P. Cheung

Digital fluoroscopy to quantify lung tumor motion: potential for patient-specific planning target volumes ☆

PURPOSEnTo apply digital fluoroscopy integrated with CT simulation to measure lung tumor motion and aid in the quantification of individualized planning target volumes.nnnMETHODS AND MATERIALSnA flat panel digital fluoroscopy unit was modified and integrated with a CT simulator. The stored fluoroscopy images were overlaid with digitally reconstructed radiographs, allowing measurement of the observed lung tumor motion in relation to the corresponding contours on the static digitally reconstructed radiographs. CT simulation and digital fluoroscopy was performed on 10 patients with non-small-cell lung cancer. Actual tumor motion was measured in three dimensions using the overlaid images.nnnRESULTSnCombining the dynamic data with digitally reconstructed radiographs allowed the tumor shadow from the fluoroscopy to be tracked in relation to the CT lung tumor contour. For all patients, the extent of tumor motion in three dimensions was unique. The motion was greatest in the superoinferior direction and minimal in the AP and lateral directions.nnnCONCLUSIONnWe have developed a tool that allows CT simulation to be combined with digital fluoroscopy. Quantitative evaluation of the tumor motion in relation to the CT plan allows for customization of the planning target volume. The variability observed clearly demonstrates the need to generate patient-specific internal motion margins.

ACCELERATED HYPOFRACTIONATION FOR EARLY-STAGE NON-SMALL- CELL LUNG CANCER

PURPOSEnTo describe the outcome of treating early-stage non-small-cell lung cancer (NSCLC) with an accelerated hypofractionated course of radiotherapy.nnnMETHODS AND MATERIALSnA policy of treating early-stage NSCLC with a dose of 48 Gy in 12 once-daily fractions without elective irradiation of radiologically uninvolved regional nodes was adopted in 1996. We describe the outcome in 33 patients with NSCLC treated with this dose-fractionation schedule.nnnRESULTSnThe median patient age was 72.0 years. Most patients (75.8%) were not surgical candidates because of medical comorbidities or old age. For staging, 97.0% underwent CT of the thorax, and mediastinoscopy was performed in 6.1%. All patients had Stage T1-T2N0, except for 4 patients with positive nodes based on pathologically involved or clinically enlarged lymph nodes adjacent to the primary tumor. The overall survival rate was 80.1% at 1 year and 46.0% at 2 years. The median survival was 22.6 months. The cause-specific survival rate was 89.8% at 1 year and 54.1% at 2 years. The recurrence-free survival rate was 66.4% at 1 year and 40.0% at 2 years. Lateral radiotherapy field margins of <2 cm predicted for inferior overall survival, cause-specific survival, and recurrence-free survival on univariate and multivariate analyses (p <0.05). The most commonly reported toxicities were acute dermatitis (30.3%) and late cutaneous/subcutaneous fibrosis (24.2%).nnnCONCLUSIONnAccelerated hypofractionation for early-stage NSCLC appears to be safe and produces promising early results. Very small radiotherapy field margins may lead to an inferior outcome. Prospective studies are needed to determine the optimal dose-fractionation schedule.

Hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer: late toxicity.

PURPOSEnTo report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy.nnnMETHODS AND MATERIALSnA prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥ 20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition.nnnRESULTSnA total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%.nnnCONCLUSIONSnA hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates of severe toxicity. The biochemical control rate at early follow-up has been promising. Additional follow-up is needed to determine the long-term biochemical control and prostate biopsy results.

Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

PURPOSEnTo evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer.nnnMETHODS AND MATERIALSnThis report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >or=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT.nnnRESULTSnThe median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity.nnnCONCLUSIONnThe results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

Predictive Factors for Local Control in Primary and Metastatic Lung Tumours after Four to Five Fraction Stereotactic Ablative Body Radiotherapy: A Single Institution's Comprehensive Experience

AIMSnWe report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control.nnnMATERIALS AND METHODSnIn total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60xa0Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses.nnnRESULTSnOf the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control.nnnCONCLUSIONSnLung SABR of 48-60xa0Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.

Intra-fraction motion during extreme hypofractionated radiotherapy of the prostate using pre- and post-treatment imaging.

AIMSnTo determine intra-fraction displacement of the prostate during extreme hypofractionated radiotherapy using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers.nnnMATERIALS AND METHODSnIn total, 265 image pairs were obtained from 53 patients who underwent extreme hypofractionated radiotherapy to a dose of 35 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal X-rays before and after treatment and were used to determine intra-fraction prostate displacement.nnnRESULTSnThe mean intra-fraction prostate displacements were -0.03 ± 0.61 mm (one standard deviation), 0.21 ± 1.50 mm and -0.86 ± 1.73 mm in the left-right, superior-inferior and anterior-posterior directions, respectively. The mean intra-fraction displacement during the first two fractions was moderately correlated with the displacement in the remaining three fractions, with correlation coefficients of 0.63 (95% confidence interval 0.43-0.77) and 0.47 (95% confidence interval 0.22-0.65) in the superior-inferior and anterior-posterior directions, respectively. There was no significant correlation in the left-right direction with a coefficient of -0.04 (95% confidence interval -0.31-0.23).nnnCONCLUSIONSnThe mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5 mm warrants further validation.

