Addition of Iodinated Contrast to Rectal Hydrogel Spacer to Facilitate MRI-Independent Target Delineation and Treatment Planning for Prostate Cancer

PurposeHydrogel spacers reduce rectal dose toxicity during prostate cancer radiation therapy. Current products require magnetic resonance imaging (MRI) for visualization during treatment planning, but MRI incompatibility and cost have prompted alternatives using computed tomography (CT). This case series evaluates the addition of iodinated contrast to hydrogel as such an alternative.Methods and materialsThree patients underwent rectal hydrogel spacer placement with iodinated contrast modification. CT was performed within 1 hour of injection and again 1 week later. MRI was obtained at the time of the second CT. Hydrogel delineation was compared between CT and MRI and between paired CT scans.ResultsSpacer enhancement was visible on CT immediately after hydrogel placement (mean Hounsfield units, 122; range, 52-193) but not at the second CT 1 week later (mean Hounsfield units, 8; range, −8 to 29). Delineated spacer volume did not significantly differ between immediate postprocedure CT and MRI ≥1 week later in 2 patients (patient 1: 16.6 vs 15.5 cm³; patient 2: 12.6 vs 14.7 cm³; paired t-test, P = .81).ConclusionsCT visualization of rectal hydrogel admixed with contrast is feasible and allows delineation of interface with rectum/prostate.     

Comparison of Techniques for Involved-Site Radiation Therapy in Patients With Lower Mediastinal Lymphoma

PurposePatients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity modulated radiation therapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML.Methods and MaterialsTwenty-one patients with LML underwent 4-dimensional computed tomography and 3 sequential DIBH scans at simulation. Involved-site radiation therapy target volumes and organ-at-risk contours were developed for both DIBH and FB scans. FB-IMRT, DIBH-IMRT, FB-PT, and DIBH-PT plans were generated for each patient for comparison.ResultsThe median difference in lung volume between the DIBH and FB scans was 1275 mL; the average difference in clinical target volume was 5.7 mL. DIBH-IMRT produced a lower mean lung dose (10.8 vs 11.9 Gy; P < .001) than FB-IMRT, with no difference in mean heart dose (MHD; 16.1 vs 15.0 Gy; P = .992). Both PT plans produced a significantly lower mean dose to the lung, heart, left ventricle, esophagus, and nontarget body than DIBH-IMRT. DIBH-PT reduced the median MHD by 4.2 Gy (P < .0001); left ventricle dose by 5.1 Gy (P < .0001); and lung V5 by 26% (P < .0001) versus DIBH-IMRT. The 2 PT plans were comparable, with DIBH-PT reducing mean lung dose (7.0 vs 7.7 Gy; P = .063) and with no difference in MHD (10.3 vs 9.5 Gy; P = .992).ConclusionsAmong patients with LML, DIBH (IMRT or PT) improved lung dosimetry over FB but had little influence on MHD. PT (DIBH and FB) significantly reduced lung, heart, esophagus, and nontarget body dose compared with DIBH IMRT, potentially reducing the risk of late complications.     

Proposed Hydrogel-Implant Quality Score and a Matched-Pair Study for Prostate Radiation Therapy

PurposeSpaceOAR hydrogel has been Food and Drug Administration approved to reduce rectal toxicity in prostate radiation therapy. Training and certification for this procedure is performed by the manufacturer, without independent quality measures. We propose a Hydrogel-Implant Quality Score (HIQS) as a surrogate to quantify hydrogel placement accuracy, to assist clinicians in tracking their implant proficiency, and to support quality improvement. A matched-pair study was designed to investigate the benefit of SpaceOAR in rectal dose reduction for low-dose-rate brachytherapy and to validate the principle of the proposed HIQS.MethodsEighty-one prostate patients were retrospectively selected for this study. Each patient had SpaceOAR implantation under manufacturer supervision. Postprocedure computed tomography and T2-weighted magnetic resonance imaging were acquired for radiation planning. A HIQS system was proposed to evaluate the hydrogel placement quality. Hydrogel implantation was performed immediately after LDR seed placement. For each LDR patient, a non-SpaceOAR patient was matched based upon intraoperative rectal dose and prostate coverage. Intraoperative and postoperative rectal dose reduction was compared between SpaceOAR and non-SpaceOAR groups.ResultsThe average HIQS was 77 ± 10.8 (range, 49-97). Rectal anatomic distortions were seen in 17 cases. Significant rectal dose reductions between intraoperative and postoperative plans were found for SpaceOAR patients compared with non-SpaceOAR patients (25.1 Gy vs −5.0 Gy for ΔD_2cc and 65.7 Gy vs 13.0 for ΔD_0.1cc). Additional rectal dose reductions (8.4 Gy for ΔD_2cc and 12.7 Gy for ΔD_0.1cc) were found for patients without rectal distortion when SpaceOAR was used.ConclusionsThe proposed HIQS system measured the hydrogel placement quality and provided insights into clinician learning and DVH outcome. SpaceOAR was shown to be effective in reducing rectal dose for LDR patients.     

