John E. McGary

Intensity modulated radiation therapy (IMRT) following prostatectomy: more favorable acute genitourinary toxicity profile compared to primary IMRT for prostate cancer

PURPOSE To report our initial experience on postprostatectomy IMRT (PPI), addressing acute genitourinary (GU) toxicity in comparison to primary IMRT (PI) for prostate cancer. METHODS AND MATERIALS From April 1998 to December 1999, 40 postprostatectomy patients were treated with intensity modulated radiation therapy (IMRT) to a median prescribed dose of 64 Gy (mean dose of 69 Gy). The Radiation Therapy Oncology Group (RTOG) scoring system was used to assess acute GU toxicity. Target volume and maximum and mean doses were evaluated. The mean doses to the bladder and irradiated bladder volume receiving >65 Gy were assessed. These were compared to those of 125 patients treated with PI to a prescribed dose of 70 Gy (mean dose of 76 Gy). RESULTS The acute GU toxicity profile is more favorable in the PPI group with 82.5% of Grade 0-1 and 17.5% of Grade 2 toxicity compared to 59.2% and 40.8%, respectively, in the PI group (p < 0.001). There was no Grade 3 or higher toxicity in either group. The target volume was larger in the PPI group, while the maximum and mean doses to the target were higher in the PI group. The mean dose delivered to the bladder was higher in the PPI group. The irradiated bladder volume receiving >65 Gy was significantly larger in the PI group (p < 0.001). CONCLUSIONS PPI can be delivered with acceptable ute GU toxicity. The larger PPI target volume may be related to the difficulty in delineating prostatic fossa. Despite a larger target volume and a higher mean dose to the bladder, PPI produced a more favorable acute GU toxicity profile. This may be related to a combination of lower mean and maximum doses and smaller bladder volumes receiving >65 Gy in the PPI group, as well as urethral rather than bladder irradiation. The findings have implications in the evaluation of IMRT treatment plan for prostate cancer, whereby the irradiated bladder volumes above 65 Gy may be more meaningful than the mean dose to the bladder. Longer term toxicity results are awaited.

The Use of Rectal Balloon During the Delivery of Intensity Modulated Radiotherapy (imrt) for Prostate Cancer: More Than Just a Prostate Gland Immobilization Device?

PURPOSEThe purpose of this study was to investigate the role of a rectal balloon for prostate immobilization and rectal toxicity reduction in patients receiving dose-escalated intensity-modulated radiotherapy for prostate cancer. PATIENTS AND METHODSPatients with localized prostate cancer who were undergoing intensity-modulated radiotherapy were treated in a prone position, immobilized with a customized Vac-Lok bag (MED-TEC, Orange City, IA). A rectal balloon with 100 cc of air was used to immobilize the prostate. The prostate displacements were measured using computed tomography (CT)-CT fusion on 10 patients who received radioactive seed implant before intensity-modulated radiotherapy. They were scanned twice weekly during 5 weeks of intensity-modulated radiotherapy, and breathing studies were also performed. Rectal toxicity was evaluated by use of Radiation Therapy Oncology Group scoring in 100 patients. They were treated to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). Dose-volume histogram of the rectum was assessed. A film phantom was constructed to simulate the 4-cm diameter air cavity that was created by the rectal balloon. Kodak XV2 films (Rochester NY) were used to measure and compare dose distribution with and without the air cavity. A fraction of 1.25 Gy was delivered to the phantom at isocenter with 15-MV photons by use of the NOMOS Peacock system and the MIMiC treatment delivery system (Sewickley, PA). RESULTSThe anterior-posterior and lateral prostate displacements were minimal, on the order of measurement uncertainty (∼1 mm). The standard deviation of superior-inferior displacement was 1.78 mm. Breathing studies showed no organ displacement during normal breathing when the rectal balloon was in place. The rectal toxicity profile was very favorable: 83% (83/100) patients had no rectal complaint, and 11% and 6% had grade 1 and 2 toxicity, respectively. Dose-volume histogram analysis revealed that in all of the patients, no more than 25% of the rectum received 70 Gy or greater. As visualized by film dosimetry, the dose at air-tissue interface was approximately 15% lower than that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, the differential was approximately 8% and 5%, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal, with or without the air cavity. DISCUSSIONThe use of a rectal balloon during intensity-modulated radiotherapy significantly reduces prostate motion. Prostate immobilization thus allows a safer and smaller planning target volume margin. It has also helped spare the anterior rectal wall (by its dosimetric effects) and reduced the rectal volume that received high-dose radiation (by rectal wall distension). All these factors may have further contributed to the decreased rectal toxicity achieved by intensity-modulated radiotherapy, despite dose escalation and higher-than-conventional fraction size.

