Harnessing the abscopal effect for gastrointestinal malignancies in the era of immunotherapy.

Gastrointestinal (GI) cancers are among the leading causes of cancer-related mortality and have traditionally been treated using a combination of surgical resection and chemoradiotherapy (CRT). While the introduction of immunotherapies over the last decade have dramatically changed the treatment landscape for some GI malignancies, including esophageal, gastric, and colorectal cancer, treatment resistance remains a major unaddressed obstacle for many patients. There has thus been emerging interest in determining the optimal treatment strategy for the delivery of immunotherapy in combination with traditional therapies. In this regard, a growing number of preclinical and clinical studies have suggested that combining radiation therapy (RT) with immunotherapy may work synergistically to improve treatment response through amplification of the abscopal effect. In this review, we discuss the rationale for RT in combination with immunotherapy. We further discuss how this knowledge may lead to a paradigm shift in the application of RT and highlight remaining issues pertaining to the delivery of combination therapy.

Image-Guided Proton Therapy: A Comprehensive Review.

Image guidance for radiation therapy can improve the accuracy of the delivery of radiation, leading to an improved therapeutic ratio. Proton radiation is able to deliver a highly conformal dose to a target due to its advantageous dosimetric properties, including the Bragg peak. Proton therapy established the standard for daily image guidance as a means of minimizing uncertainties associated with proton treatment. With the increasing adoption of the use of proton therapy over time, image guidance systems for this modality have been changing. The unique properties of proton radiation present a number of differences in image guidance from photon therapy. This paper describes CT and MRI-based simulation and methods of daily image guidance. Developments in dose-guided radiation, upright treatment, and FLASH RT are discussed as well.

Perianal basosquamous carcinoma treated with radiation therapy, a case report.

Background: Perianal basal cell carcinoma (BCC) is very rare and estimated to account for 0.08% of all BCC and 0.02% of all anorectal neoplasms. Perianal lesions are more likely to be squamous cell carcinoma (SCC) as BCC usually develops on areas of skin exposed to ultraviolet (UV) light such as the face and arms. Proper diagnosis with the assistance of immunohistochemistry (IHC) stains to distinguish the two entities can help inform the suitable course of treatment. Case Description: Our case is an 82-year-old male with a history of cutaneous BCC on the arms and trunk presenting with a symptomatic perianal lesion. Initial biopsy demonstrated BCC with subsequent IHC studies differentiating from basaloid SCC. Standard treatment includes wide local excision (WLE) but given his poor performance status, radiation only was recommended. He was successfully treated and tolerated 30 Gy in 5 daily fractions. Conclusions: Radiation only is a unique and feasible non-surgical treatment for basosquamous carcinoma of the anus.

A phase II trial of gemcitabine and erlotinib followed by ChemoProton therapy plus capecitabine and oxaliplatin for locally advanced pancreatic cancer.

Background: Epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer. EGFR expression plays a potentially important role in modulation of tumor sensitivity to either chemotherapy or radiotherapy. Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR/HER1. A phase II trial was conducted to explore the efficacy of a regimen utilizing erlotinib and proton therapy. Methods: Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the pancreas were included. Patients received 8-week systemic treatment with gemcitabine 1,000 mg/m2 and erlotinib 100 mg (GE). If there was no evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4 Gy in 28 fractions with concurrent capecitabine 825 mg/m2 (CPT). This was followed with oxaliplatin 130 mg/m2 and capecitabine 1,000 mg/m2 (CapOx) for 4 cycles. The primary study objective was 1-year overall survival (OS). The benchmark was 43% 1-year survival as demonstrated in RTOG/NRG 98-12. The Kaplan-Meier method was used to estimate the one-year OS and the median OS and progression-free survival (PFS). Results: The study enrolled 9 patients ages 47-81 years old (median 62) between January 2013 and March 2016, when the trial was closed due to low patient accrual. The 1-year OS rate was 55.6% (95% CI: 31% to 99%). The median OS was 14.1 months (95% CI: 11.4-NE) and the median PFS was 10.8 months (95% CI: 7.44-NE). A majority of patients completed CPT and GE, but only 33.3% completed the four cycles of CapOx. A third of patients experienced grade 3 toxicities, which were all hepatic along with one patient who also had grade 3 diarrhea. There were no grade 4 or 5 toxicities. Four patients were enrolled with borderline resectable disease, three of which were eligible for pancreaticoduodenectomy after GE and CPT treatment. One of two patients who underwent resection had a negative margin. Conclusions: This regimen for locally advanced pancreatic cancer (LAPC) exceeded the pre-specified benchmark and was safe and well tolerated. Additional investigations utilizing more current systemic treatment regimens with proton therapy are warranted. Trial Registration: ClinicalTrials.gov identifier (NCTNCT01683422).

