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Lateral lymph nodes in low, locally advanced, rectal cancer have proven implications for local recurrence rates, which increase drastically in the presence of persistently enlarged lateral lymph nodes. These clinical implications warrant a thorough understanding of lateral nodal disease with awareness and knowledge from all three specialties involved – radiology, radiation oncology, and surgery – to ensure proper treatment. Relevant literature for each specialty, including all current guidelines and perspectives, were examined. Variations in definitions and treatment paradigms were evaluated. There is still no consensus for the standardized treatment of lateral nodal disease. Each discipline works according to their own available evidence, but relevant data are scarce. Current international guidelines and standard recommendations for the diagnostics and treatment of lateral lymph nodes are lacking. This results in differing perspectives and interpretations between the disciplines which can lead to challenging communication in an area where multidisciplinary collaboration is essential. This review addresses this by presenting the current evidence, perspectives and practices of each specialty and makes suggestions for each phase of the diagnostic and treatment process for patients with lateral nodal disease. By doing this, steps are taken toward achieving international consensus, and multidisciplinary collaboration.

Tailoring axillary surgery to disease burden has occurred for patients treated with breast-conserving surgery, but limited data exist for patients treated with mastectomy, thus most of these patients who are clinically node-negative but found to be pathologically node-positive are treated with axillary dissection. From 2295 clinically node-negative mastectomy patients treated at our institution 2008-2018, we studied 338 with 1-2 positive sentinel nodes. Patients with a positive sentinel node identified on intraoperative frozen section pathology had a higher nodal disease burden. 66 of 108 patients (61%) whose nodal disease was identified only on permanent section pathology were treated with sentinel node surgery without axillary dissection with no 5-year regional nodal recurrences. This approach permits tailoring axillary surgery in most clinically node-negative mastectomy patients whilst avoiding a second operation. Introduction : Controversy exists regarding optimal management of the axilla in clinically node-negative (cN0) mastectomy patients with 1-2 positive sentinel nodes (+SLNs). We evaluated the influence of frozen section pathology on axillary management and recurrence. Materials and Methods : We studied cN0 breast cancer patients treated 2008-2018 with mastectomy and SLN surgery with 1-2+SLNs. Patients with 1-2+SLNs identified on frozen section intraoperatively (FS+SLN) were compared to those with 1-2+SLNs not detected by frozen section (FS–SLN). Recurrence rates were estimated using the Kaplan-Meier method. Results : Of 2295 cN0 mastectomy patients, 338 had 1-2+SLNs: 108 (32%) FS-SLN and 230 (68%) FS+SLN. In FS+SLN cases, completion axillary dissection (cALND) was more frequent (97% versus 39%, p Conclusions : Mastectomy patients with 1-2 FS+SLNs have a higher nodal disease burden than FS-SLN patients. The majority of FS+SLN patients underwent cALND and 52% received PMRT with very low 5-year regional nodal recurrence rates. A substantial proportion of FS-SLN patients successfully avoided both cALND and PMRT. Frozen section pathology analysis can guide de-escalation of axillary management.

Purpose: Typical doses of 45–50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen.Materials and Methods: A total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%).Results: Median follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2–2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively.Conclusion: Dose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

Purpose Utilization of sentinel lymph node biopsy (SLNB) in breast cancer patients with positive nodes after neoadjuvant chemotherapy (NAC) has increased. We examine axillary response rates after NAC in patients with clinical N2-3 disease to determine whether SLNB should be considered. Methods Breast cancer patients with clinical N2-3 (AJCC 7th Edition) disease who received NAC followed by surgery were selected from our institutional tumor registry (2009-2018). Axillary response rates were assessed. Results Ninety-nine patients with 100 breast cancers were identified: 59 N2 (59.0%) and 41 (41.0%) N3 disease; 82 (82.0%) treated with axillary lymph node dissection (ALND) and 18 (18.0%) SLNB. The majority (99.0%) received multiagent NAC. In patients undergoing ALND, cCR was observed in 20/82 patients (24.4%), pathologic complete response (pCR) in 15 patients (18.3%), and axillary pCR in 17 patients (20.7%). In patients with a cCR, pCR was identified in 60.0% and was most common in HER2+ patients (34.6%). Conclusion In this analysis of patients with clinical N2-3 disease receiving NAC, 79.3% of patients had residual nodal disease at surgery. However, 60.0% of patients with a cCR also had a pCR. This provides the foundation to consider evaluating SLNB and less extensive axillary surgery in this select group.

The incidence of Merkel cell carcinoma (MCC) continues to increase. Understanding of MCC biology has advanced rapidly, with current staging providing valuable prognostic information. MCC treatment often is multidisciplinary. Surgery remains an important component in the staging and treatment, most commonly involving wide excision of the cancer and sentinel lymph node biopsy. Lymphadenectomy is used to treat nodal disease. Radiotherapy enhances locoregional control and possibly survival. Systemic therapies, in particular novel immunotherapies, may be promising in the treatment of advanced or recurrent and metastatic disease.

