Faculty Bibliography

INTRODUCTION/UNASSIGNED:Brain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear. METHODS/UNASSIGNED:This single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher's exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure. RESULTS/UNASSIGNED:A total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure. DISCUSSION/UNASSIGNED:An optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy.

Purpose/Objective(s): Outcomes following accelerated partial breast irradiation in select women with early-stage breast cancer are comparable to whole breast irradiation. ASBRT is an attractive treatment option, but mature toxicity outcomes are limited. Toxicity risk with SBRT has been associated with a consecutive daily schedule in other organs. In the present study, we explore the association of treatment schedule and fat necrosis. Materials/Methods: Early-stage breast cancer patients (Stage 0 and I) were treated per an institutional protocol. A minimum of 4 gold fiducials were implanted around the lumpectomy cavity for target delineation and tracking. The clinical treatment volume (CTV) was defined as lumpectomy cavity with a uniform 0-10 mm expansion confined to breast tissue. The planning treatment volume (PTV), defined as the CTV with a 0-2 mm uniform expansion, was prescribed 30 Gy in 5 fractions. Breast examination and mammography were completed per routine institutional practice. A patient was deemed to have fat necrosis when breast examination identified a tumor bed mass with distinctive mammographic characteristics.
Result(s): Twenty women were treated over a 7-year period extending from September 2008 to September 2015 and followed for a minimum of 6 years. The median CTV expansion was 5 mm (range, 0-10), median PTV was 62.5 cm³ (range 15-142), median PTV/breast volume ratio was 8.3% (range 4.1-25.6), median prescription isodose line was 83% (range 75-87) and median treatment duration was 7 days (range 5-13). Seven patients were treated on 5 consecutive days (i.e., Monday through Friday). At a median follow up of 8 years (range, 6-12 years), 5 women developed fat necrosis. All 4 symptomatic patients had been treated on consecutive days and the symptomatic fat necrosis was diagnosed at a median follow-up of 5.9 years (range, 4.8-7.4). Cox regression analysis identified consecutive daily treatments as a predictor of symptomatic fat necrosis (OR: 26.8, p value=0.05).
Conclusion(s): Our mature findings demonstrate an association between Monday through Friday treatment and symptomatic fat necrosis. Fortunately, our research also suggests that symptomatic fat necrosis is curtailed by merely extending the treatment duration beyond 5 days. Accordingly, we believe that the Fast-Forward trial investigators should reevaluate their current assertion that 26 Gy whole breast irradiation delivered in 5 consecutive daily fractions over 5 or 7 days is a new standard treatment option. Only the yet to be completed 10-year analysis of this large prospective study will ultimately determine if delivering 5 large consecutive daily adjuvant breast radiation treatments is associated with symptomatic fat necrosis and if adding 2 additional days to the treatment course effectively curtails this adverse side-effect.
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Radiation-induced contrast enhancement (RICE) is a common side effect following radiotherapy for glioma, but both diagnosis and handling are challenging. Due to the potential risks associated with RICE and its challenges in differentiating RICE from tumor progression, it is critical to better understand how RICE prognosis depends on iatrogenic influence. We identified 99 patients diagnosed with RICE who were previously treated with either photon or proton therapy for World Health Organization (WHO) grade 1-3 primary gliomas. Post-treatment brain MRI-based volumetric analysis and clinical data collection was performed at multiple time points. The most common histologic subtypes were astrocytoma (50%) and oligodendroglioma (46%). In 67%, it was graded WHO grade 2 and in 86% an IDH mutation was present. RICE first occurred after 16 months (range: 1 - 160) in median. At initial RICE occurrence, 39% were misinterpreted as tumor progression. A tumor-specific therapy including chemotherapy or re-irradiation led to a RICE size progression in 86% and 92% of cases, respectively and RICE symptom progression in 57% and 65% of cases, respectively. A RICE-specific therapy such as corticosteroids or Bevacizumab for larger or symptomatic RICE led to a RICE size regression in 81% of cases with symptom stability or regression in 62% of cases. RICE progression went along with a worsening in progression-free survival (p = 0.04). While with chemotherapy and re-irradiation a RICE progression was frequently observed, anti-edematous or anti-VEGF treatment frequently went along with a RICE regression. For RICE, correct diagnosis and treatment decisions are challenging and critical and should be made interdisciplinarily

