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Background: Retroperitoneal sarcomas (RPS) should be surgically managed in specialized sarcoma centers. However, it is not clearly demonstrated if clinical outcome is more influenced by Center Case Volume (CCV ) or by Surgeon Case Volume (SCV ). The aim of this study is to retrospectively explore the relationship between CCV and SCV and the qual- ity of surgery in a wide region of Northern Italy. Methods: We retrospectively collected data about patients M0 surgically treated for RPSs in 22 different hospitals from 2006 to 2011, dividing them in two hospital groups according to sarcoma clinical activity volume (HCV, high case volume or LCV, low case volume hospitals). The HCV group (> 100 sarcomas observed per year) included a Comprehensive Cancer Center (HVCCC) with a high sarcoma SCV (> 20 cases/year), and a Tertiary Academic Hospital (HVTCA) with multiple surgeon teams and a low sarcoma SCV (≤ 5 cases/year for each involved surgeon). All other hospitals were included in the LCV group (< 100 sarcomas observed per year). Results: Data regarding 138 patients were collected. Patients coming from LCV hospitals (66) were excluded from the analysis as prognostic data were frequently not available. Among the 72 remaining cases of HCV hospitals 60% of cases had R0/R1 margins, with a more favorable distribution of R0/R1 versus R2 in HVCCC compared to HVTCA. Conclusions: In HCV hospitals, sarcoma SCV may significantly influence RPS treatment quality. In low-volume centers surgical reports can often miss important prognostic issues and surgical quality is generally poor. Keywords: Retroperitoneal sarcomas, Multidisciplinary management, Hospital case volume, Surgeon case volume, Quality of surgery, Retrospective analysis histotypes with liposarcoma and leiomyosarcoma as Background the most common . Retroperitoneal sarcomas (RPS) account for 10–15% The mainstay of treatment is surgical resection due to of soft tissue sarcomas (STS) with an expected its survival advantage over nonsurgical treatments . annual incidence of nearly 1500 cases in Europe and The intent of surgery is complete tumor resection with an expected 5-year overall survival (OS) of 30–35% negative margins, which may require en bloc removal . Histopathological analysis can reveal multiple of adjacent involved organs or tissues. Of course, a wide margin per se may not be enough to guarantee an improved prognosis especially in specific histotypes *Correspondence: firstname.lastname@example.org (e.g. leiomyosarcoma) thus making it crucial to balance Visceral Sarcoma Unit, University of Turin, Cso Dogliotti 14, 10126 Turin, between wider excision and multimodal treatments . Italy Given the low incidence of RPS, individual hospitals and Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Sandrucci et al. Clin Sarcoma Res (2018) 8:3 Page 2 of 7 surgeons generally observe very few cases; for this rea- Methods son available guidelines and consensus-papers state that, We retrospectively collected data concerning two regions as a complex and rare disease, every case of RPS should of northern Italy, Piedmont and Aosta Valley (with a total be referred to a specialized sarcoma center and managed amount of 4.5 million of inhabitants), to identify RPS by a multidisciplinary team [5–7]. However, it is unclear patients, without distant metastases at diagnosis, oper- what factor(s), for example, case volume, surgeon activ- ated during the period from 2006 to 2011 in order to ana- ity volume, hospital type, or the availability of adjuvant lyze care center characteristics (according to high or low therapies, is/are the principal driver(s) of improved CCV and SCV) and quality of surgical treatment. Data outcomes. collection was authorized by a partnership between the It is not clearly demonstrated if for STS, and specifically Department « Rete Oncologica del Piemonte e della Valle for RPS, clinical outcome is more influenced by center d’Aosta » (Piedmont and Aosta Valley Oncologic Net- case volume (CCV) or by surgeon case volume (SCV). work) and Italian Pathologist Association (SIAPEC) stip- In the literature, the effect of surgeon versus hospital ulated in June 2012; all data were recorded anonymously volume on outcomes after complex oncological surgery respecting Italian privacy rules. is poorly characterized . Published retroperitoneal Data of histopathological reports from January 2006 to sarcoma series are mostly collected from high volume December 2011 were collected from local databases of centers, in which the multidisciplinary aspect is most 22 different hospitals. According to the type of electronic relevant rather than the surgeon’s caseload. The lack of database available in every single hospital, site-specific surgeon-specific identifiers makes impossible to explore search strings were prepared using keywords able to the interplay between hospital and surgeon volume and describe the site and the morphology (i.e. “retroperito- their impact on oncological outcomes. Therefore, it is neum” and/or “sarcoma”) and SNOMED codes used for unclear whether the principal determinant of oncological sarcomas morphology . outcomes is high hospital case volume or high surgeon All extracted cases were screened by a skilled medi- case volume. Providing care for RPS patients frequently cal oncologist and collected in an encrypted database, requires a multidisciplinary team approach, and the team which contained clinical and histopathological data, with itself may be just as important than the surgeon in pro- particular attention to ESMO guidelines main prognos- ducing favorable outcomes. tic items such as tumor size, grading, surgical margins NICE guidelines state that a surgeon with specific (according to the R0, 1 and 2 ranking), preoperative expertise in these tumors, who is a core member of the biopsy and tumor integrity. multidisciplinary team (MDT), is needed within a refer- In our study patients data retrieved from different hos - ence center; they also consider the number of new cases pitals were split in two groups according to their yearly per year as an important quality evaluation item for sar- sarcoma caseload, adopting the 100 cases/year cut-off coma multidisciplinary teams. A sarcoma MDT should rule suggested by NICE  (Fig. 1). be expected to manage at least 100 new STS patients per In the “high volume” group two institutions year, and this caseload should be based either in a single were included: hospital or in several geographically close and closely affiliated hospitals, which would constitute a sarcoma treatment network . Due to the rarity of these diseases, it is difficult for a general surgeon to reach an adequate case volume. The only paper dealing with the problem of adequate surgical volumes in STS proposed a ≥ 5 sarcoma surgeries/year cut off, after an analysis of 4205 STS cases registered in the Florida Cancer Data System (FCDS) in which medi- cal facilities above the 67th percentile for volume were defined as high-volume centers . Concerning the treatment of retroperitoneal sarcomas, the aim of this study is to retrospectively explore the relationship between the hospital or surgeon case vol- Fig. 1 Series distribution according to activity volumes adopting the ume and the quality of surgery in a region of Northern 100 cases/year cut-off rule suggested by NICE  Italy. Sandrucci et al. Clin Sarcoma Res (2018) 8:3 Page 3 of 7 • “Candiolo Cancer Center, a high volume Compre- Results hensive Cancer Center (HVCCC) with nearly 150 Data from 22 hospitals were available: 138 patients (55% STS cases observed per year. males and 45% females) were identified with a diagnosis • “Città della Salute e della Scienza” San Giovanni Bat- of RPS from 2006 to 2011. tista hospital, a high volume Tertiary Care Academic According to care center volume 47 cases (34.1%) were hospital (HVTCA) with more than 100 STS cases treated in HVTCA, 25 (18.1%) in HVCCC: 66 cases observed per year. (47.8%) were treated in LVSCH. As regards this latter group of patients, the lack of In the “low volume” group all other hospitals were essential information impaired any statistical analysis. In included (low volume secondary care hospitals, LVSCH). particular, no useful informations were available concern- In this series three different approaches to RPS are ing tumor diameter, preoperative biopsy, margins evalua- represented: tion and FNLCLCC grading. For this reason, data from this latter group was not considered in the subsequent • HVCCC, a high-volume cancer center with a sar- analysis, which has been conducted only on HTVCA and coma-committed surgical team (high CCV and HVCCC patients. SCV > 20 surgeries