Background Matted nodes in human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPC) is an independent predictor of distant metastases and decreased overall survival. We aimed to classify imaging patterns of metastatic lymphadenopathy, analyze our classification system for reproducibility, and assess its prognostic value. Methods The metastatic lymphadenopathy was classified based on radiological characteristics for 216 patients with HPV-mediated OPC. Patient outcomes were compared and inter-rater reliability was calculated. Results The presence of ≥3 abutting lymph nodes with imaging features of surrounding extranodal extension (ENE), one subtype of matted nodes, was associated with worse 5-year overall survival, overall recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival (p ≤ 0.03). Other patterns were not significantly associated with outcome measures. Overall inter-rater agreement was substantial (κ = 0.73). Conclusion One subtype of matted nodes defined by ≥3 abutting lymph nodes with imaging features of surrounding ENE is the radiological marker of worst prognosis.

Preoperative evaluation of clinical N-stage (cN) is difficult in breast cancer patients with invasive lobular carcinoma (ILC). Our goal was to assess the predictive value of axillary imaging in ILC by comparing imaging cN and pathologic N-stage (pN). A single-institution retrospective review was performed for newly diagnosed stage I–III ILC patients undergoing preoperative breast imaging from 2011 to 2016. Clinicopathologic factors; mammogram, MRI, and ultrasound findings; and surgical pathology data were reviewed. Sub-analysis for pN2-N3 patients was performed to determine imaging sensitivity for patients with a larger nodal disease burden. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality. Of the total 349 patients included, 70.5% were cN0, and 62% were pN0 (p = 0.03). For all patients, mammogram sensitivity was 7%, specificity 97%, PPV 50%, NPV 72%; ultrasound sensitivity was 26%, specificity 86%, PPV 52%, NPV 67%; MRI sensitivity was 7%, specificity 98%, PPV 80%, NPV 51%. For pN2/N3 patients, 38% were identified as cN0. Mammogram sensitivity was 10%; ultrasound 42%; MRI 65%. Pathology evaluation of N2/N3 patients indicated LN were replaced with ILC but maintained normal architecture. The average largest pathologic tumor deposit (1.5 ± 0.8 cm) correlated with average largest imaging LN size (1.4 ± 0.6 cm) (p = 0.58). A statistically significant difference between clinical and pathologic N-stage exists for ILC patients. MRI was most sensitive for identification of pN2-N3 patients and should be considered part of routine axillary imaging evaluation for ILC patients.

Axillary nodal disease is significantly less likely in both clinically node-negative (cN0) and node-positive (cN+) breast cancer patients after neoadjuvant chemotherapy (NAC). There have thus been significant efforts to “de-escalate” axillary surgery in this setting. This review discusses modern axillary surgical paradigms and techniques after NAC. In cN0 patients, the accuracy and feasibility of sentinel lymph node biopsy (SLNB) after NAC is well-established, with prospective evidence supporting its oncologic safety. SLNB is also acceptable in select cN+ patients when certain criteria are met. There is mounting “real-world” evidence for the technical feasibility of this approach, including various methods of localizing and excising biopsy-proven nodes, with the ability to avoid axillary lymph node dissection in a substantial proportion of patients. However, outcome data is limited to small retrospective series. In appropriately selected patients, there is increasing opportunity to leverage the benefits of NAC to minimize the burden of axillary surgery.

Background Recent reports have investigated the nascent role of induction chemotherapy for sinonasal undifferentiated carcinoma (SNUC). The goal of this study was to ascertain trends in treatment pattern changes for SNUC at a single institution and design a treatment algorithm utilized at our institution. Methods Retrospective chart analysis of 21 cases of SNUC from 2010 to 2018. Results Of 21 patients in this cohort, 18 (85.7%) presented with T4 disease, 7 (33.3%) presented with nodal disease, and 3 (14.3%) presented with distant metastasis. Since 2016, patients have been managed by induction chemotherapy followed by concurrent chemoradiation. To this point, patients treated with TPF induction chemotherapy followed by concurrent chemoradiation show no evidence of disease; however, the average follow up time is 16.8 months. Conclusions The multimodality treatment for SNUC continues to evolve, as highlighted by this study, toward increased use of induction chemotherapy followed by chemoradiotherapy.

The European Society of Gynaecologic Oncology (ESGO) guidelines cover the whole field of common clinical situations in gynecologic oncology. Their elaboration follows a strict process including a systematic review of the literature, the setting up of a group of expert on the basis of scientific production, geographical balance, and multidisciplinarity, and an external review by users and patients. The recommendations for the management of vulvar cancer were elaborated in 2015 and published in 2017. They are available in open access on the ESGO website, and can be incorporated in clinical practice using the free ESGO guidelines smartphone application. This review is a selection of the sections addressing the diagnostic and strategical aspects of the management of lymph nodal disease in vulvar cancer. An additional review of the recent literature published since 2015 has been carried out. The management of nodal disease in vulvar cancer encompasses a diagnostic and a therapeutic component. Clinical and imaging assessment still play a major role, whilst the identification of the sentinel node is currently a mainstay of assessment of the nodal status in early vulvar cancer. The therapeutic component is based on the rational use of full lymph node dissection and (chemo)radiation.

