≥2 acute (any) and acute GI toxicity, respectively. Higher overall RT dose and RT dose to small bowel were found to be signicantly associated with increased risk of grade ≥2 acute toxicities (OR=1.041 per unit Gy, 95% CI 1.005-1.084, p=0.034 and OR=1.046, 95% CI 1.018-1.082, p=0.003, respectively). Between IBD and control cohorts, there were no significant differences in grade ≥2 acute (any) and acute GI toxicities (p=0.710 and p=0.704, respectively). ConclusionIn patients with IBD treated with abdominal/pelvic RT for malignancy, RT was effective and well-tolerated. RT treatment planning should carefully consider the location(s) of IBD inflammation and dose to bowel structures, in particular, dose to small bowel.

Feasibility and Toxicity of Hypofractionated Radiation Therapy in Patients Undergoing Post Mastectomy Radiation Therapy

Introduction: Post mastectomy radiation (PMRT) plays major role in breast cancer treatment. Hypofractionated radiation is a relatively newer modality. Hypofractionation is more commonly used after breast conservation surgery. Landmark trials that studied hypofractionation had fewer PMRT subjects. Here we report our study on feasibility and toxicity profile of hypofractionated PMRT. Aim: To describe the clinical and toxicity profile of patients undergoing hypofractionated 3D conformal radiation therapy in breast cancer patients. Materials & Methods: This study included patients who are eligible for post mastectomy radiation therapy above 18 years planned for adjuvant PMRT (40.05Gy in 15 fractions delivered over 3 weeks in 3D conformal radiation) to the chest wall and supraclavicular nodes between April 2021 to October 2022., active lung infection, patient preference for conventional fractionation. Dosimetric parameters to target & organs at risk were analyzed. Toxicities including hematologic, dermatitis, pharyngitis & other were monitored. Results: Of 71 patients, 70 patients were female and 1 is male. Majority (46%) of patients belonged to 46-55 years age group. Age ranged from 34 to 85 years. Mean age is 52 years. Clinical Stage IIIA was the most common stage with 29.5% patients followed by Stage IIB with 25.3% patients. Majority received adjuvant chemotherapy (52%). Mean treatment time is 21 days. All patients completed treatment without any major complications. Follow up ranged from 17 months to 27 months. Out of 71 patients, 1 patient expired on follow up after 4 months of radiation therapy due to non cancer related cause (Chronic pancreatitis). On follow up, 3 patients had distant metastasis alone (lung, bone metastasis, brain metastases) and 1 patient had both local disease and distant metastasis. 3 patients who progressed had stage IIIC disease & 1 had stage IIIB disease. The V90 to the Planned Target volume (PTV) ranged from 90.4% to 99% to right sided disease, 90.3% to 96.5% to left sided disease. Heart V17Gy ranged from 1.27% to 12.5% & heart V35Gy was 0.16% to 7.2%. Dermatitis was the most common adverse effect in this study. 31 patients (43.6%) developed fatigue during treatment. They continued their daily activities without any limitations. 35 patients (49.2%) had throat pain, of which 2 patients had it in 1st week, 21 patients had it in 2nd week and 12 patients had it in 3rd week. They were treated with non opioid analgesics. Shoulder pain was observed in 10 patients (14%) during treatment. Blood parameters were monitored weekly during treatment. No changes were observed. Conclusion: Hypofractionated post mastectomy radiation therapy is well tolerated in our study group. None of them developed any major acute reactions during and post treatment in the follow up period. Patients completed their treatment without any breaks during treatment. Respiratory motion management especially left sided disease patients should be used for achieving dose constraints.

Safety of Radiation Therapy for Treatment of Malignancy in Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities, however, there is limited toxicity data using modern RT techniques. This study aims to assess toxicity outcomes in patients with IBD treated with abdominal or pelvic RT. After institutional review board approval, patients with IBD who received RT to the abdomen or pelvis were filtered from an institutional research repository and their electronic medical records were reviewed. Acute toxicity was defined as that occurring within 3 months of RT. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Univariable Cox proportional hazards regression was used to assess rates of grade ≥2 toxicity-free survival. We identified 62 patients with median age of 69 years (interquartile range [IQR] 62-77) who received RT from 2006-2022. Median follow up was 15 months (IQR 4-33). Most patients were male (42; 68%) and had a diagnosis of ulcerative colitis (44; 71%). The most common primary malignancy was colorectal/anal (26; 42%). Intensity-modulated RT (IMRT) was most frequently used (38; 61%) followed by 3-dimensional conformal RT (3D-CRT) (12; 19%) and stereotactic body RT (SBRT)/brachytherapy (12; 19%). For IMRT/3D-CRT, median dose delivered was 50 Gy (IQR 49-59) in 25 fractions (IQR 25-30), and median maximum dose (Dmax) to bowel was 48 Gy (IQR 43-52); whereas for SBRT/brachytherapy, the median dose was 32 Gy (IQR 27-40) in 3 fractions (IQR 2-5) and median bowel Dmax was 32 Gy (IQR 20-37). The median biologically effective dose delivered with an assumed alpha/beta ratio of 10 (BED10) across all RT modalities was 63 Gy (IQR 60-72). After initiation of RT, 31 patients (50%) and 14 patients (23%) experienced grade ≥2 acute and late toxicity, respectively. Thirteen patients (21%) and 7 patients (11%) experienced grade 3 acute and late toxicity, respectively. No patients experienced grade >3 toxicity. Acute toxicity resulted in interruption to RT for 5 patients (8%), 2 of which did not resume RT. Four patients (6%) required adjustment to chemotherapy or IBD medication dosage as a result of their acute toxicity. Median time from RT start to acute toxicity onset was 41 days (IQR 32-46), whereas median time to onset of late toxicity was 9 months (IQR 5-15). The most common acute and late toxicities were diarrhea (21; 34%) and bowel obstruction/perforation/fistula (4; 6%), respectively. Rates of grade ≥2 toxicity-free survival overtime were not significantly associated with IBD status (active vs quiescent), delivered BED10, or bowel Dmax BED3. In patients with IBD treated with abdominal or pelvic RT for malignancy, RT was feasible with acceptable rates of toxicity and active versus quiescent IBD status did not impact toxicity outcomes. Future research is needed to elucidate specific dose constraints when treating patients with IBD.