per year) and a regular RPS-mul- The main characteristics of this series are summarized tidisciplinary board (RMB); in Table 1. • HVTCA, a high-volume tertiary care academic hos- Seventeen different histotypes were observed. The pital without a sarcoma-committed surgical team most frequent was liposarcoma (55.5%), followed by leio- (high CCV and SCV ≤ 5 cases per year for each myosarcoma (14%), sarcoma NOS (11%) and other his- involved surgeon) and a formalized RMB; totypes. The difference between the two groups was not • LVSCH, a group of low volume hospitals (low CCV significant. and SCV < 5 RPS surgeries per year) without a for- The tumor was primitive in 63.8% and recurrent malized RMB. in 36.2%: in HVCCC primaries were 56% and recur- rences 44%; in HVTCA 68 and 32%. (Chi Squared test, P = 0.30). Missing clinical informations concerning the “high vol- According to FNCLCC grading, 14% of tumors were ume” group were sorted from the institutional internal G1, 31% were G2 and 37.5% G3. In 17.5% of cases, this electronic chart database of each institution. information was not recorded. The subdivision of grades Missing data about the patients in charge to LVSCH G1/G2–3 in HVCCC and HVTCA was 31/52 and 53/30 were not obtained, due to the absence of a reliable data- (Chi Squared test, P = 0.91), respectively. base or, in case of an existing one, to access restrictions Tumor diameter was smaller than 10 cm in 30.5% of for external investigators. cases (32% for HVTCA and 28% for HVCCC), greater Follow up was available only for the HV hospital than 10 cm in 69.5% (68% for HVTCA and 72% for patients; the median value was of 85 months (range HVCCC) (Chi Squared test, P = 0.2622). 72–100). A preoperative biopsy was performed in 63.8% of patients, of which 66.5% coming from HVTCA and 60% Statistical analysis from HVCCC. Data were analyzed with SAS system 9.2 software. According to previous experiences [12, 13] surgical The crude and adjusted hazard ratios were calculated resections were classified as macroscopically complete (R0 according to hospital, patient’s age, tumor size, grading, or R1) or incomplete (R2). 60% of RPS had a R0/R1 resec- recurrent or primitive tumor. Two logistic regression tion, 25% had R2 resection. In 15% of cases the status of models were adopted: for tumor integrity and for surgical surgical margins was not recorded. In HVCCC group the margins (confidence limits 95%). distribution R0/R1 versus R2 was 80 and 12%; in HVTCA, The Kaplan–Meier survival curve for primary/recur - 49 and 32% (Chi Squared test, P = 0.0133; Fig. 2). rent RPS was calculated on HV series. The Kaplan–Meier Tumors were removed intact in 50% of cases. In survival curve according to surgical margins was built HVCCC group the rate of fragmented/intact specimens with the high HCV hospitals data, and is based on 57 was 24 and 76%, and in HVTCA, 63.8 and 36.2% (Chi patients. Squared test, P = 0.01, Fig. 2), respectively. Sandrucci et al. Clin Sarcoma Res (2018) 8:3 Page 4 of 7 Table 1 patients from high volume centers (HCV) main characteristics Global HVC % HVTCA % HVCCC % HVTCA versus HVCCC Age < 60 15 21.0 11 23.5 4 19.0 P = 0.81 ≥ 60 57 79.0 36 76.5 21 81.0 Sex M 43 59.7 24 51.0 19 76.0 P = 0.62 F 29 40.3 23 49.0 6 24.0 Primary/recurrent Primary 46 63.8 32 68.0 14 56.0 P = 0.30 Recurrent 26 36.2 15 32.0 11 44.0 Diameter < 10 cm 22 30.5 15 32.0 7 28.0 P = 0.26 ≥ 10 cm 50 69.5 32 68.0 18 72.0 Histotype Liposarcoma 40 55.5 24 51.0 16 64.0 P = ns Leiomyosarcoma 10 14.0 9 19.0 1 4.0 Sarcoma NOS 8 11.0 1 2.0 7 28.0 Others 14 19.5 13 28.0 1 4.0 Grading 1 10 14.0 7 14.8 3 12.0 P = 0.9 2 22 31.0 18 38.2 4 19.0 3 27 37.5 14 30.0 13 52.0 Unknown 13 17.5 8 17.0 5 17.0 Preoperative biopsy Yes 46 63.8 31 66.5 15 60.0 P = 0.45 No 26 36.2 16 33.5 10 40.0 Margins R0 20 28.0 10 21.0 10 40.0 R0 + R1 versus R2 P = 0.013 R1 23 32.0 13 28.0 10 40.0 R2 18 25.0 15 32.0 3 12.0 Unknown 11 15.0 9 19.0 2 8.0 Fragmentation Yes 36 50.0 30 63.8 6 24.0 P = 0.01 No 36 50.0 17 36.2 19 76.0 Statistically significant P values are in italic HVTCA high volume Tertiary Care Academic Hospital, HVCCC high volume Comprehensive Cancer Center We compared HVTCA and HVCCC groups with the Chi squared test for grading, surgical margins, tumor size and intact specimen removal. In both logistic regression models concerning intact speci- men and surgical margins (Table 2), only the “care center” item demonstrated a statistically significant correlation (i.e. HVCCC versus HVTCA) (P = 0.03, adjusted effects). 