Distant Metastasis Rate Research Articles

Multi-institutional study on the role of post-operative radiotherapy in elderly patients with endometrial cancer

ObjectiveTo investigate the prognostic factors for survival and toxicities in elderly (≥65 years) patients with endometrial cancer who underwent post-operative radiotherapy. Additionally, to compare the treatment outcomes between the older...

PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer

Protein diversity due to alternative mRNA splicing or post-translational modifications (PTMs) plays a vital role in various cellular functions. The mitotic kinases polo-like kinase 1 (PLK1) and Aurora B (AURKB) phosphorylate survivin, an inhibitor of apoptosis (IAP) family member, thereby regulating cell proliferation. PLK1, AURKB, and survivin are overexpressed in triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. TNBC is associated with high proliferative capacity, high rates of distant metastasis, and treatment resistance. The proliferation-promoting protein survivin and its activating kinases, PLK1 and AURKB, are overexpressed in TNBC. In this study, we investigated the role of survivin phosphorylation in racial disparities in TNBC cell proliferation. Analysis of TCGA TNBC data revealed higher expression levels of PLK1 (P = 0.026) and AURKB (P = 0.045) in African Americans (AAs; n = 41) than in European Americans (EAs; n = 86). In contrast, no significant racial differences in survivin mRNA or protein levels were observed. AA TNBC cells exhibited higher p-survivin levels than EA TNBC cells. Survivin silencing using small interfering RNAs significantly attenuated cell proliferation and cell cycle progression in AA TNBC cells, but not in EA TNBC cells. In addition, PLK1 and AURKB inhibition with volasertib and barasertib significantly inhibited the growth of AA TNBC xenografts, but not of EA TNBC tumors. These data suggest that inhibition of PLK1 and AURKB suppresses cell proliferation and tumor growth, specifically in AA TNBC. These findings suggest that targeting survivin phosphorylation may be a viable therapeutic option for AA patients with TNBC.

Predictors of Oncologic Outcome in Patients Receiving Phase I Investigational Therapy for Recurrent or Metastatic Cervical Cancer.

We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials. Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed. We included 65 patients with a median age of 41 years (range, 20-74), 3 prior therapies (range, 1-7), and 67.7% squamous carcinoma. The rate of distant metastasis at trial entry was 84.6%. The most common molecular alterations included PIK3CA (46.5%), PD-L1+ (46.2%), EPH (30.0%), and CREBBP (23.1%); 23.1% had received a prior checkpoint inhibitor. Phase I trials were for immunotherapy (58.5%) or targeted therapy (41.5%). The rate of biomarker matching was 21.5%. For all patients, median PFS was 3.6 months (95% CI, 2.0-5.2) and OS was 9.3 months (95% CI, 7.0-10.6). Factors at study entry associated with worse survival were presence of bone metastasis (PFS 1.6 vs 4.4 months: hazard ratio [HR], 2.8; p = 0.001; OS 3.8 vs 10.0 months: HR, 3.9; p < 0.0001) and absolute lymphocyte count below 1000/μL (PFS 1.8 vs 5.2 months: HR, 2.9; p = 0.0004; OS 7.0 vs 10.6 months: HR, 3.2; p = 0.0009). Factors associated only with worse OS were absolute neutrophil count above 4700/μL, hemoglobin below 10.5 g/dL, and smoking status. Grade 3+ treatment-related adverse events were seen in 16.9% of cases. Bone metastasis and absolute lymphocyte count below normal range at phase I study entry portend poor survival in patients with recurrent or metastatic cervical cancer.

Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study.

The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p<0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p<0.01). SNCEC tumors >4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

Long-term outcomes in a retrospective cohort of patients with rectal cancer with complete response after total neoadjuvant therapy: a propensity-score weighted analysis.