Safety of concurrent use of radiotherapy for second primary malignancy (SPM) in patients with chronic lymphocytic leukemia (CLL) receiving novel agent therapy.

e19507 Background: Patients (pts) with CLL are at elevated risk of developing non-hematologic malignancies. Radiation therapy (RT) is a critical component of management in localized solid organ malignancies. Novel agents (NA) are widely used in CLL treatment; however, safety data are lacking to guide treatment of pts requiring concurrent RT and NA. Methods: We identified pts treated concurrently with NA for CLL and RT for second primary malignancy (SPM) at Mayo Clinic from 2014-2022. Adverse events within 3 months of RT were evaluated using the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematological toxicity and the Common Terminology Criteria for Adverse Events (CTCAE) version 5 for non-hematological toxicity. Patients without seamless, concurrent treatment with NA and RT were excluded. Results: Twenty-six pts were included. NA therapy consisted of ibrutinib (n = 23), acalabrutinib (n = 2), and venetoclax (n = 1). Median follow up time since RT completion was 1.5 years. The median age at NA initiation was 67 years (range:46-85) and at RT start was 68 years (range: 51-85); 92% of pts were male. NA was first treatment in 23% of pts; the median number of prior lines of therapy was 1 (range: 0-4). IGHV was unmutated in 82% and TP53 aberration was present in 24% of evaluable patients. SPM sites included prostate (n = 9), head/neck (n = 8), lung (n = 3), and brain, breast, bone, skin, kidney, and thymus (n = 1 each). The most common conventionally fractionated prescriptions (cGy/fx) were 6000/30 (n = 6) and > 6000-7020/20-33 (n = 7). SBRT ranged from 3300/5 to 5400/3 (n = 8). Five pts received other, varied RT prescriptions. Overall, 3 (12%) pts experienced at least one grade 3/4 toxicity. Grade 3/4 thrombocytopenia was observed in 2 (8%) pts and grade 3/4 neutropenia was observed in 2 pts per iwCLL criteria. Grade ≥3 non-hematological toxicities occurred in two pts that required hospitalization for critical illness, including 1 pt with grade 5 respiratory failure within 6 weeks after RT. Dose de-escalation of ibrutinib was reported in one case for pancytopenia attributed to use of a radiosensitizing agent. There were no cases of RT dose modification. Conclusions: Continuing NA CLL therapy during RT did not result in unexpected toxicities. This approach may maintain CLL disease control without compromising management of the SPM. [Table: see text]

Predictors of benefit to radiation for oligoprogressive disease in EGFR-mutant metastatic non-small cell lung cancer patients treated with osimertinib.

e21127 Background: While osimertinib has transformed the treatment paradigm of EGFR-mutant lung cancers (EGFR+ LC), all patients inevitably progress. Oligoprogression is a common pattern of progression for which radiation therapy (RT) can be utilized to prolong the time on osimertinib. However, data supporting the benefit of osimertinib in prolonging progression is limited. Furthermore, predictors of response to RT in the setting of oligoprogression are unknown. We aim to identify clinical and genomic factors associated with robust progression-free survival (PFS) after RT for oligoprogression in EGFR+ LC in patients treated with osimertinib. Methods: Patients with metastatic EGFR+ LC on osimertinib who underwent radiation from 2010 to 2022 for oligoprogression (i.e. progression in 5 or less lesions) were identified. Patients received RT to all active sites of intra- and extra- thoracic disease. Patients who progressed within 3 months of radiation therapy were classified as “rapid progressors,” and those that had longer PFS were “late progressors.” All cases underwent clinical and genomic annotation. Comparisons of categorical variables were performed by Fisher’s exact test. Results: 84 patients were identified who underwent RT for oligoprogression on osimertinib, of which 25% (n = 21) were rapid progressors. Median time from radiation to subsequent progression was 6 months (range 1-26mo) and upon progression most patients had growth of more than one lesion (71%). Median time to death or last follow-up was 13.5 months (range 1-48mo). There was no significant difference in gender, ethnicity, and baseline KPS between rapid and late progressors. Patients with baseline exon 19 deletion (63% vs 76%, p = 0.3) and atypical mutations (14% vs 3%, p = 0.1) were more likely to be rapid progressors while those with exon 21 L858R (10% vs 33%, p = 0.03) were more likely to be late progressors. Among the rapid progressors, 50% underwent radiation to the lung, 10% to the brain, 35% to the bone, and 5% to lymph nodes. Median size of the largest lesion and number of lesions was similar between the two groups (rapid 2.5 cm and 1.5 lesions vs late 2.7 cm and 1 lesion). In-field recurrence rate was 18% and did not differ between rapid and late progressors (14% vs 19%). Conclusions: Radiation therapy for oligoprogression results in clinically meaningful time on osimertinib beyond progression for many patients. However, 25% of patients rapidly progress after radiation therapy and should be directed to switch systemic therapy. Further study is needed to better elucidate benefit at the time of radiation, so that the systemic treatment approach for these patients can be optimized.