Proton stereotactic body radiation therapy for liver metastases-results of 5-year experience for 81 hepatic lesions.

BACKGROUND: To report on our institutional experience using Proton stereotactic body radiation therapy (SBRT) for patients with liver metastases. METHODS: All patients with liver metastases treated with Proton SBRT between September 2012 and December 2017 were retrospectively analyzed. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method calculated from the time of completion of Proton SBRT. LC was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: Forty-six patients with 81 lesions were treated with Proton SBRT. The median age was 65.5 years old (range, 33-86 years) and the median follow up was 15 months (range, 1-54 months). The median size of the gross tumor volume (GTV) was 2.5 cm (range, 0.7-8.9 cm). Two or more lesions were treated in 56.5% of patients, with one patient receiving treatment to a total of five lesions. There were 37 lesions treated with a biologically effective dose (BED) ≤60, 9 lesions with a BED of 61-80, 22 lesions with a BED of 81-100, and 13 lesions with a BED >100. The 1-year and 2-year LC for all lesions was 92.5% (95% CI, 82.7% to 96.8%). The grade 1 and grade 2 toxicity rates were 37% and 6.5%, respectively. There were no grade 3 or higher toxicities and no cases of radiation-induced liver disease (RILD). CONCLUSIONS: Proton SBRT for the treatment of liver metastases has promising LC rates with the ability to safely treat multiple liver metastases. Accrual continues for our phase II trial treating liver metastases with Proton SBRT to 60 GyE (Gray equivalent) in 3 fractions.

A phase I trial of Proton stereotactic body radiation therapy for liver metastases.

BACKGROUND: A phase I trial to determine the maximum tolerated dose (MTD) of Proton stereotactic body radiation therapy (SBRT) for liver metastases in anticipation of a subsequent phase II study. METHODS: An institutional IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5 cm, and no metastases location within 2 cm of the GI tract. Dose escalation was conducted with three dose cohorts. The low, intermediate, and high dose cohorts were planned to receive 36, 48, and 60 respectively to the internal target volume (ITV) in 3 fractions. At least 700 mL of normal liver had to receive <15. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort. RESULTS: Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume (GTV) 11.1 mL (range, 2.14-89.3 mL); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the low dose cohort had local recurrence and repeat SBRT was done to previously treated lesions without any toxicities. CONCLUSIONS: Biologically ablative Proton SBRT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II Proton SBRT study of 60 over 3 fractions for liver metastases.

Individualized 4-dimensional computed tomography proton treatment for pancreatic tumors.

BACKGROUND: The goal of this study is to determine whether a phase or reconstruction of a 10-phase 4 dimensional computed tomography (4D CT) scan can be used as the primary planning scan for proton treatment of the pancreas, thus eliminating the need for second a slow CT or free breathing CT. METHODS: Ten patients with pancreatic adenocarcinoma were simulated with 4D CT and a proton treatment plan generated based upon one of three primary planning scans, the T0 phase, T50 phase or average reconstruction. These plans were then exported to each of the remaining phases of the 4D CT and the dose to 95% of the target (D95) calculated. Plans were deemed adequate if the D95 remained at 99% of the prescribed dose or greater. RESULTS: For the ten patients in this study anterior abdominal motion was found to range from 2-27 mm (mean 7.50±6.79 mm). For 9 of 10 patients the anterior abdominal motion was ≤8 mm and all three primary planning scans provided adequate target coverage, resulting in minimum D95 coverage per plan of T0_plan 99.7%, T50_plan 99.3% and AVE_plan 99%. However no plan provided adequate target coverage on the single patient with the largest anterior abdominal motion, 27 mm, and cranio-caudal motion, 20 mm, with minimum D95 values of T0_plan 96.3%, T50_plan 68%, and AVE_plan 68%. CONCLUSIONS: The primary plans tested based up on the T0, T50 and average reconstructions provided adequate D95 coverage throughout the respiratory cycle as long as the anterior abdominal motion was ≤8 mm and can be considered for use as the primary proton planning scan.

