Preoperative Radiotherapy Research Articles

Visceral Artery Pseudoaneurysm Rates after Pancreatoduodenectomy in Patients Who Received Pre-Operative Radiation for Pancreatic Cancer

The role of pre-operative radiation therapy (RT) for localized pancreatic ductal adenocarcinoma (PDAC) with peri-pancreatic vascular involvement remains controversial, with two recent randomized controlled trials, namely PREOPANC-1 and Alliance A021501, showing conflicting results. Opponents of pre-operative radiation point towards the unclear oncologic benefit and potential added toxicity. While hemorrhage from a pseudoaneurysm (PsA) rupture is a known rare but potentially fatal complication after pancreaticoduodenectomy (PD), with published incidence rates of around 2 to 5%, it has been increasingly common in the pancreatic cancer surgical community for pre-operative RT to be cited as a risk factor for PsA development, despite the absence of data supporting this notion. Certainly, accurate characterization of relevant RT-related toxicities is critical to prevent inaccurate decision-making regarding foregoing its use. As such, we aim to report on the incidence of PsA in a cohort of patients with PDAC who underwent pre-operative RT prior to PD at a high-volume center. Consecutive patients treated with pre-operative RT via stereotactic body radiation therapy (SBRT) or intensity modulated radiation therapy (IMRT) prior to PD for borderline resectable or locally advanced PDAC were retrospectively reviewed. Incidence of radiographic or clinically apparent PsA was reported. We also characterized the timing of PsA identification in relation to surgery and RT, the artery in which the PsA developed, and the clinical outcomes of patients after PsA identification. One hundred seventy-five patients met eligibility criteria for our analysis. Most of our cohort (163 patients, 93%) received SBRT to a median dose of 6.6 Gy x 5 (median BED10 54.78 Gy, range: 48 Gy - 61.92 Gy), and only 12 patients (7%) received IMRT in various fractionation and dose patterns (median BED10 62.94 Gy, range 59.47 Gy - 97.5 Gy). The median time between surgery and last contrast-enhanced abdominal imaging was 17 months (range: 0.23 - 68 months). There were fourteen visceral arteries among thirteen patients (7%) that were found to have a PsA on routine follow-up imaging or after a post-PD hemorrhage. The median time between completion of radiation and surgery to PsA were 19.5 weeks (range: 8.6 to 98.1 weeks) and 13 weeks (range: 1.6 to 87.9 weeks), respectively. The two most commonly involved arteries were the gastroduodenal and superior mesenteric arteries. Rate of PsA development was similar among patients treated with SBRT (7%) and IMRT (8%). In terms of Clavien-Dindo classification of complications, there were six patients with grade 3a complications, five patients with grade 4b complications, and two patients with grade 5 complications. Compared to historical data, pre-operative RT does not appear to significantly increase the risk of PsA development after PD. More data on the impact of pre-operative radiation dose-fraction regimen and longer follow-up are needed.

Evaluating the Utility of Traditional Bowel Dose Constraints when Treating Abdominal and Pelvic Sarcomas with Preoperative Radiation Therapy

Abdominopelvic soft tissue sarcomas (AP-STS) are selectively treated with preoperative radiation therapy (RT) followed by surgery. Due to their rarity, most bowel dose constraints are extrapolated from dosimetric studies for other abdominal or pelvic malignancies where concurrent chemotherapy is often given in addition to RT. We sought to investigate associations between dosimetric bowel constraints and the risk for developing acute and long-term toxicities in patients who received preoperative RT for AP-STS. We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic AP-STS between 2005 and 2020. Dosimetric parameters for the "bowel bag" organ at risk structure were extracted for each patient. Chi-Square or Fisher's Exact Test, where appropriate, was utilized to compare the proportion of patients who exceeded constraints to the bowel bag contour as per the consensus RT retroperitoneal sarcoma guidelines, and the development of acute and long-term toxicities. We identified 39 patients with available dosimetric data. The median follow-up was 34 months (IQR 20-47). Approximately half of the tumors were located in the pelvis (n = 20, 51%), and the majority were treated with IMRT/VMAT (n = 35, 90%). 31 patients (80%) presented with de novo disease, and 20% (n = 8) were recurrent presentations but had not received prior RT. The most common histology was leiomyosarcoma (n = 15, 38%), followed by de-differentiated liposarcoma (n = 8, 21%). The median bowel max dose (defined as D0.1cc) was 5309cGy [IQR 5262-5830]. Thirteen patients (33%) exceeded the volumetric V15 Gy <830cm3 bowel bag constraint, and 18 (46%) exceeded the V45 Gy ≤ 195cm3 bowel bag constraint. Overall, 17 patients (44%) had acute grade 1 diarrhea, and 11 (28%) had grade 1-2 nausea. Five patients (13%) had long-term radiation-related toxicities, including 1 patient who developed an enterocutaneous fistula. There was no association between exceeding V15 Gy>830 cm3 (p = 0.31) or V45 Gy≥195cm3 (p = 0.65) bowel bag constraints and developing a long-term RT toxicity. Similarly, exceeding V15 Gy>830 cm3 or V45 Gy≥195cm3 did not lead to increased risks of developing acute diarrhea, nausea, or any other acute RT toxicity (all p>0.05). Traditional volumetric bowel bag dose constraints are frequently exceeded given the large size of AP-STS at presentation and thus the large RT target volumes. Despite a significant proportion of patients exceeding these constraints, these data suggest that RT is overall well-tolerated, and the risk of developing toxicities does not correlate with traditional bowel bag volumetric constraints. There are ongoing efforts to substantially expand this cohort for further investigation into the relationship between dosimetric data and bowel toxicities in order to identify more predictive bowel constraints that can be used during treatment planning of AP-STS.

Outcomes for Patients with Head and Neck Sarcoma Treated Curatively with Radiation Therapy and Surgery

