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.     

A comparison of optic nerve dosimetry in craniospinal radiotherapy planned and treated with conventional and intensity modulated techniques

Background and purpose

Some CNS tumours present leptomeningeal dissemination. Craniospinal radiotherapy is complex and recurrences may occur at sites of target volume underdosage. IMRT, being highly conformal to the target, could theoretically underdose the optic nerves if they are not specifically targeted leading to optic nerve recurrences. We analyzed optic nerve dosimetry when they are not specifically targeted.

Materials and methods

We designed 3D-conformal and tomotherapy plans for our last five patients treated to the craniospinal axis, not including the optic nerves in the target volume. We analyzed the dose delivered to the optic nerves, to the anterior and posterior half of the optic nerves, and to a theoretical optic nerve-PTV.

Results

The dose delivered to the optic nerves was similar for both plans in all patients (V95% close to 100%) except one in whom tomotherapy considerably underdosed the anterior optic nerves. The dose to the optic nerve-PTV was lower with tomotherapy in all patients.

Conclusion

Despite not intentionally targeting the optic nerves, the dose to the optic nerves with IMRT was similar to 3D-conformal plans in most cases but left no margin for setup error. In individual cases the anterior half of the optic nerves could be significantly underdosed.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

Time course of hypothalamic-pituitary deficiency in adults receiving cranial radiotherapy for primary extrasellar brain tumors

Background

No longitudinal data on hypothalamic-pituitary (HP) function are available in patients who had received cranial radiation therapy (CRT) for primary extrasellar brain tumors (PBT).

Purpose

To investigate the effects of CRT on HP function in adults with PBT.

Patients and methods

Twenty-six adults irradiated for PBT and six CRT naive controls were studied. CRT was delivered with 6 MV X-ray by a linear accelerator (2 Gy fraction schedule). Gross Tumor Volume (GTV) excluded the HP region that was contoured on the planning CT. Median dose to the HP region was 41.8 Gy (IQR: 30.7-49.8).

Results

All controls maintained normal HP function. Hypopituitarism developed in 38% of CRT patients (GH deficiency 29%, ACTH 22%, TSH 14%, gonadotropin 4%, no abnormal prolactin level or diabetes insipidus). All HP failures occurred within 32 months after CRT.

Conclusions

Adults undergoing CRT for PBT are at increased risk for HP dysfunction within 3 years from CRT. Endocrine surveillance is recommended also in adults patients exposed to CRT for primary brain tumors distant from HP region.     

Comparison of gating around end-expiration and end-inspiration in radiotherapy for lung cancer

Purpose

To evaluate the advantages and disadvantages of gating around end-expiration and end-inspiration.

Materials and methods

We created five irradiation protocols to treat 15 patients with lung cancer. They were non-gated irradiation (protocol 1, P1), amplitude-based gating around end-expiration (P2) and end-inspiration (P3), and phase-based gating around end-expiration (P4) and end-inspiration (P5). We compared the lung dosimetric parameters and the treatment time.

Results

Compared to P2, in P3 the mean lung dose was reduced by 0.5 ± 0.4 Gy, V20 by 1.2 ± 0.9%, V10 by 1.4 ± 0.8%, and V5 by 1.5 ± 0.9% (p < 0.01). There was no statistically significant difference in these parameters between P4 and P5. At a dose rate of 600 monitor units/min (MUs/min), the average treatment time required for 100 MUs was 10, 26, 64, 33, and 33 s, respectively, for P1, P2, P3, P4, and P5.

Conclusions

With amplitude-based gating, gating around end-inspiration (P3) produced a greater decrease in the lung dose, however, the treatment time was longest among the four gated protocols. There was no significant difference between the two phase-based gating protocols (P4 and P5) with respect to the radiation dose to the lungs and the treatment time.     

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

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 50 Gy 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.     

Brain-sparing holo-cranial radiotherapy: a unique application of helical tomotherapy

Aims

Diffuse and extensive involvement of the scalp/skull by malignancy mandates holo-cranial radiotherapy with the aim to deliver homogeneous doses to the planning target volume (PTV) while minimising the dose to surrounding organs at risk (OARs). Previously described techniques result in significant heterogeneity, suboptimal coverage or poor conformity and need complicated beam matching. Here we report our preliminary experience of planning and delivery of brain-sparing holo-cranial radiotherapy with helical tomotherapy.

