Actuarial Rate Research Articles

Fat necrosis after accelerated partial breast irradiation or hypofractionated whole breast irradiation: A case-control study.

This study aimed to compare the incidence of fat necrosis after accelerated partial breast irradiation (APBI) vs hypofractionated whole breast irradiation (WBI) in patients with early-stage breast cancer. Data from early-stage breast cancer patients who underwent breast-conserving surgery and adjuvant radiotherapy between 2009 and 2022 were retrospectively collected. Radiation therapy consisted of APBI of 30 Gy in 5 daily fractions (Fx) (delivered in one week, consecutively) to the tumour bed or WBI (42.4 Gy in 16 Fx). Reports on fat necrosis were extracted from yearly mammograms and breast ultrasound imaging. The primary endpoint was the incidence of radiologically detected fat necrosis. A total of 536 patients were included among the APBI and WBI cohorts, with 268 and 268 patients respectively. The three-year Kaplan-Meier actuarial rate of fat necrosis was 32.8% (95% CI: 30.0% - 35.6%) for APBI and 22.3% (95% CI: 19.7% - 24.9%) for WBI patients. Univariate Kaplan-Meier survival analysis revealed a Hazard Ratio of 1.6 [95% CI: 1.1 - 2.2; p = 0.0055] for the fat necrosis rate within the APBI group compared to WBI. Multivariate Cox proportional hazard regression confirmed significant associations between fat necrosis and APBI (HR = 2.2 95% CI: 1.2 - 4.0; p = 0.01). The occurrence of radiologically diagnosed fat necrosis was higher in the APBI group compared to the WBI. Further investigations aiming to identify a lower-dose schedule with comparable efficacy to 30 Gy in 5 Fx but fewer toxicities, particularly for high-risk patients, are warranted.

Early and Late Surgery-Free Rates of Conservative Management Strategy for Thrombosed Type A Acute Aortic Dissection and Acute Intramural Hematoma.

Background: We have employed a conservative management approach, including intensive control of both blood pressure and heart rate, in patients with aortic intramural hematoma (AIMH) and retrograde thrombosed type A acute aortic dissection (RT-TAAAD), sharing common clinical and imaging characteristics. Methods: To evaluate the outcomes of our conservative management approach, we retrospectively reviewed the clinical records of 98 patients diagnosed with AIMH or RT-TAAAD from January 2008 to March 2023. A conservative management approach was applied, except for those patients with an aortic diameter ≥ 55 mm, false lumen expansion, or cardiac tamponade, who underwent emergency aortic repair. Results: Besides 2 patients, who declined surgery and subsequently died from aortic rupture, 18 patients underwent urgent aortic surgery, while 78 did not. Multivariable logistic regression analysis identified the extrusion type of ulcer-like projections (ULPs) on admission and a maximum aortic diameter ≥ 45 mm on Day 1 as risk factors for acute aortic surgery. Among the 78 patients who were discharged, 9 (12%) underwent aortic surgery, while 69 (88%) did not, with a median follow-up of 44 months. The overall actuarial aortic surgery-free rates were 78% at 1 year and 72% at 5 years, respectively. A Cox proportional hazards analysis identified ULPs and an aortic diameter ≥ 45 mm at discharge as risk factors for late aortic surgery. Conclusions: The early and late outcomes of our conservative strategy for AIMH and RT-TAAAD demonstrate favorable surgery-free rates. The extrusion type of ULPs on admission and an aortic diameter ≥ 45 mm on Day 1 are predictors of acute aortic surgery, while ULPs and an aortic diameter ≥ 45 mm at discharge are predictors of late surgery.

Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP‐Ribose)‐Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study

The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients. Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS). From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS. This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

Stereotactic Ablative Radiation Therapy for Oligometastatic Ovarian Cancer Lymph Node Disease: The MITO-RT3/RAD Phase II Trial

PurposeMITO-RT3/RAD (NCT04593381) is a prospective multicenter Phase II trial designed to assess the effectiveness and safety of stereotactic body radiotherapy (SBRT) in patients diagnosed with oligometastatic ovarian cancer (oligo-MPR-OC). In this report, we provide the results of the trial in the setting of lymph node disease. MethodsThe primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival (PFS), overall survival (OS), treatment-free interval (TFI), and toxicity rates. Sample size was based on a previous study reporting an average 70.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 70.0% to 85.0%, with an α error of 0.05 (one-side) and a β error of 0.1. ResultsThe study met its primary endpoint of a statistically significant improvement of CR. 135 patients with 249 lesions were enrolled across fifteen Institutions from May 2019 to November 2023. CR were observed in 194 lesions (77.9%), PR in 40 (16.1%), SD in 14 (5.6%), and Progressive Disease (PD) in one lesion (0.4%). The ORR was 94%, with an overall clinical benefit rate of 99.6%. CR lesions exhibited a significantly higher LC rate than partial or not responding lesions (12-month LC: 92.7% vs. 63.1%, p<0.001). The 12-months actuarial rates for PFS and for OS were 36.6% (CR 38.3% vs not-CR 18.8%; p: 0.022) and 97.2% (CR 97.8% vs not-CR 93.8%; p: 0.067), respectively. The 12-months actuarial rate for Treatment Free Interval was 52.7% (CR 58.4% vs not-CR 24.4%; p: 0.004). CR was substantially associated with higher PFS (p: 0.036) and TFI (p: 0.006) rates at the univariate analysis. Twenty-three patients (17.0%) experienced mild acute toxicity. Late toxicity was reported in 9 patients (6.7%), mostly Grade 1. ConclusionsThis trial confirms the efficacy of ablative SBRT, with minimal toxicity observed. SBRT offered a high CR rate, promising long-term outcomes and systemic-therapy-free survival rate for complete responders.

A single institution retrospective study of efficacy and complications perspective of Gamma Knife Radiosurgery for benign skull base meningioma: A 12-year follow-up

Background and Objectives: Gamma knife radiosurgery (GKRS) has established its role as an effective treatment modality for inaccessible, recurrent, and residual benign skull base meningioma. Therefore, it is necessary to study the outcome in the long term. The current retrospective study aims to analyze and report the clinical and radiological outcomes after long-term follow-up of GKRS for skull base meningiomas &gt;= 12 years. Patients and methods: The present study was conducted on 106 consecutive patients harboring benign skull base meningiomas treated by GKRS at our IMC center between 2005 and 2012 and was followed till the end of 2023. Results: After a median follow-up of 13 years (3.6-18 years), a tumor control rate was reported in 88.7% of patients (n 94/106). Recurrences and tumor progression occurred in 11.3% (n 12/106) at a median follow-up period of 5.4 years (3–10.3 years). The 3, 5-, 10-, 12-and 15-year actuarial tumor control rate was 100%, 95.3%, 89.7%, 88.7%, and 78.1% respectively. Conclusions: The current retrospective study provides a long-term 12-year follow-up and comprises one of the longest follow-up studies of GKRS-treated benign skull base meningiomas. The current series documents a persistent long-term high local tumor control and an acceptable low incidence of neurological deficits. Benign skull base meningioma volume variant at the time of GKRS is a statistically significance predictor factor for tumor control at long-term outcomes.

Hypofractionated radiation therapy alone for human papillomavirus-related oropharyngeal cancer.

To report a single-institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)-positive oropharyngeal cancer. A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16-positive squamous cell carcinoma of the oropharynx. Sixty-seven patients (67%) were never smokers. The 3-year actuarial rates of overall survival, local-regional control, and progression-free survival were 94%, 93%, and 89%, respectively. Among never-smokers, the 3-year rates of overall survival and local-regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV-positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de-escalation is currently underway.

