Michaela Benassi

Analysis of Salivary Flow and Dose-Volume Modeling of Complication Incidence in Patients With Head-and-Neck Cancer Receiving Intensity-Modulated Radiotherapy

PURPOSE To investigate dose-volume effects of salivary flow and the functional recovery over time, using salivary function data and different models of normal tissue complication probability (NTCP). METHODS AND MATERIALS A total of 59 patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT) were analyzed in the present study. The toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale and salivary flows, both unstimulated (USF) and stimulated (SSF). The assessments were done before radiotherapy (RT) and at 3, 6, 12, 18, and 24 months after RT. Grade 3 toxicity was the primary endpoint. Analyses of toxicity incidence at 3, 6, and 12 months after RT were performed by both the Lyman-Kutcher-Burman (LKB) and relative seriality (S) models. RESULTS A significant correlation was found between the incidence of Grade 3 toxicity and the incidence of patients with a reduction in SSF to <25% of the pre-RT value. Better correlations resulted between the RTOG toxicity score and the dosimetric parameters, compared with USF/SSF. The TD(50), assessed by the LKB model, was 21.4, 27.8, and 41.6 Gy at 3, 6, and 12 months after RT, respectively. The TD(50), assessed by the S model, was 20.0, 26.3, and 40.0 Gy at 3, 6, and 12 months after RT, respectively. CONCLUSION Recovery of salivary gland function vs. time after RT took place mostly within 1 year after RT. The RTOG Grade 3 was a reliable score to perform the NTCP modeling. The choice of NTCP model had no influence on the accuracy of predictions.

Cone-beam computed tomography in hypofractionated stereotactic radiotherapy for brain metastases

BackgroundTo assess interfraction translational and rotational setup errors, in patients treated with image-guded hypofractionated stereotactic radiotherapy, immobilized by a thermoplastic mask and a bite-block and positioned using stereotactic coordinates.Methods37 patients with 47 brain metastases were treated with hypofractionated stererotactic radiotherapy. All patients were immobilized with a combination of a thermoplastic mask and a bite-block fixed to a stereotactic frame support. Daily cone-beam CT scans were acquired for every patient before the treatment session and were matched online with planning CT images, for 3D image registration. The mean value and standard deviation of all translational (X, Y, Z) and rotational errors (θx, θy, θz) were calculated for the matching results of bone matching algorithm.ResultsA total of 194 CBCT scans were analyzed. Mean +/- standard deviation of translational errors (X, Y, Z) were respectively 0.5 +/- 1.6 mm (range -5.7 and 5.9 mm) in X; 0.4 +/- 2.7 mm (range -8.2 and 12.1 mm) in Y; 0.4 +/- 1.9 mm (range -7.0 and 14 mm) in Z; median and 90th percentile were respectively within 0.5 mm and 2.4 mm in X, 0.3 mm and 3.2 mm in Y, 0.3 mm and 2.2 mm in Z. Mean +/- standard deviation of rotational errors (θx, θy, θz) were respectively 0.0 degrees+/- 1.3 degrees (θx) (range -6.0 degrees and 3.1 degrees); -0.1 degrees +/- 1.1 degrees (θy) (range -3.0 degrees and 2.4 degrees); -0.6 degrees +/- 1.4 degrees (θz) (range -5.0 degrees and 3.3 degrees). Median and 90th percentile of rotational errors were respectively within 0.1 degrees and 1.4 degrees (θx), 0.0 degrees and 1.2 degrees (θy), 0.0 degrees and 0.9 degrees (θz). Mean +/- SD of 3D vector was 3.1 +/- 2.1 mm (range 0.3 and 14.9 mm); median and 90th percentile of 3D vector was within 2.7 mm and 5.1 mm.ConclusionsHypofractionated stereotactic radiotherapy have the significant limitation of uncertainty in interfraction repeatability of the patient setup; image-guided radiotherapy using cone-beam computed tomography improves the accuracy of the treatment delivery reducing set-up uncertainty, giving the possibility of 3-dimensional anatomic informations in the treatment position.

Acute and Late Toxicity after Three-Dimensional Conformal Image-Guided Radiotherapy for Localized Prostate Cancer

We evaluated the clinical impact of a high definition micro-multileaf collimator and a linac-integrated cone-beam computed tomography in 142 patients treated with conformal radiotherapy for localized prostate cancer to a total dose of 76 Gy. Details on treatment toxicity and tumour control were collected. The 3 years biochemical relapse-free survival was 90%. Acute and late gastrointestinal toxicities were low (3-year actuarial late toxicity of 11.2%). Acute genitourinary toxicity was relatively high, the 3-year actuarial genitourinary late toxicity was 12%. Conformal image-guided radiotherapy for localized prostate cancer leads to low rates of late toxicity with a high rate of tumor control.

Image-guided-radiotherapy retreatment of spine metastasis: a case report and radiobiological evaluation.