Evaluation of normal tissue exposure in patients receiving radiotherapy for pancreatic cancer based on RTOG 0848.

BACKGROUND: Pancreatic cancer is a highly aggressive malignancy. Chemoradiotherapy (CRT) is utilized in many cases to improve locoregional control; however, toxicities associated with radiation can be significant given the location of the pancreas. RTOG 0848 seeks to evaluate chemoradiation using either intensity-modulated radiation therapy (IMRT) or 3D conformal photon radiotherapy (3DCRT) modalities as an adjuvant treatment. The purpose of this study is to quantify the dosimetric changes seen when using IMRT or 3D CRT photon modalities, as well as proton radiotherapy, in patients receiving CRT for cancer of the pancreas treated per RTOG 0848 guidelines. MATERIALS: Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using IMRT and 3DCRT as well as proton radiotherapy were created for each patient. All planning volumes were created per RTOG 0848 protocol. Dose-volume histograms (DVH) were calculated and analyzed in order to compare plans between the three modalities. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord. RESULTS: There was no difference between the IMRT and 3DCRT plans in dose delivered to the kidneys, liver, or bowel. The proton radiotherapy plans were found to deliver lower mean total kidney doses, mean liver doses, and liver D1/3 compared to the IMRT plans. The proton plans also gave less mean liver dose, liver D1/3, bowel V15, and bowel V50 in comparison to the 3DCRT. CONCLUSIONS: For patients receiving radiotherapy per ongoing RTOG 0848 for pancreatic cancer, there was no significant difference in normal tissue sparing between IMRT and 3DCRT treatment planning. Therefore, the choice between the two modalities should not be a confounding factor in this study. The proton plans also demonstrated improved OAR sparing compared to both IMRT and 3DCRT treatment plans.

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients.

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

Palliative radiation therapy for primary gastric melanoma.

INTRODUCTION: Primary gastric melanoma is an exceedingly rare cause of upper gastrointestinal bleeding (GI bleeding). Prior reports of primary gastric melanoma have mostly been treated with surgery with utilization of radiation therapy being unreported. Radiation therapy has been used to palliate bleeding of other cancers including lung, bladder, cervix, and more recently primary gastric cancers. CASE PRESENTATION: This case documents an 87-year-old male who presented with fatigue and melena, and was found to have severe anemia. Endoscopy with biopsy revealed an isolated focus of melanoma. After discharge, he presented two days later and was found to have continued bleeding. Because he was deemed a poor surgical candidate he elected to undergo palliative radiation therapy for bleeding control. DISCUSSION: The diagnosis of primary verses metastatic melanoma is a topic of debate. Case reports of patients with no known extra-gastric primary have undergone surgical treatment with varying outcomes. Patients with metastatic gastric melanoma have relied on chemotherapy and radiation in addition to surgery, with radiation being used in the palliative setting. The use of radiation to control bleeding in other cancers including primary gastric adenocarcinoma has been previously studied. This case documents the utilization of radiation therapy in bleeding due to primary gastric melanoma. CONCLUSIONS: Radiation therapy can provide adequate bleeding palliation in patients with primary gastric melanoma.

Surgical and radiation therapy management of recurrent anal melanoma.

