FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma.

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. METHODS: We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. RESULTS: From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. CONCLUSION: There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

PURPOSE: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. METHODS: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). RESULTS: A total of 49 patients were evaluated with a median age of 81 years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50 Gy (range, 40-50 Gy) in 5 fractions. 1 Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6 months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. CONCLUSIONS: A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

Neoadjuvant chemotherapy and stereotactic body radiation therapy for borderline resectable pancreas adenocarcinoma: influence of vascular margin status and type of chemotherapy.

BACKGROUND: The influence of chemotherapy type and vascular margin status after sequential chemotherapy and stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer (BRPC) is unknown. METHODS: A retrospective review was performed on BRPC patients treated with chemotherapy and 5-fraction SBRT from 2009 to 2021. Surgical outcomes and SBRT-related toxicity were reported. Clinical outcomes were estimated by Kaplan-Meier with log rank comparisons. RESULTS: A total of 303 patients received neoadjuvant chemotherapy and SBRT to a median dose of 40 Gy prescribed to the tumor-vessel interface and median dose of 32.4 Gyto 95% of the gross tumor volume. One hundred and sixty-nine patients (56%) were resected and benefited from improved median OS (41.1 vs 15.5 months, P < 0.001). Close/positive vascular margins were not associated with worse OS or FFLRF. Type of neoadjuvant chemotherapy did not influence OS for resected patients, but FOLFIRINOX was associated with improved median OS in unresected patients (18.2 vs 13.1 months, P = 0.001). CONCLUSION: For BRPC, the effect of a positive or close vascular margin may be mitigated by neoadjuvant therapy. Shorter duration neoadjuvant chemotherapy as well as the optimal biological effective dose of radiotherapy should be prospectively explored.

The role of dose escalation and proton therapy in perioperative or definitive treatment of chondrosarcoma and chordoma: An analysis of the National Cancer Data Base.

BACKGROUND: Chordomas and chondrosarcomas are a rare but challenging subset of tumors to treat; however, previous studies have shown benefits from proton therapy, which are thought to be primarily driven by prescription conformality permitting homogeneous tumor dosing and the allowance of higher doses. No retrospective studies to date have directly compared the outcomes of conventional and particle therapy or examined the role of high doses (specifically ≥70 Gy) in definitive radiotherapy (DRT) or perioperative radiotherapy (PRT) for both types of malignancies. METHODS: A total of 863 patients with chondrosarcoma and 715 patients with chordoma treated with nonpalliative proton or conventional radiation therapy with a dose range of 20 to 80 Gy and at least 15 months of follow-up were identified from the National Cancer Data Base for the years 2003-2014. The primary endpoint of overall survival (OS) was evaluated, and clinical features, including age, sex, grade, clinical stage, and Charlson-Deyo comorbidity index, were compared. RESULTS: Patients receiving DRT were older and had more advanced disease. In DRT for chondrosarcoma, a high dose (40.6% vs 16.9%; P = .006) and proton therapy (75.0% vs 19.1%; P = .046) were associated with improved OS at 5 years in a multivariate analysis. In DRT for chordoma, proton therapy was associated with improved OS at 5 years in a multivariate analysis (100% vs 34.1%; P = .031), and a high dose for chordoma was significant for improved OS in a univariate analysis with both DRT (79.0% vs 54.1%; P = .027) and PRT (83.3% vs 77.4%; P = .007). CONCLUSIONS: In the largest retrospective series to date, dose escalation and proton radiotherapy were associated with improved OS in patients with chondrosarcoma and chordoma despite limited follow-up and access to particle therapy.

The Role of MRI in Breast Cancer and Breast Conservation Therapy.

Contrast-enhanced breast MRI has an established role in aiding in the detection, evaluation, and management of breast cancer. This article discusses MRI sequences, the clinical utility of MRI, and how MRI has been evaluated for use in breast radiotherapy treatment planning. We highlight the contribution of MRI in the decision-making regarding selecting appropriate candidates for breast conservation therapy and review the emerging role of MRI-guided breast radiotherapy.

