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The tumor suppressor TP53 is the most frequently mutated gene in human cancers. Mutant p53 (mutp53) proteins often accumulate to very high levels in human cancers to promote cancer progression through the gain-of-function (GOF) mechanism. Currently, the mechanism underlying mutp53 accumulation and GOF is incompletely understood. Here, we identified TRIM21 as a critical E3 ubiquitin ligase of mutp53 by screening for specific mutp53-interacting proteins. TRIM21 directly interacted with mutp53 but not WT p53, resulting in ubiquitination and degradation of mutp53 to suppress mutp53 GOF in tumorigenesis. TRIM21 deficiency in cancer cells promoted mutp53 accumulation and GOF in tumorigenesis. Compared with p53R172H knockin mice, which displayed mutp53 accumulation specifically in tumors but not normal tissues, TRIM21 deletion in p53R172H knockin mice resulted in mutp53 accumulation in normal tissues, an earlier tumor onset, and a shortened life span of mice. Furthermore, TRIM21 was frequently downregulated in some human cancers, including colorectal and breast cancers, and low TRIM21 expression was associated with poor prognosis in patients with cancers carrying mutp53. Our results revealed a critical mechanism underlying mutp53 accumulation in cancers and also uncovered an important tumor-suppressive function of TRIM21 and its mechanism in cancers carrying mutp53.

BackgroundPostmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT.MethodsA retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician.ResultsA total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946).ConclusionsAcute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities.

Purpose: Radiation to breast, chest wall, and/or regional nodes is an integral component of breast cancer management in many situations. Irradiating left-sided breast and/or regional nodes may be technically challenging because of cardiac tolerance and subsequent risk of long-term cardiac complications. Deep inspiratory breath-hold (DIBH) technique physically separates cardiac structures away from radiation target volume, thus reducing cardiac dose with either photon (Ph) or proton beam therapy (PBT). The utility of combining PBT with DIBH is less well understood. Methods and Materials: We compared photon-DIBH (Ph-DIBH) versus proton DIBH (Pr-DIBH) for different planning parameters, including target coverage and organ at risk (OAR) sparing. Necessary ethical permission was obtained from the institutional review board. Ten previous patients with irradiated, intact, left-sided breast and Ph-DIBH were replanned with PBT for dosimetric comparison. Clinically relevant normal OARs were contoured, and Ph plans were generated with parallel, opposed tangent beams and direct fields for supraclavicular and/or axillae whenever required. For proton planning, all targets were delineated individually and best possible coverage of planning target volume was achieved. Dose-volume histogram was analyzed to determine the difference in doses received by different OARs. Minimum and maximum dose (Dmin and Dmax)as well as dose received by a specific volume of OAR were compared. Each patient’s initial plan (Ph-DIBH) was used as a control for comparing newly devised PBT plan (Pr-DIBH). Matched, paired t tests were applied to determine any significant differences between the 2 plans. Results: Both the plans were adequate in target coverage. Dose to cardiac structure subunits and ipsilateral lung were significantly reduced with the proton breath-hold technique. Significant dose reduction with Pr-DIBH was observed in comparison to Ph-DIBH for mean dose (Dmean) to the heart (0.23 Gy versus 1.19 Gy; P < .001); Dmean to the left ventricle (0.25 Gy versus 1.7 Gy; P < .001); Dmean, Dmax, and the half-maximal dose to the left anterior descending artery (1.15 Gy versus 5.54 Gy; P < .003; 7.7 Gy versus 22.15 Gy; P < .007; 1.61 Gy versus 4.42 Gy, P < .049); Dmax of the left circumflex coronary artery (0.13 Gy versus 1.35 Gy; P < .001) and Dmean, the volume to the ipsilateral lung receiving 20 Gy and 5 Gy (2.28 Gy versus 8.04 Gy; P < .001; 2.36 Gy