Background: The detection of regional lymph node metastases (LNM), in particular significant LNM (≥N2), is important to guide treatment decisions in women with breast cancer. The purpose of this study was to determine whether a coronal pulse sequence as part of pre-operative breast MRI is useful to identify women without significant LNM. Material: Retrospective study between January 2017 and December 2019 on 414 consecutive women with breast cancer who underwent pre-operative breast MRI on a 1.5 T system. For lymph node (LN) staging, a coronal pre-contrast non-fat-suppressed T1-weighted TSE sequence was acquired with the system’s built-in body coil, covering the chest wall; acquisition time 3:12 min. Two radiologists rated the likelihood of LNM on a 3-point scale (absent/possible/present). Validation was obtained by histology from sentinel LN biopsy, axillary LN dissection, and/or PET/CT. Results: 368/414 women were staged to have no or non-significant LNM (pN0 in 282/414, pN1 in 86/414), and significant LNM (≥pN2) in 46/414. For identification of women with significant LNM, MRI was true-positive in 42/46, false-negative in 4/46, true-negative in 327/368, and false-positive in 41/83, the latter mostly caused by women with N1-disease (38/41), yielding an NPV and PPV for significant LNM of 98.8% [95%-CI: 97.0–100%] and 50.6% [43.1–58.1%], respectively. Conclusions: A 3 min coronal T1-weighted pulse sequence covering the chest wall as part of pre-operative breast MRI is useful to rule out significant LNM with high NPV. Where MRI staging is positive for significant LNM, additional work-up is indicated to improve the distinction of N1 and N2 disease.

OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2–4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY BACKGROUND DATA: There is minimal literature to substantiate the National Comprehensive Cancer Network (NCCN) guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2–4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004–2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: 403 patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2–4aN0M0 esophageal adenocarcinoma.

Background Definite concurrent chemoradiation is the standard of care for locally advanced unresectable oesophageal cancers. However, heterogeneity exists in the practice of concurrent chemoradiation approaches. Here we describe the efficacy and toxicities of the standard arm of SCOPE1 protocol implemented at our institute. Methods Treatment records of 36 patients with unresectable oesophageal cancers treated with concurrent chemoradiation between January 2015 and June 2019 were audited. Treatment was based on the standard arm of SCOPE1 protocol (neoadjuvant and concurrent platinum and capecitabine with external beam radiation to a dose of 50 Gy/25 fractions/5 weeks). The electronic hospital information system and oncology information system were queried to obtain information on patient characteristics and treatment delivery patterns. Results Out of 36 patients, 35 had squamous cell carcinomas. 25% of the patients (9/36) were 70 years or older. 66.7% of patients (24/36) had T4 disease, and 16 (44.4%) had N2-N3 nodal disease at presentation. A total of 30 patients (83.3%) could not undergo surgery because of the location and locoregional extent of the disease. The median follow-up of the entire cohort and the surviving patients was 10 months (range 3-51 months) and 13 months (range 4-51 months), respectively. The median overall survival (OS) of the entire cohort was 28 months. The 2-year local progression-free survival and OS were 71.2% (95% CI: 48.5%-85.3%) and 57.4% (95%CI: 29.6%-77.6%), respectively. Commonly observed acute Grade 3 toxicities were dysphagia (22.2%) and thrombocytopenia (19.4%). Conclusion The outcomes of the SCOPE1 protocol have been validated for the first time in a different geographical, racial and ethnic population. Implementation of the standard arm of SCOPE1 protocol is feasible in our setting with acceptable adverse effects and good treatment compliance. Results are comparable to the results of the published trial.

Background The role of molecular biomarkers in oropharyngeal squamous cell carcinoma (OPSCC) has recently been increasingly recognized. There is conflicting evidence in the literature with regards to the prognostic value of p53 and Bcl-xL. Objective The purpose of this study was to investigate the association between p53 and Bcl-xL expression profiles and survival outcomes in OPSCC. Methods Patients diagnosed with OPSCC and treated with curative intent between 1998 and 2009 were included in the study. Patient demographics, disease, treatment, and oncologic outcomes were collected prospectively. A tissue microarray (TMA) from patients' biopsies or surgical specimens was retrospectively constructed. The expression levels of p53, Bcl-xL, and p16 were digitally quantified and correlated to patient survival outcomes. Results One hundred and sixty-six patients were included (mean age 56.7 years; standard deviation (SD) ± 10.0; 78% male). High expression of Bcl-xL (p= 0.04) was significantly associated with nodal disease at presentation, and decreased overall survival (OS) (p= 0.04). Combined expression of low Bcl-xL and low p53 conferred a survival advantage in non-smokers (p= 0.04). Multivariate analysis supported smoking and p16 status as independent prognosticators for OS. Conclusions This study suggests that biomarker profiling using Bcl-xL and p53 levels may be of prognostic value in select patients with OPSCC.

