Technical note: Comparison of the internal target volume (ITV) contours and dose calculations on 4DCT, average CBCT, and 4DCBCT imaging for lung stereotactic body radiation therapy (SBRT)

PURPOSE: To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique. METHODS: For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass (COM) were averaged over four fractions to compare the ITVs contoured on the 4DCT, avgCBCT, and 4DCBCT for each patient. Planning was done on the average CT, and using the online registration, plans were calculated on each phase of the 4DCBCT and on the avgCBCT. Plan dose calculations were tested by measuring ion chamber dose in the CIRS lung phantom. RESULTS: The Dice coefficients were similar for all three comparisons: avgCBCT-to-4DCBCT (0.7 ± 0.1), 4DCT-to-avgCBCT (0.7 ± 0.1), and 4DCT-to-4DCBCT (0.7 ± 0.1); while the mean COM differences were also comparable (2.6 ± 2.2mm, 2.3 ± 1.4mm, and 3.1 ± 1.1mm, respectively). The Hausdorff distances for the comparisons with 4DCBCT (8.2 ± 2.9mm and 8.1 ± 3.2mm) were larger than the comparison without (6.5 ± 2.5mm). The differences in ITV D95% between the treatment plan and avgCBCT calculations were 4.3 ± 3.0% and -0.5 ± 4.6%, between treatment plan and 4DCBCT plans, respectively, while the ITV V100% coverages were 99.0 ± 1.9% and 93.1 ± 8.0% for avgCBCT and 4DCBCT, respectively. CONCLUSION: There is great potential for 4DCBCT to evaluate the extent of tumor motion before treatment, but image quality challenges the clinician to consistently delineate lung target volumes

Magnetic resonance imaging-only-based radiation treatment planning for simultaneous integrated boost of multiparametric magnetic resonance imaging-defined dominant intraprostatic lesions

Objective: To assess the feasibility of using synthetic computed tomography for treatment planning of the dominant intraprostatic lesion (DIL), a high-risk region of interest that offers potential for increased local tumor control. Methods: A dosimetric study was performed on 15 prostate cancer patients with biopsy-proven prostate cancer who had undergone magnetic resonance imaging. DILs were contoured based on the turbo spin echo T2-weighted and diffusion weighted images. Air, bone, fat, and soft tissue were segmented and assigned bulk-density HU values of –1000, 285, –50, and 40, respectively, to create a synthetic computed tomography. Simultaneous integrated boost (SIB) and standard treatment plans were created for each patient. The total dose was 79.2 Gy to the non-boosted planning target volume for both plans with a boost of 100 Gy for the DIL in the SIB plan. A radiobiological model was created to determine individualized dose–response curves based on the patient\u27s apparent diffusion coefficient maps. Results: Mean doses to the non-boost planning target volume were 81.2 ± 0.3 Gy with the SIB and 81.0 ± 0.4 Gy without. For the DIL, the boosted mean dose was 102.6 ± 0.6 Gy. Total motor unit was 860 ± 100 with the SIB and 730 ±100 without. Femoral heads, rectum, bladder, and penile bulb were within established dose guidelines for either treatment technique. The average tumor control probability was 94% with the SIB compared with 78% without boosting the DIL. Conclusion: This study showed the feasibility of magnetic resonance imaging-only treatment planning for patients with prostate cancer with a SIB to the DIL. DIL dose can be escalated to 100 Gy on synthetic computed tomography, while maintaining the original 79.2 Gy prescription dose and the organ of interest clinical dose limits

Geometric and dosimetric impact of anatomical changes for MR-only radiation therapy for the prostate

