Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GISTs) is Effective and Safe: Results from a Prospective Single-Center Study with 108 Patients.

BACKGROUND: Neoadjuvant imatinib is considered for gastrointestinal stromal tumors (GISTs) when decreased tumor size provides less extensive surgery and higher R0 resection rates. This study evaluates the effectivity and safety of neoadjuvant imatinib for large or locally advanced GIST. PATIENTS AND METHODS: From the prospective database of the Dutch GIST Consortium, all patients who underwent surgery after neoadjuvant imatinib at our center between 2009 and 2022 were selected. Independent and blinded assessment of surgical strategy was performed by two surgeons, based on anonymized computed tomography (CT) scans before and after neoadjuvant imatinib. RESULTS: Of 113 patients that received neoadjuvant imatinib, 108 (95%) [mean age 61.6, standard deviation (SD) 11.5, 54% male] underwent a GIST resection. Of all GISTs, 67% was localized in the stomach and 25% in the duodenum or small intestine. In 74% of the patients with GIST, a KIT exon 11 mutation was found. Decreased tumor size was seen in 95 (88%) patients. Having a KIT exon 11 mutation [odds ratio (OR) 5.64, 95% confidence interval (CI) 1.67-19.1, p < 0.01] or not having a mutation (OR 0.19, 95% CI 0.04-0.89, p = 0.04) were positive and negative predictive values for partial response, respectively. In 55 (51%) patients, there was deescalation of surgical strategy after neoadjuvant imatinib. Surgical complications were documented in 16 (15%) patients (n = 8, grade II; n = 5, grade IIIa; n = 3, grade IIIb) and R0 resection was accomplished in 95 (89%) patients. The 5-year disease-free and overall survival were 80% and 91%, respectively. CONCLUSION: This study shows that neoadjuvant imatinib is effective and safe for patients with large or locally advanced GIST.

Prognosis of Patients with Cutaneous Angiosarcoma After Surgical Resection with Curative Intent: Is There a Difference Between the Subtypes?

BACKGROUND: The etiology of cutaneous angiosarcoma (cAS) may be idiopathic (I-cAS), or arise secondary to radiotherapy (RT-cAS), in chronic lymphedema (ST-cAS), or related to UV exposure (UV-cAS). The aim of this study was to evaluate oncological outcomes of different cAS subtypes. PATIENTS AND METHODS: Non-metastatic cAS patients, treated with surgery for primary disease with curative intent, were retrospectively analyzed for oncological outcome, including local recurrence (LR), distant metastases (DM), and overall survival (OS). RESULTS: A total of 234 patients were identified; 60 I-cAS, 122 RT-cAS, 9 ST-cAS, and 43 UV-cAS. The majority was female (78%), the median age was 66 years (IQR 57-76 years), the median tumor size was 4.4 cm (IQR 2.5-7.0 cm), and most common site of disease was the breast (59%). Recurrence was identified in 66% (44% LR and/or 41% DM), with a median follow up of 26.5 months (IQR 12-60 months). The 5-year OS was estimated at 50%, LRFS at 47%, and DMFS at 50%. There was no significant difference in LR, DM, or OS between the subtypes. Age < 65 years and administration of radiotherapy (RT) were significantly associated with lower LR rates (HR 0.560, 95% CI 0.3373-0.840, p = 0.005 and HR 0.421, 95% CI 0.225-0.790, p = 0.007, respectively), however no prognostic factors were identified for development of DM. Development of DM, but not LR (p = 0.052), was significantly associated with decreased OS (HR 6.486, 95% CI 2.939-14.318 p < 0.001). CONCLUSION: We found no significant difference in oncological outcome between the different cAS subtypes. OS remains relatively poor, and RT is associated with lower LR rates.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. METHODS: A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). RESULTS: For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p = .038). CONCLUSION: RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.

