Node Distant Metastasis Research Articles

Subphrenic Lymph Node Metastasis Predicts Poorer Prognosis for Nasopharyngeal Carcinoma Patients With Metachronous Metastasis.

AimWe retrospectively analyzed the distribution of distant lymph node metastasis and its impact on prognosis in patients with metastatic NPC after treatment.MethodsFrom 2010 to 2016, 219 NPC patients out of 1,601 (182 from the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, and 37 from the Affiliated Dongguan Hospital, Southern Medical University) developed distant metastasis after primary radiation therapy. Metastatic lesions were divided into groups according to location: bones above the diaphragm (supraphrenic bone, SUP-B); bones below the diaphragm (subphrenic bone, SUB-B); distant lymph nodes above the diaphragm (supraphrenic distant lymph nodes, SUP-DLN); distant lymph nodes below the diaphragm (subphrenic distant lymph nodes, SUB-DLN), liver, lung, and other lesions beyond bone/lung/distant lymph node above the diaphragm (supraphrenic other lesions, SUP-OL); other lesions beyond bone/liver/distant lymph node below the diaphragm (subphrenic other lesions, SUB-OL); the subtotal above the diaphragm (supraphrenic total lesions, SUP-TL); and the subtotal below the diaphragm (subphrenic total lesions, SUB-TL). Kaplan–Meier methods were used to estimate the probability of patients’ overall survival (OS). Univariate and multivariate analyses were applied using the Cox proportional hazard model to explore prediction factors of OS.ResultsThe most frequent metastatic locations were bone (45.2%), lung (40.6%), liver (32.0%), and distant lymph nodes (20.1%). The total number of distant lymph node metastasis was 44, of which 22 (10.0%) were above the diaphragm, 18 (8.2%) were below the diaphragm, and 4 (1.8%) were both above and below the diaphragm. Age (HR: 1.02, 95% CI: 1.00, 1.03, p = 0.012), N stage (HR: 1.26, 95% CI: 1.04, 1.54, p = 0.019), number of metastatic locations (HR: 1.39, 95% CI: 1.12, 1.73, p = 0.003), bone (HR: 1.65, 95% CI: 1.20, 2.25, p = 0.002), SUB-B (HR: 1.51, 95% CI: 1.07, 2.12, p = 0.019), SUB-DLN (HR: 1.72, 95% CI: 1.03, 2.86, p = 0.038), and SUB-O L(HR: 4.46, 95% CI: 1.39, 14.3, p = 0.012) were associated with OS. Multivariate analyses revealed that a higher N stage (HR: 1.23, 95% CI: 1.00, 1.50, p = 0.048), SUB-DLN (HR: 1.72, 95% CI: 1.02, 2.90, p = 0.043), and SUB-OL (HR: 3.72, 95% CI: 1.14, 12.16, p = 0.029) were associated with worse OS.ConclusionSubphrenic lymph node metastasis predicts poorer prognosis for NPC patients with metachronous metastasis; however, this needs validation by large prospective studies.

BASP1 is up-regulated in tongue squamous cell carcinoma and associated with a poor prognosis

To study the relationship between expression of brain acid soluble protein 1 (BASP1) in tongue squamous cell carcinoma (TSCC) tissue and the clinicopathological characteristics and prognosis of patients with TSCC. Western blotting was performed to detect BASP1 expression in fresh-frozen specimens of tumor tissue and adjacent normal tissue obtained from 6 patients with TSCC. Immunohistochemical methods were used to detect BASP1 expression in 100 paraffin-embedded specimens of TSCC tissue. The chi-square test was used to analyze the association between BASP1 expression and a variety of clinicopathological parameters. A Kaplan-Meier analysis and the Cox proportional hazard model were used to further evaluate the impact of BASP1 on patient survival. The Oncomine database showed that BASP1 expression was increased in TSCC tissues. The PrognoScan and GEPIA databases suggested that a high level of BASP1 expression is related to a poor prognosis for patients with head and neck cancer. Experimental results showed that when compared to normal tissues adjacent to a cancer, BASP1 was more highly expressed in the TSCC tissues. Univariate and multivariate Cox regression analyses showed that BASP1 expression and the tumor's stage may be independent risk factors that affect the growth and prognosis of TSCC. A survival analysis showed that patients with a low level of BASP1 expression had a higher survival rate. Overexpression of BASP1 was found to be associated with distant node metastasis and a poor prognosis among patents with TSCC. BASP1 could possibly serve as a molecular marker for diagnosing and treating the disease.

