Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer.

PURPOSE: To relate lung dose-volume histogram-based factors to symptomatic radiation pneumonitis (RP) in patients with lung cancer undergoing 3-dimensional (3D) radiotherapy planning. METHODS AND MATERIALS: Between 1991 and 1999, 318 patients with lung cancer received external beam radiotherapy (RT) with 3D planning tools at Duke University Medical Center. One hundred seventeen patients were not evaluated for RP because of <6 months of follow-up, development of progressive intrathoracic disease making scoring of pulmonary symptoms difficult, or unretrievable 3D dosimetry data. Thus, 201 patients were analyzed for RP. Univariate and multivariate analyses were performed to test the association between RP and dosimetric factors (i.e., mean lung dose, volume of lung receiving >or=30 Gy, and normal tissue complication probability derived from the Lyman and Kutcher models) and clinical factors, including tobacco use, age, sex, chemotherapy exposure, tumor site, pre-RT forced expiratory volume in 1 s, weight loss, and performance status. RESULTS: Thirty-nine patients (19%) developed RP. In the univariate analysis, all dosimetric factors (i.e., mean lung dose, volume of lung receiving >or=30 Gy, and normal tissue complication probability) were associated with RP (p range 0.006-0.003). Of the clinical factors, ongoing tobacco use at the time of referral for RT was associated with fewer cases of RP (p = 0.05). These factors were also independently associated with RP according to the multivariate analysis (p = 0.001). Models predictive for RP based on dosimetric factors only, or on a combination with the influence of tobacco use, had a concordance of 64% and 68%, respectively. CONCLUSIONS: Dosimetric factors were the best predictors of symptomatic RP after external beam RT for lung cancer. Multivariate models that also include clinical variables were slightly more predictive.

Relating radiation-induced regional lung injury to changes in pulmonary function tests.

PURPOSE: To determine whether the sum of radiotherapy (RT)-induced reductions in regional lung perfusion is quantitatively related to changes in global lung function as assessed by reductions in pulmonary function tests (PFTs). METHODS AND MATERIALS: Two hundred seven patients (70% with lung cancer) who received incidental partial lung irradiation underwent PFTs (forced expiratory volume in 1 s and diffusion capacity for carbon monoxide) before and repeatedly after RT as part of a prospective clinical study. Regional lung function was serially assessed before and after RT by single photon emission computed tomography perfusion scans. Of these, 53 patients had 105 post-RT evaluations of changes in both regional perfusion and PFTs, were without evidence of intrathoracic disease recurrence that might influence regional perfusion and PFT findings, and were not taking steroids. The summation of the regional functional perfusion changes were compared with changes in PFTs using linear regression analysis. RESULTS: Follow-up ranged from 3 to 86 months (median 19). Overall, a significant correlation was found between the sum of changes in regional perfusion and the changes in the PFTs (p = 0.002-0.24, depending on the particular PFT index). However, the correlation coefficients were small (r = 0.16-0.41). CONCLUSIONS: A statistically significant correlation was found between RT-induced changes in regional function (i.e., perfusion) and global function (i.e., PFTs). However, the correlation coefficients are low, making it difficult to relate changes in perfusion to changes in the PFT results. Thus, with our current techniques, the prediction of changes in perfusion alone does not appear to be sufficient to predict the changes in PFTs accurately. Additional studies to clarify the relationship between regional and global lung injury are needed.

Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V(30) and transforming growth factor beta.