The watch-and-wait (W&W) strategy is a novel treatment option for patients with rectal cancer who have a strong desire for organ preservation. The study aimed to explore the long-term outcomes of the W&W strategy in a large cohort of rectal cancer patients who achieved a clinical complete response (cCR) after consolidation total neoadjuvant therapy (TNT), and to compare with patients who achieved a pathological complete response (pCR) after radical surgery. The W&W group comprised patients who were assessed as having a cCR after consolidation TNT and adopted the W&W strategy. Patients who underwent standard resection and achieved a pCR were compared as a reference. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier analysis with log-rank test was used to compare survival outcomes. We included 89 and 171 patients in the W&W and pCR groups, respectively. The median follow-up period was 45 and 58 months for the W&W and pCR groups, respectively. After IPTW adjustment, the 2-year local regrowth/recurrence rate for the W&W and pCR groups were 9.9% and 2.0%, respectively (p < 0.001). The W&W and pCR groups had similar 5-year outcomes, including overall survival, disease-free survival, and distant metastasis-free survival (all p > 0.05). No significant difference was observed in the rates of distant metastasis between patients in the W&W group with local regrowth and those without local regrowth (25% versus 6.2%, p = 0.119). Patients who were managed with a W&W strategy after consolidation TNT had favorable survival outcomes, which were similar to those of patients with a pCR. The rate of local regrowth in W&W patients was lower in our study than in other studies as a result of the implementation of consolidation TNT.

Breast-Conserving Surgery in Triple-Negative Breast Cancer: A Retrospective Cohort Study.

The aim of the study is to evaluate the efficacy and prognosis of neoadjuvant chemotherapy (NAC) combined with breast-conserving surgery (BCS) in treating triple-negative breast cancer (TNBC) and analyze the influencing factors and predictors of the efficiency and prognosis of NAC. A retrospective cohort study was conducted by dividing patients into two groups according to two different therapy methods. With BCS as the exposure factor, 46 cases were assigned to the exposed group and 80 cases to the nonexposed group. We compare the difference in operation-related indicators, postoperative complications, local recurrence rate, distant metastasis rate, and overall survival (OS) rate between the two groups. The factors affecting the efficiency and prognosis of NAC were analyzed by binary logistic regression, and the optimal cutoff value was determined by the area under the ROC curve (AUC). The survival curve was plotted, and the univariate log-rank test was performed to analyze the difference in OS between the two groups. The influencing factors of OS were analyzed by the Cox risk regression model. NAC + BCS resulted in significantly less intraoperative blood loss, lower incidence of postoperative complications, and shorter operative time and length of hospital stay than that in NAC (P < 0.05). There was no significant difference in local recurrence, distant metastasis, or OS between the two groups (P > 0.05). Multivariate analysis showed that the clinical stage I and Ki-67 high expression were independent protective factors of the efficacy of NAC. The high expression of Ki-67 and nondecline expression of Ki-67 were independent risk factors of prognosis. Ki-67 high expression was an independent risk factor of OS (P < 0.05). The ROC curve showed that the AUC of Ki-67 for NAC efficacy, prognosis, and OS were 0.706, 0.820, and 0.687, respectively, with optimal cutoff values of 25.5%, 29.0%, and 32.5%, respectively. Survival analysis showed that the OS of patients with NAC + BCS was 73.9% and NAC + MRM was 70.0% (P > 0.05). In the low expression subgroup of Ki-67, the OS of the two groups were 100.0% and 77.8%, respectively (P=0.060). In the high expression subgroup of Ki-67, the OS of the two groups were 53.8% and 63.6%, respectively (P=0.419). NAC + BCS is a good method for treating TNBC, which has an obvious short-term effect and a good long-term prognosis. Clinical stage I and the high expression of Ki-67 are independent protective factors for the efficacy of NAC. The high expression of Ki-67 and nondecline expression of Ki-67 are independent risk factors of prognosis. Ki-67 is a potential predictor for the efficacy, prognosis, and OS of NAC in TNBC patients. The high expression of Ki-67 indicates better NAC efficacy, a poorer prognosis, and a lower OS.

Conjunctival Melanoma in 430 Cases: Comparative Analysis of the Impact of Orbital Invasion on Tumor Recurrence, Metastasis, and Death.

