Cellular Radiosensitivity of Soft Tissue Sarcoma.

Currently, all soft tissue sarcomas (STS) are irradiated by the same regimen, disregarding possible subtype-specific radiosensitivities. To gain further insight, cellular radiosensitivity was investigated in a panel of sarcoma cell lines. Fourteen sarcoma cell lines, derived from synovial sarcoma, leiomyosarcoma, fibrosarcoma and liposarcoma origin, were submitted to clonogenic survival assays. Cells were irradiated with single doses from 1-8 Gy and surviving fraction (SF) was calculated from the resulting response data. Alpha/beta (α/ß) ratios were inferred from radiation-response curves using the linear-quadratic (LQ)-model. Cellular radiosensitivities varied largely in this panel, indicating a considerable degree of heterogeneity. Surviving fraction after 2 Gy (SF2) ranged from 0.27 to 0.76 with evidence of a particular radiosensitive phenotype in only few cell lines. D37% on the mean data was 3.4 Gy and the median SF2 was 0.52. The median α/ß was 4.9 Gy and in six cell lines the α/ß was below 4 Gy. A fairly homogeneous radiation response was observed in myxoid liposarcoma cell lines with SF2 between 0.64 and 0.67. Further comparing sarcomas of different origin, synovial sarcomas, as a group, showed the lowest SF2 values (mean 0.35) and was significantly more radiosensitive than myxoid liposarcomas and leiomyosarcomas (P = 0.0084 and 0.024, respectively). This study demonstrates a broad spectrum of radiosensitivities across STS cell lines and reveals subtype-specific radiation responses. The particular cellular radiosensitivity of synovial sarcoma cells supports consideration of the different sarcoma entities in clinical studies that aim to optimize sarcoma radiotherapy.

Adequate surgical margins for dermatofibrosarcoma protuberans - A multi-centre analysis.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumour. Adequate margins have a positive impact on recurrence rates. The aim of this study is to assess how adequate margins are achieved and secondly which additional treatment modalities might be necessary to achieve adequate margins. MATERIAL & METHODS: Patients with DFSP treated between 1991 and 2016 at three tertiary centres were included. Patient- and tumour characteristics were obtained from a prospectively held database and patient files. RESULTS: A total of 279 patients with a median age of 39 (Interquartile range [IQ], 31-50) years and a median follow-up of 50 (IQ, 18-96) months were included. When DFSP was preoperatively confirmed by biopsy and resected with an oncological operation in a tertiary centre, in 86% was had clear pathological margins after one excision. Wider resection margins were significantly correlated with more reconstructions (p = 0.002). A substantial discrepancy between the primary surgical macroscopic and the pathological margins was found with a median difference of 22 (range, 10-46) mm (Fig. 1). There was no significant influence of the width of the pathological clear margins (if > 1 mm) and the recurrence rate (p = 0.710). CONCLUSION: The wider the resection margins, the more likely it is to obtain clear pathological margins, but the more likely patients will need any form of reconstruction after resection. The aim of the primary excision should be wide surgical resection, where the width of the margin should be balanced against the need for reconstructions and surgical morbidity.

Isolated limb perfusion for soft tissue sarcoma: Current practices and future directions. A survey of experts and a review of literature.

Soft tissue sarcomas constitute 1% of adult malignant tumors. They are a heterogeneous group of more than 50 different histologic types. Isolated limb perfusion is an established treatment strategy for locally advanced sarcomas. Since its adoption for sarcomas in 1992, after the addition of TNFα, few modifications have been done and although indications for the procedure are essentially the same across centers, technical details vary widely. The procedures mainly involves a 60 min perfusion with melphalan and TNFα under mild hyperthermia, achieving a limb preservation rate of 72-96%; with an overall response rates from 72 to 82.5% and an acceptable toxicity according to the Wieberdink scale. The local failure rate is 27% after a median follow up of 14-31 months compared to 40% of distant recurrences after a follow up of 12-22 months. Currently there is no consensus regarding the benefit of ILP per histotype, and the value of addition of radiotherapy or systemic treatment. Further developments towards individualized treatments will provide a better understanding of the population that can derive maximum benefit of ILP with the least morbidity.

