Voichita Bar-Ad

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

Esophagitis, Treatment-Related Toxicity in Non-Small Cell Lung Cancer

OBJECTIVES Radiation esophagitis represents a significant complication experienced by non-small cell cancer (NSCLC) patients receiving thoracic irradiation. The objective of the current review was to assess the clinical and dosimetrical parameters that may predict radiation esophagitis. METHODS Studies were identified by searching PubMed electronic databases. Both prospective and retrospective studies were included. Information regarding clinical and dosimetrical parameters predicting for radiation-induced esophagitis was extracted and analyzed. RESULTS The esophageal clinical and dosimetric parameters that best predict acute esophagitis remain unclear. In many reports, Vx (the volume of esophagus receiving x Gy) stands out, with values of x ranging from 20-70 Gy. Other studies conclude that the maximal dose received by any point of the esophagus is the best predictor of esophagitis. Another metric implicated with esophageal toxicity in some reports is the proportion of the esophageal circumference or surface area that receives high doses of radiation. CONCLUSIONS Technological advancements in patient immobilization, setup verification, and radiotherapy delivery are increasingly being employed to limit the toxicity of thoracic irradiation. Future efforts are required to determine how these complex techniques should best be implemented to minimize the risks of acute and long-term esophageal injury.

Current Management of Locally Advanced Head and Neck Cancer: The Combination of Chemotherapy With Locoregional Treatments

This review will discuss the evolution of the role of chemotherapy in the treatment of locally advanced head and neck cancer (HNC), over the last few decades. Studies were identified by searching PubMed electronic databases. Surgery followed by radiotherapy (RT) or definitive RT are potentially curative approaches for locally advanced HNC. While chemotherapy itself is not curative, it can improve cure rates when given as an adjunct to RT. The benefit of combining chemotherapy with RT is related to the timing of the chemotherapy. Several prospective randomized trials have demonstrated that concurrent delivery of chemotherapy and RT (CRT) is the most promising approach, given that locoregional recurrence is the leading pattern of failure for patients with locally advanced HNC. Induction chemotherapy before CRT has not been shown to be superior to CRT alone and the added toxicity may negatively impact the compliance with CRT. Sequential chemotherapy administration, in the form of induction chemotherapy followed by RT or CRT, has been successful as a strategy for organ preservation in patients with potentially resectable laryngeal and hypopharyngeal cancer. Systemic chemotherapy delivered concurrently with RT is used as a standard treatment for locally advanced HNC.

Clinical experience transitioning from IMRT to VMAT for head and neck cancer.

To quantify clinical differences for volumetric modulated arc therapy (VMAT) versus intensity modulated radiation therapy (IMRT) in terms of dosimetric endpoints and planning and delivery time, twenty head and neck cancer patients have been considered for VMAT using Nucletron Oncentra MasterPlan delivered via an Elekta linear accelerator. Differences in planning time between IMRT and VMAT were estimated accounting for both optimization and calculation. The average delivery time per patient was obtained retrospectively using the record and verify software. For the dosimetric comparison, all contoured organs at risk (OARs) and planning target volumes (PTVs) were evaluated. Of the 20 cases considered, 14 had VMAT plans approved. Six VMAT plans were rejected due to unacceptable dose to OARs. In terms of optimization time, there was minimal difference between the two modalities. The dose calculation time was significantly longer for VMAT, 4 minutes per 358 degree arc versus 2 minutes for an entire IMRT plan. The overall delivery time was reduced by 9.2 ± 3.9 minutes for VMAT (51.4 ± 15.6%). For the dosimetric comparison of the 14 clinically acceptable plans, there was almost no statistical difference between the VMAT and IMRT. There was also a reduction in monitor units of approximately 32% from IMRT to VMAT with both modalities demonstrating comparable quality assurance results. VMAT provides comparable coverage of target volumes while sparing OARs for the majority of head and neck cases. In cases where high dose modulation was required for OARs, a clinically acceptable plan was only achievable with IMRT. Due to the long calculation times, VMAT plans can cause delays during planning but marked improvements in delivery time reduce patient treatment times and the risk of intra-fraction motion.

Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography.

Objectives:To report outcomes after yttrium-90 microsphere brachytherapy for unresectable liver metastases from uveal melanoma and to evaluate factors predictive for overall survival (OS) and hepatic progression-free survival (PFS). Methods:A total of 71 patients were consecutively treated with microsphere brachytherapy for unresectable liver metastases from uveal melanoma between 2007 and 2012. Clinical, radiographic, and positron emission tomography–derived, functional tumor parameters were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. OS and hepatic PFS were estimated by Kaplan-Meier analysis. Results:A total of 134 procedures were performed in 71 patients with a median age of 63 years (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9 to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex, pretreatment metabolic tumor volume, and total glycolic activity (TGA) were significantly correlated with hepatic PFS and OS. In multivariate analysis, female sex and TGA retained significance as independent predictors of hepatic PFS and OS. A low pretreatment TGA (<225 g) was associated with a significantly longer median OS than was a TGA≥225 g (17.2 vs. 9.7 mo, P=0.01). Conclusions:Yttrium-90 microsphere brachytherapy provided favorable survival times in patients with unresectable liver metastases from uveal melanoma. Metabolic tumor volume and TGA are predictive functional tumor parameters, which may aid patient selection and risk stratification.

