Extent Of Node Involvement Research Articles

Actual Five-year Survival After Upfront Resection for Pancreatic Ductal Adenocarcinoma: Who Beats the Odds?

To determine actual five-year survival (5YS) rates associated with a strategy of upfront surgery and adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC). The rate of actual 5YS in PDAC remains controversial. Available data is restricted to cohorts acquired over several decades and series of resection after patient selection by neoadjuvant therapy. All patients undergoing upfront resection for resectable and borderline-resectable PDAC from 10/2001 to 12/2011 were identified from a prospective database. Actual overall survival was assessed after a follow-up of at least 5 years. Uni- and multivariable logistic regression analyses were performed. Median survival of 937 patients was 22.1 months. The actual 5YS rate was 17.0% (n = 159) including 89 (9.5%) patients without evidence of disease >5 years after resection. 5YS rates in patients with or without adjuvanttherapy were 18.8% vs. 12.2%, respectively. Tumorgrading, number of positive lymph nodes, a context of intraductal papillary mucinous neoplasia, and vascular resections were independently associated with 5YS. Patient-related parameters and CA 19-9 levels were associated with observed survival up to 3 years, but lost relevance thereafter. The extent of lymph node involvement was the strongest predictor of 5YS. Patients with pN0R0 had a 5YS rate of 38.2%. in patients with exclusively favorable factors the observed 5YS rate was above 50%. This is the largest series of long-term survivors with histologically confirmed PDAC. With upfront resection and adjuvant therapy an actual overall 5YS rate of 18.8% can be expected. in favorable subgroups actual 5YS is above 50%.

A phase III, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC).

TPS10084 Background: CSCC is the second most common skin cancer. While the surgical cure rate for CSCC is > 95%, a proportion of pts are considered to have high risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti‒PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Methods: This randomized, placebo-controlled, double-blind, multicenter, Phase 3 study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT (NCT03969004). Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion, and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomized 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. This study is currently open for enrollment. Clinical trial information: NCT03969004.

Ordinal logistic regression model describing factors associated with extent of nodal involvement in oral cancer patients and its prospective validation

BackgroundOral cancer is the most common cancer among Indian men, and has strong tendency of metastatic spread to neck lymph node which strongly influences prognosis especially 5 year survival-rate and also guides the related managements more effectively. Therefore, a reliable and accurate means of preoperative evaluation of extent of nodal involvement becomes crucial. However, earlier researchers have preferred to address mainly its dichotomous form (involved/not-involved) instead of ordinal form while dealing with epidemiology of nodal involvement. As a matter of fact, consideration of ordinal form appropriately may increase not only the efficiency of the developed model but also accuracy in the results and related implications. Hence, to develop a model describing factors associated with ordinal form of nodal involvement was major focus of this study.MethodsThe data for model building were taken from the Department of Surgical Oncology, Dr.BRA-IRCH, AIIMS, New Delhi, India. All the OSCC patients (duly operated including neck dissection) and confirmed histopathologically from 1995 to 2013 were included. Further, another data of 204 patients collected prospectively from 2014 to 2015 was considered for the validation of the developed model. To assess the factors associated with extent of nodal involvement, as a first attempt in the field of OSCC, stepwise multivariable regression procedure was used and results are presented as odds-ratio and corresponding 95% confidence interval (CI). For appropriate accounting of ordinal form, the ordinal models were assessed and compared. Also, performance of the developed model was validated on a prospectively collected another data.ResultsUnder multivariable proportional odds model, pain at the time of presentation, sub mucous fibrosis, palpable neck node, oral site and degree of differentiation were found to be significantly associated factors with extent of nodal involvement. In addition, tumor size also emerged to be significant under partial-proportional odds model.ConclusionsThe analytical results under the present study reveal that in case of ordinal form of the outcome, appropriate ordinal regression may be a preferred choice. Present data suggest that, pain, sub mucous fibrosis, palpable neck node, oral site, degree of differentiation and tumor size are the most probable associated factors with extent of nodal involvement.

