Ablative Radiotherapy for Unfavorable Prostate Tumors (ABRUPT): Analysis of Toxicity and Quality of Life from a Prospective Study.

AIM: To assess late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single dose ablative radiotherapy (SDRT). METHODS: Thirty patients enrolled in a single-arm prospective trial received 24 Gy SDRT to the whole prostate with urethra sparing and organ motion control delivered on a Linac platform with a 10MV FFF single partial arc. ADT was prescribed as per standard of care. Treatment-related acute and late GU and GI toxicities (CTCAE_v5 scale) and QoL outcomes (EORTC QLQ-PR25/C30, IPSS) were assessed at different time points. Minimal Important Difference (MID) was established as a change of >0.5 pooled SD from baseline. Statistical analysis included ANOVA test and logistic regression. RESULTS: Median follow-up was 18 months (range, 6-31), with no ≥G3 late side effects observed. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. GI toxicity of any grade correlated with maximum rectal dose (P=0.021). Lower baseline QoL score (P=0.025), higher baseline IPSS score (P=0.049), acute GU toxicity (P=0.029), and acute urinary domain MID (P=0.045) predicted GU toxicity of any grade. In MVA, only baseline QoL score (OR, 0.95, P=0.031) and acute GU toxicity (OR, 8.4, P=0.041) remained significant. Significant QoL change was observed only in the urinary domain (P=0.005), with a median increase from 8 to 17. Late urinary MID correlated with acute urinary MID (P=0.003), acute QoL MID (P=0.029), acute GU toxicity (P=0.030), and lower baseline urinary score (P=0.033). In MVA, only acute urinary MID predicted late urinary MID (OR, 9.7, P=0.035). CONCLUSION: Our findings provide promising data on the feasibility and safety of 24 Gy whole gland SDRT with urethra sparing and organ motion control, in association with ADT and an adequate prophylactic medication, in organ confined unfavorable PCa. Long-term follow-up is needed to confirm these results.

Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

PURPOSE: To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. METHODS: A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35 years, 198 embryos) and AMA (≥ 35 years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. RESULTS: Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). CONCLUSION: Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

The paradigm shift in advanced ovarian cancer: Outcomes of extensive primary cytoreductive surgery. A single-center retrospective analysis.

OBJECTIVE: The standard surgical treatment of advanced ovarian carcinoma is primary debulking surgery (PDS) aiming to complete cytoreduction. The need to achieve complete cytoreduction has shifted the surgical paradigm to more complex procedures, whose impact on morbidity is controversial. The objective of this retrospective analysis is to explore the impact of extensive PDS on morbidity and oncologic outcomes in a real-world scenario. METHODS: A retrospective single-center analysis was performed on 137 patients with advanced high-grade ovarian carcinoma (HGOC) who received PDS in 2015-2020. Patients treated in 2015-2017 (Group 1) were compared to patients treated in 2018-2020 (Group 2). The two periods were chosen according to the higher complexity of surgical procedures introduced in 2018. RESULTS: The increase in complete cytoreduction observed in Group2 (RD 0: 33 % vs 61 %, p = 0,008) was related to a higher surgical complexity (Aletti Score: 4 vs 6, p = 0,003) and did not reflect an increase in peri-operative complications (CCI: 20,9 vs 20,9, p = 0,11). After a median FUP of 44 months, PFS and OS at 24 months were 33,60 % vs 47,33 % (p = 0,288) and 72,10 % vs 80,37 % (p = 0,022) in Group 1 and 2, respectively. CONCLUSIONS: An extensive surgical effort leads to a significant increase in complete cytoreduction with acceptable morbidity. Arm-in-arm with novel maintenance therapies, it contributes to increasing the outcomes of patients with advanced HGOC.

Long-term mandibular growth in patients with airway obstruction treated with mandibular distraction.

