Macroscopic Nodal Disease Research Articles

Genetic Factors Associated with Clinical Response in Melanoma Patients Treated with Talimogene Laherparapvec: A Single-Institution Retrospective Analysis.

Talimogene laherparapvec (T-VEC) is a modified herpes simplex virus type 1 (HSV-1) and the first oncolytic virus to be approved for the treatment of unresectable melanoma. We assessed whether there are tumor-intrinsic genetic factors that are associated with tumor control. A single-institution, retrospective analysis of melanoma patients treated with T-VEC was performed. Demographics, histopathologic reports, treatment history, clinical outcomes, and tumor genomic analysis of approximately 100 genes were collected. Ninety-three patients who had received T-VEC were identified, of whom 84 (91%) were diagnosed with cutaneous melanoma. Sixty-nine (69) patients received more than one dose of T-VEC and had sufficient data available for clinical analysis. Of these patients 30.0% (n=21) had evidence of a complete response, defined as complete regression of all lesions without the need for additional treatment or procedures. Stage III disease (p<0.001), absence of macroscopic nodal disease (p<0.001), and absence of visceral/central nervous system metastases (p=0.004) were all associated with evidence of any clinical response or local control by univariate analysis. At the time of analysis, 54 patients had tumor genetic data available. Sixty genes were mutated in at least one patient, and all but one patient had at least one gene mutation identified. Presence of TERT promotor mutation was associated with evidence of any clinical response (p=0.043) or local control (p=0.039) by multivariate analysis. This work describes the experience using T-VEC in melanoma at a single institution and highlights the presence of TERT promotor mutations as a possible driver of clinical response.

Multidisciplinary Treatment of Merkel Cell Carcinoma of the Extremities: Outcomes and Factors Associated with Poor Survival in Nodal Disease.

Merkel cell carcinoma (MCC) has a tendency for lymphatic spread and locoregional recurrence, although there is little data examining the risk factors for patients with lymph node-positive extremity lesions. The purpose of the current study was to examine the outcomes and risk factors associated with nodal metastasis in extremity MCC. We retrospectively reviewed the medical record of 120 patients with extremity MCC evaluated at our institution between 1994 and 2021. The mean age of this cohort was 71 years; 33% of patients were female; and 98% were Caucasian. Seventy-eight (65%) patients presented with localized disease. Thirty-seven (31%) patients had stage III disease, and five (4%) patients had stage IV disease. Treatment of primary lesions consisted primarily of margin-negative excision and adjuvant radiotherapy. Nodal metastases were most treated with adjuvant radiation or completion lymph node dissection. Five-year disease-specific survival in our series was 88% for patients with localized disease, 89% for stage IIIa disease, 40% for stage IIIb disease and 42% for stage IV. Factors associated with worse survival included immunosuppression and macroscopic nodal disease. In conclusion, extremity MCC has a low rate of local recurrence when treated with margin-negative excision and adjuvant radiation. However, treatment of nodal metastases remains a challenge with high rates of recurrence and mortality, particularly for patients who are immunosuppressed or who have macroscopic nodal disease.

Isolated Tumor Cells and Micrometastatic Nodal Disease in Breast Cancer Patients After Neoadjuvant Chemotherapy: Is Post Mastectomy Radiation Therapy Indicated?

