Regional Metastatic Disease Research Articles

Abstract 5052: MicroRNA alterations following radiation in melanoma

Abstract Purpose: Melanoma only accounts for 4% of skin cancer while causing 75% of cancer related deaths. Also, the incidence is increasing with the annual percent change in the United States reported as 2.4% for the period 1986-2006 and currently increasing faster than any other cancer worldwide. Moreover, patients who develop locally advanced or metastatic melanoma have limited treatment options with 5-year survival rates of 65% and 16%, for regional disease and metastatic disease, respectively. Historically, melanoma was regarded as resistant to radiation therapy (RT), however, recently the utility of RT has been re-explored in the adjuvant setting with fractionated radiotherapy (FRT) and also in the oligometastatic setting with stereotactic radiotherapy (SBRT), and does show increase in local control in appropriately selected patients. The importance of microRNA (miRNA) in cancer continues to be elucidated and in melanoma they are extensively reported as having significant roles in melanoma transformation, progression, invasiveness, metastasis, and outcome/prognosis. However, there are no reports of melanoma miRNA profiling and RT. miRNA expression profiles change as a consequence of RT in several tumor types. Experiments show delivery of miRNA in vivo appears both feasible and tolerable in murine models. Additionally, correcting miRNA deregulation has been shown to mitigate the tumorigenic phenotype and also induce radiosensitivity in vitro and in vivo. Materials/Methods: We cultured more than a dozen melanoma cell lines and sequenced for mutations in key genes such as B-RAF, N-RAS, etc. to group them. Next we isolated their miRNA of untreated and treated with 6 Gray dose of radiation isolated at 5 days. The miRNA expression was quantified using RT-qPCR of TaqMan Low Density Arrays (TLDA) cards. The data is reported using hierarchical clustering and those miRNAs significantly deregulated have been delineated. Results/Discussion: We have characterized the miRNA expression profiles of melanoma cell lines when comparing untreated and those treated with radiation. Our data indicate that miRNA profiles done pre and post RT are significantly different. To this end we have identified clusters of miRNA associated with RT sensitivity/resistance. Thus, these miRNAs could be important factors in response to RT and their differential expression may be linked to resistance to RT. Consequently, it is conceivable that these miRNA and/or their mRNA targets could be used in the future as targets for drug development to radiosensitize melanoma and thus further improve outcomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5052. doi:1538-7445.AM2012-5052

951 PROGNOSTIC VALUE OF PATHOLOGIC GLEASON SCORE AFTER NEOADJUVANT HORMONAL THERAPY FOR PREDICTING SYSTEMIC PROGRESSION FOLLOWING RADICAL PROSTATECTOMY

2007, we identified all men with a diagnosis of prostate cancer who received chemotherapy commonly used to treat prostate cancer and androgen suppression therapy (AST) (n 109,794). After eliminating those diagnosed at autopsy, from Louisiana (2005 year), inadequate information about AST or 6 months of AST, prior or subsequent diagnosis of a second primary and with unknown or missing variables, we identified a cohort of 23,618 men. We compared cancer specific survival and overall survival among men who had previously undergone radical prostatectomy, radiation therapy/brachytherapy and neither of these types of therapy for primary tumor. Cox proportional hazard models were used to assess survival. RESULTS: A majority of the patients were 70 years and Caucasian. They had medium or high grade tumors and were diagnosed at stage T1-2. 5% had undergone RP and 93% had received prior radiation while 1.7% received no therapy for primary tumor. About 88% of the patients had a Charlson score of 0-1. Cancer specific survival was significantly worse among men who had neither surgery nor radiation for primary tumor when compared to those who had prior radical prostatectomy (HR 5.313 p 0.0001). There was no difference in cancer specific survival among those who underwent surgery or radiation for their primary tumor. Overall survival was worse among those who received radiation (HR 1.4 p 0.0001) or neither surgery nor radiation (HR 4.06 p 0.0001) compared to those who had surgery. CONCLUSIONS: Prior therapy to the primary prostate cancer in the form of radical prostatectomy or radiation appears to confer a survival advantage in patients who subsequently go on to develop metastatic disease and receive androgen suppressive therapy and chemotherapy. If further validated, this suggests that radical prostatectomy or radiation therapy could be considered even among men found to have incidental regional metastatic disease at the time of surgery or on imaging.

