A sub-Saharan African experience in the surgical management of soft tissue sarcomas in an oncology unit in: a retrospective cohort study

A sub-Saharan African experience in the surgical management of soft tissue sarcomas in an oncology unit in: a retrospective cohort study

Omobolaji Oladayo Ayandipo^1,2,&, Oludolapo Ola Afuwape^1,2, Oluwafunmilayo Yewande Soneye², Akintunde Taiwo Orunmuyi¹, Gbolahan Oladeles Obajimi^1,2

 

¹College of Medicine, University of Ibadan, Nigeria, ²University College Hospital, Ibadan, Nigeria

 

 

^&Corresponding author
Omobolaji Oladayo Ayandipo, College of Medicine, University of Ibadan, Nigeria

 

 

 

 

Soft tissue sarcomas (STS) represents the uncommon, but ubiquitous group of neoplasms of mesenchymal tissue which although apt to be found in most organ systems are all the same rare in overall prevalence. They constitute only one percent (1%) of all adult malignancies [1-4]; but have over 70 histologic subtypes [5] with proven heterogeneity in terms of anatomic primary site, clinical presentation, prognosis and therapeutic features [6, 7]. Partly because of this rarity, management of soft tissue sarcomas remains complex and challenging and is dependent on various factors; such as tumor and treatment-related factors like the histologic subtype, tumor depth, grade, primary or recurrent, surgical margins and the need for neoadjuvant or adjuvant chemo-radiation [8-10]. The standard of care in managing STS is surgical resection with neoadjuvant or adjuvant chemo-radiation [11-14]. However, the main therapeutic burden is placed on surgery worldwide because of the need for local control via negative margins. The inadequacy of radiotherapy services in Low and Middle Income Country (LMIC) like Nigeria [15], the potential for toxicity to adjacent structure when employing radiotherapy and the unproven role of chemotherapy in managing different subtypes of STS all serve to magnify the importance of surgery [3, 16, 17]. The prognosis of patients with STS generally is poor when assessed over an extended period [18-20]. There are many publications on the outcome of surgical management of STS from developed countries [2, 6, 10] but few from developing ones. In this paper, we present our findings from a 10-year review of STS patients who had surgery in an academic surgical oncology practice in Ibadan, a University Teaching Hospital in Nigeria.

 

 

We reviewed the case records of consecutive STS patients who had surgery at the UCH, Ibadan between October 2007 and October 2017. Data extraction was from the admission and operative registers, the theatre records, as well as the log of the histology reports. Only STS of connective, subcutaneous and muscular tissues were considered, with exclusion of bone-related sarcomas. The patients’ demographic data, clinico-pathologic profiles like primary or recurrent STS, anatomic site, tumor size, histologic types and grade, lymph node involvement, metastases, clinical stage, treatment outcome (margins, morbidity and mortality) and long-term outcomes were all recorded.

 

Ethical issues

 

This study was conducted in compliance with the guidelines of the Helsinki declaration on biomedical research in human subjects. Confidentiality of the identity of the patients and personal health information was maintained. Individual patients consent was not required for this study since it is a retrospective study and a review of routine clinical activities. Approval for using the hospital records only for this study was obtained from the institution’s chairman, Medical Advisory Committee (CMAC), the chair of the hospital’s research and ethics committee before accessing the patients’ information at the medical records department.

 

Clinical management of STS in our unit

 

A clinical review (history taking and thorough physical examination) preceded the diagnostic pathologic evaluation achieved by core-biopsy in cases presenting primarily to the division. Standard radiologic staging investigations included chest radiography, abdominopelvic ultrasound scanning, chest computed tomography (CT) and magnetic resonance imaging (MRI) of the anatomic region of the soft tissue swelling (if available and affordable). Following the decision to offer surgery, consideration for post-excision wound cover necessitated oncoplastic consult while those requiring neoadjuvant chemo-radiation were managed as such prior to surgery. The decision for adjuvant chemoradiation was taken after reviewing a combination of the clinical staging, intra-operative findings (tumor margins, resectability and relationship to contiguous structures) and the histology reports.