Oncological Outcome After Diagnostic Biopsies in Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

OBJECTIVE: To analyze whether the route of preoperative biopsy influences oncological outcome in GIST patients. SUMMARY OF BACKGROUND DATA: Preoperative biopsies are widely used for diagnosing GIST. Little is known about the risk of tumor seeding after different routes of biopsy. METHODS: Patients who underwent resection of a primary GIST between 1996 and 2014 were identified from 2 databases from 2 tertiary referral centers. Survival data were obtained using the Kaplan-Meier method. Possible confounders were identified using Cox regression analysis. The primary endpoint was local recurrence free survival (RFS) and the secondary endpoint was DSS. RESULTS: A total of 228 patients were included, with a median age of 62 years (range 17-86) and a median follow-up time of 53 months (range 1-204). From these patients, 42 patients did not have a biopsy (18%), 70 underwent a transcutaneous biopsy (31%), and 116 a transluminal biopsy (51%). A total of 42 patients (19.0%) had a local and/or distant recurrence. From the 70 patients with a transcutaneous biopsy, only 1 patient developed a needle tract recurrence (1.4%). Local RFS and DSS were both significantly shorter in the transcutaneous biopsy group on univariate analysis compared to the other groups; however, in multivariate analysis the route of biopsy did not influence local RFS (P = 0.128) or DSS (P = 0.096). CONCLUSIONS: Transluminal or transcutaneous biopsies for diagnosing GIST do not significantly alter the risk of local recurrent disease or DSS in multivariate Cox regressions. The risk of needle tract seeding after transcutaneous biopsy was low.

Has the Outcome for Patients Who Undergo Resection of Primary Retroperitoneal Sarcoma Changed Over Time? A Study of Time Trends During the Past 15 years.

BACKGROUND: This study aimed to investigate changes in treatment strategy and outcome for patients with primary retroperitoneal sarcoma (RPS) undergoing resection at referral centers during a recent period. METHODS: The study enrolled consecutive adult patients with primary non-metastatic RPS who underwent resection with curative intent between 2002 and 2017 at 10 referral centers. The patients were grouped into three periods according to date of surgery: t1 (2002-2006), t2 (2007-2011), and t3 (2012-2017). Five-year overall survival (OS), disease-specific survival (DSS), and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariable analyses for OS and DSS were performed. RESULTS: The study included 1942 patients. The median follow-up period after resection varied from 130 months (interquartile range [IQR], 124-141 months) in t1 to 37 months (IQR, 35-39 months) in t3. The 5-year OS was 61.2% (95% confidence interval [CI], 56.4-66.3%) in t1, 67.0% (95 CI, 63.2-71.0%) in t2, and 71.9% (95% CI, 67.7-76.1%) in t3. The rate of macroscopically incomplete resection (R2) was 7.1% in t1 versus 4.7% in t3 (p = 0.066). The median number of resected organs increased over time (p < 0.001). In the multivariable analysis resection during t3 was associated with better OS and DSS. The 90-day postoperative mortality improved over time (4.3% in t1 to 2.3% in t3; p = 0.031). The 5-year CCI of LR and DM did not change significantly over time. CONCLUSIONS: The long-term survival of patients who underwent resection for primary RPS has increased during the past 15 years. This increased survival is attributable to better patient selection for resection, quality of surgery, and perioperative patient management.

Surgical navigation for challenging recurrent or pretreated intra-abdominal and pelvic soft tissue sarcomas.

BACKGROUND: This study assessed whether electromagnetic navigation can be of added value during resection of recurrent or post-therapy intra-abdominal/pelvic soft tissue sarcomas (STS) in challenging locations. MATERIALS AND METHODS: Patients were included in a prospective navigation study. A pre-operatively 3D roadmap was made and tracked using electromagnetic reference markers. During the operation, an electromagnetic pointer was used for the localization of the tumor/critical anatomical structures. The primary endpoint was feasibility, secondary outcomes were safety and usability. RESULTS: Nine patients with a total of 12 tumors were included, 7 patients with locally recurrent sarcoma. Three patients received neoadjuvant radiotherapy and three other patients received neoadjuvant systemic treatment. The median tumor size was 4.6 cm (2.4-10.4). The majority of distances from tumor to critical anatomical structures was <0.5 cm. The tumors were localized using the navigation system without technical or safety issues. Despite the challenging nature of these resections, 89% were R0 resections, with a median blood loss of 100 ml (20-1050) and one incident of vascular damage. Based on the survey, surgeons stated navigation resulted in shorter surgery time and made the resections easier. CONCLUSION: Electromagnetic navigation facilitates resections of challenging lower intra-abdominal/pelvic STS and might be of added value.

