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The implementation and early adoption of online adaptive radiotherapy (oART) has required the presence of clinicians, physicists and radiation therapists (RTT) at the treatment console. The impact on each of them is unique to their profession and must be considered for safe and efficient implementation. In the short term future, widespread adoption will depend on the development of innovative workflows, and rethinking of traditional roles and responsibilities may be required. For the future, technologies such as artificial intelligence promise to change the workflow significantly in terms of speed, automation and decision-making. However, overall communication within the team will persist in being one of the most important aspects. [ABSTRACT FROM AUTHOR]

Prospective data demonstrate that non-ablative stereotactic body radiation therapy (SBRT) for pancreas cancer is well tolerated and results in stable patient-reported quality of life (QOL) although few studies have evaluated long-term QOL beyond ∼3 months after SBRT. Ablative SBRT (BED 10 ∼100 Gy) is increasingly being adopted and its effects on QOL are unknown. We now present QOL outcomes from a phase 2 trial evaluating ablative 5-fraction stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreas cancer. The multi-center single-arm phase 2 SMART trial enrolled 136 patients from January 2019 to January 2022 who received ≥3 months of induction chemotherapy without disease progression and were treated on a 0.35T MR-guided device with a prescribed dose of 50 Gy in 5 fractions (BED 10 = 100 Gy). Intrafraction cine-MRI, soft tissue tracking, and automatic beam gating were mandatory. On-table adaptive replanning using an isotoxicity approach was performed prior to each fraction as needed. A secondary study endpoint was QOL using the NCCN-FACT FHSI-18 survey instrument at 3 times (T): prior to SMART (T1), 3 months after SMART (T2), and 12 months after SMART (T3). The total FHSI-18 score was calculated as a sum of the following subscale scores: disease related symptoms-physical, disease related symptoms-emotional, treatment side effects, and function/well-being. Surgery was performed in 44 patients (32.4%) after SMART. QOL assessment was completed at T1, T2, and T3 by 133 (97.8%) and 106 (77.9%), and 55 (40.4%) patients, respectively. Mean total score and subscale scores remained stable from T1-T2 or T1-T3. Mean individual question scores were stable from T1-T2 except for general pain (0.8 vs. 1.1; p=0.002) and localized stomach pain (1.0 vs. 1.3; p=0.013); a significant increase in pain scores was present among patients who had surgery after SMART while pain scores did not increase among those who did not have surgery. Mean individual scores were stable from T1-T3 except for increased stomach area pain (p<0.001) regardless of surgery and scores for feeling ill increased among patients who did not have surgery (p=0.004). This is the first prospective evaluation of QOL after ablative radiation therapy for pancreas cancer demonstrating that overall QOL remains stable at 3 and 12 months after SMART. Additional analysis is warranted to clarify factors significantly associated with QOL including disease progression and additional therapy after SMART. [ABSTRACT FROM AUTHOR]

Historical prospective trials have shown that hydrogel rectal spacers can be very effective at decreasing rectal wall dose, and in turn rectal toxicity, in patients undergoing curative intent fractionated courses of radiotherapy for prostate cancer. However, in the modern era of stereotactic online adaptive MR guided radiation (MRgRT), it's not yet determined if rectal spacers improve the potential daily need for plan adaptation. A prospective database of MRgRT patients were queried for intact prostate cancer patients who received stereotactic online adaptive MR guided radiation. Patients were reviewed for the presence of a hydrogel rectal spacer present on the planning images. The number of adaptive fractions as well as the organs at risk out of tolerance were noted for each patient. Comparisons between number of fractions adapted as well as the number of fractions adapted for rectal constraints, were noted. For each case within this patient group that required plan adaptation, pre-specified dose constraints were finally met prior to treatment delivery. A total of 27 patients were treated with stereotactic online adaptive MRgRT from 2020 to 2022. 