Radiotherapy & Oncology

Editorial Board

2012-01-01

Editorial Board

2012-01-01

Is it time for tailored treatment of rectal cancer? From prescribing by consensus to prescribing by numbers

Vincenzo Valentini, Philippe Lambin, Robert J. Myerson — 2011-12-19

In the past two decades a series of multi-institution clinical trials have done much to define the role of multi-modality treatment in the management of rectal adenocarcinoma. These trials have addressed a number of questions about sequencing of modalities, integration of radiation and chemotherapy, and radiation dose fractionation in the adjunctive management of patients undergoing extirpative surgery. Findings from single randomized trials include:

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: A phase II trial

2011-09-07

Abstract: Purpose: We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique.Materials and methods: Patients with resectable locally advanced mid-low rectal cancer (node-negative ⩾T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8Gy in 22 fractions) with concurrent capecitabine 825mg/m2 twice daily 5days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS).Results: Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1–42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively.Conclusions: The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.

Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer – A two stage phase II clinical trial

2011-07-11

Abstract: Background and purpose: The aim of this single-arm multicenter phase II clinical trial was to assess the feasibility and tolerability of preoperative radiotherapy and simultaneous capecitabine and bevacizumab. Secondary endpoints were downstaging-rate and induction of complete pathological response.Material and methods: Patients with cT3 rectal cancer were eligible. Capecitabine (825mg/sqm twice daily on radiotherapy-days weeks 1–4) and bevacizumab (5mg/kg on days 1, 15 and 29) were administered concurrently to pelvic radiotherapy (1.8Gy daily up to 45Gy in 5weeks). Surgery followed 6–8weeks later. A two-stage trial was designed with early termination at eight patients if more than three patients had experienced a common toxicity criteria ⩾grade 3 according to the NCI CTC guidelines.Results: In the first stage eight patients were enrolled. Median age was 70years (range 55–76) and ECOG PS 0/1 (%) was 87.5/12.5. Major side effects were mostly intestinal bleeding (grade 3, 25%), diarrhea (grade 3, 25%), perianal and abdominal pain (grades 3 and 4, 25%) followed by anemia (grade 3, 12.5%). Tumor downstaging was observed in 37.5% of patients with complete pathological response in two patients (25%).Conclusions: After interim analysis of feasibility and tolerability, accrual was terminated according to protocol due to ⩾grade 3 toxicities in 50% of patients. Complete pathological response was seen in 25% of patients but was accompanied by considerable toxicity. Further clinical trials are needed to clarify the role of bevacizumab in this setting.

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands

2011-09-07

Abstract: Purpose: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer.Methods and materials: The CTV’s for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed.Results: The average delineated CTV volume decreased from 620 to 460cc (p<0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2cm SD (p=0.01), while it remained 0.7cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively.Conclusions: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement.

Bowel exposure in rectal cancer IMRT using prone, supine, or a belly board

2011-07-04

Abstract: Purpose: To investigate bowel exposure using prone, supine, or two different belly boards for rectal cancer intensity modulated RT plans using a full bladder protocol.Methods and materials: For 11 volunteers four MR scans were acquired, on a flat table in prone, supine, and on two different belly boards (IT-V Medizintechnik GmbH® (BB1) and CIVCO® (BB2)), using a full bladder protocol. On each scan a 25×2Gy IMRT plan was calculated.Results: BB2 led to an average bowel area volume reduction of 20–30% at any dose level compared to prone. BB1 showed a smaller dose reduction effect, while no differences between prone and supine were found. Differences between BB2 and prone, supine or BB1 were significant up to a level of respectively, 45, 35, and 30Gy. The reducing effect varied among individuals, except for the 50Gy region, where no effect was found. An increase in bladder volume of 100cc led to a significant bowel area V15 reduction of 16% independent of scan type.Conclusions: In the low and intermediate dose region a belly board still attributes to a significant bowel dose reduction when using IMRT and a full bladder protocol. A larger bladder volume resulted in a significant decreased bowel area dose.

Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: A planning study with clinical implications

2011-11-23

Abstract: Background and purpose: Ongoing clinical trials aim to improve local control and overall survival rates by intensification of therapy regimen for patients with locally advanced rectal cancer. It is well known that whenever treatment is intensified, risk of therapy-related toxicity rises. An irradiation with protons could possibly present an approach to solve this dilemma by lowering the exposure to the organs-at-risk (OAR) without compromising tumor response.Material and methods: Twenty five consecutive patients were treated from 04/2009 to 5/2010. For all patients, four different treatment plans including protons, RapidArc, IMRT and 3D-conformal-technique were retrospectively calculated and analyzed according to dosimetric aspects.Results: Detailed DVH-analyses revealed that protons clearly reduced the dose to the OAR and entire normal tissue when compared to other techniques. Furthermore, the conformity index was significantly better and target volumes were covered consistent with the ICRU guidelines.Conclusions: Planning results suggest that treatment with protons can improve the therapeutic tolerance for the irradiation of rectal cancer, particularly for patients scheduled for an irradiation with an intensified chemotherapy regimen and identified to be at high risk for acute therapy-related toxicity. However, clinical experiences and long-term observation are needed to assess tumor response and related toxicity rates.

Increased organ sparing using shape-based treatment plan optimization for intensity modulated radiation therapy of pancreatic adenocarcinoma

2011-06-16

Abstract: Purpose: To develop a model to assess the quality of an IMRT treatment plan using data of prior patients with pancreatic adenocarcinoma.Methods: The dose to an organ at risk (OAR) depends in large part on its orientation and distance to the planning target volume (PTV). A database of 33 previously treated patients with pancreatic cancer was queried to find patients with less favorable PTV-OAR configuration than a new case. The minimal achieved dose among the selected patients should also be achievable for the OAR of the new case. This way the achievable doses to the OARs of 25 randomly selected pancreas cancer patients were predicted. The patients were replanned to verify if the predicted dose could be achieved. The new plans were compared to their original clinical plans.Results: The predicted doses were achieved within 1 and 2Gy for more than 82% and 94% of the patients, respectively, and were a good approximation of the minimal achievable doses. The improvement after replanning was 1.4Gy (range 0–4.6Gy) and 1.7Gy (range 0–6.3Gy) for the mean dose to the liver and the kidneys, respectively, without compromising target coverage or increasing radiation dose to the bowel, cord or stomach.Conclusions: The model could accurately predict the achievable doses, leading to a considerable decrease in dose to the OARs and an increase in treatment planning efficiency.

Repeated cycles of peptide receptor radionuclide therapy (PRRT) – Results and side-effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE therapy in patients with disseminated NET

2011-09-01

Abstract: Purpose: PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs.Material and methods: Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed.Results: Disease stabilization was observed in 10 patients 6months after the repeated PRRT cycle and in 5 patients after 12 and 18months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18months the mean values of creatinine levels were higher than the normal range (only in 2 patients).Conclusions: The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease.

Adjuvant chemoradiotherapy with or without intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma

2011-12-19

Abstract: Purpose: To document the long-term efficacy of intraoperative electron radiotherapy (IOERT) followed by concurrent chemotherapy and external-beam radiotherapy (EBRT) in the management of locally advanced gastric cancer.Materials and methods: A total of 97 consecutive patients with T3/4 or N+ gastric adenocarcinoma were enrolled. Fifty-one patients received adjuvant chemoradiotherapy (EBRT group) and 46 received IOERT (dose range, 12–15Gy) followed by chemoradiotherapy (EBRT+IOERT group).Results: The 5-year locoregional control rates were 50% and 35% in the two groups with or without IOERT, respectively (p=0.04). Two patients had recurrence within the IOERT field in the EBRT+IOERT group and 14 patients recurred in the same area in the EBRT group (p=0.02). Multivariate analyses revealed that adjuvant IOERT was an independent prognosticator for both local–regional control (p=0.02) and disease-free survival (p=0.05). G3/4 late toxicity was observed in 5 patients in the EBRT+IOERT group, but none in the EBRT group (p=0.02).Conclusions: Higher radiation dose may contribute to the improvement of local control, especially in the field encompassed by IOERT. The addition of IOERT to surgery and adjuvant chemoradiation deserves further investigation in a randomized trial.

Treatment of primary liver cancer using highly-conformal radiotherapy with kv-image guidance and respiratory control

