Radiotherapy & Oncology

Editorial Board

2012-02-01

Radiotherapy in small cell lung cancer: Limited volumes in limited disease and adding thoracic radiotherapy in extended disease?

Lucyna Kepka, Michael Baumann — 2012-01-30

Improving the outcome of treatment of lung cancer remains a formidable and multidisciplinary task . Although distant metastases occur early and frequently in lung cancer it is important to realize that failure to achieve loco-regional control is an equally important reason for todays’ overall poor outcome in this disease . Therefore considerable recent research in the field of radiotherapy has been directed towards technological improvements in target identification by advanced imaging, conformal and motion corrected treatment planning methodologies, more precise as well as better monitored radiotherapy application, and bioimaging for individualized and adaptive treatment approaches . In parallel a large number of retrospective and prospective studies have addressed optimization of total dose, dose per fraction, and overall treatment time, identification of dose–volume constraints for normal tissues, and integration of radiotherapy with chemotherapy . From this research improved loco-regional tumor control, reduced normal tissue toxicity and better survival is expected.

Treatment of brain metastases: Review of phase III randomized controlled trials

Silvia Scoccianti, Umberto Ricardi — 2011-10-13

Abstract: The optimal management of brain metastases remains controversial. Both whole brain radiotherapy (WBRT) and local treatment [surgery (S) or radiosurgery (RS)] are the cornerstones of treatment. The role of systemic therapy is also being explored. Randomized controlled trials (RCT) have tried to assess the individual and combined effects of different therapeutic strategies.(1) RCT in oligometastatic patients: WBRT alone vs. local treatment+WBRT. Combined treatment may improve both overall survival and local control in patients with a single metastasis, but it also leads to a local control benefit in patients with two to four lesions.Exclusive local treatment vs. WBRT plus local treatment. The addition of WBRT to local treatment may result in improved local control, improved freedom from new brain metastases and improved overall brain control.S+WBRT vs. RS+WBRT. There is no evidence of superiority of a combined treatment over the other one.(2) RCT addressing the point of improving WBRT outcome: differences in WBRT fractionation do not significantly alter outcome of treatments. Only a few systemic drugs may cause some significant advantages.(3) RCT that assessed neurocognitive impairment and quality of life: the baseline cognitive performance of most patients is significantly impaired. Intracranial tumor control is an essential factor in stabilizing neurocognitive function. The data on neurocognitive toxicity related to WBRT are still contradictory. Impairment of both neurocognitive function and quality of life of patients with brain metastases needs to be further addressed in RCT.

A pooled analysis of arc-based image-guided simultaneous integrated boost radiation therapy for oligometastatic brain metastases

2011-06-06

Abstract: Purpose: To report pooled overall survival and time to radiological intracranial progression results related to arc-based image-guided radiotherapy for dose-escalation of oligometastatic disease of the brain.Methods and materials: Anonymized patient, tumor, and treatment data were pooled from the VU University medical center (VUmc) and the London Regional Cancer Program (LRCP) for patients treated with whole brain radiotherapy (20Gy/5 VUmc, 30Gy/10 LRCP) with simultaneous integrated boost (SIB) to individual intracranial lesions (40Gy/5 VUmc, 35–60Gy/10 LRCP) to perform survival/intracranial control outcome analyses.Results: A total of 120 patients were treated by both the LRCP (n=70) and VUmc (n=50) between 2005 and 2010. Median lesional dose BED3,10 for the entire cohort of patients were 147 and 72Gy, respectively. Median follow-up for the entire cohort of patients was 4.7months with median follow-up of 5.2months for living patients. On multivariable analysis, primary lung cancer (HR 2.044), presence of systemic metastatic disease (HR 1.937), and lower baseline WHO performance status (HR 1.742) were significant (p<0.05) predictors of shorter overall survival. Cumulative brain metastases volume (HR 1.014, p=0.06) was of borderline significance on analysis of intracranial control.Conclusions: This pooled analysis has provided robust outcome data regarding the use of arc-based radiotherapy with SIB.

Whole-brain irradiation with concomitant daily fixed-dose Temozolomide for brain metastases treatment: A randomised phase II trial

Carlos Gamboa-Vignolle, Tabaré Ferrari-Carballo, Óscar Arrieta, Alejandro Mohar — 2012-01-18

Abstract: Background and purpose: This randomised phase II study evaluated the use of Temozolomide (TMZ) concomitant with 30Gray (Gy) of Whole-brain irradiation (WBI) for 2weeks without adjuvant TMZ vs. WBI alone in patients with Brain metastases (BM) from solid tumours.Materials and methods: Fifty-five patients were randomised into the following groups: 28 patients received WBI (30Gy in 10 fractions over 2weeks) concomitant with once-daily 200mg TMZ on Mondays, Wednesdays, and Fridays, and 300mg TMZ on Tuesdays and Thursdays (TMZ plus WBI arm). Twenty-seven patients received the same schedule of WBI alone (control arm).Results: The objective response (OR) was 78.6% for the TMZ plus WBI arm, (95% confidence interval [CI], 63.4–93.8%) and 48.1% (29.3–66.9%) for the control arm (p=0.019). Median Progression-free survival (PFS) of BM was 11.8months (CI, 4.7–8.9months) and 5.6months (4.9–6.2months) for the TMZ plus WBI and control arms, respectively, (Hazard ratio [HR], 0.24; CI, 0.09–0.65; p=0.005). Overall survival (OS) of 8.0 Months for the TMZ plus WBI arm and 8.1months for the control arm, were not significantly different.Conclusion: A daily fixed dose of TMZ during WBI without adjuvant TMZ was well tolerated and significantly improved local control of BM compared with WBI alone. These findings require confirmation in a phase III trial (ClinicalTrials.gov number, NCT01015534).