Abstract Purpose To develop a novel approach to accurately verify patient set up in proton radiotherapy, especially for the verification of the nozzle – body surface air gap and source-to-skin distance (SSD), the consistency and accuracy of which is extremely important in proton treatment. Methods Patient body surfaces can be captured and monitored with the optical surface imaging system during radiation treatment for improved intrafraction accuracy. An in-house software package was developed to reconstruct the patient body surface in the treatment position from the optical surface imaging reference capture and to calculate the corresponding nozzle – body surface air gap and SSD. To validate this method, a mannequin was scanned on a CT simulator and proton plans were generated for a Mevion S250 Proton machine with 20 gantry/couch angle combinations, as well as two different snout sizes, in the Varian Eclipse Treatment Planning Systems (TPS). The surface generated in the TPS from the CT scan was imported into the optical imaging system as an RT Structure for the purpose of validating and establishing a benchmark for ground truth comparison. The optical imaging surface reference capture was acquired at the treatment setup position after orthogonal kV imaging to confirm the positioning. The air gaps and SSDs calculated with the developed method from the surface captured at the treatment setup position (VRT surface) and the CT based surface imported from the TPS were compared to those calculated in TPS. The same approach was also applied to 14 clinical treatment fields for 10 patients to further validate the methodology. Results The air gaps and SSDs calculated from our program agreed well with the corresponding values derived from the TPS. For the phantom results, using the CT surface, the absolute differences in the air gap were 0.45 mm ± 0.33 mm for the small snout, and 0.51 mm ± 0.49 mm for the large snout, and the absolute differences in SSD were 0.68 mm ± 0.42 mm regardless of snout size. Using the VRT surface, the absolute differences in air gap were 1.17 mm ± 1.17 mm and 2.1 mm ± 3.09 mm for the small and large snouts, respectively, and the absolute differences in SSD were 0.81 mm ± 0.45 mm. Similarly, for patient data, using the CT surface, the absolute differences in air gap were 0.42 mm ± 0.49 mm, and the absolute differences in SSD were 1.92 mm ± 1.4 mm. Using the VRT surface, the absolute differences in the air gap were 2.35 mm ± 2.3 mm, and the absolute differences in SSD were 2.7 mm ± 2.17 mm. Conclusion These results showed the feasibility and robustness of using an optical surface imaging approach to conveniently determine the air gap and SSD in proton treatment, providing an accurate and efficient way to confirm the target depth at treatment.

Providing high-quality radiation therapy in medically underserved, low-resource environments can be challenging in the United States. During the American Society of Radiation Oncology 2020 Annual Meeting, the American Society for Radiation Oncology Committee on Health Equity, Diversity, and Inclusion hosted 4 radiation oncologists from both academic and community practices in an educational session. Speakers discussed creative ways to overcome barriers to equitable cancer care and outcomes for their vulnerable patient populations in both rural and urban settings. Successful tactics have included applying for state-sponsored grants, lobbying hospital leadership for equipment upgrades, implementing quality improvement programs specifically targeting the needs of the patient population, studying novel hypofractionation schedules, monitoring toxicities using wearable devices, and expanding transportation options.

Purpose: Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. Methods and Materials: Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. Results: Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. Conclusions: Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Purpose/ObjectivesDespite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.Materials/MethodsUnder an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.ResultsMedian time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).ConclusionsKilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.

Abstract Background To investigate the setup uncertainties and to establish an optimal imaging schedule for the prone-positioned whole breast radiotherapy. Methods Twenty prone-positioned breast patients treated with tangential fields from 2015 to 2017 were retrospectively enrolled in this study. The prescription dose for the whole breast treatment was 266 cGy × 16 for all of the patients and the treatments were delivered with the SSD setup technique. At every fraction of treatment, patient was firstly set up based on the body localization tattoos. MV portal imaging was then taken to confirm the setup; if discrepancy (> 3 mm) was found between the portal images and corresponding plan images, the patient positioning was adjusted accordingly with couch movement. Based on the information acquired from the daily tattoo and portal imaging setup, three sets of data, named as weekly imaging guidance (WIG), no daily imaging guidance (NIG), and initial 3 days then weekly imaging guidance (3 + WIG) were sampled, constructed, and analyzed in reference to the benchmark of the daily imaging guidance (DIG). We compared the setup uncertainties, target coverage (D95, Dmax), V5 of the ipsilateral lung, the mean dose of heart, the mean and max dose of the left-anterior-descending coronary artery (LAD) among the 4 imaging guidance (IG) schedules. Results Relative to the daily imaging guidance (IG) benchmark, the NIG schedule led to the largest residual setup uncertainties; the uncertainties were similar for the WIG and 3 + WIG schedules. Little variations were observed for D95 of the target among NIG, DIG and WIG. The target Dmax also exhibited little changes among all the IG schedules. While V5 of the ipsilateral lung changed very little among all 4 schedules, the percent change of the mean heart dose was more pronounced; but its absolute values were still within the tolerance. However, for the left-sided breast patients, the LAD dose could be significantly impacted by the imaging schedules and could potentially exceed its tolerance criteria in some patients if NIG, WIG and 3 + WIG schedules were used. Conclusions For left-side whole breast treatment in the prone position using the SSD treatment technique, the daily imaging guidance can ensure dosimetric coverage of the target as well as preventing critical organs, especially LAD, from receiving unacceptable levels of dose. For right-sided whole breast treatment in the prone position, the weekly imaging setup guidance appears to be the optimal choice.

