Sparing the penile bulb in the radical irradiation of clinically localised prostate carcinoma: A comparison between MRI and CT prostatic apex definition in 3DCRT, Linac-IMRT and Helical Tomotherapy

Background and purpose

To assess the impact of using MRI and Helical Tomotherapy (HT) compared to 3DCRT and dynamic IMRT on the dose to the penile bulb (PB).

Materials and methods

Eight patients diagnosed with prostate cancer entered a treatment protocol including CT and MRI simulation. The prostate apex was defined on both MRI and CT. Treatment plans (HT, Linac-IMRT, 3DCRT and conventional technique), were elaborated on both MRI and CT images. A dose of 71.4 Gy (2.55 Gy/fraction) was prescribed; it was requested that PTVs be covered by 95% isodose line. The mean dose and V50 of PB were evaluated.

Results

PTV-MRI plans reduced PB mean dose and V50 compared to PTV-CT plans. This improvement, deriving also from the treatment modality, was 89% for 3DCRT, 99% for Linac-IMRT and 97% for HT (p < 0.01), considering V50. Conventional plans resulted in a significantly higher mean PB dose/V50 compared to 3DCRT-PTV-CT (+27%/+38%), Linac-IMRT-PTV-CT (+42%/+57%) and HT-PTV-CT (+32%/+48%) (p < 0.01). The comparison between conventional and PTV-MRI techniques showed a still larger increase: +73%/+93% 3DCRT; +86%/+99% Linac-IMRT; +56%/+99% HT (p < 0.01). The PB mean dose reduction with Linac-IMRT compared to 3DCRT was 24% (p = 0.034) and 40% (p = 0.027) for PTV-CT and PTV-MRI, respectively. This gain remained significant even when comparing Linac-IMRT to HT: 21% (p = 0.07) PTV-CT and 68% (p = 0.00002) PTV-MRI. HT was superior to 3DCRT with respect to PTV-CT (average gain 4%, p = 0.044), whereas it resulted to be detrimental considering PTV-MRI (26 Gy vs 16.5 Gy), possibly due to the helical delivery of HT; however, in a patient where the distance bulb-PTV <1 cm, HT provided better PB sparing than 3DCRT (29.5 Gy vs 45.2 Gy).

Conclusions

MRI allowed efficient sparing of PB irrespective of the treatment modality. Linac-IMRT was shown to further reduce the dose to the bulb compared to 3DCRT and HT.     

AAA and PBC calculation accuracy in the surface build-up region in tangential beam treatments. Phantom and breast case study with the Monte Carlo code penelope

Background and purpose

In tangential beam treatments accurate dose calculation of the absorbed dose in the build-up region is of major importance, in particular when the target has superficial extension close to the skin. In most analytical treatment planning systems (TPSs) calculations depend on the experimental measurements introduced by the user in which accuracy might be limited by the type of detector employed to perform them. To quantify the discrepancy between analytically calculated and delivered dose in the build-up region, near the skin of a patient, independent Monte Carlo (MC) simulations using the penelope code were performed. Dose distributions obtained with MC simulations were compared with those given by the Pencil Beam Convolution (PBC) algorithm and the Analytical Anisotropic Algorithm (AAA) implemented in the commercial TPS Eclipse.

Material and methods

A cylindrical phantom was used to approximate the breast contour of a patient for MC simulations and the TPS. Calculations of the absorbed doses were performed for 6 and 18 MV beams for four different angles of incidence: 15°, 30°, 45° and 75° and different field sizes: 3 × 3 cm², 10 × 10 cm² and 40 × 40 cm². Absorbed doses along the phantom central axis were obtained with both the PBC algorithm and the AAA and compared to those estimated by the MC simulations. Additionally, a breast patient case was calculated with two opposed 6 MV photon beams using all the aforementioned analytical and stochastic algorithms.

