J Gastrointest Canc DOI 10.1007/s12029-015-9706-3
CASE REPORT
Successful Treatment Toward Gastrointestinal Stromal Tumors with Aggressive Behavior Landolsi Sana 1,2,3 & Mannai Saber 1,2
# Springer Science+Business Media New York 2015
Introduction Gastrointestinal stromal tumors are rare [1–3]. Their treatment is still challenging especially for those with aggressive behavior. We herein report two cases of successful treatment toward gastrointestinal stromal tumors having aggressive behavior.
First Case Report A 59-year-old woman presented with pelvic pain, dysuria, constipation, and painful defecation lasting for 2 months. She had a medical history of diabetes mellitus. Physical examination revealed a hypogastric tender mass 10 cm in diameter. The distance from the anal verge to the location of the tumor was 3 cm in digital rectal examination. Colonoscopy showed a circumferential bulge with no mucosal abnormalities. Pelvic computed tomography and magnetic resonance imaging demonstrated a heterogenous mass 20 cm in diameter. The entire pelvis was occupied by this clear boundary mass (Fig. 1). On T1 weighted
Landolsi Sana holds an M.D. and Mannai Saber holds a Ph.D. from the University of Medicine El Manar Tunis. * Landolsi Sana [email protected]
images, the mass has an intermediate signal intensity with an irregular enhancement after intravenous gadolinium injection. On T2 weighted images, it demonstrated a heterogeneous signal intensity. The uterus was displaced to the right and upwards and the rectum to the left and backwards (Fig. 2). A computed tomography fine needle-guided biopsy (Fig. 3) concluded a gastrointestinal stromal tumor with spindle cells, fascicular growth pattern, and cytoplasmic vacuoles indenting the nuclear poles. Immunohistochemically, the tumor cells were positive for CD34 and negative for CD117. No metastases were detected at computed tomography. Since this gastrointestinal stromal tumor was locally advanced, imatinib mesylate therapy was administrated with 400 mg per day for a year. The abdominopelvic computed tomography demonstrated tumoral shrinkage and central necrosis (Fig. 4). The patient was operated on in the lithotomy position with an abdominal and transvaginal approach. An en bloc resection of the tumor and the posterior wall of the vagina was performed with an intact capsula (Fig. 5). No resulting defect in the rectal mucosa or the anal sphincter was observed. Vaginal layers were closed vertically. Microscopic examination revealed a mitotic rate of 5 in 50 high-power fields. The necrosis was observed in 98 % of the cells. The resection margins were safe. The postoperative course was uneventful. The patient did not develop impaired anal sphincter function and fecal incontinence. Imatinib mesylate therapy was being prescribed. No recurrence has been observed yet after 36 months.
1
Department of Surgery, Jendouba’s Hospital, University of Medicine El Manar, Tunis, Tunisia
Second Case Report
2
Department of Surgery, Charles Nicolle Hospital, University of Medicine El Manar, Tunis, Tunisia
3
5, rue Arif Ben Mohamed Salah, cité Essedik, 2042 Tunis, Tunisia
A 29-year-old man, with no medical history, presented with abdominal pain. Computed tomography revealed the existence of two cystic masses in the pelvis and in hepatic
J Gastrointest Canc Fig 1 Pelvic computed tomographies revealing a large tumor of the pelvis with a central necrosis
segments VI and VII (Fig. 6). Percutaneous biopsy was not carried out since it was thought to be risky and there was no sufficient tissular component to give an accurate diagnosis. A laparotomy was then performed. It showed a locally advanced tumor of the mesentery involving the posterior wall of the bladder and a small intestine loop located at 20 cm from the duodeno-jejunal junction. An en bloc resection was carried out without infraction of the capsula. Suture of the bladder and intestine anastomosis were performed. The postoperative course was uneventful. The histopathological exam concluded to a gastrointestinal stromal tumor 15 cm in diameter and 1 mitosis in 50 high-power fields. The patient received Glivec® 400 mg per day during only 6 months for financial problems. Thus, a resection of segments VI and VII was done. The medical treatment was given postoperatively for only 6 months since the patient has been lost to follow-up for 30 months. After that, he complained from a mass in the right upper part of the abdomen. This mass corresponded to a hepatic relapse. A tumorectomy was carried out with uneventful outcomes. No relapse was diagnosed after a follow-up of 12 months. The patient is still receiving Glivec® 400 mg per day.
