Incorporation of SPECT bone marrow imaging into intensity modulated whole-pelvic radiation therapy treatment planning for gynecologic malignancies.

BACKGROUND AND PURPOSE: To incorporate single-photon emission computed tomography (SPECT) bone marrow (BM) imaging into the treatment planning process to reduce the volume of BM irradiated in gynecologic patients receiving intensity-modulated whole-pelvic radiation therapy (IM-WPRT). MATERIALS AND METHODS: A planning CT scan was obtained of a patient with early stage endometrial cancer. The same patient also underwent a Tc-99m sulfur colloid SPECT scan of the pelvis. Tc-99m sulfur colloid is sequestered by the macrophages in the BM thereby identifying areas of active (red) BM. Using image fusion software, the SPECT scan was aligned with the planning CT scan and used to delineate regions of active BM. An IMRT plan was then generated to provide coverage of the planning target volume (PTV) while sparing areas of active BM and other normal pelvic structures. RESULTS: The areas of high active BM density were observed predominantly in the lumbar vertebrae, sacrum and medial iliac crests. IMRT planning reduced the dose to these areas by 50% for doses greater than 30Gy compared to conventional planning. Furthermore, the IMRT plan did not compromise coverage of the PTV or sparing of normal tissues. CONCLUSIONS: Our results suggest that SPECT-BM imaging is a useful adjunct to IMRT planning in gynecologic patients undergoing IM-WPRT.

Setup errors in patients treated with intensity-modulated whole pelvic radiation therapy for gynecological malignancies.

Intensity-modulated whole pelvic radiation therapy (IM-WPRT) has decreased the incidence of gastrointestinal complications by reducing the volume of normal tissue irradiated in gynecologic patients. However, IM-WPRT plans result in steep dose gradients around the target volume, and thus accurate patient setup is essential. To quantify the accuracy of our patient positioning, we examined the weekly portal films of 46 women treated with IM-WPRT at our institution. All patients were positioned using a customized immobilization device that was indexed to the treatment table. Setup errors were evaluated by comparing portal images to simulation images using an algorithm that registers user-defined open curve segments drawn on both sets of film. The setup errors, which were separated into systematic and random components, ranged from 1.9 to 3.7 mm for the translations and 1.3 degrees to 4.4 degrees for the 2 in-plane translations. The systematic errors were all less than the respective random errors, with the largest error in the anterior/posterior direction. In addition, there was no correlation between the magnitude of these errors and patient-specific factors (age, weight, height). In the future, we will investigate the effect of these setup errors on the delivered dose distribution.

Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans.

We report a methodology for comparing and combining dose information from external beam radiotherapy (EBRT) and interstitial brachytherapy (IB) components of prostate cancer treatment using the biological effective dose (BED). On a prototype early-stage prostate cancer patient treated with EBRT and low-dose rate I-125 brachytherapy, a 3-dimensional dose distribution was calculated for each of the EBRT and IB portions of treatment. For each component of treatment, the BED was calculated on a point-by-point basis to produce a BED distribution. These individual BED distributions could then be summed for combined therapies. BED dose-volume histograms (DVHs) of the prostate, urethra, rectum, and bladder were produced and compared for various combinations of EBRT and IB. Transformation to BED enabled computation of the relative contribution of each modality to the prostate dose, as the relative weighting of EBRT and IB was varied. The BED-DVHs of the prostate and urethra demonstrated dramatically increased inhomogeneity with the introduction of even a small component of IB. However, increasing the IB portion relative to the EBRT component resulted in lower dose to the surrounding normal structures, as evidenced by the BED-DVHs of the bladder and rectum. Conformal EBRT and low-dose rate IB conventional dose distributions were successfully transformed to the common "language" of BED distributions for comparison and for merging prostate cancer radiation treatment plans. The results of this analysis can assist physicians in quantitatively determining the best combination and weighting of radiation treatment modalities for individual patients.

A dosimetric analysis of acute gastrointestinal toxicity in women receiving intensity-modulated whole-pelvic radiation therapy.

PURPOSE: To identify dosimetric factors correlated with acute gastrointestinal (GI) toxicity in gynecology patients undergoing intensity-modulated whole pelvic radiation therapy (IM-WPRT). MATERIAL AND METHODS: Fifty gynecology patients received IM-WPRT (45-1.8Gy/fraction) between 2/00 and 3/02. All patients were treated to a clinical target volume (CTV) consisting of the upper vagina, parametria, uterus, presacral region and pelvic lymph nodes. Grade 2 acute GI toxicity requiring frequent medications and grade 3-5 toxicities were designated as clinically significant and analyzed as a function of patient and dosimetric variables. The most significant volumetric factors were fit to a normal tissue complication probability (NTCP) function. RESULTS: Fourteen women (28%) developed clinically significant acute GI toxicity. None of the patient factors were correlated with acute GI toxicity. In addition, the volume of rectum receiving 25, 50, 75, 90, 100 and 110% of the prescription dose did not reach statistical significance. In contrast, a correlation was observed between the volume of small bowel (SB) irradiated and acute GI toxicity, particularly the SB volumes receiving 90 and 100% of the prescription dose (p=0.009 and p=0.009, respectively). Controlling for patient and other dosimetric factors, the SB volume receiving the 100% (Vol(SB,100)) of the prescription dose remained the sole significant factor on multivariate analysis (p=0.012). Subsequently, a NTCP curve, quantifying the risk of acute GI toxicity, was generated based on the Vol(SB,100). CONCLUSIONS: The most significant factor correlated acute GI toxicity in gynecology patients undergoing IM-WPRT is Vol(SB,100).

