Radiotherapy & Oncology - Articles in Press

Analysis of dose–volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer - Corrected Proof

2010-03-11

Abstract: Purpose: To evaluate dose–volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy.Patients and methods: Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2Gy per fraction to a total of 60Gy. For most of the patients, two weeks of interruption was scheduled after 30Gy. The percentage of lung volume receiving more than 5–50Gy in increments of 5Gy (V5–V50, respectively), and the mean lung dose (MLD) were analyzed.Results: Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3; 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5–V50 and MLD) were significantly associated with grade ⩾2 RP (p<0.01). The incidences of grade ⩾2 RP were 13%, 33%, and 78% in patients with V20s of ⩽24%, 25–36%, and ⩾37%, respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis.Conclusion: DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer.

Erythropoiesis stimulating agents, thrombosis and cancer - Corrected Proof

Lisa Barbera, Gillian Thomas — 2010-03-11

Abstract: Venous thromboembolism (VTE) is common in cancer and is associated with both morbidity and mortality. Erythropoiesis stimulating agents (ESAs) were originally developed to correct anemia. Recent trials in cancer patients however, raise concerns over both increased VTE rates and the possibility of worse tumour outcomes and increased mortality with ESA use.The most common reason offered for explaining the possible negative impact of ESAs on cancer outcomes has been the stimulation of erythropoietin receptors on tumour cells. Despite an extensive literature, it is unlikely that most practicing appreciate the intricate relationship and interaction between the coagulation pathways, angiogenesis and tumour progression and ESA effects.This paper will review these connections and interactions and examine the hypothesis that other mechanisms may underlie the possible negative impact of ESAs on cancer outcomes.

Distance learning in the Applied Sciences of Oncology - Corrected Proof

Michael B. Barton, Richard J. Thode — 2010-03-11

Abstract: Background: The major impediment to the expansion of oncology services is a shortage of personnel.Purpose: To develop a distance learning course for radiation oncology trainees.Materials: Under the sponsorship of the Asia Pacific Regional Cooperative Agreement administered by the International Atomic Energy Agency (IAEA), a CD ROM-based Applied Sciences of Oncology (ASOC) distance learning course of 71 modules was created. The course covers communications, critical appraisal, functional anatomy, molecular biology, pathology. The materials include interactive text and illustrations that require students to answer questions before they can progress.The course aims to supplement existing oncology curricula and does not provide a qualification. It aims to assist students in acquiring their own profession’s qualification. The course was piloted in seven countries in Asia, Africa and Latin America during 2004. After feedback from the pilot course, a further nine modules were added to cover imaging physics (three modules), informed consent, burnout and coping with death and dying, Economic analysis and cancer care, Nutrition, cachexia and fatigue, radiation-induced second cancers and mathematical tools and background for radiation oncology. The course was widely distributed and can be downloaded from http://www.iaea.org/Publications/Training/Aso/register.html. ASOC has been downloaded over 1100 times in the first year after it was posted. There is a huge demand for educational materials but the interactive approach is labour-intensive and expensive to compile. The course must be maintained to remain relevant.

IMRT can be faster to deliver than conformal radiotherapy - Corrected Proof

2010-03-11

To the Editor, Van der Werf et al. present some interesting and informative data concerning the treatment timing, and cost, of IMRT compared to those of conformal radiotherapy. Across the United Kingdom (UK), IMRT has been implemented relatively sparsely, partly because of concerns about the in-room treatment delivery time on the linac.

Radiotherapy on the neck nodes predicts severe weight loss in patients with early stage laryngeal cancer - Corrected Proof

2010-03-11

Abstract: Background and purpose: Although patients with early stage (T1/T2) laryngeal cancer (LC) are thought to have a low incidence of malnutrition, severe weight loss is observed in a subgroup of these patients during radiotherapy (RT). The objective of this study was to evaluate weight loss and nutrition-related symptoms in patients with T1/T2 LC during RT and to select predictive factors for early identification of malnourished patients.Methods: Of all patients with T1/T2 LC, who received primary RT between 1999 and 2007, the following characteristics were recorded: sex, age, TNM classification, tumour location, radiation schedule, performance status, quality of life, weight loss, and nutrition-related symptoms. The association between baseline characteristics and malnutrition (>5% weight loss during RT) was investigated by Cox regression analysis.Results: The study population consisted of 238 patients. During RT, 44% of patients developed malnutrition. Tumour location, TNM classification, RT on the neck nodes, RT dose, nausea/vomiting, pain, swallowing, senses problems, trouble with social eating, dry mouth and the use of painkillers were all significantly associated with malnutrition. In the multivariate analysis, RTs on both the neck nodes (HR 4.16, 95% CI 2.62–6.60) and dry mouth (HR 1.72, 95% CI 1.14–2.60) remained predictive. Nevertheless, RT on the neck nodes alone resulted in the best predictive model for malnutrition scores.Conclusions: Patients with early stage laryngeal cancer are at risk of malnutrition during radiotherapy. Radiotherapy on the neck nodes is the best predictor of malnutrition during radiotherapy. Therefore, we suggest to offer nutritional counselling to all the patients who receive nodal irradiation.

Loose seeds versus stranded seeds in I-125 prostate brachytherapy: Differences in clinical outcome - Corrected Proof

2010-03-10

Abstract: Purpose: To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy.Methods: From December 2000 until October 2006, we treated 896 T⩽2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n=538) or loose seed (n=358) I-125 implants. A total of 211 patients received a 6months course of anti-androgen therapy, before treatment, for prostate volume reduction to <50cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary.Results: The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82–90) and 90% (85–95), the total 5-year bNED rate was 87% (85–90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34–0.97) for loose seeds versus stranded seeds.Conclusions: These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants.

Comment on Moerland et al. study of decline of dose coverage between different implant techniques for I125 prostate brachytherapy - Corrected Proof

Bashar Al-Qaisieh — 2010-03-08

This paper describes a retrospective comparison of the dose coverage between loose and stranded seeds implants. The goal of the study is to investigate which implant technique gives the best agreement between planned and achieved prostate dosimetry. The main conclusions are that the dose coverage expressed as D90 in the post planning is lower than the intra-operative value, and more importantly that this decline is more obvious when using a stranded implant technique.

Phase II study of preoperative chemoradiotherapy (CRT) with irinotecan plus S-1 in locally advanced rectal cancer - Corrected Proof

2010-03-08

Abstract: Background and purpose: The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC.Materials and methods: Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40mg/m2 irinotecan were intravenously administered once per week during weeks 1–5 of radiotherapy. S-1 (70mg/m2) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8Gy for 5days for a total dose of 50.4 (45+5.4)Gy. Surgery was performed 4–6weeks following the completion of chemoradiation.Results: Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N− (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3–G4) was observed in five patients.Conclusions: This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer.

Dose homogeneity in accelerated partial breast irradiation - Corrected Proof

Birgitte Vrou Offersen — 2010-03-08

Dear Editor, Firstly, we would like to thank Dr. Nairz and Sedlmayer for their valuable comments.

Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines - Corrected Proof

2010-03-04

Abstract: Purpose: This study aims to determine magnitude, causes and consequences of post-operative breast tumour target volume delineation variation among radiation oncologists in the presence of guidelines.Materials and methods: Excision cavities, CTVs and PTVs of eight breast cancer patients were delineated on CT scans by 13 Dutch radiation oncologists (observers) from 12 Dutch institutes participating in the international Young Boost Trial. Delineated volumes and conformity indices were determined. CTV delineation variation (SD) was determined for anatomically relevant regions. Non-parametric statistics were performed to establish effects of observers, patient characteristics and regions on delineation variation.Results: Even in the presence of delineation guidelines considerable delineation variation is present (0.24

Carbon ion radiation therapy for high-risk meningiomas - Corrected Proof

2010-03-02

Abstract: Background: We analyzed outcome after a carbon ion boost in combination with precision photon radiation therapy in patients with meningiomas.Patients and methods: Ten patients with meningiomas were treated with carbon ion RT as part of a Phase I/II trial. Carbon ion RT was conducted in conjunction with fractionated stereotactic RT (FSRT) or intensity-modulated RT (IMRT). Eight patients were treated as primary RT, in 2 patients carbon ion RT was performed as re-irradiation. Carbon ion RT was applied with a median dose of 18GyE, and photon RT was applied with a median dose of 50.4Gy. Two patients with a history of former irradiation received 18GyE of carbon ion RT and a reduced dose of photon treatment.Results: The median follow-up time was 77months. Five patients died during follow-up, of which four died of tumor progression. In the group treated in the primary situation, actuarial survival rates after RT were 75% and 63% at 5 and 7years. After re-irradiation, both patients died at 10 and 67months, respectively. Actuarial local control rates after primary RT were 86% and 72% at 5 and 7years. Two patients developed tumor recurrence after re-irradiation, 6 and 67months after treatment.Conclusion: In conclusion, carbon ion radiation shows promising results in patients with atypical or anaplastic meningiomas. Further evaluation in a larger, prospective study in comparison to proton RT or modern photon RT is needed to corroborate these results.

Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma: A report of 1077 cases - Corrected Proof

2010-03-02

Abstract: Purpose: To study the pattern of lymph node metastases after esophagectomy and clarify the clinical target volume (CTV) delineation of thoracic esophageal squamous cell carcinoma (ESCC).Methods and materials: Total 1077 thoracic ESCC patients who had undergone esophagectomy and lymphadenectomy were retrospectively examined. The clinicopathologic factors related to lymph node metastasis were analyzed using logistic regression analysis.Results: The rates of lymph node metastases in patients with upper thoracic tumors were 16.7% (9/54) cervical, 38.9% (18/54) upper mediastinal, 11.1% (6/54) middle mediastinal, 5.6% (3/54) lower mediastinal, and 5.6% (3/54) abdominal, respectively. The rates of lymph node metastases in patients with middle thoracic tumors were 4.0% (27/680), 3.8% (26/680), 32.9% (224/680), 7.1% (48/680), and 17.1% (116/680), respectively. The rates of lymph node metastases in patients with lower thoracic tumors were 1.0% (5/343), 3.0% (10/343), 22.7% (78/343), 37.0% (127/343), and 33.2% (114/343), respectively. T stage, the length of tumor and the histological differentiation emerged as statistically significant risk factors of lymph node metastases of thoracic ESCC (P<0.001).Conclusions: T stage, the length of tumor and the histologic differentiation influence the pattern of lymph node metastases in thoracic ESCC. These factors should be considered comprehensively to design the CTV for radiotherapy (RT) of thoracic ESCC. Selective regional irradiation including the correlated lymphatic drainage regions should be performed as well.

Intra-fraction prostate displacement in radiotherapy estimated from pre- and post-treatment imaging of patients with implanted fiducial markers - Corrected Proof

2010-03-02

Abstract: Purpose: To determine intra-fraction displacement of the prostate gland from imaging pre- and post-radiotherapy delivery of prostate cancer patients with three implanted fiducial markers.Methods and materials: Data were collected from 184 patients who had two orthogonal X-rays pre- and post-delivery on at least 20 occasions using a Varian On Board kV Imaging system. A total of 5778 image pairs covering time intervals between 3 and 30min between pre- and post-imaging were evaluated for intra-fraction prostate displacement.Results: The mean three dimensional vector shift between images was 1.7mm ranging from 0 to 25mm. No preferential direction of displacement was found; however, there was an increase of prostate displacement with time between images. There was a large variation in typical shifts between patients (range 1±1 to 6±2mm) with no apparent trends throughout the treatment course. Images acquired in the first five fractions of treatment could be used to predict displacement patterns for individual patients.Conclusion: Intra-fraction motion of the prostate gland appears to be a limiting factor when considering margins for radiotherapy. Given the variation between patients, a uniform set of margins for all patients may not be satisfactory when high target doses are to be delivered.

Normal Tissue Complication Probability after hypofractionation increased due to the high dose per fraction or the high total Biological Equivalent Dose? - Corrected Proof

Gerben R. Borst, Jan-Jakob Sonke, Jose S. Belderbos, Joos V. Lebesque — 2010-03-02

Two recently published studies analysed the toxicity after hypofractionated radiotherapy (RT) . An important question is: could this toxicity be predicted from the delivered dose and historical toxicity models or was it unexpectedly high?

A comparison of two immobilization systems for stereotactic body radiation therapy of lung tumors - Corrected Proof

2010-03-02

Abstract: Purpose: This study aims to compare the efficacy, efficiency and comfort level of two immobilization systems commonly used in lung stereotactic body radiation therapy (SBRT): the Bodyfix and the abdominal compression plate (ACP).Materials and methods: Twenty-four patients undergoing SBRT for medically inoperable stage I lung cancer or pulmonary metastases were entered on this prospective randomized study. All underwent 4DCT simulation with free breathing, the Bodyfix, and the ACP to assess respiratory tumor motion. After CT simulation, patients were randomly assigned to immobilization with either the Bodyfix or the ACP for the actual SBRT treatment. Cone beam CTs (CBCTs) were acquired before and after each treatment to assess intrafraction tumor motion. Setup time and patient comfort were recorded.Results: There were 16 upper lobe, two middle lobe and seven lower-lobe lesions. Both the Bodyfix and the ACP significantly reduced the superior–inferior (SI) and overall respiratory tumor motion compared to free breathing (4.6 and 4.0 vs 5.3mm; 5.3 and 4.7 vs 6.1mm, respectively, p<0.05). The ACP further reduced the SI and overall respiratory tumor motion compared to the Bodyfix (p<0.05). The mean overall intrafraction tumor motion was 2.3mm with the Bodyfix and 2.0mm with the ACP (p>0.05). The ACP was faster to set up and rated more comfortable by patients than the Bodyfix (p<0.05).Conclusions: While there is no significant difference between the Bodyfix and ACP in reducing intrafraction tumor motion, the ACP is more comfortable, faster to set up, and superior to the Bodyfix in reducing SI and overall respiratory tumor motion.

Quality of life as predictor of survival: A prospective study on patients treated with combined surgery and radiotherapy for advanced oral and oropharyngeal cancer - Corrected Proof

2010-03-02

Abstract: Background and purpose: The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy.Materials and methods: Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale).Results: Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning.Conclusion: Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer.

