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e23539 Background: Induction isolated limb perfusion (ILP) followed by limb-sparing resection or extended resection are frequently used limb salvation strategies (LSS) in locally advanced extremity soft tissue sarcoma (eSTS) to prevent amputation. However little is known about the long term health-related quality of life (HRQoL) in these patients. The aim of this study was to compare long-term patient reported outcomes (PROs) such as HRQoL after ILP compared to extended resection or amputation. Methods: Patients treated with an ILP, extended resection, or amputation were selected from the respondents of a multi-institutional cross-sectional cohort survivorship study (SURVSARC) conducted 2-10 years after diagnosis among sarcoma survivors registered in the Netherlands Cancer Registry (NCR). Extended resection was defined as resection for stage III eSTS, details regarding amputation levels other than upper or lower extremity are unknown. Used PROs were the EORTC QLQ-C30, Cancer worry scale (CWS), the Hospital Anxiety and Depression Scale (HADS), and the Toronto Extremity Salvage Score (TESS). Results: We identified 96 eSTS survivors and assigned them into four groups: ILP (N = 20), extended resection (N = 48), primary amputation (N = 20), and amputation after ILP (N = 8). While there were no differences in PROs between ILP and extended resections, results showed better functioning and functionality after these two LSS groups versus the amputation groups. The amputation groups scored significantly lower on the EORTC QLQ-C30 physical functioning scale (p < 0.001, 62.7 and 65.7 versus 78.0 and 84.1) and role functioning scale (p = 0.038, 67.5 and 52.8 versus 79.2 and 80.9), which both account for a difference with ‘medium’ clinical relevance. Also for the TESS, the scores were significantly lower for the amputation groups compared to the LSS groups (upper extremity p = 0.007 with 68.9 and 71.6 versus 93.3 and 91.1; lower extremity p < 0.001 with 72.2 and 50.9 versus 84.5 and 85.5). There were no significant differences on cancer worry, anxiety and depression were found between all groups. Conclusions: Based on this survivorship study, HRQoL in eSTS survivors treated with ILP followed by limb-sparing resection is not inferior to extended resections, however it is superior in maintenance of physical functioning and functionality compared to an amputation.[Table: see text]

Hyperthermic-isolated limb perfusion (HILP) is an established modality of treatment for patients with advanced malignant melanoma of the limb in which diseased limb is infused with high concentration of chemotherapeutic agent. There is a lack of literature addressing its perioperative implications. We present a case and discuss the need for multipronged approach, team effort, and invasive hemodynamic and metabolic monitoring.

Introduction The management of locally advanced extremity soft tissue sarcomas, particularly in terms of a limb salvage strategy, represents a challenge, especially in recurrent tumors. In the context of a patient-tailored multimodal therapy, hyperthermic isolated limb perfusion (ILP) is a promising limb-saving treatment option. We report the outcome of patients with primarily irresectable and locally recurrent soft tissue sarcoma (STS) treated by ILP. Patients and methods Data about patient demographics, clinical und histopathological characteristics, tumor response, morbidity and oncological outcome of all patients with STS, who underwent an ILP at our institution in a 10-year period, were retrospectively detected and analyzed. Results The cohort comprised 30 patients. Two patients were treated with ILP for palliative tumor control, 13 patients because of a local recurrent soft tissue sarcoma (rSTS) and 15 patients because of primarily unresectable soft tissue sarcoma (puSTS). 25 of the 28 patients with curative intention received surgery after ILP (11 pts with rSTS and 14 pts with puSTS). Histopathologically we observed complete response in 6 patients (24%) and partial responses in 19 patients (76%) with a significant better remission in patients with puSTS (p = 0,043). Limb salvage rate was 75%. Mean follow-up was 69 months [range 13–142 months]. Seven (7/11; 64%) patients with rSTS and one (1/14; 7%) patient with puSTS developed local recurrence after ILP and surgery, whereas eight (8/13; 62%) rSTS patients and seven (7/15; 47%) puSTS patients developed distant metastasis. During follow-up, eight patients (28.5%) died of disease (5/13; 38%) rSTS and 3/15 (20%) puSTS. ILP in the group of previously irradiated sarcoma patients (n = 13) resulted in a limb salvage rate of 69% and was not associated in an increased risk for adverse events. Discussion ILP for advanced extremity STS is a treatment option for both puSTS and rSTS resulting in good local control and should be considered in multimodal management. ILP is also a good option for patients after radiation history.