A method for incorporating organ motion due to breathing into 3D dose calculations in the liver: sensitivity to variations in motion.

Organ motion has been previously described using a probability distribution function that depends solely upon the amplitude of motion and the degree of asymmetry in the breathing cycle, and that function has been used with patient specific parameters to correct static dose distributions for patient breathing using a dose convolution method. In this study, the consequences of errors in the selection of those two parameters were evaluated. Patients previously treated using a focal liver dose escalation protocol were selected with tumors located in the superior or inferior portion of the liver. For a fixed degree of asymmetry (amplitude), the amplitude (asymmetry) of motion was varied about its nominal value and the consequences of organ motion on the dose distribution and the (potentially new) prescription dose were evaluated. These comparisons show that small (+/- 3 mm) variations of the amplitude of motion about the nominally measured value may not result in clinically significant changes (< a single fraction change in the prescription dose), however, larger variations (> 5 mm) can lead to significant changes. Assuming from measurement that the patient breathes asymmetrically (spends more time at expiration), variations in the assumed degree of asymmetry rarely lead to clinically significant changes; the most significant cause for concern being when the patient breathing cycle is maximally different from the treatment planning case (e.g., patient assumed to spend more time at expiration, but later breaths symmetrically). The results point out where quality assurance efforts should be concentrated to help assure the validity of the assumptions used to correct the static dose distributions for patient breathing using the convolution method.

Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy.

PURPOSE: To evaluate intensity-modulated whole pelvis radiotherapy (IM-WPRT) (with bone marrow [BM] as a planning constraint) as a means to reduce the volume of pelvic BM irradiated. METHODS AND MATERIALS: Ten women with cervical or endometrial cancer previously treated using IM-WPRT were selected for this analysis. Using the treatment planning CT scan, the clinical target volume was defined to encompass the gross tumor, parametrial tissues, uterus (if present), and regional lymph nodes. The clinical target volume was expanded by a 1-cm margin to form the planning target volume (PTV). The bladder, rectum, small bowel, and pelvic BM were delineated in each patient. Three plans were created for each patient: a standard four-field WPRT plan, an IM-WPRT treatment plan designed to conform the dose to the PTV while minimizing dose to the normal tissues (excluding BM), and a BM-sparing (BMS) IM-WPRT plan that included the BM as an additional treatment planning constraint. Dose-volume histograms for the PTV, small bowel, and BM were compared for each patient. RESULTS: For each of the 10 patients, BMS IM-WPRT treatment plans demonstrated a significant reduction of the volume of BM receiving >40% (18 Gy) of the prescription dose (45 Gy) compared with both IM-WPRT and four-field treatment. On average, BMS IM-WPRT resulted in only 60% of the BM volume irradiated to >50% of the dose compared with 87.4% (p <0.001) of the BM volume in a four-field plan and 75.7% (p < 0.003) of the volume in an IM-WPRT plan. Furthermore, the BMS IM-WPRT plans resulted in significant sparing of all other normal tissues that was comparable to the original IM-WPRT. In all 10 cases, the BMS IM-WPRT treatment plan did not result in any significant differences in the PTV and small bowel dose-volume histograms compared with the IM-WPRT treatment plans. CONCLUSION: BMS IM-WPRT significantly reduces the volume of pelvic BM irradiated compared with conventional WPRT. In addition, BMS IM-WPRT did not compromise the improvements previously seen in IM-WPRT treatment plans that did not consider BM. Clinical studies are necessary to assess the significance of BMS IM-WPRT in reducing hematologic toxicity.

Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies.

