Wenyin Shi

Tumor Localization Using Cone-Beam CT Reduces Setup Margins in Conventionally Fractionated Radiotherapy for Lung Tumors

PURPOSEnTo determine whether setup margins can be reduced using cone-beam computed tomography (CBCT) to localize tumor in conventionally fractionated radiotherapy for lung tumors.nnnMETHODS AND MATERIALSnA total of 22 lung cancer patients were treated with curative intent with conventionally fractionated radiotherapy using daily image guidance with CBCT. Of these, 13 lung cancer patients had sufficient CBCT scans for analysis (389 CBCT scans). The patients underwent treatment simulation in the BodyFix immobilization system using four-dimensional CT to account for respiratory motion. Daily alignment was first done according to skin tattoos, followed by CBCT. All 389 CBCT scans were retrospectively registered to the planning CT scans using automated soft-tissue and bony registration; the resulting couch shifts in three dimensions were recorded.nnnRESULTSnThe daily alignment to skin tattoos with no image guidance resulted in systematic (Sigma) and random (sigma) errors of 3.2-5.6 mm and 2.0-3.5 mm, respectively. The margin required to account for the setup error introduced by aligning to skin tattoos with no image guidance was approximately 1-1.6 cm. The difference in the couch shifts obtained from the bone and soft-tissue registration resulted in systematic (Sigma) and random (sigma) errors of 1.5-4.1 mm and 1.8-5.3 mm, respectively. The margin required to account for the setup error introduced using bony anatomy as a surrogate for the target, instead of localizing the target itself, was 0.5-1.4 cm.nnnCONCLUSIONnUsing daily CBCT soft-tissue registration to localize the tumor in conventionally fractionated radiotherapy reduced the required setup margin by up to approximately 1.5 cm compared with both no image guidance and image guidance using bony anatomy as a surrogate for the target.

Gene therapy delivery of endostatin enhances the treatment efficacy of radiation.

BACKGROUND AND PURPOSEnTo evaluate whether sustained expression of mouse endostatin by adeno-associated virus (AAV)-mediated gene transfer can enhance the treatment efficacy of ionizing radiation.nnnMATERIALS AND METHODSnMouse endostatin was cloned into recombinant AAV (rAAV) under the control of CMV beta-actin promoter. Recombinant mouse endostatin expressed via AAV gene transfer was tested for biological activity in endothelial cells. The impact of elevated serum levels of endostatin on tumor-induced angiogenesis was evaluated using an in vivo angiogenesis assay. The anti-tumor efficacy of combining rAAV-mediated endostatin delivery with radiation was evaluated in a human colorectal tumor model (HT29).nnnRESULTSnRecombinant mouse endostatin expressed through an AAV vector (rAAV-mEndo) inhibited endothelial cell proliferation (by 40-45%) and migration (by 22-33%). Intramuscular injection of rAAV-mEndo (1x10(9) i.u.) led to a sustained serum endostatin level of approximately 500 ng/ml. Compared to control animals this endostatin level was sufficient to inhibit tumor cell-induced vessel formation (37 vs. 28.5, P<0.05) and delay the growth of HT29 xenografts (time from 200 to 1,000 mm(3), 21 vs. 34.5 days, P<0.05). When combined with ionizing radiation, elevated serum endostatin levels significantly enhanced the time for tumors to grow from 200 to 1,000 mm(3) (radiation, 34 days; endostatin plus radiation, 50 days, P<0.05).nnnCONCLUSIONnThe delivery of endostatin via rAAV vectors may provide an effective means of enhancing the anti-tumor efficacy of radiation therapy.

Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo

A variety of approaches has demonstrated that interfering with tumor-induced angiogenesis may be an effective strategy in cancer therapy. However, it is likely that to be most effective such strategies will require extended suppression of the angiogenic process. Gene therapy offers a possible approach to achieve sustained release of a therapeutically potent transferred gene product. In the present study the angiogenesis inhibitor endostatin was expressed through a recombinant adeno-associated viral (rAAV) vector and shown to be biologically active in vitro and in vivo. Intramuscular injection of rAAV-HuEndo (1×109 i.u.) led to a sustained serum endostatin level of ∼35–40 ng/mL. This endostatin level was sufficient to inhibit tumor cell–induced angiogenesis and to suppress both the initiation and subsequent growth of a human colorectal cancer model.