Bridging Implantable Cardioverter-Defibrillator Patients Undergoing Radiotherapy with a Wearable Cardioverter-Defibrillator

Background: Chest radiation therapy (RT) in patients with an implantable cardioverter defibrillator (ICD) can be problematic and cause transitory malfunction or permanent damage to the device. If the ICD cannot be properly shielded from the radiation necessary for the treatment, then it may be necessary to turn off certain aspects (i.e. tachy-therapy) of the device or to temporarily remove the device leaving the patient without protection and exposing to high risk of complications. The wearable cardioverter defibrillator (WCD) is guideline recommended as bridging therapy in patients requiring temporary removal or inactivation of an ICD. Objectives: The objective of this analysis was to assess the wearable cardioverter defibrillator as a tool in high-risk implantable cardioverter defibrillator patients with cancer during the weeks to months of radiation therapy. Methods: Two retrospective cohorts were analyzed from the University of Padova (Italy) and from the manufacturer’s US registry. Patients undergoing RT who had their ICD removed or deactivated and were prescribed a WCD were included. Demographic, medical history and device usage data collected. Results: Eighty patients were analyzed (76 US, 4 Padova). The median age was 69 years and 56% were female. The most common cancer types were breast (44%) and lung (33%). Median wear time of the WCD was 22.2 hours/day over 57 days. Strategies to protect ICDs from RT involved either removing the device (82.5%) or turning off therapy in the remaining 14 (17.5%). Ventricular arrhythmias (VA) were recorded by the wearable cardioverter defibrillator in four patients, with two sustained episodes in a patient that were successfully cardioverter by the wearable cardioverter defibrillator, and three patients with non-sustained ventricular arrhythmias that did not receive shocks. Five deaths occurred four with an asystole event and one while not wearing the device. Conclusions: This study supports a role for the wearable cardioverter defibrillator in protecting implantable cardioverter defibrillator patients while undergoing radiation therapy. Back-up pacing considered for patients at risk of Bradyarrhythmias.

Serum Tumor Marker Response Predicts Survival and Intracranial Control after Radiation Therapy for Germ Cell Tumor Brain Metastases

<h3>Purpose/Objective(s)</h3> Patients with brain metastases (BM) from germ cell tumors (GCT) demonstrate poor overall survival (OS). However, multimodality treatment enables durable disease control in some patients. Serum tumor markers including beta-human chorionic gonadotropin (β-HCG) and alpha-fetoprotein (AFP) are used to evaluate response to systemic therapy. However, their utility in assessing the efficacy of intracranial radiation therapy (RT) is unclear. We evaluated whether changes in β-HCG and AFP after RT for GCT BM predict OS and freedom from intracranial progression (iPFS). <h3>Materials/Methods</h3> Patients with GCT BM who received intracranial RT at our institution were identified retrospectively. At least one β-HCG or AFP value before and after RT was required for inclusion. Serum tumor marker values were obtained prior to RT and 1 month after RT. Univariate and multivariate Cox regression analyses evaluated changes in β-HCG and AFP as predictors of OS and iPFS. Patients with normal tumor markers prior to RT were excluded from analyses. <h3>Results</h3> Sixty-two male patients who received RT between 2002 and 2021 were included. Median age was 30 years (range, 2 to 61). The primary tumor was testicular in 81% and mediastinal in 15%. Histology was seminoma in 10%. At diagnosis, the median number of BM was 2, and the median largest diameter was 1.8 cm. Initial RT included whole brain radiation therapy in 55%, stereotactic radiosurgery in 34%, and both in 10%. 31% had resection preceding RT. Most patients had extracranial disease (79%) and received chemotherapy within a month of RT (66%). During RT, radiographic progression of extracranial disease occurred in 34% of patients. Median OS and iPFS were 20.6 and 27.7 months, respectively. Among 41 patients with baseline β-HCG above the normal range, β-HCG decreased at 1 month after RT in 51%. Patients with decreased β-HCG, versus those with increased β-HCG, had significantly better OS (median not reached versus 5.4 months) and iPFS (median not reached versus 4.7 months). These correlations remained significant on multivariate analysis, controlling for largest BM diameter and RT modality (OS: HR = 13, 95% CI = [4.6, 37], p = 1 × 10⁻⁶; iPFS: HR = 6.4, 95% CI = [2.2, 19], p = 6 × 10⁻⁴). These correlations also remained significant whether or not patients had extracranial disease progression during RT (p < 0.05). Among 20 patients with baseline AFP above the normal range, AFP decreased at 1 month after RT in 75%. Likewise, decreased AFP was correlated with better OS on univariate regression (p = 0.04). <h3>Conclusion</h3> To our knowledge, this is the first study to evaluate changes in serum tumor markers as predictors of outcomes after RT for GCT BM. Decrease in β-HCG one month after RT was associated with better OS and iPFS on multivariate analysis, and likewise, decrease in AFP was associated with better OS on univariate analysis. These data indicate that post-RT β-HCG and AFP levels are useful predictors of outcomes in patients with GCT BM.

Is hospitalization within 6 months of completion of radiation therapy for endometrial cancer associated with decreased survival? (584)

