The potential advantages of FDG PET/CT-based target volume delineation in radiotherapy planning of head and neck cancer

Purpose

This study investigated two fixed threshold methods to delineate the target volume using ¹⁸FDG PET/CT before and during a course of radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Materials and methods

Patients were enrolled into the study between March 2006 and May 2008. ¹⁸FDG PET/CT scans were carried out 72 h prior to the start of radiotherapy and then at 10, 44 and 66 Gy. Functional volumes were delineated according to the SUV Cut Off (SUVCO) (2.5, 3.0, 3.5, and 4.0 bwg/ml) and percentage of the SUVmax (30%, 35%, 40%, 45%, and 50%) thresholds. The background ¹⁸FDG uptake and the SUVmax within the volumes were also assessed.

Results

Primary and lymph node volumes for the eight patients significantly reduced with each increase in the delineation threshold (for example 2.5-3.0 bwg/ml SUVCO) compared to the baseline threshold at each imaging point. There was a significant reduction in the volume (p ? 0.0001-0.01) after 36 Gy compared to the 0 Gy by the SUVCO method. There was a negative correlation between the SUVmax within the primary and lymph node volumes and delivered radiation dose (p ? 0.0001-0.011) but no difference in the SUV within the background reference region. The volumes delineated by the PTSUVmax method increased with the increase in the delivered radiation dose after 36 Gy because the SUVmax within the region of interest used to define the edge of the volume was equal or less than the background ¹⁸FDG uptake and the software was unable to effectively differentiate between tumour and background uptake.

Conclusions

The changes in the target volumes delineated by the SUVCO method were less susceptible to background ¹⁸FDG uptake compared to those delineated by the PTSUVmax and may be more helpful in radiotherapy planning. The best method and threshold have still to be determined within institutions, both nationally and internationally.     

F-FDG PET bio-metabolic monitoring of neoadjuvant therapy effects in rectal cancer: Focus on nodal disease characteristics

Objective

To evaluate efficacy of ¹⁸F-FDG PET(CT) in the staging and re staging of patients with locally advanced rectal cancer, its potential role in predicting pathological response to neoadjuvant therapy.

Patients and methods

Patients with confirmed diagnosis of rectal cancer (T2-4 or N+) were prospectively studied with ¹⁸F-FDG PET before and after neoadjuvant therapy. Surgery was programmed 4-6 weeks after treatment followed by an expert histological analysis of the surgical specimen. Response to neoadjuvant treatment was assessed using two specific variables: difference in SUV (difSUV) pre/post-neoadjuvant treatment and response index (RI).

Results

A total of 64 patients were enrolled for pathological and bio-metabolic response assessment. Compared to cN0, cN+ patients had a higher SUV₁ mean value (6.5 vs. 7.6, p = 0.04) and ypN+ patients had higher SUV₂ mean values (2.4 vs 3.5, p = 0.06). difSUV values of ?4 was the most efficient diagnostic parameter (sensitivity = 45.8%, specificity = 86.2%, positive predictive value (PPV) = 73.3%, negative predictive value(NPV) = 65.7%). With an RI of 66.6%, the sensitivity was 38.5%, specificity = 81.5%, PPV = 66.6%, and NPV = 57.8%. Patients who experienced disease progression had an RI ? 66% and a difSUV ? 4.

Conclusion

¹⁸F-FDG PET has proven to be an accurate diagnostic technique for assessing rectal cancer response to neoadjuvant therapy. The results in terms of sensitivity, specificity, PPV and NPV were similar, if not superior, to those reported with other diagnostic imaging techniques.     

Comparison of (immuno-)fluorescence data with serial [F]Fmiso PET/CT imaging for assessment of chronic and acute hypoxia in head and neck cancers

Purpose

Both, acute and chronic hypoxia can have unfavorable impacts on tumor progression and therapy response. The aim of this study was to optimize a macroscopic technique for the quantification of acute and chronic hypoxia (Wang model assessment of serial [¹⁸F]Fmiso PET/CT imaging) by comparing with a microscopic technique [(immuno-)fluorescence staining in tumor cryosections].

