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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., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: November 2022 and January 2023, travel expenses were partially supported by View Ray. October 2022, meal expense support from Galera Therapeutics.

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.

Background: Tumor response to neoadjuvant therapy is heterogenous and prognostically important for locally advanced rectal adenocarcinoma (LARC) patients. Commonly applied response classification approaches including tumor regression grading (TRG) and TN downstaging can be discordant. The aim of this study is to compare the prognostic value of discordant tumor response measurement categorized according to the AJCC/CAP TRG schema and ypTN stage., Methods: This is a single-center retrospective review of 90 consecutive patients with stage II-III rectal cancer receiving neoadjuvant chemoradiation (nCRT), total mesorectal excision (TME) and adjuvant chemotherapy (ACT) between 2007 and 2018. Two pathologists re-examined each case to assign a consensus AJCC TRG. A Cox proportional hazards ratio model assessed the effect of patient, tumor, and treatment factors on disease-free survival (DFS)., Results: Median follow-up after surgery was 46 months (95% CI: 41-50 months). Median age at diagnosis was 55 years (range: 27-80). Most patients were male (58%) and Caucasian (92%) with clinical stage III disease (68%). Seventy-three patients (81%) underwent low anterior resection (LAR), 17 (19%) underwent abdominoperineal resection (APR). The median interval from completion of nCRT to surgery was 62 days (IQR: 56-70 days). The 4-year OS, DFS, and LC was 92.4%, 74.4%, and 90.2%, respectively. In the multivariate analysis, ypTN downstaging was not prognostically significant; however, AJCC TRG score 3 (minimal tumor response to treatment) was strongly predictive for inferior DFS (3-year DFS 79% vs. 25%, P<0.001). Patients with TRG 3 had a significantly higher risk of both local (75% vs. 5%) and distant failure (75% vs. 19%)., Conclusions: Minimal tumor response to neoadjuvant therapy, AJCC TRG 3, irrespective of ypTN downstaging, is a pattern of residual disease that is at highest risk for recurrence. Response categorization discrepancies may be partly explained by alternative patterns of residual disease, including tumor fragmentation, and may be best reflected by TRG. The optimal tumor response categorization method requires further study to best stratify patient risk and management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-477/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Introduction: Neoadjuvant rectal (NAR) score may serve as a surrogate short-term endpoint for overall survival (OS) in clinical trials. This study aims to test the NAR score using a large, national cancer registry., Methods: National Cancer Database patients with clinical stage II/III rectal adenocarcinoma (RAC) treated with neoadjuvant chemoradiation (CRT) followed by surgery were selected and divided into low-, intermediate-, and high-NAR subgroups. OS outcomes were analyzed using Kaplan-Meier and logistic regression models., Results: A total of 12 452 patients were selected, of which 5071 (40.7%) were in clinical stage II and 7381 (59.3%) were in clinical stage III; 15.2% had pathologic complete response. The mean NAR score was 10.01 ± 10.61. Six thousand nine hundred and forty-one (55.7%) did not receive adjuvant chemotherapy (AC) and were propensity-matched across NAR subgroups (966 in each group). A significant difference in 5-year OS between low-, intermediate-, and high-NAR groups was observed (85% vs. 76% vs. 68%; p < 0.001). Five thousand five hundred and eleven (44.3%) received AC and 1045 triplets were propensity-matched per NAR groups. A significant difference was again observed for 5-year OS (93% vs. 88% vs. 75%; p < 0.001). Logistic regression confirmed NAR strata as a significant predictor of 5-year OS., Conclusion: NAR score, as a neoadjuvant response measure, is a strong predictor of 5-year OS, regardless of AC receipt in a heterogenous population of locally advanced RAC patients., (© 2022 Wiley Periodicals LLC.)

The increasing complexity of healthcare emphasizes the need for continued physician leadership and leadership training. This study aims to determine baseline attitudes toward the perceptions and utility of a leadership development curriculum (LDC) for radiation oncology (RO) residents. A novel longitudinal LDC was implemented for RO residents at our institution from 2018 to 2019. Prior to the curriculum, current and past residents in our institution's RO residency program were surveyed on their attitudes towards leadership in healthcare, emotional intelligence competencies, and leadership training interests. After the completion of the LDC, a post-curriculum survey was forwarded to current residents. The response rate was 84% (21 of 24) for the baseline survey and 90% (9 of 10) for the post-curriculum survey. Having a leadership training curriculum during residency was rated as extremely useful, with top training interests involving leading clinical teams, effective communication strategies, and conflict management. After the LDC, the residents reported high satisfaction with the curriculum and utilization of leadership training into their daily work. Our LDC demonstrates significant potential to engage trainees and improve their leadership skills at the graduate medical education level., (© 2021. American Association for Cancer Education.)