Soft tissue sarcomas (STS) of the head and neck are rare and diverse entities that are challenging to manage. Definitive treatment requires surgery, often with radiation therapy (RT). We sought to describe the outcomes of patients treated curatively with surgery and RT for head and neck STS. We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic STS of the head and neck between 1968 and 2020; over half were treated in the modern era defined as 2005 or after. Patients with rhabdomyosarcomas or cutaneous angiosarcoma were excluded. The Kaplan-Meier method was used to estimate actuarial overall survival (OS), disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVA) were conducted using Cox proportional hazards model. Median follow-up was 82 months. Of the 192 patients, the majority were male (n = 111, 58%), White (n = 158, 82%), and median age was 49.5 [IQR 32.5-64]. The highest proportion of tumors were in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). The most common histology was sarcoma, not otherwise specified (n = 44, 23%), followed by undifferentiated pleomorphic sarcoma (n = 32, 17%), and neurogenic sarcoma (n = 15, 8%). Most patients were treated with postoperative RT (n = 134, 70%). Patients treated with preoperative RT were older (median 56.5 yrs vs post-op 44 yrs, p = 0.009). Post-op RT doses were higher (median 60 Gy, pre-op 50 Gy, p<0.001), and margins were more likely to be negative in those treated with pre-op RT (n = 39, 67%, post-op 69, 51%, p = 0.02). 5-year LC, DSS, and OS for the entire cohort was 76% (95% CI 69-82), 74% (67-80), and 71% (64-77), respectively. LC was not affected by treatment sequence (pre-op RT 78% (63-88), post-op RT 75% (66-82), p = 0.48). Patients with negative margins had improved 5-yr LC (86% (77-92), positive/uncertain 65% (53-74), p = 0.003). On MVA, positive/uncertain margin was the only variable associated with LC (HR 2.54 (1.34-4.82), p = 0.004). Poorer 5-yr DSS was associated with higher grade (grade 3 75% (63-84), grade 1-2 89% (75-94), p = 0.02), and treatment era (pre-2005 68% (57-76), on/after 2005 80% (70-87), p = 0.04). These both remained significant on MVA (grade 3 HR 2.39 (1.07-5.36), p = 0.034; pre-2005 HR 2.31 (1.03-5.21), p = 0.043). Sixteen patients (8%) developed a late RT toxicity, including fibrosis (n = 4, 2%), necrosis (osteoradionecrosis n = 2, brain necrosis n = 1, soft tissue necrosis n = 1), and eye dryness (n = 2, 1%). Neither the timing of RT nor dose was found to be associated with developing a late RT toxicity. Head and neck STS continues to have relatively poorer local control than STS of the trunk or extremities. Timing of RT did not impact oncologic or long-term RT-related toxicity outcomes. However, more data are needed to ascertain whether preoperative RT may impact acute surgical toxicities. These data contribute to multidisciplinary care planning for patients with STS in these challenging anatomic locations.

Comparison of Estimated Late Toxicities between IMRT and IMPT when Treating Retroperitoneal Sarcoma Preoperatively with Ultra-Hypofractionation

While preoperative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. The risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. Thus, finding methods to mitigate the issues of delaying surgery and irradiating normal tissue may provide a path towards affording the benefits of radiation while limiting its downside. One potential solution involves the use of hypofractionation to limit delay from radiation initiation to surgery, and proton therapy to limit dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of preoperative ultra-hypofractionated intensity-modulated photon radiotherapy (IMRT) and proton therapy (IMPT) for RPS, comparing estimated rates of late toxicity using published normal tissue complication probability (NTCP) models. Volumetric modulated arc therapy IMRT and IMPT plans were generated on 10 RPS patients previously treated with preoperative radiation. The prescription was 25 Gy radiobiological equivalent (GyE) to the clinical target volume (CTV) and 30 GyE to the margin-at-risk, all in five fractions. Proton doses were calculated using a radiobiological effective dose of 1.1. NTCPs were calculated for each OAR as a function of equivalent uniform dose. The ΔNTCP (difference in absolute NTCP between IMRT and IMPT plans) for each of the toxicity domains was calculated. Student T-tests were used to compare differences in dosimetric and NTCP outcomes. CTV coverage was met for all IMRT and IMPT plans with >99% of CTVs receiving ≥100% of prescription doses. The following endpoints were significantly lower with IMPT than IMRT: mean doses to liver, bone, and all analyzed genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. No OAR endpoint was significantly higher with IMPT. The average ΔNTCP for grade 3 bowel ulceration/perforation and renal toxicity was 1.9% (p = .037) and 43.0% (p = .023), respectively, favoring IMPT. Using a model-based selection threshold of any ΔNTCP >10%, 50% (n = 5) of patients would be eligible for IMPT. IMPT maintained target coverage while significantly reducing dose to adjacent OARs and integral dose compared to IMRT. This translated to significantly lower risks of estimated late gastrointestinal and renal toxicities with IMPT. Further investigation is warranted to validate these findings and potential clinical benefit in the management of RPS. A prospective trial treating RPS with preoperative ultra-hypofractionated IMPT at our institution is currently being pursued (NCT05302570).

Association between Tumor Volume Change on MRI with Surgical Margin Status, Pathological Response, and Local Control Following Pre-Operative Radiation Therapy for Soft Tissue Sarcoma

The clinical significance of radiographic progression during pre-operative radiation therapy (RT) for soft tissue sarcoma (STS) remains unclear. We sought to evaluate associations between radiographic change on T1 post-contrast (T1c) and T2 weighted magnetic resonance imaging (MRI) with percent pathological response (PR%), positive surgical margins (+SM), and local control (LC). We retrospectively identified patients with STS undergoing neoadjuvant RT who had both pre- and post-RT MRI prior to surgical resection. Gross tumor volumes were contoured on pre- and post-RT T1c and T2 MRI sequences and relative change in volume from baseline was calculated. Radiographic classification was defined as response (>30% reduction), progression (>30% increase), or stable (≤30% reduction or ≤30% increase). Chi squared, Fishers Exact, and Kruskal Wallis (KW) tests were used to assess differences between groups. Linear and binary logistic regression models used to assess associations between MRI response and PR% and +SM, respectively. LC was modeled with Kaplan Meier methods and log rank tests. A total of 68 STS patients were identified, with a median follow up of 49 months (range 7-229). With a median age of 60.5 years (25-88) and tumor size of 10.8cm (2.7-25.7), the most common histologies were undifferentiated pleomorphic sarcoma (UPS; 32.4%) and myxoid liposarcoma (ML; 16.2%), and were primarily grade 2-3 disease (89.7%). With a median RT dose of 50 Gy in 25 fractions (44-60Gy), the median radiographic volume change was 2% (-86.4 to 953.6%) and -2.1% (-89.6 to 962.5%) for T1c and T2, respectively. Radiographic classification of response/stable/progression was 25.4%/49.2%/25.4% and 27.9%/52.5%/19.7% for T1c and T2, respectively. Histology (ML vs. UPS) and grade (1 vs. 3) were predictors for radiographic response on both T1c (72.7% vs 18.8%, p = 0.03 and 71.4% vs. 10.4%, p = 0.03) and T2 (71.5% vs. 18.2%, p = 0.02 and 71.4% vs. 14.6%, p = 0.002), respectively. With 6 +SM (8.8%), the rate of +SM for response/stable/progression was 20%/10.3%/0% in T1c (p = 0.2) and 5.9%/12.5%/0% in T2 (p = 0.5). As a continuous variable, neither relative change on T1c (p = 0.2) or T2 (p = 0.4) were associated with +SM. With an overall median PR% of 64% (0-100%), the median PR% was significantly different for response/stable/progression for both T1c (95%/42%/73%, p = 0.02) and T2 (95%/50%/87.5%, p = 0.04). Radiographic change on neither T1c (p = 0.4) or T2 (p = 0.5) were associated with PR% on a continuous basis. With a total of 4 local recurrences, there was no significant difference in LC by radiographic classification on either T1c (p = 0.65) or T2 (p = 0.85). While radiographic response may be correlated with pathological response, radiographic progression on either T1c or T2 following neoadjuvant RT was not associated with a detriment in surgical margins or local control. These findings suggest that STS radiographic "pseudoprogression" is not associated with worse outcome.