PURPOSE: To correlate the volume of lung irradiated with changes in plasma levels of the fibrogenic cytokine transforming growth factor beta (TGFbeta) during radiotherapy (RT), such that this information might be used to predict the development of symptomatic radiation-induced lung injury (SRILI). METHODS AND MATERIALS: The records of all patients with lung cancer treated with RT with curative intent from 1991 to 1997 on a series of prospective normal tissue injury studies were reviewed. A total of 103 patients were identified who met the following inclusion criteria: (1) newly diagnosed lung cancer of any histology treated with RT +/- chemotherapy with curative intent; (2) no evidence of distant metastases or malignant pleural effusion; (3) no thoracic surgery after lung RT; (4) no endobronchial brachytherapy; (5) follow-up time more than 6 months; (6) plasma TGFbeta1 measurements obtained before and at the end of RT. The concentration of plasma TGFbeta1 was measured by an enzyme-linked immunosorbent assay. Seventy-eight of the 103 patients were treated with computed tomography based 3-dimensional planning and had dose-volume histogram data available. The endpoint of the study was the development of SRILI (modified NCI [National Cancer Institute] common toxicity criteria). RESULTS: The 1-year and 2-year actuarial incidence of SRILI for all 103 patients was 17% and 21%, respectively. In those patients whose TGFbeta level at the end of RT was higher than the pre-RT baseline, SRILI occurred more frequently (2-year incidence = 39%) than in patients whose TGFbeta1 level at the end of RT was less than the baseline value (2-year incidence = 11%, p = 0.007). On multivariate analysis, a persistent elevation of plasma TGFbeta1 above the baseline concentration at the end of RT was an independent risk factor for the occurrence of SRILI (p = 0.004). The subgroup of 78 patients treated with 3-dimensional conformal radiotherapy, who consequently had dose-volume histogram data, were divided into groups according to their TGFbeta1 kinetics and whether their V(30) level was above or below the median of 30%. Group I (n = 29), with both a TGFbeta1 level at the end of RT that was below the pre-RT baseline and V(30) < 30%; Group II (n = 35), with a TGFbeta1 level at the end of irradiation that was below the baseline but a V(30) > or = 30% or with a TGFbeta1 level at the end of RT that was above the pre-RT baseline but V(30) < 30%; Group III (n = 14), with both a TGFbeta1 level at the end of RT that was above the baseline and V(30) > or = 30%. A significant difference was found in the incidence of SRILI among these three groups (6.9%, 22.8%, 42.9%, respectively, p = 0.02). CONCLUSIONS: (1) An elevated plasma TGFbeta1 level at the end of RT is an independent risk factor for SRILI; (2) The combination of plasma TGFbeta1 level and V(30) appears to facilitate stratification of patients into low, intermediate, and high risk groups. Thus, combining both physical and biologic risk factors may allow for better identification of patients at risk for the development of symptomatic radiation-induced lung injury.

A practical and easy method to locate the first three internal mammary lymph node-bearing areas.

PURPOSE: To assess the distance from a clinically recognized anatomic landmark to the different costocondral interspaces in female patients to facilitate the design of radiation fields intended to include specific internal mammary nodal areas. METHODS AND MATERIALS: The distance from the suprasternal notch (SSN) to the caudal portion of the first through fourth interspace was measured on a computer display of the chest skeleton of 65 female patients with left-sided breast cancer. The relationship between these distances and bone size (sternal length and standing height) was assessed via linear regression. In 21 of the 65 patients where myocardial perfusion imaging of the heart was available, the relationship between the location of the 3rd costochondral interspace and the left ventricle was assessed. RESULTS: In 90% of patients (59/65), the first, second, third, and fourth interspace were within 5, 8.5, 11, and 14 cm of the SSN, respectively. The SSN-interspace distances did not correlate well with sternal length (r = 0.28) or standing height (r = 0.31). In 20 of 21 patients (95%), the third interspace "shadowed" the cephalad aspect of the left heart ventricle. Median "shadowing" was 3 cm (range 0.5-6 cm). CONCLUSION: The caudal portion of the third costochondral interspace is < or = 11 cm caudal to the SSN in 90% of patients. These measurements can be used to clinically design radiation therapy fields intended to treat the upper three interspaces. The distance from the SSN to the 1st through 4th interspaces is not related to sternal length or to standing height. In patients with left-sided breast cancer, radiation treatment fields designed to include the internal mammary lymph nodes in the upper three interspaces may incidentally include a portion of the heart.

Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results.

