Nail melanoma in situ: clinical, dermoscopic, pathologic clues, and steps for minimally invasive treatment

BACKGROUND Nail unit melanoma (NUM) is a variant of acral lentiginous melanoma. The differential diagnosis is wide but an acquired brown streak in the nail of a fair-skinned adult person must be considered a potential melanoma. Dermoscopy helps clinicians to more accurately decide if a nail apparatus biopsy is necessary. OBJECTIVE Detailed evaluation of clinical and dermoscopy features and description of conservative surgery of in situ NUM. METHODS Retrospective study of in situ NUM diagnosed and treated with conservative surgical management in the authors' center from 2008 to 2013. RESULTS Six cases of NUM were identified: 2 male and 4 female patients, age range at diagnosis of 44 to 76 years. All patients underwent complete nail unit removal with at least 6-mm security margins around the anatomic boundaries of the nail. The follow-up varies from 4 to 62 months. CONCLUSION Nail unit melanomas pose a difficult diagnostic and therapeutic challenge. Wide excision is sufficient, whereas phalanx amputation is unnecessary and associated with significant morbidity for patients with in situ or early invasive melanoma. Full-thickness skin grafting or second-intention healing after total nail unit excision is a simple procedure providing a good functional and cosmetic outcome.

Radiation dose in pneumatic reduction of ileo-colic intussusceptions--results from a single-institution study

BACKGROUND Air enema under fluoroscopy is a well-accepted procedure for the treatment of childhood intussusception. However, the reported radiation doses of pneumatic reduction with conventional fluoroscopy units have been high in decades past. OBJECTIVE To compare current radiation doses at our institution to past doses reported by others for fluoroscopic-guided pneumatic reduction of ileo-colic intussusception in children. MATERIALS AND METHODS Since 2007 radiologists and residents in our department who perform reduction of intussusceptions have received a radiation risk training. We retrospectively analyzed the data of 45 children (5 months-8 years) who underwent a total of 48 pneumatic reductions of ileo-colic intussusception between 2008 and 2012. We analyzed data for screening time and dose area product (DAP) and compared these data to those reported up to and including the year 2000. RESULTS Our mean screening time measured by the DAP-meter was 53.8 s (range 1-320 s, median 33.0 s). The mean DAP was 11.4 cGy ∙ cm(2) (range 1-145 cGy ∙ cm(2), median 5.45 cGy ∙ cm(2)). There was one bowel perforation, in a 1-year-old boy requiring surgical revision. Only three studies in the literature presented radiation exposure results on children who received pneumatic or hydrostatic reduction of intussusception under fluoroscopy. Screening times and dose area products in those studies, which were published in the 1990 s and in the year 2000, were substantially higher than those in our sample. CONCLUSION Low-frequency pulsed fluoroscopy and other dose-saving keys as well as the radiation risk training might have helped to improve the quality of the procedure in terms of radiation exposure.

Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ

BACKGROUND Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Robustness of the Voluntary Breath-Hold Approach for the Treatment of Peripheral Lung Tumors Using Hypofractionated Pencil Beam Scanning Proton Therapy.

PURPOSE The safe clinical implementation of pencil beam scanning (PBS) proton therapy for lung tumors is complicated by the delivery uncertainties caused by breathing motion. The purpose of this feasibility study was to investigate whether a voluntary breath-hold technique could limit the delivery uncertainties resulting from interfractional motion. METHODS AND MATERIALS Data from 15 patients with peripheral lung tumors previously treated with stereotactic radiation therapy were included in this study. The patients had 1 computed tomographic (CT) scan in voluntary breath-hold acquired before treatment and 3 scans during the treatment course. PBS proton treatment plans with 2 fields (2F) and 3 fields (3F), respectively, were calculated based on the planning CT scan and subsequently recalculated on the 3 repeated CT scans. Recalculated plans were considered robust if the V95% (volume receiving ≥95% of the prescribed dose) of the gross target volume (GTV) was within 5% of what was expected from the planning CT data throughout the simulated treatment. RESULTS A total of 14/15 simulated treatments for both 2F and 3F met the robustness criteria. Reduced V95% was associated with baseline shifts (2F, P=.056; 3F, P=.008) and tumor size (2F, P=.025; 3F, P=.025). Smaller tumors with large baseline shifts were also at risk for reduced V95% (interaction term baseline/size: 2F, P=.005; 3F, P=.002). CONCLUSIONS The breath-hold approach is a realistic clinical option for treating lung tumors with PBS proton therapy. Potential risk factors for reduced V95% are small targets in combination with large baseline shifts. On the basis of these results, the baseline shift of the tumor should be monitored (eg, through image guided therapy), and appropriate measures should be taken accordingly. The intrafractional motion needs to be investigated to confirm that the breath-hold approach is robust.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION ISRCTN71502099 on 19 May 2014.