5 years survival according to the quality of mar- gins was 65% for R0–R1 and 31% for R2 patients (Chi Squared test, P < 0.001) without differences between Fig. 2 Analysis of margin involvement and specimen fragmenta- HVCCC and HVTCA cases (Chi Squared test, P = 0.06 tion according to the hospital of treatment (HVCCC versus HVTCA). P Fig. 3). values are derived from Chi square test Sandrucci et al. Clin Sarcoma Res (2018) 8:3 Page 5 of 7 Table 2 Logistic regression model about the factors potentially affecting the quality of surgical margins (R0/1 versus R2) Covariates Rough effects P IC95% Adjusted effects P IC95% HVCCC – – – – – – HVTCA 5.262 0.0192 1.311–21.115 8.335 0.0306 1.220–57.242 Liposarcoma – – – – – – Leiomyosarcoma 1.094 0.9059 0.248–4.829 1.193 0.8388 0.218–6.543 Others 1.176 0.8551 0.206–6.731 0.470 0.5620 0.037–6.034 Age 0.970 0.3390 0.912–1.032 0.973 0.4823 0.903–1.049 Primary – – – – – – Recurrent 1.450 0.5490 0.430–4.889 3.252 0.1608 0.626–16.897 < 10 cm – – – – – – > 10 cm 1.107 0.8830 0.285–4.297 0.808 0.8104 0.141–4.617 G1 – – – – – – G2/G3 0.288 0.0797 0.071–1.159 0.365 0.3485 0.045–2.999 Unknown 3.718 0.2369 0.422–32.759 1.687 0.7363 0.080–35.384 HVCCC high volume Comprehensive Cancer Center, HVTCA high volume Tertiary Care Academic Hospital 1.00 0.75 0.50 0.25 0.00 0 20 40 60 80 100120 Months R2 HVTCA R0/R1 HVCCC R0/R1 HVTCA R2 HVTCCC Fig. 3 Kaplan-Meyer curves according with the status of surgical margins (R0/R1 versus R2) patients from HVCCC versus patients from HVTCA surgery more adherently to clinical STS guidelines than Discussion low-volume ones [19, 20]. The outcome of surgical treatment of many common In real life, up to 63% of STS in UK are referred to tumors (as for example rectal cancer, breast cancer, non-specialized centers ; up to 50% of non-oncology lung cancer, prostate cancer, head and neck cancers and committed surgeons perform extremity soft tissue sar- esophageal cancer) are clearly influenced by both center coma resections in California . In a recent survey the case volume (CCV) and surgeon case volume (SCV) [14, German Interdisciplinary Sarcoma Group  analyzed 15]. university medical centers plus those ones treating more In STS, several studies state that HCV hospital may than 10 RPS per year in comparison to centers follow- assure higher survival rate [10, 16]. ing less than 10 RPS per year, finding relevant differences Some retrospective data show that the management of regarding tumor biopsy policy, resection strategies and RPS in sarcoma-specialized centers is associated with a multimodal therapies. Only 11 surgical departments on lower loco-regional relapse rate and a 5-year OS of nearly 191 surveyed treated more than 10 RPS patients per year; 60–65% [17, 18] and that high-volume centers perform Functionof SurvivalDistribution Sandrucci et al. Clin Sarcoma Res (2018) 8:3 Page 6 of 7 in only 19 hospitals a multidisciplinary sarcoma board Maintaining tumor specimen integrity is often a daunt- was active and in 54% of the departments pretreatment ing challenge given the large size, location, and adjacent tumor biopsy was a standard procedure. These results organ involvement of many of these tumors, and there- suggest the need for dedicated RPS education programs fore, tumor integrity can be considered a proxy of surgi- and centralized registration for RPS treatment. cal quality. Berger et al.  identified 2762 patients from the US It is expected that outcomes directly under the sur- National Cancer Database treated for retroperitoneal geon’s control, that is, the completeness of resection, sarcoma. The majority (59.4%, n = 1642) underwent are more strongly associated with surgeon volume, a resection at an academic cancer center. Resection for marker of surgical expertise, rather than by hospital vol- retroperitoneal sarcoma performed at academic cancer ume, which is a somewhat imprecise marker of surgeon center was an independent predictor of margin-negative experience as well as hospital structure and process resection but was not a statistically significant risk factor characteristics. for survival, suggesting that site of care may contribute to Important limitations of this study are its