Faculty Bibliography

BACKGROUND AND PURPOSE/UNASSIGNED:To evaluate the dosimetric and toxicity profiles of stereotactic body radiotherapy (SBRT) for prostate cancer, comparing cohorts with and without intraprostatic boost (IPB) to assess feasibility and safety of IPB, with particular attention to urethral and bladder dose and toxicity. MATERIALS AND METHODS/UNASSIGNED:This retrospective cohort study analyzed 349 patients with localized prostate cancer treated between 2018 and 2023. Of these, 266 received SBRT with IPB, and 83 received SBRT without IPB. Patients were treated using a robotic SBRT platform with fiducial tracking. Dosimetric parameters for the urethra, including D0.03cc, D0.3cc, and V40Gy, and for the bladder, including D0.03cc, D5cc, D10cc, and V37Gy, were evaluated. Acute and late toxicities were assessed using CTCAE criteria. RESULTS/UNASSIGNED:For the urethra, median values for D0.03cc, D0.3cc, and V40Gy, and for the bladder, median values D0.03cc, D5cc, D10cc, and V37Gy were compared and no statistically significant differences were observed between the two cohorts. Late urinary toxicity of grade 3 or higher occurred in 2.25 % of patients in the IPB group and 2.47 % in the no IPB group, with no grade 3 acute toxicities reported. DISCUSSION/UNASSIGNED:These findings support the use of SBRT using an IPB as a feasible and safe approach to achieve focal dose escalation to dominant intra-prostatic lesions (DILs) without significantly increasing urethra or bladder dose or toxicity. Future research should focus on standardizing DIL contouring, exploring adaptive planning techniques to increase accuracy, and prospectively studying toxicity and quality of life in patients treated with IPB with SBRT.

INTRODUCTION/BACKGROUND:High-volume (≥ 50 %) biopsy core involvement (HVCI) is an independent risk factor for unfavorable intermediate-risk prostate cancer by NCCN guidelines. The studies demonstrating increased recurrence in high-volume disease were conducted in an era of conventional fractionation, often without dose-escalation. In the SBRT era, we explore the value of this pathologic criteria in intermediate-risk disease. METHODS:A large institutional database was reviewed to identify patients diagnosed with localized intermediate-risk (Gleason Grade [GG] 2 and 3) disease, who were treated with definitive five-fraction SBRT without ADT. HVCI was analyzed (1) traditionally with all positive cores given equal weight as well as weighted with a positive core of GG1 to GG3 given (2) linearly and (3) exponentially increased weight. Oncologic outcomes were analyzed using Cox and linear regression analysis. RESULTS:From 2009 to 2018, 888 patients with intermediate-risk prostate cancer were treated with five-fraction SBRT monotherapy to a median dose of 3500 cGy. The majority (68 %) had GG2 disease. HVCI was present in the 22 % and was inversely related to prostate volume and directly related to T-stage. Biochemical disease-free survival (BDFS) was not significantly associated with HVCI in the cohort (p = 0.47) nor in the GG2 (p = 0.85) and GG3 (p = 0.26) sub-cohorts. Similarly, when linear or exponential weight was given to a core with higher-grade disease, there was no association with BDFS. Finally, PSA nadir was not associated with HVCI; however, time to PSA nadir (TTN) was negatively associated with HVCI in the GG3 sub-cohort (p = 0.04). CONCLUSION/CONCLUSIONS:With a median follow-up of 4.1 years, HVCI was not associated with BDFS following SBRT monotherapy, particularly in patients with otherwise favorable intermediate-risk disease (GG2). TTN analysis suggests that HVCI may remain prognostic in GG3 disease (by definition unfavorable intermediate-risk). Further work should prospectively confirm whether HVCI is unnecessary in risk-stratifying GG2 disease in the SBRT era.

BACKGROUND:Meningiomas represent the most common primary intracranial tumors in adults, with WHO grade 1 typically associated with favorable outcomes following gross total resection (GTR). METHODS:This retrospective study included patients with CNS WHO grade 1 meningioma and available DNA methylation profiles (n=210). Clinical tumor characteristics and treatment course (e.g., surgical resection, extent of resection, radiotherapy) were evaluated. Integrated Scores (InS) were calculated based on methylation family using the DKFZ brain tumor classifier, CNS WHO grading, and chromosomal losses, categorized as low, intermediate, or high. Survival analyses employed Kaplan-Meier and Cox regression methods, with local progression-free survival defined as primary endpoint. RESULTS:In newly diagnosed cases, GTR was associated with a 93.0% 3-year progression-free survival (PFS), compared to 69.3% following subtotal resection (STR). Stratification by IntS showed that patients in the IntS-low group had superior outcomes: 3-y PFS of 93.4 after GTR and 77.4% after STR. In contrast, patients with IntS-intermediate/high profiles showed significantly worse outcomes, with PFS of 85.9% after GTR and 40.0% after STR. Following tumor recurrence, particularly those with IntS-intermediate/high, postoperative radiotherapy (RT) after STR may improve 3-year PFS to 88.9%, compared to much lower PFS rates in newly diagnosed cases managed without adjuvant RT after STR (3-year PFS: 40.0%). CONCLUSION/CONCLUSIONS:Our findings highlight the combined impact of both the extent of resection (EoR) and molecular risk profile on prognosis in newly diagnosed cases. While conservative management is feasible in lower-risk primary cases, recurrent or higher-risk patients may benefit from early postoperative RT.