2011-06-06

Abstract: Purpose: To implement a reliable, practical and reproducible treatment procedure, based on in-room kV-image guidance and respiratory control, for liver cancer patients treated with high dose conformal radiotherapy using a commercially available treatment system.Materials and methods: CT stimulation was conducted under voluntary breath hold or gating using the Varian Real-time Position Management™ (RPM) System. Treatments were delivered daily under kV image guidance to verify the diaphragmatic or lipiodol-defined tumor position.Results: Thirty-three patients with liver confined hepatocellular carcinoma were treated between May 2006 and Dec 2009. After a median follow-up period of 16.5months (range: 3.5–40.7), all but 2 patients demonstrated radiological tumor regression. Eight patients (24%) achieved complete remission. The median tumor shrinkage was 42% (27–100%). Subsequent in-field tumor progression was observed in only three patients (10%). For the 23 patients with abnormal alpha fetoprotein level, 22 of them showed biochemical response with a median AFP level drop of 78%. The treatment was well tolerated: Grade 3 toxicities occurred in 5 patients (1 leucopenia, 1 elevated liver enzyme and 3 elevated bilirubin level) but there was no grade 4 toxicity or treatment related death. The 1year overall survival rate is 71.7% and median survival time is 17.2months (3.5–40.7months).Conclusions: Excellent treatment results with minimal toxicities could be achieved in a clinical environment with a commercially available highly sophisticated radiotherapy system.

Node-negative T1–T2 anal cancer: Radiotherapy alone or concomitant chemoradiotherapy?

2011-10-13

Abstract: Purpose: To evaluate the influence of concomitant chemotherapy on loco-regional control (LRC) and cancer-specific survival (CSS) in patients with T1–T2 N0 M0 anal cancer treated conservatively by primary radiotherapy (RT).Materials and methods: Between 1976 and 2008, 146 patients with T1 (n=29) or T2 (n=117) N0 M0 anal cancer were treated curatively by RT alone (n=71) or by combined chemoradiotherapy (CRT) (n=75) consisting of mitomycin C±5-fluorouracil. Univariate and multivariate analyses were performed to assess patient-, tumor- and treatment-related factors influencing LRC and CSS.Results: With a median follow-up of 62.5months (interquartilerange, 26–113months), 122 (84%) patients were locally controlled. The five-year actuarial LRC, CSS and overall survival for the population were 81.4%±3.6%, 91.9%±2.6%, and 75.4%±3.9%, respectively. The five-year LRC and CSS for patients treated with RT alone and with CRT were 75.5%±6.0% vs. 86.8%±4.1% (p=0.155) and 88.5%±4.5% vs. 94.9%±2.9% (p=0.161), respectively. In the multivariate analysis, no clinical or therapeutic factors were found to significantly influence the LRC and CSS, while the addition of chemotherapy was of borderline significance (p=0.065 and p=0.107, respectively).Conclusions: In the management of node negative T1–T2 anal cancer, LRC and CSS tend to be superior in patients treated by combined CRT, even though the difference was not significant. Randomized studies are warranted to assess definitively the role of combined treatment in early-stage anal carcinoma.

Performance of an atlas-based autosegmentation software for delineation of target volumes for radiotherapy of breast and anorectal cancer

2011-10-03

Abstract: Background and purpose: To validate atlas-based autosegmentation for contouring breast/anorectal targets.Methods and materials: ABAS uses atlases with defined CTVs as template cases to automatically delineate target volumes in other patient CT-datasets. Results are compared with manually contoured CTVs of breast/anorectal cancer according to RTOG-guidelines. The impact of using specific atlases matched to individual patient geometry was evaluated. Results were quantified by analyzing Dice Similarity Coefficient (DSC), logit(DSC) and Percent Overlap (PO). DSC >0.700 and logit(DSC) >0.847 are acceptable. In addition a new algorithm (STAPLE) was evaluated.Results: ABAS produced good results for the CTV of breast/anorectal cancer targets. Delineation of inguinal lymphatic drainage, however, was insufficient. Results for breast CTV were (DSC: 0.86–0.91 ([0,1]), logit(DSC): 1.82–2.36 ([−∞,∞]), PO: 75.5–82.89%) and for anorectal CTVA (DSC: 0.79–0.85, logit(DSC): 1.40–1.77, PO: 68–73.67%).Conclusions: ABAS produced satisfactory results for these clinical target volumes that are defined by more complex tissue interface geometry, thus streamlining and facilitating the radiotherapy workflow which is essential to face increasing demand and limited resources. STAPLE improved contouring outcome. Small target volumes not clearly defined are still to be delineated manually. Based on these results, ABAS has been clinically introduced for precontouring of CTVs/OARs.