68Ga-PSMA-11 PET, 18F-PSMA-1007 PET,and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability

PurposeTo assess the intermodality and intertracer variability of gallium-68 (⁶⁸Ga)- or fluorine-18 (¹⁸F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer.MethodsNineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between ⁶⁸Ga-PSMA-11 and ¹⁸F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTV^majority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTV^majority SUV% / median prostate gland without GTV^majority SUV%) was calculated according to the tracer used.ResultsA significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the ¹⁸F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the ⁶⁸Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sørensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the ¹⁸F cohort compared with the ⁶⁸Ga cohort. For the bpMRI-based delineations, the median Sørensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for ¹⁸F-PSMA and 3.3 (IQR, 2.7-5.9) for ⁶⁸Ga-PSMA PET images were found.ConclusionsBoth MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.     

Evaluation of a Novel Absorbable Radiopaque Hydrogel in Patients Undergoing Image Guided Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

PurposeWe assessed the feasibility and safety of placing a radiopaque hydrogel in the pancreaticoduodenal groove via endoscopic ultrasound guidance in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC).Methods and MaterialsHydrogel injections were done at time of fiducial placement to form blebs in the pancreaticoduodenal groove. Patients subsequently underwent simulation computed tomography (sim-CT) followed by hypofractionated stereotactic body radiotherapy (SBRT; 33 Gy in 5 fractions). Four to 8 weeks after SBRT, patients underwent CT re-evaluation for surgical candidacy and assessment of hydrogel location and size. Hydrogel placement was considered successful if identified in the pancreaticoduodenal groove on sim-CT scan. Stability was evaluated using equivalence testing analyses, with a null hypothesis of the presence of a ≥20% mean percentage change in volume and ≥2 mm change in the median and mean interbleb surface distance with a P value <.05 required to reject the null hypothesis and conclude equivalence. For patients undergoing pancreaticoduodenectomy, hydrogel sites were histologically examined for location and local inflammatory reactions.ResultsHydrogel placement was successful in 6 of the 6 evaluable patients. The average changes in median and mean interbleb distances were −0.43 mm and −0.35 mm, respectively, with P < .05. The average change in volume from sim-CT to post-SBRT CT was −1.0%, with P < .05. One patient experienced grade 3 nausea after fiducial/hydrogel placement, with no other adverse events to date.ConclusionsThese data demonstrate feasibility and safety of injecting a hydrogel marker in the pancreaticoduodenal groove in patients with BR/LAPC and set the stage for a follow-up clinical trial to place hydrogel as a spacer between the pancreatic tumor and dose-limiting, radiosensitive duodenum.     

Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile

BackgroundThis study aimed to evaluate the influence of hormone receptor (HR) and Ki-67 proliferation markers in predicting the accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in patients with HER2-negative (HER2^?) breast cancer receiving neoadjuvant chemotherapy (NAC).Patients and MethodsFifty-four women were studied. Patients received AC (doxorubicin (Adriamycin)/cyclophosphamide) and/or taxane-based regimens. The accuracy of MR-determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathologically diagnosed tumor size using the Pearson correlation.ResultsMRI correctly diagnosed 16 of the 17 cases of pCR. There were 8 false-negative diagnoses: 7 HR⁺ and 1 HR^?. The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI vs. pathologically determined tumor size correlation, HR^? cancers showed a higher correlation (R = 0.79) than did HR⁺ cancers (R = 0.58). A worse MRI/pathology size discrepancy was found in HR⁺ cancer than in HR^?cancer (1.6 ± 2.8 cm vs. 0.56 ± 0.9 cm; P = .05). Tumors with low Ki-67 proliferation (< 40%) showed a larger size discrepancy than did those with high Ki-67 proliferation (≥ 40%) (1.2 ± 2.0 cm vs. 0.4 ± 0.8 cm; P = .05).ConclusionsThe results showed that the diagnostic performance of MRI for patients with breast cancer undergoing NAC is associated with a molecular biomarker profile. Among HER2^?tumors, the accuracy of MRI was worse in HR⁺cancers than in HR^?cancers and was also worse in low-proliferation tumors than in high-proliferation tumors. These findings may help in surgical planning.     

Minimum Required Interval Between Hydrogel Spacer Injection and Treatment Planning for Stereotactic Body Radiation Therapy for Prostate Cancer

PurposeThe present study evaluated the short-term characteristics (<3 days) of a hydrogel spacer from the time of injection during stereotactic body radiation therapy (SBRT) for prostate cancer.Methods and MaterialsFifteen patients treated with SBRT via the CyberKnife system (36.25 Gy/5 fractions) were enrolled in this retrospective study. Two magnetic resonance (MR) images were obtained with a hydrogel spacer: one on a computed tomography (CT) simulation day (MR pretreatment [MR_pre]) and the other on the last treatment day (MR posttreatment [MR_post]). Two medical physicists contoured the hydrogel spacer on each MR image. The changes of the shapes and the volume for the hydrogel spacer between 2 MR images were evaluated.ResultsThe median period between hydrogel spacer injection and CT simulation was 1 day (range, 1-9 days). The median period between CT simulation and the last treatment was 17 days (range, 14-25 days). Regarding the volume change of the hydrogel spacer, the 2 observers observed significant differences between the volumes of the hydrogel spacer on the MR_pre and MR_post. However, the average volume difference between them was less than 1 cm³. The average dice similarity coefficient between the MR_pre and MR_post to compare the shape was more than 0.83. In addition, no clear correlation was confirmed between the volume change and the period from hydrogel spacer injection to CT simulation.ConclusionsA single day is an acceptable interval between hydrogel spacer injection and treatment planning for SBRT for prostate cancer.     

Assessing Inter-Fraction Changes in The Size and Position of The Penile Bulb During Daily MR-Guided Radiation Therapy to The Prostate Bed: Do We Need to Adjust How We Plan Radiation in The Post-Radical Prostatectomy Setting to Reduce Risk of Erectile Dysfunction?

BackgroundWe evaluated inter-fraction penile bulb (PB) changes in prostate cancer (PCa) patients undergoing MR-guided RT in the post-radical prostatectomy (RP) setting.Materials and Methods10 patients with PCa status-post RP received MR-guided RT from 2017-2019. Patients received daily setup volumetric MRI scans prior to RT delivery for alignment and target localization. Setup MRI datasets from Fx 1, Fx 19, and Fx 37 were fused for each patient based on soft tissue anatomy. The PB was contoured on each MRI. Data on volume (cc), superior/inferior positional change (cm), and mean dose (Gy) was collected. Differences were assessed by Student’s t-test (sig. p<0.05).ResultsThe mean PB volume change from Fx 1→ 19 was +0.34 ± 0.34 cc (p=0.11) and from Fx 1→ 37 was +0.22 ± 0.28 cc (p=0.31). The mean positional change from Fx 1→ 19 was +0.08±0.26 cm (p=0.37) and from Fx 1→ 37 was +0.05 ±0.25 cm (p=0.57). The mean change in mean PB dose from Fx 1→ 19 was +0.19±4.86 Gy (p=0.98) and from Fx 1→ 37 was -1.51≖7.46 Gy (p=0.88).ConclusionWe present the first study evaluating inter-fraction changes to the PB during MR-guided RT. We found no clinically meaningful difference in the volume, positional change, or mean dose during RT in the post-prostatectomy setting, suggesting that PB organ motion may not need to be accounted for in radiation treatment planning.     