PURPOSE: To determine the incidence and dose dependence of regional cardiac perfusion abnormalities in patients with left-sided breast cancer treated with radiation therapy (RT) with and without doxorubicin (Dox). METHODS: Twenty patients with left-sided breast cancer underwent cardiac perfusion imaging using single photon emission computed tomography (SPECT) prechemotherapy, pre-RT, and 6 months post-RT. SPECT perfusion images were registered onto 3-dimensional (3D) RT dose distributions. The volume of heart in the RT field was quantified, and the regional RT dose was calculated. A decrease in regional cardiac perfusion was assessed subjectively by visual inspection and objectively using image fusion software. Ten patients received Dox-based chemotherapy (total dose 120-300 mg/m(2)), and 10 patients had no chemotherapy. RT was delivered by tangent beams in all patients to a total dose of 46-50 Gy. RESULTS: Overall, 60% of the patients had new visible perfusion defects 6 months post-RT. A dose-dependent perfusion defect was seen at 6 months with minimal defect appreciated at 0-10 Gy, and a 20% decrease in regional perfusion at 41-50 Gy. One of 20 patients had a decrease in left ventricle ejection fraction (LVEF) of greater than 10% at 6 months; 2/20 patients had developed transient pericarditis. No instances of myocardial infarction or congestive heart failure (CHF) have occurred. CONCLUSIONS: RT causes cardiac perfusion defects 6 months post-RT in most patients. Long-term follow-up is needed to assess whether these perfusion changes are transient or permanent and to determine if these findings are associated with changes in overall cardiac function and clinical outcome.

Can we predict radiation-induced changes in pulmonary function based on the sum of predicted regional dysfunction?

PURPOSE: To determine whether changes in whole-lung pulmonary function test (PFT) values are related to the sum of predicted radiation therapy (RT)-induced changes in regional lung perfusion. PATIENTS AND METHODS: Between 1991 and 1998, 96 patients (61% with lung cancer) who were receiving incidental partial lung irradiation were studied prospectively. The patients were assessed with pre- and post-RT PFTs (forced expiratory volume in one second [FEV1] and diffusion capacity for carbon monoxide [DLCO]) for at least a 6-month follow-up period, and patients were excluded if it was determined that intrathoracic recurrence had an impact on lung function. The maximal declines in PFT values were noted. A dose-response model based on RT-induced reduction in regional perfusion (function) was used to predict regional dysfunction. The predicted decline in pulmonary function was calculated as the weighted sum of the predicted regional injuries: equation [see text] where Vd is the volume of lung irradiated to dose d, and Rd is the reduction in regional perfusion anticipated at dose d. RESULTS: The relationship between the predicted and measured reduction in PFT values was significant for uncorrected DLCO (P = .005) and borderline significant for DLCO (P = .06) and FEV1 (P = .08). However, the correlation coefficients were small (range,.18 to.30). In patients with lung cancer, the correlation coefficients improved as the number of follow-up evaluations increased (range,.43 to.60), especially when patients with hypoperfusion in the lung adjacent to a central mediastinal/hilar thoracic mass were excluded (range,.59 to.91). CONCLUSION: The sum of predicted RT-induced changes in regional perfusion is related to RT-induced changes in pulmonary function. In many patients, however, the percentage of variation explained is small, which renders accurate predictions difficult.

Functional imaging of normal tissues with nuclear medicine: applications in radiotherapy.

Functional imaging techniques are gaining significant interest from radiation oncologists. Many now claim the need for physical and physiological information during both treatment planning and in the study of normal tissue injury. Toward this goal, the nuclear medicine functional imaging modalities, single-photon emission computed tomography and positron-emission computed tomography, have been used. This article reviews the studies performed in radiotherapy that used these modalities, and attempts to stimulate further interest in this topic.

Routine 3D treatment planning: opportunities, challenges, and hazards.

Three-dimensional (3D) treatment planning refers to the use of software and hardware tools to design and implement more accurate and conformal radiation therapy. This is a major advance in oncology that should lead to the reduction of treatment-associated morbidity and facilitate safe dose escalation for many tumor sites. This technology affords the incorporation of physiologic and anatomic information into the treatment planning process, further enhancing our ability to improve the therapeutic ratio. However, as with any new technology, care must be taken when applying it in the clinic. The introduction of 3D planning presents new challenges to existing quality assurance systems. These need to be addressed to maintain patient safety. Based on our experience with over 1,500 patients treated at Duke University, the benefits, challenges, and hazards of routine 3D treatment planning are discussed.

Variability of the depth of supraclavicular and axillary lymph nodes in patients with breast cancer: is a posterior axillary boost field necessary?