PURPOSE: With the move towards magnetic resonance imaging (MRI) as a primary treatment planning modality option for men with prostate cancer, it becomes critical to quantify the potential uncertainties introduced for MR-only planning. This work characterized geometric and dosimetric intra-fractional changes between the prostate, seminal vesicles (SVs), and organs at risk (OARs) in response to bladder filling conditions. MATERIALS AND METHODS: T2-weighted and mDixon sequences (3-4 time points/subject, at 1, 1.5 and 3.0 T with totally 34 evaluable time points) were acquired in nine subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed pre-imaging, 10 oz mid-session). Using mDixon images, Magnetic Resonance for Calculating Attenuation (MR-CAT) synthetic computed tomography (CT) images were generated by classifying voxels as muscle, adipose, spongy, and compact bone and by assignment of bulk Hounsfield Unit values. Organs including the prostate, SVs, bladder, and rectum were delineated on the T2 images at each time point by one physician. The displacement of the prostate and SVs was assessed based on the shift of the center of mass of the delineated organs from the reference state (fullest bladder). Changes in dose plans at different bladder states were assessed based on volumetric modulated arc radiotherapy (VMAT) plans generated for the reference state. RESULTS: Bladder volume reduction of 70 ± 14% from the final to initial time point (relative to the final volume) was observed in the subject population. In the empty bladder condition, the dose delivered to 95% of the planning target volume (PTV) (D95%) reduced significantly for all cases (11.53 ± 6.00%) likely due to anterior shifts of prostate/SVs relative to full bladder conditions. D15% to the bladder increased consistently in all subjects (42.27 ± 40.52%). Changes in D15% to the rectum were patient-specific, ranging from -23.93% to 22.28% (-0.76 ± 15.30%). CONCLUSIONS: Variations in the bladder and rectal volume can significantly dislocate the prostate and OARs, which can negatively impact the dose delivered to these organs. This warrants proper preparation of patients during treatment and imaging sessions, especially when imaging required longer scan times such as MR protocols

Interfraction contour comparison on 4DCBCT Vs. 4DCT for lung SBRT patients.

Purpose: To investigate the differences between the internal target volumes (ITV) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT). Methods: 4DCBCTs were acquired before each fraction for Lung SBRT patients to assess tumor motion before treatment. A 4DCBCTwas acquired with a full trajectory (gantry speed of 3 deg/sec), and a total of 1800 projections. The Varian RPM device was used to bin the projections into 10 phases and reconstructed with filtered back projection. An ITV was contoured on each of the 10 phases at each fraction delivered and the ITV was the union of the contours on each phase. The ITV was also drawn on the average CBCT used for the patient localization. The dice coefficient, hausdorff distance, and center of mass were used for comparison of the ITV contoured on the maximum intensity projection generated from 4DCT, Average CBCT, and 4DCBCT. Results: Preliminary results show a higher dice coefficient (better similarity) between average CBCT and 4DCBCT ITVs (0.91 ± 0.07) over four fractions for a patient compared to average CBCT and 4DCBCT comparisons with the 4DCT ITV (0.83 ± 0.02 and 0.78 ± 0.03, respectively). Greater hausdorff distances were found for comparisons with the 4DCBCT ITV, likely due to the streak artifacts in the 10 phase 4DCBCT. The center of mass difference for the 4DCT ITV compared to average CBCT ITV increased throughout treatment (from 0.94 mm in the first fraction to 1.6 mm in the fourth fraction) and compared to the 4DCBCT ITV (0.65 mm to 2.39 mm). Conclusion: Daily 4DCBCT has the potential to assess the tumor motion before lung SBRT patient treatment. Differences in 4DCBCT ITV and 4DCT ITV are due to a number of factors including poor image quality and tumor shrinkage. Therefore, further investigation on the fidelity of 4DCBCT for ITV delineation is necessary

Geometric and dosimetric impact of anatomical changes for MR-only radiation therapy for the prostate

PURPOSE: With the move towards magnetic resonance imaging (MRI) as a primary treatment planning modality option for men with prostate cancer, it becomes critical to quantify the potential uncertainties introduced for MR-only planning. This work characterized geometric and dosimetric intra-fractional changes between the prostate, seminal vesicles (SVs), and organs at risk (OARs) in response to bladder filling conditions. MATERIALS AND METHODS: T2-weighted and mDixon sequences (3-4 time points/subject, at 1, 1.5 and 3.0 T with totally 34 evaluable time points) were acquired in nine subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed pre-imaging, 10 oz mid-session). Using mDixon images, Magnetic Resonance for Calculating Attenuation (MR-CAT) synthetic computed tomography (CT) images were generated by classifying voxels as muscle, adipose, spongy, and compact bone and by assignment of bulk Hounsfield Unit values. Organs including the prostate, SVs, bladder, and rectum were delineated on the T2 images at each time point by one physician. The displacement of the prostate and SVs was assessed based on the shift of the center of mass of the delineated organs from the reference state (fullest bladder). Changes in dose plans at different bladder states were assessed based on volumetric modulated arc radiotherapy (VMAT) plans generated for the reference state. RESULTS: Bladder volume reduction of 70 ± 14% from the final to initial time point (relative to the final volume) was observed in the subject population. In the empty bladder condition, the dose delivered to 95% of the planning target volume (PTV) (D95%) reduced significantly for all cases (11.53 ± 6.00%) likely due to anterior shifts of prostate/SVs relative to full bladder conditions. D15% to the bladder increased consistently in all subjects (42.27 ± 40.52%). Changes in D15% to the rectum were patient-specific, ranging from -23.93% to 22.28% (-0.76 ± 15.30%). CONCLUSIONS: Variations in the bladder and rectal volume can significantly dislocate the prostate and OARs, which can negatively impact the dose delivered to these organs. This warrants proper preparation of patients during treatment and imaging sessions, especially when imaging required longer scan times such as MR protocols