Prostate immobilization using a rectal balloon

We use a rectal balloon for prostate immobilization during intensity modulated radiotherapy (IMRT) prostate treatment. To improve the accuracy of our prostate planning target volume, we have measured prostate displacements using computed tomography (CT)‐CT fusion on patients that previously received gold seed implants. The study consists of ten patients that were scanned twice per week during the course of IMRT treatment. In addition to biweekly scans, breathing studies were performed on each patient to estimate organ motion during treatment. The prostate displacement in the anterior‐posterior and the lateral direction is minimal, on the order of measurement uncertainty (~1mm). The standard deviation of the superior‐inferior (SI) displacements is 1.78 mm. The breathing studies show that no organ displacement was detected during normal breathing conditions with a rectal balloon. PACS number(s): 87.53.–j, 87.90.+y

CLINICAL EXPERIENCE WITH INTENSITY-MODULATED RADIATION THERAPY (IMRT) FOR PROSTATE CANCER WITH THE USE OF RECTAL BALLOON FOR PROSTATE IMMOBILIZATION

The implementation of intensity-modulated radiation therapy (IMRT) is the result of advances in imaging, radiotherapy planning technologies, and computer-controlled linear accelerators. IMRT allows both conformal treatment of tumors and conformal avoidance of the surrounding normal structures. The first patient treated with Peacock IMRT at Baylor College of Medicine took place in March 1994. To date, more than 1500 patients have been treated with IMRT; more than 700 patients were treated for prostate cancer. Our experience in treating prostate cancer with IMRT was reviewed. Patient and prostate motions are important issues to address in delivering IMRT. The Vac-Lok bag-and-box system, as well as rectal balloon for immobilization of patient and prostate gland, respectively, are employed. Treatment planning also plays a very important role. IMRT as a boost after conventional external beam radiotherapy is not our treatment strategy. To derive maximal benefits with this new technology, all patients received full course IMRT. Three separate groups of patients receiving (1) primary IMRT, (2) combined radioactive seed implant and IMRT, and (3) post-prostatectomy IMRT were addressed. Overall, toxicity profiles in these patients were very favorable. IMRT has the potential to improve treatment outcome with dose escalation while minimizing treatment-related toxicity.

IMRT for prostate cancer : defining target volume based on correlated pathologic volume of disease

PURPOSE The intensity-modulated radiation therapy (IMRT) treatment planning system generates tightly constricted isodose lines. It is very important to define the margins that are acceptable in the treatment of prostate cancer to maximize the dose escalation and normal tissue avoidance advantages offered by IMRT. It is necessary to take into account subclinical disease and the potential for extracapsular spread. Organ and patient motion as well as setup errors are variables that must be minimized and defined to avoid underdosing the tumor or overdosing the normal tissues. We have addressed these issues previously. The purpose of the study was twofold: to quantify the radial distance of extracapsular extension in the prostatectomy specimens, and to quantify differences between the pathologic prostate volume (PPV), CT-based gross tumor volume (GTV), and planning target volume (PTV). MATERIALS AND METHODS Two related studies were undertaken. A total of 712 patients underwent prostatectomy between August 1983 and September 1995. Pathologic assessment of the radial distance of extracapsular extension was performed. Shrinkage associated with fixation was accounted for with a linear shrinkage factor. Ten patients had preoperative staging studies including a CT scan of the pelvis. The GTV was outlined and volume determined from these CT scans. The PTV, defined as GTV with a 5-mm margin in all dimensions, was then calculated. The Peacock inverse planning system (NOMOS Corp., Sewickley, PA) was used. The PPV, GTV, and PTV were compared for differences and evaluated for correlation. RESULTS Extracapsular extension (ECE) (i.e., prostatic capsular invasion level 3 [both focal and established]) was found in 299 of 712 patients (42.0%). Measurable disease extending radially outside the prostatic capsule (i.e., ECE level 3 established) was noted in 185 of 712 (26.0%). The median radial extension was 2.0 mm (range 0.50-12.00 mm) outside the prostatic capsule. As a group, 20 of 712 (2.8%) had extracapsular extension of more than 5 mm. In the volumetric comparison and correlation study of the GTV and PTV to the PPV, the average GTV was 2 times larger than the PPV. The average PTV was 4.1 times larger than the PPV. CONCLUSIONS This is the largest series in the literature quantitatively assessing prostatic capsular invasion (i.e., the radial extracapsular extension). It is the first report of a comparison of PPV to CT-planned GTV and PTV. Using patient and prostate immobilization, 5 mm of margin to the GTV in this study provided sufficient coverage of the tumor volume based on data gathered from 712 patients. In the absence of prostate immobilization, additional margins of differing amounts depending on the technique employed would have to be placed to account for target, patient, and setup uncertainties. The large mean difference between CT-based estimates of the tumor volume and target volume (GTV+PTV) and PPV added further evidence for adequacy of tumor coverage. Target immobilization, setup error, and coverage of subclinical disease must be addressed carefully before successful implementation of IMRT to maximize its ability to escalate dose and to spare normal tissue simultaneously and safely.

