Cancers originating in the esophagus, gastroesophageal junctions, and stomach constitute a major health problem worldwide. In the United States, 37,600 new diagnoses of and 25,150 deaths from upper gastrointestinal cancers were estimated in 2009. 1 A dramatic shift in the location of upper gastrointestinal tumors has occurred in the United States, 2 and changes in histology and location of them were observed in some parts of Europe. 3,4 In countries in the Western Hemisphere, the most common sites of gastric cancer are the proximal lesser curvature, cardia, and gastro-The NCCN

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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.

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Objectives: To investigate the incidence of carcinoembryonic antigen (CEA) surge in patients with metastatic colorectal cancer (MCRC) and its implications on clinical outcome. Methods: A retrospective chart review of patients with MCRC treated with chemotherapy at Roswell Park Cancer Institute from January 2000 to May 2004 was conducted. A CEA surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CEA levels compared to baseline. The incidence of CEA surge and its association with clinical outcome was investigated. Results: Eighty-nine patients were evaluable for CEA surge. A CEA surge was documented in 10 patients. The CEA surge lasted <4 months in all 10 patients and was associated with a clinical benefit. No significant correlation was noted between CEA surge and site of primary tumor, site of metastatic disease, or tumor differentiation. Conclusions: CEA surges can be observed in patients receiving chemotherapy for MCRC and are often associated with a clinical benefit. None of the CEA surges satisfied the American Society of Clinical Oncology definition of CEA progression. A rise in CEA after initiation of chemotherapy, unless lasting >4 months, cannot be used as an indicator of progressive disease.

Given the complexity of prostate cancer progression and metastasis, multimodalities that target different aspects of tumor biology, e.g., radiotherapy (RT) in conjunction with immunotherapy, may provide the best opportunities for promoting clinical benefits in patients with high risk localized prostate cancer. Here we show that intratumoral administration of unmodified dendritic cells (DCs) failed to synergize with fractionated RT. However, ionizing radiation combined with in situ vaccination with DCs, in which the immunosuppressive scavenger receptor A (SRA/CD204) has been downregulated by lentivirus-mediated gene silencing, profoundly suppressed the growth of two mouse prostate cancers (e.g., RM1 and TRAMP-C2), and prolonged the lifespan of tumor-bearing animals. Treatment of subcutaneous tumors with this novel combinatorial radio-immunotherapeutic regimen resulted in a significant reduction in distant experimental metastases. SRA/CD204-silenced DCs were highly efficient in generating antigen or tumor-specific T cells with increased effector functions (e.g., cytokine production and tumoricidal activity). SRA/CD204 silencing-enhanced tumor cell death was associated with elevated IFN-γ levels in tumor tissue and increased tumor-infiltrating CD8+ cells. IFN-γ neutralization or depletion of CD8+ cells abrogated the SRA/CD204 downregulation-promoted antitumor efficacy, indicating a critical role of IFN-γ-producing CD8+ T cells. Therefore, blocking SRA/CD204 activity significantly enhances the therapeutic potency of local RT combined with in situ DC vaccination by promoting a robust systemic antitumor immunity. Further studies are warranted to test this novel combinatorial approach for translating into improved clinical outcomes in prostate cancer patients.

Approximately one out of every three patients with non-small cell lung cancer (NSCLC) has locally advanced disease that is surgically unresectable. If their performance status allows, it is current practice to treat these patients with a combination of chemotherapy and external beam irradiation. There have been several studies supporting the addition of chemotherapy to radiation, particularly when delivered concurrently. There is debate over which treatment agents and schedules are most optimal, even with the most proven treatments delivering only modest results, with high rates of local and distant disease failure. Advances in imaging and radiation planning and delivery technology have allowed for the potential for improvement of the therapeutic ratio by reducing normal tissue exposure and ensuring for more precise delivery, while new systemic agents show promising activity in NSCLC. Pemetrexed is a pyrrolopyrimidine-based folate anti-metabolite that works by inhibiting a variety of enzymes of thymidylate and purine synthesis, thus leading to cell stasis and death. Similar to other cytotoxic antifolates, pemetrexed has been shown in pre-clinical study to act as an effective radiosensitizer. At present, it is being studied in phase I and II studies when combined with other systemic agents and radiation therapy in the treatment of locally advanced NSCLC, and the results have been promising. It has the advantage of allowing for relatively safe delivery of full systemic doses when combined other agents and radiation therapy, a distinction over combined modality treatments. Its efficacy, particularly in non-squamous NSCLC, in phase I and II studies has lead to investigations in the phase III setting where a more defined role for pemetrexed in locally advanced non-squamous NSCLC will potentially be defined. This review summarizes the use of combined modality treatment in locally advanced NSCLC, outlines recent advances in radiation planning and treatment, and reviews the current data on the use concurrent chemoradiation regimens featuring pemetrexed.

Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through ROS and ROS-driven oxidative stress, the role of anti-oxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the anti-oxidant response of the lung correlated well with that of RBC. We then proceeded to test whether differences of RBC anti-oxidant response would predict the pneumonitis development in patients. SOD, GPX, CAT activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in fifteen eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pre-treatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.