retrospec- the quality of retroperitoneal sarcoma surgery. tive nature, based on histopathological reports, the omis- The management of soft tissue sarcomas requires inte - sion of non-surgically treated patients, the retrieval of grated care at a referral center, as suggested by existing missing data from different databases and the absence of guidelines and consensus statements. Diagnosis of the clinical history and follow-up information, particularly primary lesion, distant metastasis, or subsequent local about RFS, in patients treated in LVSCH. recurrence require the use of advanced imaging as well as the expertise of appropriately trained teams. Experts Conclusion involved in soft tissue sarcoma care suggest treatment Outside reference or tertiary care centers, the quality of with respect to using, dosing, and timing of radiation and RPS management may be lower because the relevance of chemotherapy tailored for every individual patient [5, both tumor integrity and surgical margin quality are not 24]. completely understood and therefore, documented. Surgery of RPS, especially for wide re-excision after In light of the persistent association between improved unplanned primary excision of a mass, requires specific surgical oncology outcomes and high-volume activ- multidisciplinary teamwork [25, 26]. There are data con - ity, the centralization of high-risk cancer surgery has cerning RPS which show that patients treated in sarcoma been proposed [26–28]. A volume-outcome relationship reference centers can achieve better oncological out- exists for RPS so, centralization may improve outcomes comes [17, 18]. for RPS keeping in mind that surgical experience plays In this study, we collected data concerning the treat- a larger role for these outcomes than structural/process ment of RPS from 22 hospitals, of which 20 (90%) treated characteristics. less than 5 cases per year; the low quality of retrieved Authors’ contributions information from this low volume activity hospitals SS: study design, manuscript editing. AP, CG, PL, GG data input and comple- (LVSCH), mirrors the incidental character of this type of tion, MM, OB data collection. DDC, GC. Statistic workout. BM manuscript revision. All authors read and approved the final manuscript. surgery. We considered margins as macroscopically negative Author details (R0/R1) or macroscopically positive (R2), as available lit- Visceral Sarcoma Unit, University of Turin, Cso Dogliotti 14, 10126 Turin, Italy. Medical Oncology 1 Division, Città della Salute e della Scienza, Turin, Italy. erature shows that this margin classification has a defi - 3 4 Department of Surgical Sciences, University of Turin, Turin, Italy. Depart- nite prognostic value without great differences between ment of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, 5 6 R0 and R1 in the retrospective setting; is often difficult Italy. Regional Oncologic Network Department, Turin, Italy. Cancer Epidemi- ology Unit, Città della Salute e della Scienza, Turin, Italy. to correctly assess microscopic margins in big retroperi- toneal masses in absence of a real compartment or of the Acknowledgements possibility of a wide excision [6, 12, 13, 27–30]. The mul - Not applicable. tivariate analysis confirmed that, within high CCV cent - Competing interests ers, the one with a dedicated surgical team and a RMB The authors confirm that there are no known competing interests associated (HVCCC) had a better quality of macroscopic margins with this publication and there has been no significant financial support for this work that could have influenced its outcome. and a higher rate of intact tumor resection. Keung et al.  highlights the importance of maintaining tumor Availability of data and materials specimen integrity during surgery because tumor frag- Not applicable. mentation is independently associated with worse PFS Consent for publication and OS. Bonvalot and colleagues  similarly reported All authors have seen and approved the final manuscript and a have agreed that tumor rupture was associated with worse OS. for the publication on sarcoma research. Sandrucci et al. 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Clinical Sarcoma Research – Springer Journals
Published: Dec 1, 2018
Keywords: cancer research; oncology; surgical oncology
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