Congenital craniofacial malformations play an important role in upper airway obstruction. One of the main causes is mandibular hypoplasia which is present in the pierre robin sequence. Mandibular distraction osteogenesis (MDO) is one of the most commonly used treatments for the resolution of upper airway obstruction in patients that do not respond to a conservative treatment. We performed a long term follow up of syndromic and non-syndromic patients with pierre robin sequence where the lateral xrays were studied before surgery (T1), after MDO (T2) and long-term follow-up (T3, at least 5 years). Possible complications of the surgery were also studied through panoramic x-rays and clinical controls. The results evidenced an increase of mandibular length comparing T1-T2 and a good stability during the long-term follow-up. The Sd patients presented smaller mandible dimensions. We had not found any complications during the follow-up. The scars outcomes are modest, but none of the patients requested a surgical correction. Mandibular distraction osteogenesis is a treatment to be considered in patients with upper airway obstruction that do not respond to conservative treatments. The results of the surgery are stable and the complications in experienced hands are low.

Lexicographic optimization-based planning for stereotactic radiosurgery of brain metastases.

AIM: To validate a fully-automated lexicographic optimization-planning system (mCycle, Elekta) for single-(SL) and multiple-(ML, up to 4 metastases) lesions in intracranial stereotactic radiosurgery (SRS, 21 Gy, single fraction). METHODS: A pre-determined priority list, Wish-List (WL), represents a dialogue between planner and clinician, establishing strict constraints and pursuing objectives. In order to satisfy the clinical protocol without manual intervention, four patients were required to tweak and fine-tune each WL (SLp, MLp) for coplanar arcs. Thirty-five testing plans (20 SLp, 15 MLp) were automatically re-planned (mCP). Automatic and manual plans were compared including dose constraints, conformality, modulation complexity score (MCS), delivery time, and local gamma analysis (2%/2 mm). To ensure plan clinical acceptability, two radiation oncologists conducted an independent blind plan choice. RESULTS: Each WL-tuning took 3 days. Estimated median manual plans and mCP calculation time were 8 and 3 h, respectively. Significant increases in SLp and MLp target coverage and conformity were registered. mCP showed a not significant and clinically acceptable higher median brain V12Gy. SLp registered a -5.8% MU decrease with comparable median delivery time (MP 2.0 min, mCP 1.9 min) while MLp showed a +9.8% MU increase and longer delivery time (MP 3.5 min, mCP 4.4 min). mCP MCS resulted significantly higher without affecting gamma passing rates. At blind choice, mCP were preferred in the majority of cases. CONCLUSIONS: Lexicographic optimization produced acceptable SRS plans with coplanar arcs significantly reducing the overall planning time in cases with up to 4 brain metastases. These planning improvements suggest further investigations by setting high-quality non-coplanar arc plans as a reference.

Correlation between Malocclusion and Mandibular Fractures: An Experimental Study Comparing Dynamic Finite Element Models and Clinical Case Studies.

