Single Node Metastasis Research Articles

Role of Pathologic Single-Nodal and Multiple-Nodal Descriptors in Resected Non-Small Cell Lung Cancer

BackgroundThe 8th edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single- and multiple-N descriptors. Research QuestionDo the single- and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and MethodsUsing the National Cancer Database, we analyzed patients with pathologically staged N1–2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pSingle-N2, and pMulti-N2. Survival analysis was performed using Kaplan–Meier method and multivariate Cox regression models. ResultsIn the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 NSCLC patients had pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2, respectively. Patients with pMulti-N1 and pMulti-N2 had a shorter survival than those with pSingle-N1 and pSingle-N2, respectively (hazard ratio [HR]: 1.22, P < 0.0001 for N1 and 1.39, P < 0.0001 for N2). After adjusting age, sex, and histology, the HR for pSingle-N2 compared with pMulti-N1 was 1.05 (P = 0.0031). Patients with pN1 were categorized by metastatic lymph node count (1, 2, 3, 4+), showing significant prognostic differences among groups (P < 0.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy or more, survival ≥ 30 days, ≥ 10 examined lymph nodes, and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708) analyses supported these results. InterpretationNSCLC patients with 1 metastatic lymph node, whether in N1 or N2 stations, had better survival than those with more than 1 lymph node involved. NSCLC patients with a single skip N2 lymph node metastasis had survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to ≥ 4 was sequentially prognostic.

Predictive value and potential association of PET/CT radiomics on lymph node metastasis of cervical cancer

Objective: Due to the information-rich nature of positron emission tomography/computed tomography (PET/CT) images, the authors hope to explore radiomics features that could distinguish metastatic lymph nodes (LNs) from hypermetabolic benign LNs, in addition to conventional indicators. Methods: PET/CT images of 106 patients with early-stage cervical cancer from 2019 to 2021 were retrospectively analyzed. The tumor lesions and LN regions of PET/CT images were outlined with SeeIt, and then radiomics features were extracted. The least absolute shrinkage and selection operator (LASSO) was used to select features. The final selected radiomics features of LNs were used as predictors to construct a machine learning model to predict LN metastasis. Results: The authors determined two morphological coefficient characteristics of cervical lesions (shape – major axis length and shape – mesh volume), one first order characteristics of LNs (first order – 10 percentile) and two gray-level co-occurrence matrix (GLCM) characteristics of LNs (GLCM – id and GLCM – inverse variance) were closely related to LN metastasis. Finally, a neural network was constructed based on the radiomic features of the LNs. The area under the curve of receiver operating characteristic (AUC-ROC) of the model was 0.983 in the training set and 0.860 in the test set. Conclusion: The authors constructed and demonstrated a neural network based on radiomics features of PET/CT to evaluate the risk of single LN metastasis in early-stage cervical cancer.

Hereditary breast and ovarian cancer triggered by occult fallopian tube cancer: a case report

BackgroundAt the time of benign gynecological surgery, a prophylactic salpingo-oophorectomy or salpingectomy is increasingly being performed concurrently to reduce the risk of future ovarian and fallopian tube cancer. We herein describe a case of hereditary breast and ovarian cancer syndrome in which a hysterectomy and bilateral adnexectomy were performed with a preoperative diagnosis of benign tumor. A detailed pathological examination revealed occult fallopian tube cancer, and additional staging surgery provided an accurate pathology diagnosis.Case presentationA 72-year-old Japanese woman with a past history of breast cancer underwent a hysterectomy and bilateral oophoro-salpingectomy for the preoperative diagnosis of uterine myoma and a right para-ovarian cyst. In the detailed pathological examination, high-grade serous carcinoma of the right fallopian tube was detected incidentally, and a subsequent staging laparotomy confirmed single para-aortic lymph node metastasis. Furthermore, a mutation in germline BRCA2 was detected postoperatively, and the patient was finally diagnosed with hereditary breast and ovarian cancer syndrome. She was diagnosed with fallopian tube cancer International Federation of Gynecology and Obstetrics Stage IIIA1(i) and started on adjuvant therapy (six courses of paclitaxel and carboplatin followed by maintenance therapy with olaparib), and 18 months after surgery, she was free of disease.ConclusionThis is a case of fallopian tube cancer that was diagnosed incidentally and then accurately staged with additional advanced staging surgery. Even in the absence of grossly malignant findings, a detailed pathological search of the fallopian tubes and accurate staging surgery are important to make the necessary treatment decisions for the patient.