Materials and methods

Tumor pieces from the human squamous cell carcinoma lines from the head and neck FaDu and CAL33 were xenografted into the hind leg of NMRI nu/nu mice. Tumor-bearing mice were placed on an in-house developed multi-point fixation system and subjected to two consecutive dynamic [¹⁸F]Fmiso PET/CTs within a 24 h interval. The Wang model was applied to SUV (standard uptake values) to quantify the fractions of acute and chronic hypoxia. Hypoxia subtypes were also assessed in vital tumor tissue of cryosections from the same tumors for (immuno-)fluorescence distributions of Hoechst 33342 (perfusion), pimonidazole (hypoxia), and CD31 (endothelium) using pattern recognition in microcirculatory supply units (defined as vital tumor tissue area supplied by a single microvessel).

Results

Using our multi-point fixation system, acceptable co-registration (registration errors ε ranged from 0.34 to 1.37) between serial PET/CT images within individual voxels was achieved. The Wang model consistently yielded higher fractions of acute hypoxia than the MCSU method. Through specific modification of the Wang model (Wang_mod), it was possible to reduce the fraction of acute hypoxia. However, there was no significant correlation between the fractions of acute hypoxia in individual tumors assessed by the Wang_mod model and the MCSU method for either tumor line (FaDu: r = 0.68, p = 0.21 and CAL33: r = 0.71, p = 0.18). This lack of correlation is most-likely due to the difference between the non-linear uptake of [¹⁸F]Fmiso and the spatial assessment of MCSUs.

Conclusions

Whether the Wang model can be used to predict radiation response after serial [¹⁸F]Fmiso PET imaging, needs to be confirmed in experimental and clinical studies.     

Influence of C-choline PET/CT on the treatment planning for salvage radiation therapy in patients with biochemical recurrence of prostate cancer

Background and purpose

The present study evaluates the incidence of ¹¹C-choline PET/CT positive findings in patients with recurrent prostate cancer referred for salvage radiotherapy (SRT) and the influence on the definition of the planning target volume (PTV).

Material and methods

Thirty-seven patients treated with radical prostatectomy and referred to SRT to the prostatic fossa because of biochemical relapse, were analysed retrospectively. All patients underwent ¹¹C-choline PET/CT before radiotherapy. The influence of PET/CT on the extent of the PTV was analysed. The median total follow up after SRT was 51.2 months.

Results

11/37 (30%) patients had a positive finding in the ¹¹C-choline PET/CT, 5 (13%) outside of the prostatic fossa (iliac lymph nodes), implicating an extension of the PTV. Patients with positive ¹¹C-choline PET/CT had a significant higher PSA value than patients with no pathologic uptake (p = 0.03). Overall, at the end of follow up 56% of the patients had a PSA ? 0.2 ng/ml and 44% had a biochemical relapse of prostate cancer.

Conclusions

¹¹C-choline PET/CT detects abnormalities outside of the prostatic fossa in 13% of patients referred for SRT because of biochemical relapse after radical prostatectomy, affecting the extent of the PTV. Prospective studies need to be implemented to evaluate the benefit of SRT with a PTV based on ¹¹C-choline PET/CT.     

Biologic correlates of F-FDG uptake on PET in pulmonary pleomorphic carcinoma

Background

Pulmonary pleomorphic carcinoma is a rare epithelial tumor, and little is also known about the information on the usefulness of 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography (PET). Therefore, we conducted the study including the underlying biologic analysis of ¹⁸F-FDG uptake.

Methods

Fifteen patients with pulmonary pleomorphic carcinoma who underwent ¹⁸F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); cell proliferation (Ki-67 labeling index); vascular endothelial growth factor (VEGF); microvessels (CD34); cell cycle control marker (p53); and apoptosis marker (bcl-2). These parameters were correlated with a control group of patients with other non-small cell lung cancer (NSCLC) (n = 33).

