Distant Metastasis Rate Research Articles

427 Systemic Imaging for Early Laryngeal Cancer; a Single Centre Review of Guideline Application in Contemporary Clinical Practice

Abstract Aim Early-stage laryngeal cancer (T1 and T2) has low rate of locoregional and distant metastasis. Therefore, National Institute for Health and Care Excellence (NICE) guidelines were updated in 2016 and recommended to no longer offer systemic staging for early laryngeal cancer because systemic imaging was not deemed to be cost effective. Our study aims to evaluate (1) if NICE guidance on the role of systemic imaging in the assessment and management of early laryngeal cancer is being followed in our centre (2) assess the impact of this practice on our patients (3) perform a cost analysis relevant to our institution. Method We retrospectively reviewed all laryngeal cases at a major H&N cancer centre between 01/01/2020 and 01/01/2022. The following information was collected for all the patients: neck/systemic imaging modalities performed on patients, demographics, site of original laryngeal tumour and any metastatic disease detected by systemic imaging. Next, we performed a cost analysis based on the cost analysis method undertaken by NICE. Results Our results showed n = 83 patients had laryngeal cancer between 01/01/2020 and 01/01/2022. Of which n = 30 had T1N0 and T2N0 disease. Systemic imaging found no metastatic disease, however n = 2 primary lung tumours and n = 1 lung infection was detected. The total cost for systemic imaging was £4,207.12 and total cost for neck imaging investigations it was £12,335.07. Conclusions Our study concludes NICE guidance is not being followed at our centre. Systemic imaging provides little benefit to patients and is an expensive practice.

HIF1A-repressed PUS10 regulates NUDC/Cofilin1 dependent renal cell carcinoma migration by promoting the maturation of miR-194-5p.

Renal cell carcinoma (RCC) is characterized by a high rate of distant metastasis, which leads to poor prognosis in patients with advanced RCC. PUS10 has been recognized as a member of the pseudouridine synthase family, and recently other functions beyond the synthesis of the RNA modification have been uncovered. However, little is known about its role in diseases such as cancer. RT-qPCR, western blot and immunohistochemistry were used to measure the expression of PUS10 in RCC tissues. Transwell assay, wound healing assay, and in vivo metastasis model were conducted to determine the function of PUS10 in RCC progression. MicroRNA sequencing and GEO database were used to screen for the downstream microRNAs of PUS10. RNA immunoprecipitation, dual luciferase reporter assay, immunostaining, and rescue experiments were employed to establish the PUS10/miR-194-5p/nuclear distribution protein C(NUDC)/Cofilin1 axis in RCC migration. Chromatin immunoprecipitation and dual luciferase reporter assay were used to verify its upstream transcriptional regulator. The expression of PUS10 was significantly decreased in RCC tissues, and low expression predicted poor prognosis. In vitro and in vivo experiments showed that PUS10 suppressed RCC migration, which, however, was independent of its classical pseudouridine catalytic function. Mechanically, PUS10 promoted the maturation of miR-194-5p, which sequentially inhibited RCC migration via disrupting NUDC-dependent cytoskeleton. Furthermore, hypoxia and HIF-1A were found involved in the downregulation of PUS10. We unraveled PUS10 restrained RCC migration via the PUS10/miR-194-5p/NUDC/Cofilin1 pathway, which independent of its classical catalytic function. Furthermore, a linkage between the critical tumor microenvironment hallmark with malfunction of the forementioned metastasis inhibition mechanism was presented, as demonstrated by repressed expression of PUS10 due to hypoxia and HIF-1A.

Postoperative recurrence in locally advanced rectal cancer: how does neoadjuvant treatment affect recurrence pattern?

