R0 Margin Research Articles

The Role of MRI-Guided Radiotherapy for Soft Tissue Sarcomas.

Soft tissue sarcomas (STS) are a rare class of tumors that originate from mesenchymal tissues and occur most frequently in the extremities, trunk, and retroperitoneum. Surgical resection with R0 margins is the primary curative treatment for most localized STS. In this setting, radiation therapy is used either pre-operatively or post-operatively to reduce the rate of local recurrence. Modern pre- or post-operative radiation therapy rely on the use of MRI sequences to guide target delineation during treatment planning. MRI-guided radiotherapy also offers unique advantages over CT-guided approaches in differentiating STS from surrounding normal soft tissues and enabling better identification of target volumes on daily imaging. For patients with unresectable STS, radiation therapy may offer the best chance for local tumor control. However, most STS are relatively radioresistant with modest rates of local control achieved using conventionally fractionated radiation. Specialized techniques such as hypofractionated radiation may allow for dose intensification and may increase rates of local control for STS. In these settings, MRI becomes even more critical for the delineation of targets and organs at risk and management of tumor and organ at risk motion during and between radiotherapy treatment fractions.

The significance of subdivisions of microscopically positive (R1) margins in colorectal cancer

Background: Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, little is known of the differential impact of subdivisions of R1 margins, be they to the primary tumour (R1tumour) or to lymph node metastases/tumour deposits (R1LNM).

Radial and Longitudinal Margins in Surgery of Perihilar Cholangiocarcinoma: When R1 Definition Is Associated with Different Prognosis

Background: The purpose of study is to evaluate the impact of positive margins on long-term outcome of patients affected by perihilar cholangiocarcinoma (PHC) depending on the pattern of neoplastic infiltration (radial versus longitudinal) and to analyze predictive factors for survival specifically in the population of R1. Methods: Data regarding histopathological data were prospectively collected in patients submitted to surgery for PHC between 2004 and 2019 at San Raffaele Hospital, Milano. The outcome of patients with R1 (88 out of 264, 33.3% of the whole series) and R0 margins was compared. Within R1 group, the long term outcome was compared between patients with radial only infiltration (n=31), longitudinal only infiltration (n=30) and radial+longitudinal infiltration (n=27). Results: 3 years and 5 years long term survival was significantly different between the R0 (55% and 42% respectively) and the R1 group (42% and 18% respectively) with p<0.05. Within R1 group, patients with radial only and radial + longitudinal infiltration had a worse long term outcome compared with patients with longitudinal only infiltration(median DFS was 18 and 23 months respectively, p<0.05, while median OS was 33 and 39 months respectively, p<0.05). Together with R1 margin status, factors associated with long term outcome at multivariate analysis were nodal status, side of hepatectomy, grading and radial margin infiltration. Conclusion: Infiltration of radial resection margins in PHC is associated with a worse prognosis among patients with R1 margins and should be specifically taken into consideration to determine the indication for adjuvant treatments.

Pancreatic Solid Pseudopapillary Tumor Have Racial Difference But Same Good Prognosis in Three International Cohorts

Introduction: Solid pseudopapillary neoplasm (SPN) of the pancreas are a rare and low-grade malignant entity. The rarity and lack of concern makes its clinicopathological features unclarified. This study aims to examine the clinicopathologic features and racial difference. Methods: The SPN of the pancreas database from 3 cohort, including one high volume medical center in USA, Asian and National Cancer Institution’s Surveillance, Epidemiology, and End Results (SEER) were queried from 2004 to 2020. We compared the perioperative variable, clinical data and overall survival (OS) and prognostic factor of recurrence. Result: A total of 286 patients with SPN were included. Most patients were female (81%), median age 38 years with peak incidence at 20-39 year-old female. While male SPN had peak incidence at age 50-59 year-old (p=.002). The variation of treatment strategy among institutions was noted. Higher lymphovascular invasion(LVI) (p=.02), perineural invasion (PNI) (p<.001) and R1 margin(p<.001) in one institution did not accompany with worse long-term survival in respective to overall survival (p=.43), SPN-specific survival (p=.69) and recurrence-free survival (p=.067). The lymph node positive was only predictor (reported as OR[95%CI]) of postoperative recurrence (2.2[1.38-2.99]; p=.007). Nor dose LVI, PNI, R1 margin, recurrence, and metastasis were significant factors in predicting survival. Conclusion: The survival is excellent in regard of metastasis or recurrence. The lymph node positive is the only recurrence predictor. Different surgical radicality, LVI, PNI and R1 margin do not differ survival. Indicated less radical resection is appropriate in SPN and treatment strategy could be different from pancreatic adenocarcinoma.