<b>Objectives:</b> Radiation therapy (RT) is a core component in the management of women with locally advanced endometrial cancer (EC). For patients with early-stage (I and II), intermediate-risk disease, adjuvant RT is considered the standard of care. We hypothesized that hospitalization within six months of the completion of RT was associated with decreased overall survival (OS) and progression-free survival (PFS). We tried to identify factors predictive of a patients' likelihood of hospitalization within a short term of RT completion. <b>Methods:</b> An IRB-approved, retrospective cohort study included all patients who were diagnosed with EC and treated with radiation at our institution from January 2019 through December 2020. Data collected included functional status, disease stage, treatment course, hospitalizations, and demographics. Performance status was monitored via the Kamofsky Performance Scale. Common terminology criteria for adverse event (CTCAE) constipation and fatigue grades were gathered to provide insight into a patient's tolerance of RT. Statistical analysis was performed via Fisher's exact test. The Kaplan-Meier product estimator was utilized to derive survival curves, which were then compared via log-rank test. A critical value of p <0.05 was set for statistical significance. <b>Results:</b> Of 287 eligible patients, 27 (9.4%) were hospitalized within six months of RT. Of those patients, 13 of 27 (48%) were hospitalized within 30 days of completion of RT, and an additional five patients were hospitalized within 45 days of completion of radiation. The median length of hospitalization was six days, with hospital stays ranging from one to 20 days. Of patients who were hospitalized, 15 received EBRT alone, ten received vaginal brachytherapy alone, and two received a combination of EBRT + brachytherapy. The most common indications for hospitalization included disease progression, vaginal bleeding, altered mental status, failure to thrive, infection, and cardiovascular events. Most patients (21/27) did not undergo procedural intervention during their hospitalization, although two patients were admitted to the intensive care unit, and ultimately five of 27 patients expired during the hospitalization. Of the patients who expired, 40% of deaths were disease-related, while 60% were from other causes. Of the six patients who underwent procedural intervention during their admission, interventions included palliative RT, uterine artery embolization, biopsy, pleural catheter placement, and scheduled procedures unrelated to their disease process, inclusive of cholecystectomy and colonoscopy. Hospitalization within six months was associated with both decreased OS (p < 0.0001) and decreased PFS (p <0.0001). There was no significant variation in performance status, as indicated by Kamofsky's performance score, between patients who were and were not hospitalized within six months of completion of RT. BMI, age, constipation, and fatigue were not statistically significant predictors of a patients' likelihood of short interval hospitalization. <b>Conclusions:</b> Women with EC who received RT as part of their treatment and were hospitalized within six months had a statistically significant decreased OS and PFS. Age, BMI, race, and performance status were not found to be predictive of a patient's risk of short interval hospitalization.

The Use of Contralateral Autologous Breast Grafting Tissue In Breast Reconstruction: A New Approach

Background: Breast reconstruction surgery is an exceptionally important tool for repair of defects and asymmetries caused by the various types of surgical breast cancer treatment. Reconstruction is indicated regardless of lesion location in the breast when a quadrantectomy or sector resection has been performed. Although several surgical techniques are available for reconstruction, we propose a method based on contralateral breast graft replacement to preserve shape and symmetry. Methods: This quasi-experimental study was performed with a sample of 42 women who had undergone quadrantectomy or wide resection, followed by radiation therapy, for treatment of breast cancer. The outcomes of interest were breast aesthetics and symmetry in the immediate postoperative period and after 3 months of radiation therapy. All patients were photographed preoperatively, pre-radiation therapy, and 3 months post radiation therapy. Before-and-after photographs were sent to four independent experts in the field, who, in a blinded manner, used a continuous visual analogue scale (VAS) of 0 to 10 to assess breast symmetry and aesthetic appearance. Results: The mean (SD) VAS score was 8.74 (0.75) for symmetry and 8.76 (0.80) for aesthetics (p&gt;0.50 for both). Comparison of VAS scores assigned to preoperative and postoperative images revealed that autologous breast tissue grafting was useful. Conclusion: These findings suggest that, when combined with established techniques, autologous contralateral breast tissue grafting is a feasible alternative for breast reconstruction that provides satisfactory aesthetics and symmetry.

Radiation Oncology-Specific Surveillance After Palliative Radiation Treatment for Spine and Non-Spine Bone Metastases

Palliative radiation therapy (RT) can be an effective tool for bone metastases. NCCN guidelines recommend imaging every 3 months after RT for spine metastases (SM), yet no standard surveillance guidelines exist after RT for non-spine bone metastases (NSBM). We sought to evaluate factors associated with radiation oncology-specific follow-up after palliative RT.In a large single-institution retrospective cohort analysis, we identified all patients receiving RT for bone metastases by ICD-10 codes and RT prescription from 2017-2019. Demographic, clinical, and RT data were collected. Overall survival (OS) was calculated using Kaplan-Meier analysis. Factors associated with urgent care (UC) evaluation and radiation oncology follow-up were evaluated with multivariable logistic regression among patients surviving or followed to 3 months post-RT.Overall, 3082 patients (39% NSBM, 61% SM) received RT for bone metastases. Within 3 months of RT, 49% had radiation oncology follow-up, 79% underwent imaging, and 27% were seen in the UC. For patients with NSBM, follow-up CT was most common (55%) while for SM, MRI and CT were common (both 54%). Median OS was 10.0 months for SM (95% CI 8.9-11.0) and 13.5 months for NSBM (95% CI 11.5-15.5), with 1343 (71%) SM patients and 923 (77%) NSBM patients surviving to > = 3 months post-RT. Of the 2266 3-month survivors (41% NSBM, 59% SM), 1619 (71%) had radiation oncology follow-up, with higher performance status (OR 2.1, 95% CI 1.44-3.05) and younger patients (< 65yo; OR 1.2 95% CI 1.04-1.50) more likely to have follow-up. Median time-to-visit was 59 days (IQR 38-77), with follow-up time distributions significantly different between SM and NSBM (U = 333075, P = 0.01). Of the 3-month survivors, 553 (24%) patients were seen in the UC, with older and white patients less likely to visit the UC (P < 0.05). Median OS for NSBM was longer than the OS for SM patients (22.1 v 17.5 months; HR 0.87 [95% CI 0.78-0.98]). A minority of patients (397, 18%) underwent a subsequent RT course, occurring within 3 months for 183 patients and at a median time of 95 days [IQR 61-130]. Younger age and race were associated with a subsequent RT course (P < 0.05), while performance status and gender were not associated.After RT for bone metastases, most patients had radiation oncology-specific surveillance, which was associated with younger age and improved performance status. Most patients survived to 3 months post-RT, with a substantial minority receiving a second RT course. Patients with NSBM had longer survival and different time-to-follow-up compared to SM, highlighting the need for further clarification on what the optimal follow-up should be for NSBM. Race was a predictor of UC visits, likely reflecting health disparities that require further investigation. These data support radiation oncology specific follow-up after RT, particularly among younger patients and those with higher performance status with specific attention to racial disparities.