BackgroundThe treatment strategy for locally advanced rectal cancer (LARC) has recently expanded from total mesorectal excision to additional neoadjuvant chemoradiotherapy (nCRT) and/or systemic chemotherapy (NAC). Data on disease recurrence after each treatment strategy are limited.MethodsClinical stage II to III rectal cancer patients who underwent curative surgery between July 2005 and February 2021 were analyzed. The cumulative incidence and site of first recurrence were assessed. The median follow-up duration was 4.6 years.ResultsAmong the 332 patients, we performed nCRT and NAC in 15.4% (N=51) and 14.8% (N=49), respectively. The overall recurrence rate was 23.5% (N=78). Although several differences in tumor stage or location were observed, there was no significant difference in the rate among the surgery alone (N=54, 23.3%), nCRT (N=11, 21.6%), and NAC (N=13, 26.5%) groups. In this cohort, the local recurrence rate (18.4%) was higher than the rate of distant metastasis in the NAC group (14.3%). All patients with recurrence in the nCRT group had distant metastases (N=11: one patient had distant and local recurrences simultaneously). For pathological stage 0-I, the recurrence rate was higher in the nCRT and NAC groups than in the surgery-alone group (nCRT, 10.0%; NAC, 15.4%; and surgery-alone, 2.0%). Curative-intent resection of distant-only recurrences significantly improved patients’ overall survival (hazard ratio [95% confidence interval], 0.34 [0.14–0.84]), which was consistent even when stratified according to neoadjuvant treatment. Regardless of neoadjuvant treatment, >80% of recurrences occurred in the first 2.2 years, and 98.7% within 5 years after surgery.ConclusionRegardless of neoadjuvant treatment, detecting distant metastases with intensive surveillance, particularly in the first 2 years after surgery, is important. Also, even if neoadjuvant treatment can downstage LARC to pathological stage 0-I, careful follow-up is needed.

Comprehensive molecular characterization of adenoid cystic carcinoma reveals tumor suppressors as novel drivers and prognostic biomarkers.

Adenoid cystic carcinoma (ACC) is a MYB-driven head and neck malignancy with high rates of local recurrence and distant metastasis and poor long-term survival. New effective targeted therapies and clinically useful biomarkers for patient stratification are needed to improve ACC patient survival. Here, we present an integrated copy number and transcriptomic analysis of ACC to identify novel driver genes and prognostic biomarkers. A total of 598 ACCs were studied. Clinical follow-up was available from 366 patients, the largest cohort analyzed to date. Copy number losses of 1p36 (70/492; 14%) and of the tumor suppressor gene PARK2 (6q26) (85/343; 25%) were prognostic biomarkers; patients with concurrent losses (n = 20) had significantly shorter overall survival (OS) than those with one or no deletions (p < 0.0001). Deletion of 1p36 independently predicted short OS in multivariate analysis (p = 0.02). Two pro-apoptotic genes, TP73 and KIF1B, were identified as putative 1p36 tumor suppressor genes whose reduced expression was associated with poor survival and increased resistance to apoptosis. PARK2 expression was markedly reduced in tumors with 6q deletions, and PARK2 knockdown increased spherogenesis and decreased apoptosis, indicating that PARK2 is a tumor suppressor in ACC. Moreover, analysis of the global gene expression pattern in 30 ACCs revealed a transcriptomic signature associated with short OS, multiple copy number alterations including 1p36 deletions, and reduced expression of TP73. Taken together, the results indicate that TP73 and PARK2 are novel putative tumor suppressor genes and potential prognostic biomarkers in ACC. Our studies provide new important insights into the pathogenesis of ACC. The results have important implications for biomarker-driven stratification of patients in clinical trials. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

HDS screening with patient-derived primary cells guided individualized therapy for esophageal squamous cell carcinoma-in vivo and vitro.

To analyze and evaluate the role of the High-throughput Drug Sensitivity (HDS) screening strategy in identifying highly sensitive drugs against esophageal squamous cell carcinoma (ESCC). A total of 80 patients with progressive ESCC were randomly divided into the observation (40 cases) and the control groups (40 cases). In the observation group, primary ESCC cells were isolated from the tumor tissues with a gastroscope, and drug sensitivity screening was performed on cells derived from the 40 ESCC cases using the HDS method, followed by verification in a patient-derived tumor xenograft (PDX) mouse model. Finally, the differences in the therapeutic efficacy (levels of CEA, CYFRA21-1, SCCA after chemotherapy and the rates of overall survival, local progression, and distant metastasis at 12 months and 18 months time points after chemotherapy) were compared between the observation group (Screened drug-treated) and the control group (Paclitaxel combined with cisplatin regimen-treated). Forty ESCC patients were screened for nine different high-sensitive chemotherapeutics, with the majority showing sensitivity to Bortezomib. Experiments on animal models revealed that the tumor tissue mass of PDX mice treated with the HDS-screened drug was significantly lower than that of the Paclitaxel-treated mice (p < 0.05), and the therapeutic efficacy of the observation group was better than the control group (p < 0.05). HDS screening technology can be beneficial in screening high-efficacy anticancer drugs for advanced-stage ESCC patients, thereby minimizing adverse drug toxicity in critically ill patients. Moreover, this study provides a new avenue for treating advanced ESCC patients with improved outcomes.

