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Physics in Medicine and Biology 06/2011; 56(11):3445-6. · 2.83 Impact Factor
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ABSTRACT: In ITV-based 3D-planning, the information of volume occupancy versus respiratory phase is not utilized. We propose a motion-weighted CTV (mwCTV) delineation method, which carries some 4D-information into planning. This method allows plan optimization based on occupancy-weighting and generation of motion-weighted DVH (mwDVH) that approximate the DVHs of full 4D-dose accumulation.
Occupancy information from contours in 4D-CT is incorporated in the mwCTV generation. Higher-occupancy volumes receive higher dosimetric priority in planning. The temporally-weighted mwCTV is converted to a spatially-weighted mwCTV incorporating the temporal-weighting in mwDVH generation using the 3D-dose distribution. The mwDVHs were compared with DVHs of deformable-image-registration (DIR)-based 4D-dose accumulation and 3D-method for 10 cases.
For all the cases, the mwDVH curves are closer to the 4D-calculated DVH than the 3D-DVHs are, indicating a better approximation of the 4D-DVH. The 70 Gy-covered percentage-CTV volume differed by -2.8% ± 0.8% between 3D and 4D, and 0.3% ± 0.7% between mwDVH and 4D-methods. The mean RMS values of the percentage-volume differences for the 4D-3D is 1.7 ± 1.1, while for the 4D-mwDVH is 0.4 ± 0.3.
The mwCTV and mwDVH method, which is simple in implementation and does not require DIR, is a practical approximation of DIR-based 4D-planning and evaluation.
Radiotherapy and Oncology 03/2011; 99(1):67-72. · 5.58 Impact Factor
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ABSTRACT: We introduce a logical process of three distinct phases to begin the evaluation of a new 3D dosimetry array. The array under investigation is a hollow cylinder phantom with diode detectors fixed in a helical shell forming an "O" axial detector cross section (ArcCHECK), with comparisons drawn to a previously studied 3D array with diodes fixed in two crossing planes forming an "X" axial cross section (Delta⁴). Phase I testing of the ArcCHECK establishes: robust relative calibration (response equalization) of the individual detectors, minor field size dependency of response not present in a 2D predecessor, and uncorrected angular response dependence in the axial plane. Phase II testing reveals vast differences between the two devices when studying fixed-width full circle arcs. These differences are primarily due to arc discretization by the TPS that produces low passing rates for the peripheral detectors of the ArcCHECK, but high passing rates for the Delta⁴. Similar, although less pronounced, effects are seen for the test VMAT plans modeled after the AAPM TG119 report. The very different 3D detector locations of the two devices, along with the knock-on effect of different percent normalization strategies, prove that the analysis results from the devices are distinct and noninterchangeable; they are truly measuring different things. The value of what each device measures, namely their correlation with--or ability to predict--clinically relevant errors in calculation and/or delivery of dose is the subject of future Phase III work.
