Use of lung treatment plans to evaluate DIR algorithms.

The purpose of the study is to evaluate the accuracy of two deformable image registration algorithms by examining their influence on the dose summation results obtained using 4DCT (four dimensional computed tomography) dose distributions based on '4D' planned and '4D optimal' IMRT (intensity modulated radiation therapy) plans. For ten lung cancer patients, 4D step and shoot IMRT plans were produced. The breathing cycle was divided into ten parts and for each part a set of CT images was acquired. For each patient the treatment plan was copied to the CTs of each phase and subsequently recalculated. Each phase CT was then registered to the average intensity projection (AIP) CT using a deformable image registration (DIR) algorithm and the composite dose distribution was then calculated by summing up the deformed dose distributions from all the phases ('4D' treatment plan). The '4D optimal' treatment plan was created by producing an optimal plan on the CTs of each phase of the respiratory cycle and summing up the deformed dose distributions from all the phases. The results indicate that it is possible to map the dose distributions of different breathing phases in lung using DIR, and that different DIR methods and target characteristics (motion amplitude, size, location) affect the differences between original plan, '4D' and '4D optimal' dose distributions. Although the '4D optimal' plans were designed to achieve 95% target coverage, both of the used DIR methods failed to translate that coverage in some instances. The same variation between these methods was also observed in the '4D' plan comparison. This study shows that it is feasible to perform an acceptably accurate calculation of the composite deformed dose. However, it is important to account for tumor motion and body deformation especially when the tumor volume is small and/or located in the lower lobe of the lung.

Treatment and Outcomes of Primary Urethra Cancer.

BACKGROUND: Urethral cancer is a rare malignancy, representing <1% of all malignancies. Optimal management, due to its rarity, presents as a treatment dilemma for physicians. There is a lack of consensus regarding treatment as large randomized trials cannot be performed; thus, optimal management decisions rely on study of retrospective cases. This is a review of our institutional experience with urethral cancer treated with various treatment modalities. METHODS: A retrospective chart review was performed on 31 patients treated for primary cancer of the urethra from 1958 to 2008. The patients were stratified by sex, histologic type, stage, date of diagnosis, type of treatment, and last follow-up. Early stage cases were designated as Tis-T2N0M0 and advanced cases were designated as T3-4, N+ or M+. Analysis was performed based on clinical stage, treatment modalities and outcomes. RESULTS: Fourteen early stage cases and 17 advanced stage cases of urethral cancer were analyzed. The majority of early stage cases occurred in men (M:F=8:6) and the majority of advanced stage cases occurred in women (M:F=5:12). The most common histology was squamous cell carcinoma for both early and advanced stage cases. Surgery was the preferred modality of treatment for early stage cases (surgery used in 13 cases vs. chemo/radiotherapy used in 1 case) while for advanced cases, radiation ±chemotherapy was commonly used. Overall survival for this series was 45% at mean follow-up of 7 years. Eight of the 14 cases of early stage cancer remained disease free at last follow-up. Comparatively, only 5 of 17 with advanced cancers had no apparent disease at last follow-up. All but one of those patients were treated with combined modality therapy. CONCLUSIONS: Patients with early stage urethral cancers do well with single modality therapy, whereas patients who present with advanced cancers may benefit from combined modality therapy. More extensive study is required to recommend a particular treatment protocol. However, in this rare malignancy, institutional experiences provide the best evidence currently due to the lack of multi-institutional trials.

Persistent Disparities in Hispanics with Cervical Cancer in a Major City.