Efficacy and Safety of Immediate Latissimus Dorsi Breast Reconstruction after Breast Cancer Surgery

Background: Most traditional breast reconstruction surgeries require the removal of the patient's own tissue or the use of artificial implants for reconstruction. The improvement of the efficiency and safety of breast reconstruction surgery assumes critical importance for the rehabilitation of breast cancer patients. Immediate latissimus dorsi breast reconstruction surgery, which utilizes the patient's own tissue to perform immediate reconstruction, can address this issue in a targeted manner, avoiding the cumbersome and complex nature of multiple surgeries. Objectives: To analyze the efficacy and safety of immediate latissimus dorsi breast reconstruction (BR) after breast cancer surgery. Methods: A total of 91 female patients with breast cancer diagnosed and treated by breast surgery in our hospital from August 2017 to July 2021 were retrospectively analyzed. The patients were assigned to the prosthetic implant group (n=39) and latissimus dorsi group (n=52) according to the method of immediate postoperative BR. The difference in curative effect can be analyzed by comparing the operation time, intraoperative bleeding, postoperative drainage time, and aesthetic evaluation of BR. The safety of postoperative BR was analyzed by comparing the postoperative complications, local recurrence rate, distant metastasis rate of breast cancer, and rehabilitation rate. Results: There was no dramatic difference in intraoperative bleeding, postoperative drainage time, and rehabilitation rate between the latissimus dorsi and prosthetic implantation groups (P&gt;0.05). Nonetheless, there was a significant difference in operation time, aesthetic evaluation of BR, postoperative complications, local recurrence rate, and distant metastasis rate of breast cancer in the latissimus dorsi group than the prosthetic implant group(P&lt;0.05). In general, the latissimus dorsi group exhibited better therapeutic effects. Conclusion: Immediate latissimus dorsi BR dramatically affects postoperative breast repair of breast cancer patients and is safer than prosthesis implantation. As an evaluation of their safety and effectiveness, it is necessary to provide patients with more stable and reliable medical outcomes to ensure their surgical safety.

Odontogenic Carcinosarcoma: Clinicopathologic and Molecular Features of Three Cases, a Literature Review and Nomenclature Proposal.

Odontogenic carcinosarcoma (OCS) is a rare odontogenic malignancy with limited characterization and unexplored molecular features. We report clinicopathologic and molecular findings in 3 additional OCS and review the literature. 3 OCS (5.1%) were identified among 59 malignant odontogenic tumors (in our archives from 1992 to 2022). Clinical, radiologic, histopathologic, immunophenotypic, and molecular findings were reviewed. Data from prior case reports and systematic or non-systematic reviews were extracted for analysis. Three mandibular OCS (age range: 66 to 72 years; 1 male, 2 females) were identified. Case 1 had novel clear-cell morphology, multiple recurrences, and a lethal outcome 28 months after resection. EWSR1 rearrangements were negative, but the tumor showed focal nuclear β-catenin and strong LEF-1 immunoreactivity. Case 2 demonstrated ameloblastic and sclerosing features and encased the inferior alveolar nerve; the patient was disease-free 22 months after resection with adjuvant chemoradiation therapy. LEF-1 was again strongly positive, and next-generation sequencing demonstrated 9p region-(CDKN2A, CDKN2B) copy number loss, and 12q region-(MDM2, CDK4) copy number gain. Case 3 showed clear-cell and markedly sclerosing features; no follow-up information was available. Literature review along with the current cases yielded 20 cases. OCS showed a male predilection (1.5:1), mandibular predominance (80%, typically posterior), and a bimodal age distribution (modes: 27.7 years, 62.7 years). OCS presented as masses (100%), often with pain (55%), and paresthesia (45%). Tumors were typically radiolucent (88.9%), with bone destruction (61.1%), and/or tooth effacement (27.8%). Preoperative biopsy was sensitive for malignancy (85.7%). At least 45% show evidence for a precursor lesion. 3-year DSS and DFS were 58% and 35%, respectively. Regional and distant (usually lung) metastatic rates were 25% and 31.3%, respectively. Increased mitotic rates and presence of tumor necrosis trended toward worse DSS and DFS. OCS is a rare but aggressive malignancy, often arising from precursor tumors and may represent a terminal phenotype rather than a distinct entity. We describe novel clear-cell and sclerosing morphologies. Wnt pathway alterations appear important. Mitotic rates and necrosis may be adverse prognosticators. In keeping with nomenclature trends in other sites, OCS may be more appropriately designated as "biphasic sarcomatoid odontogenic carcinomas."

