Oesophageal IGRT considerations for SBRT of LA-NSCLC: barium-enhanced CBCT and interfraction motion.

BACKGROUND: To determine the optimal volume of barium for oesophageal localisation on cone-beam CT (CBCT) for locally-advanced non-small cell lung cancers (NSCLC) and quantify the interfraction oesophageal movement relative to tumour. METHODS: Twenty NSCLC patients with mediastinal and/or hilar disease receiving radical radiotherapy were recruited. The first five patients received 25 ml of barium prior to their planning CT and alternate CBCTs during treatment. Subsequent five patient cohorts, received 15 ml, 10 ml and 5 ml. Six observers contoured the oesophagus on each of the 107 datasets and consensus contours were created. Overall 642 observer contours were generated and interobserver contouring reproducibility was assessed. The kappa statistic, dice coefficient and Hausdorff Distance (HD) were used to compare barium-enhanced CBCTs and non-enhanced CBCTs. Oesophageal displacement was assessed using the HD between consensus contours of barium-enhanced CBCTs and planning CTs. RESULTS: Interobserver contouring reproducibility was significantly improved in barium-enhanced CBCTs compared to non-contrast CBCTs with minimal difference between barium dose levels. Only 10 mL produced a significantly higher kappa (0.814, p = 0.008) and dice (0.895, p = 0.001). The poorer the reproducibility without barium, the greater the improvement barium provided. The median interfraction HD between consensus contours was 4 mm, with 95% of the oesophageal displacement within 15 mm. CONCLUSIONS: 10 mL of barium significantly improves oesophageal localisation on CBCT with minimal image artifact. The oesophagus moves substantially and unpredictably over a course of treatment, requiring close daily monitoring in the context of hypofractionation.

Long-term treatment outcomes of patients with primary optic nerve sheath meningioma treated with stereotactic radiotherapy.

We analysed the long-term outcomes of patients with primary optic nerve sheath meningioma (ONSM) treated with stereotactic radiotherapy (SRT). 26 patients with primary ONSM were treated with SRT between 2004 and 2013 at a single institution. SRT was delivered with image guidance to a median dose of 50.4 Gy in 28 fractions. 4 patients had prior surgical debulking. At a median radiological follow-up of 68 months, the MRI based tumour control was 100%. Visual acuity improved in 10 (38.4%), remained stable in 10 (38.4%) and was reduced in 6 (23.1%) patients following treatment. Stable or improved vision post-treatment was seen in 92.3% of patients with good pre-treatment vision (best corrected visual acuity 6/18 or better), compared to only 61.5% of patients with poor pre-treatment vision (best corrected visual acuity 6/24 or worse). Overall, the treatment was well tolerated with no Grade 2 or greater acute toxicity. Minimal other ophthalmic complications were seen with only one patient developing late onset Grade 3 radiation retinopathy.

Contrast enhanced oesophageal avoidance for stereotactic body radiotherapy: Barium vs. Gastrografin.

INTRODUCTION: SABR may facilitate treatment in a greater proportion of locally-advanced NSCLC patients, just as it has for early-stage disease. The oesophagus is one of the key dose-limiting organs and visualization during IGRT would better ensure toxicity is avoided. As the oesophagus is poorly seen on CBCT, we assessed the extent to which this is improved using two oral contrast agents. MATERIALS & METHODS: Six patients receiving radiotherapy for Stage I-III NSCLC were assigned to receive 50 mL Gastrografin or 50 mL barium sulphate prior to simulation and pre-treatment CBCTs. Three additional patients who did not receive contrast were included as a control group. Oesophageal visibility was determined by assessing concordance between six experienced observers in contouring the organ. 36 datasets and 216 contours were analysed. A STAPLE contour was created and compared to each individual contour. Descriptive statistics were used and a Kappa statistic, Dice Coefficient and Hausdorff distance were calculated and compared using a t-test. Contrast-induced artefact was assessed by observer scoring. RESULTS: Both contrast agents significantly improved the consistency of oesophagus localisation on CBCT across all comparison metrics compared to CBCTs without contrast. Barium performed significantly better than Gastrografin with improved kappa statistics (p = 0.007), dice coefficients (p < 0.001) and Hausdorff distances (p = 0.002), although at a cost of increased image artefact. DISCUSSION: Barium produced lower delineation uncertainties but more image artefact, compared to Gastrografin and no contrast. It is feasible to use oral contrast as a tool in IGRT to help guide clinicians and therapists with online matching and monitoring of the oesophageal position.

Fractionated Stereotactic Radiotherapy for Cavernous Venous Malformations of the Orbital Apex.

