Incidence and management of early postoperative complications in lamellar corneal transplantation.

PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1 month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.

Reproducibility and stability of spirometer-guided deep inspiration breath-hold in left-breast treatments using an optical surface monitoring system.

The aim of this study was to evaluate the reproducibility and stability of left breast positioning during spirometer-guided deep-inspiration breath-hold (DIBH) radiotherapy using an optical surface imaging system (AlignRT). The AlignRT optical tracking system was used to monitor five left-sided breast cancer patients treated using the Active Breathing Coordinator spirometer with DIBH technique. Treatment plans were created using an automated hybrid-VMAT technique on DIBH CTs. A prescribed dose of 60 Gy to the tumor bed and 50 Gy to the breast in 25 fractions was planned. During each treatment session, the antero-posterior (VRT), superior-inferior (LNG), and lateral (LAT) motion of patients was continuously recorded by AlignRT. The intra-breath-hold stability and the intra- and inter-fraction reproducibility were analyzed for all breath-holds and treatment fractions. The dosimetric impact of the residual motion during DIBH was evaluated from the isocenter shifts amplitudes obtained from the 50%, 90%, and 100% cumulative distribution functions of intra-fractional reproducibility. The positional variations of 590 breath-holds as measured by AlignRT were evaluated. The mean intra-breath-hold stability during DIBH was 1.0 ± 0.4 mm, 2.1 ± 1.9 mm, and 0.7 ± 0.5 mm in the VRT, LNG, and LAT directions, with a maximal value of 8.8 mm in LNG direction. Similarly, the mean intra-breath-hold reproducibility was 1.4 ± 0.8 mm, 1.7 ± 1.0 mm, and 0.8 ± 0.5 mm in the VRT, LNG, and LAT directions, with a maximal value of 4.1 mm in LNG direction. Inter-fractional reproducibility showed better reliability, with difference in breathing levels in all fractions of 0.3 mm on average. Based on tolerance limits corresponding to the 90% cumulative distribution level, gating window widths of 1 mm, 2 mm, and 5 mm in the LAT, VRT, and LNG directions were considered an appropriate choice. In conclusion, despite the use of a dedicated spirometer at constant tidal volume, a non-negligible variability of the breast surface position has been reported during breath-holds. The real-time monitoring of breast surface using surface-guided optical technology is strongly recommended.

Gender medicine in corneal transplantation: influence of sex mismatch on rejection episodes and graft survival in a prospective cohort of patients.

To evaluate the effect of donor-to-recipient sex mismatched (male donor corneas to female recipients) on the incidence of rejection episodes and failures up to 1 year after corneal transplantation. Prospective observational cohort study, with donor corneas randomly assigned and surgeons blind to the sex of donor. A unique eye bank retrieved and selected the donor corneas transplanted in 4 ophthalmic units in patients with clinical indication for primary or repeated keratoplasty for optical reasons, perforating or lamellar, either anterior or posterior. Rejection episode defined as any reversible or irreversible endothelial, epithelial or stromal sign, with or without development of corneal edema, and graft failure as a permanently cloudy graft or a regraft for any reason detected or acknowledged during a postoperative ophthalmic visit at any time up to 1 year after surgery were recorded.156 (28.6%) patients resulted donor-to-recipient gender mismatched for H-Y antigen (male donor to female recipient). During the 12 months follow-up, 83 (14.7%, 95% CI 12.0-17.9) grafts showed at least 1 rejection episode and 17 (3.2%, 95% CI 2.0-5.0) failed after immune rejection, among 54 (9.6%, 95% CI 7.4-12.3) grafts failed for all causes. No significant differences between matched and mismatched patients were found for cumulative incidence of both rejection episodes (15.2% and 13.5%) and graft failures following rejection (3.2% and 2.6%), respectively. Multivariable analyses showed that H-Y matching either is not a predictive factor for rejection or graft failure nor seems to influence incidence of failures on respect to patient's risk category. The lack of influence of donor-to-recipient mismatched on the rate of rejections and graft failures resulting from this study do not support the adoption of donor-recipient matching in the allocation of corneas for transplantation.

Automated treatment planning as a dose escalation strategy for stereotactic radiation therapy in pancreatic cancer.