8 patients had a hydrogel rectal spacer placed prior to treatment. Out of the 95 fractions delivered to non-hydrogel patients, 78 were adapted, with 52 for urethra, 31 for bladder, 5 for bladder neck, and 35 for rectum. Of the 40 fractions delivered to patients with a hydrogel spacer, 20 were adapted. The corresponding reasons for adaptation in this group were 14 times for the urethra, 19 times for the bladder, 8 times for the bladder neck, and 8 times for the rectum. It was common for multiple at-risk organs to require adaptation for a single fraction within both cohorts. Although the percentage of patients requiring adaptation for rectal constraints was greater in the non-hydrogel patients (36.8% vs. 20%), this was not found to be statistically significant; p value greater than 0.1. The presence of a rectal spacer did not significantly reduce the need for online plan adaptation of the rectum for stereotactic online adaptive MRgRT. Furthermore, patients with a rectal spacer continued to often require adaptation to meet other prescription constraints. Further work is necessary to better select patients who would benefit from hydrogel spacers in the setting of online adaptive MRgRT. Additionally, longer follow-up of this patient population coupled with a larger patient cohort overall remains needed to increase the power of this analysis and to further explore the clinical outcomes of this patient group. [ABSTRACT FROM AUTHOR]

Retrospective studies demonstrate that ablative stereotactic MR-guided on-table adaptive radiation therapy (SMART) achieves favorable local control (LC) and overall survival (OS) with limited grade 3+ toxicity compared to historical non-ablative outcomes for locally advanced and borderline resectable pancreatic cancer (LAPC/BRPC). We conducted an international multi-center single-arm phase 2 trial of ablative 5-fraction SMART for LAPC/BRPC. Subjectswere required to have biopsy-confirmed adenocarcinoma, receive ≥3 months of chemotherapy, have no distant metastasis and CA19-9 ≤500 U/mL. SMART was delivered on a 0.35T MR-60Co or MR-linac system prescribed to 50 Gy in 5 fractions (biologically effective dose 10 [BED 10 ]=100 Gy) using continuous intrafraction cine-MRI, soft tissue tracking, and automatic beam gating. The original plan was recomputed onto the daily anatomy and if that plan would not have met constraints, on-table adaptive replanning using an isotoxicity approach was performed. The primary objective was to demonstrate <15.8% acute grade 3+ gastrointestinal (GI) toxicity definitely related to SMART measured through 90 days and evaluated according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE). All patients have completed 90-day follow-up. Secondary objectives included OS, distant progression free survival (DPFS), and patient-reported quality of life. 136 patients across 13 sites were enrolled between 2019-2021. Mean age was 65.7 years. Head of pancreas lesions were most common (66.9%; n=91). 43.4% (n=59) had BRPC, 56.6% (n=77) LAPC. Mean induction chemotherapy duration was 155.7 days, typically with FOLFIRINOX 65.4% (n=89) or gemcitabine doublet 16.9% (n=23). Mean CA19-9 after induction chemotherapy was 71.7 U/mL. On-table adaptive replanning was used for 93.1% of fractions. SMART was delivered in consecutive days (56.6%) or every other day (43.4%). Median follow-up was 16.4 months and 8.8 months from diagnosis and SMART, respectively. 31.6% (n=43) had surgery after SMART. The incidence of acute grade 3+ GI toxicity definitely and probably related to SMART were 0% and 2.2% (n=3), respectively. 1-year LC and DPFS from SMART were 82.9% and 50.6%, respectively. 1-year OS was 93.9% from diagnosis and 65.0% from SMART. This is the first prospective, multi-institutional study of ablative SMART with prescribed BED 10 of 100 Gy delivered in 5 fractions for BRPC/LAPC. The primary objective was met, signaling that further prospective evaluation of ablative SMART for BRPC/LAPC is warranted with a focus on long-term LC and OS compared to chemotherapy alone. [ABSTRACT FROM AUTHOR]