Materials and methods

Three patients with extensive involvement of the scalp/skull by malignancy were planned and treated with image-guided intensity-modulated radiation therapy on helical tomotherapy. The plan evaluation was carried out using standardised dose metrics.

Results

Helical tomotherapy achieved highly conformal and homogeneous dose distributions with substantial OAR sparing in all three patients. The volume of PTV receiving ≥95% of prescribed dose (V_95%) was ≥98% in all three patients. The mean (standard deviation) homogeneity index and conformity index was 0.046 (0.006) and 0.783 (0.035), respectively. The mean dose to the brain parenchyma outside the PTV was 17.32 Gy (74%), 28.76 Gy (63.9%) and 26.7 Gy (59.3%) for the three patients. The mean (standard deviation) monitor units and beam-on time was 6939 (985) and 8.10 (1.137) min, respectively. Overall the treatment was very well tolerated with no significant acute toxicity. Early follow-up evaluation revealed a good clinicoradiological response and the absence of local disease progression with no significant sequelae, implying successful application of the treatment paradigm.

Conclusion

Helical tomotherapy is ideally suited for brain-sparing holo-cranial radiotherapy with its exceptional ability of tangential beam delivery resulting in highly conformal and homogenous dose distribution across large, complex target volumes with substantial OAR sparing.     

The relationship between external beam radiotherapy dose and chronic urinary dysfunction - A methodological critique

Purpose

To perform a methodological critique of the literature evaluating the relationship between external beam radiotherapy dose/volume parameters and chronic urinary dysfunction to determine why consistent associations between dose and dysfunction have not been found.

Methods and materials

The radiotherapy literature was reviewed using various electronic medical search engines with appropriate keywords and MeSH headings. Inclusion criteria comprised of; English language articles, published between 1999 and June 2009, incorporating megavoltage external beam photons in standard-sized daily fraction. A methodological critique was then performed, evaluating the factors affected in the quantification of radiotherapy dose and chronic urinary dysfunction.

Results

Nine of 22 eligible studies successfully identified a clinically and statistically significant relationship between dose and dysfunction. Accurate estimations of external beam radiotherapy dose were compromised by the frequent use of dosimetric variables which are poor surrogates for the dose received by the lower urinary tract tissue and do not incorporate the effect of daily variations in isocentre and bladder position. The precise categorization of chronic urinary dysfunction was obscured by reliance on subjective and aggregated toxicity metrics which vary over time.

Conclusions

A high-level evidence-base for the relationship between external beam radiotherapy dose and chronic urinary dysfunction does not currently exist. The quantification of the actual external beam dose delivered to the functionally important tissues using dose accumulation strategies and the use of objective measures of individual manifestations of urinary dysfunction will assist in the identification of robust relationships between dose and urinary dysfunction for application in widespread clinical practice.     

3D dose delivery verification using repeated cone-beam imaging and EPID dosimetry for stereotactic body radiotherapy of non-small cell lung cancer

Purpose

To implement a 3D dose verification procedure, based on in-room cone-beam CT imaging and portal dosimetry, for lung cancer patients treated with stereotactic body radiotherapy (SBRT).

Materials and methods

MV cone-beam CT scans were made for patient positioning and calibrated for dose calculation purposes. Prior to treatment, the treatment fields were captured using a calibrated electronic portal imaging device (EPID). A Monte Carlo dose reconstruction model was used to estimate the 3D dose delivered to the patient inside the cone-beam CT images. The planned and delivered dose distributions were compared for 4 patients and 10 treatment fractions using dose-volume histograms and gamma analysis.

Results

The gamma analysis showed a good agreement between the planned and delivered dose distributions for patients without changes in anatomy. The delivered mean dose per fraction inside the target volume deviated on average 1.1 ± 1.4% from the planned dose. For the critical organs, only minor differences were observed between the reconstructed and planned dose.

Conclusions

A method was presented that allows verification of the dose delivered in 3D for lung cancer patients treated with SBRT. The procedure is independent of the treatment planning system and uses in-room MV cone-beam CT imaging and portal dosimetry.     