Simple Summary The tumor, lymph node, and metastases classification of lung cancer describes how big the tumor is and what structures it invades; whether the lymph nodes are involved or not, and, if they are involved, where they are in the chest; and whether there are tumor implants in other organs distant from the lung. This classification of lung cancer was proposed in 1966 and it has undergone periodic revisions. The revisions for its 7th and 8th editions were based on a large amount of international data from patients treated with different therapeutic modalities. New data are being registered now to inform the forthcoming 9th edition. A potential innovation of this edition will be the combination of this classification with other prognostic factors, such as mutations of the genetic code of the cancer cells among others, to achieve a more personalized prognosis for individual patients. Abstract Since its conception by Pierre Denoix in the mid-20th century, the tumor, node, and metastasis (TNM) classification has undergone seven revisions. The North American database managed by Clifton Mountain was used to inform the 2nd to the 6th editions, and an international database collected by the International Association for the Study of Lung Cancer, promoted by Peter Goldstraw, was used to inform the 7th and the 8th editions. In these two latest editions, it was evident that the impact of tumor size was much greater than it was suggested in previous editions; that the amount of nodal disease had prognostic relevance; and that the number and location of the distant metastases had prognostic implications. However, the TNM classification is not the only prognostic factor. Data are being collected now to inform the 9th edition of the TNM classification, scheduled for publication in 2024. Patient-, environment-, and tumor-related factors, including biomarkers (genetic biomarkers, copy number alterations, and protein alterations) are being collected to combine them in prognostic groups to enhance the prognosis provided by the mere anatomic extent of the tumor, and to offer a more personalized prognosis to an individual patient. International collaboration is essential to build a large and detailed database to achieve these objectives.

Contains fulltext : 231723.pdf (Publisher’s version ) (Open Access) In head and neck cancer, the presence of nodal disease is a strong determinant of prognosis and treatment. Despite the use of modern multimodality diagnostic imaging, the prevalence of occult nodal metastases is relatively high. This is why in clinically node negative head and neck cancer the lymphatics are treated "electively" to eradicate subclinical tumor deposits. As a consequence, many true node negative patients undergo surgery or irradiation of the neck and suffer from the associated and unnecessary early and long-term morbidity. Safely tailoring head and neck cancer treatment to individual patients requires a more accurate pre-treatment assessment of nodal status. In this review, we discuss the potential of several innovative diagnostic approaches to guide customized management of the clinically negative neck in head and neck cancer patients.

Background and purpose CTV delineation guidelines for the para-aortic nodal region for patients with cervical cancer have been proposed (Keenan et al., 2018). The purpose of this study was to validate these guidelines with the use of CT datasets of cervical cancer patients with macroscopic PALN treated with definitive (chemo)radiation (CTRT) at our center. Materials and methods Planning CT datasets of 71 cervical cancer patients with gross PA nodal disease treated with EFRT were used. Two hundred and two PALN were identified based on size and morphology on diagnostic CECT, PET CT, or histologically proven PALN. LN regions were divided into upper, middle, and lower and based on their relation to the aorta and IVC. Macroscopic PALN were contoured, and the CTV for PALN irradiation was generated based on the proposed guidelines on ECLIPSE (Version 13.5). The centre of mass (COM N) was calculated for each gross PALN . The evaluation was done to review the presence of COM N in relation to the CTV PALN. Results The most common location of PALN was Left para-aortic (105 LN- 52%), Aortocaval (55 LN-27.2%), and Precaval (14 LN-6.9%). Lower PALN were the commonest (104 LN-51.5%). Ninety-three were middle PALN (46%), and 5 were upper PALN (2.5%). After excluding upper PALN, COM N for 11 PALN (5.5%) were outside the CTV while 20 were junctional. Conclusion Our study shows that more than 95% of PALN in this patient cohort were covered using the se guidelines with the addition of an extra 5mm margin laterally on the left .

OBJECTIVE Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p��=��0.416, log-rank test) and overall survival (p��=��0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

Background: The impact of magnetic resonance imaging–detected extramural vascular invasion (mrEMVI) in distant metastasis is well known but its correlation with prevalence of lymph node metastasis is less studied. The aim of this systematic review and meta-analysis was to assess the prevalence of nodal disease in mrEMVI–positive and negative cases in rectal cancer. Methods: Following guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic literature search in PubMed, Web of Science, Cochrane Library, and EMBase was carried out to identify relevant studies published up to May 2019. Results: Our literature search generated 10 studies (863 and 1212 mrEMVI–positive and negative patients, respectively). The two groups (mrEMVI–positive and negative) were significantly different in terms of nodal disease status (odds ratio [OR] 3.15; 95% confidence interval [CI] 2.12–4.67; p < 0.001). The prevalence of nodal disease was 75.90% vs 52.56% in the positive mrEMVI vs negative mrEMVI group, respectively ( p < 0.001). The prevalence of positive lymph node in positive mrEMVI patients treated with neoadjuvant/adjuvant chemoradiotherapy (nCRT/CRT) (OR 2.47; 95% CI 1.65–3.69; p < 0.001) was less compared with the patients who underwent surgery alone (OR 6.25; 95% CI 3.74–10.44; p < 0.001). Conclusion: The probability of positive lymph nodes in cases of positive mrEMVI is distinctly greater compared with negative cases in rectal cancer. Positive mrEMVI indicates risk of nodal disease prevalence increased by threefold in rectal cancer.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant. ispartof: Current Oncology Reports vol:23 issue:1 pages:1-12 ispartof: location:United States status: Published online