Definitive chemoradiotherapy in patients with squamous cell cancers of the head and neck - results from an unselected cohort of the clinical cooperation group \u201cPersonalized Radiotherapy in Head and Neck Cancer\u201d

BackgroundDefinitive chemoradiotherapy (dCRT) is a standard treatment for patients with locally advanced head and neck cancer. There is a clinical need for a stratification of this prognostically heterogeneous group of tumors in order to optimize treatment of individual patients. We retrospectively reviewed all patients with head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, or larynx, treated with dCRT from 09/2008 until 03/2016 at the Department of Radiation Oncology, LMU Munich. Here we report the clinical results of the cohort which represent the basis for biomarker discovery and molecular genetic research within the framework of a clinical cooperation group.MethodsPatient data were collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors.ResultsWe identified 184 patients with a median follow-up of 65 months and a median age of 64 years. Patients received dCRT with a median dose of 70 Gy and simultaneous chemotherapy in 90.2% of cases, mostly mitomycin C / 5-FU in concordance with the ARO 95–06 trial. The actuarial 3-year overall survival (OS), local, locoregional and distant failure rates were 42.7, 29.8, 34.0 and 23.4%, respectively. Human papillomavirus-associated oropharynx cancer (HPVOPC) and smaller gross tumor volume were associated with significantly improved locoregional tumor control rate, disease-free survival (DFS) and OS in multivariate analysis. Additionally, lower hemoglobin levels were significantly associated with impaired DFS und OS in univariate analysis. The extent of lymph node involvement was associated with distant failure, DFS and OS. Moreover, 92 patients (50%) of our cohort have been treated in concordance with the ARO 95–06 study, corroborating the results of this study.ConclusionOur cohort is a large unselected monocentric cohort of HNSCC patients treated with dCRT. Tumor control rates and survival rates compare favorably with the results of previously published reports. The clinical data, together with the available tumor samples from biopsies, will allow translational research based on molecular genetic analyses.

Predictors of disease free survival in node negative ampullary adenocarcinoma

Background: Pancreatico-duodenectomy is the only curative treatment option for patients with resectable ampullary adenocarcinoma (AA). Excellent disease free survival (DFS) can be achieved in patients with clear resection margins and no lymph node involvement. The potential role of adjuvant chemotherapy in this patient cohort is not fully understood. The aim of this study was to assess predictors of DFS in patients with node negative AA. Material & Methods: Consecutive patients undergoing pancreatico-duodenectomy for AA at our institution from 1996-2017 were included. Following institutional approval, demographic, surgical and histopathological data were analysed retrospectively. Independent pathological review confirmed diagnosis of AA. Patients were divided into lymph node positive and lymph node negative groups. Lymph node involvement was assessed by lymph node ratio (LNR). Using visual binning a threshold of 0.25 was selected for categorisation. Cox proportional hazard modelling was used to identify independent predictors of DFS. Factors with p<0.1 on univariate analysis were included in multivariate analysis. Results: 39 out of 108 included patients did not have nodal involvement (N0) (Table 1). Average DFS in the N0 group was 122±20 vs. 33±5 months in the N1 group (p<0.0001). Tumour stage T1/T2 (Hazard ratio[HR] 0.14, p=0.003) and lymph node count>12 (HR 3.94, p=0.047) were statistically significantly associated with improved DFS in the N0 group. In the N1 group, male gender (HR 0.4, p=0.003), absence of post-operative complications (HR 0.48, p=0.023), posterior margin R0 status (HR 0.45, p=0.046) and extent of nodal involvement<0.25 (HR 0.53, p=0.03) were associated with improved DFS. Conclusion: The majority of patients with lymph node negative AA has excellent long-term DFS. Advanced tumour stage and specimen lymph node number<12 were found to be independent predictors of DFS. In lymph node negative AA these predictors may allow identification of a patient subgroup that could benefit from adjuvant chemotherapy.Tabled 1

The Possibilities of Diffusion-Weighted Magnetic Resonance Imaging in Determining the Burden of a Tumor in Patients with Follicular Lymphoma

