Excision Of Primary Tumor Research Articles

Primary Tumor Excision in Stage IV Breast Cancer at Diagnosis without Influence on Survival: A Retrospective Analysis and Review of the Literature

Background: Patients with synchronous metastastic breast cancer and intact primary tumor traditionally undergo systemic treatment. Surgical intervention at the primary site is typically reserved for palliation and often replaceable by radiation. Nevertheless, local surgery in metastatic breast cancer has become an issue of great controversy since retrospective studies published during the recent years suggested a slight benefit from an operative procedure. We evaluated the effect of surgery on long-term survival and progression-free survival in synchronous stage IV breast cancer. Methods: We retrospectively reviewed the records of all breast cancer patients treated at our institution between 1986 and 2007. Information recorded for each patient included age, tumor characteristics, metastasis characteristics, therapy, progression-free survival, and overall survival. Survival data were compared between surgical and nonsurgical patients. Results: 61 patients with synchronous metastastic breast cancer and intact primary tumor were analyzed. 26 patients (43%) received no primary site surgery and 35 (57%) patients had surgery. Overall survival and progression-free survival determined via the Kaplan-Meier method showed no significant difference between the surgery and the non-surgery group. Conclusion: In patients with metastatic breast cancer, the operation of the primary tumor did not influence overall survival or progression-free survival.

Protective CD8 Memory T Cell Responses to Mouse Melanoma Are Generated in the Absence of CD4 T Cell Help

BackgroundWe have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma.Methodology and Principal FindingsTo induce melanoma/melanocyte antigen-specific CD8 T cells, B16 tumor bearing mice were depleted of regulatory T cells (Treg) by either temporary, or long-term continuous treatment with anti-CD4 (mAb clone GK1.5). Total depletion of CD4 T cells led to significant priming of IFN-γ-producing CD8 T cell responses to TRP-2 and gp100. Surprisingly, treatment with anti-CD25 (mAb clone PC61), to specifically deplete Treg cells while leaving help intact, was ineffective at priming CD8 T cells. Thirty to sixty days after primary tumors were surgically excised, mice completely lacking CD4 T cell help developed autoimmune vitiligo, and maintained antigen-specific memory CD8 T cell responses that were highly effective at producing cytokines (IFN-γ, TNF-α, and IL-2). Mice lacking total CD4 T cell help also mounted protection against re-challenge with B16 melanoma sixty days after primary tumor excision.Conclusions and SignificanceThis work establishes that CD4 T cell help is dispensable for the generation of protective memory T cell responses to melanoma. Our findings support further use of CD4 T cell depletion therapy for inducing long-lived immunity to cancer.

Stage IV breast cancer in the community hospital setting: Primary tumor extirpation effect on overall survival.

90 Background: Publications from academic centers and national cancer databases suggest a survival advantage for women who undergo primary tumor extirpation in the setting of known distant disease. We asked if similar findings exist in a community hospital setting. Methods: 15,887 patients entered in a longitudinally maintained breast cancer database (encompassing a system network of 13 community hospitals) during 1985-2009 were analyzed for those diagnosed with stage IV disease upon initial presentation. The cohort was divided into those who underwent primary tumor resection, and those who did not. The two subgroups were compared for patient demographics, tumor characteristics, sites of distant metastases, systemic treatment, and overall survival (OS). Results: 643 (4.05%) presented with an intact primary breast malignancy and synchronous distant metastasis. Median age at diagnosis: 66 years (range 22-96). Median OS: 15 months (range 0-249). 264 (41.1%) patients underwent primary tumor resection as part of first course treatment. On Kaplan-Meier univariate analysis, patients who underwent surgical extirpation of the primary tumor demonstrated improved median OS compared to those who did not (26 vs 10 months; p<0.0001, HR 0.52). Age at diagnosis <50 (p=0.0003, HR 0.65) and oligometastasis to bone (p=0.0002, HR 0.72) were statistically significant predictors of improved OS. Race, primary tumor size, and ER status alone did not influence OS. Those ER+ patients who underwent primary tumor excision in addition to chemotherapy and/or hormonal therapy fared significantly better than those treated with systemic therapy alone (32 vs 17 months; p<0.0001). Chemotherapy 16+ weeks prior to surgery improved OS compared to those who had surgery <16 weeks after starting chemotherapy. While there was no difference with regards to type of resection (partial vs simple vs modified radical mastectomy), clear margins were imperative to optimize OS. Conclusions: Patients with stage IV breast cancer treated at community hospitals also demonstrate improved OS after primary tumor extirpation, especially in the context of a multimodality approach combining chemotherapy and/or hormonal therapy preceding surgery.

