F. van Coevorden

Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy; Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon, Portugal; University Hospital Essen, Essen, Germany; Department of Oncological Orthopedics, Musculoskeletal Tissue Bank, IFO, Regina Elena National Cancer Institute, Rome, Italy; Klinikum Stuttgart-Olgahospital, Stuttgart, Germany; Institut Curie, Paris, France; NORDIX, Athens, Greece; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Vienna General Hospital (AKH), Medizinische Universität Wien, Vienna, Austria; Hospital Universitario Virgen del Rocio-CIBERONC, Seville, Spain; Centro di Riferimento Oncologico di Aviano, Aviano; Ospedale Regionale di Treviso “S.Maria di Cà Foncello”, Treviso, Italy; Integrated Unit ICO Hospitalet, HUB, Barcelona, Spain; Sarcoma Unit, University College London Hospitals, London, UK; Skane University Hospital-Lund, Lund, Sweden; N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation; Institute of Scientific Hospital Care (IRCCS), Regina Elena National Cancer Institute, Rome; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Istituto Ortopedico Rizzoli, Bologna; Azienda Ospedaliera Universitaria Careggi Firenze, Florence, Italy; Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands; Institut Jules Bordet, Brussels, Belgium; Candiolo Cancer Institute, FPO IRCCS, Candiolo, Italy; Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam and Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands; Turku University Hospital (Turun Yliopistollinen Keskussairaala), Turlu, Finland; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Mannheim University Medical Center, Mannheim; Department of Medicine III, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; Helsinki University Central Hospital (HUCH), Helsinki, Finland; Royal Marsden Hospital, London; The Institute of Cancer Research, London, UK; University Medical Center Groningen, Groningen; Radboud University Medical Center, Nijmegen, The Netherlands; University Hospital Motol, Prague; Masaryk Memorial Cancer Institute, Brno, Czech Republic; Gustave Roussy Cancer Campus, Villejuif, France; Maria Skłodowska Curie Institute, Oncology Centre, Warsaw, Poland; Tel Aviv Sourasky Medical Center (Ichilov), Tel Aviv, Israel; Medical Oncology, University Hospital of Lausanne, Lausanne, Switzerland; Azienda Ospedaliera, Universitaria, Policlinico S Orsola-Malpighi Università di Bologna, Bologna; Azienda Ospedaliero, Universitaria Cita della Salute e della Scienza di Torino, Turin, Italy; Fundacio de Gestio Sanitaria de L’hospital de la SANTA CREU I Sant Pau, Barcelona, Spain; Helios Klinikum Berlin Buch, Berlin, Germany; YCRC Department of Clinical Oncology, Weston Park Hospital NHS Trust, Sheffield, UK; Aarhus University Hospital, Aarhus, Finland; Leuven Cancer Institute, Leuven, Belgium; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway; Institute of Oncology of Ljubljana, Ljubljana, Slovenia; Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, The Netherlands; University College Hospital, London, UK; Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Münster, Germany; Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; Centre Leon Bernard and UCBL1, Lyon, France

Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal carcinomatosis of colorectal origin

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.

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.

Adverse effects of radiofrequency ablation of liver tumours in the Netherlands

Radiofrequency ablation (RFA) is a new treatment for liver tumours. Complications encountered after RFA in the Netherlands were evaluated in the present study.

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.

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.

The role of radiotherapy in the local management of dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP), a fibrohistiocytic tumour of intermediate malignancy, has a strong tendency to recur locally. Wide local excision is the recommended treatment modality. A retrospective analysis was performed on 38 consecutive DFSP patients presenting to The Netherlands Cancer Institute, to define the role of radiotherapy. Of the 21 patients treated surgically (all with negative resection margins) seven recurred, a local control probability of 67%. Combined modality treatment was given to 17 patients. Prior to radiotherapy, these patients experienced 33 occurrences of DFSP, but after irradiation only three recurrences were seen, a local control probability of 82%. These results are in keeping with the recent literature where increasing value is being given to both adjuvant and curative radiotherapy in the local management of DFSP. We recommend radiotherapy in DFSP patients where repeated surgery may cause mutilation or functional impairment.

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.

Alveolar soft part sarcoma: a report of 15 cases

The aim of this study was to evaluate the presentation, course and treatment outcome of 15 patients with this rare type of sarcoma. The files of the patients were retrospectively analysed. Overall survival was calculated according to the Kaplan-Meier method. There were 15 patients, 8 male and 7 female. The mean age at diagnosis was 29 years for men and 24 years for women. The median survival was 48 months with an overall 5-year survival of 38%. 5 patients had haematogenic metastases at the time of diagnosis. For the remaining 10 patients with localised disease, the median survival was 48 months and the 5-year survival 48%. The median disease-free survival for these patients was 12 months with a 5-year disease free survival of 40%. After the occurrence of haematogenic metastases, patients survived a median period of 8 months (range 0-45 months). 5 patients are still free of disease after a median period of 234 months (12-295 months). Alveolar soft part sarcoma is found especially in young adults. When diagnosed, it is often metastasised with a poor prognosis. However, when radically resected, long-term survival is possible.

Forequarter amputation for malignancy

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.