A phase II study on the neo-adjuvant combination of pazopanib and radiotherapy in patients with high-risk, localized soft tissue sarcoma.

PURPOSE: A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination. PATIENTS AND METHODS: Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4-8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells. RESULTS: 25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension. CONCLUSION: Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation.

Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival. METHODS: EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged ≥18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50·4 Gy (in 28 daily fractions of 1·8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov, NCT01344018. FINDINGS: Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43·1 months (IQR 28·8-59·2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71-1·44; log rank p=0·95). The most common grade 3-4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events. INTERPRETATION: Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma. FUNDING: European Organisation for Research and Treatment of Cancer, and European Clinical Trials in Rare Sarcomas.

Outcome after surgical treatment of dermatofibrosarcoma protuberans: Is clinical follow-up always indicated?

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma for which clinical examination up to 10 years is recommended. The objective of this study was to identify prognostic factors for recurrences and metastases that can be used to evaluate the validity of follow-up schedules after treatment for DFSP. METHODS: Patients with DFSP who received treatment between 1991 and 2016 at 3 tertiary centers were included. Cox regression analyses were conducted to identify variables associated with the primary endpoints. RESULTS: In total 357 patients were included, with a median age of 38 years (age range, 2-87 years) and a median follow-up of 60 months (interquartile range, 24-115 months). Eighty-one patients developed recurrent disease (22.7%), and the median time to recurrence was 55.5 months (interquartile range, 20-90 months). Of these, 50 tumors (61.7%) were identified by patient self-examination, whereas 3 recurrences (3.7%) were identified at clinical surveillance. For the remaining 28 tumors, no information was available on how the recurrences were identified (34.6%). Fibrosarcomatous change (hazard ratio, 21.865; P < .001), and positive resection margins (hazard ratio, 14.645; P < .001), were independent prognostic factors for recurrence. Metastases occurred in 4 patients (1.1%). All tumors were identified by imaging after patients presented with symptomatic metastases. Fibrosarcomatous change (P < .001) and tumor size >5 cm (P = .014) were associated with the development of metastases. CONCLUSIONS: Disease recurrence after resection of DFSP remains a significant issue, whereas metastases are uncommon. The majority of recurrences are identified by patient self-examination. Consideration should be given to individualized follow-up schedules based on risk factors for recurrences and metastases.

Radiotherapy for retroperitoneal liposarcoma: A report from the Transatlantic Retroperitoneal Sarcoma Working Group.

BACKGROUND: The current study investigated the role of radiotherapy (RT) in patients with primary nonmetastatic retroperitoneal liposarcomas. METHODS: A total of 607 patients with localized retroperitoneal well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) underwent surgical resection with or without RT at 8 high-volume sarcoma centers (234 patients with WDLPS, 242 patients with grade 1 to 2 DDLPS, and 131 patients with grade 3 DDLPS; grading was performed according to the National Federation of Centers for the Fight Against Cancer [Federation Nationale des Centres de Lutte Contre le Cancer; FNCLCC]). RT was administered in 19.7%, 34.7%, and 35.1%, respectively, of these 3 cohorts. Overall survival (OS) was estimated using the Kaplan-Meier method, and the incidences of local recurrence and distant metastasis (DM) were estimated in a competing risk framework. To account for bias consistent with nonrandom RT assignment, propensity scores were estimated. Cox univariable analysis of the association between RT and oncological endpoints was performed by applying inverse probability of treatment weighting (IPTW) using propensity scores. RESULTS: Age, tumor size, and the administration of chemotherapy were found to be significantly imbalanced between patients who did and did not undergo RT in all cohorts. IPTW largely removed imbalances in key prognostic variables. Although the 8-year local recurrence incidences in patients treated with surgery plus RT versus surgery only were 11.8% and 39.2%, respectively, for patients with WDLPS (P = .011;); 29.0% and 56.7%, respectively, for patients with grade 1 to 2 DDLPS (P = .008); and 29.8% and 43.7%, respectively, for patients with grade 3 DDLPS (P = .025), this significant benefit was lost after IPTW analyses. There were no significant differences noted with regard to DM and OS between irradiated and unirradiated patients across all 3 cohorts. CONCLUSIONS: Perioperative RT was found to be associated with better local control in univariable unadjusted analysis in all 3 cohorts, but not after accounting for imbalances in prognostic variables. RT did not impact on DM or OS. The appropriate selection of RT in this disease remains challenging. The results of the European Organization for Research and Treatment of Cancer (EORTC)-Soft Tissue and Bone Sarcoma Group (STBSG) 62092-22092 prospective randomized trial are awaited.

