Geel, A.N. van

Long-term outcome of isolated limb perfusion with tumour necrosis factor-α for patients with melanoma in-transit metastases (Article)

2011-11-01T00:00:00Z

Background: The use of tumour necrosis factor (TNF) α in isolated limb perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted. This article reports the long-term results of adding TNF-α to standard melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases. Methods: Data for patients treated between 1991 and 2005 were retrieved from a prospectively maintained database. Hyperthermic ILP was performed with 1-4 mg TNF-α. With a median potential follow-up of 13 years, response rates, time to local progression and disease-specific survival were analysed in relation to standard baseline factors. Results: Some 118 TM-ILPs were analysed in 105 patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The overall response rate was 93·2 per cent; the response was complete in 67·8 per cent and partial in 25·4 per cent. The response rate was significantly influenced by stage of disease (IIIA versus IIIAB; P = 0·006). The complete response was maintained until the end of follow-up in 35 patients (33·3 per cent), and local control was achieved with one additional intervention in 12 others (11·4 per cent). Local progression occurred after 66 ILPs (55·9 per cent). Number of in-transit metastases (P = 0·008) and complete response after ILP (P < 0·001) were strong prognostic factors for time to local progression. The 5-year disease-specific survival rate was 27·3 per cent; survival was positively influenced by age, stage of disease, previous ILP and complete response after ILP. Conclusion: ILP with TNF-α may obtain long-term local control in selected patients with in-transit metastases from melanoma. Copyright

Long-term results of tumor necrosis factor α- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas (Article)

2011-10-20T00:00:00Z

Purpose: Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS. Patients and Methods: We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors. Results: The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P<.001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%. Conclusion: We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.

Outcome After Therapeutic Lymph Node Dissection in Patients with Unknown Primary Melanoma Site (Article)

2011-05-25T00:00:00Z

Purpose: The aim of this study was to evaluate the incidence and outcome of melanoma of unknown primary site (MUP) after therapeutic lymph node dissection (TLND) of palpable nodal melanoma metastases. Disease-free (DFS) and overall survival (OS) time of MUP patients were analyzed and compared to patients undergoing a TLND for known primary melanomas (MKP). Methods: This single institution retrospective study analyzed 342 consecutive patients who were treated with 415 TLNDs for palpable nodal disease from 1982 to 2009. Univariate and multivariate analyses included: MUP versus MKP, gender, Breslow thickness, ulceration of primary tumor, site of primary tumor, site of dissection, extracapsular extension, number of collected nodes, number of positive nodes and the node positive ratio. Results: A total of 47 MUP were identified in 342 patients (13.7%). In univariate analysis, a trend was seen toward better survival for MUP patients compared to MKP patients having 5-year OS rates of 40% and 27%, respectively (P = 0.06). Multivariate analysis for OS showed two highly significant factors associated with worse prognosis: extracapsular extension and N3 status (both P < 0.001). Two factors were associated with a significant better prognosis: MUP (P = 0.03) and a neck dissection (P = 0.04). Conclusions: Patients with MUP showed a statistically significant better OS compared to patients with melanoma metastases from known primary tumors. Presence of extracapsular extension and an increased number of positive nodes are statistically significantly negative prognostic factors for OS. The absence of a primary melanoma in stage III melanoma patients does not preclude surgery.

Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined Superficial and Deep Groin Lymph Node Dissection (Article)

2011-05-03T00:00:00Z

Background: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. Methods: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. Results: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. Conclusions: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan.

Partial mastectomy and m. latissimus dorsi reconstruction for radiation-induced fibrosis after breast-conserving cancer therapy (Article)

2011-03-01T00:00:00Z

Background: Patients with severe complaints of radiation-induced fibrosis after breast-conserving therapy and not responding to conservative therapy, were treated by partial mastectomy and m. latissimus dorsi reconstruction. Method: To determine the feasibility and outcome of this approach, a retrospective study of nine patients was carried out. Results: After a mean follow-up of 46 months, eight of the nine patients experienced improvement of their complaints and shape of the breast. In only one case did the procedure fail, as evidenced by continuation of all complaints. Conclusions: Partial mastectomy and m. latissimus dorsi reconstruction is the ultimate option in the treatment of radiation fibrosis. The procedure is safe with satisfying results.