DEFINITIVE RADIOTHERAPY FOR EWING TUMORS OF EXTREMITIES AND PELVIS: LONG-TERM DISEASE CONTROL, LIMB FUNCTION, AND TREATMENT TOXICITY

PURPOSEnMore than 70% of Ewing tumors occur in the extremities and pelvis. This study identified factors influencing local control and functional outcomes after management with definitive radiotherapy (RT).nnnPATIENTS AND METHODSnA total of 75 patients with a localized Ewing tumor of the extremity or pelvis were treated with definitive RT at the University of Florida between 1970 and 2006 (lower extremity tumors in 30, pelvic tumors in 26, and upper extremity tumors in 19). RT was performed on a once-daily (40%) or twice-daily (60%) basis. The median dose was 55.2 Gy in 1.8-Gy daily fractions or 55.0 Gy in 1.2-Gy twice-daily fractions. The median observed follow-up was 4.7 years. Functional outcome was assessed using the Toronto Extremity Salvage Score.nnnRESULTSnThe 10-year actuarial overall survival, cause-specific survival, freedom from relapse, and local control rate was 48%, 48%, 42%, and 71%, respectively. Of the 72 patients, 3 required salvage amputation. Inferior cause-specific survival was associated with larger tumors (81% for tumors <8 cm vs. 39% for tumors >/=8 cm, p <0.05). No patient characteristics or treatment variables were predictive of local failure. No fractures occurred in patients treated with hyperfractionation or with tumors of the distal extremities. Severe late complications were more frequently associated with use of <8-MV photons and fields encompassing the entire bone or hemipelvis. A significantly better Toronto Extremity Salvage Score was associated with a late-effect biologically effective dose of <91.7 Gy(3).nnnCONCLUSIONSnLimb preservation was effectively achieved through definitive RT. Treating limited field sizes with hyperfractionated high-energy RT could minimize long-term complications and provides superior functional outcomes.

Evaluation of kV cone-beam ct performance for prostate IGRT: a comparison of automatic grey-value alignment to implanted fiducial-marker alignment.

Purpose: Cone-beam computed tomography (CBCT) is a new image-guided radiation therapy (IGRT) technique for patient alignment in radiotherapy. The CBCT x-ray volume imaging system from Elekta allows for a variety of alignment methods. The aim of this study is to assess the accuracy of soft-tissue-based automatic alignment as compared with manual alignment using intraprostatic fiducials. Methods and Materials: All patients were treated on an Elekta Synergy S linear accelerator with kilovoltage CBCT. All alignments were performed using the x-ray volume imaging system and associated software. Automatic alignment with gray-value-based registration and manual alignment to fiducial markers were performed. Transitional corrections along each axis as well as 3-dimensional vectors were compared with evaluate the accuracy of gray-value-based registration compared with fiducials. Results: The distribution of the 3-dimensional vectors between gray-value and fiducial registrations demonstrated notable differences. The mean summed vector was 0.75 cm, with a standard deviation (SD) of 0.52 cm and range from 0.04 to 2.06 cm. There was minimal difference along the lateral direction, with a mean ± SD of −0.02 cm ± 0.13 cm. However, there were large discrepancies along the superior-inferior and anterior-posterior direction alignments, with mean ± SD values of −0.55 ± 0.48 cm and −0.31 ± 0.43 cm, respectively. Conclusions: CBCT with soft-tissue-based automatic corrections is not an accurate alignment compared with manual alignment to fiducial markers for prostate IGRT. We have concluded that a daily manual alignment to fiducials is one of the most reliable methods to maintain accuracy in prostate IGRT.

Radiotherapy in the management of giant cell tumor of bone.

Objectives:To evaluate the long-term treatment outcomes for patients with giant cell tumor of bone (GCTB) treated with radiotherapy with or without surgical resection. Methods:This retrospective review includes 34 patients with GCTB treated with megavoltage radiotherapy between January 1973 and January 2008 at the University of Florida. Patients’ ages ranged from 16 to 85 years (median, 29). Tumor sizes ranges from 2.5 to 12 cm (median, 4.8 cm) in the maximum dimension. Twenty-one patients received radiation for gross disease, either de novo (22 patients) or recurrent (12 patients). Thirteen patients were treated with postoperative radiation after gross total resection. The median dose was 45 Gy in both the definitive and adjuvant settings. Results:The median follow-up was 16.8 years. The 5- and 10-year local-control (LC) rates were 85% and 81%, respectively. Six patients developed an isolated local recurrence (2/13 treated postoperatively and 4/21 who were treated for gross disease). All 6 patients who developed a local recurrence were successfully salvaged with surgery; therefore, the ultimate LC rate was 100%. Both the 5- and 10-year freedom from distant metastasis rates were 91%. Three patients developed lung metastases, including 1 patient who experienced GCTB transformation into a high-grade sarcoma. The 5- and 10-year progression-free survival rates were both 78%. Conclusions:Moderate-dose radiotherapy for GCTB provides a long-term LC >80%, justifying its role as an alternative to morbid surgery.

