Monte Carlo modeling of the Elekta Versa HD and patient dose calculation with EGSnrc/BEAMnrc.

INTRODUCTION: Numerous studies have proven the Monte Carlo method to be an accurate means of dose calculation. Although there are several commercial Monte Carlo treatment planning systems (TPSs), some clinics may not have access to these resources. We present a method for routine, independent patient dose calculations from treatment plans generated in a commercial TPS with our own Monte Carlo model using free, open-source software. MATERIALS AND METHODS: A model of the Elekta Versa HD linear accelerator was developed using the EGSnrc codes. A MATLAB script was created to take clinical patient plans and convert the DICOM RTP files into a format usable by EGSnrc. Ten patients' treatment plans were exported from the Monaco TPS to be recalculated using EGSnrc. Treatment simulations were done in BEAMnrc, and doses were calculated using Source 21 in DOSXYZnrc. Results were compared to patient plans calculated in the Monaco TPS and evaluated in Verisoft with a gamma criterion of 3%/2 mm. RESULTS: Our Monte Carlo model was validated within 1%/1-mm accuracy of measured percent depth doses and profiles. Gamma passing rates ranged from 82.1% to 99.8%, with 7 out of 10 plans having a gamma pass rate over 95%. Lung and prostate patients showed the best agreement with doses calculated in Monaco. All statistical uncertainties in DOSXYZnrc were less than 3.0%. CONCLUSION: A Monte Carlo model for routine patient dose calculation was successfully developed and tested. This model allows users to directly recalculate DICOM RP files containing patients' plans that have been exported from a commercial TPS.

The role of chemotherapy and radiation in the treatment of locally advanced non-small cell lung cancer (NSCLC).

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.

Management of stage II/III rectal cancer.

Pelvic and distant recurrences in rectal cancer can be associated with substantial morbidity, and patients with stage II and III disease are at increased risk for both local and distant failure when compared to patients with earlier stage disease. Refinement of surgical techniques have helped to reduce the risk of recurrence, and adjuvant therapies such as radiation to the tumor and regional lymph nodes and 5-fluorouracil-based systemic therapies have helped to further provide local control and may have an impact on overall survival. Numerous studies have been completed internationally in an effort to determine the optimal treatment regimen for this patient population. The importance of pre-therapy staging is of key importance as sequencing of therapy appears to significantly impact outcome. In the United States, patients with stage II/III rectal cancer are recommended to undergo preoperative concurrent pelvic radiation and chemotherapy followed by surgery several weeks later in order to maximize treatment response, which is then followed by approximately 4 months of adjuvant 5-fluorouracil-based systemic therapy. In Europe, there is substantial evidence supporting the use of neoadjuvant radiation therapy, however the role of concurrent chemotherapy remains a question of debate. Regardless of definitive management strategy, close follow-up in the post-treatment setting is important for early tumor detection and for managing treatment-related side-effects.

Clinical T2N0M0 carcinoma of thoracic esophagus.

The incidence of esophageal cancer continues to rise. Historically, the majority of patients had been diagnosed with more advanced stages of disease. However, with screening programs, like those in place for patients with Barrett's esophagus, many patients are being diagnosed earlier in their disease course. Results of randomized trials and meta-analyses have led to emerging guidelines advocating for neoadjuvant therapy as part of the treatment algorithm for esophageal cancer, particularly for T3 or greater T-stage and/or node-positive disease. And for those patients that present with disease localized to the esophageal mucosa, endoscopic mucosal resection has proved to be an effective and less morbid alternative to radical resection. However, there is a group of patients that lie between these two extremes for which evidence is sparse and treatment recommendations vary. In this manuscript, recent data regarding work-up and treatment are reviewed along with a closer look at those patients clinically staged with T2N0M0 (Stage IIA) esophageal cancer. Pertinent data in this subset of patients is analyzed as potential treatment algorithms are discussed.

Combination short-course preoperative irradiation, surgical resection, and reduced-field high-dose postoperative irradiation in the treatment of tumors involving the bone.

PURPOSE: To assess the feasibility and outcomes of combination short-course preoperative radiation, resection, and reduced-field (tumor bed without operative field coverage) high-dose postoperative radiation for patients with solid tumors mainly involving the spine and pelvis. METHODS AND MATERIALS: Between 1982 and 2006, a total of 48 patients were treated using this treatment strategy for solid tumors involving bone. Radiation treatments used both photons and protons. RESULTS: Of those treated, 52% had chordoma, 31% had chondrosarcoma, 8% had osteosarcoma, and 4% had Ewing's sarcoma, with 71% involving the pelvis/sacrum and 21% elsewhere in the spine. Median preoperative dose was 20 Gy, with a median of 50.4 Gy postoperatively. With 31.8-month median follow-up, the 5-year overall survival (OS) rate is 65%; 5-year disease-free survival (DFS) rate, 53.8%; and 5-year local control (LC) rate, 72%. There were no significant differences in OS, DFS, and LC according to histologic characteristics. Between primary and recurrent disease, there was no significant difference in OS rates (74.4% vs. 51.4%, respectively; p = 0.128), in contrast to DFS (71.5% vs. 18.3%; p = 0.0014) and LC rates (88.9% vs. 30.9%; p = 0.0011) favoring primary disease. After resection, 10 patients experienced delayed wound healing that did not significantly impact on OS, DFS, or LC. CONCLUSION: This approach is promising for patients with bone sarcomas in which resection will likely yield close/positive margins. It appears to inhibit tumor seeding with an acceptable rate of wound-healing complications. Dose escalation is accomplished without high-dose preoperative radiation (likely associated with higher rates of acute wound healing delays) or large-field postoperative radiation only (likely associated with late normal tissue toxicity). The LC and DFS rates are substantially better for patients with primary than recurrent sarcomas.