BACKGROUND: Melanoma of the anorectal mucosa is a rare but highly aggressive tumor. Its presenting symptoms are frequently confused with hemorrhoids, thereby causing a delay in diagnosis. Anorectal melanoma carries with it a very poor prognosis. There is a paucity of data investigating management options for anorectal melanoma, and even fewer data reporting recurrent or refractory cases. CASE PRESENTATION: This case documents a 41-year-old female with a long history of hemorrhoids presenting with anorectal discharge. She was incidentally found have anorectal melanoma following surgical resection. Systemic diagnostic work-up demonstrated PET-avid lymphadenopathy in her right groin. She underwent right groin dissection. However, seven months later she recurred in her right groin and a new recurrent mass was found in her pelvis. She underwent a second groin dissection and resection of the pelvic recurrence. This was followed by a course of hypofractionated radiation therapy then systemic immunotherapy. DISCUSSION: Surgery has been the mainstay of treatment. However, the extent of surgery has been the topic of investigation. Historically, radical resections have been performed but they result in high rates of post-operative morbidity. Newer studies have compared radical resection with wide local excisions and found comparable outcomes. Anorectal melanoma is frequently a systemic disease. The ideal systemic therapy regimen has not yet been determined but numerous studies show a benefit to multi-agent treatments. Radiation therapy is typically given in the post-operative or palliative setting. CONCLUSIONS: Anorectal mucosal melanoma is a very rare but aggressive disease with a poor prognosis. The overall treatment goal should strive to optimize quality of life and tumor control while minimizing treatment-related morbidities.

Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer.

PURPOSE: RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials. METHODS AND MATERIALS: Between December 1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil-based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival. RESULTS: Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of >90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02). CONCLUSIONS: Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.

Treatment of locally advanced unresectable pancreatic cancer: a 10-year experience.

PURPOSE: We retrospectively analyzed the results of patients with locally advanced unresectable pancreatic cancer (LAPC) treated with either chemoradiation (CRT) or chemotherapy alone over the past decade. METHODS AND MATERIALS: Between December 1998 and October 2009, 116 patients with LAPC were treated at our institution. Eighty-four patients received concurrent chemoradiation [RT (+) group], primarily 5-flourouracil based (70%). Thirty-two patients received chemotherapy alone [RT (-) group], the majority gemcitabine based (78%). Progression-free survival (PFS) and overall survival (OS) were calculated from date of diagnosis to date of first recurrence and to date of death or last follow-up, respectively. Univariate statistical analysis was used to determine significant prognostic factors for overall survival. RESULTS: Median patient age was 67 years. Sixty patients were female (52%). Median follow-up was 11 months (range, 1.6-59.4 months). The RT (+) group received a median radiation dose of 50.4 Gy, was more likely to present with ECOG 0-1 performance status, and experienced less grade 3-4 toxicity. PFS was 10.9 versus 9.1 months (P=0.748) and median survival was 12.5 versus 9.1 months (P=0.998) for the RT (+) and RT (-) groups respectively (P=0.748). On univariate analysis, patients who experienced grade 3-4 toxicity had worse overall survival than those who did not (P=0.02). CONCLUSIONS: Optimal management for LAPC continues to evolve. Patients who developed treatment-related grade 3-4 toxicity have a poorer prognosis. Survival rates were not statistically significant between chemotherapy and chemoradiotherapy groups.

Proton therapy for hepatocellular carcinoma.

Proton radiotherapy has seen an increasing role in the treatment of hepatocellular carcinoma (HCC). Historically, external beam radiotherapy has played a very limited role in HCC due to a high incidence of toxicity to surrounding normal structures. The ability to deliver a high dose of radiation to the tumor is a key factor in improving outcomes in HCC. Advances in photon radiotherapy have improved dose conformity and allowed dose escalation to the tumor. However, despite these advances there is still a large volume of normal liver that receives a considerable radiation dose during treatment. Proton beams do not have an exit dose along the beam path once they enter the body. The inherent physical attributes of proton radiotherapy offer a way to maximize tumor control via dose escalation while avoiding excessive radiation to the remaining liver, thus increasing biological effectiveness. In this review we discuss the physical attributes and rationale for proton radiotherapy in HCC. We also review recent literature regarding clinical outcomes of using proton radiotherapy for the treatment of HCC.