We evaluated the impact of postmastectomy radiotherapy (PMRT) or supraclavicular radiation therapy (SCV RT) in women with cT1-3N1 breast cancer (BC) who became node negative (ypN0) after neoadjuvant chemotherapy (NAC).We retrospectively reviewed 485 women treated with NAC for BC between 2005 and 2019. Radiation treatment fields were reviewed in detail. Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients who had residual nodal disease were defined as ypN+. Those who achieved complete response in the lymph nodes but not in the breast were defined as ypT+ypN0.After excluding patients with cT4 and cN0 disease at diagnosis, a total of 185 patients with cT1-3N1 BC were included. Patients were more likely to receive PMRT if they had ypN+ disease (P.001) and/or lymphovascular invasion (P = .03). Patients who underwent lumpectomy were more likely to receive SCV RT if they did not achieve pCR (P = .04) and/or if they had ypN+ disease (P = .01). The 5-year rates of locoregional recurrence (LRR) were 15% for all patients, 14% for patients who attained ypT+ypN0, and 5% for patients who achieved pCR. Of ypT+ypN0 patients (n = 98), 53 received PMRT or SCV RT and 45 did not. For these patients, there were no differences in LRR based on whether a patient did or did not receive PMRT or SCV RT (P = .23).Recommendations for or against PMRT or SCV RT after NAC vary based on final pathologic response. We await the results of ongoing randomized clinical trials to help guide clinical decision making in this context.

Axillary management after NET has not been well studied and the significance of residual axillary node disease after NET remains uncertain. We used the National Cancer Data Base to examine the prognostic significance of residual nodal disease after NET. From 2010–2016, 4,496 patients received NET for cT1–3N0–1M0 hormone receptor-positive, HER2-negative breast cancer. Among cN0 patients treated with NET, final node status was ypN0 in 65%, isolated tumor cells (ITCs) in 3%, ypN1mi in 6%, and ypN1 in 26%. In cN1 patients, nodal pathologic complete response was uncommon (10%), and residual nodal disease included ITCs in 1%, ypN1mi in 3%, and ypN1 in 86%. There were no differences in 5-year overall survival (OS) between patients with pathologic node-negative disease, ITCs, or micrometastases after NET. When compared to a matched cohort of upfront surgery patients, there were also no differences in 5-year OS between NET and upfront surgery patients for any residual nodal disease category. These findings suggest NET patient outcomes mirror those of upfront surgery patients and present an opportunity to consider de-escalation of axillary management strategies in NET patients.

Introduction Mean platelet volume (MPV) is an inflammatory marker suggesting the activation of platelets. Many studies observed an association between MPV and cancer spread and metastasis. Hence, we have conducted a retrospective study to find the role of MPV as a prognostic marker in locally advanced gastric cancer. Materials and methods The present study included a retrospective review of 149 patients with gastric cancer who had neoadjuvant chemotherapy followed by surgery. MPV was obtained and then statistically analyzed to find an association between tumor (T), node (N), and overall stage as per the American Joint Committee on Cancer (AJCC) staging system, using Statistical Package for the Social Sciences (SPSS) software (IBM Corp., Armonk, NY). Results In our study, we observed that MPV values were significantly high in N+ disease (OR 3.794 (95% CI 1.903 - 7.563); p-value 0.0001), higher T stage (OR for >T2 3.692 (95% CI 1.876 - 7.266); p-value 0.0001), and advanced stage (OR 7.708 (95% CI 3.258 - 18.237); p-value 0.0001) of gastric cancer. Conclusions MPV is an inflammatory marker that correlates with nodal disease and aids in the staging and prognostication of locally advanced gastric cancer. This inexpensive, convenient marker can aid in the risk stratification of locally advanced gastric cancer.

Clinical trials have shown that axillary lymph node dissection (ALND) can be avoided for many breast cancer patients with limited nodal involvement. However, whether its omission is safe for those with invasive lobular carcinoma (ILC) is still questioned. We sought to evaluate the impact of ALND on recurrence-free survival (RFS) by extent of nodal disease in patients with ILC. We performed a retrospective, cross-sectional analysis of ILC patients treated between 1990 and 2019 at our institution. Patients underwent either breast conservation surgery (BCS) or mastectomy. We used univariate and multivariate statistics in Stata 14.2 to evaluate associations between extent of axillary surgery and time to recurrence stratified by nodal burden. Of 520 cases, 387 (78.4%) were node negative, 74 (14.9%) had 1–2 positive nodes, and 59 (11.4%) had three or more positive nodes. Most patients (93.3%) had hormone receptor-positive disease, and 94.8% had low or intermediate-grade tumors. The rate of ALND significantly decreased over time (p

Primary melanomas >1 mm thickness are potentially curable by resection, but can recur metastatically. We assessed the prognostic value of T cell fraction (TCFr) and repertoire T cell clonality, measured by high-throughput-sequencing of the T cell receptor beta chain (TRB) in T2-T4 primary melanomas (n=199). TCFr accurately predicted progression-free survival (PFS) and was independent of thickness, ulceration, mitotic rate, or age. TCFr was second only to tumor thickness in its predictive value, using a gradient boosted model. For accurate PFS prediction, adding TCFr to tumor thickness was superior to adding any other histopathological variable. Furthermore, a TCFr >20% was protective regardless of tumor ulceration status, mitotic rate or presence of nodal disease. TCFr is a quantitative molecular assessment that predicts metastatic recurrence in primary melanoma patients whose disease has been resected surgically. This study suggests that a successful T cell-mediated antitumor response can be present in primary melanomas.

