Extensive Nodal Disease Research Articles

Autoimmune haemolytic anaemia in mantle cell lymphoma : an insidious complication associated with leukemic disease

Autoimmune haemolytic anaemia in mantle cell lymphoma : an insidious complication associated with leukemic disease

SMARCB1-deficient Vulvar Neoplasms: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 14 Cases.

Loss of expression of the SMARCB1 (INI1/BAF47/SNF5) tumor-suppressor protein, originally identified in pediatric malignant rhabdoid tumors, has been noted in significant percentages of epithelioid sarcomas of classical and proximal-type and in myoepithelial carcinomas. Epithelioid sarcoma and myoepithelial carcinoma are very rare in the vulvar region, and few of these cases have been evaluated for SMARCB1 protein loss by immunohistochemistry (IHC) or for SMARCB1 gene alterations by molecular genetic techniques. We studied the clinicopathologic, IHC, and molecular genetic features of 14 SMARCB1-deficient vulvar neoplasms. All available routinely stained sections were reexamined, and IHC analysis for wide-spectrum cytokeratins, high-molecular weight cytokeratins, epithelial membrane antigen, S100 protein, CD34, smooth muscle actin, desmin, and SMARCB1 was performed. Multiplex ligation-dependent probe amplification and DNA sequencing of the SMARCB1 gene was performed on 12 cases with sufficient available tissue. The 14 vulvar tumors occurred in adult women (mean age 46 y, range 22 to 62 y) and measured 1.1 to 8.8 cm in size (mean 4.7 cm). Tumors were classified as classical-type epithelioid sarcoma (N=1), proximal-type epithelioid sarcoma (N=6), myoepithelial carcinoma (N=4), and "SMARCB1-deficient vulvar sarcoma, not otherwise specified" (N=3) on the basis of combined histopathologic and IHC findings. One myoepithelial carcinoma showed divergent rhabdomyoblastic differentiation. All tested cases showed partial or complete SMARCB1 deletions (homozygous: 9 cases; heterozygous: 3 cases). One case with a heterozygous deletion also showed a c.528delC mutation in exon 5. Fluorescence in situ hybridization for EWSR1 rearrangement was performed for 3 cases classified as myoepithelial carcinoma and was negative. Follow-up (13 patients, range 5 to 72 mo, mean 31 mo) data showed 3 patients dead of disease, 1 alive with unresectable metastatic disease, 1 alive with radiographic evidence of extensive lymph nodal disease, and 8 alive without disease. We conclude that SMARCB1-deficient vulvar neoplasms chiefly comprise epithelioid sarcoma and myoepithelial carcinoma, although some defy easy classification. No association was seen between clinical behavior and the type of SMARCB1 alteration.

The relationship between pathologic nodal disease and residual tumor viability (RV) in patients with locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (E/GEJ) receiving induction chemotherapy, surgery, and postoperative chemoradiotherapy (CRT).

165 Background: A complete pathologic response to induction CRT has been identified as a favorable prognostic factor for patients with LRA ACA of the E/GEJ. Less is known, however, about the impact of pathologic regression after induction chemotherapy. Methods: Between 2/08 and 1/12, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. RV was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results: Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier (KM) projected 3 year OS for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (p<0.001). The KM projected 3 year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) RV was 67%, 42%, and 17% respectively (p=0.004). On multivariable analysis, both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3yr OS 85% (0-25% viable) v 51% (>25% viable), p=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3yr OS 20% (0-25% viable) v 21% (>25% viable), p=0.55]. Conclusions: RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of viability. Clinical trial information: NCT00601705.

Abstract P1-01-22: Which cytologically proven node-positive breast cancer patients can avoid axillary lymph dissection after neaodjuvant chemotherapy?