Robotically assisted total gastrectomy for lymphadenopathy after long-term follow-up for multiple type 1 gastric neuroendocrine tumor (NET): a case report

BackgroundType 1 gastric neuroendrine tumor (NET) is usually associated with chronic atrophic gastritis and forms multiple lesions. While most cases of type 1 gastric NET are generally slowly growing, some develop regional lymph node metastases even after long-term dormancy.Case presentationA 73-year-old male patient with a 32-year history of multiple gastric NET was being followed-up at the study center after endoscopic submucosal dissection (ESD) of a large gastric NET. A blood examination revealed high serum gastrin (> 3000 pg/ml). An endoscopic examination found atrophic mucosa and multiple, elevated lesions in the upper to lower stomach body. Computed tomography (CT) revealed regional lymphadenopathy in the greater omentum along the gastroepiploic artery. Robotically assisted total gastrectomy was performed with D2 lymphadenectomy and Roux-en-Y reconstruction. Pathological analysis revealed a large number of gastric NET (grade 1) with a maximum size of 4.5 mm invading the submucosal layer. A single lymph node metastasis was also detected pathologically at station #4d. The postoperative course was uneventful, and serum gastrin normalized postoperatively. At postoperative year 3, the patient has been doing well without any recurrences.ConclusionsThe present case of multiple gastric NET with a single regional lymph node metastasis at year 32 of follow-up was successfully treated with a robotically assisted total gastrectomy.

Surgically treated cervical cancer in a high-risk group in the era of the 2018 FIGO staging schema: a nationwide study

The 2018 International Federation of Gynecology and Obstetrics (FIGO) revision to the staging criteria for uterine cervical cancer adopted pathological staging for patients who underwent surgery. We investigated the correlation between clinicopathological factors and prognosis in patients with high-risk factors in accordance with the FIGO 2018 staging criteria by analyzing a real-world database of 6,192 patients who underwent radical hysterectomy at 116 institutions belonging to the Japan Gynecologic Oncology Group. A total of 1,392 patients were categorized into the high-risk group. Non-squamous cell carcinoma histology, regional lymph node metastasis, pT2 classification, and ovarian metastasis were identified as independent risk factors for mortality. Based on pathological findings, 313, 1003, and 76 patients were re-classified into FIGO 2018 stages IIB, IIIC1p, and IIIC2p, respectively. Patients with stage IIIC2p disease showed worse prognoses than those with stage IIB or IIIC1p disease. In patients with stage IIIC1p disease, overall survival was significantly better if their tumors were localized in the uterine cervix, except for single lymph node metastasis, with a 5-year overall survival rate of 91.8%. This study clarified the heterogeneity of the high-risk group and provided insights into the feasibility of upfront radical hysterectomy for a limited number of patients harboring high-risk factors.

Single Lymph Node Metastasis and Adjuvant Therapy in Stage III Tongue Cancer

Background and Objectives We analyzed treatment results among stage III oral tongue squamous cell carcinoma (OTSCC) patients and performed subgroup analyses according to the depth of invasion (DOI) and node positivity.Subjects and Method We retrospectively analyzed the medical records of 87 stage III OTSCC patients.Results A total of 32 recurrences occurred during the study period, eight cases of local recurrence, 12 cases of regional recurrence, eight cases of distant metastasis, and four cases of loco-regional recurrence. During the study period, 27 patients died due to disease progression. The 5-year recurrence-free survival of the patients was 62.9%, and the 5-year disease-specific survival (DSS) was 75.3%. When prognostic factors related to disease recurrence and survival were analyzed through univariate and multivariate analyses, only the N classification was significantly associated with patient survival (hazard ratio 0.36, confidence interval 0.14-0.91). The 5-year DSS of N0 patients was 87.6%, and the 5-year DSS of N1 patients was 63.9%. Among N1 patients, the 5-year DSS was 90.5% when adjuvant therapy was administered and 63.9% when adjuvant therapy was not administered, which is a statistically significant difference. We did not observe any difference in treatment outcome or survival between patients with superficial (DOI ≤10 mm) or deep lesions (DOI &gt;10 mm).Conclusion Among the stage III OTSCC patients, patients with single lymph node (LN) metastasis (N1) showed a distinct prognostic difference from other patients (N0), and the administration of adjuvant therapy to patients having single LN metastasis without other risk factors significantly improved their 5-year DSS.

