Dose-response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy

Purpose

To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT).

Materials and methods

A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n = 21) or pulmonary metastases (n = 54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n = 29) or three fractions of 12.5 Gy to 65% (n = 40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/β ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ? grade II SWOG were fitted using NTCP models.

Results

Eleven patients developed RP grade II. With an average MLD of 10.3 ± 5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5 ± 4.3 Gy and 9.9 ± 5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V_2.5-V₅₀) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses.

Conclusions

The MLD and V_2.5-V₅₀ of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.     

A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy

Background and purpose

The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [¹⁸F]FLT PET imaging.

Materials and methods

We have developed an IMRT planning methodology to incorporate functional PET imaging using [¹⁸F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ? 4; 4 > SUV3 ? 3; and 3 > SUV2 ? 2. Dose objectives were set to reduce bone marrow volume that received 10 (V₁₀) and 20 (V₂₀) Gy.

Results

Active bone marrow regions identified by [¹⁸F]FLT with an SUV ? 2, SUV ? 3, and SUV ? 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V₁₀, and V₂₀ were achieved without clinically significant changes to PTV or OAR doses.

Conclusions

Incorporation of [¹⁸F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.     

Unilateral radiotherapy for tonsil cancer: Potential dose distribution optimization with a simple two-field intensity-modulated radiation therapy beam arrangement

Background and purpose

To evaluate the feasibility and dosimetric optimization potential of a unilateral two-field intensity-modulated radiotherapy (IMRT) technique in the curative treatment of lateralized tonsil cancer.

Materials and methods

Six patients with lateralized tonsillar carcinoma were treated unilaterally with a two-field IMRT technique (oblique-anterior and oblique-posterior fields, with or without collimator and couch rotation). Alternative IMRT plans using seven non-opposed coplanar fields were compared with the two-field plans for each patient.

Results

Planning target volume (PTV) coverage was excellent with the two-field technique, using a relatively low number of monitor units (MU) (median, 441; range, 309-550). Dose constraints were respected for all organs at risk (OAR). Mean doses to contralateral parotid and submandibular glands were 3.9 and 17.7 Gy, respectively. Seven-field IMRT provided similar PTV coverage, with statistically significant better dose homogeneity and conformality. However, the mean delivered dose to the contralateral parotid (3.9 vs. 9.0 Gy, p = 0.001) as well as the mean number of MU (437 vs. 814, p = 0.002) and consequently machine time were lower with two-field IMRT.

Conclusions

Unilateral two-field IMRT is a simple and feasible technique providing excellent tumor coverage and optimal OAR sparing while reducing the number of MU and treatment time.     

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

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 42.4 Gy to the whole breast and an additional 10.08 Gy 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 (V_49.9Gy ? 99%) and DEV (V_49.9Gy ? 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 1 year, 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 3.28 Gy. While resource utilization was greater, overall treatment time was reduced.     

Endorectal balloons in the post prostatectomy setting: Do gains in stability lead to more predictable dosimetry?

Purpose

To perform a comparative study assessing potential benefits of endorectal-balloons (ERB) in post-prostatectomy patients.

Method and materials

Ten retrospective post-prostatectomy patients treated without ERB and ten prospective patients treated with the ERB in situ were recruited. All patients received IMRT and IGRT using kilovoltage cone-beam computed tomography (kVCBCT). kVCBCT datasets were registered to the planning dataset, recontoured and the original plan recalculated on the kVCBCTs to recreate anatomical conditions during treatment. The imaging, structure and dose data were imported into in-house software for the assessment of geometric variation and cumulative equivalent uniform dose (EUD) in the two groups.

Results

The difference in location (ΔCOV) for the bladder between planning and each CBCT was similar for each group. The range of mean ΔCOV for the rectum was 0.15–0.58 cm and 0.15–0.59 cm for the non-ERB and ERB groups. For superior-CTV and inferior-CTV the difference between planned and delivered D_95% (mean ± SD) for the non-ERB group was 2.1 ± 6.0 Gy and −0.04 ± 0.20 Gy. While for the ERB group the difference in D_95% was 8.7 ± 12.6 Gy and 0.003 ± 0.104 Gy.