 

Statistical analysis

 

All informations obtained were recorded in Microsoft Excel spreadsheet. Patients’ demography, clinico-pathologic profile, stage treatment offered as well as outcomes of treatment was summarized as percentages, proportions, mean and standard deviation. Statistical analysis was done using SPSS version 20 and the results were presented in charts and graphs.

 

 

We retrieved the records of 596 cases of STS over the ten-year period. Of these, 383 (64.3%) patients had surgery making an average of 38 oncologic excisions of STS per year. Figure 1 shows the number of cases diagnosed and those who had surgery within each year of the study. The case files of 326 patients constituting 85.1% of all surgeries were available for review. One hundred and sixty-seven (51.3%) were males and 159 (48.7%) were females. A total of 238 (73%) had primary disease, 88 (27%) were for local recurrence after initial surgical treatment at referring hospitals and 75 (23%) had metastasis to the lungs. The patients clinicopathologic and treatment characteristics are shown in Table 1. The duration of soft tissue swelling before presentation at the UCH, Ibadan ranged from 1 to 96 months with a mean (SD) of 13 (15.6) months. The swelling was described as painless in majority, 284 (87%) of the patients. The tumor size was less than 5cm in 59 (18%), between 5cm and 10cm in 94 (28.8%) and greater than 10cm in 173 (53.7%). Extremity lesions constituted 21.7%, while truncal, retroperitoneal, head and neck, visceral and other anatomical parts constituted 54.5%, 8.0%, 3.4%, 4.9%, 10.9% respectively.

 

About a third (32%) of the tumors were adjudged superficial while 222 (68%) were deep-seated lesions. Histologically, they were low-grade neoplasms in 95 (29.1%), intermediate grade in 51 (17%) and high grade in 176 (53.9%). The three commonest histologic subtypes in descending order were liposarcoma (22.6%), leiomyosarcoma (19%) and malignant fibrous histiocytoma (11%). Neoadjuvant chemoradiation was administered in 57 (17.3%) while primary surgical excision was done in 269 (82.7%). Only 48 (14.7%) had adjuvant radiotherapy treatment and 65 (19.9%) had adjuvant chemotherapy. Oncoplastic reconstruction (split thickness skin grafts, local flaps) was done in 42 (13%). Some 7 limbs disarticulations were done at joint surgical resections with the orthopaedic team despite being of soft tissue origin. The tumor resection margin was grossly negative in 88% and positive in 12%; the histology was reported micro-negative in 81% and micro-positive in 19%. Thirteen percent of the positive margins were seen in the retroperitoneal and truncal STS. We found peritoneal sarcomatosis in 18 cases (5.5%) amongst the visceral group of STS, that is, the retroperitoneal and gastrointestinal stromal tumors (GIST).

 

Surgical drains were removed between the 4^th and 14^th post-operative day with a mean of 8 days in the proportion that needed a drain inserted. Drain removal was predicated on output being clear or straw colored and less than 50mls in the preceding 24 hours. Post-operative complications occurred in 61 (18.7%) with seroma, flap dehiscence, necrosis, wound infection being the commonest. The average length of hospital admission ranged from 5-15 days with a mean S.D of 11 days (SD). At least two-thirds, 238(67%) of the patients were available for as much as 15 months post hospital discharge for clinical evaluation in the surgical outpatient department (SOP). Two hundred and two (62%) were seen regularly for between 24-36 months; and then a decline in the follow-up rate ensued thereafter, such that by 36 months post-surgery most patients had dropped out of follow-up, except those that had local recurrence 56 (17%) and or metastatic disease 36 (11.0%) diagnosed (Figure 2, Figure 3).

