Evidence Of Nodal Disease Research Articles

Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC.

Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma. Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.

Adjuvant Radiation Therapy Improves Local Control in the Treatment of Adnexal Carcinoma

Adnexal carcinoma (AC) is a rare subset of cutaneous malignancies derived from skin adnexa. There are limited data on the role of adjuvant radiation therapy (RT). This study investigates outcomes associated with adjuvant RT at our high-volume referral center. Using an institutional pathology database we identified 45 patients with locoregionally-confined AC treated between 2001-2020 with curative intent surgery and RT at initial diagnosis or at the time of locoregionally-confined recurrence. Clinicopathologic variables were described and time to relapse events were assessed by the Kaplan-Meier method. Median age was 64 yrs (IQR 57-71). Primary tumors were in the head and neck (H&N, n = 36, 80%), trunk/extremities (n = 8, 18%) or unknown (n = 1). The most common histologic subtypes were: sebaceous-14 (31%), microcystic adnexal carcinoma-9 (20%), eccrine-6 (13%), and trichilemmal-5 (11%). Twenty-two (50% of known primaries) had PNI. All patients had primary tumor excision. Six had clinically evident lymphadenopathy (13%), all of whom had lymph node dissection (LND). Five patients without evidence of nodal disease (13%) had sentinel lymph node biopsy (SLNB) with one having SLN+ disease. Thirty patients (67%) received adjuvant locoregional RT at initial diagnosis with the following targets: 21 (30%) primary only, 4 (13%) nodal only, and 5 (17%) both. Of those receiving nodal RT, 7 (78%) had LN+ LND with 2 of those receiving concurrent platinum-based chemoradiation. Sixteen were treated at recurrence with the following targets: 4 (25%) primary only (1 having had prior adjuvant nodal RT), 4 (25%) nodal only, and 8 (50%) both. Across the full cohort, median RT dose was 60 Gy in 30 fractions. Median follow-up from initial surgical resection was 60 months (IQR 30-160). 5-year LC, NC, DFS and DSS were 71%, 86%, 66%, and 91% respectively. The only evaluated factor associated with better outcome was adjuvant primary site RT (5-yr LC 83% vs. 56%, p = 0.01 and 5-yr DFS 83% vs. 46%, p = 0.0003). All 15 patients with local recurrence (LR) had salvage surgery with median subsequent follow-up of 75 months (IQR 2-94). Overall, 5 patients receiving adjuvant primary site RT at any time (initial or salvage) developed subsequent local recurrence (13%). Of the 8 patients who developed nodal recurrence (NR) during follow-up, 1 received adjuvant nodal RT at initial diagnosis. Six of 7 who did not receive prior RT then received adjuvant nodal RT after LND and only 1 developed subsequent NR. AC is a rare skin cancer with a primarily locoregional recurrence pattern. In our experience, adjuvant RT was associated with improved LC which, depending on the tumor location, may help prevent morbid or cosmetically-impactful salvage surgery. Patients with AC would benefit from radiation oncology referral to discuss adjuvant treatment.

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

ALK rearrangement is an independent predictive factor of unexpected nodal metastasis after surgery in early stage, clinical node negative lung adenocarcinoma

ObjectivesDespite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. Given the promising role of neoadjuvant targeted treatments, the definition of novel predictive factors of nodal metastases is an extremely important issue. In this study we aim to analyze the upstaging rate in patients with early stage NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Material and methodsPatients who underwent lobectomy and systematic lymphadenectomy for early stage LUAD without evidence of nodal disease at the preoperative staging using NGS analysis for actionable molecular targets evaluation after surgery were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. ResultsA total of 359 patients were included in the study. 172 patients were female, and the median age was 68 (61–72). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the ALK rearrangement, the number of resected lymph nodes and the diameter of the tumor. This result was confirmed in the multivariate analysis, with an OR of 8.052 (CI95% 3.123–20.763, p = 0.00001) for ALK rearrangement, 1.087 (CI95% 1.048–1.127, p = 0.00001) for the number of resected nodes and 1.817 (CI95% 1.214–2.719, p = 0.004) for cT status. ConclusionOur results showed that in a homogeneous cohort of patients with clinical node early stage LUAD the ALK rearrangement, the number of resected lymph nodes and the tumor diameter can significantly predict nodal metastasis.