950 IMPACT OF PRIOR LOCAL THERAPY ON SURVIVAL IN MEN RECEIVING CHEMOTHERAPY FOR METASTATIC PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2012950 IMPACT OF PRIOR LOCAL THERAPY ON SURVIVAL IN MEN RECEIVING CHEMOTHERAPY FOR METASTATIC PROSTATE CANCER Oluwakayode Adejoro, Sean Elliott, and Badrinath Konety Oluwakayode AdejoroOluwakayode Adejoro Minneapolis, MN More articles by this author , Sean ElliottSean Elliott Minneapolis, MN More articles by this author , and Badrinath KonetyBadrinath Konety Minneapolis, MN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1048AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The benefit of prior local therapy in the form of radiation or radical prostatectomy in men who subsequently go on to develop metastatic disease and receive chemotherapy is not well characterized. We sought to assess the impact of a previously treated primary tumor in the prostate on survival following androgen suppression therapy and chemotherapy for metastatic prostate cancer in men who progress to develop metastatic disease. METHODS Using the SEER Medicare dataset from 1992-2007, we identified all men with a diagnosis of prostate cancer who received chemotherapy commonly used to treat prostate cancer and androgen suppression therapy (AST) (n=109,794). After eliminating those diagnosed at autopsy, from Louisiana (2005 year), inadequate information about AST or < 6 months of AST, prior or subsequent diagnosis of a second primary and with unknown or missing variables, we identified a cohort of 23,618 men. We compared cancer specific survival and overall survival among men who had previously undergone radical prostatectomy, radiation therapy/brachytherapy and neither of these types of therapy for primary tumor. Cox proportional hazard models were used to assess survival. RESULTS A majority of the patients were >70 years and Caucasian. They had medium or high grade tumors and were diagnosed at stage T1-2. 5% had undergone RP and 93% had received prior radiation while 1.7% received no therapy for primary tumor. About 88% of the patients had a Charlson score of 0-1. Cancer specific survival was significantly worse among men who had neither surgery nor radiation for primary tumor when compared to those who had prior radical prostatectomy (HR 5.313 p<0.0001). There was no difference in cancer specific survival among those who underwent surgery or radiation for their primary tumor. Overall survival was worse among those who received radiation (HR 1.4 p<0.0001) or neither surgery nor radiation (HR 4.06 p<0.0001) compared to those who had surgery. CONCLUSIONS Prior therapy to the primary prostate cancer in the form of radical prostatectomy or radiation appears to confer a survival advantage in patients who subsequently go on to develop metastatic disease and receive androgen suppressive therapy and chemotherapy. If further validated, this suggests that radical prostatectomy or radiation therapy could be considered even among men found to have incidental regional metastatic disease at the time of surgery or on imaging. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e386-e387 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Oluwakayode Adejoro Minneapolis, MN More articles by this author Sean Elliott Minneapolis, MN More articles by this author Badrinath Konety Minneapolis, MN More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

EGFR expression in advanced head and neck cutaneous squamous cell carcinoma

The significance of epidermal growth factor receptor (EGFR) expression in advanced cutaneous squamous cell carcinoma (SCC) of the head and neck remains poorly understood. We performed a retrospective review of patients with advanced-stage (stage III or stage IV) cutaneous SCC of the head and neck (n = 56). The majority of patients (91%) had stage III disease, with 54% having regional metastasis and 9% with distant metastasis. Two-year survival was 64% and the 5-year survival was 56%. EGFR was found to be overexpressed in 56% of primary tumors and 58% of regional metastatic disease. Overall survival did not correlate with EGFR (p = .47) expression in primary lesions, nor was it associated with an increase in regional (p = .74) or distant metastasis (p = .56). Furthermore, there was no correlation between clinicopathologic characteristics and EGFR expression These data do not suggest upregulation of EGFR is associated with poor survival or aggressive disease.

Prognostic factors for survival in melanoma patients with brain metastases

One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS). An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS. Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded. The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials.