Effectiveness of PET/CT in the preoperative evaluation of neck disease

To evaluate the utility of positron emission tomography (PET)/computed tomography (CT) for staging the neck in the preoperative setting by comparing it to both CT/magnetic resonance imaging (MRI) and pathologic staging.

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target.

The impact of stool and gas volume on intrafraction prostate motion in patients undergoing radiotherapy with daily endorectal balloon

PURPOSE The aim of this study was to quantify the impact of rectal stool/gas volumes on intrafraction prostate motion for patients undergoing prostate radiotherapy with daily endorectal balloon (ERB). METHODS Total and anterior stool/gas rectal volumes were quantified in 30 patients treated with daily ERB. Real-time intrafraction prostate motion from 494 treatment sessions, at most 6 min in length, was evaluated using Calypso(®) tracking system. RESULTS The deviation of prostate intrafraction motion distribution was a function of stool/gas volume, especially when stool/gas is located in the anterior part of the rectum. Compared to patients with small anterior stool/gas volumes (<10 cm(3)), those with large volume (10-60 cm(3)) had a twofold increase in 3D prostate motion and interquartile data range within the 6th minute of treatment time. The 10% of the overall CBCT session where large anterior rectal volumes were observed demonstrated larger percentage of time at displacement greater than our proposed internal margin 3 mm. CONCLUSION Volume and location of stool/gas can directly impact the ERBs intrafraction immobilization ability. Although our patient preparation protocol and the 100 cm(3) daily ERB effectively stabilized prostate motion for 90% of the fractions, a larger-sized ERB may improve prostate fixation for patients with greater and/or variable daily rectal volume.

Chondrosarcoma of the hyoid bone: case report and review of current management options.

We describe a 53‐year‐old man who presented with a painless neck mass and underwent a resection that identified the tumor as a low‐grade chondrosarcoma of the hyoid bone. We reviewed the literature for diagnosis and management options of this exceptionally rare diagnosis.

Impact of a Radiation Oncology Elective on the Careers of Young Physicians: Update on a Prospective Cohort Study

Received Jan 27, 2013. Accepted for publication Feb 2, 2013Cancer is the second leading cause of death in the United Statesand Western Europe. Approximately 60% of cancer patientsreceive radiation therapy. Although European medical schoolshave significantly improved oncologic training in the past decade(1), the United States has not, and radiation oncology is particu-larly underrepresented in US medical curricula (2). As survivor-ship from cancer continues to increase, medical practitionersthroughout the world will need to know the basics of radiationtherapy and its role in the multimodal management of cancers,outcomes, and toxicities.In July 2010, Jefferson Medical College of Thomas JeffersonUniversity began offering a 3-week clinical rotation in radiationoncology. The rotation was structured on Accreditation Councilfor Graduate Medical Education core competencies (3), interna-tional oncologic training recommendations (4), and previouslyreported methods shown to be successful in teaching radiationoncology, including didactic lectures, hands-on contouringsessions, student presentations, clinical time with patients andphysicians, and examinations (5, 6).The rotation improved studentknowledge of radiation oncology, including aspects of clinicaloncology, radiobiology, and medical physics, and was appreciatedby students and faculty (7). In 2012, young physicians were sentfollow-up surveys and examinations to (1) evaluate the long-lasting impact of the rotation on young physicians’ careers; (2)assess memory retention; (3) identify ideal methods of teachingradiation oncology; and (4) make a recommendation regarding theintegration of a radiation oncology rotation in medical curricula.Of the 56 students who initially took the rotation, 41 respondedto the survey (response rate, 73%). The median follow-up timewas approximately 1.5 years. Most students enrolled in the rota-tion planned to go into primary care. All respondents considereda career in academics. Sixty-four percent of respondents plannedon seeing oncologic patients frequently or very frequently in theircareer. The long-term effects of the rotation (Fig. 1A) spanned allAccreditation Council for Graduate Medical Education corecompetencies, including patient care, medical knowledge,practice-based learning and improvement, interpersonal andcommunication skills, professionalism, and systems-based prac-tice (3). Additional benefits included knowing when to consultradiation oncologists, learning about advanced technology, iden-tifying radiation therapy emergencies, and taking care of cancerpatients (mean weighted Likerts, >4.5/5). Young physiciansrecommended teaching their peers about radiation oncologythrough an optional rotation (4.4) and did not believe it affectedother graduate medical training (1.6). On examinations (Fig. 1B),the prerotation, immediate postrotation, and survey results inclinical oncology were 58%, 83%, 64%; radiobiology, 21%, 44%,60%; and radiophysics, 62%, 94%, 83%.We conclude that a clinical rotation in radiation oncology haspositive effects on the careers of young physicians, independent ofcareer plan. After taking the rotation, young physicians were moreprepared to treat cancer patients and consult radiation oncologistsfor appropriate conditions. Moreover, previous studies have shownbenefits of teaching medical professionals end-of-life situation