Abstract BACKGROUND: It is still controversial whether axillary lymph node dissection can be omitted after negative sentinel lymph node biopsy in breast cancer patients with clinically positive axilla at presentation treated with neoadjuvant chemotherapy (NAC). The aim of this study was to analyze whether SLN biopsy could be useful in these patients. METHODS: After NAC of 112 patients with cytology-proven axillary node metastasis at the time of diagnosis, SLNB using radioisotope and blue dye was performed including completion node dissection between 2008 and 2012. The results of SLNB and clinicopathological characteristics were analyzed for correlation with pathological axillary lymph node status. RESULTS: SLN was successfully identified in 107 (95.5%) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Axillary status was predicted with 94% accuracy and a false negative rate of 8.7%. Axillary nodal status before NAC (cN2 versus cN12) was associated with higher false-negative rates (p = 0.02). Conversion to node-negative disease was achieved in 38 (35%) patients: 23% of patients with the luminal A subtype, 12% of patients with the luminal B, 39% of patients with the HER2-enriched, and 26% of patients with the triple-negative breast cancer subtype. The tripple negative and HER2-enriched breast cancer subtypes had a significantly better false negative rate and accuracy. CONCLUSIONS: SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NAC. However, acceptable performance was noted for tripple negative and HER2-enriched breast cancer patients presented with N1 axillary status in the beginning of NAC, and thus SLNB might be safely considered in these selected patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-22.

Current attitudes of head and neck oncologists in the United Kingdom to induction chemotherapy for locally advanced head and neck cancer: A survey of centres participating in a national randomised controlled trial

Induction chemotherapy (IC) followed by chemoradiation (CRT) for locally advanced squamous cell head and neck cancer (SCCHN) remains controversial in the absence of clear evidence to define its role. As part of a prospective, randomised, multicentre study of CRT for stage III/IV laryngeal/hypopharyngeal cancers (ART DECO, CRUK/10/018), we have examined the attitudes of oncologists in the United Kingdom (UK) to IC. Head and neck oncologists across the UK who expressed an interest in participating in the ART DECO trial were asked to complete a short written questionnaire designed to identify current UK practice of IC for stage III-IVb SCCHN. Completed questionnaires were returned to the clinical trials office prior to patient recruitment. Clinicians from twenty-five/48 centres (52.1%) responded. Twenty centres (80%) elected to use IC in the trial. For stage III disease, 80% of centres did not prescribe IC for T1N1 disease and 60% did not offer IC for T3N0 disease. Patients with bulky primary tumours or extensive nodal disease were more likely to receive IC. Thirteen prescribing centres (65%) use 3 drugs (docetaxel, cisplatin, and 5-fluorouracil) compared to 7 (35%) using 2 drugs (cisplatin and 5-fluorouracil). Fifteen centres (75%) prescribed 2 cycles of IC, and 5 (25%) prescribed 3 cycles. There was variation in the dosage for both the 2- and 3-drug regimens. Results suggest that clinical practice in the UK is currently divided between a 2- versus 3-drug regimen for IC for specific subgroups of patients. A consensus regarding the optimal combinations and dosages is required before further optimization of systemic therapy with other cytotoxics and biological agents is attempted.

68Ga-DOTANOC PET-CT Demonstrating In Vivo Somatostatin Receptor Expression in Idiopathic Gynecomastia

Gynecomastia is abnormal enlargement of the male breasts due to the excess growth of glandular component. A 65-year-old man with medullary carcinoma of thyroid underwent (68)Ga-DOTANOC PET-CT for somatostatin receptor (SSTR) scintigraphy. Extensive nodal, bone, and bone marrow disease was seen. Interestingly, increased (68)Ga-DOTANOC uptake was also noted in bilateral enlarged mammary glands (gynecomastia). Although SSTR types 1 and 3 have been identified in the normal female breast, no report exists regarding SSTR expression in gynecomastia.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients with Cytologically Proven Node-positive Breast Cancer at Diagnosis

The performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC). After NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed. SLNB was successfully performed in 169 (94.9%) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0%, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8%) patients: 24% of patients with the luminal A subtype, 51.6% of patients with the luminal B, 51.7% of patients with the HER2-enriched, and 58.5% of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy. SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.