Characterization and Predication of Signal Changes in Normal Liver Parenchyma on Gadoxetic Acid Enhanced Magnetic Resonance Imaging After Liver Directed Radiation Therapy

Focal liver reactions (FLR) in areas of prior radiation therapy (RT) on MRI are a phenomenon that has been reported in small series. However, little is known about the temporality and dosimetry of FLR and how they evolve over time. Understanding dosimetry, temporality, and clinical predictors for FLR formation might help us understand the biology of radiation induced liver changes and prevent toxicity.We identified 122 patients who received RT to the liver. The 1-6 month and 6-12 month post-RT MRI scans (hepatobiliary phase with gadoxetic acid) were fused to treatment planning CT scans in areas of prior RT. FLR were delineated by two independent raters. A dose-volume-histogram was used to identify the threshold isodose line (IDL) for each FLR. IDL were converted to a bioequivalent dose (BED) using α/β = 9 for liver parenchyma. MRI scans with no FLR were evaluated by a radiologist to assess for adequate contrast excretion.146 MRI scans for 100 patients were available for analysis. The median age was 65 years. Hepatocellular carcinoma accounted for 79% of cases. Baseline ALBI scores of 1,2 and 3 were observed in 26%, 57% and 17% of patients, respectively. 66% of patients had cirrhosis, with hepatitis C being most common cause (37%). The median dose delivered was 45 gray in 5 fractions. FLR were identified for 73% and 67% of patients at 1-6 months and 6-12 months. Of 26 patients with no FLR at 1-6 months, 54% exhibited poor contrast excretion. The median volume of FLR was 99 cc at 1-6 months, contracting to 43 cc at 6-12 months (P < 0.001). The median (IDL) for FLR was 3541 cGy at 1-6 months, increasing to 4519 cGy (P < 0.001). The median BED was 6355 cGy at 1-6 months, increasing to 8871 cGy (P < 0.001). There was excellent agreement between raters for the presence of FLR at 1-6 (κ = 0.82) and 6-12 months (κ = 0.83) and for FLR volumes (ICC of 0.94 at 1-6 and 0.88 at 6-12-months). 45 patients were evaluated at both time points. Of the 33 patients with an FLR at 1-6 months, 15% experienced resolution at 6-12 months. None of the 12 patients without an FLR on 1-6 months MRI demonstrated one at 6-12 months. On multivariate analysis, cirrhosis (PR: 1.35; P = 0.05) was associated with a higher likelihood of FLR. ALBI score 2 (PR: 0.77; P = 0.04), ALBI score 3 (PR 0.61; P = 0.01), and receipt of systemic therapy within 1 month of RT (PR: 0.74; P = 0.03) were associated a lower likelihood. Prior RT or treatment with Y-90 did not predict for FLR.We report the median volume, IDL and BED associated with FLR at two time points and demonstrate resolution or improvement in a significant proportion of patients over time. Absence of FLR was associated with poor liver function and contrast excretion. Excellent inter-rater agreement indicates that our results are reproducible. Additional analysis is needed to determine the clinical significance of these findings.

Brain Metastases in Metastatic Cutaneous Melanoma: Patterns of Care and Clinical Outcomes in the Era of Immunotherapy and Targeted Therapy

Immune checkpoint inhibitors (CPIs) and BRAF inhibitors (BIs) are standard treatments for metastatic melanoma and have intracranial activity against melanoma brain metastases (MBMs). However, optimal use of CPI/BI with radiation therapy (RT) is not well established. This study evaluates the current practice pattern of how these systemic therapies are chosen and combined with either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for MBMs. The study also examines if upfront SRS+CPI results in superior intracranial control (IC) than upfront SRS without CPI or upfront CPI/BI followed by salvage RT.Patients with MBMs who received their first course of intracranial RT with between 1/2014 and 12/2019 at a tertiary cancer center were retrospectively reviewed. Patients with leptomeningeal disease and MBMs from non-cutaneous melanoma were excluded. Prior exposure before MBM diagnosis and concomitant use of CPIs/BIs within 3 months of RT were evaluated. Binary logistic regression was performed to determine predictors of SRS or CPI use. Cox regression analysis was used to assess the association with IC, which was calculated from the time of MBM diagnosis to the first intracranial progression after upfront MBM treatment.A total of 123 patients with MBMs with a median age of 61 (IQR: 51-69) were identified, and 55% were BRAF-mutant. There were 75 patients (61%) with 1-4 MBMs, 31 patients (25%) with 5-10 MBMs, and 17 (14%) patients with > 10 MBMs. Before MBM diagnosis, 30% had prior CPI and 18% had prior BI. For the upfront MBM treatment, 64% received SRS (66% with CPI and 23% with BI), 27% received WBRT (42% with CPI and 30% with BI), 9% received upfront CPI/BI. The baseline characteristics were balanced between the patients who received upfront SRS and upfront CPI/BI except patients who received upfront CPI/BI were more likely to have a BRAF mutation (82% vs. 49%, P = 0.04). The median follow-up was 8.7 mo (IQR: 2.8-22) for all patients and 32 mo (IQR: 18-45) for living patients. For patients who received upfront CPI/BI, 73% underwent salvage SRS and 27% with salvage WBRT at a median of 5.7 mos [IQR: 3.0-7.7] after MBM diagnosis. Fewer number of MBMs, higher KPS, and craniotomy were significant predictors of SRS use on multivariable logistic regression. For the upfront SRS cohort, treatment after 2016, BRAF-wild type status, and prior CPI exposure were associated with higher likelihood of concomitant CPI use with SRS. After adjusting for the number of MBMs, upfront SRS+CPI was associated with higher IC than upfront SRS without CPI (HR: 0.43, 95% CI: 0.22-0.84, P = 0.02). Upfront SRS+ CPI also trended towards a higher IC than upfront CPI/BI with salvage RT (HR: 0.54, 95% CI: 0.27-1.1, P = 0.07) after adjusting for the number of MBMs.Upfront SRS with concomitant CPI was the most frequently used approach to treat newly diagnosed favorable MBMs and may yield superior IC than upfront SRS without CPI or upfront CPI/BI.R. Chin: None. K. Chen: None. C.D. Abraham: None. C.G. Robinson: Research Grant; Varian. Consultant; Varian, AstraZeneca, EMD Serono. Advisory Board; Radialogica. Stock Options; Radialogica. S.M. Perkins: I serve on the Medical Advisory Committee for Mevion Medical Systems and receive compensation for this role.; Mevion Medical Systems. T.M. Johanns: None. L.F. Hernandez-Aya: None. J.W. Keller: None. J. Dowling: None. K. Rich: None. M. Chicoine: None. A.H. Kim: None. G.P. Dunn: None. G. Ansstas: None. J. Huang: None.