Immunotherapy eradicates metastases with reversible defects in MHC class I expression.

Tumor or metastatic cells lose MHC class I (MHC-I) expression during cancer progression as an escape mechanism from immune surveillance. These defects in MHC-I may be reversible by cytokines or different agents (soft lesions) or irreversible due to structural defects (hard lesions). The nature of these MHC-I alterations might determine the success or failure of immunotherapy treatments. In this study, we have used an MHC-I-positive murine fibrosarcoma tumor clone, GR9-A7, which generates multiple lung and lymph node metastases with reversible MHC-I alterations after treatment with IFN-γ. Four different antitumor treatments were carried out after primary tumor excision to determine their capacity to inhibit spontaneous metastatic colonization of the GR9-A7 tumor clone. We found that 2 different immunotherapy protocols (CpG plus autologous irradiated-GR9-A7 cells and protein-bound polysaccharide K (PSK) and 1 chemoimmunotherapy (docetaxel plus PSK) induced eradication of metastases. In contrast, chemotherapy with docetaxel alone produced only partial reduction in the number of metastases. Flow cytometric analysis of lymphocyte populations showed an immunosuppression in GR9-A7 tumor-bearing host, which could be reverted by immunotherapy treatments. Our results suggest that irreversible or reversible MHC-I alterations in tumor target cells may determine its progression or regression independently of the type of immunotherapy used.

Lymphangiectases Are Common Underlying Warts and in Normal Peritumoral Skin: Histologic Evidence of Decreased Immune Surveillance

Lymphangiectases are a histologic sign of lymphostasis, which is associated with decreased immune cell trafficking and cell-mediated immunity. To determine if latent lymphedema is apparent underlying warts and in skin affected by cutaneous neoplasia. The number and maximal dilation of lymphangiectases were measured in the upper half of the dermis of 51 consecutive biopsies of warts, 230 consecutive normal skin samples from primary skin tumor excisions, and 14 normal skin samples from breast reduction (11) and panniculectomy (3) specimens. All warts had one or more underlying lymphangiectases compared with 79% of peritumor normal skin samples and 50% of cosmetic specimens. The mean number of lymphangiectases and mean maximal dilation were significantly greater in warts than in peritumor skin, which was significantly greater than cosmetic skin samples (3.6 vs. 1.3 vs. 0.12 lymphangiectases per square millimeter and 54 vs. 23 vs. 1 μm, respectively; P = 0.0001). Warts exhibited mild fibrosis significantly more frequently than peritumor skin (57% vs. 5%; P = 0.0001). For peritumor (normal) skin, age, solar elastosis, and adjacent malignancy correlated with greater dilation of lymphatics. Solar elastosis also correlated with increased number of lymphangiectases. Minor trauma and solar elastosis from chronic ultraviolet radiation exposure are likely the etiologic factors in the development of lymphostasis. By decreasing immune surveillance, latent lymphedema ostensibly facilitates human papillomavirus infection and carcinogenesis.

P318 Does primary tumor excision affect survival in metastatic breast cancer?

P318 Does primary tumor excision affect survival in metastatic breast cancer?