Background and Objectives: The gold standard for locoregional esophageal cancer (LEC) treatment includes preoperative chemoradiation and surgical resection, with possible perioperative or adjuvant systemic therapy. With few data associating histologic grade and prognosis in LEC patients receiving neoadjuvant chemoradiation followed by resection, we seek to evaluate this association., Methods: Our institutional esophagectomy database between 1999 and 2019 was queried, selecting esophageal adenocarcinoma patients who completed neoadjuvant therapy (NAT), followed by esophagectomy. Propensity-score matching of low- and high-histologic grade groups was performed to assess survival metrics using initial clinical grade (cG) and final pathologic grade (pG). We performed a multivariable logistic regression to study predictors of pathologic complete response as a secondary objective., Results: A total of 518 patients met the inclusion criteria. Kaplan-Meier analysis of the matched dataset showed no difference in initial or 5-year recurrence-free survival or overall survival (OS) between cG1 and cG2 versus cG3 based on original grade. When matched according to pG, cG1-2 had improved median survival parameters compared to cG3, with 5-year OS for cG1-2 of 45% versus 27% (p = 0.001). Higher pG, pathologic N stage, and poor response to NAT are predictors of poor survival., Conclusion: Patients with post-NAT pG1-2 demonstrated improved survival. Integrating histologic grade into postneoadjuvant staging may be warranted., (© 2022 Wiley Periodicals LLC.)

Transarterial radioembolization (TARE) with yttrium-90 glass microspheres is widely used to treat primary and secondary malignancies in the liver. However, the safety and efficacy of TARE in patients with liver-dominant metastatic castration-resistant prostate cancer (mCRPC) is unknown. A proof-of-concept, retrospective analysis of 7 consecutive patients with liver-dominant mCRPC who were treated with TARE was performed. The median overall survival was 27.2, 32.1, and 108.1 months from the time of TARE, the diagnosis of liver metastases, and initial cancer diagnosis, respectively. The median liver progression-free survival was 7.3 months. No grade 3 or higher adverse effects were noted. TARE was found to be a safe and effective tool for treating patients with liver-dominant mCRPC in this limited cohort., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Background: There is no curative treatment option for patients with unresectable intrahepatic, cholangiocarcinoma (IHC). The aim of this study was to evaluate the efficacy of; radiation segmentectomy/lobectomy using Y90-labeled glass microspheres in patients with; unresectable IHC., Methods: This IRB-approved, single-center study included, 16 patients (age: 67 ± 7.7 years) with IHC who received radiation segmentectomy or lobectomy, treatment using Y90-labeled glass microspheres between May 2009 and October 2019. Radiation, segmentectomy/lobectomy was defined as at least 190 Gy dose delivered into treated liver; volume., Results: The median OS from IHC diagnosis was 22.7 months (95% CI: 13.9-66.1) and from, radioembolization it was 7 months (95% CI: 4.33-54.17). Patients who did not receive, chemotherapy before the radioembolization had significantly longer median OS (26.8 vs. 5.9, months, P  = 0.03). Four patients had >20 months survival after radioembolization, including 2, patients with survival of 42 and 54 months. There was no 30-day mortality and no severe, complications., Conclusion: Radiation segmentectomy/lobectomy is safe with minimal side effects. The median, OS of the study group is modest; however, 4 patients (25%) showed excellent survival. These results suggest a need for a larger study to define the IHC patient group who could, most benefit from this procedure., Competing Interests: The author has none to declare., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (© 2022 The Authors.)

Background: Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation., Methods: In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer., Results: A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes., Conclusion: The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified., Clinical Trial Registration: NCT02935309., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: Homologous recombination mutations (HRM) have led to increased responses to platinum chemotherapy in pancreatic cancer. However, HRMs' role in nonpancreatic gastrointestinal (GI) cancers remains to be determined. Our objective was to evaluate the prognostic and predictive role of core (BRCA1, BRCA2, PALB2) and noncore HRM in nonpancreatic GI cancers receiving platinum therapy., Materials and Methods: This study performed at Moffitt Cancer Center included metastatic nonpancreatic GI cancer patients treated with platinum therapy. All patients had either a core or noncore HRM, determined by next generation sequencing. Response rates, median progression-free survival (PFS), and median overall survival (OS) were determined and compared between core versus noncore HRM patients., Results: In the study, 69 patients with one or more HRM were included: 63.8% were male, 87.0% were Caucasian, and 47.9% had colorectal cancer. Twenty-one (30.4%) patients had a core HRM and 48 (69.6%) had a noncore HRM. Among evaluable patients (n=64), there was no significant difference in objective response: 20.0% with core HRM versus 22.7% with noncore HRM responded to platinum therapy (P=0.53). Median PFS was 10.4 months versus 7.1 months for core HRM versus noncore HRM, respectively (P=0.039). Median OS was 68.9 months versus 24.3 months (P=0.026) for core HRM versus noncore HRM, respectively., Conclusions: Our study demonstrated response of core and noncore HRM to platinum therapy in metastatic nonpancreatic GI malignancies, suggesting benefit in both groups. Core HRM patients had significantly increased median OS and median PFS compared with those with noncore HRM, suggesting potential prognostic and predictive significance. Larger prospective studies are needed to confirm our findings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with hepatobiliary malignancies are especially vulnerable to treatment delays. This study sought to evaluate the impact of implementing a new delivery-of-care model centered around a hepatobiliary multidisciplinary tumor board (HB-MTB) and integrated with an optimized patient workflow process to expedite treatment initiation., Methods: A hybrid type 2 study (effectiveness-implementation) was performed. Implementation measures were examined prospectively using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) approach during 5 years after the HB-MTB program deployment (2015-2020). The primary outcome was effectiveness, measured as time to treatment initiation (TTI) using a before and after design (1 year each). The patients were grouped into before (BP) and after (AP) categories based on date of HB-MTB program implementation. Multivariable Cox and linear regression analyses were performed to examine and compare time to treatment initiation between groups., Results: The HB-MTB program enrolled 2457 patients (reach). The RE-AIM measures were favorable and improved over time (P < 0.01 for all). The median TTI was lower for the AP group than for the BP group (17 vs 24 days; P < 0.01). In the multivariable Cox and linear regressions, treatment in the AP group was associated with a faster TTI (hazard ratio, 1.75; 95 % confidence interval, 1.31-2.35; p < 0.01), and a mean of 13 days faster treatment initiation than the BP group (P < 0.01)., Conclusions: Implementation of an HB-MTB program integrated with an optimized patient workflow was successful and led to faster treatment initiation. This delivery-of-care model can serve as a blueprint to expedite treatment of patients with cancer., (© 2021. Society of Surgical Oncology.)