Reirradiation of brain metastases with radiosurgery

2011-08-31

Abstract: Purpose: To assess the outcome of reirradiation with stereotactic radiosurgery (SRS) of brain metastases (BM) recurring after whole brain radiotherapy (WBRT).Methods and materials: Between September 2001 and October 2008, 69 patients who recurred after WBRT were re-irradiated with SRS using a linear accelerator. The dose prescription was generally chosen according to maximum diameter of the tumor as suggested by Radiation Therapy Oncology Group (RTOG) 90-05 protocol. Patients were stratified by Karnofsky Performance Status (KPS), Neurologic Functional Score (NFS), RTOG Recursive Partitioning Analysis (RPA), Score Index for Radiosurgery (SIR), primary disease, dimension and number of BM, and time to first brain recurrence after WBRT. Response, survival, and toxicity were analyzed.Results: At time of this retrospective analysis all patients had died. The 69 patients reirradiated with SRS had 150 metastases. Median interval between prior WBRT and SRS was 11months and median SRS prescribed dose was 20Gy. Response was obtained in 91% of lesions with 1-year local control rate of 74±4%. Significantly longer duration of response was associated with higher doses (⩾23Gy) and response achieved after SRS (complete and partial response better than stable disease). Cause of death was brain failure only in 36 (52%) patients. Median overall survival after reirradiation was 10months. Variables which significantly conditioned survival were KPS and NFS. Four (6%) patients had asymptomatic radionecrosis that developed prevalently when lesion diameters were larger and cumulative doses exceeded the values recommended by RTOG 90-05 protocol. About three-fourth of the patients had a good KPS and NFS after reirradiation.Conclusions: Reirradiation of BM with SRS resulted feasible and effective. A correct patient selection and an accurate evaluation of the cumulative irradiation dose were suggested.

Clinical comparison of positional accuracy and stability between dedicated versus conventional masks for immobilization in cranial stereotactic radiotherapy using 6-degree-of-freedom image guidance system-integrated platform

2011-11-21

Abstract: Purpose: To compare the positioning accuracy and stability of two distinct noninvasive immobilization devices, a dedicated (D-) and conventional (C-) mask, and to evaluate the applicability of a 6-degrees-of-freedom (6D) correction, especially to the C-mask, based on our initial experience with cranial stereotactic radiotherapy (SRT) using ExacTrac (ET)/Robotics integrated into the Novalis Tx platform.Materials and methods: The D- and C-masks were the BrainLAB frameless mask system and a general thermoplastic mask used for conventional radiotherapy such as whole brain irradiation, respectively. A total of 148 fractions in 71 patients and 125 fractions in 20 patients were analyzed for the D- and C-masks, respectively. For the C-mask, 3D correction was applied to the initial 10 patients, and thereafter, 6D correction was adopted. The 6D residual errors (REs) in the initial setup, after correction (pre-treatment), and during post-treatment were measured and compared.Results: The D-mask provided no significant benefit for initial setup. The post-treatment median 3D vector displacements (interquatile range) were 0.38mm (0.22, 0.60) and 0.74mm (0.49, 1.04) for the D- and C-masks, respectively (p<0.001). The post-treatment maximal translational REs were within 1mm and 2mm for the D- and C-masks, respectively, and notably within 1.5mm for the C-mask with 6D correction. The pre-treatment 3D vector displacements were significantly correlated with those for post-treatment in both masks.Conclusions: The D-mask confers positional stability acceptable for SRT. For the C-mask, 6D correction is also recommended, and an additional setup margin of 0.5mm to that for the D-mask would be sufficient. The tolerance levels for the pre-treatment REs should similarly be set as small as possible for both systems.

Dosimetric consequences of rotational errors in radiation therapy of pediatric brain tumor patients

Chris Beltran, Alexander Pegram, Thomas E. Merchant — 2011-07-04

Abstract: Purpose: To quantify the rotational offsets and estimate the dose effect of rotation on the target volume and normal tissues in children with brain tumor.Methods: Twenty-one pediatric patients with brain tumors were included in this study. Cone-beam CT was performed before each treatment and at the end of every other treatment. Translational offsets were corrected before the treatment. An offline analysis was performed to quantify rotational errors. The treatment plans were altered and recalculated to simulate a rotation of 2° and 4°, and the dose changes were quantified.Results: 1016 CBCT datasets were analyzed for this report. The mean of the rotations were not meaningfully different from zero. 18.1% of the fractions had rotations with a magnitude ⩾2°, 5.0% had rotations ⩾3° and 0.9% had rotations ⩾4°. For the 2° rotational simulation, the gEUD values of the PTV and critical structures changed by less than 2%. For the 4° simulation, parallel type normal structures had minor changes (<2%), but serial type normal structures and the PTV had changes of 10% and 5%, respectively.Conclusions: The majority of rotational errors observed were less than 1°. A rotational error of 2° produced negligible changes in the gEUD to critical structures or target volumes. Rotational errors ⩾4° produced undesirable results, therefore, at a minimum, errors >2° should be corrected.