Stereotactic MRI-guided adaptive radiation therapy (SMART) enables safe dose escalation for locally advanced, borderline resectable, and medically inoperable pancreatic cancer and has shown favorable toxicity and survival outcomes. In late 2018, our institution commissioned SMART for these patients, making it available to all patient referrals. We wanted to review changes in our patient population and differences in clinical outcomes for patients before and after the implementation of SMART. In this IRB approved analysis, we retrospectively reviewed 167 consecutive patients from 2015-2021 with locally advanced, borderline resectable, or medically unresectable pancreatic cancer who were treated with radiation therapy. Chemoradiation (chemoRT) was defined as any 28-30 fraction radiation regimen that included concurrent chemotherapy. SMART was defined as 50 Gy over 5 consecutive daily fractions without concurrent chemotherapy. Baseline patient characteristics were compared between groups. Overall survival (OS) was evaluated by Kaplan-Meier (KM) and log-rank test. Univariate (UVA) and multivariate analysis (MVA) were also performed on multiple treatment variables. Of the patients included, 58 received chemoRT (2015-2018) and 109 received SMART (2018-2021). Median follow up from time of diagnosis for the chemoRT and SMART cohorts were 53.7 months and 29.2 months respectively. Cohorts did not have significant differences in age, gender, race, T or N staging, rates of surgery or surgical margin status. Patients receiving SMART had overall worse performance (p = 0.011) including a lower percentage of PS 0 patients (22.9% vs 44.8%) and a higher percentage of PS 2+ patients (34% vs 15.5%). Similarly, the SMART patients did numerically more often have locally advanced (50% vs 43%) and medically inoperable (26% vs 21%) disease (p = 0.294). The SMART cohort did have longer neoadjuvant chemotherapy with mean of 3.5 months vs 2.3 months in the chemoRT cohort (p = 0.002). There was no OS difference between each group when measured from diagnosis (p=0.79) or from first day of radiation (p=0.2). Median survival in the chemoRT and SMART groups was 18.7 vs 17.4 months from diagnosis. When including only PS 0-1 patients, the median survival in the chemoRT and SMART groups was 18.8 vs 22.3 months (p=0.37). There was also no difference in locoregional control, distant control, or progression free survival using KM. On MVA positive prognostic factors for OS from diagnosis included ECOG <2 (HR 0.54, p=0.015), increasing months of neoadjuvant chemo (HR 0.88, p=0.004) and pancreatectomy (HR 0.14, p <0.001). Despite the fact that the patient cohort receiving radiation therapy per the SMART approach had poorer performance status compared with chemoRT, OS was not significantly different. The multidisciplinary team was highly supportive of SMART with increased patients being treated. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Magnetic resonance imaging-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning. Our objective was to describe patterns of 0.35T-MRgRT utilization in the United States (US) among early adopters of this novel technology.Materials/methods: Anonymized administrative data from all US 0.35T-MRgRT treatment systems were extracted for patients completing treatment from 2014-2020. Detailed treatment information was available for all 0.35T-MR Linac system and some cobalt system patients. Most cobalt patients were included in total only.Results: 17 systems at 16 centers treated 5,733 patients, delivering 40,171 fractions (fractions unavailable for 1,225 cobalt patients), of which 6,244 (15.5%) were adapted. Thirteen centers (81.3%) had treated for > = 1 year, of which 9 treated > 100 patients/year and 6 treated > 150 patients/year. Ultra-hypofractionation (1-5 fractions) was delivered for 72.9% of all patients. The proportion of fractions adapted in patients receiving ultra-hypofractionation was 28.6%, with an average of 3.2 adapted fractions per course. The most commonly treated tumor types were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%), respectively, with