Megavoltage cone beam digital tomosynthesis (MV-CBDT) for image-guided radiotherapy: a clinical investigational system

Cone beam digital tomosynthesis (CBDT) is a new imaging technique proposed recently as a rapid approach for creating tomographic images of a patient in the radiotherapy treatment room. The purpose of this work is to investigate the feasibility of performing megavoltage (MV) CBDT clinically. A clinical investigational MV-CBDT system was installed on an existing LINAC. After the installation, the treatment machine can be operated in two distinct modes: (1) normal clinical treatment mode; (2) CBDT mode, in which tomographic images of the patient can be obtained using MV-CBDT. Various calibration and phantom measurements were performed on the system, followed by a patient study. Our phantom measurements have shown that: (1) for the same imaging dose, MV-CBDT has the same signal-difference-to-noise ratio as megavoltage cone beam computed tomography (MV-CBCT); (2) MV-CBDT has a better spatial resolution than MV-CBCT in the planes of reconstruction but a worse spatial resolution in the direction perpendicular to the planes of reconstruction. MV-CBDT patient images were also obtained and compared to that of MV-CBCT. We have demonstrated that it is clinically feasible to perform MV-CBDT in the treatment room for image-guided radiotherapy.

The effect of radiation technique and bladder filling on the acute toxicity of pelvic radiotherapy for localized high risk prostate cancer

PURPOSEnThe goal of this project was to see if using IMRT to deliver elective pelvic nodal irradiation (EPNI) for prostate cancer reduced acute treatment toxicity.nnnMETHODSnTwo hundred and thirty patients were enrolled into prospective trials delivering EPNI with a concomitant hypofractionated IMRT boost to the prostate. During accrual, the method of EPNI delivery changed as new literature emerged. Three methods were used (1) 4FB, (2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al. (2005) [7] (IMRT-Shih), and (3) IMRT with nodal volumes suggested by the RTOG (IMRT-RTOG). Initially patients were treated with an empty bladder, with the remainder treated with bladder full.nnnRESULTSnPatients in the 4FB group had higher rates of grade 2 acute GI toxicities compared to the IMRT-Shih and IMRT-RTOG groups (31.9% vs 20.8% vs 7.2%, p=0.0009). Patients in the 4FB group had higher rates of grade 3 urinary frequency compared to the two IMRT groups (8.5% vs 0% vs 0%, p=0.027). However, multivariate analysis suggested the factor that most influenced toxicity was bladder filling followed by IMRT.nnnCONCLUSIONSnBladder filling appeared to be the dominant factor which predicted for acute toxicity, followed by the use of IMRT.

Comparison of Helical and Average Computed Tomography for Stereotactic Body Radiation Treatment Planning and Normal Tissue Contouring in Lung Cancer

AIMSnTo compare average computed tomography (CT(AVE)) datasets with free breathing helical computed tomography (CT(HEL)) for contouring organs at risk (OARs) and radiation treatment planning in patients receiving stereotactic body radiation therapy (SBRT) in the lung.nnnMATERIALS AND METHODSnTen SBRT patients with peripheral stage I non-small cell lung cancer underwent a CT(HEL) and a four-dimensional computed tomography scan in the treatment position. CT(AVE) datasets were generated from the four-dimensional computed tomography scan. The following OARs were delineated on the CT(HEL) and CT(AVE) datasets of each patient: lung minus internal target volume, trachea/main bronchus, heart, oesophagus and spinal cord. Volumes and geometric centres of the OARs, as well as the dosimetric impact of planning with these different datasets, were examined.nnnRESULTSnThere were no statistical differences in the OAR geometric centre coordinates nor in the OAR volumes between the CT(HEL) and CT(AVE) datasets, except that CT(AVE)-defined trachea/main bronchus and lung minus internal target volume mean volumes were larger than those defined on the CT(HEL) (46, 43 cm³ and 3516, 3378 cm³, respectively, P<0.05). Despite this, there were no significant differences in the mean and maximum doses to the OAR contours when using the CT(HEL) or CT(AVE) for planning (<4% average change in the maximum and mean doses for all OARs, P>0.05). There were also no significant differences in the locations of the hotspots within OARs among the CT(HEL) or CT(AVE) datasets (P>0.05).nnnCONCLUSIONSnCT(AVE) datasets may be used in place of CT(HEL) for OAR contouring and dose calculations. When four-dimensional computed tomography is available, it may not be necessary to acquire a separate CT(HEL) scan for OAR contouring or dosimetric purposes.

Predictors of Chest Wall Toxicity after Lung Stereotactic Ablative Radiotherapy

AIMSnTo determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR).nnnMATERIALS AND METHODSnPatients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity.nnnRESULTSnThe median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture.nnnCONCLUSIONSnNone of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.