Incremental Impact of [68\xa0Ga]Ga-PSMA-11 PET/CT in Primary N and M Staging of Prostate Cancer Prior to Curative-Intent Surgery: a Prospective Clinical Trial in Comparison with mpMRI

PurposeThe main objective of this prospective study was to assess the value of gallium-68 prostate-specific membrane antigen ([68 Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in primary N and M staging of intermediate- and high-risk prostate cancer (PCa) patients before planned curative-intent radical prostatectomy (RPE) and extended pelvic lymph node dissection (ePLND). The second objective was to compare the [68 Ga]Ga-PSMA-11 PET/CT findings with standard of care pelvic multi-parametric magnetic resonance imaging (mpMRI) in the detection of locoregional lymph node metastases and intraprostatic prostate cancer.ProceduresA total of 81 patients (mean age: 64.5 years, baseline mean trigger PSA (tPSA) 15.4 ng/ml, ± 15.9) with biopsy proven PCa (24 intermediate- and 57 high risk) scheduled for RPE and ePLND were enrolled in this prospective study. In 52 patients [68 Ga]Ga-PSMA-11 PET/CT, pelvic mpMRI, and RPE with ePLND have been performed. Clinical risk stratification and related biomarkers as well as Gleason score (GS) were recorded. The location of the index lesion (IL) was documented systematically for each modality using a standardized segmentation of the prostate in six segments. Distant bone and lymph node metastasis detected by [68 Ga]Ga-PSMA-11 PET/CT were documented. [68 Ga]Ga-PSMA-11 PET/CT findings were correlated with results of mpMRI and histopathology. A consensus of imaging, clinical and/or follow-up findings were used for determining the distant metastases, which were not verified by histopathology.ResultsIn the patient cohort who underwent RPE, [68 Ga]Ga-PSMA-11 PET/CT and mpMRI detected the IL in 86.5% and 98.1% of the patients, respectively. The median of the maximum standardized uptake value (SUVmax) in the intraprostatic IL was 12 (range, 4.7–67.8). Intraprostatic IL of the high-risk patients showed significantly higher SUVmax than those in patients with intermediate risk for distant metastases (n = 48; median: 17.84 vs. 8.77; p = 0.02).In total 729 LN were removed by ePLND in 48 patients. The histopathology verified 26 pelvic lymph node metastases (pLNM) in 20.8% (10/48) of the patients, which have been correctly identified in 60% of the patients on [68 Ga]Ga-PSMA-11 PET/CT, and in 50% on mpMRI. All but one pLNM had a maximum diameter below 10 mm.Bone metastases (BM) and distant LNM (dLNM) were found in 17.3% of the patients on [68 Ga]Ga-PSMA-11 PET/CT imaging. 39.0% of the [68 Ga]Ga-PSMA-11 PET-positive BM showed no suspicious morphological correlation on CT.Conclusion[68 Ga]Ga-PSMA-11 PET/CT shows high diagnostic performance for N and M staging of patients with intermediate- and high-risk prostate cancer and seems to be superior to pelvic mpMRI in the detection of locoregional lymph node metastases. A significant correlation was found between SUVmax of the intraprostatic index lesion and risk stratification based on tPSA level and GS. The results of this study emphasize again on the role of metabolic molecular imaging using specific tracers in selected patients, leading to tailored therapy approach.

Survival advantage for chemoradiation compared with monotherapy in stage IVB cervical cancer: a propensity score balanced observational investigation