Single Arc Volumetric Modulated Arc Therapy of head and neck cancer - Corrected Proof

Anders Bertelsen, Christian R. Hansen, Jørgen Johansen, Carsten Brink — 2010-02-26

Abstract: Background: The quality of Volumetric Modulated Arc Therapy (VMAT) plans is highly dependent on the performance of the optimization algorithm used. Recently new algorithms have become available which are capable of generating VMAT plans for Elekta accelerators. The VMAT algorithm in Pinnacle3® is named SmartArc and its capability to generate treatment plans for head and neck cancer was tested.Methods: Twenty-five patients with oropharyngeal or hypopharyngeal carcinoma, previously treated with IMRT by means of Pinnacle3® and Elekta accelerators, were replanned with single arc VMAT. The VMAT planning objectives were to achieve clinical target coverage and sparing of the organs at risk (OAR). Comparison with the original clinically used IMRT was made by evaluating (1) dose–volume histograms (DVHs) for PTVs, (2) DVHs for OARs, (3) delivery time and monitor units (MU), and (4) treatment accuracy.Results: Equivalent or superior target coverage and sparing of OARs were achieved with VMAT compared to IMRT. Volumes in the healthy tissues receiving between 17.3Gy and 49.4Gy were significantly reduced and the conformity (CI95%) of the elective PTV was improved from 1.7 with IMRT to 1.6 with VMAT. Compared to step-and-shoot IMRT, VMAT reduced the number of MUs by 8.5% to 460±63MUs per fraction, and delivered on an Elekta Synergy accelerator, the treatment time was on average reduced by 35% to 241±16s. In Delta4® measurements of the VMAT treatments, 99.6±0.5% of the detector points passed a 3mm and 3% gamma criterion, identical to the results of IMRT.Conclusions: The target coverages obtained in the IMRT and VMAT plans were found to be very similar. SmartArc generated single arc VMAT plans with equivalent or better target coverage and sparing of OARs compared to IMRT, while both delivery time and MUs were decreased. Very good dose accuracy results were obtained delivering the plans on an Elekta accelerator.

Proton vs carbon ion beams in the definitive radiation treatment of cancer patients - Corrected Proof

2010-02-25

Abstract: Background and purpose: Relative to X-ray beams, proton [1H] and carbon ion [12C] beams provide superior distributions due primarily to their finite range. The principal differences are LET, low for 1H and high for 12C, and a narrower penumbra of 12C beams. Were 12C to yield a higher TCP for a defined NTCP than 1H therapy, would LET, fractionation or penumbra width be the basis?Methods: Critical factors of physics, radiation biology of 1H and 12C ion beams, neutron therapy and selected reports of TCP and NTCP from 1H and 12C irradiation of nine tumor categories are reviewed.Results: Outcome results are based on low dose per fraction 1H and high dose per fraction 12C therapy. Assessment of the role of LET and dose distribution vs dose fractionation is not now feasible. Available data indicate that TCP increases with BED with 1H and 12C TCPs overlaps. Frequencies of GIII NTCPs were higher after 1H than 12C treatment.Conclusions: Assessment of the efficacy of 1H vs 12C therapy is not feasible, principally due to the dose fractionation differences. Further, there is no accepted policy for defining the CTV–GTV margin nor definition of TCP. Overlaps of 1H and 12C ion TCPs at defined BED ranges indicate that TCPs are determined in large measure by dose, BED. Late GIII NTCP was higher in 1H than 12C patients, indicating LET as a significant factor. We recommend trials of 1H vs 12C with one variable, i.e. LET. The resultant TCP vs NTCP relationship will indicate which beam yields higher TCP for a specified NTCP at a defined dose fractionation.

Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: Recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009) - Corrected Proof

2010-02-24

Abstract: Purpose: To give recommendations on patient selection criteria for the use of accelerated partial-breast irradiation (APBI) based on available clinical evidence complemented by expert opinion.Methods and materials: Overall, 340 articles were identified by a systematic search of the PubMed database using the keywords “partial-breast irradiation” and “APBI”. This search was complemented by searches of reference lists of articles and handsearching of relevant conference abstracts and book chapters. Of these, 3 randomized and 19 prospective non-randomized studies with a minimum median follow-up time of 4years were identified. The authors reviewed the published clinical evidence on APBI, complemented by relevant clinical and pathological studies of standard breast-conserving therapy and, through a series of personal communications, formulated the recommendations presented in this article.Results: The GEC-ESTRO Breast Cancer Working Group recommends three categories guiding patient selection for APBI: (1) a low-risk group for whom APBI outside the context of a clinical trial is an acceptable treatment option; including patients ageing at least 50years with unicentric, unifocal, pT1–2 (⩽30mm) pN0, non-lobular invasive breast cancer without the presence of an extensive intraductal component (EIC) and lympho-vascular invasion (LVI) and with negative surgical margins of at least 2mm, (2) a high-risk group, for whom APBI is considered contraindicated; including patients ageing ⩽40years; having positive margins, and/or multicentric or large (>30mm) tumours, and/or EIC positive or LVI positive tumours, and/or 4 or more positive lymph nodes or unknown axillary status (pNx), and (3) an intermediate-risk group, for whom APBI is considered acceptable only in the context of prospective clinical trials.Conclusions: These recommendations will provide a clinical guidance regarding the use of APBI outside the context of a clinical trial before large-scale randomized clinical trial outcome data become available. Furthermore they should promote further clinical research focusing on controversial issues in the treatment of early-stage breast carcinoma.

Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study - Corrected Proof

2010-02-24

Abstract: Background and purpose: To report the 12-year updated results of accelerated partial-breast irradiation (APBI) using multicatheter interstitial high-dose-rate (HDR) brachytherapy (BT).Patients and methods: Forty-five prospectively selected patients with T1N0-N1mi, nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI after breast-conserving surgery (BCS) using interstitial HDR BT. A total dose of 30.3Gy (n=8) and 36.4Gy (n=37) in seven fractions within 4days was delivered to the tumour bed plus a 1–2cm margin. The median follow-up time was 133months for surviving patients. Local and regional control, disease-free (DFS), cancer-specific (CSS), and overall survival (OS), as well as late side effects, and cosmetic results were assessed.Results: Four (8.9%) ipsilateral breast tumour recurrences were observed, for a 5-, 10-, and 12-year actuarial rate of 4.4%, 9.3%, and 9.3%, respectively. A total of two regional nodal failures were observed for a 12-year actuarial rate of 4.4%. The 12-year DFS, CSS, and OS was 75.3%, 91.1%, and 88.9%, respectively. Grade 3 fibrosis was observed in one patient (2.2%). No patient developed grade 3 teleangiectasia. Fat necrosis requiring surgical intervention occurred in one woman (2.2%). Cosmetic results were rated excellent or good in 35 patients (77.8%).Conclusions: Twelve-year results with APBI using HDR multicatheter interstitial implants continue to demonstrate excellent long-term local tumour control, survival, and cosmetic results with a low-rate of late side effects.

IMRT-based optimization approaches for volumetric modulated single arc radiotherapy planning - Corrected Proof

2010-02-22

Abstract: This paper reports on an evaluation of 5 RapidArc® optimization approaches vs IMRT. This study includes 11 patients with adenocarcinoma of the prostate. Rectal Normal Tissue Complication Probability is used as a constraint in a dose escalation. RapidArc® rectal NTCP’s are lower than those of IMRT (p=0.007). This allows a mean dose escalation of 2.1Gy([0.7Gy,3.5Gy]).

