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How Can a Multidisciplinary Approach Improve Prognosis of Soft-Tissue Sarcomas of Extremities?

How Can a Multidisciplinary Approach Improve Prognosis of Soft-Tissue Sarcomas of Extremities? Hindawi International Journal of Surgical Oncology Volume 2021, Article ID 8871557, 8 pages https://doi.org/10.1155/2021/8871557 Research Article How Can a Multidisciplinary Approach Improve Prognosis of Soft-Tissue Sarcomas of Extremities? 1 2 2 3 Asmae Mazti , Mohamed El Idrissi, Abdelhalim El Ibrahimi, Mustapha El Maaroufi, 4 5 6 7 2 Ghizlane El Koubaiti, Touria Bouhafa, Samira El Fakir, Samia Arifi, Abdelmajid Mrini, 1,4 and Laila Chbani Department of Pathology, Hassan II University Hospital, Fez, Morocco Department of Traumatology and Orthopedics, Hassan II University Hospital, Fez, Morocco Department of Radiology, Hassan II University Hospital, Fez, Morocco Medical Center of Biomedical and Translational Research, Hassan II University Hospital, Fez, Morocco Department of Radiotherapy, Hassan II University Hospital, Fez, Morocco Laboratory of Epidemiology, Faculty of Medicine and Pharmacy, Fez, Morocco Department of Oncology, Hassan II University Hospital, Fez, Morocco Correspondence should be addressed to Asmae Mazti; maztiasmae@gmail.com Received 18 August 2020; Revised 21 February 2021; Accepted 10 March 2021; Published 24 March 2021 Academic Editor: C. H. Yip Copyright © 2021 Asmae Mazti et al. &is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Soft-tissue sarcomas are malignant tumors that require good management within specialized centers. Our study aims to assess the benefit of handling these kinds of tumors using the Multidisciplinary Meeting (MDM) approach. &e current paper details this approach through a prospective study that has lasted for 42 months in the HASSAN II University Hospital Center, Fez, Morocco. During this research work, 116 cases were selected with an average age of 53 years. In 95.7% of the cases, it was found that the lower limb was the most frequent tumor type (78.4%). Also, ninety-two (92) patients (79.3%) have had a prior biopsy. Ninety-nine (99) patients (85.3%) have received a magnetic resonance imaging scan (MRI) before surgery. Sixty-three (63) patients were operated on, including R0 resection used for 37 patients, R1 used for 21 patients, and R2 used for five patients. As a result, liposarcomas were the most frequent type (30.1%), followed by synovial sarcomas (14.6%), leiomyosarcomas (9.5%), ewing sarcoma (8.6), and undifferentiated pleomorphic sarcomas (7.7%). In addition, neoadjuvant chemotherapy was used for 36 patients. &e other 22 patients received adjuvant chemotherapy and/or radiotherapy. &e overall survival rate was 60.56 months, which proves a significant improvement, thanks to the multidisciplinary meeting approach. Conclusion. &e conducted investigation has shown that using MDM for managing soft-tissue sarcomas of extremities improves the patients’ survival rate. Moreover, results have proven MDM might allow optimal treatment regarding less local recurrence and metastasis. relies on surgical resection of the tumor. Such inter- 1. Introduction vention depends on a good functional procedure sup- Soft-tissue sarcomas are rare, heterogeneous, and vicious. ported by prior imaging and early biopsy that is According to their location, the sarcoma tumor could be absolutely vital. divided into three categories: the soft-tissue sarcomas of &erefore, this paper advocates that a multidisciplinary extremities that are the most frequent (60%), the viscera meeting (MDM) should be conducted before any response (30%), and the bones (10%) [1]. to a suspected sarcoma. Such a consultation process should Note that the treatment of each type can be handled involve at least an oncologist, a radiologist, a pathologist, a differently. Generally, the treatment of sarcomas depends radiotherapist, and a surgeon. &e negligence in carrying out on early and good prognosis. Practically, surgery can be a such a meeting would lead to inefficient handling of the solution to soft-tissue sarcomas. &is curative treatment tumor and, therefore, ruin any chance of recovery [2, 3]. 2 International Journal of Surgical Oncology multidisciplinary meetings. In this article, several parame- Accordingly, the current study aims to examine and assess the importance and the impact of such a procedure on ters have been listed and studied. &us, the impact of soft-tissue sarcoma management can be accurately assessed the management of soft-tissue sarcomas. Keeping this as an objective, this work investigates 116 cases of soft-tissue regarding quality and performance. For example, these sarcomas. parameters include MRI imaging, biopsy, the evaluation of In the second section of this paper, we introduce the the surgical resection margins regarding the local disease methods used for conducting this study, including design, control, and metastatic status. data collection, and statistical analysis. In the third section, we detail the obtained results. Next, in the fourth section, 2.3. Statistical Analysis. &e collected data were examined these results are discussed, and the last section summarizes and analyzed using the software “SPSS 20.0.” Qualitative conclusions. variables are expressed using means and medians, whereas quantitative variables are represented using numbers and 2. Methods and Materials percentages. 