Background: Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC., Materials/methods: This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type., Results: There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis., Conclusion: BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: The impact of adjuvant sequential chemoradiotherapy (CRT) on survival in resected pancreatic ductal adenocarcinoma (PDAC) remains unclear and warrants further investigation., Methods: NCDB patients with R0/R1 resected PDAC who received adjuvant chemotherapy without CRT or followed by CRT per RTOG-0848 protocol were included. Cox regression for 5-year overall survival (OS) was performed and used to construct a pathologic nomogram in patients who did not receive CRT. A risk score was calculated and patients were divided into low-risk and high-risk groups. Patients from each risk stratum were matched for the receipt of CRT to assess the added benefit of CRT on survival. The Kaplan-Meier analysis was performed to compare OS., Results: A total of 7146 patients were selected, 1308 (18.3%) received CRT per RTOG-0848. Cox regression concluded grade, T stage, N stage, node yield < 12, R1, and LVI as significant predictors of 5-year OS which were used to construct the risk score. Matched analysis in low-risk patients (score 0-79) showed no difference in OS between CRT vs. no CRT (47.6 ± 5.7 vs. 45.1 ± 3.9 months; p = 0.847). OS benefit was 3% at 1 year, - 4% at 2 years, and 4% at 5 years. In high-risk patients (score 80-100), median OS was higher in CRT vs. no CRT (24.8 ± 0.7 vs. 21.7 ± 0.8 months; p = 0.043). Absolute OS benefit was 13% at 1 year, 5% at 2 years, and - 1% at 5 years., Conclusion: CRT has a short-lived impact on OS in resected PDAC that is only evident in high-risk patients. In this subset, survival benefit peaks at 1 year and subsides at 3 to 5 years following PDAC resection., (© 2021. The Society for Surgery of the Alimentary Tract.)

Purpose: The management of Renal cell carcinoma (RCC) patients with liver metastases is challenging. Liver-directed therapy, such as Transarterial radioembolization (TARE), is a reasonable option for these patients; however, its safety and efficacy are not well characterized. This study evaluated the safety and efficacy of TARE in patients with liver-dominant metastatic RCC., Materials and Methods: This is a retrospective, single-center study. Thirty-eight patients' medical records were reviewed who underwent TARE between January 1, 2009, and December 31, 2019, in a tertiary cancer center. Two were excluded from further analysis. Thirty-six patients received 51 TARE treatments. Median follow-up time was 18.2 months. Imaging data were evaluated using mRECIST or RECIST 1.1 criteria. Toxicities, treatment responses, liver progression-free survival (LPFS), and median overall survival (OS) were calculated. Univariate and multivariate analyses were conducted to reveal predictors of OS., Results: Median OS from TARE was 19.3 months (95% CI, 22.6-47.4) and from diagnosis of liver metastases was 36.5 months (95% CI: 26.4-49.8). Mild, grade 1 or 2, biochemical toxicity developed in 27 patients (75%). Grade 3-4 toxicity was noted in two patients (5.5%). The objective response rate was 89%; the disease control rate was 94% (21 complete response, 11 partial response, two stable disease, and two progressive disease). Univariate and multivariate analyses showed longer survival in patients who had objective response, lower lung shunt fraction, and better baseline liver function., Conclusions: TARE is safe and effective and led to promising overall survival in patients with liver-dominant metastatic RCC., Level of Evidence: Level 3, retrospective cohort study., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose: Our purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease., Methods and Materials: This retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors., Results: Median overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P  = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P  = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%., Conclusions: The treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases., (© 2021 The Authors.)

