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L B Marks

Publications and source records attributed to L B Marks.

At least 55 records · Page 3Linked to original sources
PubMed1999

Mounting evidence for postmastectomy locoregional radiation therapy.

Postmastectomy locoregional radiation therapy markedly reduces the risk of locoregional recurrence. Several randomized trials, including two recently updated studies with 10- to 15-year follow-up, demonstrate an improvement in overall survival with radiation therapy. This improvement is seen in patients with one to three positive axillary lymph nodes, as well those with four positive nodes. Therefore, postmastectomy radiation therapy should be considered in all patients with node-positive breast cancer. Computed tomography (CT)-based treatment planning is recommended to minimize the cardiopulmonary morbidity of radiation therapy.

Antineoplastic Agents↗
PubMed1998

Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients.

PURPOSE: To determine the relation between the incidence of radiation pneumonitis and the three-dimensional dose distribution in the lung. METHODS AND MATERIALS: In five institutions, the incidence of radiation pneumonitis was evaluated in 540 patients. The patients were divided into two groups: a Lung group, consisting of 399 patients with lung cancer and 1 esophagus cancer patient and a Lymph./Breast group with 78 patients treated for malignant lymphoma, 59 for breast cancer, and 3 for other tumor types. The dose per fraction varied between 1.0 and 2.7 Gy and the prescribed total dose between 20 and 92 Gy. Three-dimensional dose calculations were performed with tissue density inhomogeneity correction. The physical dose distribution was converted into the biologically equivalent dose distribution given in fractions of 2 Gy, the normalized total dose (NTD) distribution, by using the linear quadratic model with an alpha/beta ratio of 2.5 and 3.0 Gy. Dose-volume histograms (DVHs) were calculated considering both lungs as one organ and from these DVHs the mean (biological) lung dose, NTDmean, was obtained. Radiation pneumonitis was scored as a complication when the pneumonitis grade was grade 2 (steroids needed for medical treatment) or higher. For statistical analysis the conventional normal tissue complication probability (NTCP) model of Lyman (with n=1) was applied along with an institutional-dependent offset parameter to account for systematic differences in scoring patients at different institutions. RESULTS: The mean lung dose, NTDmean, ranged from 0 to 34 Gy and 73 of the 540 patients experienced pneumonitis, grade 2 or higher. In all centers, an increasing pneumonitis rate was observed with increasing NTDmean. The data were fitted to the Lyman model with NTD50=31.8 Gy and m=0.43, assuming that for all patients the same parameter values could be used. However, in the low dose range at an NTDmean between 4 and 16 Gy, the observed pneumonitis incidence in the Lung group (10%) was significantly (p=0.02) higher than in the Lymph./Breast group (1.4%). Moreover, between the Lung groups of different institutions, also significant (p=0.04) differences were present: for centers 2, 3, and 4, the pneumonitis incidence was about 13%, whereas for center 5 only 3%. Explicitly accounting for these differences by adding center-dependent offset values for the Lung group, improved the data fit significantly (p < 10(-5)) with NTD50=30.5+/-1.4 Gy and m=0.30+/-0.02 (+/-1 SE) for all patients, and an offset of 0-11% for the Lung group, depending on the center. CONCLUSIONS: The mean lung dose, NTDmean, is relatively easy to calculate, and is a useful predictor of the risk of radiation pneumonitis. The observed dose-effect relation between the NTDmean and the incidence of radiation pneumonitis, based on a large clinical data set, might be of value in dose-escalating studies for lung cancer. The validity of the obtained dose-effect relation will have to be tested in future studies, regarding the influence of confounding factors and dose distributions different from the ones in this study.

Dose-Response Relationship, Radiation↗
PubMed1998

Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis.