Prospective study on image-guided navigation surgery for pelvic malignancies.

BACKGROUND AND OBJECTIVES: Surgery of advanced tumors and lymph nodes in the pelvis can be challenging due to the narrow pelvic space and vital surrounding structures. This study explores the application of a novel electromagnetic navigation system to guide pelvic surgery. METHODS: This was a prospective study on surgery for malignancies in the pelvis. Preoperatively obtained imaging was used to create a patient-specific three-dimensional (3D) roadmap. In the operating room, the 3D roadmap was registered to an intraoperative computed tomography scan. A tracked pointer was used during surgery for guidance. Primary endpoint was safety and feasibility, secondary endpoints were accuracy and usability. RESULTS: Twenty-eight colorectal, four liposarcomas, and one gynecological patient were included. There were no safety issues. Navigation was feasible in 31 patients. The mean target registration errors of 4.0 and 6.3 mm were achieved for straight and French position, respectively. In seven of seven patients with a locally advanced rectal tumor and in seven of eight patients with recurrences, negative margins were achieved. Thirty-three of 36 target lymph nodes were successfully removed. Surgeons using the system indicated faster localization of the tumor and improved decisiveness. CONCLUSION: This novel surgical navigation system was safe and feasible during pelvic surgery and can facilitate its users.

Liver Resection for Hepatic Metastases from Soft Tissue Sarcoma: A Nationwide Study.

BACKGROUND: This study aims to evaluate the feasibility and safety of resection of sarcoma liver metastases, and to identify possible prognostic factors for long-term survival. METHODS: All patients who underwent resection of liver metastases of sarcoma in the Netherlands from 1998 to 2014 were included. Study data was retrospectively collected from patient files. Survival rates were calculated using Kaplan-Meier survival analysis. RESULTS: Some 38 patients treated in 16 hospitals were included (15 male, 23 female). The median age was 57 years (37-80 years). The most common histological subtype was leiomyosarcoma (63%). The predominant site of primary tumour was the abdomen (59%). R0 resection was achieved in 16 patients. Mortality was 3 and 16% of included patients had 1 or more complications. The median follow-up period was 18 months (range 1-161). After liver resection, 1-, 3-, and 5-year survival were 88, 54, and 42% respectively. Median overall survival was 46 months (1-161 months). One- and three-year progression-free survival (PFS) after liver resection were 54 and 19% respectively. Median PFS was 16 months (1-61 months). CONCLUSIONS: Liver surgery for sarcoma metastases is safe and leads to a relatively good survival. The choice for surgical treatment should always be discussed in a multidisciplinary sarcoma and liver team.

Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma: A Report From the Transatlantic RPS Working Group.

OBJECTIVE: To investigate the safety of radical resection for retroperitoneal sarcoma (RPS). BACKGROUND: The surgical management of RPS frequently involves complex multivisceral resection. Improved oncologic outcomes have been demonstrated with this approach compared to marginal excision, but the safety of radical resection has not been shown in a large study population. METHODS: The Transatlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaborative of sarcoma centers. A combined experience of 1007 consecutive resections for primary RPS from January 2002 to December 2011 was studied retrospectively with respect to adverse events. A weighted organ score was devised to account for differences in surgical complexity. Univariate and multivariate logistic regression analyses were performed to investigate associations between adverse events and number and patterns of organs resected. Associations between adverse events and overall survival, local recurrence, and distant metastases were investigated. RESULTS: Severe postoperative adverse events (Clavien-Dindo ≥3) occurred in 165 patients (16.4%) and 18 patients (1.8%) died within 30 days. Significant predictors of severe adverse events were age (P = 0.003), transfusion requirements (P < 0.001), and resected organ score (P = 0.042). Resections involving pancreaticoduodenectomy, major vascular resection, and splenectomy/pancreatectomy were found to entail higher operative risk (odds ratio >1.5). There was no impact of postoperative adverse events on overall survival, local recurrence, or distant metastases. CONCLUSIONS: A radical surgical approach to RPS is safe when carried out at a specialist sarcoma center. High-risk resections should be carefully considered on an individual basis and weighed against anticipated disease biology. There appears to be no association between surgical morbidity and long-term oncologic outcomes.