<h3>Objectives:</h3> Stage IVB cervical cancer is rare representing less than 5% of all cervical cancers. Treatment options include radiation (RT), chemotherapy (CT), surgery in rare cases and/or multimodality combinations. Current evidence suggests that chemoradiation (CRT) may be more effective than CT or RT alone. This study evaluated the impact of the different types of adjuvant treatment on overall survival (OS) in stage IVB cervical cancer after excluding patients who underwent surgery. <h3>Methods:</h3> Women diagnosed with stage IVB cervical cancer between 2004 and 2014 and treated with RT alone, CT alone or CRT were evaluated. The source of data was the National Cancer Database. Surgical patients and those with multiple malignancies were excluded. Differences in clinical characteristics between the treatment groups were identified and then balanced using a propensity score approach. Survival was evaluated using weighted Kaplan-Meier method. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) for risk of death were estimated in cohorts before and after balancing using weighted multivariate Cox modeling. <h3>Results:</h3> There were 3,670 eligible participants including 62.1% treated with CRT, 23.6% with CT alone and 14.3% with RT alone. Median follow-up time was 51 months with 2,962 deaths at the time of the analysis. Patients treated by RT were older and had a higher comorbidity score than those treated with CRT or CT (<i>P</i><0.0001). Women with adenocarcinoma were more likely to be treated with CT than CRT or RT (<i>P</i><0.0001). Treatment with CRT was more common in those with a distant lymph node metastasis (<i>P</i><0.0001). There was an incremental and persistent survival advantage for CT alone and CRT relative to RT alone in the cohort before balancing (Fig. 1A). The best survival was seen for CRT vs RT (aHR = 0.48, 95% CI=0.42-0.54; <i>P</i><0.0001). The median survival time pre-balancing was 3.9 months for RT alone, 9.0 months for CT alone and 13.5 months for CRT. After balancing, CRT was associated with superior survival (Fig 1B) over CT alone (aHR = 0.75, 95% CI=0.68-0.84; <i>P</i><0.0001) or RT alone (aHR = 0.52, 95% CI=0.44-0.62; <i>P</i><0.0001). Median survival time after balancing was 12.7 months for CRT, 9.1 months for CT alone, and 5.2 months for RT alone. The difference in survival between CT and RT was restricted to the first 12 months after diagnosis and then became similar with longer follow up (Fig 1B). The survival advantage of CRT over CT alone persisted across age, race/ethnic, comorbidity score, facility type, histology, grade, tumor size and site of distant metastasis groups with the exception of non-Hispanic Blacks and those with grade 3 disease, tumor size ≥8.0 cm, and patients who received palliative care (Fig. 1C). <h3>Conclusions:</h3> CRT was associated with superior survival compared with CT or RT in this observational, hospital-based cohort after adjustment for prognostic covariates and merits further investigation in a prospective clinical trial. The contents of this abstract are those of the authors and do not reflect the views, opinions or policies of the USUHS, the Henry Jackson Foundation, the Department of Defense, the Departments of the Army, Navy, or Air Force or the U.S. Government.

Clinical and Imaging Features of Non-Small Cell Lung Cancer with G12C KRAS Mutation.

Simple SummaryKRAS G12C mutations are important oncogenic mutations in lung cancer that can now be targeted by allosteric small molecule inhibitors. We assessed the imaging features and patterns of metastases in these lung cancers compared to other mutated lung cancers. We found that KRAS G12C NSCLC has distinct primary tumor imaging features and patterns of metastasis when compared to those of NSCLC driven by other genetic alterations. These distinct imaging features may offer clues to its presence and potentially guide management in the future.KRAS G12C mutations are important oncogenic mutations that confer sensitivity to direct G12C inhibitors. We retrospectively identified patients with KRAS+ NSCLC from 2015 to 2019 and assessed the imaging features of the primary tumor and the distribution of metastases of G12C NSCLC compared to those of non-G12C KRAS NSCLC and NSCLC driven by oncogenic fusion events (RET, ALK, ROS1) and EGFR mutations at the time of initial diagnosis. Two hundred fifteen patients with KRAS+ NSCLC (G12C: 83; non-G12C: 132) were included. On single variate analysis, the G12C group was more likely than the non-G12C KRAS group to have cavitation (13% vs. 5%, p = 0.04) and lung metastasis (38% vs. 21%; p = 0.043). Compared to the fusion rearrangement group, the G12C group had a lower frequency of pleural metastasis (21% vs. 41%, p = 0.01) and lymphangitic carcinomatosis (4% vs. 39%, p = 0.0001) and a higher frequency of brain metastasis (42% vs. 22%, p = 0.005). Compared to the EGFR+ group, the G12C group had a lower frequency of lung metastasis (38% vs. 67%, p = 0.0008) and a higher frequency of distant nodal metastasis (10% vs. 2%, p = 0.02). KRAS G12C NSCLC may have distinct primary tumor imaging features and patterns of metastasis when compared to those of NSCLC driven by other genetic alterations.