significantly increased number of fractions delivered from 2018-2020 compared to 2014-2017 for each (pancreas: 5,161 vs. 1,155; liver: 3,597 vs. 921; prostate: 5,795 vs. 1,398; breast: 2,221 vs. 1,876; lung: 2,589 vs. 660). The compound annual growth rate (CAGR) in the number of patients was 59.5%, growing from 111 in 2014 to 1,830 in 2020. Ultra-hypofractionation increased from 31.8% of all treated MR-Linac patients in 2014 to 87.0% in 2020 (n = 1,576/1,811). The proportion of adapted fractions in all patients and ultra-hypofractionation patients increased from 0% in the first two years to 24.3% (n = 3,071/12,639) and 33.8% (n = 2,677/7,911) respectively, by the end of 2020. No patient had adaptive treatment in 2014 although adaptive replanning steadily increased over time. For example, in 2020 vs. 2018 the proportion of adaptive fractions was highest for pancreas (60.6% vs. 50.8%), liver (17.8% vs. 9.9%), and lung (17.8% vs. 1.8%) cancers.Conclusion: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in the US. Intrafraction MR guidance, advanced motion management, and increasing adoption of adaptive RT has accelerated a transition to ultra-hypofractionation regimens. MRgRT has been predominantly used to treat abdominal and pelvic tumors, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Recent data support the use of total neoadjuvant therapy (TNT) for treatment of locally advanced rectal cancer (LARC), although the optimal TNT regimen and therapy sequence is unclear for non-operative management (NOM). We performed a multi-institutional comparison of short-course radiation (SCRT) followed by consolidation chemotherapy (SC-TNT) versus long-course chemoradiation (CRT) preceded by induction chemotherapy (LC-TNT), after adoption of NOM at both institutions.Materials/methods: The records of 187 patients with cT2-4N0-2 rectal cancer treated between 2016-2020 with TNT at two academic institutions were reviewed under an IRB-approved protocol. The SC-TNT cohort (institution 1) included 85 patients treated with SCRT (25-30 Gy in 5 fx) followed by FOLFOX/CAPOX (n = 82) or capecitabine (n = 3). The LC-TNT cohort (institution 2) included 102 patients treated with FOLFOX/CAPOX followed by CRT (45-56 Gy at 1.8-2 Gy/fx) with concurrent fluoropyrimidine-based chemotherapy. Patients with a clinical complete response (cCR) were offered NOM. The rates of cCR were compared between SC- and LC-TNT. Disease-free survival (DFS) was compared using the log-rank test. To account for any differences in NOM selection between institutions, local-only tumor regrowth was censored from DFS if salvaged with R0 resection, and the overall complete response (CR) rate, defined as cCR + pCR rate for patients undergoing surgery, was assessed. Multivariate analysis (MVA) was performed with logistic and Cox regression to determine factors associated with CR and DFS, respectively.Results: The median age at diagnosis was 60 and 54 years for SC-TNT and LC-TNT cohorts, respectively (P = 0.002). All other characteristics including performance status, tumor location, and clinical stage were balanced. The median duration of neoadjuvant FOLFOX/CAPOX chemotherapy was 105 vs 98 days for the SC-TNT and LC-TNT cohorts, respectively (P = 0.001). The median follow-up was 27 months. The cCR rate was higher in the SC-TNT cohort (44/85, 52.8% vs 21/102, 20.6%, P < 0.001), with a trend for improved CR rate for SC-TNT (54.1% vs 40.2%, P = 0.057). On MVA, use of SC-TNT was associated with improved CR (HR = 2.24, 95% CI: 1.13-4.45, P = 0.021). Among patients undergoing NOM, 33/39 patients (84.6%) in the SC-TNT group and 10/17 patients (58.8%) in the LC-TNT group (P = 0.27) were free from local recurrence at 1 year. Two-year DFS was 93.4% and 95.4% for the SC-TNT and LC-TNT cohorts with improved DFS on log-rank test for LC-TNT (P = 0.023), but no DFS difference on MVA between SC-TNT and LC-TNT (HR = 2.29, 95% CI: 0.8-6.51, P = 0.121).Conclusion: SC-TNT demonstrated a greater rate of cCR compared to LC-TNT, without DFS difference on MVA. Although future studies are warranted to compare SC-TNT with a CRT and consolidative chemotherapy TNT approach, our data support SC-TNT as a suitable regimen for LARC NOM. [ABSTRACT FROM AUTHOR]