Comparison of three-dimensional versus intensity-modulated radiotherapy techniques to treat breast and axillary level III and supraclavicular nodes in a prone versus supine position

Rajni A. Sethi, Hyun Soo No, Gabor Jozsef, Jane P. Ko, Silvia C. Formenti — 2011-10-12

Abstract: Background and purpose: To determine the optimal method of targeting breast and regional nodes in selected breast cancer patients after axillary dissection, we compared the results of IMRT versus no IMRT, and CT-informed versus clinically-placed fields, in supine and prone positions.Materials and methods: Twelve consecutive breast cancer patients simulated both prone and supine provided the images for this study. Four techniques were used to target breast, level III axilla, and supraclavicular fossa in either position: a traditional three-field three-dimensional conformal radiotherapy (3DCRT) plan, a four-field 3DCRT plan using a posterior axillary boost field, and two techniques using a CT-informed target volume consisting of an optimized 3DCRT plan (CT-planned 3D) and an intensity-modulated radiotherapy (IMRT) plan. The prescribed dose was 50Gy in 25 fractions.Results: CT-planned 3D and IMRT techniques improved nodal PTV coverage. Supine, mean nodal PTV V50 was 50% (3-field), 59% (4-field), 92% (CT-planned 3D), and 94% (IMRT). Prone, V50 was 29% (3-field), 42% (4-field), 97% (CT-planned 3D), and 95% (IMRT). Prone positioning, compared to supine, and IMRT technique, compared to 3D, lowered ipsilateral lung V20.Conclusions: Traditional 3DCRT plans provide inadequate nodal coverage. Prone IMRT technique resulted in optimal target coverage and reduced ipsilateral lung V20.

Preoperative radio-chemotherapy in early breast cancer patients: Long-term results of a phase II trial

2011-09-12

Abstract: Purpose: This phase II trial aimed to investigate the efficacy of concurrent radio- (RT) and chemotherapy (CT) in the preoperative setting for operable, non-metastatic breast cancer (BC) not amenable to initial breast-conserving surgery (BCS).Patients and methods: From 2001 to 2003, 59 women were included. CT consisted of four cycles of 5-FU, 500mg/m2/d, continuous infusion (d1–d5) and vinorelbine, 25mg/m2 (d1 and d6). Starting concurrently with the second cycle, RT delivered 50Gy to the breast and 46Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and lymph node dissection were then performed. Adjuvant treatment consisted of a 16Gy boost to the tumor bed after BCS, FEC (four cycles of fluorouracil 500mg/m2, cyclophosphamide 500mg/m2, and epirubicin 100mg/m2, d1; d21) for pN1-3 and hormone-therapy for positive hormone receptors BC.Results: The in-breast pathological complete response rate was 27%. BCS was performed in 41 (69%) pts. Overall and distant-disease free survivals at 5years were respectively 88% [95% CI 80–98] and 83% [95% CI 74–93] whereas locoregional and local controls were 90% [95% CI 82–97] and 97% [95% CI 92–100]. Late toxicity (CTCAE-V3) was assessed in 51 pts (86%) with a median follow-up of 7years [5–8]. Four (8%) experienced at least one grade III toxicities (one telangectasia and three fibroses). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in four pts (11%).Conclusion: Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association deserves further evaluations in prospective trials.

Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy – A feasibility and toxicity study

2011-11-23

Abstract: Background: Breast cancer sensitivity to large fraction size may be enhanced using hypofractionated concomitant boost radiotherapy (CBRT), thereby shortening overall treatment time. This ethics approved, prospective single cohort feasibility study was designed to evaluate the dosimetry and toxicity of CBRT using an intensity-modulated radiotherapy (IMRT) technique, compared with a standard sequential boost technique (SBT).Methods: Fifteen women (11 right-sided; 4 left-sided) received 42.4Gy to the whole breast and an additional 10.08Gy to the tumor bed in 16 daily fractions, using IMRT and standard dose constraints. Each patient was replanned with the SBT, using mixed photon–electrons. Clinical target volume (CTV), dose evaluation volume (DEV), and organs at risk (OAR) dose distributions were compared with the SBT. Toxicity and treatment times were prospectively recorded.Results: All 15 CBRT plans achieved the desired CTV (V49.9Gy⩾99%) and DEV (V49.9Gy⩾95%), coverage of the boost, compared with only 10 (66.7%, p=0.03), and 12 (80%, p=0.125) SBT plans, respectively. Ipsilateral lung (p<0.0001), and heart (right-sided, p=0.001; left-sided, p=0.13) doses were lower. Grade 3 acute toxicity occurred in 1 (6.7%) patient. At 1year, two (13.3%) additional patients had overall grade 2 late toxicity, compared with baseline. No grade 3–4 late toxicity was observed.Conclusions: CBRT using IMRT improved boost coverage and lowered OAR doses, compared with SBT. Toxicities were acceptable using a daily boost of 3.28Gy. While resource utilization was greater, overall treatment time was reduced.