Mandibular fractures are very common in maxillofacial trauma surgery. While previous studies have focused on possible risk factors related to post-operative complications, none have tried to identify pre-existing conditions that may increase the risk of mandibular fractures. We hypothesized, through clinical observation, that anatomical conditions involving poor dental contacts, such as malocclusions, may increase the risk of mandibular fractures. This work was subdivided into two parts. In the first part, Digital Imaging and Communications in Medicine (DICOM) data of four healthy patients characterized by different dentoskeletal occlusions (class I, class II, class III, and anterior open bite) have been used to develop four finite element models (FEMs) that accurately reproduce human bone structure. A vertical and lateral impact have been simulated at increasing speed on each model, analyzing the force distribution within the mandibular bone. Both vertical and lateral impact showed higher level of stress at the impact point and in the condylar area in models characterized by malocclusion. Specifically, the class III and the open bite models, at the same speed of impact, had higher values for a longer period, reaching critical stress levels that are correlated with mandibular fracture, while normal occlusion seems to be a protective condition. In the second part of this study, the engineering results were validated through the comparison with a sample of patients previously treated for mandibular fracture. Data from 223 mandibular fractures, due to low-energy injuries, were retrospectively collected to evaluate a possible correlation between pre-existing malocclusion and fracture patterns, considering grade of displacement, numbers of foci, and associated CFI score. Patients were classified, according to their occlusion, into Class I, Class II, Class III, and anterior open bite or poor occlusal contact (POC). Class I patients showed lower frequencies of fracture than class II, III, and open bite or POC patients. Class I was associated with displaced fractures in 16.1% of cases, class II in 47.1%, class III in 48.8% and open bite/POC in 65.2% of cases (p-value < 0.0001). In class I patients we observed a single non-displaced fracture in 51.6% of cases, compared to 12.9% of Class II, 19.5% of Class III and 22.7% of the open bite/POC group. Our analysis shows that class I appears to better dissipate forces applied on the mandible in low-energy injuries. A higher number of dental contacts showed a lower rate of multifocal and displaced fractures, mitigating the effect of direct forces onto the bone. The correlation between clinical data and virtual simulation on FEM models seems to point out that virtual simulation successfully predicts fracture patterns and risk of association with different type of occlusion. Better knowledge of biomechanics and force dissipation on the human body may lead to the development of more effective safety devices, and help select patients to plan medical, orthodontic/dental, and/or surgical intervention to prevent injuries.

Association between Physical Activity and Menstrual Cycle Disorders in Young Athletes.

Our study aims to evaluate clinical predictors of menstrual cycle disorders in female athletes who compete in running disciplines. This is a prospective observational study. Women were recruited between January and May 2022. Fifty-three patients were enrolled and completed a questionnaire about menstrual cycle, physical activity, and food habit characteristics. Of the women in our population, 39.6% had menstrual irregularities and reported a significantly higher number of kilometers run per week (67 vs. 35, p:0.02). The number of kilometers run per week was associated with menstrual irregularities (for 10 km, OR 1.35; IC95% 1.05-1.73; p: 0.02) after adjusting for BMI, age, level of sport and caloric intake. The variable of "km run per week" appeared as a diagnostic indicator of irregular menstrual cycle with statistical significance (AUC ROC curve 0.71, IC95% 0.54-0.86, p-value=0.01) and the cut-off of 65 km run per week is a good indicator of the presence of irregular menstrual cycle (sensitivity (SE) and specificity (SP) of 55% and 81.48%). Menstrual cycle disorders are very frequent in female athletes, and the variable of km run per week may play a role in screening endurance athletes at high risk for these disorders.

Outcome of patients with stage I immature teratoma after surveillance or adjuvant chemotherapy.

Objective: Immature teratomas are rare malignant ovarian germ cell tumours, typically diagnosed in young women, where fertility-sparing surgery is the treatment of choice. The role of adjuvant chemotherapy in stage I disease remains controversial. We evaluated the impact of surveillance versus chemotherapy on the recurrence rate in stage I immature teratomas. Methods: We collected a single centre retrospective series of patients with stage I immature teratomas treated with fertility-sparing surgery at San Gerardo Hospital, Monza, Italy, between 1980 and 2019. Potential risk factors for recurrence were investigated by multivariate logistic regression. Results: Of the 74 patients included, 12% (9/74) received chemotherapy, while 88% (65/74) underwent surveillance. Median follow-up was 188 months. No difference in recurrence was found in stage IA/IB and IC immature teratomas [10% (6/60) vs. 28.6% (4/14) (P=0.087)], grade 1, grade 2, and grade 3 [7.1% (2/28) vs. 14.3% (4/28) vs. 22.2% (4/18) (p=0.39)], and surveillance versus chemotherapy groups [13.9% (9/65) vs. 11.1% (1/9)) (p = 1.00)]. In univariate analysis, the postoperative approach had no impact on recurrence. The 5-year disease-free survival was 87% and 90% in the surveillance and chemotherapy groups, respectively; the overall survival was 100% in both cohorts. Conclusions: Our results support the feasibility of surveillance in stage I immature teratomas. Adjuvant chemotherapy may be reserved for relapses. However, the potential benefit of chemotherapy should be discussed, especially for high-risk tumours. Prospective series are warranted to confirm our findings. What is already known on this topic: To date, no consensus has been reached regarding the role of adjuvant chemotherapy in stage I immature teratomas of the ovary. Some studies suggest that only surveillance is an acceptable choice. However, guidelines are not conclusive on this topic. What this study adds: No difference in terms of recurrence was observed between the surveillance and the adjuvant chemotherapy group. All patients who relapsed were successfully cured with no disease-related deaths. How this study might affect research practice or policy: Adjuvant chemotherapy should be appropriately discussed with patients. However, it may be reserved for relapse according to our data.