Results

The maximal standardized uptake value (SUV_max) of the primary tumors in 15 patients ranged from 6.1 to 26.8 (median 19.3). There were positive correlation between ¹⁸F-FDG uptake and Glut1 (p = 0.0016), Glut3 (p = 0.0080), VEGF (p = 0.0048), and microvessel density (MVD) (p = 0.0005). HIF-1α, p53 and bcl-2 showed no positive correlation with ¹⁸F-FDG uptake. ¹⁸F-FDG uptake, Glut1, Glut3, HIF-1α, VEGF and Ki-67 were significantly higher in patients with pulmonary pleomorphic carcinoma than those with other NSCLC.

Conclusion

¹⁸F-FDG uptake in pulmonary pleomorphic carcinoma is closely associated with the presence of glucose metabolism (Glut1 and Glut3) and angiogenesis (VEGF and MVD). The relationship between ¹⁸F-FDG uptake and these biomarkers may lead to a more rational use of PET scan in pulmonary pleomorphic carcinoma.     

Early assessment of treatment response in patients with AML using [F]FLT PET imaging

Assessment of treatment response in acute leukemia is routinely performed after therapy via bone marrow biopsy. We investigated the use of positron emission tomography (PET) for early assessment of treatment response in patients with acute myeloid leukemia (AML), using the proliferation marker 3′-deoxy-3′-[¹⁸F]fluoro-l-thymidine (FLT). Eight adult AML patients receiving induction chemotherapy underwent whole-body FLT PET/CT scans acquired at different time points during therapy. Patients who entered complete remission (CR) exhibited significantly lower FLT uptake in bone marrow than those patients with resistant disease (RD). In bone marrow, mean and maximum standardized uptake values were 0.8, 3.6 for CR and 1.6, 11.4 for RD, p < 0.001. FLT PET results for CR and RD patients were independent of assessment time point, suggesting that FLT PET scans acquired as early as 2 days after chemotherapy initiation may be predictive of clinical response. This pilot study suggests that FLT PET imaging during induction chemotherapy may serve as an early biomarker of treatment response in AML.     

Dosimetric predictors of asymptomatic heart valvular dysfunction following mediastinal irradiation for Hodgkin’s lymphoma

Purpose

To identify dose-heart-volume constraints that correlate with the risk of developing asymptomatic valvular defects (VD) in Hodgkin’s lymphoma (HL) patients treated with three-dimensional radiotherapy (RT).

Patients and methods

Fifty-six patients undergoing cytotoxic chemotherapy (CHT) and involved-field radiation treatment for HL were retrospectively analyzed. Electro-echocardiography was performed before CHT, after CHT, and after RT. For the entire heart, for right and left ventricle (RV, LV), right and left atrium (RA, LA) percentage of volume exceeding 5-30 Gy in increment of 5 Gy (V_x), and dosimetric parameters were calculated using 1.6 Gy fraction as reference. To evaluate clinical and dosimetric factors possibly associated with VD, univariate and multivariate logistic regression analyses were performed.

Results

At a median follow up of 70.5 months, 32.1% of patients developed VD (regurgitation and/or stenosis): 25.0% developed mitral, 5.4% developed aortic, and 14.3% tricuspid VD. In particular the percentage of LA exceeding 25 Gy (LA-V₂₅) and the percentage of LV exceeding 30 Gy (LV-V₃₀) correlated with mitral and aortic VD with an odds ratio (OR) of 5.7 (LA-V₂₅ > 63.0% vs. LA-V₂₅ ? 63.0%) and OR of 4.4 (LV-V₃₀ > 25% vs. LV-V₃₀ ? 25%), respectively. RV-V₃₀ correlated with tricuspid VD (OR = 7.2, RV-V₃₀ > 65% vs. RV-V₃₀ ? 65%).

Conclusion

LA-V₂₅, LV- and RV-V₃₀ prove to be predictors of asymptomatic alteration of valve functionality.     