Surgical and medical management of small bowel gastrointestinal stromal tumors: A report of the Dutch GIST registry.

BACKGROUND: A cohort of 201 patients with small bowel gastrointestinal stromal tumors (GIST) treated between January 1st, 2009 and December 31st, 2016 in five GIST expertise centers in the Netherlands was analyzed. Goal of this study was to describe the clinical, surgical and pathological characteristics of this rare subpopulation of GIST patients, registered in the Dutch GIST registry. METHODS: Clinical outcomes and risk factors of patients with small bowel GIST who underwent surgery or treated with systemic therapy were analyzed. A classification was made based on disease status at diagnosis (localized vs. metastasized). RESULTS: 201 patients with small bowel GIST were registered of which 138 patients (69%) were diagnosed with localized disease and 63 patients (31%) with metastatic disease. Approximately 19% of the patients had emergency surgery, and in 22% GIST was an accidental finding. In patients with high risk localized disease, recurrence occurred less often in patients who received adjuvant treatment (4/32) compared to patients who did not (20/31, p < 0.01). Disease progression during palliative imatinib treatment occurred in 23 patients (28%) after a median of 20.7 (range 1.8-47.1) months. Ongoing response was established in 52/82 patients on first line palliative treatment with imatinib after a median treatment time of 30.6 (range 2.5-155.3) months. CONCLUSION: Patients with small-bowel GIST more frequently present with metastatic disease when compared to patients with gastric GIST in literature. We advocate for Prospective registration of these patients and investigate the use of surgery in patients with limited metastatic disease.

Using textbook outcome as a measure of quality of care in oesophagogastric cancer surgery.

BACKGROUND: Textbook outcome is a multidimensional measure representing an ideal course after oesophagogastric cancer surgery. It comprises ten perioperative quality-of-care parameters and has been developed recently using population-based data. Its association with long-term outcome is unknown. The objectives of this study were to validate the clinical relevance of textbook outcome at a hospital level, and to assess its relation with long-term survival after treatment for oesophagogastric cancer. METHODS: All patients with oesophageal or gastric cancer scheduled for surgery with curative intent between January 2009 and June 2015 were selected from an institutional database. A Cox model was used to study the association between textbook outcome and survival. RESULTS: A textbook outcome was achieved in 58 of 144 patients (40·3 per cent) with oesophageal cancer and in 48 of 105 (45·7 per cent) with gastric cancer. Factors associated with not achieving a textbook outcome were failure to achieve a lymph node yield of at least 15 (after oesophagectomy) and postoperative complications of grade II or more. After oesophagectomy, median overall survival was longer for patients with a textbook outcome than for patients without (median not reached versus 33 months; P = 0·012). After gastrectomy, median survival was 54 versus 33 months respectively (P = 0·018). In multivariable analysis, textbook outcome was associated with overall survival after oesophagectomy (hazard ratio 2·38, 95 per cent c.i. 1·29 to 4·42) and gastrectomy (hazard ratio 2·58, 1·25 to 5·32). CONCLUSION: Textbook outcome is a clinically relevant measure in patients undergoing oesophagogastric cancer surgery as it can identify underperforming parameters in a hospital setting. Overall survival in patients with a textbook outcome is better than in patients without a textbook outcome.

Outcomes after prophylactic gastrectomy for hereditary diffuse gastric cancer.

BACKGROUND: Patients with hereditary diffuse gastric cancer and a CDH1 mutation have a 60-80 per cent lifetime risk of developing diffuse gastric cancer. Total prophylactic gastrectomy eliminates this risk, but is associated with considerable morbidity. The effectiveness (removal of all gastric mucosa) and outcomes of this procedure were evaluated retrospectively. METHODS: All consecutive individuals undergoing a prophylactic gastrectomy for a CDH1 mutation or gastric signet ring cell foci at the authors' institute between 2005 and 2017 were included. RESULTS: In 25 of 26 patients, intraoperative frozen-section examination (proximal resection margin) was used to verify complete removal of gastric mucosa. All definitive resection margins were free of gastric mucosa, but only after the proximal margin had been reresected in nine patients. In the first year after surgery, five of the 26 patients underwent a relaparotomy for adhesiolysis (2 patients) or jejunostomy-related complications (3 patients). Six patients were readmitted to the hospital within 1 year for nutritional and/or psychosocial support (4 patients) or surgical reintervention (2 patients). Mean weight loss after 1 year was 15 (95 per cent c.i. 12 to 18) per cent. For the 25 patients with a follow-up at 1 year or more, functional complaints were reported more frequently at 1 year than at 3 months after the operation: bile reflux (15 versus 11 patients respectively) and dumping (11 versus 7 patients). The majority of patients who worked or studied before surgery (15 of 19) had returned fully to these activities within 1 year. CONCLUSION: The considerable morbidity and functional consequences of gastrectomy should be considered when counselling individuals with an inherited predisposition to diffuse gastric cancer. Intraoperative frozen-section examination is recommended to remove all risk-bearing gastric mucosa.