Feasibility of stereotactic MRI-based image guidance for the treatment of vascular malformations: a phantom study.

PURPOSE Treatment of vascular malformations requires the placement of a needle within vessels which may be as small as 1 mm, with the current state of the art relying exclusively on two-dimensional fluoroscopy images for guidance. We hypothesize that the combination of stereotactic image guidance with existing targeting methods will result in faster and more reproducible needle placements, as well as reduced radiationexposure, when compared to standard methods based on fluoroscopy alone. METHODS The proposed navigation approach was evaluated in a phantom experiment designed to allow direct comparison with the conventional method. An anatomical phantom of the left forearm was constructed, including an independent control mechanism to indicate the attainment of the target position. Three interventionalists (one inexperienced, two of them frequently practice the conventional fluoroscopic technique) performed 45 targeting attempts utilizing the combined and 45 targeting attempts utilizing the standard approaches. RESULTS In all 45 attempts, the users were able to reach the target when utilizing the combined approach. In two cases, targeting was stopped after 15 min without reaching the target when utilizing only the C-arm. The inexperienced user was faster when utilizing the combined approach and applied significantly less radiation than when utilizing the conventional approach. Conversely, both experienced users were faster when using the conventional approach, in one case significantly so, with no significant difference in radiation dose when compared to the combined approach. CONCLUSIONS This work presents an initial evaluation of a combined navigation fluoroscopy targeting technique in a phantom study. The results suggest that, especially for inexperienced interventionalists, navigation may help to reduce the time and the radiation dose. Future work will focus on the improvement and clinical evaluation of the proposed method.

A novel treatment planning methodology for high dose 166Ho-DOTMP therapy in patients with multiple myeloma

Bone marrow ablation, i.e., the complete sterilization of the active bone marrow, followed by bone marrow transplantation (BMT) is a comment treatment of hematological malignancies. The use of targeted bone-seeking radiopharmaceuticals to selectively deliver radiation to the adjacent bone marrow cavities while sparing normal tissues is a promising technique. Current radiopharmaceutical treatment planning methods do not properly compensate for the patient-specific variable distribution of radioactive material within the skeleton. To improve the current method of internal dosimetry, novel methods for measuring the radiopharmaceutical distribution within the skeleton were developed. 99mTc-MDP was proven as an adequate surrogate for measuring 166Ho-DOTMP skeletal uptake and biodistribution, allowing these measures to be obtained faster, safer, and with higher spatial resolution. This translates directly into better measurements of the radiation dose distribution within the bone marrow. The resulting bone marrow dose-volume histograms allow prediction of the patient disease response where conventional organ scale dosimetry failed. They indicate that complete remission is only achieved when greater than 90% of the bone marrow receives at least 30 Gy. ^ Comprehensive treatment planning requires combining target and non-target organ dosimetry. Organs in the urinary tract were of special concern. The kidney dose is primarily dependent upon the mean transit time of 166 Ho-DOTMP through the kidney. Deconvolution analysis of renograms predicted a mean transit time of 2.6 minutes for 166Ho-DOTMP. The radiation dose to the urinary bladder wall is dependent upon numerous factors including patient hydration and void schedule. For beta-emitting isotopes such as 166Ho, reduction of the bladder wall dose is best accomplished through good patient hydration and ensuring a partially full bladder at the time of injection. Encouraging the patient to void frequently, or catheterizing the patient without irrigation, will not significantly reduce the bladder wall dose. ^ The results from this work will produce the most advanced treatment planning methodology for bone marrow ablation therapy using radioisotopes currently available. Treatments can be tailored specifically for each patient, including the addition of concomitant total body irradiation for patients with unfavorable dose distributions, to deliver a desired patient disease response, while minimizing the dose or toxicity to non-target organs. ^