Simultaneous integrated boost in breast conserving treatment of breast cancer: A dosimetric comparison of helical tomotherapy and three-dimensional conformal radiotherapy - Corrected Proof

2010-02-22

Abstract: Background and purpose: To evaluate the dosimetry of helical tomotherapy (HT) and three-dimensional conformal radiotherapy (3D-CRT) in breast cancer patients undergoing whole breast radiation with simultaneous integrated boost (SIB) of the tumor bed.Material and methods: Thirteen patients with breast cancer treated by lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned using both HT and 3D-CRT using the field-in-field technique. The whole breast and tumor bed were prescribed 50.68Gy and 64.4Gy, respectively, in 28 fractions. Dosimetries for both techniques were compared.Results: Coverage of the whole breast was adequate with both techniques (V95%=96.22% vs. 96.25%, with HT and 3D-CRT, respectively; p=0.64). Adequate tumor bed coverage was also achieved, although it was significantly lower with HT (V95%=97.18% vs. 99.72%; p<0.001). Overdose of the breast volume outside the tumor bed was significantly lower with HT (V54.23Gy=12.47% vs. 30.83%; p<0.001). Ipsilateral lung V20Gy (6.34% vs. 10.17%; p<0.001), V5Gy (16.54% vs. 18.53%; p<0.05) and mean dose (4.05Gy vs. 6.36Gy; p<0.001) were significantly lower with HT. In patients with left-sided tumors, heart V30Gy (0.03% vs. 1.14%; p<0.05) and mean dose (1.35Gy vs. 2.22Gy; p<0.01) were significantly lower with HT, but not V5Gy. Contralateral breast V5Gy (0.27% vs. 0.00%; p<0.01) and maximum dose were significantly increased with HT.Conclusions: In breast cancer treated with SIB, both HT and 3D-CRT provided adequate target volume coverage and low heart doses. Tumor bed coverage was slightly lower with HT, but HT avoided unnecessary breast overdosage while improving ipsilateral lung dosimetry.

In response to the “Letter to the editor” by Al-Qaisieh et al.: Decline of dose coverage between intraoperative planning and post implant dosimetry for I-125 permanent prostate brachytherapy: Comparison between loose and stranded seed implants - Corrected Proof

2010-02-22

We have read with interest the comments of Al-Qaisieh et al. on our study concerning the decline of dose coverage between intraoperative planning and post implant dosimetry for I-125 permanent prostate brachytherapy .

Blood glucose level normalization and accurate timing improves the accuracy of PET-based treatment response predictions in rectal cancer - Corrected Proof

2010-02-22

Abstract: Purpose: To quantify the influence of fluctuating blood glucose level (BGLs) and the timing of PET acquisition on PET-based predictions of the pathological treatment response in rectal cancer.Material and methods: Thirty patients, diagnosed with locally advanced-rectal-cancer (LARC), were included in this prospective study. Sequential FDG–PET–CT investigations were performed at four time points during and after pre-operative radiochemotherapy (RCT). All PET-data were normalized for the BGL measured shortly before FDG injection. The metabolic treatment response of the tumor was correlated with the pathological treatment response.Results: During RCT, strong intra-patient BGL-fluctuations were observed, ranging from −38.7 to 95.6%. BGL-normalization of the SUVs revealed differences ranging from −54.7 to 34.7% (p<0.001). Also, a SUVmax time-dependency of 1.30±0.66 every 10min (range: 0.39–2.58) was found during the first 60min of acquisition. When correlating the percent reduction of SUVmax after 2weeks of RCT with the pathological treatment response, a significant increase (p=0.027) in the area under the curve of ROC-curve analysis was found when normalizing the PET-data for the measured BGLs, indicating an increase of the predictive strength.Conclusions: This study strongly underlines the necessity of BGL-normalization of PET-data and a precise time-management between FDG injection and the start of PET acquisition when using sequential FDG–PET–CT imaging for the prediction of pathological treatment response.

A “Red Shell” concept of increased radiation damage hazard to normal tissues just outside the PTV target volume - Corrected Proof

Jack Fowler, Jun Yang, John Lamond, Rachelle Lanciano, Jing Feng, Luther Brady — 2010-02-22

To the Editor New methods of radiation dose delivery – SBRT, Cyberknife, Protons, Tomotherapy, Rapid Arc – can deliver large doses per fraction, which includes a zone or shell of potentially damaged tissue just outside the PTV, before the dose has fallen to a low enough dose to be regarded as “safe” for normal tissues. Doses prescribed as 3×20Gy, 4×15Gy or 5×12Gy deliver EQDs at the PTV border of 275, 216 or 180Gy EQD, respectively which are 2–4 times greater doses than any known to be tolerable to normal tissues. [EQD means equivalent dose in 2Gy fractions, assuming alpha/beta=3Gy for late complications]. It may be many mm outside the PTV before these doses fall to the 70 or 80Gy EQD, or less, that are known to be tolerable, with volume limitation, from conventional radiotherapy experience.

Limited benefit of inversely optimised intensity modulation in breast conserving radiotherapy with simultaneously integrated boost - Corrected Proof

2010-02-22

Abstract: Background and purpose: To examine whether in breast-conserving radiotherapy (RT) with simultaneously integrated boost (SIB), application of inversely planned intensity-modulated radiotherapy (IMRT-SIB) instead of three-dimensional RT (3D-CRT-SIB) has benefits that justify the additional costs, and to evaluate whether a potential benefit of IMRT-SIB depends on specific patient characteristics.Material and methods: 3D-CRT-SIB and various IMRT-SIB treatment plans were constructed and optimised for 30 patients with early stage left-sided breast cancer. Coverage of planning target volumes (PTVs) and dose delivered to organs at risk (OARs) were determined for each plan. Overlap between heart and breast PTV (OHB), size of breast and boost PTVs and boost location were examined in their ability to identify patients that might benefit from IMRT-SIB.Results: All plans had adequate PTV coverage. IMRT-SIB generally reduced dose levels delivered to heart, lungs, and normal breast tissue relative to 3D-CRT-SIB. However, IMRT-SIB benefit differed per patient. For many patients, comparable results were obtained with 3D-CRT-SIB, while patients with OHB>1.4cm and a relatively large boost PTV volume (>125cm3) gained most from the use of IMRT-SIB.Conclusions: In breast-conserving RT, results obtained with 3D-CRT-SIB and IMRT-SIB are generally comparable. Patient characteristics could be used to identify patients that are most likely to benefit from IMRT-SIB.

Radiosurgery scope of practice in Canada: A report of the Canadian association of radiation oncology (CARO) radiosurgery advisory committee - Corrected Proof

2010-02-19

Abstract: Radiosurgery has a long history in Canada. Since the treatment of the first patient at the McGill University Health Center in 1985, radiosurgery programs have been developed from coast to coast. These have included multidisciplinary teams of radiation oncologists, neurosurgeons, medical physicists, radiation technologists and other health professionals.In 2008, the CARO Board of Directors requested that a working group be formed to define the role of the radiation oncologist in the practice of radiosurgery. Taking into account evolving technology, changing clinical practice and current scope of practice literature, the working group made recommendations as to the role of the radiation oncologists. These recommendations were endorsed by the Canadian Association of Radiation Oncology board of directors in September 2009 and are present herein. It is recognized that patients benefit from a team approach to their care but it is recommended that qualified radiation oncologists be involved in radiosurgery delivery from patient consultation to follow-up. In addition, radiation oncologists should continue to be involved in the administrative aspects of radiosurgery programs, from equipment selection to ongoing quality assurance/quality improvement.

Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-κB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation - Corrected Proof

2010-02-19

Abstract: Background and purpose: This study aimed to characterize a link between X-linked inhibitor of apoptosis protein (XIAP) expression, apoptosis induction, Nuclear Factor kappa B (NF-κB) activity and the anti-inflammatory properties of low-dose ionising-radiation (LD-RT).Material and methods: EA.hy.926 endothelial cells (ECs) were irradiated with doses ranging from 0.3 to 3Gy, and subsequently stimulated by TNF-α, and XIAP expression was either detected by immunoblotting or TaqMan-PCR. Apoptosis was quantified by AnnexinV staining or by caspase 3/7 activity assays. NF-κB transcriptional activity was analysed by a luciferase reporter assay, secretion of Transforming Growth Factor beta 1 (TGF-β1) and adhesion of peripheral blood mononuclear cells (PBMC) to EC were quantified using ELISA and adhesion assays.Results: LD-RT of the activated EA.Hy.926 EC induces XIAP expression in a discontinuous manner with a relative maximum at 0.5Gy and 3Gy which parallels a discontinuity in apoptosis induction and caspase 3/7 activity. siRNA-mediated attenuation of XIAP resulted in an increased rate of apoptosis, a hampered NF-κB transcriptional activity and a diminished secretion of TGF-β1. As compared to control-siRNA treated cells, adhesion of PBMC to EC was increased in XIAP depleted EA.Hy.926 EC.Conclusion: The modulation of apoptosis, NF-κB activity and TGF-β1 by XIAP in irradiated and subsequent stimulated EC contributes to an impaired PBMC/EC adhesion and to the anti-inflammatory properties of LD-RT.

Association of single nucleotide polymorphisms in ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with clinical and cellular radiosensitivity - Corrected Proof

2010-02-19

Abstract: Purpose: To examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position -509), XPD (codon 751), and XRCC1 (codon 399) with fibrosis and also individual radiosensitivity.Methods and materials: Retrospective analysis with 69 breast cancer patients treated with breast-conserving radiotherapy; total dose delivered was restricted to vary between 54 and 55Gy. Fibrosis was evaluated according to LENT/SOMA score. DNA was extracted from blood samples; cellular radiosensitivity was measured using the G0 assay and polymorphisms by PCR–RFLP and MALDI-TOF, respectively.Results: Twenty-five percent of all patients developed fibrosis of grade 2 or 3. This proportion tends to be higher in patients being polymorphic in TGFB1 or XRCC1 when compared to patients with wildtype genotype, whereas for ATM, GSTP1, SOD2 and XPD the polymorphic genotype appears to be associated with a lower risk of fibrosis. However, none of these associations are significant. In contrast, when a risk score is calculated based on all risk alleles, there was significant association with an increased risk of fibrosis (per risk allele odds ratio (ORs)=2.09, 95% confidence interval (CI): 1.32–3.55, p=0.0005). All six polymorphisms were found to have no significant effect on cellular radiosensitivity.Conclusions: It is most likely that risk for radiation-induced fibrosis can be assessed by a combination of risk alleles. This finding needs to be replicated in further studies.

Retrospective analysis of definitive radiotherapy for patients with superficial esophageal carcinoma: Consideration of the optimal treatment method with a focus on late morbidity - Corrected Proof

2010-02-15

Abstract: Purpose: To evaluate the clinical efficacy of definitive radiotherapy for patients with superficial esophageal cancer.Material and methods: From 1990 through 2006, 97 patients with stage I disease were treated with radiotherapy with or without chemotherapy. All patients were diagnosed with panesophagoscopy and computed tomography. Chemotherapy was added in 61 patients, and intra-cavitary brachytherapy (ICBT) was used in 27 patients.Results: The patients were 90 men and seven women with a median age of 65.7years (range; 41–89). At last follow-up with a median follow-up duration of 35.7months, 3year-overall and progression-free survival (PFS) rates were 81.5% (95% C.I.=73.3–89.7%) and 55.8% (95% C.I.=45.2–66.4%), respectively. Shorter tumor length was a significantly favorable factor for the PFS rate (P=0.02) and local failure-free (LFF) rate (P=0.007) on both univariate and multivariate analyses. Although the addition of ICBT had no apparent benefit for survival or tumor control, the rate of severe adverse effects including lethal esophageal ulcers, showed a higher tendency in patients receiving ICBT.Conclusions: Our results regarding efficacy from the viewpoint of organ preservation are promising. Special care would be taken for the use of ICBT for patients with superficial esophageal cancer, especially if they have received chemoradiotherapy.

Prognostic significance of CD24 protein expression in patients treated with adjuvant radiotherapy after radical hysterectomy for cervical squamous cell carcinoma - Corrected Proof

2010-02-15

Abstract: Background and purpose: The CD24 marker is expressed in various carcinomas and is associated with shorter survival rates. We evaluated the prognostic significance of CD24 protein overexpression in patients treated with post-operative radiotherapy (RT) after surgery, and its prognostic significance and specific role stratified by adjuvant treatment modalities.Materials and methods: We determined the CD24 expression status of 140 patients with cervical squamous cell carcinoma treated with RT alone or with chemoradiotherapy (CRT) after radical hysterectomy procedures.Results: CD24 expression was detected in 59 patients (42%) and was significantly associated with locoregional failure-free survival (LRFFS) (p=0.0218), distant metastasis-free survival (DMFS) (p=0.0001), and overall survival (OS) (p=0.0053). In the multivariate analysis, CD24 positivity was also significantly associated with DMFS (p=0.025) and OS (p=0.045). CD24 expression stratified by post-operative treatments (CRT or RT alone) was associated with DMFS (p=0.0001) but not with LRFFS (p=0.4423) in the CRT group. However, CD24 expression was associated with LRFFS (p=0.0198) but not with DMFS (p=0.5269) in the RT alone group.Conclusions: CD24 expression is an independent prognostic marker in patients with cervical squamous cell carcinoma, even adjuvant treatment after surgery. And this study reveals different prognostic role of CD24 expression in two subgroups treated differently after surgery. Therefore, new therapeutic strategies targeting CD24 expression stratified by subgroups might have important clinical implications.

Radiotherapy in early stage Hodgkin’s lymphoma: The importance of volume and treatment position - Corrected Proof

Bart Reymen, Sylvie Spiessens, Yolande Lievens — 2010-02-15

Abstract: This planning study in Hodgkin’s disease confirmed smaller irradiated volumes and subsequently lower doses to lungs, heart and breasts for involved node radiotherapy compared to involved field irradiation. However, shifting the arms from alongside the body to above the head offsets the observed benefit on dose to heart and breasts.

Clinical performance of a transmission detector array for the permanent supervision of IMRT deliveries - Corrected Proof

2010-02-08

Abstract: Background and purpose: Clinical evaluation of a novel dosimetric accessory serving the permanent supervision of MLC function.Materials and methods: The DAVID system (PTW-Freiburg, Germany) is a transparent, multi-wire transmission ionization chamber, placed in the accessory holder of the treatment head. Since each of the 37 individual wires is positioned exactly below the associated leaf pair of the MLC, its signal records the opening of this leaf pair during patient treatment.Results: The DAVID system closes a gap in the quality assurance program, permitting the permanent in-vivo verification of IMRT plans. During dosimetric plan verification with the 2D-ARRAY (PTW-Freiburg, Germany), reference values of the 37 DAVID signals are collected, with which the DAVID readings recorded during daily patient treatment are compared. This comparison is visually displayed in the control room, and warning and alarm levels of any discrepancies can be defined. The properties of the DAVID system as a transmission device, its sensitivity to beam delivery and leaflet errors as well as its stability have been analyzed for clinically relevant examples. In a recent version, the DAVID system has been equipped with 80 wires.Conclusions: The DAVID system permits the on-line detection of clinically relevant MLC discrepancies in IMRT deliveries.