Freezing Nodal Disease: Local Control Following Percutaneous Image-Guided Cryoablation of Locoregional and Distant Lymph Node Oligometastases: A 10-Year, Single-Center Experience

PurposeTo retrospectively assess the technical feasibility, safety, and oncologic outcomes of percutaneous image-guided cryoablation (PCA) of locoregional and distant lymph node metastases (LNMs). MethodsAll consecutive patients undergoing PCA of LNMs between February 2009 and December 2019 were identified using a retrospective database search. Every patient was followed up at 1, 3, 6, and 12 months after treatment using contrast-enhanced magnetic resonance imaging and at approximately 3–6-month intervals using computed tomography or positron emission tomography–computed tomography. The Kaplan-Meier method was used to calculate local tumor progression-free survival, disease-free survival, and overall survival. Locoregional and distant groups were compared using the Fisher test. Technical success, technique efficacy, complications, and oncologic outcomes were analyzed. ResultsFifty-six metachronous oligometastatic LNMs (median size, 15 mm [interquartile range, 13–15 mm; range, 9–36 mm]) were treated in 37 sessions in 29 patients and defined as locoregional (26/37 sessions) or distant (11/37 sessions). Seventeen patients had undergone prior surgery or radiotherapy. Six patients underwent 8 retreatments for locoregional progression. An additional visceral oligometastasis was treated in 4 of the 11 distant LNM PCA sessions. The technical success and primary technique efficacy rates were 100%. The complication rate was 5.4% (2 transient nerve palsies). At a median follow-up of 23 months, there were 2 instances of local tumor progression (5.6%); the 1-, 2-, and 3-year local tumor progression-free survival was 100%, 94.3%, and 94.3%, respectively. Thirteen (45%) patients demonstrated no disease progression. The 1-, 2-, and 3-year overall survival was 96.2%, 90.5%, and 70%, respectively. The patients were free from systemic oncologic therapy following 20 (54%) sessions, with a mean treatment break of 19.1 months. ConclusionsThe PCA of lymph node oligometastases is feasible and safe, and offers promising local tumor control at midterm follow-up.

The Effect Of Beclin 1, P53 Mutation, Ki-67 Proliferation İndex, Tumor Necrosis and Microvascular İnvasion On Prognosis İn Renal Cell Carcinomas and Their Relationship With Known Prognostic Parameters

Aim: The aim of this study was to help identify new prognostic markers in renal cell carcinomas (RCC), to show the role of autophagy in the pathogenesis of RCC and to shed light on new treatment modalities in RCC. Material and Methods: Clinicopathological stages, tumor necrosis and microvascular invasion (MVI) were determined retrospectively and Beclin-1, Ki-67, and p53 were studied immunohistochemically. Results: Tumor necrosis, MVI, Ki-67, and p53 in RCCs were positively correlated with Fuhrman nuclear grade and pathologic tumor stage, while Beclin-1 was only associated with nuclear grade. MVI and Ki-67 were associated with distant organ and lymph node metastasis. Ki-67 and necrosis correlated positively with p53 and Beclin-1 expression, but not with MVI. Beclin-1 were positively correlated necrosis, but not with p53 and MVI. p53, Ki-67 and MVI were negatively correlated with survival, while the effect of Beclin -1 and necrosis on survival couldn’t be demonstrated. Conclusion: Ki-67, p53, and MVI in RCCs are prognostic parameters with effects on survival. Although Beclin-1 was not a prognostic parameter associated with survival, its expression in tumor tissue was found to be increased. At the same time, there is less staining in non-tumor renal parenchyma. Beclin-1 is a marker of autophagy and is thought to be involved in RCC pathogenesis rather than its prognostic significance.

Curative para-Aortic lymph node dissection Via INfra-mesocolonic approach in laparoscopic Gastrectomy (CAVING approach).