Totally minimally invasive laparoscopic robot-assisted Ivor Lewis esophagectomy: improved technique and outcomes over 200 cases.

Background: Surgical resection of esophageal and gastroesophageal junction cancers is a very complex procedure with step learning curve. New technologies have made minimally invasive surgery possible, but challenges still remain for wide spread adoption of these techniques. This article aims to describe the outcomes and salient technical points of a totally minimally invasive, laparoscopic, robot-assisted Ivor Lewis esophagectomy (LRAMIE). Methods: Retrospective observational cohort study performed at a specialty cancer center using a prospectively maintained institutional database. Patients undergoing LRAMIE (laparoscopic abdomen, robotic chest) from 2014-2023 were included. Patients undergoing transhiatal and three-field esophagectomy were excluded. Operative and postoperative outcomes were compared over the study period to identify potential associations between outcomes over time. Results: Two-hundred patients were identified who underwent LRAMIE. Median age was 65 years and most were male (87.5%). The open conversion rate was 1% (n=2), which occurred within the first 30 cases. Operative time and blood loss were improved at the 60-case mark (P<0.001). Anastomotic stricture rate improved after 50 cases, and leak rate improved after 80 cases. Postoperative length of stay improved at both 50 and 100 cases with a median LOS of 6 days after 100 cases. Rate of postoperative pneumonia, 30- and 90-day mortality were reduced after 100 cases, although not statistically significant for mortality due to too few events. Conclusions: Totally minimally invasive Ivor Lewis esophagectomy at a high-volume center is a safe procedure. Operative outcomes improved significantly after 50-80 cases, followed by improvement in anastomotic results and postoperative outcomes, with corresponding excellent oncologic outcomes.

Intricacies of Human-AI Interaction in Dynamic Decision-Making for Precision Oncology: A Case Study in Response-Adaptive Radiotherapy.

Background: Adaptive treatment strategies that can dynamically react to individual cancer progression can provide effective personalized care. Longitudinal multi-omics information, paired with an artificially intelligent clinical decision support system (AI-CDSS) can assist clinicians in determining optimal therapeutic options and treatment adaptations. However, AI-CDSS is not perfectly accurate, as such, clinicians' over/under reliance on AI may lead to unintended consequences, ultimately failing to develop optimal strategies. To investigate such collaborative decision-making process, we conducted a Human-AI interaction case study on response-adaptive radiotherapy (RT). Methods: We designed and conducted a two-phase study for two disease sites and two treatment modalities-adaptive RT for non-small cell lung cancer (NSCLC) and adaptive stereotactic body RT for hepatocellular carcinoma (HCC)-in which clinicians were asked to consider mid-treatment modification of the dose per fraction for a number of retrospective cancer patients without AI-support (Unassisted Phase) and with AI-assistance (AI-assisted Phase). The AI-CDSS graphically presented trade-offs in tumor control and the likelihood of toxicity to organs at risk, provided an optimal recommendation, and associated model uncertainties. In addition, we asked for clinicians' decision confidence level and trust level in individual AI recommendations and encouraged them to provide written remarks. We enrolled 13 evaluators (radiation oncology physicians and residents) from two medical institutions located in two different states, out of which, 4 evaluators volunteered in both NSCLC and HCC studies, resulting in a total of 17 completed evaluations (9 NSCLC, and 8 HCC). To limit the evaluation time to under an hour, we selected 8 treated patients for NSCLC and 9 for HCC, resulting in a total of 144 sets of evaluations (72 from NSCLC and 72 from HCC). Evaluation for each patient consisted of 8 required inputs and 2 optional remarks, resulting in up to a total of 1440 data points. Results: AI-assistance did not homogeneously influence all experts and clinical decisions. From NSCLC cohort, 41 (57%) decisions and from HCC cohort, 34 (47%) decisions were adjusted after AI assistance. Two evaluations (12%) from the NSCLC cohort had zero decision adjustments, while the remaining 15 (88%) evaluations resulted in at least two decision adjustments. Decision adjustment level positively correlated with dissimilarity in decision-making with AI [NSCLC: ρ = 0.53 ( p < 0.001); HCC: ρ = 0.60 ( p < 0.001)] indicating that evaluators adjusted their decision closer towards AI recommendation. Agreement with AI-recommendation positively correlated with AI Trust Level [NSCLC: ρ = 0.59 ( p < 0.001); HCC: ρ = 0.7 ( p < 0.001)] indicating that evaluators followed AI's recommendation if they agreed with that recommendation. The correlation between decision confidence changes and decision adjustment level showed an opposite trend [NSCLC: ρ = -0.24 ( p = 0.045), HCC: ρ = 0.28 ( p = 0.017)] reflecting the difference in behavior due to underlying differences in disease type and treatment modality. Decision confidence positively correlated with the closeness of decisions to the standard of care (NSCLC: 2 Gy/fx; HCC: 10 Gy/fx) indicating that evaluators were generally more confident in prescribing dose fractionations more similar to those used in standard clinical practice. Inter-evaluator agreement increased with AI-assistance indicating that AI-assistance can decrease inter-physician variability. The majority of decisions were adjusted to achieve higher tumor control in NSCLC and lower normal tissue complications in HCC. Analysis of evaluators' remarks indicated concerns for organs at risk and RT outcome estimates as important decision-making factors. Conclusions: Human-AI interaction depends on the complex interrelationship between expert's prior knowledge and preferences, patient's state, disease site, treatment modality, model transparency, and AI's learned behavior and biases. The collaborative decision-making process can be summarized as follows: (i) some clinicians may not believe in an AI system, completely disregarding its recommendation, (ii) some clinicians may believe in the AI system but will critically analyze its recommendations on a case-by-case basis; (iii) when a clinician finds that the AI recommendation indicates the possibility for better outcomes they will adjust their decisions accordingly; and (iv) When a clinician finds that the AI recommendation indicate a worse possible outcome they will disregard it and seek their own alternative approach.