OBJETIVO describir la experiencia inicial en Colombia en el manejo del melanoma de extremidad con perfusion aislada y comparar la respuesta de los subtipos histologicos mas frecuentes en Colombia con la literatura. MATERIALES Y METODOS estudio descriptivo, retrospectivo de una serie de pacientes con diagnostico de melanoma con metastasis en transito tratados con perfusion aislada de extremidad, seleccionados entre 2007 y 2016. Las variables cualitativas se analizaron con frecuencias absolutas y relativas. Las cuantitativas con medidas de tendencia central y dispersion. RESULTADOS 11 pacientes fueron tratados con perfusion aislada de extremidad. Hubo respuesta parcial en siete pacientes (63,6%), enfermedad estable en dos pacientes (18,2%) y progresion en dos pacientes (18,2%). Despues del tratamiento, cinco pacientes (45,5%) presentaron complicaciones menores. CONCLUSIONES la perfusion aislada sigue siendo importante para el tratamiento del melanoma localmente avanzado con el fin de mejorar la calidad de vida de los pacientes. La respuesta puede cambiar segun el tipo clinico de melanoma, siendo menor, segun este estudio, en pacientes con melanoma lentiginoso acral y nodular, aunque por el bajo poder, esto no se puede concluir. OBJECTIVE to describe the initial experience in Colombia of locally advanced melanoma treated by isolated limb perfusion and compare the response rate of our melanoma subtypes with the literature. METHODS descriptive, retrospective study of a series of patients selected between 2007 and 2016. Qualitative variables were analyzed with proportions and frequencies, and quantitative variable with central tendency measures and measures of dispersion. RESULTS 11 patients were treated by isolated limb perfusion. After the treatment, seven patients (63.6%) had partial response, two patients (18.2%) had stable disease and two patients (18.2%) had disease progression. Five patients (45.5%) had mild complications. CONCLUSIONS Isolated limb perfusion is still an important treatment strategy for locally advanced melanoma, with the goal of improving the patient quality of life. The response can change according to the type of melanoma, and could be smaller in patients with acral lentiginous and nodular melanoma, although we cannot make this conclusion with this type of study because it has low power and lack of a comparison group.

Background In-transit metastasis is considered a locoregional disease in cutaneous melanoma (CM) patients. Isolated limb perfusion (ILP) is among the treatment options in selected cases. The aim of this study was to determine the success of pre- and post-perfusion mSIS values in predicting the potential complications and the prognosis of the disease by investigating the early and long-term results of mSIS values calculated before and after ILP in CM cases with in-transit metastases. Materials and methods Patients who underwent ILP within the period from 2014 to 2020 in our department were retrospectively scanned. A total of 20 patients were found to undergo ILP. The scores obtained from modified inflammation score (mSIS) were formulated according to albumin (Alb) and lymphocyte to monocyte ratio (LMR) scores. Results The mean follow-up time was 20.47 months. Complications requiring surgical intervention developed in three patients. According to the Wieberdink local toxicity classification, the majority (70%) of the patients were found to be grade II. Based on pre-perfusion mSIS values, 8 patients were classified as mSIS 0 while six patients were classified as mSIS 1 and 2. Based on post-perfusion mSIS values, 14 patients and one patient were classified as mSIS 2 (70%) and mSIS 0, respectively. Accordingly, univariate analysis showed that mSIS 1 and mSIS 2 were negative prognostic factors for mean survival in the pre-perfusion period (HR 0.162, 95% CI 0.036–0.729; p = 0.018 and HR: 0.223, 95% CI 0.049–1.019; p = 0.053) whereas albumin (Alb) and lymphocyte to monocyte ratio (LMR) were not independent prognostic factors for mean survival. Conclusion The mSIS values calculated in the pre-perfusion period can give an opinion about the OS of the patients whereas post-perfusion mSIS values may predict potential surgical complications and local toxicities.

Isolated limb perfusion (ILP) is widely accepted as treatment for recurrent melanoma limited to the limbs. The use of ILP has decreased in recent years with the introduction of potentially effective new systemic therapies. We evaluated retrospectively if ILP still may be a treatment option in locally advanced melanoma. In Finland, ILP is centralized to the Comprehensive Cancer Center of Helsinki University Hospital. We included all ILP patients treated at our hospital between 2007 and 2018. Clinical factors and treatment outcomes were retrospectively evaluated. Altogether 60 patients received ILP. Toxicity was mostly transient. The overall response rate was 77% with 35% complete responses and 42% partial responses. The median progression-free survival (PFS) was 6.1 months (range 0.6-116.5 months) and the median melanoma-specific survival (MSS) was 29.9 months (range 3.5-138.7 months). Patients with CR had superior median PFS (19.7 months, range 2.5-116.5 vs. 4.5 months, range 0.6-39.7 months, P = 0.00003) and median MSS (median MSS not reached vs. 25.9 months, range 3.5-98.7 months, P = 0.0005) compared to other responders. Younger patients (

Background and objectives Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department. Patients and methods Eighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months. Results The study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1–219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016). Conclusion HILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.