PURPOSE: To determine the variability of the depth of supraclavicular (SC) and axillary (AX) lymph nodes in patients undergoing radiation therapy for breast cancer and to relate this variability with the patient's anterior/posterior (A/P) diameter. The dosimetric consequences of the variability in depth are explored and related to the need for a posterior axillary boost field. METHOD AND MATERIALS: In 49 patients undergoing treatment-planning computed tomography (CT) scanning in the treatment position, the maximum depth of the SC and AX lymph nodes was measured on CT images. The A/P diameter was measured at the location of the SC and AX, respectively. The relationship between the SC/AX lymph node depth and patient diameter was determined using linear regression. For an anterior SC and AX field, the relative dose to the SC and AX lymph nodes were calculated for a 6 MV photon beam. RESULTS: The maximum depth of the SC lymph nodes ranged from 2.4 to 9.5 cm (median, 4.3 cm). The depth was less than 3 cm in 4 patients, 3-6 cm in 39 (80%), and greater than 6 cm in 6 patients. There was a linear relationship between the SC lymph node depth and the A/P diameter. The depth of the SC lymph nodes in cm equals approximately one-half of the A/P diameter minus 3.5 (r(2) = 0.69). In 94% (46 of 49) of patients, the SC lymph node depth was between one-fifth and one-half of the A/P diameter. The depth of the axillary lymph nodes ranged from 1.4 to 8 cm (median, 4.3 cm). The depth was less than 3 cm in 8 patients, 3-6 cm in 32 (65%), and greater than 6 cm in 9 patients. The AX lymph node depth in cm equals approximately one-half of the A/P diameter minus 3 (r(2) = 0.81). In all patients, the AX lymph nodes were shallower than mid-depth. The depth of the SC and AX lymph nodes was within +/- 1 cm in 53% (26 of 49) of patients. The AX lymph nodes were located at >/= 1 cm shallower or greater depth than the SC in 24.5% (12 of 49) and 22.5% (11 of 49) of patients, respectively. If an anterior 6-MV beam only is used to treat the SC and AX lymph nodes in these 49 patients, the dose to the AX is within +/- 5% of the SC dose in 53% (26 of 49) patients and is 90% or more of the dose delivered in the SC in 90% (44 of 49) of patients. CONCLUSION: The maximum depth of the SC and AX lymph nodes varies widely and is related to the patient's size represented by the A/P diameter. In most patients, the AX lymph nodes lie at approximately the same depth or shallower than the SC. Therefore, the rationale for a posterior axillary boost field needs to be further assessed. When the AX and SC lymph nodes are deep, opposed supraclavicular and axillary fields and/or the use of a higher energy beam might be reasonable.

Radiation-induced pulmonary injury: symptomatic versus subclinical endpoints.

PURPOSE: To assess the relationship between radiation (RT)-induced pulmonary symptoms and subclinical changes in pulmonary functions tests (PFT) and radiographs. MATERIALS AND METHODS: A total of 184 patients irradiated between 1992 and 1998 were prospectively evaluated for RT-induced pulmonary symptoms, changes in computed tomography (CT) density, reductions in single photon emission CT (SPECT) perfusion, and changes in pulmonary functions tests (forced expiratory volume in 1 s [FEV1] and diffusion capacity to carbon monoxide [DLCO]). Comparisons between the evaluable patients with (N=34) and without (N=106) RT-induced pulmonary symptoms were made. RESULTS: Within 6 months of RT, 80% of the RT-induced symptoms were noted. There was no association between the presence or absence of RT-induced pulmonary symptoms and the frequency of RT-induced radiographic changes (p=0.53), or in the dose-response curve for RT-induced reductions in regional perfusion. Overall, RT-induced changes in SPECT images were more commonly seen than increased density changes on CT (p<0.001). Most patients with pulmonary symptoms had relatively low pre-RT PFTs and experienced further declines following RT. CONCLUSIONS: Regional radiographic changes in CT-defined tissue density or SPECT-defined tissue perfusion are similar in patients with and without RT-induced pulmonary symptoms because these endpoints do not consider the volume of lung affected. RT-induced pulmonary symptoms are better related to post-RT PFT because they are an assessment of whole lung function. Additional studies are necessary to better define models that can predict the degree of radiation-induced changes in whole lung function.

The role of lung perfusion imaging in predicting the direction of radiation-induced changes in pulmonary function tests.