4HPR-X radiation mechanisms of interactions in non-small cell lung cancer (NSCLC) cells in vitro

Lung cancer is the leading cause of cancer death. However, poor survival using conventional therapies fuel the search for more rational interventions. The objective of this study was to design and implement a 4HPR-radiation interaction model in NSCLC, employing a traditional clinical modality (radiation), a relatively new, therapeutically unexplored agent (4HPR) and rationally combining them based on molecular mechanistic findings pertaining to their interactions. To test the hypothesis that 4HPR sensitizes cells to radiation-induced cell death via G2+M accumulation, we designed a working model consisting of H522 adenocarcinoma cells (p53, K-ras mutated) derived from an NSCLC patient; 4HPR at concentrations up to 10 μM; and X radiation up to 6 Gy generated by a patient-dedicated Phillips RT-250 X ray unit at 250 KV, 15 mA, 1.85 Gy/min. We found that 4HPR produced time- and dose-dependent morphological changes, growth inhibition, and DNA damage-inducing enhancement of reactive oxygen species. A transient G2+M accumulation of cells maximal at 24 h of continuous 4HPR exposure was used for irradiation time scheduling. Our data demonstrated enhanced cell death (both apoptotic and necrotic) in irradiated cells pre-treated with 4HPR versus those with either stressor alone. 4HPR's effect of increased NSCLC cells' radioresponse was confirmed by clonogenic assay. To explore these practical findings from a molecular mechanistic perspective, we further investigated and showed that levels of cyclin B1 and p34cdc2 kinase—both components of the mitosis promoting factor (MPF) regulating the G2/M transition—did not change following 4HPR treatment. Likewise, cdc25C phosphatase was not altered. However, enhanced p34cdc2 phosphorylation on its Thr14Tyr15 residues—indicative of its inactivation and increased expression of MPF negative regulators chk1 and wee1 kinases—were supportive of explaining 4HPR-treated cells' accumulation. Hence, p34cdc2 phosphorylation, chk1, and wee1 warrant further evaluation as potential molecular targets for 4HPR-X radiation combination. In summary, we (1) demonstrated that 4HPR not only induces cell death by itself, but also increases NSCLC cells' subsequent radioresponse, indicative of potential clinical applicability, and (2) for the first time, shed light on deciphering 4HPR-X radiation molecular mechanisms of interaction, including the finding of 4HPR's role as a p34cdc2 inactivator via Thr14Tyr15 phosphorylation. ^

Maternal ingestion of radon-222 in drinking water and the absorbed radiation dose to the embryo

Maternal ingestion of high concentrations of radon-222 (Rn-222) in drinking during pregnancy may pose a significant radiation hazard to the developing embryo. The effects of ionizing radiation to the embryo and fetus have been the subject of research, analyses, and the development of a number of radiation dosimetric models for a variety of radionuclides. Currently, essentially all of the biokinetic and dosimetric models that have been developed by national and international radiation protection agencies and organizations recommend calculating the dose to the mother's uterus as a surrogate for estimating the dose to the embryo. Heretofore, the traditional radiation dosimetry models have neither considered the embryo a distinct and rapidly developing entity, the fact that it is implanted in the endometrial layer of the uterus, nor the physiological interchanges that take place between maternal and embryonic cells following the implantation of the blastocyst in the endometrium. The purpose of this research was to propose a new approach and mathematical model for calculating the absorbed radiation dose to the embryo by utilizing a semiclassical treatment of alpha particle decay and subsequent scattering of energy deposition in uterine and embryonic tissue. The new approach and model were compared and contrasted with the currently recommended biokinetic and dosimetric models for estimating the radiation dose to the embryo. The results obtained in this research demonstrate that the estimated absorbed dose for an embryo implanted in the endometrial layer of the uterus during the fifth week of embryonic development is greater than the estimated absorbed dose for an embryo implanted in the uterine muscle on the last day of the eighth week of gestation. This research provides compelling evidence that the recommended methodologies and dosimetric models of the Nuclear Regulatory Commission and International Commission on Radiological Protection employed for calculating the radiation dose to the embryo from maternal intakes of radionuclides, including maternal ingestion of Rn-222 in drinking water would result in an underestimation of dose. ^

