Impact of resection margin on outcomes in high-grade soft tissue sarcomas of the extremity-A USSC analysis.

BACKGROUND: The optimal margin of resection for high-grade extremity sarcomas and its impact on survival has long been questioned in the setting of adjuvant radiotherapy. The objective of this study was to investigate the impact of resection status on recurrence and survival. METHODS: All patients with primary, nonmetastatic, high-grade extremity sarcomas that underwent surgical resection from January 2000 to April 2016 in the U.S. Sarcoma Collaborative (USSC) were retrospectively reviewed. Recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were examined in multivariate analyses (MVA). RESULTS: A cohort of 959 patients was identified with a median follow-up of 34.7 months from diagnosis. R0 resection was achieved in 86.7% (831) while R1 resection in 13.3% (128). Locoregional recurrence for R0 and R1 groups occurred in 9.1% (76) versus 14.8% (19; p = .05) while distant recurrence occurred in 24.7% (205) versus 26.6% (34; p = .65), respectively. Median RFS was 171.2 versus 48.5 (p = .01) while median OS was 149.8 versus 71.5 months (p = .02) for the R0 versus R1 group, respectively. On MVA, female gender (hazard ratio [HR] = 0.69, p = .007) and adjuvant radiotherapy (0.7, p = .04) were associated with improved OS, whereas older age (HR = 1.03, p < .001) and tumor size (HR = 1.01, p < .001) were associated with worse OS. R0 resection status was associated with improved locoregional RFS (HR = 0.56, p = .03) but not with distant RFS (HR = 0.84, p = .4) or OS (HR = 0.7, p = .052). CONCLUSIONS: In high-grade extremity sarcomas, tumor size and gender are predictive of OS while R0 resection status is associated with improved locoregional recurrence rate without a significant impact on distant RFS or OS.

Impact of resection margin status on survival in advanced N stage pancreatic cancer - a multi-institutional analysis.

BACKGROUND: The present study aimed to examine the impact of microscopically tumour-infiltrated resection margins (R1) in pancreatic ductal adenocarcinoma (PDAC) patients with advanced lymphonodular metastasis (pN1-pN2) on overall survival (OS). METHODS: This retrospective, multi-institutional analysis included patients undergoing surgical resection for PDAC at three tertiary university centres between 2005 and 2018. Subcohorts of patients with lymph node status pN0-N2 were stratified according to the histopathological resection status using Kaplan-Meier survival analysis. RESULTS: The OS of the entire cohort (n = 620) correlated inversely with the pN status (26 [pN0], 18 [pN1], 11.8 [pN2] months, P < 0.001) and R status (21.7 [R0], 12.5 [R1] months, P < 0.001). However, there was no statistically significant OS difference between R0 versus R1 in cases with advanced lymphonodular metastases: 19.6 months (95% CI: 17.4-20.9) versus 13.6 months (95% CI: 10.7-18.0) for pN1 stage and 13.7 months (95% CI: 10.7-18.9) versus 10.1 months (95% CI: 7.9-19.1) for pN2, respectively. Accordingly, N stage-dependent Cox regression analysis revealed that R status was a prognostic factor in pN0 cases only. Furthermore, there was no significant survival disadvantage for patients with R0 resection but circumferential resection margin invasion (≤ 1 mm; CRM+; 10.7 months) versus CRM-negative (13.7 months) cases in pN2 stages (P = 0.5). CONCLUSIONS: An R1 resection is not associated with worse OS in pN2 cases. If there is evidence of advanced lymph node metastasis and a re-resection due to an R1 situation (e.g. at venous or arterial vessels) may substantially increase the perioperative risk, margin clearance in order to reach local control might be avoided with respect to the OS.

Impact of Positive Radial Margin on Recurrence and Survival in Perihilar Cholangiocarcinoma.

In resected perihilar cholangiocarcinoma (PHC), positive ductal margin (DM) is associated with poor survival. There is currently little knowledge about the impact of positive radial margin (RM) when DM is negative. The aim of this study was to evaluate the incidence and the role of positive RM. Patients who underwent surgery between 2005 and 2017 where retrospectively reviewed and stratified according to margin positivity: an isolated RM-positive group and DM ± RM group. Of the 75 patients identified; 34 (45.3%) had R1 resection and 17 had positive RM alone. Survival was poorer in patients with R1 resection compared to R0 (p = 0.019). After stratification according to margin positivity; R0 patients showed better survival than DM ± RM-positive patients (p = 0.004; MST 43.9 vs. 23.6 months), but comparable to RM-positive patients (p = 0.361; MST 43.9 vs. 39.5 months). Recurrence was higher in DM ± RM group compared to R0 (p = 0.0017; median disease-free survival (DFS) 15 vs. 30 months); but comparable between RM and R0 group (p = 0.39; DFS 20 vs. 30 months). In univariate and multivariate analysis, DM positivity resulted as a negative prognostic factor both for survival and recurrence. In conclusion, positive RM resections appear to have different recurrence patterns and survival rates than positive DM resections.