Advances in MRI-Guided Radiation Therapy.

Image guidance for radiation therapy (RT) has evolved over the last few decades and now is routinely performed using cone-beam computerized tomography (CBCT). Conventional linear accelerators (LINACs) that use CBCT have limited soft tissue contrast, are not able to image the patient's internal anatomy during treatment delivery, and most are not capable of online adaptive replanning. RT delivery systems that use MRI have become available within the last several years and address many of the imaging limitations of conventional LINACs. Herein, the authors review the technical characteristics and advantages of MRI-guided RT as well as emerging clinical outcomes.

Effect of Favorable Pathologic Response After Neoadjuvant Radiation Therapy Alone in Soft-tissue Sarcoma.

Purpose: Whether the therapeutic response of soft-tissue sarcoma to neoadjuvant treatment is predictive for clinical outcomes is unclear. Given the rarity of this disease and the confounding effects of chemotherapy, this study analyzes whether a favorable pathologic response (fPR) after neoadjuvant radiation therapy (RT) alone is associated with clinical benefits. Methods and Materials: An institutional review board-approved retrospective review was conducted on a database of patients with primary soft-tissue sarcoma treated at our institution between 1987 and 2015 with neoadjuvant RT alone followed by surgical resection. Time-to-event outcomes estimated with a Kaplan-Meier analysis included overall survival, progression-free survival (PFS), locoregional control, and distant control (DC). Cox regression analyses were performed to determine prognostic variables associated with clinical outcomes. Results: Of the overall cohort of 315 patients, 181 patients (57%) were included in the primary analysis with documented pathologic necrosis (PN) rates (mean: 59%) and a median follow up from diagnosis of 48 months (range, 4-170 months). The median neoadjuvant RT dose was 50 Gy (range, 40-60 Gy), and the majority of patients had negative surgical margins (79%). Only 35 patients (19%) achieved a fPR (PN ≥95%), which was associated with a higher R0 resection rate (94% vs. 75%; P = .013), a significant 5-year PFS benefit (74% vs. 43%; P = .014), and a nonsignificant 5-year DC benefit (76% vs. 62%; P = .12) compared with PN <95%. On multivariable analysis, fPR was an independent predictor for PFS (hazard ratio: 0.47; 95% confidence interval, 0.25-0.90; P = .022). Conclusions: Achieving fPR with neoadjuvant RT alone is associated with a higher R0 resection rate and possible DC benefit, translating into a significant improvement in PFS. Further studies to improve pathologic response rates and prospectively validate this endpoint are warranted.