Tolerance of endorectal balloon in 396 patients treated with intensity-modulated radiation therapy (IMRT) for prostate cancer.

Purpose:To report patient tolerance and acute anorectal toxicity of an endorectal balloon used for prostate immobilization during 35 daily fractions. Materials and Methods:The records of 396 patients treated for prostate cancer from October 1997 to November 2001 were reviewed. Patients were treated with intensity modulated radiation therapy (IMRT). Endorectal balloon catheter was inserted daily, inflated with 100 mL of air for immobilizing the prostate gland. Patient and treatment factors were analyzed. Patients received a mean dose of 77 Gy/35 fractions/7 weeks with no rectal block. Results:None of the 396 patients halted treatment because of associated ano-rectal toxicity. No patient stated that he would decline to be treated again with rectal balloon. Three of 396 (0.8%) patients required a reduction in the volume of the balloon to 50 mL. Seventeen of 396 (4.3%) patients required Lidocaine jelly with the insertion of balloon. Radiation Therapy Oncology Group (RTOG) grades 1 and 2 rectal toxicity occurred in 55/396 (13.9%) and 73/396 (18.4%), respectively. No RTOG grade 3 or 4 toxicities occurred. Topical anal medications were prescribed for 46 of 396 (11.6%) patients and antidiarrhea medication for 27 of 396 (6.8%) patients. Of patients with pretreatment anorectal disease, 50% developed rectal toxicities over the 7 weeks. Rectal toxicity occurred most frequently in the third, fourth, fifth, or sixth week; 19.5%, 20.8%, 18.2%, and 16.9%, respectively. The duration of the toxicity measured lasted 1 week, 35.2%; 2 weeks, 31.0%; 3 weeks, 15.5%; 4 weeks, 11.3%; 5 weeks, 4.2%; and 6 weeks, 2.8%. Conclusion:Most of the patients, 393/396 (99.2%), tolerated a 100 mL endorectal immobilization balloon for IMRT. The rate of acute anorectal toxicity was acceptable with no grade 3 or 4 toxicities. Duration of the toxicities typically was 1 to 2 weeks. Patients with pre-existing anorectal disease are at higher risk of developing acute anorectal toxicity with the use of an endorectal balloon.

A clinical evaluation of setup errors for a prostate immobilization system

A prostate treatment immobilization system was evaluated with respect to setup errors and efficiency for a specific treatment setup. Prostate patients were treated in the prone position with a rectal catheter using the NOMOS intensity modulated radiotherapy system. Immobilization and setup consisted of a Vac‐Lok™ bag (MED‐TEC, Orange City, IO) fitted within a registration carrier box where patients were aligned to the bag using skin marks along the lower leg. Daily setup errors were analyzed using lateral portal films, registration plates mounted to the carrier box, and the pubic symphasis as a bony reference. Two studies were conducted to evaluate setup technique. In the first study, patient setup required 3–5 minutes for patient positioning and the corresponding superior/inferior errors were found to have a standard deviation of 3.5 mm. In the second study, the technique standards were reduced to allow for faster setup times and, consequently, larger errors; setup times were 1–2 minutes and the mean and standard deviation errors were ~2 and 5 mm, respectively. PACS number(s): 87.53.–j, 87.90.+y