Cetuximab: its use in combination with radiation therapy and chemo-therapy in the multimodality treatment of head and neck cancer.

Dimerization of epidermal growth factor receptor (EGFR) on the cell membrane of tumor cells has been implicated in triggering a complex signal cascade that leads to increased tumor proliferation and survival. Cetuximab is a human-murine chimeric monoclonal antibody designed to target EGFR and competitively inhibit dimerization by circulating ligands. By this mechanism, it works to prevent this signal cascade thus hindering tumor proliferation. Cetuximab has been shown in a randomized phase III clinical trial to significantly increase overall survival when it is added to radiation therapy in the treatment of locally advanced squamous cell carcinoma of the head and neck. In this manuscript, the mechanism of cetuximab with its associated patents is reviewed, with its role with chemotherapy and radiation in the management of head and neck cancer along with future directions of this targeted cancer therapy.

The role of positron emission tomography in esophageal cancer.

The most common methods for staging esophageal cancer are endoscopic ultrasonography (EUS) and computed tomography (CT). EUS is well established in differentiating between early tumor stages and more advanced primary lesions. When combined with fine needle aspiration, EUS has become an important tool in assessing the regional lymph nodes, as well. EUS has its limitations, esophageal obstruction makes passage of the endoscope beyond the tumor nearly impossible and with a narrow field of evaluation, it is not useful for detecting metastatic disease. CT allows for assessment of local tumor invasion while simultaneously providing information regarding distant disease. Its usefulness locally, however, is limited. CT and EUS yield anatomic visualization. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can provide functional information and is an effective diagnostic modality in esophageal cancer. Its role in the management of esophageal cancer includes staging as well as potential utility in the evaluation of neoadjuvant therapy response and in follow-up after definitive therapy. FDG-PET will likely be more readily used in combination with anatomical imaging like CT to provide additional diagnostic information to aid radiation oncologists in target delineation and planning. In addition, FDG-PET has also been shown to have prognostic value that can be applied to patient management and aid in development of emerging therapies.

Long-term outcome of stage I seminoma.

PURPOSE: To report on long-term outcomes among patients with stage I seminoma treated by orchiectomy with or without adjuvant radiation. MATERIALS AND METHODS: A retrospective review of medical records of patients treated between 1974 and 2002 was undertaken to identify factors associated with patient outcomes. RESULTS: With a median follow-up of 7.7 years, 80% (4 of 5) of the surveillance group experienced a disease relapse, while only 3% (2 of 70) in the radiation therapy group had disease relapse. This difference in relapse rates was statistically significant, but there was no significant difference in overall survival between the 2 groups. There was a significant relationship between patient age and disease relapse, whereby all of the relapses were seen in patients younger than 36 years at diagnosis (P = 0.03). Of the total 75 patients, 7 (9%) developed second primary tumors. Six of them (6 of 7) were treated with adjuvant radiation, and 1 patient (1 of 7) was on surveillance. CONCLUSION: In this study, risk of relapse was significantly associated with surveillance and in patients younger than 36 years at diagnosis. These results suggest that surveillance can only be safely adopted for patients who can be followed up closely. We consider adjuvant radiation a very effective choice despite the low risk of associated secondary malignancies.

Misrepresentation of publications among radiation oncology residency applicants.

INTRODUCTION: Authorship misrepresentations have been described for residency and fellowship applications for various medical specialties. This study assessed the prevalence of misrepresented publications in radiation oncology residency applications. MATERIALS AND METHODS: The authors reviewed 117 applications to their residency program for a single 2004 position offered through the National Resident Matching Program. Publications listed on the applications were verified for accuracy, with the results and applicants' demographic information recorded. RESULTS: A total of 49 applicants (42%) claimed authorship of published research citations. The number of published citations averaged 3.6 per applicant (range, 1-23). Of the applicants reporting citations, 22% (11 of 49) listed inaccurate citation information. Overall, 9% of the citations (15 of 174) were considered misrepresentations, with 9% of the total number of applicants (11 of 117) responsible for inaccurate bibliographies. There was a significant relationship of United States Medical Licensing Examination score with publication misrepresentation, in which those with scores of 235 or greater who listed publications were more than 7 times more likely to have inaccurately listed citations (odds ratio, 7.67; 95% confidence interval, 1.12-52.31; P = .04). CONCLUSION: The misrepresentation of bibliographic citations does exist among radiation oncology residency applicants. Using a comprehensive search, the authors found that 22% of those who had listed at least 1 article had misrepresented publications on their applications.

Multimodality approaches for pancreatic cancer.

The role of combined-modality therapy for pancreatic cancer is evolving with the recent development and completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive chemoradiotherapy or adjuvant chemoradiotherapy for local and/or regionally advanced disease. Our aim is to summarize the current state-of-the-art management and future directions regarding the multimodality approach to pancreatic cancer.