Journal of Applied Clinical Medical Physics 01/2011; 12(2):3346. · 1.29 Impact Factor
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ABSTRACT: Compared with multileaf collimator (MLC)-based intensity-modulated radiotherapy (IMRT) for moving targets, compensator-based IMRT has advantages such as shorter beam-on time, fewer monitor units with potentially decreased secondary carcinogenesis risk, better optimization-to-deliverable dose conversion, and often better dose conformity. Some of the disadvantages include additional time for the compensators to be built and delivered, as well as extra cost. Patients undergoing treatment of abdominal cancers often experience weight loss. It would be necessary to account for this change in weight with a new plan and a second set of compensators. However, this would result in treatment delays and added costs. We have developed a method to re-plan the patient using the same set of compensators. Because the weight changes seen with the treatment of abdominal cancers are usually relatively small, a new 4D computed tomography (CT) acquired in the treatment position with markers on the original isocenter tattoos can be registered to the original planning scan. The contours of target volumes from the original scans are copied to the new scan after fusion. The original compensator set can be used together with a few field-in-field (FiF) beams defined by the MLC (or beams with cerrobend blocks for accelerators not equipped with a MLC). The weights of the beams with compensators are reduced so that the FiF or blocked beams can be optimized to mirror the original plan and dose distribution. Seven abdominal cancer cases are presented using this technique. The new plan on the new planning CT images usually has the same dosimetric quality as the original. The target coverage and dose uniformity are improved compared with the plan without FiF/block modification. Techniques combining additional FiF or blocked beams with the original compensators optimize the treatment plans when patients lose weight and save time and cost compared with generating plans with a new set of compensators.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 03/2010; 36(1):102-8. · 1.26 Impact Factor
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ABSTRACT: For an institution that already owns the licenses, it is economically advantageous and technically feasible to use Pinnacle TPS (Philips Radiation Oncology Systems, Fitchburg, WI) with the BrainLab Novalis delivery system (BrainLAB A.G., Heimstetten, Germany). This takes advantage of the improved accuracy of the convolution algorithm in the presence of heterogeneities compared with the pencil beam calculation, which is particularly significant for lung SBRT treatments. The reference patient positioning DRRs still have to be generated by the BrainLab software from the CT images and isocenter coordinates transferred from Pinnacle. We validated this process with the end-to-end hidden target test, which showed an isocenter positioning error within one standard deviation from the previously established mean value. The Novalis treatment table attenuation is substantial (up to 6.2% for a beam directed straight up and up to 8.4% for oblique incidence) and has to be accounted for in calculations. A simple single-contour treatment table model was developed, resulting in mean differences between the measured and calculated attenuation factors of 0.0%-0.2%, depending on the field size. The maximum difference for a single incidence angle is 1.1%. The BrainLab micro-MLC (mMLC) leaf tip, although not geometrically round, can be represented in Pinnacle by an arch with satisfactory dosimetric accuracy. Subsequently, step-and-shoot (direct machine parameter optimization) IMRT dosimetric agreement is excellent. VMAT (called "SmartArc" in Pinnacle) treatments with constant gantry speed and dose rate are feasible without any modifications to the accelerator. Due to the 3 mm-wide mMLC leaves, the use of a 2 mm calculation grid is recommended. When dual arcs are used for the more complex cases, the overall dosimetric agreement for the SmartArc plans compares favorably with the previously reported results for other implementations of VMAT: gamma(3%,3mm) for absolute dose obtained with the biplanar diode array passing rates above 97% with the mean of 98.6%. However, a larger than expected dose error with the single-arc plans, confined predominantly to the isocenter region, requires further investigation.
Journal of Applied Clinical Medical Physics 01/2010; 11(3):3240. · 1.29 Impact Factor
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ABSTRACT: Currently there are no commercially available tools to generate composite plans across different treatment modalities and/or different planning image sets. Without a composite plan, it may be difficult to perform a meaningful dosimetric evaluation of the overall treatment course. In this paper, we introduce a method to generate composite biological effective dose (BED) plans over multiple radiotherapy treatment modalities and/or multistage plans, using deformable image registration. Two cases were used to demonstrate the method. Case I was prostate cancer treated with intensity-modulated radiation therapy (IMRT) and a permanent seed implant. Case II involved lung cancer treated with two treatment plans generated on two separate computed tomography image sets. Thin-plate spline or optical flow methods were used as appropriate to generate deformation matrices. The deformation matrices were then applied to the dose matrices and the resulting physical doses were converted to BED and added to yield the composite plan. Cell proliferation and sublethal repair were considered in the BED calculations. The difference in BED between normal tissues and tumor volumes was accounted for by using different BED models, alpha/beta values, and cell potential doubling times. The method to generate composite BED plans presented in this paper provides information not available with the traditional simple dose summation or physical dose summation. With the understanding of limitations and uncertainties of the algorithms involved, it may be valuable for the overall treatment plan evaluation.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 06/2009; 35(2):143-50. · 1.26 Impact Factor
