Median Maximum Tumor Diameter Research Articles

Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6–76 Gy (RBE) in 20–22 fr, 13 received 74.0–76.0 Gy (RBE) in 37–38 fr, and 6 received 60–70.2 Gy (RBE) in 20–30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age: 71 years; range: 41–91 years) had PS of 0 (n = 47), 1 (n = 10), and 2 (n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n = 46), B (n = 7), and unknown (n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0–15.2 cm); and the clinical stage was I (n = 12), II (n = 19), III (n = 10), and IV (n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1–49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8–34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1–11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. Conclusion: PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.

Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma

Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%-100%), median maximum tumor diameter (range, 1.8-5.0 cm), and the proportion with multinodular HCC (range, 15.4%-60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82-9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P < .0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18-0.46). Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.

Bilateral, single-session, laparoscopic adrenalectomy was associated with favorable outcomes in a cohort of dogs.

To report perioperative characteristics and outcome following bilateral, single-session, laparoscopic adrenalectomy (BSSLA) in dogs. Client-owned dogs (n = 6). Medical records were reviewed and perioperative data collected, including preoperative diagnostic imaging, operative details, complications, and need for conversion to open laparotomy. Bilateral, single-session, laparoscopic adrenalectomy was performed on the right or left side with a standard 3- or 4-portal transperitoneal technique. The dog was repositioned to contralateral recumbency, and laparoscopic adrenalectomy was repeated. Follow-up information was collected by telephone interviews with the owners and/or referring veterinarian. Median age and weight of dogs were 126 months and 14.75 kg, respectively. Contrast-enhanced CT (CECT) was performed in all dogs. Median maximal tumor diameter was 2.6 and 2.3 cm for the right and left-sided tumors, respectively. Median surgical and anesthesia times were 158 and 240 minutes, respectively. Conversion to open laparotomy was performed in 1 dog following renal vein laceration during initial adrenalectomy. Left adrenalectomy and ureteronephrectomy were performed, and the right adrenal tumor was left in situ. Cardiac arrest occurred in 1 dog following initial adrenalectomy (left); however, the dog was resuscitated successfully, and contralateral laparoscopic adrenalectomy was performed without complication. All dogs survived to hospital discharge. Follow-up ranged from 60 to 730 days (median, 264 days) for dogs that successfully underwent BSSLA. BSSLA was associated with favorable outcomes in this cohort of dogs. Laparoscopy may be considered in dogs with bilateral, modestly sized, noninvasive adrenal tumors.

MP47-09 URINE LEAK AND VASCULAR COMPLICATIONS FOLLOWING ROBOTIC PARTIAL NEPHRECTOMY: A CONTEMPORARY SINGLE CENTER EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023MP47-09 URINE LEAK AND VASCULAR COMPLICATIONS FOLLOWING ROBOTIC PARTIAL NEPHRECTOMY: A CONTEMPORARY SINGLE CENTER EXPERIENCE Olivia Kola, Michael Smigelski, Shavy Nagpal, Samir S. Taneja, James S. Wysock, and William C. Huang Olivia KolaOlivia Kola More articles by this author , Michael SmigelskiMichael Smigelski More articles by this author , Shavy NagpalShavy Nagpal More articles by this author , Samir S. TanejaSamir S. Taneja More articles by this author , James S. WysockJames S. Wysock More articles by this author , and William C. HuangWilliam C. Huang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003293.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Historically, the incidence of urine leak (UL) and vascular complications (VC) following robotic-assisted partial nephrectomy (RAPN) have been as high as 17%. To reduce the incidence of these complications, we implemented a standardized technique of renorrhaphy utilizing a running suture along the base of the tumor defect. We report the contemporary experience of RAPN complications from a single, high-volume center. METHODS: We identified 378 patients from an IRB-approved Renal Tumor Database of 1908 cases who underwent RAPN from 1/2017 to 8/2022. The time frame was selected to reflect the utilization of the renorrhaphy technique. RESULTS: VC occurred in 8 (2.1%) cases and UL occurred in 8 (2.1%), including 1 patient who had both complications (Table 1 and 2). The collecting system was entered in 5 (62.5%) VC cases and 4 (50%) UL cases. For VCs, the median nephrometry score and maximal tumor diameter was 8 (2.5) and 3.8 (0.9) cm, respectively. Patients with UL had a median nephrometry score of 7.5 (2.5) and a median maximal tumor diameter of 3.8 (0.8) cm. The majority of cases of VC and UL had tumors ≤ 4 mm from the collecting system (both 6/8). VCs presented a median of 18.5 (6.3) days postoperatively and 6/8 were symptomatic. Angioembolization was performed in 7 (87.5%) VC cases and 0/8 required transfusion. Patients with UL presented after a median of 4.5 (6.8) days. The duration of UL was 13 (34.5) days with only 2/8 cases requiring intervention with a stent. CONCLUSIONS: Standardization of contemporary RAPN techniques has resulted in low rates of VC and UL. Complications occurred in patients with high nephrometry scores or tumors located close to the collecting system. Both UL and VC generally present early with symptoms and can be managed without kidney re-operation or removal of the kidney. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e647 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Olivia Kola More articles by this author Michael Smigelski More articles by this author Shavy Nagpal More articles by this author Samir S. Taneja More articles by this author James S. Wysock More articles by this author William C. Huang More articles by this author Expand All Advertisement PDF downloadLoading ...