The role and outcomes of palliative surgery for retroperitoneal sarcoma.

Categories of noncurative surgery for retroperitoneal sarcoma include: i) grossly incomplete resection (R2) of primary or locally recurrent tumor; ii) resection in the setting of distant metastatic disease; and iii) true palliative-intent symptom-directed surgery. The value of R2 resection is debatable, since most series do not report initial operative intent. Debulking surgery provides symptom relief in the majority of patients, but relief is generally not durable. Quality of life is poorly studied.

Radiation therapy in retroperitoneal sarcoma management.

Surgery is potentially curative for primary non-metastatic retroperitoneal soft tissue sarcomas (RPS), although patients remain at risk for local recurrence. To reduce this risk, the addition of radiotherapy to radical surgery may be considered. Nevertheless, level I evidence to support radiotherapy is currently lacking. The results from the EORTC-STBSG 62092-22092 studying this question are awaited. This manuscript addresses issues to consider when radiation-oncologists engage in a multidisciplinary treatment approach for RPS patients, including radiotherapy.

Nerve detection during surgery: optical spectroscopy for peripheral nerve localization.

Precise nerve localization is of major importance in both surgery and regional anesthesia. Optically based techniques can identify tissue through differences in optical properties, like absorption and scattering. The aim of this study was to evaluate the potential of optical spectroscopy (diffuse reflectance spectroscopy) for clinical nerve identification in vivo. Eighteen patients (8 male, 10 female, age 53 ± 13 years) undergoing inguinal lymph node resection or resection or a soft tissue tumor in the groin were included to measure the femoral or sciatic nerve and the surrounding tissues. In vivo optical measurements were performed using Diffuse Reflectance Spectroscopy (400-1600 nm) on nerve, near nerve adipose tissue, muscle, and subcutaneous fat using a needle-shaped probe. Model-based analyses were used to derive verified quantitative parameters as concentrations of optical absorbers and several parameters describing scattering. A total of 628 optical spectra were recorded. Measured spectra reveal noticeable tissue specific characteristics. Optical absorption of water, fat, and oxy- and deoxyhemoglobin was manifested in the measured spectra. The parameters water and fat content showed significant differences (P < 0.005) between nerve and all surrounding tissues. Classification using k-Nearest Neighbor based on the derived parameters revealed a sensitivity of 85% and a specificity of 79%, for identifying nerve from surrounding tissues. Diffuse Reflectance Spectroscopy identifies peripheral nerve bundles. The differences found between tissue groups are assignable to the tissue composition and structure.

Post-relapse outcomes after primary extended resection of retroperitoneal sarcoma: A report from the Trans-Atlantic RPS Working Group.

BACKGROUND: Despite a radical surgical approach to primary retroperitoneal sarcoma (RPS), many patients experience locoregional and/or distant recurrence. The objective of this study was to analyze post-relapse outcomes for patients with RPS who had initially undergone surgical resection of their primary tumor at a specialist center. METHODS: All consecutive patients who underwent macroscopically complete resection for primary RPS at 8 high volume centers from January 2002 to December 2011 were identified, and those who developed local recurrence (LR) only, distant metastasis (DM) only, or synchronous local recurrence and distant metastasis (LR+DM) during the follow-up period were included. Overall survival (OS) was calculated for all groups, as was the crude cumulative incidence of a second recurrence after the first LR. Multivariate analyses for OS were performed. RESULTS: In an initial series of 1007 patients with primary RPS, 408 patients developed recurrent disease during the follow-up period. The median follow-up from the time of recurrence was 41 months. The median OS was 33 months after LR (n = 219), 25 months after DM (n = 146), and 12 months after LR+DM (n = 43), and the 5-year OS rates were 29%, 20%, and 14%, respectively. Predictors of OS after LR were the time interval to LR and resection of LR, while histologic grade approached significance. For DM, significant predictors of OS were the time interval to DM and histologic subtype. The subgroup of patients who underwent resection of recurrent disease had a longer median OS than patients who did not undergo resection. CONCLUSIONS: Relapse of RPS portends high disease-specific mortality. Patients with locally recurrent or metastatic disease should be considered for resection. Cancer 2017;123:1971-1978. © 2017 American Cancer Society.