Repeat stereotactic radiosurgery for progressive vestibular schwannomas after primary gamma knife radiosurgery

PurposeLimited data provides guidance on the management of vestibular schwannomas (VSs) that have progressed despite primary Gamma Knife radiosurgery (GKRS). The present article reports our long-term experience after repeat GKRS for VS with sustained progression after solely primary GKRS management.MethodsA retrospective review of 1997 patients managed between 1987 and 2023 was conducted. Eighteen patients had sustained tumor progression after primary GKRS and underwent repeat GKRS. The median repeat GKRS margin dose was 11 Gy (IQR: 11–12), the median tumor volume was 2.0 cc (IQR: 1.3–6.3), and the median cochlear dose in patients with preserved hearing was 3.9 Gy (IQR: 3-4.1). The median time between initial and repeat GKRS was 65 months (IQR: 38–118).ResultsThe median follow-up was 70 months (IQR: 23–101). After repeat GKRS, two patients had further tumor progression at 4 and 21 months and required partial resection of their tumors. The 10-year actuarial tumor control rate after repeat GKRS was 88%. Facial nerve function was preserved in 13 patients who had House-Brackmann grade 1 or 2 function at the time of repeat GKRS. Two patients with serviceable hearing preservation (Gardner-Robertson grade 1 or 2) at repeat GKRS retained that function afterwards. In patients with tinnitus, vestibular dysfunction, and trigeminal neuropathy, symptoms remained stable or improved for 16/16 patients, 12/15 patients, and 10/12 patients, respectively. One patient developed facial twitching in the absence of tumor growth 21 months after repeat GKRS.ConclusionsRepeat GKRS effectively controlled tumor growth and preserved cranial nerve outcomes in most patients whose VS had sustained progression after initial primary radiosurgery.

Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240)

PurposeGlioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl).MethodsTen patients were included (May 2017 – April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed.ResultsAt the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7–71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan–Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence).ConclusionAt 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects.Trial registration NCT numberNCT03048240. EudraCT number: 2016–002706-39.

ESHO 1–85. Hyperthermia as an adjuvant to radiation therapy in the treatment of locally advanced breast carcinoma. A randomized multicenter study by the European Society for Hyperthermic Oncology

BackgroundThe ESHO protocol 1–85 is a multicenter randomized trial initiated by the European Society for Hyperthermic Oncology with the aim to investigate the value of hyperthermia (HT) as an adjuvant to radiotherapy (RT) in treatment of locally advanced breast carcinoma. The trial is one of the largest studies of hyperthermia in radiotherapy but has not been previously published. Patients and methodsBetween February 1987 and November 1993, 155 tumors in 151 patients were included. Tumors were stratified according to institution and size (T2-3/T4) and randomly assigned to receive radiotherapy alone (2 Gy/fx, 5 fx/wk) to a total dose of 65–70 Gy, incl. boost, or the same radiotherapy followed once weekly by hyperthermia (aimed for 43 °C for 60 min). Radiation was given with high voltage photons or electrons. The primary endpoint was persistent complete response (local control) in the treated area. ResultsA total of 146 tumors in 142 patients were evaluable, with a median observation time of 19 (range 1–134) months. Seventy tumors were randomized to RT alone and 76 to RT + HT. Size was T4 in 92, and T2-3 in 54 tumors, respectively. The compliance to RT was good with all but 4 patients fulfilling the planned RT treatment. The tolerance to HT was fair, but associated with moderate to severe pain and discomfort in 15 % of the treatments. In 84 % of the heated patients a least one heat treatment achieved the target temperature, but the temperature variation was large. Addition of heat did not significantly increase the acute nor late radiation reactions.Overall, the 5-year actuarial local failure rate was 57 %. Univariate analysis showed a significant influence of hyperthermia (RT alone 68 % versus RT + HT 50 %, p = 0.04, and T-size (T4 75 % versus T2-3 36 %, p < 0.01). A Cox multivariate analysis showed the same factors to be the only significant prognostic parameters: hyperthermia (HR: 0.61 [0.38–0.98], and small tumor strata (HR: 0.46 [0.26–0.92]. Consequentially, more patients given RT + HT (36 %) survived without disease (DFS), than after RT alone (19 %), p = 0.021) ConclusionA randomized multicenter trial investigating the addition of a weekly hyperthermia treatment to radiotherapy of patients with locally advanced breast cancer significantly enhanced the 5-year tumor control and yielded more patients surviving free from cancer. The results substantiate the potential clinical benefit of hyperthermic oncology.