Surgical Outcomes in Patients Treated with 5-Day Preoperative Radiotherapy for Soft Tissue Sarcoma

Treatment for high-risk soft tissue sarcoma (STS) of the extremity/trunk includes radiation therapy (RT) and surgical resection. Initial results of a phase 2 single arm trial of 5-day preoperative RT demonstrated acceptable safety and local control. Here we report an update of detailed surgical outcomes among patients treated with 5-day preoperative RT alone on the original phase 2 study, as well as an ongoing expansion cohort. We conducted an updated analysis of surgical complications from a previously reported phase 2 trial of 50 patients with high-risk extremity/trunk STS treated with 5-day preoperative RT (30 Gy over 5 consecutive daily fractions) and surgery. The current analysis includes additional patients from an ongoing IRB-approved expansion cohort of the phase 2 study, which was designed to compare wound complication rates between patients receiving neoadjuvant chemotherapy and those receiving RT alone. However, given that the primary endpoint of this study has not matured, here we present only the data for patients treated with 5-day preoperative RT alone (n = 44; data cutoff date: February 17, 2022). We generated a secure prospective patient database and extracted data including demographic variables, cancer characteristics and surgical outcomes. Minimum post-operative follow-up was 90 days. Statistical analysis was performed using R (v4.2). From a total of 94 patients, mean age was 57 (17-90), 40 (42.5%) were female, 10 (10.6%) were diabetic and 8 patients (8.5%) were active smokers or had a >10 pack-year smoking history. Median follow up was 24 months (IQR 10.6-41.8). The most common histologic diagnosis was undifferentiated pleomorphic sarcoma (n = 38, 40.4%). The most common location was the lower extremity (n = 57, 60.6%). Overall, 26 (27.7%) patients experienced surgical wound complications. In the lower extremity, wound complications occurred in 18 patients (31.6%). In all other sites, wound complications occurred in 8 patients (21.6%) (p = 0.41). Twenty-seven (28.7%) cases required local tissue advancement for primary closure and 12 of these patients (44.4%) experienced a wound complication (p = 0.04). Wound dehiscence occurred in 18 patients at a median duration of 43.5 days (IQR 40.3-85.3) from surgery, comprising 69.2% of all wound complications. Secondary surgical intervention was required in 28 patients (29.8%), of which 7 were oncologic re-excisions and 15 were irrigation and debridement. On multivariate analysis, the use of advancement flaps (OR = 5.39; p = 0.004) and diabetes (OR = 4.08; p = 0.07) were associated with wound complications. Five-day preoperative RT for STS results in rates of wound complications comparable to standard fractionation. We identified local advancement flaps as the primary factor associated with wound complications. STS of the lower extremity that require complex closure warrant close attention for dehiscence.

Post-Hypofractionated Radiotherapy Neutrophil-to-Lymphocyte Ratio in Soft Tissue Sarcomas is a Prognostic Biomarker of Recurrence and Distant Metastases

The neutrophil-to-lymphocyte ratio (NLR) is a measure of systemic inflammation, and known to be prognostic of outcomes and treatment response across different cancer types, including soft tissue sarcomas (STS). Our study aims to determine if in patients with STS treated with pre-operative hypofractionated radiotherapy (HFRT), post-RT NLR is prognostic of recurrence, metastasis, and overall survival. We performed a single-center retrospective analysis of patients treated pre-operatively with 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, radiation therapy (RT), and complete blood count (CBC) data were collected from medical records. The NLR calculation was performed by dividing the absolute neutrophils count by the absolute lymphocytes count. We dichotomized the variable into NLR ≤4 and >4. The CBC utilized to calculate NLR was only used if done <6 months post-RT. For post-RT NLR outcomes associations, we used univariable and multivariable logistic regression analyses adjusting for age, gender, tumor size, and histology. For continuous variables we used mean ± standard deviation. Analyses were done with SPSS. A p-value <0.05 was considered significant. We identified 40 patients that received HFRT and had a CBC within 6 months after RT. The mean age was 66 ± 17.5 years. There were 17 (42.5%) females and 23 (57.5%) males. The histologies were myxofibrosarcoma (17.5%), leiomyosarcoma (7.5%), pleomorphic spindle cell sarcoma (10%), myxoid liposarcoma (5%). Other histologies with n<2 accounted for 65%. The mean tumor size was 7.1cm (± 6.4) and the mean NLR 5.3 ± 0.6. The median follow-up was 15.4 ±2.2 months. The patients with recurrence and metastases were the same {n = 13 (32.5%)}, and 3 patients died of disease. Univariable analyses for NLR > 4 showed increased recurrence and metastases (Odds ratio (OR): 8, CI 95% = {1.48 - 43.4}, p = 0.016). The multivariable analyses also showed that post-RT NLR > 4, was associated with increased recurrence and metastases (OR: 7.73, CI 95% = {1.17- 50.9}, p- value = 0.034). Age, gender, histology, and tumor size were not significant variables (Table 1). In both univariable and multivariable analyses NLR > 4 was not associated with decreased overall survival (p = 0.998). To our knowledge, this is the first study assessing the immune response using neutrophil-to-lymphocyte ratio as a prognostic biomarker in STS treated with pre-operative hypofractionated radiotherapy. In this population, an NLR > 4 was prognostic for recurrence and distant metastasis, but not for overall survival. This study highlights the need for a better understanding of the immuno-biological effects of RT, which should be further addressed in the context of clinical trials due to its simplicity and potential prognostic value.

Pre-Operative Radiotherapy in STS: Does Downsizing Matter?