Rate of occult neck nodal metastasis in primary and salvage laryngectomy.

Rate of occult neck nodal metastasis in primary and salvage laryngectomy.

Are staging bone scans necessary in patients with T3a prostate cancer? A multicentre study

Objective: Studies reporting increased risk of metastases in T3a disease are based on clinical staging (Digital rectal examination) in the pre-multiparametric–magnetic resonance imaging (MRI) (mp-MRI) era. The aim of our study was to assess the rate of positive bone scans in patients ascribed with T3a prostate cancer on a pre-biopsy mp-MRI. Methods: We performed a multicentre, retrospective analysis of all patients with T3a prostate cancer staged by mp-MRI who had a bone scan between January 2017 and April 2020. Results: A total of 586 patients were diagnosed with T3a prostate cancer on mp-MRI, with a median age of 71 years (range: 47–87). The median presenting PSA was 11 ng/mL (range: 1–537); 125 patients (21.3%) had a PSA ⩽ 20 and either grade group (GG) 1 or 2 in their prostate biopsy; none of these patients had bone metastases. Eighteen patients (3.1%) were found to have bone metastases: 11 patients had GG ⩾ 3 disease on biopsy and nodal disease, 6 had GG ⩾ 3 without evidence of nodal disease and 1 had a PSA of 103. Conclusion: The use of bone scans in patients with T3a prostate cancer staged on mp-MRI but without other evidence of high-risk disease (GG ⩾ 3 and PSA > 20 ng/mL) appears to be unnecessary and could be safely avoided. Level of evidence: 2b

Elective neck dissection versus observation in patients with head and neck cutaneous squamous cell carcinoma.

The survival benefit of elective neck dissection (END) for patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck and no evidence of regional metastasis (cN0) has never been reported. The aim of this study was to determine the effect of END on patient survival. The authors included patients with head and neck cSCC who had undergone primary surgery from 1995 to 2017. The primary end point was survival, and the secondary end points were the incidence of occult regional disease and regional disease control. To assess the impact of END on survival, the authors used multivariable Cox proportional hazards models with propensity score and matching techniques for internal validation. A total of 1111 patients presented with no evidence of nodal disease; 173 had END, and 938 were observed. Adjuvant radiotherapy to the neck was administered to 101 patients (9%). END resulted in a 5-year overall survival rate of 52%, whereas the rate was 63% in the observation group (P=.003 [log-rank]). The 5-year disease-free survival rate for patients undergoing END was similar to that for the observation group (73% vs 75%; P=.429). A multivariate regression model showed that the performance of END was not associated with improved rates of overall, disease-specific, or disease-free survival; similarly, among patients with advanced disease (T3-4), those who underwent END did not have improved survival rates. Among patients with cSCC of the head and neck, observation of the neck nodes resulted in noninferior survival rates in comparison with END at the time of primary surgery. Further studies are required to elucidate the role of END in patients with advanced disease.

Clinicopathologic characteristics of laryngeal chondrosarcoma: An analysis of the National Cancer Database

ObjectivesLaryngeal Chondrosarcoma (LC) is a rare malignancy with limited studies documenting its clinicopathologic characteristics and treatment options. This study reports demographic and clinical determinants of outcomes for this rare tumor. MethodsThe National Cancer Database (NCDB) was queried for cases of LC reported from 2004–2016. 274 cases that met inclusion criteria were analyzed for demographic and clinicopathologic characteristics. Kaplan-Meier (KM) and Cox proportional hazard analyses were conducted to identify variables that impacted the overall survival of these patients. ResultsLC was found to be more common in males (74.8%). The mean age of patients was 61.8 years and 92.3% of the patients were white. 91.3% of patients were treated with only surgical resection, most commonly: partial laryngectomy (31.6%), total laryngectomy (25.7%), and local resection (22.4%). 98.8% of patients had no evidence of nodal disease and 99.6% of patients did not have distant metastasis at presentation. KM analysis revealed a 5-year overall survival (5YOS) of 89.0%. Age, insurance status, facility type, and surgery type were significant predictors of 5YOS (p<0.05). On Cox Proportional Hazard analysis, private insurance significantly improved survival (HR 0.21; p = 0.048) while increasing age was a poor prognostic indicator (HR 1.10; p = 0.004). ConclusionThe majority of LC patients present with no nodal involvement or distant metastasis at diagnosis, and overall this tumor has a favorable prognosis. Increasing age was found to be a poor prognostic factor while private insurance status was associated with improved survival.