Stereotactic Radiosurgery for WHO Grade 2 and 3 Oligodendroglioma: An International Multicenter Study

INTRODUCTION: Oligodendrogliomas are primary brain tumors classified as IDH-mutant and 1p19q co-deleted in the 2021 WHO Classification. Surgery, fractionated radiotherapy and chemotherapy are well established treatments for these tumors, but there are few studies evaluating the efficacy of stereotactic radiosurgery (SRS). As these tumors are less infiltrative than astrocytomas and typically recur locally, they could be appropriate for local therapy such as SRS. METHODS: This was a retrospective multicenter study performed through the International Radiosurgery Research Foundation (IRRF). Adult patients were included if they underwent single-fraction SRS for a grade 2 or 3 oligodendroglioma. The primary endpoints were overall survival and progression-free survival. Secondary endpoints included clinical evolution and occurrence of adverse radiation events or other complications. RESULTS: Eight institutions submitted data for a total of 55 patients with a median clinical follow-up of 24 months. Median age at treatment was 46 years old and median pre-treatment KPS was 90. Median treatment volume was 4cc and median marginal dose delivered was 15Gy. The KPS remained stable post-SRS in 51% and worsened in 46.7% of patients, most often due to tumor progression (73.1%). Radiation-induced changes occurred in 29.6% of which 4 patients were symptomatic. Median progression-free survival was 17 months, with actuarial rates of 60.1% at 1 year, 31% at 2 years and 24.4% at 5 years after SRS. Median overall survival post-SRS was 58 months, with actuarial rates of 91.5% at 1 year, 83.4% at 2 years and 49.3% at 5 years post-SRS. Factors significantly associated with worsened survival were WHO grade 3 and prior radiotherapy and chemotherapy. Factors significantly associated with worsened PFS were WHO grade 3, prior radiotherapy and chemotherapy and higher treatment marginal dose. CONCLUSIONS: SRS appears to be a valuable management option for oligodendrogliomas.

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer.

There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification.

Radiosurgery as a Stand-Alone Treatment Option for Cerebral Dural Arteriovenous Fistulas: the Vienna Series.

Gamma Knife radiosurgery (GKRS) has been demonstrated to be an effective and safe treatment method for dural arteriovenous fistulas (DAVFs). However, only few studies, mostly with limited patient numbers, have evaluated radiosurgery as a sole and upfront treatment option for DAVFs. Thirty-three DAVF patients treated with GKRS as a stand-alone management at our institution between January 1992 and January 2020 were included in this study. Obliteration rates, time to obliteration, neurologic outcome, and complications were evaluated retrospectively. Complete overall obliteration was achieved in 20/28 (71%) patients. The postradiosurgery actuarial rates of obliteration at 2, 5, and 10 years were 53, 71, and 85%, respectively. No difference in time to obliteration between carotid-cavernous fistulas (CCFs; 14/28, 50%, 17 months; 95% confidence interval [CI]: 7.4-27.2) and non-CCFs (NCCFs; 14/28, 50%, 37 months; 95% CI: 34.7-38.5; p = 0.111) were found. Overall, the neurologic outcome in our series was highly favorable at the time of the last follow-up. A complete resolution of symptoms was seen in two-thirds (20/30, 67%) of patients. One patient with multiple DAVFs suffered from an intracranial hemorrhage of the untreated lesion and died during the follow-up period, resulting in a yearly bleeding risk of 0.5%. No complications after radiosurgery were observed in our series. Our results show that GKRS is a safe and effective stand-alone management option for selected DAVF patients.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100Gy was delivered to all lesions. With a median follow-up of 23.1months (range: 13.4-30.9months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8months, respectively. The actuarial median overall survival (OS) was 27.7months from SBRT and 52.5months from metastases diagnosis. Patients with lesion diameter ≤ 5cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Surgical treatment in the chronic phase for uncomplicated Stanford type B aortic dissection.