A Practical Workflow for Magnetic Resonance-Guided Stereotactic Body Radiation Therapy to the Pancreas.

The increased adoption of stereotactic body radiation therapy has allowed for delivery of higher doses, potentially associated with better outcomes but at the risk of higher toxicity. The intimate association of radiosensitive organs at risk (eg, stomach, duodenum, bowel) has historically limited the delivery of ablative doses to the pancreas. The advent of magnetic resonance-guided radiation therapy with improved soft-tissue contrast allows for gated delivery without an internal target volume and online adaptive replanning to maximize the therapeutic ratio. Patient selection requires additional resources, including increased patient on-table time, physician time, and physics support. Within our center's workflow, integrating an educational video at consultation as well as optimizing biofeedback mechanisms have significantly improved the experience for our patients.

Neoadjuvant Simultaneous Integrated Boost Radiation Therapy Improves Clinical Outcomes for Retroperitoneal Sarcoma.

PURPOSE: Neoadjuvant radiation therapy (RT) with standard techniques (ST) offers a modest benefit in retroperitoneal sarcoma (RPS). As the high-risk region (HRR) at risk for a positive surgical margin and recurrence is posterior and away from radiosensitive organs at risk, using a simultaneous integrated boost (SIB) allows targeted dose escalation to the HRR while sparing these organs. We hypothesized that neoadjuvant SIB RT can improve disease control compared with ST, without increasing toxicity. METHODS AND MATERIALS: We retrospectively identified patients with resectable nonmetastatic RPS from 2000 to 2021 who received neoadjuvant RT of 180 to 200 cGy/fraction to standard volumes. SIB patients received 205 to 230 cGy/fraction to the appropriate HRR. Clinical endpoints included abdominopelvic control (APC), recurrence-free survival (RFS), overall survival (OS), and acute toxicity. RESULTS: With a median follow-up of 57 months (95% confidence interval [CI], 50-64), there were 103 patients with RPS who received either ST (n = 69) or SIB (n = 34) RT. Median standard volume dose was 5000 cGy (ST) and 4500 cGy (SIB), with a median HRR SIB dose of 5750 cGy. Liposarcomas (79% vs 53%; P = .004) and cT4 tumors (59% vs 19%; P < .001) were more common in the SIB cohort, without a significant difference in the rate of resection (82% vs 81%; P = .88) or R1 margin (53.5% vs 50%; P = .36); there were no R2 resections. SIB was associated with a significant improvement in 5-year APC (96% vs 70%; P = .046) and RFS (60.2% vs 36.3%; P = .036), with a nonsignificant OS difference (90.1% vs 67.5%; P = .164). On multivariable analysis, SIB remained a predictor for APC (hazard ratio, 0.07; 95% CI, 0.01-0.74; P = .027) and RFS (hazard ratio, 0.036; 95% CI, 0.13-0.98; P = .045). SIB showed no significant detriment in toxicity, albeit with a lower rate of overall grade 3 acute toxicity (3% vs 22%; P = .023) compared with ST. CONCLUSIONS: In RPS, dose escalation with neoadjuvant SIB RT may be independently associated with improved APC and RFS, without a detriment in toxicity, compared with ST. With the addition of standard RT having only a modest benefit compared with surgery alone, our study suggests that future prospective studies evaluating for the benefit of SIB RT should be considered.