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity. ^

Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. ^ The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. ^ The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only weakly on uncertainties in the risk model and inter-patient variations. Second cancer risks were sensitive to changes in the RBE of neutrons. However, the findings of the study were qualitatively consistent for all patient sizes and risk models considered, and for all neutron RBE values less than 100. ^

Racial/ethnic differences in factors influencing screening and treatment among prostate cancer patients

Background. Racial/ethnic differences have been found in various aspects of cancer care. But a limited number of studies have examined the racial/ethnic differences in predictors of prostate-specific antigen (PSA) screening in a group of prostate cancer patients and have attempted to identify the racial/ethnic differences in treatment discussions, treatment choice and treatment received for organ-confined localized prostate cancer (PCa) among three major racial/ethnic groups of the USA. This study was conducted to redress this lack of information. ^ Methods. This study was conducted on a group of 935 prostate cancer patients representing all three major race/ethnic groups (Whites, African Americans and Hispanics) who were treated at various medical institutes of the Texas Medical Center, Houston between 1996 and 2004 to identify the racial/ethnic differences in predictors of PSA screening. A subset of 640 patients who had organ-confined localized prostate cancer was selected to examine the racial/ethnic differences in treatment discussions, treatment choice and treatment received for their localized prostate cancer. They were interviewed by trained research interviewers of MD Anderson Cancer Center using a validated structured questionnaire. ^ Results. The results showed that African American (54.4%) and Hispanic patients (42.3%) were significantly less likely (p=0.004 and p<.001, respectively) than White patients (63.2%) to report having had PSA screening before their prostate-cancer diagnosis. Among Whites, only education and annual check-ups predicted the use of PSA screening, whereas in African Americans two more additional factors, marital status and bode-mass index (BMI), significantly predicted PSA screening. Among Hispanics, like two other groups, education and annual check-ups also appeared as a significant predictor of PSA screening. ^ Results from multivariable logistic regression showed that African American patients were 15% less likely (OR=0.85, 95% CI=0.61-1.17, p=0.32) and Hispanics patients were 40% less likely (OR=0.60, 95% CI=0.41-0.87, p=0.008) to undergo PSA screening than Whites after adjusting for education and age at diagnosis for African Americans, and for education, annual check-ups and age at diagnosis for Hispanics. ^ This study revealed that health professionals were less likely to discuss surgery (79.9% vs. 93.2%) and watchful waiting (27.9% vs. 43.9%) with Hispanics compared to Whites. African Americans were more likely to choose (35.1% vs. 27.7%) and receive radiation therapy (38.3% vs.31.4%) than Whites. A comparison of concordance between treatment choice and treatment received showed that the highest concordance was found for watchful waiting and radiation therapy among African Americans (100% and 85.9%, respectively) whereas the highest concordance (96.9%) was found for surgery among Hispanics. ^ Conclusions. In this multiethnic study, the rates of PSA screening and its potential predictors varied by racial/ethnic groups. Substantial racial/ethnic variations were also found in treatment discussion, but the differences were not evident for treatment choice and treatment received. Health-education programs and culturally appropriate educational outreach efforts, especially targeted for high-risk groups, are needed to reduce these disparities. In the current climate of uncertainty about the benefits of PSA screening, or the benefit of one treatment over others, men should have access to information and services regardless of race/ethnicity so that they can make informed decisions. Further in-depth studies are needed in other settings to confirm these findings with the goal of developing an intervention to address these concerns. ^

Near infra-red-activatable nanocarriers for selective cancer diagnosis and treatment