The most appropriate surgical method for patients with uncomplicated type B aortic dissection (UTBAD) in the chronic phase remains controversial. This study evaluated the outcomes of patients with UTBAD who needed aortic treatment as well as the impact of the treatment method or indication criteria on their prognosis. This retrospective review of 106 consecutive patients with aortic events in the chronic phase who underwent initial treatment for UTBAD between 2004 and 2021 comprised three groups: 19 patients who underwent endovascular repair (TEVAR), 38 who underwent open aortic repair and the medication group that included 49 patients. Aortic events were defined as a late operation or indication for operation for dissected aorta, aortic diameter (AD) ≥ 55 mm, rapid aortic enlargement (≥5 mm/6 months), and saccular aneurysmal change. The endpoint was all-cause death. We assessed the association between treatment methods or surgical indication criteria and mortality using a Cox regression analysis. The 5-year actuarial mortality rates were 27.1% in the TEVAR group, 19.6% in the open aortic repair group, and 38.4% in the medication group (p = 0.86). Moreover, the 5-year actuarial mortality rates in patients who had AD ≥ 55 mm were significantly higher than those patients with other surgical indication criteria (41.2% vs. 18.7%, p < 0.01). Multivariable analysis revealed a significant difference in AD ≥ 55 mm (hazard ratio [HR]: 2.88, 95% confidence interval [CI] 1.38-6.02, p < 0.01) and age (HR: 1.09, 95% CI 1.05-1.13, p < 0.01). Under the existing surgical indication criteria, there was no difference in mortality rates among patients with UTBAD based on their surgical treatment.

The effect of the conduit size on middle-term outcomes in patients with extracardiac total cavopulmonary connection.

The 18- and 16-mm conduits in extracardiac total cavopulmonary connection (eTCPC) were reported to be optimal based on energy loss and flow stagnation at the relatively early phase. However, because the artificial conduit lacks growth potential, we have recently encountered some cases in which the conduit needs to be changed several years after eTCPC. These cases prompted us to reconsider the surgical strategy for eTCPC. We reviewed our 20-year single-centre experience with eTCPC patients (n = 256) to compare the 18-mm conduit (n = 195) and 16-mm conduit (n = 61) in terms of mortality and morbidity. The 16-mm conduit was used significantly more frequently in patients whose main chamber was right ventricle (P < 0.001). There was also a significant difference in preoperative inferior vena cava pressure (P = 0.008). There was a significant difference in the actuarial rate of freedom from late-occurring complications, including mortality, between the 2 groups (P = 0.003). There was a significant difference in the actuarial rate of reoperation-free survival (P = 0.042); however, there was no significant difference in resurgical intervention for the conduit (P = 0.333). In multivariate analysis, preoperative inferior vena cava pressure was an independent predictor for late-occurring complications (hazard ratio 1.19; P = 0.026). Conduit size (18 or 16 mm) itself was not an independent predictive factor for late-occurring complications (P = 0.690). The mid-term clinical outcomes in patients who underwent eTCPC were excellent with low mortality. Preoperative inferior vena cava pressure was the only predictive risk factor for postoperative morbidity, and the 16 mm conduit was not predictive thereof.

Dosimetric Correlation of Acute Radiation Dermatitis in Patients With Breast Cancer Undergoing Hypofractionated Proton Beam Therapy Using Pencil Beam Scanning.

Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2-3 dermatitis. Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D10cc, respectively. To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.

Hearing preservation after stereotactic radiosurgery for sporadic intracanalicular vestibular schwannomas classified as Koos grade 1.

The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs. A total of 37 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed. The median age was 55 years old. The median tumor volume was 0.089 cm3 , and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. In a multivariate analysis, only baseline pure tone average > 30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratio. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm3 , and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration. Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS.

The Promising Effects of Lattice Radiotherapy for Large, Fungating, or Ulcerating Breast Cancers: A Prospective Single-center Study.