Conditional survival predictions after surgery for patients with penile carcinoma

Conditional survival (CS) implies that, on average, long-term cancer survivors have a better prognosis than newly diagnosed individuals. The objective of the current study was to devise an accurate predictive tool that accounts for CS in men diagnosed with penile cancer. Overall, 1245 patients treated with primary tumor excision (PTE) for pT(1-3)M0 squamous cell carcinoma of the penis (SCCP) between 1998 and 2006 were identified. Cox regression models were fitted for prediction of cancer-specific mortality (CSM). Nomogram development for prediction of CSM using CS methodology at 2 and 5 years was performed on 670 patients. External validation and calibration of the conditional nomogram was performed in 575 patients. The 5-year CSM-free survival of patients at surgery was 84.3% and increased to 95.0% and 97.8% after 2 and 5 years of disease-free survival (DFS), respectively. The predicted probabilities varied by as much as 49% (57% vs 85%) when, for example, predictions of CSM-free survival at 5 years were made after PTE versus after 2 years of DFS. Within the external validation cohort, the accuracy of the conditional nomogram was 75.3% and 78.1% at 2 and 5 years after PTE. The authors developed and externally validated the first conditional nomogram for predicting SCCP CSM-free survival that allows consideration of the length of survivorship.

Pseudomyogenic Hemangioendothelioma

A 1992 report described 5 keratin-positive spindle cell neoplasms with multifocal presentation in a single limb, which were proposed at that time to be a variant of epithelioid sarcoma. This tumor type is not widely recognized and is incompletely characterized. We examined 50 cases of this distinctive tumor to evaluate histologic, immunophenotypic, and clinical features. There was a 4.6:1 male predominance (mean age, 31 y; 82% ≤40 y). Half of the patients presented with painful nodules and the other half with painless nodules. Mean tumor size was 1.9 cm (range, 0.3 to 5.5 cm). Tumors arose in the lower limb (54%), the upper limb (24%), trunk (18%), or head and neck (4%). Thirty-three (66%) were multifocal lesions (ranging from 2 to 15 lesions), including 32 cases with involvement of multiple tissue planes. Of 205 total lesions, 64 (31%) involved the dermis, 42 (20%) involved the subcutis, 70 (34%) lesions involved muscle, and 29 (14%) lesions involved bone; all the lesions had infiltrative margins. The tumors were composed of loose fascicles and sheets of plump spindle cells with vesicular nuclei, variably prominent nucleoli, and abundant brightly eosinophilic cytoplasm, some with a strikingly rhabdomyoblast-like appearance. In all cases, a minority of cells were epithelioid. Twenty-seven tumors contained a prominent neutrophilic inflammatory infiltrate. Most tumors showed only mild nuclear atypia; 6 tumors contained foci of notably pleomorphic cells. The median mitotic rate was 1 per 10 HPF (range, 1 to 10). Seven tumors showed vascular invasion; 7 tumors had areas of necrosis. By immunohistochemistry, all tumors were diffusely positive for AE1/AE3 and FLI1; 22 of 47 tumors were variably positive for CD31. Focal positivity was seen for CAM5.2 (21 of 35), smooth muscle actin (14 of 42), epithelial membrane antigen (7 of 49 weak), and PAN-K (MNF116) (1 of 47). All were negative for CD34, desmin, and S100 protein and showed intact INI1 expression. Follow-up was available for 31 patients and ranged from 9 months to 17 years (mean, 4 y). Most lesions were treated by local excision. Eighteen (58%) patients had local recurrence or developed additional nodules in the same region, all but one, within 1 year of first presentation. Eight patients had postoperative radiation therapy and 6 patients had chemotherapy. Four patients had amputations for multifocal disease. One patient had a regional lymph node metastasis, and, thus far, only 1 patient has developed distant metastases (disseminated), 16 years after primary tumor excision. At the time of the last follow-up, 27 patients were alive with no evidence of the disease, 1 patient was alive with unknown disease status, 2 patients were alive with recurrent disease, and 1 patient died of the disease. In summary, we describe a distinctive type of rarely metastasizing ("intermediate") tumor affecting mainly young men and usually characterized by multifocality in different tissue planes of a limb. Although sharing some features with epithelioid sarcoma (skin/soft tissue of distal extremities, young adults, keratin positive), it differs by having predominantly myoid-appearing spindle cell morphology, expression of FLI1, common reactivity for CD31, lack of epithelial membrane antigen, CD34, and PAN-K expression, and intact INI1. The overall immunophenotypic findings favor endothelial differentiation. Despite the ominous presentation, follow-up thus far suggests an indolent clinical course with a small risk of distant metastasis. Although the precise nosologic status of this tumor type is uncertain, we propose the interim designation "pseudomyogenic hemangioendothelioma."