Induction Fluorouracil-Based Chemotherapy and PET-Adapted Consolidation Chemoradiation with Esophagectomy for High-Risk Gastroesophageal Adenocarcinoma.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal adenocarcinoma. Induction chemotherapy with a tailored approach to chemoradiation based on metabolic response to therapy on PET was explored as an alternative strategy in the CALGB 80803 trial. We sought to describe real-world institutional experience implementing this approach outside of a clinical trial. Methods: Patients who were treated with induction fluorouracil-leucovorin-oxaliplatin (FOLFOX) or fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) with tailored chemoradiation based on PET response and subsequent esophagectomy were identified from a prospectively maintained database. Primary outcomes were pathologic complete response (pCR) and overall survival (OS) following completion of all therapy. Results: There were 35 patients who completed induction chemotherapy, chemoradiation, and esophagectomy. Thirty-three completed restaging PET following induction chemotherapy with metabolic response seen in 76% (n = 25/33). The pCR rate was 31% (n = 11/35) and the ypN0 rate was 71% (n = 25/35). Among the patients who demonstrated metabolic response to induction FOLFOX/FLOT and subsequently continued fluorouracil-based chemoradiation, the pCR rate was 39% (n = 9/23). The rate of pathologically negative lymph nodes in this group was high (n = 19/23, 83%) with 100% R0 resection rate (n = 23/23). With the median follow-up of 43 months, the median OS was not reached for this group and was significantly longer than the OS for the remainder of the cohort (p = 0.027, p = 0.046 adjusted for clinical stage). Conclusions: Induction FOLFOX/FLOT chemotherapy with evaluation of sensitivity via metabolic response and tailored chemoradiation seems to lead to high pCR and ypN0 rates in high-risk patients with adenocarcinoma of the esophagus and GE junction. This approach in clinical practice seems to recapitulate encouraging results in clinical trials.

Surgical and Pathologic Outcomes of Pancreatic Adenocarcinoma (PA) After Preoperative Ablative Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy (A-SMART).

Purpose: Preoperative radiation therapy (RT) for pancreatic adenocarcinoma reduces positive surgical margin rates, and when delivered to an ablative dose range it may improve local control and overall survival for patients with unresectable disease. Use of stereotactic body RT to achieve a higher biologically effective dose has been limited by toxicity to adjacent radiosensitive structures, but this can be mitigated by stereotactic magnetic resonance image guided adaptive radiation therapy (SMART). Methods and Materials: We describe our single-institution experience of high biologically effective dose SMART before resection of localized pancreatic adenocarcinoma. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (V 5.0). Tumor response was evaluated according to the College of American Pathologists tumor regression grading criteria. Results: We analyzed 26 patients with borderline resectable (80.8%), locally advanced (11.5%), and resectable (7.7%) tumors who received ablative dose SMART (A-SMART) followed by surgical resection. Median age at diagnosis was 68 years (range, 34-86). Most patients received chemotherapy (80.8%) before RT. All patients received A-SMART to a median dose of 50 (range, 40-50) Gy in 5 fractions. Toxicity data were collected prospectively and there were no acute grade 2+ toxicities associated with RT. The median time to resection was 50 days (range, 37-115), and the procedure types included Whipple (69%), distal (23%), or total pancreatectomy (8%). The R0 resection rate was 96% and no perioperative deaths occurred within 90 days. Pathologic response was observed in 88% of cases. The time from RT to surgery was associated with tumor regression grade (P = .0003). The median follow-up after RT was 16.5 months (range, 3.9-26.2). The derived median progression-free survival from RT was 13.2 months. Conclusions: The initial surgical and pathologic outcomes after A-SMART are encouraging. Preoperative A-SMART was associated with low toxicity rates and no surgical or RT-associated mortality. The surgical morbidity was comparable to historic rates after upfront resection. These data also suggest that the time from stereotactic body RT to surgical resection is associated with pathologic response.

Assessment of MRI-Linac Economics under the RO-APM.