Factors Associated With Premature Ovarian Insufficiency in Young Women With Locally Advanced Rectal Cancer Treated With Pelvic Radiation Therapy

PurposePelvic radiation therapy (RT) is standard of care for patients with locally advanced rectal cancer (LARC). Premature ovarian insufficiency (POI) in premenopausal women is a possible side effect. The purpose of our study was to evaluate factors associated with POI in women younger than 50 years, treated with pelvic RT for LARC, including those who underwent ovarian transposition (OT). Methods and MaterialsWe retrospectively reviewed the records of women younger than 50 years treated with pelvic RT for LARC at our institution between 2001 and 2019. Clinical and hormonal data were used to determine ovarian function. The ovaries and uterus were contoured and dose volume histograms were generated. Association of clinical and dosimetric factors with POI within 12 months of RT was evaluated using Wilcoxon-rank sum test and Fisher's exact test. ResultsWe identified 76 premenopausal women at time of RT with median age of 43 years (range, 20-49). Twenty-six women (34%) underwent OT. Neoadjuvant, concurrent, and adjuvant chemotherapy was administered in 56 (74%), 69 (91%), and 26 (34%) women, respectively. Median RT dose was 50 Gy/25 fractions. Among 75 women with 12 months of follow-up, 25% had preservation of ovarian function, all in the OT group. Ovarian function was preserved in 19 (76%) women who underwent OT. The median of ovarian mean dose was 1.7 Gy in the OT group versus 44.8 Gy in the non-OT group (P < .001). OT and age at RT were significantly associated with POI (P < .001). No patient with ovarian mean dose less than 1.36 Gy developed POI. ConclusionsOT was significantly associated with reduced risk of POI by enabling lower radiation doses to the ovaries. OT should be considered in young patients undergoing pelvic RT. Although there appears to be a significant association between ovarian mean dose and POI, larger studies are needed to find a dosimetric threshold. Our results suggest keeping the dose to the ovaries as low as reasonably achievable in patients who undergo OT and pelvic RT.

Diagnostic utility of (18)f-fluciclovine positron emission tomography (FACBC) in biochemically recurrent (BCR) prostate cancer (PCa) based on prior primary treatment modality for localized disease and the impact of FACBC findings on treatment selection.

34 Background: Management of BCR PCa requires accurate assessment of location and extent of recurrent disease. FACBC has been shown to be a sensitive modality for detection and localization of recurrent disease but treatment guidelines are based on the findings of conventional (conv) imaging, including computed tomography, magnetic resonance imaging, or bone scintigraphy, and little is known about how prior treatment impacts FACBC findings and concordance with conv scans. Methods: This single-center retrospective study included 137 patients (pts) who had FACBC for BCR at the University of Wisconsin-Madison from 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts were classified by type of primary treatment for localized PCa, either radical prostatectomy (RP) or radiation therapy (RT). Findings of conv scans performed within 4 weeks prior or any time after FACBC were collected. Results: 105 pts had RP and 32 pts had RT as their primary PCa treatment. Gleason score and PSA at diagnosis were similar between groups. Median PSA at time of FACBC was higher in the RT compared to RP group (3.3 vs 0.7 ng/dL) and median time from initial diagnosis to FACBC was longer (70 vs 55 months). Frequency of (+) FACBC findings was higher in the RT group (66% vs 47%); only 3% of pts in the RT group had a (-) FACBC compared to 29% in the RP group. The rate of (+) lesions in the prostate/prostate bed was higher in the RT group (41% vs 22%), while the rate of (+) lesions in pelvic nodes and distant sites was similar between groups. Of 69 pts who also had conv imaging, 61% had concordant conv imaging findings. In the RT group, conv and FACBC findings were similar in 47% of pts and not similar in 28%. In the RP group, conv and FACBC findings were similar in 26% of pts and not similar in 17%. Management after FACBC is listed in table. Median time from FACBC to first (+) conv scans was 6 (range: 0-18) and 5 (range: 0-17) months for RT and RP groups, respectively. Conclusions: In this large retrospective cohort, pts treated with initial RT had a longer median time from diagnosis to FACBC and higher median PSA at the time of FACBC compared to the RP group. RT patients had a higher rate of (+) FACBC findings but were more likely to continue on observation. The median time from FACBC to first (+) conv scan was 5-6 months, supporting the role of FACBC in earlier detection of recurrent disease in both groups of patients. Further analysis of concordance between FACBC and conv imaging is in process. [Table: see text]

Changes in functional status associated with radiation for prostate cancer in older veterans

