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The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

EKB-569 (Pelitinib), an irreversible EGFR tyrosine kinase inhibitor has shown potential therapeutic efficiency in solid tumors. However, cell-killing potential in combination with radiotherapy and its underlying molecular orchestration remain to be explored. The objective of this study was to determine the effect of EKB-569 on ionizing radiation (IR)-associated NFκB-dependent cell death. SCC-4 and SCC-9 cells exposed to IR (2Gy) with and without EKB-569 treatment were analyzed for transactivation of 88 NFκB pathway molecules, NFκB DNA-binding activity, translation of the NFκB downstream mediators, Birc1, 2 and 5, cell viability, metabolic activity and apoptosis. Selective targeting of IR-induced NFκB by EKB-569 and its influence on cell-fate were assessed by overexpressing (p50/p65) and silencing (ΔIκBα) NFκB. QPCR profiling after IR exposure revealed a significant induction of 74 NFκB signal transduction molecules. Of those, 72 were suppressed with EKB-569. EMSA revealed a dose dependent inhibition of NFκB by EKB-569. More importantly, EKB-569 inhibited IR-induced NFκB in a dose-dependent manner, and this inhibition was sustained up to at least 72 h. Immunoblotting revealed a significant suppression of IR-induced Birc1, 2 and 5 by EKB-569. We observed a dose-dependent inhibition of cell viability, metabolic activity and apoptosis with EKB-569. EKB-569 significantly enhanced IR-induced cell death and apoptosis. Blocking NFκB improved IR-induced cell death. Conversely, NFκB overexpression negates EKB-569 -induced cell-killing. Together, these pre-clinical data suggest that EKB-569 is a radiosensitizer of squamous cell carcinoma and may mechanistically involve selective targeting of IR-induced NFκB-dependent survival signaling. Further pre-clinical in-vivo studies are warranted. [ABSTRACT FROM AUTHOR]

The present study was carried out to evaluate the levels of plasma fibronectin (Fn) in cancer patients undergoing radiation therapy (RT) in correlation with outcomes in terms of radiation toxicity. A total of 26 patients with lung and gastrointestinal (GI) cancer, treated with RT were enrolled in this study. Plasma Fn levels were determined before and following a course of RT. The Radiation Therapy Oncology Group (RTOG) criteria were used to determine the grade of RT toxicity. Statistical analysis utilised the nonparametric Mann--Whitney U-test as well as bivariate linear regression. Pre-RT Fn levels were significantly higher in cancer patients without toxicity (median ± SE) (485.0 ± 87 µg/ml) as compared with the levels of plasma Fn in patients with grade I--II RTOG acute toxicity (354.0 ± 74 µg/ml, p = 0.01). No significant difference in Fn levels was found in patients with grade I toxicity compared with patients with grade II toxicity. In addition, low baseline Fn levels (148 and 299 µg/ml) were observed in two lung cancer patients who developed symptomatic pneumonitis during the first 2 months after RT. These preliminary results suggest that low baseline Fn may have potential as a predictive marker for development of RT-induced toxicity. [ABSTRACT FROM AUTHOR]

The article discusses a study which analyzed the prospective database of the U.S. Gastrointestinal Intergroup trial RTOG 98-11. The study included 644 patients with anal cancer, whose five-year overall survival (OS) and disease-free survival (DFS) were analyzed. It found that greater than five centimeter (cm) tumor size is associated with poorer DFS and OS. Study authors concluded that N+ and male sex are poor prognostic factors for DFS and OS.

Simple Summary: Recent studies have shown that the incidence of age disparities in cancer clinical trials may be increasing over time. Excluding patients with prior malignancies is one such eligibility criterion through which elderly may inadvertently be excluded from clinical trial participation. While strict enrollment criteria may improve internal validity of studies, they can also negatively impact generalizability of results. As such, we sought to characterize the incidence of prior malignancy exclusion criteria in phase III cancer clinical trials and assess if this eligibility criterion may directly contribute to age disparities. These data support efforts to modernize eligibility criteria and inform best practices regarding acceptable versus unacceptable exclusionary timeframes for prior malignancy exclusion criteria. Prior malignancy exclusion criteria (PMEC) are often utilized in cancer clinical trials; however, the incidence of PMEC and the association of PMEC with trial participant age disparities remain poorly understood. This study aimed to identify age disparities in oncologic randomized clinical trials as a result of PMEC. Using a comprehensive collection of modern phase III cancer clinical trials obtained via ClinicalTrials.gov, we assessed the incidence and covariates associated with trials excluding patients with prior cancers within 5+ years from registration (PMEC-5). Using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we further sought to determine the correlation between PMEC-5 and age disparities. PMEC-5 were used in 41% of all trials, with higher PMEC-5 utilization among industry-supported trials as well as trials evaluating a targeted therapy. Comparing trial patient median ages with population-matched median ages by disease site and time-period, we assessed the association between PMEC-5 and age disparities among trial participants. PMEC-5 were independently associated with heightened age disparities, which further worsened with longer exclusionary timeframes. Together, PMEC likely contribute to age disparities, suggesting that eligibility criteria modernization through narrower PMEC timeframes may work toward reducing such disparities in cancer clinical trial enrollment. [ABSTRACT FROM AUTHOR]

