F Liu

Characterization and Management of Interfractional Anatomic Changes for Pancreatic Cancer Radiotherapy

PURPOSE To quantitatively characterize interfractional anatomic variations in pancreatic cancer radiotherapy (RT) and to study dosimetric advantages for using an online adaptive replanning scheme to account for these variations. METHODS AND MATERIALS Targets and organs at risk (OAR) were delineated by autosegmentation based on daily computed tomography (CT) images acquired using a respiration-gated in-room CT during daily image-guided RT (IGRT) for 10 pancreatic cancer patients. Various parameters, including the maximum overlap ratio (MOR) between the volumes based on planning and daily CTs for a structure, while the overlapping volumes were maximized, were used to quantify the interfractional organ deformation with the intrafractional variations largely excluded. An online adaptive RT (ART) was applied to these daily CTs. To evaluate the dosimetric benefits of ART, the dose distributions from the online ART were compared to those from the repositioning in the current standard IGRT practice. RESULTS The interfractional anatomic variations, particularly the organ deformation, are significant during pancreas irradiation. For the patients studied, the average MORs of all daily CTs were 80.2%, 61.7%, and 72.2% for pancreatic head, duodenum, and stomach, respectively. The online ART leads to improved dosimetric plan with better target coverage and/or OAR sparing than IGRT repositioning. For the patients studied, the mean V(50.4 Gy) (volume covered by 50.4 Gy) for the duodenum was reduced from 43.4% for IGRT to 15.6% for the online ART scheme. CONCLUSIONS The online adaptive RT scheme can effectively account for the significant interfractional anatomic variations observed in pancreas irradiation. The dosimetric advantages with the online ART may enable safe dose escalation in radiation therapy for pancreatic cancer.

Development of an online adaptive solution to account for inter- and intra-fractional variations

PURPOSE The current IGRT repositioning cannot fully account for the organ deformation and rotation. We introduce a comprehensive solution using gated IMRT with online adaptive replanning to manage both inter- and intra-fractional variations. METHODS AND MATERIALS The solution includes (1) generating respiration-gated IMRT plans based on 4DCT, (2) acquiring daily gated CT in treatment position prior to the treatment using a diagnostic-quality in-room CT (CTVision, Siemens) with the same gating window as that for the planning CT, (3) performing online repositioning or adaptive replanning based on the gated CT of the day, and (4) delivering the treatment with gating. The entire solution is demonstrated with RT data from 10 selected pancreatic cancer cases. The dosimetric impact of various advanced delivery technologies was investigated. RESULTS The online adaptive replanning based on the CT of the day combining with gating significantly improves normal tissue sparing during RT for pancreatic cancer. As the complexity of the delivery technology increases from no IGRT to with IGRT, gating and online adaptive replanning, the inter- and intra-fractional variations can be accounted for with increased adequacy. CONCLUSION The online adaptive replanning technique based on daily respiration-gated diagnostic-quality CT combined with gated delivery can effectively correct for inter- and intra-fraction variations during radiation therapy.

Tumor control probability modeling for stereotactic body radiation therapy of early-stage lung cancer using multiple bio-physical models

This work is to analyze pooled clinical data using different radiobiological models and to understand the relationship between biologically effective dose (BED) and tumor control probability (TCP) for stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC). The clinical data of 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP from 46 selected studies were collected for SBRT of NSCLC in the literature. The TCP data were separated for Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED was calculated at isocenters using six radiobiological models. For each model, the independent model parameters were determined from a fit to the TCP data using the least chi-square (χ2) method with either one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. The fits to the clinic data yield consistent results of large α/β ratios of about 20Gy for all models investigated. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1Gy physical dose at isocenters per fraction (⩽5 fractions) to achieve the optimal TCP when compared to the T1 tumors. In conclusion, this systematic analysis of a large set of published clinical data using different radiobiological models shows that local TCP for SBRT of early-stage NSCLC has strong dependence on BED with large α/β ratios of about 20Gy. The six models predict that a BED (calculated with α/β of 20) of 90Gy is sufficient to achieve TCP⩾95%. Among the models considered, the regrowth model leads to a better fit to the clinical data.

Comparison of various online strategies to account for interfractional variations for pancreatic cancer.

PURPOSE To identify practical techniques to address the large interfractional variations for pancreas irradiation by comparing various used/proposed online strategies. METHODS AND MATERIALS The daily computed tomography (CT) images acquired using a respiration-gated in-room CT (CTVision; Siemens) for 10 pancreatic cancer patients treated with image guided radiation therapy (IGRT) were analyzed. The contours of the pancreas and organs at risk on each daily CT set were generated by populating from the planning CT using a deformable registration tool (ABAS; Elekta) with manual editing. Nine online strategies were considered: (1) standard IGRT (ie, IGRT with 0-mm additional margin [AM]); (2) IGRT with 2-mm AM; (3) IGRT with 5-mm AM; (4) IGRT with plan renormalized to maintain 95% planning target volume (PTV) coverage; (5) full-scale reoptimization; (6) reoptimization starting from the original plan; (7) segment aperture morphing (SAM) from the original plan, based on PTV shape change; (8) SAM plus segment weight optimization; and (9) reoptimization starting from the SAM plan. One-way analysis of variance was applied to plan qualities for the 9 strategies to assess statistical significance in difference. RESULTS The 3 IGRT strategies (1-3) lead to either inadequate PTV coverage or higher doses to critical structures, indicating that the additional margins alone are not adequate to account for the changes. The full-scale reoptimization results in the best plan but requires the delineation of several structures, which is time consuming. The SAM strategy (7) was the fastest one, because it requires delineating only 1 structure (target), and its plan quality was comparable to that for the full-scale reoptimization. CONCLUSION Online replanning strategies can lead to either reduced organs-at-risk dose and/or improved target coverage as compared with the current practice of IGRT. The SAM-based online replanning is comparable to full-scale reoptimization and is efficient for practical use.