Standard treatment strategies for cancer patients include surgery, radiation therapy, and chemotherapy. Although these strategies have been proven effective, they also have associated limitations. An attractive and innovative approach that can be used alone or in combination with the above modalities is based on the systemic or topical administration of a nanomaterial-based photoactive compound. Interaction with light in the near infrared (NIR) region results in either emission of fluorescence, which can be used for photodetection, or absorption of light which results in phototherapy. Nanomaterials have the advantage of providing multi-functional and unique properties in a single device that cannot be readily acquired with conventional small molecular weight compounds. ^ In this study, three different novel nanocarrier systems were designed and evaluated in mediating photodetection and phototherapy in the NIR. The first compound synthesized was a dual-labeled magnetic resonance/optical imaging agent for sentinel lymph node mapping and biopsy. This dual-labeled agent combines the high resolution of magnetic resonance imaging with the highly sensitive detection of optical imaging. The second imaging agent was an activatable optical imaging agent used to monitor cathepsin B activity in vivo and to probe the degradation of poly(L-glutamic acid). This polymeric nanocarrier offers highly sensitive technique for the detection of enzymatic activity, with is not yet possible with small molecular weight compounds. The third agent was a C225-conjugated hollow nanoshell that is targeted to epidermal growth factor receptors. This targeting agent has been demonstrated to mediate photothermal therapy both in vitro and in vivo. ^ These nanocarrier systems are an invaluable tool for the detection of cancer and many other diseases. With improved targeted delivery of these agents, the ability to diagnose diseases will become more sensitive and more specific. Finally, when designed properly, these agents would allow concurrent diagnosis and treatment of patients of various diseases. ^

Ethnic differences in tumor characteristics, treatment and survival in glioma patients

Purpose. A descriptive analysis of glioma patients by race was carried out in order to better elucidate potential differences between races in demographics, treatment, characteristics, prognosis and survival. ^ Patients and Methods. Among 1,967 patients ≥ 18 years diagnosed with glioma seen between July 2000 and September 2006 at The University of Texas M.D. Anderson Cancer Center (UTMDACC). Data were collated from the UTMDACC Patient History Database (PHDB) and the UTMDACC Tumor Registry Database (TRDB). Chi-square analysis, uni- /multivariate Cox proportional hazards modeling and survival analysis were used to analyze differences by race. ^ Results. Demographic, treatment and histologic differences exist between races. Though risk differences were seen between races, race was not found to be a significant predictor in multivariate regression analysis after accounting for age, surgery, chemotherapy, radiation, tumor type as stratified by WHO tumor grade. Age was the most consistent predictor in risk for death. Overall survival by race was significantly different (p=0.0049) only in low-grade gliomas after adjustment for age although survival differences were very slight. ^ Conclusion. Among this cohort of glioma patients, age was the strongest predictor for survival. It is likely that survival is more influenced by age, time to treatment, tumor grade and surgical expertise rather than racial differences. However, age at diagnosis, gender ratios, histology and history of cancer differed significantly between race and genetic differences to this effect cannot be excluded. ^

AN INVESTIGATION OF THE MODIFYING EFFECTS OF VITAMIN A AND HYPOXIC CELL SENSITIZERS IN RADIATION CARCINOGENESIS IN MICE

The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed.^ In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. The circulating level of plasma vitamin A in all four groups of mice was monitored. A difference in circulating vitamin A in the mice maintained on high and low vitamin A diet became evident by 20 weeks and continued for the duration of the experiment. Mice were killed 18, 26, and 40 weeks post irradiation, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet (p < 0.05). Under the conditions of this experiment the development of pulmonary adenomas in irradiated strain A mice appears to relate directly to circulating levels of vitamin A.^ In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2mg/g and 0.6mg/g, were used either alone or in combination with 900 rad of gamma radiation in a fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p < 0.10) in the higher dose group (0.6mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group. Thus, under the experimental exposure conditions used in this investigation, which were very similar to the exposure conditions occurring in clinical treatment, all three hypoxic cell sensitizers did not sensitize the mouse to the carcinogenic effects of gamma radiation.^