Arif N. Ali

Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies

Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V(25) (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V(15) (53.4 Gy vs. 45.9 Gy, p = 0.035), V(20) (32.2 Gy vs. 25.5 Gy, p = 0.016), and V(25) (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

Tumor size on abdominal MRI versus pathologic specimen in resected pancreatic adenocarcinoma: implications for radiation treatment planning.

PURPOSE We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. METHODS AND MATERIALS The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. RESULTS The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, -34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. CONCLUSIONS Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before routine integration into the treatment planning process.

Matrix metalloproteinases: Their functional role in lung cancer

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors that control the tumor microenvironment. In this review, we have summarized and critically reviewed the published works on the role of MMPs in non-small-cell lung cancer. We have also explored the structure of MMPs, their various types and roles in lung cancer metastasis including invasion, migration and angiogenesis.

Bevacizumab-induced hypertension is a predictive marker for improved outcomes in patients with recurrent glioblastoma treated with bevacizumab

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor and is approved for the treatment of patients with recurrent glioblastoma (GBM). Previous authors have reported differential response to bevacizumab on an individual basis. Bevacizumab‐induced hypertension is a well‐documented side effect, and some reports have suggested this occurrence to be related to treatment outcome in other cancers. In the current study, the authors analyzed patients with recurrent GBM who were treated with bevacizumab based on whether the patients developed drug‐induced hypertension.

Dosimetric and cost comparison of first fraction imaging versus fractional re-imaging on critical organ dose in vaginal cuff brachytherapy.

PURPOSE Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of the most common procedures performed in the treatment of early-stage endometrial cancer. However, current recommendations by the American Brachytherapy Society regarding fractional re-imaging and dose calculation for organs at risk for HDR vaginal cuff brachytherapy are not well defined. In this study, we aim to compare a fractional re-imaging approach using computed tomographic (CT) scans prior to each fraction with a first fraction imaging-only approach with respect to bladder, rectal, and bowel dosimetry. METHODS AND MATERIALS Nineteen endometrial cancer patients undergoing vaginal cuff brachytherapy for endometrial cancer were imaged with CT scanning prior to every HDR fraction (fractional re-imaging [FRI]). Dose to the bowel, bladder, and rectum were calculated and compared with the estimated dose if imaging and planning were done only on the first fraction (first fraction imaging [FFI]). RESULTS In the analysis of FFI versus FRI, we observed mean bladder doses of 8.34 Gy vs 8.33 Gy (P = .98), mean rectal doses of 12.19 Gy versus 12.14 Gy (P = .81), and mean bowel doses of 2.82 Gy versus 2.76 Gy (P = .81). The FFI approach underestimated the FRI doses to the bladder, rectum, and bowel by 20% or more in 11%, 5%, and 29% of patients, respectively. Cost analysis revealed an estimated

Impact of magnetic resonance imaging on computed tomography-based treatment planning and acute toxicity for prostate cancer patients treated with intensity modulated radiation therapy

663.06, or a 35% savings per patient treated with FFI. CONCLUSIONS There is no statistically significant difference in the mean dose to the bladder, rectum, or bowel in patients undergoing HDR vaginal cuff brachytherapy with a first fraction imaging scheme versus a fractional re-imaging scheme. These results indicate that fractional re-imaging is not necessary except in patients whose estimated dose to critical organs is near the maximum limit.

Comparing Central Nervous System (CNS) and Extra-CNS Hemangiopericytomas in the Surveillance, Epidemiology, and End Results Program Analysis of 655 Patients and Review of Current Literature