Adaptive 18fluoro-2-deoxyglucose positron emission tomography/computed tomography-based target volume delineation in radiotherapy planning of head and neck cancer

Aims

This study investigated an adaptive threshold-based method to delineate the target volume using ¹⁸fluoro-2-deoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) before and during a course of radical radiotherapy or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Materials and methods

Ten patients were enrolled between March 2006 and May 2008. ¹⁸FDG PET/CT scans were carried out 72 h before the start of radiotherapy and then at three time points during radiotherapy (8-18, 36-50 and 66 Gy). Functional volumes were delineated using an adaptive iterative algorithm weighted according to the mean standard uptake value (SUV_mean) within the region of interest. The background ¹⁸FDG uptake, maximum standard uptake value (SUV_max) and SUV_mean within the volumes were assessed.

Results

There was no significant reduction in the primary target volumes defined by the adaptive threshold during radiotherapy. However, the SUV_max significantly reduced within the primary (P = 0.003-0.011) and lymph node (P < 0.0001) target volume at 36-50 and 36-66 Gy compared with 0 Gy. The SUV_mean was negatively correlated to radiation dose (P < 0.0001-0.014). The ratio between the background uptake of ¹⁸FDG and the SUV_mean significantly reduced for both the lymph node target volume at 36-50 Gy and the primary volume at 66 Gy. The lack of significant correlation between the defined volume and radiation dose was because the SUV_mean within the region of interest used to define the edge of the volume was equal to or less than the background ¹⁸FDG uptake and the software was unable to effectively differentiate between tumour and background uptake.

Conclusions

The adaptive threshold method may be of benefit when used to define the target volume before the start of radiotherapy. This method was not beneficial during radiotherapy because the software is not sensitive enough to distinguish tumour from background and define a volume. ¹⁸FDG PET/CT-guided volumes delineated by automatic adaptive thresholding methods should only be used for dose escalation with the pretreatment imaging.     

Diagnostic and staging impact of radiotherapy planning FDG-PET-CT in non-small-cell lung cancer

Background and purpose

To evaluate whether FDG-PET performed for radiotherapy (RT) planning can detect disease progression, compared with staging PET.

Materials and methods

Twenty-six patients with newly-diagnosed non-small-cell lung cancer underwent planning PET-CT for curative RT within 8 weeks (mean: 33 ± 14 days) of staging PET-CT. Progressive disease (PD) was defined as >25% increase in tumour size (transaxial) or volume, as delineated by SUV threshold of 2.5, or new sites (SUV > 2.5).

Results

The planning PET detected PD in 16 patients (61%), compared to four patients (15%) by CT component of PET-CT. The mean scan interval was longer in patients with progression: 40 ± 12 days, compared to 22 ± 11 days without progression. Planning PET detected PD in 13/17 (76%), 12/14 (86%) and 7/7 patients if the interval was ?4, 5 and 6 weeks, respectively, compared with 3/9 patients if interval <4 weeks. Planning PET detected PD in primary metabolic volume in seven patients, 20 new nodal sites in 12 new nodal stations and nine patients, five extra-nodal sites in five patients. This resulted in upstaging in nine patients (35%): stage IIIA in three, IIIB in three and IV in three.

Conclusions

RT-planning FDG-PET can provide incremental diagnostic information and may impact on staging in a significant number of patients.     

Accessing radiation response using hypoxia PET imaging and oxygen sensitive electrodes: A preclinical study

Purpose

Tumor hypoxia is a known cause of resistance to radiotherapy. The aim of this study was to investigate the prognostic value of hypoxia measured by ¹⁸F-fluoroazomycin arabinoside (¹⁸F-FAZA) PET or the Eppendorf oxygen electrode in a pre-clinical tumor model.

Material/methods

Pretreatment ¹⁸F-FAZA PET scans and blood sampling was conducted in 92 Female CDF1 mice with subcutaneous C3H mammary carcinomas grown in the right foot. Similarly, oxygenation status of 80 equivalent tumors was assessed using an invasive oxygen sensitive electrode. Tumors were then irradiated with a single dose of 55 Gy and local tumor control up to 90 days after the treatment was determined.