Surgical Treatment Outcomes of Patients with Non-Small Cell Lung Cancer and Lymph Node Metastases

This study aimed to investigate the appropriate subgroups for surgery and adjuvant chemotherapy in patients with non-small-cell lung cancer (NSCLC) and nodal metastases. We retrospectively reviewed 210 patients with NSCLC and nodal metastases who underwent surgery and examined the risk factors for poor overall survival (OS) and recurrence-free probability (RFP) using multivariate Cox proportional hazards analysis. Pathological N1 and N2 were observed in 114 (52.4%) and 96 (47.6%) patients, respectively. A single positive node was identified in 102 patients (48.6%), and multiple nodes were identified in 108 (51.4%). Multivariate analysis revealed that vital capacity &lt; 80% (hazard ratio [HR]: 2.678, 95% confidence interval [CI]: 1.483–4.837), radiological usual interstitial pneumonia pattern (HR: 2.321, 95% CI: 1.506–3.576), tumor size &gt; 4.0 cm (HR: 1.534, 95% CI: 1.035–2.133), and multiple-node metastases (HR: 2.283, 95% CI: 1.517–3.955) were significant independent risk factors for poor OS. Tumor size &gt; 4.0 cm (HR: 1.780, 95% CI: 1.237–2.562), lymphatic permeation (HR: 1.525, 95% CI: 1.053–2.207), and multiple lymph node metastases (HR: 2.858, 95% CI: 1.933–4.226) were significant independent risk factors for recurrence. In patients with squamous cell carcinoma (n = 93), there were no significant differences in OS or RFP between those who received platinum-based adjuvant chemotherapy (n = 25) and those who did not (n = 68), at p = 0.690 and p = 0.292, respectively. Multiple-node metastases were independent predictors of poor OS and recurrence. Patients with NSCLC and single-node metastases should be considered for surgery despite N2 disease. Additional treatment with platinum-based adjuvant chemotherapy may be expected, especially in patients with squamous cell carcinoma.

Carboplatin Induction Chemotherapy in Clinically Lymph Node–positive Bladder Cancer

BackgroundThere are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). ObjectiveTo investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participantsThis was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. InterventionIC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysisThe primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitationsAfter PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. ConclusionsCisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summaryIn this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Magnetic resonance imaging evaluation of single axillary lymph node metastasis in breast cancer: Emphasis on the location of lymph nodes

To evaluate the frequency and location of abnormal lymph nodes (LNs) in breast cancer patients with a single axillary lymph node (ALN) metastasis on breast magnetic resonance imaging (MRI). We retrospectively reviewed the MRI findings of 219 consecutive patients with breast cancer with single ALN metastasis who were surgically confirmed at our institution between January 2018 and December 2018. The morphological features and locations of the abnormal LN on MRI were analyzed. Pathology reports were reviewed to evaluate the size of the metastases and whether they were sentinel LNs (SLNs). Of the 219 patients with a single ALN metastasis, 56 (25.6%) showed abnormal MRI findings. Of these, 54 (96.4%) had either the lowest or second-lowest LN in the level I axilla. In 184 (91.5%) of 201 patients who underwent SLN biopsy, the metastatic LN were SLN. Macrometastases were found more frequently in cases with abnormal LNs than in those with normal-looking LNs (P = .004). The most frequent morphological feature of metastatic ALNs was a diffuse cortical thickening of 3 to 5 mm (37.5%). Although MRI findings of single ALN metastasis in breast cancer patients are none or minimal, abnormalities are observed in the lowest or second-lowest LN in the lower axilla when present, suggesting the location of the SLNs.

The predictors and surgical outcomes of different distant metastases patterns in upper tract urothelial carcinoma: A SEER-based study.