BACKGROUND: Follicular lymphoma (FL) is a B-cell tumor, which in most patients is characterized by slow growth and an "indolent" clinical course. In 80% of patients bone marrow is affected, which is a reflection of the pathogenesis of the tumor. The "watch and wait" tactic is a frequently used variant of patient management. For effective therapy, it is necessary to establish the stage of the disease, which requires the examination of the bone marrow (bilateral trepanobiopsy) and the identification of nodal and extranodal lesions (using PET/CT or CT of the whole body). The use of these methods is associated with high radiation exposure and the risk of complications in the intravenous radiopharmaceuticals and contrast agents. Whole body diffusion-weighted magnetic resonance imaging (WB-DWI) makes it possible to detect the burden of the tumor process without the use of contrast agents. AIM: Assess the capabilities of the WB-DWI method for determining the prevalence of a tumor and the detection of BM lesions in patients with FL. PATIENTS AND METHODS: The study was conducted during the fourth quarter of 2018 in the National Research Center for Hematology (Moscow), covered 8 patients (3 men and 5 women, with an average age of 53 years). According to the developed design of the study at the time of diagnosis of PL, all patients underwent a WB-MRI study, and then performed (with masking of participants): PET/CT, a histological examination of the bone marrow and the determination of B-cell clonality in bone marrow punctate (using PCR method). The results of the last two examinations were taken as reference (true) estimates for the detection of bone marrow lesions, and compared with the results obtained using the WB-MRI and PET/CT methods. Cohen's kappa statistical coefficient was used to assess the agreement between comparing methods. RESULTS: All 8 patients had a generalized lesion of the lymph nodes and extranodal foci (stage 4 according to An-Arbor). It was found that the measured diffusion coefficient in the lesions of the BM was 0,5‒0,9 х 10-3 mm/s. Reference tests showed that in 7 out of 8 patients, BM was affected. PET/CT gave two false-negative results, WB-DWI - one false-negative results (Tables 1‒2). Estimates of the prevalence of lesions of the lymph nodes and extranodal foci by WB-DWI and PET/CT were consistent with the accuracy of the methods. Estimates of the extent of lymph node involvement and extranodal lesions using WB-DWI and PET/CT were coincided with the accuracy of the methods errors. CONCLUSION: The results (Table 3.) of this exploratory research show that the WB-DWI method reveals a bone marrow damage not worse than the PET/CT method: kappa coefficient for WB-DWI was 0.6 and for PET/CT ‒ 0,5, respectively (due to the small sample size, strict statistical significance was not reached). WB-DWI allows you to quickly and informatively determine the affected areas and the involvement of BM, and thereby establish the stage of the disease. The results suggest an opportunity (along with the PET/CT method) to use the WB-DWI method as well. Disclosures No relevant conflicts of interest to declare.

1372TiP - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)

BackgroundCSCC is the second most common skin cancer. While the surgical cure rate for CSCC is>95%, a proportion of pts are considered to have high-risk for recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Post-operative RT is recommended for pts with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur. This study evaluates the efficacy of cemiplimab, a human anti–PD-1 monoclonal antibody, as an adjuvant therapy for pts with CSCC with high-risk features, after surgery and RT. Trial designThis randomised, placebo-controlled, double-blind, multicentre, Phase III study will evaluate cemiplimab as an adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who have completed surgery and post-operative RT. Immunocompromised pts were excluded. The trial will enrol 412 pts from about 100 sites in North America, Europe, and Asia-Pacific regions. Pts with at least one of the following high-risk features are eligible: a) nodal disease with extracapsular extension b) in-transit metastases c) T4 lesion d) perineural invasion and e) recurrent CSCC with at least one other risk factor. In Part 1 (blinded), pts will be randomised 1:1 to receive 350mg cemiplimab or placebo intravenously every 3 weeks (Q3W) for up to 48 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence or pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 will be eligible to receive open-label 350mg Q3W cemiplimab for up to 96 weeks. Key objectives are to compare disease-free survival (primary) as well as overall survival, freedom from locoregional relapse, and distant relapse (secondary) of adjuvant cemiplimab vs placebo in pts with high-risk CSCC. Editorial acknowledgementMedical writing support and typesetting was provided by Bu Reinen of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the studyRegeneron Pharmaceuticals, Inc., and Sanofi. FundingRegeneron Pharmaceuticals, Inc., and Sanofi. DisclosureD. Rischin: Research grant / Funding (institution), Non-remunerated activity/ies: Regeneron Pharmaceuticals, Inc.; Research grant / Funding (institution), Non-remunerated activity/ies: GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck; Research grant / Funding (institution), Non-remunerated activity/ies: Bristol-Myers Squibb; Research grant / Funding (institution): Roche. M.G. Fury: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. I. Lowy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. E. Stankevich: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. S. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. H. Han: Full / Part-time employment: Regeneron Pharmaceuticals, Inc. S.V. Porceddu: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy: UpToDate; Advisory / Consultancy: Oral Oncology.

Oesophagectomy with en bloc resection of the thoracic duct: risk factors for post-operative chyle leak and current management