PURPOSE: The objective of this study was to investigate the efficacy and safety of fractionated stereotactic radiotherapy in the treatment of cavernous venous malformation of the orbital apex. METHODS: The authors reviewed a prospective database from a single center of patients with cavernous venous malformation of the orbital apex who had treatment with fractionated stereotactic radiotherapy. The authors compared the symptoms, visual function and the size of the tumor pre- and posttreatment as well as reviewed the treatment details and the incidence of complications. RESULTS: Six patients received treatment with fractionated stereotactic radiotherapy for cavernous venous malformation involving the orbital apex. The median age was 48 (range, 32-63), and 50% were female. Patients received a dose of 45 to 50.4 Gy in 1.8 to 2 Gy fractions. Median follow up was 33 months (range, 18-66 months). The average tumor volume reduction at posttreatment imaging after 12 months was 63%. All lesions reduced in size postradiotherapy and remained controlled for the duration of follow up. All patients who had proptosis or a visual field defect had an improvement in the symptoms posttreatment. There were no complications of the treatment. CONCLUSION: Fractionated stereotactic radiotherapy appears to be a safe and effective management option for cavernous venous malformation of the orbital apex and leads to a sustained reduction of the volume of the lesion with associated improvement in symptoms and visual function.

Lung cancer radiation therapy in Australia and New Zealand: Patterns of practice.

INTRODUCTION: The RANZCR Faculty of Radiation Oncology Lung Interest Cooperative (FROLIC) surveyed patterns of lung cancer radiation therapy practice for non-small cell (NSCLC) and small cell lung cancer (SCLC) to evaluate current patterns of care and potential for improvement. METHODS: In October 2014, Radiation Oncologists (ROs) from all 62 departments in Australia and New Zealand were invited to a web-based survey directed at those treating lung cancer. Questions covered current radiation therapy practice as well as quality measures. RESULTS: Fifty-eight per cent of respondents used 4D-CT simulation. For curative treatment, 98% employed 3D-CRT and 34% intensity modulated radiotherapy (IMRT) techniques. Treatment verification was primarily performed using cone-beam CT (86%). In NSCLC, the commonest curative dose-fractionation regime was 60 Gy/30# (96%) and for palliative intent, 30 Gy/10# (76%). Forty-four per cent treated patients with stereotactic ablative body radiotherapy (SABR) and half treated central tumours with this technique. In fit patients with synchronous solitary brain metastases, 80% would give radical treatment. For curative-intent SCLC, 45-50.4 Gy/25-28# (61%) and 45 Gy/30#/1.5 Gy b.d. (48%) were used. Ninety-four per cent discussed lung cancer patients at multidisciplinary meetings. Contours were peer-reviewed by 74% and 50% for conventional fractionation and SABR respectively. CONCLUSION: A significant proportion of ROs did not have access to 4D-CT. The majority used 3D image verification and consistently prescribed evidence based doses. A significant number did not participate in peer-review of contours. Practice in IMRT and synchronous oligo-metastatic disease is variable and should be an area of future research. Utilising survey findings, FROLIC is developing consensus recommendations to guide practice.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

BACKGROUND: Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). METHODS: Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. RESULTS: IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. CONCLUSIONS: Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Multimodality guidance for accurate bronchoscopic insertion of fiducial markers.

INTRODUCTION: Fiducial markers act as visible surrogates of tumor position during image-guided radiotherapy. Marker placement has been attempted percutaneously but is associated with high rates of pneumothorax and chest drain placement. METHODS: Patients undergoing radical radiation treatment for non-small-cell lung cancer underwent bronchoscopic implantation of gold fiducials using radial probe endobronchial ultrasound (EBUS) with virtual bronchoscopy and fluoroscopic guidance to achieve tumor localization and placement within/adjacent to peripheral lung tumors. For tumors not localized using radial EBUS, fiducial placement was achieved by electromagnetic navigation to the vicinity of the tumor. RESULTS: Eighteen fiducials were placed to mark 16 lesions in 15 patients. In nine patients (60%), fiducials were implanted at the time of diagnostic bronchoscopy. No procedural complications occurred. EBUS localization allowed marker implantation within the target lesion in 12 cases. In four lesions, electromagnetic navigation bronchoscopy-guided implantation achieved a median fiducial-lesion distance of 6 mm (mean 12 mm). No marker migration occurred after the implantation of two-band markers; however, early migration was observed in two of eight (25%) of the smaller linear fiducials. No migration during the course of radiation therapy was observed. CONCLUSION: Fiducial marker placement is easily and safely performed bronchoscopically, including at the time of diagnostic bronchoscopy. Marker geometry appears important in stability of bronchoscopically inserted fiducials. Future studies are required to confirm the optimal marker size, geometry, and spatial relationship with the target lesion.