PURPOSE: To investigate prospectively the utility of plasma transforming growth factor beta1 (TGFbeta1) as a marker for the development of symptomatic radiation pneumonitis. MATERIALS AND METHODS: Seventy-three patients with lung cancer treated with curative intent are reported herein. Plasma TGFbeta1 samples were obtained before, weekly during, and at each follow-up after radiation therapy (RT). TGFbeta1 was extracted using an acid/ethanol method. An enzyme-linked immunosorbent assay was used to quantify plasma TGFbeta1 concentrations. The TGFbeta1 level at the end of RT was considered "normal" if it was both < or = 7.5 ng/ml and less than the pretreatment value. All patients were followed for at least 6 months, unless symptomatic pneumonitis developed sooner. Pneumonitis was defined by National Cancer Institute (NCI) common toxicity criteria. RESULTS: Fifteen of the 73 patients (21%) developed symptomatic pneumonitis and the remaining 58 (79%) did not. A normal plasma TGFbeta1 by the end of RT, as defined above, was more common in patients who did not develop pneumonitis. A return of the plasma TGFbeta1 to normal accurately identified patients who would not develop pneumonitis with both a sensitivity and positive predictive value of 90%. CONCLUSION: Plasma TGFbeta1 levels appear to be a useful means to identify patients at low risk for the development of pneumonitis from thoracic RT. Thus, monitoring of plasma TGFbeta1 levels may identify candidates for dose escalation studies in the treatment of lung cancer.

Adult↗
PubMed1998

Defining the superior border of posterior fossa radiation treatment fields.

PURPOSE: Lateral posterior fossa treatment fields are usually defined on traditional simulation films based on bony landmarks. The superior field border, intended to include the apex of the tentorium cerebelli, is frequently difficult to define. While sagittal magnetic resonance imaging (MRI) images or three-dimensional treatment planning tools are good means to locate the tentorial apex, these are not always available. We herein describe a method for locating the tentorial apex based on bony landmarks. METHODS AND MATERIALS: Midsagittal magnetic resonance images of 53 patients were reviewed. Using a Cartesian grid, the geometric relationship between the tentorial apex and several bony landmarks was assessed. Two lines were defined: the first connected the posterior clinoid and the internal occipital protuberance (AB). The second was perpendicular to the first, included the tentorial apex, and extended from the base of the skull inferiorly to the "crown" of the skull superiorly (DE). Relationships between measurements were made using linear regression and least square fits. RESULTS: Line DE was within 5 mm of the perpendicular bisector of line AB in 83% (44/53) of patients. The tentorial apex was located within 10 mm of the midpoint of DE in 91% (48/53) of patients. CONCLUSION: In the majority of patients, the location of the tentorial apex can be estimated based on bony landmarks, to within approximately 10 mm. The technique described is a useful means of estimating the location of the tentorial apex in patients where sagittal MRI imaging or three-dimensional treatment planning tools are not available.

Adolescent↗
PubMed1998

Radiotherapy alone for medically inoperable stage I non-small-cell lung cancer: the Duke experience.

PURPOSE: To review our experience treating clinical Stage I non-small-cell lung carcinoma with radiotherapy alone using modern techniques and staging. The effect of dose and volume on outcome is to be analyzed. METHODS: Between January 1980 and December 1995, 156 patients with Stage I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administration Medical Center. Fifteen patients were excluded from analysis (7 treated with palliative intent, and 8 lost to follow-up immediately following radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenocarcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; presenting symptoms: weight loss 26%, cough 23%, none (incidental diagnosis) 57%. All patients underwent simulation prior to radiotherapy using linear accelerators of > or = 4 MV. No patients received surgery or chemotherapy as part of their initial treatment. The median dose of radiotherapy (not reflecting lung inhomogeneity corrections) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractionation. The majority of cases included some prophylactic nodal regions (73%). RESULTS: Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- and 5-year overall survival was 39% and 13%, respectively (median 18 months). The corresponding cause-specific survival was 60%, and 32% (median 30 months). On multivariate analysis, significant factors influencing overall and/or cause-specific survival were age, squamous cell histology, incidental diagnosis, and pack-years of smoking. There was a nonsignificant trend towards improved cause-specific survival with higher radiotherapy doses and larger treatment volumes. On patterns of failure analysis, 42% of failures were local-only and 38% were distant-only. Regional-only failure occurred in 4 patients (7%), 3 of whom failed solely in an unirradiated nodal site. Analysis of factors correlating with local failure at 2 years was performed using a multinominal logistic regression analysis. Significant factors associated with a lower local failure included incidental diagnosis and absence of cough with a strong trend toward significance for higher radiotherapy dose (p = 0.07) and larger treatment volume (p = 0.08). Patients who were locally controlled had an improved cause-specific survival at 5 years over those who were not controlled (46% vs. 12%, p = 0.03). Grade III-V complications occurred in 2 patients (1.5%). CONCLUSION: Patients with clinical Stage I medically inoperable non-small-cell lung cancer treated with contemporary radiotherapy alone achieved a 5-year cause-specific survival of 32%. Uncontrolled lung cancer was the primary cause of death in these patients, and local failure alone represented the most common mode of failure (42%). Patients who were locally controlled had a significantly improved cause-specific survival over those who failed locally. Because higher doses of radiotherapy appear to provide improved local control, studies of dose escalation are warranted until dose-limiting toxicity is observed.