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes.

Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity. We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab. Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen. Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. 4.

Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer.

We report the outcomes of cisplatin-ineligible HNSCC patients treated with definitive chemoradiation and concurrent carboplatin and paclitaxel. We included consecutive HNSCC patients treated from 2013 to 2021 that received definitive chemoradiation with carboplatin and paclitaxel. Locoregional recurrences (LRR) and distant metastases (DM) were estimated using cumulative incidence functions. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Sixty-five patients were identified with median age of 71 years (range 44-85). Median radiation dose was 70 Gy and the median doses of carboplatin and paclitaxel were AUC 1 and 40 mg/m2 , respectively. At a median follow-up of 29 (range 5-91) months, the 2-year rates of LRR, DM, PFS, and OS were 8.8%, 9.4%, 72.2%, and 88.7%, respectively. In total, there were 5 LRR, 7 DM, and 12 deaths. Chemoradiation with carboplatin and paclitaxel is an excellent option for cisplatin-ineligible HNSCC patients.

Breast-conserving surgery versus mastectomy for treatment of breast cancer after neoadjuvant chemotherapy.

To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). The data of 730 patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. A total of 104 (14.2%) patients received BCS and 626 (85.8%) received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were analyzed using the Kaplan-Meier method. The impact of BCS versus mastectomy on outcomes was assessed by multivariate Cox models. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the two groups. The median follow-up of BCS and mastectomy groups were 86.5 and 87.4 months, respectively. There were significant differences in distribution of most baseline characteristics between two groups. Compared with those who underwent mastectomy, the patients with BCS had similar 5-year LRR, DM, and DFS rates, but had significantly higher 5-year BCSS (98.9% vs. 90.4%, P = 0.005) and OS (98.9% vs. 90.1%, P = 0.003) rates. Multivariate analysis also showed that BCS significantly improved BCSS (HR = 0.27, 95% CI: 0.08-0.85, P = 0.025) and OS (HR = 0.25, 95% CI: 0.08-0.79, P = 0.018). After IPTW adjustment, the LRR, DM, DFS, BCSS and OS between two groups had no significant differences. The recurrence and survival outcomes are comparable with BCS and mastectomy. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.

Single axillary incision reverse-order endoscopic nipple/skin-sparing mastectomy followed by subpectoral implant-based breast reconstruction: Technique, clinical outcomes, and aesthetic results from 88 preliminary procedures