[Neoadjuvant treatment of primarily resectable and borderline resectable pancreatic cancer]. / Neoadjuvante Therapie beim primär resektablen und Borderline-resektablen Pankreaskarzinom.

Due to the increasing prevalence pancreatic cancer represents a severe tumor burden to the population and will be ranked second for cancer-related mortality by the year 2030. If a curative approach is pursued a radical R0 resection of the tumor with sufficient cancer-free resection margins (≥1 mm) should be performed. This has been shown to be associated with a clear benefit for survival. For treatment planning of pancreatic cancer the tumor stage plays a pivotal role. In cases of distant metastases a palliative concept is normally initiated. If no distant metastases are detected neoadjuvant treatment can be performed in cases of borderline resectability or locally advanced stages in order to downsize these tumors. In this situation a neoadjuvant treatment has been shown to significantly increase resectability rates and to improve the tumor stage (downstaging). The most recent randomized trials were able to show a significant survival advantage of neoadjuvant treatment for borderline resectable pancreatic cancer. In cases of primarily resectable pancreatic cancer the current standard of care is an upfront resection followed by adjuvant chemotherapy. Initial data are also available indicating a survival benefit even for resectable pancreatic cancer after neoadjuvant treatment; however, reliable randomized controlled trials showing a survival advantage of neoadjuvant treatment compared to the current standard treatment of adjuvant chemotherapy following resection are missing. Numerous randomized controlled trials investigating the efficacy of neoadjuvant chemotherapy for resectable pancreatic cancer are currently underway.

[Surgery of pancreatic cancer: techniques to avoid local recurrence]. / Chirurgie des Pankreaskarzinoms: Techniken zur Vermeidung des Lokalrezidivs.

BACKGROUND: In addition to the prognostically important systemic recurrence, a high rate of local recurrence is a relevant problem of pancreatic cancer surgery. Improvement of local control is a requirement for surgical resection as a prerequisite for a potentially curative treatment. OBJECTIVES: Summary of the current evidence on frequency, relevance, and risk factors of local recurrence. Presentation of strategies for reduction of local recurrence with a special focus on surgical resection techniques. MATERIAL AND METHODS: Analysis and appraisal of currently available scientific literature on the topic. RESULTS AND CONCLUSION: Local recurrences occur as the first manifestation of tumor recurrence in 20-50% of patients after resection of pancreatic cancer. The considerable variations of reported local recurrence rates depend on the quality of surgery, regimens of (neo)adjuvant therapy as well as the design of surveillance and duration of follow-up. An R1 status is an important risk factor for local recurrence highlighting the relevance of a local radical resection. The majority of local recurrences consist of perivascular and lymph node recurrences. Therefore, lymphadenectomy, radical dissection directly at the celiac and mesenteric vessels including resection of the periarterial nerve plexus and vascular resection are starting points for improving surgical resection techniques. The safety and efficacy of radical resection techniques in the context of multimodal treatment of pancreatic cancer have to be further evaluated in prospective studies.

External Beam Re-irradiation in Rectal Cancer.

Locally recurrent rectal cancer results in significant symptoms and is associated with prognosis of less than 1 year unless radical resection can be offered. Unfortunately, radical resection rates are low and therefore strategies to palliate symptoms and to maximise downstaging are of significant interest. As the majority of those presenting with locally recurrent rectal cancer will have received previous irradiation for their primary tumour, re-irradiation may offer benefit in this setting. The literature to date is considered in both palliative patients and those with potentially operable disease. Palliative patients gain significant symptomatic relief from standard dose fractionations of up to 30 Gy. In potentially operable patients, the evidence is discussed in the context of key questions; including indications for treatment, dose and fractionation, radiotherapy technique, margins and constraints. Finally, we highlight some additional areas of interest for consideration in future research and development.

Pancreatic adenocarcinoma: A simple CT score for predicting margin-positive resection in patients with resectable disease.

