[The future of hyperbaric oxygen therapy: added value in the treatment of late radiation injury?]. / De toekomst van hyperbare zuurstoftherapie: Toegevoegde waarde bij de behandeling van late radiatieschade?

There is some evidence for the benefit of hyperbaric oxygen therapy in late radiation tissue injury (LRTI) affecting the head, neck and lower bowel, but there is little evidence for or against the benefit in other tissues (e.g. the breast) affected by LRTI. There is a need for large prospective trials including quality-of-life and cost-effectiveness studies, because hyperbaric oxygen therapy is becoming more popular.

Effect of a combined surgery, re-irradiation and hyperthermia therapy on local control rate in radio-induced angiosarcoma of the chest wall.

PURPOSE: Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor prognosis due to the high percentage of local failures. The efficacy and side effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in combination with surgery were assessed in RAS patients. PATIENTS AND METHODS: RAS was diagnosed in 23 breast cancer patients and 1 patient with melanoma. These patients had previously undergone breast conserving therapy (BCT, n = 18), mastectomy with irradiation (n=5) or axillary lymph node dissection with irradiation (n = 1). Treatment consisted of surgery followed by reRT + HT (n = 8), reRT + HT followed by surgery (n = 3) or reRT + HT alone (n = 13). Patients received a mean radiation dose of 35 Gy (32-54 Gy) and 3-6 hyperthermia treatments (mean 4). Hyperthermia was given once or twice a week following radiotherapy (RT). RESULTS: The median latency interval between previous radiation and diagnosis of RAS was 106 months (range 45-212 months). Following reRT + HT, the complete response (CR) rate was 56 %. In the subgroup of patients receiving surgery, the 3-month, 1- and 3-year actuarial local control (LC) rates were 91, 46 and 46 %, respectively. In the subgroup of patients without surgery, the rates were 54, 32 and 22 %, respectively. Late grade 4 RT toxicity was seen in 2 patients. CONCLUSION: The present study shows that reRT + HT treatment--either alone or combined with surgery--improves LC rates in patients with RAS.

No evidence of benefit from class-II compression stockings in the prevention of lower-limb lymphedema after inguinal lymph node dissection: results of a randomized controlled trial.

Graduated compression stockings have been advocated for prevention of lymphedema after inguinal lymph node dissection (ILND) although scientific evidence of their efficacy in preventing lymphedema is lacking. The primary objective of this study was to assess the efficacy of class II compression stockings for the prevention of lymphedema in cancer patients following ILND. Secondary objectives were to investigate the influence of stockings on the occurrence of wound complications and genital edema, health-related quality of life (HRQoL) and body image. Eighty patients (45 with melanoma, 35 with urogenital tumors) who underwent ILND at two specialized cancer centers were randomly allocated to class II compression stocking use for six months or to a usual care control group. Lymphedema of the leg and genital area, wound complications, HRQoL, and body image were assessed at regular intervals prior to and up to 12 months after ILND. No significant differences were observed between groups in the incidence of edema, median time to the occurrence of edema, incidence of genital edema, frequency of complications, HRQoL, or body image. Based on the results of the current study, routine prescription of class II graduated compression stockings after ILND should be questioned and alternative prevention strategies should be considered.

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

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.

Therapeutic surgical management of palpable melanoma groin metastases: superficial or combined superficial and deep groin lymph node dissection.

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.

Forequarter amputation for malignancy.

BACKGROUND: Forequarter amputation (FQA) is an important treatment for malignant disease of the shoulder girdle. The aim of this study was to elucidate its role in surgical oncology. METHODS: This retrospective study analysed 40 patients who had an FQA. In nine, the chest wall was resected. The most frequent diagnoses were soft-tissue sarcoma (28 patients) and recurrent breast cancer (five). RESULTS: Median follow-up was 16 (range 1-184) months. The 1-year, 2-year and 5-year overall survival for patients with malignant disease was 71, 59 and 38 per cent respectively. The median time to local recurrence (eight patients) was 4 (range 1-19) months. Thirty-two patients had curative FQA with a 1-year, 2-year and 5-year overall survival of 90, 75 and 48 per cent respectively, and a median overall survival of 51 months. The 5-year overall and disease-free survival for soft-tissue sarcoma was 41 and 26 per cent respectively. Eight patients had a palliative FQA with a median survival of 5 (range 1-12) months. CONCLUSION: In locoregional disease such as sarcoma, FQA may offer the only possibility of cure. However, in patients with axillary metastasis, FQA has no impact on survival, although local control may improve the patient's quality of life.

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

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 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.

[Long-term results of the multidisciplinary surgical treatment of non-small-cell bronchial carcinoma in the superior sulcus (Pancoast tumour): a retrospective study]. / Langetermijnresultaten van de multidisciplinaire chirurgische behandeling van niet-kleincellig bronchuscarcinoom in de thoraxkoepel (pancoasttumor); retrospectief onderzoek.