Adenocarcinoma↗
PubMed1998

Regional dose response to pulmonary irradiation using a manual method.

PURPOSE: To better understand the dose dependence of radiation therapy (RT)-induced changes in regional lung perfusion and tissue density, using a manual method to reduce inaccuracies that might be present in previously described automated methods. MATERIALS AND METHODS: Patients who were to receive RT for tumors in and around the thorax, wherein portions of healthy lung would be incidentally irradiated, were prospectively studied. Changes in regional perfusion and tissue density were assessed by comparison of pre- and post-RT single photon emission computed tomography (SPECT), lung perfusion scans and computed tomography (CT) scans, respectively. The three-dimensional dose distribution was calculated on the pre-RT CT scan and correlated to the other scans via image registration. Study volumes were defined by hand and individually visualized on pre- and post-RT scans. The manually generated dose response data were compared to data generated using automated methods. The relationship between CT density and SPECT perfusion was also determined. RESULTS: Thirteen patients with lung cancer were evaluated for changes in tissue density and 11 patients were evaluated for changes in regional perfusion at 12 months post-RT. In general, density increases with increasing regional dose, with marked changes at >60 Gy. Regional perfusion decreases with increasing regional dose. In the low dose regions, relative perfusion increases by 35% on average. Manually measured dose responses correlated well with those determined automatically. The relationship between regional perfusion and CT density indicates a wide range of perfusion over a narrow range of CT density, with markedly reduced perfusion at CT densities of > -600 and < -900 H. CONCLUSIONS: The manually generated CT density dose response data broadly agree with data previously generated using automated methods. The manually generated perfusion dose response data are in fairly good agreement with automated data, lending credibility to the accuracy of the automated methods. Regional perfusion is markedly diminished where CT density is outside the range of normal lung tissue.

Dose-Response Relationship, Radiation↗
PubMed1998

Standard vs conformal radiation therapy for adenocarcinoma of the prostate: no difference.

Objective: To compare results of treatment of adenocardinoma of the prostate using Standard (2D) vs Conformal (3D) treatment planning. Methods: The records of all patients with adenocarcinoma of the prostate treated curatively with radiation therapy alone from July 1991 to June 1994 were reviewed. Acute and late complications were scored by the RTOG criteria. Biochemical failure was defined as a rising PSA of at least 10% on two measurements separated >/=1 month or either a PSA nadir >4 ng/ml or >1 ng/ml. Disease free survival (DFS) was defined as no evidence of local, distant, or biochemical failure. 2D planning included standard simulation with target volume drawn from the treatment planning or diagnostic CT. 3D planning included a CT in the treatment position with computer simulation using beam's-eye-view for field design. Results: Two-hundred and seventeen 2D and 45 3D patients had similar median age and pre-treatment PSA, T-stage, and dose to the prostate. The median follow-up periods for the 2D and 3D groups were 32.0 and 21.5 months, respectively. The two-year actuarial survival, local or biochemical control, and DFS were not different. The 3D group had a significantly higher incidence of acute bladder side effects of all grades and acute grade 1/2 rectal complications. There were no differences in the incidence of late bladder or rectal complications. Conclusions: Careful 2D planning for the treatment of localized adenocarcinoma of the prostate is an acceptable means of treatment. Within the dose range of 64-70 Gy, this preliminary analysis demonstrated no reduction in complications nor improvement in local or biochemical control, or DFS was seen with the the use of 3D treatment planning.

Journal Article↗
PubMed1998

Serial in vivo observations of cerebral vasculature after treatment with a large single fraction of radiation.