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ABSTRACT: The purpose of this paper is to validate a dose mapping program using optical flow method (OFM), and to demonstrate application of the program in radiotherapy follow-up evaluation. For the purpose of validation, the deformation matrices between four-dimensional (4D) CT data of different simulated respiration phases of a phantom were calculated using OFM. The matrices were then used to map doses of all phases to a single-phase image, and summed in equal time weighting. The calculated dose should closely represent the dose delivered to the moving phantom if the deformation matrices are accurately calculated. The measured point doses agreed with the OFM calculations better than 2% at isocenters, and dose distributions better than 1mm for the 50% isodose line. To demonstrate proof-of-concept for the use of deformable image registration in dose mapping for treatment evaluation, the treatment-planning CT was registered with the post-treatment CT image from the positron emission tomography (PET)/CT resulting in a deformation matrix. The dose distribution from the treatment plan was then mapped onto the restaging PET/CT using the deformation matrix. Two cases in which patients had thoracic malignancies are presented. Each patient had CT-based treatment planning for radiotherapy and restaging fluorodeoxy glucose (FDG)-PET/CT imaging 4-6 weeks after completion of treatments. Areas of pneumonitis and recurrence were identified radiographically on both PET and CT restaging images. Local dose and standard uptake values for pneumonitis and recurrence were studied as a demonstration of this method. By comparing the deformable mapped dose to measurement, the treatment evaluation method which is introduced in this manuscript proved to be accurate. It thus provides a more accurate analysis than other rigid or linear dose-image registration when used in studying treatment outcome versus dose.
Computer Methods and Programs in Biomedicine 05/2008; 90(1):25-37. · 1.52 Impact Factor
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ABSTRACT: A 3-dimensional (3D) optical flow program that includes a multi-resolution feature has been developed and applied to 3D anatomical structure and gross tumor volume (GTV) contour mapping for 4-dimensional (4D) CT data. The study includes contour mapping for 3 real patient CT data sets, and also for a thoracic phantom in which the displacement for each voxel is known. Of the real patient CT data sets, one set has been used to map contours of lung and GTV over all the respiration phases, while the others were studied using only the end inspiration and end expiration phases, in which the displacement between the phases were the largest. Including the residual motion in the 4D CT data and motion table shaking, the optical flow calculation agrees to within 1 mm with the known displacement. Excluding those errors that are not introduced by optical flow algorithm, the agreement can be within 0.1 mm with a displacement magnitude of 24 mm. The mapped contours of lungs, liver, esophagus, GTV, etc. in real patient 4D CT images were acceptable to clinicians. The 3D optical flow program is a good tool for anatomical structure and tumor volume contour mapping across 4D CT scans.
Journal of Applied Clinical Medical Physics 02/2008; 9(1):2738. · 1.29 Impact Factor
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ABSTRACT: To quantify the relationship between the local radiation dose received and the posttreatment positron emission tomography/computed tomography (PET/CT) [(18)F]2-fluoro-2-deoxyglucose (FDG) uptake in the lung.
The data from 36 patients treated for esophageal cancer with thoracic radiotherapy who underwent restaging PET/CT imaging between 4 and 12 weeks after radiotherapy completion were evaluated. Their treatment planning CT was registered with the restaging PET/CT. Using histogram analysis, the voxel average FDG-PET uptake vs. radiation dose was obtained for each case. Hierarchical linear regression models for each patient were applied to study the variation in the linear trends between cases. Deviation of the dose-response curve from a linear model was tested.
The median time between radiotherapy completion and FDG-PET imaging was 40 days (range, 26-70 days). The median of the mean standard uptake value in the lung that received 0-5 Gy was 0.63 (range, 0.36-1.27), 5-10 Gy was 0.77 (range, 0.40-1.35), 10-20 Gy was 0.80 (range, 0.40-1.72), and >20 Gy was 1.08 (range, 0.44-2.63). A hierarchical linear regression model of the radiation dose and normalized FDG uptake per case found an adequate fit with the linear model, and the addition of quadratic and logarithmic functions did not improve the fit. The 36 cases had a posterior mean of slopes range of 0.0048-0.069.