Fig 2 Pelvic magnetic resonance showing the adherence of the tumor to the rectum (red arrow) and the bladder (green arrow)
Discussion These cases focused on treatment planning, resection strategy, and perioperative molecular targeted therapy success for locally advanced gastrointestinal stromal tumor of the spatium rectovaginale and metastatic intestinal gastrointestinal stromal tumor. The particularities of our first report were a downstaging of a locally advanced tumor allowing a curative resection in one hand and a minimally invasive approach in the other hand. As for the second case, a first resection of the liver metastases was done in order to make the diagnosis. A reresection of hepatic relapse was performed with a twelve months disease-free survival. These reports suggest the utility of an aggressive approach toward locally advanced and metastatic gastrointestinal stromal tumors. The resection of a locally advanced tumor is still challenging because of the need for invasive surgery and the risk of incomplete tumor removal. For our first patient, the location of this large gastrointestinal stromal tumor in the spatium rectovaginale needed treatment planning in order to achieve complete excision without pseudocapsule rupture or anal dysfunction. A downsizing of the tumor is mandatory by means of perioperative imatinib [4–9]. A fine needle biopsy is recommended for the diagnosis of the gastrointestinal stromal tumor before neoadjuvant imatinib administration [10]. It
Fig 3 Computed tomography-guided biopsy of the tumor
J Gastrointest Canc Fig 4 Computed tomographies 1 year after the beginning of imatinib concluding to a reduction of the tumor size (arrow: rectum)
Fig 5 Preoperative views showing the tumor before and after en bloc excision
has a sensitivity of 80 % [11]. Computed tomography represents the standard method allowing therapy response assessment [12]. Since procedures on the lower rectum may lead to fecal incontinence as a consequence of dissection down to the levator ani muscles, less invasive procedures should be attempted [13] as in our first case. The transvaginal approach is efficient for large tumors [13]. It allows to achieve surgery goals of histologically negative margins [4, 5] and absence of capsule rupture. This rupture constitutes a major prognostic factor since it reduces the disease-free and overall survival [14]. Almost all patients develop abdominal metastases after rupture of a gastrointestinal stromal tumor [15]. The risk of recurrence depends also on the size of the tumor, its location, and the mitotic count [16]. For our first patient, the risk was
about 71 %. This high relapse risk recommends the adjuvant therapy based on imatinib in cases of positive margins, capsule rupture, tumor size greater than 10 cm, and/or more than 5 mitoses per 50 high-power fields [4–6, 15]. Our first patient had two pejorative prognostic factors: the size of the tumor and the number of mutations. The optimal duration of imatinib administration in adjuvant therapy has not yet been determined [17]. Our second patient had a metastatic gastrointestinal stromal tumor. Laparotomy allowed the positive diagnosis since the percutaneous biopsy was judged risky and not beneficial for accurate diagnosis. Our attitude is in accordance with the recommendations of the European Sarcoma Network Working Group [18]. The treatment for metastatic gastrointestinal
Fig 6 Computed tomographies showing cystic tumors in the pelvis and the liver
J Gastrointest Canc
stromal tumor is challenging. Recommendations are in favor of medical treatment [17, 18], but complete excision of the metastatic tumor is related with a good prognosis [19–21] as for our second patient.
9.
10.
Conclusion
11.
Treatment planning is mandatory in order to achieve successful treatment toward gastrointestinal stromal tumors with aggressive behavior.
12.
Conflict of Interest The authors declare that they have no conflict of interest.
13.
14.
References 1.