<h3>Purpose/Objective(s)</h3> The prognostic and treatment implications of isolated tumor cells (ypN0i+) and micrometastatic (ypN1mi) nodal disease after neoadjuvant chemotherapy (NACT) is not well-studied. These patients are excluded from the ongoing NSABP B-51 trial which only includes patients with macroscopic nodal disease after NACT. We evaluate the long-term outcomes and the role of post-mastectomy radiation therapy (PMRT) in breast cancer patients with ypN0i+ and ypN1mi disease after NACT and mastectomy (MX). <h3>Materials/Methods</h3> Using the National Cancer Database (NCDB), we identified patients (≥ 18 year old) with breast cancer who were treated with NACT and MX diagnosed between 2004 and 2016. Patients with cT4 or metastatic disease were excluded. Chi-square testing was used to evaluate clinicopathological parameters of those treated with and without PMRT. Kaplan-Meier analysis was used to evaluate the effect of PMRT on overall survival (OS). Univariate and multivariate Cox proportional hazard models with and without inverse probability treatment weighting (IPTW) were used to identify prognostic factors associated with OS. <h3>Results</h3> Our final cohort consisted of 3,253 patients (34.0% ypN0i+, 66.0% ypN1mi) with a median age at diagnosis of 49 years (29 – 74 years). PMRT was utilized in 60.4% of the entire cohort, 51.8% of ypN0i+ patients and in 64.9% of ypN1mi patients. There was an increase in use of PMRT throughout the study period (56.2% in 2004-2011 vs. 61.9% in 2012-2016). With a median follow up of 36.8 months, the 5-year OS was 84.3% and 79.9% for ypN0i+ and ypN1mi patients, respectively (HR 1.23 [0.97-1.55], <i>P</i> = 0.092). Without accounting for covariates, there was no significant effect of PMRT on OS in ypN0i+ patients, ypN1mi patients, or in the entire cohort. In IPTW-MVA, PMRT had no significant effect on OS (HR 0.93 [0.74-1.18], <i>P</i> = 0.565]. Factors that were significant for worse OS on IPTW-MVA were higher comorbidity score, higher grade, hormone-receptor negative subtype, higher ypT stage, presence of lymphovascular invasion, Asian/Pacific Islander race, and more recent year of diagnosis. HER-2 positive subtype, receipt of hormone therapy, and private insurance were associated with improved OS. <h3>Conclusion</h3> Patients with ypN1mi disease had a trend towards worse OS in comparison to patients with ypN0i+ disease. The majority of patients with ypN0i+ and ypN1mi are receiving PMRT with higher rates of PMRT in ypN1mi vs. ypN0i+. PMRT rates are increasing with time. There is no association of PMRT with improved OS. Prospective randomized controlled data is needed to further evaluate the role of PMRT in these patients who were excluded from the ongoing NSABP B-51.

Current management of melanoma patients with nodal metastases.

The management of melanoma patients with nodal metastases has undergone dramatic changes over the last decade. In the past, the standard of care for patients with a positive sentinel lymph node biopsy (SLNB) was a completion lymph node dissection (CLND), while patients with palpable macroscopic nodal disease underwent a therapeutic lymphadenectomy in cases with no evidence of systemic spread. However, studies have shown that SLN metastases present as a spectrum of disease, with certain SLN-based factors being prognostic of and correlated with outcomes. Furthermore, the results of key clinical trials demonstrate that CLND provides no survival benefit over nodal observation in positive SLN patients, while other clinical trials have shown that adjuvant immune checkpoint inhibitor therapy or targeted therapy after CLND is associated with a recurrence-free survival benefit. Given the efficacy of these systemic therapies in the adjuvant setting, these agents are now being evaluated and utilized as neoadjuvant treatments in patients with regionally-localized or resectable metastatic melanoma. Multiple options now exist to treat melanoma patients with nodal disease, and determining the best treatment course for a particular case requires an in-depth knowledge of current data and an informed discussion with the patient. This review will provide an overview of the various options for treating melanoma patients with nodal metastases and will discuss the data that supported the development of these treatment options.

Lymph node dissections in cutaneous malignancy: Where are we now? A review of 10 years’ experience at a tertiary centre

The surgical management of cutaneous malignancies has evolved over recent years with the introduction of novel medical therapies and an increasing emphasis upon early adjuvant systemic therapy. As such, completion lymph node dissection (cLND) is now no longer recommended following a positive sentinel lymph node biopsy (SLNB) in melanoma. We evaluated our ten-year practice at a regional tertiary centre, assessing the change in lymph node dissection (LND) caseload volume, anatomical distribution, and indication for the procedure. A retrospective search was carried out of all LNDs performed by the Plastic Surgery department at Cambridge University Hospitals NHS Trust, UK from 1 January 2010 to 31 December 2019. Case notes were retrospectively analysed for each procedure, with the site and pathology recorded. A total of 491 LNDs were performed over the 10-year period. Surgical volume peaked in 2015 with 67 cases, followed by a decline to 41 cases in 2019. The number of neck dissections increased over the decade, as well as the proportion of cases due to macroscopic nodal disease. We sub-analysed the number of LNDs in three contiguous 18-month intervals, corresponding to changes in practice due to evidence from the DeCOG and MSLT-II Trials. We found a 41.67% reduction in LNDs caseload between July 2018-Dec 2019, compared to a similar period prior to trial evidence (July 2015-Dec 2016) (p=0.0.14). In summary, the surgical volume of LNDs has decreased significantly since 2018, reflecting emerging evidence and changes to national guidelines. This will require ongoing monitoring for workforce planning and surgical training.