 

 

In this review from the surgical oncology practice of a developing country, patients who benefitted from definitive surgical treatment for soft tissue sarcomas were found to be in the young and middle age group, with extended duration of symptoms, and most had > 5cm sized lesions with intermediate grade and high-grade disease. This in general is the same prototype clinicopathologic characteristics of STS reported worldwide [3, 6, 11, 14]. A further review of the treatment modalities revealed that slightly less than a fifth of our patient population had the benefits of either neoadjuvant chemotherapy and or radiotherapy. In comparison to previous publications, a larger proportion of our patients had primary surgical management [6]. This, in part, may be due to the predominance of truncal, rather than extremity, lesions in our series when comparing the anatomic locations with other studies [6, 21, 22]. The significance of the site in determining the use of neoadjuvant treatment (particularly radiotherapy) is that except in some histologic subtypes (embryonal rhabdomyosarcoma, synovial sarcoma, Ewing’s sarcoma) found responsive to neoadjuvant chemoradiation, the risk of toxicity in delivering maximal radiotherapy dose to the truncal/ visceral STS exclusive of contiguous organs and neuro-osseo-vascular structure [6, 23-27] is high. Of equal importance is the varied and inconsistent response to chemotherapy noted between different histologic subtypes along with chemotoxicity [28-32]. These factors make surgery the gold standard; albeit more so in anatomic locations that precludes the use of chemoradiation. The adjuvant treatment options available in our practice setting, a sub-Sahara African developing country, were very limited compared to the standards of care in other parts of the world like the Asian-Pacific region [6]. We believe this is due to the challenges of instituting early radiotherapy in our setting which may be due to competing volume from other commoner radiosensitive malignancies.

 

Liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma were the predominant subtypes of STS in our review. Although the same pattern was noted in other reports subtle differences in proportional ranking exist across continental boundaries [6, 22, 33]. In the period under review about two-third of our patients had surgical treatment but only about a fifth received oncoplastic reconstruction to cover the wide defect created after extirpative surgery. This suggests that a viable reconstructive unit enhances the ability to resect hitherto unresectable lesions. Closely related to this is our positive margin rate which is directly proportional to the size and proximity to vital structures with the culprit in our case being mostly anatomic constraints. While adjudged not ideal, it is however acceptable to leave planned microscopic positive surgical margins, after weighing the risk of recurrence and morbidity of radical surgery along with full discussion with the patient [3, 34]. A positive resection margins is an independent prognostic factor for local recurrence [8, 35], but since neither a positive surgical margin with or without local recurrence adversely affects overall survival [36], then substantial functional compromise or amputation of a limb may not be a worthwhile endeavor. Other reasons that possibly contributed to unresectability include late/delayed presentation, inability to pay out of pocket for treatment and sometimes unwillingness on the part of the patient or caregiver to undergo surgery.

 

Truncal and visceral STS (GIST and retroperitoneal STS) have a worse prognosis [37] than extremity lesions mainly because local recurrence in the former can lead to mortality whereas it does not in the latter except in the setting of metastases [38]. Local recurrence may be a reflection of tumor biology and the acknowledged pivotal role of neoadjuvant radiotherapy in reducing local recurrence [39]. Our post- operative morbidity/mortality rate and duration of hospital admission compared favorably with other, more advanced centers [11, 40, 41], despite not matching their operative volume.

 

Over a third of our patients were attending the surgical out-patient’s clinics 20 months after surgery. The reasons for loss of many to long term follow-up are not known, thus the survival pattern of this cohort might never be determined. A local recurrence rate of 17% and distant metastases of 11% at eighteen months post-surgery in the setting of little or no adjuvant care suggest adequacy of surgical care as it compares with findings by other authors [3, 6, 22].

 

The epidemiology of GIST is completely unknown [42] and it is suggested that it constitutes a sixth of all STS; our review however showed a lower percentage which is not inclusive of autopsy and incidental finding by other authors [42, 43]. We found most cases of GIST in our series to be of gastric origin, which is similar to findings in North America and Asia [44, 45]. GIST have a high tendency to seed with florid peritoneal sarcomatosis noted in our patients who could not have resection at laparotomy, en-bloc resection was achievable in those with contiguous organ involvement; usual culprit being the spleen and tail of the pancreas.