Late recurrences of gastrointestinal stromal tumours (GISTs) after 5 years of follow-up

In practice, relapses of gastrointestinal stromal tumours after long time of surgical resection occur. However, few published data are available for duration, intensity and imaging sources of follow-up in radically excised patients with localized disease. Therefore, every single institution chooses the surveillance schedule according to its experience. The aim of this study was to describe the late recurrences of disease 5 years after the primary tumour's excision in a series of patients with recurrent GIST from our institution. We retrospectively reviewed 42 patients with "recurrent" GIST, collected since 2001. Ten patients were always followed at our institution, and 32 patients came to our attention at the time of recurrence. The analysed series were divided into two groups: patients who developed recurrence before 5 years and patients who developed recurrence 5 years after the primary tumour's excision. Among 42 patients, 36 patients developed the recurrence within 5 years of the primary tumour excision, whereas 6 patients developed the recurrence 5 years after primary tumour excision diagnosed during follow-up or casually for other reasons. All patients had distant recurrence, involving liver and peritoneum, whereas no local relapse was observed. These patients were heterogeneous in primary tumour site, risk classification and molecular analysis. Duration of the follow-up for radically excised patients with GIST remains still unsettled; however, the integration of every clinical, pathological and molecular parameter is essential to optimize the duration and intensity of the follow-up for each single patient.

FDG-PET/CT as prognostic factor and surveillance tool for postoperative radiation recurrence in locally advanced head and neck cancer

PurposeTo evaluate the prognostic value of metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) on initial positron emission tomography-computed tomography (PET-CT) and investigate the clinical value of SUVmax for early detection of locoregional recurrent disease after postoperative radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Materials and MethodsA total of 100 patients with locally advanced HNSCC received primary tumor excision and neck dissection followed by adjuvant radiotherapy with or without chemotherapy. The MTV and SUVmax were measured from primary sites and neck nodes. The prognostic value of MTV and SUVmax were assessed using initial staging PET/CT (study A). Follow-up PET/CT scan available after postoperative concurrent chemoradiotherapy or radiotherapy were evaluated for the SUVmax value and correlated with locoregional recurrence (study B). A receiver operating characteristic (ROC) curve analysis was used to define a threshold value of SUVmax with the highest accuracy for recurrent disease assessment.ResultsHigh MTV (>41 mL) is negative prognostic factor for disease free survival (p = 0.041). Postradiation SUVmax was significantly correlated with locoregional recurrence (hazard ratio, 1.812; 95% confidence interval, 1.361 to 2.413; p < 0.001). A cut-off value of 5.38 from follow-up PET/CT was identified as having maximal accuracy for detecting locoregional recurrence by ROC analysis.ConclusionMTV at staging work-up was significantly associated with disease free survival. The SUVmax value from follow-up PET/CT showed high diagnostic accuracy for the detection of locoregional recurrence in postoperatively irradiated HNSCC.