To compare the clinical features at presentation and treatment outcomes of conjunctival melanoma by absence/presence of orbital invasion. A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Of 430 patients with conjunctival melanoma, 21 (5%) had orbital invasion at presentation. A comparison between the 2 groups (orbital invasion absent vs. present) revealed that the orbital invasion group had a higher frequency of prior eyelid incisional biopsy (5% vs. 24%, P = 0.006), greater tumor basal diameter (12.2 vs. 17.3, P = 0.009), greater tumor thickness (2.4 vs. 7.0, P < 0.001), more quadrants involved (1.8 vs. 2.5, P = 0.002), and more clock hours involved (4.4 vs. 5.8, P = 0.037). In addition, those with orbital invasion were more likely to undergo exenteration as primary treatment (1% vs. 24%, P < 0.001). Multivariate relative risk regression analysis revealed that variables predictive of orbital invasion included greater tumor thickness (P < 0.001) and greater involvement of the fornix (P = 0.031) and tarsus (P = 0.033). Outcomes revealed orbital invasion group with greater 5-year/10-year distant metastatic rate (16%/21% vs. 63%/63%, P = 0.005), and greater melanoma-related death rate (7%/13% vs. 38%/53%, P = 0.001). Conjunctival melanoma with orbital invasion at presentation demonstrate larger, more extensive tumors involving the fornix or tarsus, and with greater rate of melanoma-related metastasis and death.

Stereotactic radiosurgery in brain metastasis: treatment outcomes and patterns of failure

Abstract Introduction: Stereotactic radiosurgery (SRS) has become a preferred treatment in the initial management of brain metastases (BM). This study reported treatment outcomes and identified the patient, tumour, and treatment-related factors that predict failure, survival, and brain necrosis (BN). Methods: We retrospectively reviewed the electronic medical records of all BM patients treated with SRS. Patient, tumour characteristics and treatment details data were collected. All recurrences and BN were defined in the neurooncological tumour board. Results: From December 2016 to April 2020, 148 patients were analysed. The median follow-up was 14·8 months (range 6–51). At the time of analyses, 72·3% of the patients were alive. Presence of initial neurological deficit (HR; 2·71 (1·07–6·9); p = 0·036) and prior RT (HR; 2·55 (1·28–5·09); p = 0·008) is associated with worse overall survival. The local recurrence rate was 11·5 %. The distant brain metastasis rate was 53·4 %. Leptomeningeal metastasis was seen in 11 patients (7·4%). Symptomatic BN was seen in 19 patients (12·8 %). Bigger lesions (13 versus 23 mm diameter; p = 0·034) and cavity radiosurgery are associated with more BN (63·2 % versus 36·8%; p: 0·004). Conclusions: Distant BM is the leading cause of CNS recurrences and, salvage SRS is possible. Due to the increasing risk of developing BN routine metastasectomy should be made with caution.

Abdominoinguinal approach in en bloc resection of retroperitoneal sarcoma involving iliac vessels with graft interposition.

Retroperitoneal sarcomas (RPSs) located in the lower abdominal quadrants involving iliac vessels are difficult to manage. This study introduced a 5-step method for en bloc resection with graft interposition using the abdominoinguinal approach and evaluated its efficacy and safety. Data of 24 consecutive patients who met the inclusion criteria from 272 patients with RPS who underwent surgical treatment between April 2015 and April 2022 were retrospectively collected and analyzed. The patients underwent left- or right-sided abdominoinguinal incision. In all patients, the abdominoinguinal approach provided good exposure, and complete resection was achieved. Iliac artery+vein, vein, and artery resection and replacement by graft were performed in 70.8%, 25.0%, and 4.2% of patients, respectively. Additional resected organs mainly included the colon, ureter, bladder, kidney, and abdominal wall. The median number of organs resected was 5. In 37.5% of patients, reconstruction of the lower abdominal wall and inguinal ligament was performed using a mesh. Venous graft thrombosis occurred in 21.7% of patients, while no patient had pulmonary embolism or arterial occlusion. Major complications occurred in 20.8% of patients, and no 30-day mortality was observed. The estimated 5-year local recurrence and distant metastasis rates were 54.4% and 22.1%, respectively, with a median recurrence-free survival of 27 months. En bloc resection of RPS involving iliac vessels with graft interposition using the abdominoinguinal approach is feasible and advantageous. Good complete resection rate and safety can be achieved. The long-term survival benefit of this surgical approach should be verified by further large-scale prospective controlled studies.

Risk factors to identify the indication for regional nodal irradiation in T1-2N1M0 breast cancer: A joint analysis of 4,243 real-world cases from two institutions.