Regional Recurrences and Hyams Grade in Esthesioneuroblastoma.

Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% ( p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% ( p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [ p = 0.04], 49 vs. 91% [ p = 0.04], 44 vs. 92% [ p = 0.02], and 44 vs. 80% [ p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

Metastatic screening for patients with newly diagnosed breast cancer: Who and how?

Background: Staging for breast cancer patients, as defined by the American Joint Committee on Cancer (AJCC), has historically been limited to anatomical staging. However, the eighth version of the AJCC guidelines has been altered to include tumour biology. Anatomical staging still has a place especially in low-middle income countries where the majority of patients present with locally advanced or metastatic disease. Aim: This review article considers which newly diagnosed breast cancer patients should be referred for anatomical staging and the pros and cons of the different modalities available in South Africa. Method: The different modalities available were reviewed with respect to metastatic screening for asymptomatic women. The usefulness of the modalities were considered with reference to organ-specific disease rather than the stage of the patient. Results: Any person with newly diagnosed breast cancer and symptoms suggestive of systemic involvement should be investigated. All symptomatic women who present with a tumour larger than 5 cm, radiological or clinical evidence of nodal disease, triple negative or HER2+ve tumours should have metastatic screening. This gives information about the primary as well as the metastatic status. Conclusion: However, increasingly, the major determinant of treatment is the biology of the cancer and not the anatomical stage. In future, this trend is likely to increase with anatomical staging becoming less important.

Perioperative chemotherapy for upper tract urothelial carcinoma: A microsimulation Markov model.

508 Background: Upper tract urothelial carcinoma (UTUC) accounts for less than 5% of all urothelial cancers. As a result, this disease is clinically understudied and there are no definitive recommendations regarding use and timing of peri-operative chemotherapy. The objective of this study was to create a decision model comparing three treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC). Methods: A Markov microsimulation model was constructed using TreeAge Pro to compare treatment strategies for patients with newly diagnosed UTUC. Our primary outcome was quality adjusted life expectancy (QALE). Secondary outcomes included rates of adverse chemotherapy events, bladder cancer diagnoses, and crude survival. Markov cycle length was 3 months to mimic the follow up interval used in clinical practice for patients with UTUC. A systematic literature review was used to generate probabilities to populate the model. The base case was a 70-year-old patient with a radiographically localized upper tract tumor. Patients could have evidence of nodal disease, but no distant metastasis. Results: A total of 100,000 microsimulations were generated. NAC was preferred with an estimated QALE of 7.52 years versus 6.80 years with NU alone and 7.20 years with AC. Overall, 39.6% of patients in the AC group with invasive pathology received and were able to complete chemotherapy. A total of 37.5% of patients in the NAC group experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 66.0%, and 67.1% over the patient’s lifetime in the NU, NAC, and AC groups, respectively. Conclusions: This study provides evidence to support the increased use of NAC in UTUC until robust randomized trials can be completed. While the use of NAC in this population appears favourable, the ultimate choice rests with the clinician and should be based on patient and tumor factors.

Occult Nodal Disease and Occult Extranodal Extension in Patients With Oropharyngeal Squamous Cell Carcinoma Undergoing Primary Transoral Robotic Surgery With Neck Dissection