Therapeutic neck dissection in head and neck melanoma patients: Comparing extent of surgery and clinical outcome in two cohorts

BackgroundThe extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach. MethodsSixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I–V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3–4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS). ResultsClinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92). ConclusionThis study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.

Surgery for Metastatic Melanoma: an Evolving Concept.

This review describes the evolving role of surgery in stage III and IV melanoma. Surgery has been the first option to cure melanoma patients at initial diagnosis of metastatic spread: a complete surgical excision of the disease either in stage III or IV has been the gold standard for decades. A positive sentinel node biopsy (SNB) has been followed by a complete lymph node dissection (CLND) since the early stages of modern surgical oncology. However, since two randomized trials have indicated that a CLND does not improve survival in patients with a positive SNB, a CLND is no longer considered mandatory. A therapeutic lymph node dissection (TLND) is still offered to patients with macroscopic nodal disease and in highly selected cases, patients with distant melanoma metastases can be treated surgically as well. Also the availability of adjuvant, and in the future possibly neoadjuvant, systemic therapy have shifted the landscape to less extensive surgery in metastatic melanoma. With the development of new systemic options, surgery in metastatic melanoma has become more and more part of a multidisciplinary treatment: surgical indications are moving from previous standards to a new role.

Synchronous Bilateral Breast Cancer: Implications for Adjuvant Radiation

We present the case of a 55-year old postmenopausal female with bilateral early stage clinically node negative breast cancer who was treated with bilateral lumpectomy with axillary lymph node dissection revealing N1a nodal disease in her right breast with extra-nodal extension and micrometastatic disease in her left breast. Given the controversy in management for low nodal burden for macroscopic and microscopic nodal disease, we review the key trials in regional nodal management that have included patients with low nodal burden to explain our reasoning for treatment decisions. Our patient was treated with both hypofractionation and conventional treatment. She is an excellent teaching case to demonstrate how much of an impact the decision regarding fractionation can have on long term breast cosmesis and toxicity.

Mapping the distribution of nodal metastases in papillary thyroid carcinoma: Where exactly are the nodes?

To characterize nodal disease of patients presenting with papillary thyroid carcinoma (PTC) STUDY DESIGN: Retrospective chart review. PTC patients who underwent thyroidectomy and/or neck dissection (revision/primary) from 2004 to 2009 at a tertiary-care hospital were reviewed. Preoperative computed tomography (CT) scan and ultrasonography were utilized to identify macroscopic, clinically apparent nodal metastasis (cN+). Demographic data, type of surgery, nodal disease, and primary tumor information were recorded. Of 416 patients reviewed, 35% had cN+ on initial presentation (IP); of these, 88% and 50% had central (CND) and lateral nodal disease (LND), respectively. The presence of ectopic nodal (END) metastases (nodal disease outside typical CND or LND locations) was absent on IP but occurred in 9% of patients with nodal recurrence. END was typically found in the retropharyngeal area but also was noted in the sublingual region, subcutaneous location, axilla, and chest wall. Extrathyroidal extension (ETE) was found in 8.9% without nodal disease, 33.1% with nodal disease, and 57.1% with END (P < 0.0001). Primary tumor size greater than 4 cm (P = 0.05) was associated with nodal disease. This report represents a large series describing characteristics of the primary PTC tumor and associated nodal disease not only in the central and lateral neck but also in the ectopic locations. Our results suggest that a significant proportion of patients will have nodal disease in the central compartment on IP, especially younger patients. ETE and tumor size are associated with macroscopic nodal disease (including END). Nine percent of the patients with nodal recurrence had ectopic nodes occurring in various locations, most commonly in the retropharynx. CT scan can assist with identification and surgical planning of recurrent nodal disease. 4. Laryngoscope, 127:1959-1964, 2017.

