Melanie M Green

Inter-fraction motion and dosimetric consequences during breast intensity-modulated radiotherapy (IMRT)

BACKGROUND AND PURPOSE Intensity-modulated radiotherapy (IMRT) can improve dose homogeneity within the breast planned target volume (PTV), but may be more susceptible to patient/organ motion than standard tangential radiotherapy (RT). We used daily cone-beam CT (CBCT) imaging to assess inter-fraction motion during breast IMRT and its subsequent impact on IMRT and standard RT dose homogeneity. MATERIALS AND METHODS Ten breast cancer patients selected for IMRT were studied. CBCT images were acquired immediately after daily treatment. Automatic image co-registration was used to determine patient positioning variations. Daily PTV contours were used to calculate PTV variations and daily delivered IMRT and theoretically planned tangential RT dose. RESULTS Group systematic (and random) setup errors detected by CBCT were 5.7 (3.9)mm laterally, 2.8 (3.5)mm vertically and 2.3 (3.2)mm longitudinally. Rotations >2 degrees in any axis occurred on 53/106 (50%) occasions. Daily PTV volume varied up to 23%. IMRT dose homogeneity was superior at planning and throughout the treatment compared with standard RT (1.8% vs. 15.8% PTV received >105% planned mean dose), despite increased motion sensitivity. CONCLUSIONS CBCT revealed inadequacies of current patient positioning and verification procedures during breast RT and confirmed improved dose homogeneity using IMRT for the patients studied.

Quantifying motion for pancreatic radiotherapy margin calculation.

BACKGROUND AND PURPOSE Pancreatic radiotherapy (RT) is limited by uncertain target motion. We quantified 3D patient/organ motion during pancreatic RT and calculated required treatment margins. MATERIALS AND METHODS Cone-beam computed tomography (CBCT) and orthogonal fluoroscopy images were acquired post-RT delivery from 13 patients with locally advanced pancreatic cancer. Bony setup errors were calculated from CBCT. Inter- and intra-fraction fiducial (clip/seed/stent) motion was determined from CBCT projections and orthogonal fluoroscopy. RESULTS Using an off-line CBCT correction protocol, systematic (random) setup errors were 2.4 (3.2), 2.0 (1.7) and 3.2 (3.6)mm laterally (left-right), vertically (anterior-posterior) and longitudinally (cranio-caudal), respectively. Fiducial motion varied substantially. Random inter-fractional changes in mean fiducial position were 2.0, 1.6 and 2.6mm; 95% of intra-fractional peak-to-peak fiducial motion was up to 6.7, 10.1 and 20.6mm, respectively. Calculated clinical to planning target volume (CTV-PTV) margins were 1.4 cm laterally, 1.4 cm vertically and 3.0 cm longitudinally for 3D conformal RT, reduced to 0.9, 1.0 and 1.8 cm, respectively, if using 4D planning and online setup correction. CONCLUSIONS Commonly used CTV-PTV margins may inadequately account for target motion during pancreatic RT. Our results indicate better immobilisation, individualised allowance for respiratory motion, online setup error correction and 4D planning would improve targeting.

Assessment of bladder motion for clinical radiotherapy practice using cine-magnetic resonance imaging.

PURPOSE Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion. METHODS AND MATERIALS We used cine-magnetic resonance imaging (cine-MRI) to study bladder motion relevant to intrafraction RT delivery. On two occasions, a 28 minute cine-MRI sequence was acquired from 10 bladder cancer patients and 5 control participants immediately after bladder emptying, after abstinence from drinking for the preceding hour. From the resulting cine sequences, bladder motion was subjectively assessed. To quantify bladder motion, the bladder was contoured in imaging volume sets at 0, 14, and 28 min to measure changes to bladder volumes, wall displacements, and center of gravity (COG) over time. RESULTS The dominant source of bladder motion during imaging was bladder filling (up to 101% volume increase); rectal and small bowel movements were transient, with minimal impact. Bladder volume changes were similar for all participants. However for bladder cancer patients, wall displacements were larger (up to 58 mm), less symmetrical, and more variable compared with nondiseased control bladders. CONCLUSIONS Significant and individualized intrafraction bladder wall displacements may occur during bladder RT delivery. This important source of inaccuracy should be incorporated into treatment planning and verification.

Ultrasound Imaging to Assess Inter- and Intra-fraction Motion during Bladder Radiotherapy and its Potential as a Verification Tool