Short-term pain control after palliative radiotherapy for uncomplicated bone metastases: a prospective cohort study.

This study aimed at evaluating the efficacy of different radiotherapy (RT) fractionation regimens in managing uncomplicated painful bone metastases (BM) and identifying predictive factors for pain control. Patients with 1 to 4 symptomatic BM from any primary solid tumors and a life expectancy exceeding 3 months were included in the study and received palliative RT, with SBRT restricted in the context of oligometastatic disease or in patients with good prognosis. Pain analysis using the Brief Pain Inventory (BPI) tool was conducted at baseline, 1 and 3 months after RT. Analgesic intake was recorded as morphine-equivalent doses (OME). Pain response was assessed using the International Consensus on Palliative Radiotherapy Endpoint (ICPRE). Multivariate logistic regression analyzed patient-related, tumor-related, and treatment-related factors predicting BM pain control at 3 months post-RT. From Feb 2022 to Feb 2023, 44 patients with 65 symptomatic BM were investigated. Breast (32%) and lung (24%) tumors were the most common primary tumors. Treatment plans included 3DCRT (60%) and VMAT (40%), with a median biological effective dose for tumors (BED) of 29 Gy [14-108]. All patients completed the 3-month follow-up. Pain response rates were 62% at 1 month and 60% at 3 months. Responders had better PS ECOG scores (67%; P = 0.008) and received active systemic therapies (67%: P = 0.036). Non-responders had lower pretreatment BPI (mean: 13.7 vs. 58.2; P = 0.032), with significantly higher values after 1 month (mean: 9.1 vs. 5.3, P = 0.033). Baseline BPI (OR: 1.17; 95% CI: 1.032-1.327; P = 0.014) and BPI at 1 month (OR: 0.83; 95% CI: 0.698-0.976; P = 0.025) were independent predictors of pain response at 3 months. Our findings show that palliative RT ensured short-term pain control in patients with BM, regardless of tumor type and dose-fractionation regimen. A larger sample size and a longer follow-up could potentially identify which patients are likely to benefit most from RT, and which fractionation might be indicated for achieving a durable pain relief. A multidisciplinary approach is paramount to provide a better care to BM patients.

Updating approach for lexicographic optimization-based planning to improve cervical cancer plan quality.

BACKGROUND: To investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy. MATERIAL AND METHODS: Twenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation. RESULTS: The WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6-99.3], mCP01 99.2 [89.7-99.9], mCP02 96.9 [89.4-99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D50% (Gy): MP 41.7 [30.2-47.0], mCP01 40.3 [31.4-45.8], mCP02 32.6 [26.9-42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP. CONCLUSIONS: This study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans.

Single-Isocenter Linac-Based Radiosurgery for Brain Metastases with Coplanar Arcs: A Dosimetric and Clinical Analysis.