Results

A significant difference in local tumor control between “more hypoxic” or “less hypoxic” groups separated either by a median ¹⁸F-FAZA PET determined tumor-to-blood ratio (P = 0.007; hazard ratio, HR = 0.21 [95% CI: 0.06-0.74]), or the fraction of oxygen partial pressure (pO₂) values ?2.5 mmHg (P = 0.018; HR = 0.31 [95% CI: 0.11-0.87]), was found. Both assays showed that the more hypoxic tumors had significantly lower tumor control.

Conclusion

¹⁸F-FAZA PET analysis showed that pre treatment tumor hypoxia was prognostic of radiation response. Similar results were obtained when oxygenation status was assessed by the Eppendorf pO₂ Histograph. The results of this study support the role of ¹⁸F-FAZA as a non-invasive prognostic marker for tumor hypoxia.     

Interstitial brachytherapy using stereotactic implanted (125)iodine seeds for recurrent medulloblastoma

Aims

To evaluate the efficacy of interstitial brachytherapy using ¹²⁵iodine (¹²⁵I) seeds for the treatment of recurrent multimodal treated medulloblastoma.

Materials and methods

Between September 1989 and August 2009, 12 patients (female:male = 3:9, median age 19 years, range 7-55 years) with 23 recurrent medulloblastomas underwent interstitial brachytherapy using ¹²⁵I seeds. Before brachytherapy, all patients underwent microsurgical resection; six patients underwent a combined adjuvant treatment consisting of craniospinal irradiation and chemotherapy; three received craniospinal irradiation alone and two received chemotherapy alone. One patient was treated by surgery alone. The median tumour volume was 4.9 ml (range 0.4-44.2 ml), the median tumour surface dose 50 Gy (range 32-50 Gy) and the median implantation time 42 days (range 42-90 days). A median follow-up of 26 months was available (range 5-116 months).

Results

After brachytherapy, nine of 23 tumours (39%) presented a complete remission, nine (39%) a partial remission and five (22%) stable disease on magnetic resonance images. The neurological status improved in six patients and remained unchanged in four. Two patients deteriorated: one developed spinal metastasis and another a treatment-related adverse radiation effect. Ten patients died due to disseminated disease despite local tumour control. The median survival after treatment was 15 months (range 5-68 months).

Conclusions

Our results show a good response of recurrent medulloblastoma after interstitial brachytherapy. High rates of tumour remission were yielded with low rates of treatment-related morbidity. Thus, ¹²⁵I seed brachytherapy should be considered as a treatment option for recurrent medulloblastoma.     

Dose-volume histogram and dose-surface histogram analysis for skin reactions to carbon ion radiotherapy for bone and soft tissue sarcoma

Background and purpose

To evaluate the usefulness of the dose-volume histogram (DVH) and dose-surface histogram (DSH) as clinically relevant and available parameters that helped to identify bone and soft tissue sarcoma patients at risk of developing late skin reactions, including ulceration, when treated with carbon ion radiotherapy.

Materials and methods

Thirty-five patients with bone and soft tissue sarcoma treated with carbon ion beams were studied. The clinical skin reactions were evaluated. Some pretreatment variables were compared with the grade of late skin reactions.

Results

Average DVH and DSH were established in accordance with the grading of the skin reactions. Prescribed dose, the difference in depths between the skin surface and the proximal extent of the tumor, and some DVH/DSH parameters were correlated with late skin reaction (≧grade 3) according to univariate analysis. Furthermore, the area irradiated with over 60 GyE (S₆₀ > 20 cm²) on DSH was the most important factor by multivariate analysis.

Conclusions

The area irradiated with over 60 GyE (S₆₀ > 20 cm²) on DSH was found to be a parameter for use as a predictor of late skin reactions.     