Calcifications intraprostatiques : marqueurs fiduciels naturels dans la radiothérapie guidée par l’image du cancer de la prostate

PurposeTo establish whether intraprostatic calcifications can serve as natural fiducials for image-guided radiotherapy (IGRT), replacing the implantation of intraprostatic fiducial markers.Patients and methodsPatients with prostate cancer, having intraprostatic calcifications visible on CT scan were selected and underwent intensity-modulated radiotherapy/3D conformal radiotherapy with IGRT in the department of radiotherapy of Henri-Mondor Hospital. All cone-beam computed tomographies (CBCT) were repositioned on intraprostatic calcifications. For each acquired image, displacements of intraprostatic calcifications were calculated with reference to position on planning CT in three directions: lateral, longitudinal and vertical.ResultsBetween 2011 and 2013, nine patients had 183 CBCT. For each image, three displacements and space coordinates were calculated using a single reference (intraprostatic calcification). Mean lateral, longitudinal and vertical movements were 0.26 ± 5.7 mm, −1 ± 4.6 mm and 0.42 ± 3.5 mm, respectively.ConclusionStudies exploring prostatic movements with fiducial markers as reference and ours with natural fiducials yield similar results. Our data confirm previous studies that have suggested that intraprostatic calcifications can be used as natural fiducials with potential reduction of iatrogenic risks and costs associated with the implantation of fiducial markers.     

Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate

PurposeImage-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility.Patients and methodsOver a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife^® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6 Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6 Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25 Gy and 11 patients five fractions of 6.25 Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1 cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2 cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients.ResultsThe tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4–113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment.ConclusionsIntraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.     

Separation Effect and Development of Implantation Technique of Hydrogel Spacer for Prostate Cancers

PurposeThe purpose of this study is to improve the placement of a hydrogel spacer in patients with prostate cancer receiving radiation therapy.Methods and MaterialsA total of 160 patients with prostate cancer were classified into 3 groups: No spacer (group 1; n = 30), spacer placed using conventional technique (group 2; n = 100), and spacer placed using new technique (group 3; n = 30). When placing the spacer, the tip of the needle is placed at the middle of the prostate gland (group 2), or at a level corresponding to a cranial:caudal ratio of 6:4 and as close to the prostate gland as possible (group 3). The separation effect was examined and compared among the groups.ResultsThe separation in group 2 was larger than that in group 1 from the base to the apex level of the prostate (4 mm), but the separation in group 3 was larger than that in group 2 from the middle to the apex level of the prostate (4 mm). The separation values for the middle to the apex, the spacer thickness from the apex level to the apex (10 mm), the rectal exclusion from the middle to the apex, and the laterality were correlated with the 50 and 60 Gy relative biologic effectiveness (Gy[RBE]) rectal dose (P = 4.1 × 10⁻⁹ – .046). The separation vales were strongly correlated with the spacer thickness at the apex (10 mm) and the apex (4 mm; P = 1.1 × 10⁻¹⁸ – 1.8 × 10⁻¹⁷). The rectal volumes at 10 to 60 Gy(RBE) differed among the groups (P = 5.1 × 10⁻¹⁹ – 5.4 × 10⁻³). The rectal volumes in group 2 were smaller than those in group 1 at all dose levels, but those in group 3 were smaller than those in group 2 at dose levels of 30 to 50 Gy(RBE).ConclusionsThe separation, spacer thickness, and rectal exclusion from the middle to the apex of the prostate and the laterality of the hydrogel spacer affected the reduction in the rectal dose. The rectal dose can be further reduced by implanting a spacer on the caudal and prostate side.     