Differential Protein Expression Profiling by iTRAQ-Two-dimensional LC-MS/MS of Human Bladder Cancer EJ138 Cells Transfected with the Metastasis Suppressor KiSS-1 Gene

KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 gene expression has been shown to be inversely correlated with increasing tumor stage, distant metastases, and poor overall survival in bladder tumors. To identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteomics analysis of bladder cancer cells (EJ138) transiently transfected with a vector encompassing the full-length KiSS-1 gene using an iTRAQ (isobaric tags for relative and absolute quantitation) approach. Protein extracts collected after 24- and 48-h transfection were fractionated and cleaved with trypsin, and the resulting peptides were labeled with iTRAQ reagents. The labeled peptides were separated by strong cation exchange and reversed phase LC and analyzed by MALDI-TOF/TOF MS. Three software packages were utilized for data analysis: ProteinPilot for identification and quantification of differentially expressed proteins, Protein Center for gene ontology analysis, and Ingenuity Pathways Analysis to provide insight into biological networks. Comparative analysis among transfected, mock, and empty vector-exposed cells identified 1529 proteins with high confidence (>99%) showing high correlation rates among replicates (70%). The involvement of the identified proteins in biological networks served to characterize molecular pathways associated with KiSS-1 expression and to select critical candidates for verification analyses by Western blot using independent transfected replicates. As part of complementary clinical validation strategies, immunohistochemical analyses of proteins regulated by KiSS-1, such as Filamin A, were performed on bladder tumors spotted onto tissue microarrays (n = 280). In summary, our study not only served to uncover molecular mechanisms associated with the metastasis suppressor role of KiSS-1 in bladder cancer but also to reveal the biomarker role of Filamin A in bladder cancer progression and clinical outcome.

Risk factors for central nervous system (CNS) metastases in patients with stage I-III breast cancer.

1063 Background: Some subpopulations of breast cancer patients have an increased risk of developing CNS metastases. The aim of this study is to identify risk factors for developing CNS metastases in stage I-III breast cancer patients. Methods: A retrospective review of 1,232 stage I-III breast cancer patients who had undergone chemotherapy, surgery, and/or radiotherapy, was performed. Estrogen/progesterone receptor (ER, PR) and HER2 status was determined by immunohistochemistry. The endpoint was CNS metastases-free survival. Tumor phenotypes were classified as luminal A (ER+ and/or PR+, HER2-); luminal B (ER+ and/or PR+, HER2+); triple- negative (ER-, PR-, HER2-); HER2/neu (ER-, PR-, HER2+). The association between histologic features and occurrence of CNS metastases was evaluated with univariate and multivariate analyses. Results: Median follow-up was 7.6 years, 416 (34%) patients had local, regional, or distant metastatic disease, 62 (5%) of whom had CNS metastases at any time before last follow-up, and 36 (39%) patients had CNS metastases as site of first recurrence. Comparison of median time to diagnosis of CNS metastases showed significant differences by molecular subtype (p=0.04). Triple-negative and HER2 subtypes had the shortest time to recurrence (21.9 and 29.7 months, respectively) versus luminal A and B subtypes (48.7 and 30.4 months, respectively). Main univariate predictive factors for CNS recurrence were: negative hormone receptor (7.8% of CNS metastases), positive nodal status (8.4% of CNS metastases >3 N+), molecular subtype HER2 (8.2%), p<0.001 for all. Main multivariate predictive factor was molecular subtype (p<0.001), using luminal A as reference, other molecular subtypes were expressed by hazard ratios (HR); luminal B (HR=3.4, 95%CI; 1.6 – 7.2), triple-negative (HR=4.0, 95%CI; 1.9–8.4), HER2 (HR=4.3, 95%CI; 2.0–9.1). Conclusions: Molecular subtype is the strongest risk factor for developing CNS metastases in stage I-III breast cancer. Time to diagnosis of CNS metastases Molecular subtype N N pt CNS metastases Median time (mo) P (Kruskal Wallis) Luminal A 577 12 (2.1%) 48.3 0.04 Luminal B 207 15 (7.2%) 30.4 Triple-negative 254 19 (7.5%) 21.9 HER2 194 16 (8.2%) 29.7 No significant financial relationships to disclose.

Cutaneous head and neck SCCs and risk of nodal metastasis – UK experience

To identify the risk of developing metastases to regional nodes in patients with cutaneous squamous cell carcinomas (CSCCs) of the head and neck. A retrospective study of patients with CSCC treated with surgical excision alone between 2000 and 2002 was performed. Demographic details of the patients, the site, size, differentiation, depth of invasion, clearance of surgical margins, and the presence of perineural or lymphovascular invasion of the lesion were documented. During the follow up period, patients with regional metastases were identified. The site of the metastasis and the time after the primary resection were documented and statistical analysis was performed using Chi-square and logistic regression analysis. One hundered and ninety-four patients were included and 218 CSCCs were excised in total during the period of 3 years. The scalp was the most common site of skin lesion, followed by the ear. The incidence of regional metastatic disease was found to be 5.15%. The parotid gland was the most common area of regional metastasis. No metastases occurred after the first 2 years of follow up. The pinna, the poor differentiation and incomplete excision margins were found to be associated with regional metastasis independently, with odds ratio of 16, 21, and 2 respectively. The rate of regional metastasis from CSCC remains low. The parotid gland was the most favoured metastatic site. Patients with poorly differentiated squamous cell carcinoma (SCC) located on the ear and incomplete excision margins were at the greatest risk for developing regional lymph node metastasis and require close follow up.

