D Parda

Patient dose and image quality from mega-voltage cone beam computed tomography imaging

The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo-voltage and mega-voltage cone-beam computed tomography (MV-CBCT), CT on rail or helical tomography. One of the attractive aspects of mega-voltage cone-beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega-voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV-CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a 20-cm-diam cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was 5-9 cGy and the maximum dose was between 9 and 17 cGy for our clinical MV-CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three-dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV-CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV-CBCT dose in the treatment planning process. The TPS-calculated doses agreed well with measurements for a wide range of imaging protocols.

A region growing method for tumor volume segmentation on PET images for rectal and anal cancer patients.

The application of automated segmentation methods for tumor delineation on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images presents an opportunity to reduce the interobserver variability in radiotherapy (RT) treatment planning. In this work, three segmentation methods were evaluated and compared for rectal and anal cancer patients: (i) Percentage of the maximum standardized uptake value (SUV% max), (ii) fixed SUV cutoff of 2.5 (SUV2.5), and (iii) mathematical technique based on a confidence connected region growing (CCRG) method. A phantom study was performed to determine the SUV% max threshold value and found to be 43%, SUV43% max. The CCRG method is an iterative scheme that relies on the use of statistics from a specified region in the tumor. The scheme is initialized by a subregion of pixels surrounding the maximum intensity pixel. The mean and standard deviation of this region are measured and the pixels connected to the region are included or not based on the criterion that they are greater than a value derived from the mean and standard deviation. The mean and standard deviation of this new region are then measured and the process repeats. FDG-PET-CT imaging studies for 18 patients who received RT were used to evaluate the segmentation methods. A PET avid (PETavid) region was manually segmented for each patient and the volume was then used to compare the calculated volumes along with the absolute mean difference and range for all methods. For the SUV43% max method, the volumes were always smaller than the PETavid volume by a mean of 56% and a range of 21%-79%. The volumes from the SUV2.5 method were either smaller or larger than the PETavid volume by a mean of 37% and a range of 2%-130%. The CCRG approach provided the best results with a mean difference of 9% and a range of 1%-27%. Results show that the CCRG technique can be used in the segmentation of tumor volumes on FDG-PET images, thus providing treatment planners with a clinically viable starting point for tumor delineation and minimizing the interobserver variability in radiotherapy planning.

IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging.

The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 degrees gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6 +/- 1.0 Gy for the bladder and comparable for the rectum (-0.3 +/- 1.4 Gy). In addition, an average mean dose increase of 1.9 +/- 0.8 Gy in the femoral heads and 1.7 +/- 0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3 +/- 1.5% and 2.4 +/- 2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows for daily treatment modifications where other volumetric tomographic imaging techniques may not be feasible and/or available and where accurate patient localization with a high degree of precision is required.

Dosimetric and technical aspects of intraoperative I-125 brachytherapy for stage I non-small cell lung cancer

Initial treatment outcome data from our institution for stage I non-small cell lung cancer (NSCLC) patients have shown that sublobar resection in combination with iodine-125 (I-125) brachytherapy is associated with recurrence rates of 2.0%, compared to 18.6% with sublobar resection alone. In this work, the technical and dosimetric aspects required to execute this procedure from the radiation oncology perspective as well as an analysis of the dose distributions of patients treated with this technique are presented. In this treatment technique, I-125 seeds in vicryl suture are embedded into vicryl mesh and surgically inserted providing a 2.0 cm margin on each side of the resection staple line. A nomogram is developed to determine the suture spacing in the vicryl mesh, as a function of seed activity in order to deliver 120 Gy at a distance of 0.5 cm above and below the seed array. Post-operative dosimetry consists of a CT-based planning and dose volume analysis. Dose distributions, dose volume histograms and mean dose data for lung are analysed in a group of patients. Dosimetric results show significant lung sparing with only a small volume of lung irradiated for all patients with mean lung dose values ranging from 1.5 Gy to 5.4 Gy. Lung brachytherapy with I-125 at the time of sublobar resection is a highly conformal option of dose delivery for stage I NSCLC patients with compromised physiologic reserve. Patient-related toxicity clinically measured by loss of pulmonary function and radiation-induced pneumonitis have not been linked to this procedure.

Breast conservation surgery and interstitial brachytherapy in the management of locally recurrent carcinoma of the breast: the Allegheny General Hospital experience.