The historically reported rates of subclinical cervical nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) predate the emergence of human papillomavirus as the predominant causative agent. The rate of occult nodal disease with changing etiology of OPSCC is not known, and it is challenging to anticipate which patients will be upstaged postoperatively and will require adjuvant therapy. To assess the rate of nodal upstaging and occult extranodal extension (ENE) in a multi-institutional population of patients with pathologic (p)T1-2 OPSCC treated by transoral robotic surgery and neck dissection. This retrospective, multicenter cohort study of 92 participants at 2 US institutions (Albert Einstein College of Medicine, Bronx, New York [n = 38], and Icahn School of Medicine at Mount Sinai, New York, New York [n = 39]) and 1 Canadian institution (Princess Margaret Hospital, Toronto [n = 15]) examined the rate of postoperative pathologic upstaging for 92 patients with pT1-2 OPSCC undergoing transoral robotic surgery with neck dissection from August 2007 to December 2016. A neuroradiologist at each site blinded to final pathologic diagnosis reviewed preoperative imaging; these findings were compared with operative pathology and applied for tumor staging using the eighth edition of the American Joint Committee on Cancer Cancer Staging Manual. The statistical analysis was performed on December 18, 2018. Occult pathologic nodal disease and change in nodal category postoperatively. Of 92 patients who met the inclusion criteria, 76 (83%) were male, and they had a mean (SD) age at surgery of 59.5 (10.5) years; 70 patients (84%) with available p16 status were positive. Five of 18 patients (28%) who had no evidence of nodal disease on imaging had occult pathologic nodal disease. Seven of 32 patients (22%) presenting with no nodal disease or with a single metastatic node on imaging received pathologic upstaging because of multiple positive nodes, indicating implementation of additional adjuvant treatment not anticipated after a priori imaging. Changes included 12 patients (13%) who had pathologic nodal upstaging and 12 (13%) with pathologic nodal downstaging in the eighth edition of staging. In the cohort, 24 patients (27%) had pathologic ENE, and 5 of 39 patients (13%) had occult ENE in the absence of radiographic evidence. Predicting pathologic staging preoperatively for patients with OPSCC undergoing transoral robotic surgery and neck dissection remains a challenge. Although nodal size, tumor size, and location do not help predict ENE, the presence of nodes on imaging and nodal category may help predict ENE. Our findings suggest a small proportion of patients might benefit from further adjuvant therapies not predicted by preoperative imaging based on occult nodal upstaging and ENE.

PS02.117: OUTCOMES FOR SQUAMOUS CELL CARCINOMA OF THE OESOPHAGUS IN A WESTERN POPULATION

Abstract Background Squamous cell carcinoma of the oesophagus comprises approximately 30% of oesophageal malignancies in the ‘west’. Different approaches in management have been advocated. In the UK patients may receive conventional neoadjuvant chemotherapy (OEO2) or neoadjuvant chemoradiotherapy (CROSS). The aim of this study was to evaluate outcomes of patients receiving potentially curative surgical treatment for squamous cell carcinoma of the oesophagus. Methods A retrospective review of patients who underwent treatment with curative intent for oesophageal squamous cell carcinoma between 2006 to 2016 at a single institution was performed. Patients underwent a standardised staging protocol and were assigned to the treatment modality based on the stage of the disease by a multi-disciplinary team. Outcomes were evaluated according to the treatment received. Results Overall 199 patients underwent curative treatment in the 10 year period. This comprised 26% of the oesophagectomies for carcinoma. Of these, 168 patients had disease which was staged T3 and above or had evidence of nodal disease. 81% of these patients received neo-adjuvant treatment, 108 receiving chemotherapy alone and 29 receiving chemoradiotherapy. The remaining 31 patients underwent surgery alone. There was no significant difference in the clinical staging between the three treatment modalities, (P = 0.25). There were 31 patients with early (T1/2 N0) cancer that underwent unimodality treatment in the form of surgery. Estimated median survival was 85 months for those that received chemotherapy and 53 months chemoradiotherapy (P = 0.45). Within the surgical group those patients with locally advanced disease (T3 + or N + ) median survival was 19 months; median survival was not reached for early cancers. Conclusion Both chemoradiotherapy and chemotherapy in the neoadjuvant setting combined with radical surgery enable excellent long-term outcomes to be achieved. Data from the Neo-aegis trial will hopefully inform which neoadjuvant treatment confers the greatest survival advantage. Disclosure All authors have declared no conflicts of interest.