Transarterial Chemoembolization for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and is responsible for ~500,000 deaths worldwide annually.1 The incidence almost equals the mortality. It is the most common cause of death in patients with compensated liver cirrhosis. HCC usually arises in the setting of chronic liver disease, commonly from hepatitis B, C, or alcohol abuse. In fact, 80% of HCC arises in the setting of cirrhosis. Despite available treatment, survival rates of HCC remain poor, with an estimation of 54% at 1 year, 40% at 2 years, and 28% at 3 years.2 The only definitive therapy is liver transplantation. Resection, when possible, is not curative as cirrhosis remains a comorbidity. Even with transplantation in early HCC associated with cirrhosis, there is still a potential risk for HCC recurrence.3 Typically, transplantation is reserved for candidates with a single lesion up to 5 cm in diameter, or multiple lesions up to three with a total diameter of 9 cm, with no vascular invasion and no regional or distant nodal metastatic disease. The 4-year survival rate for transplantation is ~80%. Similar survival rates have been reported for larger HCCs.4 With transplantation the only curative option, qualified patients often languish on the waiting list due to the current organ shortage. It has been shown that a 6- to 12-month waiting time for orthotopic liver transplantation (OLT) is associated with reduced overall survival compared with subjects with lesser waiting time due to progression of tumor beyond favorable criteria or due to drop-out for other reasons.5 In fact, the average waiting time can exceed one-year, at which point the drop-out rate is 30 to 40%. Drop-out rate from HCC progression beyond favorable criteria is estimated at 10% at 6 months.6 Surgical resection can increase the OLT rate to 3.7% and 10.7% for a waiting list of 6 and 24 months, respectively. However, surgical resection is associated with significant risks in the setting of cirrhosis, including hemorrhage and hepatic decompensation.7 It is in this setting that other therapies have been developed to treat, though not necessarily cure, patients with HCC to prevent HCC progression and increase the chance of organ transplantation, to downstage patients into favorable criteria for liver transplantation, and to prolong survival and improve quality of life for those who do not qualify for liver transplantation. Therapies that have been in use include transarterial chemoembolization (TACE), ablative therapies (including both thermal and cryoablation), radio embolization, and percutaneous alcohol injection. The focus of this article is on the rationale, technique, and results of TACE in HCC in the setting of cirrhosis.

Surgery and radiotherapy in the treatment of cutaneous melanoma

Adequate surgical management of primary melanoma and regional lymph node metastasis, and rarely distant metastasis, is the only established curative treatment. Surgical management of primary melanomas consists of excisions with 1–2 cm margins and primary closure. The recommended method of biopsy is excisional biopsy with a 2 mm margin and a small amount of subcutaneous fat. In specific situations (very large lesions or certain anatomical areas), full-thickness incisional or punch biopsy may be acceptable. Sentinel lymph node biopsy provides accurate staging information for patients with clinically unaffected regional nodes and without distant metastases, although survival benefit has not been proved. In cases of positive sentinel node biopsy or clinically detected regional nodal metastases (palpable, positive cytology or histopathology), radical removal of lymph nodes of the involved basin is indicated. For resectable local/in-transit recurrences, excision with a clear margin is recommended. For numerous or unresectable in-transit metastases of the extremities, isolated limb perfusion or infusion with melphalan should be considered. Decisions about surgery of distant metastases should be based on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases.

