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Although fistulization is a well-studied late toxic effect of radiation therapy (RT), anorectal cancers (ARCs) can present with malignant fistulae (MF) and negatively affect quality of life. The effect of RT, often combined with concurrent chemotherapy, on MF needs systematic analysis, because practitioners are concerned that RT may exacerbate MF. We reviewed our institutional series evaluating the hypothesis that RT worsens MF. A single-institutional retrospective analysis of patients with ARC receiving RT from 2006 to 2019 was performed. These patients were screened for MF. Any MF resected before RT and RT not directed at the site of MF were excluded. Effects were assessed by review of available follow-up documentation and imaging. A total of 639 patients with ARC were reviewed, and 47 had MF (7.4%). With a median follow-up of 22 months (range, 2-133 months), RT improved MF in 17 of 29 evaluable patients (59%), with 9 of 29 (31.0%) having resolution. The median time to improvement was 50 days (range, 25-117 days); the median duration of improvement was 161 days (range, 0-1941 days). Malignant fistulae persisted in 12 of 29 patients (41%), with persistent local disease in all cases; in 2 cases, MF worsened concomitant with local progression. In all, 7.4% of patients with ARC presented with MF. Radiation therapy led to improvement or resolution in more than half of evaluable patients. Persistence or worsening of MF was only observed in patients with refractory or progressive local disease. Based on our findings, MF is not a contraindication to RT and may be considered as an independent indication for palliative RT. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) exhibits distinct molecular subtypes: classical/progenitor and basal-like/squamous. Our study aimed to identify genes contributing to the development of the basal-like/squamous subtype, known for its aggressiveness. Transcriptome analyses revealed consistent upregulation of SERPINB3 in basal-like/squamous PDAC, correlating with reduced patient survival. SERPINB3 transgene expression in PDAC cells enhanced in vitro invasion and promoted lung metastasis in a mouse PDAC xenograft model. Metabolome analyses unveiled a metabolic signature linked to both SERPINB3 and the basal-like/squamous subtype, characterized by heightened carnitine/acylcarnitine and amino acid metabolism, associated with poor prognosis in patients with PDAC and elevated cellular invasiveness. Further analysis uncovered that SERPINB3 inhibited the cysteine protease calpain, a key enzyme in the MYC degradation pathway, and drove basal-like/squamous subtype and associated metabolic reprogramming through MYC activation. Our findings indicate that the SERPINB3-MYC axis induces the basal-like/squamous subtype, proposing SERPINB3 as a potential diagnostic and therapeutic target for this variant. [Display omitted] • SERPINB3 is linked to poor patient survival in pancreatic ductal adenocarcinoma (PDAC) • SERPINB3 enhances tumor metastasis in an orthotopic preclinical PDAC mouse model • SERPINB3-MYC axis induces the aggressive basal-like/squamous molecular subtype • SERPINB3-MYC axis increases carnitine/acylcarnitine and amino acid metabolism Ohara et al. use a comprehensive transcriptome and metabolome analysis to show that the SERPINB3-MYC axis drives the aggressive basal-like/squamous molecular subtype in pancreatic ductal adenocarcinoma. This axis also promotes subtype-associated metabolic alterations, including heightened carnitine/acylcarnitine and amino acid metabolism, correlating with poorer patient prognosis. [ABSTRACT FROM AUTHOR]

Cardiac fibromas (CF) have a reported incidence of 0.03-0.32% and have an excellent prognosis. Most cardiac tumors are found incidentally, and symptoms are related to location and size. Most CF are amenable to surgical removal, but some are deemed unresectable due to their size and/or invasion of vital cardiac structures that warrant heart transplants. 66-year-old male with a history of prior cardiac fibroma resection at age 13, followed by dual-chamber pacemaker insertion due to complete heart block and recent ventricular tachycardia ablation. He came to our facility for a second opinion regarding heart transplants because he was previously considered high-risk by another facility. Echo showed an EF of 55%, with CF noted on the anterior wall. Heart CT reported a LV anterior wall mass measuring 6 × 8.5 × 8.9 cm, markedly displacing the LAD and first diagonal with a non-hypermetabolic mass on PET scan. He was presented during our multidisciplinary team rounds; the decision was to proceed with biopsy of the left ventricular cardiac mass showing CF with abundant collagen in the stroma separating the tumor cells (Figure 1A), and the CF is composed of slender spindle cells admixed with undulant and wavy collagenized stroma. No nuclear pleomorphism or mitotic activity is present (Figure 1B). Postoperatively, the patient developed incessant VT requiring amiodarone and lidocaine. EP was consulted, and due to prior VT ablation and limited options, the patient was listed for an orthotopic heart transplant (OHT). He underwent successful OHT without complications. The explanted heart has a whorled, well-circumscribed, tan appearance mass measuring 14 × 10 × 9 cm involving the LV, the interventricular septum, and epicardium (Figure 2). Cardiac fibromas are connective tissue tumors that originate from fibroblasts, typically grossly well demarcated. CF are considered benign tumors, but they are well known to be the most common arrhythmogenic tumors than other cardiac tumors; It is essential that cardiologists be aware of CF presentation, diagnosis and treatment. Careful selection of potential candidates based on patient characteristics, type of tumor, and life-threatening complications for OHT by a multidisciplinary team is imperative in such complex cases. We report a case that required orthotopic heart transplantation due to incessant ventricular tachycardia secondary to recurrent unresectable fibroma. [ABSTRACT FROM AUTHOR]