For locally advanced soft tissue sarcomas and metastases from melanoma located in the extremities, mutilating surgery or amputation may be necessary to achieve local control. Isolated limb perfusion with high-dose chemotherapy may represent an alternative to amputation for this patient group.

Nonmelanoma skin cancer (NMSC) is more prevalent than all the other cancers combined together. The most common regions affected by skin cancer are the head and neck, but there is a large proportion of the cases located on the limbs. They could be bulky, very extensive and/or located in specialized regions like the hands or near to a joint. Most of those cases should be amputated, with several compromises of the function and a negative impact on the patients' quality of life. Isolated limb perfusion is a proven alternative to limb salvage on soft tissue sarcomas, but there are just a few reports about its application on non-melanoma skin cancer. The aim of the article is to describe the outcomes and prove the benefits and effectiveness to avoid limb amputation when using isolated limb perfusion on locally advanced non-melanoma skin cancer. We present clinical, retrospective study as a case series report. The study includes four patients with locally advanced non-melanoma skin cancer in the limb - three cases with squamous cell carcinoma (SCC), and one patient with Merkel cell carcinoma (MCC) who underwent to tumor necrosis factor-alpha (TNFα) and melphalan based isolated perfusion of the limb (TM-ILP). Toxicity, clinical response, and limb salvage were described. Patients were treated in the oncological surgical department in a referral hospital in Mexico. The limb salvage rate was achieved in 75%. All patients had a favorable response to TM-ILP. Complete response of the tumor was noted on two (50%) of the patients (one with histopathological confirmation), the other 50% had a partial response to the TM-ILP. No serious toxicity related to TM-ILP was observed. One patient (25%) developed regional lymph involvement six months after perfusion. Lymphadenectomy was performed, and the patient subsequently has a six-year disease-free survival. In conclusion, TM-ILP could be an effective, reliable, and safe therapy on limb salvage in selected patients with non-melanoma skin cancer who are not adequate surgical candidates.

INTRODUCTION: Kaposi sarcoma (KS) is a rare soft tissue sarcoma. In case of locally advanced disease, mutilating surgery such as amputations or major reconstructive procedures are sometimes inevitable. The aim of this study was to evaluate the effectiveness of isolated limb perfusion (ILP) in patients with locally advanced KS of the extremities.MATERIAL AND METHODS: All patients who underwent ILP for KS between 1996 and 2018 at Erasmus MC, Rotterdam were identified. Clinical data was obtained from either a prospectively maintained database or retrospective assessment of patient files.RESULTS: A total of 14 primary ILP's were performed in 11 patients. Median follow-up from primary ILP was 30 months (range, 5-98). The overall response rate of primary ILP was 100%, with a complete response (CR) rate of 50%. Only minimal local toxicity (Wieberdink I-III) was observed. Local progressive disease occurred after eight primary ILP's (57%) with a median local progression free survival (PFS) of 18 months (95% confidence interval [CI]: 7.0-28.9). Subsequently, four (46%) patients received a total of 5 recurrent ILP's. After the recurrent ILP on the same leg, the overall response rate was 75% and a CR-rate of 50%. One patient needed amputation post-operatively resulting in a limb salvage rate of 91%. One (9%) patient developed metastases four months after ILP.CONCLUSIONS: ILP is a highly effective treatment modality with very limited morbidity rates for patients with locally advanced KS of the extremity. ILP should be considered as a treatment modality for locally advanced KS of the extremities.

The aim of the present study was to investigate the incidence of organ dysfunction, and to describe the clinical characteristics and intensive care unit (ICU) outcomes of critically ill cancer patients who were admitted to an oncological ICU during the isolated limb perfusion post-operative period. The present study was an observational investigation of 42 critically ill cancer patients who were admitted to the ICU of the Instituto Nacional de Cancerología, during the isolated limb perfusion post-operative period, between July 2010 and February 2016. The mean age of the patients was 45.7±16.9 years, and 45.2% (19 cases) were female. Soft tissue sarcoma was the most common pre-operative diagnosis (38.1%), and the mean duration of surgery was 267.6±50.1 min. Furthermore, a mean blood loss volume of 732.3±526.1 ml during the procedure was recorded, and the patients received a mean volume of 3.88±1.28 l crystalloid fluid during the surgical procedure, subsequently requiring an additional 2.95±6.28 l on the first post-operative day. The incidence of organ dysfunction was 90.5% and was most frequently noted in the respiratory (81%), hepatic (33%), hematologic (31%) and renal (11.9%) systems. No patients succumbed to the disease during the ICU and hospital stay. Nevertheless