PURPOSE To evaluate lumpectomy followed by interstitial brachytherapy as an acceptable salvage therapy for women who have developed localized recurrence of breast cancer after conservation surgery and postoperative external radiotherapy. METHODS AND MATERIALS Between 1/1998 and 10/2006, 21 patients with T0 or T1 in-breast recurrence of carcinoma were offered interstitial low-dose rate brachytherapy after tumor re-excision as an alternative to salvage mastectomy. All patients had failed lumpectomy followed by standard postoperative external beam radiotherapy (range, 5000-6040cGy) as treatment for the initial breast carcinoma. Seven recurred as ductal carcinoma in situ, 2 as infiltrating lobular carcinoma, and 12 as recurrent invasive carcinoma. The recurrent tumors were excised with final margins of resection free of residual disease per National Surgical Adjuvant Breast and Bowel Project definition. Tumor bed implantation was then carried out with an interstitial technique using (192)Ir with the target volume consisting of the tumor bed plus a minimum 1.0-cm clinical margin. The required minimum dose delivered to the target volume was 4500-5000cGy (range, 4500-5530). RESULTS Twenty of 21 patients were free of local disease with a median observation time of 40 months (range, 3-69). The single patient who developed a second local recurrence was treated successfully with simple mastectomy. Two patients succumbed to systemic disease at 17 and 24 months after salvage implant therapy. One patient developed a contralateral breast cancer. Cosmetic results defined by the National Surgical Adjuvant Breast and Bowel Project cosmesis scale were acceptable. One patient developed a localized seroma requiring multiple needle aspirations before complete resolution. Two patients developed localized skin breakdown in the tumor bed. One healed after 6 months of conservative treatment. The other healed 9 months later with Grade II cosmesis. This patient also developed a concurrent postoperative wound infection. CONCLUSIONS Repeat lumpectomy followed by brachytherapy is feasible and may be an acceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy; however, longer followup and greater patient numbers may be needed to better define the role of salvage brachytherapy.

Tolerance of the aorta using intraoperative iodine-125 interstitial brachytherapy in cancer of the lung

PURPOSE A retrospective review to assess the efficacy and morbidity of surgical resection and (125)I interstitial lung brachytherapy placed in approximation to the aorta. METHODS AND MATERIALS The records and postoperative films of 278 patients who had undergone intrathoracic (125)I brachytherapy at our institution were reviewed. All patients had undergone a gross total resection of a non-small-cell lung cancer using segmental resection, wedge resection, or sublobar resection. Frozen section margins of resection were required to be negative before the intraoperative delivery of the implant. Of those reviewed, 29 patients were implanted with (125)I impregnated Vicryl mesh that contacted greater than 50% with the aorta. Implants consisted of (125)I seeds sewn into a nomographically guided geometric array. Only implants where 50% or greater of the implant volume directly approximated the aorta were selected for inclusion into this study. The mean aortic volume receiving the entire prescribed dose was 17.2cc (mean surface area=34.4cm(2)) and the mean prescribed dose was 114Gy (range, 85-120) over the permanent life of the implant calculated by isodose curve distribution at a depth of 0.5cm from the plane of the implant. Five patients have received postoperative mediastinal dose supplementation with external beam irradiation to further address occult mediastinal nodal disease not revealed during the intraoperative frozen section analysis. RESULTS All patients tolerated the surgery and brachytherapy well with no perioperative mortality. With a median followup of 45.3 months (range, 1-117), 1 of the 29 patients suffered a fatal hemorrhage from suspected great vessel rupture. A review of this case demonstrated that the interstitial therapy had been supplemented with 4500cGy of external irradiation, which overlapped a small portion of the implant volume overlying the aorta. No other patients suffered even minor events referable to the implant and have continued to do well without symptomatic evidence of chronic sequelae as of the publication of this article or the time of their death. Local control has been achieved in all patients still living and had been achieved in all patients who died from subsequent progression of metastatic disease or other cause. CONCLUSIONS Interstitial (125)I intrathoracic brachytherapy is a safe and effective method when used with sublobar resection in high-risk stage I non-small-cell lung cancer patients and may be used even in situations that require placement of the sources in close approximation to the aorta. The tolerance of the aorta seems to be greater than previously thought, and may well exceed 12,000cGy over the permanent life of the interstitial implant. Interstitial (125)I brachytherapy can safely be used to deliver significant radiation dose in direct contact with the aorta but supplemental, overlapping external beam irradiation should be avoided.

Long-term Cosmesis After Lumpectomy and Brachytherapy in the Management of Carcinoma of the Previously Irradiated Breast