PS02.119: THE IMPACT OF RECEIVING ADJUVANT CHEMOTHERAPY ON SURVIVAL IN PATIENTS WITH LOCALLY ADVANCED ADENOCARCINOMA OF THE OESOPHAGUS

Abstract Background Surgery remains the fundamental modality for achieving disease cure in patients with oesophageal adenocarcinoma In those with locally advanced disease, in the UK, is usually used in conjunction with perioperative chemotherapy as per the Magic trial. Not all patients manage to progress to the adjuvant component of the chemotherapy regimen, and its impact on outcome has not been determined. The aim of this review was to compare outcomes in those patients that received neoadjuvant treatment only with those that received neoadjuvant and adjuvant chemotherapy. Methods A retrospective review of patients who underwent treatment with curative intent for locally advanced oesophageal adenocarcinoma between 2006 to 2016 at a single institution was performed. Outcomes of patients who were staged T3 and above or had evidence of nodal disease and received perioperative chemotherapy were reviewed. Outcomes were stratified according to whether patients received only neoadjuvant chemotherapy or both neoadjuvant and adjuvant chemotherapy. Results A total of 413 patients underwent transthoracic oesophagectomy and two field lymphadenectomy with perioperative chemotherapy. 276 (67%) received only neoadjuvant chemotherapy, with 137 (33%) receiving at least one cycle of adjuvant chemotherapy. Pathological staging was comparable between groups (P = 0.17). Overall estimated median survival was 30 months (neoadjuvant only) Versus 37 months (Both) P = 0.2. In patients that were found to be node positive median survival was 22 months (neoadjuvant) versus 28 months (both) P = 0.21. For node negative patients median survival was not reached in both groups. Conclusion These results indicate a trend towards improved survival with the addition of adjuvant chemotherapy. This may be of greater impact in those patients with nodal involvement. Further studies are required to fully evaluate the impact of adjuvant chemotherapy in patients surgically treated for oesophageal cancer. Disclosure All authors have declared no conflicts of interest.

Regional Nodal Failure in Head and Neck Alveolar Rhabdomyosarcoma

To assess clinical outcomes and patterns of failure, particularly regional control, for pediatric patients treated with proton therapy for head and neck alveolar rhabdomyosarcoma (HN-ARMS). Between 2006 and 2015, 14 patients with HN-ARMS were enrolled on a prospective registry protocol and treated with proton therapy at a single institution. Eight patients (57%) presented with localized disease, and 6 (43%) presented with regional nodal metastases. One patient (7%) with regional disease also had distant metastases. Ten patients (71%) were assessed for FOX01 status, and all had PAX3-FOX01 fusion transcripts. Primary site was parameningeal for 8 patients (57%), orbital for 3 patients (21%), and other head and neck for 3 patients (21%). All patients were enrolled on either COG or EpSSG protocols and treated with chemotherapy per protocol. All patients were treated with proton therapy to the primary site and involved nodal disease to median dose of 50.4 Gy(RBE) (range 39.6 – 50.4 Gy[RBE]). Elective nodal irradiation (ENI) was not used for patients without evidence of nodal disease (clinically or radiographically) at time of diagnosis. Median follow-up for surviving patients was 4.3 years. Five-year overall survival for the cohort (n = 14) was 50.2%. One patient (7%) experienced local failure, while 8 patients (57%) had regional nodal failures. Of 8 patients with no nodal disease at presentation, 6 had regional nodal failures (75%). There were no local or distant failures among these 8 patients. All 6 of these nodal regional failures involved first-echelon draining lymph node stations from the primary tumor site. Of 6 patients with nodal disease at presentation, one experienced concurrent in-field local failure and out-of-field regional failure in a nodal level where only the gross disease was treated. Another patient with nodal disease at presentation developed regional marginal failure, in a nodal basin initially involved by disease without target volume coverage of the entire nodal station. Additionally, there was no effect of the timing of proton therapy initiation on treatment failure. Proton therapy provides excellent local control for HN-ARMS. However, regional nodal failures were common among patients who did not have nodal disease at presentation. These data suggest that HN-ARMS patients may benefit from ENI. For node-positive patients, we recommend coverage of the entire nodal level due to observed high risk of failure at these sites.

An Update on the Risk of Lymph Node Metastasis for the Follicular Variant of Papillary Thyroid Carcinoma with the New Diagnostic Paradigm.