Survival of 736 Cholangiocarcinoma Patient Receiving Surgical Treatment in O. Viverrini Endemic Area, Thailand

Introduction: Cholangiocarcinoma is a common cancer in Thailand, endemic area of O. Viverrini. This study aims to investigate survival outcome and prognostic factors in Cholangiocarcinoma patient receiving surgical treatment. Methods: We retrospectively reviewed 736 consecutive patients with cholangiocarcinoma who underwent surgical treatment between October 2013 to December 2018. Patients were divided into Intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) groups. Principle outcomes were long-term survival and 90-day mortality. Results: Of the 736 patients, 407 (55%) were iCCA, 240 (33%) were pCCA and 89 (12%) were dCCA. Overall resectable rate was 78.3%; 75.2% in iCCA, 83.8% in pCCA and 77.5% in dCCA. In resectable patients, overall 90-day mortality was 10.9%; 11.0% in iCCA, 11.6% in pCCA and 8.9% in dCCA. Long-term survival for resectable patients was higher in patients with CA19-9 <200 U/mL (p<0.001), intraductal growth type (p<0.001), well-differentiation (p=0.001), negative nodal status (p<0.001), R0 margin (p<0.001), absence of LVI (p=0.001), absence of PNI (p<0.001) and absence of metastasis (p<0.001). In mutivariale analysis, R0 margin (p=0.001), negative nodal status (p=0.003) and absence of metastasis (p=0.002) were significant independent prognostic factors. The median survival was better in resectable group than unresectable group (11.6 vs 3.2 months, respectively, p<0.001). Furthermore, the median survivals for R0-resection with pM0 was 19.3 months (18.2, 24.5 and 18.4 in iCCA, pCCA and dCCA, respectively). Conclusion: Negative resection margin, absence of LN and absence of distant metastasis were the important factor affecting survival in CCA patients in the endemic area of O. Viverini.

Prediction of Early Recurrence After R0 Resection for Gallbladder Carcinoma of Stage T1b-T3.

PurposeThe time-to-tumor recurrence can predict the prognosis of hepatobiliary cancers following curative-intent resection. Therefore, for patients with gallbladder carcinoma (GBC) of stage T1b–T3 who had undergone R0 resection, we investigated the risk factors for early recurrence of GBC and their prognosis.Patients and MethodsA total of 260 patients with GBC with T1b–T3 disease and an R0 margin were identified. Their clinicopathologic characteristics, perioperative details and prognostic data were reviewed. Survival analyses were carried out using the Kaplan–Meier method. Logistic regression models were used to identify the risk factors for early recurrence.ResultsThe optimal cutoff for early recurrence was 29 months. Early recurrence tended to result in relapse far from the primary tumor, and such patients tended to have significantly worse overall survival. Multivariate analysis revealed that T3 disease, N1/N2 stage, poor differentiation of tumor, and lymphovascular invasion (LI) were associated with a greater risk of early recurrence. Patients diagnosed as having GBC incidentally and who had the risk factors of early recurrence were more likely to benefit from re-resection 2–4 weeks after a cholecystectomy.ConclusionT3 stage, N1–N2 stage, poor differentiation, and LI were independent risk factors associated with early recurrence for patients with GBC with stage T1b–T3 disease after R0 resection.