PURPOSE: To assess the feasibility of automated stereotactic volumetric modulated arc therapy (SBRT-VMAT) planning using a simultaneous integrated boost (SIB) approach as a dose escalation strategy for SBRT in pancreatic cancer. METHODS: Twelve patients with pancreatic cancer were retrospectively replanned. Dose prescription was 30 Gy to the planning target volume (PTV) and was escalated up to 50 Gy to the boost target volume (BTV) using a SIB technique in 5 fractions. All plans were generated by Pinnacle3 Autoplanning using 6MV dual-arc VMAT technique for flattened (FF) and flattening filter-free beams (FFF). An overlap volume (OLV) between the PRV duodenum and the PTV was defined to correlate with the ability to boost the BTV. Dosimetric metrics for BTV and PTV coverage, maximal doses for serial OARs, integral dose, conformation numbers, and dose contrast indexes were used to analyze the dosimetric results. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Differences between FF and FFF plans were quantified using the Wilcoxon matched-pair signed rank. RESULTS: Full prescription doses to the 95% of PTV and BTV can be delivered to patients with no OLV. BTV mean dose was >90% of the prescribed doses for all patients at all dose levels. Compared to FF plans, FFF plans showed significant reduced integral doses, larger number of MUs, and reduced beam-on-times up to 51% for the highest dose level. Despite plan complexity, pre-treatment verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all FF and FFF plans for 3%-2 mm criteria. CONCLUSIONS: The SIB-SBRT strategy with Autoplanning was dosimetrically feasible. Ablative doses up to 50 Gy in 5 fractions can be delivered to the BTV for almost all patients respecting all the normal tissue constraints. A prospective clinical trial based on SBRT strategy using SIB-VMAT technique with FFF beams seems to be justified.

Epid-based in vivo dose verification for lung stereotactic treatments delivered with multiple breath-hold segmented volumetric modulated arc therapy.

We evaluated an EPID-based in-vivo dosimetry (IVD) method for the dose verification and the treatment reproducibility of lung SBRT-VMAT treatments in clinical routine. Ten patients with lung metastases treated with Elekta VMAT technique were enrolled. All patients were irradiated in five consecutive fractions, with total doses of 50 Gy. Set-up was carried out with the Elekta stereotactic body frame. Eight patients were simulated and treated using the Active Breath Control (ABC) system, a spirometer enabling patients to maintain a breath-hold at a predetermined lung volume. Two patients were simulated and treated in free-breathing using an abdominal compressor. IVD was performed using the SOFTDISO software. IVD tests were evaluated by means of (a) ratio R between daily in-vivo isocenter dose and planned dose and (b) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ% ) and mean γ-values (γmean ) using a 3%(global)/3 mm criteria. Alert criteria of ±5% for R ratio, γ%  < 90%, and γmean  > 0.67 were chosen. 50 transit EPID images were acquired. For the patients treated with ABC spirometer, the results reported a high level of accuracy in dose delivery with 100% of tests within ±5%. The γ-analysis showed a mean value of γmean equal to 0.21 (range: 0.04-0.56) and a mean γ% equal to 96.9 (range: 78-100). Relevant discrepancies were observed only for the two patients treated without ABC, mainly due to a blurring dose effect due to residual respiratory motion. Our method provided a fast and accurate procedure in clinical routine for verifying delivered dose as well as for detecting errors.

Predicting Long-Term Endothelial Cell Loss after Preloaded Descemet Membrane Endothelial Keratoplasty in Fuchs' Endothelial Corneal Dystrophy: A Mathematical Model.

(1) Background: This study offers a biexponential model to estimate corneal endothelial cell decay (ECD) following preloaded "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) in Fuchs' endothelial corneal dystrophy (FECD) patients; (2) Methods: A total of 65 eyes undergoing DMEK alone or combined with cataract surgery were evaluated. The follow-up period was divided into an early phase (first 6 months) and a late phase (up to 36 months). Endothelial cell count (ECC) and endothelial cell loss (ECL) were analyzed; (3) Results: The half time of the ECD was 3.03 months for the early phase and 131.50 months for the late phase. The predicted time-lapse interval to reach 500 cells/mm2 was 218 months (18.17 years), while the time-lapse interval to reach 250 cells/mm2 was 349 months (29.08 years). There was no statistically significant difference between the ECL in DMEK combined with cataract extraction and DMEK alone at 24 months (p ≥ 0.20). At the late phase, long-term ECL prediction revealed a lower ECC half time in patients undergoing DMEK combined with cataract surgery (98.05 months) than DMEK alone (250.32 months); (4) Conclusions: Based on the mathematical modeling, a predicted average half-life of a DMEK graft could reach 18 years in FECD. Moreover, combining cataract extraction with DMEK could result in excessive ECL in the long term.