In transit metastases (ITM) from extremity or trunk melanomas are subcutaneous or cutaneous lymphatic deposits of melanoma cells, distant from the primary site but not reaching the draining nodal basin. Superficial ITM metastases develop in 5-10% of melanoma patients and are thought to be caused by cells spreading along lymphatics; ITM appear biologically different from distant cutaneous metastases, these probably due to a haematogenous dissemination. The diagnosis is usually clinical and by patients, but patients need to be adequately educated in the recognition of this clinical situation. Ultrasound or more sophisticated instrumental devices may be required if the disease develops more deeply in the soft tissues. According to AJCC 2009 staging classification, ITM are included in stages IIIb and IIIc, which are considered local advanced disease with quite poor 5-year survival rates and outcomes of 24-54% at 5 years.2 Loco-regional recurrence is in fact an important risk factor for distant metastatic disease, either synchronous or metachronous. Therapy for this pattern of recurrence is less standardised then in most other clinical situations and options vary based on the volume and site of the disease. Definitive surgical resection remains the preferred therapeutic approach. However, when surgery cannot be performed with a reasonable cosmetic and functional outcome, other options must be utilized.3-6 Treatment options are classified as local, regional or systemic. The choice of therapy depends on the number of lesions, their anatomic location, whether or not these are dermal or subcutaneous, the size and the presence or absence of extra-regional disease.

Data on isolated limb perfusion (ILP) in elderly melanoma patients are scarce. We aimed to evaluate the efficacy and safety of ILP in our institutional cohort of melanoma patients. We performed retrospective analysis of stage IIIB/C melanoma patients who underwent ILP for melanoma in-transit metastases (ITMs) in our institution between 2000 and 2016. Normothermic ILP was performed with either melphalan or melphalan and tumor necrosis factor. Baseline and treatment characteristics, locoregional progression-free survival (LPFS) and melanoma-specific survival (MSS) were assessed and prognostic factors for response, recurrence, and survival were analyzed using univariable and multivariable analysis. Overall, 91 patients were included in this study. Based on the median age of 70 years, we split patients into younger and elderly groups. No differences in response rates were observed between age groups, with an overall response rate of 81% and complete response (CR) rate of 47%. LPFS did not differ between age groups, and median LPFS was 16 months for patients with a CR. Median MSS was 38 months and differed between younger (45 months) and elderly patients (18 months). Toxicity was generally mild and did not differ between age groups. Two patients (2.2%) suffered Wieberdink IV toxicity, while no patients required amputation because of severe toxicity. CR was prognostic for improved LPFS and MSS, while patients >70 years of age and patients with stage IIIC disease had a higher risk of melanoma-specific death. Because of its safety profile and high CR rates, ILP is a viable option for patients with bulky or multiple melanoma ITMs, including elderly (>70 years of age) patients.

Background This novel study compared the use of tumor necrosis factor (TNF)-alpha and melphalan-based isolated limb perfusion (TM-ILP) to the standard treatment of locally recurrent soft tissue extremity sarcoma. The aim was to assess whether TM-ILP positively influences the recurrence-free survival of locally recurrent high-grade soft tissue sarcoma (STS) of the extremities. Methods We retrospectively analyzed our clinical database for patients with STS. Variables were analyzed using chi-square test or Mann-Whitney rank-sum test. Furthermore, Kaplan-Meier survival plots were calculated and a proportional hazard regression model was developed. Results Out of 448 patients with extraabdominal STS treated between August 2012 and December 2015, 52 cases involving 47 patients had locally recurrent STS. Twenty-eight of these patients were treated with TM-ILP prior to surgical resection (TM-ILP-group), and 24 were treated with standard therapy (without TM-ILP). The 3-year recurrence-free survival for the TM-ILP-group was estimated at 75% (95% confidence interval (CI), 71.5–78.5). Local recurrence-free survival in the standard group was significantly lower (LRFS: 43.4%, 95% CI 38.7–48.1, p = 0.026). Multivariable analysis revealed resection with negative margins, lower number of previous recurrences, and TM-ILP as positive predictors for recurrence-free survival. Conclusions TM-ILP and consecutive resection of residual tumor with negative resection margins significantly improves local recurrence-free survival for patients with a first local recurrence of high-grade STS in the extremities.

Melanoma is an aggressive cutaneous malignancy that can recur in the form of in-transit lesions. In-transit disease can present challenges for both physician and patient, particularly when unresectable and bulky. Multiple new therapeutic modalities have been introduced in recent time, but regional chemotherapy for extremity in-transit disease in the form of hyperthermic isolated limb perfusion and isolated limb infusion are useful tools in achieving disease response, improving survival in those that do not recur distantly, and helping to salvage limbs in cases where amputation is the only other treatment alternative. This chapter serves to cover the modern literature that guides current clinic practice using these modalities. While both are effective treatments, isolated limb infusion has gained momentum with increasing use due to its simplicity and similar disease response rates. With the introduction of new systemic agents, further research will need to look into the best ways that regional chemotherapy can be utilized within the scheme of a multimodality treatment plan for patients with in-transit extremity disease.