Abstract Background ONC201 is a small molecule antagonist of DRD2, a G protein-coupled receptor overexpressed in several malignancies, that has prolonged antitumor efficacy and immunomodulatory properties in preclinical models. The first-in-human trial of ONC201 previously established a recommended phase II dose (RP2D) of 625 mg once every three weeks. Here, we report the results of a phase I study that evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of weekly ONC201. Methods Patients ≥ 18 years old with an advanced solid tumor refractory to standard treatment were enrolled. Dose escalation proceeded with a 3 + 3 design from 375 mg to 625 mg of ONC201. One cycle, also the dose-limiting toxicity (DLT) window, was 21 days. The primary endpoint was to determine the RP2D of weekly ONC201, which was confirmed in an 11-patient dose expansion cohort. Results Twenty patients were enrolled: three at 375 mg and 17 at 625 mg of ONC201. The RP2D was defined as 625 mg with no DLT, treatment discontinuation, or dose modifications due to drug-related toxicity. PK profiles were consistent with every-three-week dosing and similar between the first and fourth dose. Serum prolactin and caspase-cleaved cytokeratin-18 induction were detected, along with intratumoral integrated stress response activation and infiltration of granzyme B+ Natural Killer cells. Induction of immune cytokines and effectors was higher in patients who received ONC201 once weekly versus once every three weeks. Stable disease of > 6 months was observed in several prostate and endometrial cancer patients. Conclusions Weekly, oral ONC201 is well-tolerated and results in enhanced immunostimulatory activity that warrants further investigation. Trial registration NCT02250781 (Oral ONC201 in Treating Patients With Advanced Solid Tumors), NCT02324621 (Continuation of Oral ONC201 in Treating Patients With Advanced Solid Tumors).

Purpose: This study aimed to evaluate whether the coronavirus disease of 2019 (COVID-19) pandemic resulted in treatment delays in patients scheduled for or undergoing brachytherapy. Methods and Materials: A retrospective cohort study was conducted across 4 affiliated sites after local institutional review board approval. The eligibility criteria were defined as all patients with cancer whose treatment plan included brachytherapy during the COVID-19 pandemic from February 24, 2020 to June 30, 2020. Treatment delays, cancellations, alterations of fractionation regimens, and treatment paradigm changes were evaluated. Results: A total of 47 patients were eligible for the analysis. Median patient age at the time of treatment was 62 years (interquartile range, 56-70 years). Endometrial, cervical, and prostate cancers were the most common sites included in this analysis. Three patients (6.4%) with cervical cancer were diagnosed with COVID-19 during the course of their treatment. Interruptions of external beam radiation therapy (EBRT), cancellations of EBRT, cancellations of brachytherapy, and treatment delays due to COVID occurred in 5 (10.6%), 3 (6.4%), 8 (17%), and 9 (19%) patients, respectively. The mean and median number of days delayed for patients who experienced treatment interruptions were 16.3 days (standard deviation: 13.9 days) and 14 days (interquartile range, 5.75-23.75 days), respectively. For patients with cervical cancer, the mean and median overall treatment times defined as the time from the start of EBRT to the end of brachytherapy were 56 and 49 days, respectively. Conclusions: Despite the challenges the health care system faced during the pandemic, most patients with cancer were safely treated with minor treatment delays and interruptions. Long-term follow up is needed to assess the impact of COVID-19 and treatment interruptions on oncologic outcomes.