Partial breast irradiation for locally recurrent breast cancer within a second breast conserving treatment: Alternative to mastectomy? Results from a prospective trial

2011-09-12

Abstract: Purpose: To assess the outcome of multi-catheter pulse dose rate (PDR) brachytherapy of re-irradiation for local ipsilateral breast tumour recurrence (IBTR) in regard to local control, survival, morbidity and quality of life (QoL).Patients and methods: Between 1999 and 2006, 39 patients were included with histologically confirmed IBTR, Karnofsky index ⩾80% and refusal of mastectomy. Exclusion criteria were multicentric invasive growth pattern, unclear surgical margins, distant metastasis and a postoperative breast not suitable for interstitial brachytherapy. Primary endpoint was local tumour control. Morbidity, cosmetic outcome and QoL were assessed in 24/39 patients.Results: The five year actuarial local control rate was 93% after a mean follow up of 57 (±30) months with two second local relapses. Overall survival and disease free survival, both at 5years, were 87% and 77%, respectively. Late side effects Grade 1–2 were observed in 20/24 patients after a mean follow-up of 30 (±18) months. Late side effects ⩾Grade 3 occurred in 4/24 patients. Cosmetic outcome was excellent to fair in 76% of women. Overall QoL was comparable to a healthy control group. Mean scores of scales and items of QLQ-BR23 were comparable to primary breast conserving therapy.Conclusions: Accelerated PDR-brachytherapy following breast conserving surgery (BCS) for local IBTR results in local tumour control comparable to mastectomy. Morbidity is moderate; the cosmetic outcome is good and hardly any impairment on QoL is observed.

Superficial dose distribution in breast for tangential radiation treatment, Monte Carlo evaluation of Eclipse algorithms in case of phantom and patient geometries

2011-07-11

Abstract: Purpose: The aim of this study is to examine experimentally and by the Monte Carlo method the accuracy of the Eclipse Pencil Beam Convolution (PBC) and Analytical Anisotropic Algorithm (AAA) algorithms in the superficial region (0–2cm) of the breast for tangential photon beams in a phantom case as well as in a number of patient geometries. The aim is also to identify differences in how the patient computer tomography data are handled by the treatment planning system and in the Monte Carlo simulations in order to reduce influences of these effects on the evaluation.Materials and methods: Measurements by thermoluminescent dosimeters and gafchromic film are performed for six MV tangential irradiation of the cylindrical solid water phantom. Tangential treatment of seven patients is investigated considering open beams. Dose distributions are obtained by the Eclipse PBC and AAA algorithms. Monte Carlo calculations are carried out by BEAMnrc/DOSXYZnrc code package. Calculations are performed with a calculation grid of 1.25×1.25×5mm3 for PBC and 2×2×5mm3 for AAA and Monte Carlo, respectively. Dose comparison is performed in both dose and spatial domains by the normalized dose difference method.Results: Experimental profiles from the surface toward the geometrical center of the cylindrical phantom are obtained at the beam entrance and exit as well as laterally. Full dose is received beyond 2mm in the lateral superficial region and beyond 7mm at the beam entrance. Good agreement between experimental, Monte Carlo and AAA data is obtained, whereas PBC is seen to underestimate the entrance dose the first 3–4mm and the lateral dose by more than 5% up to 8mm depth. In the patient cases considered, AAA and Monte Carlo show agreement within 3% dose and 4mm spatial tolerance. PBC systematically underestimates the dose at the breast apex. The dimensions of region out of tolerance vary with the local breast shape. Different interpretations of patient boundaries in Monte Carlo and the Eclipse are found to influence the evaluation. Computer tomography marker wire may introduce local disturbance effects on the comparison as well. These factors are not related to the accuracy of the calculation algorithms and their effect is taken into account in the evaluation.Conclusions: The accuracy of AAA in the case of the solid water phantom is comparable with that of the Monte Carlo method. The AAA–Monte Carlo differences in the patient cases considered are within 3%, 4mm tolerance. The PBC algorithm does not give equivalent results. In the phantom case, PBC underestimates the lateral dose by more than 5% up to 8mm depth. The PBC-Monte Carlo differences in the patient cases are outside the tolerance at the breast apex. The dimension of region varies with the breast shape being typically 8–10mm long and 6–8mm deep.