Neoadjuvant chemotherapy for gastric cancer in Japan: a standing position by comparing with adjuvant chemotherapy

Adjuvant chemotherapy aims to eradicate micrometastatic tumor cells before and after curative surgery. Many Phase III trials have been conducted to study the efficacy of postoperative adjuvant chemotherapy; however, most trials have failed to show any survival benefit because of their low statistical power and/or poor patient compliance. Since 2000, two pivotal Phase III trials, the ACTS-GC and the CLASSIC, have demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. Although treatment with S-1 for 1year or combination therapy with capecitabine and oxaliplatin for 6months is effective, more intensive chemotherapy is necessary to further improve the survival rates. In Europe, two Phase III trials, the MAGIC and the FNCLCC/FFCD, have produced results that strongly suggest that neoadjuvant chemotherapy is beneficial. The advantages of neoadjuvant chemotherapy include a high rate of R0 resection, tumor regression, high compliance and the avoidance of unnecessary surgery. The disadvantage of neoadjuvant chemotherapy is over-diagnosis. In Japan, the Japan Clinical Oncology Group has conducted several clinical trials using neoadjuvant chemotherapy to target extensive nodal disease and/or scirrhous carcinomas. The optimal courses and regimens of neoadjuvant chemotherapy should, therefore, be clarified in the future.

Abstract P1-01-23: Increased Diagnostic Performance of Sentinel Lymph Node Biopsy Combined with Radiologic-pathologic Factors After Neoadjuvant Chemotherapy in Breast Cancer Patients with Cytologically Proven Node Metastasis at Diagnosis

Abstract Background: It is undetermined whether sentinel lymph node biopsy (SLNB) is feasible and accurate for predicting final nodal status after neoadjuvant chemotherapy (NCT) in breast cancer patients with cytologically proven node metastasis at the time of diagnosis, although currently completion node dissection is a standard surgical procedure for the management of axilla. The aim of this study was to investigate diagnostic performance of SLNB after NCT in this subgroup. Methods: Of 374 patients with T1-T3 breast cancer who received NCT, 178 had initially biopsy proven axillary/supraclavicular metastasis and subsequently underwent SLNB using radioisotope alone followed by completion node dissection between 2008 and 2011. Detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV), and accuracy of SLNB were retrospectively analyzed and it was explored using regression analysis whether combination with clinicopathologic factors improved performance. Results: At initial presentation, 60.7% of patients were cT2 stage and 88.2% treated with concurrent or sequential anthracycline plus taxane preoperatively. SLNB was successfully performed in 169 (94.9%) patients. The mean number of sentinel and regional nodes retrieved was 2.1 ± 1.6 and 12.8 ± 6.3, respectively. Tumoral non-responder and extensive residual nodal disease were significantly associated with detection failure of SLNB. Conversion to node-negative disease was noted in 69 (40.8%) patients. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0%, 22.0%, 75.8%, and 87.0%, respectively and diagnostic performance increased when ≥ 3 sentinel nodes were evaluated. By logistic regression model, tumoral and nodal responder, absent lymphovascular invasion (LVI), estrogen receptor (ER)-negativity, and HER2-positivity were significantly associated with node-negative disease after NCT. Area under the receiver operating characteristic curve increased from 0.890 to 0.949 when considering radiologic-pathologic factors and FNR was the lowest value of 14.3% in 46 patients with tumoral responder, absent LVI, and ER-negative tumor. Conclusions: SLNB was technically feasible but solely showed higher FNR in this study. Improved diagnostic performance of SLNB combined with radiologic-pathologic characteristics suggests possible clinical value of SLNB after NCT in highly selected patients with node metastasis at diagnosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-23.

Abstract P5-02-01: Discrepancy between CT and FDG-PET/CT in the staging of patients with inflammatory breast cancer: Implications for radiation therapy treatment planning