Soft tissue sarcomas (STS) are a rare but insidious tumor that arises from mesenchymal tissue. Preoperative RT, followed by resection, is routinely used in extremity and truncal STS. The impact of RT on tumor volume and implications for prognosis is a great concern for patients, as changes in volume is often perceived as a reflection of treatment response. To date, data between tumor volume changes after RT and overall survival (OS) and distant metastasis-free survival (DMFS) in STS is sparse. In this study, we investigate changes in tumor volume after preoperative RT and its impact on OS and DMFS. Between 2000 and 2022, patients with stage I-III primary sarcoma of the extremity or trunk treated with pre-operative RT and wide resection were retrospectively reviewed from a prospective repository. Tumors were contoured using T2 sequences on MRIs within 2 weeks of initiation of RT and within 4 weeks post-RT. Tumor volume was determined using the medical image merge software. Univariate analysis (UVA) was performed using the log-rank test. Multivariate analysis (MVA) was performed using the Cox proportional hazards model. One hundred thirty-two patients had both pre- and post-RT MRIs available for contours. Median follow-up was 6 years. Median age at diagnosis was 56 years (range = 19-92). Most patients had stage III (73%) disease in the lower extremity (75%). The most common histology was undifferentiated sarcoma (30%). Median dose was 50 Gy in 25 fractions. Chemotherapy was administered in 44 (33%) patients. Median tumor volume prior to and after RT was 198 cc (range = 7.49 - 3899.87) and 225.21 cc (range = 0-9879.2), respectively. A decrease in tumor volume was seen in 90 patients (68%) from pre- to post-RT. In these patients, the mean percent change was -35%. Forty-two patients had an increase in tumor volume post-RT with a mean percent change of 56%. Overall local control was 98%. The 2- and 5-year OS were 89% and 76%, respectively. The 2- and 5-year DMFS was 76% and 70%, respectively. On UVA, increased age (p < 0.001), KPS ≤80 (p = 0.002), and smokers (p = 0.009) were associated with decreased OS. No variables were associated with DMFS. On MVA, age (p = 0.01) was associated with decreased OS and female gender (p = 0.03) and high-grade disease was associated with decreased DMFS (p = 0.04) Change in tumor volume did not impact OS (p = 0.15) or DMFS (p = 0.75). The 2- and 5-year DMFS for patients with a decrease in tumor volume was 79% and 71%, respectively. The 2 and 5-year DMFS for patients with an increase in tumor volume was 77% and 70%, respectively. The 2- and 5-year OS for patients with a decrease in tumor volume was 92% and 80%, respectively. The 2 and 5-year OS for patients with an increase in tumor volume was 83% and 69%, respectively. Change in tumor volume did not significantly impact OS and DMFS. Further studies with an increased sample size are warranted to corroborate these findings, however these results may assuage patient anxieties about the perceived tumor response to RT.

A Single-Institution Experience of Acute Neuropathic Lumbosacral Pain in Patients Treated with Short Course Hypofractionated Radiotherapy in Locally Advanced Rectal Cancer

There has been increased interest in the use of short course hypofractionated radiotherapy as part of a total neoadjuvant treatment (TNT) approach in the management of rectal cancer since publication of the RAPIDO trial. However, the literature on short course radiation for rectal cancer has not reported significant acute toxicities in the weeks immediately following the completion of treatment. Anecdotally, a subset of patients has experienced acute neuropathic pain characterized in a lumbosacral distribution. This study investigates acute lumbosacral toxicity for patients receiving hypofractionated short course radiation as part of their definitive treatment for rectal cancer. We retrospectively analyzed 75 patients with locally advanced rectal adenocarcinoma treated with hypofractionated short course radiation (25 Gy in 5 fractions) at our institution between 2016 and 2022. Acute toxicity caused by radiation was defined as that occurring from the start of radiation treatment to either 30 days post radiation completion, the start of chemotherapy, or date of surgery, whichever occurred first. Among 75 patients treated with hypofractionated short course preoperative radiation with definitive intent, we identified 10 patients (13.3%) who experienced significant lumbosacral neuropathic pain and initiated a report to their medical providers during the acute toxicity time frame. Commonly, this was described as an achy pain in the bilateral buttocks radiating down to the knees or posterior claves. Patients rated this pain between moderate to extreme and management included steroids after failure of improvement with conservative measures, gabapentin, and conservative treatment with NSAIDs and Tylenol. Average time to onset of acute lumbosacral neuropathic pain was 3.7 days (SD 2.05) from start of RT. We have identified a previously underappreciated acute toxicity of neuropathic lumbosacral pain in short course hypofractionated radiation therapy, which may be due to a lumbosacral plexus toxicity. Further analysis will seek to identify predictive factors such as comorbidities and dose to the lumbosacral plexus, and to determine whether there is a correlation between these observed acute toxicities and long-term outcomes.

Utilization of the Triangle Volume in Patients with Localized PDAC Undergoing Pre-Operative SBRT: Report of Early Outcomes

In patients with borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), advances in neoadjuvant therapy have led to an increased proportion of patients undergoing margin negative resection. Nevertheless, locoregional recurrence rates remain high. We have previously reported that the location of locoregional recurrences in this setting map to the "Triangle Volume (TV)," the anatomical space between the celiac artery, superior mesenteric artery, common hepatic artery, and portal vein, which is enriched in extrapancreatic perineural tracts at risk for microscopic residual disease after resection. At the beginning of 2021, we systematically changed our target volume to include the TV, in addition to gross disease and involved vasculature. Herein, we report early locoregional failure outcomes after resection in the setting of BRPC or LAPC treated with pre-operative stereotactic body radiation therapy (SBRT) to the TV, as compared to historical rates. Patients who received a diagnosis of BRPC or LAPC and who were treated at our institution with neoadjuvant chemotherapy (CTX) and SBRT between 2016 and 2022 were retrospectively reviewed. Between 2016 and 2020, the SBRT clinical tumor volume (CTV) included gross disease and full circumference of involved vasculature at the level of involvement. From 2021 onward, the CTV also included the TV. Survival was estimated using the Kaplan-Meier method. Statistical analyses were performed using scientific 2-D graphing and statistics software. From January 2016 to December 2022, 204 patients with localized PDAC underwent neoadjuvant CTX followed by SBRT. After completion of SBRT, all patients proceeded with surgical exploration. Of these patients, 111 (54%) had LAPC and 92 (45%) had BRPC disease. All patients were treated with induction CTX, mostly commonly with FOLFIRINOX (N = 166, 81%). Following CTX, the most frequently used SBRT regimen was 33 Gy in 5 fractions (N = 191, 94%). 155 (67%) patients were treated between 2016 and 2020 to the traditional CTV, while 49 (24%) patients were treated after 2020 to a CTV that included the TV. The 2-year local progression free survival rate of patients treated with SBRT using the TV was 77.6% as compared to 47.5% in patients treated with the traditional CTV. Over a median follow up of 15.7 months (range: 1 to 78.2 months), 47% (N = 73 out of 155) of patients who underwent SBRT with the traditional CTV developed locoregional recurrence, but only 12% (N = 6 out of 49) treated with SBRT to the TV have thus far developed locoregional recurrence (p<0.0001). In patients with localized PDAC who undergo pre-operative SBRT for BRPC/LAPC, targeting the TV may help reduce locoregional recurrence. More data and longer follow-up are needed to verify these findings and inform whether the TV may serve as a new standard for target volume delineation in this setting.

