Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Chalazion-mimicked eyelid angiosarcoma in a young Asian with good prognosis: a case report.

BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.

Selaginella tamariscina Ethanol Extract Attenuates Influenza A Virus Infection by Inhibiting Hemagglutinin and Neuraminidase.

Selaginella tamariscina is a perennial plant that is used for diverse diseases. This study investigated whether Selaginella tamariscina has an antiviral effect against influenza A virus (IAV) infection. We used green fluorescent protein (GFP)-tagged influenza A virus (IAV) to examine the effect of Selaginella tamariscina ethanol extract (STE) on influenza viral infection. Fluorescence microscopy and flow cytometry showed that STE potently represses GFP expression by the virus, dose-dependently. STE significantly inhibited the expression of the IAV M2, NP, HA, NA, NS1, and PB2 proteins. Time-of-addition and hemagglutination inhibition assays showed that STE has an inhibitory effect on hemagglutinin and viral binding on the cells at an early infection time. In addition, STE exerted a suppressive effect on the neuraminidase activity of the H1N1 and H3N2 IAVs. Furthermore, dose-dependently, STE inhibited the cytopathic effect induced by H3N2, as well as by H1N1 IAV. Especially in the presence of 200 µg/mL STE, the cytopathic effect was completely blocked. Our findings suggest that STE has antiviral efficacy against IAV infection; thus, it could be developed as a natural IAV inhibitor.

Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer: The POHIM-CCRT Nonrandomized Controlled Trial.

Importance: Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. Objective: To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. Design, Setting, and Participants: The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Intervention: Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. Main Outcomes and Measures: The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Results: Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Conclusions: Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03239613.

Anti-Fibrosis Effect of Panax ginseng and Inula japonica Formula in Human Pulmonary Fibroblasts.

Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-ß1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-ß1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.

Radiation Oncologists' Perspectives on Oligometastatic Prostate Cancer: A Survey from Korean Oligometastasis Working Group.

BACKGROUND: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.

The Clinical Efficacy of Colorectal Cancer Patients with Pulmonary Oligometastases by Sterotactic Body Ablative Radiotherapy: A Meta-Analysis.

PURPOSE: There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. MATERIALS AND METHODS: Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. RESULTS: A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. CONCLUSION: Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.

Salvage Radiotherapy for Loco-Regional Recurrence of Esophageal Cancer Following Surgery.

Purpose: There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. Materials and Methods: We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). Results: The patients' median age was 65 (41-86). The median disease-free interval (DFI) was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Conclusion: Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

PURPOSE: The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. METHODS: ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. DISCUSSION: Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Outcomes of whole breast radiation therapy in Asian breast cancer patients with prior cosmetic implants.

BACKGROUND: As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. METHODS: We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8 cc, with a median interval of 84.7 months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50 Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6 Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. RESULTS: After a median follow-up of 43.5 months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260 cc) and a higher ratio of breast tissue to implant volume. CONCLUSIONS: This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach.