A novel QA phantom based on scintillating fiber ribbons with implementation of 2D dose tomography for small-field radiotherapy.

PURPOSE: To develop a novel instrument for real-time quality assurance (QA) procedures in radiotherapy. The system implements a scintillation-based phantom and associated signal acquisition and processing modules and aims to monitor two-dimensional (2D) dose distributions of small fields. MATERIALS AND METHODS: For the proposed phantom, we have designed and realized a prototype implementing six high-resolution tissue-equivalent scintillating fiber ribbons stacked with in-plane 30° rotated orientations from each other. Each ribbon output is coupled to a silicon photodiode linear array (with an element pitch of 400 µm) to detect scintillating signal, which represents the projected irradiation profile perpendicular to the ribbon's orientation. For the system providing six acquired projected dose profiles at different orientations, we have developed a two-step signal processing method to perform 2D dose reconstruction. The first step is to determine irradiation field geometry parameters using a tomographic geometry approach, and the second one is to perform specific penumbra estimation. The QA system prototype has been tested on a Novalis TrueBeam STX with a 6-MV photon beam for small elliptic fields defined by 5- and 10-mm cone collimators and for 10 × 10- and 20 × 10-mm2 rectangular fields defined by the micro-multileaf collimator. Gamma index analysis using EBT3 films as reference has been carried out with tight 2%-dose-difference (DD)/700-µm-distance-to-agreement (DTA) as well as 1%-DD/1-mm-DTA criteria for evaluating the system performances. The testing also includes an evaluation of the proposed two-step field reconstruction method in comparison with two conventional methods: filtered back projection (FBP) and simultaneous iterative reconstruction technique (SIRT). RESULTS: The reconstructed 2D dose distributions have gamma index pass rates higher than 95% for all the tested configurations as compared with EBT3 film measurements with both 2%-DD/700-µm-DTA and 1%-DD/1-mm criteria. 2D global gamma analysis shows that the two-step and FBP radiation field reconstruction methods systematically outperform the SIRT approach. Moreover, higher gamma index success rates are obtained with the two-step method than with FBP in the case of the fields defined with the stereotactic cones. CONCLUSIONS: The proposed small-field QA system makes a use of six water-equivalent scintillating detectors (fiber ribbons) to acquire dose distribution. The developed two-step signal processing method performs tomographic 2D dose reconstruction. A system prototype has been built and tested using hospital facilities with small rectangular and elliptic fields. Testing results show 2D reconstructed dose distributions with high accuracy and resolution. Such a system could potentially be an alternative approach to film dosimetry for small-field QA, which is still widely used as reference in clinical practice.

Tissue dose estimation after extravasation of 177Lu-DOTATATE.

BACKGROUND: Extravasation of radiopharmaceuticals used for vectorized internal radiotherapy can lead to severe tissue damage (van der Pol et al., Eur J Nucl Med Mol Imaging 44:1234-1243, 2017). Clinical management of these extravasations requires the preliminary estimation of the dose distribution in the extravasation area. Data are scarce regarding the dose estimation in the literature. This work presents a methodology for estimating the dose distribution after an extravasation occurred in September 2017, in the arm of a patient during a 7.4-GBq infusion of Lutathera ® (AAA). METHODS: A local quantification procedure initially developed for renal dosimetry was used. A calibration factor was determined and verified by phantom study. Extravasation volume of interest and its variation in time were determined using 4 whole body (WB) planar acquisitions performed at 2 h (T2h), 5 h (T5h), 20 h (T20h), and 26 h (T26h) after the beginning of the infusion and three SPECT/CT thoracic acquisitions at T5h, T20h, and T26h. For better estimation of initial extravasation volume, 3 volumes were defined on SPECT images using a 3D activity threshold. Cumulated activities and associated absorbed doses (D1, D2, D3) were calculated in the 3 volumes using the MIRD formalism. RESULTS: Volumes estimated using 3D threshold were V1 = 1000 mL, V2 =400 mL, and V3 =180 mL. Cumulated activities were evaluated using a monoexponential fit on activities calculated on SPECT images. Estimated local absorbed doses in V1, V2, and V3 were D1 = 2.3 Gy, D2 = 4.1 Gy, and D3 = 6.8 Gy. Evolution in time of local activity in the extravasation area was consistent with an effective local half-life (Teff) of 2.3 h. CONCLUSIONS: Rapid local dose estimation was permitted thanks to knowledge of the calibration factor determined previous to accidental extravasation. Lutathera® lymphatic drainage was quick in the arm (Teff = 2.3h). Estimated doses were in the lower range of deterministic effects and far under soft tissue necrosis threshold. Thus, no surgical rinse was proposed. The patient did not show any clinical consequence of the extravasation.