Impact of local management on long-term outcomes in Ewing tumors of the pelvis and sacral bones: the University of Florida experience.

PURPOSEnThis retrospective analysis describes our 35-year experience with respect to disease control and functional status.nnnPATIENTS AND METHODSnThirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years.nnnRESULTSnThe 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors <8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications.nnnCONCLUSIONnCombined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.

Long-term treatment outcomes for patients with synovial sarcoma: a 40-year experience at the University of Florida.

Objectives:The objective of the study was to evaluate our long-term outcomes and prognostic factors for patients treated for localized synovial sarcoma. Methods:We retrospectively reviewed the medical records of 92 patients treated for nonmetastatic synovial sarcoma at the University of Florida from 1967 to 2007. Most patients were treated with limb-sparing surgery and radiation (63%), 27% received surgery alone and 10% received radiation only as definitive treatment. Among patients treated with surgery and radiation, 69% received preoperative radiation and 31% received postoperative radiation. Results:Median follow-up of living patients was 12.5 years. Overall survival rates at 5 and 10 years were 61% and 56%, respectively. Progression-free survival rates were 56% and 53%, respectively. Local control (LC) rates at 5 and 10 years were 90% and 88%, respectively. Freedom from distant metastasis rates were 57% at 5 years and 55% at 10 years. The severe complication (requiring surgery) rate was 13%. Size >5 cm predicted worse overall survival, progression-free survival, and freedom from distant metastasis, but not LC. No other prognostic factor was significant on multivariate analysis. Conclusions:Selectively adding radiotherapy to surgery results in excellent LC for these patients. However, distant metastasis remains the principal factor limiting survival and seems directly related to primary tumor size at presentation.

Radiation Treatment for Ewing Family of Tumors in Adults: The University of Florida Experience

PURPOSEnTo review the clinical characteristics and outcomes of adult patients with Ewing family of tumors treated with radiation at the University of Florida.nnnMETHODS AND MATERIALSnClinical features, treatment, and outcomes of 47 patients older than 18 years with Ewing family of tumors treated with combined radiation therapy and chemotherapy from 1970 to 2005 were retrospectively reviewed. Analysis was stratified by age older or younger than 30 years. Patients with metastatic disease at the time of diagnosis were excluded from the study.nnnRESULTSnThe 29 men and 18 women had a median age of 24 years. Thirty-three patients were 18-30 years old and 14 patients were older than 30 years. Median follow-up of living patients was 8.2 years. The 5-year overall survival rate for all patients was 43% (p = 0.8523). The 5-year local control rate for all patients was 75% (p = 0.9326). The 5-year rate of freedom from distant metastasis for all patients was 45% (p = 0.5471). There were no significant differences in 5-year overall survival, local control, and freedom from distant metastasis rates; patterns of distant failure; or toxicity profiles between older adult patients and younger adult patients.nnnCONCLUSIONSnWe found that the natural history and treatment outcomes of the Ewing family of tumors were consistently similar in adults (young and old) and children. Thus, aggressive combined modality approaches should be considered for adult patients.

The Effect of Intravenous Contrast on Photon Radiation Therapy Dose Calculations for Lung Cancer

Objective:The aim of this study was to evaluate the effect of intravenous contrast-enhanced computed tomography (CT) scans on the photon radiation dose calculations for lung cancer treatment planning. Materials and Methods:Nonionic iodinated intravenous contrast (Iohexol) was administered during the treatment planning CT scan of 9 patients with node-positive non–small-cell lung cancer (NSCLC). The potential effect of intravenous contrast was studied by changing the density of the contrast-enhanced vessels. A total of 9 patients were treated in this study: 5 patients with intensity-modulated radiation therapy (IMRT), and 4 patients with three-dimensional (3D) conformal radiation therapy. A treatment plan was generated from an unmanipulated “normal contrast” planning scan. The same planning parameters were then applied to a “no contrast” planning scan. The effect of intravenous contrast was quantified by calculating the percent change of dose in a variety of target and normal structures. To evaluate a worst-case scenario, the comparison between “normal contrast” and “no contrast” planning scans was repeated, assigning each vessel the artificial high density of 1.3 g/cm3. Results:Dose differences between the planning image set using intravenous contrast and the image set without contrast were less than 2.5% for planning target volumes. A worst-case scenario in which normal contrast was overridden with an artificially high density of 1.3 g/cm3 led to small dose differences of less than 3%. Conclusions:Planning lung radiation therapy treatment using CT scans that contain intravenous contrast does not result in clinically significant errors in dose delivery.