The Characteristics and Prognosis of Alpha-Fetoprotein and Des-Gamma-Carboxy Prothrombin Double-Negative Hepatocellular Carcinoma at Baseline in Higher BCLC Stages.

Alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) are widely used as tumor markers to diagnose hepatocellular carcinoma (HCC). Some advanced HCCs demonstrate neither AFP nor DCP. This study investigated the characteristics and prognosis of AFP (&lt;20 ng/mL) and DCP (&lt;40 mAU/ml) double-negative HCC (DNHC) in higher-stage HCC. Between April 2012 and March 2022, 419 consecutive patients were enrolled with newly diagnosed HCC and 372 patients were selected that were diagnosed by histopathology and/or imaging. AFP-negative, DCP-negative, and double-negative HCC were identified in 262 patients (70.4%), 143 patients (38.2%), and 120 patients (32.3%), respectively. In higher-BCLC stages (BCLC-B, C, and D), 17 patients (14.7%) were DNHC. Although there was no difference in BCLC staging, there were more cases under TNM Stage III in DNHC (71.0% vs. 41.4%, p = 0.026). The median maximum tumor diameter was smaller in DNHC [3.2 (1.8-5.0) vs. 5.5 (3.5-9.0) cm, p = 0.001] and their median survival time was significantly better, even in higher-stage HCC [47.0 (24.0-84.0) vs. 19.0 (14.0-30.0) months, p = 0.027). DNHC in higher-BCLC stage HCC is independent of BCLC staging, characterized by a tumor diameter &lt; 5 cm, and is treatable with a good prognosis.

RADT-13. CLINICAL OUTCOMES COMPARING RADIOSURGERY TECHNIQUES FOR MANAGING LARGE BRAIN METASTASES

Abstract INTRODUCTION Large brain metastases (BM) are associated with poor local control with single-fraction radiosurgery (SRS) alone. We sought to compare outcomes with various alternative management strategies to assess disease control rates. METHODS Consecutive patients diagnosed with BM ≥ 2 cm in maximum diameter between 3/2019-2/2021 and treated at a single tertiary institution were included. Primary endpoints included freedom-from-local-failure (FFLF) calculated on a per-lesion basis from the date of initial intervention to local failure, and overall survival (OS). Kaplan-Meier analysis and the log-rank test were used. RESULTS 86 patients with 102 large BM met inclusion criteria. The median age was 66 years (range: 31-98), median KPS was 90 (50-100), and 57.8% were female. The most common primary tumor was lung in 40 (39.2%) lesions. The median tumor volume was 9.7 cm3 (2.1-35.5 cm3) and the median maximum tumor diameter was 3.3 cm (2.9-5.6 cm). 37 (36.3%) lesions were treated with staged-SRS, 31 (30.4%) with resection and postoperative-SRS, 21 (20.6%) with preoperative-SRS and resection, and 13 (12.7%) with fractionated-SRS (FSRS). Lesions treated with preoperative-SRS or postoperative-SRS were associated with higher rates of no- or stable-extracranial disease, and larger tumor volumes (preoperative-SRS: median 14.5 cm3 [4.2-33.1]; postoperative-SRS: 18.0 cm3 [2.5-35.5]; FSRS: 5.9 cm3 [2.1-24.6]; staged-SRS: 6.5 cm3 [2.2-27.8]).With a median follow-up of 15.6 months, 12 (11.8%) local failures and 42 (41.2%) deaths occurred. 1-year FFLF and OS for entire cohort were 85.6% (95% CI: 77.9-93.3%) and 64.4% (95% CI: 54.7-74.1%), respectively. The 1-year FFLF (p=0.542)/OS (p=0.043) rates were 94.1%/100% for preoperative-SRS, 84.0%/43.4% for staged-SRS, 81.8%/74.1% for FSRS, and 81.5%/63.4% for postoperative-SRS, respectively. CONCLUSION Although limited by patient numbers, selection bias, and high attrition rate, preoperative-SRS had the numerically most favorable outcomes, supporting this approach for large BM. Prospective evaluation is warranted to determine the optimal management strategy.