2.1. Study Design. Our work is a prospective study that was For some criteria, the distribution comparison of carried out between 01/01/2017 and 30/06/2020 at the qualitative parameters was represented by a chi-squared test, HASSAN II University Hospital in Fez (a tertiary-level where p< 0.05 was considered as being significant. For hospital). &is study is part of a larger research project, survival, the method of Kaplan–Meier was adopted. A se- which has lasted over 42 months. During the data collection, lected event refers to its first occurrences such as locore- patients’ anonymity and confidentiality were respected. &e gional progression, metastatic progression, and death (all inclusion and exclusion criteria are listed as follows: causes are combined). Hence, the original date of the study was the date of diagnosis. (i) Inclusion: patients’ age ≥18 years (ii) Patients that are diagnosed with soft-tissue sarcoma 3. Results of the extremities (iii) Exclusion: other sarcomas (i.e., bone and viscera) Of the 116 cases, 71 were males (61.2%) and 45 were females (iv) Other histological types of cancer (38.8%). Ages ranged from 18 years to 115 years (age’s average was 53.5 years). Most tumors were in the lower limb Consequently, 183 soft-tissue tumors were initially (78.4%), and the rest were in the upper limb (21.6%). Tumors recruited, where 116 cases were diagnosed with a sarcoma at deep locations were the most frequent (95.7%), while tumor. &e other 67 were excluded because the pathological superficial tumors were less frequent (4.3%). &e average diagnosis revealed a benign tumor or a different histological size was 12.28 cm (4–32 cm) (Table 1). type. Afterward, the patients were subdivided into two Table 2 highlights various indicators. &ese are used to groups. Group 1 includes 75 cases whose files are collected describe the quality of soft-tissue sarcoma management. from the university hospital. &ese cases were examined &us, ninety-nine (99) patients (85.3%) have had magnetic using an MDM procedure before any treatment. Group 2 resonance imaging (MRI) to evaluate the characteristics of consists of 41 patients, which involves files from private the tumor and to plan a surgical procedure. Ninety-two (92) health instances or patients who received radiological as- patients (79.3%) underwent tests and examinations. Most of sessments, biopsies, or surgery before being sent to the them (66%) had a prior biopsy, ultrasound, or CT-guided, university hospital (Figure 1). whereas the other cases (34%) had surgical treatments. Hence, among all the studied cases, 63 were subject to 2.2. Data Collection. Data are organized according to three surgical procedures. For 37 patients, the resection was features: (1) the clinical characteristics of patients that in- satisfying the (R0) requirement. In 24 cases, it was micro- clude age, gender, sex, history, date of diagnosis, and survival scopically positive (R1), while only two patients were pre- status, (2) the properties of the lesion that involve size, sented as grossly positive (R2). Among all the patients who depth, histological type, primary site, and surgical margins, did not have an “in sano: resection R1 or R2,” eight (6.9%) and (3) the structure that initially carries out the manage- had a surgical operation in our university hospital. ment of sarcomas. Figure 2 depicts the histological types in terms of per- &e quality of surgical excision (R0, R1, and R2) was centages. In this presented series, the most frequent histo- assessed as specified by the Union for International Cancer logical diagnoses were liposarcomas (31%). &e other ones Control (UICC). &erefore, the margin is considered as are established as follows: synovial sarcomas (15%), leio- grossly positive (R2), microscopically positive (R1) (within myosarcomas (9%), Ewing sarcoma (9%), and undifferen- 1 mm of the inked border), and microscopically negative tiated pleomorphic sarcomas (8%). Accordingly, thirty-six (R0) (at least 1 mm of normal tissue exists between the (36) patients have received chemotherapy treatment. Most tumor and the inked resection margin). of them (30 patients) were subject to neoadjuvant chemo- Moreover, our work was conducted in compliance with therapy (based on the MAI: Adriamycin, isofosfamide, and the international recommendations already available in mesna), EMPTY (vincristine, isofosfamide, doxorubicin, NCCN and ESMO (4.5). Also, we have compared these and etoposide), and VAC (vincristine protocols, doxoru- recommendations with local practices during the bicin, and cyclofosfamide). &e other six patients were International Journal of Surgical Oncology 3 183 so-tissue tumors 3 cases: refusal of treatment 7 cases: lost to follow-up 173 tumors with biopsies and/or operated 28: before IHC / FISH 38 cases: benign tumors 10: aer FISH 12 cases: no evidence of tumor 7 cases: other malignant tumors (1 melanoma,1 carcinoma, 3 osteosarcomas, 1 adenocarcinoma, and 1 lymphoma) 116 so-tissue sarcomas Figure 1: Flowchart of the study. Table 1: Description of the population. Total Group 1 Group 2 Characteristics p value N � 116 N � 75 N � 41 Gender Male 71 (61.2%) 46 (39.6%) 25 (21.5%) Female 45 (38.8) 30 (25.8%) 15 (13.1%) 0.499 Age at first diagnosis Mean (min-max) 53.56 (18–115) 54.81 (18–115) 51.29 (19–85) <20 6 (5.2%) 4 (3.4%) 2 (1.7%) 21–40 31 (26.7%) 18 (15.5%) 13 (11.2%) 41–60 41 (35.5%) 28 (24.1%) 13 (11.2%) 61–80 30 (25.9%) 20 (17.2%) 10 (8.6%) >80 8 (6.9%) 5 (4.3%) 3 (2.8%) 0.924 Size of the tumor (cm) Average 12.28 12.3 11 Median 10 10 9.5 0.292 Site of the tumor Lower limb 91 (78.4%) 59 (50.8%) 32 (27.6%) Upper limb 25 (21.6%) 17 (14.6%) 8 (7%) 0.483 Depth Deep seated 111 (95.7%) 73 (62.9%) 38 (32.7%) Superficial 5 (4.3%) 2 (1.7%) 3 (2.7%) 0.236 Histological subtype (most frequent) Liposarcoma 35 (30.1%) 26 (22.4%) 9 (7.7%) Leiomyosarcoma 11 (9.5%) 8 (6.9%) 3 (2.7%) Ewing sarcoma 10 (8.6%) 7 (6%) 3 (2.7%) Synovial sarcoma 17 (14.6%) 11 (9.5%) 6 (5.2%) UPS 9 (7.7%) 6 (5.2%) 3 (2.7%) 0.238 Grade (FNCLCC) 1 15 (12.9%) 8 (6.9%) 7 (6%) 2 67 (57.7%) 46 (39.6%) 21 (18%) 3 34 (29.4%) 22 (19%) 12 (10.5%) 0.525 Fluorescence in situ hybridization Realized 56 (48%) 42 (36.2%) 14 (12.1%) Not realized 60 (52%) 37 (29.3%) 26 (22.4%) 0.030 4 International Journal of Surgical Oncology Table 2: Quality criteria for the management of soft-tissue of the patient’s care, including imaging, biopsy, surgery, and sarcoma. adjuvant and neoadjuvant treatments. Such a specific pro- cedure should be conducted mainly within specialized Total Group 1 Group 2 Parameters p value medical structures and requires an oncologist, radiologist, N � 116 N � 75 N � 41 pathologist, radiotherapist, and surgeon. MRI before surgery In such a context, this work endeavors to demonstrate 99 66 33 Yes the positive impact of managing tissue sarcomas patients (85.3%) (56.9%) (28.4%) using the MDM approach. &ese results are specifically No 17 (14.7%) 9 (7.7%) 8 (7%) 0.008 Biopsy before related to patients’ survival and prognosis. Such findings are surgery indeed supported by previous studies [2, 6–8]. &us, the 92 68 24 cited authors have shown that the overall survival and R0 Yes (79.3%) (58.6%) (20.7%) resection rates were statistically higher when patients are examined within specialized structures. Besides the constant No 8 (7%) 16 (13.7%) < 0.001 (20.7%) demographic and biological risk factors, other observational Surgical margins studies [9, 10] have noticed that patients’ survival is also 37 20 R0 17 (27%) influenced by how much recommendations and practices (58.7%) (31.7%) are being correctly applied in the management of sarcoma R1 21 (33%) 14 (22%) 4 (6.3%) patients. Note that the proposed MDM procedure strives to R2 5 (8.3%) 2 (3.3%) 3 (4.7%) 0.650 Metastatic status address different aspects of these parameters. 