The aim of this study is to evaluate the role of regional nodal irradiation (RNI) in patients with T1-2N1M0 breast cancer and to identify the subgroup that could benefit from RNI. A total of 4,243 women with pT1-2N1M0 breast cancer treated at two institutions in China were retrospectively reviewed. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. The association of risk factors with survival outcomes was evaluated using multivariable proportional hazards regression. A total of 932 patients (22.0%) received RNI. At a median follow-up of 5.9 years, the 5-year locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were 4.0% and 7.2% (P = 0.001), 13.2% and 10.6% (P = 0.465), 85.0% and 84.7% (P = 0.131), and 93.9% and 92.8% (P = 0.004) in the RNI and non-RNI groups, respectively. Multivariate analysis revealed that RNI was an independent prognostic factor for lower LRR (P = 0.001) and longer DFS (P = 0.013). Patients were stratified into low-, intermediate-, and high-risk groups based on the eight non-therapeutic risk factors. RNI significantly decreased the 5-year LRR (2.2% vs. 7.0%, P = 0.001) and improved the 5-year DFS (88.8% vs. 84.9%, P = 0.015) and OS (95.8% vs. 93.9%, P = 0.010) in the intermediate-risk group. However, neither the low-risk group nor the high-risk group had survival benefit from RNI. T1-2N1M0 breast cancer is a heterogeneous disease. We found that RNI only improved survival in the intermediate-risk group. It might be omitted in low-risk patients, and the role of RNI in high-risk patients needs further study.

Treatment Outcome of Gamma Knife Radiosurgery for Brain Metastasis from Thyroid Cancer: Favorable Local Control but Poor Survival

Brain metastasis from thyroid cancer (TCBM) is extremely rare; thus, despite a good treatment outcome for thyroid cancer, TCBM has shown poor clinical outcomes. Considering the short survival and poor general condition of patients with TCBM, stereotactic radiosurgery may be preferred to achieve local control. A total of 25 patients with TCBM who underwent Gamma Knife radiosurgery (GKS) were initially included in this study; however, 3 patients were excluded because of a lack of data. There were 7 men (31.8%) and 15 women (68.2%) and the mean age was 63.7 years. The most common type of thyroid cancer histology was papillary carcinoma. Fourteen patients (63.6%) harbored single brain metastatic tumor and 8 (36.3%) had multiple brain metastatic tumors. The mean duration from thyroid cancer diagnosis to detection of brain metastasis was 7.7 years (range, 0-23 years). The median dose of radiation of GKS was 22 Gy (range, 18-25 Gy). There was no radiation-induced complication after GKS. The median overall survival (OS) was 15 months and the 1-year OS of patients with TCBM was 63%, the 2-year OS was 38%, and the 5-year OS was 28%. The 6-month progression-free survival (PFS) for local recurrence of TCBM was 90.4%, the 1-year PFS was 84%, and the 3-year PFS was 84%. GKS showed favorable local control for TCBM. However, the rate of distant brain metastasis was high and median survival of patients with TCBM was only 15 months.

High-risk subtype: Clinical manifestations and molecular characteristics of submandibular gland adenoid cystic carcinoma.

Adenoid cystic carcinoma of the head and neck mainly occurs in the major salivary glands, of which the parotid gland and submandibular gland are the most common. The purpose of this study was to clarify the site-specific differences in prognosis and molecular expression characteristics of the patients and to achieve stratified risk management of the clinical prognosis. By performing a single-centre retrospective analysis combined with analyses of the Surveillance, Epidemiology, and End Results (SEER) database, cBioPortal and GEO databases, the clinical prognostic characteristics and the differences in molecular expression patterns of ACC in the submandibular gland and parotid gland were analysed. Cox regression analysis, the chi-square test, Fisher's test and the log-rank test were used to compare the significance of differences. Compared with patients with parotid gland ACC, the submandibular gland ACC is more likely to have metastases in the cervical lymph node (21.7% vs. 3.3%) and shows a higher rate of distant metastasis within 1 year after the primary site diagnosis (47.8% vs. 23.3%), a worse overall prognosis, more frequent mutations of MYB/MYBL1 (50% vs. 25%) and abnormal upregulation of the phosphatidylinositol-3 kinase (PI3K) pathway. Submandibular gland ACC is associated with site-specific early cervical lymph node metastasis and hidden distant metastasis, along with rapid progression and a poor prognosis. A high MYB/MYBL1 mutation rate and abnormal upregulation of the PI3K pathway with MYB involvement were identified.