BACKGROUND: The aim of this study was to determine whether preradiation (pre-RT) single photon emission computed tomography (SPECT) lung perfusion scans can be used to predict RT-induced changes in pulmonary function tests (PFTs). METHODS: Ninety-four patients irradiated for thoracic tumors had pre-RT SPECT lung perfusion scans. The presence of SPECT hypoperfusion distal to a central mediastinal tumor was qualitatively assessed visually without knowledge of PFT changes. Patients were grouped based on whether the diffusion capacity (DLCO) ever increased post-RT. Comparisons of patient groups were performed using 1-tailed Fisher exact tests. Patient follow-up was 6-56 months (mean, 30 months). To assess SPECT hypoperfusion objectively, the average dose to the computed tomography (CT)-defined lung was compared with the weighted-average dose (based on relative perfusion) to the SPECT-defined lung. The ratio between the CT- and SPECT-defined mean lung dose provided a quantitative assessment of hypoperfusion. The mean ratio for patients with central tumor and adjacent hypoperfusion was compared with that of the others (Wilcoxon rank-sum one-sided test). RESULTS: In patients with central tumors, 41% (9 of 22) with adjacent hypoperfusion had improvements in DLCO following radiation, versus 18% (3 of 17) of those without hypoperfusion (P = 0.11). In patients with lung carcinoma, the corresponding ratios were 40% (8 of 20) and 10% (1 of 10), respectively (P = 0.10). The mean ratio of CT dose to SPECT dose was 1.35 for patients with central tumors and adjacent hypoperfusion versus 1.16 for others (P = 0.017). CONCLUSIONS: The presence of SPECT hypoperfusion adjacent to a central mediastinal mass may identify patients likely to have improved PFTs following RT. Thus, SPECT imaging may be useful in models for predicting radiation-induced changes in PFTs.

Can angiotensin-converting enzyme inhibitors protect against symptomatic radiation pneumonitis?

This study was designed to determine whether patients taking angiotensin-converting enzyme (ACE) inhibitors while receiving radiation therapy for lung cancer are protected from developing symptomatic radiation pneumonitis. The records of 213 eligible patients receiving thoracic irradiation for lung cancer with curative intent at Duke University Medical Center from 1994-1997 were reviewed. Of the 213 patients, 26 (12.2%) were on ACE inhibitors (usually for the management of hypertension) during radiotherapy (group 1); the remaining 187 patients (group 2) were not. Patients were irradiated, with fields shaped to protect normal tissues, with total doses of 50-80 Gy. After treatment, patients were generally followed every 3 months for 2 years, then every 6 months thereafter. Symptomatic radiation pneumonitis was scored according to modified National Cancer Institute Common Toxicity Criteria (i.e., radiographic changes alone were not sufficient for the diagnosis of pneumonitis). There was no difference in the incidence of pneumonitis between the two groups (P = 0.75). Fifteen percent of the patients on ACE inhibitors (group 1) developed symptomatic radiation-induced lung injury compared to 12% of the patients not receiving these drugs (group 2). Although patients in group 1 tended to develop pneumonitis slightly sooner than did patients in group 2, this difference also was not significant (P = 0. 8). Within the dose range prescribed for treating hypertension, ACE inhibitors do not appear to either decrease the incidence or delay the onset of symptomatic radiation pneumonitis among lung cancer patients receiving thoracic irradiation.

The effect of pressure from the table top and patient position on pelvic organ location in patients with prostate cancer.

PURPOSE: To assess the impact of pressure from the table top and patient position on the relationship of the prostate, rectum, and bladder to the bony pelvis. METHODS AND MATERIALS: In 9 patients with prostate cancer (3 status postprostatectomy), computed tomography (CT) scans were obtained in four positions: supine with and without false table top under the buttocks, prone with and without false table top under the lower abdomen. In four patients, a fifth scan was obtained in the first position (supine with table top in place) to assess the impact of changes in bladder/rectal fullness over time. Urination and defecation were not permitted between scans. For each patient, the four (or five) CT scans were registered to each other. RESULTS: The anal canal and the rectum caudal to the coccyx shifted posteriorly in 7/9 patients when the support under the buttocks was removed in the supine position. When pressure from the table top was removed in the prone position, the anterior bladder extension increased. The superior rectum was adjacent to the prostate in all scans and the prostate/superior rectum/bladder generally moved together. Rectal fullness changed with time and rectal gas position was gravity-dependent and shifted with patient position. Bladder volume increased with time. Organs had shifted and/or changed fullness between the first and fifth scan obtained in the same patient position approximately 90 min apart, mostly due to increase in bladder volume. All patients found the supine position most comfortable. CONCLUSIONS: The bladder and rectal fullness vary with time, confounding the ability to attribute changes in organ location to positional factors. Pressure from the table top affects the relative location of pelvic organs and, in part, is responsible for changes previously attributed to position/gravity.