OBJECTIVE: To establish the long-term results of a combination of radiotherapy or chemoradiotherapy and surgery for the treatment of patients with a Pancoast tumour in the Erasmus MC-Daniel den Hoed, Rotterdam, the Netherlands, with special attention for the prognostic factors. DESIGN: Retrospective. METHODS: During the period from 1 January 1991 to 31 December 2004, 36 patients underwent surgical treatment combined with radiotherapy or chemoradiotherapy for a non-small-cell bronchial carcinoma with invasion of the superior sulcus. The study was terminated on 31 January 2006. The data were analysed according to the intention-to-treat principle, with overall survival and disease-free survival as the outcome variables. Cox regression analysis revealed differences between the subgroups on the basis of which prognostic factors could be studied. RESULTS: 36 patients with a non-small-cell bronchial carcinoma invading the superior sulcus (Pancoast tumour) underwent multidisciplinary treatment consisting of pre-operative radiotherapy (since 2002 concomitant chemoradiotherapy), superior-sulcus resection and (partial) lung resection with intra-operative brachytherapy. 2 patients died postoperatively. In 80% of the patients there was a positive histological effect of the preoperative treatment. The median follow-up was 26 months. The 2-year overall and disease-free survival was 45 and 31%, respectively, and at 5 years this was 28 and 19%. These results were comparable with those for stage IIB lung cancer without invasion. Favourable prognostic factors were: at least 75% necrosis of the tumour after pre-treatment, lack of positive mediastinal lymph nodes, and younger age.

[Oncoplastic surgery of the breast: a combination of oncological and plastic surgery]. / Oncoplastische chirurgie van de mamma: combinatie van oncologische en plastische chirurgie.

The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage ofoncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: mastectomy and immediate reconstruction of the breast, partial mastectomy and reconstruction, excision of the tumour by reduction mammoplasty, and tumour excision followed by remodelling mammoplasty. Oncoplastic surgery requires careful preoperative planning, which is essential in all forms of breast-sparing surgery. Oncoplastic principles can easily be applied to basic breast-sparing surgery, but one can also choose to increase the possibilities of breast surgery by organising good cooperation between the oncological surgeon and the plastic surgeon.

Who is prone to high levels of distress after prophylactic mastectomy and/or salpingo-ovariectomy?

BACKGROUND: The present study aimed to assess predictors of distress after 'prophylactic mastectomy (PM) and salpingo-ovariectomy (PSO), in order to enable the early identification of patients who could benefit from psychological support. PATIENTS AND METHODS: General distress and cancer-related distress were assessed in 82 women at increased risk of hereditary breast and/or ovarian cancer undergoing PM and/or PSO, before and 6 and 12 months after prophylactic surgery. Neurotic lability and coping were assessed before surgery. RESULTS: Cancer-related distress and general distress at both follow-up moments were best explained by the level of cancer-related and general distress at baseline. Being a mutation carrier was predictive of increased cancer-related distress at 6-month follow-up (but not at 12 months), and of lower general distress 12 months after prophylactic surgery. Also, coping by having comforting thoughts was predictive of less cancer-related distress at 6-month follow-up. CONCLUSIONS: Genetically predisposed women who are at risk of post-surgical distress can be identified using one or more of the predictors found in this study. Exploration of and/or attention to cancer-related distress and coping style before prophylactic surgery may help physicians and psychosocial workers to identify women who might benefit from additional post-surgical support.

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.

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.

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.

Long-term prognosis of primary retroperitoneal soft tissue sarcoma.

AIMS: To evaluate the result of treatment and long-term outcome of a population-based cohort of patients with retroperitoneal soft tissue sarcoma (RSTS). METHODS: Between 1 January 1989 and 1 January 1994, 143 patients diagnosed as having primary RSTS were selected from a national pathology database (PALGA) in the Netherlands. In this population-based group of patients, the result of surgery, overall survival (OS) and disease-free survival (DFS) were analysed as well as factors affecting OS and DFS. Median follow-up was 10.2 years. RESULTS: Operative treatment resulted in a complete tumour resection in 55% of the patients (n=78), low- and intermediate-grade tumours were more often completely resected than high-grade tumours (P=0.016). Five- and 10-year cumulative OS was 39% and 21%, respectively, while DFS was 22% and 17%, respectively. In a multivariate analysis low malignancy grade (P=0.017) and a complete tumour resection (P<0.001) were associated with better OS. CONCLUSIONS: Complete tumour resection and low malignancy grade were independent favourable prognosticators. However, these factors were related too, since surgical success was influenced by malignancy grade.

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.

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.

Extra-axial chordoma.

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.

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

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.

Aggressive angiomyxoma: multimodality treatments can avoid mutilating surgery.

AIMS: Aggressive angiomyxoma is a soft-tissue tumour of the pelvi-perineum. The recurrence rate is high, and often extensive resections are performed with considerable morbidity. In search of alternative treatment methods we present our experience in seven patients. METHODS: The medical charts of seven patients treated in the last 20years were reviewed. Follow-up data were obtained. In addition, a literature review from 1994 to 2004 regarding treatment and clinical outcome was performed. RESULTS: All patients were female, and three were pregnant at the time of diagnosis. All patients underwent primary surgical treatment. In five patients the surgical margins were involved; one patient received adjuvant radiotherapy treatment. Three patients experienced a total of four recurrences after 2-10years. These patients were treated with selective embolisation or surgery. At present all patients are disease-free, with follow-up ranging from 2 to 20years after last treatment. CONCLUSION: Radical surgery does not seem to lead to a significant lower recurrence rate of aggressive angiomyxoma when compared to incomplete resection (R1), with or without radiotherapy or arterial embolisation. This casts doubt on the necessity of extensive surgery, especially in cases where an extensive surgical procedure will lead to great morbidity.

Sentinel node biopsy for clear cell sarcoma.

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.