AIMS Organ motion is the principle source of error in bladder cancer radiotherapy. The aim of this study was to evaluate ultrasound bladder volume measurement as a surrogate measure of organ motion during radiotherapy: (1) to assess inter- and intra-fraction bladder variation and (2) as a potential treatment verification tool. MATERIALS AND METHODS Twenty patients receiving radical radiotherapy for bladder cancer underwent post-void ultrasound bladder volume measurement at the time of radiotherapy treatment planning (RTP), and immediately before (post-void) and after receiving daily fractions. RESULTS Ultrasound bladder volume measurement was found to be a simple and acceptable method to estimate relative bladder volume changes. Six patients showed significant changes to post-void bladder volume over the treatment course (P<0.05). The mean inter-fraction post-void bladder volume of five patients exceeded their RTP ultrasound bladder volume by more than 50%. Intra-fraction bladder volume increased on 275/308 (89%) assessed fractions, with the mean intra-fraction volume increases of seven patients exceeding their RTP ultrasound bladder volume by more than 50%. CONCLUSIONS Both day-to-day bladder volume variation and bladder filling during treatment should be considered in RTP and delivery. Ultrasound may provide a practical daily verification tool by: supporting volume limitation as a method of treatment margin reduction; allowing detection of patients who may require interventions to promote bladder reproducibility; and identifying patients with prominent volume changes for the selective application of more advanced adaptive/image-guided radiotherapy techniques.

Expression of the proapoptotic protein Bid is an adverse prognostic factor for radiotherapy outcome in carcinoma of the cervix

The Bcl-2 family of apoptotic regulators is thought to play an essential role in cancer development and influence the sensitivity of tumour cells to radiotherapy. Bid is an abundantly expressed Bcl-2 family protein playing a central role in various pathways of apoptosis by integrating and converging signals at the mitochondria. The relevance of apoptotic modulation by Bcl-2 and related proteins in tumour development and radiation response for human tumours remains undefined. Therefore, a study was made regarding the expression of Bid in patients with locally advanced cervix carcinoma who received radiotherapy. Bid expression was assessed using immunohistochemistry in pretreatment archival biopsies from 98 patients. The data were correlated with clinicopathologic characteristics and treatment outcome. Pretreatment tumour radiosensitivity data were available for 60 patients. Strong Bid expression was associated with a patient age less than the median of 52 years (P=0.034) and poor metastasis-free survival. In multivariate analysis, after allowing for stage, Bid expression was a significant prognostic factor for both disease-specific and metastasis-free survival (P=0.026). It is concluded that strong tumour Bid expression is associated with poor outcome following radiotherapy regardless of intrinsic tumour cell radiosensitivity, and is adverse prognostic for disease-specific and metastasis-free survival in younger patients.

Efficacy and Tolerability of Limited Field Radiotherapy with Concurrent Capecitabine in Locally Advanced Pancreatic Cancer

AIMS Patients with locally advanced pancreatic cancer (LAPC) are most commonly managed with chemotherapy or concurrent chemoradiotherapy (CRT), which may or may not include non-involved regional lymph nodes in the clinical target volume. We present our results of CRT for LAPC using capecitabine and delivering radiotherapy to a limited radiation field that excluded non-involved regional lymph nodes from the clinical target volume. MATERIALS AND METHODS Thirty patients were studied. Patients received 50.4 Gy external beam radiotherapy in 28 fractions, delivered to a planning target volume expanded from the primary tumour and involved nodes only. Capecitabine (500-600 mg/m2) was given twice daily continuously during radiotherapy. Toxicity and efficacy data were prospectively collected. RESULTS Nausea, vomiting and tumour pain were the most common grade 2 toxicities. One patient developed grade 3 nausea. The median time to progression was 8.8 months, with 20% remaining progression free at 1 year. The median overall survival was 9.7 months with a 1 year survival of 30%. Of 21 patients with imaged progression, 13 (62%) progressed systemically, three (14%) had local progression, two (10%) had locoregional progression and three (14%) progressed with both local/locoregional and systemic disease. CONCLUSION CRT using capecitabine and limited field radiotherapy is a well-tolerated, relatively efficacious treatment for LAPC. The low toxicity and low regional progression rates support the use of limited field radiotherapy, allowing evaluation of this regimen with other anti-cancer agents.

Positron emission tomography imaging approaches for external beam radiation therapies: current status and future developments

In an era in which it is possible to deliver radiation with high precision, there is a heightened need for enhanced imaging capabilities to improve tumour localisation for diagnostic, planning and delivery purposes. This is necessary to increase the accuracy and overall efficacy of all types of external beam radiotherapy (RT), including particle therapies. Positron emission tomography (PET) has the potential to fulfil this need by imaging fundamental aspects of tumour biology. The key areas in which PET may support the RT process include improving disease diagnosis and staging; assisting tumour volume delineation; defining tumour phenotype or biological tumour volume; assessment of treatment response; and in-beam monitoring of radiation dosimetry. The role of PET and its current developmental status in these key areas are overviewed in this review, highlighting the advantages and drawbacks.

