Search PubMed⌕ Search

Biomedical subjects

Jeffrey D Bradley

Publications and source records attributed to Jeffrey D Bradley.

At least 19 recordsLinked to original sources

Comparison of helical, maximum intensity projection (MIP), and averaged intensity (AI) 4D CT imaging for stereotactic body radiation therapy (SBRT) planning in lung cancer.

BACKGROUND AND PURPOSE: To compare helical, MIP and AI 4D CT imaging, for the purpose of determining the best CT-based volume definition method for encompassing the mobile gross tumor volume (mGTV) within the planning target volume (PTV) for stereotactic body radiation therapy (SBRT) in stage I lung cancer. MATERIALS AND METHODS: Twenty patients with medically inoperable peripheral stage I lung cancer were planned for SBRT. Free-breathing helical and 4D image datasets were obtained for each patient. Two composite images, the MIP and AI, were automatically generated from the 4D image datasets. The mGTV contours were delineated for the MIP, AI and helical image datasets for each patient. The volume for each was calculated and compared using analysis of variance and the Wilcoxon rank test. A spatial analysis for comparing center of mass (COM) (i.e. isocenter) coordinates for each imaging method was also performed using multivariate analysis of variance. RESULTS: The MIP-defined mGTVs were significantly larger than both the helical- (p=0.001) and AI-defined mGTVs (p=0.012). A comparison of COM coordinates demonstrated no significant spatial difference in the x-, y-, and z-coordinates for each tumor as determined by helical, MIP, or AI imaging methods. CONCLUSIONS: In order to incorporate the extent of tumor motion from breathing during SBRT, MIP is superior to either helical or AI images for defining the mGTV. The spatial isocenter coordinates for each tumor were not altered significantly by the imaging methods.

Humans↗

Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response.

PURPOSE: Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. PATIENTS AND METHODS: Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. RESULTS: Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. CONCLUSION: For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.

Adenocarcinoma↗

Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters.

PURPOSE: To determine the clinical, dosimetric, and spatial parameters that correlate with radiation pneumonitis. METHODS AND MATERIALS: Patients treated with high-dose radiation for non-small-cell lung cancer with three-dimensional treatment planning were reviewed for clinical information and radiation pneumonitis (RP) events. Three-dimensional treatment plans for 219 eligible patients were recovered. Treatment plan information, including parameters defining tumor position and dose-volume parameters, was extracted from non-heterogeneity-corrected dose distributions. Correlation to RP events was assessed by Spearman's rank correlation coefficient (R). Mathematical models were generated that correlate with RP. RESULTS: Of 219 patients, 52 required treatment for RP (median interval, 142 days). Tumor location was the most highly correlated parameter on univariate analysis (R = 0.24). Multiple dose-volume parameters were correlated with RP. Models most frequently selected by bootstrap resampling included tumor position, maximum dose, and D35 (minimum dose to the 35% volume receiving the highest doses) (R = 0.28). The most frequently selected two- or three-parameter models outperformed commonly used metrics, including V20 (fractional volume of normal lung receiving >20 Gy) and mean lung dose (R = 0.18). CONCLUSIONS: Inferior tumor position was highly correlated with pneumonitis events within our population. Models that account for inferior tumor position and dosimetric information, including both high- and low-dose regions (D(35), International Commission on Radiation Units and Measurements maximum dose), risk-stratify patients more accurately than any single dosimetric or clinical parameter.

Adult↗

A comparison between amplitude sorting and phase-angle sorting using external respiratory measurement for 4D CT.