Proton beam radiotherapy (PRT) is used in the treatment of low-grade glioma (LGG) to mitigate long-term sequelae. Following PRT, increased rates of radiation-induced contrast enhancements (RICE) are suspected but poorly understood. We analyzed consecutive 227 patients (42 children and 185 adults) treated with PRT (54Gy RBE) for LGG from 2010 to 2020 and followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. Tumors were graded WHO 1 in a minority (n = 22, 12%) of adults, but a majority of children (n = 29, 69%). In contrast, tumors were graded WHO 2 in the majority (n = 160, 87%) of adults and a minority of children (n = 10, 24%). Five-year overall survival following PRT was 81% in adults and 91% in children. The risk of RICE was 5-fold more frequent in adults (25%) versus children (5%) (p = 0.0043). Also, within the adult cohort, RICE risk increases with age (p = 0,00128). In children and adults, RICE were symptomatic in 50% and 55% (n = 1 and 26) of cases with CTCAE grade 0 in 47% (n = 23), grade 1 in 25% (n = 12), 0% grade 2 (n = 0) and 29% grade 3 (n = 14), respectively. In adults, RICE risk was associated to WHO grading (8% in WHO grade 1 vs. 24% in WHO grade 2, p = 0.026), independent of age (p = 0.44) and irradiation dose (p = 0.005), but not independent of IDH mutational status. These data demonstrate effectiveness of PRT for LGG in both children and adults. The RICE risk is lower in children which are a main target group for PRT and differs with WHO grading

OBJECTIVE:The purpose of this study is to compare oncologic and functional outcomes of men with unilateral, localized PCa treated with stereotactic body radiotherapy (SBRT) versus focal cryoablation (FC). METHODS:Patients from our IRB-approved PCa database who underwent FC or SBRT and were eligible for both treatments were included. Patients with less than 1 year of follow-up or prior PCa treatment were excluded. The primary outcome was treatment failure, defined as salvage treatment or a Gleason group (GG) of ≥ 2 on post-treatment biopsy. Biochemical recurrence (BCR) was evaluated with Phoenix. Functional outcomes were based on EPIC surveys. Complications were categorized with the CTCAE 5.0. Outcomes were compared using descriptive statistics, univariate analyses, and Kaplan-Meier curve for failure-free survival (FFS) and BCR-free survival. P < 0.05 was significant. RESULTS:68 FC and 51 SBRT patients with a median age of 68 years (48-86) and a median follow-up time of 84 (70-101) months were included in this analysis. There was no difference in tumor risk (p = 0.47), GG (p = 0.20), or PSA (p = 0.70) among the two cohorts at baseline. At 7-year follow-up, no difference in FFS was found between the two cohorts (p = 0.70); however, significantly more FC patients had BCR (p < 0.001). At 48 months, no differences existed in urinary or bowel function; however, SBRT patients had significantly worse sexual function (p = 0.032). CONCLUSION/CONCLUSIONS:FC and SBRT are associated with similar oncologic and functional outcomes 7-year post-treatment. These results underscore the utility of FC and SBRT for the management of unilateral low-to-intermediate-risk PCa.

OBJECTIVE:To review quality-of-life (QoL) metrics between patients who underwent definitive stereotactic body radiotherapy (SBRT) versus active surveillance (AS) for management of low- to intermediate-risk prostate cancer (PCa). METHODS:A prospectively maintained PCa database was reviewed containing results of patient-reported QoL surveys. Patients with localized disease who chose AS or SBRT and completed at least one survey within four years of treatment were included. Patients who received salvage therapy were excluded. Survey results were compared across time using mixed-effects repeated measures analysis of covariance models that adjusted for factors significant in univariate analysis. A group x time interaction effect was examined to compare rate of change over time between AS and SBRT. P < 0.05 was significant. RESULTS:148 AS and 161 SBRT patients were included. Significantly more SBRT patients had intermediate-risk disease (p < 0.0001). AS had significantly worse sexual function compared to SBRT across time. While not significant, bowel function scores were lower for SBRT patients across time points. SBRT patients had significantly lower anxiety than AS patients at 24 months (p < 0.011) and 36 months (p < 0.010). Urinary function though worse in SBRT patients at 12 months in EPIC, was not significantly different in both groups across time points. CONCLUSION/CONCLUSIONS:SBRT patients have excellent QoL compared to AS with regard to anxiety post treatment. Though SBRT patients initially have worse urinary and bowel function than AS, scores were eventually similar in both cohorts by 48 months. SBRT patients have significantly worse sexual function post treatment. This study may help facilitate counseling in patients choosing PCa treatment.