Chest wall resection for adult soft tissue sarcomas and chondrosarcomas: Analysis of prognostic factors (Article)

2011-01-01T00:00:00Z

Background: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. Methods: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. Results: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. Conclusions: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis.

Sternal resection for sarcoma, recurrent breast cancer, and radiation-induced necrosis (Article)

2010-10-01T00:00:00Z

Background: The purpose of this study was to investigate the long-term outcome and technical feasibility of sternal resection. Methods: We performed a 25-year retrospective study of 68 patients who underwent a sternectomy for sarcoma, recurrent breast cancer (BC) or radiation-induced necrosis between 1981 and 2006 in two tertiary referral centres (Erasmus Medical Center/Daniel den Hoed Cancer Center and Netherlands Cancer Center/Antoni van Leeuwenhoek Hospital, Netherlands). Patients were treated with curative intent and followed until May 2009. Medical records were reviewed for patient characteristics, indications for surgery, surgical technique, postoperative complications, and survival. Results: Sternal resection was performed in 43 sarcoma patients, 17 recurrent BC and 8 patients with radiation-induced necrosis with additional rib resection in the majority of patients and with clavicle resection in 13% of patients. Additional scapula, lung, breast or axilla resection, or both, was performed in 10%. Two patients died postoperatively (3%). Mild complications occurred in 24%, and severe complications (namely, pulmonary complications and reinterventions) in 16% of patients. Radical resection was achieved in 80% and 53% of sarcoma and recurrent BC patients, respectively. Five-year overall survival was 64% and 40% in sarcoma and recurrent BC patients, respectively, with 5-year disease-free survivals of 52% and 15%, respectively. Conclusions: Sarcomas, recurrent BC, and radiation-induced necrosis can be successfully managed by sternal resection and reconstruction with curative intent. Low mortality and acceptable morbidity rates justify this operation in a palliative setting as well. Disease-free survival is poor among recurrent BC patients.

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients? (Article)

2010-01-01T00:00:00Z

Background: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity. Methods: In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation. Results: Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up. Conclusions: In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit.

Prognostic factors in 77 curative chest wall resections for isolated breast cancer recurrence (Article)

2009-12-01T00:00:00Z

Background: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. Methods: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. Results: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2(P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. Conclusions: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.

Isolated limb perfusion with TNF-α and melphalan in locally advanced soft tissue sarcomas of the extremities (Article)

2009-08-21T00:00:00Z

Limb-sparing surgery has become all the more important in soft tissue sarcoma (STS) of the extremities since we learned that amputation does not improve survival of these patients. In bulky tumours, however, preoperative strategies to reduce tumour size are then required. Isolated limb perfusion (ILP) with tumour necrosis factor (TNF) has been developed as a biochemotherapeutic therapy to act both on the tumour-associated vasculature and on the tumour itself. It has shown to be a very potent treatment modality, as in early reports response rates were around 80%. Limb salvage could then be achieved in a quite similar percentage. Many confirmatory studies have been performed since, with consistent results even in patients with multiple tumours, after extensive radiotherapy or with metastatic disease, all at the cost of very limited toxicity. This chapter gives an overview of the ILP studies performed in patients with soft tissue limb sarcoma, discusses the mechanism of TNF-mediated vasculotoxic effects on tumour vasculature, and places TNF-based ILP in the multimodality treatment of these patients with extensive STS of the extremities.