MR-only planning for simultaneous integrated boost of MRI-defined dominant intraprostatic lesions.

Purpose: To assess the feasibility of using synthetic CT images for treatment planning of dominant intraprostatic lesions (DILs), a known high risk region of interest that may offer potential for increased local control. Methods: A retrospective study was performed on three patients with biopsy-proven prostate cancer who underwent T2-weighted, mDixon, and diffusion-weighted imaging (DWI) 3T MRI. A radiologist interpreted MR examinations and the suspicious DIL was contoured based on the T2 and DWI MR images. Air, bone, fat, and soft tissue were segmented (assigned -1000, 285, -50, 40 HU respectively) to create a synthetic CT from the water and fat mDixon sequences. A 5 mm margin was added to the prostate and the DIL to compensate for setup uncertainty RapidArc treatment plans were created with the total dose being 79.2 Gy and a boost of 100 Gy to the DIL. All plans were evaluated using the dose volume histogram curves. Results: The maximum dose and mean dose to the PTV were 87.0 ± 2.1 Gy and 79.6 ± 0.5 Gy. For the DIL, the maximum dose and mean dose were 108.1 ± 1.5 Gy and 104.4 ± 0.5 Gy. The total MU were 603, 574, and 634 for patients 1, 2, and 3. For each patient, the hotspot was located within the DIL. The femoral heads, rectum, bladder, and penial bulb all received a mean dose of 50 Gy or less with the highest mean dose being 50.3 Gy for the bladder of patient 2. The bladder and rectum received the highest doses for the organs at risk (OARs), but both were within the established clinical NRG guidelines. Conclusion: We demonstrated the feasibility of implementing MR-only treatment planning for prostate cancer with a simultaneous integrated boost for DILs. The dose to the DIL can be escalated to 100 Gy on the synthetic CTs while maintaining the original prescription of 79.2 Gy and remaining in clinical criteria for the OARs

The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study

OBJECTIVE: The aim of the study was to characterize the impact of adjuvant therapy on survival in women with stage I/II uterine carcinosarcoma after primary surgery. METHODS: We reviewed records of 118 consecutively treated women with 2009 International Federation of Gynecology and Obstetrics stage I/II uterine carcinosarcoma who underwent hysterectomy between 1990 and 2014 at 4 academic institutions. Patients were categorized by adjuvant treatment group into observation, chemotherapy only, radiation only, and combined chemotherapy and radiation. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: Median follow-up was 28 months (range, 1-244 months). Lymphadenectomy was performed in 94 patients (80%). Postoperative management included observation (n = 37 [31%]), chemotherapy alone (n = 19 [16%]), radiation therapy (RT) alone (n = 24 [20%]), and combined RT and chemotherapy (n = 38 [32%]). Radiation therapy modality included vaginal brachytherapy in 22 patients, pelvic external beam RT in 21 patients, and combination in 19 patients. In 58% of women, chemotherapy consisted of carboplatin/paclitaxel. Median overall survival for all women was 97 months. On univariate analysis, adjuvant treatment group was associated with improved overall survival (hazard ratio [HR], 0.74; confidence interval [CI], 0.58-0.96; p = 0.02), freedom from vaginal recurrence (HR, 0.55; CI, 0.37-0.82]; p = 0.004), and freedom from any recurrence (HR, 0.70; CI, 0.54-0.92; p = 0.01). Pairwise comparisons demonstrated a significant benefit to chemoradiation over other adjuvant treatments. Adjuvant treatment group remained a significant covariate for all 3 end points on multivariate analysis as well. In addition, lymphadenectomy improved overall survival on multivariate analysis (HR, 0.24; CI, 0.09-0.61; p = 0.003). Of patients under observation only who had a recurrence, 8 (44%) of 18 had a recurrence in the vagina as the sole site of recurrence. By contrast, of women who received vaginal brachytherapy, significantly fewer had a recurrence in the vagina (1/42 [2.3%]; p \u3c 0.003, log-rank test). CONCLUSIONS: In women with early-stage uterine carcinosarcoma, our data suggest superior survival end points with combined RT and chemotherapy. The frequency of vaginal recurrence suggests a role for incorporating vaginal brachytherapy in the adjuvant management of this disease