Electronic portal images (EPIs) based position verification for the breast simultaneous integrated boost (SIB) technique

2011-11-18

Abstract: Background and purpose: To develop a method based on electronic portal images (EPIs) for the position verification of breast cancer patients that are treated with a simultaneous integrated boost (SIB) technique.Method: 3D setup errors of the breast outline and the thoracic wall were determined from EPIs of the tangential treatment fields and anterior posterior (AP) verification field. The method was verified with repeated CT scans of 38 patients with an average setup error larger than 5mm.Result: The 3D position deviation of the boost volume can best be determined from the position deviation of the breast outline in the ventrodorsal direction and the thoracic wall in the lateral and longitudinal directions from the tangential and AP EPIs. The method gives an average overestimation of the deviation of the boost volume in the ventrodorsal, lateral and longitudinal directions by 28%, 20% and 6%, respectively and an average underestimation of the deviation of the whole breast by 32%, 17% and 39%.Conclusions: The described method is superior to using tangential EPIs only and is recommended for position verification of breast cancer patients that are treated with a SIB technique if no Cone beam CT (CBCT) or fiducial markers can be used.

Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer

2011-11-21

Abstract: Background and purpose: It has been established that radiotherapy can increase cardiovascular disease (CVD) risk. Genetic variants, which play a role in the tissue, damage response and angiogenesis regulating TGFβ pathway might give us insight into the mechanisms underlying radiation-induced CVD. We examined the effects of two polymorphisms, TGFβ1 29C>T and PAI-1 5G>4G, on CVD incidence.Materials and methods: This retrospective cohort study included 422 10-year breast cancer survivors, aged <50years at diagnosis, treated between 1977 and 1995. We collected information on treatment, oncological follow-up, CVD, CVD risk factors and genotypes.Results: During a mean follow-up of 19.4years, 61 patients developed CVD. Internal mammary chain (IMC) irradiation, exposing a part of the heart to radiation, was associated with a hazard ratio of 2.36 (95% CI: 1.27–4.37, p=0.01) compared to no IMC irradiation. Compared to the C/C+C/T genotype, the T/T genotype of the TGFβ1 polymorphism was associated with hazard ratios of 1.79 (0.99–3.26, p=0.06) and 1.74 (0.90–3.34, p=0.10) in the total and IMC-irradiated group, respectively. We found no evidence for an association between PAI-1 5G>4G and CVD risk.Conclusion: Our study suggests there might be an association between the TGFβ1 29C>T polymorphism and CVD risk in long-term breast cancer survivors.

Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck

2011-10-13

Abstract: Purpose: To validate the predictive impact of a hypoxia gene expression classifier in identifying patients with head and neck squamous cell carcinoma (HNSCC) having benefit from hypoxic modification of radiotherapy.Patients and methods: Gene expressions were quantified from formalin-fixed, paraffin-embedded tumour biopsies of 323 HNSCC patients randomized for placebo or nimorazole in conjunction with radiotherapy in the DAHANCA 5 study. Tumours were classified as either “more” or “less” hypoxic with a classifier constituting of 15 hypoxia responsive genes. The predictive impact was evaluated by analysing the response to nimorazole vs. placebo in terms of loco-regional tumour control (LRC) and disease-specific survival (DSS) in the two classified groups.Results: Hundred and fourteen patients (35%) were classified as having “more” hypoxic tumours. These patients had a significant benefit of hypoxic modification with nimorazole compared with placebo in terms of LRC (5-year actuarial values 49% vs. 18%; p=0.001) and DSS (48% vs. 30%; p=0.04). “Less” hypoxic tumours had no significant effect of hypoxic modification (LRC: 50% vs. 44%; p=0.39, DSS: 57% vs. 51%; p=0.49) and generally an outcome, which was similar to “more” hypoxic tumours treated with nimorazole. In contrast to HPV-negative tumours, HPV-positive tumours had a substantially better outcome in response to radiotherapy, which was irrespective of hypoxic modification.Conclusions: A predictive 15-gene hypoxia classifier could identify patients associated with improved outcome after combining radiotherapy with hypoxic modification and underlines the relevance of such therapy. The impact of the classifier was limited to HPV-negative tumours.