Complications in wound healing after chest wall resection in cancer patients; A multivariate analysis of 220 patients (Article)

2009-05-01T00:00:00Z

Extensive chest wall resections can provoke a wide variety of complications, in particular, complicated wound healing. A lower complication rate will be achieved when local factors contributing to wound healing can be identified and improved. The aim of this study is to describe these factors, irrespective of prognosis, survival, or systemic complications. Methods: Retrospectively, the files of all patients undergoing an extended chest wall resection in a single institute during a 20-year period were retrieved. Patient demographics, use of preoperative therapy, tumor histology, the type of prosthesis (if any), and postoperative wound complications were recorded. Univariate and multivariate analysis were performed to identify factors contributing significantly to wound healing problems. Results: From January 1987 to December 2006, 220 patients underwent a chest wall resection, defined as resection of at least one rib, and/or part of the sternum. In 145 patients (66%) this procedure was uneventful. Multivariate analysis showed that ulceration of tumor and the use of omentum for soft tissue reconstruction comprised independent factors contributing to impaired wound healing. Conclusion: Several factors leading to wound healing problems exist preoperatively. In a multidisciplinary setting, these factors should be weighed carefully against the possible benefits of an extended chest wall resection. Especially when ulceration of a tumor exists, or when omentum is considered for soft tissue reconstruction, increased risk on wound healing problems occurs. For the majority of patients chest wall resection will remain a safe and suitable procedure.

Chest wall resection for internal mammary lymph node metastases of breast cancer (Article)

2009-04-01T00:00:00Z

Evaluation of morbidity, mortality and oncologic outcome of patients treated with a chest wall resection for isolated breast cancer recurrences in the Internal Mammary Chain. Retrospectively we retrieved data from 29 patients. Multivariate analysis was performed to identify prognostic factors for (disease-free) survival. There were no postoperative deaths. Complications occurred in 11 patients. The median follow-up after CWR for all 16 patients still alive at the end of this study is 18.4 months. Nine patients were free of cancer. The 3-year overall and disease-free survival is 59.2% and 8.6%. The median survival is 40.7 months. After multivariate analysis for each of the four endpoints studied, only one prognostic factor remains significant for survival: systemic therapy before CRW (p = 0.004). For local recurrence-free survival a first CRW recurrence (p < 0.00001) and for disease-free survival radicality of the resection (p = 0.008) are independent prognostic factors. Chest wall resection is a safe and effective treatment for isolated breast cancer recurrences in the IMC. Surgically treated patients have a fair survival and some of them are even cured.

Glomus tumor of the mesentery with atypical features: A case report (Article)

2008-10-01T00:00:00Z

Glomus tumors usually occur in the acral soft tissue and rarely in visceral locations, such as the stomach, intestines, mediastinum, lung, pancreas, bladder, and vagina. The authors present a 74-year-old woman with an exceptionally large glomus tumor of the mesentrium with malignant features. Previously reported cases of intraabdominal glomus tumor in the abdominal cavity exhibited benign behavior and few cases with metastatic disease. Criteria for malignancy in acral glomus tumors, such as unusually large size, infiltrative growth, necrosis, nuclear atypia, and mitotic activity, seem not to translate to abdominal glomus tumors. As very few intraabdominal glomus are described, the malignant potential of these tumors stays uncertain for longer period.

Decrease of CD117 expression as possible prognostic marker for recurrence in the resected specimen after imatinib treatment in patients with initially unresectable gastrointestinal stromal tumors: A clinicopathological analysis (Article)