Results

For the 6 MV photon beam in the phantom case, both the PBC algorithm and the AAA tend to underestimate the absorbed dose in the build-up region in comparison to MC results. These differences are clinically irrelevant and are included in a 1 mm range. This tendency is also confirmed in the breast patient case. For the 18 MV beam the PBC algorithm underestimates the absorbed dose with respect to the AAA. In comparison to MC simulations the PBC algorithm tends to underestimate the dose after the first 2-3 mm of tissue for larger angles but seems to be in good agreement for smaller angles. In the first millimetre of depth instead the PBC tends to overestimate the dose for smaller angles and underestimate it for larger angle of incidence. Instead, the AAA overestimates absorbed doses with respect to MC results for all angles of incidence and at all depths. This behaviour seems to be due to the electron contamination model, which is not able to provide accurate absorbed doses in the build-up region. Even for this case the differences are unlikely to be of clinical significance as 18 MV is not usually used to treat superficial targets.

Conclusions

The PBC algorithm and the AAA implemented in the TPS Eclipse system version 8.0.05, both yield equivalent calculations, after the first 2 mm of tissue, of the absorbed dose for 6 MV photon beams when a grid size smaller than 5 mm is used. When 18 MV photon beams are used care should be taken because the results of the AAA are highly dependent on the beam configuration.     

Boosting the tumor bed from deep-seated tumors in early-stage breast cancer: A planning study between electron, photon, and proton beams

Purpose

To assess the potential dosimetric advantages and drawbacks of photon beams (modulated or not), electron beams (EB), and protons as a boost for the tumor bed in deep-seated early-stage breast cancer.

Material and methods

Planning CTs of 14 women with deep-seated tumors (i.e., ?4 cm depth) were selected. The clinical target volume (CTV) was defined as the area of architectural distortion surrounded by surgical clips. The planning treatment volume (PTV) was the CTV plus 1 cm margin. A dose of 16 Gy in 2 Gy fractions was prescribed. Organs at risk (OARs) were heart, lungs, breasts, and a 5-mm thick skin segment on the breast surface. Dose-volume metrics were defined to quantify the quality of concurrent treatment plans assessing target coverage and sparing of OAR. The following treatment techniques were assessed: photon beams with either static 3D-conformal, dynamic arc (DCA), static gantry intensity-modulated beams (IMRT), or RapidArc (RA); a single conformal EB; and intensity-modulated proton beams (IMPT). The goal for this planning effort was to cover 100% of the CTV with ?95% of the prescribed dose and to minimize the volume inside the CTV receiving >107% of the dose.

Results

All techniques but DCA and EB achieved the planning objective for the CTV with an inhomogeneity ranging from 2% to 11%. RA showed the best conformity, EB the worst. Contra-lateral breast and lung were spared by all techniques with mean doses <0.5 Gy (zero for protons). The ipsi-lateral lung received a mean dose <10% of that prescribed with photon beams and <2% with IMPT, increasing to 17% with EB. The heart, in left-sided breast tumors, received also the highest dose with EB. The skin was best protected with RA with a mean dose of 5.4 Gy and V_15Gy = 2.4%.

Conclusions

Boosting the tumor bed in early-stage breast cancer with optimized photon or proton beams may be preferred to EB especially for deep-seated targets. The marked OAR (i.e., ipsi-lateral breast, lung, heart, and skin surface) dose-sparing effect may allow for a potential long-term toxicity risk reduction and better cosmesis. DCA or RA may also be considered alternative treatment options for patients eligible for accelerated partial breast irradiation trials.     

Modulated electron radiotherapy treatment planning using a photon multileaf collimator for post-mastectomized chest walls

Background and purpose

To evaluate the feasibility of using a photon MLC (xMLC) for modulated electron radiotherapy treatment (MERT) as an alternative to conventional post-mastectomy chest wall (CW) irradiation. A Monte Carlo (MC) based planning system was developed to overcome the inaccuracy of the ‘pencil beam’ algorithm. MC techniques are known to accurately calculate the dose distributions of electron beams, allowing the explicit simulation of electron interactions within the MLC.

Materials and methods

Four real clinical CW cases were planned using MERT which were compared with the conventional electron treatments based on blocks and by a straightforward approach using the MLC, and not the blocks (as an intermediate step to MERT) to shape the same segments with SSD between 60 and 70 cm depending on PTV size. MC calculations were verified with an array of ionization chambers and radiochromic films in a solid water phantom.