Purpose: To provide an overview of the major randomized trials that support the use of hypofractionated post-mastectomy radiation therapy for locally advanced breast cancer patients. Methods and Materials: PubMed was systematically reviewed for publications reporting use of of hypofractionated radiation therapy in patients requiring post-mastectomy radiation. Results: Standard fractionation, which is typically delivered over 5 to 7 weeks, is considered the standard of care in setting of post-mastectomy radiation therapy (PMRT). Modern data has helped to establish hypofractionated whole breast irradiation, which consists of a 3- to 4-week regimen, as a new standard of care for early-stage breast cancer. Hypofractionated whole breast irradiation has also laid the groundwork for the exploration of a hypofractionated approach in the setting of hypofractionated post-mastectomy radiation therapy. Conclusions: While standard fractionation remains the most commonly utilized regimen for PMRT, recently published trials support the safety and efficacy of a hypofractionated approach. Ongoing trials are further investigating the use of hypofractionated PMRT.

Purpose: Strong mentorship has been shown to improve mentee productivity, clinical skills, medical knowledge, and career preparation. We conducted a survey to evaluate resident satisfaction with mentorship within their radiation oncology residency programs.Methods and Materials: In January 2019, 126 radiation oncology residents training at programs in the northeastern United States were asked to anonymously complete the validated Munich Evaluation of Mentoring Questionnaire (MEMeQ). Results of residents with a formal mentoring program were compared to those without a formal program.Results: Overall response rate was 42%(n = 53). Participants were 25% post-graduate year two (PGY-2), 21% PGY-3, 26% PGY-4, and 28% PGY-5. Only 38% of residents reported participation in a formal mentoring program, while 62% had no formal program, and 13% reported having no mentor at all. Residents participating in a formal mentoring program reported strikingly higher rates of overall satisfaction with mentoring compared to those who were not (90% vs. 9%, p < 0.001). Overall, 38% of residents were either satisfied/very satisfied with their mentoring experience, while 49% of residents were unsatisfied/very unsatisfied.Conclusion: Residents participating in a formal mentorship program are significantly more likely to be satisfied with their mentoring experience than those who are not. Our results suggest that radiation oncology residency programs should strongly consider implementing formal mentorship programs.

Parkin is an E3 ubiquitin ligase involved in Parkinson’s disease. Parkin has also been linked to cancer suppression but the mechanisms are unclear. Here the authors show that Parkin regulates HIF-1α through ubiquitin-dependent degradation, thus inhibiting metastasis of breast cancer cells.

Abstract Background Dysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions. Methods We analyzed the BCCIP protein level in 470 cases of human breast cancer to determine the associations between BCCIP and 53BP1, p53, and subtypes of breast cancer. We further constructed a unique BCCIP knockdown mouse model to determine whether a partial BCCIP deficiency leads to spontaneous breast cancer formation. Results We found that the BCCIP protein level is downregulated in 49% of triple-negative breast cancer and 25% of nontriple-negative breast cancer. The downregulation of BCCIP is mutually exclusive with p53 mutations but concurrent with 53BP1 loss in triple-negative breast cancer. In a K14-Cre-mediated conditional BCCIP knockdown mouse model, we found that BCCIP downregulation causes a formation of benign modules in the mammary glands, resembling the epidermal inclusion cyst of the breast. However, the majority of these benign lesions remain indolent, and only ~ 10% of them evolve into malignant tumors after a long latency. This tumor progression is associated with a loss of 53BP1 and p16 expression. BCCIP knockdown did not alter the latency of mammary tumor formation induced by conditional Trp53 deletion. Conclusions Our data suggest a confounding role of BCCIP deficiency in modulating breast cancer development by enhancing tumor initiation but hindering progression. Furthermore, secondary genetic alternations may overcome the progression suppression imposed by BCCIP deficiency through a synthetic viability mechanism.