The efficacy of linac-based SRS/fSRS treatments using the single-isocenter coplanar FFF-VMAT technique for both single and multiple BM was investigated. Seventy patients (129 BM) treated with 15-21 Gy in 1 (n = 59) or 27 Gy in 3 (n = 11) fractions were analyzed. For each fraction, plans involving the intra-fractional errors measured by post-treatment CBCT were recalculated. The relationships of BM size, distance-to-isocenter, and barycenter shift with the difference in target coverage were evaluated. Clinical outcomes were assessed using logistic regression and Kaplan-Meier analysis. The median delivery time was 3.78 min (range, 1.83-9.25). The median post-treatment 3D error was 0.5 mm (range, 0.1-2.7) and the maximum rotational error was 0.3° (range, 0.0-1.3). In single BM patients, the GTV D95% was never reduced by >5%, whereas PTV D95% reductions >1% occurred in only 11 cases (29%). In multiple BM patients, dose deficits >5% and >1% occurred in 2 GTV (2%) and 34 PTV (37%), respectively. The differences in target coverage showed a moderate-to-strong correlation only with barycenter shift. Local failure of at least one treated BM occurred in 13 (21%) patients and the 1-year and 2-year local control rates for all lesions were 94% and 90%, respectively. The implemented workflow ensured that the degradation of target and brain dose metrics in delivered treatments was negligible. Along with encouraging clinical outcomes, these findings warrant a reduction in the PTV margins at our institution.

Survival after sentinel node biopsy alone in early-stage cervical cancer: a systematic review.

OBJECTIVE: To assess the oncologic outcomes of sentinel lymph node biopsy alone as part of surgical management in patients with early-stage cervical cancer. METHODS: A systematic search of the literature was performed following the PRISMA checklist. MEDLINE (through PubMed), EMBASE, and Scopus databases were searched from June 1991 to May 2023. Studies of women with early-stage cervical cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IIA, of any age or histology, and articles only in English language were included. After the removal of duplicates, only articles including sentinel node mapping alone compared with full pelvic lymphadenectomy were retained. RESULTS: Four studies with a total of 2226 patients were included. Among these, 354 (15.9%) underwent sentinel lymph node biopsy alone. A total of 2210 (99.2%) patients had FIGO 2009 stage I disease and 1514 (68%) patients had squamous cell carcinoma. Median body mass index was 25.5 kg/m2 (range 23.5-27). Lymph vascular space invasion was present in 633 patients (34%) who underwent full lymphadenectomy and in 78 patients (22%) who underwent sentinel node biopsy alone. The results of the survival analysis showed that there was no significant difference in the 3-year progression-free survival rates of patients who underwent either sentinel biopsy alone or lymphadenectomy. Three-year recurrence-free survival was 93.1% (95% CI 28.3% to 64.7%) for patients who underwent sentinel node biopsy alone and 92.5% (95% CI 39.0% to 53.4%) for patients who underwent sentinel node biopsy and lymphadenectomy (p=0.773). CONCLUSIONS: In patients with early-stage cervical cancer, performing sentinel lymph node biopsy alone compared with pelvic lymphadenectomy does not appear to independently confer a higher risk or recurrence.

The impact of oocyte central granularity on ICSI practice: developmental competence of dysmorphic and morphologically normal companion oocytes.

PURPOSE: To assess the effects of oocyte central granularity and its underlying endocrine environment on developmental competence of dysmorphic and morphologically normal oocytes. METHODS: Retrospective cohort study including 1,082 patients undergoing autologous ICSI cycles. Of these, 211 patients provided 602 oocytes with central granularity (CG) and 427 morphologically normal cycle companion oocytes (NCG). The remaining 871 patients provided only morphologically normal oocytes in cycles not yielding dysmorphic oocytes (N). Patient profile associated with CG was characterized, and fertilization rates, early morphokinetics and live birth rates were compared between N, CG and NCG groups. Patient characteristics associated with implantation and delivery performance of CG-derived embryos were assessed. RESULTS: CG was associated with higher maternal age, basal FSH concentrations and total FSH dose, but with lower circulating AMH (p ≤ 0.035). Fertilization rates were reduced and early morphokinetic parameters were delayed in CG (p < 0.025) and NCG (p < 0.05) groups as compared to the N group. Embryos derived from CG oocytes achieved a markedly lower live birth rate (14.9%) as compared to those derived from NCG (36.8%; p = 0.03) and N oocytes (29.8%; p = 0.002). The negative relationship between CG and live birth was confirmed by a multivariate analysis controlling for potential confounders (OR:2.59, IC:1.27-5.31; P = 0.009). Implantation and delivery rates following transfers of CG-derived embryos were inversely associated with maternal age. CONCLUSION: CG oocytes, but not their morphologically normal cycle companions, have severely compromised developmental competence. Maternal age should be a key parameter in deciding whether or not to utilize CG oocytes in ICSI cycles.