Para-aortic lymph node (PAN) metastasis for gastric cancer is considered a distant lymph node metastasis. Meanwhile, multidisciplinary treatments have improved survival of patients with PAN metastases. We developed a novel technique of curative para-aortic lymph node dissection via infra-mesocolonic approach in laparoscopic gastrectomy (CAVING approach). This method minimizes the mobilization of the pancreas and the spleen and maximizes the view from the caudal side resembling cave exploration. After laparoscopic gastrectomy, PAN dissection is performed using the same ports setup. The retroperitoneum is widely exposed to ease anatomical cognition and for troubleshooting. The inferior vena cava, the left gonadal vein, the left renal vein, and the aorta are recognized under Gerota's fascia. The retroperitoneum is then divided into four sections. We perform PAN dissection in the order of 16blat, 16b1int, 16a2lat, and then 16a2int. Using the CAVING approach, the caudal side of the root of the superior mesenteric artery can then be dissected below the pancreas, and only the cranial side of the SMA root requires a suprapancreatic approach. In three cases, preoperative chemotherapy and laparoscopic gastrectomy plus D2 with PAN dissection were performed for gastric cancer and esophagogastric junction cancer. The median operation totaled 484 min, 142 min for the PAN dissection. The median whole blood loss was 130 ml. The median harvested number of PAN was 25. The minimal mobilization of pancreas and the wide surgical fields by CAVING approach may facilitate safe and reliable PAN dissection.

Added Value of 68Gallium-PSMA PET/CT Over Contrast Enhanced CT in Prostate Cancer Patients

Background: 68Gallium (68Ga) -ligand- (PSMA) is a new radiotracer with great diagnostic potential in prostate cancer patients. The imaging is usually performed using PET/CT system, and PET/MRI system when available.The results of PSMA PET/CT in identifying intra-prostatic disease are very impressive. The use of PSMA PET/CT has a higher detection rate of predicted local or distant metastasis compared to CT.Aim of the Work: The aim of this study is to appraise the added value of 68Gallium PSMA PET/CT over the contrast enhanced CT in patients with prostatic cancer.Patients and Methods: The study included 29 male patients in this comparative study (their aged ranged from 50 and 75 years, with mean age of 64.28 years), (the mean of PSA level was 16.86 with range from 0.02 to 150) were referred to the PET/CT unit with different scenarios related to prostate cancer (Biochemical recurrence, initial staging and follow up) at MISR Radiology Center “MRC” in Cairo, Egypt using hybrid PET/CT machine (PET/CT 128 slices machine). Comparative 68Ga-PSMA PET/CT and contrast enhanced CT scans were conducted for all patients. Each patient included in the study was subjected to full history taking and reviewing PSA and serum creatinine levels.Results: 68Ga PSMA PET showed high accuracy in the detection of the prostate cancer, seminal vesicles invasion, local and distant lymph nodes metastasis, lung metastasis, liver metastasis and bone metastasis compared to CECT.

Impact of Inferior Mesenteric Artery Lymph Node Metastasis on the Prognosis of Left-sided Colorectal Cancer.

This study aimed to investigate the impact of the inferior mesenteric artery (IMA) lymph node metastasis [IMALN (+)] on prognosis in left-sided colorectal cancer (LCRC). A total of 285 patients with stage III LCRC and 118 patients with stage IV LCRC who underwent resection of primary tumor between 2005 and 2016 were included. IMALN (+) patients (n=10) had worse overall survival (OS) than patients without IMA lymph node metastasis [IMALN (-); n=275] in stage III LCRC (p=0.007). Multivariate analysis revealed that IMALN (+) was a prognostic factor in stage III LCRC (OS, HR=3.09, p=0.043). Conversely, there was no difference between the OS of IMALN (+) and stage IV LCRC with distant lymph node metastasis only [stage IV LCRC (LYM); n=21; p=0.434]. The prognosis of IMALN (+) was worse than that of IMALN (-); it was similar to that of stage IV LCRC (LYM).

Comparison of Survival Outcomes Among Patients With Breast Cancer With Distant vs Ipsilateral Supraclavicular Lymph Node Metastases