2008-07-01T00:00:00Z

Gastrointestinal stromal tumors (GIST) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The principal treatment modality for primary GIST is surgery whereas for metastatic GIST, imatinib has an established role. In patients with locally advanced and metastatic GIST, the role of surgery in the imatinib era is still unclear. Fifteen patients with locally advanced (n≤9) and/or metastatic GIST (n≤6) were treated with imatinib followed by resection. Detailed histopathological examination was performed before and after treatment with imatinib, which was given for a median of 11 months before surgery. Ten patients showed a radiographic partial response, four patients had stable disease, and one patient progressed. At the time of surgery, the median tumor diameter was 6.5g cm. In all the nine patients with locally advanced GIST, a R0 resection could be performed. Histopathological examination showed imatinib effects in all tumors, including the case with progressive disease. All patients with locally advanced disease (n≤9) were alive after a median follow-up of 40 months (range: 18g-59), of which seven patients were free of disease. Four of the six patients treated for metastatic GIST died of disease after 30, 45, 50, and 74 months of follow-up. Remarkably, in five of six patients in whom CD117 expression was diminished or lost in the resection specimen, disease recurrence was observed. In patients with retained CD117 expression, one of the nine patients had recurrent disease. In conclusion, preoperative imatinib treatment in patients with locally advanced GIST resulted in a decrease of tumor load in most patients, enabling complete surgical resection. For patients with metastatic GIST, the role of surgery remains less clear. Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence.

Blindness: A Rare and Serious Complication After Extensive Mediastinal Resection (Article)

2008-04-01T00:00:00Z

We describe the case of a patient in whom blindness developed as a result of superior vena cava syndrome after resection of a primary mediastinal nonseminomatous germ cell tumor.

Should internal mammary chain (IMC) sentinel node biopsy be performed?. Outcome in 90 consecutive non-biopsied patients with a positive IMC scintigraphy (Article)

2008-04-01T00:00:00Z

Introduction: Although the status of the regional lymph nodes is an important determinant of prognosis in breast cancer, harvesting sentinel nodes (SN) detected in the internal mammary chain (IMC) is still controversial. Aims: To determine in how many patients a positive IMC-SN might change the systemic or locoregional adjuvant therapy, with a possible benefit in outcome. Patients and methods: During 6 frac(1, 2)years data of T1-2 breast cancer patients, having an SN procedure, were prospectively collected. Our policy was not to explore the IMC even if it was the only localization of an SN. Results: In 86 of 571 patients lymphoscintigraphy showed an IMC-SN. In 64 of these, the axillary SN was negative and only 25 of these patients did not have an indication for adjuvant systemic treatment based on their tumor characteristics. In the literature, IMC metastases are found in 0-10% of axillary negative patients. Routine IMC-SN biopsies would have resulted in an indication for adjuvant systemic therapy in 2-3 of our patients. Four parasternal recurrences were found during a median follow-up of 51 months. Conclusions: Harvesting IMC-SNs is a procedure of which only a limited number of patients have therapeutical benefit. Even with a thorough selection of patients, the extra morbidity of the procedure should be weighed against the potential benefit for the patient.

Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: Long-term experiences at the Rotterdam family cancer clinic (Article)

2007-12-01T00:00:00Z

Background: BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce. Methods: From 358 high-risk women (including 236 BRCA1/2 carriers) undergoing PM between 1994 and 2004, relevant data on the occurrence of BC in relation to PM, complications in relation to breast reconstruction (BR), mutation status, age at PM and preoperative imaging examination results were extracted from the medical records, and analyzed separately for women without (unaffected, n = 177) and with a BC history (affected, n = 181). Results: No primary BCs occurred after PM (median follow-up 4.5 years). In one previously unaffected woman, metastatic BC was detected almost 4 years after PM (primary BC not found). Median age at PM was younger in unaffected women (P < .001), affected women more frequently were 50% risk carriers (P < .001). Unexpected (pre)malignant changes at PM were found in 3% of the patients (in 5 affected, and 5 unaffected women, respectively). In 49.6% of the women opting for BR one or more complications were registered, totaling 215 complications, leading to 153 surgical interventions (71%). Complications were mainly related to cosmetic outcome (36%) and capsular formation (24%). Conclusions: The risk of developing a primary BC after PM remains low after longer follow-up. Preoperative imaging and careful histological examination is warranted because of potential unexpected (pre)malignant findings. The high complication rate after breast reconstruction mainly concerns cosmetic issues.