Previously important roles for adjuvant radiotherapy (RT) in melanoma patients included improved regional control after resection of high-risk nodal disease, to reduce local recurrence for desmoplastic, and other subtypes of melanoma with neurotropism, reducing in-brain relapse of brain metastases after surgery and other situations on a case-by-case basis. This review evaluates the integration of adjuvant RT into clinical practice at this time of rapidly evolving knowledge and improving outcomes from effective systemic therapy.

Some melanomas develop a striking avidity for lymphatic spread. In spite of multiple recurrences, patients can remain years without visceral metastasis. There is clearly a biologic reason for this lymphotrophic pattern of growth and dissemination, which we have yet to uncover. In-transit metastases have widely diverse clinical presentations and can be a stubborn disease to cure. As a result, a host of treatments exist that should be tailored to the individual patient.

To characterize patterns of neck lymph node (LN) metastases in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma, represented by p16 positivity (p16+OPSCC).Case series with chart review.Tertiary care center.Neck dissection (ND) specimens of nonirradiated p16+OPSCC patients were analyzed for frequencies of clinically evident and occult LNs by neck level. Local, regional, and distant recurrences were reviewed.Seventy p16+OPSCC patients underwent primary site transoral robotic surgery and 82 NDs of varying levels. Metastatic pathologic LNs were found at the following frequencies: 0% (0/28) in level I, 75.6% (62/82) in level II with 57.4% (35/61) in level IIA and 13.1% (8/61) in level IIB, 22.0% (18/82) in level III, 7.0% (5/71) in level IV, and 6.3% (1/16) in level V. The level V LN was clinically evident preoperatively. Five of 21 (23.8%) elective NDs contained occult LNs, all of which were in level II and without extranodal extension. Twenty-seven (38.6%) patients underwent adjuvant radiation; 19 (27.1%) patients underwent adjuvant chemoradiation. With a mean follow-up of 29 months, 3 patients had developed recurrences, with all but 1 patient still alive. All patients who recurred had refused at least a component of indicated adjuvant treatment.For p16+OPSCC, therapeutic NDs should encompass any levels bearing suspicious LNs and levels IIA-B, III, and IV, while elective NDs should be performed and encompass at least levels IIA-B and III. These selective ND plans, followed by indicated adjuvant treatment, are associated with a low nodal recurrence rate.

The aim of this study was to report on the influence of tumor lymphovascular invasion on overall survival and in patients with resected non-small cell lung cancer and identify prognostic factors for survival.This is a retrospective observational study of a consecutive series of patients who had surgical resection of non-small cell lung cancer in a single institution. The study covers a 3-year period. Overall survival was estimated by Kaplan-Meier method and multivariate Cox regression analysis was used to evaluate the relationship of lymphovascular invasion and other clinicopathologic variables. A multivariate regression was used to assess the relationship between tumor lymphovascular invasion and other clinical and pathologic characteristics.A total of 524 patients were identified and included in the study. Two hundred twenty-five patients (43%) had tumors with lymphovascular invasion. Patients with tumor lymphovascular invasion had a lower overall survival (P .0001). Tumor lymphovascular invasion was independently associated with visceral pleural involvement (P .0001). In a multivariable model, lymphovascular invasion (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.63-4.09; P .0001), parietal pleural invasion (HR, 45.4; 95% CI, 2.08-990; P = .015), advanced age (HR, 1.028; 95% CI, 1.009-1.048; P = .004), and N2 lymph node involvement (HR, 1.837; 95% CI, 1.257-2.690; P = .002) were independent prognostic factors for lower overall survival.Lymphovascular invasion is associated with a worse overall survival in patients with resected non-small cell lung cancer regardless of tumor stage. Parietal pleural involvement, N2 nodal disease, and advanced age independently predict poor overall survival.

Axillary ultrasound with fine needle aspiration (AXUSFNA) in early-stage breast cancer has required reappraisal. ACOSOG Z-0011 and after mapping of the axilla: radiotherapy or surgery have shown that women with limited nodal disease at sentinel lymph node biopsy got no survival advantage with completion axillary node dissection. We hypothesize that AXUSFNA may be sufficiently accurate for staging for some patients and sentinel lymph node biopsy need not be performed. We define the false negative rate (FNR) of AXUSFNA in different subsets of patients.This retrospective cohort study included node positive patients who also underwent AXUSFNA between 1/2006 and 12/2010 followed by axillary surgery. The FNR was calculated for the entire group and for subgroups determined by tumor, nodal, and ultrasound findings.Out of ∼700 AXUSFNA patients, 128 node positive patients were included in the study. The overall AXUSFNA FNR was 35.9% (95% confidence interval, 28.1%-44.6%). There was a significantly higher FNR with smaller tumors and presence of ductal carcinoma in situ on multivariate analysis. On ultrasound, benign-appearing nodes had a higher FNR than indeterminate nodes (78.9% vs. 60.9%, P=0.2) and significantly higher than suspicious nodes (78.9% vs. 2.9%, P0.0001).In our cohort, the FNR for AXUSFNA was comparable with the rate of residual disease in the control arms of Z-0011 (27.4%) and after mapping of the axilla: radiotherapy or surgery (33%). However, our analysis suggests that we may be able to identify more appropriate patients for AXUSFNA and halve the FNR. As primary tumor characteristics and genomics drive systemic therapeutic recommendations, there may be an ongoing role for AXUSFNA in axillary staging.