Oncologists’ view of informed consent and shared decision making in paediatric radiation oncology

Robert A. Olson, Mary Ann Bobinski, Anita Ho, Karen J. Goddard — 2011-09-02

Abstract: Background and purpose: Cure rates of paediatric malignancies have dramatically improved with therapy intensification, at the cost of late treatment side effects. A survey was developed, centred around medulloblastoma scenarios, in order to explore paediatric oncology physicians’ views on discussing late effects and involving parents in treatment decisions.Materials and methods: Participants were 59 paediatric radiation and medical oncologists or fellows from USA (22), Canada (18), Europe (16), Australia (2), and Asia (1).Results: Ninety-five percent of respondents indicated late effects discussion prior to multimodality treatment was important. Of those who supported it, 100%, 83%, 64%, and 48% thought discussing cognitive impairment, infertility, stroke, and seizures as potential late effects was important, respectively. Only 71% of respondents believed parents should be involved in treatment decisions, which did not significantly vary by respondent age, country, specialty, gender, or years in practice.Conclusions: The majority of oncologists who treat children believe discussing late effects with parents is important. However, there is mixed opinion on which late effects should be discussed and whether parents should be involved in deciding which treatments should be pursued. Research into perceived barriers to shared decision making and effective methods of improving the informed consent process in paediatric malignancies is needed.

A prospective study of supine versus prone positioning and whole-body thermoplastic mask fixation for craniospinal radiotherapy in adult patients

2011-08-22

Abstract: Purpose: To evaluate neuroaxis irradiation for adults in the supine position using head body thermoplastic mask fixation, from the aspects of dose distribution, patient comfort and set-up accuracy.Methods and materials: Nine of the 12 adult patients were positioned for craniospinal axis irradiation in both prone and supine positions. After mask fixation and planning CTs in both positions, a questionnaire relating to the comfort was completed. The doses to the target and to the organs at risk of the 3D conformal plans in the supine and prone positions were compared. Portal images of all 12 patients irradiated in the supine position were evaluated, the van Herk formulas being used to calculate the systemic and random errors.Results: No significant difference was found between the prone and supine positions target coverage, the dose homogeneity and the dose to the organs at risk. The supine position was considered more comfortable by the patients (scores of 2.8 versus 4.29), with a vector random error of 3.27mm, and a systematic error of 0.32mm. The largest random set-up error was observed in the lateral direction: 4.83mm.Conclusions: The more comfortable supine position is recommended for craniospinal irradiation in adult patients. Whole-body thermoplastic mask immobilization provides excellent repositioning accuracy.

Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results

2011-08-24

Abstract: Purpose: To determine local control, late toxicity and metastatic free survival (MFS) of patients treated with fractionated stereotactic radiation therapy (fSRT) for uveal melanoma (UM).Methods and materials: Between 1999 and 2007, 102 UM patients were included in a prospective study of a single institution (median follow-up (FU) 32months; median tumor thickness 6mm); five fractions of 10Gy were given. Primary endpoints were local tumor control and late toxicity (including visual outcome and eye preservation). Secondary endpoint was MFS.Results: Local tumor control was achieved in 96% of the patients. Fifteen enucleations were performed, 2–85months after radiation. Four eyes were enucleated because of local tumor progression. Nine patients developed grade 3 or 4 neovascular glaucoma (NVG), 19 developed severe retinopathy, 13 developed opticoneuropathy grade 3 or 4, 10 developed cataract grade 3, and 10 patients suffered from keratitis sicca. Best corrected visual acuity (BCVA) decreased from a mean of 0.26 at diagnosis to 0.16, 3months after radiation and it gradually declined to 0.03, 4years after therapy. The 5-year actuarial MFS was 75% (95% CIs: 62–84%).Conclusions: fSRT is an effective treatment modality for uveal melanoma with a good local control. With that, fSRT is a serious eye sparing treatment modality. However, our FU is relatively short. Also, the number of secondary enucleations is substantial, mainly caused by NVG.

A practical technique to avoid the hippocampus in prophylactic cranial irradiation for lung cancer

2011-12-22

Abstract: A practical technique is presented to deliver hippocampus avoiding prophylactic cranial irradiation for lung cancer patients, using two lateral fields. For a prescribed dose of 12×2.5Gy, sparing of the hippocampi to 6.1Gy was achieved with a V95% of the brain of 81.7%.

Individualised isotoxic accelerated radiotherapy and chemotherapy are associated with improved long-term survival of patients with stage III NSCLC: A prospective population-based study

2011-11-21

Abstract: Background: Individualised, isotoxic, accelerated radiotherapy (INDAR) allows the delivery of high biological radiation doses, but the long-term survival associated with this approach is unknown.Methods: Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included.Results: Patients (1002) with stage III NSCLC were diagnosed, of which 938 had T4 and/or N2–N3 disease. Patients treated with curative intent were staged with FDG-PET scans and a contrast-enhanced CT or an MRI of the brain. There were no shifts over time in the patient or tumour characteristics at diagnosis. The number of stage III NSCLC patients remained stable over time, but the proportion treated with palliative intent decreased from 47% in 2002 to 37% in 2008, and the percentage treated with chemo-radiation (RT) increased from 24.6% in 2002 to 47.8% in 2008 (p<0.001). The proportion of surgical patients remained below 5%. Sequential chemotherapy and conventional RT resulted in a median and a 5-year survival of 17.5months and 8.4%, respectively, whereas with sequential chemotherapy and INDAR this was 23.6months and 31%, respectively (p<0.001). Concurrent chemotherapy and INDAR was associated with a median and 2-year survival that was not reached and 66.7%, respectively (p=0.004).Conclusions: The proportion of patients treated with a curative intention with chemo-RT has increased markedly over time of observation. INDAR is associated with longer survival when compared to standard dose RT alone given with or without chemotherapy.

Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer

2011-09-19

Abstract: Background and purpose: To define the rate of development of symptomatic chest failures in extensive stage small cell lung cancer (ES-SCLC) after undergoing post-chemotherapy chest radiotherapy (RT).Materials and methods: Patients had ES-SCLC, attained an objective response to chemotherapy and signed study consent. Target accrual was 33 patients. Patients were offered prophylactic cranial irradiation (PCI) as per department policy. PCI (25Gy/10 fractions) and chest RT (40Gy/15 fractions) were given simultaneously 4–8weeks after chemotherapy completion. Thoracic target volume was the post-chemotherapy residual chest disease plus margin. Patients were evaluated for RT toxicities, local control, disease-free and overall survival.Results: Thirty-two patients were evaluable. Twenty-nine patients completed RT without delay. There were 4 complete responses and 28 partial responses to chemotherapy. All study patients received PCI. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no RT-related deaths. Median time to disease progression and overall survival were 4.2 and 8.3months, respectively (median follow-up=21.8months). Of 16 chest recurrences, 7 were in the irradiated region and 5 were symptomatic.Conclusions: Post-chemotherapy consolidation chest RT for ES-SCLC patients on this trial was well tolerated and associated with symptomatic chest recurrences in only 5/32 treated patients.

Combined PET/CT image characteristics for radiotherapy tumor response in lung cancer

2011-11-18

Abstract: Background and Purpose: Prediction of local failure in radiotherapy patients with non-small cell lung cancer (NSCLC) remains a challenging task. Recent evidence suggests that FDG–PET images can be used to predict outcomes. We investigate an alternative multimodality image-feature approach for predicting post-radiotherapy tumor progression in NSCLC.Material and methods: We analyzed pre-treatment FDG–PET/CT studies of twenty-seven NSCLC patients for local and loco-regional failures. Thirty-two tumor region features based on SUV or HU, intensity-volume-histogram (IVH) and texture characteristics were extracted. Statistical analysis was performed using Spearman’s correlation (rs) and multivariable logistic regression.Results: For loco-regional recurrence, IVH variables had the highest univariate association. In PET, IVH-slope reached rs=0.3426 (p=0.0403). Motion correction slightly improved correlation of texture features. In CT, coefficient of variation had the highest association rs=−0.2665 (p=0.0871). Similarly for local failure, a CT-IVH parameter reached rs=0.4530 (p=0.0105). For loco-regional and local failures, a 2-parameter model of PET-V80 and CT-V70 yielded rs=0.4854 (p=0.0067) and rs=0.5908 (p=0.0013), respectively. Addition of dosimetric variables provided improvement in cases of loco-regional but not local failures.Conclusions: We proposed a feature-based approach to evaluate radiation tumor response. Our study demonstrates that multimodality image-feature modeling provides better performance compared to existing metrics and holds promise for individualizing radiotherapy planning.

Mediastinal lymph nodes staging by 18F-FDG PET/CT for early stage non-small cell lung cancer: A multicenter study

2011-11-21

Abstract: Purpose: Accurate staging of mediastinal lymph nodes metastases is critical for determining the application of stereotactic body radiation therapy (SBRT) for patients with early stage non-small cell lung cancer (NSCLC). In this multicenter study the accuracy of 18F-FDG PET/CT to detect lymph node metastases was evaluated for early stage NSCLC.Materials and methods: The data from the patients with stage1 NSCLC who received preoperative 18F-FDG PET/CT staging and radical surgery was retrospectively reviewed of five centers from February 2004 to August 2010. The lymph node metastases were confirmed histopathologically after radical surgery. And the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for PET/CT staging.Results: Two hundred patients were enrolled. The sensitivity, specificity, accuracy, PPV and NPV for lymph node metastases on PET/CT were 44%, 83%, 78%, 29% and 91%, respectively. There were eight and 19 cases positive for lymph node metastases with central (n=62) and peripheral (n=138) NSCLC (P>0.05), respectively.Conclusion: 18F-FDG PET/CT was specific in N0 staging for T1–2 NSCLC. The NPV was about 91% in clinical N0 patients, suggested that 18F-FDG PET/CT may help to accurately stage N0 patients and thus identify patients for SBRT.

Serial assessment of FDG-PET FDG uptake and functional volume during radiotherapy (RT) in patients with non-small cell lung cancer (NSCLC)