The purpose of this study was to investigate the predictors of metastatic patterns of upper tract urothelial carcinoma (UTUC) and to analyze the surgical outcomes of different metastatic patterns of UTUC. Data on patients with UTUC from 2010 to 2017 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier analysis was applied to compare the patients' survival distributions. Univariate and multivariate logistic regression was used to assess the specific predictors of site-specific metastases, while competitive risk regression was applied to estimate the predictors of cancer-specific mortality in patients with metastases. A total of 9,436 patients were enrolled from the SEER database, of which 1,255 patients had distant metastases. Lung metastasis (42.5%) was most common and patients with single distant lymph node metastasis had a better prognosis. Clinical N stage (N1, N2, N3) was the strongest predictors of the site specific metastatic sites. Renal pelvis carcinoma was more prone to develop lung metastases (OR = 1.67, P < 0.01). Resection of the primary tumor site is beneficial for the prognosis of patients with metastatic UTUC, whether local tumor resection (HR = 0.72, P < 0.01) or nephroureterectomy (HR = 0.64, P < 0.01). Patients with single distant lymph node metastasis have the greatest benefit in nephroureterectomy compared to other specific-site metastases (median survival 19 months vs. 8 months). An understanding of distant metastatic patterns and surgical outcomes in patients with UTUC is important in clinical settings and helpful in the design of personalized treatment protocols.

Multiparametric Dual-Time-Point [18F]FDG PET/MRI for Lymph Node Staging in Patients with Untreated FIGO I/II Cervical Carcinoma.

[18F]FDG PET/MRI was shown to have limited sensitivity for N-staging in FIGO I/II cervical carcinoma. Therefore, this prospective study aimed to investigate the additional value of multiparametric dual-time-point PET/MRI and to assess potential influencing factors for lymph node metastasis (LNM) detection. A total of 63 patients underwent whole-body dual-time-point [18F]FDG PET/MRI 60 + 90 min p.i., and 251 LN were evaluated visually, quantified multiparametrically, and correlated with histology. Grading of the primary tumor (G2/G3) had a significant impact on visual detection (sens: 8.3%/31%). The best single parameter for LNM detection was SUVavg, however, with a significant loss of discriminatory power in G2 vs. G3 tumors (AUC: 0.673/0.901). The independent predictors SUVavg, ∆SUVpeak, LN sphericity, ADC, and histologic grade were included in the logistic-regression-based malignancy score (MS) for multiparametric analysis. Application of MS enhanced AUCs, especially in G2 tumors (AUC: G2:0.769; G3:0.877) and improved the accuracy for single LNM from 34.5% to 55.5% compared with the best univariate parameter SUVavg. Compared with visual analysis, the use of the malignancy score increased the overall sensitivity from 31.0% to 79.3% (Youden optimum) with a moderate decrease in specificity from 98.3% to 75.6%. These findings indicate that multiparametric evaluation of dual-time-point PET/MRI has the potential to improve accuracy compared with visual interpretation and enables sufficient N-staging also in G2 cervical carcinoma.

Role of adjuvant radiation therapy for squamous cell carcinoma (SCC) of the vulva and single lymph node metastasis (159)

<b>Objectives:</b> To evaluate the utilization and outcomes of adjuvant radiation therapy for early-stage squamous cell carcinoma of the vulva with single inguinal lymph node metastasis following comprehensive inguinal lymphadenectomy. <b>Methods:</b> The National Cancer Database and patients without a history of another tumor, diagnosed between 2004 and 2015 with T1b squamous cell carcinoma of the vulva who underwent surgical excision and inguinal lymphadenectomy with at least ten lymph nodes removed and had only one positive lymph node per pathology report were identified. Clinical-pathologic and demographic characteristics were compared based on the receipt of adjuvant radiotherapy (defined as receipt of external beam radiation at a dose of at least 50 Gy within six months from surgery). Overall survival (OS) was calculated and compared with the log-rank test following the generation of Kaplan-Meier curves. A Cox model was constructed to control for a priori selected confounders. <b>Results:</b> A total of 250 patients who met the inclusion criteria were identified; 77 (30.8%) received adjuvant radiation therapy at a median of 57 days from surgery (IQR: 22) with a median dose of 50.4 Gy and a median treatment duration of 44 days (IQR: 12), while 32 (41.6%) of them received radio-sensitizing chemotherapy. Patients who received adjuvant radiation were more likely to have tumors ≥4 cm (46.8% vs 29.5%, p=0.046). Patient age, race, insurance status, presence of comorbid conditions, type of treatment facility, tumor grade, and surgical margin status were comparable between the two groups. By univariate analysis, patients who received adjuvant chemoradiation or radiation therapy alone did not have better OS compared to patients who did not receive any treatment (p=0.45); 5-year OS rates were 61.1% compared to 53.4% and 56.5%, respectively. After controlling for patient age, presence of comorbid conditions, insurance status, and tumor size, administration of adjuvant chemoradiation (HR: 0.74, 95% CI: 0.45-1.23) or radiation therapy alone (HR: 0.87, 95% CI: 0.43-1.76) were not associated with a survival benefit. <b>Conclusions:</b> Administration of adjuvant radiation therapy following comprehensive inguinal lymphadenectomy may not be associated with a survival benefit for patients with early-stage SCC of the vulva and single lymph node metastasis.