PURPOSE/UNASSIGNED:Screening colonoscopies (CS) performed before prostate stereotactic body radiation therapy (SBRT) allow for identifying synchronous malignancies and comorbid gastrointestinal (GI) conditions. Performing these procedures prior to radiation precludes the necessity of post-SBRT pelvic instrumentation, which may lead to severe toxicity and fistulization. We review compliance of CSs, incidence of GI pathology, and the impact of pretreatment CS findings on subsequent physician-reported toxicity and patient-reported quality of life (QoL). METHODS AND MATERIALS/UNASSIGNED:We reviewed an institutional database of patients treated for prostate cancer with SBRT including toxicity and QoL outcomes. A detailed review of pretreatment CS findings was reviewed including identification of diverticulosis, location of polyp resection, and presence of hemorrhoids. Pretreatment CS findings were then correlated with outcomes following SBRT. RESULTS/UNASSIGNED:Identification of comorbid GI conditions was a common event, with the presence of diverticulosis in 49.5% (n = 100), hemorrhoids in 67% (n = 136), and polyps in 48% (n = 98). More than half of patients with polyps removed had at least 1 removed from the rectosigmoid. Pretreatment CS did not introduce a delay in SBRT start date. Grade 1 toxicity was significantly lower in patients who underwent CS closer to the initiation of SBRT. There was no increased risk of physician-graded toxicity in the presence of diverticulosis, hemorrhoids, or polyps. Patient-reported GI QoL pattern in our screening cohort mimicked that seen in the previously published nonscreened population. There was no overt QoL detriment observed in patients who had GI pathology identified before SBRT. CONCLUSIONS/UNASSIGNED:GI pathology identified in our elderly patient population was commonly identified on pretreatment CS. Screening CS may optimize bowel health for patients heading into radiation therapy. Toxicity and QoL for patients with GI pathologies identified on pretreatment CS do not preclude the delivery of prostate SBRT. We advocate for pretreatment CS in patients eligible prior to SBRT.

INTRODUCTION/UNASSIGNED:Brain metastases (BM) are the most common malignancy in the central nervous system (CNS) and observed in approximately 30% of cancer patients. Brainstem metastases (BSM) are challenging because of their location and the associated neurological risks. There are still no general therapeutic recommendations in this setting. Stereotactic radiosurgery (SRS) is one of few possible local therapy options but limited due to the tolerance dose of the brainstem. There is still no standard regarding the optimal dose und fractionation. METHODS/UNASSIGNED:We retrospectively analyzed 65 patients with fractionated stereotactic radiotherapy (fSRT) for 69 BSM. FSRT was delivered at a dose of 30 Gy in six fractions prescribed to the 70 % isodose performed with Cyberknife. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analyzed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. RESULTS/UNASSIGNED:Median follow-up was 27.3 months. One-year TIBC was 35.0 % and one-year LC was 84.1 %. Median OS was 8.9 months. In total, local progression occurred in 7.7 % and in 8.2 % symptomatic radiation-induced contrast enhancements (RICE) were diagnosed. In univariate analysis the Karnofsky performance scale index (KPI) (p = 0,001) was an independent prognostic factor for longer OS. Acute CTCAE grade 3 toxicities occurred in 18.4 %. CONCLUSION/UNASSIGNED:FSRT for BSM is as an effective and safe treatment approach with high LC rates and reasonable neurological toxicity despite the poor prognosis in this patient cohort is still very poor. Clinical and imaging follow-up is necessary to identify cerebral progression and adverse toxicity including RICE.

OBJECTIVES/UNASSIGNED:To evaluate the incidence and degree of rectal wall infiltration (RWI) of spacer gel used during prostate radiotherapy among two practitioners experienced in using rectal spacers. MATERIALS AND METHODS/UNASSIGNED:Consecutive patients with prostate cancer who received prostate radiotherapy after hydrogel rectal spacer insertion in August 2023-August 2024 by two experienced practitioners were retrospectively included. Post-implant magnetic resonance imaging examinations were evaluated by two radiologists for RWI: 0 (no abnormality), 1 (rectal wall edema), 2 (superficial RWI), and 3 (deep RWI). Scores 2-3 were considered positive for RWI and their location and degree of RWI (radial, longitudinal, and circumferential) were also categorized. Inter-reader agreement was assessed with Cohen's Kappa. RESULTS/UNASSIGNED:215 men were included. Agreement was substantial between the radiologists for RWI scores (Kappa, 0.697; 95% confidence interval, 0.594-0.800). RWI scores were 0 in 80.5% (173/215), 1 in 7.9% (17/215), 2 in 10.7% (23/215), and, 3 in 0.9% (2/215) of the men. Altogether, RWI was present (scores 2-3) in 11.6% (25/215), most commonly in the mid-gland and apex with median radial, longitudinal, and circumferential involvement of 3.2 mm, 8.6 mm, and 11.5%. None of these patients demonstrated any significant rectal toxicity. CONCLUSION/UNASSIGNED:RWI was very uncommon for experienced practitioners. The degree of RWI was focal and not associated with increased complications.