To test whether single high doses of radiation, similar to those used with radiosurgery, given to normal cerebral vasculature can cause changes in leukocyte-vessel wall interactions and tissue perfusion, a rat pial window model was used to view the cerebral vasculature, facilitating repeated in vivo observations of microcirculatory function. An attachment for a 4 MV linear accelerator was designed to deliver a well-collimated 2.2-mm beam of radiation to a selected region of rat brain. Sequential measurements of leukocyte-endothelial cell interactions, relative change in blood flow with laser Doppler flowmetry and vessel length density were performed prior to and at 24 h and 3 weeks after treatment with 15, 22.5 or 30 Gy, given in a single fraction. Significant increases in leukocyte-endothelial cell interactions were seen 24 h and 3 weeks after irradiation that were dependent on dose, particularly in arteries. Changes were apparent in both arteries and veins at 24 h, but by 3 weeks the effects in arteries predominated. Decreases in vessel length density and blood flow were observed and became greater with time after treatment. A variety of morphological changes were observed in irradiated arteries, including formation of aneurysmal structures, endothelial denudation and thrombus formation. These results suggest that: (1) An increase in leukocyte-vessel wall interactions occurs after irradiation; (2) cerebral arterioles are more sensitive than veins to radiation administered in this fashion; and (3) the increase in leukocyte-vessel wall interactions likely contributes to reduction of or loss of arteriolar flow, with resultant loss of flow to dependent microvascular vessels.

Animals↗
PubMed1997

Physical and biological predictors of changes in whole-lung function following thoracic irradiation.

PURPOSE: To develop methods of predicting the pulmonary consequences of thoracic irradiation (RT) by prospectively studying changes in pulmonary function following RT. METHODS AND MATERIALS: 100 patients receiving incidental partial-lung irradiation during treatment of tumors in or adjacent to the thorax had whole-lung function assessed via symptoms and pulmonary function tests (PFTs: FEV1-forced expiratory volume 1 s; DLCO-diffusion capacity) before and repeatedly 6-48 months following RT. All had computed tomography-based three-dimensional (3D) dose calculations with lung density heterogeneity corrections for dose-volume histogram (DVH) and normal tissue complication probability (NTCP) calculations. Functional DVHs (DVfH) based on SPECT (single photon emission computed tomography) lung perfusion scans, and serial transforming growth factor-beta (TGF-beta1) levels were available in 50 and 48 patients, respectively. The incidence and severity of changes in whole-lung function were correlated with clinical, physical, and biological factors. Exploratory statistical analyses were performed using chi-square, Pearson correlations, logistic regression, and multiple linear regression. RESULTS: RT-induced symptoms developed in 21 patients. In the overall group, the single best predictor for the development of symptoms was the NTCP (p < 0.05). Pre-RT PFTs alone were less predictive (p = 0.1 for FEV1, p = 0.08 for DLCO). A multivariate model based on pre-RT DLCO and CT-based NTCP was strongly predictive for the development of symptoms (p < 0.001). NTCPs based on SPECT-derived DVf Hs and TGF-beta1 levels did not appear to provide additional predictive value. The presence or absence of pulmonary symptoms was correlated with the decline in PFT 6 months following RT (p < 0.05). In the overall group, the degree of decline in PFTs was not well correlated with any of the dose-volume variables considered. In patients with "good" pre-RT PFTs, there was a relationship between the percent reduction in PFT and dose-volume parameters such as the percent of lung volume receiving > 30 Gy (p < 0.05). CONCLUSION: The extent of alteration in whole-lung function (symptoms or PFT changes) appears to be related to both dose-volume and pre-RT PFT parameters. The data suggest that no one variable is likely to be an adequate predictor and that multivariate predictive models will be needed. Additional studies are underway to develop better predictive models that consider physical factors such as the DVH and regional perfusion, as well as biological/clinical factors such as pre-RT PFTs and TGF-beta1.

Adult↗
PubMed1997

Comparison of two head and neck immobilization systems.