First of all, we would like to congratulate Dr. Verdial et al . for their recently published article entitled “A prediction model for nodal disease among patients with non-small cell lung cancer” (1). Dr. Verdial and co-workers have analyzed their experience in mediastinal nodal staging for non-small cell lung cancer (NSCLC), based on the recommendations of the current guidelines, in order to find out a better model to predict nodal disease and reduce the need of invasive staging procedures.

PURPOSE/OBJECTIVE(S) To determine the impact of daily shifts based on rigid registration to intraprostatic markers (IPMs) on coverage of boost doses delivered to gross nodal disease for prostate cancer. MATERIALS/METHODS Seventy-five cone-beam CTs (CBCTs) from 15 patients treated with definitive radiation for clinically node-positive prostate cancer underwent fiducial-based and pelvic bony-based registration to the initial planning scans. Gross tumor volumes of nodal boost targets were contoured directly on each CBCT registration. The nodal displacement (3-dimensional translation from the node centroid on planning CT to node centroid on registered CBCT) and dose coverage (minimum dose [Dmin], mean dose [Dmean], dose delivered to 95% of the GTV [D95]) were calculated for each registration on all nodal targets. All doses for each node were normalized to its prescription dose (dose covering 95% of a 3 mm PTV expansion). RESULTS Forty-one gross nodal targets were analyzed. Most boosted nodes (80.5%, 33/41) were treated with volumetric-arc radiation therapy (VMAT), while 19.5% (8/41) underwent stereotactic body radiation therapy (SBRT). Dmin, Dmean, and D95 were all significantly lower with fiducial-based registration compared to bony-based registration (P < 0.0001). Nodal displacement was significantly higher for fiducial-based registrations (P < 0.0001). The 3-dimensional translation between the fiducial-based and bony-based registrations (bony-to-fiducial vector) was the most significant predictor of nodal displacement (P < 0.0001). On fiducial-based registrations, a 3-5 mm gross nodal PTV margin is sufficient in most directions; however, superior and posterior margins of 8-9 mm are required as a result of asymmetric prostatic motion. CONCLUSION Large and anisotropic PTV margins are likely needed to adequately dose gross nodal targets when patient setup is based on rigid registration to IPMs. Alternative approaches such as adaptive replanning may be required to overcome these limitations.

To develop and internally validate a new simplified model 'prostascore' to help predict the outcomes of treatment-naive patients with advanced prostate cancer.Through the SEER*Stat program, the Surveillance, Epidemiology and End Results (SEER) database was queried for eligible records spanning the period from 2010 to 2013. The resulting group of patients was equally divided into two sets: training group (to guide model development) and validation group (to validate the model prediction). Multivariate analysis for the candidate prognostic factors (extent of extra-prostatic disease, prostate-specific antigen [PSA] level and grade) was conducted through a Cox proportional model. Prostascore was then calculated for each patient. Cancer-specific and overall survival analyses according to prostascore were conducted through Kaplan-Meier analysis/Log-rank testing.In total, 8727 patients with treatment-naive advanced prostate cancer and complete baseline data were identified in the period from 2010 to 2013. The following factors were associated with better cancer-specific survival in the training set (isolated regional nodal disease, lower PSA level and lower grade group; P 0.0001). After assignment of a prostascore for each patient, cancer-specific survival was compared according to the score. Pairwise comparisons between all different scores were conducted. For cancer-specific survival evaluation according to the prostascore model, P values for pairwise comparisons among different score points were significant (P 0.05) in the validation set.Prostascore is an easy and reliable tool for predicting the outcomes of patients with treatment-naive advanced prostate cancer. Further validation within the context of other treatment settings and population-based cohorts is recommended.

The National Comprehensive Cancer Network (NCCN) guidelines, in addition to other international societies, recommend surgery for American Joint Committee on Cancer clinical stage I small cell lung cancer (SCLC) after a careful radiographic evaluation excludes distant metastases and invasive mediastinal staging excludes nodal disease. However, the data to support these guidelines are limited and therefore it is suspected that these guidelines are not universally followed (1). Yang and colleagues recently published their analysis of data from the National Cancer Database (NCDB) comparing overall survival (OS) in patients with cT1-2N0M0 SCLC who underwent surgery with adjuvant chemotherapy with or without adjuvant radiation therapy to OS in those treated with only concurrent chemoradiation (2).