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix

2011-09-01

Abstract: Purpose: Trans-abdominal ultrasonography (US) is capable of determining size, shape, thickness, and diameter of uterus, cervix and disease at cervix or parametria. To assess the potential value of US for image-guided cervical cancer brachytherapy, we compared US-findings relevant for brachytherapy to the corresponding findings obtained from MR imaging.Materials and methods: Twenty patients with biopsy proven cervical cancer undergoing definitive radiotherapy with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy were invited to participate in this study. US and MR were performed in a similar reproducible patient positioning after intracavitary application. US mid-sagittal and axial image at the level of external cervical os was acquired. Reference points D1 to D9 and distances were identified with respect to central tandem and flange, to delineate cervix, central disease, and external surface of the uterus.Results: Thirty-two applications using CT/MR compatible applicators were evaluable. The D1 and D3 reference distances which represent anterior surface had a strong correlation with R=0.92 and 0.94 (p<0.01). The D2 and D4 reference distances in contrast, which represent the posterior surface had a moderate (D2) and a strong (D4) correlation with R=0.63 and 0.82 (p<0.01). Of all, D2 reference distance showed the least correlation of MR and US. The D5 reference distance representing the fundal thickness from tandem tip had a correlation of 0.98. The reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96, and 0.93, respectively.Conclusions: Our study evaluating the use of US, suggests a reasonably strong correlation with MR in delineating uterus, cervix, and central disease for 3D conformal intracavitary brachytherapy planning.

Postal dosimetry audit test for small photon beams

2011-07-07

Abstract: Background and purpose: Small radiation beams (<4cm width) are being increasingly used in the delivery of advanced techniques as Intensity Modulated Radiotherapy (IMRT) and Stereotactic Radiosurgery (SRS). Dose measurements in small beams present challenges not encountered for larger beams. A postal audit with Thermoluminiscent Dosimeters (TLD) was developed to check the doses in small photon beams. A validation test in real conditions was carried out in fourteen centres.Material and methods: The TLD postal audit employs very small chips (1×1×1mm3) of TLD-100 inserted at 5 and 10cm of depth in a cylindrical PMMA phantom designed for this purpose. This experimental system is mailed to the audited centres to be irradiated with beams of 1 and 3cm of side or diameter. The prescribed dose is 1.5Gy at 10cm. The properties of this system were studied experimentally and by Monte Carlo (MC) simulation, before the external test.Results: Deviations between the prescribed and measured absorbed doses are below 5% for 69% (1×1cm2 beam) and 64% (3×3cm2 beam) of the audited centres. When deviations are above 5%, their causes have been investigated and led to corrections.Conclusion: The developed postal audit is suitable to verify the absorbed doses in small photon beams with an accuracy of 2.9% (1s).

Applying usability heuristics to radiotherapy systems

2011-07-06

Abstract: Background and purpose: Heuristic evaluations have been used to evaluate safety of medical devices by identifying and assessing usability issues. Since radiotherapy treatment delivery systems often consist of multiple complex user-interfaces, a heuristic evaluation was conducted to assess the potential safety issues of such a system.Material and methods: A heuristic evaluation was conducted to evaluate the treatment delivery system at Princess Margaret Hospital (Toronto, Canada). Two independent evaluators identified usability issues with the user-interfaces and rated the severity of each issue.Results: The evaluators identified 75 usability issues in total. Eighteen of them were rated as high severity, indicating the potential to have a major impact on patient safety. A majority of issues were found on the record and verify system, and many were associated with the patient setup process. While the hospital has processes in place to ensure patient safety, recommendations were developed to further mitigate the risks of potential consequences.Conclusions: Heuristic evaluation is an efficient and inexpensive method that can be successfully applied to radiotherapy delivery systems to identify usability issues and improve patient safety. Although this study was conducted only at one site, the findings may have broad implications for the design of these systems.

The cost of radiotherapy in a decade of technology evolution

Evelyn Van de Werf, Jan Verstraete, Yolande Lievens — 2011-08-29

Abstract: Purpose: To quantify changes in radiotherapy costs occurring in a decade of medical–technological evolution.Materials and methods: The activity-based costing (ABC) model of the University Hospitals Leuven (UHL) radiotherapy (RT) department was adapted to current RT standards. It allocated actual resource costs to the treatments based on the departmental work-flow and patient mix in 2009. A benchmark with the former model analyzed the cost increases related to changes in RT infrastructure and practice over 10years.Results: A considerable increase in total RT costs was observed, resulting from higher capital investments (96%) and personnel cost (103%), the latter dominating the total picture. Treatment delivery remains the most costly activity, boosted by the cost of improved quality assurance (QA), 23% of total product costs, coming along with more advanced RT techniques. Hence, cost increases at the product level are most obvious for complex treatments, such as intensity-modulated radiotherapy (IMRT), representing cost increases ranging between 38% and 88% compared to conformal approaches.Conclusions: The ABC model provides insight into the financial consequences of evolving technology and practice. Such data are a mandatory first step in our strive to prove RT cost-effectiveness and thus support optimal reimbursement and provision of radiotherapy departments.