Patterns of Failure for Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer

Peri-operative chemotherapy has emerged as the standard of care in the treatment of locally advanced gastric cancer. Improved treatment strategies are needed for patients with a poor response to neoadjuvant chemotherapy and postoperative chemoradiation has been proposed as a potential method of treatment intensification. We aimed to describe the patterns of failure for patients with no or partial response (NR, PR) to pre-operative chemotherapy. We retrospectively reviewed charts of patients with locally advanced gastric cancer treated at our institution from 2008 to 2022 with pre-operative chemotherapy followed by surgery with a D2 resection. We excluded patients who received pre-operative or post-operative radiation therapy, or patients who had a complete response (CR) following neoadjuvant chemotherapy. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated from the time of diagnosis with competing risk analysis with death as a competing risk and censored at the last follow up. Overall survival (OS) was analyzed using Kaplan-Meier. A total of 57 patients were identified and 60% are male. Median follow-up time was 31.3 months (range 6.9-181.5 months), and the median age at diagnosis was 68 years old (range 30-86). The most used pre-operative chemotherapy regimen was FLOT (38.6%), followed by FOLFOX (29.8%), and ECF/ECX/EOX (19.3%), and a majority of patients (57.9%) received adjuvant chemotherapy. The most common histology was adenocarcinoma (85.9%), and 61.4% of patients had poorly differentiated disease. Thirty-three (57.9%), and 9 patients (15.8%) were characterized as PR and NR to neoadjuvant therapy by pathology, respectively. The distribution of pathologic stages following neoadjuvant chemotherapy were as follows: 17 patients (29.8%) with Stage IA-B, 12 patients (21.1%) with Stage IIA-B, 15 patients (26.3%) with Stage IIIA, 9 patients (15.8%) with Stage IIIB, and 3 patients (5.3%) with Stage IIIC disease. Two patients had positive lymph nodes with a T0 primary tumor. Median OS was 51.4 months (95% confidence interval [CI] 39.8-68.4) for the entire cohort, and 92.1 months (95% CI 34.6-73.0) versus 42.8 months (95% CI 23.1-88.0) for patients with a PR, and NR, respectively (p = 0.14). The 2-year cumulative incidence of LRF and DM was 7.4% (95% CI 0.4-14.3) and 36.3% (95% CI 23.6-49.1), respectively. Of the five patients who experienced LRF, three of the patients also eventually or concurrently developed DM. 60% of these patients would have had their first site of recurrence covered by standard post-operative radiation treatment volumes. Patients with locally advanced gastric cancer who do have less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival while DM is the predominant pattern of progression. Further studies are needed to identify adjuvant therapies to improve distant control.

Dynamic Changes of Molecular Subtype Classification and Genomic Classifier Scores in High-Risk Prostate Cancer Patients Undergoing Pre-Operative Stereotactic Body Radiation Therapy

The radiobiology of irradiated human prostate cancer (PCa) remains poorly understood as irradiated tissues often remain in situ. PREPARE-SBRT (NCT03663218) is a clinical trial testing the safety of neoadjuvant MRI-guided stereotactic body radiation therapy (SBRT) for men with high-risk PCa. We leveraged paired samples from pre-treatment biopsy and irradiated prostatectomy (RP) specimens to evaluate transcriptomic changes in irradiated tumors at acute timepoints following SBRT. Tumor RNA expression profiles were generated using Decipher GRID by Veracyte on 12 subjects enrolled on NCT03663218 with paired pre/post-SBRT tissues (n = 24). Descriptive statistics using Decipher Genomic Classifier (GC) Score [0-1] and GC risk group (low/int/high) were generated from a validated 22-gene GC. Tumor biology signatures reported as dichotomous variables evaluated changes in androgen receptor (AR) activity [higher v lower] and cell cycle progression (CCP) [lower v higher]. Decipher prostate subtype classifier [PSC, luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), basal neuroendocrine like (BN)] classification and PAM50 molecular subtype [luminal A (lumA), luminal B (lumB), basal] at pre/post-SBRT timepoints were reported. A control cohort of transcriptomic profiles of 803 matched untreated biopsy and RP samples from the same patients were used to control for signature differences attributable to sample type. The median pre- and post-SBRT GC scores were 0.55 and 0.72 (Δ+0.17), respectively. By comparison, median GC scores in a control cohort (n = 803) of biopsy and RP specimens were 0.50 and 0.56 (Δ+0.06), respectively. SBRT increased GC score in 9/12 subjects (75%) with a median increase of 0.3. Changes in GC score resulted in reclassification of baseline GC risk in 7 of 12 subjects with 71% of reclassified subjects (5/7) transitioning to a higher genomic risk. 92% of subjects (11/12) had higher AR activity scores at baseline. Of this subgroup, 5/11 (45%) converted to lower AR activity score after SBRT. CCP signatures remained stable in 9 of 12 subjects (75%) with 7/12 subjects exhibiting lower CCP score at baseline and only 1 subject transitioning from lower to higher CCP score. Distribution of PAM50 molecular subtype at baseline and after SBRT was lumA (33>53%), lumB (25>17%), basal (42>25%) resulting in 83% of subjects (10/12) annotated to a different PAM50 molecular subtype at pre/post-SBRT assessment. PSC subtype distribution at baseline was LD (33%), LP (25%), BI (33%) and BN (8%). Strikingly, after SBRT, 92% (11/12) of subjects were classified as BI molecular subtype with several immune activation signatures also increased after SBRT. A majority of subjects demonstrate a post-SBRT increase in GC score with reclassification of genomic-prognostic risk group in 58%. An enrichment of the basal-immune molecular subtype was observed following SBRT suggesting a convergence towards this biology in irradiated tumors.