Isolated limb perfusion for locally advanced angiosarcoma in extremities: A multi-centre study.

BACKGROUND: Angiosarcomas are rare and aggressive soft-tissue sarcomas. The only potential curative treatment is complete surgical excision. This study reports the outcome of isolated limb perfusion (ILP) with high-dose melphalan and tumour necrosis factor α for locally advanced angiosarcoma. MATERIAL AND METHODS: All patients who underwent an ILP for angiosarcomas between 1991 and 2016 in three tertiary referral centres were identified from prospectively maintained databases. RESULTS: A total of 39 patients were included, with a median follow-up of 18 months (interquartile range 6.1-60.8). Of these patients, 23 (58.9%) patients had a complete response (CR) after ILP, 10 (25.6%) had a partial response, 4 (10.3%) had stable disease and 2 (5.1%) patients had progressive disease immediately after ILP. A total of 22 patients developed local progression (56.4%), whereas nine (23.1%) developed distant metastases. The patients with CR had a significantly prolonged median local progression-free survival (PFS) (15.4 versus 7.3 months, p = 0.015) when compared with non-CR patients, and a trend towards better median overall survival (81.2 versus 14.5 months, p = 0.054). Six patients underwent multiple ILPs, whereby the CR rate of the first, second and third ILPs were 60%, 80% and 67%, respectively. Thirteen (33.3%) patients needed further surgical intervention, consisting of resection in eight patients (20.5%) and amputation in five patients (12.8%). CONCLUSION: ILP is an effective treatment option for patients with locally advanced angiosarcoma in the extremities, resulting in a high number of CRs, a high limb salvage rate and prolonged local PFS.

Needle tract seeding following core biopsies in retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal tumours often require a preoperative core needle biopsy to establish a histological diagnosis. Literature is scarce regarding the risk of biopsies in retroperitoneal sarcomas, so the aim of this study is to identify the potential risks of core needle biopsies causing needle tract recurrences or local recurrences. METHOD: Patients who underwent resection of a primary retroperitoneal sarcoma between 1990 and 2014 were identified from a prospectively maintained database from two tertiary referral centres. Patient demographics, tumour characteristics and biopsy techniques were examined. The primary endpoint was needle tract recurrence and local intra-abdominal recurrence. RESULTS: 498 patients were included in the analysis. The most common histological subtypes were liposarcoma (66%) and leiomyosarcoma (18%). Of the 498 patients that underwent resection, 255 patients were diagnosed with a preoperative biopsy. Five patients (2%) developed a biopsy site recurrence: 3 patients with leiomyosarcomas and 2 patients with dedifferentiated liposarcomas. All biopsy site recurrences occurred after trans-abdominal biopsies and were not performed with a co-axial technique. There was no significant difference in local recurrence rate between the patients with or without a biopsy (=0.30) or for the biopsy route (trans-abdominal or trans-retroperitoneal (p = 0.72)). CONCLUSION: The risk of a needle tract metastasis after core needle biopsy for retroperitoneal sarcoma is very low but not zero. The safest method seems a trans-retroperitoneal approach with a co-axial technique. Local recurrence rate is not altered after doing a core needle biopsy.

[Network of specialized sarcoma centres]. / Netwerk van expertisecentra voor sarcoombehandeling.