The article presents a study comparing the efficacy of cisplatin-based therapy in combination with fluorouracil and radiotherapy versus the standard mitomycin-based therapy to treat anal carcinoma. The objectives, design and setting of the controlled patient trial are defined. Research showed that cisplatin-based therapy failed to improve recurrence and disease-free survival rates in anal cancer patients. Researcher's conclude that their findings do not support the use of cisplatin-based therapy to treat anal canal carcinoma.

The article presents information on a study which investigated whether the mortality from heart disease, a maniifestation of intercurrent disease after postoperative radiotherapy (PORT), has decreased over time for patients with nonsmall cell lung cancer (NSCLC). The multivariate analysis of the study reveals that PORT use was associated with an increase in heart disease mortality. The study also suggests that the decline may be associated to improvements in the treatment planning and delivery of thoracic radiotherapy.

Background: Treatment of choroidal melanoma with radiation often involves placement of customized brachytherapy eye-plaques. However, the dosimetric properties inherent in sourcebased radiotherapy preclude facile dose optimization to critical ocular structures. Consequently, we have constructed a novel system for utilizing small beam low-energy radiation delivery, the Beamlet Low-kVp X-ray, or "BLOKX" system. This technique relies on an isocentric rotational approach to deliver dose to target volumes within the eye, while potentially sparing normal structures. Methods: Monte Carlo N-Particle (MCNP) transport code version 5.0(14) was used to simulate photon interaction with normal and tumor tissues within modeled right eye phantoms. Five modeled dome-shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively, were simulated distinct positions with respect to the macula iteratively. A single fixed 9 × 9 mm2 beamlet, and a comparison COMS protocol plaque containing eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of the eye adjacent to the tumor, were utilized to determine dosimetric parameters at tumor and adjacent tissues. After MCNP simulation, comparison of dose distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye-plaque) was performed. Results: Tumor-base doses ranged from 87.1-102.8 Gy for the BLOKX procedure, and from 335.3-338.6 Gy for the eye-plaque procedure. A reduction of dose of at least 69% to tumor base was noted when using the BLOKX. The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic nerve occurred when the BLOKX was used. Conclusion: The BLOKX technique allows more favorable dose distribution in comparison to standard COMS brachytherapy, as simulated using a Monte Carlo iterative mathematical modeling. Future series to determine clinical utility of such an approach are warranted. [ABSTRACT FROM AUTHOR]

Background: Keloids are common benign tumors of the dermis, typically arising after insult to the skin. While typically only impinging on cosmesis, large or recurrent keloids may require therapeutic intervention. While no single standardized treatment course has been established, several series report excellent outcomes for keloids with post-surgery radiation therapy. Case presentation: We present a patient with a history of recurrent keloids arising in the absence of an ascribed trauma and a maternal familial history of keloid formation, whose physical examination several large perineal keloids of 6-20 cm in the largest dimension. The patient was treated with surgical extirpation and adjuvant radiation therapy. Radiotherapy was delivered to the scar bed to a total dose of 22 Gy over 11 daily fractions. Acute radiotherapy toxicity necessitated a treatment break due to RTOG Grade III acute toxicity (moderate ulceration and skin breakdown) which resolved rapidly during a 3-day treatment break. The patient demonstrated local control and has remained free of local recurrence for more than 2 years. Conclusion: Radiotherapy for keloids represents a safe and effective option for post-surgical keloid therapy, especially for patients with bulky or recurrent disease. [ABSTRACT FROM AUTHOR]

The article summarizes current state-of-the-art management and future directions regarding combined-modality therapy for pancreatic cancer. Specific topics discussed include: the presenting symptoms, diagnostic imaging and procedures, general treatment principles, surgery, adjuvant therapy, the treatment of unresectable disease, advances in chemotherapy, evolving radiation therapies, and targeted therapies.