The role of radiation in the perioperative treatment of esophagogastric cancer.

Cancers of the esophagus, stomach, and the esophagogastric junction (EGJ) remain a global health problem. There has been a dramatic increase in the incidence of adenocarcinoma of the distal esophagus and EGJ in the past two decades with little change in the poor prognosis associated with these cancers. Previously surgery alone was the mainstay of therapeutic intervention, but high rates of local and systemic failure have prompted investigation into neoadjuvant and adjuvant therapy. Treatment paradigms differ across continents, but the unifying theme that has emerged in the past decade implies that surgery alone can no longer be considered the standard of care. The multi-disciplinary management of patients with locally advanced esophagogastric carcinomas using trimodality therapy with radiotherapy, chemotherapy, and surgery confers the greatest opportunity for margin negative resection, improved loco-regional control and cure, and should be the accepted treatment paradigm. The traditional backbone of platinum plus fluorouracil concurrent with radiotherapy may be supplanted by more modern, easier-to-administer regimens incorporating taxanes and irinotecan. The current generation of clinical trials in this heterogeneous group of diseases is examining targeted therapy, newer methods of radiotherapy, and predictors of response to therapy aiming to tailor management to an individual patient.

FDG PET imaging in the staging and management of gastric cancer.

Gastric cancer is a leading cause of cancer death worldwide. Complete resection offers the only chance for permanent control, and accurate staging and evaluation of treatment response are crucial for appropriate management. Positron Emission Tomography (PET) is increasingly used to complement anatomic imaging in cancer management. PET use in gastric cancer has been limited by 1) some gastric histologies are not PET avid, 2) spatial resolution limits the ability to distinguish between primary tumor and compartment I or II lymph nodes, and 3) the lack of a unified criteria in how to interpret PET for management decisions. New criteria have been proposed establishing response metrics in the utilization of PET. More study is needed to support these criteria in routine practice and establish the place of PET in the staging and management of gastric cancer.

Positron emission tomography as predictor of rectal cancer response during or following neoadjuvant chemoradiation.

Positron emission tomography (PET) shows great promise as a tool to evaluate the effectiveness of rectal cancer neoadjuvant therapy as it has demonstrated high predictive value in several studies. Creating a standardized method of using PET has the potential to reduce ineffective treatments. However, relevant studies have been heterogenous in approach, making any unified standard difficult to establish. PET related parameters used to assess treatment response include magnitude and change of standard uptake value, total lesion glycolysis, and visual response. Finding the best evaluation interval and parameters to use for interpreting PET results in the neo-adjuvant treatment of rectal cancer needs additional study.

Intensity modulated radiation therapy in the treatment of esophageal cancer.

Chemoradiation plays a core role in the definitive and preoperative management of esophageal cancer. Remarkable advances in technology now allow for the implementation of intensity modulated radiation therapy (IMRT) to minimize normal organ damage and to maximize coverage of tumorous targets. While IMRT is commonly accepted in the treatment of prostate and head and neck cancers, there have been clinical and dosimetric studies supporting the use of IMRT in esophagus cancer. In addition, the IMRT technique was recently enhanced by the availability of volumetric intensity modulated arc therapy (VMAT). VMAT may allow for faster delivery of IMRT with the advantage of normal organ protection compared to the stop-and-shoot IMRT, with faster delivery time and reduced monitor units. This review summarizes the use of chemoradiation in esophageal cancer, discusses current dosimetric data and clinical outcomes with the use of IMRT, and reviews IMRT as part of multi-modality treatment in esophageal cancer.

Renal atrophy secondary to chemoradiotherapy of abdominal malignancies.

PURPOSE: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. METHODS AND MATERIALS: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. RESULTS: Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving ≥10 Gy (V(10)), 15 Gy (V(15)), and 20 Gy (V(20)) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V(10), V(15), and V(20) to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. CONCLUSIONS: Significant detriments in PK size and renal function were seen after abdominal RT. The V(10), V(15), and V(20) were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.