Non-specialized centres see relatively few patients with rare cancers like soft tissue sarcoma. This leads to inappropriate diagnostic work-up and treatment resulting in a worse oncological outcome. We believe that modern tailor-made therapy for rare cancers requires not only the multidisciplinary expertise of specialized cancer centres but also, occasionally, the expert knowledge of an international network of specialist centres. Here, we emphasize the importance of national and international networks for the treatment of patients with rare tumours. The importance is placed in perspective using the treatment of sarcoma patients as an example.

Resection of liver metastases in patients with gastrointestinal stromal tumors in the imatinib era: A nationwide retrospective study.

INTRODUCTION: Liver metastases are common in patients with gastrointestinal stromal tumors (GIST). In the absence of randomized controlled clinical trials, the effectiveness of surgery as a treatment modality is unclear. This study identifies safety and outcome in a nationwide study of all patients who underwent resection of liver metastases from GIST. METHODS: Patients were included using the national registry of histo- and cytopathology (PALGA) of the Netherlands from 1999. Kaplan Meier survival analysis was used for calculating survival outcome. Univariate and multivariate regression analyses were carried out for the assessment of potential prognostic factors. RESULTS: A total of 48 patients (29 male, 19 female) with a median age of 58 (range 28-81) years were identified. Preoperative and postoperative tyrosine kinase inhibitor therapy was given to 30 (63%) and 36 (75%) patients, respectively. A minor liver resection was performed in 32 patients, 16 patients underwent major liver resection. Median follow-up was 27 (range 1-146) months. Median progression-free survival (PFS) was 28 (range 1-121) months. One-, three-, and five-year PFS was 93%, 67%, and 59% respectively. Median overall survival (OS) was 90 (range 1-146) months from surgery. The one-, three-, and five-year OS was 93%, 80%, and 76% respectively. R0 resection was the only independent significant prognostic factor for DFS and OS at multivariate analysis. CONCLUSION: Resection of liver metastases in GIST patients combined with imatinib may be associated with prolonged overall survival when a complete resection is achieved.

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials.

BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.

Treatment and prognostic factors of radiation-associated angiosarcoma (RAAS) after primary breast cancer: a systematic review.

BACKGROUND: Radiation-associated angiosarcoma (RAAS) of the breast is a rare, aggressive disease. The incidence is increasing with the prolonged survival of women irradiated for primary breast cancer. Surgery is the current treatment of choice. Prognosis is poor. This review aims to evaluate all publications on primary treatment of RAAS to identify prognostic factors and evaluate treatment modalities. METHODS: Databases were searched for articles with published individual patient data on prognostic factors, treatment and follow-up of patients with RAAS. A regression analysis was performed to test the prognostic values of age, interval between primary treatment and RAAS, tumour size and grade on the local recurrence-free interval (LRFI) and overall survival (OS). The effects of treatment modalities surgery, radiation (with or without hyperthermia) and chemotherapy or combinations were evaluated. RESULTS: 74 articles were included, representing data on 222 patients. In these patients, the 5-year OS was 43% and 5-year LRFI was 32%. Tumour size and age were significant prognostic factors on LRFI and OS. Of all patients, 68% received surgery alone, 17% surgery and reirradiation and 6% surgery with chemotherapy. The remaining 9% received primary treatments without surgery. Surgery with radiotherapy had a better 5-year LRFI of 57% compared to 34% for surgery alone (p=0.008). The value of other treatment modalities could not be assessed. CONCLUSIONS: This systematic review confirms the poor prognosis of RAAS. Tumour size and age were of prognostic value. The addition of reirradiation to surgery in the treatment of RAAS appears to enhance local control.

Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib -- analysis of prognostic factors (EORTC-STBSG collaborative study).