Background: Routine ligation of the thoracic duct during oesophagectomy has been reported to reduce the rate of chyle leak (CL) following oesophagectomy. This study aims to identify risk factors for developing a CL with this approach and review current management. Methods: All patients who underwent transthoracic oesophagectomy over a 3-year period were identified from a prospectively collected database and their medical records reviewed. Results: A total of 147 oesophagectomies were performed in the period January 2012–December 2014. Eighteen patients with anastomotic leak were excluded. Eleven (8.5%) of the remaining 129 patients developed a CL. Statistically significant predictive factors for CL were squamous cell carcinoma (6/16, 37.5% vs . 5/113, 4.4% in other tumour types, P=0.0005) and high total chest drain volumes on day 2 post operatively measured prior to commencing enteric feeding. Using a threshold of 600 mL on day 2, the sensitivity and specificity for predicting CL are 92% and 82% respectively. Low BMI (mean 24.1 with CL vs . 27.5 without CL) was also associated with a CL, but was not statistically significant. Neither the extent of lymphadenectomy nor the extent of lymph node involvement (N stage) were associated with CL. Six patients with a low volume CL ( Conclusions: This study demonstrates squamous cell carcinoma remains a significant risk factor for the development of post-oesophagectomy chylothorax despite the routine ligation of the thoracic duct. In the knowledge that with this approach the main thoracic duct is never the source of CL, patients with a chest drainage of 600 mL/24 h despite conservative management should undergo re-thoracotomy at an early stage.

Local radicality and survival outcome of pancreatic cancer surgery.

Pancreatic cancer remains a therapeutic challenge. Surgical resection in combination with systemic chemotherapy is the only option promising long‐term survival and potential cure. However, only about 20% of patients are diagnosed with tumors that are still in a resectable stage. Even after potentially curative resection and modern regimens for adjuvant chemotherapy, the majority of patients develop local and systemic recurrence resulting in median overall survival times of 28‐54 months. The predominance of systemic recurrence and its impact on survival may lead to the assumption that surgical radicality and local control play only minor roles in the treatment of pancreatic cancer. This review provides an overview of the recent literature on surgical radicality and survival outcome in pancreatic cancer. The current evidence on the extent of lymphadenectomy, the prognostic impact of the extent of lymph node involvement, and the impact of the resection margin status on postresection survival are reviewed. Data from recent studies performed in the context of modern surgery and adjuvant therapy provide good evidence of a considerable impact of local radicality on survival after pancreatic cancer surgery. Surgical techniques that have been developed to refine oncological resections and to increase local control as well as resectability are highlighted. These techniques include artery‐first approaches, level‐3 dissection with removal of the periarterial nerve plexus, the triangle operation, and extended resections. Local radicality and quality of surgical resection remain among the most important parameters that determine the chances for survival in patients with non‐metastatic pancreatic cancer.

Artificial neural network models to predict nodal status in clinically node-negative breast cancer

BackgroundSentinel lymph node biopsy (SLNB) is standard staging procedure for nodal status in breast cancer, but lacks therapeutic benefit for patients with benign sentinel nodes. For patients with positive sentinel nodes, individualized surgical strategies are applied depending on the extent of nodal involvement. Preoperative prediction of nodal status is thus important for individualizing axillary surgery avoiding unnecessary surgery. We aimed to predict nodal status in clinically node-negative breast cancer and identify candidates for SLNB omission by including patient-related and pathological characteristics into artificial neural network (ANN) models.MethodsPatients with primary breast cancer were consecutively included between January 1, 2009 and December 31, 2012 in a prospectively maintained pathology database. Clinical- and radiological data were extracted from patient’s files and only clinically node-negative patients constituted the final study cohort. ANN-based models for nodal prediction were constructed including 15 risk variables for nodal status. Area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow goodness-of-fit test (HL) were used to assess performance and calibration of three predictive ANN-based models for no lymph node metastasis (N0), metastases in 1–3 lymph nodes (N1) and metastases in ≥ 4 lymph nodes (N2). Linear regression models for nodal prediction were calculated for comparison.ResultsEight hundred patients (N0, n = 514; N1, n = 232; N2, n = 54) were included. Internally validated AUCs for N0 versus N+ was 0.740 (95% CI = 0.723–0.758); median HL was 9.869 (P = 0.274), for N1 versus N0, 0.705 (95% CI = 0.686–0.724; median HL: 7.421; P = 0.492) and for N2 versus N0 and N1, 0.747 (95% CI = 0.728–0.765; median HL: 9.220; P = 0.324). Tumor size and vascular invasion were top-ranked predictors of all three end-points, followed by estrogen receptor status and lobular cancer for prediction of N2. For each end-point, ANN models showed better discriminatory performance than multivariable logistic regression models. Accepting a false negative rate (FNR) of 10% for predicting N0 by the ANN model, SLNB could have been abstained in 27.25% of patients with clinically node-negative axilla.ConclusionsIn this retrospective study, ANN showed promising result as decision-supporting tools for estimating nodal disease. If prospectively validated, patients least likely to have nodal metastasis could be spared SLNB using predictive models.Trial registrationRegistered in the ISRCTN registry with study ID ISRCTN14341750.Date of registration 23/11/2018. Retrospectively registered.