The quality of radiation care: The results of focus group interviews and concept mapping to explore the patient’s perspective

2011-09-12

Abstract: Background and purpose: In this study, we explore the quality aspects of radiation care from the patient’s perspective in order to develop a draft Consumer Quality Index (CQI) Radiation Care instrument.Materials and methods: Four focus group discussions with (former) cancer patients were held to explore the aspects determining the quality of radiation care. The list of aspects generated was categorised based on similarity and importance in a concept mapping procedure.Results: Four focus group discussions revealed seven main themes related to the quality of radiation care: information provision, a patient-centred approach, professional competence, planning and waiting times, accessibility, cooperation and communication, and follow-up care. Results of concept mapping procedures revealed which items the patients considered to be most important. A radiation oncologist who is up to date about the patient’s file is of paramount importance for cancer patients receiving radiotherapy.Conclusions: The quality aspects found through focus group discussions provided useful insight into how patients experience radiation care. Furthermore, concept mapping made these results more solid. To evaluate the quality of radiation care from the patient’s perspective, these quality aspects will be guiding in the development of a CQI Radiation Care.

Radiotherapy and oncology

Rob Glynne-Jones — 2011-07-06

We read with interest the Trans Tasman Radiation Oncology Group study TROG 99/02 . The authors attribute the high rate of inguinal node recurrence observed (22.5%) to a failure to encompass the inguinal region in the initial radiation fields. Their conclusion is not wholly supported by the data presented.

Comment on Trans Tasman Radiation Oncology Group Study TROG 99/02

John Matthews — 2011-07-04

We thank Dr. Glynne-Jones for his comments. The aim of the study was to reduce significant short and long term morbidity in a group thought to be only at local risk and we found that the relapse rate in the inguinal nodes was higher than expected. Anal margin lesions were not included.

MRI prostate radiation therapy planning: When the patient distorts his own image (Regarding Lambert et al., Radiother Oncol 2011; 98: 330–334)

David Pasquier, Eric Lartigau — 2011-06-27

We read the article by Lambert et al. with great interest. The work provides a further demonstration of the feasibility of prostate cancer radiotherapy planning based on MRI alone.

Important ESTRO dates

2012-01-01

Radiotherapy & Oncology

Editorial Board

Editorial Board

Contents

Is it time for tailored treatment of rectal cancer? From prescribing by consensus to prescribing by numbers

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: A phase II trial

Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer – A two stage phase II clinical trial

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands

Bowel exposure in rectal cancer IMRT using prone, supine, or a belly board

Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: A planning study with clinical implications

Increased organ sparing using shape-based treatment plan optimization for intensity modulated radiation therapy of pancreatic adenocarcinoma

Repeated cycles of peptide receptor radionuclide therapy (PRRT) – Results and side-effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE therapy in patients with disseminated NET

Adjuvant chemoradiotherapy with or without intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma

Treatment of primary liver cancer using highly-conformal radiotherapy with kv-image guidance and respiratory control

Node-negative T1–T2 anal cancer: Radiotherapy alone or concomitant chemoradiotherapy?

Performance of an atlas-based autosegmentation software for delineation of target volumes for radiotherapy of breast and anorectal cancer

Comparison of three-dimensional versus intensity-modulated radiotherapy techniques to treat breast and axillary level III and supraclavicular nodes in a prone versus supine position

Preoperative radio-chemotherapy in early breast cancer patients: Long-term results of a phase II trial

Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy – A feasibility and toxicity study

Partial breast irradiation for locally recurrent breast cancer within a second breast conserving treatment: Alternative to mastectomy? Results from a prospective trial

Superficial dose distribution in breast for tangential radiation treatment, Monte Carlo evaluation of Eclipse algorithms in case of phantom and patient geometries

Electronic portal images (EPIs) based position verification for the breast simultaneous integrated boost (SIB) technique

Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer

Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck

Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation for conformal intracavitary brachytherapy in carcinoma of the uterine cervix

Postal dosimetry audit test for small photon beams

Applying usability heuristics to radiotherapy systems

The cost of radiotherapy in a decade of technology evolution

The quality of radiation care: The results of focus group interviews and concept mapping to explore the patient’s perspective

Radiotherapy and oncology

Comment on Trans Tasman Radiation Oncology Group Study TROG 99/02

MRI prostate radiation therapy planning: When the patient distorts his own image (Regarding Lambert et al., Radiother Oncol 2011; 98: 330–334)

Important ESTRO dates