Melanoma of Unknown Prognosis

Melanoma in which macroscopic nodal disease derives from an unknown primary (MUP) is difficult to classify and manage. Depending on the cryptic primary

Addition of an Iliac/Obturator Lymph Node Dissection Does Not Improve Nodal Recurrence or Survival in Melanoma

Controversy exists regarding the value and indications for inguinal dissection alone or in combination with an iliac/obturator lymph node dissection for melanoma. We reviewed patients from a multicenter prospective clinical trial and a single center who underwent inguinal dissection alone or combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were stratified and compared by microscopic or macroscopic (palpable or detected by imaging) disease. The study was composed of 134 patients with a median follow-up of 39 months. Indications for inguinal dissection were microscopic disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients. An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55% in the microscopic vs macroscopic groups, respectively (p= 0.10). No risk factors for positive pelvic nodes were identified. For both microscopic and macroscopic disease, addition of an iliac/obturator dissection to an inguinal dissection did not significantly reduce the risk of pelvic nodal recurrence. Five-year overall survival rates for 4 groups were compared: microscopic disease, inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic disease, iliac/obturator dissection (44%) (p= 0.0163). On survival analysis, addition of an iliac/obturator dissection in either microscopic or macroscopic disease did not affect disease-free survival or regional lymph node recurrence-free survival. The addition of an iliac/obturator dissection to an inguinal dissection for both microscopic and macroscopic nodal disease did not significantly affect lymph node recurrence rates, disease-free survival, or overall survival.

Significance of core needle biopsies with ductal carcinoma in situ suspicious for microinvasive carcinoma.

86 Background: Sentinel lymph node biopsy (SLNB) is not routinely recommended for women diagnosed with ductal carcinoma in situ (DCIS); however, when the pathologist cannot rule out microinvasion on core biopsy (CB), the surgeon must decide whether to perform a SLNB at the time of surgical excision. Up to 10% of patients with T1mi are found to have breast cancer cells in the axillary lymph nodes, but less than 2% contain macrometastasis making the utility of SLNB in this setting unclear. Methods: The University of Chicago pathology database was queried for patients whose CB showed DCIS suspicious for microinvasion (Smic) or definite microinvasion (Mic) from 2000 to 2012. We analyzed histology, imaging, nodal status, core needle size, and the use of myoepithelial immunohistochemistry (IHC) markers to identify microinvasion. Results: We identified 60 women with Smic and 19 women with Mic on CB. In the Smic group, 33% had infiltrating ductal carcinoma (IDC) in the surgical specimen (35, 30, 30, 1 and 0% for T1mi, T1a, T1b, T1c, and T2 respectively compared to 58, 21, 0, 10.5 and 10.5% in the Mic group). A SLNB was performed at the initial surgery in 38/60 (63%) of Smic and in all Mic biopsies; they were positive in 3/42 (7%) and 2/19 (11%) respectively (p=0.64). When N1mic was excluded, the incidence of macroscopic nodal disease was 1/42 (2.4%) and 1/19 (5.3%) p=0.53. Of those with Smic, we observed a higher proportion of IDC associated with a lesion size ≥ 14 mm on imaging (75% versus 15% for &lt; 14 mm, p&lt;0.02); smaller CB needle size (69% with 11, 12 and 14 gauge versus 0% with 9 gauge, p&lt;0.01); and the use of IHC on the CB to identify microinvasion (58% versus 22% without IHC, p&lt;0.01). There was no association to IDC with respect to grade, necrosis, mass on imaging, or biopsy guidance. Conclusions: The incidence of clinically positive nodal disease in patients with Smic on CB is extremely low. However, those with tumors ≥ 14 mm, the use of smaller gauge CB needles, and Smic based on myoepithelial IHC may be at higher risk for IDC. Of the Smic group with DCIS after excision, none harbored nodal disease; therefore, the use of SLNB only after a definitive diagnosis of IDC may prevent overtreatment.

Ulceration and stage are predictive of interferon efficacy in melanoma: Results of the phase III adjuvant trials EORTC 18952 and EORTC 18991