There is a lack of studies exploring whether the survival of patients with distant lymph node metastases (DLNM) is different from that of patients with ipsilateral supraclavicular lymph node metastases (ISLM) and other stage IV breast cancer. To assess the survival of patients with DLNM from breast cancer vs ISLM and other stage IV breast cancer. This cohort study included 2033 patients diagnosed with breast cancer between January 1, 2010, and December 31, 2014, from the Surveillance, Epidemiology and End Results registries database. Three groups of patients were included: (1) patients with ISLM without any distant metastasis, (2) patients with DLNM, and (3) patients with distant metastases (DLNM excluded). Patients younger than 18 years or older than 100 years were excluded. The data were analyzed in February 2020. Surgery for primary tumor, surgery for distant lymph nodes, and radiotherapy. Overall survival (OS) and breast cancer-specific survival (BCSS). Of the 2033 women (mean [SD] age, 62.03 [14.62] years [range, 23.00-99.00 years]; 1510 White participants [74.3%]) with breast cancer included in the study, 346 patients (17.0%) had DLNM, 212 (10.4%) had ISLM, and 1475 (72.6%) had distant metastases (DLNM excluded). The 3-year BCSS rates were 63.24% for ISLM, 64.54% for DLNM, and 41.20% for distant metastases. The 3-year OS rates were 53.46% for ISLM, 62.67% for DLNM, and 38.21% for distant metastases. Compared with patients with ISLM, patients with DLNM showed similar BCSS (hazard ratio [HR], 0.81; 95% CI, 0.52-1.25; P = .34) and OS (HR, 0.73; 95% CI, 0.51-1.05; P = .09), whereas patients with distant metastases showed significantly poorer BCSS (HR, 1.99; 95% CI, 1.43-2.78; P < .001) and OS (HR, 1.79; 95% CI, 1.35-2.38; P < .001). Of the 346 patients with DLNM, primary surgery (HR, 0.21; 95% CI, 0.12-0.39; P < .001) and radiotherapy (HR, 0.46; 95% CI, 0.25-0.87; P = .02) were significantly associated with improved OS. The results of this cohort study suggest that DLNM of breast cancer, with similar survival to N3c disease (indicating metastases to the ipsilateral supraclavicular lymph nodes), might be a regional disease, and reassessment of the role of lymph node metastases in breast cancer may be necessary. Given these findings, aggressive locoregional therapies for this disease are recommended, although future studies are still needed to confirm these results.

Distant Lymph Node Metastases From Breast Cancer—Is it Time to Review TNM Cancer Staging?

Distant Lymph Node Metastases From Breast Cancer—Is it Time to Review TNM Cancer Staging?

Incidental Detection of Ovarian Cancer as a Solitary Peridiaphragmatic Distant Lymph Node Metastasis without Pelvic Lesions on 18F-FDG PET/CT.

The spreading pattern of ovarian carcinoma is unique and unlike most other cancers, because exfoliated ovarian cancer cells primarily disseminate within the abdominal cavity, which are then transported throughout the peritoneum by physiological peritoneal fluid. An initial manifestation of a solitary peridiaphragmatic distant metastatic lymph node without peritoneal involvement is very rare. This study reports a case with an incidentally found single hypermetabolic mass in the peridiaphragmatic space without a pelvic lesion in the baseline staging 18 F-FDG PET/CT that histologically turned out to be metastatic serous papillary carcinoma due to ovarian cancer. 18F-FDG PET/CT may allow the identification of the initial manifestation of unexpected distant oligometastatic statuses of an unknown primary ovarian cancer.

Metastasis of Breast Cancer Promoted by Circadian Rhythm Disruption due to Light/Dark Shift and its Prevention by Dietary Quercetin in Mice.

Epidemiological studies have indicated that a disturbed circadian rhythm resulting from night-shift work is a potential risk factor for breast cancer. However, the mechanism of increased risk of breast cancer by night-shift work remains unclear, and there have been few in vivo studies conducted to definitively associate the two factors. In this study, BJMC3879Luc2 mouse breast cancer cells were transplanted into BALB/c mice. Mice were maintained under lighting conditions that modeled the two-shift system and were investigated for the effect of light/dark cycle disruption on tumor growth and lymph node metastasis. Circadian dysfunction, which was confirmed by measuring circadian locomotor activities using a nano tag device in our light/dark shift model, did not affect tumor growth. However, a significant increase in the number of lymph nodes with distant metastasis was observed. Neutrophil-to-lymphocyte ratio, which is an adverse prognostic factor of breast cancer and also indicator of inflammation, also increased. It has been demonstrated that a chronic inflammatory response is associated with cancer malignancy and poor prognosis in various cancers. These results suggest that night-shift work may also affect distant metastasis and prognosis. In addition, we investigated whether dietary quercetin has anti-metastatic activity against light/dark shift-induced metastasis. A diet containing 0.3 % quercetin significantly inhibited distant lymph node metastasis, particularly metastasis to the iliac and kidney lymph nodes. Our results contribute to our understandings of the effects of the external light environment on breast cancer metastasis and provide a glimpse into potential protective effects of dietary quercetin on light/dark disturbance-induced metastasis.