Stereotactic radiotherapy for peripheral lung tumors: A comparison of volumetric modulated arc therapy with 3 other delivery techniques

Purpose

Volumetric modulated arc therapy (RapidArc) allows for fast delivery of stereotactic body radiotherapy (SBRT) delivery in stage I lung tumors. We compared dose distributions and delivery times between RapidArc and common delivery techniques in small tumors.

Methods

In 18 patients who completed RapidArc SBRT for tumors measuring <70 cm³, new treatment plans were generated using non-coplanar 3D conformal fields (conf-SBRT) and dynamic conformal arc radiotherapy (DCA). For 9 patients with tumors adjacent to the chest wall, co-planar intensity-modulated radiotherapy (IMRT) plans were also generated. PTV dose coverage, organs at risk (OAR) doses and treatment delivery times were assessed.

Results

RapidArc plans achieved a superior conformity index (CI) and lower V_45Gy to chest wall (p < 0.05) compared to all other techniques. RapidArc led to a small increase in V_5Gy to contralateral lung compared to conf-SBRT (4.4 ± 4% versus 1.2 ± 1.8%, p = 0.011). For other OAR, RapidArc and conf-SBRT plans were comparable, and both were superior to DCA plans. Delivery of a 7.5 Gy-fraction required 3.9 min (RapidArc), 11.6 min (conf-SBRT), and 12 min (IMRT).

Conclusions

In stage I lung tumors measuring <70 cm³, RapidArc plans achieved both the highest dose conformity and shortest delivery times.     

Endorectal balloon reduces anorectal doses in post-prostatectomy intensity-modulated radiotherapy

Background and purpose

To investigate the effect of an endorectal balloon (ERB) on anal wall (Awall) and rectal wall (Rwall) doses in high-dose post-prostatectomy intensity-modulated radiotherapy (IMRT).

Materials and methods

For 20 patients, referred for salvage IMRT after prostatectomy for prostate cancer, two planning CT-scans were performed: one with and one without an air-filled ERB. A planning target volume (PTV) was defined, using international guidelines. Furthermore, the Awall and Rwall were delineated. In both the scans, IMRT plans were generated with a prescribed dose of 70 Gy. The mean dose (D_mean), maximum dose, minimum dose, and volumes exposed to doses ranging from ?20 to ?70 Gy (V₂₀-V₇₀) to the Awall and Rwall were calculated. Finally, inner Rwall surface areas exposed to doses ranging from ?20 to ?70 Gy (A₂₀-A₇₀) were calculated. Dose-parameters were compared between plans with and without ERB.

Results

All Awall parameters, except V₇₀, were significantly reduced by the ERB with an overall D_mean reduction of 6 Gy. Absolute reductions in dose-volume parameters varied from 5% to 11%. Significantly reduced Rwall V₃₀, V₄₀, and A₄₀ were observed with ERB, irrespective of the target volume size.

Conclusion

ERB application significantly reduces Awall and to a lesser degree Rwall doses in high-dose post-prostatectomy IMRT.     

Prognostic impact of postoperative, pre-irradiation F-fluoroethyl-l-tyrosine uptake in glioblastoma patients treated with radiochemotherapy

Background and purpose

Resection is considered as essential for the efficacy of modern adjuvant treatment of glioblastoma multiforme (GBM). Previous studies have indicated that amino acid PET is more specific than contrast enhancement on MRI for detecting residual tumor tissue after surgery. In a prospective study we investigated the prognostic impact of postoperative tumor volume and tumor/brain ratios (TBR) in PET using O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET) in comparison with MRI.

Materials and methods

Forty-four patients with GBM were investigated by FET PET and MRI after surgery. Tumor volume in FET PET with a tumor/brain ratio (TBR) > 1.6 and a TBR > 2, mean and maximum TBR and gadolinium contrast-enhancement on MRI (Gd-volume) were determined. Thereafter patients received a fractionated radiotherapy with concomitant temozolomide (RCX). The median follow-up was 15.4 (3-35) months. The prognostic value of postoperative residual tumor volume in FET PET, TBR_mean, TBR_max and Gd-volume was evaluated using Kaplan-Maier estimates for disease-free survival (DFS) and overall survival (OS).