Laparoscopic Liver Resection for Colorectal Cancer Liver Metastases: Long-Term Five- and Ten-Year Survival

Introduction: Laparoscopic liver resection (LLR) for colorectal cancer liver metastases (CRLM) is well-established with clinical short-term benefits, however data is lacking on long-term oncologic outcomes. Methods: A retrospective review of a Western center database was performed to identify patients who underwent LLR for CRLM between 2002-2017. Results: 140 patients were identified. Median age at surgery was 64 years. The mean number of CRLM was 1.4 and the average size of the largest lesion was 2.6cm. Disease distribution was unilobar in 88% of patients. Liver resection was performed in a pure laparoscopic fashion in 44%, hand-assisted in 44% and robot-assisted in 10% of cases. Major hepatectomy was performed in 15% and simultaneous ablation in 11% of patients. R0 margin was achieved in 87% of cases. The average length of hospital stay was 4.5 days. With a median follow-up of 48 months, 61% of patients were alive at 5 years and 38% at 10 years. At the time of last follow-up, 50% of patients had disease recurrence, with a 39% 5-year and 37% 10-year RFS. Conclusions: These findings indicate that minimally-invasive liver resection for CLRM can lead to excellent long-term oncologic outcomes, as more than one-third of patients were alive and cancer-free at 10 years. Although most recurrences were observed within five years, some patients did recur between years 5-10, and therefore should be followed at least for 10 years post-operatively. However, no recurrences or deaths were observed after patients reached the 10-year mark and therefore could be reasonably considered oncologically cured.

Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront Surgery?

Purpose: Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery. 1.2. Methods and materials: In this retrospective study we enrolled patients with upper rectal or sigmoid junction locally advanced tumors (stages II-III). At the first Institution patients received NCRT followed by surgery (study group); at the second Institution patients were referred to upfront surgery (control group). Overall survival was the main endpoint of the analysis. Local relapse and other clinical variables were also analyzed. 1.3. Results: Fifty patients in the study group and 32 patients in the control group were analyzed. In the NCRT group there were more N-positive patients (p&lt;0.001); T-stage was similar for both groups. All surgical procedures were performed with R0 margins. Among NCRT patients, in seven cases (14%) complete pathologic response was found. In 27 cases (54%) downstaging in T-stage was achieved. Comparing OS between NCRT and control group there was no significant difference at five years: 84% for NCRT group and 79% for control group (p 0.37). In univariate analysis, clinical T-stage had a statistically significant impact on survival. Patients with cT3 disease did better than patients with cT4 (p = 0.014). Two cases of G4 toxicity were observed and only one case of local relapse was observed in NCRT group. 1.4. Conclusion: NCRT achieved a high rate of downstaging alongside tolerable toxicity profile, but did not affect survival outcome in this selected group, as compared to surgery alone.

The Impact of Positive Resection Margin in Perihilar Cholangiocarcinoma, Ductal Margin vs Radial Margin

Introduction: Resection margin status is the most important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the incidence and the effect of positive RM on survival. Methods: Patients with pCCA who underwent curative resection between October 2013 to December 2018 were retrospectively reviewed. Resection margin status were divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Results: Of the 170 pCCA patients, 63 (37%) had R1 margin. Among 63 R1 patients; 18 (28.6%) had positive DM alone, 20 (31.7%) had positive RM alone and 25 (39.7%) had both positive DM and RM. The R1 patients had a significantly greater number of LN metastasis and advanced tumor staging than R0 patients, however there was no difference between the RM+ and DM+ patients. The median survival time of patients with RM+ was significantly poorer than R0 patients (13.8 vs 24.7 months; p<0.001, respectively) and similar to the DM+ patients (9.1 months, p=0.561). In multivariable analysis, positive resection margin and lymph node metastasis were independently prognostic factors. Conclusion: Positive resection margin remains the most important prognostic factors and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM. Tabled 1EP03A-039CharacteristicsUnivariableMultivariableNMST (months)p-valueHR95%CIp-valueBismuth type0.0441.3770.838-2.2620.207 1-314416.8 42310.6Portal vein invasion0.0291.0920.212-5.6130.916 Absence8418.4 Present6714.8Hepatic artery invasion0.0410.8560.465-1.5780.619 Absence10018.4 Present5114.2pT stage (AJCC 8th)0.0190.9970.211-4.7090.997 pT 1-29818.4 pT 3-46914.2pN stage (AJCC 8th)<0.0012.2931.437-3.6620.001 pN09025.7 pN1/2778.0Staging (AJCC 8th)<0.0011.3630.729-2.5490.332 Stage 1-24930.7 Stage 3-411810.6Surgical margin status<0.001 R010524.711.613-4.180<0.001 DM+429.12.5971.231-3.8510.008 RM+2013.82.177Surgical margin status<0.001 R010524.70.3850.239-0.620<0.001 DM+429.110.463-1.5190.561 RM+2013.80.838 Open table in a new tab