Results

Tests based on gamma analysis between MC dose distributions and radiochromic film measurements showed an excellent agreement. Differences in the absolute dose measured with a plane-parallel chamber at a reference point were below 3% for all cases. MERT solution showed a better PTV coverage and a significant reduction of the doses to the organs at risk (OARs).

Conclusion

MERT can effectively improve the current electron treatments by obtaining a better PTV coverage and sparing healthy tissues. More directly, block-shaped treatments could be replaced by MLC-shaped non-modulated segments providing similar results.     

On-line cone beam CT image guidance for vocal cord tumor targeting

Background and purpose

We are developing a technique for highly focused vocal cord irradiation in early glottic carcinoma to optimally treat a target volume confined to a single cord. This technique, in contrast with the conventional methods, aims at sparing the healthy vocal cord. As such a technique requires sub-mm daily targeting accuracy to be effective, we investigate the accuracy achievable with on-line kV-cone beam CT (CBCT) corrections.

Materials and methods

CBCT scans were obtained in 10 early glottic cancer patients in each treatment fraction. The grey value registration available in X-ray volume imaging (XVI) software (Elekta, Synergy) was applied to a volume of interest encompassing the thyroid cartilage. After application of the thus derived corrections, residue displacements with respect to the planning CT scan were measured at clearly identifiable relevant landmarks. The intra- and inter-observer variations were also measured.

Results

While before correction the systematic displacements of the vocal cords were as large as 2.4 ± 3.3 mm (cranial-caudal population mean ± SD Σ), daily CBCT registration and correction reduced these values to less than 0.2 ± 0.5 mm in all directions. Random positioning errors (SD σ) were reduced to less than 1 mm. Correcting only for translations and not for rotations did not appreciably affect this accuracy. The residue random displacements partly stem from intra-observer variations (SD = 0.2-0.6 mm).

Conclusion

The use of CBCT for daily image guidance in combination with standard mask fixation reduced systematic and random set-up errors of the vocal cords to <1 mm prior to the delivery of each fraction dose. Thus, this facilitates the high targeting precision required for a single vocal cord irradiation.     

Dosimetric characteristics of 6 and 10 MV unflattened photon beams

Purpose

To determine dosimetric properties of unflattened megavoltage photon beams.

Materials and methods

Dosimetric data including depth dose, profiles, output factors and phantom scatter factors from three different beam qualities provided by Elekta Precise linacs, operated with and without flattening filter were examined. Additional measurements of leaf transmission, leakage radiation and surface dose were performed. In flattening filter free (FFF) mode a 6-mm thick copper filter was placed into the beam to stabilize it.

Results

Depths of dose maxima for flattened and unflattened beams did not deviate by more than 2 mm and penumbral widths agreed within 1 mm. In FFF mode the collimator exchange effect was found to be on average 0.3% for rectangular fields. Between maximum and minimum field size head scatter factors of unflattened beams showed on average 40% and 56% less variation for 6 and 10 MV beams than conventional beams. Phantom scatter factors for FFF beams differed up to 4% from the published reference data. For field sizes smaller than 15 cm, surface doses relative to the dose at d_max increased for unflattened beams with maximum differences of 7% at 6 MV and 25% at 10 MV for a 5 × 5 cm² field. For a 30 × 30 cm² field, relative surface dose decreased by about 10% for FFF beams. Leaf transmission on the central axis was 0.3% and 0.4% lower for unflattened 6 and 10 MV beams, respectively. Leakage radiation was reduced by 52% for 6 MV and by 65% for 10 MV unflattened beams.

Conclusions

The results of the study were independently confirmed at two radiotherapy centres. Phantom scatter reference data need to be reconsidered for medical accelerators operated without a flattening filter.     

Functional image-based radiotherapy planning for non-small cell lung cancer: A simulation study

Background and purpose

To investigate the incorporation of data from single-photon emission computed tomography (SPECT) or hyperpolarized helium-3 magnetic resonance imaging (³He-MRI) into intensity-modulated radiotherapy (IMRT) planning for non-small cell lung cancer (NSCLC).