Objectives: Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum. Morbidity and mortality are almost invariably owing to locoregional progression. Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome. Methods: Between January 1992 and 2010, 211 patients with MPM treated at 3 major referral centers with operative CRS and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were analyzed. Results: The median, actuarial overall survival was 38.4 months; the actuarial 5- and 10-year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were younger age <60 years (P < .01), complete or near complete (R0–1) versus incomplete (R2–3) resection (P < .02), low versus high histologic grade (P < .01), and the use of cisplatin versus mitomycin-C during HIPEC (P < .01). There was a trend toward female sex and improved survival (male hazard ratio, 1.46; 95% confidence interval, 0.89–2.41; P = .13). Conclusion: Operative CRS with HIPEC is associated with prolonged survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM. [Copyright &y& Elsevier]

Background: TNFeradeBiologic (AdGVEGR.TNF.11D) is a replication-deficient adenoviral vector that expresses tumor necrosis factor-α (TNF-α) under the control of the Egr-1 promoter, which is inducible by chemotherapy and radiation. Objective: This study was conducted to determine the maximal tolerated dose of TNFeradeBiologic with standard chemoradiotherapy and preliminary activity and safety of the combination in the treatment of locally advanced pancreatic cancer (LAPC). Design: TNFeradeBiologic was injected into locally advanced pancreatic carcinomas by using EUS or percutaneous administration once a week for 5 weeks together with 50.4 Gy radiation and 5-fluorouracil (5-FU) 200 mg/m2 daily over 5.5 weeks. Dose levels from 4 × 109 to 1 × 1012 particle units (PU) were studied. Setting: Multicentered, academic institutions. Patients: Fifty patients with LAPC were treated. Interventions: Doses of TNFerade Biologic were administered to patients. Main Outcome Measurements: Toleration of TNFerade Biologic was measured through toxicity and tumor response, by using the criteria of the Response Evaluation Criteria in Solid Tumors and the World Health Organization, and was reviewed by a central radiology facility. Overall survival and progression-free survival were also measured. Results: Dose-limiting toxicities of pancreatitis and cholangitis were observed in 3 patients at the 1 × 1012 PU dose, making 4 × 1011 PU the maximum tolerated dose. One complete response, 3 partial responses, and 12 patients with stable disease were noted. Seven patients eventually went to surgery, 6 had clear margins, and 3 survived >24 months. Limitations: This is a Phase1/2 non-randomized study. Conclusions: Intratumoral delivery of TNFerade Biologic by EUS with fine-needle viral injection or percutaneously, combined with chemoradiation, shows promise in the treatment of LAPC. There appeared to be better clinical outcome at the maximal tolerated dose than at lower doses. The dose of 4 ×1011 PU TNFerade Biologic was generally well tolerated, with encouraging indications of activity, and will be tested in the randomized phase of this study. Delivery of TNFerade Biologic did not interfere with subsequent surgical resection. [Copyright &y& Elsevier]

Purpose: To determine the maximum tolerated dose of upper abdominal low-dose fractionated radiotherapy (<1.0 Gy per fraction) given in combination with, and as a chemopotentiator for, gemcitabine. Methods and Materials: Gemcitabine was given at 1,250 mg/m2 at 10 mg/m2/min on Days 1 and 8 of a 3-week cycle. Low-dose fractionated radiotherapy was tested at two dose levels: 60 cGy per fraction and 70 cGy per fraction. Radiotherapy was given b.i.d. on Days 1, 2, 8, and 9. Four cycles were planned. Results: Twenty-seven patients have been put on study. Ten patients have been entered in Phase I: 6 with metastatic/recurrent pancreatic carcinoma and 4 with unresectable pancreatic/small bowel carcinoma. Two of four patients at Dose Level 2 experienced dose-limiting toxicity. The overall radiographic response was 30%, and median survival was 11 months (range, 4–37 months). Conclusion: Low-dose fractionated radiotherapy to the upper abdomen is well tolerated at 60 cGy per fraction when combined with gemcitabine. Phase II evaluation is ongoing. [Copyright &y& Elsevier]