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered.

Assessment and management of interfractional variations in daily diagnostic-quality-CT guided prostate-bed irradiation after prostatectomy

PURPOSE To quantify interfractional anatomic variations and limitations of the current practice of image-guided radiation therapy (IGRT) for prostate-bed patients and to study dosimetric benefits of an online adaptive replanning scheme that addresses the interfractional variations. METHODS Contours for the targets and organs at risk (OARs) from daily diagnostic-quality CTs acquired with in-room CT (CTVision, Siemens) were generated by populating the planning contours using an autosegmentation tool based on deformable registration (ABAS, Elekta) with manual editing for ten prostate-bed patients treated with postoperative daily CT-guided IMRT. Dice similarity coefficient (DSC) obtained by maximizing the overlap of contours for a structure between the daily and plan contours was used to quantify the organ deformation between the plan and daily CTs. Three interfractional-variation-correction schemes, the current standard practice of IGRT repositioning, a previously developed online adaptive RT (ART), and the full reoptimization, were applied to these daily CTs and a number of dose-volume quantities for the targets and organs at risk were compared for their effectiveness to account for the interfractional variations. RESULTS Large interfractional organ deformations in prostate-bed irradiation were seen. The mean DSCs for CTV, rectum, and bladder were 86.6 ± 5.1% (range from 61% to 97%), 77.3% ± 7.4% (range from 55% to 90%), and 75.4% ± 11.2% (range from 46% to 96%), respectively. The fractional and cumulative dose-volume quantities for CTV and PTV: V100 (volume received at least 100% prescription dose), and rectum and bladder: V45Gy and V60Gy (volume received at least 45 or 60 Gy), were compared for the repositioning, adaptive, reoptimization, and original plans. The fractional and cumulative dosimetric results were nearly the same. The average cumulative CTV V100 were 88.0%, 98.4%, 99.2%, and 99.3% for the IGRT, ART, reoptimization, and original plans, respectively. The corresponding rectal V45Gy (V60Gy) were 58.7% (27.3%), 48.1% (20.7%), 43.8% (16.1%), and 44.9% (16.8%). The results for bladder were comparable among three schemes. Paired two-tailed Wilcoxon signed-rank tests were performed and it was found that ART and reoptimization provide better target coverage and better OAR sparing, especially rectum sparing. CONCLUSIONS The interfractional organ motions and deformations during prostate-bed irradiation are significant. The online adaptive replanning scheme is capable of effectively addressing the large organ deformation, resulting in cumulative doses equivalent to those originally planned.

An analysis of tumor control probability of stereotactic body radiation therapy for lung cancer with a regrowth model.

We report a modeling study of tumor response after stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung carcinoma using published clinical data with a regrowth model. A linear-quadratic inspired regrowth model was proposed to analyze the tumor control probability (TCP) based on a series of published data of SBRT, in which a tumor is controlled for an individual patient if number of tumor cells is smaller than a critical value K cr. The regrowth model contains radiobiological parameters such as α, α/β the potential doubling time T p. This model also takes into account the heterogeneity of tumors and tumor regrowth after radiation treatment. The model was first used to fit TCP data from a single institution. The extracted fitting parameters were then used to predict the TCP data from another institution with a similar dose fractionation scheme. Finally, the model was used to fit the pooled TCP data selected from 48 publications available in the literature at the time when this manuscript was written. Excellent agreement between model predictions and single-institution data was found and the extracted radiobiological parameters were α  =  0.010  ±  0.001 Gy(-1), α /β  =  21.5  ±  1.0 Gy and T p  =  133.4  ±  7.6 d. These parameters were α  =  0.072  ±  0.006 Gy(-1), α/β  =  15.9  ±  1.0 Gy and T p  =  85.6  ±  24.7 d when extracted from multi-institution data. This study shows that TCP saturates at a BED of around 120 Gy. A few new dose-fractionation schemes were proposed based on the extracted model parameters from multi-institution data. It is found that the regrowth model with an α/β around 16 Gy can be used to predict the dose response of lung tumors treated with SBRT. The extracted radiobiological parameters may be useful for comparing clinical outcome data of various SBRT trials and for designing new treatment regimens.