Previous data has shown that the risk of nodal metastases is significantly greater for classical papillary thyroid carcinoma (PTC) as compared to the follicular variant (FVPTC). Given a recent change in diagnostic paradigm and definition of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) we intended to investigate if there remains a significant difference in nodal involvement between classical PTC and FVPTC. A 6-year retrospective review of all cases with FVPTC in the diagnostic line from the University of Utah/ARUP Laboratories was conducted. Two pathologists reviewed the remaining cases using the recently described histologic criteria of NIFTP to determine the total number the FVPTCs fitting the new classification paradigm. Histologic and clinical follow-up was tracked for all patients to determine the rate of nodal disease for all groups. 127 cases were identified using the above listed criteria. Forty-seven cases (37%) were classified as NIFTPs. None of the 47 patients had nodal disease either at the time of surgery or on follow-up. Twenty-eight cases met the current criteria for FVPTC (21%); of these 7/28 (25%) had evidence of nodal disease. By comparison, 17/45 (38%) of patients with mixed classical and FVPTC had nodal disease. Overall, there was no statistically significant difference in the risk of nodal metastasis between the pure FVPTC and mixed classical/FVPTC groups (p = 0.43). Our data indicates that implementing new definition for FVPTC will narrow the gap in the risk of nodal metastases between the classical PTC and FVPTC histologic subtypes.

Indications for invasive mediastinal staging in patients with early non-small cell lung cancer staged with PET-CT

Purpose/Objective(s)Appropriate use of invasive mediastinal staging in patients with clinically node-negative NSCLC staged by PET-CT is critical in selecting patients for curative-intent therapy such as surgery or SBRT, but little data exists to guide this decision-making. We examined a large population of patients with clinical stage I NSCLC referred for mediastinoscopy or EBUS to find risk factors for occult N2 lymph nodes and determine which patients benefit from invasive staging. Materials/MethodsWe identified consecutive clinical T1-2N0 NSCLC patients being evaluated for curative-intent therapy between 2011 and 2015. None had evidence of nodal disease by PET-CT; the endpoint was pathologic confirmation of occult N2 disease by EBUS or mediastinoscopy. Tumor size, location, histology, SUVmax, and radiographic appearance were evaluated as determinants of occult N2 disease. Two group comparisons of continuous variables were done with independent t-tests and categorical variables were compared with χ2 or Fisher’s exact test. ResultsIn 284 patients with PET-CT-staged clinical T1-2N0 disease, the prevalence of occult N2 metastases was 7.0%. The negative predictive value of PET-CT was 92.9% and the negative predictive value of mediastinoscopy/EBUS was 96.3%.T2 tumors were more likely to have occult N2 disease than T1 tumors (11.8% v 3.6% p=0.009). Pure solid tumors had greater involvement of N2 nodes than tumors with any ground glass component (12.6% v 3.1%, p<0.001). 17.5% of central tumor cases were found to have occult N2 metastases while 4.4% of patients with peripheral tumors (P<0.001). 33.3% of patients with solid central T2 tumors had occult N2 metastases whereas 2.0% of patients with peripheral T2 tumors with a ground glass component, 1.2% of patients with peripheral T1 tumors with a ground glass component and 3.6% of patients with peripheral T1 solid tumors had N2 metastases. ConclusionsInvasive mediastinal staging should be strongly encouraged in central tumors and solid T2 tumors because the risk of occult nodal involvement is greater than 10% in these cohorts. However, for patients with peripheral T1 tumors or peripheral T2 tumors with a significant ground glass component, the yield of invasive staging after a negative PET-CT is very low and invasive staging may not be warranted.