Background and objectives Isolated limb perfusion (ILP) and infusion (ILI) are treatment modalities for unresectable melanoma in-transit metastases and extremity soft tissue sarcomas (STS). We sought to characterize the national trend in their utilization in the context of novel melanoma therapies introduced in 2011. Methods Using the National Inpatient Sample (2005-2014), patients with a primary diagnosis of limb melanoma or STS who underwent ILP/ILI were identified by diagnosis and procedure codes. Annual percent change (APC) in ILP/ILI procedures was determined. Results From 2005 through 2014, 670 and 130 ILP/ILI procedures were performed for melanoma and STS, respectively. Mean age was 64 (SD 15) years for melanoma and 59 (SD 18) years for STS. Over time, procedures for melanoma decreased with an APC of -17 (P = .019). Comparing 2005-2010 and 2011-2014, the mean number of procedures for melanoma decreased from 91 to 32 per year (P = .007). In contrast, there was no change for STS (APC 6.5, P = .39; mean 11 and 16 per year in 2005-2010 and 2011-2014, respectively, P = .46). Conclusions ILI/ILP utilization has decreased for melanoma, but not for STS. Whether trends for ILP and ILI differed could not be determined. ILP/ILI remains an important option to consider for regional disease control.

Introduction Hyperthermic isolated limb perfusion (HILP) has an established role in the management of melanoma, but its role for Merkel cell carcinoma (MCC) is less well defined. Methods Retrospective review of our institutional experience with HILP for MCC was conducted (2009–2015). Literature search was performed through 04/2015 and 10 studies met inclusion criteria. Results Four patients underwent HILP for MCC at our institution. There were no major complications and complete response was achieved in all patients. Early metastatic recurrence developed in two patients. The remaining two had no evidence of disease at last follow-up (36 months) or death (39 months). Systematic review identified an additional 12 pts that underwent HILP for MCC, for a total of 16 cases. Median age was 73 [IQR 69–78] years and 56% were men. Of the patients with reported follow-up, 12 (86%) had complete response, 1 had stable disease, and 1 partial response. Four patients developed local–regional recurrence and six distant metastases, all within 6 months. Overall median follow-up time was 15 [7–36] months. Conclusion Among a highly selective group of patients, regional perfusion for MCC is safe and has a high complete response rate. HILP is an acceptable therapeutic modality for obtaining durable loco-regional control but early distant metastatic disease remains a significant cause of mortality. J. Surg. Oncol. 2016;114:187–192. © 2016 Wiley Periodicals, Inc.

Isolated limb perfusion (ILP) and isolated limb infusion (ILI) are treatment options for patients with locally advanced melanomas and sarcomas of the extremities. ILP potentially have higher response rates, but requires open surgery for vascular access, whereas ILI is minimally invasive and easier to perform. We now present the technical details and outcome of a new approach to ILP by a minimally invasive vascular access (MI-ILP).Six patients, five with melanoma in-transit metastases and one with squamous cell carcinoma, were included in a phase I feasibility trial. Percutaneous vascular access of the extremity vessels was performed and the inserted catheters were then connected to a perfusion system.All six treated patients underwent the procedure without the need for conversion to open surgery. The median operating time was 164 min and the median leakage rate was 0.1%. The complete response rate was 67%. Four patients (67%) had a Wieberdink grade II reaction and two patients (33%) had a grade III reaction.MI-ILP is feasible and gives the same treatment characteristics as open ILP, but with the advantage of a minimally invasive vascular access.

Background Induction chemotherapy by isolated limb perfusion (ILP) with melphalan and tumour necrosis factor-α is an effective strategy to facilitate limb-conserving surgery in locally advanced extremity sarcoma. In a comparison of cohorts matched for grade, size and surgical resectability, we compared the outcome of patients undergoing induction ILP prior to limb-conserving surgery and selective post-operative radiotherapy with patients undergoing limb-conserving surgery and routine post-operative radiotherapy. Methods Patients with primary, grade 2/3 sarcomas of the lower limbs over 10 cm in size were identified from prospectively maintained databases at 3 centres. Patients treated at a UK centre underwent limb-conserving surgery and post-operative radiotherapy (Standard cohort). Patients at two German centres underwent induction ILP, limb-conserving surgery and selective post-operative radiotherapy (ILP cohort). Results The Standard cohort comprised 80 patients and the ILP cohort 44 patients. Both cohorts were closely matched in terms of tumour size, grade, histological subtype and surgical resectability. The median age was greater in the Standard vs the ILP cohort (60.5 years vs 56 years, p = 0.033). The median size was 13 cm in both cohorts. 5-year local-recurrence (ILP 12.2%, Standard 20.1%, p = 0.375) and distant metastases-free survival rates (ILP 49.6%, Standard 46.0% p = 0.821) did not differ significantly between cohorts. Fewer patients received post-operative radiotherapy in the ILP cohort compared with the Standard cohort (27% vs 82%, p