Respiratory motion can cause significant dose delivery errors in conformal radiation therapy for thoracic and upper abdominal tumors. Four-dimensional computed tomography (4D CT) has been proposed to provide the image data necessary to model tumor motion and consequently reduce these errors. The purpose of this work was to compare 4D CT reconstruction methods using amplitude sorting and phase angle sorting. A 16-slice CT scanner was operated in ciné mode to acquire 25 scans consecutively at each couch position through the thorax. The patient underwent synchronized external respiratory measurements. The scans were sorted into 12 phases based, respectively, on the amplitude and direction (inhalation or exhalation) or on the phase angle (0-360 degrees) of the external respiratory signal. With the assumption that lung motion is largely proportional to the measured respiratory amplitude, the variation in amplitude corresponds to the variation in motion for each phase. A smaller variation in amplitude would associate with an improved reconstructed image. Air content, defined as the amount of air within the lungs, bronchi, and trachea in a 16-slice CT segment and used by our group as a surrogate for internal motion, was correlated to the respiratory amplitude and phase angle throughout the lungs. For the 35 patients who underwent quiet breathing, images (similar to those used for treatment planning) and animations (used to display respiratory motion) generated using amplitude sorting displayed fewer reconstruction artifacts than those generated using phase angle sorting. The variations in respiratory amplitude were significantly smaller (P < 0.001) with amplitude sorting than those with phase angle sorting. The subdivision of the breathing cycle into more (finer) phases improved the consistency in respiratory amplitude for amplitude sorting, but not for phase angle sorting. For 33 of the 35 patients, the air content showed significantly improved (P < 0.001) correlation with the respiratory amplitude than with the phase angle, suggesting a stronger relationship between internal motion and amplitude. Overall, amplitude sorting performed better than phase angle sorting for 33 of the 35 patients and equally well for two patients who were immobilized with a stereotactic body frame and an abdominal compression plate.

Algorithms↗

Deblurring of breathing motion artifacts in thoracic PET images by deconvolution methods.

In FDG-PET imaging of thoracic tumors, blurring due to breathing motion often significantly degrades the quality of the observed image, which then obscures the tumor boundary. We demonstrate a deblurring technique that combines patient-specific motion estimates of tissue trajectories with image deconvolution techniques, thereby partially eliminating breathing-motion induced artifacts. Two data sets were used to evaluate the methodology including mobile phantoms and clinical images. The clinical images consist of PET/CT co-registered images of patients diagnosed with lung cancer. A breathing motion model was used to locally estimate the location-dependent tissue location probability function (TLP) due to breathing. The deconvolution process is carried by an expectation-maximization (EM) iterative algorithm using the motion-based TLP. Several methods were used to improve the robustness of the deblurring process by mitigating noise amplification and compensating for motion estimate uncertainties. The mobile phantom study with controlled settings demonstrated significant reduction in underestimation error of concentration in high activity case without significant superiority between the different applied methods. In case of medium activity concentration (moderate noise levels), less improvement was reported (10%-15% reduction in underestimation error relative to 15%-20% reduction in high concentration). Residual denoising using wavelets offered the best performance for this case. In the clinical data case, the image spatial resolution was significantly improved, especially in the direction of greatest motion (cranio-caudal). The EM algorithm converged within 15 and 5 iterations in the large and small tumor cases, respectively. A compromise between a figure-of-merit and entropy minimization was suggested as a stopping criterion. Regularization techniques such as wavelets and Bayesian methods provided further refinement by suppressing noise amplification. Our initial results show that the proposed method provides a feasible framework for improving PET thoracic images, without the need for gated/4-D PET imaging, when 4-D CT is available to estimate tumor motion.

Algorithms↗

A semi-automatic method for peak and valley detection in free-breathing respiratory waveforms.

The existing commercial software often inadequately determines respiratory peaks for patients in respiration correlated computed tomography. A semi-automatic method was developed for peak and valley detection in free-breathing respiratory waveforms. First the waveform is separated into breath cycles by identifying intercepts of a moving average curve with the inspiration and expiration branches of the waveform. Peaks and valleys were then defined, respectively, as the maximum and minimum between pairs of alternating inspiration and expiration intercepts. Finally, automatic corrections and manual user interventions were employed. On average for each of the 20 patients, 99% of 307 peaks and valleys were automatically detected in 2.8 s. This method was robust for bellows waveforms with large variations.

Algorithms↗

18F-FDG PET definition of gross tumor volume for radiotherapy of non-small cell lung cancer: is a single standardized uptake value threshold approach appropriate?