BackgroundSingle axillary incision reverse-order endoscopic nipple-sparing mastectomy overcomes the limitations of conventional endoscopic nipple-sparing mastectomy application. We introduce this technique and report the preliminary results of this study. MethodsPatients who received single axillary incision reverse-order endoscopic nipple-/skin-sparing mastectomy from May 2020 to May 2022 were enrolled from a single institution. Data were analyzed to evaluate the safety and effectiveness of this technique. Patient-reported and surgeon-reported cosmetic outcomes were collected. ResultsIn total, 68 patients who underwent 88 single axillary incision reverse-order endoscopic nipple-/skin-sparing mastectomy combined with subpectoral implant-based breast reconstruction were enrolled in the current study. The overall complication rate was 10.3%. In total, 2.9% of patients suffered from major complications, and 5 (7.4%) experienced minor complications. Only 1 patient experienced partial nipple-areola complex necrosis. During a median follow-up time of 24 months, the locoregional recurrence and distant metastasis rate was both 1.6%. In the surgeon-reported cosmetic results, 92.1% of patients achieved good or excellent results. The mean SCAR-Q scores were 82.07 ± 8.86, and 85.3% evaluated their breasts as good or excellent. The mean overall cost was 5,670.4 ± 1,351.3 USD. The total mean operation time and maturity-stage mean operation time were 234.3 ± 80.4 and 172.55 ± 41.29 min, respectively. According to cumulative sum plot analysis, approximately 18 cases were needed for surgeons to decrease their operation time significantly and complication rate. ConclusionSingle axillary incision reverse-order endoscopic nipple-sparing mastectomy is a safe, less expensive, and efficient surgical technique with reliable intermediate-term oncologic safety. For suitable candidates, the technique with subpectoral implant-based breast reconstruction can provide a good cosmetic outcome.

Regional transarterial chemoembolization combined with chemoradiotherapy for locally advanced rectal cancer: a retrospective study of a new combination.

Locally advanced rectal cancer (LARC) has a high risk of distant metastasis (DM). Currently, many treatment courses of LARC have arisen, but patients' DM status has not significantly improved. This study was designed to compare the effect between preoperative regional transarterial chemoembolization combined with neoadjuvant chemoradiotherapy and standard neoadjuvant therapy on preventing DM in patients with LARC. A total of 81 LARC patients between July 2013 and May 2018 were enrolled in this retrospective study. Among them, 44 patients received preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy (the interventional group), and 37 patients received only neoadjuvant chemoradiotherapy (the control group). The baseline data; preoperative toxicities; postoperative DM rate within 1, 2, and 3 years; and postoperative complications were compared between the two groups. All patients successfully completed their treatments. There were no significant differences between the two groups in age, gender, tumor size, distance between the tumor and anal verge, CEA level, lymphovascular invasion, or tumor stage before treatment. The pathological T staging post-treatment in the interventional group was significantly reduced compared to that of the control group (p = 0.025). There were no significant differences between groups in DM rates within 1 and 2 years after surgery. In terms of DM rate within 3 years after surgery, the interventional group was significantly lower than that of the control group (9.1% vs. 29.7%, p = 0.036). Preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy may play an important role in reducing postoperative DM in LARC.

Does high [18F]FDG uptake always mean poor prognosis? Colon cancer with high-level microsatellite instability is associated with high [18F]FDG uptake on PET/CT.

High-level microsatellite instability (MSI-high) is generally associated with higher F-18 fluorodeoxyglucose ([18F]FDG) uptake than stable microsatellite (MSI-stable) tumors. However, MSI-high tumors have better prognosis, which is in contrast with general understanding that high [18F]FDG uptake correlates with poor prognosis. This study evaluated metastasis incidence with MSI status and [18F]FDG uptake. We retrospectively reviewed 108 right-side colon cancer patients who underwent preoperative [18F]FDG PET/CT and postoperative MSI evaluations using a standard polymerase chain reaction at five Bethesda guidelines panel loci. The maximum standard uptake value (SUVmax), SUVmax tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using SUV 2.5 cut-off threshold. Student's t-test or Mann-Whitney U test was performed for continuous variables, and χ2 test or Fisher's exact test was performed for categorical variables (p value of < 0.05 for statistical significance). Medical records were reviewed for metastasis incidence. Our study population had 66 MSI-stable and 42 MSI-high tumors. [18F]FDG uptake was higher in MSI-high tumors than MSI-stable tumors (TLR, median (Q1, Q3): 7.95 (6.06, 10.54) vs. 6.08 (4.09, 8.82), p = 0.021). Multivariable subgroup analysis demonstrated that higher [18F]FDG uptake was associated with higher risks of distant metastasis in MSI-stable tumors (SUVmax: p = 0.025, MTV: p = 0.008, TLG: p = 0.019) but not in MSI-high tumors. MSI-high colon cancer is associated with high [18F]FDG uptake, but unlike MSI-stable tumors, the degree of [18F]FDG uptake does not correlate with the rate of distant metastasis. MSI status should be considered during PET/CT assessment of colon cancer patients, as the degree of [18F]FDG uptake might not reflect metastatic potential in MSI-high tumors. • High-level microsatellite instability (MSI-high) tumor is a prognostic factor for distant metastasis. • MSI-high colon cancers had a tendency of demonstrating higher [18F]FDG uptake compared to MSI-stable tumors. • Although higher [18F]FDG uptake is known to represent higher risks of distant metastasis, the degree of [18F]FDG uptake in MSI-high tumors did not correlate with the rate at which distant metastasis occurred.