PURPOSE To evaluate rectal and bladder dosimetric and clinical acute toxicity endpoints for prostate patients treated with intensity modulated radiation therapy (IMRT) using magnetic resonance images (MRI) registered to computed tomographic (CT) simulation images versus CT alone. MATERIALS AND METHODS The charts of 155 consecutive prostate cancer patients at our institution from 2004 to 2008 were reviewed. A cohort of 15 IMRT treatment plans was created to compare dosimetric endpoints for CT-MRI vs CT alone. A subsequent clinical comparison involved 81 patients (CT-MRI [n = 28] vs CT alone [n = 53]). Acute genitourinary and rectal toxicity rates for the CT-MRI and CT cohorts were compared; also, univariate and multivariate regression analyses were performed using all major demographic, disease, and treatment factors as covariates. RESULTS Contoured prostate volumes were 43.0 vs 55.7 cm(3) (P < .001, n = 15) for CT-MRI vs CT definition, with significant reductions in all bladder dose endpoints and rectal V20, V30, and V70. Grades 0, 1, and 2 toxicity rates for CT-MRI (n = 28) vs CT (n = 53) were, respectively, 25%, 25%, and 50% vs 8%, 21%, and 72% (acute genitourinary [GU], P = .024) and 39%, 29%, and 32% vs 32%, 28%, and 40% (acute rectal, P = .495). On univariate regression, only MRI use and International Prostate Symptom Scores reached significance for acute GU toxicity. On multivariate regression, age, prostate volume, and MRI use reached statistical significance for acute GU toxicity. No factor reached significance for rectal toxicity. CONCLUSIONS This study demonstrates a statistically significant reduction in clinical acute GU toxicity with the clinical implementation of MRI in the treatment planning process.

Evaluating the special needs of the military for radiation biodosimetry for tactical warfare against deployed troops: comparing military to civilian needs for biodosimetry methods

Hemangiopericytomas (HPCs) are rare tumors in the central nervous system (CNS) and in extra‐CNS sites. The authors of this report used the Surveillance, Epidemiology, and End Results (SEER) Program to study prognostic factors in patients with HPC.

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

Abstract The aim of this paper is to delineate characteristics of biodosimetry most suitable for assessing individuals who have potentially been exposed to significant radiation from a nuclear device explosion when the primary population targeted by the explosion and needing rapid assessment for triage is civilians vs. deployed military personnel. The authors first carry out a systematic analysis of the requirements for biodosimetry to meet the military’s needs to assess deployed troops in a warfare situation, which include accomplishing the military mission. Then the military’s special capabilities to respond and carry out biodosimetry for deployed troops in warfare are compared and contrasted systematically, in contrast to those available to respond and conduct biodosimetry for civilians who have been targeted by terrorists, for example. Then the effectiveness of different biodosimetry methods to address military vs. civilian needs and capabilities in these scenarios was compared and, using five representative types of biodosimetry with sufficient published data to be useful for the simulations, the number of individuals are estimated who could be assessed by military vs. civilian responders within the timeframe needed for triage decisions. Analyses based on these scenarios indicate that, in comparison to responses for a civilian population, a wartime military response for deployed troops has both more complex requirements for and greater capabilities to use different types of biodosimetry to evaluate radiation exposure in a very short timeframe after the exposure occurs. Greater complexity for the deployed military is based on factors such as a greater likelihood of partial or whole body exposure, conditions that include exposure to neutrons, and a greater likelihood of combined injury. These simulations showed, for both the military and civilian response, that a very fast rate of initiating the processing (24,000 d−1) is needed to have at least some methods capable of completing the assessment of 50,000 people within a 2‐ or 6‐d timeframe following exposure. This in turn suggests a very high capacity (i.e., laboratories, devices, supplies and expertise) would be necessary to achieve these rates. These simulations also demonstrated the practical importance of the military’s superior capacity to minimize time to transport samples to offsite facilities and use the results to carry out triage quickly. Assuming sufficient resources and the fastest daily rate to initiate processing victims, the military scenario revealed that two biodosimetry methods could achieve the necessary throughput to triage 50,000 victims in 2 d (i.e., the timeframe needed for injured victims), and all five achieved the targeted throughput within 6 d. In contrast, simulations based on the civilian scenario revealed that no method could process 50,000 people in 2 d and only two could succeed within 6 d.

A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes

AbstractCurrent radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min−1. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.