Aims and background The present case report describes vertebral metastasis retreatment using kilovoltage cone-beam computed tomography (CBCT) for setup error correction, in order to improve target irradiation and prevent spinal cord toxicity. We evaluated the feasibility of the second radiation therapy course on the overlapping treatment volume. Methods and study design A patient with metastatic kidney cancer, previously treated to the tenth dorsal vertebra with conventional radiation planning (21 Gy; 3 × 7 Gy), underwent retreatment. In order to deliver 30 Gy (15 × 2 Gy) to the target volume with the second irradiation, we evaluated the residual dose that could be received by the spinal cord. We calculated the biologically effective dose according to the linear-quadratic model, using an α/β ratio of 2 Gy. A 3-dimensional conformal plan was generated; CBCT imaging was used to ensure accurate repositioning. Results A total of 15 CBCT scans were performed; the mean setup corrections in the lateral, longitudinal and vertical directions were 3.38 mm (SD 2.09; range, −0.2 mm ÷ 7.6 mm), 2.13 mm (SD 3.38; range, −5.9 mm ÷ 6 mm), and −1.28 mm (SD 2.02; range, −7.1 mm ÷ 0.3 mm), respectively. Conclusion Image-guided radiotherapy is an alternative approach for the retreatment of spine tumors; it ensures accurate patient setup correction and high-precision treatment delivery, which are required for target volumes very close to critical structures. Free full text available at www.tumorionline.it

COMPARISON OF DIFFERENT EXTERNAL BEAM TREATMENT TECHNIQUES TO DELIVER HIGH-DOSE IRRADIATION TO LOCAL RECURRENT RECTAL CARCINOMA

Aims and background Treatment of local-regional recurrent rectal carcinoma is a challenging problem, and local control may be dose dependent; doses should probably exceed 60 Gy. Our aim was to verify the possibility to deliver 66 Gy to the target, but less than 35 Gy to the small bowel, comparing different 3D irradiation techniques, in a selected group of patients. Methods Five patients with local recurrent rectal carcinoma were selected as representative of different presentations of the disease. Gross tumor volume and clinical target volume were defined [by RS]. Tumors ranged between 182 and 540 cc, and small bowel volumes between 748 and 1050 cc. A three-field technique, coplanar multiple fields, noncoplanar fields and a proton beam were compared using dose volume histograms. A positive result was scored when ≥90% of the target received the prescribed dose with no more than 5% of the small bowel receiving more than 35 Gy. Doses were escalated in steps of 2 Gy from 60 to 66 Gy. Results The number of plans fitting the constraints were 7/19, 11/19, 18/19 for doses of 66 Gy, 64 Gy and 62 Gy, respectively. The stage of the tumor did not seem to correlate with the possibility to homogeneously cover the target with the prescribed dose. Conclusions Simple coplanar and complex coplanar techniques (up to six fields), positioning the patient in a prone position with dislocation of the bowel, seem to be the best solutions to treat almost all of the patients with doses of 64 Gy. Where higher doses are concerned, it is not possible to suggest a “standard” solution. More personalized techniques have to be tested to define the best option.

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3–4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0–1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0–1, Odds Ratio 25.8, p 0.049. AJCC grade 0–1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

Optimal scheduling of hypofractionated radiotherapy for localized prostate cancer: A systematic review and metanalysis of randomized clinical trials

PURPOSE We sought to determine the optimal hypofractionated regimens of moderately hypofractionated (HFRT) versus conventionally fractionated (CFRT) external beam radiotherapy for localized prostate cancer (LPCA), having as primary endpoints the 5-year biochemical failure (BF) and late gastrointestinal (GI) and genitourinary (GU) toxicity. METHODS AND MATERIALS We performed a systematic literature review of the Medline and National Library of Medicine databases according to the PRISMA guidelines. Only phase III trials of CFRT versus moderate HFRT for LPCa, reporting 5-year BF and/or minimum 3-year late ≥G2 toxicity rates were considered. RESULTS A total of 11 manuscripts reporting the outcomes of 8145 patients gathered from 9 randomized trials met the eligibility criteria. No significant difference between CFRT and HFRT was found in any of the investigated outcome measures. 80%, 15% and 29% isolevel curves for freedom from BF (FFBF), GI and GU toxicity, respectively, resulting from grouping the median values of all endpoints, were calculated as a function of both total dose (Dtot) and dose per fraction (d). Trials using fractionation schedules (d × n) lying above the FFBF and below toxicity isolevels are expected to produce the best therapeutic ratio. CONCLUSIONS Our analysis indicates an optimal therapeutic window within which Dtot, d and n can be safely adjusted. Owing to both the risks of uncertainty due to inclusion of trials with d up to 3.5 Gy, and the exploitation of different cell killing mechanisms associated to larger d, the extrapolation to extremely hypo-fractionated regimens is not warranted.

Technical solutions to reduce mediastinal irradiation in young patients undergoing treatment for lymphomas: Preliminary experience

This study aims at optimizing treatment planning in young patients affected by lymphoma (Stage II to III) by using an inclined board (IB) that allows reducing doses to the organs at risk. We evaluated 19 young patients affected by stage I to III lymphomas, referred to our Department for consolidation radiotherapy (RT) treatment on the mediastinum. Patients underwent 2 planning computed tomography (CT) scans performed in different positions: flat standard position and inclined position. A direct comparison between the different treatment plans was carried out analyzing dosimetric parameters obtained from dose-volume histograms generated for each plan. Comparison was performed to evaluate the sparing obtained on breast and heart. Dosimetric evaluation was performed for the following organs at risk (OARs): mammary glands, lungs, and heart. A statistically significant advantage was reported for V5, V20, and V30 for the breast when using the inclined board. A similar result was obtained for V5 and V10 on the heart. No advantage was observed in lung doses. The use of a simple device, such as an inclined board, allows the optimization of treatment plan, especially in young female patients, by ensuring a significant reduction of the dose delivered to breast and heart.