Robotic approach for ovarian cancer: Perioperative and survival results and comparison with laparoscopy and laparotomy

ObjectiveComparison of perioperative outcomes and survival of patients undergoing primary surgical treatment for epithelial ovarian cancer (EOC) by a robotic, laparoscopy, or laparotomy approach. MethodsRetrospective case–control analysis of 25 patients with EOC undergoing robotic surgical treatment between March 2004 and December 2008. Comparison was made with similar patients treated by laparoscopy and laparotomy and matched by age, body mass index (BMI), and type of procedures between January 1999 and December 2006. ResultsThe mean operating times were 314.8, 253.8 and 260.7min for robotic, laparoscopy and laparotomy patients, respectively (p<0.05); the mean blood loss was 164.0, 266.7, and 1307.0ml, respectively (p=0.001); the mean length of hospital stay was 4.2, 3.2, and 9.4days, respectively (p=0.001). The overall survival (OS) for robotics, laparoscopy and laparotomy patients was 67.1%, 75.6% and 66.0%, respectively (p=0.08). Patients were subdivided and compared according to the extent of surgery by the type and number of major procedures. Type I and II debulking patients operated by robotics and laparoscopy had improved perioperative outcomes as compared to laparotomy. For patients undergoing a type III debulking, robotic outcomes were not improved over laparotomy. ConclusionLaparoscopy and robotics are preferable to laparotomy for patients with ovarian cancer requiring primary tumor excision alone or with one additional major procedure. Laparotomy is preferable for patients requiring two or more additional major procedures. Survival is not affected by the type of surgical approach.

Tumor Grade Improves the Prognostic Ability of American Joint Committee on Cancer Stage in Patients With Penile Carcinoma

Penile cancer is rare. Thus, predicting cancer specific mortality may be difficult. We devised an accurate and yet easily applicable predictive rule that compares favorably with 2 previous models (73.8% and 74.7% accuracy, respectively). We identified patients treated with primary tumor excision for all stages of penile squamous cell carcinoma between 1998 and 2006. Disease stage definitions using Surveillance, Epidemiology and End Results stage, American Joint Committee on Cancer stage and TNM classification, and tumor grade were used to predict cancer specific mortality. Predictive accuracy estimates were compared using the DeLong method for related AUCs. Surveillance, Epidemiology and End Results stage alone (1 predictor variable) was least accurate (74.5%). American Joint Committee on Cancer stage with tumor grade (2 predictor variables) was the most simple and most accurate (80.9%, p <0.001). A benefit similar to that of American Joint Committee on Cancer stage with tumor grade was seen for TNM classification and TG (80.7%, p = 0.8). However, this rule (4 predictor variables) was more complex than American Joint Committee on Cancer stage and tumor grade. American Joint Committee on Cancer stage combined with tumor grade is the simplest, most accurate cancer specific mortality prediction rule after primary tumor excision for penile squamous cell carcinoma. This method is also more accurate than 2 previous cancer specific mortality prediction rules.

Metastatic Adenocarcinoma of the Colon: Early Manifestation in Gingival Tissue

A case of gingival metastasis of adenocarcinoma of the colon is reported, the lesion being an early clinical indication of a primary malignant tumor. The diagnosis of metastatic lesion in the oral region is always challenging, both to clinician and to the pathologist, due to its rarity and complexity. In the present case, the clinical hypothesis was peripheral ossifying fibroma or pyogenic granuloma. Histologically, the biopsy tissue revealed a malignant neoplasm not connected to the mucosal surface. Immunohistochemically, the lesion was positive for 35ßH11 and cytokeratin 20 and focally positive for cytokeratin 7. Treatment involved excision of primary tumor and follow-up chemotherapy. The clinical, histological and immunohistochemical characteristics are discussed.

A Contemporary Population-Based Assessment of the Rate of Lymph Node Dissection for Penile Carcinoma