Abstract Background: To compare suspected areas of cancer involvement based on the findings of CT and FDG-PET/CT in patients with inflammatory breast cancer (IBC) and to determine if discrepancies would modify radiation therapy treatment fields. Methods: This is a retrospective study of 29 consecutive female patients with IBC (median age 49 years, range 28–78) who had both CT and PET/CT scans prior to the initiation of systemic therapy. CT and PET/CT scans were obtained within a median of 3 days (range 0–64). CT and PET/CT scans were independently reviewed by a board-certified radiologist (PD) and a board-certified nuclear medicine physician (HJ), respectively. Findings were recorded by anatomic site and graded as negative, equivocal or positive for malignancy. Radiation fields were then determined by a breast radiation oncologist (JB) after separately reviewing the CT and PET/CT images. Discrepancies between the two modalities were recorded. The study was approved by the hospital institutional review board. Results: Seven of 29 patients (24%) had discrepant findings that likely would have resulted in a modification of radiation treatment fields and/or radiation dose. In four patients, internal mammary nodal involvement was suspected on PET/CT but not on CT. In two of these four patients, PET/CT also detected additional disease (supraclavicular in one patient and chest wall in the other) that likely would have required a change in radiation field and/or dose. Another patient had subpectoral adenopathy on PET/CT that was not considered abnormal on CT. One patient had equivocal findings in the infraclavicular region on CT which was negative on PET/CT. In one patient, body habitus limited the CT evaluation; more extensive infiltrative soft tissue and nodal disease was seen on PET/CT. In four patients, there were discrepant findings for distant disease that likely would have resulted in a change in management or additional imaging studies. In two of these cases, PET/CT showed a clearly positive finding that was negative or equivocal on CT. In an additional two cases, equivocal PET/CT findings would have resulted in additional testing that would not have been recommended by CT alone. In another 4 cases, metastatic disease was suspected based on CT, but additional sites (all in bone and not seen on CT) were suspected on PET/CT. Conclusions: Inflammatory breast cancer patients have a high probability of presenting with extensive local/regional disease and distant metastases. In our IBC population, PET/CT imaging would have likely resulted in a change of radiation field or dose in 7 of 29 (24%) patients. Additionally, in four instances PET/CT suspected additional metastatic disease (14%). These discrepancies most commonly involved inclusion of an internal mammary nodal radiation field and identification of distant metastases. Pathologic verification of abnormal findings is necessary to verify these results. PET/CT imaging should be considered a standard component of radiographic staging for patients with IBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-02-01.

Diffusion‐weighted MRI compared to FDG PET‐CT in the staging and response assessment of Hodgkin lymphoma

A 29-year-old man presented with a large right supraclavicular mass, weight loss and night sweats. A diagnosis of stage 4B nodular sclerosis Hodgkin lymphoma was made. F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) and whole-body magnetic resonance imaging with diffusion-weighting (DW-MRI) were performed before and after escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy. The pre-treatment FDG PET-CT (top left) demonstrated extensive nodal disease above and below the diaphragm, including the right supraclavicular fossa. Post-treatment FDG PET-CT (top right) showed physiological FDG uptake only. The pre-treatment DW-MRI (bottom left) showed extensive nodal disease in the same distribution as the pre-treatment FDG PET-CT. DW-MRI revealed a bone lesion (arrow) not diagnosed on the FDG PET-CT, confirmed on the source axial images. Post-treatment morphological MRI (not shown) demonstrated residual nodal disease in the right lower neck and upper abdomen but this was all inactive on DW-MRI (bottom right). FDG PET-CT and DW-MRI independently established a complete response. FDG PET-CT is a recommended imaging method for determining disease activity in residual masses after treatment for Hodgkin lymphoma. There is an increasing body of evidence to support its use in the assessment of early response to chemotherapy and it has been established as reliable for staging Hodgkin lymphoma. However, it involves radiation exposure for both the CT and FDG components of the test. MRI does not use ionizing radiation and offers higher soft tissue contrast compared with CT. The reduction of exposure to ionizing radiation is of particular significance in patients with lymphoma who have a high chance of cure, especially in younger patients. Water diffusion whole body MRI also allows functional assessment of lymphoma response. DW-MRI relies on measuring the random motion of water molecules in tissues. Many malignant tumours, including lymphomas, are more cellular than benign/normal tissue and therefore show more restricted water diffusion, appearing bright on normal images or dark on inverted images such as those shown above. The disadvantages of MRI include the exclusion of patients with pacemakers, implantable defibrillators or significant claustrophobia. In addition, bulk tissue movements and physiological water motion can sometimes affect DW-MRI image quality. In general, FDG PET-CT is accurate for diagnosis of marrow and bone involvement in Hodgkin lymphoma but, in this case, DW-MRI revealed bone disease not diagnosed on FDG PETCT. Further research is needed to compare the relative merits of DW whole-body MRI with FDG PET-CT in the staging and monitoring of lymphoma.