Gastric Radiotherapy in the UK – Current Practice and Opinion on Future Directions

Gastric radiotherapy (RT) is more commonly practiced in the US compared to the UK, where postoperative chemoradiotherapy (CRT) is reserved for selected high-risk patients, and preoperative CRT is not standard of care pending the results of phase 3 trials, TOPGEAR and CRITICSII. CRT for inoperable, non-metastatic gastric cancer is also not recommended in the UK, despite being listed in NCCN guidelines. Recent systematic review of definitive gastric CRT (dCRT) conducted by the authors found median overall survival of 11-26.4 months, clinical complete response rates of 8-45% and acceptable rates of ≥G3 toxicity, supporting further research. Given these promising findings and perceived low uptake of gastric RT in the UK, we set out to establish current UK practice, opinion and RT technique to inform the development of a UK gastric RT protocol and future clinical trials. A 19 question survey was developed. Following local ethical approval and pilot by 4 clinical oncologists, the final survey was distributed electronically on 13/12/22 to UK Consultant Clinical Oncologists specializing in esophago-gastric (OG) cancer. Responses were anonymous. Survey was closed 6/2/23 and data analyzed using JISC/spreadsheet software. A total of 43 clinicians completed the survey. For gastric cancer, 28.6%, 7.1% and 9.5% would agree/strongly agree with use of postoperative (postopRT), preoperative (preopRT) or definitive RT (dRT) respectively, compared to 26.2%, 45.2% and 46.6% for type III gastro-esophageal junction tumors. 93% had prescribed palliative gastric RT in the last 3 years compared to 40.5% postopRT, 16.7% dRT and 9.5% preopRT. Main reasons for infrequent use were; rarely indicated within standard UK practice 88.4%, lack of UK gastric RT protocol 53.5%, toxicity concerns 44.2%. 45Gy/25# was most commonly used for preopRT (66%) and postopRT (86%), and 50Gy/25# for dRT (58%). 96% use IMRT/VMAT, 85% CT simulation with IV/oral contrast, 69% gastric filling protocol and 54% 4DCT. When ranked out of 10 (1 = low 10 = high), clinician confidence in accurately delineating gastric volumes mean rank was 4.33 for postopRT, with 9% rating ≥8/10, and 4.52 for dCRT/preopRT with 17% rating ≥8/10. However, 48.8% were experienced in outlining upper abdominal nodes and 62.8% duodenum. 93% would find a detailed outlining protocol useful, 81.4% wanted some form of peer review, 76.7% a nodal atlas, and 74.4% a workshop with an expert. 77.6% would be supportive of a future clinical trial of dCRT, with 23.4% needing more supporting evidence. No-one would not support a future trial in this setting. Gastric RT is not often practiced in the UK, due to lacking evidence and toxicity concerns. Given the growing evidence and supportive OG community, it is time to consider a trial of dCRT in the UK, which must include detailed RT protocols, atlases and educational materials to improve clinician confidence and ensure good RT quality assurance.

Patient-Reported Adverse Effects in 15-Fraction Pancreatic Cancer Radiation Therapy

Fifteen-fraction radiotherapy (RT) regimens have emerged as a standard option in the treatment of patients with pancreas cancer. Patient-reported outcomes (PROs) during and after pancreas cancer RT have not been well characterized. There is an even greater paucity of data among patients treated with 15-fraction regimens. We aimed to characterize gastrointestinal (GI) PROs in a cohort of patients treated with 15-fraction pancreas RT. This was an IRB-approved retrospective cohort study including patients with primary pancreas tumors treated with pre-operative or definitive 15-fraction RT from 2013 to 2022. PROs, including anorexia, nausea, diarrhea, stool incontinence, and abdominal pain, were prospectively collected and characterized per PRO-common terminology criteria for adverse events (PRO-CTCAE). Acute PROs were defined as occurring during RT through 110 days post-RT but prior to oncological surgery. Grade 3 or 4 PROs were respectively scored as "quite a bit" or "very much" in symptom interference questions, "frequently" or "almost constantly" in symptom frequency questions, and "severe" or "very severe" in symptom severity questions. A total of 330 patients were analyzed. Patient characteristics included a median age of 67 years (IQR: 60 - 72), ECOG 0-1 (96%), and male sex (56%). Most patients had pancreatic ductal adenocarcinoma (96%). Resectability status included resectable (12%), borderline resectable (46%), and locally advanced (42%). 37% had lymph node involvement. 97% of patients received neoadjuvant chemotherapy and 98% received concurrent chemotherapy, most commonly with 5-fluorouracil or capecitabine (88%) or gemcitabine (11%). 99% were treated with intensity modulated RT. Median RT dose was 4500 cGy (IQR 4500 - 4500) to gross disease with margin and 3750 cGy (IQR 3750 - 3750) to elective nodal regions. 59% proceeded with oncologic resection. Grade 3 or higher acute PROs are demonstrated in the table. Often considered more sensitive than physician assessments, PROs provide vital metrics that allow for a better understanding of the patient experience during cancer treatment. We report a comprehensive assessment of prospectively collected PROs per standardized PRO-CTCAE with the goals of raising awareness of the patient experience during 15-fraction pancreas cancer RT and helping guide future clinical trial designs focused on patient quality of life endpoints.

Preoperative Radiotherapy of Soft Tissue Sarcoma with Simultaneous Integrated Boost: A Phase II Study

Neoadjuvant radiotherapy to 50 Gy in 25 fractions is delivered in operable Soft Tissue Sarcoma (STS) patients to downstage the tumor and improve resectability, although at the expense of increased risk of wound dehiscence. Nonetheless, clear margin resection (R0) may not be achieved in tumors located in proximity of critical structures such as the neurovascular bundle (NVB), resulting in impaired local control. The aim of this study is to increase R0 rate through addition of an IMRT boost to the potential sites of suboptimal resection in STS patients receiving neoadjuvant RT. We report hereby the dosimetric results and safety results from the first 5 patients enrolled in this trial. We designed a prospective monocentric interventional single-arm Phase II study enrolling locally advanced STS eligible for surgery. RT is administered in 25 daily fractions to include the MRI-based Gross Tumor Volume (GTV) and peritumoral tissue at risk of microscopic spread (CTV1) to a dose of 50 Gy (2Gy/fraction), with SIB (Simultaneous Integrated Boost) intensification to the tumor/dissection plane interface (CTV2) to a dose of 60 Gy (2.4 Gy/fraction). CTV2 delineation is approved by both a Radiation Oncologist and Surgeon. A margin of 0.5 cm is applied to both CTV to obtain PTV1 and PTV2. Concurrent anthracyclines-based chemotherapy (ChT) is allowed up to 3 cycles. Primary endpoint is R0 resection rate. Secondary endpoints include pathologic complete response rate, objective response rate, overall survival, local and distant progression-free survival, acute and chronic toxicity rate. To assess an increase in R0 rate from 81% to 97% assuming β = 80% e α = 0.05, 33 patients will be included. Dose constraints are summarized in Table1. At least 95% of the PTV1 and PTV2 should be covered by 95% the prescription dose up to a maximum allowed dose of 107%. Five patients were included. Tumor was located in the limbs and in the trunk in respectively 4 and 1 patient. Mean age was 47 years (range: 19-67). Concurrent chemotherapy was performed in 2 patients. Mean GTV size was 228.6 cm3 (range: 59.8-314.5). Mean PTV coverage by the 95% of the dose prescription was 98% (95-100) and 97% (95-100) in PTV1 and PTV2, respectively. Mean PTV1 and PTV2 Dmax were 61.6 Gy (range: 59-63) and 64.1 Gy (range:63-66), in both cases below the 107% threshold. Mean Bone Dmax was 55 Gy (56.6-61.8 Gy). Dmax to the skin corridor exceeded 20 Gy in 1 patient (range 12.5-58.1). While the NVB was overlapping the PTV2 in all cases, Dmax was below 66 Gy. At the time of this report, no Grade ≥3 acute skin toxicity was observed. Two patients underwent surgery with a radiological partial response (RECIST) and pathological complete response. No major wound complication was reported. Planning goals of the first 5 enrolled patients are achieved in most cases. Preliminary results show a benign safety profile and promising tumor response rate.