SummaryAdjuvant interferon has modest activity in melanoma patients at high risk for relapse. Patient selection is important; stage and ulceration of the primary tumour are key prognostic factors. MethodsIn this post hoc meta-analysis of European Organisation for Research and Treatment of Cancer (EORTC) trials 18952 (intermediate doses of interferon α-2b [IFN] versus observation in stage IIb-III patients) and 18991 (pegylated [PEG]-IFN versus observation in stage III patients), the predictive value of ulceration on the efficacy of IFN/PEG-IFN with regard to relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) was assessed in the overall population and in subgroups stratified by stage (IIb and III-N1 [microscopic nodal disease] and III-N2 [macroscopic nodal disease]). FindingsIn the overall population, the comparison of IFN/PEG-IFN versus observation for RFS, DMFS and OS yielded estimated hazard ratios (HR) of 0.85 (p=0.004), 0.89 (p=0.04) and 0.94 (p=0.36), respectively. The impact of treatment was greater in the ulceration group (n=849) compared with the non-ulceration group (n=1336) for RFS (test for interaction: p=0.02), DMFS (p<0.001) and OS (p<0.001). The greatest risk reductions were observed in patients with ulceration and stage IIb/III-N1, with estimated HR for RFS, DMFS, and OS of 0.69 (p=0.003), 0.59 (p<0.0001) and 0.58 (p<0.0001), respectively. The efficacy of IFN/PEG-IFN was lower in stage III-N2 patients with ulceration and uniformly absent in patients without ulceration. There was consistency between the data of both trials. InterpretationThis meta-analysis of the EORTC 18952 and 18991 trials indicated that both tumour stage and ulceration were predictive factors for the efficacy of adjuvant IFN/PEG-IFN therapy.

Patterns Of Progression Following Hypofractionated Image-guided Radiotherapy (HIGRT) To Abdominal Lymph Nodes In Oligometastatic (OM) Patients

HIGRT to macroscopic nodal disease, without elective coverage of adjacent nodal regions, is often employed for limited volume metastases. Progression in adjacent lymph nodes (LNs) after HIGRT to abdomino-pelvic (AP) LN metastases from AP primary tumors is poorly described.

DERMA phase III trial of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) as adjuvant therapy in patients with MAGE-A3-positive resected stage III melanoma.

TPS232 Background: Clinical activity of the MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) was observed in a Phase II study in patients with metastatic melanoma (NCT00086866) and in a Phase II study in patients with completely resected non-small cell lung cancer (NSCLC) (NCT00290355). Based on these positive signals for the activity of MAGE-A3 ASCI, a Phase III trial is currently ongoing in patients with resectable regionally advanced melanoma (DERMA Phase III trial, NCT00796445). Methods: DERMA is a double-blind, placebo-controlled, 2:1 randomized trial of MAGE-A3 ASCI vs. Placebo. Eligible patients must have cutaneous melanoma expressing MAGE-A3 with histologically proven macroscopic nodal disease (AJCC Stage IIIB-C). Central randomization uses an internet-based algorithm accounting for the following factors: Stage of the disease (IIIB, IIIC and IIITx), TNM nodal category (N1, N2 and N3), primary category (Tx-0 or T1-2 or T3 or T4), extracapsular extension (Yes, No), study center, prior treatment with IFN or anti-CTLA-4 (Yes, No). Patients must have had complete surgical resection of all tumor. Disease-Free Survival (DFS) in the overall patient population is the primary endpoint, while overall survival, safety and health-related quality of life (EQ-5D) are secondary endpoints. A previously-defined gene signature associated with MAGE-A3 ASCI benefit is also being validated as a secondary endpoint of this trial (Louahed et al., EORTC-NCI-AACR 2009). The MAGE-A3 ASCI combines the tumor-specific antigen MAGE-A3, delivered as a recombinant protein, with the immunostimulant AS15. A maximum of 13 doses are administered by intramuscular injection over 27 months; the first 5 are given at 3-week intervals followed by 8 at 12-week intervals. This Phase III trial is designed to enroll 1300 patients from 250 centers worldwide. Since Dec 1, 2008, 2426 patients have been screened. From 1917 tumor samples valid for testing the expression of MAGE-A3, 1265 express MAGE-A3 (MAGE-A3 expression rate of 66%). 832 patients are currently enrolled to this study.

Ulceration of primary melanoma and responsiveness to adjuvant interferon therapy: Analysis of the adjuvant trials EORTC18952 and EORTC18991 in 2,644 patients