BACKGROUND AND PURPOSE/OBJECTIVE:Radiation-induced contrast enhancements (RICE) are a common side effect following radiotherapy for glioma, but both diagnosis and handling are challenging. Due to the potential risks associated with RICE and its challenges in differentiating RICE from tumor progression, it is critical to better understand how RICE prognosis depends on iatrogenic influence. MATERIALS AND METHODS/METHODS:We identified 99 patients diagnosed with RICE who were previously treated with either photon or proton therapy for World Health Organization (WHO) grade 1-3 primary gliomas. Post-treatment brain MRI-based volumetric analysis and clinical data collection was performed at multiple time points. RESULTS:The most common histologic subtypes were astrocytoma (50%) and oligodendroglioma (46%). In 67%, it was graded WHO grade 2 and in 86% an IDH mutation was present. RICE first occurred after 16 months (range: 1-160) in median. At initial RICE occurrence, 39% were misinterpreted as tumor progression. A tumor-specific therapy including chemotherapy or re-irradiation led to a RICE size progression in 86% and 92% of cases, respectively and RICE symptom progression in 57% and 65% of cases, respectively. A RICE-specific therapy such as corticosteroids or Bevacizumab for larger or symptomatic RICE led to a RICE size regression in 81% of cases with symptom stability or regression in 62% of cases. CONCLUSIONS:While with chemotherapy and re-irradiation a RICE progression was frequently observed, anti-edematous or anti-VEGF treatment frequently went along with a RICE regression. For RICE, correct diagnosis and treatment decisions are challenging and critical and should be made interdisciplinarily.

BACKGROUND:Proton beam radiotherapy (PBT) offers physical dose advantages that might reduce the risk for secondary malignancies (SM). The aim of the current study is to calculate the risk for SM after X-ray-based 3D conformal (3DCRT) radiotherapy, intensity-modulated radiotherapy (IMRT), and active pencil beam scanned proton therapy (PBS) in patients treated for thymic malignancies. METHODS:Comparative treatment plans for each of the different treatment modalities were generated for 17 patients. The risk for radiation-induced SM was estimated using two distinct prediction models-the Dasu and the Schneider model. RESULTS:≤ 0.001). CONCLUSIONS:PBS achieved superior sparing of relevant OARs compared to 3DCRT and IMRT, leading to a lower risk for radiation-induced SM. PBS should therefore be considered in patients diagnosed with thymic malignancies, particularly young female patients.

BACKGROUND AND PURPOSE/OBJECTIVE:Proton beam radiotherapy (PRT) is used in the treatment of low-grade glioma (LGG) to mitigate long-term sequelae. Following PRT, increased rates of radiation-induced contrast enhancements (RICE) are suspected but poorly understood. MATERIALS AND METHODS/METHODS:We analyzed consecutive 227 patients (42 children and 185 adults) treated with PRT (54Gy RBE) for LGG from 2010 to 2020 and followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. RESULTS:Tumors were graded WHO 1 in a minority (n = 22, 12%) of adults, but a majority of children (n = 29, 69%). In contrast, tumors were graded WHO 2 in the majority (n = 160, 87%) of adults and a minority of children (n = 10, 24%). Five-year overall survival following PRT was 81% in adults and 91% in children. The risk of RICE was 5-fold more frequent in adults (25%) versus children (5%) (p = 0.0043). In children and adults, RICE were symptomatic in 50% and 55% (n=1 and 26) of cases with CTCAE grade 0 in 47% (n=23), grade 1 in 25% (n=12), 0% grade 2 (n=0) and 29% grade 3 (n=14), respectively. In adults, RICE risk was associated to WHO grading (8% in WHO grade 1 vs. 24% in WHO grade 2, p = 0.026), independent of age (p=0.44) and irradiation dose (p=0.005), but not independent of IDH mutational status. CONCLUSIONS:These data demonstrate effectiveness of PRT for LGG in both children and adults. The RICE risk is lower in children which are a main target group for PRT and differs with WHO grading.

Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the use of in-house social services and post-treatment inpatient rehabilitation, and RTW were assessed for 424 women, diagnosed with cervical, uterine, or vaginal/vulvar cancer, receiving curative radio(chemo)therapy. Progression-free RTW rate at 3 months was 32.3%, and increased to 58.1% and 63.2% at 12 and 18 months, respectively. Patients with advanced FIGO stages and intensified treatments significantly suffered more from acute pain and fatigue. A higher Charlson-Comorbidity-Index reliably predicted patients associated with a higher risk of acute fatigue during RT. Aside from the presence of children, no other household or lifestyle factor was correlated with increased fatigue rates. Women aged ≤ 45 years had a significantly higher risk of developing depression requiring treatment during follow-up. Post-treatment inpatient cancer rehabilitation, including exercise and nutrition counseling, significantly relieved fatigue symptoms. The burdens for recovery from cancer therapy remain multi-factorial. Special focus needs to be placed on identifying high-risk groups experiencing fatigue or pain. Specialized post-treatment inpatient cancer rehabilitation can improve RTW rates.