Material and methods

Seven scenarios were simulated that represent cases of NSCLC with significant functional lung defects. Two independent IMRT plans were produced for each scenario; one to minimise total lung volume receiving ?20 Gy (V₂₀), and the other to minimise only the functional lung volume receiving ?20 Gy (FV₂₀). Dose-volume characteristics and a plan quality index related to planning target volume coverage by the 95% isodose (V_PTV95/FV₂₀) were compared between anatomical and functional plans using the Wilcoxon signed ranks test.

Results

Compared to anatomical IMRT plans, functional planning reduced FV₂₀ (median 2.7%, range 0.6-3.5%, p = 0.02), and total lung V₂₀ (median 1.5%, 0.5-2.7%, p = 0.02), with a small reduction in mean functional lung dose (median 0.4 Gy, 0-0.7 Gy, p = 0.03). There were no significant differences in target volume coverage or organ-at-risk doses. Plan quality index was improved for functional plans (median increase 1.4, range 0-11.8, p = 0.02).

Conclusions

Statistically significant reductions in FV₂₀, V₂₀ and mean functional lung dose are possible when IMRT planning is supplemented by functional information derived from SPECT or ³He-MRI.     

Comparison of conventional radiotherapy and intensity-modulated radiotherapy for post-operative radiotherapy for primary extremity soft tissue sarcoma

Introduction

Doses in conventional radiotherapy for extremity soft tissue sarcoma (STS) potentially exceed normal tissue tolerances. This study compares 3D-conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) in optimising target volume coverage and minimising integral dose to organs-at-risk (OAR).

Methods and materials

Ten patients undergoing post-operative radiotherapy for extremity STS were assessed. PTV₁ was defined as tumour bed plus 5 cm superiorly/inferiorly and 3 cm circumferentially, PTV₂ was defined as 2 cm isotropically. OAR were defined as whole femur, neurovascular bundle, tissue corridor and normal tissue outside PTV₁. For each patient 2-phase 3D-CRT was compared to 2/3 field (2/3f) and 4/5 field (4/5f) IMRT with simultaneous integrated boost (SIB). The primary planning objective was to minimise femur and skin corridor dose. Volumetric analysis and conformity and heterogeneity indices were used for plan comparison.

Results

A planning protocol containing dose/volume constraints for target and OAR was defined. 4/5f IMRT showed greatest conformity and homogeneity. IMRT resulted in significantly lower femur V45 using 2/3f (p = 0.01) and 4/5f (p = 0.0009) than 3D-CRT. 4/5f IMRT resulted in significantly lower normal tissue V55 (p = 0.004) and maximum dose (p = 0.04) than 3D-CRT.

Conclusions

A reproducible set of planning guidelines and dose-volume constraints for 3D-CRT and IMRT planning for extremity sarcomas was devised. 4/5f IMRT with SIB resulted in better target coverage and significantly decreased OAR dose. Further evaluation of this technique within a clinical trial is recommended to demonstrate that the technical benefit of the more complex technique translates into patient-derived benefit by reducing late toxicity.     

Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment

Background

Tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are approved as treatment of non-small-cell lung cancer (NSCLC). Despite an initially impressive response to EGFR-TKIs, patients with an activating EGFR mutation invariably relapse. For these patients few treatment options are available after additional progression during or after chemotherapy. The aim of this study is to examine the effect of retreatment with an EGFR-TKI after a drug holiday.

Patients and methods

We retrospectively reviewed the medical records of 14 patients with stage IV NSCLC who progressed after long-term disease control with EGFR-TKI, who were subsequently treated with standard chemotherapy and at renewed progression retreated with EGFR-TKI.

Results

Fourteen patients (five male, nine female, median age 55 years (39-70 years) received retreatment with erlotinib. The median interval from the discontinuation of EGFR-TKI to the 2nd episode was 9.5 months (3-36 months). Before starting retreatment 36% (n = 5) had a T790M mutation. Retreatment resulted in 36% (n = 5) partial response, 50% stable disease (n = 7) and 14% progressive disease (n = 2). Among patients with a T790M mutation this number was two, one and two, respectively. Seven patients are still on therapy without signs of progression. Median follow up is 9 months (1.5-16+ months) and median PFS is 6.5 months (1-16+ months).