Frameless Cobalt60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

<h3>Purpose/Objective(s)</h3> Frameless, gated, image-guided, Cobalt⁶⁰-based hypofractionated stereotactic radiosurgery (Co⁶⁰-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the Co⁶⁰ based stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control (LC) and adverse radiation effects (ARE) outcomes following 5 fraction Co⁶⁰-HSRS for intact brain metastases. <h3>Materials/Methods</h3> All patients with intact brain metastases treated with 5-fraction Co⁶⁰-HSRS between 2017-2020 were retrospectively reviewed. Patients were typically selected for HSRS as opposed to single fraction SRS if the metastases were larger (>2cm diameter), were in eloquent areas, or were in proximity to another lesion receiving HSRS. Survival estimates were determined per patient using Kaplan Meier methods, and LC as well as symptomatic ARE rates were determined per lesion using competing risk methods. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression using a backwards step-wise selection technique generated the final adjusted models. <h3>Results</h3> In total 299 metastases in 146 patients were identified. The median clinical and radiologic follow-up was 10.6 (range 0.5-49.9) and 10.7 months (range 0.5-47.6), respectively. The median maximum tumor diameter and volume were 1.7 cm (range, 0.2-3.9 cm) and 2.38 cc (range, 0.004-24.92 cc), respectively. The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5 Gy) in 5 daily fractions and 52% (range, 45%-93%), respectively. The median overall survival (OS) was 12.7 months and the 1-year LC rate was 85%. MVA identified a total dose of 27.5 Gy vs. ≤25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥4.5cc (HR 7.29, p < 0.001) and a mean intra-tumoral dose of ≥39 Gy (HR 3.17, p = 0.034) as significant predictors of symptomatic ARE. <h3>Conclusion</h3> Moderate total doses in 5 daily fractions of Co⁶⁰-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE. A prescription dose of 27.5 Gy was superior with respect to local control versus ≤25 Gy in 5 daily fractions. Target volumes of 4.5cc or larger as well as mean dose >39 Gy, were associated with higher rates of symptomatic necrosis. Further study will help refine the optimal dosimetric constraints for Co⁶⁰-HSRS.

Clinical results of active surveillance for extra-abdominal desmoid-type fibromatosis.

The treatment of choice for desmoid-type fibromatosis (DF) has been changed to active surveillance (AS). However, few studies have reported clinical outcomes of AS modality in Asian countries. This study aimed to clarify the significance of AS as a DF treatment modality. A total of 168 lesions from 162 patients with extra-abdominal DF were included. The mean age at diagnosis was 39 years (1-88 years), and the median maximum tumor diameter at the first visit was 64.1 mm (13.2-255.8 mm). The clinical outcomes of AS and the risk factors requiring active treatment (AT) (defined as an event) from AS modality were investigated. Of the 168 lesions, 94 (56%) were able to continue AS, with a 5-year event-free survival of 54.8%. Of the 68 lesions with PD, 21 (30.9%) lesions were able to continue AS. Neck location (p= 0.043) and CTNNB1 S45F mutation (p= 0.003) were significantly associated with the transition to AT, and S45F mutation was a significant factor associated with the transition to AT by multivariate analysis (hazard ratio: 1.96, p= 0.048). AT outcomes after AS were evaluable in 65 lesions, and 49 (75%) lesions did not require a transition to a second AT. AS was revealed as an effective treatment modality. The transition to AT needs to be considered for neck location and CTNNB1 S45F mutation DF. Good results can be obtained by selecting a treatment method that considers the tumor location even in cases that require intervention.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Clinical Outcomes of Scanning Carbon-ion Radiotherapy for Soft Tissue Sarcoma of the Extremities.