Permanent Interstitial Reirradiation With 198Au as Salvage Therapy for Low Volume Recurrent Gynecologic Malignancies

To examine the Indiana University experience using 198Au permanent interstitial reirradiation (198Au-IRI) in the treatment of selected patients with recurrent gynecologic malignancies. A retrospective review of 19 patients with recurrent gynecologic malignancies treated with 198Au-IRI between 1994 and 2006 was performed to evaluate disease response, local control, disease-free survival, overall survival, and toxicity. All patients had no evidence of regional or distant metastatic disease at the time of treatment. Median age at treatment was 76 years (range, 38-87). Median tumor volume was 3.3 cm3 (range, 0.8-21.3). Median previous radiation dose from all radiation modalities was 67 Gy (range, 38.7-91.6). Median prescribed dose was 50 Gy (range, 25-55). With a median follow-up of 21 months, complete responses were obtained in 94.7% of patients, with local control being achieved after 198Au-IRI in 63.1% of patients. Including further salvage therapy, local control was ultimately achieved in 78.9% of patients. At the time of the analysis, 52.6% of patients were alive with no evidence of disease. Treatment-related toxicity was limited, with only 1 grade III toxicity (5.3%). 198Au-IRI is a safe, cost-effective, and reasonably efficacious method for controlling locally recurrent, low-volume, well-selected gynecologic malignancies, and treated with previous full-dose radiotherapy. It represents a reasonable potential therapeutic option in the salvage setting in patients who meet these criteria, particularly in women who are not candidates for or are unwilling to undergo radical salvage surgery.

Microcystic adnexal carcinoma: a diagnostic and therapeutic challenge

Microcystic adnexal carcinoma (MAC) is a rare cutaneous neoplasm that is often diagnosed after having been present for a significant period of time. It appears bland on histologic evaluation despite its locally aggressive behavior. Actual skin involvement is significantly more extensive than can be determined clinically and because of this, therapy is challenging. Though metastasis is rare, there have been reports of both regional and distant metastatic disease. Several treatment modalities have been used to date, including standard excision (SE), Mohs micrographic surgery (MMS), irradiation, chemotherapy, and observation. There has also been discussion in the literature regarding techniques than can aid in assurance of clear margins with MMS. We review the literature on MAC, including the various therapeutic options, addressing when one modality may be preferable over others. In general, MMS offers the highest likelihood of clear margins and cure with the fewest procedures.

Preoperative 18F-FDG-PET/CT imaging and sentinel node biopsy in the detection of regional lymph node metastases in malignant melanoma

The objective of this study was to evaluate the role of preoperative 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning, preoperative lymphoscintigraphy (LS), and sentinel lymph node biopsy in patients with malignant melanoma. Fifty-two patients (36 men: 16 women; mean age 55.0+/-13.0 years; median age 61 years; range 17-76 years) with malignant melanoma were selected. According to the latest version of the American Joint Committee on Cancer staging system, the disease in the study patients was initially classified as either stage I or II. The other primary tumor characteristics were mean Breslow depth=2.87 mm and median=2 mm; range 1-12.0 mm and Clarks levels III-V. None of the study patients had clinical or radiological evidence of regional lymph node metastatic disease. At least one sentinel node was identified in all patients. Preoperative LS detected a total of 111 sentinel lymph nodes (average 2.13 sentinel lymph node per patient) and demonstrated a single nodal draining basin in 38 (73%) patients and multiple (2-3 draining basins) in the remaining 14 (27%) patients. Fourteen out of the 52 patients (27%) had at least one involved sentinel node. Positron emission tomography was true positive in two patients with a sentinel node greater than 1 cm and false positive in two other patients. In this study, the detection of sentinel lymph node by LS and gamma probe had a sensitivity of 100%. In contrast, 18F-FDG-PET imaging demonstrated very low sensitivity (14.3%; 95% CI, 2.5 to 44%) and positive predictive value (50%; 95% CI, 9 to 90%) for localizing the subclinical nodal metastases. The specificity, net present value, and diagnostic accuracy were 94.7, 75, and 73%, respectively. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography imaging is not able to substitute LS/sentinel lymph node biopsy in patients at stage I or II.

Can extra capsular spread of nodal metastasis be predicted from primary tumour histopathology in oral squamous cell carcinoma?

Introduction: It is well established that the presence of regional nodal metastatic disease in oral squamous cell carcinoma halves overall survival rates. When extra capsular spread is also found, the prognosis is further reduced. Specific histological features of the primary tumour may predict for the presence of extra capsular spread.

Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma

Selective neck dissection (SND) is known to be a valid procedure to stage the clinically N0 neck but its reliability to control metastatic neck disease remains controversial. This study analysed if selective neck dissection is a reliable procedure to prevent regional metastatic disease in head and neck squamous cell carcinoma (HNSCC). We retrospectively analysed the medical records of 163 previously untreated patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx treated initially in our department from January 1990 to December 2002. All patients had unilateral or bilateral SND, in combination with surgical resection of the primary tumour. SND was performed in 281 necks. Finally, 146 patients who underwent 249 SND (39 I-III, I-IV, 210 II-IV, II-V) had adequate follow-up and were assessed for the regional control. The median follow-up was 37 months (1-180 months). The end points of the study were neck control following SND and overall survival. Twenty-five percent (30/119) of patients staged cN0 had lymph node (LN) metastasis. Overall, regional recurrence was observed in 2.8% of the necks (7/249): 1.6% (4/249) in dissected field and 1.2% (3/249) in undissected field. Seventy-eight percent (194/249) of the necks were staged pN0 with a subsequent failure rate of 1.5% (3/194); 16% (39/249) were staged pN1 and postoperative radiotherapy (PORT) was proposed in 21 of these patients. The failure rate with PORT was 9.5% and 5.5% without PORT. Six percent (16/249) of the necks were staged pN2b and all had PORT with one subsequent recurrence. Extracapsular spread (ECS) was reported in 16.5% of positive SND specimens (9/55); all by one were treated by PORT with a subsequent failure rate of 22% (2/9). At 3 years, overall survival for the whole population was 70% and statistically highly correlated with pN stage (p<0.001). These results support the reliability of SND to stage the clinically N0 neck. SND is a definitive operation not only in pN0 but also in most pN1 and pN2b necks. PORT is not justified in pN1 neck without ECS. In pN2b necks, the low rate of recurrence supports adjuvant PORT. The presence of ECS, despite adjuvant PORT, remains associated with a higher risk of recurrence.

Fluorescent labeled anti‐EGFR antibody for identification of regional and distant metastasis in a preclinical xenograft model

Detection of regional and distant metastatic disease has significant implications for patient management. Fluorescent imaging may be a useful technique for metastasis detection and removal. Anti-epidermal growth factor receptor antibody (cetuximab) and isotype-matched control antibody (immunoglobulin G [IgG]) were labeled with a near-infrared fluorophore (Cy5.5), then systemically administered to mice with tumors resulting from either intraoral or intravenous injections of head and neck squamous cell carcinoma. Mice were sacrificed before undergoing fluorescent stereomicroscopy to assess pulmonary or cervical lymph node metastasis. Fluorescent areas were serially excised until wound bed demonstrated negative fluorescence. Mice bearing pulmonary metastases displayed diffuse background after IgG-Cy5.5 injection, but demonstrated a speckled fluorescent pattern across lung surface following cetuximab-Cy5.5 injection. Mice bearing cervical metastases demonstrated clear fluorescence of primary tongue tumor and bilateral cervical nodes. Fluorescence correlated with histopathology. These data suggest that cetuximab-Cy5.5 may have clinical utility in the detection and guided the removal of regional and distant micrometastasis.

Lymphatic invasion revealed by multispectral imaging is common in primary melanomas and associates with prognosis

Lymphatic invasion by tumor cells has been noted infrequently in primary melanomas. Our primary hypotheses were that using immunohistochemical markers of lymphatic vessels and of tumor cells would improve detection of lymphatic invasion and that lymphatic invasion would correlate with regional nodal metastatic disease. This study included 106 patients who were diagnosed between 1972 and 1991 and who had 10 years or more of follow-up. We performed dual immunohistochemical stains for podoplanin (for lymphatic vessels) and S-100 (for melanoma cells). Lymphatic invasion was identified by light microscopy and confirmed by multispectral imaging analysis. Lymphatic invasion was detected by morphology alone in 5 cases (4.7%) in contrast to immunohistochemical staining augmented by multispectral imaging analysis where 35 cases (33%) were identified (P < .0001). Lymphatic invasion was significantly associated with time to regional nodal metastatic disease, as well as first metastasis and melanoma-specific death. "Local metastasis," defined by immunohistochemistry-detected lymphatic invasion, satellites, or neural invasion, identified 64% of those who had regional nodal metastatic disease within 5 years of diagnosis. Lymphatic invasion is an underobserved phenomenon in primary melanomas that can be better detected by immunohistochemical staining. The presence of lymphatic invasion may be a clinically useful predictor of regionally metastatic disease.