Squamous cell anal cancer remains an uncommon entity; however, the incidence appears to be increasing in at-risk populations, especially those infected with human papilloma virus (HPV) and human immuno- deficiency virus (HIV). Given the ability to cure this cancer using synchronous chemoradiotherapy, management practices of this disease are critical. This article considers treatment strategies for HIV-positive patients with anal cancer, including the impact on chemoradiation-induced toxicities and the role of highly active antiretroviral therapy in the treatment of this patient population. The standard treatment has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation. Consideration to modifying the standard treatment regime is based on the fact that patients with HIV tend to experience greater toxicity, especially when CD4 counts are below 200; these patients also require longer treatment breaks. Additional changes to the chemotherapy dosing, such as giving 5-FU continuously and decreasing mitomycin dose, are evaluated and considered in relation to radiation field sizes in an effort to reduce toxicity, maintain local tumor control, and limit need for colostomy. The opportunity for decreasing the radiation field size and using intensity-modulated radiation therapy (IMRT) is also considered, particularly in light of the fact that IMRT provides dose-sparing while maximizing target volume dose to involved areas. The impact of the immune system in patients with HIV and squamous cell carcinoma of the anus and the associated response to therapy remains unknown. Continued studies and phase III trials will be needed to test new treatment strategies in HIV-infected patients with squamous cell cancer of the anus to determine which treatment protocols provide the greatest benefits. [ABSTRACT FROM AUTHOR]

The article presents information related to superior sulcus tumors (SSTs). Tumors located above the groove in the lung formed by the subclavian artery are referred to as SSTs. The primary and most common cause of SSTs is non-small cell lung cancer. SSTs represent only about 3% of primary lung cancers. Reflecting the trend of non-small cell lung cancer over the past 20 years, adenocarcinoma is the most common type in the larger series; previously, squamous cell carcinoma was the predominant type. Frequently, patients are evaluated by orthopedists and rheumatologists for presumed arthritis and bursitis.

: PurposeTo analyze the relative contributions of uniformly collected pretreatment patient- and tumor-related variables to survival and to identify the terminal nodes via recursive partitioning analysis (RPA) that could be used as a stratification variable for future Phase III trials.: Methods and materialsFrom two Intergroup trials (85-01, n = 130; and 94-05, n = 218) and one Radiation Therapy Oncology Group trial (92-07, n = 68), we identified 416 patients who were treated with definitive concomitant cisplatin and 5-FU–based chemoradiotherapy and analyzed their data for survival by RPA to define prognostic classes. The following pretreatment factors were evaluated: histologic type, age, weight loss, Karnofsky performance status, gender, race, T stage, tumor location, tumor size, N stage, and degree of dysphagia. The entire data set was considered as the initial node. The criterion for split points was the smallest p value less than unadjusted 0.05.: ResultsOf the 416 patients, 336 (81%) were dead at the time of the analysis. The RPA identified only one significant split: pretreatment weight loss in the prior 6 months of <10% vs. ≥10%. After adjusting for multiple comparisons, no other split approached statistical significance.: ConclusionUnlike our experience with malignant glioma, brain metastases, and locally advanced non–small-cell lung cancer, RPA failed to identify novel prognostic information that could be incorporated into the stratification scheme of future chemoradiotherapy trials for esophageal cancer. Furthermore, our analysis validated the percentage of weight loss as a stratification variable for esophageal cancer. [Copyright &y& Elsevier]

Prostate cancer in men is similar to breast cancer in women; both cancers rank first, respectively, in incidence and are normally responsive to radiation therapy. In addition, advances in mammography help detect earlier breast cancers, and the development and refinement of prostatic specific antigen (PSA) has resulted in early detection of low-stage localized prostate cancers. This has generated debate over the proper management of localized prostate cancer. While there have not been any controlled, prospective, randomized trials of sufficient power to compare the various local therapies, based on the current available data, the three commonly used local modalities, surgery, and external beam radiation therapy and brachytherapy (radioactive seed implant), have similar efficacy controlling the disease up to 10 years in many patients. Technological advances in treatment delivery and planning have improved the treatment of prostate cancer with external-beam radiotherapy using three-dimensional conformal radiotherapy (3DCRT), ultrasound-guided transperineal implant, or intensity-modulated radiotherapy (IMRT), as well as proton or neutron beam based therapies. [Copyright &y& Elsevier]

Characterizes PHR1, a pH regulated gene important for cell wall integrity of Pneumocystis carinii. Factors that influence the stability and solubility of glucans under alkaline conditions; Role of defective cell walls on the virulence of PHR-deleted mutants; Correlation between fungal proliferation and cell wall integrity.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted. [ABSTRACT FROM AUTHOR]

The article reviews the article "Intensity-Modulated Radiation Therapy for Anal Cancer: Toxicity versus Outcomes," by Timothy M. Zagar, Christopher G. Willett and Brian G. Czito, which appeared in the August 2010 issue of the journal.