Stereotactic radiation therapy for large vestibular schwannomas - Corrected Proof

2010-02-08

Abstract: Background and purpose: To evaluate the morbidity and tumor-control rate in the treatment of large vestibular schwannomas (VS) after stereotactic radiation therapy in our institution.Material and methods: Twenty-five consecutive patients (17 men, 8 women) with large VS (diameter 3.0cm or larger), treated with stereotactic radiotherapy (SRT) or stereotactic radiosurgery (SRS) between 1992 and 2007, were retrospectively studied after a mean follow-up period of three years with respect to tumor-control rate and complications.Results: Actuarial 5-year maintenance of pre-treatment hearing level probability of 30% was achieved. Five of 17 patients suffered permanent new facial nerve dysfunction. The actuarial 5-year facial nerve preservation probability was 80%. Permanent new trigeminal nerve neuropathy occurred in two of 15 patients, resulting in an actuarial 5-year trigeminal nerve preservation probability of 85%. Tumor progression occurred in four of 25 (16%) patients. The overall 5-year tumor control probability was 82%.Conclusion: Increased morbidity rates were found in patients with large VS treated with SRT or SRS compared to the published series on regular sized VS and other smaller retrospective studies on large VS.

Interstitial fluid pressure of tumors as a function of parameters derived by dynamic contrast-enhanced magnetic resonance imaging: Response to letter by Farace and Boschi - Corrected Proof

Kristine Gulliksrud, Tormod A.M. Egeland, Jon-Vidar Gaustad, Einar K. Rofstad — 2010-02-01

We read with interest the letter by Farace and Boschi sharing their thoughts on strategies for assessing the interstitial fluid pressure (IFP) of tumors by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Interstitial fluid pressure as a function of DCE-MRI derived parameters - Corrected Proof

Paolo Farace, Federico Boschi — 2010-02-01

To the Editor, We read with interest the study of Gulliksrud et al. on interstitial fluid pressure (IFP) – a parameter associated with radiocurability . They investigated high-resolution dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), by Gd-DTPA bolus injection, to provide interstitial fluid pressure (IFP) mapping, alternatively to the slow infusion method proposed by other Authors. They concluded that the bolus injection method is feasible for assessing IFP in tumours without necrosis, but to be clinically useful, a relationship between IFP and the pharmacokinetic parameters should be provided. The slow infusion method, proposed by Hassid et al. , proved that the interstitial (i.e. in the extracellular extravascular space – EES) concentration of Gd-DTPA at steady state of infusion () reflected the spatial distribution of IFP, assuming a negative linear relation between and IFP.

Inter-observer and intra-observer reliability for lung cancer target volume delineation in the 4D-CT era - Corrected Proof

2010-02-01

Abstract: Background and purpose: To investigate inter-observer and intra-observer target volume delineation (TVD) error in 4D-CT imaging of thoracic tumours.Materials and methods: Primary and nodal gross tumour volumes (GTV) of 10 lung tumours on the 10 respiratory phases of a 4D-CT scan were contoured by six radiation oncologist observers. Inter-observer and intra-observer variability were assessed by the coefficient of variation (COV) and the volume overlap index (VOI). ANOVA was performed to assess differences in inter-observer and intra-observer variability based on patient case difficulty, respiratory phase, physician seniority, and physician observer.Results: VOI analysis determined that inter-observer was a more significant source of error than intra-observer variability. VOI improved with the use of 4D-CT as compared to conventional CT. ANOVA analysis for COVs found case difficulty (easy versus difficult) to be significant for inter-observer primary tumour and intra-observer nodal disease delineation. Physician seniority, respiratory phase, and individual physician were not found to be significant for TVD error.Conclusion: Variability in TVD is a major source of error in 4D-CT treatment planning. Development of measures to reduce inter-observer and intra-observer TVD variability are necessary in order to deliver high quality radiotherapy.

A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery system for intracranial lesions - Corrected Proof

2010-02-01

Abstract: Background and purpose: A comparison of patient positioning and intra-fraction motion using invasive frame-based radiosurgery with a frameless X-ray image-guided system utilizing a thermoplastic mask for immobilization.Materials and methods: Overall system accuracy was determined using 57 hidden-target tests. Positioning agreement between invasive frame-based setup and image-guided (IG) setup, and intra-fraction displacement, was evaluated for 102 frame-based SRS treatments. Pre and post-treatment imaging was also acquired for 7 patients (110 treatments) immobilized with an aquaplast mask receiving fractionated IG treatment.Results: The hidden-target tests demonstrated a mean error magnitude of 0.7mm (SD=0.3mm). For SRS treatments, mean deviation between frame-based and image-guided initial positioning was 1.0mm (SD=0.5mm). Fusion failures were observed among 3 patients resulting in aberrant predicted shifts. The image-guidance system detected frame slippage in one case. The mean intra-fraction shift magnitude observed for the BRW frame was 0.4mm (SD=0.3mm) compared to 0.7mm (SD=0.5mm) for the fractionated patients with the mask system.Conclusions: The overall system accuracy is similar to that reported for invasive frame-based SRS. The intra-fraction motion was larger with mask-immobilization, but remains within a range appropriate for stereotactic treatment. These results support clinical implementation of frameless radiosurgery using the Novalis Body Exac-Trac system.

Is the Roach formula predictive for biochemical outcome in prostate cancer patients with minimal residual disease undergoing local radiotherapy after radical prostatectomy? - Corrected Proof

Gregor Goldner, Johannes Dimopoulos, Richard Pötter — 2010-02-01

Abstract: Purpose: To find out if the risk of biochemical failure can be predicted applying the risk assessment for lymph-node metastases as suggested by the Roach formula for patients with minimal residual disease after radical prostatectomy undergoing adjuvant radiotherapy.Materials and methods: Patients after radical prostatectomy presenting with pT3-tumours or positive surgical margins, negative nodes and with a post-operative and pre-radiotherapy PSA level ⩽0.1ng/ml and without hormonal therapy were selected. Patients had received local 3D-conformal radiotherapy in the prostatic region with 66–72Gy. According to the risk stratification of the Roach formula patients were divided into two groups: Group 1 with probability of positive lymph-nodes <15% and Group 2 with ⩾15%. Biochemical recurrence was defined by reaching a PSA level ⩾0.2ng/ml.Results: A total of 55/288 patients could be identified, 26 patients in Group 1 and 29 patients in Group 2. Mean follow-up was 45months. Biochemical recurrence free survival after 5years was 78% for all patients and showed a significant difference between Group 1 (100%) and Group 2 with (58%; p=0.004).Conclusion: The risk for biochemical failure after adjuvant radiotherapy in post-operative patients presenting with minimal residual disease is significantly influenced by the Roach formula. These findings are considered to provide a rationale for the decision on the volume of post-operative radiotherapy.

Current technological clinical practise in breast radiotherapy; results of a survey in EORTC-Radiation Oncology Group affiliated institutions - Corrected Proof

2010-02-01

Abstract: Purpose: To evaluate the current technological clinical practise of radiation therapy of the breast in institutions participating in the EORTC-Radiation Oncology Group (EORTC-ROG).Materials and methods: A survey was conducted between August 2008 and January 2009 on behalf of the Breast Working Party within the EORTC-ROG. The questionnaire comprised 32 questions on 4 main topics: fractionation schedules, treatment planning methods, volume definitions and position verification procedures.Results: Sixty-eight institutions out of 16 countries responded (a response rate of 47%). The standard fraction dose was generally 2Gy for both breast and boost treatment, although a 2.67Gy boost fraction dose is routinely given in British institutions. The main boost modality was electrons in 55%, photons in 47% and brachytherapy in 3% of the institutions (equal use of photon and electron irradiation in 5% of the institutions). All institutions used CT-based treatment planning. Wide variations are seen in the definition of the breast and boost target volumes, with margins around the resection cavity, ranging from 0 to 30mm. Inverse planned IMRT is available in 27% and breath-hold techniques in 19% of the institutions. The number of patients treated with IMRT and breath-hold varied per institution. Electronic portal imaging for patient set-up is used by 92% of the institutions.Conclusions: This survey provides insight in the current practise of radiation technology used in the treatment of breast cancer among institutions participating in EORTC-ROG clinical trials.