BACKGROUND: Long-term complete remissions remain a rare exception in patients with metastatic gastrointestinal stromal tumors (GIST) treated with IM (imatinib). To date the therapeutic relevance of surgical resection of metastatic disease remains unknown except for the use in palliative intent. PATIENTS AND METHODS: We analyzed overall survival (OS) and progression-free survival (PFS) in consecutive patients with metastatic GIST who underwent metastasectomy and received IM therapy (n = 239). RESULTS: Complete resection (R0+R1) was achieved in 177 patients. Median OS was 8.7 y for R0/R1 and 5.3 y in pts with R2 resection (p = 0.0001). In the group who were in remission at time of resection median OS was not reached in the R0/R1 surgery and 5.1 y in the R2-surgery (p = 0.0001). Median time to relapse/progression after resection of residual disease was not reached in the R0/R1 and 1.9 years in the R2 group of patients, who were resected in response. No difference in mPFS was seen in patients progressing at time of surgery. CONCLUSIONS: Our analysis implicates possible long-term survival in patients in whom surgical complete remission can be achieved. Incomplete resection, including debulking surgery does not seem to prolong survival. Despite the retrospective character and likely selection bias, this analysis may help in decision making for surgical approaches in metastatic GIST.

Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983.

AIM: The aim of this study is to describe local tumour control after radiofrequency ablation (RFA) and surgical resection (RES) of colorectal liver metastases (CLM) in two independent European Organisations for Research and Treatment of Cancer (EORTC) studies. BACKGROUND: Only 10-20% of patients with newly diagnosed CLM are eligible for curative RES. RFA has found a place in daily practice for unresectable CLM. There are no prospective trials comparing RFA to RES for resectable CLM. METHODS: The CLOCC trial randomised 119 patients with unresectable CLM between RFA (±RES)+adjuvant FOLFOX (±bevacizumab) versus FOLFOX (±bevacizumab) alone. The EPOC trial randomised 364 patients with resectable CLM between RES±perioperative FOLFOX. We describe the local control of resected patients with lesions ≤4 cm in the perioperative chemotherapy arm of the EPOC trial (N=81) and the RFA arm of the CLOCC trial (N=55). RESULTS: Local recurrence (LR) rate for RES was 7.4% per patient and 5.5% per lesion. LR rate for RFA was 14.5% per patient and 6.0% per lesion. When lesion size was limited to 30 mm, LR rate for RFA lesions was 2.9% per lesion. Non-local hepatic recurrences were more often observed in RFA patients than in RES patients, 30.9% and 22.3% respectively. Patients receiving RFA had a more advanced disease. CONCLUSIONS: LR rate after RFA for lesions with a limited size is low. The local control per lesion does not appear to differ greatly between RFA and surgical resection. This study supports the local control of RFA in patients with limited liver metastases. Future studies should evaluate in which patients RFA could be an equal alternative to liver resection.

Surgical treatment results of intestinal and diffuse type gastric cancer. Implications for a differentiated therapeutic approach?

AIM: To study the outcome of patients who were surgically treated for primary gastric cancer with specific attention to differences in treatment results for intestinal and diffuse type tumours. METHODS: All patients who underwent a potentially curative gastric resection between 1995 and 2011 in our institute were included. Patient, tumour and treatment characteristics were obtained retrospectively. Binary logistic and Cox regression models were used for multivariate analysis. RESULTS: A consecutive series of 132 patients was included. Median follow-up was 53 months. There were no significant differences between patients with intestinal (N = 62) versus diffuse type (N = 70) gastric cancer with regard to the proportion of patients who underwent (neo)adjuvant treatment. Postoperative mortality was 2%. Pathological T- and N-stage were significantly more advanced for patients with diffuse type tumours. There was a significant difference in the percentage of microscopically irradical resections (2% versus 24%, p < 0.001) and median overall survival (129 versus 17 months, p < 0.001) between patients with intestinal type tumours and those with diffuse type tumours. On multivariate analysis, diffuse type histology was the only factor significantly associated with an R1 resection. In a multivariate Cox regression model, diffuse type histology was a significant adverse prognostic factor for overall survival. CONCLUSIONS: Striking differences were found between patients with diffuse type tumours and those with intestinal type tumours. These differences call for a differentiated approach in the potentially curative treatment of these two tumour types.

Optical sensing for tumor detection in the liver.