Principles and Applications of Dual-Layer Spectral CT in Gastrointestinal Imaging.

The advance in technology allows for the development of different CT scanners in the field of dual-energy computed tomography (DECT). In particular, a recently developed detector-based technology can collect data from different energy levels, thanks to its layers. The use of this system is suited for material decomposition with perfect spatial and temporal registration. Thanks to post-processing techniques, these scanners can generate conventional, material decomposition (including virtual non-contrast (VNC), iodine maps, Z-effective imaging, and uric acid pair images) and virtual monoenergetic images (VMIs). In recent years, different studies have been published regarding the use of DECT in clinical practice. On these bases, considering that different papers have been published using the DECT technology, a review regarding its clinical application can be useful. We focused on the usefulness of DECT technology in gastrointestinal imaging, where DECT plays an important role.

The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study.

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Spatio-temporal generalized Model Observers methods for Low Contrast Detectability assessment in digital angiography: Application to moving targets.

The purpose of this work is to investigate the feasibility of spatio-temporal generalized Model Observer methods for protocol optimization programs in the field of interventional radiography. Two Model Observers were taken under examination: a Channelized Hotelling Observer with 24 spatio-temporal Gabor channels and a Non Pre-Whitening Model Observer with two different implementations of the spatio-temporal contrast sensitivity function. The images of targets, both stationary and in motion, were acquired in fluoroscopic mode using a CDRAD phantom for signal-present images and an homogenous slab of PMMA for signal-absent ones. After the processing, these images were used to build three series of two alternative forced choice experiments, designed to simulate tasks of clinical interest, and submitted to three human observers in order to set a goal on detectability. A first set of images was used for model tuning and subsequently the verified models were validated throughout a second set of images. Results from the validation phase, for both models, show good agreement with the human observer performances (Root Mean Square Error RMSE ≤ 12%). The tuning phase emerges as a crucial step in building models for angiographic dynamic images; the final agreement underlines the good capability of these spatio-temporal models in simulating human performances, allowing to consider them as a useful and worthwhile tool in protocol optimization when dynamic images are involved.

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT.

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments.

Treatment Optimization in Linac-Based SBRT for Localized Prostate Cancer: A Single-Arc versus Dual-Arc Plan Comparison.

This study aimed to comprehensively present data on treatment optimization in linac-based SBRT for localized prostate cancer at a single institution. Moreover, the dosimetric quality and treatment efficiency of single-arc (SA) versus dual-arc (DA) VMAT planning and delivery approaches were compared. Re-optimization was performed on twenty low-to-intermediate-risk- (36.25 Gy in 5 fractions) and twenty high-risk (42.7 Gy in 7 fractions) prostate plans initially administered with the DA FFF-VMAT technique in 2021. An SA approach was adopted, incorporating new optimization parameters based on increased planning and clinical experience. Analysis included target coverage, organ-at-risk (OAR) sparing, treatment delivery time, and the pre-treatment verification's gamma analysis-passing ratio. The SA optimization technique has consistently produced superior plans. Rectum and bladder mean doses were significantly reduced, and comparable target coverage and homogeneity were achieved in order to maintain a urethra protection strategy. The mean SA treatment delivery time was reduced by 22%; the mean monitor units increased due to higher plan complexity; and dose measurements demonstrated optimal agreement with calculations. The substantial reduction in treatment delivery time decreased the probability of prostate motion beyond the applied margins, suggesting potential decrease in treatment-related toxicity and improved target coverage in prostate SBRT. Further investigations are warranted to assess the long-term clinical outcomes.