Constituent components of out-of-field scatter dose for 18-MV intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy: a comparison with 6-MV and implications for carcinogenesis.

PURPOSE: To characterize and compare the components of out-of-field dose for 18-MV intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) and their 6-MV counterparts and consider implications for second cancer induction. METHODS AND MATERIALS: Comparable plans for each technique/energy were delivered to a water phantom with a sloping wall; under full scatter conditions; with field edge abutting but outside the bath to prevent internal/phantom scatter; and with shielding below the linear accelerator head to attenuate head leakage. Neutron measurements were obtained from published studies. RESULTS: Eighteen-megavolt IMRT produces 1.7 times more out-of-field scatter than 18-MV 3D-CRT. In absolute terms, however, differences are just approximately 0.1% of central axis dose. Eighteen-megavolt IMRT reduces internal/patient scatter by 13%, but collimator scatter (C) is 2.6 times greater than 18-MV 3D-CRT. Head leakage (L) is minimal. Increased out-of-field photon scatter from 18-MV IMRT carries out-of-field second cancer risks of approximately 0.2% over and above the 0.4% from 18-MV 3D-CRT. Greater photoneutron dose from 18-MV IMRT may result in further maximal, absolute increased risk to peripheral tissue of approximately 1.2% over 18-MV 3D-CRT. Out-of-field photon scatter remains comparable for the same modality irrespective of beam energy. Machine scatter (C+L) from 18 versus 6 MV is 1.2 times higher for IMRT and 1.8 times for 3D-CRT. It is 4 times higher for 6-MV IMRT versus 3D-CRT. Reduction in internal scatter with 18 MV versus 6 MV is 27% for 3D-CRT and 29% for IMRT. Compared with 6-MV 3D-CRT, 18-MV IMRT increases out-of-field second cancer risk by 0.2% from photons and adds 0.28-2.2% from neutrons. CONCLUSIONS: Out-of-field photon dose seems to be independent of beam energy for both techniques. Eighteen-megavolt IMRT increases out-of-field scatter 1.7-fold over 3D-CRT because of greater collimator scatter despite reducing internal/patient scatter. Out-of-field carcinogenic risk is thus increased (but improved in-field dose conformity may offset this). Potentially increased carcinogenic risk should be weighed against any benefit 18-MV IMRT may provide.

The efficacy of PET staging for small-cell lung cancer: a systematic review and cost analysis in the Australian setting.

INTRODUCTION: This study aimed to establish from the published literature the efficacy of a positron emission tomography (PET)-based strategy for the staging of small-cell lung cancer compared to conventional methods, the potential impact on patient management and outcomes, and cost implications for the Australian health system. METHODS: EMBASE, Current Contents, PubMed, and OVID, databases were searched using relevant search terms. Reference lists of identified studies were examined for additional pertinent papers. Literature review identified 22 relevant studies containing data for 1663 patients. Studies were evaluated regarding the adequacy of pathological or clinical correlation of imaging findings. Efficacy of PET-staging was analyzed. The Medicare benefits schedule was used to compare costs of the two strategies. RESULTS: Published data confirm that PET staging has a sensitivity approaching 100% and specificity exceeding 90%. Data suggest that compared to conventional staging, PET can alter management (including radiotherapy portal changes) in at least 28% of patients, can result in the addition of life-prolonging radiotherapy in 6%, and avert unnecessary radiotherapy with associated toxicity in 9%. PET-based staging costs 1603 Australian dollars (AUD) and conventional staging 1610 AUD per patient. An additional 540,354 AUD may be saved annually through avoidance of unnecessary radiotherapy. CONCLUSIONS: PET-based staging seems superior to conventional staging, and can significantly alter patient management particularly with regard to the inclusion, omission, and portal design of radiotherapy. The initial costs of the two strategies do not seem significantly different. PET may ultimately reduce healthcare costs through avoidance of inappropriate thoracic radiotherapy. The major advantages of PET-staging may, however, lie in averting unnecessary toxicity and in the appropriate addition of thoracic radiotherapy with potential survival gains.

A comparison of out-of-field dose and its constituent components for intensity-modulated radiation therapy versus conformal radiation therapy: implications for carcinogenesis.