 

Anthracycline and alkylating agents have been our first line chemotherapy over the years of review in view of the non-availability of newer agents like the monoclonal antibodies (olaratumab, pembolizumab, sunnitumab), eribulin, aldoxorubicin and trabectidin. Beyond this, is the fact that histology staining techniques/molecular diagnosis which unravels the heterogeneity and guides the escalation to 2^nd or 3^rd line regimens are expensive and available strictly only in the research or investigative settings [46].

 

About 750 cases of adult malignancies are seen per anum in this center. The age standardized ratio for STS in males is 0.8/100,000 while that in females is 0.5/100,000 [47]. This is similar to the global prevalence of STS of 1% seen in literature review [1-4].

 

 

There is scarcity of concise report on STS in sub-Saharan Africa hence the importance of assessing and auditing its outcome in a developing country like Nigeria. The low local recurrence rate and distant metastasis following surgical resection despite little or no adjuvant therapy emphasizes the importance of surgical care and negative resection margins in a LMIC like ours. There can be improvement in the reported outcomes if patients present with early stage disease. Secondly, noted gaps in our surgical practice such as absence of intra-operative frozen section, multi-disciplinary tumor (MDT) board for STS and absence of a proper follow up protocol to be able to find out survival patterns needs to be inculcated at the institutional level to monitor and evaluate quality of care.

 

 

The authors declare no competing interests.

 

 

Ayandipo OO participated in the patients’ management, conceived the study, coordinated and co-wrote the manuscript. OO Afuwape participated in the patients’ management, study design and co-wrote the manuscript. Obajimi GO co-wrote the manuscript. Orunmuyi AT co-wrote the manuscript and Soneye OY participated in the patients’ management and co-wrote the manuscript. All authors read and approved the final manuscript.

 

 

To Dr. A. Olufemi Adeleye, senior lecturer in surgery for reading through and criticising the manuscript.

 

 

Table 1: patients’ clinic-pathologic characteristics

Figure 1: showing the number of patients seen and the number of surgeries done in each year

Figure 2: anatomic location of the soft tissue sarcoma

Figure 3: histologic subtypes

 

 

1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A et al. Cancer statistics, 2005. CA Cancer J Clin. 2005 Feb; 55(1):10-30. PubMed | Google Scholar


2. Brennan M, Alektair K, Maki R. Principles and practice of oncology. Philadelphia: Lippincott Williams and Wilkins; 2001.


3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al. Cancer statistics, 2008. CA Cancer J Clin. 2008 Apr; 58(2):71-96. PubMed | Google Scholar


4. World Health Organisation classification of Tumours. Pathology and genetics of tumours of soft tissue and bone. World Health Organisation; 2002.


5. Fletcher CDM, Bridge JA, Hogendorn PCW, Mertens F. WHO classification of tumours of soft tissue and bone. Lyon. IARC. 2013.


6. Ngan R, Wang E, Porter D, Desai J, Prayogo N, Devi B et al. Soft-tissue sarcomas in the Asia-Pacific region: a systematic review. Asian Pac J Cancer Prev. 2013;14(11):6821-32. PubMed | Google Scholar


7. Grobmyer SR, Brennan MF. Predictive variables detailing the recurrence rate of soft tissue sarcomas. Curr Opin Oncol. 2003 Jul;15(4):319-26. PubMed | Google Scholar


8. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol Off J Am Soc Clin Oncol. 1996 May;14(5):1679-89. PubMed | Google Scholar


9. Singer S, Corson JM, Gonin R, Labow B, Eberlein TJ. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg. 1994 Feb;219(2):165-73. PubMed | Google Scholar


10. Singer S, Demetri GD, Baldini EH, Fletcher CD. Management of soft-tissue sarcomas: an overview and update. Lancet Oncol. 2000 Oct;1:75-85. PubMed | Google Scholar


11. Gutierrez JC, Perez EA, Moffat FL, Livingstone AS, Franceschi D, Koniaris LG. Should soft tissue sarcomas be treated at high-volume centers? An analysis of 4205 patients. Ann Surg. 2007 Jun;245(6):952-8. PubMed | Google Scholar