89 62 27 Regarding the treatment path, the abovementioned M0 (76.7%) (53.4%) (23.3%) recommendations refer to MRI examination and radio- M1 20 (17.2%) 9 (7.7%) 11 (9.5%) guided and surgical biopsy. &ese combined elements would Mx 7 (6.1%) 5 (4.3%) 2 (1.8%) 0.105 allow a specific histological diagnosis and successive surgical Local relapse treatment. In this context, an expert surgeon can easily plan Yes 18 (15.5%) 8 (6.9%) 10 (8.6%) and correctly carry out sarcoma patients. 98 67 31 No 0.048 Typically, the radiologist plays a crucial role, especially in (84.5%) (57.7%) (26.8%) selecting suspicious tumors that require specific manage- Data of only operated patients. ment. Accordingly, looking at our cases, one can see that 66 patients (88%) from group 1 and 33 patients (80%) from subject to adjuvant chemotherapy. Also, one patient was group 2 underwent a radiological exploration with MRI. subject to doxorubicin monotherapy. &e other twenty-two &ese results sound good enough compared to previous (22) patients have benefited from external adjuvant radiation publications such as the work of Ray-Coquard et al. [13] therapy, which was exclusive in nine (9) patients. (52% of patients) and Haddad et al. [14] (76.5% of patients). As shown in Figure 3, during the evolution course, 23 In the present study, members of MDM discussed all cases as patients died, and 18 ones have shown local recurrences. the patients benefited from coma chest CT in search of Also, the overall survival is 60.561 months. distant metastases. In Table 3, one can see the performed multivariate &e radiological characteristics that are required during analysis along with the parameters of the univariate one. &is multidisciplinary meetings can be listed as follows [15, 16]: analysis showed a significant difference between the two (i) Diameter> 50 mm groups, especially in terms of the mentioned quality indi- cators. Compared to the patients treated without being (ii) Deep localization discussed in MDM, results have proven that the patients (iii) Irregular or lobulated contours whose files were discussed during an MDM have benefited (iv) Presence of irregular and thick intratumoral walls from better treatment management and more consistency in and septa clinical practice recommendations. Moreover, for the two groups, the current study has shown that some parameters (v) Heterogeneity on the T1 and T2 sequences have no significant impact on patients’ treatment (man- (vi) Early and prolonged contrast enhancement agement), such as age, sex, tumor size, tumor location, (vii) Presence of necrosis depth, histologic type, or FNCLCC grade. Our study indeed emphasizes the importance of MRI examination before starting patients’ treatment. &ere is 4. Discussion indeed a significant difference between the two studied Soft-tissue sarcomas are rare and malignant tumors. &ese groups as p � 0.008. Moreover, we proved that sarcomas patients that have received treatment without prior imaging are referred to as heterogeneous groups of tumors with a severe prognosis and a banal clinical presentation. Although were the most exposed to a high risk of inappropriate surgery (p � 0.028) and local relapse (p � 0.001). the handling of sarcomas tumor is well codified through reference systems [4] and recommendations [5], the diag- After MRI, a biopsy is the first examination to perform in case of a suspected tumor. By comparison with the work of nosis is often a complicated task. &erefore, we advocate multidisciplinary meetings (MDMs) are vital for each stage Haddad et al. (72.4%) and Ray-Coquard et al. (42%), in the International Journal of Surgical Oncology 5 Well- Myxoid differentiated liposarcoma liposarcoma 46% 19% Dedifferentia Others ted 17% Liposarcoma liposarcoma Dermatofibrosarcoma 31% 19% 5% Round-cell Sclérosing UPS liposarcoma liposarcoma 8% 8% 8% Myxofibrosarcoma 3% Rhabdomyosarcoma 3% Ewing sarcoma Synovial sarcoma 9% 15% Leiomyosarcoma 9% Figure 2: Patients according to histological types. 1.0 1.0 Group 1 0.8 0.8 0.6 0.6 Group 1 0.4 0.4 Group 2 0.2 0.2 p = 0.023 0.0 Group 2 p = 0.028 0.0 0.00 20.00 40.00 60.00 80.00 100.00 0.00 20.00 40.00 60.00 80.00 100.00 Months from diagnosis Months from diagnosis (a) (b) 1.0 Group 1 0.8 Group 1 0.6 0.4 0.2 p = 0.044 0.0 0.00 20.00 40.00 60.00 80.00 100.00 Months from diagnosis (c) Figure 3: Patient survival of studied groups (overall survival, relapse-free survival, and metastasis-free survival). Overall survival Metastasis-free survival Local relapse-free survival 6 International Journal of Surgical Oncology Table 3: Multivariate analysis. Parameters Univariate analysis Multivariate analysis Gender 0.499 0.836 Age at the first diagnosis 0.924 0.183 Size of the tumor 0.292 0.198 Site of the tumor 0.483 0.765 Depth 0.236 0.220 Histological subtype 0.238 0.049 Grade 0.525 0.287 Fluorescence in situ hybridization 0.030 0.034 MRI before surgery 0.008 0.022 Biopsy before surgery <0.001 0.000 Surgical margins 0.650 0.028 Metastatic status 0.105 0.034 Local relapse 0.048 0.001 A Cox model was carried out including all variables in univariate analysis and using a backward selection procedure which entails including all the covariates in the model. current work, the biopsy was performed for 68 patients network), and ResOs (reference network for rare bone (90.6%) from group 1 and 58.5% from group 2. sarcomas and rare bone tumors). &e organization adopts an Typically, using needles>16G, a surgeon or a radiologist approach that revolves around a centralized care system performs a radioguided percutaneous microbiopsy in using multidisciplinary discussion and benefiting from ex- compliance with the required standards [17]. In this study, pert treatment. 