Carbon-ion radiotherapy (CIRT) has been reported to obtain favorable results in the treatment of bone and soft tissue malignancies; however, studies on CIRT for soft tissue sarcomas (STS) of the extremities are limited. Here, we have retrospectively evaluated the therapeutic efficacy and adverse events associated with scanning CIRT (sCIRT) for STS of the extremities at our institution. Thirteen consecutive patients with STS who underwent sCIRT between January 2017 and January 2020 were included in the study. The total dose of sCIRT was set at 67.2-70.4 Gy (RBE), which was provided in 16 fractions. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. Toxicity was evaluated using Common Terminology Criteria for Adverse Events v5.0. The cohort consisted of 10 males and 3 females with a median age of 69 years (range=38-95 years). Median duration of observation was 31.8 months (range=7.4-56.4 months). Tumors were localized to the upper extremity in 2 cases and to the lower extremity in 11 cases. Median maximum tumor diameter was 11.7 cm (range=3.0-36.6 cm), while 3-year OS, PFS, and LC were 61.5%, 44.9%, and 79.1%, respectively. Acute toxicity of grade 3 or higher was not observed. Late toxicity included grade 3 peripheral nerve palsy and decreased range of motion in 1 and 1 patient each. Late toxicity of Grade 4 or higher was not observed. sCIRT for STS of the extremities demonstrates favorable therapeutic results with acceptable toxicity.

Definitive high-dose, proton-based radiation for unresected mobile spine and sacral chordomas

Background/PurposeTreatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy.In certain locations, resection may result in significant neurological dysfunction, so definitive radiation has been used as an alternative to surgery. The purpose of this study is to report the results of high-dose, proton-based definitive radiotherapy for unresected spinal and sacral chordomas. Materials/MethodsRetrospective review of 67 patients with newly diagnosed, unresected spinal chordomas treated with high-dose definitive, proton-based radiotherapy at our center from 1975 to 2019. ResultsReasons for radiotherapy alone included medical inoperability and/or concern for neurological dysfunction based on spine level or patient choice. Tumor locations included cervical (n = 10), thoracic (n = 1), lumbar (n = 4) spine, and sacrum (n = 52). Median maximal tumor diameter was 7.4 cm (range 1.8–25 cm). Median total dose was 77.4 Gy (RBE) (range 73.8–85.9 Gy RBE). Analysis with median follow-up of 56.2 months (range, 4–171.7 months) showed overall survival of 83.5 % (95%CI: 69.4–91.5%) and 65.9% (95%CI: 47.3–79.3%), disease-free survival of 64% (95%CI: 49.3–75.4) and 44.1% (95%CI: 27.8–59.2%), local control of 81.8% (95%CI: 67.6–90.2%) and 63.6% (95%CI: 44.7–77.5%), and distant control of 77.4% (95%CI: 63.6–86.5%) and 72.5% (95%CI: 55.7–83.8%) at 5 and 8 years respectively. The most common late side effect was insufficiency fracture. ConclusionThese results continue to support the use of high-dose definitive radiotherapy for patients with medically inoperable or otherwise unresected mobile spine or sacrococcygeal chordomas. There is a trend towards better disease-free survival with doses > 78 Gy (RBE).

Reconstructive Surgery versus Primary Closure following Vulvar Cancer Excision: A Wide Single-Center Experience.

Simple SummaryWhen it comes to advanced vulval cancer management, there is a critical quandary to consider. This is owing to the severe negative impact of demolitive surgery on women who are afflicted by both functional and psychological consequences of the procedure. Primary closure of vulvar and/or perineal defects can be accomplished without difficulty in many situations, but this is accompanied by tension of the skin closure and distortion of the anatomy. In these circumstances, reconstructive surgery will be required to restore the anatomical and functional characteristics of the vulva. In this paper, we share our substantial expertise of primary closure versus reconstruction after demolitive surgery of advanced vulvar cancer, and we discuss our findings in light of the literature.(1) Background: plastic reconstruction in vulvar surgery can lead to a better treatment outcome than primary closure. This study aims to compare the preoperative parameters (co-morbidities and tumor size) and postoperative results (tumor free margins and wound healing) between the primary closure and reconstructive surgery after vulvar cancer surgery; (2) Methods: this is a retrospective analysis of prospectively collected data from 2009 to 2021 at a tertiary cancer institution; (3) Results: 177 patients were included in the final analysis (51 patients had primary closure PC and 126 had reconstructive surgery RS). About half (49%) of the PC patients had no co-morbidities (p = 0.043). The RS group had a 45 mm median maximal tumor diameter compared to the PC group’s 23 mm (p = 0.013). More than 90% of RS and 80% of PC had tumor-free margins (p = 0.1). Both groups had anterior vulvar excision as the most common surgery (52.4% RS vs. 23.5% PC; p = 0.001). Both groups had identical rates of wound healing disorders. In a median follow-up of 39 months; recurrent disease was found in 23.5% of PC vs. 10.3% in RS (p = 0.012). In terms of overall survival there was no significant difference between the both groups; (4) Conclusions: reconstructive vulvar surgery enables enhanced complete resection rates of larger vulvar tumors with better anatomical restoration and a comparable wound recovery in comparison to primary closure. This results in a lower recurrence rate despite the increased tumor volume.