Isolated limb perfusion for an irresectable melanoma recurrence in a Jehovah's witness (Article)

2007-08-01T00:00:00Z

Isolated limb perfusion (ILP) is a treatment option for irresectable melanoma lesions, because with ILP 20-fold higher concentrations of chemotherapy can be achieved locally than is systemically possible and high response rates are subsequently achieved. Jehovah's witnesses do not accept any form of blood transfusion, either autologous or homologous blood or only blood products. The use of an extracorporeal circuit, without the use of any blood products is acceptable for Jehovah's witnesses. The case of a 59-year-old Jehovah's witness with an irresectable melanoma recurrence for which an ILP. Because of adequate blood flow through the perfused limb, the limb did not become acidotic, even though there was a significant drop in the Hb concentration in the limb during the ILP. Isolated limb perfusions without the use of any blood transfusion products are technically possible, but an adequate preoperative hemoglobin concentration is a prerequisite.

Prognosis of Primary Mucosal Penile Melanoma: A Series of 19 Dutch Patients and 47 Patients from the Literature (Article)

2007-07-01T00:00:00Z

Objectives: To analyze the clinical features, prognostic factors, and survival of male patients with primary mucosal melanoma on the glans penis, meatus, fossa navicularis, and distal urethra. Methods: We analyzed the clinical features, prognostic factors, and survival of 66 male patients with primary mucosal melanoma on the glans penis, meatus, fossa navicularis, and distal urethra diagnosed over the past 25 years. Data from our series of 19 patients were combined with those of 47 patients reported in the literature. Results: The overall 2 and 5-year survival rates were 63% and 31%, respectively. All patients with nodal and/or distant metastases at presentation died within 2 years. Presence of ulceration, tumor depth of 3.5 mm or more, and tumor diameter greater than 15 mm had a significantly adverse effect on prognosis. Conclusions: The prognosis of primary mucosal penile melanoma is not worse than that for cutaneous melanoma with comparable tumor thickness. Treatment should be similar to that for cutaneous melanoma, with wide radical excision and sentinel node biopsy in clinically lymph node-negative patients.

Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases (Article)

2007-03-01T00:00:00Z

Aim of the study: Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known. Methods: We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing ≥2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC. Results: We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy. Conclusions: Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.

Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma (Article)

2007-02-01T00:00:00Z

Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.

The course of distress in women at increased risk of breast and ovarian cancer due to an (identified) genetic susceptibility who opt for prophylactic mastectomy and/or salpingo-oophorectomy (Article)

2007-01-01T00:00:00Z

The levels and course of psychological distress before and after prophylactic mastectomy (PM) and/or prophylactic salpingo-oophorectomy (PSO) were studied in a group of 78 women. General distress was measured through the hospital anxiety and depression scale (HADS), cancer-related distress using the impact of events scale (IES). Measurement moments were baseline (2-4 weeks prior to prophylactic surgery), and 6 and 12 months post-surgery. After PM, anxiety and cancer-related distress were significantly reduced, whereas no significant changes in distress scores were observed after PSO. At one year after prophylactic surgery, a substantial amount of women remained at clinically relevant increased levels of cancer-related distress and anxiety. We conclude that most women can undergo PM and/or PSO without developing major emotional distress. More research is needed to further define the characteristics of the women who continue to have clinically relevant increased scores after surgery, in order to offer them additional counselling.

Sentinel node biopsy for clear cell sarcoma (Article)

2006-11-01T00:00:00Z

Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described. Two patients had positive SNs, with additional tumor positive nodes in both lymph node dissection specimens. Only the patients with tumor positive SNs developed recurrent disease during an average follow-up of 33 months. None of the negative SN patients developed recurrent disease and all were alive after an average follow-up of 39 months. SN status seems to predict additional nodal involvement and recurrent disease as well as survival. The SN procedure might be a useful and accurate staging procedure in CCS patients, comparable to the situation in melanoma.

Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? (Article)

2006-10-01T00:00:00Z

As only about 20% of sentinel node (SN) positive melanoma patients have additional non-SN lymph node involvement in the Completion Lymph Node Dissection (CLND) specimen, we tried to identify a SN positive patient group, which can be spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify patient/tumor and/or SN factors predicting additional non-SN positivity as well as disease-free and overall survival. SN positivity was found in 77 of 262 stage I/II patients, included into a prospective database (10/97-5/04). Of 74 patients pathology material was available for re-evaluation. Micro anatomic analyses categorized topography of SN-metastases, Starz classification and amount of SN tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0); mean FU was 35 (6-81) months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm. Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for the different groups of <0.1 mm, 0.1-1.0 mm and >1.0 mm SN tumor burden were 100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 = 6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor burden was the most important prognostic factor for DFS (P = 0.005) and OS (P = 0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN negative patients, the estimated 5-yr OS was 100% for these patients and additional non-SN positivity was not observed. Therefore, our data suggest that patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN negative, as non-stage III, and are highly unlikely to benefit from CLND, which we no longer recommend.

Extra-axial chordoma (Article)

2006-09-01T00:00:00Z

A chordoma which occurs as a primary tumour outside the axial skeleton is known as an extra-axial chordoma, parachordoma or chordoma periphericum. It is extremely rare and therefore survival, recurrence and the rates of metastasis are not known. Whilst few recurrences have been described, the extra-axial chordoma has the potential for late recurrence at up to 12 years. Metastases are even less frequent. We report the case of a 56-year-old woman who developed an extra-axial chordoma of the right thoracic wall in close relationship with the tenth rib. The tumour was completely removed and the prognosis is excellent.

High positive sentinel node identification rate by EORTC melanoma group protocol (Article)

2006-02-01T00:00:00Z

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.

Schildwachtklierbiopsie bij het melanoom: prognostische betekenis en nadelen bij 300 patienten (Letter To Editor)

2005-11-01T00:00:00Z

De Vries et al. ( 2005:1845-51 ) concluderen dat de uitslag van de schildwachtklier(SWK)-procedure bij melanoompatiënten de belangrijkste prognostische factor is. Tevens concluderen zij, volgens ons ten onrechte, dat de kans op in-transitmetastasen na een SWK-procedure mogelijk toeneemt. Een aantal zeer recente publicaties van grote studies met meer dan 5000 patiënten weerlegt deze opmerking...

One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases (Article)

2004-01-01T00:00:00Z

OBJECTIVE: The aim of this study is to describe the experience with 100 TNF-based ILP for locally advanced melanoma and to determine prognostic factors for response, time to local progression, and survival. METHODS: One hundred TNF-based ILPs were performed between 1991 and 2003 in 87 patients for whom local control by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac, 33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume. RESULTS: Overall response was 95%, with 69% complete response, 26% partial response, and 5% no change. Complete response rate differed significantly for patients with IIIA disease versus IIIAB and IV. Local and systemic toxicity was mild to moderate in almost all cases, with no treatment-related death and one treatment-related amputation. Five-year overall survival was 32%; local progression occurred in 55% after a median of 16 months. In complete response patients, 5-year survival was 42% with local progression in 52% at a median of 22 months. Response rate and survival were significantly influenced by stage of disease; (local progression free) survival was influenced by response rate. CONCLUSIONS: TNF-based ILP results in excellent response rates in this patient population with unfavorable characteristics. Response on ILP predicts outcome in patients and reflects aggressiveness of the tumor.

Fifty tumor necrosis factor-based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors (Article)

2003-01-01T00:00:00Z

BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan is highly effective in treating limb-threatening soft tissue sarcoma (STS) and other bulky tumors. Because of fear of TNF-associated toxicity, ILP with TNF is not offered to older patients in some cancer centers, although especially in older patients, every attempt to avoid an amputation that may end their independence must be considered. METHODS: Out of 306 TNF-based ILPs, 50 ILPs were performed for limb salvage in 43 patients >75 years old (range, 75-91 years): 29 STS and 14 melanoma patients. RESULTS: In the STS patients, a response rate of 76% and a limb-salvage rate of 76% were achieved; in the melanoma patients, a 100% response rate and a 93% limb-salvage rate were achieved. Local toxicity was mild. The three postoperative deaths that occurred in the total series of 306 TNF-based ILPs in Rotterdam (<1%) occurred in patients >75 years old after leakage-free perfusions and were not related to TNF but to extremely high-risk profiles in these three patients. CONCLUSIONS: Older patients should not be withheld a TNF-based ILP for limb salvage, because the procedure is safe and highly effective in these patients.