Delineation of a Cardiac Planning Organ-At-Risk Volume Using Real-Time Magnetic Resonance Imaging for Cardiac Protection in Thoracic and Breast Radiation Therapy

PurposeCardiac radiation is associated with cardiotoxicity in patients with thoracic and breast malignancies. We conducted a prospective study using cine magnetic resonance imaging (MRI) scans to evaluate heart motion. We hypothesized that cine MRI could be used to define population-based cardiac planning organ-at-risk volumes (PRV).Methods and MaterialsA total of 16 real-time acquisitions were obtained per subject on a 1.5 Tesla MRI (Philips Ingenia). Planar cine MRI was performed in 4 sequential sagittal and coronal planes at free-breathing (FB) and deep-inspiratory breath hold (DIBH). In-plane cardiac motion was assessed using a scale-invariant feature transformation–based algorithm. Subject-specific pixel motion ranges were defined in anteroposterior (AP), left-right (LR), and superoinferior (SI) planes. Averages of the 98% and 67% of the maximum ranges of pixel displacement were defined by subject, then averaged across the cohort to calculate PRV expansions at FB and DIBH.ResultsData from 20 subjects with a total of 3120 image frames collected per subject in coronal and sagittal planes at DIBH and FB, and 62,400 total frames were analyzed. Cohort averages of 98% of the maximum cardiac motion ranges comprised margin expansions of 12.5 ± 1.1 mm SI, 5.8 ± 1.2 mm AP, and 6.6 ± 1.0 mm LR at FB and 6.7 ± 1.5 mm SI, 4.7 ± 1.3 mm AP, and 5.3 ± 1.3 mm LR at DIBH. Margins for 67% of the maximum range comprised 7.7 ± 0.7 mm SI, 3.2 ± 0.6 mm AP, and 3.7 ± 0.6 mm LR at FB and 4.1 ± 0.9 mm SI, 2.7 ± 0.8 mm AP, and 3.2 ± 0.8 mm LR at DIBH. Subsequently, these margins were simplified to form PRVs for treatment planning.ConclusionsWe implemented scale-invariant feature transformation-based motion tracking for analysis of the cardiac cine MRI scans to quantify motion and create cohort-based cardiac PRVs to improve cardioprotection in breast and thoracic radiation.     

Quantification of Esophageal Tumor Motion and Investigation of Different Image-Guided Correction Strategies

PurposeTo accurately quantify esophageal tumor position variability and to optimize image guided correction strategies.Material and MethodsEsophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations.ResultsFifty-six patients with tumors located in the proximal (n = 1), mid (n = 7), or distal esophagus (n = 25) or at the gastroesophageal junction (n = 23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left–right (LR), cranial–caudal (CC), and anterior–posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins.ConclusionsSubstantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy.     

Image guided radiation therapy for bladder cancer: Assessment of bladder motion using implanted fiducial markers

PurposeTo determine bladder wall position variability during external beam radiation therapy (EBRT) for bladder cancer with intravesical fiducial markers using 2-dimensional (2D) and volumetric (3D) imaging registration.Methods and MaterialsTwenty T2-4aN0-1 bladder cancer patients underwent definitive EBRT with concurrent chemotherapy between May 2001 and January 2012, and had intravesical fiducial marker placement before simulation. Computed tomographic (CT)-based treatment planning was used for an initial phase to deliver 45 Gy (1.8 Gy/fraction) to the bladder and pelvic lymphatics followed by a boost to the involved bladder wall for an additional 21.6 Gy (1.8 Gy/fraction). Orthogonal kilovoltage radiograph images (34-37 images/patient) were obtained daily, registered with digitally reconstructed radiographs from the planning scan. Translational corrections were made daily. A kilovoltage cone-beam CT (kVCBCT) was acquired weekly and its registration with the planning scan was compared with that day's 2D registration results.ResultsOf 739 treatments, 6% resulted in ≥ 15 mm displacement in 1 or more directions and 26% resulted in ≥ 10 mm displacement in 1 or more directions. Based on 2D registrations, the average millimeter difference between bony registration and fiducial marker registration (BR-FMR) in the right-left (RL) (R +), anterior-posterior (AP) (A +), and superior-inferior (SI) (I +) directions were: 0.5 ± 1.0 (range, −2.0 to + 3.8), 1.7 ± 4.4 (range, −8.1 to + 13.5) and −3.7 ± 5.8 (range, −16.8 to + 8.3), respectively. For kVCBCT registrations, the average mm difference in the RL, AP, and SI directions were 0.3 ± 2.1 (range, −2.4 to + 5.1), 3.1 ± 5.9 (range, −2.9 to + 13.3) and −4.8 ± 8.0 (range, −16.4 to + 9.5), respectively.ConclusionsUsing intravesical fiducial markers, the largest difference in bladder motion based BR-FMR differences was in the superior-inferior direction. Because fiducial markers are target surrogates, setup using bony anatomy alone can lead to target displacements up to 13.5 mm anteriorly and 16.8 mm superiorly. This confirms a 1.5-1.7 cm minimum in planning target margins. These findings suggest a significant advantage in using intravesical fiducial markers to determine daily translational corrections.     