Clinical Outcomes and Prognostic Factors of Fractionated Stereotactic Radiosurgery for Brain Metastases ≥20 mm as a Potential Alternative to Surgery

This study investigated the outcomes and prognostic factors of fractionated stereotactic radiosurgery (FSRS) for treatment of brain metastases (BMs) ≥20 mm and determined whether FSRS could replace surgery, the primary treatment for large BMs. Patients with BMs ≥20 mm treated with FSRS were retrospectively examined. Patients who underwent FSRS postoperatively were excluded. Local failure, intracranial failure, and adverse events were evaluated. Overall, 116 lesions in 105 patients were evaluated. The performance status was 0-1, 2-4, and unknown for 86, 28, and 2 patients, respectively. The median maximum tumor diameter was 25 mm, and the median prescribed dose was 35 Gy in 3 fractions. The median follow-up period after FSRS was 8 months. The 1-year local failure, intracranial failure, and overall survival rates were 12.5%, 56.6%, and 49.0%, respectively. A maximum dose of ≥135 Gy (biological equivalent dose [α/β= 10 Gy]) and good performance status were independent favorable prognostic factors for local control. After FSRS, 21 (20%) patients were treated with whole-brain radiotherapy because of multiple intracranial recurrences, and 4 (3.4%) patients underwent surgery because of local recurrence. FSRS for BMs ≥20 mm achieved good local control. Only 3.4% of patients required surgery after FSRS, suggesting that FSRS is a potential alternative to surgery. For FSRS, a higher maximum tumor dose was useful for local control.

Modern Therapy for Chest Wall Ewing Sarcoma: An Update of the University of Florida Experience

Owing to adjacent critical organs, the aggressive multimodality local therapy necessary for Ewing sarcoma of the chest wall is a challenge. Our previous review of historical outcomes at our institution revealed suboptimal disease control and a high incidence of grade ≥3 toxic effects in patients treated before 2006. The purpose of this study was to evaluate changes during the past decade since the introduction of proton therapy. Thirty-nine consecutive pediatric patients with a chest wall Ewing sarcoma treated between 2006 and 2020 at the University of Florida were identified. The median maximum tumor diameter was 10 cm (range, 4-28 cm). At diagnosis, 19 patients had local disease and the others had a pleural effusion (11), pleural nodules (5), or pulmonary metastases (4). Patients were treated with chemotherapy regimens according to contemporary North American and European protocols: 7 were treated with preoperative, 18 with postoperative, and 14 with definitive radiation. Preceding primary site treatment, 15 patients required hemithorax radiation and 4 patients underwent whole-lung irradiation using photon techniques. The total median radiation dose to the primary tumor was 52.8 GyRBE [relative biological effectiveness] (range, 44.4-55.8 GyRBE). With a median follow-up of 4 years (range, 0.7-14.7 years), the 5-year local control, progression-free survival, and overall survival rates were 97.2%, 74.4%, and 81.6%, respectively, for the whole cohort. For the 19 patients with nonmetastatic disease, the 5-year local control, progression-free survival, and overall survival rates were 100%, 78.9%, and 78.9%, respectively. No patients developed grade ≥4 toxic effects. Two patients (5%) experienced grade 3 toxic effects related to multimodality treatment; both were patients who required surgery to correct scoliosis. Two patients (5%) developed grade 2 pneumonitis. Compared with our prior published institutional experience, our data suggest improvements in disease control and multimodality toxic effects since the introduction of proton therapy. This should be confirmed with a larger sample size and longer follow-up.

A prospective observational study of lenvatinib as an initial treatment for patients with intermediate-stage hepatocellular carcinoma.