A nonoperative management strategy, or Watch-and-Wait, following neoadjuvant therapies of locally advanced rectal adenocarcinoma is increasingly considered for select patients. Yet, standardized tumor response assessment to best select and surveil suitable patients remains an unmet clinical challenge. Endoscopic and MRI currently provide the most reliable tumor response estimations. However, resources illustrating variable tumor responses to neoadjuvant therapies remain limited. This pictorial review aims to provide detailed and annotated examples of common endoscopic and MRI findings of rectal cancer treatment response, while also emphasizing their respective diagnostic shortcomings and consequently, the necessity for a multidisciplinary approach to optimally manage these patients.

Background: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T)., Materials and Methods: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET., Results: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs . TRG 1-3; 91% accuracy in predicting TRG 0-1 vs . TRG 2-3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs . intermediate vs . high NAR scores., Conclusion: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation., Competing Interests: Conflicts of interest None were declared., (© 2021 Greater Poland Cancer Centre.)

Introduction: To develop a radiomic-based model to predict pathological complete response (pCR) and outcome following neoadjuvant chemoradiotherapy (NACRT) in oesophageal cancer., Methods: We analysed 68 patients with oesophageal cancer treated with NACRT followed by esophagectomy, who had staging 18F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) and computed tomography (CT) scans performed at our institution. An in-house data-chjmirocterization algorithm was used to extract 3D-radiomic features from the segmented primary disease. Prediction models were constructed and internally validated. Composite feature, F c  = α * F PET  + (1 - α) * F CT , 0 ≤ α ≤ 1, was constructed for each corresponding CT and PET feature. Loco-regional control (LRC), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis, and compared using log-rank test., Results: Median follow-up was 59 months. pCR was achieved in 34 (50%) patients. Five-year RFS, LRC, MFS and OS were 67.1%, 88.5%, 75.6% and 57.6%, respectively. Tumour Regression Grade (TRG) 0-1 indicative of complete response or minimal residual disease was significantly associated with improved 5-year LRC [93.7% vs 71.8%; P = 0.020; HR 0.19, 95% CI 0.04-0.85]. Four sepjmirote pCR predictive models were built for CT alone, PET alone, CT+PET and composite. CT, PET and CT+PET models had AUC 0.73 ± 0.08, 0.66 ± 0.08 and 0.77 ± 0.07, respectively. The composite model resulted in an improvement of pCR predicting power with AUC 0.87 ± 0.06. Stratifying patients with a low versus high radiomic score showed clinically relevant improvement in 5-year LRC favouring low-score group (91.1% vs. 80%, 95% CI 0.09-1.77, P = 0.2)., Conclusion: The composite CT/PET radiomics model was highly predictive of pCR following NACRT. Validation in larger data sets is warranted to determine whether the model can predict clinical outcomes., (© 2020 The Royal Australian and New Zealand College of Radiologists.)

Purpose: To retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 ( 90 Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease., Materials and Methods: This retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months., Results: Median overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5-87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0-86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0-84.1 months). Grade 1-2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1-2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment., Conclusions: TARE with 90 Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Background: US health care is increasingly defined by over expenditure and inefficiency. Optimizing patient follow-up is critical, especially in cancers treated with high control rates. To optimize patient care, this study assessed time to disease recurrence or toxicity in patients with anal carcinoma., Materials and Methods: In total, 140 patients with biopsy-proven, nonmetastatic anal carcinoma, treated with chemoradiation utilizing intensity-modulated radiation therapy, were identified from our institutional database. This retrospective study evaluated local recurrence (LR), distant metastasis (DM), overall survival (OS), and late ≥grade 3 toxicity (LG3T). Patients were followed posttreatment every 3 months for 2 years, every 6 months in years 3 to 5, then yearly thereafter per NCCN recommendations., Results: The median age and follow-up was 58 years and 27 months, respectively. Patients were categorized into high (n=61; 44%) and low (n=77; 55%) risk groups based on stage. The 2-year LC, DMFS, and OS were 93%, 94%, and 89% and 5-year LC, DMFS, OS were 92%, 87%, and 85%, respectively. Overall, there were 29 events (9 LR, 11 DM, and 9 LG3T), with 62% of events occurring within year 1 and 79% within 2 years. Stratified by event type, at 2 years 89% of LR, 64% of DM, and 89% LG3T were identified. At the remaining follow-up points, the event incidence rate was 1.3%., Conclusion: With the majority of recurrences/toxicities occurring within the first 2 years, a reduction in follow-up during years 3 to 5 may provide adequate surveillance. Revisions of the current recommendations could maximize resources while improving patient quality of life.