Early Outcomes and Decision Regret Using PSMA/MRI-Guided Focal Boost for Prostate Cancer SBRT

PurposeStereotactic body radiation therapy (SBRT) is a recognized treatment for low- and intermediate-risk prostate cancer, with 36.25 Gy in 5 fractions the most commonly used regimen. We explored the preliminary efficacy, patient recorded toxicity, and decision regret in intermediate- and high-risk prostate cancer receiving SBRT with prostate-specific membrane antigen (PSMA)/magnetic resonance imaging (MRI) guided focal gross tumor volume boost to 45 Gy.Methods and MaterialsBetween July 2015 and June 2019, 120 patients received SBRT across 2 institutions with a uniform protocol. All patients had fiducial markers and hydrogel, MRI and PSMA positron emission tomography (PET) scan. All patients received a questionnaire asking the degree of urinary, bowel, and sexual bother experienced at set time points, including questions about treatment choice and decision regret.ResultsOne hundred twelve of 120 patients consented. Their median age was 72 years and median follow-up was 2.3 years. As per National Comprehensive Cancer Network guidelines, 78% had intermediate risk and 20% high risk. Androgen deprivation was combined with radiation in 6 patients. Most patients (74%) reported that receiving SBRT significantly influenced their choice of treatment. Five men (4%) expressed “quite a lot” (n = 4) or “very much” regret (n = 1) regarding their choice of treatment, while 89% expressed “no regret.” Similar to pretreatment levels, “quite a lot” or “very much” urinary or bowel bother was expressed in 8% and 6% of patients, respectively. Two patients experienced nadir +2 biochemical failure, both found to have bone metastases. A third patient underwent PSMA PET at nadir +1.7 and had disease at the penile bulb, which was out of field. Three year estimated freedom from biochemical failure was 99% for intermediate and 85% for high-risk groups.ConclusionsWe have demonstrated promising efficacy and low toxicity with PSMA/MRI-guided SBRT focal boost. Less than 5% of patients expressed significant decision regret for their choice of treatment.     

La radiothérapie (conformationnelle avec modulation d’intensité) adaptative est-elle nécessaire pour les carcinomes du col utérin ?

PurposeTo observe on ten patients, the changes of different pelvic structures during a Stade IB2-IIB cervix cancer tomotherapy course delivering 60 Gy over 5.5 weeks and evaluate the rationale of adaptive treatments.Materials and methodsEach of the six weekly mega voltage CT-scan (MVCT) exams performed the same day of the week were analyzed. The centro-pelvic CTV volume was contoured as well as the organs at risk (OAR). The dose delivered was recalculated while those to 2%, 50% and 98% of the centro-pelvic CTV as well as to 2 cm³, 10 cm³ and 50 cm³ of the OAR were analyzed.ResultsThe mean decrease in volume of the centro-pelvic CTV was 13% and non-significant (P > 0.2). However four tumors decreased from 21% to 42%. This decrease was centripetal. Likewise, the fraction doses to 2%, 50% and 98% were respectively 2.14 ± 0.08 Gy, 2.02 ± 0.14 Gy, 1.8 ± 0.34 Gy at week 1 and 2.13 ± 0.1 Gy, 2.06 ± 0.12 Gy, 1.88 ± 0.24 Gy at week 6 (P > 0.2). The doses delivered to 2 cm³, 10 cm³ and 50 cm³ of the different OAR did not change at a significant level (P > 0.05) too, except the dose to 50 cm³ of non-sigmoid bowel moving from 1.69 ± 0.16 Gy at week 1 to 1.78 ± 0.14 Gy at week 6 (P = 0.05).ConclusionAs a whole, adaptive therapy does not seem mandatory in this population of stages IB2-IIB cancers. A complementary study on more advanced stages is however necessary.     