Predictive factors for lymph node metastases in vulvar cancer. An analysis of the AGO-CaRE-1 multicenter study

BackgroundLymph node (LN) metastasis is the most important prognostic factor in primary vulvar cancer. Assessing risk factors for the incidence and extent of LN metastases may help to select the optimal treatment strategy for each individual patient. MethodsIn a subgroup analysis of the large multicenter AGO-CaRE-1 study we included all patients treated with radical groin dissection. Univariate and multivariate regression analyses were performed in order to detect factors associated with the prevalence and extent of nodal involvement. ResultsIn total, 1162 patients were analyzed. Univariate analyses detected age, ECOG as well as multiple tumor characteristics such as FIGO stage, grading, depth of invasion, tumor diameter, and (lymph)vascular space invasion to be related with the prevalence of LN metastases. Interestingly, only tumor stage, tumor diameter and depth of infiltration were found to be significantly associated with the number of LN metastases. In multivariate analysis, age (OR 1.03), lymphvascular space invasion (OR 4.97), tumor stage (OR 2.22) and depth of infiltration (OR 1.08) showed an association with the prevalence of LN metastases. Regarding the number of metastatic LNs, only tumor stage (OR 2.21) or, if excluded, tumor diameter (OR 1.02) were tested significant. ConclusionThis large analysis of the multicenter AGO-CaRE-1-study identified lymphvascular space invasion, tumor stage, and depth of infiltration as factors with the strongest association regarding the prevalence of LN metastasis. Interestingly, tumor stage or, if excluded, tumor diameter were the only factors associated with the prevalence as well as the extent of LN metastases.

Evaluating the Effect of Axillary Lymph Node Involvement and Dissection in the Development of Post-Mastectomy Lymphedema

Background: Lymphedema of the upper extremity is a serious consequence of breast cancer surgery. Postmastectomy lymphedema of the upper limb is usually related to many risk factors, like axillary surgery, radiotherapy, venous obstruction, obesity, and infection. In the current study, the objective was to identify the relationship between the extent of lymph node involvement and axillary dissection on the development of lymphedema. Patients and methods: One hundred and seventy patients managed by modified radical mastectomy with axillary dissection for mammary-invasive adenocarcinoma between January 2009 and December 2016 in Al-Fayhaa Teaching Hospital. The patients were divided into three groups according to the number of lymph nodes involvd, by pathology. The patients had been followed up for at least two years and assessed by standard lymphedema assessment, then categorized into three groups, according to the severity of lymphedema. Results: After the analysis of patient parameters, the highest age group was 36–45 years. More than 60% of the patients had 4–9 lymph nodes involved. Forty-one patients from the 170 developed lymphedema postoperatively. Forty patients had seroma and twenty-one patients had wound infection postoperatively. Conclusion: Post-mastectomy lymphedema is a sequelae of disease process related to the extent of lymph-node involvement and resection rather than operative fault. Key words: breast cancer, mastectomy, lymphedema.

CLASSIFICATION OF PULMONARY METASTASES: POTENTIAL APPLICATION IN CLINICAL PRACTICE

Background. There is currently no information on the results of randomized studies evaluating the surgical treatment outcomes in patients with pulmonary metastases. Therefore, there is a strong need for a staging system that can permit the stratification of patients with intrapulmonary metastasis. Aim: To analyze the overall survival of patients who underwent pulmonary metastasectomy using a new classification taking account the extent of pulmonary metastasis. Material and methods. The study included 568 lung cancer patients who underwent pulmonary metastasectomy. All patients were stratified according to a new classification taking into account the number of metastatic sites and the extent of lymph node involvement. The median age of the patients was 49 years (range: 18 to 81 years). Results. Histological study revealed no evidence of metastases in 72 patients. In patients having no lymph node involvement, better results were observed in patients with a solitary site of metastasis (M s ), with a median survival of 58 months. In patients with oligometastatic lesions (up to 5 sites) and limited metastatic sites (6–24 sites), the median survival was 36 and 26 months, respectively. In patients with multiple metastatic lesions (more than 25 sites), the median survival was 12 months. Among patients with lymph node metastases, the median survival was 32 months for patients with a solitary metastasis (M s ) and 27 months for patients with oligometastases (M o ). In patients with limited number of metastatic sites (6–24 sites), the median survival was 12 months. In patients with multiple metastases (M m ), the median survival was 6 months (p=0.00012). Conclusion. A new classification will help to stratify patients into identical subgroups. Its use should be considered as one of the selection criteria in future multicentre randomized trials.

The dosimetric effects of limited elective nodal irradiation in volumetric modulated arc therapy treatment planning for locally advanced non-small cell lung cancer.