The regional dose vs. radiation pneumonitis response was evaluated with FDG-PET/CT imaging. Statistical modeling found a linear relationship. The slope of this relationship varied over an order of magnitude, reflecting the range of the underlying biological response to radiation among the study population.
International Journal of Radiation OncologyBiologyPhysics 07/2007; 68(4):1030-5. · 4.11 Impact Factor
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ABSTRACT: Histone deacetylase (HDAC) inhibitors have emerged recently as promising anticancer agents. They arrest cells in the cell cycle and induce differentiation and cell death. The antitumor activity of HDAC inhibitors has been linked to their ability to induce gene expression through acetylation of histone and nonhistone proteins. However, it has recently been suggested that HDAC inhibitors may also enhance the activity of other cancer therapeutics, including radiotherapy. The purpose of this study was to evaluate the ability of HDAC inhibitors to radiosensitize human melanoma cells in vitro.
A panel of HDAC inhibitors that included sodium butyrate (NaB), phenylbutyrate, tributyrin, and trichostatin A were tested for their ability to radiosensitize two human melanoma cell lines (A375 and MeWo) using clonogenic cell survival assays. Apoptosis and DNA repair were measured by standard assays.
NaB induced hyperacetylation of histone H4 in the two melanoma cell lines and the normal human fibroblasts. NaB radiosensitized both the A375 and MeWo melanoma cell lines, substantially reducing the surviving fraction at 2 Gy (SF2), whereas it had no effect on the normal human fibroblasts. The other HDAC inhibitors, phenylbutyrate, tributyrin, and trichostatin A had significant radiosensitizing effects on both melanoma cell lines tested. NaB modestly enhanced radiation-induced apoptosis that did not correlate with survival but did correlate with functional impairment of DNA repair as determined based on the host cell reactivation assay. Moreover, NaB significantly reduced the expression of the repair-related genes Ku70 and Ku86 and DNA-dependent protein kinase catalytic subunit in melanoma cells at the protein and mRNA levels. Normal human fibroblasts showed no change in DNA repair capacity or levels of DNA repair proteins following NaB treatment. We also examined gamma-H2AX phosphorylation as a marker of radiation response to NaB and observed that compared with controls, gamma-H2AX foci persisted long after ionizing exposure in the NaB-treated cells.
HDAC inhibitors radiosensitize human tumor cells by affecting their ability to repair the DNA damage induced by ionizing radiation and that gamma-H2AX phosphorylation can be used as a predictive marker of radioresponse.
Clinical Cancer Research 08/2005; 11(13):4912-22. · 7.74 Impact Factor
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ABSTRACT: The melanoma differentiation-associated gene-7 (mda-7) was identified by virtue of its enhanced expression in human melanoma cells induced into terminal differentiation. Enforced expression of mda-7 in human cancer cell lines of diverse origins results in the suppression of growth and induction of apoptosis. We have shown that adenoviral-mediated mda-7 (Ad-mda7) radiosensitizes non-small-cell lung cancer (NSCLC) cells by enhancing the apoptotic pathway. To identify the mechanism of this radiosensitization, we examined the level of proteins involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Western blot analysis indicated that the expression of NHEJ pathway components Ku70, XRCC4, and DNA ligase IV was downregulated in NSCLC cells--A549 with Ad-mda7 treatment. No such change was observed in normal human CCD16 fibroblasts previously shown not to be radiosensitized by Ad-mda7. The biological significance of these changes of expression of proteins critical for repair of radiation-induced DSBs was confirmed via the analysis of DSB rejoining kinetics using pulsed field gel electrophoresis and assessment of host cell reactivation capacity following Ad-mda7 treatment. Based on these results, we hypothesize that Ad-mda7 sensitizes NSCLC cells to ionizing radiation by suppressing the activity of NHEJ, a pathway essential for repair of radiation-induced DSBs.