Adjuvant External Radiation Impacts Outcome of Pelvis-limited Stage III Endometrial Carcinoma: A Multi-institutional Study

BACKGROUND: Adjuvant therapy choice for women with FIGO stage III endometrial carcinoma (EC) is controversial. We investigate the comparative benefit of adjuvant chemotherapy (CT) alone, radiation therapy alone (RT) or in combination (chemotherapy and radiation therapy [CRT]) with respect to recurrence-free survival (RFS) and overall survival (OS) in women with pelvis-limited (PL) EC (stage IIIA, IIIB, and IIIC1). MATERIALS AND METHODS: A multi-institutional database of 270 surgically staged women with PLEC was analyzed. Univariate log-rank analyses and Cox regression multivariate analyses (MVA) were performed to identify factors associated with RFS and OS. RESULTS: Median RFS and OS were 112 and 130 months, respectively, for the full cohort. Adjuvant treatment was CT in 21%, RT in 27%, and CRT in 47%. Age, year of treatment, grade, histology, and adjuvant treatment were significantly associated with RFS and OS on univariate analysis. PLEC patients receiving CT alone fared worse in terms of RFS (P=0.07 relative to RT and \u3c0.01 relative to CRT). On MVA, CRT retained significantly improved RFS relative to CT (hazard ratio for recurrence 0.38, P\u3c0.01). PLEC patients receiving RT or CRT had improved OS compared with CT, P\u3c0.01 and 0.03, respectively. On MVA, both RT only and CRT retained association with improved OS relative to CT alone (hazard ratio for death, 0.43, P=0.02 and 0.40, P\u3c0.01, respectively). CONCLUSIONS: For surgically staged PL stage III EC, treatment regimens incorporating RT were associated with improved survival endpoints relative to CT alone. As such, RT should be considered an important component in the adjuvant management of stage III PLEC

Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases

BackgroundLaser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.MethodsDemographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.ResultsNinety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure.ConclusionsLITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients

Estimation of daily interfractional larynx residual setup error after isocentric alignment for head and neck radiotherapy: quality assurance implications for target volume and organs-at-risk margination using daily CT on- rails imaging.

Larynx may alternatively serve as a target or organs at risk (OAR) in head and neck cancer (HNC) image-guided radiotherapy (IGRT). The objective of this study was to estimate IGRT parameters required for larynx positional error independent of isocentric alignment and suggest population-based compensatory margins. Ten HNC patients receiving radiotherapy (RT) with daily CT on-rails imaging were assessed. Seven landmark points were placed on each daily scan. Taking the most superior-anterior point of the C5 vertebra as a reference isocenter for each scan, residual displacement vectors to the other six points were calculated postisocentric alignment. Subsequently, using the first scan as a reference, the magnitude of vector differences for all six points for all scans over the course of treatment was calculated. Residual systematic and random error and the necessary compensatory CTV-to-PTV and OAR-to-PRV margins were calculated, using both observational cohort data and a bootstrap-resampled population estimator. The grand mean displacements for all anatomical points was 5.07 mm, with mean systematic error of 1.1 mm and mean random setup error of 2.63 mm, while bootstrapped POIs grand mean displacement was 5.09 mm, with mean systematic error of 1.23 mm and mean random setup error of 2.61 mm. Required margin for CTV-PTV expansion was 4.6 mm for all cohort points, while the bootstrap estimator of the equivalent margin was 4.9 mm. The calculated OAR-to-PRV expansion for the observed residual setup error was 2.7 mm and bootstrap estimated expansion of 2.9 mm. We conclude that the interfractional larynx setup error is a significant source of RT setup/delivery error in HNC, both when the larynx is considered as a CTV or OAR. We estimate the need for a uniform expansion of 5 mm to compensate for setup error if the larynx is a target, or 3 mm if the larynx is an OAR, when using a nonlaryngeal bony isocenter