Automated single-isocenter stereotactic body radiotherapy for multiple metastases from breast cancer: A case study.

Oligometastatic breast cancer patients can today could benefit from a multimodal approach, combining systemic therapy with metastasis-directed treatment using stereotactic body radiotherapy (SBRT). However, the possibility to synchronously treat multiple lesions is still challenging, needing the ability to generate complex dose distributions with steep dose gradients outside the lesions and major sparing of surrounding organs at risk and accurately track and reproduce the patient's position before and during radiation therapy. We report the case of an oligometastatic patient from left breast cancer, which occurred after a full course of whole breast radiotherapy, treated using the potential of modern technology including single-isocenter setup, plan automation, breath-hold technique and surface guided tracking and reproducibility of patient's position before and during radiation therapy. A 44-year-old female patient with a history of left breast cancer, specifically a luminal-B-like invasive ductal carcinoma with Her2 overexpression, was admitted to our department. The patient previously underwent a left mastectomy (pT2N0M0), 4 cycles of adjuvant chemotherapy, adjuvant radiotherapy on the chest wall and lymph nodes drainage, and 5 years of hormonal therapy. A chest wall ultrasound and positron emission tomography revealed the presence of new lesions in the area of the surgical scar from the previous mastectomy, internal mammary, axillary and retropectoral levels. The 3 lesions were simultaneously treated with a mono-isocentric VMAT plan using SBRT technique with a total dose of 30 Gy delivered in 5 fractions. Due to the technical challenges, this treatment was supported by the use of planning automation, breath-hold technique and surface-guided radiation therapy to improve the accuracy of the dose delivery. Two different plans were generated and compared to pursue the best dosimetric result, including a summed plan obtained from 3 individual SBRT plans for each lesion with a separate isocenter placed in each of them (MIP), and a single-isocenter SBRT plan able to treat multiple lesions synchronously (SIP). Because of the advantages in terms of dosimetry and dose delivery efficiency, the patient was successfully treated with the SIP plan. The treatment time was reduced to about 4.5 minutes, allowing the comfortably use of breath-hold technique. After treatment, the condition of the patient was normal, and no toxicities have been observed in follow-up. SBRT with mono isocentric VMAT planning represents the recommended approach to simultaneously treat multiple lesions in close proximity in the thoracic district.

Preoperative Posterior Stromal Ripples as Predictive Biomarkers of Visual Recovery After DMEK.

PURPOSE: To investigate the role of preoperative posterior stromal ripples (pre-PSR) on visual acuity recovery after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This is a comparative case series retrospectively analyzing patients who underwent DMEK. Electronic records and imaging of DMEK patients were reviewed. The last preoperative and first postoperative available anterior segment optical coherence tomography scans for each eye were analyzed for the presence of pre-PSR. The difference in longitudinal trends of visual acuity recovery after DMEK was assessed in eyes with and without pre-PSR. The frequency of rebubbling and measures of proportional relative risk of rebubbling were analyzed according to the presence of preoperative and postoperative PSR. RESULTS: A total of 66 patients (71 eyes) were included. Pre-PSR were associated with lower preoperative visual acuity [0.6 (0.5) vs. 0.9 (0.6) LogMAR, P = 0.02] and higher central corneal thickness [613 (73.8) vs. 715.7 (129.6) micron, P < 0.001]. Eyes with pre-PSR had a slower visual recovery up to 3.5 months after surgery compared to eyes without pre-PSR and achieved lower final visual acuity [0.1 (0.2) vs. 0.3 (0.3) LogMAR, P = 0.02]. Cox proportional hazard ratios showed that postoperative PSR were associated with a greater risk of rebubbling [hazard ratio (95% CI), 7.1 (1.3, 39.5), P = 0.02] while pre-PSR were not. CONCLUSIONS: The presence of pre-PSR is associated with slower visual recovery and lower final visual acuity after DMEK while postoperative PSR confer a higher risk of rebubbling. PSR represent a valuable prognostic biomarker both before and after DMEK.

Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty With Endothelium Inward: A 24-Month Comparative Analysis Between Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

PURPOSE: The aim of this study was to compare long-term clinical outcomes of preloaded Descemet membrane endothelial keratoplasty (DMEK) between Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). METHODS: In this single-center retrospective clinical case series, 71 eyes of 64 patients indicated with FECD (62%) or BK (38%) (with or without cataract) were treated with preloaded DMEK grafts between March 2018 and February 2020. Standard DMEK peeling, followed by manual folding of the tissue with endothelium-inward orientation and storing in a preloaded fashion inside a 2.2-mm intraocular lens cartridge. All tissues were delivered using a bimanual pull-through technique, followed by air tamponade. Graft unfolding time, endothelial cell loss, corrected distance visual acuity, central corneal thickness, rebubbling rate, and intraoperative and postoperative complications at 1, 3, 6, 12, and 24 months were recorded. RESULTS: The mean intraoperative graft unfolding time in FECD did not differ from the BK group ( P = 0.6061). Cystoid macular edema did not differ in either group ( P = 0.6866). The rebubbling rate was found to be significantly higher in FECD compared with the BK group ( P = 0.0423). Corrected distance visual acuity significantly improved at the first month after surgery ( P = 0.0012), with no differences between FECD and BK at 24 months ( P = 0.2578). Central corneal thickness was stable postoperatively and showed no differences between the groups ( P = 0.3693). Significantly higher endothelial cell counts were observed in the FECD group at 24 months ( P = 0.0002). CONCLUSIONS: Preloaded DMEK with "endothelium-in" offers acceptable intraoperative time, rebubbling rate, and clinical outcomes in both FECD and BK groups. Patients with FECD show better postoperative clinical outcomes even if the rebubbling rate is relatively high.

Yogurt Technique for Descemet Membrane Endothelial Keratoplasty Graft Preparation: Early Clinical Outcomes.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of the Yogurt technique for Descemet membrane endothelial keratoplasty (DMEK) graft preparation. METHODS: This study included patients who underwent DMEK combined or not with phacoemulsification surgery using donor tissues prepared by a surgeon with the DMEK Tzamalis disposable punch at 2 referral hospitals between October 2019 and June 2021. Primary outcomes were duration of graft preparation, surgeon grading of graft quality, and endothelial cell density measured at 1 and 6 months after surgery. Secondary outcomes were best-corrected visual acuity (BCVA) measured at 1 and 6 months postoperatively and DMEK intraoperative and postoperative complications. RESULTS: Forty-nine patients were included in this study. The mean DMEK graft preparation time was 7.2 ± 1.4 minutes. Donor grafts were rated good in 67.3% of cases (33 of 49), sufficient in 24.5% (12 of 49), and poor in 8.2% (4 of 49). Donor mean endothelial cell density was 2580 ± 155 preoperatively, which were reduced to 2269 ± 191 ( P < 0.000) and 1697 ± 142 ( P < 0.0001) at 1 and 6 months, respectively. No significant difference was found in graft preparation outcome ( P = 0.543). The preoperative BCVA was 0.65 ± 0.44 logMAR, which improved to 0.31 ± 0.43 logMAR ( P < 0.0001) and 0.12 ± 0.14 logMAR ( P < 0.0001) at 1 and 6 months after surgery, respectively. CONCLUSIONS: This study shows that the DMEK Tzamalis punch can be used as an effective and safe method for DMEK graft preparation with a shallow learning curve that allows it to be successfully performed by relatively inexperienced surgeons.

Feasibility-guided automated planning for stereotactic treatments of prostate cancer.