2011-09-01

Abstract: Objectives: The objectives were (i) to confirm that diagnostic FDG-PET images could be obtained during thoracic radiotherapy, (ii) to verify that significant changes in FDG uptake or volume could be measured early enough to adapt the radiotherapy plan and (iii) to determine an optimal time window during the radiotherapy course to acquire a single FDG-PET examination that would be representative of tumour response.Methods: Ten non-small cell lung carcinoma (NSCLC) patients with significant PET/CT-FDG tumour radioactivity uptake (versus the background level), candidates for curative radiotherapy (RT, n=4; 60–70Gy, 2 Gray per fraction, 5 fractions per week) or RT plus chemotherapy (CT-RT, n=6), were prospectively evaluated. Using a Siemens Biograph, 5 or 6 PET/CT scans (PETn, n=0–5) were performed for each patient. Each acquisition included a 15-min thoracic PET with respiratory gating (RG) 60±5min post-injection of the FDG (3.5MBq/kg), followed by a standard, 5-min non-gated (STD) thoracic PET. PET0 was performed before the first RT fraction. During RT, PET1–5 were performed every 7 fractions, i.e., at 14Gy total dose increment. FDG uptake was measured as the variation of SUVmax,PETn versus SUVmax,PET0. Each lesions’ volume was measured by (i) visual delineation by an experienced nuclear physician, (ii) 40% SUVmax fixed threshold and (iii) a semi-automatic adaptive threshold method.Results: A total of 53 FDG-PET scans were acquired. Seventeen lesions (6 tumours and 11 nodes) were visible on PET0 in the 10 patients. The lesions were located either in or near the mediastinum or in the apex, without significant respiratory displacements at visual inspection of the gated images. Healthy lung did not cause motion artefacts in the PET images. As measured on 89 lesions, both the absolute and relative SUVmax values decreased as the RT dose increased. A 50% SUVmax decrease was obtained around a total dose of 45Gy. Out of the 89 lesions, 75 remained visually identifiable during the entire course of treatment. The 40% fixed threshold and adaptive threshold methods failed to delineate otherwise visible lesions in 16/33 (48%) and 3/33 (9%) lesions, respectively. The failure rate increased with increasing RT doses. Restricting the analysis to the manually-defined volumes in 89 visible lesions, the relative volumes decreased with increased dose.Conclusions: FDG-PET images can be analysed during thoracic RT, given either alone or with chemotherapy, without disturbing radiation-induced artefacts. An average 50% decrease in SUVmax was observed around 40–45Gy (i.e., during week 5 of RT). The three delineation methods yielded consistent volume measurements before RT and during the first week of RT, while manual delineation appeared to be more reliable later on during RT.

Is involved-field radiotherapy based on CT safe for patients with limited-stage small-cell lung cancer?

2011-11-07

Abstract: Purpose: To examine the pattern of failures in patients with limited-stage small-cell lung cancer (LS-SCLC) treated with involved-field radiotherapy (IFRT) and chemotherapy, with the aim of investigating the safety of IFRT.Methods and materials: Two consecutive clinical phase II trials in patients with LS-SCLC conducted in our center from 1997 to 2010 were reviewed retrospectively. Both trials had the same inclusion criteria. All patients (n=108) received combined chemotherapy and thoracic radiotherapy. Only the primary tumor and involved lymphatic regions based on computed tomography (CT) scan were irradiated. Isolated nodal failure (INF) was defined as a failure in an initially uninvolved lymph node region in the absence of local recurrence or distant metastasis.Results: With a median follow-up of 21months, 78 patients experienced treatment failures. Out of 28 patients with local–regional recurrences, 16 in-field, 10 out-of-field, and 2 both in-field and out-of-field recurrences were observed. INF occurred in 5 patients (4.6%), all in the ipsilateral supraclavicular area. Four patients developed simultaneously supraclavicular nodal failures and distant metastases. The median overall survival was 27months (95% confidence interval, 24–30months) and the median progression-free survival was 16months (95% confidence interval, 12–21months). For the 5 patients with INF, the median time to INF from the end of thoracic radiotherapy was 5months (range, 1–18months).Conclusions: IFRT based on CT scan in our patients resulted in a low rate of INF (4.6%), all in the ipsilateral supraclavicular area; but another four supraclavicular nodal failures with simultaneously distant metastases were also observed. The modern imaging with higher diagnostic capabilities of lymph node especially for supraclavicular area should be incorporated in the assessment of LS-SCLC when IFRT is being contemplated.

Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma

2012-01-30

Abstract: Purpose: To determine the patterns of loco-regional (LR) and distant failure in patients with limited-stage small cell lung carcinoma (LS-SCLC) treated with curative intent.Methods: From 1997 to 2008, 253 LS-SCLC patients were treated with curative intent chemo-radiation at our institution. A retrospective review identified sites of failure. The cumulative LR failure (LRF) rate was calculated. Distant failure-free survival (FFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Volumetric images of LR failures were delineated and registered with the original radiation treatment plans if available. Dosimetric parameters for the delineated failure volumes were calculated from the original treatment information.Results: The median follow-up was 19months. The site of first failure was LR in 34, distant in 80 and simultaneous LR and distant in 31 patients. The cumulative LRF rate was 29% and 38% at 2 and 5years. OS was 44% at 2years. Seventy patients had electronically archived treatment plans of which there were 16 LR failures (7 local and 39 regional failure volumes). Of the local and regional failure volumes 29% and 31% were in-field, respectively.Conclusions: The predominant pattern of LR failure was marginal or out-of-field. LR failures may be preventable with improved radiotherapy target definition.