O-L07 Role of liver resection for metastases from uveal melanoma: Experience from a supra-regional centre, current evidence, and future prospects

Abstract Background Management of liver metastases from uveal melanoma (LMUM) requires a ‘multi-modal’ approach including surgical resection. This study aimed to evaluate the role, safety, and oncological effectiveness of liver surgery for patients with LMUM in the context multidisciplinary management. A comprehensive treatment pathway developed upon current published evidence, prevalent national guidelines and novel treatment options is presented (Figure 2) Methods Retrospective review of prospectively maintained database between February 2005 to August 2018 was performed using the institutional electronic patient record system from oncology and surgical department. Demographic data, MDT outcome letters, operative records, clinic letters, letters from referring hospitals, discharge summaries, radiology reports, and histology findings were reviewed. Focused literature review was conducted to identify all relevant publications. All advanced statistical analysis was performed using SPSS version 27.0 software (IBM Corp., Armonk, NY, USA). A p-value of &amp;lt; 0.05 was considered to be statistically significant. The work was approved by the institutional clinical governance department (Audit ID 6661). Results 31 patients underwent diagnostic laparoscopy and 17 patients received 19 liver resections locally (Figure 1). 7 major (≥ 3 seg) and 12 minor liver resections (14 laparoscopic) were done without any mortality or major complications. 10/19 (52.6%) were R0 resections. Overall survival positively correlated with the time from UM to LMUM (rs = 0.859, p&amp;lt;0.0001). R0 or R1 resection margin status did not significantly influence survival outcomes (OS 25 Vs 28, p = 0.404; RFS 13 Vs 6 months, p = 0.596), though R1 cohort had longer lead time (100 Vs 24 months, p = 0.0408). Conclusions Liver resection for LMUM is safe, effective and complements multimodal management. Lead time from development of UM to LMUM remains a key factor affecting survival outcomes. As novel treatment modalities for regional and systemic disease control for metastatic uveal melanoma continue to develop, surgical intervention will also continue to evolve as part of the multi-disciplinary management. We emphasise the need for developing a collaborative database at a national and international level. We present an evidence-based, multi-disciplinary management pathway for LMUM patients (Figure 2).

Characteristics and Outcomes of Locally Recurrent Retroperitoneal Sarcoma After First Relapse in a Single Tertiary Asian Centre and Applicability of the Sarculator.