Significant improvements in plan quality using automated planning have been previously demonstrated. The aim of this study was to develop an optimal automated class solution for stereotactic radiotherapy (SBRT) planning of prostate cancer using the new Feasibility module implemented in the pinnacle evolution. Twelve patients were retrospectively enrolled in this planning study. Five plans were designed for each patient. Four plans were automatically generated using the 4 proposed templates for SBRT optimization implemented in the new pinnacle evolution treatment planning systems, differing for different settings of dose-fallout (low, medium, high and veryhigh). Based on the obtained results, the fifth plan (feas) was generated customizing the template with the optimal criteria obtained from the previous step and integrating in the template the "a-priori" knowledge of OARs sparing based on the Feasibility module, able to estimate the best possible dose-volume histograms of OARs before starting optimization. Prescribed dose was 35 Gy to the prostate in 5 fractions. All plans were generated with a full volumetric-modulated arc therapy arc and 6MV flattening filter-free beams, and optimized to ensure the same target coverage (95% of the prescription dose to 98% of the target). Plans were assessed according to dosimetric parameters and planning and delivery efficiency. Differences among the plans were evaluated using a Kruskal-Wallis 1-way analysis of variance. The requests for more aggressive objectives for dose falloff parameters (from low to veryhigh) translated in a statistically significant improvement of dose conformity, but at the expense of a dose homogeneity. The best automated plans in terms of best trade-off between target coverage and OARs sparing among the 4 plans automatically generated by the SBRT module were the high plans. The veryhigh plans reported a significant increase of high-doses to prostate, rectum, and bladder that was considered dosimetrically and clinically unacceptable. The feas plans were optimized on the basis on high plans, reporting significant reduction of rectum irradiation; Dmean, and V18 decreased by 19% to 23% (p = 0.031) and 4% to 7% (p = 0.059), respectively. No statistically significant differences were found in femoral heads and penile bulb irradiation for all dosimetric metrics. feas plans showed a significant increase of MU/Gy (mean: 368; p = 0.004), reflecting an increased level of fluence modulation. Thanks to the new efficient optimization engines implemented in pinnacle evolution (L-BFGS and layered graph), mean planning time was decreased to less than 10 minutes for all plans and all techniques. The integration of dose-volume histograms a-priori knowledge provided by the feasibility module in the automated planning process for SBRT planning has shown to significantly improve plan quality compared to generic protocol values as inputs.

Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol.

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.

Prediction and classification of VMAT dosimetric accuracy using plan complexity and log-files analysis.

PURPOSE: We presented different machine learning models based on log files analysis and complexity indexes to predict and classify the dosimetric accuracy of VMAT plans. METHODS: A total of 1302 VMAT arcs from 651 treatment plans were analyzed using the modulation complexity score (MCS) and the dynamic log-files generated by the linac. Predicted and measured fluences were compared using γ-analysis in terms of mean γ-values (γmean) and γ-pass rate (γ%). A kernel regression model was developed aiming to predict individual γ% and γmean values. Multinomial logistic regression (LR), Naïve-Bayes (NB) and support vector machine (SVM) models were developed based on MCS values to classify QA results as "pass" (γ%greater than90 % and γmean < 0.5), "control" (80 % < Î³% < 90 % and 0.50 < Î³mean < 0.75) and "fail" (γ% < 80 % and γmean > 0.75). Training, validation and testing groups were used to evaluate the model reliability. A complexity-based traffic light protocol was implemented to flag pass (green light), control (orange light) and failed plans (red light). RESULTS: Prediction accuracy of residuals for γ% was 2.1 % and 2.2 % in the training and testing cohorts, respectively. For 2 %(local)/2mm, both γ% and γmean classification performances reported weighted precision, recall and F1-values greater than 90 % for all machine learning models. The optimal MCS threshold value for the identification of failed plans was 0.130, with a sensibility and specificity of 0.994 and 0.952, respectively. The optimal MCS threshold for reliable plans was 0.270, with a sensitivity and specificity of 0.925 and 0.922, respectively. CONCLUSIONS: Machine learning can accurately predict the dosimetric accuracy of VMAT treatments, representing an efficient tool to assist patient-specific QA.

Prediction of VMAT delivery accuracy using plan modulation complexity score and log-files analysis.

The purpose of this study was to develop a predictive model based on plan complexity metrics and linac log-files analysis to classify the dosimetric accuracy of VMAT plans. A total of 612 VMAT plans, corresponding to 1224 arcs, were analyzed. All VMAT arcs underwent pre-treatment verification that was performed by means of the dynamic log-files generated by the linac. The comparison of predicted (by TPS) and measured (by log-files) integral fluences was performed usingγ-analysis in terms of the percentage of points withγ-value smaller than one (γ%) and using a stringent 2%(local)/2 mm criteria. Thisγ-analysis was performed by a commercial software LinacWatch. The action limits (AL) were derived from the mean values, standard deviations and the confidence limit (CL) of theγ% distribution. A plan complexity metric, the modulation complexity score (MCS), based on the aperture beam area variability and leaf sequence variability was used as input variable of the model. A binary logistic regression (LR) model was developed to classify QA results as 'pass' (γ% ≥ AL) or 'fail' (γ% < AL). Receiver operator characteristics (ROC) curves were used to determine the optimal MCS threshold to flag 'failed' plans that need to be re-optimized. The model reliability was evaluated stratifying the plans in training, validation and testing groups. The confidence and action limits forγ% were found 20.1% and 79.9%, respectively. The accuracy of the model for the training and testing dataset was 97.4% and 98.0%, respectively. The optimal MCS threshold value for the identification of failed plans was 0.142, providing a true positive rate able to flag the plans failing QA of 91%. In clinical routine, the use of this MCS threshold may allow the prompt identification of overly modulated plans, then reducing the number of QA failures and improving the quality of VMAT plans used for treatment.