An effective deep-inspiration breath-hold radiotherapy technique for left-breast cancer: impact of post-mastectomy treatment, nodal coverage, and dose schedule on organs at risk

Background We developed, applied, and prospectively evaluated a novel deep-inspiration breath-hold (DIBH) screening and delivery technique to optimize cardiac sparing in left-breast radiotherapy (RT) at our clinic. The impact of set-up and dose variables upon organs at risk (OAR) dose in DIBH RT was investigated. Methods and materials All patients with left-breast cancer referred between 2011 and 2014 – of all disease stages, set-up variations, and dose prescriptions – were included. Radiographers used simple screening criteria at CT simulation, to systematically assess patients for obvious DIBH benefit and capability. Selected patients received forward-planned intensity-modulated RT (IMRT) based on a DIBH CT scan. A 3D-surface monitoring system with visual feedback assured reproducible DIBH positioning during gated radiation delivery. Patient, target set-up, and OAR dose information were collected at treatment. Results Of 272 patients who were screened, 4 withdrew, 56 showed no obvious advantage, and 56 showed benefit but had suitability issues; 156 patients were selected and successfully completed DIBH treatment. The technique was compatible with complex set-up and optimal target coverage was maintained. Comparison of free-breathing (FB) and DIBH treatment plans in the first five patients enrolled confirmed DIBH reduced heart radiation by ~80% (p = 0.032). Low OAR doses were achieved overall: the mean (95% confidence interval [CI]) heart dose was 1.17 (1.12–1.22) Gy, and the mean ipsilateral lung dose was 5.26 (5.01–5.52) Gy. Patients who underwent a standard radiation schedule (40 Gy/15#) after breast-conserving surgery had the lowest OAR doses: post-mastectomy treatment, simultaneous supraclavicular (SCV) node coverage, and alternative dose schedule (50 Gy/25#) were interrelated variables associated with increased OAR risk and compromised ipsilateral lung dose constraints. Conclusion The DIBH technique was successfully implemented and resulted in optimally low heart radiation. All patients who demonstrate sufficient DIBH technique at planning CT are now offered DIBH RT at our clinic. Patients with more advanced disease, particularly those with additional pulmonary risk factors, warrant additional focus to improve lung sparing.

CyberKnife Radiosurgery of Skull-base Tumors: A UK Center Experience

The study aim was to evaluate patient individualized Cyberknife® treatment for heterogeneous skull-base tumors. Patients treated between 2009 and 2013 at The Harley Street Clinic were studied. In total, 66 patients received 15–30 Gy in 1–5 fractions to a median planning target volume (PTV) of 6.4 cc, including patients with secondary, multiple, residual and recurrent tumors, and those with tumors of uncertain pathological type. Outcome analysis was pragmatically restricted to 35 patients who had single, primary tumors treated with curative intent, and sufficient diagnostic and outcome information. Sixteen vestibular schwannoma patients with median PTV 3.8 cc (range 0.81–19.6) received 18–25 Gy in 3–5 fractions: 81% showed no acute toxicity, 50% reported no late toxicity, 71% of symptoms were stable/improved and local control was 100% at 11.4 months median follow-up. Twelve meningioma patients with median PTV of 5.5 cc (range 0.68–22.3) received 17–30 Gy in 1–5 fractions: 83% experienced no acute toxicity, 33% reported no late toxicity, 88% of symptoms were stable/improved and local control was 100% at 22.1 months median follow-up. Seven patients with other tumor types with median PTV of 24.3 cc (range 7.6–100.5) received 15–28.5 Gy in 1–5 fractions: 57% experienced no acute toxicity, 57% reported no late toxicities, 66% of symptoms were stable and local control was 43% at 14.9 months median follow-up. When tumor types were considered together, smaller tumors (PTV < 6.4 cc) showed reduced acute toxicity (p = 0.01). Overall, smaller benign tumors showed low acute toxicity, excellent local control, and good symptom management: a focus on enhanced neurological preservation may refine outcomes. For other tumor types outcome was encouraging: a focus on optimal dose and fractionation scheduling may reduce toxicity and improve local control. Individual patient experiences are detailed where valuable lessons were gained for optimizing local control and minimizing toxicity.

Deep inspiration breath-hold (DIBH) technique applied in right breast radiotherapy to minimize liver radiation

A right-sided breast cancer patient (stage T1N0M0) was referred for post-surgical radiotherapy to minimize risk of local tumour recurrence. During the CT simulation and intensity-modulated radiotherapy planning process undertaken in free breathing, it was apparent that an unusually large volume of normal liver tissue (134 cc) was in the high-dose region of the tangential radiation field. This raised concern for risk of liver side effects and was considered suboptimal for this excellent prognosis patient. A deep inspiration breath-hold (DIBH) technique using three-dimensional (3D) surface monitoring—primarily developed and applied in left breast cancer to displace cardiac tissue from the target field—was investigated to determine potential benefit to optimize radiotherapy delivery. Resimulation of DIBH resulted in considerable displacement of the liver, reducing the volume of liver tissue in the target field by 63% (to 50 cc) and the mean liver dose by 46% (to 2.6 Gy). As the patient was deemed suitable for the DIBH technique, treatment was delivered according to the DIBH plan. A total of 40.05 Gy in 15 fractions was successfully delivered in the DIBH position using a technique that incorporated 3D body surface imaging with automated radiation beam hold-off when out of tolerance. Additional advantages were optimal set up without extensive immobilization and the elimination of respiratory motion. Acute mild skin erythema was the only side effect experienced—no liver sequalae were experienced by the patient up to 6 months after treatment. DIBH treatment may improve liver sparing in other similar right breast cancer patients.