ObjectiveRetroperitoneal sarcomas (RPS) comprise of 15% of soft tissue sarcomas where five-year overall survival rate is about 50%. Locoregional recurrences are observed in up to 50% of patients within the first five years following resection. Various factors have been shown to influence survival outcomes, such as histological subtype and tumour size. A nomogram for first relapse locally recurrent RPS was developed using 602 patients from 22 centres. The recurrent RPS Sarculator is available in an electronic interface and includes variables of age, size, margins of re-resection, radiotherapy, chemotherapy and histology to predict for 6-year disease-free survival (DFS) and overall survival (OS). It has not been validated externally. This study aims to validate the Sarculator recurrence nomogram in predicting the survival outcomes of recurrent RPS in an Asian population as well as examine relapse patterns.MethodsPatients diagnosed with first recurrent RPS from 1 January 2000 to 31 December 2017 with first local relapse and eligible for curative re-resection were retrospectively analysed. The type of surgery was unique for individual patients and suggestions of adjuvant therapy were based on globally recognised standards. Patients were followed up every 3 to 4 months post-operatively for the first 2 to 3 years and 6-monthly to a year thereafter. A R0 or R1 margin is deemed as complete resection, including a microscopically negative margin (R0) and microscopically positive but macroscopically clear margin (R1). R2 is classified as an incomplete resection with tumour rupture or remaining disease. Harrell’s C concordance index was used to determine the nomogram’s discriminative ability and calibration plots were used to assess accuracy. For the calibration, the patients were divided into 3 groups. Death data was retrieved from the National Birth and Death registry for accuracy.ResultsThere were 53 patients included in this study. Patient and tumour characteristics have been summarised in Table 1. All patients had their second resection at a single centre. 66.0% had their first resection at the same centre. The median age was 53 (range 21- 79) at diagnosis, median tumour size was 17cm (12cm to 28cm) and median follow-up duration was 44.1 months. The most commonly encountered subtypes were de-differentiated liposarcoma (DDLPS) (56.6%), well-differentiated liposarcoma (WDLPS) (20.8%) and leiomyosarcoma (LMS) (11.3%) with a majority being high-grade (75.5%). The median disease-free interval was 2.9 years (2- 5.3 years) from the first surgery. The median age at second surgery was 56 (21- 79) and all patients had a complete resection (R0/R1). Recurrence patterns differed with subtypes where 90.9% and 9.1% of WDLS, 76.7% and 16.7% of DDLPS and 83.3% and 16.7% of LMS had local and distant relapses respectively from the second surgery. 62.5% of distant relapses was in the lung followed by nodes (18.8%) and liver (12.5%). The 5-year OS from the second surgery was 66.2% (95% CI: 54.3%- 80.8%). The 1-year, 3 years and 6 years DFS were 50.2% (95% CI: 38.2% - 65.9%), 10.4% (4.26% - 25.5%) and 3.91% (0.684% - 22.4%) respectively. Overall, 32 patients (60.4%) had passed away from sarcoma. The concordance indices for 6-year OS and DFS were 0.7 and 0.65 (Figure 1) respectively which represents a fairly accurate prediction by Sarculator.ConclusionOur study has shown the Sarculator nomogram for primary recurrent was applicable in our cohort and its potential application in an Asian setting. The Sarculator nomogram will be a useful tool in clinical practice to improve risk stratification and facilitate prognosis-based decision-making. Moving forward, novel therapeutic strategies are required to enhance the prognosis of patients with recurrent RPS.

Impact of establishing a specialized hepatobiliary unit on liver resections in a non-specialized tertiary centre in regional Australia.

In April 2018, a dedicated hepatobiliary unit was established in a tertiary hospital in North Queensland. Changes included the employment of a hepatobiliary-trained surgeon, centralized referrals, and formalized multidisciplinary team meetings. This study aimed to evaluate the impact of establishing a hepatobiliary unit on outcomes after liver resection, in a regional centre where such procedures were previously performed by non-specialist general surgeons. Adult patients who underwent elective liver resection in Townsville from 2013 to 2020 were included in the study. Outcomes after liver resection were collected across two study periods - before and after the hepatobiliary unit was established. The primary end points were a before and after comparison of the 90-day morbidity and mortality and the R1 margin rates. Across the two study periods, 76 and 77 patients, respectively, underwent liver resection. Rates of R1 resection, 90-day mortality and major complications were not significantly different between the two study periods. Primary tumours (14.5% before versus 50.6% after) and cirrhosis (1.3% before versus 14.3% after) were significantly higher in the latter period, as was the median length of stay (4 days before versus 6 days after). Annual surgical volume increased by 75% in the period after 2018 compared to the 5 years preceding it. Establishing a centralized hepatobiliary unit in a tertiary regional centre resulted in increased surgical volume and case complexity, with no change in early outcomes after liver resection. Overall, this dedicated unit improved the accessibility of a subspecialty surgical service in regional Australia.