External validation of a multi-institutional retroperitoneal sarcoma nomogram.

BACKGROUND: A multi-institutional nomogram for predicting disease-free survival (DFS) and overall survival (OS) in patients with primary retroperitoneal sarcoma (RPS) incorporating relevant prognostic factors not included in the American Joint Committee on Cancer staging system for soft tissue sarcoma has been reported. The authors validated this nomogram with an independent, transatlantic cohort. METHODS: Data from patients with RPS who were undergoing definitive resection at 1 of 6 sarcoma centers in Europe and North America ("validation set") were used to validate a RPS nomogram developed from 3 other centers ("development set"). The nomogram incorporated 6 variables: age, tumor size, grade, histologic subtype, multifocality, and quality of surgery. Nomogram-predicted probabilities were stratified into 6 subgroups and compared with observed outcomes. Discriminative ability was quantified by Harrell C statistics. RESULTS: The validation and development sets included 631 and 523 patients, respectively, all of whom underwent surgical resection at the institutions represented. The 7-year DFS and OS rates for the validation set were 38% (95% confidence interval, 34%-43%) and 58% (95% confidence interval, 53%-63%), respectively. All 6 nomogram variables were found to be independently prognostic. The corrected Harrell C statistics concordance index values for the validation set were 0.69 for DFS and 0.73 for OS, which were similar to those for the development set, suggesting good calibration of the nomogram in the validation cohort. CONCLUSIONS: The RPS nomogram was externally validated using a larger, independent cohort. The nomogram can be generalized to patients undergoing surgery for RPS by specialized sarcoma surgeons at sarcoma centers. The nomogram provides a more individualized and disease-relevant estimation of OS compared with the American Joint Committee on Cancer classification. Cancer 2016;122:1417-1424. © 2016 American Cancer Society.

Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors composed of several well defined histologic subtypes. The aim of this study was to analyze patterns of recurrence and treatment variations in a large population of patients, treated at reference centers. METHODS: All consecutive patients with primary RPS treated at 6 European and 2 North American institutions between January 2002 and December 2011 were included. Five, 8, and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariate analyses for OS, CCI of LR, and DM were performed. RESULTS: In all, 1007 patients were included. Median follow-up was 58 months (first and third quartile range 36-90). The 5, 8, and 10-year OS were 67% [95% confidence interval (CI), 63, 70), 56% (95% CI, 52, 61), and 46% (95% CI, 40, 53). The 5, 8, and 10-year CCI of LR and DM were 25.9 (95% CI, 23.1, 29.1), 31.3 (95% CI, 27.8, 35.1), 35% (95% CI, 30.5, 40.1), and 21% (95% CI, 18.4, 23.8%), 21.6 (95% CI, 19.0, 24.6), and 21.6 (95% CI, 19.0, 24.6), respectively. Tumour size, histologic subtype, malignancy grade, multifocality, and completeness of resection were significant predictors of outcome. Patterns of recurrence varied depending on histologic subtype. Different treatment policies at participating institutions influenced LR of well differentiated liposarcoma without impacting OS, whereas discrepancies in adjuvant systemic therapies did not impact LR, DM, or OS of leiomyosarcoma. CONCLUSIONS: Reference centers are critical to outcomes of RPS patients, as the management strategy requires specific expertise. Histologic subtype predicts patterns of recurrence and should inform management decision. A prospective international registry is under preparation, to further define our understanding of this disease.