Conclusion

Our findings suggest that retreatment with erlotinib is an option for patients with NSCLC who initially benefited from previous EGFR-TKI treatment and progressed after standard cytotoxic chemotherapy.     

Double-scattered proton-based stereotactic body radiotherapy for stage I lung cancer: A dosimetric comparison with photon-based stereotactic body radiotherapy

Purpose

Stereotactic body radiotherapy (SBRT) has gained popularity in the treatment of early-stage non-small-cell lung cancer (NSCLC) because of its ability to deliver conformal radiation doses to small targets. However, photon-based SBRT (xSBRT) is associated with significant grade 3+ toxicities. In this study, we compare xSBRT treatment plans with proton-based SBRT (pSBRT) to determine whether dose to normal structures could be reduced if SBRT was delivered with protons.

Materials and methods

Eight patients with medically inoperable, peripherally located stage I NSCLC were treated with xSBRT to 48 Gy in 4 12-Gy fractions. These patients were retrospectively re-planned using the same treatment volumes with 3-dimensional conformal double-scatter proton therapy. A Wilcoxon paired test compared dosimetric parameters between the plans for each patient.

Results

Compared with xSBRT there was a dosimetric improvement with pSBRT for these volumes: lung V5 (median difference [MD] = 10.4%, p = 0.01); V10 (MD = 6.4%, p = 0.01); V20 (MD = 2.1%, p = 0.01); V40 (MD = 1.5%, p = 0.05); and mean lung dose (MD = 2.17 Gy, p = 0.01). There were also benefits (p = <0.05) in D0.1cm3 and D5cm3 with pSBRT to the heart, esophagus, and bronchus.

Conclusions

In a dosimetric comparison between photon and proton-based SBRT, protons resulted in lower doses to critical organs at risk and a smaller volume of non-targeted normal lung exposed to radiation (V5, V10, V20, and V40). The clinical significance and relevance of these dosimetric improvements remain unknown.     

Dose escalation with proton or photon radiation treatment for pancreatic cancer

Purpose

The purpose was to determine the optimal radiation therapy modality (three-dimensional conformal photon-radiation therapy [3DCRT], intensity-modulated photon-radiation therapy [IMRT], or passive-scattering proton therapy [PT]) for safe dose escalation (72 Gy) in pancreatic tumors in different positions relative to organs at risk (OAR) anatomy.

Methods and materials

A 3-cm pancreatic tumor was virtually translated every 5 mm over 5 cm laterally. We generated two plans for each of the three techniques (3DCRT, IMRT, and PT), one that adhered to target coverage objectives and another to meet OAR sparing constraints with best coverage. We evaluated distances between gross tumor volumes and isodoses and compared dose-volume histograms.

Results

IMRT was more conformal in higher gradient dose regions circumferentially, but tumor positions with anteriorly located small bowel benefited more from PT. 3DCRT plans resulted in inadequate target coverage. The V_15Gy (mean ± SD) were as follows for the IMRT and PT plans, respectively: stomach, 48% ± 4% vs 5% ± 3% (p < 0.0001); and small bowel, 61% ± 8% vs 9% ± 4% (p < 0.0001).

Conclusions

Our study showed that the optimal radiation therapy modality for safe dose escalation depends on pancreatic tumor position in relation to OAR anatomy.     

The influence of the use of CT-planning on the irradiated boost volume in breast conserving treatment

Background and purpose

The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials.

Patients and methods

Data from 1331 patients (?50 years) were analyzed with a reported boost volume from a simulation-based treatment plan (EORTC boost vs no boost trial, n = 922), and a CT-scan-based treatment plan (Young Boost Trial, n = 409) group. Tumour diameter, irradiation technique (photons vs electrons), lumpectomy size, and age were used as covariates.

Results

Median V_95% in the conventional simulation-based treatment plans was 99 cc (range 9-628) for photons and was 98 cc (13-651) for electrons, whereas in the CT-planned patients, these figures were 178 cc (37-2699) and 150 cc (43-1272), respectively. Multivariable analysis showed an association of the irradiated boost volume with tumour size (p < 0.0067), lumpectomy size (p < 0.0002), and boost technique (p < 0.0004). The use of a CT-scan for volume delineation and treatment planning remained significant (p < 0.0001).