UNLABELLED: PET with (18)F-FDG has been used in radiation treatment planning for non-small cell lung cancer (NSCLC). Thresholds of 15%-50% the maximum standardized uptake value (SUV(max)) have been used for gross tumor volume (GTV) delineation by PET (PET(GTV)), with 40% being the most commonly used value. Recent studies indicated that 15%-20% may be more appropriate. The purposes of this study were to determine which threshold generates the best volumetric match to GTV delineation by CT (CT(GTV)) for peripheral NSCLC and to determine whether that threshold can be generalized to tumors of various sizes. METHODS: Data for patients who had peripheral NSCLC with well-defined borders on CT and SUV(max) of greater than 2.5 were reviewed. PET/CT datasets were reviewed, and a volume of interest was determined to represent the GTV. The CT(GTV) was delineated by using standard lung windows and reviewed by a radiation oncologist. The PET(GTV) was delineated automatically by use of various percentages of the SUV(max). The PET(GTV)-to-CT(GTV) ratios were compared at various thresholds, and a ratio of 1 was considered the best match, or the optimal threshold. RESULTS: Twenty peripheral NSCLCs with volumes easily defined on CT were evaluated. The SUV(max) (mean +/- SD) was 12 +/- 8, and the mean CT(GTV) was 198 cm(3) (97.5% confidence interval, 5-1,008). The SUV(max) were 16 +/- 5, 13 +/- 9, and 3.0 +/- 0.4 for tumors measuring greater than 5 cm, 3-5 cm, and less than 3 cm, respectively. The optimal thresholds (mean +/- SD) for the best match were 15% +/- 6% for tumors measuring greater than 5 cm, 24% +/- 9% for tumors measuring 3-5 cm, 42% +/- 2% for tumors measuring less than 3 cm, and 24% +/- 13% for all tumors. The PET(GTV) at the 40% and 20% thresholds underestimated the CT(GTV) for 16 of 20 and 14 of 20 lesions, respectively. The mean difference in the volumes (PET(GTV) minus CT(GTV) [PET(GTV) - CT(GTV)]) at the 20% threshold was 79 cm(3) (97.5% confidence interval, -922 to 178). The PET(GTV) at the 20% threshold overestimated the CT(GTV) for all 4 tumors measuring less than 3 cm and underestimated the CT(GTV) for all 6 tumors measuring greater than 5 cm. The CT(GTV) was inversely correlated with the PET(GTV) - CT(GTV) at the 20% threshold (R(2) = 0.90, P < 0.0001). The optimal threshold was inversely correlated with the CT(GTV) (R(2) = 0.79, P < 0.0001). CONCLUSION: No single threshold delineating the PET(GTV) provides accurate volume definition, compared with that provided by the CT(GTV), for the majority of NSCLCs. The strong correlation of the optimal threshold with the CT(GTV) warrants further investigation.

Carcinoma, Non-Small-Cell Lung↗

CT localization of axillary lymph nodes in relation to the humeral head: significance of arm position for radiation therapy planning.

Irradiation of the axillary nodes is often indicated in the clinical radiotherapy of patients with lymphoma and breast cancer. The relative location of the axillary nodes and the humeral head has historically been estimated based on lymphangiographic data. Since CT offers more precise definition, the axillary nodal region in relation to the humeral head was systematically studied in 61 patients undergoing CT simulation for breast conservation therapy. Differences in arm position (degree of abduction) significantly affected the location of the axillary nodal region in relation to the humeral head. With the arm abducted beyond 55 degrees, humeral head blocking would result in blocking of some of the axillary nodes.

Axilla↗

Novel breathing motion model for radiotherapy.