Fan-Beam Based Virtual Fluoroscopy for Navigated Catheterization in Interventional Radiology.

Personalized medicine implies reducing invasiveness of therapeutic procedures. Although interventional radiology proved a very interesting alternative to surgical procedures, it still raises concerns due to the irradiation dose received by the medical team (and by the patient). We propose a novel concept allowing to reduce very significantly the irradiation dose during the phases where tools inserted in the patient have to be tracked with respect to previously acquired images. This implies inserting a miniaturized X-ray detector in the tip of the tools, and reducing the dose by a "rotating collimator". We demonstrate that real-time processing of the signals allows accurate localization of the tip of the tools, with a dose reduction of at least ten times.

Prospective evaluation of a specific technique of sexual function preservation in external beam radiotherapy for prostate cancer.

OBJECTIVE: Sexual preservation is an important issue in the treatment of localized prostate cancer. A technique of irradiation was developed to better preserve this function and has been evaluated. METHODS: Eleven patients, with no erectile dysfunction (ED), were treated with daily IMRT-IGRT (total dose: 76-78 Gy). The pudendal arteries, penile bulb and cavernous body were delineated on the planning CT scan. The doses to these structures (with a 5 mm margin) were optimized to be as low as possible. The erectile function was documented using IIEF-5 scores at baseline, 6 months, 1 and 2 years. No ED was defined by an IIEF5 ≥ 20/25, a mild ED by an IIEF5 score of 17-19 and an important ED by a score <17. RESULTS: The mean age was 68.4 years. At the median follow-up of 36 months, there was no biochemical relapse. Before RT, the mean IIEF5 score in all 11 patients was 23.4 (range, 20-25). At 6, 12, 18 and 24 months after RT, the mean IIEF scores were 21.2 (14-25), 21.3 (14-25), 21.8 (16-25) and 21.8 (16-25), respectively. At 2 years, 8 patients (72.7%) had no ED and 2 patients (18.2%) experienced a mild ED. The only patient with an important ED had a medical treatment and recovered a satisfactory IIEF score from 16 to 24. CONCLUSION: The results of this technique of optimisation for sexual preservation are encouraging. Despite a mean age close to 70 years at the time of treatment, 90.9% of the patients had no to mild ED at 2 years. This rate increases at 100% with medical treatment. Advances in knowledge: Dose optimization on sexual organs is possible and could decrease the ED rates.

Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.

PURPOSE: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. METHODS AND MATERIALS: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. RESULTS: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. CONCLUSIONS: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

Dosimetric implications of an injection of hyaluronic acid for preserving the rectal wall in prostate stereotactic body radiation therapy.

PURPOSE: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose-volume histogram, and the prostate-rectum separation was measured at 7 levels of the prostate on the center line of the organ. RESULTS: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). CONCLUSIONS: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

Targeting head and neck cancer stem cells to overcome resistance to photon and carbon ion radiation.

Although promising new radiation therapy techniques such as hadrontherapy are currently being evaluated in the treatment of head and neck malignancies, local control of head and neck squamous cell carcinoma (HNSCC) remains low. Here, we investigated the involvement of cancer stem-like cells (CSCs) in a radioresistant HNSCC cell line (SQ20B). Stem-like cells SQ20B/SidePopulation(SP)/CD44(+)/ALDH(high) were more resistant to both photon and carbon ion irradiation compared with non-CSCs. This was confirmed by a BrdU labeling experiment, which suggests that CSCs were able to proliferate and to induce tumorigenicity after irradiation. SQ20B/SP/CD44(+)/ALDH(high) were capable of an extended G2/M arrest phase in response to photon or carbon ion irradiation compared with non-CSCs. Moreover, our data strongly suggest that resistance of CSCs may result from an imbalance between exacerbated self-renewal and proliferative capacities and the decrease in apoptotic cell death triggering. In order to modulate these processes, two targeted pharmacological strategies were tested. Firstly, UCN-01, a checkpoint kinase (Chk1) inhibitor, induced the relapse of G2/M arrest and radiosensitization of SQ20B-CSCs. Secondly, all-trans retinoic acid (ATRA) resulted in an inhibition of ALDH activity, and induction of the differentiation and radiosensitization of SQ20B/SP/CD44(+)/ALDH(high) cells. The combination of ATRA and UCN-01 treatments with irradiation drastically decreased the surviving fraction at 2Gy of SQ20B-CSCs from 0.85 to 0.38 after photon irradiation, and from 0.45 to 0.21 in response to carbon ions. Taken together, our results suggest that the combination of UCN-01 and ATRA represent a promising pharmacological-targeted strategy that significantly sensitizes CSCs to photon or carbon ion radiation.

Prostate hypofractionated radiation therapy: injection of hyaluronic acid to better preserve the rectal wall.