Association of Single Nucleotide Polymorphisms in Transforming Growth Factor-β1 Pathway and Risk of Radiation Pneumonitis in Lung Cancer Patients Treated with Thoracic Radiation Therapy

Several clinical and dosimetric parameters are known to be associated with radiation-induced lung toxicity, including radiation pneumonitis (RP). Also, single nucleotide polymorphisms (SNPs) of genes in TGF-β1 pathway have a notable association with the RP. However, studies on the predictive value of SNPs for RP are still limited. Herein, we tried to develop a novel integrated predictive model for severe RP in lung cancer patients. A total of 59 patients who were treated with definitive or preoperative radiotherapy for primary lung cancer and had DNA samples were included. Potentially functional and tagging SNPs of TGF-β1 (rs1800469, rs1800471, rs1982073, and rs11466345), BMP2 (rs235768, rs3178250, rs1979855, and rs170986), and BMP4 (rs17563, rs4898820, and rs762642) were genotyped. Logistic regression was performed to build severe (grade ≥2) RP prediction models, and best subset selection algorithm with L0 and L2 regulations was used for variable selection. Only clinical/dosimetric variables were evaluated in model 1, and those variables as well as SNPs were included in model 2. Using beta coefficient obtained by the logistic regression, a scoring system was also developed. With median follow-up of 39.7 months, severe RP occurred in 20.3% of patients. In model 1, age (>66) and PTV volume (≥300 cc) were significant factors (p = 0.016, OR 8.820 [95% CI, 1.730-63.800]; and p = 0.024, OR 7.440 [95% CI, 1.460-52.100], respectively). In model 2, the above two factors (p = 0.010, OR 16.200 [95% CI, 2.440-187.000] and p = 0.025, OR 10.100 [95% CI, 1.610-105.000]) and the AG/GG genotype in BMP2 rs1979855 were significant factors (p = 0.031, OR 7.260 [95% CI, 1.380-59.100]). The AUC was significantly higher in model 2 than in model 1 (0.822 vs. 0.741, p = 0.029). According to developed scoring system, patients with a score >2.8 are more likely to experience severe RP (AUC 0.829). BMP2 rs1979855 could serve as a reliable biomarker for predicting RP while significantly improving predictive power compared to when only clinical factors were used.

Hypofractionated Preoperative Radiotherapy 30Gy in Five Fractions for Soft Tissue Sarcoma of the Extremity

Hypofractionated preoperative radiotherapy (HypoRT) is being used with increasing frequency for soft tissue sarcomas (STS) of the extremities. Besides the social and economic advantages, HypoRT has a theoretical advantage in STS because of their low α/β ratio. The objective of this study is to review our experience using HypoRT to a dose of 30Gy in 5 fractions in STS of the extremities. This study is a retrospective review of patients with extremity STS treated at our center with preoperative HypoRT to a dose of 30Gy in 5 fractions given on alternate days over 2 weeks. Inclusion criteria were age ≥18 years, biopsy-proven primary STS in an extremity, and fitness for surgery. The primary endpoint was major wound complications (MWC) defined as the need for wound management or secondary operation under general or regional anesthesia within 120 days from surgery. Secondary objectives were: early toxicity grade ≥ 2 and clinical outcomes, including local control (LC), and metastasis-free survival (MFS). Descriptive statistics were used to evaluate patient and treatment characteristics. The Kaplan-Meier method was used to estimate survival. A total of 40 patients received preoperative HypoRT at our center between 2016 and 2022. The median age was 70 years (30 - 91). Males accounted for 57.5% of the patients. The most common primary site was the lower extremity (62.5%). The most prevalent histologic type was myxofibrosarcoma (27.5%), followed by pleomorphic spindle cell sarcoma (20%). All patients were treated with image-guided intensity modulated radiotherapy with margins for the CTV as tested in the RTOG 0630 study. Median follow-up was 14.8 months (5 - 86). Acute side effects were seen in 80% of the patients, all grade <3. The most common toxicity was dermatitis (37.5%), the second was fatigue (20%), and the third was pain (15%). Surgery was performed in all cases after a median interval from completion of HypoRT of 34 days (16-59). Amputation was performed in one patient with a fungating tumor, HypoRT having been aborted at only 24Gy because of worsening symptoms. On pathologic examination, positive margins were found in four cases (10%). The percentage of necrosis was ≥ 90% in 7 patients and 50%-90% in 10. MWC occurred in 13 patients (32.5%), including 10 who underwent a procedure with anesthesia. Sixteen patients were treated for a wound infection. Only one patient recurred locally. Two-year LC was 91.7%. MFS was 87.4% at 6 months and 60.8% at 2 years. DFS was 84.9% at 6 months and 64.8% at 2 years. The preoperative HypoRT regimen of 30Gy in 5 fractions given on alternate days for extremity STS is safe. Acute toxicity was not different from our previous experience using the conventional regimen of 50Gy in 25 fractions over 5 weeks and the MWC rate was comparable to that reported for the conventional regimen. Local control was excellent.

Prospective Clinical Trial of Premastectomy Radiotherapy Followed by Immediate Breast Reconstruction for Operable Breast Cancer