Comprehensive dosimetric and clinical evaluation of lexicographic optimization-based planning for cervical cancer.

Aim: In this study, a not yet commercially available fully-automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), was validated for cervical cancer. Material and methods: Twenty-four mono-institutional consecutive treatment plans (50 Gy/25 fx) delivered between November 2019 and April 2022 were retrospectively selected. The automatic re-planning was performed by mCycle, implemented in the Monaco TPS research version (v5.59.13), in which the LO and Multicriterial Optimization (MCO) are coupled with Monte Carlo calculation. mCycle optimization follows an a priori assigned priority list, the so-called Wish List (WL), representing a dialogue between the radiation oncologist and the planner, setting hard constraints and following objectives. The WL was tuned on a patient subset according to the institution's clinical protocol to obtain an optimal plan in a single optimization. This robust WL was then used to automatically re-plan the remaining patients. Manual plans (MP) and mCycle plans (mCP) were compared in terms of dose distributions, complexity (modulation complexity score, MCS), and delivery accuracy (perpendicular diode matrices, gamma analysis-passing ratio, PR). Their clinical acceptability was assessed through the blind choice of two radiation oncologists. Finally, a global quality score index (SI) was defined to gather into a single number the plan evaluation process. Results: The WL tuning requested four patients. The 20 automated re-planning tasks took three working days. The median optimization and calculation time can be estimated at 4 h and just over 1 h per MP and mCP, respectively. The dose comparison showed a comparable organ-at-risk spare. The planning target volume coverage increased (V95%: MP 98.0% [95.6-99.3]; mCP 99.2%[89.7-99.9], p >0.05). A significant increase has been registered in MCS (MP 0.29 [0.24-0.34]; mCP 0.26 [0.23-0.30], p <0.05) without affecting delivery accuracy (PR (3%/3mm): MP 97.0% [92.7-99.2]; mCP 97.1% [95.0-98.6], p >0.05). In the blind choice, all mCP results were clinically acceptable and chosen over MP in more than 75% of cases. The median SI score was 0.69 [0.41-0.84] and 0.73 [0.51-0.82] for MP and mCP, respectively (p >0.05). Conclusions: mCycle plans were comparable to clinical manual plans, more complex but accurately deliverable and registering a similar SI. Automated plans outperformed manual plans in blinded clinical choice.

Effectiveness of Resective Surgery in Complex Ameloblastoma of the Jaws: A Retrospective Multicenter Observational Study.

Ameloblastoma is a rare, benign, odontogenic tumor of epithelial origin, characterized by locally aggressive, expansive growth. Treatment is controversial due to the risk of relapse. The aim of this multicenter retrospective study was to evaluate the effectiveness of complete resection in cases of complex ameloblastoma, which is considered at a higher risk of recurrence. Patients who met at least one of these criteria were included: recurrence, soft-tissue involvement, complete erosion of internal/external cortical walls with involvement of the inferior margin of the mandible, and invasion of the maxillary sinus or nasal cavity. Demographic data, tumor site, type of surgery, histological features, and follow-up information were collected for each patient. The cohort included 55 patients with a mean follow-up of 108 ± 66 months. A multivariate logistic model was used to evaluate variables independently associated with relapse. There were six soft-tissue or maxillary sinus relapses, with a recurrence rate of 10.9%. Most of them arose in patients previously treated. The statistical analysis identified the maxillary location as a fundamental relapse risk factor. En bloc resection with large surgical safety margins seemed to be effective in preventing the relapses. However, complete resection was less effective in preventing recurrences in the soft tissues or maxillary sinus.