Objective:To evaluate the cosmetic outcome of brachytherapy after lumpectomy in the management of carcinoma of the previously irradiated breast. Materials and Methods:Between January 1998 and April 2008, 26 patients with TIS or T1 breast carcinoma were offered interstitial or intracavitary brachytherapy after lumpectomy in a previously irradiated breast as an alternative to salvage mastectomy. Twenty-five of 26 patients had prior lumpectomy followed by standard postoperative external beam radiotherapy for early stage carcinoma of the breast [dose range 5000–6040 cGy]. One patient developed breast cancer after full mantle irradiation [4500 cGy to the mediastinum and axillae] for Hodgkin Lymphoma 27 years earlier. All tumors were excised with final margins of resection free of disease per National Surgical Adjuvant Breast and Bowel Project definition. After lumpectomy, tumor bed implantation was carried out utilizing a low dose rate interstitial technique in 22 patients, whereas 3 patients were treated with high dose rate brachytherapy using the MammoSite brachytherapy catheter and 1 patient was treated with high dose rate brachytherapy using the Contura catheter. The low dose rate treatment consisted of 4500 to 5000 cGy at 35 to 50 cGy per hour to the tumor bed plus a 1.0 cm margin, whereas the high dose rate treatment consisted of 3400 cGy in twice daily fractions of 340 cGy currently used in National Surgical Adjuvant Breast and Bowel Project B-39. Cosmesis was graded according to the B-39 cosmesis scale for de novo treatments: grade I as excellent, grade II as good, Grade III as fair, and Grade IV as poor. Results:Eighteen patients were scored as grade I, 6 as grade II, and 2 as grade III. No patient received a Grade IV score. All 4 balloon brachytherapy patients were scored as Grade I. Twenty-five of 26 patients remained free of local failure with a median follow-up of 38 months (range 6–75 months). The only patient to develop a second local recurrence was graded as grade I before salvage mastectomy. Two patients developed wound dehiscence after immediate postlumpectomy implantation. Two have succumbed to metastatic breast carcinoma at 17 and 24 months after salvage implant therapy. An additional patient has succumbed to chronic obstructive pulmonary disease. All patients, regardless of cosmesis grade were satisfied with their decision for repeat conservation therapy. Factors affecting cosmesis were distance from the implant to the skin, the type of device used, and the amount of residual breast tissue after repeat lumpectomy. Conclusions:The cosmetic effect of brachytherapy after lumpectomy in the management of recurrent carcinoma of the previously irradiated breast is acceptable in highly selected patients. Intracavitary technique may provide superior cosmetic results for patients retreated with brachytherapy for salvage.

MATURE FOLLOW-UP FOR HIGH-RISK STAGE I NON-SMALL-CELL LUNG CARCINOMA TREATED WITH SUBLOBAR RESECTION AND INTRAOPERATIVE IODINE-125 BRACHYTHERAPY

PURPOSE To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative (125)I Vicryl mesh brachytherapy. METHODS AND MATERIALS Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of (125)I seeds along the resection line. The (125)I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. RESULTS The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm(2) (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. CONCLUSION (125)I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.

EUCLID: an outcome analysis tool for high-dimensional clinical studies

Treatment management decisions in three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) are usually made based on the dose distributions in the target and surrounding normal tissue. These decisions may include, for example, the choice of one treatment over another and the level of tumour dose escalation. Furthermore, biological predictors such as tumour control probability (TCP) and normal tissue complication probability (NTCP), whose parameters available in the literature are only population-based estimates, are often used to assess and compare plans. However, a number of other clinical, biological and physiological factors also affect the outcome of radiotherapy treatment and are often not considered in the treatment planning and evaluation process. A statistical outcome analysis tool, EUCLID, for direct use by radiation oncologists and medical physicists was developed. The tool builds a mathematical model to predict an outcome probability based on a large number of clinical, biological, physiological and dosimetric factors. EUCLID can first analyse a large set of patients, such as from a clinical trial, to derive regression correlation coefficients between these factors and a given outcome. It can then apply such a model to an individual patient at the time of treatment to derive the probability of that outcome, allowing the physician to individualize the treatment based on medical evidence that encompasses a wide range of factors. The softwares flexibility allows the clinicians to explore several avenues to select the best predictors of a given outcome. Its link to record-and-verify systems and data spreadsheets allows for a rapid and practical data collection and manipulation. A wide range of statistical information about the study population, including demographics and correlations between different factors, is available. A large number of one- and two-dimensional plots, histograms and survival curves allow for an easy visual analysis of the population. Several visual and analytical methods are available to quantify the predictive power of the multivariate regression model. The EUCLID tool can be readily integrated with treatment planning and record-and-verify systems.

A genetic algorithm for variable selection in logistic regression analysis of radiotherapy treatment outcomes

A given outcome of radiotherapy treatment can be modeled by analyzing its correlation with a combination of dosimetric, physiological, biological, and clinical factors, through a logistic regression fit of a large patient population. The quality of the fit is measured by the combination of the predictive power of this particular set of factors and the statistical significance of the individual factors in the model. We developed a genetic algorithm (GA), in which a small sample of all the possible combinations of variables are fitted to the patient data. New models are derived from the best models, through crossover and mutation operations, and are in turn fitted. The process is repeated until the sample converges to the combination of factors that best predicts the outcome. The GA was tested on a data set that investigated the incidence of lung injury in NSCLC patients treated with 3DCRT. The GA identified a model with two variables as the best predictor of radiation pneumonitis: the V30 (p=0.048) and the ongoing use of tobacco at the time of referral (p=0.074). This two-variable model was confirmed as the best model by analyzing all possible combinations of factors. In conclusion, genetic algorithms provide a reliable and fast way to select significant factors in logistic regression analysis of large clinical studies.