Conclusions

The use of ERBs in the post-prostatectomy setting did improve geometric reproducibility of the target and surrounding normal tissues, however no improvement in dosimetric stability was observed for the margins employed.     

Does atlas-based autosegmentation of neck levels require subsequent manual contour editing to avoid risk of severe target underdosage? A dosimetric analysis

Background and purpose

To investigate the dosimetric impact of not editing auto-contours of the elective neck and organs at risk (OAR), generated with atlas-based autosegmentation (ABAS) (Elekta software) for head and neck cancer patients.

Materials and methods

For nine patients ABAS auto-contours and auto-contours edited by two observers were available. Based on the non-edited auto-contours clinically acceptable IMRT plans were constructed (designated ‘ABAS plans’). These plans were then evaluated for the two edited structure sets, by quantifying the percentage of the neck-PTV receiving more than 95% of the prescribed dose (V₉₅) and the near-minimum dose (D₉₉) in the neck PTV. Dice coefficients and mean contour distances were calculated to quantify the similarity of ABAS auto-contours with the structure sets edited by observer 1 and observer 2. To study the dosimetric importance of editing OAR auto-contours a new IMRT plan was generated for each patient-observer combination, based on the observer’s edited CTV and the non-edited salivary gland auto-contours. For each plan mean doses for the non-edited glands were compared with doses for the same glands edited by the observer.

Results

For both observers, edited neck CTVs were larger than ABAS auto-contours (p ? 0.04), by a mean of 8.7%. When evaluating ABAS plans on the PTVs of the edited structure sets, V₉₅ reduced by 7.2% ± 5.4% (1 SD) (p < 0.03). The mean reduction in D₉₉ was 14.2 Gy (range 1-54 Gy). Even for Dice coefficients >0.8 and mean contour distances <1 mm, reductions in D₉₉ up to 11 Gy were observed. For treatment plans based on observer PTVs and non-edited auto-contoured salivary glands, the mean doses in the edited glands differed by only −0.6 Gy ± 1.0 Gy (p = 0.06).

Conclusions

Editing of auto-contoured neck CTVs generated by ABAS is required to avoid large underdosages in target volumes. Often used similarity measures for evaluation of auto-contouring algorithms, such as dice coefficients, do not predict well for expected PTV underdose. Editing of salivary glands is less important as mean doses achieved for non-edited glands predict well for edited structures.     

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

Introduction

To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT).

Materials and methods

From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years.

Results

Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V₁₂₀ (urethral volume receiving ?120% of the prescribed HDR-B dose) was associated with acute (P = .047) and late ? grade 2 GU toxicities (P = .049).

Conclusions

Late grades 3 and 4 GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V₁₂₀ on GU toxicity should be validated in further studies.     

Is there a role for endorectal balloons in prostate radiotherapy? A systematic review

Background and purpose

Endorectal balloons (ERBs) are being used in prostate radiotherapy for prostate immobilization and rectal wall (Rwall) sparing. Some of their aspects, however, have been questioned, like patient’s tolerance and their value in modern high-precision radiotherapy. This paper gives an overview of published data concerning ERB application in prostate radiotherapy.

Materials and methods

Systematic literature review based on PubMed/MEDLINE database searches.

Results

Overall, ERBs are tolerated well, although patients with pre-existing anorectal disease have an increased risk of developing ERB-related toxicity. Planning studies show reduced Rwall and anal wall (Awall) doses with ERB application. Clinical data, however, are scarce, as only one study shows reduced late rectal damage. There is no consensus about the immobilizing properties of ERBs and it is recommended to use additional set-up and correction protocols, especially because there are potential pitfalls.