BACKGROUND Oropharyngeal squamous cell carcinoma (SCC) frequently presents with cervical metastasis. Roles of human papillomavirus (HPV) status, among other factors, on laterality are elusive. METHODS The National Cancer Database was reviewed for oropharyngeal SCC diagnosed from 2010-2014. Predictors of clinically evident contralateral or bilateral nodal disease were identified. RESULTS A total of 15 517 patients with oropharyngeal SCC met criteria. The majority was HPV-positive. Histologically poorly differentiated tumors were more frequent in the HPV-positive group (55.7% vs 37.6%; P < .001). By incidence, there was no statistical difference in contralateral or bilateral nodal disease between HPV-positive and HPV-negative patients (14.2% vs 14.5%, respectively; P = .769). On multivariable analysis, notable predictors of contralateral or bilateral nodal disease included HPV-positivity (odds ratio [OR] 1.26; 99% confidence interval [CI] 1.10-1.44), base of tongue (BOT) location (OR 2.15; 99% CI 1.88-2.45), poorly differentiated tumor (OR 1.72; 99% CI 1.20-2.46), and T4 classification (OR 6.65; 99% CI 5.34-8.28). CONCLUSION Patients with HPV-associated oropharyngeal SCC have increased likelihood of contralateral or bilateral nodal disease. Tumor grade, tumor location, and tumor size are also independent predictors.

Background There is a paucity of data regarding head and neck squamous cell carcinomas (HNSCCs) and N3 nodal disease. Methods Retrospective analysis of patients with N3 HNSCC identified in the National Cancer Database (NCDB) was performed. Results We identified 4867 patients with N3 HNSCC treated with primary surgery or chemoradiotherapy (CRT). Propensity-adjusted median survival was 54.2 and 44.8 months for surgery and CRT, respectively (P = .06). Oropharyngeal primary subsite demonstrated a survival advantage with surgery versus CRT with propensity-adjusted median survivals of 86.0 and 61.9 months, respectively (P < .05). Conclusion Management of N3 HNSCC relies largely on CRT. Patients with N3 nodal disease with nonoropharyngeal primary tumors exhibit 5-year overall survival approaching 30% independent of initial treatment modality. Patients with oropharyngeal primaries exhibit improved outcomes with surgery largely influenced by the human papillomavirus (HPV)-negative subset. These data represent the most comprehensive analysis of N3 HNSCC outcomes and serves as a foundation for future research and clinical management.

Background Squamous cell carcinomas (SCCs) of the external ear have a significant rate of metastasis. The purpose of this study was to present analyzed factors associated with auricular SCC metastasis in order to identify a group that may benefit from sentinel lymph node biopsy (SLNB). Methods We performed a retrospective review of all operable SCCs between 2009 and 2014. The association between high-risk features and metastasis were analyzed. Results One hundred eighty-nine auricular SCCs were excised. Local recurrence was noted in 11% and 9.5% developed metastases. Cartilage, perineural, and lymphovascular invasion were significantly associated with metastasis, as were increased tumor depth and diameter (P < .001). All patients with metastasis developed nodal disease. Conclusion Factors, including poor differentiation, perineural, cartilage, and lymphovascular invasion, are associated with auricular SCC metastasis. Patients with 2 or more high-risk features may benefit from SLNB in order to identify and treat early nodal disease and possibly reduce the risk of further spread.

Background Lip cancer is one of the most curable primary head and neck malignancies, as the prominent location typically lends to an early diagnosis. The incidence of lip cancer varies by sex, ethnicity, and region, but is estimated to be up to 2.5/100 000 in the United States (squamous cell carcinoma [SCC]). Methods This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of lip cancer. Results Resection of lip cancer with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy. Conclusion Lip cancer remains highly curable when diagnosed at an early stage. A multidisciplinary approach is crucial to treating patients with advanced-stage lip cancer.

In the UK, more than 3,200 new cases of cervical cancer are diagnosed each year. Early stage cervical cancer (IA2-IB1) treatment comprises central surgery mainly in the form of radical hysterectomy or fertility sparing surgery including trachelectomy as well as systematic pelvic lymphadenectomy to detect metastases and adjust treatment accordingly. Given the variation in determining the lymph node (LN) status, a major prognosticator, we reviewed the current UK practice of LN assessment in women undergoing surgery for early cervical cancer. A 7-question, web-based survey, screened by the BGCS committee, was circulated amongst BGCS members. The overall response rate was 51%. Only 12.5% of the respondents routinely performed frozen section examination (FSE); the main reasons for not doing FSE were the pressure on theatre time (54.5%) and the lack of available facilities (48.5%). When positive pelvic nodal disease was detected, in 21 out of 50 (42%) the planned radical hysterectomy (RH) was aborted. More than 70% of the respondents routinely performed RH without any prior resort to pelvic lymphadenectomy. Pretreatment surgical para-aortic LN assessment was performed by 20% of the respondents. The survey confirms the diversity of the UK practice patterns in the surgical treatment of early cervical cancer.

OBJECTIVES: To assess the relationship between nodal disease burden and overall survival (OS) among patients with lymph node (LN) metastases from renal cell carcinoma (RCC) METHODS: The National Cancer Data Base was used to identify 2,975 patients with RCC who were treated with radical nephrectomy and were found to have regional LN metastases. Associations between the number of positive and negative LN removed and overall survival (OS) were assessed using Cox proportional hazards regression. The median follow-up time among survivors was 3.6 years. RESULTS: The median number of positive LN was one (interquartile range 1, 3). A higher number of positive LN was associated with higher all-cause mortality on multivariable analysis (HR 1.06 per one positive LN, 95% CI 1.04, 1.07, p