BACKGROUND: There is an increasing trend for optical guidance techniques in surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can distinguish different tissue types through a specific "optical fingerprint". We investigated whether DRS could discriminate metastatic tumor tissue from normal liver tissue and thus if this technique would have potential for further implementation into surgical instruments or radiological intervention tools. METHODS: A miniaturized optical needle was developed able to collect DRS spectra between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal liver metastases were analyzed with DRS immediately after resection. Multiple measurements were performed and DRS results were compared to the histology analysis of the measurement locations. In addition, normal liver tissue was scored for the presence or absence of steatosis. RESULTS: A total of 780 out of the 828 optical measurements were correctly classified into either normal or tumor tissue. The resulting sensitivity and specificity were both 94%. The results of the analysis for each patient individually showed an accuracy of 100%. The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis in liver tissue compared to that of the pathologist was 0.86. CONCLUSIONS: DRS demonstrates a high accuracy in discriminating normal liver tissue from colorectal liver metastases. DRS can also predict the degree of hepatic steatosis with high accuracy. The technique, here demonstrated in a needle like probe, may as such be incorporated into surgical tools for optical guided surgery or percutaneous needles for radiological interventions.

Surgical treatment of locally advanced, non-metastatic, gastrointestinal stromal tumours after treatment with imatinib.

AIMS: Patients with locally advanced gastrointestinal stromal tumours (GISTs) have a high risk of tumour perforation, incomplete tumour resections and often require multivisceral resections. Long-term disease-free and overall survival is usually impaired in this group of patients. Induction therapy with imatinib followed by surgery seems to be beneficial in terms of improved surgical results and long-term outcome. We report on a large cohort of locally advanced GIST patients who have been treated in four centres in the Netherlands specialized in the treatment of sarcomas. METHODS: Between August 2001 and June 2011, 57 patients underwent surgery for locally advanced GISTs after imatinib treatment. Data of all patients were retrospectively collected. Endpoints were progression-free and overall survival. RESULTS: The patients underwent surgery after a median of 8 (range 1-55) months of imatinib treatment. Median tumour size before treatment was 12.2 (range 5.2-30) cm and reduced to 6.2 (range 1-20) cm before surgery. No tumour perforation occurred and a surgical complete (R0) resection was achieved in 48 (84%) patients. Five-year PFS and OS were 77% and 88%. Eight patients had recurrent/metastatic disease. CONCLUSIONS: Imatinib in locally advanced GIST is feasible and enables a high complete resection rate without tumour rupture. The combination of imatinib and surgery in patients with locally advanced GIST seems to improve PFS and OS.

Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004).

BACKGROUND: This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. METHODS: This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA ( ± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. RESULTS: The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2-73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1-70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42-0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7-22.1) and 9.9 months (95% CI 9.3-13.7), respectively. CONCLUSIONS: This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain.

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.

[Radiofrequency ablation of colorectal metastases to the liver: results since the first application in the Netherlands]. / Radiofrequente ablatie van colorectale levermetastasen: resultaten vanaf de eerste toepassing in Nederland.

OBJECTIVE: To provide an overview of the morbidity, mortality and survival following the introduction of radiofrequency ablation (RFA) of colorectal liver metastases in the Netherlands. DESIGN: Prospective, descriptive study. METHOD: Between June 1999 and December 2003 in eight hospitals in the Netherlands, 87 patients treated by RFA for colorectal liver metastases were included in the study. The outcome measures were morbidity, 30-day mortality and the percentage local recurrence. RESULTS: In 104 RFA procedures, 199 metastases were ablated; 31 procedures were performed percutaneously and 73 by laparotomy. In 29 procedures, RFA was combined with partial liver resection. The overall postoperative morbidity rate was 19% and the RFA-related morbidity was 14%. 1 patient died following right hemihepatectomy and RFA in the remaining parenchyma (mortality: 1%). Median survival following RFA was 25 months, with a median progression-free survival of 13 months. The overall local recurrence rate was 46%. Since January 2004, this percentage has decreased to approximately 6. Diameter and central location of the metastases were independent risk factors for the development of a local recurrence. CONCLUSION: RFA is an alternative treatment for patients who are not eligible for partial liver resection. The high local recurrence rate in this series reflects the limited experience with this technique during its introduction in the Netherlands. In specialised centres the percentage local recurrence is now 5. Treatment by RFA should always be weighed against the option of partial liver resection and possible (neoadjuvant) chemotherapy. RFA should therefore preferably be carried out in a centre with expertise in the field of liver surgery.