Multivisceral resection for gastric cancer: a systematic review

The overall prognosis and survival of patients with advanced gastric cancer is generally poor. One of the most powerful predictors of outcomes in gastric cancer surgery is an R0 resection. However, the extent of the required surgical resection and the additional benefit of multivisceral resection (MVR) are controversial. Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Seventeen studies were included in this review. Among the 1343 patients who underwent MVR, overall complication rates ranged from 11.8 to 90.5%. Perioperative mortality was found to be 0-15%. Pathological T4 disease was confirmed in 28.8-89% of patients. R0 resection and extent of nodal involvement were important predictors of survival in patients undergoing MVR. Patient outcomes may also be affected by the number of organs resected. Gastrectomy with MVR can be safely pursued in patients with locally advanced gastric cancer to achieve an R0 resection. MVR may not be beneficial in patients with extensive nodal disease.

Systematic Review of Prognostic Factors Related to Overall Survival in Patients with Stage IV Colorectal Cancer and Unresectable Metastases

With the improvements in newer chemotherapeutic agents, the role of primary tumour resection in patients with stage IV colorectal cancer is controversial. In many cases primary tumour resection is still favoured as first-line management. However, a detailed understanding of independent prognostic factors related to survival is necessary before making this decision. A literature search was conducted using Medline and Embase. Studies that performed multivariate analysis on overall survival of patients with incurable stage IV colorectal cancer were included in this review. Fourteen retrospective studies involving 3209 patients were included. Clinical variables analysed to consistently have independent prognostic significance for long-term survival included the patients' performance status (<2), volume of liver metastases (<50%), nodal stage (N0), disease-free resection margins, and treatment with chemotherapy and/or primary tumour resection. Cancer antigen (CA) 19-9, low albumin, elevated ALP levels, apical lymph node involvement, presence of ascites, and postoperative transfusion were each assessed by only one study and found to be independently associated with survival. Factors inconsistently reported to have independent prognostic significance were age, ASA score, preoperative CEA levels, primary tumour location, tumour size and differentiation, peritoneal dissemination, and extrahepatic metastases. Each patient should be reviewed individually on the basis of the above independent prognostic factors before deciding to resect the primary tumour. Patients with a poor performance status, extensive hepatic metastases, and extensive nodal disease detected preoperatively are less likely to have a survival benefit. Nonsurgical approaches to manage these patients should be given careful consideration.

Relapse of Lymphoma After Allogeneic Hematopoietic Cell Transplantation: Management Strategies and Outcome.

AbstractAbstract 4503 Background&Objective:The management of lymphoma which has relapsed after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), withdrawal of immunosuppression, rituximab, chemotherapy, radiation, immunotherapy and experimental treatments, but response and survival are uncertain. Result:We analyzed 72 patients with relapsed or progressive lymphoma after allogeneic HCT (1991-2007); 44 non-Hodgkin's lymphoma (7 mantle cell, 5 indolent, 19 diffuse large B [DLBCL], and 13 T/NK cell) and 28 Hodgkin's lymphoma (HL). At HCT, 62 patients (86%) were in remission (22 CR, 40 PR); nine (13%) had progressive disease and one had stable disease. Conditioning was myeloablative (n=17) or reduced intensity conditioning (RIC) (n=55). Relapse or progression occurred at a median of 99 days (0-1898 days; 25–75% 43–194 days). At relapse, 41 (57%) had extensive nodal disease and 56 (78%) had extranodal organ involvement. Management of relapse included: no therapy (n=5, 7%), reduction of immunosuppression (RIS) (n=58, 81%), chemotherapy alone (n=14, 19%), immunotherapy alone (n=20, 28%), combined chemo-immunotherapy (n=7, 10%) donor lymphocyte infusion (DLI) (n=7, 10%), second allogeneic HCT (n=2, 3%), radiation (n=23, 32%) and other therapy (n=7, 8%). Twenty-four patients achieved a remission (15 CR, 9 PR) to the initial salvage therapy: RIS (n=13), combined chemo-immunotherapy(n=5), chemotherapy alone (n=2), radiation (n=3) or DLI (n=1). Overall, 40 (56%) patients responded (30 CR, 8 PR, 2 stable disease) with a median post-relapse overall survival of 28 months (range 0–147 months). At 3 years following relapse, 44% (95% CI, 32–56%) survive. Favorable prognostic factors for improved 3-year survival after relapse include stage I-III at relapse, single site of relapse and most importantly, later relapse (>100 days after HCT [3 year survival 53% vs. 36%, p=0.02]). Conclusion:The overall prognosis of relapsed lymphoma after allogeneic HCT differs based upon extent of disease at relapse and time of relapse. Appropriate therapeutic approaches (RIS, combined chemo-immunotherapy, radiation or DLI) in these high risk, post transplant relapsed patients can yield promising outcome. Prospective study of post-relapse therapy to determine the most effective management strategies are warranted. Disclosures:No relevant conflicts of interest to declare.