Objectives: The role of local disease control in the oligometastatic setting is evolving. Stereotactic body radiation therapy (SBRT) is a noninvasive treatment option for oligometastases; however, using ablative radiation doses for adrenal metastases raises concern given the proximity to radiosensitive organs. Novel treatment techniques may allow for selective dose escalation to improve local control (LC) while minimizing dose to nearby critical structures., Materials and Methods: We retrospectively reviewed patients with adrenal oligometastases treated with SBRT from 2013 to 2018. LC, disease-free survival, and overall survival were estimated using Kaplan-Meier methods. Predictors of outcomes were evaluated by log-rank and Cox proportional hazard analyses., Results: We identified 45 adrenal oligometastases in 41 patients treated with SBRT. The median age at treatment was 67 years (range, 40 to 80). The most common primary histologies were non-small cell lung cancer (51%), renal cell carcinoma (24%), and small cell lung cancer (10%). The median prescription dose was 50 Gy (range, 25 to 60 Gy), with 30 (67%) lesions receiving ≥50 Gy and 14 (31%) receiving 60 Gy. In total, 26 (58%) lesions received a simultaneous-integrated boost. Of the 42 treatment simulations, 26 (62%) were supine, 5 (12%) prone, and 11 (26%) in the left lateral decubitus position. At a median follow-up of 10.5 months, there were 3 local failures with a 12-month LC rate of 96%., Conclusions: Adrenal SBRT for oligometastatic disease is a feasible, noninvasive option with excellent LC and minimal toxicity. Lesions in close proximity to radiosensitive organs may benefit from dynamic patient positioning and selective simultaneous-integrated boost techniques to allow for dose escalation, while also limiting toxicity risks.

Background & Aims: Fiducial markers are inert radiopaque gold or carbon markers implanted in or near pancreatic tumor to demarcate areas for image-guided radiation therapy. Endoscopic ultrasound (EUS) pre-loaded fiducial needles (PLNs) have been developed to circumvent technical issues associated with traditional back-loaded fiducials (BLNs). We performed a randomized controlled trial to compare procedure times in patients with pancreatic adenocarcinoma undergoing EUS-guided placement of BLNs vs PLNs., Methods: In a prospective study, 44 patients with pancreatic adenocarcinoma referred for fiducial marker placement at 2 tertiary care centers were assigned to groups that received PLNs (n = 22) or BLNs (n = 22); each group had the same proportion of patients with tumors of different locations (head or neck vs body or tail).The procedure was standardized among all endoscopists and placement of a minimum of 3 markers inside the tumor was defined as technical success. The times for procedure and fiducial placement were recorded, total number of fiducial markers used documented, and grade of procedure difficulty ranked by passing the needle or deploying the fiducials. Other recorded variables included tumor characteristics, fluoroscopy use, and the number of fiducials clearly seen by EUS and fluoroscopy. The primary aim was to compare the duration of EUS-guided fiducial insertion of BLNs vs PLNs., Results: The median placement time was significantly shorter in the PLN group (9 min) than the BLN group (16 min) (P < .001). However, the 44% reduction in time did not reach pre-specified levels (≥60%). Similar results were found after stratifying by tumor location. Deployment of BLNs was easier than deployment of PLNs (P = .03). There was no significant difference between groups in technical success, number of fiducials placed, EUS or fluoroscopic visualization, or adverse events. During simulation computed tomography and image-guided radiation therapy, there was no difference between groups in visualization of fiducials, migration rate, or accuracy of placement., Conclusions: In a randomized controlled trial of 44 patients with pancreatic adenocarcinoma, we found EUS-guided placement of PLNs to require less time and produce similar results compared with BLNs. Further refinements in PLN delivery system are needed to increase the ease of deployment. Clinicaltrials.gov no: NCT02332863., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated., Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method., Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX., Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The optimal dose of neoadjuvant radiation for locally advanced, resectable esophageal cancer remains controversial in the absence of randomized clinical trials, with conventional practice favoring the use of 50.4 vs. 41.4 Gy., Methods: Retrospective analysis of adults with non-metastatic esophageal cancer in the National Cancer Database (2004-2015) treated with neoadjuvant chemoradiotherapy. Outcomes were compared between patients undergoing 41.4, 45, or 50.4 Gy. Primary outcome was overall survival. Secondary outcomes included T and N downstaging and perioperative mortality adjusted for demographics, clinicopathologic factors, and facility volume., Results: Eight thousand eight hundred eighty-one patients were included: 439 (4.9%) received low-dose (41.4 Gy), 2194 (24.7%) received moderate-dose (45 Gy), and 6248 (70.4%) received high-dose (50.4 Gy) neoadjuvant radiation. Compared to high-dose, low-dose radiation was associated with superior median overall survival (52.6 vs. 40.7 months) and 5-year survival (48.3% vs. 40.2%), and lower unadjusted 90-day mortality (2.3% vs. 6.5%, all p ≤ 0.01). Multivariable proportional hazards models confirmed an increased hazard of death associated with high-dose radiation therapy (HR = 1.38, 95% CI 1.10-1.72, p = 0.005). There was no significant difference in T and/or N downstaging between low-dose vs. high-dose therapy (p > 0.1 for both). Patients receiving 45 Gy exhibited the lowest median overall survival (37.2 months) and 5-year survival (38.7%, log-rank p = 0.04)., Conclusions: Compared to 50.4 Gy, 41.4 Gy is associated with reduced perioperative mortality and superior overall survival with similar downstaging in locally advanced esophageal cancer. In the absence of randomized clinical data, our findings support the use of 41.4 Gy in patients with chemoradiation followed by esophagectomy. Prospective trials are warranted to further validate these results.