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors

2011-11-21

Abstract: Purpose/objective(s): IMRT allows dose escalation for large lung tumors, but respiratory motion may compromise delivery. A treatment plan that modulates fluence predominantly in the transversal direction and leaves the fluence identical in the direction of the breathing motion may reduce this problem.Materials/methods: Planning-CT-datasets of 20 patients with Stage I–IV non small cell lung cancer (NSCLC) formed the basis of this study. A total of two IMRT plans and one 3D plan were created for each patient. Prescription dose was 60Gy to the CTV and 70Gy to the GTV. For the 3D plans an energy of 18MV photons was used. IMRT plans were calculated for 6MV photons with 13 coplanar and with 17 noncoplanar beams. Robustness of the used method of anisotropic modulation toward breathing motion was tested in a 13-field IMRT plan.Results: As a consequence of identical prescription doses, mean target doses were similar for 3D and IMRT. Differences between 3D and 13- and 17-field IMRT were significant for CTV Dmin (43Gy vs. 49.1Gy vs. 48.6Gy; p<0.001) and CTV D95 (53.2Gy vs. 55.0Gy vs. 55.4Gy; p=0.001). The Dmean of the contralateral lung was significantly lower in the 17-field plans (17-field IMRT vs. 13- vs. 3D: 12.5Gy vs. 14.8Gy vs. 15.8Gy: p<0.05). The spinal cord dose limit of 50Gy was always respected in IMRT plans and only in 17 of 20 3D-plans. Heart Dmax was only marginally reduced with IMRT (3D vs. 13- vs. 17-field IMRT: 38.2Gy vs. 36.8Gy vs. 37.8Gy). Simulated breathing motion caused only minor changes in the IMRT dose distribution (∼0.5–1Gy).Conclusions: Anisotropic modulation of IMRT improves dose delivery over 3D-RT and renders IMRT plans robust toward breathing induced organ motion, effectively preventing interplay effects.

Monitoring tumor motion by real time 2D/3D registration during radiotherapy

2011-09-01

Abstract: Background and purpose: In this paper, we investigate the possibility to use X-ray based real time 2D/3D registration for non-invasive tumor motion monitoring during radiotherapy.Materials and methods: The 2D/3D registration scheme is implemented using general purpose computation on graphics hardware (GPGPU) programming techniques and several algorithmic refinements in the registration process. Validation is conducted off-line using a phantom and five clinical patient data sets. The registration is performed on a region of interest (ROI) centered around the planned target volume (PTV).Results: The phantom motion is measured with an rms error of 2.56mm. For the patient data sets, a sinusoidal movement that clearly correlates to the breathing cycle is shown. Videos show a good match between X-ray and digitally reconstructed radiographs (DRR) displacement. Mean registration time is 0.5s.Conclusions: We have demonstrated that real-time organ motion monitoring using image based markerless registration is feasible.

A dual centre study of setup accuracy for thoracic patients based on Cone-Beam CT data

Tine B. Nielsen, Vibeke N. Hansen, Jonas Westberg, Olfred Hansen, Carsten Brink — 2011-12-23

Background and purpose: To compare setup uncertainties at two different institutions by using identical imaging and analysis techniques for thoracic patients with different fixation equipments.Methods and materials: Patient registration results from Cone-Beam CT (CBCT) scans of 174 patients were evaluated (1068 CBCT scans). Patients were fixated using a standard or custom made fixation at Royal Marsden Hospital and Odense University Hospital, respectively. Five imaging protocols were retrospectively simulated to compare the fixation equipments. Systematic and random setup uncertainties were calculated to estimate sufficient treatment margins.Results: The setup uncertainties are of similar sizes at the two institutions and there is no observable drift in the precision of the fixation equipments during the treatment course. When a correcting imaging protocol is performed there is a significant increase of the systematic setup uncertainties in between imaging fractions. A margin reduction of ⩾0.2cm can be achieved for patients with peak-to-peak respiration amplitudes of ⩾1.2cm when changing from 4D-CT to Active Breathing Coordinator™ (ABC).Conclusions: The setup uncertainties at the two institutions are the same despite different fixation equipments. Hence margins cannot be reduced by changing fixating equipment.

Feasibility of using anatomical surrogates for predicting the position of lung tumours

2011-12-23

Abstract: We studied the use of internal anatomical surrogates (carina and diaphragm) for the purpose of predicting the 3D position of lung tumours in 41 patients, in whom repeat 4DCT scans were available. Despite using two surrogates, significant prediction errors were observed, which varied depending on tumour position, baseline tumour motion and respiratory phase.

Clinical use of a novel in vivo 4D monitoring system for simultaneous patient motion and dose measurements

2011-10-03

Abstract: Purpose: A new 4D in vivo dosimetry tool, RADPOS, has been used on lung cancer patients to evaluate the feasibility of using the detectors to characterize variations in patient breathing patterns as well as to monitor daily variations in dose.Methods and materials: The RADPOS system combines a MOSFET dosimeter with an electromagnetic positioning sensor for simultaneous measurement of real-time dose and spatial coordinates. Three RADPOS sensors were placed on patients’ chest and abdomen during a 4DCT and daily treatments. A fourth detector was also placed on the couch as reference. Position data were collected in real-time and total dose was read at the end of each fraction.Results: Significant deviations in surface motion have been found between the day of 4DCT and treatment fractions in 9 of 10 patients. Variations in daily dose ranged from 2.5 to 13.7cGy (2.8–14.0%) and results agreed with treatment plan values for all but three points.Conclusions: Changes in breathing motion have been found that emphasize a need for continued position monitoring. RADPOS measurements can be used to monitor such variations as well as to measure surface dose without any disruption to the treatment schedule or discomfort to patients.