PURPOSE OF REVIEW/OBJECTIVE:The most common definitive treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. However, removing the bladder and surrounding organs poses risks of morbidity that can reduce quality of life, and raises the risk of death. Treatment strategies that preserve the organs can manage the local tumor and mitigate the risk of distant metastasis. Recent data have demonstrated promising outcomes in several bladder-preservation strategies. RECENT FINDINGS/RESULTS:Bladder preservation with trimodality therapy (TMT), combining maximal transurethral resection of the bladder tumor, chemotherapy, and radiotherapy (RT), was often reserved for nonsurgical candidates for radical cystectomy. Recent meta-analyses show that outcomes of TMT and radical cystectomy are similar. More recent bladder-preservation approaches include combining targeted RT (MRI) and immune checkpoint inhibitors (ICIs), ICIs and chemotherapy, and selecting patients based on genomic biomarkers and clinical response to systemic therapies. These are all promising strategies that may circumvent the need for radical cystectomy. SUMMARY/CONCLUSIONS:MIBC is an aggressive disease with a high rate of systemic progression. Current management includes neoadjuvant cisplatin-based chemotherapy and radical cystectomy with lymph node dissection. Novel alternative strategies, including TMT approaches, combinations with RT, chemotherapy, and/or ICIs, and genomic biomarkers, are in development to further advance bladder-preservation options for patients with MIBC.

BACKGROUND AND PURPOSE/UNASSIGNED:After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. METHODS/UNASSIGNED:In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. RESULTS/UNASSIGNED:Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9-40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. CONCLUSION/UNASSIGNED:FSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

BACKGROUND:Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing the radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5). METHODS:A total of 33 patients were enrolled from July 2012 until July 2020. Study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). Primary endpoint was the 3-year progression-free survival (PFS) , and secondary endpoints included overall survival, safety and treatment toxicities. RESULTS:With a median follow-up of 42 months, the 3-year estimates of PFS, local PFS and overall survival were 80.3%, 86.7% and 89.8%, respectively. Radiation-induced contrast enhancement (RICE) was encountered in 45%, particularly in patients with periventricularly-located meningiomas. Patients exhibiting RICE were mostly either asymptomatic (40%) or presented immediate neurological and radiological improvement (47%) after the administration of corticosteroids or bevacizumab in case of radiation necrosis (3/33). Treatment-associated complications occurred in one patient with radiation necrosis who died due to postoperative complications after resection of radiation necrosis. The study was prematurely terminated after recruiting 33 of the planned 40 patients. CONCLUSIONS:Our study demonstrates a bimodal approach utilizing photons with C12-boost may achieve an superior local PFS to conventional photon RT, but must be balanced against the potential risks of toxicities.

PURPOSE/OBJECTIVE:Radiation-induced cerebral contrast enhancements (RICE) are frequent after photon and particularly proton radiation therapy and are associated with a significant risk for neurologic morbidity. Nevertheless, risk factors are poorly understood. A more robust understanding of RICE risk factors is crucial to improve management and offer adaptive therapy at the outset and during follow-up. METHODS AND MATERIALS/METHODS:We analyzed the comorbidities in detail of 190 consecutive adult patients treated at a single European national comprehensive cancer center with proton radiation therapy (54 Gy relative biological effectiveness) for LGG from 2010 to 2020 who were followed with serial clinical examinations and magnetic resonance imaging for a median 5.6 years. RESULTS:Classical vascular risk factors including age (≥50 vs <50 years: 1.6-fold; P = .0024), hypertension (2.7-fold; P = .00012), and diabetes (11.7-fold; P = .0066) were observed more frequently in the cohort that developed RICE. Dyslipidemia (2.1-fold), being overweight (2.0-fold), and smoking (2.6-fold), as well as history of previous stroke (1.7-fold), were also more frequently observed in the RICE cohort, although these factors did not reach the threshold for significance. Multivariable regression modeling supported the influence of age (P = .05), arterial hypertension (P = .01), and potentially male sex (P = .02), diabetes (P = .0008), and smoking (P = .001) on RICE occurrence over time, independent of each other and further vascular risk factors. If RICE occurred, bevacizumab treatment was 2-fold more frequently needed in the cohort with vascular risk factors, but RICE long-term prognosis did not differ between the RICE subcohorts with and without vascular risk factors. CONCLUSIONS:This is the first report in the literature demonstrating that RICE strongly shares vascular risk factors with ischemic stroke, which further enhances the nebulous understanding of the multifactorial pathophysiology of RICE. Classical vascular risk factors, especially age, hypertension, and diabetes, clearly correlated independently with RICE risk. Risk-adapted screening and management for RICE can be directly derived from these data to assist in clinical management.