A reply to evidence-based radiation oncology: oesophagus - Corrected Proof

Richard S. Gillies, Mark R. Middleton, Claire Blesing — 2010-02-01

We read with interest this comprehensive review of the different therapeutic approaches to oesophageal cancer . We must, however, point out an important error in the section “neoadjuvant chemotherapy followed by surgery vs. surgery alone” (page 281), relating to the most recent meta-analysis in this area . We agree that this showed a significant benefit for neoadjuvant chemotherapy for oesophageal adenocarcinoma (hazard ratio for death 0.78; 95% CI, 0.64–0.95; p=0.014), based entirely on the data from the MRC OE02 trial – the only trial to have reported results by histology . The reviewers are incorrect, however, in stating “this benefit is lost in a pooled analysis for mixed tumour types (HR 1.07; 95% CI, 0.87–1.32; p=0.14).” In fact, the pooled analysis for both adenocarcinoma and squamous cell carcinoma showed a significant benefit for neoadjuvant chemotherapy (HR 0.90; 95% CI, 0.81–1.00; p=0.05), equivalent to a 2-year absolute survival benefit of 7%. The data quoted incorrectly relates to the only other trial to have included both tumour types but which, unfortunately, did not report results by histology ; as a result, in figure 3 of the meta-analysis (from which the incorrectly quoted data was extracted) it was described separately and labelled as “mixed tumours.”

6D image guidance for spinal non-invasive stereotactic body radiation therapy: Comparison between ExacTrac X-ray 6D with kilo-voltage cone-beam CT - Corrected Proof

2010-02-01

Abstract: Purpose: To investigate setup discrepancies measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for patients under treatments of stereotactic body radiation therapy (SBRT).Materials and methods: In this work, phantom and patient studies were performed. In the phantom studies, an anthropomorphic phantom was placed with pre-defined positions, and imaged with ExacTrac X-ray 6D and CBCT to test the accuracy of the imaging systems. In the patient studies, 16 spinal SBRT patient cases were retrospectively analyzed. The patients were initially positioned in customized immobilization cradles and then aligned with ExacTrac X-ray 6D and CBCT. The setup discrepancies were computed and quantitatively analyzed.Results: This study indicates modest discrepancies between ExacTrac X-ray 6D and CBCT with spinal SBRT. The phantom experiments showed that translational and rotational discrepancies in root-mean-square (RMS) between ExacTrac X-ray 6D and CBCT were, respectively, <1.0mm and <1°. In the retrospective patient studies, translational and rotational discrepancies in RMS between ExacTrac X-ray 6D and CBCT were <2.0mm and <1.5°.Conclusions: ExacTrac X-ray 6D represents a potential alternative to CBCT; however, pre-caution should be taken when only ExacTrac X-ray 6D is used to guide SBRT with small setup margins.

Comparison of electron IMRT to helical photon IMRT and conventional photon irradiation for treatment of breast and chest wall tumours - Corrected Proof

Tobias Gauer, Konrad Engel, Antje Kiesel, Dirk Albers, Dirk Rades — 2010-02-01

Abstract: Background and purpose: Conventional irradiation of breast and chest wall tumours may cause high doses in underlying organs. Intensity-modulated radiation therapy (IMRT) with photons achieves high conformity between treated and tumour volume but is associated with considerable low-dose effects which may induce secondary malignancies. We compare treatment plans of electron IMRT to helical photon IMRT and conventional irradiation.Material and methods: Treatment planning for three patients (breast, chest wall plus lymph nodes, sarcoma of medial chest wall/sternum) was performed using XiO 4.3.3 (CMS) for conventional photon irradiation, Hi-Art 2.2.2.05 (TomoTherapy) for helical photon IMRT, and a self-designed programme for electron IMRT.Results: The techniques resulted in similar mean and maximum target doses. Target coverage by the 95%-isodose was best with tomotherapy. Mean ipsilateral lung doses were similar with all techniques. Electron IMRT achieved best sparing of heart, and contralateral breast. Compared with photon IMRT, electron IMRT allowed better sparing of contralateral lung and total healthy tissue.Conclusions: Electron IMRT is superior to conventional irradiation, as it allows satisfying target coverage and avoids high doses in underlying organs. Its advantage over photon IMRT is better sparing of most organs at risk (low-dose effects) which reduces the risk of radiation-induced malignancies.

Information needs of early-stage prostate cancer patients: A comparison of nine countries - Corrected Proof

2010-02-01

Abstract: Background and purpose: Providing information to patients can improve their medical and psychological outcomes. We sought to identify core information needs common to most early-stage prostate cancer patients in participating countries.Material and methods: Convenience samples of patients treated 3–24months earlier were surveyed in Canada, England, Italy, Germany, Poland, Portugal, Netherlands, Spain, and Turkey. Each participant rated the importance of addressing each of 92 questions in the diagnosis-to-treatment decision interval (essential/desired/no opinion/avoid). Multivariate modelling determined the extent of variance accounted by covariates, and produced an unbiased prediction of the proportion of essential responses for each question.Results: Six hundred and fifty-nine patients responded (response rates 45–77%). On average, 35–53 questions were essential within each country; similar questions were essential to most patients in most countries. Beyond cross-country similarities, each country showed wide variability in the number and which questions were essential. Multivariate modelling showed an adjusted R-squared with predictors country, age, education, and treatment group of only 6% of the variance. A core of 20 questions were predicted to be essential to >2/3 of patients.Conclusions: Core information can be identified across countries. However, providing the core should only be a first step; each country should then provide information tailored to the needs of the individual patient.

Volumetric modulated arc therapy for delivery of hypofractionated stereotactic lung radiotherapy: A dosimetric and treatment efficiency analysis - Corrected Proof

2010-02-01

Abstract: Purpose/objective(s): Volumetric modulated arc therapy (VMAT) allows for intensity-modulated radiation delivery during gantry rotation with dynamic MLC motion, variable dose rates and gantry speed modulation. We compared VMAT plans with 3D-CRT for hypofractionated lung radiotherapy.Materials/methods: Twenty-one 3D-CRT plans for Stage IA lung cancer previously treated stereotactically were selected. VMAT plans were generated by optimizing machine aperture shape and radiation intensity at 10° intervals. A partial arc range of 180° was manually selected to coincide with tumor location. The arc was resampled down to 5° intervals to ensure dose calculation accuracy. Identical planning objectives were used for VMAT/3D-CRT. Parameters assessed included dose to PTV and organs-at-risk (OAR), monitor units, and multiple conformity and homogeneity indices. Plans were delivered to a phantom for time comparison.Results: Lung V20/12.5/10/5 were less with VMAT (relative reduction 4.5%, p=.02; 3.2%, p=.01; 2.6%, p=.01; 4.2%, p=.03, respectively). Mean/maximum-doses to PTV, dose to additional OARs, 95% isodose line conformity, and target volume homogeneity were equivalent. VMAT improved conformity at both the 80% (1.87 vs. 1.93, p=.08) and 50% isodose lines (5.19 vs. 5.65, p=.01). Treatment times were reduced significantly with VMAT (mean 6.1 vs. 11.9min, p<.01).Conclusions: Single arc VMAT planning achieves highly conformal dose distributions while controlling dose to critical structures, including significant reduction in lung dose volume parameters. Employing a VMAT technique decreases treatment times by 37–63%, reducing the chance of error introduced by intrafraction variation. The quality and efficiency of VMAT is ideally suited for stereotactic lung radiotherapy delivery.