9007 Background: Ulcerated (Ulc) melanomas have a worse prognosis than non-ulcerated (N-Ulc) melanomas. Ulc and N-Ulc primaries have different stromal characteristics and gene profiles reflecting differences in biology. We analyzed outcome after adjuvant interferon (IFN) therapy in the 2 largest phase III trials (EORTC18952 and 18991) ever conducted in stage IIB-III melanoma patients (pts). Methods: EORTC18952 compared IFNα-2b (10 MIU, sc, qd, 5 days/wk, for 4 wks) followed by either 10MIU,sc, tiw for 12 mts, or 5MIU for 24 mts) with observation in 1,388 stage IIB-III pts (Lancet 2005;366). EORTC18991 evaluated pegylated IFNα-2b (6 μg/Kg, 1×/wk, for 8 wks followed by 3μg/Kg, 1×/wk for up to 5 yrs) versus observation in 1,256 stage III pts (Lancet 2008;372). Using meta-analytical methods, predictive value for Ulc on the value of IFN on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) was assessed, overall, and according to stage (IIB, III-N1 or N2=microscopic or macroscopic-nodal disease). Results: Overall, the comparison (PEG-)IFNα-2b versus observation regarding RFS, DMFS, and OS led to a reduction in the hazard ratio (HR) of -16% (SE=5%), -13%(5%), and -8%(5%). Among 2,644 pts randomized, 849 had Ulc primaries, 1,336 N-Ulc primaries, and 459 Ulc unknown. In Ulc group the impact was much greater than in N-Ulc group for RFS (Test For Interaction: p=0.02), DMFS (p&lt;0.001), and OS (p&lt;0.001). The greatest reductions occurred in pts with Ulc and stages IIB/III-N1 In N-Ulc pts reduction was absent. Consistency in the treatment impact was seen in both trials. Conclusions: The post hoc analyses of EORTC1892 and EORTC18991 indicate strongly that pts with an Ulc primary are far more sensitive to IFN than pts with N-Ulc primaries. This hypothesis will now be tested in the EORTC18081 trial, which compares PEG-IFNα-2b versus observation in pts with Ulc primaries ≥ 1mm. [Table: see text] [Table: see text]

FIGO stage IIIC endometrial carcinoma: resection of macroscopic nodal disease and other determinants of survival.

The objective of this study was to evaluate the potential survival benefit of debulking macroscopic adenopathy and other clinical prognostic factors among patients with node-positive endometrial carcinoma. Demographic, operative, pathologic, and follow-up data were abstracted retrospectively for 41 eligible patients with FIGO stage IIIC endometrial cancer. Survival curves were generated using the Kaplan-Meier method and statistical comparisons were performed using the log rank test, logistic regression analysis, and the Cox proportional hazards regression model. All patients had positive pelvic lymph nodes and 20 patients (48.8%) had positive para-aortic lymph nodes. Postoperatively, all patients received whole pelvic radiation therapy, 17 received extended-field radiation therapy, and 15 patients received chemotherapy. The median disease-specific survival (DSS) time for all patients was 30.6 months (median follow-up 34. 0 months). Patients with completely resected macroscopic lymphadenopathy had a significantly longer median DSS time (37.5 months), compared to patients left with gross residual nodal disease (8.8 months, P = 0.006). On multivariate analysis, independent predictors of DSS were gross residual nodal disease (HR 7.96, 95% CI 2.54-24.97, P < 0. 001), age > or = 65 years (HR 6.22, 95% CI 2.05-18.87, P = 0.001), and the administration of adjuvant chemotherapy (HR 0.22, 95% CI 0.07-0.76, P = 0.016). We conclude that in patients with stage IIIC endometrial carcinoma, complete resection of macroscopic nodal disease and the administration of adjuvant chemotherapy, in addition to directed radiation therapy, are associated with improved survival.

FIGO stage IIIC endometrial carcinoma: Resection of macroscopic nodal disease and other determinants of survival

The objective of this study was to evaluate the potential survival benefit of debulking macroscopic adenopathy and other clinical prognostic factors among patients with node-positive endometrial carcinoma. Demographic, operative, pathologic, &amp; follow-up data were abstracted retrospectively for 41 eligible patients with FIGO stage IIIC endometrial cancer. Survival curves were generated using the Kaplan-Meier method and statistical comparisons were performed using the log rank test, logistic regression analysis, and the Cox proportional hazards regression model. All patients had positive pelvic lymph nodes and 20 patients (48.8%) had positive para-aortic lymph nodes. Postoperatively, all patients received whole pelvic radiation therapy, 17 received extended-field radiation therapy, and 15 patients received chemotherapy. The median disease-specific survival (DSS) time for all patients was 30.6 months (median follow-up 34. 0 months). Patients with completely resected macroscopic lymphadenopathy had a significantly longer median DSS time (37.5 months), compared to patients left with gross residual nodal disease (8.8 months,P= 0.006). On multivariate analysis, independent predictors of DSS were gross residual nodal disease (HR 7.96, 95% CI 2.54–24.97,P&lt; 0. 001), age ≥ 65 years (HR 6.22, 95% CI 2.05–18.87,P= 0.001), and the administration of adjuvant chemotherapy (HR 0.22, 95% CI 0.07–0.76,P= 0.016). We conclude that in patients with stage IIIC endometrial carcinoma, complete resection of macroscopic nodal disease and the administration of adjuvant chemotherapy, in addition to directed radiation therapy, are associated with improved survival.