Conclusions

The use of a CT-scan for delineation and treatment planning led to a significant increase of the irradiated boost volume by a factor of 1.5-1.8, compared to conventional simulator-based plans.     

Sequentially delivered boost plans are superior to simultaneously delivered plans in head and neck cancer when the boost volume is located further away from the parotid glands

Purpose

To find parameters that predict which head and neck patients benefit from a sequentially delivered boost treatment plan compared to a simultaneously delivered plan, with the aim to spare the salivary glands.

Methods and materials

We evaluated 50 recently treated head and neck cancer patients. Apart from the clinical plan with a sequentially (SEQ) given boost using an Intensity Modulated Radiotherapy Technique (IMRT), a simultaneous integrated boost (SIB) technique plan was constructed with the same beam set-up. The mean dose to the parotid glands was calculated and compared. The elective nodal areas were bilateral in all cases, with a boost on either one side or both sides of the neck.

Results

When the parotid gland volume and the Planning Target Volume (PTV) for the boost overlap there is on average a lower dose to the parotid gland with a SIB technique (−1.2 Gy), which is, however, not significant (p = 0.08).For all parotid glands with no boost PTV overlap, there is a benefit from a SEQ technique compared to a SIB technique for the gland evaluated (on average a 2.5 Gy lower dose to the parotid gland, p < 0.001). When the distance between gland and PTV is 0-1 cm, this difference is on average 0.8 Gy, for 1-2 cm distance 2.9 Gy and for glands with a distance greater than 2 cm, 3.3 Gy. When the lymph nodes on the evaluated side are also included in the boost PTV, however, this relationship between the distance and the gain of a SEQ seems less clear.

Conclusions

A sequentially delivered boost technique results in a better treatment plan for most cases, compared to a simultaneous integrated boost IMRT technique, if the boost PTV is more than 1 cm away from at least one parotid gland.     

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

Background and purpose

To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer.

Materials and methods

Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 × 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin.

Results

The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure.

Conclusion

Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.     

Influence of body mass index on outcome in advanced colorectal cancer patients receiving chemotherapy with or without targeted therapy

Purpose

Obesity is associated with an increased risk of development and recurrence of colorectal cancer. However, the role of obesity in advanced colorectal cancer (ACC) patients is unknown. We investigated the effect of body mass index (BMI) on overall survival (OS) in ACC patients receiving systemic treatment in two large phase III studies (CAIRO and CAIRO2).

Patients and methods

Treatment data were obtained and analysed from 796 ACC patients who were treated with chemotherapy in the CAIRO study, and from 730 ACC patients who were treated with chemotherapy plus targeted therapy in the CAIRO2 study. Baseline height and weight were used to assign patients to one of the following BMI categories: A (<18.5 kg/m²), B (18.5-24.9 kg/m²), C (25.0-29.9 kg/m²) and D (?30.0 kg/m²).

Results

In 796 patients of the CAIRO study a high BMI was associated with better median OS (8.0, 14.9, 18.4 and 19.5 months for BMI categories A, B, C, and D, respectively; P = 0.001), and was an independent prognostic factor for OS in a multivariate analysis. BMI was not associated with OS in 730 patients who participated in the CAIRO2 study, although a trend was observed.

Conclusions

These results show that BMI is an independent prognostic factor for survival in patients receiving chemotherapy, but not in patients receiving chemotherapy and targeted therapy. The possible decreased efficacy of bevacizumab in obese patients may explain this discrepant result. The role of BMI in patients receiving targeted therapy should be further tested.     

Dosimetry audit for a multi-centre IMRT head and neck trial

Background and purpose

PARSPORT was a multi-centre randomised trial in the UK which compared Intensity-Modulated Radiotherapy (IMRT) and conventional radiotherapy (CRT) for patients with head and neck cancer. The dosimetry audit goals were to verify the plan delivery in participating centres, ascertain what tolerances were suitable for head and neck IMRT trials and develop an IMRT credentialing program.

Materials and methods

Centres enrolling patients underwent rigorous quality assurance before joining the trial. Following this each centre was visited for a dosimetry audit, which consisted of treatment planning system tests, fluence verification films, combined field films and dose point measurements.