The Clinicopathological Features of Mixed Carcinoma in 7,215 Patients with Gastric Cancer in a Tertiary Hospital in South Korea.

There are few reports regarding mixed carcinoma, defined as a mixture of glandular and poorly cohesive components, in patients with gastric cancer (GC). The aim of this study was to evaluate the proportion and characteristics of mixed carcinoma in GC patients. A total of 7,215 patients diagnosed with GC at Seoul National University Bundang Hospital were enrolled from March 2011 to February 2020. GC was divided into four groups (well-moderately differentiated GC, poorly differentiated GC, poorly cohesive carcinoma, and mixed carcinoma). The proportion of each GC type and the clinicopathological features were analyzed and divided into early GC and advanced GC. The proportion of mixed carcinoma was 10.9% (n=787). In early GC, submucosal invasion was the most common in poorly differentiated (53.7%), and mixed carcinoma ranked second (41.1%). Mixed carcinoma showed the highest proportion of lymph node metastasis in early GC (23.0%) and advanced GC (78.3%). In advanced GC, the rate of distant metastasis was 3.6% and 3.9% in well-moderately differentiated GC and mixed carcinoma, respectively, lower than that in poorly differentiated GC (6.4%) and poorly cohesive carcinoma (5.7%), without statistical significance. Mixed carcinoma was associated with lymph node metastasis compared to other histological GC subtypes. And it showed relatively common submucosal invasion in early GC, but the rates of venous invasion and distant metastasis were lower in advanced GC. Further research is needed to uncover the mechanism underlying these characteristics of mixed carcinoma (Trial registration number: NCT04973631).

Evaluation of vaginal brachytherapy for treating early-stage endometrial cancer according to the European Society of Medical Oncology 2020 risk stratification.

The aim was to evaluate vaginal brachytherapy (VB) after surgery in early-stage endometrial cancer. The patients with Stage I-II endometrial adeno-cancer operated between 1998 and 2018 and whose adjuvant therapies had been arranged were evaluated retrospectively. A total of 618 patients were enrolled. In 409 patients in the low-risk group, the vaginal, pelvic recurrence, and distant metastasis rates were found to be higher in the VB group. When the results of 112 patients in the intermediate-risk group were evaluated, there was no statistically significant difference between the vaginal, pelvic recurrence, and distance metastasis rates. In 89 patients in the intermediate-high risk group, vaginal recurrence rates were 0%, 4.8%, 0%, and 25% for VB, external beam radiotherapy, combination radiotherapy, and the follow-up groups, respectively (p=0.010), and pelvic recurrence rates were found to be 18.2%, 0%, 1.9% and 0% (p=0.036). Distant metastasis rates were 0%, 0%, 9.6% and 0% (p=0.229). When the overall survival in all groups was examined, no significant difference was found between the groups. In conclusion, no adjuvant treatment is a proper approach for low-risk patients. Brachytherapy can be considered a suitable option for the intermediate risk group. Combined treatments instead of VB in the high-intermediate risk group would be preferred in terms of local control.

Primary Angiosarcoma of the Spleen: An Aggressive Neoplasm.

Primary tumors of the spleen are rare, with an incidence rate of about 0.1%. These tumors could be benign, usually asymptomatic, or malignant which are usually symptomatic with abdominal pain being the most common symptom. Lymphoid neoplasms are the most common primary splenic tumors. Primary angiosarcoma is one of the extremely rare malignant vascular neoplasms of the spleen, which carries a dismal prognosis. It constitutes almost 7.4% of all primary malignant splenic neoplasms and is well known as an aggressive tumor with high local recurrence and distant metastasis rates. Overall survival is up to 12 months following diagnosis, regardless of management strategy. Due to the broad differential diagnosis of splenic tumors, this tumor is often forgotten, and is very challenging to diagnose early. Less than 300 cases of primary splenic angiosarcoma have been reported in the English literature. The main issue of this article is to review the current English literature to figure out the characteristic demographic features, clinical presentation, imaging findings and management of such tumors, in order to increase awareness of the treating physicians to improve diagnosis, management, as well as overall survival.

Management and Prognosis of Cardiac Metastatic Merkel Cell Carcinoma: A Case-Control Study and Literature Review.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003-2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case-control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer.

Characteristics and prognosis of distant metastasis after primary treatment for early-stage extranodal nasal-type natural killer/T-cell lymphoma from the China Lymphoma Collaborative Group database.