Oncogene 10/2004; 23(42):7125-31. · 6.37 Impact Factor
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Hasan Murshed,
H Helen Liu,
Zhongxing Liao,
Jerry L Barker,
Xiaochun Wang,
Susan L Tucker,
Anurag Chandra,
Thomas Guerrero, Craig Stevens,
Joe Y Chang,
Melinda Jeter,
James D Cox,
Ritsuko Komaki,
Radhe Mohan,
Joe Y Change
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ABSTRACT: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC).
Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared.
Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT.
IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.
International Journal of Radiation OncologyBiologyPhysics 04/2004; 58(4):1258-67. · 4.11 Impact Factor
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Noah A Taylor,
Zhongxing X Liao,
James D Cox, Craig Stevens,
Jack Roth,
Garrett Walsh,
Joe Y Chang,
Thomas Guerrero,
Melenda Jeter,
Joe Putnam,
Frank V Fossella,
Pamela Allen,
Ritsuko Komaki
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ABSTRACT: To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non-small-cell lung cancer (NSCLC).
Between 1990 and 2000, 107 patients underwent either induction C/S (n = 55) or concurrent CRT (n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60-63 Gy in 30-35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients.
No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% (p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001).
Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.
International Journal of Radiation OncologyBiologyPhysics 02/2004; 58(1):204-12. · 4.11 Impact Factor
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ABSTRACT: Clinical trials often require homogeneous treatment plans. Many institutions, however, have begun using heterogeneous plans. Is it possible to satisfy the requirements of such a protocol while achieving the superior accuracy of heterogeneous treatment planning? At the University of Texas M. D. Anderson Cancer Center, we currently use conformal treatment planning with heterogeneities for thoracic cancers. This paper describes a procedure that has been developed to satisfy the requirements of a homogeneous protocol, such as RTOG 98-01 (A Phase III Study of Amifostine mucosal protection), while maintaining accuracy in treatment planning.
Medical Dosimetry 02/2004; 29(2):80-4. · 1.00 Impact Factor
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ABSTRACT: Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin production in pathologic states such as inflammatory processes and cancer. The enzyme is often overexpressed in premalignant lesions and cancer, including cancers of the lung and esophagus. Inhibition of this enzyme with selective COX-2 inhibitors was found to enhance tumor response to radiation in preclinical studies, suggesting that these agents can improve the response of various cancers to radiotherapy. On the basis of these preclinical findings, clinical trials of the combination of celecoxib, a selective COX-2 inhibitor, with radiotherapy were initiated in patients with lung carcinoma and with chemoradiotherapy in patients with esophageal carcinoma. The rationale for using selective COX-2 inhibitors is discussed, and the current clinical protocols and the initial findings are described.
American journal of clinical oncology 09/2003; 26(4):S85-91. · 2.21 Impact Factor
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Jaffer A Ajani,
Josephine Faust,
James Yao,
Ritsuko Komaki, Craig Stevens,
Stephen Swisher,
Joe B Putnam,
Ara Vaporciyan,
Roy Smythe,
Garrett Walsh,
David Rice,
Jack Roth
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ABSTRACT: Local-regional carcinoma of the esophagus is often diagnosed in advanced stages because the diagnosis is established when symptoms are severe. The prognosis of patients with local-regional carcinoma of the esophagus continues to be grim. While preoperative chemoradiotherapy increases the fraction of patients who achieve pathologic complete response, that percentage is approximately 25%. In an attempt to increase the number of patients with either no cancer in the surgical specimen or only microscopic cancer, we adopted a three-step strategy. The current study utilized up to two 6-week cycles of induction chemotherapy with irinotecan (CPT-11, Camptosar) and cisplatin as step 1. This was followed by concurrent radiotherapy and chemotherapy with continuous infusion fluorouracil (5-FU) and paclitaxel as step 2. Once the patients recovered from chemoradiotherapy, a preoperative evaluation was performed and surgery was attempted. All patients signed an informed consent prior to their participation on the study. A total of 43 patients were enrolled. The baseline endoscopic ultrasonography revealed that 36 patients had a T3 tumor, five patients had a T2 tumor, and two had a T1 tumor. Twenty-seven patients had node-positive cancer (N1). Thirty-nine (91%) of the 43 patients underwent surgery; all had an R0 (curative) resection. A pathologic complete response was noted in 12 of the 39 patients. In addition, 17 patients had only microscopic (< 10%) viable cancer in the specimen. Therefore, a significant pathologic response was seen in 29 (74%) of 39 taken to surgery or 29 (67%) of all 43 patients enrolled on the study. With a median follow up beyond 25 months, 20 patients remain alive and 12 patients remain free of cancer. Our preliminary data suggest that the proportion of patients with significant pathologic response can be increased by using the three-step strategy.
Oncology (Williston Park, N.Y.) 09/2003; 17(9 Suppl 8):20-2. · 1.03 Impact Factor
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ABSTRACT: To determine the relationship between the local radiation dose and the decrease in lung function associated with thoracic irradiation.
Twenty-six patients treated with thoracic irradiation for lung cancer, for whom three-dimensional CT-based dosimetry was used in treatment planning, were evaluated with before and after treatment pulmonary function tests. Six patients were treated with radiotherapy alone (2.15 Gy daily fractions), and 20 patients with concurrent chemotherapy (cisplatin, etoposide) with hyperfractionated (HF) radiation therapy (1.2 Gy in twice-daily fractions). Eleven patients treated with concurrent HF chemoradiation also received the radioprotector amifostine. The normalized decrease in the diffusing capacity for carbon monoxide (DL(CO)) was used as an objective measure of the change in lung function. The dose-volume histogram (DVH) data were used to estimate the local dose-response relationship for loss of DL(CO). In each subvolume of lung, the loss in normalized DL(CO) was assumed to be a sigmoid function of dose, ranging from no loss at low doses to total loss at high doses. The whole-lung decrease in DL(CO) was modeled as the sum of the local declines in DL(CO) over all subvolumes. Nonlinear regression analysis was used to estimate the parameters of the local dose-response function.
The data are most consistent with a pronounced decrease in DL(CO) when the local dose (for radiotherapy alone or HF concurrent chemoradiation) exceeds 13 Gy (95% CI, 11-15 Gy). In patients who received amifostine in addition to HF radiotherapy with concurrent chemotherapy, this stepwise loss of DL(CO) occurred above 36 Gy (95% CI, 25-48 Gy). Grade 2 or higher pulmonary symptoms were associated with a DL(CO) loss of >30% (p = 0.003).
The decrease in pulmonary diffusion capacity correlates with the local dose to irradiated lung. Amifostine significantly reduces the loss in DL(CO). A local dose-loss relationship for normalized DL(CO) can be extracted from DVH data. This relationship allows an estimate of the loss of function associated with a radiation treatment plan. Different plans can thus be compared without resort to an empiric DVH reduction algorithm. The very low (13 Gy) threshold for deterioration of DL(CO) suggests that it is better to treat a little normal lung to a high dose than to treat a lot to a low dose.
International Journal of Radiation OncologyBiologyPhysics 06/2003; 56(1):106-13. · 4.11 Impact Factor
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Stephen G Swisher,
Jack A Roth,
Ritsuko Komaki,
Jian Gu,
J Jack Lee,
Marshall Hicks,
Jae Y Ro,
Waun K Hong,
James A Merritt,
Kamaran Ahrar, [......],
Katherine M W Pisters,
Joe B Putnam,
Arcenio J Sarabia,
Thomas Shelton, Craig Stevens,
Daniel M Shin,
William R Smythe,
Ara A Vaporciyan,
Garrett L Walsh,
Min Yin
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ABSTRACT: We designed a prospective single arm Phase II study to evaluate the feasibility and mechanisms of apoptosis induction after Ad-p53 (INGN 201) gene transfer and radiation therapy in patients with non-small cell lung cancer.