In-transit metastases of melanoma occur in 5-8% of all melanoma patients. In case of extensive locoregional disease, Tumor necrosis factor-α and melphalan-based isolated limb perfusion (TM-ILP) had proven to yield excellent local control. Here, we report on repeat TM-ILP for locoregional recurrence after isolated limb perfusion. Between 1991 and 2013, 37 consecutive repeat TM-ILPs were analyzed in 32 different patients. Three patients underwent a third TM-ILP. During a median follow-up of 20 months after repeat TM-ILP, the overall response rate was 86%. Complete response (CR) was recorded after 24 TM-ILPs (65%). CR after first TM-ILP was a strong predictor for successful repeat TM-ILP in terms of clinical response and local recurrence. Local toxicity was mild (70% Wieberdink I-II). The local recurrence rate was 59%. Five-year overall survival was 35%. Repeat TM-ILP is a safe treatment modality in melanoma patients with recurrent in-transit metastases of melanoma. Those with a CR after first TM-ILP benefit the most from repeat TM-ILP.

Soft tissue sarcomas (STSs) gather over 80 histological entities, with even more molecular subsets, characterised by a low to very low incidence in all populations. The majority of sarcomas arise from the soft tissue (close to 75%), with ~15% gastrointestinal stromal tumours (GISTs) and 10% bone sarcomas. These ESMO–EURACAN (European Society for Medical Oncology– European Reference Network for rare adult solid cancers) Clinical Practice Guidelines cover STSs, while GISTs are covered by dedicated ESMO–EURACAN Clinical Practice Guidelines. Kaposi’s sarcoma is not considered in the present document. Extraskeletal Ewing and Ewing-like sarcoma is covered by ESMO Clinical Practice Guidelines on bone sarcomas. In general, the same principles for these tumours in children apply to adults. This is also the case for embryonal and alveolar rhabdomyosarcomas, which are exceedingly rare in adults. On the other hand, pleomorphic rhabdomyosarcoma is viewed as a high-grade, adult-type STS. Extraskeletal osteosarcoma is also a high-grade STS, whose clinical resemblance with osteosarcoma of bone is doubtful (prospective collection of data is encouraged to generate evidence on the therapeutic implications of such a diagnosis). Adult STS pathological subtypes occurring in adolescents should be managed the same way as in adult patients, though the same histotypemight display clinical peculiarities when occurring at different ages.

Hyperthermic isolated limb perfusion (HILP) represents a limb-sparing treatment for unresectable soft tissue sarcoma (STS) of the extremities with substantial complete response rates. HILP often provides good functional limb preservation, hence a significant improvement also in terms of quality of life of the patient. Notwithstanding these clear advantages, the traditional technique is still hindered by relatively high post-operative morbidity.We treated a 78-year-old female with unresectable angiosarcoma of the left leg using a new surgical approach: an entirely laparoscopic HILP.No conversion from laparoscopic to "open" surgery was necessary. Since no abdominal muscle section was performed, post-operative pain was low and easily manageable; early mobilisation and early discharge were achieved. Patient developed moderate toxicity, which resolved spontaneously within 3-4 weeks, with complete return to normal daily activities after 30 d. Complete clinical response with preservation of leg function was obtained.We describe for the first time an entirely laparoscopic HILP. Demonstration of this technique's efficacy and safety on a large series of patients is clearly necessary but its therapeutic efficacy appears to be comparable to the standard technique. Furthermore, laparoscopic HILP has shown low post-operative morbidity: no wound complications, mild and easily manageable post-operative pain and early discharge from the hospital and early resuming of daily activities.

Background and Objectives Primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30+ LPD), including primary cutaneous anaplastic large cell lymphoma (CALCL) and lymphomatoid papulosis (LyP), comprise the second most common group of cutaneous T-cell lymphomas (CTCL). The etiology of these disorders is not known. Isolated limb perfusion (ILP) and isolated limb infusion (ILI) are forms of regional chemotherapy used to treat recurrent tumors of the extremity, most commonly, melanoma. Secondary malignancy following regional therapy is rarely reported. Methods/Results We identified two cases of CD30+ LPD arising in the affected limbs of patients treated with ILP/ILI. We subsequently performed CD30 immunohistochemical stains on 11 pre- and post-treatment skin specimens from melanoma patients treated with ILP/ILI and found that 5 of the 11 cases showed an increase in CD30+ lymphocytes following ILP/ILI. Conclusions We hypothesize that ILP/ILI causes upregulation of CD30 expression in the extremities of treated patients, and suggest that this may be a marker of treatment response. However, a rare but long-term effect may be an increased risk of T-cell cutaneous lymphoproliferative disease in the affected limb. J. Surg. Oncol. 2014 110:258–264. © 2014 Wiley Periodicals, Inc.