66% of cases (n � 61) had a CT-guided biopsy. Such a task In this context, this French organization has recently conducted a study [23] that involved 12,528 cases, where should ensure one and definitive surgery for the biopsy pathway and scar. &erefore, the biopsy entrance point 9,646 were nonmetastatic and where all patients were fol- should preferably be tattooed. A surgical biopsy might be lowed for 26 months. For patients handled by the multi- another option. disciplinary focus group, the local recurrence-free survival Note that surgery is a drastic measure of soft-tissue was much better. Accordingly, 76.9% of the patients had sarcoma treatment. &us, it should be performed as a single two-year local relapse-free survival and only 65.4% in the resection and as an unfragmented specimen. It is noteworthy other cases (p< 0.001). For both groups, the multivariate that this resection should include margins of normal tissue analysis of patients included parameters such as sex, age, unless there is an anatomical barrier. &e quality of the tumor size, tumor location, histological grade, depth, and handled or not by the multidisciplinary group. &e results excision is the most important factor of local control [18]. Accordingly, in non-R0 excision, the risk of local recurrence have shown the handling parameter is a key independent factor that influences relapse-free survival. is high [19]. For instance, R1 or marginal excision exposes the patient to a local recurrence risk that could reach 70% Note that the cited work has not assessed the overall [20]. As we stated, MDM is conducted within a specialized survival. In the current paper, we have tried to evaluate this instance where, statistically, resections are performed ap- factor. Generally, the obtained results are pretty similar to propriately (R0) [8, 21, 22]. those presented by the members of the French Sarcoma &e comparison between the two studied groups (quality group. &us, the overall survival, recurrence-free survival, of the surgical margins) shows a significant difference in and metastasis-free survival were significantly higher in the multivariate analysis (p � 0.028). Moreover, the risk of local case of patients handled by the multidisciplinary consulta- recurrence and distant metastasis decreases in the case of tion meeting (p � 0.023, p � 0.028, and p � 0.044, respectively). group 1 compared to group 2 (p � 0.001 and p � 0.034, respectively). Also, the quality of the surgery is another factor that determines the quality of care. According to data from the Practically, the current work has shown the importance of MDM regarding overall survival, recurrence-free survival, NETSARC network, most patients are operable, and the and metastasis-free survival (p, p � 0.023, p � 0.028, and quality of the resection margins influences relapse-free and p � 0.044, respectively). Accordingly, the following para- overall patient survival. French national indicators show graphs will highlight the context of these results in relation patients operated on by specialized teams from the NetSarc to the data presented by the French Sarcoma Group. or ResOs networks have a better initial assessment (biopsy Moreover, we will discuss some implications in terms of and imaging) and a better rate of optimal surgery (R0) and resources and infrastructure. are less subject to revision surgery [24]. &e French Sarcoma Group has been known, among In our series, surgery “in sano” (R0) was applied in 58.7% of the cases. &e results were statistically significant re- others, as a pioneer organization of improvements in the management of sarcoma patients. &is organization was garding both groups, in the multivariate analysis (p � 0.028) with a lower risk of local recurrence in group 1 compared to established in 2010 by RRePS (reference network in the pathology of sarcomas), NetSarc (clinical reference group 2 (p � 0.001) as well as distant metastases (p � 0.034). International Journal of Surgical Oncology 7 Regarding resources and infrastructures, the implica- ESMO: European Society for Medical Oncology. tions from this study’s findings might cover methodological aspects as well as practical ones. Such a procedure would Data Availability optimize the time and canalize the treatment. It could en- hance patients’ conditions (i.e., survival rate), and the costs Data used to support the findings of this study can be ob- tained from the corresponding author on request. of recovery from inappropriate surgical treatment might decrease. Typically, the management of soft-tissue sarcoma pa- Ethical Approval tients requires specialized centers. &ese instances can &e Cancer Research Institute and the University Hospital of provide the necessary infrastructures and adequate human Fez review board gave their approval to conduct the present resources. study (n 34/16). For example, a study in Nigeria has shown the impact of the unavailability of relevant radiological tools (i.e., MRI) Consent and the absence of multidisciplinary discussions on sarco- mas patients [25]. In such a setting, one would face several &e subjects gave written informed consent. challenges to follow or assess survival. In the same context, Adigun et al. [26] have studied STS regarding the pattern, Conflicts of Interest distribution, and issues in a black African community. &e cited retrospective study has corroborated the previous &e authors declare that they have no conflicts of interest. results, and it highlighted the difference between the pro- cedures in the Western countries and the African regions Acknowledgments (i.e., modern techniques are not commonly available or are usually not affordable). &e authors are grateful to the staff and members of the Ideally, the multidisciplinary meetings should involve an Cancer Research Institute (IRC), a public interest group. experienced traumatologist, radiologist, pathologist, on- cologist, and radiotherapist. &erefore, procedures can be References triggered once a suspicious case has risen and before action could be taken. Sometimes (i.e., lack of experience in the [1] F. Ducimetiere, J.-M. Coindre, J.-M. 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Bonvalot, “Centers of excel- lence or excellence networks: the surgical challenge and quality issues in rare cancers,” European Journal of Surgical Oncology, vol. 45, no. 1, p. 19, 2019. [23] J.-Y. Blay, P. Soibinet, N. Penel et al., “Improved survival using specialized multidisciplinary board in sarcoma pa- tients,” Annals of Oncology, vol. 28, no. 11, pp. 2852–2859, [24] S. Bonvalot, C. P. Raut, R. E. Pollock et al., “Technical con- siderations in surgery for retroperitoneal sarcomas: position paper from E-surge, a master class in sarcoma surgery, and EORTC-STBSG,” Annals of Surgical Oncology, vol. 19, no. 9, pp. 2981–2991, 2012. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Surgical Oncology Hindawi Publishing Corporation