Purpose: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC)., Materials and Methods: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test., Results: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS., Conclusions: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: The 8th edition of the American Joint Committee on Cancer (AJCC) updated the staging system of anal squamous cell cancer (ASCC) by subdividing stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG 98-11 trial. We aimed to validate this new subclassification utilizing two nationally representative databases., Materials: The National Cancer Database (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER) database [1988-2013] were queried to identify patients with stage II ASCC., Results: A total of 6651 and 2579 stage IIA (2-5 cm) and 1777 and 641 stage IIB (> 5 cm) patients were identified in the NCDB and SEER databases, respectively. Compared with stage IIB patients, stage IIA patients within the NCDB were more often females with fewer comorbidities. No significant differences were observed between age, race, receipt of chemotherapy and radiation, and mean radiation dose. Demographic, clinical, and pathologic characteristics were comparable between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p < 0.001). After adjustment for available demographic and clinical confounders, stage IIB was significantly associated with worse survival in both cohorts (hazard ratio 1.58 and 2.01, both p < 0.001)., Conclusion: This study validates the new AJCC subclassification of stage II anal cancer into A and B based on size (2-5 cm vs. > 5 cm) in the general ASCC population. AJCC stage IIB patients represent a higher risk category that should be targeted with more aggressive/novel therapies.

Background: Radioembolization induces liver hypertrophy, although the extent and rate of hypertrophy are unknown. Our goal was to examine the kinetics of contralateral liver hypertrophy after transarterial radioembolization., Methods: A retrospective study (2010-2014) of treatment-naïve patients with primary/secondary liver malignancies undergoing right lobe radioembolization was performed. Computed tomography volumetry was performed before and 1, 3, and 6 months after radioembolization. Outcomes of interest were left lobe (standardized future liver remnant) degree of hypertrophy, kinetic growth rate, and ability to reach goal standardized future liver remnant ≥40%. Medians were compared with the Kruskall-Wallis test. Time to event analysis was used to estimate time to reach goal standardized future liver remnant., Results: In the study, 25 patients were included. At 1, 3, and 6 months, median degree of hypertrophy was 4%, 8%, and 12% (P < .001), degree of hypertrophy relative to baseline future liver remnants was 11%, 17%, and 31% (P = .015), and kinetic growth rate was 0.8%, 0.5%, and 0.4%/week (P = .002). In patients with baseline standardized future liver remnant <40% (N= 16), median time to reach standardized future liver remnant ≥40% was 7.3 months, with 75% accomplishing standardized future liver remnant ≥40% at 8.2 months., Conclusion: Radioembolization induces hypertrophy of the contralateral lobe to a similar extent as existing methods, although at a lower rate. The role of radioembolization as a dual therapy (neoadjuvant and hypetrophy-inducing) for selected patients needs to be studied. (Surgery 2017;160:XXX-XXX.)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Despite neoadjuvant chemoradiation (nCRT) followed by esophagectomy for locally advanced esophageal cancer, locoregional recurrence (LRR) is common and factors associated with LRR have not been clearly identified., Methods: Patients were identified from a single institution, prospectively maintained database (1996-2013). Patterns of recurrence were described and associated factors of LRR were analyzed using competing risks regression models., Results: Of the 456 patients treated with nCRT and surgery, 167 patients developed recurrence. Locoregional and distant recurrences were observed in 69 (15.1%) and 140 (30.9%) patients, respectively. Time to recurrence (13.6 vs 10.4 months, P = 0.20) and median overall survival (29.3 vs 19.1 months, P = 0.12) were no different among the 27 patients (6%) who developed a solitary LRR compared to patients who developed distant recurrence. Univariable analysis identified lymphovascular invasion (HR 1.46, P = 0.07), lymph node ratio >0.5 (HR 2.16, P = 0.02), positive margin (HR 1.95, P = 0.05), lack of response to neoadjuvant therapy (HR 1.99, P < 0.01), clinical T stage (HR 2.62, P < 0.01) and final T3/4 stage (HR 2.06, P < 0.01) as factors significantly associated with LRR. Clinical T stage and response to neoadjuvant treatment were independently associated with LRR on multivariable analysis., Conclusions: Although aggressive tumor biology plays a significant role in LRR, optimizing neoadjuvant treatments to obtain a complete pathologic response may lead to improved locoregional control., (© 2017 Wiley Periodicals, Inc.)