Personalized Automation of Treatment Planning for Linac-Based Stereotactic Body Radiotherapy of Spine Cancer.

PURPOSE/OBJECTIVES: Stereotactic ablative body radiotherapy (SBRT) for vertebral metastases is a challenging treatment process. Planning automation has recently reported the potential to improve plan quality and increase planning efficiency. We performed a dosimetric evaluation of the new Personalized engine implemented in Pinnacle3 for full planning automation of SBRT spine treatments in terms of plan quality, treatment efficiency, and delivery accuracy. MATERIALS/METHODS: The Pinnacle3 treatment planning system was used to reoptimize six patients with spinal metastases, employing two separate automated engines. These two automated engines, the existing Autoplanning and the new Personalized, are both template-based algorithms that employ a wishlist to construct planning goals and an iterative technique to replicate the planning procedure performed by skilled planners. The boost tumor volume (BTV) was defined as the macroscopically visible lesion on RM examination, and the planning target volume (PTV) corresponds with the entire vertebra. Dose was prescribed according to simultaneous integrated boost strategy with BTV and PTV irradiated simultaneously over 3 fractions with a dose of 30 and 21 Gy, respectively. Dose-volume histogram (DVH) metrics and conformance indices were used to compare clinically accepted manual plans (MP) with automated plans developed using both Autoplanning (AP) and Personalized engines (Pers). All plans were evaluated for planning efficiency and dose delivery accuracy. RESULTS: For similar spinal cord sparing, automated plans reported a significant improvement of target coverage and dose conformity. On average, Pers plans increased near-minimal dose D98% by 10.4% and 8.9% and target coverage D95% by 8.0% and by 4.6% for BTV and PTV, respectively. Automated plans provided significantly superior dose conformity and dose contrast by 37%-47% and by 4.6%-5.7% compared with manual plans. Overall planning times were dramatically reduced to about 15 and 23 min for Pers and AP plans, respectively. The average beam-on times were found to be within 3 min for all plans. Despite the increased complexity, all plans passed the 2%/2 mm γ-analysis for dose verification. CONCLUSION: Automated planning for spine SBRT through the new Pinnacle3 Personalized engine provided an overall increase of plan quality in terms of dose conformity and a major increase in efficiency. In this complex anatomical site, Personalized strongly reduce the tradeoff between optimal accurate dosimetry and planning time.

Factors Affecting the Success Rate of Preloaded Descemet Membrane Endothelial Keratoplasty With Endothelium-Inward Technique: A Multicenter Clinical Study.

PURPOSE: To evaluate factors affecting the outcomes of preloaded Descemet membrane endothelial keratoplasty (pl-DMEK) with endothelium-inward. DESIGN: Retrospective clinical case series and a comparative tissue preparation study. METHODS: Participants: Fifty-five donor tissues for ex vivo study and 147 eyes of 147 patients indicated with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy with or without cataract. INTERVENTION: Standardized DMEK peeling was performed with 9.5-mm-diameter trephination followed by second trephination for loading the graft (8.0-9.5 mm diameter). The tissues were manually preloaded with endothelium-inward and preserved for 4 days or shipped for transplantation. Live and dead assay and immunostaining was performed on ex vivo tissues. For the clinical study, the tissues were delivered using bimanual pull-through technique followed by air tamponade at all the centers. MAIN OUTCOME MEASURES: Tissue characteristics, donor and recipient factors, rebubbling rate, endothelial cell loss (ECL), and corrected distance visual acuity (CDVA) at 3, 6, and 12 months. RESULTS: At day 4, significant cell loss (P = .04) was observed in pl-DMEK with loss of biomarker expression seen in prestripped and pl-DMEK tissues. Rebubbling was observed in 40.24% cases. Average ECL at 3, 6, and 12 months was 45.87%, 40.98%, and 47.54%, respectively. CDVA improved significantly at 3 months postoperation (0.23 ± 0.37 logMAR) (P < .01) compared to the baseline (0.79 ± 0.61 logMAR). A significant association (P < .05) between graft diameter, preservation time, recipient gender, gender mismatch, and recipient age to rebubbling rate was observed. CONCLUSION: Graft loading to delivery time of pl-DMEK tissues in endothelium-inward fashion must be limited to 4 days after processing. Rebubbling rate and overall surgical outcomes following preloaded DMEK can be multifactorial and center-specific.