Radiation delivered prior to mastectomy and autologous breast reconstruction may avoid the adverse effects of radiation on autologous donor tissue while providing the psychologic benefit of immediate reconstruction. We aimed to study the feasibility of premastectomy radiation therapy (PreMRT). A total of 50 women enrolled in a prospective trial of preoperative radiation to the breast and regional nodes followed by mastectomy with axillary evaluation and immediate breast reconstruction. The trial was embedded in a randomized trial of hypofractionated versus conventionally fractionated regional nodal irradiation (NCT02912312). Eligible women enrolled from 2018-22, had cT0-T3 N0-3 breast cancer, and a pre-operative recommendation for radiation. The primary outcome was frequency of complete free flap loss. Mastectomy skin flap necrosis was assessed by validated SKIN grading score. The Satisfaction with Breast Cosmetic Outcomes Scales evaluated patient satisfaction with cosmetic result. Descriptive statistics and 95% exact confidence intervals were calculated. One patient withdrew prior to any treatment and one elected not to have breast reconstruction. Median age of the 48 women completing PreMRT and reconstruction was 48 [range 31-72]. Most had ER-positive HER2-negative (77%), cT3 (54%) or cT2 (38%), cN1 (79%) disease and received 50 Gy in 25 fractions (n = 24) or 40.05 Gy in 15 fractions (n = 23). Four received 10-16 Gy internal mammary or infraclavicular boost. 35% VMAT, 48% matched photon-electron, and 17% partially-wide-tangent technique. Median time to surgery was 23 days [14-85]. Skin reaction delayed surgery for one patient. Most had skin-sparing mastectomy (92%) and axillary lymph node dissection (67%). 12 surgeons performed the reconstructions: 35 deep inferior epigastric perforators; 4 profunda artery perforator; 2 muscle-sparing transverse rectus abdominis myocutaneous; 1 latissimus dorsi (LD); 2 LD/implant; 2 LD/tissue expander (TE); and 2 subpectoral (SP) TE. There were no complete flap losses. Two patients (4.4%, 95% CI 0.5%-14.8%) with free flaps had partial flap loss with revision surgery. Both patients with SP TEs had infections and unplanned reoperation. The protocol was subsequently amended to not allow SP TE reconstruction. Eight patients had skin flap necrosis: 5 partial and 3 full thickness necrosis; only 1 required operative debridement. Seven had pathologic complete response. At six months 19/31 (61%) reported being "quite a bit" or "very much" satisfied with how they looked in the mirror clothed. There are no recurrences with a median follow up of 33 months [5-119]. Radiation treatment of the breast and lymph node basins prior to mastectomy with immediate autologous reconstruction is feasible. There were no autologous flap loses and complication rates are similar to reconstruction after radiation series. This promising strategy reduces time to autologous reconstruction and merits further prospective study.

First Results of the Primary Outcome of a Phase II Prospective Clinical Trial to Assess the Feasibility of Preoperative Radiation Boost in Breast Cancer Patients

A radiation boost targeted at the tumor bed is an important component of breast-conserving therapy (BCT) and has been shown to improve outcomes in patients with early-stage breast cancer. This is a prospective phase II study (NCT04871516) to assess the feasibility of delivering the radiation boost pre-operatively. This approach allows more accurate targeting of the high radiation dose at the tumor that may spare more normal breast tissue. We hypothesize wound complication rates to be comparable to standard treatment. The study design was a prospective phase II with a planned accrual of 55 patients. Women with non-metastatic node negative breast cancer or DCIS who were eligible for BCT were included. Patients were treated with pre-operative radiation boost of 1332 cGy in 4 fractions, followed by lumpectomy and adjuvant hypofractionated whole breast radiation to 3663 cGy in 11 fractions. The primary outcome of the study was to demonstrate that the incidence of grade 3 or more wound complications was not inferior to the current standard of care with conventional lumpectomy, postoperative whole breast radiation and a postoperative boost (6- 20%). Secondary outcomes included cosmetic outcome, local-regional control, and immunologic biomarkers induced by the preoperative radiation boost. We report here the results of the primary outcome of the study. Fifty-five women were enrolled between June 2021 and October 2022. Of those, 48 patients had at least 1 month follow up and were included in the analysis. Median age was 64 years-old, (range 40-77). Median follow up time was 2 months, (range 1-15). Forty-three patients (90%) had invasive cancers and 5 (10 %) had DCIS. Median clinical tumor size was 13 mm, (range 5-26). Median pathologic tumor size was 9 mm, (range 0-27). Margins were negative in 47 patients (98%). Two patients were found to have node positive disease on final pathology. Grade 3 wound dehiscence requiring surgical revision occurred in one patient (2%). There were no other grade 3 adverse side effects reported. Three patients (6%) had grade 2 wound infections requiring antibiotics. Cosmetic outcome at 1st follow up was available for 45 patients and was very good or excellent in 39 patients (87%). No patient had a poor cosmetic outcome. The use of a pre-operative radiation boost prior to lumpectomy followed by whole breast radiation as administered in this prospective trial resulted in an acceptable primary outcome with a similar rate of post-operative wound complications as the standard of care. We are currently enrolling patients on an expansion cohort to assess longer term cosmetic outcomes and performing a panel of immunologic markers to assess immune response to the preoperative boost.

Early Outcomes of MR-Guided SBRT for Patients with Recurrent Pancreatic Adenocarcinoma

Local treatment options for patients with locally recurrent pancreatic adenocarcinoma (L-PAC) are limited, with expected median survival time (MST) of 8-11 months (mo) following recurrence. MRI-guided radiation therapy (MRgRT) provides the ability to dose escalate while sparing normal tissue. The literature for MR-guided Stereotactic Body Radiotherapy (MRgSBRT) for L-PAC is sparse. Here we report on the early outcomes of MRgSBRT in patients with L-PAC. Patients with prior resection of pancreatic adenocarcinoma with post-operative chemotherapy as indicated followed by local recurrence of disease at prior surgical site and treated with MRgSBRT at a single tertiary referral center from 5-2021 to 8-2022 for L-PAC were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Descriptive analysis of the patient, disease, and treatment characteristics were performed. Endpoints included local control, defined as absence of tumor progression per RECIST criteria, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events (CTCAE), version 5. Eleven patients with L-PAC were identified with median follow-up of 10.7 mo (3.2 - 22.3). Ten of those underwent surgical resection at the treating radiation facility and one patient underwent preoperative radiation for 50.4 Gy in 28 fractions followed by surgical resection at an outside hospital. MRgRT was delivered a median of 18.8 mo (3.5 - 48.0) following resection. There were 5 females and 6 males, with a median age of 72 years (52-83) and median KPS of 80 (60-100). OS rates following initial diagnosis at 12, 18 and 24 mo were 100%, 82%, and 61%, respectively, with an MST of 25.3 mo (12.4-53.1). OS rates following recurrence at 6 and 12 mo were 82% and 52%, respectively, with an MST of 10.7 mo (3.2 - 21.9). One patient experienced local failure at 7.8 mo, and 9 patients experienced distant failure at a median of 3.4 mo (0.3 - 21.9) following MRgSBRT. Five patients experienced distant failure less than 3 mo following radiation. Grade 1 or 2 acute GI toxicity was noted in 45% of patients and chronic GI toxicity, in 18% of patients. No Grade≥3 AEs were noted. MRgSBRT for recurrent pancreatic adenocarcinoma demonstrates good local control with acceptable acute and chronic toxicity as well as reasonable overall survival. Distant failure remains a substantial problem with a significant number of patients demonstrating metastases immediately following radiation, suggesting the presence of micro-metastatic disease prior to local therapy. Adequate patient selection for MRgSBRT, and proper integration of systemic therapy in this patient population remains a topic of discussion that requires further exploration.