BackgroundAlthough older men value maintaining independence and avoiding functional decline, little is known about their functional trajectories with receipt of prostate radiation. MethodsWe performed a retrospective cohort study including veterans age 65+ with localized prostate cancer who resided in a VA nursing facility while receiving prostate radiation from 2005 to 2015. We evaluated the change in Minimum Data Set (MDS) activities of daily living (ADL) score during 6 months from the start of treatment. Because prior studies have shown Charlson Comorbidity Index (CCI) to be a strong predictor of treatment-related toxicity, analysis included interaction with CCI. ResultsWe identified 487 patients with median age 73 (range 65–94). For the average patient in our cohort, the predicted MDS-ADL score worsened from 2.9 (95% CI 2.4–3.6) at the start of radiation to 3.8 (95% CI 3.1–4.8) at 3 months and then 4.5 (95% CI 3.5–5.7) at month 6. Patients with greater comorbidity (CCI ≥ 4) had worse functional outcomes in months 0–3 compared to patients with less comorbidity (CCI 0–3). MDS-ADL score worsened by 1.9 in the CCI ≥4 patients compared to 0.3 in the CCI 0–3 group During months 3–6, patients in both Charlson groups experienced similar worsening of MDS-ADL score. ConclusionsIn a vulnerable population of older patients with localized prostate cancer, radiation was associated with a decline in functional independence. Patients with higher comorbidity experienced more severe functional decline within the first 3 months of radiation therapy. In all comorbidity levels, functional status had not returned to baseline by 6 months.

Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer

PurposeHypofractionated radiation therapy can be used to treat patients with muscle-invasive bladder cancer unable to have radical therapy. Toxicity is a key concern, but adaptive plan-of the day (POD) image-guided radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy.MethodsHYBRID is a Phase II randomized trial that was conducted at 14 UK hospitals. Patients with T2-T4aN0M0 muscle-invasive bladder cancer unsuitable for radical therapy received 36 Gy in 6 weekly fractions, randomized (1:1) to standard planning (SP) or adaptive planning (AP) using a minimization algorithm. For AP, a pretreatment cone beam computed tomography (CT) was used to select the POD from 3 plans (small, medium, and large). Follow-up included standard cystoscopic, radiologic, and clinical assessments. The primary endpoint was nongenitourinary Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (≥G3) toxicity within 3 months of radiation therapy. A noncomparative single stage design aimed to exclude ≥30% toxicity rate in each planning group in patients who received ≥1 fraction of radiation therapy. Local control at 3-months (both groups combined) was a key secondary endpoint.ResultsBetween April 15, 2014, and August 10, 2016, 65 patients were enrolled (SP, n = 32; AP, n = 33). The median follow-up time was 38.8 months (interquartile range [IQR], 36.8-51.3). The median age was 85 years (IQR, 81-89); 68% of participants (44 of 65) were male; and 98% of participants had grade 3 urothelial cancer. In 63 evaluable participants, CTCAE ≥G3 nongenitourinary toxicity rates were 6% (2 of 33; 95% confidence interval [CI], 0.7%-20.2%) for the AP group and 13% (4 of 30; 95% CI, 3.8%-30.7%) for the SP group. Disease was present in 9/48 participants assessed at 3 months, giving a local control rate of 81.3% (95% CI, 67.4%-91.1%).ConclusionsPOD adaptive radiation therapy was successfully implemented across multiple centers. Weekly ultrahypofractionated 36 Gy/6 fraction radiation therapy is safe and provides good local control rates in this older patient population.

Inhibition of Nrf2 might enhance the anti-tumor effect of temozolomide in glioma cells via inhibition of Ras/Raf/MEK signaling pathway

Background Glioblastoma (GBM) is the most common aggressive primary cancer occurring in the brain tissue. GBM accounts 16% of primary brain tumors and half of gliomas. Additionally, the incidence of GBM is increases with aging, and reaches the peak at the age of 75 to 84 years. The survival of patients with GBM remains at a low level, only less than 5% patients diagnosed with GBM survive for 5 years. Temozolomide (TMZ) is a DNA alkylating agent and is currently a first line chemotherapeutic treatment for GBM. TMZ combined with radiation therapy has been shown to prolong the overall survival (OS) to 14.6 months compared with 12.1 months for radiation therapy alone. NF-E2-related factor 2 (Nrf2) is a transcription factor that contains seven functional domains. The binding of Keap1 to Nrf2 is a central regulator of the cellular defense mechanism against environmental stresses. Methods First, Nrf2 overexpression and inhibition models were constructed in U251 cells using transfection. The percentage of viable cells was detected using the MTT assay. Then, the expression of the HO-1 regulator was detected using qPCR, and the concentrations of oxidative stress related factors were detected using ELISAs. The levels of proteins related to oxidative stress and the Ras/Raf/MEK signaling pathway was detected using western blotting analysis. Results We initially established Nrf2 inhibition and activation cell models in U251 cells and found that the inhibition of Nrf2 expression decreased the mRNA and protein levels of the anti-oxidative enzymes, as well as the secretion of these enzymes into the cellular microenvironment. These effects might be mediated by the inhibition of Ras/Raf/MEK signaling pathway, leading to the inhibition of cellular proliferation. Conclusions Inhibition of Nrf2 expression might enhance the effect of TMZ on the treatment of GBM and might be a new therapeutic strategy.

The efficacy of palliative radiation therapy in the treatment of recurrent and metastatic ovarian cancer.