Clinical analysis of multimodal treatment for localized synovial sarcoma: A multicenter retrospective study

IntroductionSeveral prognostic factors for survival in synovial sarcoma have been proposed, but the role of adjuvant chemotherapy and radiotherapy is a matter of debate. The study aim was to clarify the effect of high-dose ifosfamide-containing chemotherapy and adjuvant radiotherapy for patients with localized synovial sarcoma. Materials and methodsFive tertiary musculoskeletal oncology hospitals participated in this retrospective study. The records of the patient diagnosed with synovial sarcoma without metastasis at diagnosis from 1990 to 2011 have been collected and reviewed. Overall, distant failure-free, and local failure-free survivals were calculated, and prognostic factors for each survival were evaluated by performing univariate and multivariate analyses. ResultsA total of 162 patients were enrolled in this study with a median follow-up period of 67 months (range, 5–267 months) for all surviving patients. The 5-year overall, distant failure-free, and local failure-free survival rates were 79.7%, 66.3%, and 98.4%, respectively. Univariate analyses demonstrated that high-dose ifosfamide-containing chemotherapy was significantly associated with better overall (p = 0.014) and distant failure-free survival (p = 0.0043) than that of low-dose or no ifosfamide-containing chemotherapy if we analyzed only patients with tumors >5 cm in size. Addition of radiotherapy was not a significant prognostic factor for overall survival in the univariate and multivariate analyses, but it did improve the overall survival of the patients with R1 resection (p = 0.053). ConclusionPatients with localized synovial sarcoma >5 cm in size had better overall and distant failure-free survival after receiving adjuvant chemotherapy containing high-dose ifosfamide comparing to low-dose or no ifosfamide-containing chemotherapy. The addition of adjuvant radiotherapy was beneficial for the patients who received R1 resection. Alternatively, adjuvant radiotherapy could be avoided for patients who achieved an R0 margin.

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature.

BACKGROUNDThe standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2). AIMTo analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques. METHODSIn December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review. RESULTSThe main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047). CONCLUSIONDose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications.

Impact of Pathological Response to Preoperative Radiotherapy in Soft Tissue Sarcoma

<h3>Purpose/Objective(s)</h3> The therapeutic response of soft tissue sarcoma (STS) to neoadjuvant treatment has been associated with improved margin status, disease control, and survival. Given the rarity of this disease and the confounding effects of chemotherapy, this study analyzes whether the pathological necrosis rate (PN) of preoperative radiation (RT) alone is associated with improved clinical outcomes for STS. <h3>Materials/Methods</h3> An IRB retrospective review was conducted on a database of 315 patents treated at our institution between 1987 and 2015 who received neoadjuvant RT alone followed by surgical resection, of which 203 had documented PN. Time to event outcomes estimated via Kaplan-Meier included overall survival (OS), progression-free survival (PFS), time to loco-regional failure (TTLRF), and time to distant failure (TTDF). Cox regression analyses were performed to determine prognostic variables associated with clinical outcomes. <h3>Results</h3> With a median follow up of 87 months, 157 patients (77%) obtained a clear resection margin (R0). The average PN rate was 56% and 37 patients (18%) achieved a PN≥95%. PN was significantly higher for R0 (vs. R1) resection (70% vs. 45%, <i>P</i> = 0.014) and achieving a PN≥95% was associated with an R0 resection (<i>P</i> = 0.057). PN≥95% was associated with a 5-year non-significant benefit in TTLRF (94% vs 86%, <i>P</i> = 0.274) and TTDF (70% vs 45%, <i>P</i> = 0.130), which translated to a significant 5-year PFS benefit (65% vs. 45%, <i>P</i> = 0.036). R0 margin status was associated with a 5-year TTLRF improvement (91% vs 80%, <i>P</i> = 0.046). On multivariate analysis, PN ≥95% independently associated with PFS (HR 0.4, 95% CI 0.2-0.8, <i>P</i> = 0.015), and achieving an R0 resection was independently associated with improved PFS (HR 0.5, 95% CI 0.30-0.83, <i>P</i> = 0.007) and OS (HR 0.52, 95% CI 0.29-0.91, <i>P</i> = 0.027). <h3>Conclusion</h3> Therapeutic response to preoperative radiation alone is associated with improved surgical margin status and clinical outcomes in STS. Achieving PN ≥95% independently predicts for a higher PFS and contributes to improved negative margin resection rate which was associated with improved local control, PFS, and OS. Future prospective studies are required to validate the relationship between pathologic response to radiation and outcome, and to elucidate the potential mechanisms for distant control and PFS benefit.