Lymph node surgery in papillary thyroid carcinoma.

The impact of nodal disease remains controversial in papillary thyroid carcinoma (PTC). One surgeon treated 159 unselected patients, who were followed up for 1 to 27 years. We present a retrospective analysis with respect to nodal disease. Occult nodal disease was investigated, including metachronous nodal disease (mpN(1)) in primarily node negative patients (pN(0), clinical [c]N(0)). Therapeutic lymphadenectomies, prophylactic lymphadenectomies, or no lymphadenectomy were carried out in 42 (cN(1)), 29 (cN(0)), and 88 (cN(0)) patients, respectively, with stage pN(1) in 41 (98%), in 5 (17%), and in 2 (2.3%) patients, respectively (17% versus 2.3% p < 0.005). Sensitivity and specificity of clinical staging were 85% and 99%, respectively. More frequent prophylactic lymphadenectomy during the study period (p = 0.002) led to a nonsignificant increase in stage pN(1) (26% versus 30%). Immunohistochemistry led to upstaging of only 3% of histologically negative nodes and one (4%) pN(0) patient. Nodal recurrence occurred in 8 of 156 patients (5%) treated for cure, in 12% of pN(1) versus 3% of pN(0) cN(0) tumors (p = 0.009), in 15% of TNM high-versus 3% of low-risk patients (p = 0.006), and in 5% each of patients, younger than 45 and 45 years or more. In TNM high-risk patients, tumor-related survival was 50% for stage pN(1) versus 86% for stage pN(0), cN(0) (p = 0.03) (100% and 100% in low-risk patients). The rate of occult nodal disease might be relatively low, and it does not frequently progress to clinical recurrent disease. Clinical nodal status might be valid for deciding the extent and radicality of node dissection. Prophylactic (central) lymphadenectomy should be carried out without radicality-associated morbidity. Macroscopic nodal disease warrants more rigorous, compartment-oriented lymphadenectomy. There is no rationale for detection of occult disease and micrometastasis by frozen section or immunohistochemistry.

Which lymphadenectomy in papillary thyroid gland carcinoma?

The optimal treatment of papillary thyroid carcinoma (PTC) is still debated, also with respect to nodal treatment. Retrospective analysis of a personal series of 159 patients with PTC, with respect to nodal disease, follow up 1-27 (mean 8) years. In 42 patients with clinical, macroscopic nodal disease (cN1) a therapeutic lymphadenectomy was performed, with pN1 status in 41 (98%) patients. 117 patients had no clinical or intraoperative suspicion of nodal involvement (cN0), with occult nodal disease in 5/29 (17%) patients undergoing prophylactic (elective) lymphadenectomy, and in 2/88 (2.3%) patients without primary lymphadenectomy (metachronous nodal disease) (p < 0.005). Nodal recurrences were observed (1-5 years after primary treatment for cure) in 5/42 (12%) pN1 and in 3/114 (2.6%) cN0, pN0 tumors (p = 0.009), with unfavourable outcome in 2 and 1 patients, respectively. The 20-year tumor specific survival was 100% in TNM I + II (low risk) patients (including pN1 and N0 tumors); the survival rate was deteriorated by stage pN1 vs. N0 in TNM high risk patients (50% vs. 86%; p = 0.03). The intraoperative macroscopic staging (cN) remains important:--clinical nodal disease warrants a systematic node dissection (microdissection), for preventing (curable or serious) nodal recurrences. Occult nodal disease does not evolve frequently in clinical nodal recurrence. A less radical (and only central) prophylactic lymphadenectomy, avoiding surgical morbidity, may be oncologically adequate. More sensitive detection of nodal positivity (frozen section of sampling tissue or sentinel nodes, immunohistochemistry) appears not rationale. In pN0, cN0 tumors use of prophylactic 131I may represent overtreatment, and follow up controls may be conducted less rigorously.