412 Background: The standard treatment for intermediate stage hepatocellular carcinoma (HCC) has been transarterial chemoembolization (TACE); however, it might not be suitable for patients (pts) beyond the up-to-7 criteria because of its insufficient efficacy and decline of liver function. Conversely, lenvatinib has shown a good response rate in the phase III trial REFLECT and was considered promising as an initial treatment for patients with BCLC stage B2 HCC. Methods: We conducted a multicenter prospective observational study to evaluate the efficacy of lenvatinib as an initial treatment for pts aged 20 years or older, diagnosed with BCLC stage B2 HCC, naive to TACE, and with preserved organ function. The primary endpoint was a 1-year survival rate, with a threshold of 60% and an expected survival rate of 78% based on previous reports of TACE. With a one-sided alpha error of 5% and a power of 70%, 25 pts were recruited over an enrollment period of 2 years and a follow-up period of 10 months. Results: Enrollment began in June 2018 and was closed with 31 eligible pts enrolled by June 2020. Data cut-off was done in April 2021. Patient characteristics are as follows: the median age was 77 years (range: 57–86); 94% of the pts were male; the etiology of chronic liver disease was hepatitis B virus, hepatitis C virus, alcohol abuse, and others in 3, 6, 9, and 10 pts, respectively; 20 and 11 pts had a Child-Pugh score of 5 and 6 points, respectively; the median maximum tumor diameter was 36 mm (range: 10–135); the number of pts with a tumor number of ≥10 was 8; and the median AFP level was 52.1 ng/mL (range: 2.4–49800). The 1-year survival rate was 71.0% (90% confidence interval [CI]: 68.4–73.6) and the primary endpoint was met. The median overall and progression-free survival was 17.0 months (95% CI, 15.3–19.2) and 10.4 months (95% CI, 6.6–13.8), respectively; the 2-year survival rate was 32.3%. The objective response rate according to RECIT1.1 and mRECIST was 22.6% and 70.0%, respectively. The common adverse events (AEs) were fatigue (68%), hypertension (65%), and anorexia (61%) in any grade, AST increased (23%), ALT increased (16%), and proteinuria (13%) in grade 3 or worse. Treatment interruption and dose reduction was required in 61% and 81% of the pts, respectively. The median relative dose intensity was 61.8% (range: 7.5–100). At the time of analysis, out of 24 pts, 17 (55%), nine (29%), and two (6%) discontinued lenvatinib due to disease progression, AEs, and conversion to curative treatments, respectively. One patient who showed partial response suddenly died during treatment due to unknown reasons. Systemic chemotherapy, TACE, and transarterial infusion therapy was administered in 11 (38%), six (21%) and one (3%) as a post study treatment, respectively. Conclusions: Our study indicates that initial treatment using lenvatinib prolongs the survival of pts with BCLC stage B2 HCC.

Modern Therapy for Spinal and Paraspinal Ewing Sarcoma: An Update of the University of Florida Experience

In 2010, we published a comprehensive review of our institutional outcomes about treating children with spinal and paraspinal Ewing sarcoma using photon therapy. Multimodality therapy was associated with fair disease control but also with serious toxicity, including a 37% rate of grade 3 or greater toxicity. We therefore sought to assess our more recent experience about treating children with more modern technology and treatment regimens. Between 2010 and 2021, 32 pediatric patients with nonmetastatic spinal and paraspinal Ewing sarcoma were treated at University of Florida and enrolled in a retrospective outcome study. Median age at diagnosis was 9.8 years (range, 2.1-21.8 years). Within the cervical, thoracic, and lumbar spine regions, 3, 22, and 7 tumors arose, respectively. Median maximum tumor diameter was 5 cm (range, 3-19 cm). At diagnosis, 28 of 32 patients had motor, bowel, or bladder deficits. Chemotherapy was delivered according to contemporary North American and European interval-compressed regimens. Before radiation therapy, 14 patients underwent gross total resection, whereas 18 underwent a biopsy or subtotal resection with cord decompression. All patients were treated with proton therapy; 6 with hardware stabilization also received a component of intensity modulated photon therapy. Median prescription dose was 50.4 gray relative biological effectiveness (GyRBE; range, 45-55.8 GyRBE). Median maximum dose to the spinal cord was 50.2 GyRBE (range, 0-54.9 GyRBE). With a median follow-up of 4.1 years (range, 0.7-9.4 years), the 5-year local control, progression-free survival, and overall survival rates were 92%, 79%, and 85%, respectively. Ten of 30 living patients have residual motor, bowel, or bladder deficits. Overall, 22% of patients experienced Common Terminology Criteria for Adverse Events grade 3 late toxicity related to multimodality treatment: kyphosis (n=4), esophagitis (n=2), and chronic kidney disease (n=1). No patients developed grade 4 or greater toxicity, new neurologic deficits, or second malignancy. Modern treatment advances may offer an improved therapeutic ratio for pediatric patients with spinal and paraspinal Ewing sarcoma. With appropriate management, most patients can be cured with recovery of long-term neurologic function and modest side effects.