Mastectomy by inverted drip incision and immediate reconstruction: data from 510 cases (Article)

2003-01-01T00:00:00Z

BACKGROUND: Immediate reconstruction of the breast can be performed in selected cases after mastectomy for breast cancer or after prophylactic mastectomy in patients with a high risk of developing breast cancer. Despite the frequency with which these procedures are performed, data from large series of subpectoral implantation of silicone prostheses in combination with a skin-saving approach are lacking. METHODS: In this retrospective study, data on complications and late surgical interventions in 356 patients who underwent 510 mastectomies with an inverted drip incision and immediate reconstruction (MIDIIR) were analyzed to determine potential prognostic factors of early complications. RESULTS: In 82% of the MIDIIRs, the postoperative course was uneventful. In 18%, the complications were infection (32 cases), necrosis of the skin flap (29 cases), bleeding (31 cases), and protrusion of the prosthesis (20 cases), resulting in surgery in 9, 12, 15, and 20 cases, respectively. At the end of the follow-up period, 30 (6%) prostheses were definitively removed. Age, size of the prostheses, radiotherapy, previous lumpectomy, and indication for mastectomy were not significant factors for the prognosis of early complications. CONCLUSIONS: With the right technique and indications, MIDIIR is a very safe procedure and should be one of the surgical treatments that can be offered in the overall management of patients with, or at high risk for, breast cancer.

High relapse-free survival after preoperative and intraoperative radiotherapy and resection for sulcus superior tumors (Article)

2003-01-01T00:00:00Z

STUDY OBJECTIVES: Relapse-free survival in patients with sulcus superior tumors. DESIGN: Prospective registration study. SETTING: Department of surgical oncology of a university hospital. PATIENTS: Twenty-one patients treated with preoperative radiotherapy (46 Gy), lobectomy and chest-wall resection, and intraoperative radiotherapy (10 Gy). RESULTS: After a median follow-up of 18 months, 18 patients (85%) were free from locoregional relapse, while 8 patients were still alive. CONCLUSIONS: The results show that this protocol can achieve excellent local tumor control and can even be used for palliative treatment.

Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience (Article)

1996-01-01T00:00:00Z

OBJECTIVE: The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melphalan (M) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible. SUMMARY BACKGROUND DATA: To increase the number of limb-sparing resections in the treatment of locally advanced extremity soft tissue sarcoma, preoperative radiation therapy or chemotherapy or a combination of the two often are applied. The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation. METHODS: In 8 cancer centers, 186 patients were treated over a period of almost 4.5 years. There were 107 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (110 grade III; 51 grade II; and 25 very large, recurrent, or multiple grade I sarcomas). The composition of this series of patients is unusual: 42 patients (23%) had multifocal primary or multiple recurrent tumors; median tumor size was very large (16 cm); 25 patients (13%) had known systemic metastases at the time of the ILP. Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interferon-tau. A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP. RESULTS: A major tumor response was seen in 82% of the patients rendering these large sarcomas resectable in most cases. Clinical response rates were: 33 complete response (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) (22%), and 5 progressive disease (PD) (3%). Final outcome was defined by clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (16%), and 4 PD (2%). At a median follow-up of almost 2 years (22 months; range, 6-58 months), limb salvage was achieved in 82%. Regional toxicity was limited and systemic toxicity minimal to moderate, easily managed, with no toxic deaths. CONCLUSIONS: In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.