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Hindawi International Journal of Surgical Oncology Volume 2021, Article ID 8871557, 8 pages https://doi.org/10.1155/2021/8871557 Research Article How Can a Multidisciplinary Approach Improve Prognosis of Soft-Tissue Sarcomas of Extremities? 1 2 2 3 Asmae Mazti , Mohamed El Idrissi, Abdelhalim El Ibrahimi, Mustapha El Maaroufi, 4 5 6 7 2 Ghizlane El Koubaiti, Touria Bouhafa, Samira El Fakir, Samia Arifi, Abdelmajid Mrini, 1,4 and Laila Chbani Department of Pathology, Hassan II University Hospital, Fez, Morocco Department of Traumatology and Orthopedics, Hassan II University Hospital, Fez, Morocco Department of Radiology, Hassan II University Hospital, Fez, Morocco Medical Center of Biomedical and Translational Research, Hassan II University Hospital, Fez, Morocco Department of Radiotherapy, Hassan II University Hospital, Fez, Morocco Laboratory of Epidemiology, Faculty of Medicine and Pharmacy, Fez, Morocco Department of Oncology, Hassan II University Hospital, Fez, Morocco Correspondence should be addressed to Asmae Mazti; maztiasmae@gmail.com Received 18 August 2020; Revised 21 February 2021; Accepted 10 March 2021; Published 24 March 2021 Academic Editor: C. H. Yip Copyright © 2021 Asmae Mazti et al. &is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Soft-tissue sarcomas are malignant tumors that require good management within specialized centers. Our study aims to assess the benefit of handling these kinds of tumors using the Multidisciplinary Meeting (MDM) approach. &e current paper details this approach through a prospective study that has lasted for 42 months in the HASSAN II University Hospital Center, Fez, Morocco. During this research work, 116 cases were selected with an average age of 53 years. In 95.7% of the cases, it was found that the lower limb was the most frequent tumor type (78.4%). Also, ninety-two (92) patients (79.3%) have had a prior biopsy. Ninety-nine (99) patients (85.3%) have received a magnetic resonance imaging scan (MRI) before surgery. Sixty-three (63) patients were operated on, including R0 resection used for 37 patients, R1 used for 21 patients, and R2 used for five patients. As a result, liposarcomas were the most frequent type (30.1%), followed by synovial sarcomas (14.6%), leiomyosarcomas (9.5%), ewing sarcoma (8.6), and undifferentiated pleomorphic sarcomas (7.7%). In addition, neoadjuvant chemotherapy was used for 36 patients. &e other 22 patients received adjuvant chemotherapy and/or radiotherapy. &e overall survival rate was 60.56 months, which proves a significant improvement, thanks to the multidisciplinary meeting approach. Conclusion. &e conducted investigation has shown that using MDM for managing soft-tissue sarcomas of extremities improves the patients’ survival rate. Moreover, results have proven MDM might allow optimal treatment regarding less local recurrence and metastasis. relies on surgical resection of the tumor. Such inter- 1. Introduction vention depends on a good functional procedure sup- Soft-tissue sarcomas are rare, heterogeneous, and vicious. ported by prior imaging and early biopsy that is According to their location, the sarcoma tumor could be absolutely vital. divided into three categories: the soft-tissue sarcomas of &erefore, this paper advocates that a multidisciplinary extremities that are the most frequent (60%), the viscera meeting (MDM) should be conducted before any response (30%), and the bones (10%) [1]. to a suspected sarcoma. Such a consultation process should Note that the treatment of each type can be handled involve at least an oncologist, a radiologist, a pathologist, a differently. Generally, the treatment of sarcomas depends radiotherapist, and a surgeon. &e negligence in carrying out on early and good prognosis. Practically, surgery can be a such a meeting would lead to inefficient handling of the solution to soft-tissue sarcomas. &is curative treatment tumor and, therefore, ruin any chance of recovery [2, 3]. 2 International Journal of Surgical Oncology multidisciplinary meetings. In this article, several parame- Accordingly, the current study aims to examine and assess the importance and the impact of such a procedure on ters have been listed and studied. &us, the impact of soft-tissue sarcoma management can be accurately assessed the management of soft-tissue sarcomas. Keeping this as an objective, this work investigates 116 cases of soft-tissue regarding quality and performance. For example, these sarcomas. parameters include MRI imaging, biopsy, the evaluation of In the second section of this paper, we introduce the the surgical resection margins regarding the local disease methods used for conducting this study, including design, control, and metastatic status. data collection, and statistical analysis. In the third section, we detail the obtained results. Next, in the fourth section, 2.3. Statistical Analysis. &e collected data were examined these results are discussed, and the last section summarizes and analyzed using the software “SPSS 20.0.” Qualitative conclusions. variables are expressed using means and medians, whereas quantitative variables are represented using numbers and 2. Methods and Materials percentages. 