A new lung stent tested as fiducial marker in a porcine model

2011-12-23

Abstract: Introduction: The aim of the present study was to test the feasibility of a Nickel–Titanium (Ni–Ti) stent technique (Memocore™) in a porcine model. The stent is intended as a new fiducial for gated image guided radiotherapy in the lung. The study included test of an improved insertion system and respiratory gated treatments with this new technique.Methods and materials: Tests were carried out in a porcine model using Göttingen mini-pigs. The study included 10 animals. Planning CT was performed as 4 dimensional CT (4DCT) using the Varian RPM system. Respiratory gated radiotherapy treatments were simulated using the Brainlab ExacTrac system. Reproducibility of stent position during treatment was analyzed off-line using an experimental version of the ExacTrac software. The experimental version has a dedicated algorithm for segmentation of the stent in the planning CT and subsequent registration to X-ray position images.Results: A total of 23 stents were inserted in the 10 animals. Stents could be placed in all parts of the lungs. No stent migrated within the four weeks the experiment lasted. Stent trajectories in the lung were not reproducible, even though respiration was highly standardized using a respirator. The best accuracy of stent position in the gating window was obtained using gating at the half_max amplitude as reference level. The smallest stent movement within the gating window was observed in the exhale phase. Further success of human application will depend on the possibility to insert the stent within or close to lung tumors.Conclusions: This new technique based on the Memocore™ lung stent used in connection with respiratory gated radiotherapy was demonstrated to be feasible in a porcine model. The study demonstrated lack of reproducibility in lung trajectories of inserted stents. The technique gave the best accuracy when applied to the exhale phase of respiration.

External beam radiotherapy combined with intraluminal brachytherapy in esophageal carcinoma

2011-09-01

Abstract: Purpose: To assess the effectiveness of definitive radiation therapy in patients with potentially curable esophageal cancer and to evaluate the side-effects of this treatment.Methods and materials: Sixty-two patients with esophageal cancer, who were treated with definitive, curatively intended radiotherapy consisting of external radiotherapy (60Gy in 30 fractions), preceded and followed by LDR or HDR intraluminal brachy (12Gy in 2 fractions) were retrospectively analyzed.Results: Recurrences were reported in 38 patients (61%), of which 25 (64%) failed locally first.The overall survival rates at 1, 2 and 5years were 57%, 34% and 11%, respectively. The median overall survival was 15months. No prognostic factors could be identified. Most frequently reported treatment related toxicities were esophagitis, ulcerations, (11%) and strictures (16%). In 10 patients (16%) severe toxicities, were reported including grade III ulceration (2 cases), stricture (1 case), radiation pneumonitis (1 case), perforation (1 case), esophageal-pleural-tracheal fistula (1 case), and acute esophageal bleeding (4 cases). A history of gastrectomy was significantly associated with the development of severe toxicity.Conclusion: Curatively intended radiotherapy alone can be offered to esophageal cancer patients, even when surgery and/or chemotherapy are not feasible. However, we observed severe toxicity in a substantial part of the patients. Given the relatively high rate of severe complications and the uncertainties regarding dose escalation, the addition of brachytherapy, with consequently high surface doses, should be limited to well-selected patients.

Residual setup errors and dose variations with less-than-daily image guided patient setup in external beam radiotherapy for esophageal cancer

2011-08-29

Abstract: Background and purpose: To evaluate residual patient setup errors and daily dose variations of different less-than-daily image guidance (IG) strategies in the delivery of external beam radiotherapy for esophageal cancer.Material and methods: Daily image-guided setup data for 25 consecutive esophageal cancer patients treated with helical tomotherapy were evaluated. Seven less-than-daily IG strategies with different imaging frequencies were simulated. For each IG strategy, the daily residual setup errors were calculated. Using TomoTherapy Planned Adaptive software, daily dose variations to the clinical target volume, heart, and lungs were evaluated in five representative patients.Results: With 0% (60%) IG frequency, the margins required for adequate coverage of the clinical target volume were 13mm (10mm), 14mm (11mm), and 5mm (5mm) in the left–right, superior–inferior, and anterior–posterior directions, respectively. Even with 60% IG frequency, 10% of the fractions had more than 10% decrease in the dose level covering 95% of the target, and 14% and 13% of the fractions had more than 10% increase in total lung volume receiving at least 0.8Gy per fraction, and heart volume receiving at least 1.2Gy per fraction, respectively.Conclusion: Substantial residual setup errors would occur for treatment fractions without IG even if the most frequent less-than-daily IG strategy was to be used, which could lead to significant daily dose variations for the target volume and adjacent normal tissues. Daily image guidance is recommended throughout the course of treatment in conformal radiotherapy for esophageal cancer.

Dosimetric study of volumetric modulated arc therapy fields for total marrow irradiation