Nineteen patients with nonmetastatic non-small cell lung cancer who were not eligible for chemoradiation or surgery were treated as outpatients with radiation therapy to 60 Gy over 6 weeks in conjunction with three intratumoral injections of Ad-p53 (INGN 201) on days 1, 18, and 32.
Seventeen of 19 patients completed all planned radiation and Ad-p53 (INGN 201) gene therapy as outpatients. The most common adverse events were grade 1 or 2 fevers (79%) and chills (53%). Three months after completion of therapy, pathologic biopsies of the primary tumor revealed no viable tumor (12 of 19 patients, 63%), viable tumor (3 of 19 patients, 16%), and not assessed (4 of 19 patients, 21%). Computed tomography and bronchoscopic findings at the primary injected tumor revealed complete response (1 of 19 patients, 5%), partial response (11 of 19 patients, 58%), stable disease (3 of 19 patients, 16%), progressive disease (2 of 19 patients, 11%), and not evaluable (2 of 19 patients, 11%). Quantitative reverse transcription-PCR analysis of the four p53 related genes [p21 (CDKN1A), FAS, BAK, and MDM2] revealed that Bak expression was increased significantly 24 h after Ad-p53 (INGN 201) injection and levels of CDKN1A and MDM2 expression were increased over the course of treatment.
Intratumoral injection of Ad-p53 (INGN 201) in combination with radiation therapy is well tolerated and demonstrates evidence of tumor regression at the primary injected tumor. Serial biopsies of the tumor suggest that BAK gene expression is most closely related to Ad-p53 (INGN 201) gene transfer.
Clinical Cancer Research 02/2003; 9(1):93-101. · 7.74 Impact Factor
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ABSTRACT: To evaluate the effect of q.d. or b.i.d. radiotherapy (RT) on the outcome of patients with locally advanced non-small-cell lung cancer.
We retrospectively reviewed the outcome of 261 patients with medically inoperable or surgically unresectable Stage II-IIIB non-small-cell lung cancer, who were treated with combined modality cisplatin-based chemotherapy and RT. Chemotherapy was administered either sequentially or concurrently with thoracic RT. The median follow-up was 18 months (range 2-92). Treatment groups included sequential chemotherapy and q.d. RT (n = 109), concurrent chemotherapy and q.d. RT (n = 48), and concurrent chemotherapy and b.i.d. RT (n = 104). Of the 261 patients, 97% had a Karnofsky performance score > or =80, and 86.2% had < or =5% weight loss in the 3 months before diagnosis; 66.7% had nonsquamous cell histologic features. All but 8 patients had Stage IIIA-B disease.
The 2- and 5-year locoregional control rate was 42.4% and 25.7% for the q.d. group and 70.6% and 45.8% for the b.i.d. group, respectively (p = 0.0001). The 2- and 5-year disease-free survival rate was 26.7% and 6.5% for the q.d. group and 39.6% and 27.3% for the b.i.d. group, respectively (p = 0.0114). The corresponding overall survival rates were 35.9% and 9.4% for the q.d. group and 38.7% and 26.1% for the b.i.d. group. No difference was found in the rate of distant metastasis between the 2 groups. Multivariate analysis indicated that b.i.d. RT was a favorable prognostic factor for locoregional control and disease-free survival.
RT b.i.d. significantly improved locoregional control and disease-free survival compared with RT q.d. in patients with Stage IIIA-B non-small-cell lung cancer.
International Journal of Radiation OncologyBiologyPhysics 07/2002; 53(3):558-65. · 4.11 Impact Factor