Conclusion

ERBs seem well-tolerated and in planning studies reduce anorectal wall doses. This may lead to reduced anorectal toxicity, although clinical studies are warranted to confirm this hypothesis and to further investigate the immobilizing properties of ERBs, preferably in combination with advanced techniques for position verification.     

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.     

Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer

Purpose

To demonstrate the theoretical feasibility of [¹¹C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPL’s) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV).

Methods and materials

Twelve men with intracapsular prostate carcinoma were imaged with [¹¹C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB_IMRT) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delineation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans.

Results

[¹¹C]Acetate was used to delineate the IPL’s of all 12 patients. With every patient the TCP was increased with SIB_IMRT without increasing the NTCP of the bladder or rectum. The probability of uncomplicated control (PUC) was increased on average by 28% with the SIB_IMRT treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV.

Conclusions

Our study indicates that [¹¹C]acetate can be used to define the IPL’s and in combination with SIB_IMRT the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [¹¹C]acetate PET for biological dose planning in prostate cancer.     

Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease

Purpose

To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease.

Material/methods

We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n = 13) or with IMRT alone (n = 4). Seventeen patients were treated in recurrent disease after surgery (n = 11) or with radiotherapy alone (n = 6). Median total dose to the boost volume (PTV2) was 66 Gy (range, 72-54) with 2 Gy per fraction using an integrated boost concept. Median dose to target volume (PTV1) was 54 Gy in 1.8 Gy.

Results

Local control was 35% (12/34) and overall survival 74% (25/34) after a median follow-up of 4.5 years. Actuarial local control was 79%, 55% and 27% after 1, 2 and 5 years, respectively. Local control was significantly higher in patients treated for primary tumors (p < 0.03) and in total doses >60 Gy (p < 0.01). Actuarial overall survival was 97%, 91% and 70% after 1, 2 and 5 years, respectively.

Conclusion

These data demonstrate that local control after IMRT is higher in patients treated for primary tumors and using higher radiation doses. Therefore, we recommend radiotherapy as part of initial treatment in sacral chordoma.     

The importance of patient characteristics for the prediction of radiation-induced lung toxicity

Purpose

Extensive research has led to the identification of numerous dosimetric parameters as well as patient characteristics, associated with lung toxicity, but their clinical usefulness remains largely unknown. We investigated the predictive value of patient characteristics in combination with established dosimetric parameters.

Patients and methods

Data from 438 lung cancer patients treated with (chemo)radiation were used. Lung toxicity was scored using the Common Toxicity Criteria version 3.0. A multivariate model as well as two single parameter models, including either V₂₀ or MLD, was built. Performance of the models was expressed as the AUC (Area Under the Curve).

Results

The mean MLD was 13.5 Gy (SD 4.5 Gy), while the mean V₂₀ was 21.0% (SD 7.3%). Univariate models with V₂₀ or MLD both yielded an AUC of 0.47. The final multivariate model, which included WHO-performance status, smoking status, forced expiratory volume (FEV₁), age and MLD, yielded an AUC of 0.62 (95% CI: 0.55-0.69).

Conclusions

Within the range of radiation doses used in our clinic, dosimetric parameters play a less important role than patient characteristics for the prediction of lung toxicity. Future research should focus more on patient-related factors, as opposed to dosimetric parameters, in order to identify patients at high risk for developing radiation-induced lung toxicity more accurately.     

Postmastectomy intensity modulated radiation therapy following immediate expander-implant reconstruction

Background/purpose

To evaluate radiation plans of patients undergoing mastectomy with immediate expander-implant reconstruction followed by postmastectomy radiation therapy (PMRT).

Materials/methods

We identified 41 patients from June 2004 to May 2007 who underwent mastectomy, immediate expander-implant reconstruction, and PMRT with intensity-modulated radiation therapy. We assessed chest wall (CW) coverage and volume of heart and lung irradiated.