Contemporary radiotherapy guidelines for locally advanced non-small cell lung carcinoma (LA-NSCLC) recommend omitting elective nodal irradiation, despite the fact that evidence supporting this came primarily from older reports assessing comprehensive nodal coverage using 3D conformal techniques. Herein, we evaluated the dosimetric implications of the addition of limited elective nodal irradiation (LENI) to standard involved field irradiation (IFI) using volumetric modulated arc therapy (VMAT) planning. Target volumes and organs-at-risk (OARs) were delineated on CT simulation images of 20 patients with LA-NSCLC. Two VMAT plans (IFI and LENI) were generated for each patient. Involved sites were treated to 60 Gy in 30 fractions for both IFI and LENI plans. Adjacent uninvolved nodal regions, considered high risk based on the primary tumor site and extent of nodal involvement, were treated to 51 Gy in 30 fractions in LENI plans using a simultaneous integrated boost approach. All planning objectives for PTVs and OARs were achieved for both IFI and LENI plans. LENI resulted in significantly higher esophagus Dmean (15.3 vs. 22.5 Gy, p < 0.01), spinal cord Dmax (34.9 vs. 42.4 Gy, p = 0.02) and lung Dmean (13.5 vs. 15.9 Gy, p = 0.02), V20 (23.0 vs. 27.9%, p = 0.03), and V5 (52.6 vs. 59.4%, p = 0.02). No differences were observed in heart parameters. On average, only 32.2% of the high-risk nodal volume received an incidental dose of 51 Gy when untargeted in IFI plans. The addition of LENI to VMAT plans for LA-NSCLC is feasible, with only modestly increased doses to OARs and marginal expected increase in associated toxicity.

Role of Plasma D-Dimer Levels in Breast Cancer Patients and Its Correlation with Clinical and Histopathological Stage.

Breast cancer, the most common female malignancy, represents a heterogeneous group of tumors, which presen both varied behaviors and response to therapy. This study was done with an attempt to evaluate the role of D-dimer in patients of carcinoma breast, in predicting lymph node metastasis in carcinoma patients and to look for relationship of these markers with histopathologic parameters. Clinical data was obtained from clinical examination of patients admitted in the Department of Surgery with history of breast lump and confirmed with fine needle aspiration cytology (FNAC). Clinical staging was done using TNM staging. D-dimer level was measured prior to commencement of treatment, i.e., modified radical mastectomy (MRM) or neoadjuvant chemotherapy and finally 6months after surgery or completion of 6cycles of chemotherapy. The characteristics of the study population Out of 60 study cases minimum age of the patient being 30years and maximum being 74years. Of all histopathologic variables examined, D-dimer levels directly correlated with extent of lymph node involvement and lymphovascular invasion, D-dimer levels correlated strongest with the number of positive lymph nodes, but not with tumor size, estrogen receptor status, and progesterone receptor status. This study clearly shows that plasma D-Dimer levels are elevated in carcinoma breast patients. Increased D-Dimer levels are an important marker of clinical stage, lymphovascular invasion, lymph node involvement, and tumor metastasis.

Can axillary radiotherapy replace axillary dissection for patients with positive sentinel nodes? A systematic review and meta-analysis

ObjectiveTo compare the efficacy of axillary radiotherapy (ART) with that of completion axillary lymph node dissection (cALND) in clinically node-negative breast cancer patients with a positive sentinel lymph node. MethodsA literature search was performed in PubMed, EMBASE and Cochrane Library by using the search terms “breast cancer”, “sentinel lymph node biopsy”, “axillary radiotherapy” or “regional node irradiation” for articles published between 2004 and 2016. Only randomized controlled trials that included patients with positive sentinel nodes were included in the meta-analysis. ResultsTwo randomized controlled trials and three retrospective studies were identified. The reported overall survival rate (hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 0.75–1.43, P = 0.365), disease-free survival rate (HR = 1.01, 95% CI: 0.58–1.45, P = 0.144), and axillary recurrence rate (1.2% and 0.4%, and 1.3% and 0.8%, respectively) were similar in both groups. The absence of knowledge on the extent of nodal involvement in the ART group appeared to have no major impact on the administration of adjuvant systemic therapy. ConclusionsART is not inferior to cALND in the patients with clinically node-negative breast cancer who had a positive sentinel lymph node. Information obtained by using cALND after SLNB may have no major impact on the administration of adjuvant systemic therapy.