Patterns of lymph node positivity on 11C-acetate PET imaging in correlation to the RTOG pelvic radiation field for prostate cancer

Purpose11C-acetate positron emission tomography (PET) imaging allows for the detection of occult metastatic disease that may otherwise go undetected with standard imaging for prostate cancer (PCa). The aim of this study was to evaluate lymph node coverage of the standard Radiation Therapy Oncology Group (RTOG) whole pelvic radiation therapy (WPRT) field in patients found to have node-positive PCa determined by 11C-acetate PET imaging. Methods and materialsA retrospective analysis was conducted on 125 PCa patients who underwent 11C-acetate PET scans at our institution between 2007 and 2014. Patients were included if they had evidence of nodal disease without distant metastatic cancer. Individual lymph nodes were characterized by location, size, and relationship to the RTOG WPRT field. ResultsA total of 55 11C-acetate PET scans (from 54 men) met criteria for inclusion in the study. Median age at diagnosis was 61 years. Median prostate-specific antigen values at diagnosis and at the time of the scan were 9.2 and 8.1 ng/mL, respectively. A total of 159 positive lymph nodes were identified, 78% of which were smaller than 1 cm. The most frequently involved lymphatic regions were the external iliacs (38.4%), para-aortics (19.5%), and common iliacs (16.3%). Additionally, 10.1% of positive nodes were identified as nodes of Cloquet. Of the positive nodes, 51.6% were determined to reside outside of the radiation field and, of those, the most common sites were para-aortic (36.9%), proximal common iliac (17.8%), distal external iliac (17.8%), and nodes of Cloquet (17.8%). ConclusionsBased on 11C-acetate PET imaging in patients with PCa, the standard RTOG WPRT field may miss more than one-half of all positive lymph nodes. Clinicians should be aware of the potential for insufficient nodal coverage when using the standard RTOG WPRT field in patients with node-positive PCa. 11C-acetate PET imaging may be useful in defining target volumes for these patients.

Patterns of recurrence and survival in neuroendocrine cervical cancer

ObjectiveTo analyze patterns of recurrence and survival and identify prognostic factors in women with neuroendocrine cervical cancer (NECC). MethodsWe reviewed patients with International Federation of Gynecology and Obstetrics stage I–IVA NECC who were enrolled in the Neuroendocrine Cervical Tumor Registry and treated with curative intent. Event-free survival (EFS) and overall survival (OS) according to disease and treatment characteristics were analyzed using the Kaplan-Meier method. ResultsAmong 40 patients with NECC, 25 (62%) had small cell NECC, eight (20%) had large cell NECC, and seven (18%) had unspecified neuroendocrine histology. With a median follow-up of 21.5months, 32 patients (80%) experienced progression, and 28 (70%) died. For all patients, the 5-year EFS rate was 20%, and the 5-year OS rate was 27%. Patients with large cell NECC had significantly better median EFS (median not reached vs. 10.0months, p=0.02) and showed a trend toward better median OS (153months vs. 21months, p=0.08) than patients with other histologic types. In patients with early-stage clinically node-negative disease, chemoradiation was associated with significantly better median EFS than surgery (median not reached vs. 18.0months, p=0.04). ConclusionsPatients with large cell NECC have better outcomes than patients with other subtypes of NECC. In early-stage node-negative NECC, chemoradiation yields better EFS than surgery. Most patients with NECC, even those with no evidence of nodal disease at diagnosis, rapidly develop widespread hematogenous metastases and die of their disease.

Management of advanced nodal disease following chemoradiation for head and neck squamous cell carcinoma: role of magnetic resonance imaging.

The purpose of this study was to determine the role of magnetic resonance imaging (MRI) to predict persistent nodal disease in head and neck cancer treated with chemoradiation. Retrospective chart review of 38 patients with head and neck cancer and N2/N3 neck disease who were treated with chemoradiation and who had an MRI 6 to 8 weeks following treatment. Sixteen patients had MRI findings suggestive of persistent nodal disease and were managed with neck dissections, three of whom had a persistent tumour. All of these patients have remained disease free in the neck (average follow-up 15 months). Among 22 patients without evidence of nodal disease on post-treatment MRI, 2 patients have had recurrence in the neck (average follow-up 26 months). Concomitant chemoradiation is effective for the treatment of advanced nodal disease in selected patients. Patients without MRI evidence of persistent nodal disease following chemoradiation who were observed had a low incidence (9%) of eventual neck recurrence, whereas those with evidence of persistent nodes on MRI had a 19% likelihood of residual pathologic neck disease. The optimal strategy for the evaluation of the neck following chemoradiation requires further investigation.