An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry

Purpose

To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment.

Methods and materials

The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated.

Results and conclusions

Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.     

A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer

Purpose

The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy (HypoRT) combined with sequential chemotherapy in locally advanced non-small cell lung cancer (NSCLC).

Materials and methods

A total of 34 patients with stage III NSCLC were enrolled. All patients received accelerated HypoRT (initially 50 Gy/20 fractions, then a fraction dose of 3 Gy) using three-dimensional conformal radiation therapy (3D-CRT), omitting elective nodal irradiation (ENI), to a total dose of 65-68 Gy. All patients received two cycles of induction chemotherapy; 1-2 cycles of consolidation chemotherapy were given to 31 patients. The primary outcome measure was a profile of radiation toxicity. The secondary endpoints included overall survival (OS), progression-free survival (PFS), locoregional PFS (LR-PFS) and the pattern of initial failure.

Results

Radiation toxicity was minimal. The median and 3-year OS, PFS were 19.0 months, 32.1%; 10.0 months, 29.8%, respectively. The 1-, 2-, and 3-year LR-PFS were 69.6%, 60.9% and 60.9%, respectively. No patient experienced isolated elective nodal failure as the first site of failure.

Conclusion

This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC.     

Parotid gland as a risk organ in whole brain radiotherapy

Background and purpose

Since the introduction of CT-based simulation for use in whole brain radiotherapy (WBRT), we have observed that a large volume of the parotid glands is included in the radiation fields. The purpose of this study is to analyze the dose-volume statistics of the parotid glands in patients undergoing WBRT.

Materials and methods

Thirty-two patients received WBRT using CT-based simulation with bilateral two-field arrangement. Daily fraction was 3 Gy with total dose of 30 Gy in 2 weeks. We analyzed the radiation dose from WBRT to the parotid glands.

Results

Average of the mean parotid dose was 17.5 Gy (range, 10.5-26.2) for both glands. Mean parotid doses ?20 and ?25 Gy were observed in 22 (34.4%) and 4 (6.3%) of 64 individual glands. The numbers of patients with a mean parotid dose of both glands ?20 Gy and ?25 Gy were 12 (37.5%) and 1 (3.1%), respectively.

Conclusions

Mean parotid dose was variable in patients with WBRT. According to the parotid dose and combined potential risk factors, parotid glands can be regarded as a risk organ in WBRT for improvement of patient quality of life.     

Image-guided intensity-modulated radiotherapy (IG-IMRT) for biliary adenocarcinomas: Initial clinical results

Purpose

Biliary tract lesions are comparatively rare neoplasms, with ambiguous indications for radiotherapy. The specific aim of this study was to report the clinical results of a single-institution biliary tract series treated with modern radiotherapeutic techniques, and detail results using both conventional and image-guided intensity-modulated radiation therapy (IG-IMRT).

Methods and materials

From 2001 to 2005, 24 patients with primary adenocarcinoma of the biliary tract (gallbladder and extrahepatic bile ducts) were treated by IG-IMRT. To compare outcomes, data from a sequential series of 24 patients treated between 1995 and 2005 with conventional radiotherapy (CRT) techniques were collected as a comparator set. Demographic and treatment parameters were collected. Endpoints analyzed included treatment-related acute toxicity and survival.

Results

Median estimated survival for all patients completing treatment was 13.9 months. A statistically significant higher mean dose was given to patients receiving IG-IMRT compared to CRT, 59 vs. 48 Gy. IG-IMRT and CRT cohorts had a median survival of 17.6 and 9.0 months, respectively. Surgical resection was associated with improved survival. Two patients (4%) experienced an RTOG acute toxicity score > 2. The most commonly reported GI toxicities (?RTOG Grade 2) were nausea or diarrhea requiring oral medication, experienced by 46% of patients.

Conclusion

This series presents the first clinical outcomes of biliary tract cancers treated with IG-IMRT. In comparison to a cohort of patients treated by conventional radiation techniques, IG-IMRT was feasible for biliary tract tumors, warranting further investigation in prospective clinical trials.     

Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review

Purpose

Stereotactic radiotherapy (SRT) of brain metastases is considered effective when long-term local control is obtained. However, dose-effect data are scarce. We, therefore, performed a systematic literature search to assess the evidence concerning the relation of SRT dose and local control probability.

Methods and materials

A search was performed for papers describing patients treated with SRT for brain metastases, published from 1990 through 2009, in the electronic databases Medline (Pubmed) and Embase. We selected only papers reporting actuarial local control probability, in which a fixed dose had been prescribed and in which the size of the metastases was given. Series with SRT as a boost after whole brain irradiation (WBI) or with SRT after surgery were excluded. From the selected papers we extracted data on dose, local control rates and necrosis rates. Biological effective doses of the linear-quadratic-cubic model, using an α/β of 12 Gy (BED₁₂), were calculated and a dose-response curve was constructed.

Results

Eleven papers fulfilled the selection criteria for further analysis. Six-month local control rates were higher than 80% in almost all the series irrespective of dose. Twelve-month local control rates, however, varied and were higher than 80%, higher than 60% and lower than 50% with single doses of ?21 Gy, ?18 Gy and ?15 Gy, respectively, and 70% or higher with fractionated SRT (FSRT). A BED₁₂ of at least 40 Gy was associated with a twelve-month local control rate of 70% or more.

Conclusion

Local control after single fraction SRT is highly dependent upon dose and is high (>80%) after 21 Gy or more, but low (<50%) after 15 Gy or less. We conclude that SRT for brain metastases should preferably be applied with a BED₁₂ of at least 40 Gy corresponding with a single fraction of 20 Gy, two fractions of 11.6 Gy or three fractions of 8.5 Gy.     

Dosimetric evolution of the breast electron boost target using 3D ultrasound imaging

Purpose

To investigate the effect of treatment planning, patient setup, and interfraction motion errors on the delivered dose for external beam electron boosts for postoperative early stage breast cancer patients.

Methods and materials

For 5 patients, 10-15 Gy was prescribed and administered via a conventionally defined electron boost treatment field - no dose distribution was calculated. Two computed tomography (CT) data sets were acquired on an average of 47 days apart. Using Monte Carlo techniques the clinically defined electron beams were reconstructed on CT1 and CT2, and a dosimetric comparison between the two data sets was made. Additionally, 3D ultrasound (US) imaging was performed to monitor interfraction motion. 3D US images were acquired concurrently with the CT images, as well as prior to each boost fraction in the treatment room. Taking into account interfraction motion, the dose to the clinical target volume (CTV) was calculated.

Results

Based on conventionally determined treatment fields the CT1-based CTV D95 averaged 49% (range 12-89%) of the prescribed dose. Representing setup errors, the CT2-based CTV D95 averaged 47% (range 16-91%) of the prescribed dose. Considering interfraction motion, the average radial displacement was 11 mm, and the resulting CTV D95 was further reduced in 2/5 patients.

Conclusions

Poor initial coverage at the time of planning is exacerbated by breast mobility and interfraction tumour bed motion, increasing the uncertainty in the delivered dose.     

Arsenic Trioxide in Recurrent Urothelial Cancer: A Cancer and Leukemia Group B Phase II Trial (CALGB 99903)

Background

Arsenic trioxide is highly active in patients with acute promyelocytic leukemia. There are also preclinical data to suggest that this drug might be active in nonhematopoietic malignancies, and transitional cell carcinoma cell lines are particularly sensitive to this agent.

Patients and Methods

Twelve evaluable patients with metastatic urothelial cancer were treated with arsenic trioxide in a phase II trial conducted by the Cancer and Leukemia Group B. Eligible patients were required to have measurable urothelial cancer and a maximum of 1 previous chemotherapy regimen. Arsenic trioxide was given at a dose of 0.3 mg/kg daily for 5 days every 28 days.

Results

No major responses were observed; 4 patients achieved stable disease. The median survival was 6.5 months (95% CI, 3.9-13.4 months). The most commonly observed toxicities included fatigue and malaise, anemia, nausea, emesis, and constipation.

Conclusion

Arsenic trioxide at this dose and schedule does not have significant activity in previously treated urothelial cancer and has substantial toxicity in this patient population.