129 Background: Ovarian cancer is the 2nd most common gynecologic malignancy with surgery and platinum-based chemotherapy as the mainstay of initial treatment. However, ovarian cancer has generally high rates of recurrence and metastasis after primary therapy. For patients with progressive or symptomatic disease, radiation therapy (RT) can be utilized as an effective option for palliation. Methods: A retrospective review was conducted of patients treated with palliative RT for symptomatic or recurrent ovarian cancer between 2015-2019 at a single institution. 17 women were identified who received 20 courses of RT. Response was classified as complete response (CR), partial response (PR), and progressive disease (PD). Overall response rate (ORR) was the sum of CR and PR. Results: Median age at RT was 57 (range 36-76). Histologic subtypes were high grade serous (65%), low grade serous (12%), clear cell (12%), and other (12%). The most common indications were pain (65%), bleeding (30%), and asymptomatic progression (20%). 18 of 20 RT courses were delivered to soft tissue or nodal metastases. RT techniques included 2D/3D (60%), IMRT (30%), and SBRT (10%). Dose ranged from 20-60 Gy in 3-28 fractions. 20 Gy in 5 fractions (25%) and 30-31 Gy in 10 fractions (25%) were most common. Of the 16 RT courses for symptomatic disease, clinical ORR was 87.5% within 3 months of RT (50% PR and 37.5% CR). 3 treatments had sustained response beyond 3 months. 2 developed PD. Of 11 RT courses with follow-up imaging, radiographic ORR was 36.1% (27% PR and 9.1% CR) within 3 months of RT. 1 had sustained PR beyond 3 months. Of the 10 RT courses for symptomatic high grade serous histology, PR and CR was seen in 50% and 40% of patients within 3 months (90% ORR). Conclusions: Palliative RT offers high rates of clinical response for symptomatic patients with metastatic ovarian cancer within 3 months of treatment delivery. Rapid clinical response rates were particularly favorable for those with high grade serous histology. RT should be considered as a standard palliative option for patients with symptomatic ovarian cancer metastases. Further prospective studies are warranted to establish the optimal timing, dose, and relation to chemosensitivity in this setting.

Palliative Treatment Utilization and Outcomes in Elderly Patients with Locally Advanced Esophageal Carcinoma: A Review of the National Cancer Database

A significant percentage of elderly patients with locally advanced esophageal cancer receive non-definitive treatment. The goal of this study was to further examine palliative treatment choices and outcomes in this group. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2013 who received palliative therapy were identified using the National Cancer Database and stratified based on treatment type: chemotherapy only, radiation only, or sequential chemoradiation. Sequential treatment was defined as chemotherapy and radiation start dates ≥14 days apart. Variables associated with choice of treatment modality were evaluated using logistic regression and survival was evaluated using Cox proportional hazard analysis. 3,422 patients were identified with a median age of 79. Patients were predominantly white (87.0%) and male (69.4%), with tumors in the distal esophagus (56.4%) and of adenocarcinoma histology (51.5%). Overall, 16.5% of patients received chemotherapy only, 51.0% received radiation only, and 31.6% received sequential chemoradiation. The median overall survival was 8.1 months for radiation therapy (95% CI: 7.6-8.6); 9.9 months for chemotherapy (95% CI: 8.6-11.1); and 16.1 months for sequential treatment (95% CI: 14.7-17.5). Radiation dose ≤30 Gy was more common within the radiation alone group (24.7% vs 8.0% of sequential group). Sequential chemoradiation demonstrated improved survival over single-modality therapy regardless of histology (p<.001). For adenocarcinoma, chemotherapy alone resulted in improved survival over radiation alone (p = .001), however no difference was observed between these treatments for squamous cell carcinoma (p = 0.09). Age (hazards ratio (HR) 1.10, 95% CI: 1.01 - 1.22) and high tumor grade (HR 1.35, 95% CI: 1.24 - 1.46) were associated with an increase in mortality. Treatment at an academic center (HR 0.91, 95% CI: 0.83 - 0.99) and sequential treatment (HR 0.66, 95% CI: 0.58 - 0.75) were associated with decreased mortality. Higher income (Odds ratio (OR) 1.88, 95% CI: 1.34 to 2.63) and educational status (OR 1.34, 95% CI: 1.06 to 1.69) were associated with increased likelihood of receiving sequential treatment versus chemotherapy alone, whereas clinical stage III (OR 0.73, 95% CI: 0.58 to 0.91) and adenocarcinoma histology (OR 0.72, 95% CI: 0.57 to 0.91) were associated with an increased likelihood of receiving chemotherapy only. Sequential chemoradiation was associated with improved survival when compared to single modality treatment. Chemotherapy alone demonstrated improved outcomes over radiation alone for adenocarcinoma, however these treatments demonstrated comparable survival for squamous cell carcinoma. A limitation of this study is the inability to account for selection factors such as performance status or assess important outcomes such as quality of life that also impact palliative treatment decisions and survival.

A Deep Learning Model for Predicting Xerostomia Due to Radiation Therapy for Head and Neck Squamous Cell Carcinoma in the RTOG 0522 Clinical Trial

Xerostomia commonly occurs in patients who undergo head and neck radiation therapy and can seriously affect patients' quality of life. In this study, we developed a xerostomia prediction model with radiation treatment data using a 3-dimensional (3D) residual convolutional neural network (rCNN). The model can be used to guide radiation therapy to reduce toxicity. A total of 784 patients with head and neck squamous cell carcinoma enrolled in the Radiation Therapy Oncology Group 0522 clinical trial were included in this study. Late xerostomia is defined as xerostomia of grade ≥2 occurring in the 12th month of radiation therapy. The computed tomography (CT) planning images, 3D dose distributions, and contours of the parotid and submandibular glands were included as 3D rCNN inputs. Comparative experiments were performed for the 3D rCNN model without 1 of the 3 inputs and for the logistic regression model. Accuracy, sensitivity, specificity, F-score, and area under the receiver operator characteristic curve were evaluated. The proposed model achieved promising prediction results. The performance metrics for 3D rCNN model with contour, CT images, and radiation therapy dose; 3D rCNN without contour; 3D rCNN without CT images; 3D rCNN without the dose; logistic regression with the dose and clinical parameters; and logistic regression without clinical parameters were as follows: accuracy: 0.76, 0.74, 0.73, 0.65, 0.64, and 0.56; sensitivity: 0.76, 0.72, 0.77, 0.59, 0.72, and 0.75; specificity: 0.76, 0.76, 0.71, 0.69, 0.59, and 0.43; F-score: 0.70, 0.68, 0.69, 0.56, 0.60, and 0.57; and area under the receiver operator characteristic curve: 0.84, 0.82, 0.78, 0.70, 0.74, and 0.68, respectively. The proposed model uses 3D rCNN filters to extract low- and high-level spatial features and to achieve promising performance. This is a potentially effective model for predicting objective toxicity for supporting clinical decision making.