PURPOSE: Accurate and reproducible patient positioning is fundamental to the success of fractionated radiotherapy. Concurrent with the introduction of three-dimensional treatment planning capabilities at our institution, a head and neck immobilization system consisting of a standard foam rubber head support and three casting strips was replaced by a customized mask-based device. This study was performed to analyze the impact of the customized immobilization system on the reproducibility of patient setup during irradiation of head and neck and brain tumors. METHODS AND MATERIALS: Patients treated from 1989-1991 were immobilized with the strip system while those treated from 1991-1995 were immobilized with the mask. All treatment fields were simulated and were treated on a 4 MV (where the strip, but not the mask, system was fixed to the treatment couch) or > or = 6 MV (where both the strip and the mask systems were fixed to the couch) accelerator. Port films were taken on the initial treatment day, routinely during treatment, and following shifts (requested). The number, magnitude, and direction of any isocenter shifts were retrospectively reviewed. A two-tailed chi square test was used to compare the differences in requested shifts in the strip and mask groups. RESULTS: The study population consisted of 69 brain tumor (35 strip, 34 mask) and 71 head and neck (37 strip, 34 mask) patients. A total of 1575 port films representing 1070 isocenter placements were analyzed. No differences between the immobilization systems was seen on the 4-MV accelerator (where the mask system was not fixed to the couch). On the > or = 6-MV units, the frequency of shifts was 16.1% versus 6.2% (p = 0.002) with the strips and mask, respectively. Almost all of the benefit was seen in the routine films, where the corresponding rates were 13.2% and 4.1% (p = 0.007). For the mask system, the rate of requested shifts on routine films was 4.1% (8/197) for the > or = 6-MV units and 14.5% (24/166) for the 4-MV unit (p = 0.001). CONCLUSION: Using the frequency of physician-requested isocenter shifts as an indicator of the accuracy of patient repositioning, the newer mask system appears to be an improvement over the previously used strip system, provided that the immobilization device is secured to the treatment couch. Increased accuracy of daily setup provides an opportunity to improve the therapeutic ratio both by increased likelihood of tumor control and decreased risk of normal tissue complications.

Brain Neoplasms↗
PubMed1997

Comparison of two repositioning devices used during radiation therapy for Hodgkin's disease.

PURPOSE: Patients irradiated for Hodgkin's disease are fixed in an immobilization cradle to improve repositioning. In the early 1990s, we changed our cradle system from a "short" upper torso cradle to an extended near-total body cradle that also includes the lower torso and thighs. In this study, we assess the impact of the extended cradle on the reproducibility of patient repositioning during irradiation of Hodgkin's disease. METHODS AND MATERIALS: A total of 782 port films of 56 patients treated immediately before and after the change-over were studied to assess positioning reproducibility. Patients treated prior to 1993 were positioned in the short cradle, while those treated 1993 and later were positioned in the extended cradle. All treatment were delivered via anterior and posterior fields and treatment areas above and below the diaphragm were considered separately and together. All treatment fields were simulated and the field shape was designed on anterior and posterior radiographs. Discrepancies in field placement between the simulation radiographs and subsequent port films were noted by a radiation oncologist and requests for position adjustment (both translational and rotational shifts) were noted. The number, magnitude, and direction of any physician-requested position adjustment on port films were retrospectively reviewed. For the purpose of scoring the frequency of field misplacements, when an adjustment was noted on two port films taken during the same treatment session (i.e., a left shift on both an anterior and a posterior port film), it was scored as only one event. A two-tailed chi-square test was used to compare the differences in requested shifts in the two patient groups. RESULTS: The study population consisted of 56 patients (31 short and 25 extended cradle) representing 92 treatment sites. A total of 782 port films representing 450 treatment setups were analyzed (292 above and 158 below the diaphragm). When all port films above the diaphragm (mostly mantle fields) are considered, position adjustments were requested in 13.4% (21 out of 157) of treatment setups with the upper torso cradle and in 5.9% (8 out of 135) of treatment setups with the extended cradle (p = 0.054). When all port films below the diaphragm (mostly paraaortic/spleen and pelvic fields) are considered, position adjustments were requested in 33.8% (27 out of 80) of treatment setups with the upper torso cradle and in 16.7 % (13 out of 78) of treatment setups with the extended cradle (p = 0.056). A reduction in the frequency of both translational and rotational adjustments were seen. When both treatment sites are combined, position adjustments were requested in 20.3% (48 out of 237) of treatment setups with the upper torso cradle and in 9.9% (21 out of 213) of treatment setups when the extended cradle was used (p = 0.0086). CONCLUSIONS: The extended cradle provides superior repositioning of patients undergoing radiation therapy for Hodgkin's disease. Differences observed in setup accuracy in this study underscore the importance of aggressive immobilization of patients with Hodgkin's disease. Increased accuracy of daily setup may provide an opportunity to improve the therapeutic ratio both by increased likelihood of tumor control and decreased risk of normal tissue complications.

Equipment Design↗
PubMed1997

Impact of cradle immobilization on setup reproducibility during external beam radiation therapy for lung cancer.