Chunhui Han, Timothy E. Schultheisss, Jeffrey Y.C. Wong — 2011-07-04

Abstract: Background and purpose: Normal organ toxicity is the leading factor that limits dose escalation in total body irradiation for bone marrow transplant (BMT) patients. In recent years, total marrow irradiation (TMI) using the helical tomotherapy (HT) system is being used as a more targeted form of TBI to treat BMT patients. In this study, we evaluated the feasibility of using volumetric modulated arc therapy (VMAT) to deliver TMI treatment.Materials and methods: CT data sets from two female and two male patients who had received prior total marrow and lymphatic irradiation with HT were selected for this study. The target volumes included skeletal bones from the skull to the mid-thigh level, major lymph nodes, and spleen. Twelve Gray in 8 fractions was prescribed to the target volumes. Each VMAT plan was generated with eight arc fields to cover the entire target volumes. Both the VMAT and the HT plans were normalized so that 85% of the skeletal bone volume was covered by the prescription dose. For each patient, more than 20 normal organs were included in plan optimization.Results: Both the VMAT and HT plans showed comparable dose coverage to the target volumes and significant sparing of normal organ dose. The median dose to the skeletal bone volume was 13.4 and 12.6Gy in the VMAT and HT plans, respectively. The VMAT plans showed >10% and >20% reduction of average median dose compared to the HT plans in 16 and 11 organs, respectively. The average beam-on time was 628±32s and 1122±106s in the VMAT and HT plans, respectively.Conclusions: The VMAT plans provided adequate target dose coverage and normal organ sparing compared to helical tomotherapy plans for efficient delivery of total marrow and lymphatic irradiation. This study demonstrates that the VMAT technique could be a feasible alternative to helical tomotherapy for TMI treatment.

Radioisotope-antibody conjugates selectively target bone marrow prior to stem cell therapy

Claudia Brogsitter, Jörg Kotzerke — 2011-10-10

In their recent paper, Corvo et al. propose a new concept for intensifying bone marrow dose prior to stem cell transplantation: helical tomotherapy in addition to total body irradiation (TBI) . In a previous study Einsele et al. applied the total marrow irradiation (9Gy) in patients with multiple myeloma . In their study toxicity was relatively high, but the recurrence rate was very low and the event free survival was long. Corvo et al. report no increase in acute side effects, but the incidence of long-term side effects could not be reliably assessed yet due to the relatively short follow-up. Conditioning prior to stem cell transplantation of leukaemia patients is a balancing act between dose escalation to achieve a better cure rate and dose de-escalation to get fewer side effects (so that this treatment could be used in children and elderly patients).

Cranio-spinal irradiation with volumetric modulated arc therapy: A multi-institutional treatment experience

2011-10-10

We credit Fogliata et al. for reporting the treatment of CSI with VMAT technique. It is worth commenting that VMAT delivers highly conformal radiation in less overall time. The issue of junction matching can be well taken care of at the time of planning. However the volume of lung receiving 5Gy (V5) has not been reported by the above authors. Knowledge of the same is necessary before accepting a newer modality of radiation delivery. V5 of lung is an important criterion which predicts grade 3 or more treatment related pulmonary toxicity.

Reply to the Letter to the editor on Cranio-spinal irradiation with volumetric modulated arc therapy by G. Saini et al.

2011-09-21

The authors thank Dr. Gagan Saini and coworkers for their astute comments on cranio-spinal irradiation (CSI) treatment using Volumetric Modulated Arc Therapy (VMAT). Indeed no data related to V5Gy for lungs were reported in our paper on CSI , this metric being a reported predictor for radiation induction pneumonitis.

Important ESTRO dates

2012-02-01

Radiotherapy & Oncology

Editorial Board

Contents

Radiotherapy in small cell lung cancer: Limited volumes in limited disease and adding thoracic radiotherapy in extended disease?

Treatment of brain metastases: Review of phase III randomized controlled trials

A pooled analysis of arc-based image-guided simultaneous integrated boost radiation therapy for oligometastatic brain metastases

Whole-brain irradiation with concomitant daily fixed-dose Temozolomide for brain metastases treatment: A randomised phase II trial

Reirradiation of brain metastases with radiosurgery

Clinical comparison of positional accuracy and stability between dedicated versus conventional masks for immobilization in cranial stereotactic radiotherapy using 6-degree-of-freedom image guidance system-integrated platform

Dosimetric consequences of rotational errors in radiation therapy of pediatric brain tumor patients

Oncologists’ view of informed consent and shared decision making in paediatric radiation oncology

A prospective study of supine versus prone positioning and whole-body thermoplastic mask fixation for craniospinal radiotherapy in adult patients

Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results

A practical technique to avoid the hippocampus in prophylactic cranial irradiation for lung cancer

Individualised isotoxic accelerated radiotherapy and chemotherapy are associated with improved long-term survival of patients with stage III NSCLC: A prospective population-based study

Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer

Combined PET/CT image characteristics for radiotherapy tumor response in lung cancer

Mediastinal lymph nodes staging by 18F-FDG PET/CT for early stage non-small cell lung cancer: A multicenter study

Serial assessment of FDG-PET FDG uptake and functional volume during radiotherapy (RT) in patients with non-small cell lung cancer (NSCLC)

Is involved-field radiotherapy based on CT safe for patients with limited-stage small-cell lung cancer?

Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors

Monitoring tumor motion by real time 2D/3D registration during radiotherapy

A dual centre study of setup accuracy for thoracic patients based on Cone-Beam CT data

Feasibility of using anatomical surrogates for predicting the position of lung tumours

Clinical use of a novel in vivo 4D monitoring system for simultaneous patient motion and dose measurements

A new lung stent tested as fiducial marker in a porcine model

External beam radiotherapy combined with intraluminal brachytherapy in esophageal carcinoma

Residual setup errors and dose variations with less-than-daily image guided patient setup in external beam radiotherapy for esophageal cancer

Dosimetric study of volumetric modulated arc therapy fields for total marrow irradiation

Radioisotope-antibody conjugates selectively target bone marrow prior to stem cell therapy

Cranio-spinal irradiation with volumetric modulated arc therapy: A multi-institutional treatment experience

Reply to the Letter to the editor on Cranio-spinal irradiation with volumetric modulated arc therapy by G. Saini et al.

Important ESTRO dates