Techniques classique bidimensionnelle et mono-isocentrique tridimensionnelle dans l’irradiation du sein et des aires ganglionnaires : comparaison dosimétrique

PurposeThe activity of our radiation oncology department mainly relies on breast pathology. Since July 2009, all the irradiations delivered simultaneously to the breast (CTV1), the surgical bed (CTV2), the internal mammary chain and the supra- and infraclavicular areas have been carried out using a mono-isocentric technique. This study aimed to compare dosimetric results between conventional 2D and mono-isocentric 3D techniques with or without optimization.Patients and methodsFrom January to August 2009, 20 patients with breast cancer in whom irradiation of the CTV1, CTV2, internal mammary chain and supra- and infraclavicular areas was retained, were included in a specific cohort. In each case, we have compared dosimetric results obtained with the conventional technique and with a mono-isocentric 3D technique, either with manual field in the field segmentation or with automatic segmentation (Oncentra Masterplan^® from Nucletron^®, Optimizer^® solution). Selected criteria were as follows: V95, V107 and mean dose (Dmean) to the target volumes, V20 and V30 to the ipsilateral lung, V35 and mean dose to the heart and maximal dose (Dmax) to the spinal cord.ResultsSupra- and infraclavicular areas irradiation was significantly better using the mono-isocentric 3D technique (V95 %: 89.7 % vs. 77.1 %; P = 0.001) as well as dose homogeneity (Dmean: 46.3 Gy vs. 45.1 Gy; P = 0.008). No statistical difference was observed for the other target volumes. Heart and spinal cord protection were better with the mono-isocentric 3D technique (respectively Dmean: 8.4 Gy vs. 11.1 Gy; P < 0.0001 and Dmax: 29.2 Gy vs. 35.8 Gy; P = 0.0003).ConclusionMono-isocentric irradiation of the breast and lymphatic areas is a modern technique that benefits from imaging and computer progresses while being simple to carry out using standard planning system and linear accelerators. Mono-isocentric 3D irradiation with manual segmentation of the breast and the nodal areas provides a target volume irradiation comparing with conventional technique 2D and a better protection of the heart and of the spinal cord.     

Spare the Bowel,Don't Spoil the Target: Optimal Margin Assessment for Online Cone Beam Adaptive Radiation Therapy (OnC-ART) of the Cervix

PurposeThe standard treatment for locally advanced cervical cancer involves pelvic chemoradiation. Intensity modulated radiation therapy planning requires expansion of the cervix and uterus clinical target volume (CTV) by 1.5 to 2 cm to account for motion. With online cone beam adaptive radiation therapy (OnC-ART), interfractional movement is accounted for, which can potentially lead to smaller CTV to planned target volume (PTV) margins. In this study, we attempted to determine the optimal CTV-to-PTV margin for adequate coverage with OnC-ART and factors that can affect CTV coverage.Methods and MaterialsA retrospective cohort of 21 patients with cervical cancer treated with definitive chemoradiation was included. Nine patients treated with nonadaptive radiation had the uterocervix contoured on pretreatment cone beam computed tomography (CBCT) and end-treatment CBCTs. Anterior-posterior, lateral, and superior-inferior shifts and the average shift in all directions were calculated. A CTV-to-PTV expansion was determined and verified on a validation cohort of 12 patients treated with OnC-ART.ResultsThe average anterior-posterior, lateral, and superior-inferior shifts with standard deviation were 0.32 ± 1.55 cm, 0.12 ± 2.31 cm, and 1.67 ± 3.41 cm, respectively. A uniform 5-mm expansion around the pretreatment CTV covered 98.85% ± 1.23% of the end-treatment CTV. This 5-mm expansion was applied to our validation cohort treated with OnC-ART, and 98.39% ± 3.0% of the end-treatment CTV was covered. Time between CBCTs >30 minutes and change in bladder volume were significantly correlated to CTV coverage.ConclusionsBased on our analysis, a CTV-to-PTV margin of 5 mm is adequate to encompass 98% of the CTV. A significantly reduced margin could potentially decrease the toxicities associated with radiation for patients with cervical cancer and lead to improved patient reported toxicity outcomes. We recommend physicians begin with a 5-mm margin and assess adequate coverage with image guidance during daily adaptation.     