Results

Mean dose point measurements were made at six centres. For the primary planning target volume (PTV) the differences with the planned values for the IMRT and CRT arms were −0.6% (1.8% to −2.4%) and 0.7% (2.0% to −0.9%), respectively. Ninety-four percent of the IMRT fluence films for individual fields passed gamma criterion of 3%/3 mm and 75% of the films for combined fields passed gamma criterion 4%/3 mm (no significant difference between dynamic delivery and step and shoot delivery).

Conclusions

This audit suggests that a 3% tolerance could be applied for PTV point doses. For dose distributions tolerances of 3%/3 mm on individual fields and 4%/3 mm for combined fields are proposed for multi-centre head and neck IMRT trials.     

Accuracy requirements for head and neck intensity-modulated radiation therapy based on observed dose response of the major salivary glands

Background and Purpose

We estimated accuracy requirements for dose and position of the major salivary glands in head and neck intensity-modulated radiotherapy (IMRT) based on the dose response characteristics of the glands obtained by using the sigmoidal dose response model.

Materials and methods

Dose response of the parotid and submandibular salivary glands was determined for 25 head and neck cancer patients treated by IMRT. Individual salivary gland functions were assessed by scintigraphy before and 6 months after radiotherapy. Accuracy requirements were estimated by using the maximal slope of the fitted dose response model and average value of the dose gradients within the glands. In addition, systematic and random set-up errors were estimated for each patient by at least weekly portal imaging. We investigated the changes in the salivary gland mean doses (D_mean) that would have occurred without correction of patient positioning. This was done by shifting the planned isocenter according to the obtained systematic set-up error and by recalculating the dose distribution in treatment planning system (TPS).

Results

The maximal slope and D₅₀ values of the dose response model were −0.041 1/Gy and 30.4 Gy, respectively. The results suggested that spared fraction of individual salivary gland function can be estimated with an accuracy of ±10%, if actual D_mean of the gland is within ±2.4 Gy with the planned value. On the average, this was achieved with maximal systematic positional 3D shift of 3.0 mm for the parotid glands and 2.7 mm for the submandibular glands. The magnitude of systematic 1D set-up errors was 1.7 ± 1.3 mm (mean ± SD) while that of systematic 3D errors was 3.4 ± 1.6 mm. The SD of random set-up errors was 1.5 mm. The magnitude of D_mean shifts due to set-up errors was 1.5 ± 1.4 Gy. The steepness of dose gradients within the glands was 0.8 ± 0.5 Gy/mm in the most critical direction (toward the glands).

Conclusions

When substantial part of salivary gland function is intended to be spared in head and neck IMRT, narrow dosimetric and positional tolerances should be adopted for the major salivary glands due to steep dose response curve obtained for the glands.     

Dosimetric consequences of uncorrected setup errors in helical Tomotherapy treatments of breast-cancer patients

Background and purpose

The Tomotherapy Hi-Art II system allows acquisition of pre-treatment MVCT images to correct patient position. This work evaluates the dosimetric impact of uncorrected setup errors in breast-cancer radiation therapy.

Materials and methods

Breast-cancer patient-positioning errors were simulated by shifting the patient computed-tomography (CT) dataset relative to the planned photon fluence and re-computing the dose distributions. To properly evaluate the superficial region, film measurements were compared against the Tomotherapy treatment planning system (TPS) calculations. A simulation of the integrated dose distribution was performed to evaluate the setup error impact over the course of treatment.

Results

Significant dose differences were observed for 11-mm shifts in the anterolateral and 3-mm shifts in the posteromedial directions. The results of film measurements in the superficial region showed that the TPS overestimated the dose by 14% at a 1-mm depth, improving to 3% at depths ?5 mm. Significant dose reductions in PTV were observed in the dose distributions simulated over the course of treatment.

Conclusions

Tomotherapy’s rotational delivery provides sufficient photon fluence extending beyond the skin surface to allow an up to 7-mm uncorrected setup error in the anterolateral direction. However, the steep dose falloff that conforms to the lung surface leads to compromised dose distributions with uncorrected posteromedial shifts. Therefore, daily image guidance and consequent patient repositioning is warranted for breast-cancer patients.