Purpose: Our goal was to determine whether tumour radiosensitivity is associated with activation of the immune system across all tumour types as measured by two gene expression signatures (GESs)., Methods: We identified 10,240 genomically profiled distinct solid primary tumours with gene expression analysis available from an institutional de-identified database. Two separate GESs were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity) and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumour samples and, in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterised, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumour radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation., Results: Using an RSI cut-point of ≤0.3745, RSI-low tumours (n = 4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [-0.136, 1.095]) compared with RSI-high tumours (-0.17 [-0.82, 0.42]; p < 0.001) across all tumour samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early-stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p = 0.02), with RSI (hazard ratio [HR] 0.63 [95% confidence interval 0.36, 1.09]) and 12-CK (HR 0.66 [0.41, 1.04]) each providing comparable contributions., Conclusions: Tumour radiosensitivity is associated with immune activation as measured by the two GESs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate safety and efficacy of transarterial hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC)., Materials and Methods: From July 2010 to December 2014, 18 patients with liver-dominant metastatic RCC were treated with yttrium-90 glass microsphere radioembolization. Retrospective review of medical records and imaging studies was performed to evaluate toxicities, treatment response, and overall survival. The median follow-up period from radioembolization treatment was 17.8 months (range, 3-54.4 months)., Results: Median overall survival from RCC diagnosis was 64 months (95% confidence interval [CI], 0-144.1 months), from diagnosis of liver metastasis was 29 months (95% CI, 7.2-50.8 months), and from radioembolization treatment was 22.8 months (95% CI, 13.2-32.3 months). After treatment, 10 patients reported grade 1 clinical toxicities, and 8 patients had grade 1 or 2 biochemical toxicities. The best radiographic responses of 17 patients who underwent contrast-enhanced cross-sectional imaging showed complete response in 16 patients and partial response in 1 patient evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The last available imaging of these 17 patients demonstrated complete response in 14 patients, partial response in 1 patient, and progression of disease in 2 patients. Images of a patient who underwent noncontrast CT showed stable disease as best response and stable disease on the last available imaging evaluated by RECIST., Conclusions: Radioembolization is safe and effective and led to improved hepatic disease control and overall survival in patients with liver-dominant metastatic RCC., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Flattening filter-free (FFF) beams produce higher dose rates. Combined with compensator-based intensity modulated radiotherapy (IMRT) techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or flattened beam compensator-based IMRT. This 'snap shot' IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, superficial doses in FFF beam treatment are usually higher than those from flattened beams. Due to no flattening filter, thus less photon scattering, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introduce beam hardening effects and scattering such that the superficial dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? This study applied Monte Carlo techniques to investigate the superficial and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides varying thicknesses of brass slabs to simulate varying thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC-defined FFF and flattened beams with varying apertures. After normalization to the maximum dose, D max , the superficial and peripheral doses were compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. The superficial dose at the central 0.5 mm depth was about 1% (of D max ) lower in the compensator-based 6 MV FFF (6FFF) IMRT compared to the MLC-based 6FFF IMRT, and about 8% higher than the flattened 6 MV MLC-based IMRT dose. At 8 cm off-axis at depth of central maximum dose, d max , the peripheral dose between the 6FFF and flattened 6 MV MLC demonstrated similar doses, while the compensator dose was about 1% (of D max ) higher. Compensators reduce the superficial doses slightly compared to open FFF beams, but increases the peripheral doses due to scatter in the compensator., (© 2016 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose/objectives: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology., Methods and Materials: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation., Results: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively., Conclusions: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Mucosal melanoma of the head and neck is a rare disease with limited data available on outcomes; therefore, we reviewed our institutional experience., Methods: An institutional database was queried and 38 patients with head and neck mucosal melanoma were identified. Charts were abstracted and local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated., Results: Most patients had T4 disease (86%), although nodes were positive in 11%. En bloc or endoscopic resection was performed on 93%. Adjuvant or definitive radiotherapy to a median dose of 60 Gy was utilized in 90%. Chemotherapy was given in 21%, and 16% received interferon. Three-year LC, PFS and OS were 90%, 48% and 59%, respectively. Median OS was 4.6 years. Site of first failure was distant in 52% of cases., Conclusion: With aggressive therapy median OS was 4.6 years in this cohort. Distant recurrence remains the primary mode of failure. It may be reasonable to include mucosal melanoma patients in trials of systemic agents along with high-risk cutaneous melanomas., (© 2015 The Royal Australian and New Zealand College of Radiologists.)

Background: While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described., Methods: This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score., Results: We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS., Conclusions: These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.

Background: Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management., Methods: An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed., Results: The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years., Conclusions: HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter., (© 2015 American Cancer Society.)

Introduction: Anal cancer is a relatively rare malignancy which comprises about 2.5% of all digestive system malignancies in the United States. The majority of cases are squamous cell carcinoma which is closely related to human papilloma virus (HPV) infection. Despite high cure rates with chemoradiation alone, 10 - 20% of patients do develop metastatic disease with little data to guide their treatment., Areas Covered: In this review article, the authors describe the current standard treatment of early and advanced squamous cell carcinoma of the anal canal based on published data. The authors then describe the new approaches to the disease, focusing on new radio sensitizing agents, systemic targeted drugs and immunotherapy., Expert Opinion: The authors believe that current standard treatment options for squamous cell carcinoma of the anal canal are well defined with acceptable results. However the major challenge in the treatment of anal cancer is the lack of randomized or even large single arm Phase II trials due to rarity of the disease, especially in the metastatic disease. But we are slowly making progress. Currently, the most promising areas of research are immunotherapy, targeted therapy and even HPV prevention. We are eagerly anticipating the results of these studies in order to expand the treatment armamentarium.