PURPOSE: To compare the setup accuracy during fractionated radiation therapy for two patient groups with lung cancer treated with and without an immobilization cradle. METHODS: Three hundred ninety-seven port films from 30 patients immobilized in the Alpha Cradle were compared with 329 port films from 30 patients who were not immobilized with the cradle. All patients were treated with curative intent for nonmetastatic lung cancer. The frequency of physician-requested isocenter shifts were compared in the two groups using a two-tailed chi-square test. Initial port films taken on the first day of treatment, routine films taken usually weekly during radiation therapy, and requested films taken after a requested shift were considered separately. The immobilization device consisted of a custom-made foam cradle that extended from above the head to the knees. Patients were generally treated with their arms above their heads, and treatment setup marks in the immobilized patients were placed on both the patients' skin and the immobilization cradle. For the noncradle patients, setup marks were placed only on the patients' skin. RESULTS: For the routine films, the frequency of physician-requested isocenter shifts was lower in immobilized patients than in the nonimmobilized group (p = 0.139). Most of this reduction was seen on oblique fields (p = 0.038). No benefits were seen among initial or requested films. The two groups were well balanced with regard to stage, age, field size, and total dose. CONCLUSIONS: The use of aggressive immobilization improves the setup reproducibility in patients receiving external beam radiation therapy for lung cancer, especially during treatment with oblique fields. This improvement in treatment accuracy might improve the therapeutic ratio.

Humans↗
PubMed1997

Selection of coplanar or noncoplanar beams using three-dimensional optimization based on maximum beam separation and minimized nontarget irradiation.

PURPOSE: The design of an appropriate set of multiple fixed fields to achieve a steep dose gradient at the tumor edge, with minimal normal tissue exposure, is a very difficult problem, since a virtually infinite number of possible beam orientations exists. In practice we have selected beams in an iterative and often time-consuming process. This work proposes an optimization method, based on geometric and dose elements, to effectively arrive at a set of beam orientations. METHODS AND MATERIALS: Beams are selected by minimizing a goal function including an angle function (beam separation for steep dose gradient at target edge) and a length function (related to normal tissue dose volume histogram). The relative importance of these two factors may be adjusted depending on the clinic situation. The model is flexible and can include case specific practical anatomic and physical considerations. RESULTS: In extremely simple situations, the goal function yields results consistent with well-known analytical solutions. When applied to more complex clinical situations, it provides clinically reasonable solutions similar to those empirically developed by the clinician. The optimization process takes approximately 25 min on a UNIX workstation. CONCLUSION: The optimization scheme provides a practical means for rapidly designing multiple field coplanar or noncoplanar treatments. It overcomes limitations in human three-dimensional visualization such as trying to visualize beam directions and keeping track of the hinge angle between beams while accounting for anatomic/machine constraints. In practice, it has been used as a starting point for physicians to make modifications, based on their clinical judgment.

Brain Neoplasms↗
PubMed1997

Quantification of radiation-induced regional lung injury with perfusion imaging.

PURPOSE: To better understand the dose and time dependence of radiation therapy (RT)-induced regional lung dysfunction as assessed by changes in regional lung perfusion. METHODS AND MATERIALS: Patients who were to receive RT for tumors in and around the thorax, wherein portions of healthy lung would be incidentally irradiated, were prospectively studied. Regional function was assessed pre- and post-RT with single photon emission computed tomography (SPECT) lung perfusion scans, obtained following the intravenous administration of approximately 4 mCi of technetium-99m macroaggregated albumin. Pre-RT computed tomography (CT) scans were used to calculate the three-dimensional (3D) dose distribution, reflecting tissue density inhomogeneity corrections. Each SPECT scan was correlated with the pre-RT CT scan, and the 3D dose distribution. Changes in regional lung perfusion were correlated with regional RT dose, at various time intervals following radiation. RESULTS: The data from 20 patients (7 breast cancer, 5 lymphoma, 1 esophagus, 1 sarcoma, and 6 lung cancer) have been analyzed. Patients with gross intrathoracic lung cancers causing obstruction of regional pulmonary arteries were not included. For most patients, there is a statistically significant dose-dependent reduction in regional blood flow at all time points following radiation. While a time dependence is suggested in the high dose range, the limited amount of data prevents meaningful statistical evaluation. CONCLUSIONS: Radiation therapy-induced regional lung dysfunction occurs in a dose-dependent manner and develops within 3-6 months following radiation. In contrast to classical "sigmoid" dose-response curves, described mainly for changes following whole lung irradiation, these data suggest a more gradual relationship between regional dysfunction and RT dose. Retraction of irradiated lung with secondary movement of unirradiated lung into the "3D-defined irradiated volume" may have introduced inaccuracies into this analysis. Additional studies are currently underway to assess this possibility and better refine this dose-response curve. Studies are underway to determine if changes in assessments of whole lung function, such as pulmonary function tests, can be predicted by summing the regional changes observed.