12. Mack LA, Crowe PJ, Yang JL, Schachar NS, Morris DG, Kurien EC et al. Preoperative chemoradiotherapy (modified Eilber protocol) provides maximum local control and minimal morbidity in patients with soft tissue sarcoma. Ann Surg Oncol. 2005 Aug;12(8):646-53. PubMed | Google Scholar


13. Stojadinovic A, Leung DHY, Allen P, Lewis JJ, Jaques DP, Brennan MF. Primary adult soft tissue sarcoma: time-dependent influence of prognostic variables. J Clin Oncol Off J Am Soc Clin Oncol. 2002 Nov 1;20(21):4344-52. PubMed | Google Scholar


14. von Mehren M, Randall RL, Benjamin RS, Boles S, Bui MM, Conrad EU et al. Soft Tissue Sarcoma, Version 2 2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw JNCCN. 2016;14(6):758-86. PubMed | Google Scholar


15. Kenneth Chima Nwankwo, David Dawotola A, Vinay Sharma. Radiotherapy in Nigeria: current status and future challenges. West African Journal of Radiology. 2013;20(2):84-88. Google Scholar


16. Mazanet R, Antman KH. Adjuvant therapy for sarcomas. Semin Oncol. 1991 Dec 1;18(6):603-12. PubMed | Google Scholar


17. Springer. De Schepper AM. Imaging of soft tissue Tumors. Accessed Jun 25, 2018


18. Singer S, Corson JM, Demetri GD, Healey EA, Marcus K, Eberlein TJ. Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma. Ann Surg. 1995 Feb;221(2):185-95. PubMed | Google Scholar


19. Heslin MJ, Lewis JJ, Nadler E, Newman E, Woodruff JM, Casper ES et al. Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management. J Clin Oncol Off J Am Soc Clin Oncol. 1997 Aug;15(8):2832-9. PubMed | Google Scholar


20. Gronchi A, Casali PG, Fiore M, Mariani L, Lo Vullo S, Bertulli R et al. Retroperitoneal soft tissue sarcomas: patterns of recurrence in 167 patients treated at a single institution. Cancer. 2004 Jun 1;100(11):2448-55. PubMed | Google Scholar


21. Vincent Devita T, Samuel Hellman, Steven Rosenberg A. Cancer: principles and practice of oncology 6th edition. July 2001. Cited 2018 Jun 25


22. Cormier JN, Pollock RE. Soft tissue sarcomas. CA Cancer J Clin. 2004 Mar-Apr;54(2):94-109. PubMed | Google Scholar


23. Bujko K, Suit HD, Springfield DS, Convery K. Wound healing after preoperative radiation for sarcoma of soft tissues. Surg Gynecol Obstet. 1993 Feb;176(2):124-34. PubMed | Google Scholar


24. Peat BG, Bell RS, Davis A, O’Sullivan B, Mahoney J, Manktelow RT et al. Wound-healing complications after soft-tissue sarcoma surgery. Plast Reconstr Surg. 1994 Apr;93(5):980-7. PubMed | Google Scholar


25. Cheng EY, Dusenbery KE, Winters MR, Thompson RC. Soft tissue sarcomas: preoperative versus postoperative radiotherapy. J Surg Oncol. 1996 Feb;61(2):90-9. PubMed | Google Scholar


26. Prosnitz LR, Maguire P, Anderson JM, Scully SP, Harrelson JM, Jones EL et al. The treatment of high-grade soft tissue sarcomas with preoperative thermoradiotherapy. Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):941-9. PubMed | Google Scholar


27. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet Lond Engl. 2002 Jun 29;359(9325):2235-41. PubMed | Google Scholar


28. Patel SR, Vadhan-Raj S, Papadopolous N, Plager C, Burgess MA, Hays C et al. High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence. J Clin Oncol Off J Am Soc Clin Oncol. 1997 Jun;15(6):2378-84. PubMed | Google Scholar


29. Nielsen OS, Judson I, van Hoesel Q, le Cesne A, Keizer HJ, Blay JY et al. Effect of high-dose ifosfamide in advanced soft tissue sarcomas - A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Oxf Engl. 2000 Jan;36(1):61-7. PubMed | Google Scholar