PURPOSE: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. METHODS AND MATERIALS: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). RESULTS: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. CONCLUSIONS: The injection of HA significantly limited radiation doses to the rectal wall.

Evaluation of the respiratory prostate motion with four-dimensional computed tomography scan acquisitions using three implanted markers.

BACKGROUND AND PURPOSE: During the irradiation of the prostate cancer, it is crucial to take into account the possible displacements in defining the planning target volume. The objective of this study was to specifically analyze the respiratory-induced prostate motion using a four-dimensional CT scan (4DCT). MATERIALS AND METHODS: Ten patients have been treated for prostate cancer in the supine position and with three implanted gold markers; they underwent a 4DCT using a GE LightSpeed16 CT scan (slice thickness 2.5mm). This acquisition was divided into 10 phases over the respiratory cycle using the Advantage4D software. For each phase, digitally-reconstructed radiographs (DRRs) were created at 0° and 90° with the view of the markers. The coordinates of each marker center were generated from the scan isocenter. The motion amplitude was: visually analyzed on the dynamic 4DCT sequences and then more precisely calculated by comparing the marker coordinates on the 10 scans. RESULTS: There was not any difficulty in defining the coordinates of the markers on each series. No prostate motion was observed on a simple visual analysis of the dynamic 4DCT sequences. After a more specific analysis, using the coordinates of the fiducials on the 10 phases, the prostate motion remained below 1mm in all directions, except for the cranio-caudal, where it was undetectable (thereby below the slice thickness of 2.5mm). CONCLUSIONS: To our knowledge, this is the first study that evaluates the respiratory-induced prostate motion, using a 4DCT scan. Even if important prostate displacement can occur during the prostate treatment, because of the bladder or rectum filling, in the present study no respiratory-induced prostate motion was observed.

Radiobiologic parameters and local effect model predictions for head-and-neck squamous cell carcinomas exposed to high linear energy transfer ions.

PURPOSE: To establish the radiobiologic parameters of head-and-neck squamous cell carcinomas (HNSCC) in response to ion irradiation with various linear energy transfer (LET) values and to evaluate the relevance of the local effect model (LEM) in HNSCC. METHODS AND MATERIALS: Cell survival curves were established in radiosensitive SCC61 and radioresistant SQ20B cell lines irradiated with [33.6 and 184 keV/n] carbon, [302 keV/n] argon, and X-rays. The results of ion experiments were confronted to LEM predictions. RESULTS: The relative biologic efficiency ranged from 1.5 to 4.2 for SCC61 and 2.1 to 2.8 for SQ20B cells. Fixing an arbitrary D(0) parameter, which characterized survival to X-ray at high doses (>10 Gy), gave unsatisfying LEM predictions for both cell lines. For D(0) = 10 Gy, the error on survival fraction at 2 Gy amounted to a factor of 10 for [184 keV/n] carbon in SCC61 cells. We showed that the slope (s(max)) of the survival curve at high doses was much more reliable than D(0). Fitting s(max) to 2.5 Gy(-1) gave better predictions for both cell lines. Nevertheless, LEM could not predict the responses to fast and slow ions with the same accuracy. CONCLUSIONS: The LEM could predict the main trends of these experimental data with correct orders of magnitude while s(max) was optimized. Thus the efficiency of carbon ions cannot be simply extracted from the clinical response of a patient to X-rays. LEM should help to optimize planning for hadrontherapy if a set of experimental data is available for high-LET radiations in various types of tumors.

Potential benefits of using non coplanar field and intensity modulated radiation therapy to preserve the heart in irradiation of lung tumors in the middle and lower lobes.

PURPOSE: Investigate whether the use of non coplanar fields and intensity modulated radiation therapy (IMRT) reduces the dose to the heart, in irradiation of middle and lower lung tumors. MATERIALS AND METHODS: Four plans are compared on 10 CT scans: (1) a reference plan, corresponding to coplanar plan of 3D conformal radiotherapy (3DCRT); (2) a 3DCRT(noncopl) plan, differing from reference plan by the change of one field in non coplanar fields; (3) an IMRT(copl) plan optimized on the same coplanar plan as reference plan; and (4) an IMRT(noncopl) plan optimized on the same non coplanar beams as 3DCRT(noncopl) plan. The equivalent uniform dose (EUD) for PTV was 74 Gy in 37 fractions. RESULTS: In all plans, the 95% isodose surface covers at least 99% of the PTV with very similar conformity index values. A significant reduction in EUD, V30, V40 and V50 is observed for heart when either non coplanar fields or IMRT is used. IMRT also reduces the lung NTCP, V5, V13, V20 and V30 values and esophagus NTCP. CONCLUSION: Both the use of non coplanar fields and IMRT dramatically reduces the dose received by the heart. The largest benefit is seen when the two techniques are combined.