The Benefit of Postoperative Radiotherapy and Extending Neck Dissection in pT1-2 Oral Squamous Cell Carcinoma With a Single Ipsilateral Cervical Lymph Node Metastasis (pN1).

We compared postoperative radiotherapy (PORT) to surgery only (SO), and supraomohyoidal neck dissection (SOHND) to modified radical neck dissection (MRND) in patients with pT1-T2 squamous cell carcinomas of the oral cavity (OSCC) and a single cervical lymph node metastasis (pN1) in terms of overall survival (OS), oral cancer specific survival (OCSS), and regional recurrence-free survival (RRFS), in a prospective cohort study. We included patients with pT1-T2 pN1 OSCC with no distant metastasis and estimated the survival probabilities using the Kaplan-Meier method and calculated hazards ratios (HR) for PORT vs. SO and MRND vs. SOHND using adjusted Cox regression models. A total of 51 patients (26 SO vs. 25 PORT, 9 SOHND vs. 42 MRND) were evaluated. Patients who received PORT were more likely to be younger and healthier. OS at 5 years was 41% and 87% in the SO and PORT groups, respectively. OS at 5 years was 52% and 67% in the in the SOHND and MRND groups, respectively. Both OCSS and RRFS were improved by PORT. Extending neck dissection was not associated with improved OS (HR = 0.83). PORT is associated with preferable OS, OCSS, and RRFS in pT1-2 pN1 oral cancer and should be recommended regularly.

A case of early gastric cancer with a single giant lymph node metastasis

BackgroundEarly gastric cancer (EGC) is often associated with lymphatic metastasis, but it is extremely rare to be found as a single giant lymph node. Cancer often becomes more malignant in metastatic lesions than in primary lesions, and retrodifferentiation to the fetal gastrointestinal tract during the metastatic process has been reported in gastric cancer. We report an extremely rare case of EGC with a 13-cm giant lymph node metastasis in which an adenocarcinoma with enteroblastic differentiation and yolk sac tumor-like components was observed.Case presentationThe case was a 70-year-old man who visited his local doctor with right hypochondrial pain, which was identified by computed tomography (CT) as a giant mass. Upper endoscopy revealed a 30-mm-sized 0-IIc lesion in the greater curvature of the angular incisure and a 15-mm-sized 0-IIa lesion in the anterior wall of the lower body of the gastric body. Endoscopic biopsy revealed tubular adenocarcinoma in both lesions. The gastric lesion and the giant tumor were clinically regarded as independent lesions (gastrointestinal stromal tumor, [GIST], and EGCs), and distal gastrectomy and D1 + dissection were performed to comprehensively treat all lesions. Pathological examination revealed that the giant tumor was tubular adenocarcinoma with an intestinal phenotype and was considered a lymph node metastasis of EGCs. To exclude the possibility of metastasis of adenocarcinoma other than EGCs, postoperative positron emission tomography-computed tomography (PET-CT) and colonoscopy were performed; however, no primary site other than the stomach was found. Metastatic lymph nodes have an increased degree of atypia compared with the primary tumor, and yolk sac tumor-like carcinoma morphology was observed along with α-fetoprotein (AFP) and Spalt-like 4 (SALL4) expression in this case. It was considered that retrodifferentiation to a fetal phenotype occurred during the metastatic process. Liver metastasis occurred 6 months after surgery, and chemotherapy is currently being introduced.ConclusionsWe experienced a case of EGC with a single giant lymph node metastasis. Retrodifferentiation to the fetal gastrointestinal tract during metastasis was speculated to be involved in the formation of giant lymph node metastasis and liver metastasis in this case.

Indications of Superselective Neck Dissection in Patients With Lateral Node Metastasis of Papillary Thyroid Carcinoma.