Hot Spot Not Hot Enough? Differences in Local Control for Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Maximum Point Dose within the Planning Target Volume

<h3>Purpose/Objective(s)</h3> One of the defining characteristics of stereotactic body radiation therapy (SBRT) is the creation of a steep dose gradient, resulting in a higher dose centrally within the planning target volume (PTV) than at the periphery. However, there is no consensus regarding objectives for the maximum point dose delivered to the PTV. In this study, we investigated whether higher relative maximum doses within the PTV were associated with improved tumor control. <h3>Materials/Methods</h3> We performed a single-institution retrospective review of patients with early-stage, node-negative NSCLC who received curative-intent SBRT between 2005 and 2018. Patients with biopsy-proven NSCLC or presumed NSCLC based on radiographic findings were included. All patients underwent four-dimensional computed tomography (CT) for radiation planning and were treated with a free-breathing technique, utilizing an internal target volume (ITV) to account for tumor motion during the respiratory cycle. The PTV was defined as a 5-mm expansion from the ITV. We calculated the relative maximum dose to the PTV from a ratio of the maximum point dose delivered within the PTV to the prescription dose. We analyzed outcomes using the Kaplan-Meier method and used a log-rank test to assess prognostic impact. <h3>Results</h3> The study population consisted of 175 patients and 186 individual lung nodules with a median follow-up time of 2.6 (range, 0.1 – 12) years for all patients and 3.5 (range, 0.2 – 8.4) years for living patients. The median age was 70.2 (range, 43 – 90) years, and the median maximum tumor diameter was 1.9 (range, 0.7 – 5.6) cm. Most tumors were peripheral with only 9.7% (n=18) centrally located. The median prescription dose was 50 (range, 48 – 62.5) Gy in 5 (range, 4-10) fractions. The median relative maximum dose delivered to the PTV was 110%. Among the entire cohort, the 3-year rates (95% CI) of local control (LC), cause-specific survival, and overall survival were 81.0% (73.8% – 86.5%), 72.4% (64.5 – 79.1%), and 48.3% (40.7% – 55.9%), respectively. The 3-year rate of LC was superior among patients treated with a maximum point dose ≥ 110% vs. < 110% (86% vs. 74%, p=0.03). The difference in 3-year LC was more pronounced between a maximum point dose ≥ 120% vs. < 120% (94% vs. 79%, p = 0.05). The maximum point dose was significant for LC on multivariate analysis (p = 0.03). <h3>Conclusion</h3> Patients with early-stage NSCLC treated with SBRT with a relative maximum dose in the PTV of at least 110% demonstrated improved local control. Thus, more homogeneous SBRT plans may compromise the ablative treatment. Further studies should clarify specific objectives for the maximum point dose delivered to the PTV.

MET-6 Neoadjuvant fractionated stereotactic radiotherapy followed by piecemeal resection for metastatic brain tumor

BACKGROUND: Large brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative stereotactic radiosurgery (SRS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (Na-SRS) followed by surgery was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation necrosis (RN). We treated with neoadjuvant fractionated stereotactic radiotherapy (Na-fSRT) followed by surgery for large brain metastasis with piecemeal resection. METHODS: Twelve patients received Na-fSRT followed by surgery between July 2019 and April 2021. Na-fSRT dose was based on lesion size and was standard dosing. Surgery generally followed within 7 days after radiotherapy. RESULTS: The mean age was 68 years (51–79). Sixteen men and five women. Mean follow-up period was 8.5 months (1–24.9). Primary were lung; 10 (NSCLC; 9, SCLC (recurrence); 1), esophagus; 3, colon; 2, melanoma; 2, kidney; 2 (recurrence1), uterus body; 1, and liver; 1. The median maximum tumor diameter was 3.6 cm (2.6–4.9). Median PTV, GTV volume were 21.7ml, 15.5ml, respectively. The median fSRT dose was 30Gy/5fr, and the median time from fSRT to surgery was 4 days (1–7). As preoperative adverse event, intracranial hypertension and partial seizure grade 2 (CTCAE ver.5) were occurred, but controlled with steroid and osmotic diuretics and anticonvulsant. Grade 3 and more adverse events were not occurred. Gross total removal was performed in 95.2%. Event cumulative incidence as follows: cavity local recurrence 4.8% (subtotal removal case); distant brain failure 33%; LMD 4.8%; and symptomatic RN 0%. The median intracranial progression free survival was 7 months, and median overall survival was 8.4 months. CONCLUSIONS: Na-fSRT followed by piecemeal resection is safety and feasible, and may have therapeutic value for deep large brain metastasis and eloquent lesion. Further prospective investigations in multi-institutional settings are warranted.