OBJECTIVES: Despite an overall improvement in cervical cancer screening, incidence, and mortality rates for minorities in the USA, regional differences in screening and stage at presentation have been observed. This study evaluated cervical cancer disparities in a predominately Hispanic population treated in a major treatment center in San Antonio, Texas. METHODS AND MATERIALS: Data on 446 patients with cervical cancer treated between 2000 and 2011 at the Cancer Therapy and Research Center in San Antonio, Texas, were reviewed. Sufficient information was obtained on 319 patients and was compared with the Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: Of 319 patients treated for cervical cancer between 2000 and 2011, 209 were Hispanics and 110 were Whites (82), Blacks (20), Asians (7), and others (1). The median and mean ages at diagnosis were 47 and 49, respectively. Only 36 % were known to have screening Pap tests prior to diagnosis, of which only 24 had yearly Pap tests. Forty-two patients (20 %) of those with no known screening Pap tests presented with stage IV disease at diagnosis (vs. 3 % of those with known Pap tests). Among the Hispanics, 68 % presented with regional disease (vs. 37 % SEER) and 46 % were stage III or higher disease, with stage IIIB accounting for 30 % of total. Although the overall age-adjusted death rates were higher in Hispanics due to a higher percentage of more advanced disease, survival rates appear similar, stage for stage, to the SEER data. CONCLUSION: Even in a major city, Hispanics often present with more advanced cervical cancer than the general population. In order to minimize the cervical cancer disparities, efforts and strategies are needed to study the cultural and locale effects and to implement preventive measures and adaptive health education.

Assessment of Lung Tumour Motion and Volume Size Dependencies Using Various Evaluation Measures.

The purpose of the study was to assess internal target volume changes through the breathing cycle and associated tumour motion for lung patients and to establish possible correlations between different parameters. Respiration-induced volume changes with breathing cycle and the associated tumour motion were analyzed for 11 patients. Selected phases were the maximum and average intensity projections and the 10 phases of equal duration and separation obtained through the respiratory cycle. Tumour centre of mass (COM) motion planes were generated using least square fitting, and their angles and orientations were then compared between the cases studied. Trajectories that are composed by the points of COM location in different phases were identified, and their interrelation was assessed through different similarity measures. The results were used to determine if there is any correlation between parameters chosen and if the margins conventionally used for the planning target volume creation successfully encompassed lung tumour motion and volume change. The results show that the extent of tumour motion was related to its volume and location. The tumour displacement was predominantly left and inferior. Planar fitting to COM motion data through respiratory phases demonstrated some correlation in best fit motion plane positions between different data sets. In the plane fit comparison, for each patient, the lower root mean square error values showed that a good planar fit can be achieved for the COM motion path. The evaluation of the inhale and exhale trajectories may allow, for certain tumour locations and size, contouring on only inhalation or exhalation phases, knowing that tumour motion will be adequately covered on the other phases. Taking all the data into account and knowing the tumour size and location, a good estimate can be made of the motion plane position in the three-dimensional space and the required dosimetric margins.

Trehalose uptake through P2X7 purinergic channels provides dehydration protection.

The tetra-anionic form of ATP (ATP4-) is known to induce monovalent and divalent ion fluxes in cells that express purinergic P2X7 receptors and with sustained application of ATP it has been shown that dyes as large as 831 Da can permeate the cell membrane. The current study explores the kinetics of loading alpha,alpha-trehalose (342 Da) into ATP stimulated J774.A1 cells, which are known to express the purinergic P2X7 receptor. Cells that were incubated at 37 degrees C in a 50 mM phosphate buffer (pH 7.0) containing 225 mM trehalose and 5 mM ATP, were shown to load trehalose linearly over time. Concentrations of approximately 50 mM were reached within 90 min of incubation. Cells incubated in the same solution at 4 degrees C loaded minimally, consistent with the inactivity of the receptor at low temperatures. However, extended incubation at 37 degrees C (>60 min) resulted in zero next-day survival, with adverse effects appearing even with incubation periods as short as 30 min. By using a two-step protocol with a short time period at 37 degrees C to allow pore formation, followed by an extended loading period on ice, cells could be loaded with up to 50 mM trehalose while maintaining good next day recovery (49 +/- 12% by Trypan blue exclusion, 56 +/- 20% by alamarBlue assay). Cells porated by this method and allowed an overnight recovery period exhibited improved dehydration tolerance suggesting a role for ATP poration in the anhydrous preservation of cells.