PURPOSE: An accurate model of breathing motion under quiet respiration is desirable to obtain the most accurate and conformal dose distributions for mobile lung cancer lesions. On the basis of recent lung motion measurements and the physiologic functioning of the lungs, we have determined that the motion of lung and lung tumor tissues can be modeled as a function of five degrees of freedom, the position of the tissues at a user-specified reference breathing phase, tidal volume and its temporal derivative airflow (tidal volume phase space). Time is an implicit variable in this model. METHODS AND MATERIALS: To test this hypothesis, a mathematical model of motion was developed that described the motion of objects p in the lungs as linear functions of tidal volume and airflow. The position of an object was described relative to its position -->P0 at the reference tidal volume and zero airflow, and the motion of the object was referenced to this position. Hysteresis behavior was hypothesized to be caused by pressure imbalances in the lung during breathing and was, in this model, a function of airflow. The motion was modeled as independent tidal volume and airflow displacement vectors, with the position of the object at time t equal to the vector sum -->rP(t) = -->rv(t) + -->rf(t) where -->rv(t) and -->rf(t) were displacement vectors with magnitudes approximated by linear functions of the tidal volume and airflow. To test this model, we analyzed five-dimensional CT scans (CT scans acquired with simultaneous real-time monitoring of the tidal volume) of 4 patients. The scans were acquired throughout the lungs, but the trajectories were analyzed in the couch positions near the diaphragm. A template-matching algorithm was implemented to identify the positions of the points throughout the 15 scans. In total, 76 points throughout the 4 patients were tracked. The lateral motion of these points was minimal; thus, the model was described in two spatial dimensions, with a total of six parameters necessary to describe the 30 degrees of freedom inherent in the 15 positions. RESULTS: For the 76 evaluated points, the average discrepancy (the distance between the measured and prediction positions) of the 15 locations for each tracked point was 0.75 +/- 0.25 mm, with an average maximal discrepancy of 1.55 +/- 0.54 mm. The average discrepancy was also tabulated as a fraction of the breathing motion. Discrepancies of <10% and 15% of the overall motion occurred in 73% and 95% of the tracked points, respectively. CONCLUSION: The motion tracking algorithms are being improved and automated to provide more motion data to test the models. This may allow a measurement of the motion-fitting parameters throughout the lungs. If the parameters vary smoothly, interpolation may be possible, yielding a continuous mathematical model of the breathing motion throughout the lungs. The utility of the model will depend on its stability as a function of time. If the model is only robust during the measurement session, it may be useful for determining lung function. If it is robust for weeks, it may be useful for treatment planning and gating of lung treatments. The use of tidal volume phase space for characterizing breathing motion appears to have provided, for the first time, the potential for a patient-specific mathematical model of breathing motion.

Humans↗

Phase II trial of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage II and IIIA non-small-cell lung cancer: promising long-term results of the Radiation Therapy Oncology Group--RTOG 9705.

PURPOSE: To determine the overall survival, progression-free survival, and toxicity associated with concurrent paclitaxel/carboplatin and thoracic radiotherapy for completely resected patients with stage II and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eighty-eight eligible patients had surgical resection for pathologic stage II or IIIA disease and received postoperative paclitaxel and carboplatin. Concurrent thoracic radiotherapy at 50.4 Gy in 28 fractions for 6 weeks (1.8 Gy/d, 5 days/wk) was given during cycles 1 and 2. A boost of 10.8 Gy in six fractions was given for extracapsular nodal extension or T3 lesions. RESULTS: Treatment compliance was acceptable, with 93% compliance for radiation therapy and 86% for chemotherapy completion. The median duration of follow-up was 56.7 months (range, 17 to 61 months). The median overall survival time was 56.3 months, with 1-, 2-, and 3-year survival rates of 86%, 70%, and 61%, respectively. The 1-, 2-, and 3- year progression-free survival rates were 70%, 57%, and 50%, respectively. Brain metastasis occurred as the sole site of first failure in 11%, and 9% failed in other metastatic sites as first failure. Of the 43 patients who died, the cause of death was the treated cancer in 31 (35%). Local failure was a component of first failure in 15% of patients. Toxicities were acceptable. An overall survival comparison to Eastern Cooperative Oncology Group 3590 is favorable. CONCLUSION: The mature results of this trial suggest an improved overall and progression-free survival in this group of resected NSCLC patients, compared with previously reported trials. A phase III trial comparing this treatment regimen with standard therapy seems warranted.