PURPOSE: To characterize the longitudinal relationship by gender between publication productivity, NIH funding, and academic promotion of current US academic professors of radiation oncology (RO). METHODS: For full professors of RO departments, institutional websites were accessed to obtain training information and promotion dates. A commercial database (SCOPUS, Elsevier BV, Amsterdam, the Netherlands) was used to obtain productivity metrics, including publication number, citation number, and Hirsch index (h-index) at the time of each promotion, and National Institutes of Health (NIH) RePORTER (Research Portfolio Online Reporting Tools) was used to obtain NIH funding information. Pearson chi-square test and Wilcoxon rank-sum tests were used for comparisons of variables between men and women. RESULTS: For 166 RO faculty full professors, there were no significant differences in degree, additional residency and fellowship training, year of RO residency graduation, number of institutions worked at as faculty, NIH funding status, number of publications, citations, h-indices, or m-indices. Women had a longer median time to promotion from assistant to associate professor when compared with men (8 yr, interquartile range [IQR]: 6–11 vs 6 yr, IQR: 5–8 yr; P = .049), as well as longer median time from associate to full professor (6 yr, IQR: 6–11 yr vs 5 yr, IQR: 4–6 yr; P = .004). However, there was no significant difference in time to appointment as chairperson. The h-index and NIH funding at promotion were not significantly different by gender at any of the promotion levels. CONCLUSIONS: Although the female RO full professors in our cohort were similar overall in terms of productivity and NIH funding to their male colleagues, they tended to have longer times to promotion earlier in their careers at lower academic ranks. Women may experience barriers to productivity early in their careers that may delay promotion. [ABSTRACT FROM AUTHOR]

BACKGROUND: Emotional Intelligence (EI) has attracted recent attention as a desirable trait for physicians. The Accreditation Council for Graduate Medical Education has incorporated aspects of EI into its core competencies by which resident physicians are evaluated. There is likewise emerging interest in the relationship of EI to retention, promotion, and academic productivity; however, to date, there has been no formal evaluation of EI among current department chairs. Therefore, our objectives were to assess the EI of current chairs of academic radiation oncology departments and correlate EI with self-reported assessment of burnout. METHODS: Ninety-five current chairs of academic radiation oncology departments were invited to participate in an institutional review board (IRB)-approved survey containing questions regarding general demographics and chair experience, the Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF), and the abbreviated Maslach Burnout Inventory (a-MBI). TEIQue-SF scores were evaluated for correlation with respondent demographics and self-reported burnout scores on the a-MBI. RESULTS: Sixty chairs responded to the survey, for a response rate of 63.2%. Nine respondents (15%) were female, and the remaining 51 (85%) were male. The median (interquartile range [IQR]) TEIQue-SF for the responding cohort was 172 (155–182) out of a maximum possible score of 210. The a-MBI Emotional Exhaustion and Depersonalization subscores were low for the responding cohort with a median (IQR) of 4 (2.25–6.75) and 1 (0–2.75) out of a maximum possible of 18 and 30, respectively. Higher TEIQue-SF global scores were significantly correlated with decreased burnout on all a-MBI subscores. CONCLUSIONS: Academic radiation oncology chairs have high EI, and increased EI correlates significantly with decreased rates of self-reported burnout. In the future, EI scores may be of increasing importance when it comes to recruitment and retention of academic medical leadership. [ABSTRACT FROM AUTHOR]

An exciting array of novel antiproliferative systemic agents, including angiogenesis inhibitors, vascular targeting agents and signal transduction inhibitors have recently entered into clinical trials. With the exception of imatinib however, they have had lower than anticipated response rates. The quandary of whether the agent being investigated is actually interacting with its intended molecular target and whether the target is actually relevant to the growth drive for a given tumor is becoming even more acute as tremendous resources are expended for the potential benefit of fewer patients.

An editorial is presented about the potential role of radiation oncologists (ROs) who could be functioned as service providers or as a care provider. Topics discussed include the engagement of the RO in patient management, their role in the creation and administration of innovative treatment strategies, as well in survivorship clinics, and the establishment of more RO-staffed inpatient services in the U.S.