Enquête observationnelle sur les variations d’incidence par stade des cancers de la prostate dans la région Nord-Pas-de-Calais entre 1998 et 2004

The aim of this work is to study variations of prostate cancer incidence by stage as a function of time and place in a region of France. Retrospective observational survey conducted in five private and public urology centres representative of the various demographic features of the Nord-Pas-de-Calais region. In each centre, the medical records of the first 25 cases of prostate cancer diagnosed in 1998, 2002 and 2004, identified from histology laboratory data, were studied by means of a case report form evaluating the circumstances of diagnosis, PSA level, grade, stage (TNM 97, classification) and initial management. This analysis was based on 123, 124 and 125 patients in five centres in 1998, 2002 and 2004, respectively. The age at diagnosis ranged from 71.14 to 68.9 years between 1998 and 2004 (p=0.054). Median PSA decreased over this six-year period from 18 to 10.8 ng/ml. Between 1998 and 2004, the percentage of patients with localized cancer (PSA<20 ng/ml) increased from 44.8 to 66.4% (p<0.05), the percentage of patients with locally advanced cancer (PSA between 20 and 50 ng/ml) decreased from 17 to 9.6% (p<0.05), the percentage of patients with regional or distant metastatic disease (N1 and/or M1 and/or PSA>50 ng/ml) decreased from 29.4 to 22.4% (p<0.05) and the percentage of patients receiving curative treatment increased from 30 to 54.4% (p<0.005). The prostate cancer incidence by stage varied between 1998 and 2004, with a significantly higher proportion of localized stages, which can be explained by the increased use of screening and diagnostic tests. Routine surveys can measure trends and the amplitude of incidence variations in the population of a region. A representative survey conducted in centres throughout France would allow evaluation of national trends between two publications of incidence by stage results in French registries.

A 35‐year retrospective study of carcinoid tumors in Taiwan

A comprehensive study of carcinoid tumors from United States-based databases indicated that the small intestine, colon, rectum, and bronchopulmonary system are common locations for carcinoid tumors. In addition, certain carcinoid tumors, such as rectal carcinoids, appeared to be overrepresented in nonwhite populations in the United States. High frequencies of associated noncarcinoid malignancies were reported in some articles. The objective of the current study was to address the organ distribution, frequency of metastasis, and survival rates of carcinoid tumors and the associated noncarcinoid tumors in Taiwanese, Asian populations. Two hundred twenty-eight patients with carcinoid tumors were identified and evaluated from the surgical pathology files and medical records of the Veterans General Hospital, Taipei, Taiwan from January 1970 to December 2005. In 228 carcinoid tumors that were analyzed, the rectum (60.5%) was the most common location followed by the lung (20.2%) and the thymus (6.6%). Metastatic lesions were demonstrated in 16.2% of patients. Disease extent was associated with survival. The 5-year survival rates for patients with localized, regional metastatic, and distant metastatic disease were 94.1%, 49.1%, and 0%, respectively (P< .001). Associated noncarcinoid malignancies were noted in 14% of patients with carcinoids, mainly in the gastrointestinal tract (52.9%), lung, and genitourinary system. A different organ distribution of carcinoids was observed in Taiwanese patients, who had with significantly more carcinoids located in the rectum and thymus compared with patients in Western countries. The patients with carcinoids in the current study had a high possibility of developing associated, noncarcinoid neoplasms. Surveillance of the colon, stomach, lung, and genitourinary system for second malignant tumors is recommended.

Adjuvant radiation therapy is associated with improved survival for gallbladder carcinoma with regional metastatic disease

Gallbladder carcinoma is a rare malignancy and is associated with dismal outcomes. The aim of this study was to better define the role of adjuvant radiation therapy in the management of gallbladder carcinoma. The Surveillance, Epidemiological, and End Results (SEER) survey from the National Cancer Institute was queried from 1992 to 2002. Retrospective analysis was done. The end-point of the study was overall survival. There were a total of 3,187 cases of gallbladder carcinoma in the registry from 1992 to 2002. Of the surgical group, 35% were stage I, 36% were stage II, 6% were stage III, and 21% were stage IV. Adjuvant radiation was used in 17% of the cases. The median survival for those patients receiving adjuvant radiation therapy was 14 months compared to an 8 months median survival for those treated without adjuvant radiation therapy (P < or = 0.001). The survival benefit associated with radiation use was only presenting those patients with regional spread (P = 0.0001) and tumors infiltrating the liver (P = 0.011). The use of adjuvant radiation therapy is associated with improved survival in patients with locally advanced gallbladder cancer or gallbladder cancer with regional disease.