Purpose: Radiotherapy for patients with non-metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer is commonly administered concurrently with adjuvant trastuzumab. However, there is limited data on the use of concurrent trastuzumab and hypofractionated radiotherapy (Hypo-RT), which is now standard of care for the majority of women receiving whole breast irradiation. In this study, we compared acute cardiotoxicity rates in HER2-positive breast cancer patients treated with concurrent trastuzumab and Hypo-RT or conventionally fractionated radiotherapy (Conv-RT).Methods: We performed a review of our institutional database to identify HER2-positive breast cancer patients treated with trastuzumab and Hypo-RT or Conv-RT from 2005 to 2018 who underwent serial cardiac Left Ventricular Ejection Fraction (LVEF) evaluation. Decrease in LVEF was assessed by either echocardiography (ECHO) or multiple gated acquisition (MUGA) scan performed at baseline and every 3 months during trastuzumab therapy. Significant LVEF decline was defined as an absolute decrease in LVEF of ≥10% below the lower limit of normal or ≥16% from baseline value.Results: We identified 41 patients treated with Hypo-RT and 100 patients treated with Conv-RT. Median follow-up was 32 months (range, 13–90 months). Baseline median LVEF was 62% (range, 50–81%) in Hypo-RT group and 64% (range, 51–76%) in Conv-RT group (p = 0.893). Final median LVEF was 60% (range, 50–75%) in both groups. Three patients (7%) in Hypo-RT and five (5%) in Conv-RT group developed significant asymptomatic LVEF decline (p = 0.203). There was no significant difference in mean heart dose in patients who developed significant asymptomatic LVEF decline vs. those who did not in Hypo-RT (p = 0.427) and Conv-RT (p = 0.354) groups. No symptomatic congestive heart failure was reported in either group.Conclusions: The rate of asymptomatic LVEF decline in patients receiving concurrent trastuzumab and Hypo-RT was low (7%) and was similar to the rate observed in patients receiving Conv-RT. Longer follow-up is warranted to assess late cardiotoxicity.

Breast-conserving therapy (BCT), or breast-conserving surgery with adjuvant radiation therapy, has become a standard treatment alternative to mastectomy for women with early-stage breast cancer after many long-term studies have reported comparable rates of overall survival and local control. Oncoplastic breast surgery in the setting of BCT consists of various techniques that allow for an excision with a wider margin and a simultaneous enhancement of cosmetic sequelae, making it an ideal breast cancer surgery. Because of the parenchymal rearrangement that is routinely involved in oncoplastic techniques, however, the targeted tissue can be relocated, thus posing a challenge to localize the tumor bed for radiation planning. The goals of this systematic review are to address the challenges, outcomes, and cosmesis of oncoplastic breast surgery in the setting of BCT.

Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients (P value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication (P value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication (P value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy.

Purpose. To compare the acute toxicities of IMRT to 3D-conformal radiation therapy (3DCRT) in the treatment of rectal cancer. Methods and Materials. Eighty-six patients with rectal cancer preoperatively treated with IMRT (n=30) and 3DCRT (n=56) were retrospectively reviewed. Rates of acute toxicity between IMRT and 3DCRT were compared for anorexia, dehydration, diarrhea, nausea, vomiting, weight loss, radiation dermatitis, fatigue, pain, urinary frequency, and blood counts. Fisher's exact test and chi-square analysis were applied to detect statistical differences in incidences of toxicity between these two groups of patients. Results. There were fewer hospitalizations and emergency department visits in the group treated with IMRT compared with 3DCRT (P=0.005) and no treatment breaks with IMRT compared to 20% with 3DCRT (P=0.0002). Patients treated with IMRT had a significant reduction in grade ≥3 toxicities versus grade ≤2 toxicities (P=0.016) when compared to 3DCRT. The incidence of grade ≥3 diarrhea was 9% among 3DCRT patients compared to 3% among IMRT patients (P=0.31). Conclusions. IMRT for rectal cancer can reduce treatment breaks, emergency department visits, hospitalizations, and all grade ≥3 toxicities compared to 3DCRT. Further evaluation and followup is warranted to determine late toxicities and long-term results of IMRT.