Aged↗

Quantitation of the reconstruction quality of a four-dimensional computed tomography process for lung cancer patients.

We have developed a four-dimensional computed tomography (4D CT) technique for mapping breathing motion in radiotherapy treatment planning. A multislice CT scanner (1.5 mm slices) operated in ciné mode was used to acquire 12 contiguous slices in each couch position for 15 consecutive scans (0.5 s rotation, 0.25 s between scans) while the patient underwent simultaneous quantitative spirometry measurements to provide a sorting metric. The spirometry-sorted scans were used to reconstruct a 4D data set. A critical factor for 4D CT is quantifying the reconstructed data set quality which we measure by correlating the metric used relative to internal-object motion. For this study, the internal air content within the lung was used as a surrogate for internal motion measurements. Thresholding and image morphological operations were applied to delineate the air-containing tissues (lungs, trachea) from each CT slice. The Hounsfield values were converted to the internal air content (V). The relationship between the air content and spirometer-measured tidal volume (v) was found to be quite linear throughout the lungs and was used to estimate the overall accuracy and precision of tidal volume-sorted 4D CT. Inspection of the CT-scan air content as a function of tidal volume showed excellent correlations (typically r>0.99) throughout the lung volume. Because of the discovered linear relationship, the ratio of internal air content to tidal volume was indicative of the fraction of air change in each couch position. Theoretically, due to air density differences within the lung and in room, the sum of these ratios would equal 1.11. For 12 patients, the mean value was 1.08 +/- 0.06, indicating the high quality of spirometry-based image sorting. The residual of a first-order fit between v and V was used to estimate the process precision. For all patients, the precision was better than 8%, with a mean value of 5.1% +/- 1.9%. This quantitative analysis highlights the value of using spirometry as the metric in sorting CT scans. The 4D reconstruction provides the CT data required to measure the three-dimensional trajectory of tumor and lung tissue during free breathing.

Air↗

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung.

An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung. The abdominal height was known to be affected by sensor placement and patient positioning while the spirometer exhibited signal drift. By combining these two, a normalization of the drift-free metric to tidal volume may be generated and the overall metric precision may be improved.

Abdomen↗

Reduction of motion blurring artifacts using respiratory gated CT in sinogram space: a quantitative evaluation.

Techniques have been developed for reducing motion blurring artifacts by using respiratory gated computed tomography (CT) in sinogram space and quantitatively evaluating the artifact reduction. A synthetic sinogram was built from multiple scans intercepting a respiratory gating window. A gated CT image was then reconstructed using the filtered back-projection algorithm. Wedge phantoms, developed for quantifying the motion artifact reduction, were scanned while being moved using a computer-controlled linear stage. The resulting artifacts appeared between the high and low density regions as an apparent feature with a Hounsfield value that was the average of the two regions. A CT profile through these regions was fit using two error functions, each modeling the partial-volume averaging characteristics for the unmoving phantom. The motion artifact was quantified by determining the apparent distance between the two functions. The blurring artifact had a linear relationship with both the speed and the tangent of the wedge angles. When gating was employed, the blurring artifact was reduced systematically at the air-phantom interface. The gated image of phantoms moving at 20 mm/s showed similar blurring artifacts as the nongated image of phantoms moving at 10 mm/s. Nine patients were also scanned using the synchronized respiratory motion technique. Image artifacts were evaluated in the diaphragm, where high contrast interfaces intercepted the imaging plane. For patients, this respiratory gating technique reduced the blurring artifacts by 9%-41% at the lung-diaphragm interface.

Air↗

Positron emission tomography in limited-stage small-cell lung cancer: a prospective study.