2.1. Study Design. Our work is a prospective study that was For some criteria, the distribution comparison of carried out between 01/01/2017 and 30/06/2020 at the qualitative parameters was represented by a chi-squared test, HASSAN II University Hospital in Fez (a tertiary-level where p< 0.05 was considered as being significant. For hospital). &is study is part of a larger research project, survival, the method of Kaplan–Meier was adopted. A se- which has lasted over 42 months. During the data collection, lected event refers to its first occurrences such as locore- patients’ anonymity and confidentiality were respected. &e gional progression, metastatic progression, and death (all inclusion and exclusion criteria are listed as follows: causes are combined). Hence, the original date of the study was the date of diagnosis. (i) Inclusion: patients’ age ≥18 years (ii) Patients that are diagnosed with soft-tissue sarcoma 3. Results of the extremities (iii) Exclusion: other sarcomas (i.e., bone and viscera) Of the 116 cases, 71 were males (61.2%) and 45 were females (iv) Other histological types of cancer (38.8%). Ages ranged from 18 years to 115 years (age’s average was 53.5 years). Most tumors were in the lower limb Consequently, 183 soft-tissue tumors were initially (78.4%), and the rest were in the upper limb (21.6%). Tumors recruited, where 116 cases were diagnosed with a sarcoma at deep locations were the most frequent (95.7%), while tumor. &e other 67 were excluded because the pathological superficial tumors were less frequent (4.3%). &e average diagnosis revealed a benign tumor or a different histological size was 12.28 cm (4–32 cm) (Table 1). type. Afterward, the patients were subdivided into two Table 2 highlights various indicators. &ese are used to groups. Group 1 includes 75 cases whose files are collected describe the quality of soft-tissue sarcoma management. from the university hospital. &ese cases were examined &us, ninety-nine (99) patients (85.3%) have had magnetic using an MDM procedure before any treatment. Group 2 resonance imaging (MRI) to evaluate the characteristics of consists of 41 patients, which involves files from private the tumor and to plan a surgical procedure. Ninety-two (92) health instances or patients who received radiological as- patients (79.3%) underwent tests and examinations. Most of sessments, biopsies, or surgery before being sent to the them (66%) had a prior biopsy, ultrasound, or CT-guided, university hospital (Figure 1). whereas the other cases (34%) had surgical treatments. Hence, among all the studied cases, 63 were subject to 2.2. Data Collection. Data are organized according to three surgical procedures. For 37 patients, the resection was features: (1) the clinical characteristics of patients that in- satisfying the (R0) requirement. In 24 cases, it was micro- clude age, gender, sex, history, date of diagnosis, and survival scopically positive (R1), while only two patients were pre- status, (2) the properties of the lesion that involve size, sented as grossly positive (R2). Among all the patients who depth, histological type, primary site, and surgical margins, did not have an “in sano: resection R1 or R2,” eight (6.9%) and (3) the structure that initially carries out the manage- had a surgical operation in our university hospital. ment of sarcomas. Figure 2 depicts the histological types in terms of per- &e quality of surgical excision (R0, R1, and R2) was centages. In this presented series, the most frequent histo- assessed as specified by the Union for International Cancer logical diagnoses were liposarcomas (31%). &e other ones Control (UICC). &erefore, the margin is considered as are established as follows: synovial sarcomas (15%), leio- grossly positive (R2), microscopically positive (R1) (within myosarcomas (9%), Ewing sarcoma (9%), and undifferen- 1 mm of the inked border), and microscopically negative tiated pleomorphic sarcomas (8%). Accordingly, thirty-six (R0) (at least 1 mm of normal tissue exists between the (36) patients have received chemotherapy treatment. Most tumor and the inked resection margin). of them (30 patients) were subject to neoadjuvant chemo- Moreover, our work was conducted in compliance with therapy (based on the MAI: Adriamycin, isofosfamide, and the international recommendations already available in mesna), EMPTY (vincristine, isofosfamide, doxorubicin, NCCN and ESMO (4.5). Also, we have compared these and etoposide), and VAC (vincristine protocols, doxoru- recommendations with local practices during the bicin, and cyclofosfamide). &e other six patients were International Journal of Surgical Oncology 3 183 so-tissue tumors 3 cases: refusal of treatment 7 cases: lost to follow-up 173 tumors with biopsies and/or operated 28: before IHC / FISH 38 cases: benign tumors 10: aer FISH 12 cases: no evidence of tumor 7 cases: other malignant tumors (1 melanoma,1 carcinoma, 3 osteosarcomas, 1 adenocarcinoma, and 1 lymphoma) 116 so-tissue sarcomas Figure 1: Flowchart of the study. Table 1: Description of the population. Total Group 1 Group 2 Characteristics p value N � 116 N � 75 N � 41 Gender Male 71 (61.2%) 46 (39.6%) 25 (21.5%) Female 45 (38.8) 30 (25.8%) 15 (13.1%) 0.499 Age at first diagnosis Mean (min-max) 53.56 (18–115) 54.81 (18–115) 51.29 (19–85) <20 6 (5.2%) 4 (3.4%) 2 (1.7%) 21–40 31 (26.7%) 18 (15.5%) 13 (11.2%) 41–60 41 (35.5%) 28 (24.1%) 13 (11.2%) 61–80 30 (25.9%) 20 (17.2%) 10 (8.6%) >80 8 (6.9%) 5 (4.3%) 3 (2.8%) 0.924 Size of the tumor (cm) Average 12.28 12.3 11 Median 10 10 9.5 0.292 Site of the tumor Lower limb 91 (78.4%) 59 (50.8%) 32 (27.6%) Upper limb 25 (21.6%) 17 (14.6%) 8 (7%) 0.483 Depth Deep seated 111 (95.7%) 73 (62.9%) 38 (32.7%) Superficial 5 (4.3%) 2 (1.7%) 3 (2.7%) 0.236 Histological subtype (most frequent) Liposarcoma 35 (30.1%) 26 (22.4%) 9 (7.7%) Leiomyosarcoma 11 (9.5%) 8 (6.9%) 3 (2.7%) Ewing sarcoma 10 (8.6%) 7 (6%) 3 (2.7%) Synovial sarcoma 17 (14.6%) 11 (9.5%) 6 (5.2%) UPS 9 (7.7%) 6 (5.2%) 3 (2.7%) 0.238 Grade (FNCLCC) 1 15 (12.9%) 8 (6.9%) 7 (6%) 2 67 (57.7%) 46 (39.6%) 21 (18%) 3 34 (29.4%) 22 (19%) 12 (10.5%) 0.525 Fluorescence in situ hybridization Realized 56 (48%) 42 (36.2%) 14 (12.1%) Not realized 60 (52%) 37 (29.3%) 26 (22.4%) 0.030 4 International Journal of Surgical Oncology Table 2: Quality criteria for the management of soft-tissue of the patient’s care, including imaging, biopsy, surgery, and sarcoma. adjuvant and neoadjuvant treatments. Such a specific pro- cedure should be conducted mainly within specialized Total Group 1 Group 2 Parameters p value medical structures and requires an oncologist, radiologist, N � 116 N � 75 N � 41 pathologist, radiotherapist, and surgeon. MRI before surgery In such a context, this work endeavors to demonstrate 99 66 33 Yes the positive impact of managing tissue sarcomas patients (85.3%) (56.9%) (28.4%) using the MDM approach. &ese results are specifically No 17 (14.7%) 9 (7.7%) 8 (7%) 0.008 Biopsy before related to patients’ survival and prognosis. Such findings are surgery indeed supported by previous studies [2, 6–8]. &us, the 92 68 24 cited authors have shown that the overall survival and R0 Yes (79.3%) (58.6%) (20.7%) resection rates were statistically higher when patients are examined within specialized structures. Besides the constant No 8 (7%) 16 (13.7%) < 0.001 (20.7%) demographic and biological risk factors, other observational Surgical margins studies [9, 10] have noticed that patients’ survival is also 37 20 R0 17 (27%) influenced by how much recommendations and practices (58.7%) (31.7%) are being correctly applied in the management of sarcoma R1 21 (33%) 14 (22%) 4 (6.3%) patients. Note that the proposed MDM procedure strives to R2 5 (8.3%) 2 (3.3%) 3 (4.7%) 0.650 Metastatic status address different aspects of these parameters. 