SC01.02 PET-CT for Response Assessment During Induction Therapy of N2 NSCLC

Approximately 30% of patients with non-small cell lung cancer (NSCLC) are found to have locally advanced stage III tumors at initial diagnosis. For these patients the curative therapeutic options include definitive high-dose radiotherapy with concurrent chemotherapy or, alternatively, induction treatment followed by surgery. Preoperative chemotherapy or combined radiochemotherapy protocols followed by resection result in cure rates of 25-35 percent at 3 years for locally advanced NSCLC. However, surgical resection in patients with stage IIIa N2 remains an issue of controversy depending on the extent of lymph node involvement. Neoadjuvant chemo- or radiochemotherapy is being used to reduce disease burden in the mediastinum before surgery since patients who are downstaged via neoadjuvant therapy and then undergo resection experience a significantly longer 5-year survival of 40% to 50% than those who are found to have residual N2 disease at the time of surgery. Thus, identification of patients who are N2 negative after completion of their neoadjuvant therapy is a critical component for patient selection for thoracotomy. However, clinical restaging in these patients often is challenging. Endoscopic ultrasound guided biopsies (EUS/EBUS-FNA) have increasingly become available and are currently preferred procedures for staging and restaging before surgery due to their high diagnostic accuracy.1 Serial PET-CT imaging captures anatomical changes and additionally offers semiquantitative information about morphometric and metabolic tissue changes during induction treatment. Issues of PET-CT performance and quality assurance concerning standardization have been clarified during recent years and the validity of repeated measurements has been approved.2 Successful induction treatment regimens have been frequently found to reduce 18F-FDG uptake and thus PET-CT allows to assess the therapeutic response. Reduction in FDG-uptake of mediastinal lymph nodes after induction therapy has been shown to correlate well with histopathologic response,3 while postinduction PET avidity taken alone was not consistently found to be associated with pathological N2 involvement.4 In the direct comparison of EUS-FNA with PET-CT for restaging after induction chemoradiotherapy, concordance between findings of restaging EUS-FNA and metabolic response of lymph node metastases was observed in 63% patients treated within a prospective study but the diagnostic accuracy of PET-CT was limited.5 Nevertheless, serial FDG-uptake measurements seem to provide prognostic information during induction therapy. Data collected in prospective trials suggest that a decrease in SUVmax between 45% to 60% optimally separates between responders and non-responders.6-9 In a recent large retrospective analysis, a decrease in SUVmax greater than 60% in the involved mediastinal nodes was the best predictor of overall survival, better than changes seen in the primary tumor site.10 An analysis of a randomized trial in potentially resectable stage III NSCLC of induction treatment (including a hyperfractionated accelerated radiotherapy phase) and definitive radiochemotherapy compared with induction treatment followed by surgery confirmed that as early as after two cycles of cisplatin-based induction chemotherapy percentage of SUVmax remaining represents a significant prognostic parameter.9 PET-response was of higher importance than all other clinical factors. Cut-off levels between 0.45 and 0.55 were predictive for freedom from extracerebral progression in all randomized patients. No important differences in the predictive value were observed comparing resection versus definitive radiochemotherapy. PET-response was closely related to extracerebral distant metastases but not to local recurrences, independent of treatment. One might conclude that less PET-responsive tumors are successfully controlled by intensified hyperfractionated accelerated radiochemotherapy or neoadjuvant radiochemotherapy and resection at loco-regional sites so that the highest risk of relapse remains at extracerebral distant sites. Therefore, a selection or intensification of the local therapy according to SUV-decrease is not warranted by these data. Functional imaging has not yet been fully established for treatment guidance but prospective evaluation is underway. In the group of poor-responding patients, treatment intensification by independent systemic options such as targeted therapy or immunomodulating therapy may become emerging new treatment options within clinical trials. 1. De Leyn EJCTS 2014, 2. Young, EJC 1999, 3. Pöttgen CCR 2006, 4. Ripley JTCS 2016, 5. Stigt, Lung Cancer 2009, 6. Hoekstra, JCO 2005, 7. Eschmann, Lung Cancer 2007, 8. Dooms, JCO 2008, 9. Pöttgen, JCO 2016, 10. Barnett ATS 2016. PET-CT; N2; induction, restaging

Pancreatic cancer metastatic to a limited number of lymph nodes has no impact on outcome