Background: Isolated limb perfusion (ILP) is an effective limb salvage strategy in patients with advanced soft tissue sarcoma (STS) where surgery alone would result in significant functional morbidity or mandate an amputation. Most previous reports of patients undergoing ILP focus on limb salvage rates rather than local and distant relapse rates. Here, we report the oncological outcome of sarcoma patients treated by ILP and surgery. Methods:Data wereretrieved fromprospective ILPdatabases from two ILPcenters following similar ILPtechniques and surgical approaches. Only patients with primary, intermediate, or high grade non‐metastatic STS were included. Results: The cohort comprised 90 patients. Median follow‐up was 39 months (range 3–165 months). Median tumor size was 11cm (range 5–34). Twenty of 90 (22%) patients underwent prior debulking surgery outside the centers. Twenty‐nine of 90 (32%) had postoperative irradiation. Four of 90 underwent amputation either related to local recurrence or irresectability, 4 of 90 underwent amputation for treatment‐related complications. Fifteen of 83 (18%) patients had local recurrences after ILP and limb sparing surgery, 39 of 90 (43%) developed metastatic disease. Twenty‐two of 90 (24%) died of disease. Conclusion: Preoperative ILP and tumor resection resulted in good local control in a cohort of high‐risk STS patients. J. Surg. Oncol. 2014 Wiley Periodicals, Inc.

Background Isolated limb perfusion (ILP) is used to treat in-transit metastases of melanoma of the extremities when surgical excision is not possible. The optimal setting concerning temperature and perfusion time is unknown. The purpose of this study was to analyze these factors concerning their effects on response, toxicity, and survival. Methods A retrospective analysis of 284 consecutive stage III melanoma patients treated with melphalan ILP for the first time in our institution, during a 31-year period (July 1986–May 2017), was performed. Our series was divided in four time periods, according to perfusion temperature and duration. Demographical data, stage, number, and size of lesions were retrieved from our prospective database. Results Overall response (OR) rate 83% and a complete response (CR) rate of 59%. Significant predictive factors for CR in multivariate analysis were non-bulky tumor, fewer metastases, and a perfusion time of 120 min. Predictive factors for increased local toxicity were femoral ILP and higher perfusion temperatures. The median overall survival was 30 months, and the independent negative prognostic factors were lymph-node status, bulky tumors, response, upper limb perfusion, and 120 min perfusion at 39–40 °C. Conclusions Modern ILP uses diminished perfusion time and lower temperature, leading to a decrease in toxicity. However, our data also show a decrease in response, which indicates that optimal perfusion time and temperature regimen remain to be determined.

Isolated limb perfusion (ILP) is used to treat in-transit metastases of melanoma of the extremities when surgical excision is not possible. The optimal setting concerning temperature and perfusion time is unknown. The purpose of this study was to analyze these factors concerning their effects on response, toxicity, and survival. A retrospective analysis of 284 consecutive stage III melanoma patients treated with melphalan ILP for the first time in our institution, during a 31-year period (July 1986–May 2017), was performed. Our series was divided in four time periods, according to perfusion temperature and duration. Demographical data, stage, number, and size of lesions were retrieved from our prospective database. Overall response (OR) rate 83% and a complete response (CR) rate of 59%. Significant predictive factors for CR in multivariate analysis were non-bulky tumor, fewer metastases, and a perfusion time of 120 min. Predictive factors for increased local toxicity were femoral ILP and higher perfusion temperatures. The median overall survival was 30 months, and the independent negative prognostic factors were lymph-node status, bulky tumors, response, upper limb perfusion, and 120 min perfusion at 39–40 °C. Modern ILP uses diminished perfusion time and lower temperature, leading to a decrease in toxicity. However, our data also show a decrease in response, which indicates that optimal perfusion time and temperature regimen remain to be determined.

Isolated limb perfusion with melphalan is a well‐established and effective treatment for inoperable melanoma metastases of the extremities, with an overall response rate of 80% and a complete response rate of 54%. The surgical technique is complex and serious morbidity can occur, but with attention to detail major side effects can be kept to a minimum. This article reviews the technique, results and other aspects of this sophisticated form of treatment. J. Surg. Oncol.2014;109:332–337 2014 Wiley Periodicals, Inc.