Dose-Response Relationship, Radiation↗
PubMed1997

Impact of setup variability on incidental lung irradiation during tangential breast treatment.

PURPOSE: This study aimed to determine the variability in treatment setup during a 5-week course of tangential breast treatment for patients immobilized in a customized hemibody cradle, to assess the relationship between the height of the lung shadow on the tangential port film and the percentage of lung volume irradiated, and to estimate the impact of setup variabilities on irradiated lung volume. METHODS: One hundred seventy-two port films were reviewed from 20 patients who received tangential beam treatment for breast cancer. The height of the lung shadow at the central axis (CLD) on each port film was compared to the corresponding simulator film as an assessment of setup variability. A three-dimensional dose calculation was performed, and the percentage of total lung volume within the field was correlated with the CLD. The three-dimensional dose calculation was repeated for selected patients with the location of the treatment beams modified to reflect typical setup variations. RESULTS: The CLD measured on the port films was within 3 mm of that prescribed on the simulator film in 43% (74 of 172) of the port films. The variation was 3-5 mm in 26%, 5-10 mm in 25%, and >10 mm in 6%. The height of the lung shadow correlated with the percentage of lung volume included in the radiation field (r2 = 0.6). Typical variations in treatment setup resulted in < or = 5% fluctuation in the absolute volume of ipsilateral lung irradiated. CONCLUSION: The current immobilization system used in our clinic provides a clinically acceptable reproducibility of patient setup. The height of the lung shadow is reasonably well correlated with the percentage of irradiated lung volume. During a typical 5-week course of radiotherapy, the ipsilateral irradiated lung volume fluctuates <5%.

Breast Neoplasms↗
PubMed1997

"One to three" or "four or more"?: selecting patients for postmastectomy radiation therapy.

A review of randomized trials suggesting an improvement in overall patient survival with postmastectomy radiation therapy revealed that most patients in these studies had three or fewer positive axillary lymph nodes. Therefore, it is logical to consider using postmastectomy radiation therapy in all lymph node positive patients, not just those with four or more positive lymph nodes.

Breast Neoplasms↗
PubMed1997

Changes in plasma transforming growth factor beta during radiotherapy and the risk of symptomatic radiation-induced pneumonitis.

PURPOSE: To determine whether changes in the plasma Transforming Growth Factor beta1 (TGF beta1) concentration during radiotherapy could identify patients at risk for developing symptomatic radiation pneumonitis. METHODS AND MATERIALS: Thirty-six patients who received radiation therapy with curative intent for lung cancer (n = 31), Hodgkin's disease (n = 4), or thymoma (n = 1) were evaluated prospectively. All patients had serial plasma TGF beta1 measurements obtained before, during, and after treatment. Plasma TGF beta1 was quantified using an enzyme-linked immunosorbent assay. Pneumonitis was defined clinically. Plasma TGF beta1 levels were considered to have normalized if the following occurred: the last on-treatment TGF beta1 level was both <7.5 ng/ml and lower than the pretreatment level. RESULTS: Thirteen of these 36 patients developed pneumonitis. Significant changes in plasma TGF beta1 levels during treatment were seen only in the subset of patients whose TGF beta1 levels were >7.5 ng/ml at baseline (n = 22). Failure of plasma TGF beta1 to normalize by the end of treatment, as defined above, much more accurately identified patients at risk for symptomatic pneumonitis if their baseline TGF beta1 was >7.5 ng/ml than if it was <7.5 ng/ml. CONCLUSIONS: Changes in plasma TGF beta1 levels during radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic radiation pneumonitis, particularly in the subset of patients whose pretreatment TGF beta1 levels are >7.5 ng/ml.

Biomarkers↗