Outcomes of isolated distant lymph node metastases in colorectal cancer.

84 Background: The optimal management of isolated distant lymph node metastases (IDLNM) in metastatic colorectal cancer (mCRC) is not clearly established. Small case series and prior data from the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry support the use of radical treatment with curative intent (local resection, chemo-radiation or stereotactic radiotherapy), which may lead to better outcomes in mCRC patients with IDLNM. Aims: This study investigates the clinical characteristics and outcomes of mCRC patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. Methods: Clinical data were collected and reviewed from the TRACC registry, a prospective, comprehensive registry for mCRC from multiple tertiary hospitals across Australia from 01/07/2009 to 30/06/2020. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with other organ metastases. Fisher exact test was used for significance tests and Kaplan Meier curves for survival analyses. Results: Of 3408 mCRC patients with a median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC with other organ metastases, patients with IDLNM were younger (mean age: 62.1 vs 65.6 years, p=0.0200), more likely to have metachronous disease (57.0% vs 38.9%, p=0.0005), be KRAS wild-type (74.6% vs 53.9%, p=0.0012) and BRAF mutant (12.9% vs 6.2%, p=0.0100). There was no overall survival difference between with IDLNM and those with other organ metastases (median OS 27.24 vs 25.92 months, p=0.2300). Twenty-four patients (25.8%) with IDLNM received treatment with curative intent, with a trend towards improved overall survival compared to those with other organ metastases treated with curative intent (73.5 vs 62.7 months, p=0.8200). Amongst mCRC patients with IDLNM, those who received treatment with curative intent had a significantly better overall survival than those treated with palliative intent (73.5months vs 23.2 months, p=0.0070). Conclusions: Our findings suggest that there are differences in the patterns of presentation of IDLNM and other organ metastases. Radical treatment with curative intent options should be considered for mCRC patients with IDLNM where appropriate.

Patterns of Treatment Failure after Concurrent Chemoradiotherapy or Adjuvant Radiotherapy in Patients with Locally Advanced Cervical Cancer

Objective: To identify patterns of therapy failure after radiotherapy in Chinese patients with locally advanced cervical cancer (LACC). Methods: A retrospective study was conducted at a Chinese hospital from June 2012 to July 2018. All analyses were done using SPSS 26. Results: 105 patients with treatment failure were included. After a median follow-up of 27 months (range 10–82), the 3-year survival rate after therapy failure was 19.4%. In multivariate analysis, squamous cell carcinoma antigen (SCC-Ag) <4 ng/mL (p < 0.001) and disease-free interval >12 months (p = 0.013) showed significant survival benefits. We identified 3 types of failure: distant lymph node metastasis (n = 50), hematogenous metastasis (n = 53) and pelvic failure (n = 48). Most metastatic para-aortic lymph nodes (PALN) were inferior to the level of left renal hilum (84.8%, n = 28). A total of 80% of patients with supraclavicular lymph nodes (SCLN) metastasis ignored imaging on supraclavicular region. For solitary SCLN or lung metastasis, the prognosis was better than that combined with other sites failure, respectively (p = 0.005; p = 0.001). Many patients with central sites recurrence received insufficient doses of intracavitary brachytherapy (IBT) for low tolerance to pain. Conclusion: The distribution of metastatic PALN is asymmetrical and optimizing clinical target volume to minimize toxicity of para-aortic radiation is necessary. The effect of ultrasonography as preliminary screening and follow-up means on SCLN metastasis can be expected. Pain management and psychological interventions are essential for patients receiving IBT.

Bioinformatics analysis identifies biomarkers associated with poor prognosis in diffuse‑type gastric cancer.