Real-Time Tumor Tracking for Four-Dimensional Computed Tomography Using SQUID Magnetometers

We present a method for real-time tumor tracking in external beam radiotherapy using superconducting quantum interference device (SQUID) magnetometers. The objective is to develop a localization algorithm and determine a cost effective sensor configuration that is capable of long-range localization, ~1000 mm, with an accuracy of 1-2 mm. We developed several algorithms to calculate the location of a magnetic dipole for geometry relevant for four-dimensional computed tomography (4DCT) to investigate sensor configuration and accuracy. We determined that two cube detectors, located diametrically opposite, are a feasible design for the localization system.

The evolution of quality assurance for intensity- modulated radiation therapy (IMRT): Sequential tomotherapy

PURPOSE To identify the pertinent issues to be addressed in successfully implementing IMRT using sequential tomotherapy into clinical reality and presenting the maturation of quality assurance (QA) programs for both the delivery system and patient treatments that allow routine clinical use of the system. MATERIALS AND METHODS Initially, a cubic phantom containing silver halide film was exposed to the entire treatment before patient treatment. The processed films were digitized with a laser densitometer and the dose distributions were compared with that generated by the planning system. Later, software that calculates the dose delivered to any phantom employing the intensity patterns developed in the inverse planning system for an individual patient was implemented for point checks of dose. A measurement phantom for use with this software was developed and evaluated on a large number of patients. Invasive fixation was used for all cranial patients initially. To use sequential tomotherapy for other sites and larger targets, noninvasive immobilization systems using two types of thermoplastic masks for cranial targets and reusable, evacuated body cradles were evaluated for positional accuracy and suitability for use with port films for patient QA. RESULTS The program for equipment validation is divided into daily, weekly, and monthly programs that add only small amounts of time to routine QA programs. For the first 15 patients treated with this modality, the maximum dose measured on the film was within 5% of that predicted by the planning computer. The prescription isodose line was measured in the anteroposterior and lateral dimensions and the average discrepancy between measured and predicted was less than 2 mm. For an isodose line between 50% and 70% of the prescribed dose, the agreement was better than 3 mm. Success with the volume QA program was followed by a point check QA program that reduced the time required for individual patient QA from days to hours. Phantom measurements compared with computer predictions for 588 data points resulted in only 8% being outside a +/-5% criterion. These cases were identified and allow a further reduction in the frequency of tests. Thermoplastic mask materials have adequate restraint characteristics for use with the system and port films on 21 patients resulted in one standard deviation = 1.3 mm. Body cradles are less accurate and require more frequent port films. A QA system that reduces the frequency of port films was developed. CONCLUSIONS The evolution of sequential tomotherapy in our department has been from a maximum of 3 cranial patients per day with invasive fixation to 60 patients per day for treatment of cranial, head-and-neck, and prostate tumors using different immobilization techniques. With proper preparation and refinement of tools used in commissioning and validation, sequential tomotherapy IMRT can become a routine clinical treatment modality.

Applying the equivalent uniform dose formulation based on the linear-quadratic model to inhomogeneous tumor dose distributions: Caution for analyzing and reporting.

We apply the concept of equivalent uniform dose (EUD) to our data set of model distributions and intensity modulated radiotherapy (IMRT) treatment plans as a method for analyzing large dose inhomogeneities within the tumor volume. For large dose nonuniformities, we find that the linear‐quadratic based EUD model is sensitive to the linear‐quadratic model parameters, α and β, making it necessary to consider EUD as a function of these parameters. This complicates the analysis for inhomogeneous dose distributions. EUD provides a biological estimate that requires interpretation and cannot be used as a single parameter for judging an inhomogeneous plan. We present heuristic examples to demonstrate the dose volume effect associated with EUD and the correlation to statistical parameters used for describing dose distributions. From these examples and patient plans, we discuss the risk of incorrectly applying EUD to IMRT patient plans. PACS number(s): 87.53.Tf