Study of Novel Radioenhancer NBTXR3 Plus Radiotherapy in Patients With Locally Advanced Soft Tissue Sarcoma: Results of the Long-Term Evaluation in the Phase II/III Act.In.Sarc Trial

NBTXR3, a novel radioenhancer activated by radiotherapy (RT) demonstrated superior efficacy, as preoperative treatment in patients with locally advanced soft tissue sarcoma (LA STS) compared to RT alone. Primary endpoint of pCR rate (16% vs 8%; P = 0.044) and main secondary endpoint of R0 margin rate (16% vs 8%; P = 0.042) were met while no modification of the early RT-associated safety profile was observed, leading to market authorization. Here we report on the long-term safety, limb function and quality of life.This phase II/III randomized (1:1), international trial included adult patients with LA STS of the extremity or trunk wall, requiring preoperative RT. Patients received either a single intratumoral injection of NBTXR3 (equivalent to 10% of tumor volume, at 53.3g/L), plus EBRT (arm A) or EBRT alone (arm B) (50 Gy in 25 fractions), followed by surgery. Here we report on safety of NBTXR3+RT which was evaluated as secondary endpoint. Data were recorded on the "all treated population" during at least a two-year follow-up. Important parameters related to HR-QoL including functional outcome were studied using the EQ-5D, RNLI, TESS and MSTS questionnaires.Patients had at least two-year follow-up and the lost to follow-up rate was very low (1.9%). RT-related SAEs were observed in 11.2% (10/89) vs 13.3% (12/90) in A vs B. Post-treatment AEs, any grade, were observed in 51.7% (46/89) vs 57.8% (52/90) and serious post-treatment AEs in 13.5% (12/89) vs 24.4% (22/90) of patients in A vs B. Long-term safety continues to demonstrate that NBTXR3 plus RT has no impact on post-surgical wound complications (24.7% vs 36.7%, A vs B). Furthermore, the evaluation of radiation late toxicities in limbs such as fibrosis, arthrosis and edema that may alter limb function showed no difference between arms (4.5% vs 7.7%, 2.2% vs 0.0% and 6.7% vs 2.2% respectively in A vs B). In addition, sequelae or chronic tissue disturbances at the former tumor localization were similar in both treatment arms, confirming that the increase of energy dose deposit and the physical presence of NBTXR3 did not impact post-treatment limb functions. Accordingly, HR-QoL evaluation yielded no difference in functional outcome. Finally, second primary cancer was observed in 1 patient in arm A and 6 patients in arm B and the intratumoral injection of NBTXR3 did not induce cancer cell seeding at the former tumor site.These results demonstrate that the use of NBTXR3 did not change the late onset toxicity profile of EBRT, nor modified its bystander effect. Taken together, the long-term safety data presented here, and the previously published efficacy data reinforce the favorable benefit-risk ratio of the use of NBTXR3 in patients with LA STS. NCT02379845.

Safe-margin surgery by plastic reconstruction in extremities or parietal trunk soft tissue sarcoma: A tertiary single centre experience

IntroductionTertiary centers recruit a large proportion of locally advanced or recurrent soft tissue sarcomas (STSs) that may have been preoperatively irradiated. The objective of this study was to evaluate the results of oncoplastic surgery (OPS) for patients affected by extremities or parietal trunk STS. Materials and methodsThis retrospective study includes patients who underwent a flap reconstruction after sarcoma resection between January 2018 and December 2020 at Institut Curie. The primary endpoint was the evaluation of the impact of OPS on the quality of surgical margins. The secondary endpoint was to quantify the morbidity of OPS and identify predictive factors for wound complications. ResultsOf 211 patients, 89 (42.2%) had a flap reconstruction. Surgery was realized on an irradiated field in 56 (62.9%) patients. Without OPS, all patients were candidates either for amputation (n = 9,10.1%) due to vessels/nerve infiltration, or R1/R2 resection (n = 80,89.9%). Seventy-two (80.0%) pedicle flaps and 18 (20.0%) free flaps were used. No R2 resections were performed. R0 and R1 margins were achieved in 82 (92.1%) and 7 (7.9%), respectively. The median closest margin was 3 mm (IQR 1–6 mm). Among R1 patients, 5 had positive margins along a preserved critical structure, 2 patients had well-differentiated liposarcomas. The surgical morbidity rate was 33.3% (30/90 flaps). The reoperation rate was 15.7% (14/89 patients). ConclusionsIn a referral sarcoma center, the collaboration between the surgical oncologist and the plastic surgery team should be considered upfront in the surgical plan, allowing the most adequate wide oncological resection with acceptable postoperative morbidity.