The extent of neck dissection in papillary thyroid carcinoma (PTC) patients with lateral neck metastasis is controversial. This work aims to screen the patients suitable for superselective neck dissections including only levels III-IV. Prospective observational cohort study. The study was conducted in a high-volume tertiary care setting. A total of 134 consecutive previously untreated PTC patients with lateral neck metastases and subjected to 154 therapeutic lateral neck dissections (including levels II, III, IV, and VB) between June 2018 and March 2021 were enrolled. Fine-needle aspiration was performed preoperatively at each suspicious neck level. Clinical predictors were analyzed for occult lymph node metastases at levels II and VB. As a result, 44.8% and 5.8% of neck specimens exhibited metastatic lymph nodes at levels II and VB. In addition, univariate and multivariate analyses showed that the primary tumor in the ipsilateral thyroid upper lobe (P = .016, odds ratio = 3.528) and clinically multiple metastatic lymph nodes in level III-IV (P = .005, odds ratio = 6.414) were independent predictive factors for occult level II metastases. All 3 (1.9%) occult metastases at level VB were found in necks with preoperative multiple lymph node metastases. A superselective lateral neck dissection including levels III to IV may be considered in patients with PTC when the preoperative evaluation identifies a single lymph node metastasis located at levels III to IV and the primary tumor is not in the upper lobe of the ipsilateral thyroid.

Genetic and immune characteristics of sentinel lymph node metastases and multiple lymph node metastases compared to their matched primary breast tumours.

BackgroundPatients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).MethodsGenomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.FindingsThe downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.InterpretationSingle lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.FundingThis work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).

Pattern of Lymph Node Metastasis in Oral Cancer

Background: Oral cancer is a common neoplasm worldwide which has a increased incidence and mortality rate over the past decades. In spite of skilled surgical and radio therapeutic modalities it is characterized by poor prognosis and a low survival rate. Lymph node metastasis is an important negative prognostic factor in oral cancer. In this study, pattern of cervical lymph node metastasis in oral carcinoma has been described. Such information may contribute to the understanding of oral cancer management plan.&#x0D; Methods: This cross-sectional observational study was conducted in the Otolaryngology and Head-Neck surgery department of Dhaka Medical College Hospital. The study period was from January 2018 to June 2018. A total of 50 patients were selected by purposive sampling technique. Data were collected by study physician himself. Then these collected data were recorded in structured case report forms. Clinical examination and relevant investigations were done. After planned surgical procedure post operative histopathological reports were collected. All collected questionnaire were checked very carefully. Data were processed and analyzed with the help of computer program SPSS and Microsoft excel. Quantitative data were expressed as mean and standard deviation and qualitative data as frequency and percentage. Comparison were done by tabulation and graphical presentation in the form of tables, pie chart, graphs, bar diagrams, histogram &amp; charts etc.&#x0D; Result: Overall demographic features of 50 patients revealed that, the maximum incidence was seen in the age group 31-50 years (54.0%), mean age of the patient was 49.6 ±9.2 year. Male and female ratio was 4.5:1. In this study most of the tumors were well and moderately differentiated, 34.0% and 62.0% respectively. Aetiology and predisposing factors revealed that the most common were cigarette smoking, betal quid and alcohol consumption, present in 52.0%, 28.0% and 22.0% of patients respectively. Post operative histopathology reports showed that 24 patients (48.0%) had neck node metastasis among which 59.4% were with tumor size &gt;1 cm. Tumors with the depth of invasion &gt;3 mm had a very high risk of metastasis (P&lt;0.0001), as compared to tumor less than 3 mm in thickness. Out of the 24 patients with nodal metastasis 17(34.0%) patients had a single node metastasis (N1). Level I and Level II were the commonest site to be involved (14 patients). Nodal metastasis predominantly occurred from primary tumour site of tongue (22.0%) and floor of the mouth (14.0%). It was seen that patients with higher grade had a higher risk of metastasis (grade 1:–29.4%, grade 2:- 54.8%, grade 3:– 100.0%).&#x0D; Conclusion: Oral carcinoma may appear at any sub site, although there are certain areas in which it is found more frequently, such as the oral tongue, cheek and floor of the mouth. Lymph node metastasis is more common in oral carcinoma mostly level I &amp; II, which is one of the most relevant prognostic factors. Elective neck dissection can be considered in all patients with tumors more than 3 mm in thickness.&#x0D; J Dhaka Medical College, Vol. 29, No.1, April, 2020, Page 41-46

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases

Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center. Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS). Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5). In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients.