Results

Postoperative tumor volume in FET PET had a significant independent influence on OS and DFS (OS 20.0 vs. 6.9 months; DFS 9.6 vs. 5.1 months, p < 0.001; cut-off 25 ml). Similar results were observed when a TBR ? 2 (cut-off 10 ml) was used to define the tumor volume in ¹⁸F-FET PET. The TBR_mean and TBR_max of FET uptake had a significant influence on DFS (p < 0.05). Gd-volume in MRI had significant effect on OS and DFS in the univariate analysis. No independent significant influence in OS or DFS could be observed for Gd-volume in MRI.

Conclusions

Our data indicate that the tumor volume in FET PET after surgery of GBM has a strong prognostic impact for these patients. FET PET appears to be helpful to determine the residual tumor volume after surgery of GBM and may serve as a valuable tool for optimal planning of radiation treatment.     

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.     

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.     

Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): Planning considerations and early toxicity

Purpose

To study the dosimetric predictors of early clinical toxicity following SBRT in patients with lung tumors and planning target volumes (PTV) exceeding 80 cm³.

Methods

Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc™) were assessed. All were either unfit or refused to undergo surgery or chemoradiotherapy. PTV planning objectives were as used in the ROSEL study protocol. Clinical toxicity was scored using Common Toxicity Criteria AE4.0. Lung volumes receiving 5, 10, 15, and 20 Gy (V₅, V₁₀, V₁₅ and V₂₀) and mean lung dose were assessed and correlated to symptomatic radiation pneumonitis (RP).

Results

Median age, age-adjusted Charlson-comorbidity score and PTV size were 74, 7.5 and 137 cm³, respectively. At a median follow-up of 12.8 months, 8 deaths were recorded: 5 arising from comorbidity, 2 were potentially treatment-related and 1 had local recurrence. RP was reported in 5 patients (grade 2 in 3 and grade 3 in 2). All RP occurred in plans without a high priority optimization objective on contralateral lung. Acute RP was best predicted by contralateral lung V₅ (p < 0.0001).

Conclusion

After SBRT using RapidArc in lung tumors >80 cm³, the contralateral lung V₅ best predicts RP. Limiting contralateral lung V₅ to <26% may reduce acute toxicity.     

F-fluorocholine PET-guided target volume delineation techniques for partial prostate re-irradiation in local recurrent prostate cancer

Background and purpose

We evaluate the contribution of ¹⁸F-choline PET/CT in the delineation of gross tumour volume (GTV) in local recurrent prostate cancer after initial irradiation using various PET image segmentation techniques.

Materials and methods

Seventeen patients with local-only recurrent prostate cancer (median = 5.7 years) after initial irradiation were included in the study. Rebiopsies were performed in 10 patients that confirmed the local recurrence. Following injection of 300 MBq of ¹⁸F-fluorocholine, dynamic PET frames (3 min each) were reconstructed from the list-mode acquisition. Five PET image segmentation techniques were used to delineate the ¹⁸F-choline-based GTVs. These included manual delineation of contours (GTV_man) by two teams consisting of a radiation oncologist and a nuclear medicine physician each, a fixed threshold of 40% and 50% of the maximum signal intensity (GTV_40% and GTV_50%), signal-to-background ratio-based adaptive thresholding (GTV_SBR), and a region growing (GTV_RG) algorithm. Geographic mismatches between the GTVs were also assessed using overlap analysis.

Results

Inter-observer variability for manual delineation of GTVs was high but not statistically significant (p = 0.459). In addition, the volumes and shapes of GTVs delineated using semi-automated techniques were significantly higher than those of GTVs defined manually.

Conclusions

Semi-automated segmentation techniques for ¹⁸F-choline PET-guided GTV delineation resulted in substantially higher GTVs compared to manual delineation and might replace the latter for determination of recurrent prostate cancer for partial prostate re-irradiation. The selection of the most appropriate segmentation algorithm still needs to be determined.     

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.