Management of independent motion between multiple targets in lung cancer radiation therapy

PURPOSE To quantify interfractional independent motions between multiple primary targets in radiation therapy (RT) of lung cancer and to study the dosimetric benefits of an online adaptive replanning method to account for these variations. METHODS AND MATERIALS Ninety-five on-treatment diagnostic-quality computed tomography (CT) scans acquired for 9 lung cancer patients treated with image-guided RT (IGRT) using a CT-on-rails (CTVision, Siemens) were analyzed. On each on-treatment CT set, contours of the targets (gross tumor volume, clinical target volume, or involved nodes), and organs at risk were generated by populating the planning contours using an autosegmentation tool (ABAS, Elekta) with manual editing. For each patient, an intensity modulated RT plan was generated based on the planning CT with a prescription dose of 60 Gy in 2 Gy per fraction. Three plans were generated and compared for each on-treatment CT set: an IGRT (repositioning) plan by copying the original plan with the required shifts, an online adaptive plan by rapidly modifying the aperture shapes, and segment weights of the original plan to conform to the on-treatment anatomy and a new fully reoptimized plan based on the on-treatment CT. RESULTS The interfractional deviations of the distance between centers of masses of the targets from the planning CTs varied from -1.0 to 0.8 cm with an average -0.09 ± 0.41 cm (1 standard deviation). The average combined CTV receiving at least 100% of the prescribed dose (V100) were 99.0 ± 0.7%, 97.8 ± 2.8%, 99.0 ± 0.6%, and 99.1 ± 0.6%, and the lung V20Gy 928 ± 332 cm3, 944 ± 315 cm3, 917 ± 300 cm3, and 891 ± 295 cm3 for the original, repositioning, adaptive, and reoptimized plans, respectively. Wilcoxon signed-rank tests showed that the adaptive plans were statistically significantly better than the repositioning plans and comparable with the reoptimized plans. CONCLUSION Interfractional, relative volume changes and independent motions between multiple primary targets during lung cancer RT, which cannot be accounted for by the current IGRT repositioning exist, but can be corrected by the online adaptive replanning method.

TH‐AB‐304‐04: Tumor Control Probability Modeling for Stereotactic Body Radiation Therapy of Early‐Stage Lung Cancer Using Multiple Bio‐Physical Models

Purpose: To analyze pooled clinical data using six radiobiological models and to understand the relationship between BED and TCP for SBRT of early-stage NSCLC. Methods: The clinical data of 1- , 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP data from 46 studies were collected for SBRT of early stage (T1 and T2) NSCLC. The TCP data were separated for Stage T1 and T2 tumors if possible. BED was calculated at isocenters using six radiobiological models. Model parameters were determined from a fit to the TCP data using the least chi-square (χ2) method with one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. Results: The fits to the clinic data yield consistent results of large α/β ratios of about 23 Gy for all models. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1 Gy physical dose at isocenters per fraction (≤5 fractions) to achieve the optimal TCP when compared to the T1 tumors. Sample fractionation schemes were estimated based the determined model parameters for the regrowth model. Conclusion: A systematic analysis of a large set clinical data using six radiobiological models shows that local TCP for SBRT of early stage NSCLC has strong dependence on BED with large α/β ratios of about 23 Gy. The six models considered predict that a BED of 80 Gy is sufficient to achieve a 95% TCP. The regrowth model leads to better fit to the clinical data, the LQ model is the simplest and indistinguishable with remaining models. Sample fractionation regimens that can yield TCPs larger than 95% were estimated.

SU‐E‐J‐268: Change of CT Number During the Course of Chemoradiation Therapy for Pancreatic Cancer

Purpose: It has been observed radiation can induce changes in CT number (CTN) inside tumor during the course of radiation therapy (RT) for several tumor sites including lung and head and neck, suggesting that the CTN change may be potentially used to assess RT response. In this study, we investigate the CTN changes inside tumor during the course of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily diagnostic-quality CT data acquired during IGRT for 17 pancreatic head cancer patients using an in-room CT (CTVision, Siemens) were analyzed. All patients were treated with a radiation dose of 50.4 in 1.8 Gy per fraction. On each daily CT set, The contour of the pancreatic head, included in the treatment target, was generated by populating the pancreatic head contour from the planning CT or MRI using an auto-segmentation tool based on deformable registration (ABAS, Elekta) with manual editing if necessary. The CTN at each voxel in the pancreatic head contour was extracted and the 3D distribution of the CTNs was processed using MATLAB. The mean value of CTN distribution was used to quantify the daily CTN change in the pancreatic head. Results: Reduction of CTN in pancreatic head was observed during the CRT delivery in 14 out the 17 (82%) patients studied. Although the average reduction is only 3.5 Houncefield Unit (HU), this change is significant (p<0.01). Among them, there are 7 patients who had a CTN drop larger than 5 HU, ranging from 6.0 to 11.8 HU. In contrast to this trend, CTN was increased in 3 patients. Conclusion: Measurable changes in the CT number in tumor target were observed during the course of chemoradiation therapy for the pancreas cancer patients, indicating this radiation-induced CTN change may be used to assess treatment response.