: BackgroundUnilateral or bilateral division of the parasympathetic nerves during resection of rectal cancer may result in sexual erectile dysfunction. The purposes of this project were twofold: to determine the ability to demonstrate penile tumescence in response to parasympathetic nerve stimulation after rectal cancer resection and to correlate the nerve stimulation response with clinical sexual function 6 months after operation.: Study designIn 21 consecutive male patients with normal erectile function undergoing total mesorectal excision, cavernous nerve identification and integrity before and after pelvic dissection were assessed intraoperatively, both visually by an experienced surgeon and by using the CaverMap nerve stimulator. The minimal effective current necessary to produce a 2% increase in penile tumescence was recorded for both the left- and right-sided nerves, primarily the largest nerve trunk, S3. Postclearance stimulation data were then correlated with sexual function outcomes, specifically erection and orgasm at 6 months after surgery.: ResultsThe operating surgeon’s visual assessment of the pelvic autonomic nerve’s integrity after pelvic dissection was deemed intact in 20 of the 21 patients (95.2%). Of the 20 patients who were evaluated with CaverMap after completion of total mesorectal excision, 17 (85%) had tumescence response after nerve stimulation on either side, and 3 patients (15%) had unilateral response only. Of the 19 patients evaluated for sexual function 6 months after surgery, 18 (94.7%) had normal function, including the 3 patients with only unilateral nerve stimulation tumescence response.: ConclusionsIntraoperative mapping of the parasympathetic nerve trunks with the CaverMap nerve stimulator may be a valuable aid to less experienced pelvic surgeons and may help in autonomic nerve preservation during total mesorectal excision clearance. [Copyright &y& Elsevier]

Cardiac allograft vasculopathy (CAV) is known as the primary cause of death in the first year after orthotopic heart transplant (OHT). Coronary artery spasm (CAS) in OHT is a rare and under-recognized phenomenon in patients undergoing surveillance. The mechanism of coronary vasospasm in OHT remain largely unknown. The presentation can vary from an incidental finding to severe episodes of symptomatic ventricular arrhythmias, high-degree atrioventricular block, syncope, cardiac arrest, or even myocardial infarction in cases of prolonged ischemia. 65 yo female with history of chronic kidney disease, diabetes mellitus type 2, hypertension, hyperlipidemia, and orthotopic heart transplantation with CMV mismatch in 2016 secondary to apical hypertrophic cardiomyopathy. Prior coronary angiography (CA) done at our institution had shown no evidence of vasculopathy. During one of her follow-up visits in the Clinic, she complained of increasing dyspnea on exertion, prompting urgent referral for CA, as per our surveillance protocols. Prior to the procedure, echocardiography was performed which revealed normal graft function and no valvular abnormalities. She underwent CA which showed a proximal significant diffuse luminal narrowing of the right coronary artery (RCA) (Image 1) and normal left coronary artery anatomy (Image 2). We proceed to repeat CA with intracoronary administration of nitroglycerin (ICN) and measurement of fractional flow reserve (FFR) of RCA (Image 3, 4). Angiography revealed near resolution of the RCA lesion, ultimately suggesting that transient vasospasm had been responsible for the previous angiographic appearance (Image 1). CAS can present in patients with or without vasculopathy. It can produce luminal narrowing and can be difficult to distinguish angiographically from CAV. Misdiagnosis of this entity has led to the incorrect diagnosis of CAV and subsequent unnecessary stenting. ICN use can improve angiographic visualization, and prevent the adverse effects of coronary spasm. In conclusion, CAS is a rare and potential complication post OHT. It is a difficult entity to prognosticate due to scarcity of clinical evidence, as prevalence ranges from 4.9% to 12.1%. Some authors hypothesize that CAS in OHT carries a poor prognosis as it is often an early manifestation of CAV. However, this remains largely hypothetical and further studies are needed to better understand this disease. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiotherapy followed by surgery is the primary treatment option for patients with locally advanced esophageal cancer. This multicenter phase I trial examined intratumoral injection of TNFerade biologic, an adenoviral vector that expresses the human tumor necrosis factor-α gene, with chemoradiotherapy in locally advanced esophageal cancer. Objectives: To assess pathologic complete response (pCR), time to disease progression, progression-free survival, survival, and safety and tolerance in patients treated with preoperative chemoradiation combined with endoscopy or EUS-guided intratumoral injection of TNFerade biologic. Design/Intervention: Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 108 to 4 × 1011 particle units (PU), were given in combination with cisplatin 75 mg/m2 and intravenous 5-fluorouracil 1000 mg/m2/d for 96 hours on days 1 and 29, and concurrent radiation therapy to 45 Gy. Surgery was performed 9 to 15 weeks after treatment. Setting: U.S. multicenter study. Patients: Patients with stage II and III esophageal cancer were enrolled. Main Outcome Measurements: Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival. Results: Twenty-four patients with a median age of 61 years were enrolled; 88% of the patients were men, 21% were stage II, and 79% were stage III. Six (29%) had a pCR, observed among 21 patients (20 who underwent esophagectomy and 1 at autopsy). Dose-limiting toxicities were not observed. The most frequent potentially related adverse events were fatigue (54%), fever (38%), nausea (29%), vomiting (21%), esophagitis (21%), and chills (21%). At the top dose of 4 × 1011 PU, thromboembolic events developed in 5 of 8 patients. The median OS was 47.8 months. The 3- and 5-year OS rates and disease-free survival rates were 54% and 41% and 38% and 38%, respectively. Limitations: We included primarily adenocarcinoma. Conclusions: Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 1010 PU and is associated with long survival. This regimen warrants additional studies. (Clinical trial registration number: NCT00051480.) [Copyright &y& Elsevier]