Beyond Limits: A Case of Progressive Leiomyosarcoma of the Mandible

Leiomyosarcoma (LMS) is a rare malignancy which develops from the smooth muscles. It constitutes about 3 to 10% of all sarcomas in the head and neck area. Furthermore, it is extremely rare in the area of the mouth and jaws due to the rarity of smooth muscle in these areas. Spindle cells with visible smooth muscle differentiation, distinct features of atypia and presence of actin and desmin in Immunohistochemical (IHC) stains are characteristic of LMS. The common pattern of spread is similar with other sarcomas, involving the lung and rarely the lymphatics. Surgery, Radiotherapy and Chemotherapy have been described as standard forms of management. The prognosis is usually poor as rate of local, regional and distant metastasis is high. In this paper, we present a case of a 23 year-old female who presented with Leiomyosarcoma of the mandible. She remained to have good performance status and was able to undergo multiple lines of treatment for progressive disease prior to her demise.

Treatment outcomes of the patient with sinonasal mucosal melanoma: the role of endoscopic resection and postoperative radiotherapy.

The standard of care for sinonasal mucosal melanoma is surgery and postoperative radiotherapy (PORT). Our treatment strategy comprises endoscopic resection and PORT. We performed combined endoscopic and open resection or applied an external approach alone when sufficient resection was difficult to achieve endoscopically. The objective of this study was to evaluate the validity of our treatment strategy. We assessed 30 patients with sinonasal mucosal melanoma who underwent definitive therapy between January 2002 and April 2021, and conducted a retrospective analysis. The median follow-up period was 2.2years. The primary endpoint was overall survival. The Kaplan-Meier method was used for the calculation of survival rates, the cumulative incidence of distant metastasis, and local recurrence. Twenty-eight patients underwent surgery. The other two patients were treated by definitive proton beam therapy. Twenty-one of 28 (75%) patients underwent resection by endoscopic approach alone. Postoperative radiotherapy was performed for all 28 patients who underwent surgery. Twenty-one patients (70%) experienced recurrence during the observation period. Overall, distant metastasis was observed in 19 patients. Twelve patients died during the observation period, with 10 of the 12 patients (83%) dying of distant metastasis. The overall survival rate at 2 and 5years was 70% and 46%, respectively. The cumulative incidence rate of distant metastasis at 2years was 63%, while the 2-year cumulative incidence rate of local recurrence was 6.7%. The local disease was controlled by our treatment strategy. To improve treatment outcomes, control of the distant metastasis is needed.

Efficacy of post‑mastectomy radiotherapy in patients with T1‑2N1 breast cancer aged ≤35years or with a positive HER‑2 status.