A Prospective Multi-Institutional Phase I/II Trial of Step-Wise Dose-per-Fraction Escalation in Low and Intermediate Risk Prostate Cancer

PurposeThis phase I/II, multi-institutional trial explored the tolerance and efficacy of stepwiseincreasing hypofractionation (HPFX) radiation therapy regimens for fraction sizes up to 4.3 Gy in localized prostate cancer.Methods and MaterialsThree escalating dose-per-fraction schedules were designed to yield similar predicted tumor control while maintaining equivalent predicted late toxicity. HPFX levels I, II, and III were carried out sequentially and delivered schedules of 64.7 Gy/22 fx/2.94 Gy, 58.08 Gy/16 fx/3.63 Gy, and 51.6 Gy/12 fx/4.3 Gy, respectively with next level escalations contingent upon acceptable gastrointestinal (GI) toxicity. The primary endpoints were biochemical control and toxicity.ResultsA total of 347 patients were recruited by 5 institutions with 101, 111, and 135 patients treated on HPFX levels I, II, and III with median follow-ups of 100, 85.5, and 61.7 months, respectively (83.2 months combined). The National Comprehensive Cancer Network low- or intermediate-risk group distribution was 46% and 54%, respectively. Sixteen percent of patients, primarily intermediate risk, received 6 months of androgen deprivation therapy. The 8-year nadir + 2 actuarial biochemical control rates for HPFX levels I, II, and III were 91.1% ± 3.0%, 92.7% ± 2.7%, and 88.5% ± 4.6%, respectively (Kaplan-Meier log rank, 0.903). Among clinical covariates, only Gleason score reached near significance in multivariate analysis (P = .054). Twenty-six patients failed biochemically (crude incidence of 7.5%), and there were 5 cause-specific deaths. GI and genitourinary toxicities were acceptable and similar across the 3 HPFX levels. The combined actuarial cumulative incidence of grade 2+ GI and genitourinary toxicities at 7 years were 16.3% ± 2.1% and 22.1% ± 2.4%, respectively.ConclusionsHPFX employing fraction sizes extending into the 3.6 to 4.3 Gy/fraction range can be delivered with excellent oncologic outcomes. Such schedules, positioned between moderate and ultra-HPFX, may provide additional options for patients wishing to avoid prolonged treatment schedules associated with conventionally fractionated radiation therapy for prostate cancer.     

Prognostic Significance of Total Lymphocyte Count,Neutrophil-to-lymphocyte Ratio,and Platelet-to-lymphocyte Ratio in Limited-stage Small-cell Lung Cancer

BackgroundWe sought reliable markers of survival and disease control among patients treated for limited-stage small-cell lung cancer (LS-SCLC).Patients and MethodsSubjects were 122 patients given (chemo)radiotherapy for LS-SCLC at MD Anderson in 2002 through 2015. Pretreatment total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed for associations with overall (OS) and progression-free survival. Optimal cutoff values were identified with receiver operating characteristic curves and survival probabilities with the Kaplan-Meier method.ResultsPretreatment TLC was 1.86 × 10³/μL (±0.88); NLR, 3.44 (±3.69); and PLR, 170.53 (±101.56); corresponding cutoffs were 1.9, 2.9, and 140.1. Higher TLC was associated with superior median and 2-year OS (17.4 vs. 15.7 months and 33% vs. 29%; P = .029), and higher NLR and PLR with worse median and 2-year OS (NLR: 14.9 vs. 17.8 months, 29% vs. 31%; P = .026; PLR: 14.8 vs. 18.9 months, 24% vs. 37%; P = .009). Multivariate Cox regression adjusted for age, disease stage, number of chemotherapy cycles, and use of prophylactic cranial irradiation confirmed the links between high TLC and superior OS (hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.32-0.94; P = .028) and between high NLR and PLR and inferior OS (NLR: HR, 1.86; 95% CI, 1.15-3.01; P = .011; PLR: HR, 1.72; 95% CI, 1.06-2.82; P = .030).ConclusionsBaseline lymphopenia was an indicator of poor prognosis in patients with LS-SCLC.