PURPOSE: To determine how often positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose (FDG-PET) detects extensive-stage small-cell lung cancer (SCLC) in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC. PATIENTS AND METHODS: We prospectively performed pretreatment FDG-PET on 24 patients determined by conventional staging methods to have limited-stage SCLC (defined as disease that could be encompassed within a reasonable radiotherapy portal, excluding bilateral supraclavicular disease). PET images were evaluated for evidence of extensive-stage disease. Tumor-node-metastasis system staging was also assigned for each patient, with and without PET information. RESULTS: FDG-PET demonstrated findings consistent with extensive-stage SCLC in three of 24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on computed tomography (CT) imaging, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in six (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. Brain PET images in 23 patients disclosed no evidence of brain metastasis. CONCLUSION: FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease.

Adult↗

Localization of internal mammary lymph nodes by CT simulation: implications for breast radiation therapy planning.

The efficacy of post-operative radiation therapy in breast cancer management has been evident for several decades. In recent years there has been increasing interest in treating the internal mammary lymph nodes. In an attempt to simplify their localization for treatment planning purposes, the position of the internal mammary lymph nodes was systematically studied in 65 breast cancer patients undergoing CT simulation.

Breast Neoplasms↗

Implementing biologic target volumes in radiation treatment planning for non-small cell lung cancer.

18F-FDG PET offers the radiation oncology community the ability to incorporate biologic information into radiation therapy targets. To date, most of the work in this arena has involved patients with non-small cell lung cancer (NSCLC). The literature suggests that biologic targeting with PET alters the radiation treatment volume significantly in 30%-60% of NSCLC patients for whom definitive therapy is planned. This is mostly the result of the incorporation of regional nodes with 18F-FDG avidity that were previously judged to be uninvolved by CT criteria. The development of the integrated PET/CT scanner is a valuable tool that improves diagnostic accuracy for staging this disease and will increase the accessibility of PET for radiation treatment planning. Its implementation into radiation treatment planning requires strong collaboration between radiation oncologists and nuclear physicians. In this report, we will review the literature on PET-based radiation treatment planning, its potential benefits, and future challenges.

Carcinoma, Non-Small-Cell Lung↗

Elective nodal failures are uncommon in medically inoperable patients with Stage I non-small-cell lung carcinoma treated with limited radiotherapy fields.

PURPOSE: To review the outcome for 56 Stage I non-small-cell lung cancer treated definitively with three-dimensional conformal radiotherapy (3D-CRT) and to investigate the value of elective nodal irradiation in this patient population. METHODS AND MATERIALS: Between 1992 and 2001, 56 patients were treated with 3D-CRT for inoperable Stage I histologically confirmed non-small-cell lung cancer; 31 with T1N0 and 25 with T2N0 disease. All patients were treated with 3D-CRT to a median isocenter dose of 70 Gy (range 59.94-83.85) given in daily doses of 1.8 or 2 Gy. Prognostic factors were analyzed with respect to their impact on overall survival. Twenty-two patients received radiotherapy (RT) directed to elective regional lymphatics to doses of 45-50 Gy. The remaining 33 patients were treated to limited fields confined to the primary lung cancer with a margin. The patterns of failure were reviewed. RESULTS: The median follow-up was 20 months (range 6 months to 6 years). The actuarial local control rate was 88%, 69%, and 63%, at 1, 2, and 3 years, respectively. The actuarial cause-specific survival rate was 82%, 67%, and 51% at 1, 2, and 3 years, respectively. The actuarial overall survival rate was 73%, 51%, and 34% at 1, 2, and 3 years, respectively. The actuarial metastasis-free survival rate was 90%, 85%, and 81% at 1, 2, and 3 years, respectively. The RT dose was the only factor predictive of overall survival in our analysis. No statistically significant difference was noted in cause-specific or overall survival according to whether patients received elective nodal irradiation. Two of 33 patients treated with limited fields had regional nodal failure. CONCLUSION: Many patients with medically inoperable Stage I lung cancer die of intercurrent causes. The omission of the elective nodal regions from the RT portals did not compromise either the cause-specific or overall survival rate. Elective nodal failures were uncommon in the group treated with limited RT fields. A radiation dose 70 Gy was predictive of better survival in our population. We await the results of prospective trials evaluating high-dose RT in patients treated with RT alone for Stage I lung cancer.

Aged↗

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. RESULTS: Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Acute Disease↗