ABSTRACT: Objectives: To examine cumulative survival and Medicaid-paid expenses associated with multiple courses of transarterial chemoembolization (TACE) as primary treatment for hepatocellular carcinoma (HCC). Methods: Medicare enrollees diagnosed with primary HCC from 2000 to 2007, ever treated with TACE, but not transplant/resection, followed through 2009 by using the Surveillance, Epidemiology and End-Results Program and linked Medicare databases. Cumulative all-cause/HCC-related survival was estimated by using multivariate Cox proportional hazards models stratified by the total number of TACE treatments. Multivariate weighted Cox regressions estimated the average risk of mortality faced with nonproportional hazards. Lin’s inverse probability-weighted least squares regression method estimated cumulative Medicare expenditures adjusted for censoring and covariates. Results: Of 1228 patients, 34% were stage 1, 16% stage 2, 19% stage 3, 6% stage 4, and 26% unstaged. About 44% were aged 65 to 75 years, 69% were men, and 72% were Caucasian. Over half (57%) of the patients received one course, 24% two, 11% three, and 8% four courses of TACE. One-course patients incurred an average $74,788 (95% confidence interval [CI] $71,890–$77,686), two-course patients $101,126 (95% CI $94,395–$107,856), three-course patients $111,776 (95% CI $101,931–$121,621), and four-plus-course patients $148,878 (95% CI $136,346–$161,409). One-course patients lived (all-cause) an average 1.86 (95% CI 1.82–1.90), two-course patients 2.09 (95% CI 2.05–2.13), three-course patients 2.81 (95% CI 2.66–2.97), and four-plus-course patients 3.06 (95% CI 2.95–3.18) years after diagnosis. Average risk of all-cause mortality was not significantly different between one/two courses or three/four-plus courses. Conclusions: Cumulative Medicare expenditures nearly doubled from one-course to four-plus-course patients. On average, four-plus-course patients lived over one more year than did one-course patients. Physician/patient decisions should be balanced with consideration of efficient use of limited resources, but payer’s intervention in physician discretion may not be important in this setting. [Copyright &y& Elsevier]