BACKGROUND: Negative-margin status is a prognostic indicator for long-term survival following curative intent resection for pancreatic adenocarcinoma. Patients at increased risk for positive-margin resections may benefit from neoadjuvant chemotherapy prior to resection. METHODS: We retrospectively analyzed preoperative computed-tomography (CT) scans in 108 consecutive patients that underwent curative intent resection for a resectable pancreatic ductal adenocarcinoma from 2009 to 2016 in two academic hospitals. Two radiologists independently staged the tumor, including tumor location, size, and tumor-to-superior mesenteric/portal vein (SMV/PV) contact. Uni and multivariate analysis were performed to identify independent predictors of an R1 resection. RESULTS: Twenty-nine patients had an R1 resection (26.9%). Tumor size, location, and presence of tumor-to-SMV/PV contact were significantly associated with an R1 resection. In multivariate analysis, the independent parameters associated with resection status were: tumor size (R2=9.7), and tumor location (neck R2=6.6; pancreaticoduodenal interface R2=4.4; uncinate process R2=4.1), but not tumor-to-SMV/PV contact (R2=0.1, p=0.7). A simple CT score was built based on tumor size and location. Patients with an R0 resectability score ≥3, i.e. patients with tumor size ≥30mm (except when tumor location is at the pancreatico-duodenal interface) or patients with tumor size ≥20mm AND tumor located in the uncinate process or neck, were at high-risk of an R1 resection (AUC, 0.82; sensitivity, 79%; specificity, 76%). This score also showed good diagnostic performances for predicting an R1 resection involving the medial resection margin only (AUC, 0.85). CONCLUSIONS: A simple score based on tumor location and size can accurately predict patients at high-risk of an R1 resection.

Intraoperative cell isolation for a cytological assessment of bone resection margins in patients with head and neck cancer.

The intraoperative cytological assessment of bony resection margins (ICAB) is a feasible diagnostic approach to support frozen section for assessment of invasion of margins of soft and hard tissue. However, complex resection margins could challenge both diagnostic approaches. Our objective here was to identify the limitations of intraoperative diagnostic methods for assessing margins. We present an advanced cytological approach to assess complex margins that may solve the problem. Data from 119 patients in whom frozen section was supported by ICAB, were reviewed and the reasons for false results analysed. In 35 patients with squamous cell carcinoma infiltrating bone, specimens (n=100) from the resection margin went through an intraoperative cell isolation process for the cytological assessment of bony margins (ICAB). The results were compared with the histological results of the corresponding margins of bone as a reference. Limitations to the assessment of operative bony margins intraoperatively included an infiltrative histological pattern of growth of the carcinoma, with carcinoma cells disseminated within the cancellous bone, complex and uneven resection margins with soft and bony tissue, inflammation, and signs of previous radiotherapy. Intraoperative cell isolation plus (ICICAB) allowed the microscopic assessment of up to 1cm3 of bony tissue to detect disseminated carcinoma cells within the cancellous bone with a sensitivity of 92.3% (95% CI 74.9% to 99.1%), and a specificity of 100% (95% CI 95.1% to 100%), and positive and negative predictive values of 100% (95% CI 85.8% to 100%) and 97.4% (95%CI 90.8% to 99.7%), respectively. Intraoperative cell isolation is a feasible new technique to support ICAB and frozen section in the assessment of bony and soft tissue margins.

Long-term outcome and prognostic factors of surgically treated thymic carcinoma: results of 306 cases from a Japanese Nationwide Database Study.

OBJECTIVES: Thymic carcinoma is a rare thymic malignancy. The purpose of this study was to evaluate the prognostic impact of clinicopathological variables and perioperative therapy for surgically treated thymic carcinoma using a nationwide database. METHODS: Of 2835 patients with surgically treated thymic epithelial tumours collected from 32 Japanese institutions, a total of 306 patients with thymic carcinomas, excluding neuroendocrine tumours, were enrolled in this retrospective study. Multivariable Cox regression analyses were performed for overall (OS) and recurrence-free survival (RFS) after R0 resection. RESULTS: Of 306 patients, 228 (75%) patients presented with Masaoka stage III-IV. Squamous cell carcinoma was the most common histological type (n = 216, 71%). R0 resection was performed in 181 (61%) patients, R1 in 46 (16%), R2 sub-total (≥80% tumour resection) in 43 (14%) and R2 non-resection in 27 (9%). The 5-year OS rate was 61%. Prognostic factors for OS were Masaoka stage and resection status. R0 resection was associated with most improved OS; however, both R1 and R2 sub-total resection resulted in superior OS compared with R2 non-resection [hazard ratio (95% confidence interval) for R0, R1 and R2 sub-total, 0.27 (0.15-0.48), 0.40 (0.22-0.74) and 0.38 (0.20-0.72), respectively]. Histological type and perioperative therapy did not affect OS, whereas tumour size and postoperative radiotherapy were associated with improved RFS after R0 resection. CONCLUSIONS: R0 resection is essential for prolonged OS for surgically treated thymic carcinoma, but maximal debulking surgery might be beneficial and worth evaluating for advanced disease deemed difficult for R0 resection. The benefit of postoperative radiotherapy after R0 resection should also be evaluated prospectively.