The adherence rate to National Cancer Institute (NCI) recommendations regarding inguinal lymph nodes dissection (ILND) in high grade T1 (G3T1) and T2-4 squamous cell carcinoma of the penis (SCCP) is not known. We assessed ILND rates in a North American cohort. The 17 registries of the Surveillance, Epidemiology, and End Results (SEER) database included 868 patients with SCCP, diagnosed between 1988 and 2006. Analyses consisted of univariable and multivariable logistic regression models. Overall, 27.6% of patients underwent an ILND. ILND rates were directly proportional with T stage: 19.0%, 30.5%, 30.6%, and 32.6% for, respectively, G3T1, T2, T3, and T4 SCCP (chi-square trend, P = 0.01). ILND rates also increased over time and were 19.3, 27.3, 30.7, and 30.8% for respectively, 1988-1995, 1996-2000, 2001-2003, and 2004-2006 periods (chi-square trend, P = 0.03). Finally, ILND rates decreased with patient age and were 42.6, 33.2, 24.7, and 7.3% for, respectively, patients aged ≤ 57, 58-68, 69-78 and ≥ 79 years of age (chi-square trend, P < 0.001). All 3 variables (T-stage, year of primary tumor excision and patient age) achieved independent predictor status in multivariable analyses. The overall rate of ILND is low. Nonetheless, there is an upward trend over time. Our data indicate that the adherence to the NCI ILND guidelines is suboptimal. In consequence, ILNDs should be more strongly encouraged.

Pre‐operative ultrasound with a 12–15 MHz linear probe reliably differentiates between melanoma thicker and thinner than 1 mm

Pre-operative determination of primary melanoma thickness could be a tool to identify those patients who could be treated with radical primary tumour excision and sentinel lymph node biopsy in a single procedure. An excellent correlation between sonographic and histological measurement of maximal tumour thickness has been achieved using 20-MHz transducers. To show that widely available high resolution ultrasound with 12-15 MHz linear probe could also reliably assess the thickness of primary melanoma. Sixty-nine patients underwent ultrasound evaluation of 70 clinically and dermoscopically suspicious pigmented skin lesions before surgical excision. The sensitivity, specificity, positive and negative predictive values of ultrasound to detect melanoma > 1 mm were 92%, 92%, 95% and 81% respectively. The correlation between ultrasound and histological tumour thickness was very good [Pearson's correlating index 0.823 (P < 0.001)]. Mean difference between sonographic and histological measurements was 0.045 mm with limits of agreement estimated at -1.4 and +1.49, and a bias between two methods 45 microm. Ultrasound examination with a 12-15 MHz linear transducer can reliably differentiate primary melanoma > 1 mm from those <or= 1 mm.

Effect of beta blocker combined with COX-2 inhibitor on colonic anastomosis in rats

Pharmacologic modulation of the perioperative physiologic stress response, using the beta-blocker propranolol, combined with the COX-2 inhibitor etodolac, has been shown to reduce metastatic spread and increase survival rates following surgery for primary tumor excision in rodents. Prior to implantation of this pharmacological approach in clinical trials in patients with colon cancer, the safety of this technique has to be evaluated. This study assessed the effects of these drugs on the healing of colonic anastomosis in rats. Forty-eight F344 rats were divided into two groups, which were given seven daily subcutaneous injections of either vehicle, or propranolol (up to 1.2 mg/kg/day) combined with etodolac (12.5 mg/kg/day), starting the day before surgery. Each animal underwent laparotomy, colotomy of the descending colon, and anastomosis. Anastomotic leak rate and bursting pressure were compared at 1 week after the operation. The harvested anastomosis was histologically assessed for wound healing parameters. Forty-three rats survived the operation and were eligible for analysis at 1 week. No significant difference in survival, anastomotic leakage, or bursting pressure was found between animals that received propranolol and etodolac versus those receiving vehicle (drugs 179 mmHg ± 45.4; vehicle 187 mmHg, SD ± 35.0, p = 0.54). Histologic assessment of fibrosis, necrosis, cell infiltration, and tissue reaction zone did not differ between the two groups. Perioperative administration of propranolol and etodolac seems safe in colon operations in rats and does not affect anastomotic failure or colon healing.