PURPOSE: To investigate differences in scatter and leakage between 6-MV intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3DCRT); to describe the relative contributions of internal patient scatter, collimator scatter, and head leakage; and to discuss implications for second cancer induction. METHODS AND MATERIALS: Dose was measured at increasing distances from the field edge in a water bath with a sloping wall (1) under full scatter conditions, (2) with the field edge abutting but outside the bath to prevent internal (water) scatter, and (3) with the beam aperture plugged to reflect leakage only. RESULTS: Internal patient scatter from IMRT is 11% lower than 3DCRT, but collimator scatter and head leakage are five and three times higher, respectively. Ultimately, total scattered dose is 80% higher with IMRT; however this difference is small in absolute terms, being 0.14% of prescribed dose. Secondary dose from 3DCRT is mostly due to internal patient scatter, which contributes 70% of the total and predominates until 25 cm from the field edge. For IMRT, however, machine scatter/leakage is the dominant source, contributing 65% of the secondary dose. Internal scatter predominates for just the first 10 cm from field edge, collimator scatter for the next 10 cm, and head leakage thereafter. CONCLUSIONS: Out-of-field dose is 80% higher with IMRT, but differences are tiny in absolute terms. Reductions in internal patient scatter with IMRT are outweighed by increased machine scatter and leakage, at least for small fields. Reductions from IMRT in dose to tissues within the portals and in internal scatter, which predominates close to the field edge, means that calculations based solely on dose to distant tissues may overestimate carcinogenic risks.

Effect of intensity-modulated pelvic radiotherapy on second cancer risk in the postoperative treatment of endometrial and cervical cancer.

PURPOSE: To estimate and compare intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3DCRT) in terms of second cancer risk (SCR) for postoperative treatment of endometrial and cervical cancer. METHODS AND MATERIALS: To estimate SCR, the organ equivalent dose concept with a linear-exponential, a plateau, and a linear dose-response model was applied to dose distributions, calculated in a planning computed tomography scan of a 68-year-old woman. Three plans were computed: four-field 18-MV 3DCRT and nine-field IMRT with 6- and 18-MV photons. SCR was estimated as a function of target dose (50.4 Gy/28 fractions) in organs of interest according to the International Commission on Radiological Protection. RESULTS: Cumulative SCR relative to 3DCRT was +6% (3% for a plateau model, -4% for a linear model) for 6-MV IMRT and +26% (25%, 4%) for the 18-MV IMRT plan. For an organ within the primary beam, SCR was +12% (0%, -12%) for 6-MV and +5% (-2%, -7%) for 18-MV IMRT. 18-MV IMRT increased SCR 6-7 times for organs away from the primary beam relative to 3DCRT and 6-MV IMRT. Skin SCR increased by 22-37% for 6-MV and 50-69% for 18-MV IMRT inasmuch as a larger volume of skin was exposed. CONCLUSION: Cancer risk after IMRT for cervical and endometrial cancer is dependent on treatment energy. 6-MV pelvic IMRT represents a safe alternative with respect to SCR relative to 3DCRT, independently of the dose-response model. 18-MV IMRT produces second neutrons that modestly increase the SCR.

The effect of intensity-modulated radiotherapy on radiation-induced second malignancies.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) in terms of carcinogenic risk for actual clinical scenarios. METHOD AND MATERIALS: Clinically equivalent IMRT plans were generated for prostate, breast, and head-and-neck cases treated with 3D-CRT. Two possible dose-response models for radiocarcinogenesis were generated based on A-bomb survivor data corrected for fractionation. Dose-volume histogram analysis was used to determine dose and its distribution to nontargeted tissues within the planning CT scan volume and thermoluminescent dosimetry for the rest of the body. Carcinogenic estimates were calculated with and without a correction factor accounting for cancer patients' advanced age and reduced longevity. RESULTS: For the model assuming a plateau in risk above 2-Gy single-fraction-equivalent (SFE), IMRT and 3D-CRT produced risks of 1.7% and 2.1%, respectively, for prostate; 1.9% and 1.8%, respectively, for nasopharynx; 1% each for tonsil; and 1.4-2.2% and 1.5-1.6%, respectively, depending on technique, for breast. Assuming a reduction in risk above 2-Gy SFE, risks for IMRT and 3D-CRT were 1.1% and 1.5%, respectively, for prostate; 1.4% and 1.2%, respectively, for nasopharynx; 1% each for tonsil; and 1.3-1.8% vs. 1.3-1.6%, respectively, for breast. Applying a correction factor of 0.5 for cancer patients halved these risks and their relative differences. CONCLUSIONS: Carcinogenic risks were comparable in absolute terms between modalities. Risks are dependant on technique used. Risks with IMRT are influenced by monitor unit demand and are therefore software/hardware dependant. The dose-response model accounting for cell killing at higher doses fitted best with actual observed risks.

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PURPOSE: To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. METHODS AND MATERIALS: Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. RESULTS: Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). CONCLUSIONS: Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.