89 62 27 Regarding the treatment path, the abovementioned M0 (76.7%) (53.4%) (23.3%) recommendations refer to MRI examination and radio- M1 20 (17.2%) 9 (7.7%) 11 (9.5%) guided and surgical biopsy. &ese combined elements would Mx 7 (6.1%) 5 (4.3%) 2 (1.8%) 0.105 allow a specific histological diagnosis and successive surgical Local relapse treatment. In this context, an expert surgeon can easily plan Yes 18 (15.5%) 8 (6.9%) 10 (8.6%) and correctly carry out sarcoma patients. 98 67 31 No 0.048 Typically, the radiologist plays a crucial role, especially in (84.5%) (57.7%) (26.8%) selecting suspicious tumors that require specific manage- Data of only operated patients. ment. Accordingly, looking at our cases, one can see that 66 patients (88%) from group 1 and 33 patients (80%) from subject to adjuvant chemotherapy. Also, one patient was group 2 underwent a radiological exploration with MRI. subject to doxorubicin monotherapy. &e other twenty-two &ese results sound good enough compared to previous (22) patients have benefited from external adjuvant radiation publications such as the work of Ray-Coquard et al. [13] therapy, which was exclusive in nine (9) patients. (52% of patients) and Haddad et al. [14] (76.5% of patients). As shown in Figure 3, during the evolution course, 23 In the present study, members of MDM discussed all cases as patients died, and 18 ones have shown local recurrences. the patients benefited from coma chest CT in search of Also, the overall survival is 60.561 months. distant metastases. In Table 3, one can see the performed multivariate &e radiological characteristics that are required during analysis along with the parameters of the univariate one. &is multidisciplinary meetings can be listed as follows [15, 16]: analysis showed a significant difference between the two (i) Diameter> 50 mm groups, especially in terms of the mentioned quality indi- cators. Compared to the patients treated without being (ii) Deep localization discussed in MDM, results have proven that the patients (iii) Irregular or lobulated contours whose files were discussed during an MDM have benefited (iv) Presence of irregular and thick intratumoral walls from better treatment management and more consistency in and septa clinical practice recommendations. Moreover, for the two groups, the current study has shown that some parameters (v) Heterogeneity on the T1 and T2 sequences have no significant impact on patients’ treatment (man- (vi) Early and prolonged contrast enhancement agement), such as age, sex, tumor size, tumor location, (vii) Presence of necrosis depth, histologic type, or FNCLCC grade. Our study indeed emphasizes the importance of MRI examination before starting patients’ treatment. &ere is 4. Discussion indeed a significant difference between the two studied Soft-tissue sarcomas are rare and malignant tumors. &ese groups as p � 0.008. Moreover, we proved that sarcomas patients that have received treatment without prior imaging are referred to as heterogeneous groups of tumors with a severe prognosis and a banal clinical presentation. Although were the most exposed to a high risk of inappropriate surgery (p � 0.028) and local relapse (p � 0.001). the handling of sarcomas tumor is well codified through reference systems [4] and recommendations [5], the diag- After MRI, a biopsy is the first examination to perform in case of a suspected tumor. By comparison with the work of nosis is often a complicated task. &erefore, we advocate multidisciplinary meetings (MDMs) are vital for each stage Haddad et al. (72.4%) and Ray-Coquard et al. (42%), in the International Journal of Surgical Oncology 5 Well- Myxoid differentiated liposarcoma liposarcoma 46% 19% Dedifferentia Others ted 17% Liposarcoma liposarcoma Dermatofibrosarcoma 31% 19% 5% Round-cell Sclérosing UPS liposarcoma liposarcoma 8% 8% 8% Myxofibrosarcoma 3% Rhabdomyosarcoma 3% Ewing sarcoma Synovial sarcoma 9% 15% Leiomyosarcoma 9% Figure 2: Patients according to histological types. 1.0 1.0 Group 1 0.8 0.8 0.6 0.6 Group 1 0.4 0.4 Group 2 0.2 0.2 p = 0.023 0.0 Group 2 p = 0.028 0.0 0.00 20.00 40.00 60.00 80.00 100.00 0.00 20.00 40.00 60.00 80.00 100.00 Months from diagnosis Months from diagnosis (a) (b) 1.0 Group 1 0.8 Group 1 0.6 0.4 0.2 p = 0.044 0.0 0.00 20.00 40.00 60.00 80.00 100.00 Months from diagnosis (c) Figure 3: Patient survival of studied groups (overall survival, relapse-free survival, and metastasis-free survival). Overall survival Metastasis-free survival Local relapse-free survival 6 International Journal of Surgical Oncology Table 3: Multivariate analysis. Parameters Univariate analysis Multivariate analysis Gender 0.499 0.836 Age at the first diagnosis 0.924 0.183 Size of the tumor 0.292 0.198 Site of the tumor 0.483 0.765 Depth 0.236 0.220 Histological subtype 0.238 0.049 Grade 0.525 0.287 Fluorescence in situ hybridization 0.030 0.034 MRI before surgery 0.008 0.022 Biopsy before surgery <0.001 0.000 Surgical margins 0.650 0.028 Metastatic status 0.105 0.034 Local relapse 0.048 0.001 A Cox model was carried out including all variables in univariate analysis and using a backward selection procedure which entails including all the covariates in the model. current work, the biopsy was performed for 68 patients network), and ResOs (reference network for rare bone (90.6%) from group 1 and 58.5% from group 2. sarcomas and rare bone tumors). &e organization adopts an Typically, using needles>16G, a surgeon or a radiologist approach that revolves around a centralized care system performs a radioguided percutaneous microbiopsy in using multidisciplinary discussion and benefiting from ex- compliance with the required standards [17]. In this study, pert treatment. 