The effect of patient-specific factors on radiation-induced regional lung injury.

PURPOSE: To assess the impact of patient-specific factors on radiation (RT)-induced reductions in regional lung perfusion. METHODS: Fifty patients (32 lung carcinoma, 7 Hodgkin's disease, 9 breast carcinoma and 2 other thoracic tumors) had pre-RT and > or = 24-week post-RT single photon emission computed tomography (SPECT) perfusion images to assess the dose dependence of RT-induced reductions in regional lung perfusion. The SPECT data were analyzed using a normalized and non-normalized approach. Furthermore, two different mathematical methods were used to assess the impact of patient-specific factors on the dose-response curve (DRC). First, DRCs for different patient subgroups were generated and compared. Second, in a more formal statistical approach, individual DRCs for regional lung injury for each patient were fit to a linear-quadratic model (reduction = coefficient 1 x dose + coefficient 2 x dose2). Multiple patient-specific factors including tobacco history, pre-RT diffusion capacity to carbon monoxide (DLCO), transforming growth factor-beta (TGF-beta), chemotherapy exposure, disease type, and mean lung dose were explored in a multivariate analysis to assess their impact on the coefficients. RESULTS: None of the variables tested had a consistent impact on the radiation sensitivity of regional lung (i.e., the slope of the DRC). In the formal statistical analysis, there was a suggestion of a slight increase in radiation sensitivity in the dose range >40 Gy for nonsmokers (vs. smokers) and in those receiving chemotherapy (vs. no chemotherapy). However, this finding was very dependent on the specific statistical and normalization method used. CONCLUSION: Patient-specific factors do not have a dramatic effect on RT-induced reduction in regional lung perfusion. Additional studies are underway to better clarify this issue. We continue to postulate that patient-specific factors will impact on how the summation of regional injury translates into whole organ injury. Refinements in our methods to generate and compare SPECT scans are needed.

A neural network to predict symptomatic lung injury.

A nonlinear neural network that simultaneously uses pre-radiotherapy (RT) biological and physical data was developed to predict symptomatic lung injury. The input data were pre-RT pulmonary function, three-dimensional treatment plan doses and demographics. The output was a single value between 0 (asymptomatic) and 1 (symptomatic) to predict the likelihood that a particular patient would become symptomatic. The network was trained on data from 97 patients for 400 iterations with the goal to minimize the mean-squared error. Statistical analysis was performed on the resulting network to determine the model's accuracy. Results from the neural network were compared with those given by traditional linear discriminate analysis and the dose-volume histogram reduction (DVHR) scheme of Kutcher. Receiver-operator characteristic (ROC) analysis was performed on the resulting network which had Az = 0.833 +/- 0.04. (Az is the area under the ROC curve.) Linear discriminate multivariate analysis yielded an Az = 0.813 +/- 0.06. The DVHR method had Az = 0.521 +/- 0.08. The network was also used to rank the significance of the input variables. Future studies will be conducted to improve network accuracy and to include functional imaging data.

Variability of the location of internal mammary vessels and glandular breast tissue in breast cancer patients undergoing routine CT-based treatment planning.