Real time transit dosimetry for the breath-hold radiotherapy technique: an initial experience.

INTRODUCTION: The breath-hold is one of the techniques to obtain the dose escalation for lung tumors. However, the change of the patient's breath pattern can influence the stability of the inhaled air volume, IAV, used in this work as a surrogate parameter to assure the tumor position reproducibility during dose delivery. MATERIALS AND METHOD: In this paper, an Elekta active breathing coordinator has been used for lung tumor irradiation. This device is not an absolute spirometer and the feasibility study here presented developed (i) the possibility to select a specific range epsilon of IAV values comfortable for the patient and (ii) the ability of a transit signal rate S(t), obtained by a small ion-chamber positioned on the portal image device, to supply in real time the in vivo isocenter dose reproducibility. Indeed, while the selection of the IAV range depends on the patient's ability to follow instructions for breath-hold, the S(t) monitoring can supply to the radiation therapist a surrogate of the tumor irradiation reproducibility. RESULTS: The detection of the S(t) in real time during breath-hold was used to determine the interfraction isocenter dose variations due to the reproducibility of the patient's breathing pattern. The agreement between the reconstructed and planned isocenter dose in breath-hold at the interfraction level was well within 1.5%, while in free breathing a disagreement up to 8% was observed. The standard deviation of the S(t) in breath-hold observed at the intrafraction level is a bit higher than the one obtained without the patient and this can be justified by the presence of a small residual tumor motion as heartbeat. CONCLUSION: The technique is simple and can be implemented for routine use in a busy clinic.

Comparison of measured and computed portal dose for IMRT treatment.

A new 2D array Seven 29T model (PTW, Freiburg), equipped with 729 vented plane-parallel ion chambers, projected for pretreatment verification of radiotherapy plans, was used as a detector for the transmitted or portal dose measurements below a Rando phantom. The dosimetric qualities of the 2D array make it attractive for measuring transmitted dose maps from step-and-shoot intensity-modulated radiotherapy (IMRT). It is well known that for step-and-shoot IMRT beams that use a small number of monitor units (MUs) per sequence, the early and recent electronic portal imaging devices (EPIDs) present a different response at X-ray start-up that affects the accuracy of the measured transmitted dose. The comparison of portal doses measured to those calculated by a commercial treatment-planning system (TPS) can verify correct dose delivery during treatment. This direct validation was tested by irradiating a simulated head tumor in a Rando anthropomorphic phantom by step-and-shoot IMRT beams. The absolute transmitted doses on a plane orthogonal to the beam central axis below the phantom were measured by the 2D array calibrated in terms of dose to water and compared with the computed portal dose extracted by custom software. In a previous paper, the comparison between the IMRT portal doses, computed by a commercial TPS and measured by a linear array that supplied a 1 mm spatial dose resolution, was carried out. The gamma-index analysis supplied an agreement of more than 95% of the dose point with acceptance criteria, in terms of dose difference, DeltaDmax, and distance agreement, deltadmax, equal to 4% and 4 mm, respectively. In this paper, we verify the possible use of the PTW 2D array for measurements of the transmitted doses during several fractions of head and neck tumor radiotherapy. There are two advantages in the use of this 2D array as a portal dose device for the IMRT quality assurance program: first is the ability to perform absolute dose comparisons for hundreds of measurement positions to verify the correct dose delivery in several fractions of the therapy; second is the efficiency in time to detect these kinds of dose distributions within the field of view area of the CT scanner.

Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience.

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36min/Gy. The mean number of monitor units was 3162, i.e., 121.6MU/Gy. Pretreatment verification (3%-3mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.