Background: The prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) to neoadjuvant chemoradiation (nCRT) for esophageal cancer is unknown., Methods: ypT0N+ responders were identified from a single institution database of esophageal cancer patients undergoing esophagectomy and were compared to patients without locoregional disease (ypT0N0) and to non-complete responders (ypT+)., Results: Out of 487 patients, 196 ypT0N0 and 14 ypT0N+ patients were identified. Pre-treatment stage was similar between ypT0N0 and ypT0N+ patients: 66% versus 73% of patients had uT3 disease (P = 0.50) and 76% versus 55% had nodal involvement (P = 0.49), respectively. Locoregional recurrence (43%) was more common in ypT0N+ patients. Median overall survival (OS) was worse in ypT0N+ patients (14.8 months) compared to ypT0N0 patients (92.2 months) and ypT+ patients (38.0 months, P < 0.001). Median OS of ypT0N+ patients was similar to ypT+ stage II (29.6 months, P = 0.84) and stage III (27.5 months, P = 0.95) disease. No difference in median OS existed in patients with residual nodal disease (n = 163) based on local response (14.8 months in ypT0N+ and 22.5 months in ypT+N+ patients, P = 0.55)., Conclusions: Residual nodal disease in esophageal cancer patients with complete response in the primary tumor following nCRT portends a poor prognosis and behaves similar to pathologic stage II/III disease., (© 2015 Wiley Periodicals, Inc.)

Routine treatment of clinically uninvolved internal mammary nodes in breast cancer patients requiring post-mastectomy radiation therapy is controversial. The purpose of this study was to measure the incidental radiation dose to the internal mammary lymph nodes not included in the planning target volume (PTV) in women with breast cancer receiving post-mastectomy radiation therapy. This retrospective protocol utilized CT-based 3D conformal treatment plans. Fifty consecutive patients were included in the analysis: 25 left breast and 25 right breast patients. 3D conformal treatment plans chest wall tangent fields and matched supraclavicular were used. All plans were prescribed to a total dose of 50 Gy in 25 fractions to the chest wall and 46 Gy in 23 fractions to the supraclavicular field. The internal mammary node chain was intentionally not included in the target volume. For purposes of this study, internal mammary vessels were contoured following the Radiation Therapy Oncologist Group atlas with a 7-mm PTV expansion, utilizing original CT simulation images. The internal mammary nodes were contoured in between the first 3 and first 5 intercostal spaces for comparison. Percent volume of internal mammary node PTV receiving 95 % of the prescribed dose (47.5 Gy) with 7-mm expansion and first 5 intercostal spaces for all patients was 25.2 % (range 0.04-97.6 %, standard deviation (SD) 23.5). The mean internal mammary node dose for all patients was 24.98 Gy (range 3.54-55.93 Gy, SD 16). Results of this study suggest the incidental dose to the internal mammary nodes does not achieve clinically significant therapeutic levels in post-mastectomy breast cancer patients treated with standard 3D conformal radiation therapy chest wall irradiation. If risk factors for microscopic involvement are present, internal mammary nodes must be specifically included in target volumes in order to be adequately treated.

Objective: To determine if age affects outcome in patients with resected pancreatic head cancer., Materials and Methods: An IRB-approved pancreatic cancer database was queried for patients with upfront resected pancreatic head cancer treated at our institution between 2000 and 2012. Overall survival (OS) curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis was performed using the Cox proportional hazard model., Results: We identified 193 patients. Patients ≥70 years were less likely to receive adjuvant treatment (p = 0.002); however there were no other significant differences between age groups. There was a trend towards increased pancreatic leaks in the elderly group (p = 0.06), but no difference in post-operative complications or mortality. There was no difference in overall survival based on age. Median and 5-year OS were 23 months and 26.7% in patients <70 years, 23.4 months and 23% in those 70-75, 16.1 months and 0% in those 76-80, and 18.7 months and 15.4% in those >80 years (p = 0.62). On univariate analysis, there was increased OS in patients with lower T stage, N0 status, post-operative CA19-9 level <90, and use of chemoradiotherapy (p< 0.05). Multivariate analysis revealed that lower tumor stage, N0, post-operative CA19-9 level <90, and use of any adjuvant therapy predicted decreased mortality (p < 0.05). Age, gender, tumor site, tumor grade, and positive margins were not prognostic on multivariate analysis., Conclusions: There is no difference in outcomes when comparing elderly patients with resected pancreatic cancer to those patients <70 years of age., (Copyright © 2014 Elsevier Inc. All rights reserved.)