PURPOSE: To determine the variability of position of internal mammary vessels (IMV) and glandular breast tissue (GBT) in patients undergoing breast-conserving radiation therapy. To assess the frequency and magnitude of tangential field border shifts based on preradiation therapy (RT) computed tomography (CT) imaging in breast cancer patients. METHODS AND MATERIALS: Five hundred and ninety breast cancer patients irradiated between 9/94 and 3/98 underwent routine CT-based treatment planning. Two analyses were performed. First, the position of IMV and GBT, outlined on the central axis CT image, was determined relative to the midsternum in 111 patients irradiated during a 12-month period. In the second analysis, the difference between anticipated (pre-CT) and actual (CT-based) tangential field borders was assessed in 254 patients irradiated during a 2-year period. RESULTS: In the first analysis, the depth of the IMVs varied from 1 to 6 cm (median 2.4 cm). The lateral distance from the midsternum also varied widely (range 1.7 to 3.7 cm, median 2.5 cm). Similar variability was found in the position of the GBT. In the second analysis, CT information led to changes of anticipated field borders in 65% of patients. The lateral border was shifted in 56% of patients (anteriorly 18%, posteriorly 38%). When the patients were segregated based on internal mammary node (IMN) treatment, the medial border was shifted in 49% of patients when the IMNs were treated in the tangential fields and in 24% when the GBT only was treated. The frequency of lateral field border shifts was similar in both groups. CONCLUSIONS: The position of IMVs and GBT varies widely in breast cancer patients. Tangential field borders based on surface anatomy may not be ideal. Among 254 breast cancer patients, the field borders were shifted in 65% of patients when CT information was available. Thus, in most breast cancer patients, field borders are shifted when CT-based treatment planning is used.

Acute and late morbidity of using a breast positioning ring in women with large/pendulous breasts.

PURPOSE: To assess acute and late effects of radiation therapy in women with breast cancer treated with a breast positioning ring. MATERIALS AND METHODS: Fifty-six patients with large and/or pendulous breasts were irradiated using a breast positioning ring. The incidence of acute morbidity was correlated with patient weight and breast 'size'. Cosmesis was scored at > or = 1 year following radiation therapy by the patients. Dose changes in the buildup region under the ring were measured using a computer-controlled scanning system. RESULTS: Moist desquamation (MD) occurred in 60.7% (34/56) of patients treated with the breast ring. The incidence of MD was more common in patients with larger breasts (P = 0.08), the severity necessitating a treatment interruption in 5 out of 56 (9%) patients. Cosmesis at > or = 1 year following radiation therapy was scored as > or = good by all patients. The surface dose under the ring was approximately 85% of the Dmax dose. CONCLUSIONS: The incidence or severity of acute MD in patients treated with a breast positioning ring appears high in patients with large pendulous breasts, and might be related in part, to the increased skin dose due to the positioning ring. To date, there appears to be no significant late normal tissue effects in patients treated with the positioning ring. Additional follow up is needed to assess the long-term consequences of the ring on cosmesis.

Postmastectomy radiotherapy: toxicities and techniques to reduce them.

The role of locoregional radiation therapy after mastectomy is controversial. It reduces the risk of tumor relapse, improves breast cancer-specific survival and possibly overall survival, but has potential morbidity. This article reviews the technical aspects of postmastectomy radiation therapy and its associations with treatment-related morbidity. We consider common problems that arise in the technical setup of radiation fields. Adverse effects of postmastectomy radiation therapy may be reduced or prevented by careful radiation treatment planning.

The effect of beam divergence on target coverage.

The well-known fact that radiation beams diverge is frequently not considered during the treatment planning process. Complacency with respect to beam divergence can, in some situations, lead to inappropriate field design. In this review, the potential problems arising from failure to adequately account for beam divergence in treatment planning are outlined, and commonly encountered clinical examples are illustrated.

Incorporation of functional status into dose-volume analysis.

The dose-volume histogram (DVH) has gained wide acceptance as a mechanism for reducing the voluminous data of a three-dimensional dose distribution into a two-dimensional graph. These graphs are often converted to a single figure of merit. This data reduction technique is used both for clinical treatment plan evaluation and as part of proposed systems for estimating control and complication probabilities. It has long been recognized that a major shortcoming of the DVH as an analysis tool is that all spatial information is discarded. A subtler problem, which is addressed in this work, is that the DVH also implies homogeneity of biological consequence of irradiation in what may be a functionally heterogeneous volume of tissue. An extension to the DVH, the functional dose-volume histogram, or dose-function histogram (DFH), is proposed, that explicitly includes quantitative three-dimensional functional information. The concept is illustrated by the use of SPECT imaging to assess the functional status of irradiated lung.