The Outcome of Patients with Melanoma Is Not Associated with the Time Point of Lymphatic Mapping with Respect to Excisional Biopsy of the Primary Tumor

Background: Sentinel lymph node biopsy (SLNB) has become the standard care for melanoma and is an important diagnostic procedure. It has been doubted whether lymphoscintigraphy detects the correct sentinel lymph node (SLN) when excision of the tumor and SLNB are not performed at the same time. This would imply that this sequential approach may have an increased risk of undetected micrometastases resulting in a worse outcome. Objective: The purpose of the present study was to compare the outcome of melanoma patients having received excision of the tumor and SLNB either at the same time or consecutively. Methods: A total of 854 patients with cutaneous melanoma were enrolled in this retrospective study between September 1996 and November 2007. Disease-free (DFS) and overall survivals (OS) were estimated using the Kaplan-Meier product limit method and were analyzed by the log rank test. Results: No statistically significant difference was found regarding DFS, progression rates and OS in patients with primary tumor excision and SLNB at the same time compared with patients with excisional biopsy of primary tumor and SLNB at different times. Conclusion: These data suggest that excisional biopsy of the primary tumor does not prevent the correct SLN mapping in melanoma patients.

Abstract 5618: Arming the melanoma sentinel lymph node against tumor spread: The effects of local administration of combined low-dose CpG-B PF-3512676 and GM-CSF

Abstract The sentinel lymph node (SLN) procedure has proven a useful prognostic tool for the assessment of melanoma relapse and mortality risk, but is also of great value for the assessment of immunological interventions. Since early melanoma development is accompanied by a suppressed immune state of the SLN, there is a strong rationale for therapeutic immune modulation of the SLN in order to strengthen local as well as systemic cell-mediated anti-tumor immunity. Previous Phase II studies showed promising immunostimulatory effects on the melanoma SLN of Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF) and the CpG-B oligodeoxynucleotide PF-3512676. The present 3-arm Phase II study was designed to determine the effects of combined low-dose GM-CSF+CpG-B administration. Stage I-III melanoma patients (n=28) were randomized to receive i.d. injections around the primary tumor excision site of saline, CpG-B alone (1 mg), or CpG-B combined with GM-CSF (100 μg), 7 and 2 days prior to surgical excision of the SLN. Flowcytometric DC analyses revealed significantly increased maturation of all identifiable cDC and pDC SLN subsets upon administration of CpG-B with or without GM-CSF, but remarkably, the combination resulted in significantly higher levels of co-stimulatory molecules on both cDC and pDC. In addition, a significant CpG-related increase in frequencies of CD1a−CD11chiCD14+/− cDC subsets was observed in the SLN, possibly resulting from DC and/or monocyte mobilisation from blood. Indeed, increased activation of pro-inflammatory 6-sulfo LacNac+slanDC, monocytes, and pDC was observed in peripheral blood upon administration of CpG-B alone, and additionally of CD1c+ cDC when combined with GM-CSF. In the case of slanDC this activation was accompanied by significantly reduced frequencies. Peripheral blood rates of CD14+DRlo myeloid suppressors remained unchanged after saline or combined CpG and GM-CSF administration, but significantly decreased after administration of CpG-B alone. T cell analyses revealed a CpG-related increase in CTLA-4 and FoxP3 levels on Tregs in SLN, without changes in their actual rates. Nevertheless, higher intracellular Th1 cytokine levels were detected in ex vivo expanded T cells of CpG-administered patients than of patients receiving saline or CpG-B+GM-CSF. In keeping with this, also higher frequencies were found in SLN of MAA-specific CD8+ T cells in low dose CpG-B administered patients (n=4) than in saline controls (n=5), as determined by tetramer binding and cytokine release. We conclude that the imunomodulatory effects observed in melanoma SLN upon local administration of combined low-dose GM-CSF and CpG-B are mostly attributable to CpG-B and that they are consistent with the induction of protective cell-mediated anti-tumor immunity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5618.

Factors Predicting Survival in Childhood Malignant and Intermediate Vascular Tumors

The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival. A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols. Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses. The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment.

Neurofibroma of the Tibial Nerve Mimicking Popliteal Lymph Node Metastasis in Malignant Melanoma

Approximately 15% of all patients with melanoma develop metastases, of which 50% are regional lymph node metastases after primary tumor excision. Although most metastases are detected using clinical examination, ultrasonography, when used, is more sensitive for early detection.1Case ReportA 63-year-