66% of cases (n � 61) had a CT-guided biopsy. Such a task In this context, this French organization has recently conducted a study [23] that involved 12,528 cases, where should ensure one and definitive surgery for the biopsy pathway and scar. &erefore, the biopsy entrance point 9,646 were nonmetastatic and where all patients were fol- should preferably be tattooed. A surgical biopsy might be lowed for 26 months. For patients handled by the multi- another option. disciplinary focus group, the local recurrence-free survival Note that surgery is a drastic measure of soft-tissue was much better. Accordingly, 76.9% of the patients had sarcoma treatment. &us, it should be performed as a single two-year local relapse-free survival and only 65.4% in the resection and as an unfragmented specimen. It is noteworthy other cases (p< 0.001). For both groups, the multivariate that this resection should include margins of normal tissue analysis of patients included parameters such as sex, age, unless there is an anatomical barrier. &e quality of the tumor size, tumor location, histological grade, depth, and handled or not by the multidisciplinary group. &e results excision is the most important factor of local control [18]. Accordingly, in non-R0 excision, the risk of local recurrence have shown the handling parameter is a key independent factor that influences relapse-free survival. is high [19]. For instance, R1 or marginal excision exposes the patient to a local recurrence risk that could reach 70% Note that the cited work has not assessed the overall [20]. As we stated, MDM is conducted within a specialized survival. In the current paper, we have tried to evaluate this instance where, statistically, resections are performed ap- factor. Generally, the obtained results are pretty similar to propriately (R0) [8, 21, 22]. those presented by the members of the French Sarcoma &e comparison between the two studied groups (quality group. &us, the overall survival, recurrence-free survival, of the surgical margins) shows a significant difference in and metastasis-free survival were significantly higher in the multivariate analysis (p � 0.028). Moreover, the risk of local case of patients handled by the multidisciplinary consulta- recurrence and distant metastasis decreases in the case of tion meeting (p � 0.023, p � 0.028, and p � 0.044, respectively). group 1 compared to group 2 (p � 0.001 and p � 0.034, respectively). Also, the quality of the surgery is another factor that determines the quality of care. According to data from the Practically, the current work has shown the importance of MDM regarding overall survival, recurrence-free survival, NETSARC network, most patients are operable, and the and metastasis-free survival (p, p � 0.023, p � 0.028, and quality of the resection margins influences relapse-free and p � 0.044, respectively). Accordingly, the following para- overall patient survival. French national indicators show graphs will highlight the context of these results in relation patients operated on by specialized teams from the NetSarc to the data presented by the French Sarcoma Group. or ResOs networks have a better initial assessment (biopsy Moreover, we will discuss some implications in terms of and imaging) and a better rate of optimal surgery (R0) and resources and infrastructure. are less subject to revision surgery [24]. &e French Sarcoma Group has been known, among In our series, surgery “in sano” (R0) was applied in 58.7% of the cases. &e results were statistically significant re- others, as a pioneer organization of improvements in the management of sarcoma patients. &is organization was garding both groups, in the multivariate analysis (p � 0.028) with a lower risk of local recurrence in group 1 compared to established in 2010 by RRePS (reference network in the pathology of sarcomas), NetSarc (clinical reference group 2 (p � 0.001) as well as distant metastases (p � 0.034). International Journal of Surgical Oncology 7 Regarding resources and infrastructures, the implica- ESMO: European Society for Medical Oncology. tions from this study’s findings might cover methodological aspects as well as practical ones. Such a procedure would Data Availability optimize the time and canalize the treatment. It could en- hance patients’ conditions (i.e., survival rate), and the costs Data used to support the findings of this study can be ob- tained from the corresponding author on request. of recovery from inappropriate surgical treatment might decrease. Typically, the management of soft-tissue sarcoma pa- Ethical Approval tients requires specialized centers. &ese instances can &e Cancer Research Institute and the University Hospital of provide the necessary infrastructures and adequate human Fez review board gave their approval to conduct the present resources. study (n 34/16). For example, a study in Nigeria has shown the impact of the unavailability of relevant radiological tools (i.e., MRI) Consent and the absence of multidisciplinary discussions on sarco- mas patients [25]. In such a setting, one would face several &e subjects gave written informed consent. challenges to follow or assess survival. In the same context, Adigun et al. [26] have studied STS regarding the pattern, Conflicts of Interest distribution, and issues in a black African community. &e cited retrospective study has corroborated the previous &e authors declare that they have no conflicts of interest. results, and it highlighted the difference between the pro- cedures in the Western countries and the African regions Acknowledgments (i.e., modern techniques are not commonly available or are usually not affordable). &e authors are grateful to the staff and members of the Ideally, the multidisciplinary meetings should involve an Cancer Research Institute (IRC), a public interest group. experienced traumatologist, radiologist, pathologist, on- cologist, and radiotherapist. &erefore, procedures can be References triggered once a suspicious case has risen and before action could be taken. Sometimes (i.e., lack of experience in the [1] F. Ducimetiere, J.-M. Coindre, J.-M. 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Journal

International Journal of Surgical OncologyHindawi Publishing Corporation

Published: Mar 24, 2021

References