No Difference in Outcomes for Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Pathologic Diagnosis

According to society guidelines, stereotactic body radiotherapy (SBRT) can be delivered in patients who have a lung lesion that is clinically and radiographically consistent with non-small cell lung cancer (NSCLC) and refuse biopsy, have undergone a nondiagnostic biopsy, or are at prohibitive risk of biopsy. The purpose of this study is to report outcomes of patients with stage I-II NSCLC, with or without pathologic diagnosis, treated with SBRT at our institution.We performed a single-institution retrospective review of patients with early-stage node-negative NSCLC who received curative-intent SBRT between 2005 and 2018. We included patients with biopsy-proven NSCLC or presumed NSCLC based on radiographic findings. We calculated outcomes using the Kaplan-Meier method and used a log-rank test to assess prognostic impact.The study population consisted of 175 patients and 186 individual lung nodules with a median follow-up time of 2.6 (range, 0.1 - 12) years for all patients, and 3.5 (range, 0.2 - 8.4) years for living patients. The median age was 70.2 (range, 43 - 90) years and the median maximum tumor diameter was 1.9 (range, 0.7 - 5.6) cm. Twenty-three (13.1%) patients had a history of previously treated NSCLC, and more than a third (n = 66, 37.7%) of patients were oxygen-dependent at the time of SBRT. One hundred and seven (61.1%) patients were treated empirically with SBRT without a pathologic diagnosis. Most tumors were peripheral with only 9.7% (n = 18) centrally located, and most were located in the upper lobes (n = 123, 70.3%). The median prescription dose was 50 (range, 48 - 62.5) Gy in 5 (range, 4-10) fractions. Among the entire cohort, the 3-year rates (95% confidence interval) of local control, regional control, cause-specific survival, and overall survival were 81.0% (73.8% - 86.5%), 89.5% (82.7% - 93.8%), 72.4% (64.5% - 79.1%), and 48.3% (40.7% - 55.9%), respectively. There was no difference in local-regional control (P = 0.76), cause-specific survival (P = 0.75), or overall survival (P = 0.33) between patients with a pathologic diagnosis and those without. We observed late grade 3 toxicities in 2.3% of patients and no higher-grade toxicities.Patients without a pathologic diagnosis of NSCLC had no difference in disease outcomes compared with patients that had biopsy-proven disease, suggesting that empirically treating patients with a radiographic diagnosis of NSCLC is a reasonable alternative when a biopsy cannot safely be attained.

Clinicopathological features of basal cell type dysplasia of esophagus

Objective: To investigate the clinicpathological features of basal cell type dysplasia of the esophagus. Methods: The clinicopathological data of 71 cases of basal cell type dysplasia of esophagus were collected at the People's Liberation Army Joint Logistics Support Force 989 Hospital, from 2009 to 2019, and the histomorphologic characteristics and immunophenotype were evaluated. The relevant literature was reviewed. Results: The ratio of male to female patients was 1.6∶1.0, and the median age was 65 years (range 48-81 years). The tumors were located in the upper segment of the esophagus in four cases (5.6%), the middle segment in 54 cases (76.1%), and the lower segment in 13 cases (18.3%).The median maximal tumor diameter was 12.0 mm (range 3-42 mm). According to Paris Classification, 0-Ⅱb accounted for 42.3% (30/71) of the cases. Under endoscope, the lesions were reddish with abnormal mucosal microvessels. Histologically, the neoplastic cells were small, with a high nuclear-cytoplasmic ratio, similar to basal cells, and uniform in morphology. The structural atypia was characterized by dense and disordered tumor cells, loss of basal cell polarity, and absence of normal squamous differentiation gradient. In 10 cases, the tumors were confined to the lower part of the epithelium. The tumor cells were smaller and more uniform in shape, and extend to the superficial lamina propria. Sixty-one tumors involved at least the entire layer of the upper cortex. There were 31 cases of neoplasms with superficial invasive carcinoma. The types of neoplasms included typical squamous cell carcinoma, basaloid squamous cell carcinoma, small cell neuroendocrine carcinoma, squamous cell carcinoma with sebaceous adenoid carcinoma, and differentiation of glandular/ductal epithelioid carcinoma. Immunohistochemical staining showed that the mutant expression rate of p53 protein was 41.5% (17/41). All 41 cases (100.0%) showed abnormal distribution pattern of Ki-67. According to the initial pathologic diagnosis, there were 18 cases of low grade dysplasia, 12 cases of atypical epithelial cells, and 41 cases of high grade dysplasia and superficially invasive carcinoma. Conclusions: Basal cell type dysplasia has unique morphologic characteristics and represents a tumor subtype in the morphologic lineage of esophageal squamous dysplasia. Tumor cells of basal cell type dysplasia, especially those distributed only in the lower part of the stratified squamous epithelium, may be tumor stem cells at the earliest stage of esophageal carcinogenesis and have multidirectional differentiation potential. When the tumor is confined to the lower part of the stratified squamous epithelium, it does not meet the diagnostic criteria for esophageal squamous dysplasia as defined by the current WHO classification.