Gastric cancer (GC) is one of the most common malignancies of the digestive system. In diffuse-type GC, differentiation is relatively poor, and the probability of distant metastasis and lymph node metastasis is high, resulting in poor clinical prognosis. The purpose of this study was to identify specific genes that can predict the prognosis of different types of GC. Differentially expressed genes (DEGs) were screened in the GSE62254 dataset obtained from the Gene Expression Omnibus using the ‘limma’ and ‘survival’ R packages. A total of 355 survival-related DEGs were selected according to specific screening criteria, of which 293 were associated with diffuse-type GC and 62 with intestinal-type GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for functional annotation and pathway enrichment analysis of DEGs. Using protein-protein interaction networks and Cytoscape software, three hub genes were identified in diffuse-type GC-associated DEGs, including angiotensinogen (AGT), C-X-C motif chemokine ligand 12 (CXCL12) and adrenoceptor β2 (ADRB2). Immunohistochemical staining and reverse transcription-quantitative PCR revealed that the expression levels of the three genes in diffuse-type GC samples were upregulated compared with in intestinal-type GC samples. Kaplan Meier analysis indicated that a higher expression levels of these three hub genes were associated with a poorer prognosis of diffuse-type GC. In summary, the present findings suggested that AGT, CXCL12 and ADRB2 might contribute to the progression of diffuse-type GC, and could serve as potential biomarkers or therapeutic targets for this disease.

Circular RNA circCOL6A3_030 is involved in the metastasis of gastric cancer by encoding polypeptide

ABSTRACT Gastric cancer (GC) is a serious digestive tract disease that threatens human life worldwide, and the prognosis of gastric cancer accompanied by distant lymph node or the distant metastasis organs is worse. The purpose of this study was to investigate the role of circular RNA COL6A3_030 (circBase ID: hsa_circ_0006401; circRNADb ID: hsa_circ_28198; circBank ID: hsa_circCOL6A3_030) in GC metastasis. qRT-PCR analysis using back-splicing primers and Sanger sequencing of PCR products were performed to identify circCOL6A3_030 in GC tissues and cell lines; RNA-FISH assay was performed to validate the subcellular localization of circCOL6A3_030. Transwell and wound-healing assays were carried out to evaluate the migration ability of GC cells. Western blot was conducted to detect the polypeptide encoded by circCOL6A3_030 in cells. circCOL6A3_030 was down-regulated in GC tissues and cell lines, while circCOL6A3_030 was up-regulated in GC with distant lymph node metastasis. The migration of circCOL6A3_030 silenced GC cells was significantly inhibited in both SGC-7901 and BGC-823 cell lines. Importantly, in vivo assay, silencing circCOL6A3_030 could reduce liver metastases from gastric cancer cells. Meanwhile, further studies suggested that circCOL6A3_030 encoded a small peptide that had a function as a tumor-promoting metastasis factor and immunohistochemistry confirmed the presence of this polypeptide. To sum up, our study showed that circCOL6A3_030 promoted GC cell migration by encoding a small peptide called circCOL6A3_030_198aa. Therefore, our results highlight the potential role of circCOL6A3_030 for clinical diagnosis and treatment of GC with distant lymph node metastasis.

A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer.

Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa. Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55-83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

Oncologic Feasibility of Proximal Gastrectomy in Upper Third Advanced Gastric and Esophagogastric Junctional Cancer.

PurposeThe aim of this study was to investigate the oncologic safety and identify potential candidates for proximal gastrectomy (PG) in upper third advanced gastric cancer (AGC) and esophagogastric junction (EGJ) cancers.Materials and MethodsAmong 5,665 patients who underwent gastrectomy for gastric adenocarcinoma between January 2011 and December 2017, 327 patients who underwent total gastrectomy with standard lymph node (LN) dissection for upper third AGC and Siewert type II EGJ cancers were enrolled. We analyzed the correlation between the metastatic rates of distal LNs (No. 4d, 5, 6, and 12a) around the lower part of the stomach and the clinicopathological characteristics. We identified subgroups with no metastasis to the distal LNs.ResultsThe metastatic rate of distal LNs in proximal AGC and Siewert type II EGJ cancers was 7.0% (23 of 327 patients). On multivariate analysis, pathological T stage (P=0.001), tumor size (P=0.043), and middle third invasion (P=0.003) were significantly associated with distal LN metastases. Pathological ‘T2 stage’ (n=88), or ‘T3 stage with ≤5 cm tumor size’ (n=87) showed no metastasis in distal LNs, regardless of middle third invasion. Pathological T3 stage with tumor size > 5 cm (n=61) and T4 stage (n=91) had metastasis in the distal LNs.ConclusionsIn the upper third AGC and Siewert type II EGJ cancer, pathological T2 and small-sized T3 stage groups are possible candidates for PG in cases without distal LN metastasis. Further validation studies are required for clinical application.