340 Disconcordance between number of scintigraphic and perioperatively identified sentinel lymph nodes and axillary tumour recurrence

Intraoperative assessment of sentinel lymph nodes (SLNs) has the advantage of allowing breast cancer patients with tumor-positive SLNs to avoid a second surgery by immediately proceeding to axillary lymph node dissection (ALND). However, there are several reasons why the use of intraoperative assessment should be questioned. Whereas ALND was traditionally advised for all breast cancer patients with tumor-positive lymph nodes for axillary staging and locoregional control, more recent studies have demonstrated safety of omitting ALND in a substantial number of patients.In addition, there are concerns about the accuracy of intraoperative assessment methods including frozen section analysis, touch preparation cytology and one-step nucleic acid amplification. Moreover, intraoperative assessment of SLNs denies patients the opportunity to contribute to their treatment planning. In our opinion, intraoperative assessment of axillary lymph nodes should be reserved for patients who still have a strict indication for ALND. Patients with clinical node negative disease (cN0) and one or two positive SLNs can be safely treated with breast conserving surgery and radiotherapy. There has been more controversy for cN0 patients who are treated with mastectomy since radiotherapy is not routinely administered in these patients. However, there is increasing evidence that ALND may be omitted in patients undergoing mastectomy who have a low tumor-burden in their SLNs. Therefore, we defend the position that in cN0 patients undergoing mastectomy, SLNB should be performed and full pathologic evaluation of the SLN should be awaited. In cN0 patients undergoing neoadjuvant systemic therapy (NST) intraoperative assessment of SLNs can be omitted since ALND will not provide therapeutic benefit. It is being hypothesized that patients with limited axillary disease prior to NST who remain node-positive after NST could be treated safely with axillary radiotherapy instead of ALND. In these patients, omitting intraoperative assessment might be a reasonable option. In patients with extensive nodal disease prior to NST intraoperative assessment of axillary lymph nodes should be performed.

Extensive Nodal Disease May Impair Axillary Reverse Mapping in Patients With Breast Cancer

The aim of axillary reverse mapping (ARM) is to preserve arm lymphatics in patients with breast cancer who underwent surgical axillary staging. From June 2007 to December 2008, 49 patients who required axillary dissection (AD) underwent ARM. One milliliter of patent blue dye was injected in the ipsilateral arm, and all blue nodes identified during AD were sent separately for pathologic examination. Main variables associated with the detection rates of blue lymphatics, the pathologic status of blue and nonblue nodes, and the complications of the procedure were analyzed. Results Identification rates of blue lymphatics and blue nodes were 73.5% and 55.1%, respectively. Blue node identification was influenced by the time elapsed between injection of blue dye and surgery (P = .002) but not by the learning curve of the procedure. Although the blue node was clear of metastases in 24 of 27 patients, three patients with extensive nodal metastatic involvement (ie, pN2a and pN3a) showed breast cancer metastatic cells in the blue nodes as well. The only adverse effect of the procedure was skin tattooing at the injection site, which disappeared within 4 months in almost 80% of the procedures. In patients with clinically negative axillary nodes, additional study is warranted to assess whether ARM may be used to spare the lymphatics from the arm. In the presence of extensive nodal disease, this technique may identify metastatic blue nodes, which demonstrates that there is not reliable separation of arm and breast lymphatic pathways.