This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early-stage extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM-free survival (DMFS) and overall survival (OS). The 5-year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis - distant LN, SST, extracutaneous site, and lymphoma-associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late-onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early-stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Approaches to the Management of Metastatic Adenoid Cystic Carcinoma.

High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents - cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR - in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R/M ACC.

Dentate line invasion as a predictive factor of poor distant relapse-free survival in locally advanced lower rectal cancer with anal sphincter involvement

BackgroundWhile an important surgical landmark of the dentate line has been established for locally advanced lower rectal cancer (LALRC), the prognostic significance of dentate line invasion (DLI) has not been well defined. This study aimed to explore the impact of DLI on prognosis in LALRC patients with anal sphincter involvement after neoadjuvant chemoradiotherapy followed by surgery.MethodsWe analyzed 210 LALRC patients and classified them into DLI group (n = 45) or non-DLI group (n = 165). The exact role of DLI in survival and failure patterns was assessed before and after propensity-score matching(PSM). Finally, 50 patients were matched.ResultsBefore matching, patients in the DLI group had poorer 5-year distant relapse-free survival (DRFS) (P < 0.001), disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P = 0.022) than those in the non-DLI group, with the exception of local recurrence-free survival (LRFS) (P = 0.114). After PSM, the 5-year DRFS, DFS, OS, and LRFS were 51.7% vs. 79.8%(P = 0.026), 51.7% vs. 79.8%(P = 0.029), 71.6% vs. 85.4%(P = 0.126), and 85.7% vs. 92.0%(P = 0.253), respectively, between the two groups. DLI was also an independent prognostic factor for poor DRFS with (Hazard ratio [HR] 3.843, P = 0.020) or without matching (HR 2.567, P = 0.001). The DLI group exhibited a higher rate of distant metastasis before (44.4% vs. 19.4%, P < 0.001) and after matching (48.0% vs. 20.0%, P = 0.037) and similar rates of locoregional recurrence before (13.3% vs.7.9%, P = 0.729) and after matching (16.0% vs.12.0%, P = 1.000).ConclusionsDLI may portend worse DRFS and distant metastasis in LALRC patients with anal sphincter involvement, and this may be an important variable to guide clinicians.

Negative Prognostic Impact of Tumor Deposits in Rectal Cancer: A National Study Cohort.

To investigate whether tumor deposits (TDs) in rectal cancer are associated with increased recurrence risk and decreased survival. Tumor deposits (TDs) are considered a risk factor for recurrence after colon cancer resection, and the presence of TDs prompts adjuvant chemotherapy. The prognostic relevance of TDs in rectal cancer requires further exploration. All patients treated with abdominal resection surgery for rectal cancer in Sweden between 2011 and 2014 were eligible for inclusion in this retrospective cohort study based on prospectively collected data from the Swedish Colorectal Cancer Registry. The primary endpoint was local recurrence or distant metastasis. Secondary outcomes were overall and relative survival. Five thousand four hundred fifty-five patients were identified of which 3769 patients were analyzed after exclusion. TDs were found in 404 (10.7%) patients, including 140 (3.7%) patients with N1c-status. In TD-positive patients, local recurrence and distant metastasis rates at 5 years were 6.3% [95% CI 3.8-8.8%] and 38.9% [95% CI, 33.6-43.5%] compared with 2.7% [95% CI, 2.1-3.3%] and 14.3% [95% CI, 13.1-15.5%] in TD-negative patients. In multivariable regression analysis, the risk of local recurrence and distant metastasis were increased; HR 1.86 [95% CI, 1.09-3.19; P =0.024] and 1.87 [95% CI, 1.52-2.31; P =<0.001], respectively. Overall survival at 5 years was 68.8% [95% CI, 64.4-73.4%] in TD-positive patients and 80.7% [95% CI, 79.4-82.1%] in TD-negative patients. pN1c-patients had similar outcomes regarding local recurrence, distant metastasis, and survival as pN1a-b stage patients. TD-positive pN1a-b patients had significantly worse outcomes whereas TDs did not affect outcomes in pN2a-b patients. This study suggests that TDs have a negative impact on the prognosis in rectal cancer. Thus, efforts should be made to diagnose TD-positive rectal cancer patients preoperatively.