BackgroundThe purpose of this study was to determine the association of the extent of metastatic lymph node involvement with survival in pancreatic cancer. MethodsThis is a retrospective review of a prospectively maintained database of patients who underwent resection for pancreatic adenocarcinoma, 1999–2011. Results165 patients were identified and divided into 3 groups based on the number of positive lymph nodes – 0 (group A), 1–2 (B), >3 (C). Each group had 55 patients. Those in group C were more likely to have a higher T stage, poorly differentiated grade, lymphovascular invasion (LVI), higher mean intraoperative blood loss, positive margins, tumor location involving the uncinate process, and a higher likelihood of undergoing a pancreaticoduodenectomy. Median overall survival (OS) for group A, B and C was 25.5 months (mo), 21 mo and 12.3 mo, respectively (p < 0.001). No survival difference was noted for survival between groups A and B (p = 0.86). The ratio of involved lymph nodes <0.2 was predictive of improved survival (p < 0.001). ConclusionsResected pancreatic cancer patients with only 1–2 positive lymph nodes or less than 20% involvement have a similar prognosis to patients without nodal disease. Current staging should consider stratification based on the extent of nodal involvement.

Lymph node metastases in the prognosis of gastroenteropancreatic neuroendocrine tumors.

224 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a diverse group of malignancies affecting over 65,000 patients in the United States. GEP-NETs are currently classified as lymph node positive (N1) or negative (N0). The prognostic utility of the extent of lymph node involvement remains unknown. In this study, we used a population-based registry to investigate the relationship between lymph node ratio (LNR) and survival in patients with GEP-NETs. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) data registry to identify patients with histologically confirmed, surgically resected NETs with lymph node involvement diagnosed between 1988 and 2011. Patients were divided into three groups based on the ratio of positive lymph nodes to total lymph nodes examined (LNR): ²0.20, &gt;0.2-0.5, and &gt;0.5. Kaplan-Meier, log-rank analysis, and Cox models were used to compare NET cancer-specific survival according to LNR category. Results: We identified 8,113 patients with GEP-NETs. Primary sites included small intestine (N=3,651), colon (N= 2,042), pancreas (N=1,070), appendix (N= 683), stomach (N=389), and rectum (N=278). Patients were 49% female, 76% white, and 12% black. Ten-year NET-specific survival rates were significantly different among patients in the three LNR groups and LN negative controls (p&lt;.0001). Survival was worse in patients with LNRs of &gt;0.2-0.5 (Hazard Ratio (HR) 1.338, p=.0002), and &gt;0.5 (HR 1.692, p&lt;.0001) compared to LN-negative controls. Higher LNR was correlated with worse survival. Conclusions: The degree of lymph node involvement is a prognostic factor across the most common primary sites of GEP-NETs. This information may be used clinically and in stratifying patients for clinical trials. Results across multiple sites may also be generalizable to GEP-NETs from rare primary locations that are difficult to study. [Table: see text]

Head and neck cancers: a clinico-pathological profile and management challenges in a resource-limited setting.

BackgroundHead and neck cancer (HNC) is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding head and neck cancers in Tanzania, and Bugando Medical Centre in particular. This study describes the clinicopathological profile of HNC in our local setting and highlights the challenges in the management of this disease.MethodsThis was a retrospective study of histopathologically confirmed cases of head and neck cancers treated at Bugando Medical Center between January 2009 and December 2013.ResultsA total of 346 patients (M:F = 2.1:1) were studied representing 9.5 % of all malignancies. The median age of patients was 42 years. Cigarette smoking (76.6 %) and heavy alcohol consumption (69.9 %) were the most frequently identified risk factors for head and neck cancer. The majority of patients (95.9 %) presented late with advanced stages. Twenty-five (7.2 %) patients were HIV positive with a median CD4+ count of 244 cells/μl. The oral cavity (37.3 %) was the most frequent anatomical site affected. The most common histopathological type was carcinomas (59.6 %) of which 75.7 % were squamous cell carcinoma. A total of 196 (56.6 %) patients underwent surgical procedures for HNC. Radiotherapy and chemotherapy was reported in 9.5 and 16.8 % of patients, respectively. Only 2 (0.6 %) patients received chemo-radiation therapy. The mortality rate was 24.4 %. The overall 5-year survival rate (5-YSR) was 20.6 %. The predictors of overall 5-YSR were age of patient at diagnosis, stage of disease, extent of lymph node involvement, HIV seropositivity and CD4+ count <200 cells/μl (P < 0.001). Local recurrence was reported in 22 (23.4 %) patients and this was significantly associated with positive resection margins, stage of the tumor and presence of metastasis at diagnosis and non-adherence to adjuvant therapy (P < 0.001).ConclusionHead and neck cancers are not uncommon at Bugando Medical Centre and show a trend towards a relative young age at diagnosis and the majority of patients present late with advanced stage cancer. Therefore, public enlightenment, early diagnosis, and effective cost-effective treatment and follow-up are urgently needed to improve outcomes of these patients in our environment.