Definitive Radiotherapy for T1–2 Hypopharyngeal Cancer: A Single Institution Experience

Definitive Radiotherapy for T1–2 Hypopharyngeal Cancer: A Single Institution Experience

ES03 THE DELPHIC LYMPH NODE AND THYROID CANCER

Background Named after the oracle of Delphi, the Delphic (or prelaryngeal) lymph node has long been regarded as a predictor of malignancy in thyroid cancer. It also has a notorious reputation for being a marker of advanced nodal disease. There is no current medical literature to support or refute these claims. The aim of this study was to determine the true significance of Delphic lymph node involvement in thyroid cancer.Methods 1,000 consecutive patients undergoing total thyroidectomy formed the study population. All information was obtained from a prospectively maintained database as well as from review of the histopathology records.Results 227 of 1,000 (22.7%) had a final diagnosis of thyroid cancer. In 63 of 227 (27.8%), the final diagnosis of cancer was unsuspected. The Delphic lymph node was removed in 112 of 227 patients, with 22 of 112 cancerous. Thus, 19.6% of patients had involvement of the Delphic lymph node when it was removed. Delphic node involvement was associated with significantly greater nodal disease (10.1 vs 1.4 nodes; p &lt; 0.05). No patient in either group had Delphic node involvement diagnosed on clinical grounds preoperatively.Conclusion Despite its reputation, the Delphic lymph node is not itself an independent predictor of the presence of thyroid cancer. It is however a useful marker of extensive local nodal disease. Identifying intra‐operatively whether the Delphic node is involved may assist in planning the extent of neck dissection during total thyroidectomy.

Factors influencing accrual to ACOSOG Z0011, a randomized phase III trial of axillary dissection vs. observation for sentinel node positive breast cancer

601 Background: The American College of Surgeons Oncology Group opened a phase III randomized trial to assess the value of axillary node dissection (ALND) after positive sentinel node biopsy (SNB). After 5.5 years, the trial closed due to poor accrual with only 891 patients of the planned 1900 accrued. The purpose of the current analysis is to assess factors impacting accrual to Z0011. Methods: Women having SNB for T1 or T2 breast cancer were eligible for participation in the Z0010 trial to assess the significance of micrometastases identified by immunohistochemistry. If the SN was positive for metastasis by H&amp;E, the patient was eligible for randomization on Z0011 trial. Intraoperative (IOR) and postoperative randomization were allowed. Patients having SNB outside of the Z0010 trial were eligible. Results: 1003 patients from the Z0010 trial were eligible for randomization on Z0011. Of these, only 37% were entered in Z0011. Z0010 participants accounted for 42% of patients in Z0011. 16% of patients not randomized refused ALND. 69% of those not randomized had ALND. 67% of these had no additional positive nodes. Only 14% had ≥ 4 positive nodes. Enrollment of eligible Z0010 patients varied by type of institution: 25% at academic sites, 42% at teaching affiliated and 53% at community (p &lt; 0.0001). By geographic region, sites in the South entered 42% of eligible patients compared with 24–36% in other geographic regions (p=0.0027). Only 32% of patients were consented for IOR based on frozen section of the SN. Sites in the South and West were less likely to use IOR (25% and 28%) compared to Northeast and Midwest (45% and 46%) (p &lt; 0.0001). 110 sites participated in Z0011, yet 48% of patients were enrolled by 10% of sites. Conclusions: Failure of this important trial to accrue as planned is likely related to the clinical bias of physicians and patients to standard ALND. Yet, 2/3 of patients had no additional positive nodes and extensive nodal disease was infrequent. While it was thought that IOR might improve accrual to Z0011, the most successful sites were less likely to use this approach. Community surgeons were most successful in randomizing patients. [Table: see text]

Clinicopathologic Features Associated With Having Four or More Metastatic Axillary Nodes in Breast Cancer Patients With a Positive Sentinel Lymph Node

The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset. Records were reviewed for 285 patients from 2 comprehensive cancer centers who underwent completion ALND after resection of a metastatic SLN from 1995 to 2002. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Forty-one cases (14%) were found to have at least four positive nodes after ALND. Fisher's exact test revealed the following features to be significantly (P < .05) associated with having four or more nodal metastases: tumor size >2 cm, lymphovascular invasion, an increasing ratio of positive SLNs to the total number of resected SLNs, extranodal extension, and the size of the SLN metastasis. Patients whose largest SLN metastasis was <2 mm had only a 1.4% risk of having four or more metastatic nodes (P < .0001). We conclude that patients with SLN micrometastases face an extremely low likelihood of having extensive nodal disease on completion ALND. Patients with larger primary tumors, lymphovascular invasion, and extranodal extension are more likely to have ALND findings that will affect their cancer management.