To evaluate the safety and efficacy of lattice radiotherapy (LRT) for large, inoperable breast cancers. In this prospective study, patients who underwent LRT for breast tumors that were ulcerating/fungating/extensively eroding the chest wall, and were ineligible/unwilling for surgery, were enrolled from May 2021 to Nov 2023. Baseline Eastern Cooperative Oncology Group (ECOG) status, pre- and post-LRT numerical rating scale (NRS), and post-LRT changes in quality of life (QoL) were recorded. Survival outcomes were reported at 6 months and 1-year. Median rates of survival and dosimetric parameters were calculated. Kaplan-Meier curves for overall survival (OS), cancer-specific survival (CSS), and failure of local control (LC) were constructed. Ten patients (8 females) underwent LRT. The median age was 76 years (range=57-99 years) and the median ECOG performance status was 2.5 (range=1-4). The planned schedule was completed by 9/10 patients, accounting for a 90% compliance rate. Among patients with pain (n=7), NRS rapidly reduced from 7 (range=5-10) to 3 (range=1-6). The median equivalent uniform dose was 0.71 Gy (0.09-1.59 Gy). The actuarial rates of 6-month LC, CSS, and OS were 75%, 89%, and 61%, respectively, with only LC rate changing to 50% at 1 year. Two patients had local relapse at the six-month and 1-year follow-up, respectively, after having achieved a complete response at three months, and two others died of COVID-19 infection and ischemic stroke. LRT was found to be effective and safe in palliating symptoms among patients with large inoperable breast tumors.

THE BENEFITS OF FAMILY ANNUITY CALCULATION WITH VINE’S COPULA AND FUZZY INTEREST RATE

One example of a multiple life annuity product (covering more than one person) is a reversionary annuity, which is a life annuity product for two or more annuitants whose annuity payments will begin after one of the annuitants specified in the contract dies first until the other annuitant also dies. This type of annuity is modified into a family annuity consisting of husband, wife, and child. The marginal distribution is constructed from a combined model of several mortality models such as Heligman-Pollard, Costakis, and Kannisto-Makeham models to capture mortality at young and old ages.This study takes this dependency into account when modeling the joint distribution of remaining life expectancy between the parties. The joint distribution of remaining lifetime between annuitants is modeled with a Vine’s copula constructed from the marginal distribution of each annuitant. This research also takes account the actuarial margin rate using BI-7-day (reverse) repo rate data estimated with fuzzy sets. The annuity benefits calculation is assumed with some Kendall's tau () values. The result shows the value of annuity benefits increases as the value of increases.

Actuarial aging rates in human cohorts

Aging rate is an important characteristic of human aging. Attempts to measure aging rates through the Gompertz slope parameter lead to a conclusion that actuarial aging rates were stable during the most of the 20th century, but recently demonstrate an increase over time in the majority of studied populations. These findings were made using cross-sectional mortality data rather than by the analysis of mortality of real birth cohorts. In this study we analyzed historical changes of actuarial aging rates in human cohorts. The Gompertz parameters were estimated in the age interval 50-80 years using data on one-year cohort age-specific death rates from the Human Mortality Database (HMD). Totally, data for 2,294 cohorts of men and women from 76 populations were analyzed. Changes of the Gompertz slope parameter in the studied cohorts revealed two distinct patterns for actuarial aging rate. In higher mortality Eastern European countries actuarial aging rates showed continuous decline from the 1910 to 1940 birth cohort. In lower mortality Western European countries, Australia, Canada, Japan, New Zealand, and USA actuarial aging rates declined from the 1910th to approximately 1930th cohort and then increased. Overall, in 50 out of 76 populations (68%) actuarial aging rate demonstrated decreasing pattern of change over time. Compensation effect of mortality (CEM) was tested for the first time in human cohorts and the cohort species-specific lifespan was estimated. CEM was confirmed using cohort data and human cohort species-specific lifespan estimates were similar to the estimates obtained for the cross-sectional data published earlier.