30. Frustaci S, Buonadonna A, Romanini A, Comandone A, Dalla Palma M, Gamucci T et al. Increasing dose of continuous infusion ifosfamide and fixed dose of bolus epirubicin in soft tissue sarcomas - A study of the Italian group on rare tumors. Tumori. 1999 Aug;85(4):229-33. PubMed | Google Scholar


31. Palumbo R, Palmeri S, Antimi M, Gatti C, Raffo P, Villani G et al. Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas. Annals of Oncology. 1998; 8(11): 1159-1162. PubMed | Google Scholar


32. Buesa JM, López-Pousa A, Martín J, Antón A, García del Muro J, Bellmunt J et al. Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the Spanish Group for Research on Sarcomas (GEIS). Ann Oncol. 1998 Aug;9(8):871-6. PubMed | Google Scholar


33. Coindre JM, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchère D et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001 May 15;91(10):1914-26. PubMed | Google Scholar


34. Gerrand CH, Wunder JS, Kandel RA, O’Sullivan B, Catton CN, Bell RS et al. Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence. J Bone Joint Surg Br. 2001 Nov;83(8):1149-55. PubMed | Google Scholar


35. Herbert SH, Corn BW, Solin LJ, Lanciano RM, Schultz DJ, McKenna WG et al. Limb-preserving treatment for soft tissue sarcomas of the extremities - The significance of surgical margins. Cancer. 1993 Aug 15;72(4):1230-8. PubMed | Google Scholar


36. Tanabe KK, Pollock RE, Ellis LM, Murphy A, Sherman N, Romsdahl MM. Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer. 1994 Mar 15;73(6):1652-9. PubMed | Google Scholar


37. Lewis JJ, Brennan MF. Soft tissue sarcomas. Curr Probl Surg. 1996 Oct;33(10):817-72. PubMed | Google Scholar


38. Lewis JJ, Brennan MF. Soft tissue Sarcomas In: The biological basis of modern surgical practice. 15th ed. New York: W.B. Saunders,; 997. 528-534 p.


39. Lewis JJ, Leung D, Woodruff JM, Brennan MF. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg. 1998 Sep;228(3):355-65. PubMed | Google Scholar


40. Hui AC, Ngan SY, Wong K, Powell G, Choong PFM. Preoperative radiotherapy for soft tissue sarcoma: The Peter MacCallum Cancer Centre experience. Eur J Surg Oncol. 2006 Dec 1;32(10):1159-64. PubMed | Google Scholar


41. Rudiger HA, Ngan SY, Choong PF. Surgical outcome of soft tissue sarcomas of the adductor compartment. J Orthop Surg. 2009 Dec 1;17(3):284-7. PubMed | Google Scholar


42. Joensuu H. Gastrointestinal stromal tumor (GIST). Ann Oncol Off J Eur Soc Med Oncol. 2006 Sep;17 Suppl 10:x280-286. PubMed | Google Scholar


43. Nilsson B, Bümming P, Meis-Kindblom JM, Odén A, Dortok A, Gustavsson B et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era: a population based study in Western Sweden. Cancer. 2005 Feb 15;103(4):821-9. PubMed | Google Scholar


44. Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 2005 Jan;100(1):162-8. PubMed | Google Scholar


45. Kim K-M, Kang DW, Moon WS, Park JB, Park CK, Sohn JH et al. Gastrointestinal stromal tumors in Koreans: it’s incidence and the clinical, pathologic and immunohistochemical findings. J Korean Med Sci. 2005 Dec;20(6):977-84. PubMed | Google Scholar


46. In GK, Hu JS, Tseng WW. Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations. Ther Adv Med Oncol. 2017 Aug;9(8):533-550. PubMed | Google Scholar


47. Ogunbiyi JO, Fabowale AO, Ladipo AA, Ogun GO, Adeyemi AO, Bodunmwa OM. Cancer incidence in Ibadan, including childhood cancers 2009-2012. The Ibadan Cancer Registry. 2016.