PURPOSE: To evaluate the impact of intensity-modulated whole pelvic radiotherapy (IM-WPRT) on acute hematologic toxicity (HT) in gynecology patients. METHODS AND MATERIALS: Between February 2000 and June 2001, 36 patients (24 cervix, 12 uterus) received IM-WPRT. The target consisted of the upper vagina, parametria, uterus, and presacral and pelvic lymph nodes. Using commercially available software, seven or nine coplanar IM-WPRT plans were generated. The planning goals were to irradiate the target while minimizing the dose to the small bowel, bladder, and rectum. Pelvic bone marrow (BM) was not a constraint in the planning process. The variables analyzed included white blood count (WBC), absolute neutrophil count (ANC), platelets, and hemoglobin (Hgb) obtained before and weekly during RT. As a comparison, the HT in 88 patients (44 cervix, 44 uterus) treated to the same target volume and total dose (45 Gy) with conventional four-field WPRT was analyzed. In addition, the medullary spaces within the pelvic bones in 10 women were contoured and the average dose-volume histograms representing the pelvic BM were compared between the two groups. RESULTS: IM-WPRT patients had a lower median age (p = 0.008), higher percentage of squamous histologic features (p = 0.04), and were more likely to receive chemotherapy (CTX) (p = 0.02) than were the WPRT patients. No differences were seen in the baseline WBC, ANC, platelet, or Hgb levels between the two groups. Grade 2 or greater WBC, ANC, and Hgb toxicity was seen in 19.4%, 9.1%, and 8.6% of the IM-WPRT patients, respectively. Comparable rates were seen in the WPRT patients (WBC 21.6%, p = 0.79; ANC 8.3%, p = 0.91; Hgb 9.2%, p = 0.94). No Grade 2 or greater platelet toxicity was seen in either group. Significant HT was infrequent in women treated with RT alone and was comparable in the two groups. In contrast, WPRT + CTX patients experienced more Grade 2 or greater WBC toxicity (60% vs. 31.2%, p = 0.08) and developed lower median WBC (2.8 vs. 3.6 microg/dL, p = 0.05) and ANC (1874 vs. 2669, p = 0.04) nadirs than did IM-WPRT + CTX patients. Moreover, CTX was held more often in the WPRT group secondary to HT (40% vs. 12.5%, p = 0.06). Although Grade 2 or greater ANC (23.5% vs. 15.3%) and Hgb (35.2% vs. 15.2%) toxicity were lower in the IM-WPRT + CTX group, these differences did not reach statistical significance (p = 0.58 and p = 0.22, respectively). The comparison of pelvic BM dose-volume histograms revealed that IM-WPRT planning resulted in significantly less BM volume being irradiated compared with WPRT planning, particularly within the iliac crests. CONCLUSION: IM-WPRT has a favorable impact on the risk of acute HT in gynecology patients, particularly in those receiving CTX. Future work is needed to optimize BM sparing in these patients to reduce the risk of significant HT further.

Intensity-modulated radiation therapy in gynecologic malignancies.

Radiation therapy (RT) is commonly used in the treatment of gynecologic malignancies. Unfortunately, RT exposes patients to a wide variety of sequelae. Concerns over toxicity also limit the use of higher doses in select patients. To improve the efficacy of conventional RT and to explore the possibility of dose escalation, we have turned to the use of intensity-modulated RT (IMRT). This report reviews our preclinical studies, implementation, and clinical experience to date with IMRT for gynecologic malignancies.

Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies.

PURPOSE: To describe our initial clinical experience with intensity-modulated whole pelvic radiotherapy (IM-WPRT) in women with gynecologic malignancies. METHODS AND MATERIALS: Between February 2000 and August 2001, 40 gynecology patients underwent IM-WPRT. After fabrication of customized immobilization, all patients underwent contrast-enhanced CT, and a clinical target volume was contoured consisting of the upper vagina, parametria, uterus (if present), and presacral and pelvic lymph node regions. The clinical target volume was expanded by 1 cm to create a planning target volume (PTV). Using commercially available software, 7- or 9-field, 6-MV, coplanar IM-WPRT plans were generated for all patients. The worst acute gastrointestinal and genitourinary toxicity during treatment was scored on a 4-point scale: 0, none; 1, mild, no medications required; 2, moderate, medications required; and 3, severe, treatment breaks or cessation, hospitalization. As a comparison, acute toxicities in 35 previously treated conventional WPRT patients were analyzed. No significant differences were noted in the clinicopathologic and treatment factors between the two groups. RESULTS: IM-WPRT plans provided excellent PTV coverage, with considerable sparing of the surrounding normal tissues. On average, 98.1% of the PTV received the prescription dose. The average percentage of the PTV receiving 110% and 115% of the prescription dose was 9.8% and 0.2%, respectively. IM-WPRT was well tolerated, with no patient developing Grade 3 toxicity. Grade 2 acute gastrointestinal toxicity was less common in the IM-WPRT group (60 vs. 91%, p = 0.002) than in the conventional WPRT group. Moreover, the percentage of IM-WPRT and WPRT patients requiring no or only infrequent antidiarrheal medications was 75% and 34%, respectively (p = 0.001). Although less Grade 2 genitourinary toxicity was seen in the IM-WPRT group (10% vs. 20%), this difference was not statistically significant (p = 0.22). CONCLUSION: IM-WPRT is a promising approach in gynecology patients. IMRT planning resulted in excellent PTV coverage, with considerable sparing of normal tissues. Treatment was well tolerated and associated with less acute gastrointestinal sequelae than conventional WPRT. Longer follow-up and more patients are needed, however, to evaluate the full merits of this novel approach.