The implementation of the radiation oncology alternative payment model (RO-APM) has raised concerns regarding the development of MRI-guided adaptive radiotherapy (MRgART). We sought to compare technical fee reimbursement under Fee-For-Service (FFS) to the proposed RO-APM for a typical MRI-Linac (MRL) patient load and distribution of 200 patients. In an exploratory aim, a modifier was added to the RO-APM (mRO-APM) to account for the resources necessary to provide this care. Traditional Medicare FFS reimbursement rates were compared to the diagnosis-based reimbursement in the RO-APM. Reimbursement for all selected diagnoses were lower in the RO-APM compared to FFS, with the largest differences in the adaptive treatments for lung cancer (-89%) and pancreatic cancer (-83%). The total annual reimbursement discrepancy amounted to -78%. Without implementation of adaptive replanning there was no difference in reimbursement in breast, colorectal and prostate cancer between RO-APM and mRO-APM. Accommodating online adaptive treatments in the mRO-APM would result in a reimbursement difference from the FFS model of -47% for lung cancer and -46% for pancreatic cancer, mitigating the overall annual reimbursement difference to -54%. Even with adjustment, the implementation of MRgART as a new treatment strategy is susceptible under the RO-APM.

Using the revised Edmonton symptom assessment scale during neoadjuvant radiotherapy for retroperitoneal sarcoma.

BACKGROUND AND PURPOSE: Retroperitoneal sarcoma (RPS) is a rare, complex disease requiring multidisciplinary management. We have previously reported that use of the Revised Edmonton Symptom Assessment Scale (ESAS-r-CSS) allows for proactive symptom management, and we sought to report the results of ESAS-r-CSS screening during pre-operative radiotherapy (RT) for a cadre of patients with RPS. MATERIALS AND METHODS: We reviewed records of 47 patients with RPS evaluated at our institution between 2015 and 2018. Of this group, 29 non-metastatic patients were treated with definitive intent neoadjuvant RT with at least 2 weekly ESAS-r-CSS reports. A generalized estimating equation model was used to compare 13 symptoms during weekly on-treatment visits compared to baseline scores at week 1 of RT. Additionally, covariate effects of age, gender, dose, tumor size and location were assessed. RESULTS: The population was predominantly male (66%) with median age of 65 years, KPS of 90, and tumor size of 12.8 cm. ESAS scores significantly decreased for anxiety at week 3 (P = 0.01), and pain at week 5 (P = 0.01). Worse constipation was reported at week 2 (P = 0.02). In an exploratory covariate analysis, female gender, age, high dose, and larger tumor size were associated with worse ESAS scores across all time points. CONCLUSION: Patient reporting of symptoms during radiotherapy through weekly ESAS-r-CSS facilitates timely management in patients with this unique tumor type. Expectant care during RT offers the opportunity to minimize symptom progression or treatment interruptions in a population that generally has worsening side effects.

MR-guided stereotactic body radiation therapy for intracardiac and pericardial metastases.

AIMS: To assess the safety and efficacy of MR-guided stereotactic body radiation therapy (MRgSBRT) for cardiac metastases. MATERIALS/METHODS: This single institution retrospective analysis evaluated our experience with MRgSBRT for cardiac metastases. Response rate was compared between pre-RT and post-RT imaging. Symptomatic changes were also tracked and documented. RESULTS: Between 4/2019 and 3/2020, five patients with cardiac metastases (4 intracardiac and 1 pericardial) were treated with MRgSBRT. Median age at treatment was 73 years (range 64-80) and two patients had pre-existing cardiac disease. Histologies included melanoma and breast adenocarcinoma. Median lesion diameter was 2 cm (range 1.96-5.8 cm). Three patients were symptomatic, one of whom had pulmonary hypertension and RV enlargement. Another patient had an asymptomatic arrythmia. Median PTV prescribed dose was 40 Gy (range 40-50 Gy) and delivered in five fractions on nonconsecutive days. Median PTV volume was 53.4 cc (range 8.7-116.6 cc) and median coverage was 95% (range 84.1-100%). A uniform 3 mm margin was used for real-time gating, allowing a median 7% (range 5-10%) pixel excursion tolerance. Median follow-up was 4.7 months (range 0.9-12.3). Two patients exhibited stable disease, two had a partial response and one exhibited a complete response. All symptomatic patients experienced some relief. There were no acute adverse events, however, one patient without prior cardiac disease developed atrial fibrillation 6 months after treatment. Two patients died of causes unrelated to cardiac MRgSBRT. CONCLUSION: In this largest known series of cardiac metastasis MRgSBRT, real-time image guidance enables safe treatment resulting in good response with improving presenting symptoms without acute adverse events.