Abstract: Tumour antigen targeted antibodies (mAbs) can induce natural killer (NK) cells to kill tumours through antibody dependent cellular cytotoxicity (ADCC) upon engagement of NK cell expressed FcγRIIIa. FcγRIIIa polymorphisms partially dictate the potency of the ADCC response. The high affinity FcγRIIIa-158-valine (V) polymorphism is associated with more potent ADCC response than the low affinity FcγRIIIa-158-phenylalanine (F) polymorphism. Because approximately 45% of patients are homozygous for the FcγRIIIa-158-F polymorphism (FF genotype), their ability to mount ADCC is impaired. We investigated whether a novel mAb capable of binding multiple antigen specific targets and engaging multiple low affinity FcγRIIIa receptors could further enhance ADCC against colon cancer in vitro. Specifically, we generated a novel anti-epidermal growth factor receptor (EGFR) antibody (termed a stradobody™) consisting of an unmodified Fab sequence and two Immunoglobulin G, subclass 1 (IgG1) Fc domains separated by an isoleucine zipper domain and the 12 amino-acid IgG2 hinge. The stradobody™ framework induced multimerisation and was associated with increased binding to the EGFR and FcγRIIIa. From a functional perspective, when compared to an unmodified anti-EGFR mAb with a sequence identical to cetuximab (a commercially available anti-EGFR mAb), stradobodies™ significantly enhanced ADCC. These effects were observed using both KRAS wild type HT29 and KRAS mutant SW480 colon cancer cells as targets, and by NK cells obtained from healthy donors and a cohort of patients with colon cancer. These data suggest that high avidity cross-linking of multiple tumour surface antigens and multiple NK cell associated FcγRIIIa molecules can enhance ADCC and partially overcome impaired ADCC by FF genotype individuals in vitro. [Copyright &y& Elsevier]

Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m2 per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m2 per day, Monday to Friday, plus irinotecan, 50 mg/m2 once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival. [ABSTRACT FROM AUTHOR]

Purpose: Intensity-modulated radiotherapy (IMRT) is increasingly incorporated into therapy for pancreatic cancer. A concern regarding this technique is the potential for geographic miss and decreased local control. We analyzed patterns of first failure among patients treated with IMRT for resected pancreatic cancer. Methods and Materials: Seventy-one patients who underwent resection and adjuvant chemoradiation for pancreas cancer are included in this report. IMRT was used for all to a median dose of 50.4 Gy. Concurrent chemotherapy was 5-FU–based in 72% of patients and gemcitabine-based in 28%. Results: At median follow-up of 24 months, 49/71 patients (69%) had failed. The predominant failure pattern was distant metastases in 35/71 patients (49%). The most common site of metastases was the liver. Fourteen patients (19%) developed locoregional failure in the tumor bed alone in 5 patients, regional nodes in 4 patients, and concurrently with metastases in 5 patients. Median overall survival (OS) was 25 months. On univariate analysis, nodal status, margin status, postoperative CA 19-9 level, and weight loss during treatment were predictive for OS. On multivariate analysis, higher postoperative CA19-9 levels predicted for worse OS on a continuous basis (p < 0.01). A trend to worse OS was seen among patients with more weight loss during therapy (p = 0.06). Patients with positive nodes and positive margins also had significantly worse OS (HR for death 2.8, 95% CI 1.1–7.5; HR for death 2.6, 95% CI 1.1–6.2, respectively). Grade 3-4 nausea and vomiting was seen in 8% of patients. Late complication of small bowel obstruction occurred in 4 (6%) patients. Conclusions: This is the first comprehensive report of patterns of failure among patients treated with adjuvant IMRT for pancreas cancer. IMRT was not associated with an increase in local recurrences in our cohort. These data support the use of IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial. [Copyright &y& Elsevier]

Background: Similarity between the ICU patient data acquired by the APACHE system and the patient outcomes data acquired by the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) suggests that variables in NSQIP data could be effective mortality predictors. We theorized that identifying ACS-NSQIP preoperative data points predictive of patient outcomes would assist in identifying potential complications earlier. Study Design: Between 2006 and 2008 at the University of Maryland Medical Center, we identified 340 surgical ICU patients included in both databases as our study cohort. Median APACHE score calculation permitted division of study subjects into quartiles from which to examine length of stay, mortality variables, and ACS-NSQIP−recorded postoperative occurrences and preoperative risk factors. Outcomes were compared using each database''s percentage of patients who had died. Results: Mortality was positively correlated with APACHE score increases. Initially, the average ICU length of stay increased, then declined. Most common postoperative occurrences were ventilator dependence >48 hours, pneumonia, unplanned intubation, sepsis, and septic shock. It was also noted that preoperative variables, such as American Society of Anesthesiologists classification and serum albumin levels, had an association with a poorer prognosis. Conclusions: APACHE score predictions are consistent with ACS-NSQIP−recorded postoperative outcomes. Higher APACHE scores correlated with increased incidence of postoperative outcomes and were associated with earlier mortality in the most extremely ill. Poorer states of health before surgery also correlated with poor outcomes postoperatively. [Copyright &y& Elsevier]

Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3–4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3–4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3–4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation. [ABSTRACT FROM AUTHOR]