Locally aggressive rarely metastazing tumors and low-grade sarcoma in children, adolescents and young adults: The benefits of a national network

IntroductionComplete surgical resection constitutes the mainstay of treatment for locally aggressive, rarely metastazing tumor and low-grade soft tissue sarcomas (LAS). Local relapse is the most common tumor event, especially in the presence of positive margins (R1 margins). The aims of this study are to assess the impact of the national network on patient care and to evaluate the role of immediate re-excision in children, adolescents and young adults with incompletely resected LAS. MethodsNational retrospective multicenter study of all young patients (≤25 years) included in the Sarcoma “ConticaBase” treated for LAS between 2005 and 2017 for whom pathology/biology review was available via the national NETSARC + network. ResultsA total of 96 patients were identified (median age: 16 years). Tumors were localized in 99% of cases (1 N+ tumor). With a median follow-up of 4.7 years (range: 0.1–11.9), eight local relapses and two distant metastases were observed. No patient died. Overall 5-year event-free survival (EFS) was 90.4% [95%CI, 84.3–97]. Five year EFS for R1 patients (n = 51) with (n = 24) and without (n = 27) immediate re-excision was 90.5% [95%CI, 78.8–100.0] and 80.3% [95%CI, 64.7–99.9], respectively (p = 0.34). The 37 patients directly treated in a reference center more commonly had a diagnostic biopsy (78% vs. 21%; p < 0.001), more complete surgery (R0: 65% vs. 14%; p < 0.001) and less commonly underwent re-excision (16% vs. 54%; p < 0.001). ConclusionsThis large series indicates that LAS are rare in young patients and have a favorable prognosis. Immediate management in reference centers is associated with better standard of care. The main tumor events are local relapses.

Resection of the Portal-Superior Mesenteric Vein in Pancreatic Cancer: Pathological Assessment and Recurrence Patterns.

The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS). This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010-2017). In addition, a systematic literature search was performed. In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized. Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized.

Is routine splenic flexure mobilization always necessary in laparotomic or laparoscopic anterior rectal resection? A systematic review and comprehensive meta-analysis.

Splenic flexure mobilization (SFM) is one of the most difficult steps in laparoscopic colorectal surgery and its role is harshly debated. Some surgeons considered it routinely necessary to obtain a safe anastomosis and to respect oncologic criteria; for others SFM is frequently unnecessary, not ensuring the aspects mentioned above and increasing the risk of morbidity (splenic, bowel and vessels injury, lengthened procedure). We performed a systematic review and a comprehensive meta-analysis, without any language restriction, about the peri-operative and post-operative outcomes (anastomotic leakage, intra-operative complication, conversion rate, operative time, post-operative bleeding, intra-abdominal collection, prolonged ileus, wound infection, anastomotic stricture, overall complications, hospital stay, re-operation, post-operative mortality, R0 margin resection, local recurrence) in patients undergoing elective anterior rectal resection (ARR) with or without SFM, both in laparotomic (LT) and laparoscopic (LS) approach. Fourteen studies were meta-analyzed with a total amount of 42,221 patients. The comprehensive meta-analysis shows that the mobilization or the preservation (SFP) of the splenic flexure does not statistically influence the incidence of colorectal anastomotic leakage, conversion rate, post-operative bleeding, intra-abdominal collection, prolonged ileus, wound infection, anastomotic stricture, overall complications, hospital stay, re-operation, R0 margin resection, and local recurrence results. The operative time is significantly longer in every group of patients undergoing SFM. The incidence of intra-operative complication is statistically increased in overall patients and also in the LS subgroup of patients undergoing SFM, in which also higher incidence of wound infection and re-operation is shown. The meta-analysis shows that SFM may be considered not necessary to ensure better peri-operative and post-operative outcomes in both LT and LS ARR.