Successful Use of Myocutaneous Flap in Recurrent Vulvar Carcinoma: A Case Report

Vulvar cancer being a rare gynecological malignancy, many dilemmas and controversies remain during management of such cases. Radical surgeries are associated with severe postoperative morbidity due to wound-related complications increasing the hospital stay and delaying adjuvant therapies. A case is discussed where wound complications were prevented with the use of flaps. A 58-year-old postmenopausal lady presented with itching in the vulva and a large ulcerative growth on the right side of the vulva. Biopsy from lesion diagnosed to be moderately differentiated squamous cell carcinoma. Triple incision modified radical vulvectomy with bilateral inguinofemoral lymphadenectomy with sartorius transposition was done. There were no postoperative complications. Histopathology showed keratinizing squamous cell carcinoma vulva grade 2, with a tumor-free margin of 7.8 mm, and single lymph node metastasis of ≥ 5 mm. She was advised adjuvant radiotherapy but did not follow up. Five months later, she presented again with an ulcerative lesion in the right groin. It was diagnosed to be skin bridge recurrence. She was managed with wide excision with a reconstruction of the groin wound with vertical rectus abdominis myocutaneous (VRAM) flap. The grafted wound and the donor site both healed well without any complications.. The patient was referred for adjuvant radiotherapy. Histopathology confirmed it to be skin bridge recurrence. Skin bridge recurrences are rare and occur in modified radical vulvectomies with separate groin incisions. Surgical excision of recurrences leaves large wounds that need reconstructive surgeries for management. VRAM flap is a very versatile flap which can be used for reconstruction in genital malignancies.

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases: A Single-Institutional Review of Clinical Outcomes

Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (mMHL) is challenging due to the proximity of centrally located, thoracic organs-at-risk. As limited data exist on the safety/efficacy of SBRT for mMHL, a retrospective review of clinical outcomes was conducted. We hypothesize that SBRT to mMHL is well tolerated with high rates of local control (LC). Patients were identified from a prospectively maintained SBRT database at a large tertiary cancer center. At our institution, mMHL SBRT is a strategy to delay the need to start or change systemic therapy (ST), and/or to prevent airway/great vessel compression. Eligible patients received SBRT to mMHL between 2014-2019 for the following indications: oligometastases (OM), oligoprogression (OP), or LC of a dominant area of progression (DAP). The primary endpoint was grade 3 or greater (G3+) toxicity (CTCAEv5.0). All G3+ toxicities were reviewed independently by four radiation oncologists, with final scoring and attribution achieved by consensus. Secondary endpoints were cumulative incidence (CIN) of local failure (LF), progression-free survival (PFS), overall survival (OS), and CIN of starting or changing systemic therapy (SCST). Time zero for all endpoints was SBRT completion date. Fifty-two patients (84 lesions treated) were included. Median follow-up was 19.9 months. Common primary cancer sites were kidney (54%), lung (13%), and breast (8%). Indications for SBRT were OP (n = 35; 67%), OM (n = 10; 19%), or DAP (n = 7; 14%). Thirty-two patients (62%) received ST prior to SBRT, and of these, most (n = 29; 91%) temporarily stopped ST before and during SBRT. The majority (n = 31; 60%) received SBRT to a single lymph node metastasis. Median maximum lesion size was 2.0 cm. Of the 84 metastatic lymph nodes, 53 (63%) were mediastinal and 31 (37%) were hilar. Median SBRT dose was 35 Gy (range: 30-50Gy) with a median BED10 of 59.5 Gy (range: 48-100 Gy). All treatments were delivered in 5 fractions, every other day. Seven G3+ toxicities were experienced by six patients (11.5%) and were mostly transient (5/7; 71%). One (1.9%) probable G5 event was found (radiation pneumonitis) in a patient who underwent synchronous SBRT to a parenchymal lung metastasis. The CIN of LF was 9.0% at 2 years. Median PFS was 4.0 months (95% CI: 2.8-7.3) and median OS was 31.7 months (95% CI: 23.8-87.5). The CIN of SCST was 33.2% and 57.1% at 1- and 2-years, respectively. In one of the largest series of patients undergoing SBRT for mMHL, we found that treatment was generally well tolerated and provided excellent LC. A significant proportion of patients did not require a change in ST strategy following SBRT. Most G3+ toxicities were transient; however, given the potential risk for serious toxicity, prospective evaluation of SBRT for mMHL is warranted.