Indications for treatment of melanoma in‐transit metastases (ITMs) confined to the limb with isolated limb perfusion (ILP) are not well defined. This study reports the Groningen regional therapeutic perfusion experience with melphalan (M‐ILP) and TNF‐melphalan (TM‐ILP) for ITMs, and reviews of the melanoma TNF‐melphalan ILP literature. Between 1991 and 2012, 60 patients were treated with ILP. Patients with “small” ITMs received M‐ILP (10–13mg melphalan/L limb volume) and patients with “bulky” disease TM‐ILP (1–4mg TNF); 19 M‐ILPs and 41 TM‐ILPs were performed, 26 Stage IIIB, 31 Stage IIIB and 1 stage IV disease. Overall response after 57 ILPs was 90%; CR 27 (45%), PR 27 (45%), no response 3 (5%); after 9 M‐ILPs CR 6 (32%) and 41 TM‐ILPs CR 21 (51%, P ¼0.124). For younger patients (

Patients with primary irresectable, locally advanced soft tissue sarcomas of the limbs form a challenging group for the treating physician. Multimodality treatment is necessary to guarantee optimal limb salvage and survival rates. Since the introduction of isolated limb perfusion in the late fifties, several treatment regimens have been proposed. Isolated perfusion with melphalan and TNF-alpha, as part of a multimodality treatment, is regarded as the current best treatment option today. Ongoing studies are investigating potential benefit of other doses, new chemotherapeutic agents and new techniques in perfusion and radiotherapy. This article provides a historical overview of published literature and insight in upcoming treatment techniques. (C) 2012 Elsevier Ltd. All rights reserved.

Surgical resection is the mainstay of therapy for locoregional recurrence of melanoma and the best chance for long-term cure in patients with locoregional recurrence of melanoma. In addition to true local recurrence at the site of the primary lesion, locoregional relapse can occur as regional nodal disease or as satellite or in-transit metastases, which may be unresectable and can present significant treatment challenges. Options for unresectable locoregional recurrence include regional hyperthermic isolated limb perfusion or isolated limb infusion, topical therapies, intralesional injection therapies, laser ablation, radiation therapy, and systemic therapy. Given the risk of further relapse and the negative impact on prognosis and overall survival after locoregional recurrence of melanoma, most patients should be considered for aggressive locoregional therapy.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and potentially aggressive neuroendocrine tumor of the skin, with a propensity for locoregional metastases. In two expert referral centers, isolated limb perfusion (ILP) is used to obtain locoregional control in selected locoregionally advanced MCC patients. This study describes our experience.METHOD: Patients who underwent ILP for MCC were analyzed. ILP was performed with melphalan and tumor necrosis factor (TNF) combination therapy. Depending on the institution, either a normothermic or a hyperthermic temperature regimen was used. Baseline characteristics, toxicity data, locoregional progression-free survival (LPFS) and overall survival (OS) were assessed.RESULTS: Four males and 6 females with a median age of 78 years (IQR 61-84 years) were included. Four patients underwent ILP for upper extremity disease and 6 for lower extremity disease. All patients received combination therapy with Melphalan and TNF, one patient with the addition of interferon-gamma. No signs of systemic toxicity were present post-ILP. Severe locoregional toxicity (compartment syndrome) occurred in 1 patient and 1 elderly patient with extensive atherosclerosis had to undergo transfemoral amputation due to critical ischemia. Eight patients could be included for response evaluation. The overall response rate (ORR) was 87.5% with a complete response (CR) rate of 62.5%. Two long-term responses of 53 months and 71 months were observed. Median LPFS was 5 months and median OS was 54 months.CONCLUSION: ILP shows a high CR rate that can be durable. Therefore, ILP should be considered an effective treatment modality for locally advanced MCC.

Background Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) in combination with complete tumor resection is an effective treatment option for non-resectable soft-tissue sarcoma of the extremities, with limb salvage rates greater than 80%. The aim of this study was to assess quality of life (QoL) after TM-ILP, also with regard to long-term survival. Methods We retrospectively examined 27 patients who had primarily non-resectable soft-tissue sarcoma of the leg and who had undergone TM-ILP and complete tumor resection (with limb-sparing intent) during their follow-up examinations using the Quality of Life Questionnaire (QLQ-C30) and the German Short Musculoskeletal Function Assessment (SMFA-D). The results from the QLQ-C30 were compared to the reference values for the general population, to the “all cancer patients” reference values (both reference values published by the European Organization for Research and Treatment of Cancer (EORTC)), and to the reference values of a historical amputation group from the literature. The results of the SMFA were compared with those from a reference group of healthy individuals. Results Surprisingly, we found that the global health status/QoL in the TM-ILP group was not significantly different from the general population or from patients with amputation, but it was higher than that of patients with cancer in general. Concerning the SMFA, we did find functional impairments in patients after TM-ILP compared to the reference group. With regard to long-term survival, we found no time-dependent deterioration in QoL for longer time intervals after treatment. Conclusions These results support the use of TM-ILP in limb-sparing multimodal therapy settings from a quality-of-life perspective, but they also encourage further research on this matter. Electronic supplementary material The online version of this article (doi:10.1186/s12957-017-1150-3) contains supplementary material, which is available to authorized users.