Results

In 73% of patients, all CW borders were adequately covered, and in 22%, all but 1 border were adequately covered. The total lung V₂₀ was <20% in 39/41 patients. The mean lung V₂₀ was 13% (range, 3-23%), and the mean heart D_mean was 2.81 Gy (range, 0.53-9.60 Gy). In patients with left-sided lesions without internal mammary nodes (IMNs) treatment (n = 22), the mean lung V₂₀ was 12.6% and the mean heart D_mean was 3.90 Gy, and in the patient with IMN treatment, the lung V₂₀ was 18% and heart D_mean was 8.04 Gy. For right-sided lesions without IMN treatment (n = 12), the mean lung V₂₀ was 12.4% and the mean heart D_mean was 0.90 Gy, and in patients with IMN treatment (n = 6), these numbers were 17.8% and 1.76 Gy. At a median follow-up of 29 months, the 30-month actuarial local control was 97%.

Conclusions

In women undergoing immediate expander-implant reconstruction, PMRT can achieve excellent local control with acceptable heart and lung doses. These results can be achieved even when the IMN are being treated, although doses to the heart and lungs will be higher.     

Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer

Purpose

To investigate the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography (¹⁸F-FMISO PET/CT)-guided intensity-modulated radiotherapy (IMRT) in dose escalation to attack the hypoxic volume of a tumor mass without increasing the normal tissue dose in head and neck cancer patients.

Materials and methods

Eight consecutive head and neck cancer patients underwent ¹⁸F-FMISO PET/CT simulation. Hypoxic tumor volume (HTV) was defined using a tumor-to-cerebellum ratio (T/C) of 1.3 as the threshold for ¹⁸F-FMISO PET/CT. Dose-escalation plans for treating HTVs using ¹⁸F-FMISO PET/CT-guided IMRT were performed for these patients. The standard plan was 72 Gy to the gross tumor volume (GTV) administered as 30 daily fractions of 2.4 Gy. In biologically optimized IMRT plans, the daily dose to the HTV ranged from 2.6 to 3.6 Gy. Dose-volume histograms (DVHs) were generated as part of each plan, and the results of planning were analyzed.

Results

Dose-escalation IMRT plans, delivering 30 daily doses of 2.6 Gy (total of 78 Gy) to the HTVs without increases in normal tissue doses, were feasible for six patients. Further acceptable dose escalation on HTV depended primarily on the primary tumor site and the extent of disease.

Conclusions

It was possible to dose escalate the HTV radiation to 78 Gy in six of eight head and neck cancer patients using ¹⁸F-FMISO PET/CT-guided IMRT.     

Inter-clinician variability in making dosimetric decisions in pediatric treatment: A balance between efficacy and late effects

Purpose

To investigate variability of clinical target volume (CTV) delineation and deviations according to doses delivered in normal tissue for abdominal tumor irradiation in children.

Material and methods

For a case of nephroblastoma six French pediatric radiation oncologists outlined post-operative CTV, on the same dosimetric CT scan according to the International Society for Pediatric Oncology 2001 protocol. On a reference CTV and organs at risk (OAR), we performed dosimetric planning with the constraints as 25.2 Gy for CTV, V_{20 max} to 50% for liver, V₁₂ <15% for kidney. Data were analyzed with Aquilab^© software.

Results

Final CTVs showed inter-clinician variability: 44.85-120.78 cm³. The recommended liver doses were not respected in four cases: V₂₀ from 74% to 88% of the volume; for kidney, in two cases: V₁₂ of 17.6% and 25%, respectively. For vertebral bodies, no deviations were noted.

Conclusion

Variability not only affected CTV delineation but also dose distribution to OAR with different compromises. This practice training demonstrates the hudge lack of data about correlation between dose, volume and risk of late effects in pediatric radiotherapy. We intend to record prospectively the dose/volume histogram of each OAR in a national database in order to characterize late effects occurring in relation to treatment modalities.