Post-mastectomy radiotherapy (PMRT) is highly recommended for patients with breast cancer with one to three positive nodes; however, there remains some controversy regarding its use. The present retrospective study aimed to explore which patients may be able to avoid PMRT and its associated side effects. A total of 728 patients with T1-2N1 breast cancer who were treated with or without PMRT were included in the present study. The results suggested that PMRT significantly decreased the locoregional recurrence rate (LRR) [hazard ratio (HR)=5.602, 95% confidence interval (CI)=3.139-9.998, P<0.01; 3-year LRR: 4 vs. 17%] and improved overall survival (OS) (HR=0.651, 95% CI=0.437-0.971, P=0.03; 3-year OS: 91 vs. 87%) for patients with T1-2N1 breast cancer. By contrast, PMRT had no significant effect on the distant metastasis (DM) rate (HR=0.691, 95% CI=0.468-1.019, P=0.06; 3-year DM: 10 vs. 15%). Further stratified analysis revealed that PMRT did not reduce the LRR and DM, or improve OS in patients aged ≤35 years or in those with a positive human epidermal growth factor receptor-2 (HER-2) status. The analysis of 438 patients treated with PMRT revealed that patients aged ≤35 years or those with a positive HER-2 status were more likely to experience local recurrence even following PMRT. Thus, the benefits of using PMRT in patients with T1-2N1 breast cancer who are aged ≤35 years or in those with a positive HER-2 status need to be carefully considered. Further studies are required to confirm whether this patient group may be exempted from PMRT.

The Rac inhibitor HV-107 as a potential therapeutic for metastatic breast cancer

BackgroundThe significant challenge in treating triple-negative breast cancer (TNBC) lies in its high rate of distant metastasis. To address this, inhibiting metastasis formation in TNBC is vital. Rac is a key player in cancer metastasis. Previously, we developed Ehop-016, a Rac inhibitor that successfully reduced tumor growth and metastasis in mice. In this study, we assessed the effectiveness of HV-107, a derivative of Ehop-016, in inhibiting TNBC metastasis at lower doses.MethodsRho GTPases activity assays were performed with the use of GST-PAK beads and Rac, Rho, and Cdc42 GLISA. Cell viability was assessed through trypan blue exclusion and MTT assays. Cell cycle analysis was conducted using flow cytometry. To evaluate invading capabilities, transwell assays and invadopodia formation assays were performed. Metastasis formation studies were conducted using a breast cancer xenograft mouse model.ResultsHV-107 inhibited Rac activity by 50% in MDA-MB-231 and MDA-MB-468 cells at concentrations of 250–2000 nM, leading to a 90% decrease in invasion and invadopodia activity. Concentrations of 500 nM and above caused dose-dependent reductions in cell viability, resulting in up to 20% cell death after 72 h. Concentrations exceeding 1000 nM upregulated PAK1, PAK2, FAK, Pyk2, Cdc42, and Rho signallings, while Pyk2 was downregulated at 100–500 nM. Through in vitro experiments, optimal concentrations of HV-107 ranging from 250 to 500 nM were identified, effectively inhibiting Rac activity and invasion while minimizing off-target effects. In a breast cancer xenograft model, administration of 5 mg/kg HV-107 (administered intraperitoneally, 5 days a week) reduced Rac activity by 20% in tumors and decreased metastasis by 50% in the lungs and liver. No observed toxicity was noted at the tested doses.ConclusionThe findings indicate that HV-107 exhibits promising potential as a therapeutic medication utilizing Rac inhibition mechanisms to address metastasis formation in TNBC.

Local versus radical surgery for early rectal cancer with or without neoadjuvant or adjuvant therapy.

Local versus radical surgery for early rectal cancer with or without neoadjuvant or adjuvant therapy.

Trans oral robotic surgery for oropharyngeal cancer: A multi institutional experience

ObjectivesTrans Oral Robotic Surgery (TORS) has proved to be a safe and feasible treatment for oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to analyse oncological outcomes of OPSCC patients treated with TORS. Materials and methodsThis study involved 139 patients with OPSCC, treated with TORS between 2008 and 2020. Clinicopathological characteristics, treatment details and oncological outcomes were evaluated retrospectively. ResultsThe management strategies included TORS alone in 42.5%, TORS-RT in 25.2% and TORS-CRT in 30.9%. The ENE was noted in 28.8% of neck dissections. In 19 patients clinically classified as unknown primaries, the primary was found in 73.7%. Rates of local, regional relapses and distant metastasis were 8.6%, 7.2%, and 6.5%, respectively. The 5 year- Overall Survival and Disease Free Survival were 69.6% and 71.3%, respectively. ConclusionTORS fits well in the modern management of OPSCC. Although definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of the therapeutic strategy requires evaluation by a multidisciplinary team.