Applying failure mode effects and criticality analysis in radiotherapy: Lessons learned and perspectives of enhancement - Corrected Proof

2010-02-01

Abstract: Introduction: The radiation oncology process along with its unique therapeutic properties is also potentially dangerous for the patient, and thus it should be delivered under a systematic risk control. To this aim incident reporting and analysis are not sufficient for assuring patient safety and proactive risk assessment should also be implemented. The paper accounts for some methodological solutions, lessons learned and opportunities for improvement, starting from the systematic application of the failure mode effects and criticality analysis (FMECA) technique to the radiotherapy process of an Italian hospital.Materials and methods: The analysis, performed by a working group made of experts of the radiotherapy unit, was organised into the following steps: (1) complete and detailed analysis of the process (integration definition for function modelling); (2) identification of possible failure modes (FM) of the process, representing sources of adverse events for the patient; (3) qualitative risk assessment of FMs, aimed at identifying priorities of intervention; (4) identification and planning of corrective actions.Results: Organisational and procedural corrective measures were implemented; a set of safety indexes for the process was integrated within the traditional quality assurance indicators measured by the unit. A strong commitment of all the professionals involved was observed and the study revealed to be a powerful “tool” for dissemination of patient safety culture.Conclusion: The feasibility of FMECA in fostering radiotherapy safety was proven; nevertheless, some lessons learned as well as weaknesses of current practices in risk management open to future research for the integration of retrospective methods (e.g. incident reporting or root cause analysis) and risk assessment.

How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons - Corrected Proof

2010-01-27

Abstract: Purpose: Particle therapy has potentially a better therapeutic ratio than photon therapy. However, investment costs are much higher. This study provides an estimation and comparison of the costs of these therapies.Methods: Within an extensive analytical framework capital and operational costs, cost per fraction, and four tumor specific treatment costs are calculated for three facilities: combined carbon-ion/proton, proton-only, and photon.Results: Capital costs for the combined, proton-only and photon facilities are: € 138.6 million, € 94.9 million, € 23.4 million. Total costs per year are: € 36.7 million, € 24.9 million, € 9.6 million. Cost per fraction is: € 1128 (€ 877–1974), € 743 (€ 578–1300), € 233 (€ 190–407). Cost ratio particle/photon therapy is 4.8 for the combined and 3.2 for the proton-only facility. Particle treatment costs vary from € 10,030 (c-ion: lung cancer) to € 39,610 (proton: head & neck tumors). Cost difference between particle and photon therapies is relatively small for lung and prostate cancer, larger for skull-base chordoma and head & neck tumors.Conclusion: Investment costs are highest for the combined carbon-ion/proton facility and lowest for the photon facility. Cost differences become smaller when total costs per year and specific treatment costs are compared. Lower fractionation schedule of particle therapy might further reduce its costs.

Postmastectomy intensity modulated radiation therapy following immediate expander-implant reconstruction - Corrected Proof

2010-01-25

Abstract: Background/purpose: To evaluate radiation plans of patients undergoing mastectomy with immediate expander-implant reconstruction followed by postmastectomy radiation therapy (PMRT).Materials/methods: We identified 41 patients from June 2004 to May 2007 who underwent mastectomy, immediate expander-implant reconstruction, and PMRT with intensity-modulated radiation therapy. We assessed chest wall (CW) coverage and volume of heart and lung irradiated.Results: In 73% of patients, all CW borders were adequately covered, and in 22%, all but 1 border were adequately covered. The total lung V20 was<20% in 39/41 patients. The mean lung V20 was 13% (range, 3–23%), and the mean heart Dmean was 2.81Gy (range, 0.53–9.60Gy). In patients with left-sided lesions without internal mammary nodes (IMNs) treatment (n=22), the mean lung V20 was 12.6% and the mean heart Dmean was 3.90Gy, and in the patient with IMN treatment, the lung V20 was 18% and heart Dmean was 8.04Gy. For right-sided lesions without IMN treatment (n=12), the mean lung V20 was 12.4% and the mean heart Dmean was 0.90Gy, and in patients with IMN treatment (n=6), these numbers were 17.8% and 1.76Gy. At a median follow-up of 29months, the 30-month actuarial local control was 97%.Conclusions: In women undergoing immediate expander-implant reconstruction, PMRT can achieve excellent local control with acceptable heart and lung doses. These results can be achieved even when the IMN are being treated, although doses to the heart and lungs will be higher.

No association between SNPs regulating TGF-β1 secretion and late radiotherapy toxicity to the breast: Results from the RAPPER study - Corrected Proof

2010-01-25

Abstract: Background and purpose: Several small studies have reported associations between TGFB1 single nucleotide polymorphisms (SNPs), considered to increase secretion of TGF-β1, and greater than 3-fold increases in incidence of fibrosis – an indicator of late toxicity after radiotherapy in breast cancer patients.Materials and methods: Two SNPs in TGFB1, C-509T (rs1800469) and L10P (rs1800470), were genotyped in 778 breast cancer patients who had received radiotherapy to the breast. Late radiotherapy toxicity was assessed two years after radiotherapy using a validated photographic technique, clinical assessment and patient questionnaires.Results: On photographic assessment, 210 (27%) patients showed some degree of breast shrinkage, whilst 45 (6%) patients showed marked breast shrinkage. There was no significant association of genotype at either of the TGFB1 SNPs with any measure of late radiation toxicity.Conclusion: This adequately powered trial failed to confirm previously reported increases in fibrosis with TGFB1 genotype – any increase greater than 1.36 can be excluded with 95% confidence. Similar frequent failures to replicate associations with candidate genes have been resolved using genome-wide association scans: this methodology detects common, low risk alleles but requires even larger patient numbers for adequate statistical power.

Target volume definition for external beam partial breast radiotherapy: Clinical, pathological and technical studies informing current approaches - Corrected Proof

Anna M. Kirby, Charlotte E. Coles, John R. Yarnold — 2010-01-18

Abstract: Partial breast irradiation (PBI) is currently under investigation in several phase III trials and, following a recent consensus statement, its use off-study may increase despite ongoing uncertainty regarding optimal target volume definition. We review the clinical, pathological and technical evidence for target volume definition in external beam partial breast irradiation (EB-PBI). The optimal method of tumour bed (TB) delineation requires X-ray CT imaging of implanted excision cavity wall markers. The definition of clinical target volume (CTV) as TB plus concentric 15mm margins is based on the anatomical distribution of multifocal and multicentric disease around the primary tumour in mastectomy specimens, and the clinical locations of local tumour relapse (LR) after breast conservation surgery. If the majority of LR originate from foci of residual invasive and/or intraduct disease in the vicinity of the TB after complete microscopic resection, CTV margin logically takes account of the position of primary tumour within the surgical resection specimen. The uncertain significance of independent primary tumours as sources of preventable LR, and of wound healing responses in stimulating LR, increases the difficulties in defining optimal CTV. These uncertainties may resolve after long-term follow-up of current PBI trials. By contrast, a commonly used 10mm clinical to planning target volume (PTV) margin has a stronger evidence base, although departmental set-up errors need to be confirmed locally. A CTV–PTV margin >10mm may be required in women with larger breasts and/or large seromas, whilst the role of image-guided radiotherapy with or without TB markers in reducing CTV–PTV margins needs to be explored.