Furihata M, Fujimori T, Imura J, et al. Malignant stromal tumor, so called “gastrointestinal stromal tumor”, with rhabdomyomatous differentiation occurring in the gallbladder. Pathol Res Pract. 2005;201:609–13. doi:10.1016/j.prp.2005.04.011. 2. Krska Z, Peskova M, Povysil C, Horejs J, Sedlackova E, Kudrnova Z. GIST of pancreas. Prague Med Rep. 2005;106:201–8. 3. Reith JD, Goldblum JR, Lyles RH, Weiss SW. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol. 2000;13:577–85. 4. Casali PG, Blay JY. Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v98–102. doi:10.1093/annonc/mdq208. 5. Demetri GD, von Mehren M, Antonescu CR, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw. 2010;8 Suppl 2: S1–41. quiz S42–4. 6. Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebocontrolled trial. Lancet. 2009;373:1097–104. doi:10.1016/S01406736(09)60500-6. 7. Eisenberg BL, Harris J, Blanke CD, et al. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009;99:42–7. doi:10.1002/jso.21160. 8. Fiore M, Palassini E, Fumagalli E, et al. Preoperative imatinib mesylate for unresectable or locally advanced primary gastrointestinal
15.
16.
17.
18.
19.
20.
21.
stromal tumors (GIST). Eur J Surg Oncol. 2009;35:739–45. doi:10. 1016/j.ejso.2008.11.005. Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–6. Chaudhry UI, DeMatteo RP. Advances in the surgical management of gastrointestinal stromal tumor. Adv Surg. 2011;45:197–209. Sepe PS, Moparty B, Pitman MB, Saltzman JR, Brugge WR. EUSguided FNA for the diagnosis of GI stromal cell tumors: sensitivity and cytologic yield. Gastrointest Endosc. 2009;70(2):254–61. doi: 10.1016/j.gie.2008.11.038. Kalkmanna J, Zeileb M, Antochc G, et al. Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group. Cancer Imaging. 2012;12:126–35. doi:10.1102/ 1470-7330.2012.0013. Hara M, Takayama S, Arakawa A, Sato M, Nagasaki T, Takeyama H. Transvaginal resection of a rectal gastrointestinal stromal tumor. Surg Today. 2012;42:909–12. doi:10.1007/s00595-012-0215-8. Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. 1992;215(1):68–77. Hohenberger P, Ronellenfitsch U, Oladeji O, et al. Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. Br J Surg. 2010;97(12):1854–9. doi:10.1002/bjs.7222. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70– 83. Von Mehren M, Lor Randall R, Robert SB, et al. Soft tissue sarcoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2014;12:473–83. The ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Supplement 3):iii21–6. doi:10.1093/annonc/ mdu255. Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24: 2325–31. Wang D, Zhang Q, Blanke CD, et al. Phase II trial of neoadjuvant/ adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012;19:1074–80. doi:10. 1245/s10434-011-2190-5. Mussi C, Ronellenfitsch U, Jakob J, et al. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21:403–8. doi:10.1093/annonc/mdp310.
CASE REPORT
Successful Treatment Toward Gastrointestinal Stromal Tumors with Aggressive Behavior Landolsi Sana 1,2,3 & Mannai Saber 1,2
# Springer Science+Business Media New York 2015
Introduction Gastrointestinal stromal tumors are rare [1–3]. Their treatment is still challenging especially for those with aggressive behavior. We herein report two cases of successful treatment toward gastrointestinal stromal tumors having aggressive behavior.
First Case Report A 59-year-old woman presented with pelvic pain, dysuria, constipation, and painful defecation lasting for 2 months. She had a medical history of diabetes mellitus. Physical examination revealed a hypogastric tender mass 10 cm in diameter. The distance from the anal verge to the location of the tumor was 3 cm in digital rectal examination. Colonoscopy showed a circumferential bulge with no mucosal abnormalities. Pelvic computed tomography and magnetic resonance imaging demonstrated a heterogenous mass 20 cm in diameter. The entire pelvis was occupied by this clear boundary mass (Fig. 1). On T1 weighted
Landolsi Sana holds an M.D. and Mannai Saber holds a Ph.D. from the University of Medicine El Manar Tunis. * Landolsi Sana [email protected]
images, the mass has an intermediate signal intensity with an irregular enhancement after intravenous gadolinium injection. On T2 weighted images, it demonstrated a heterogeneous signal intensity. The uterus was displaced to the right and upwards and the rectum to the left and backwards (Fig. 2). A computed tomography fine needle-guided biopsy (Fig. 3) concluded a gastrointestinal stromal tumor with spindle cells, fascicular growth pattern, and cytoplasmic vacuoles indenting the nuclear poles. Immunohistochemically, the tumor cells were positive for CD34 and negative for CD117. No metastases were detected at computed tomography. Since this gastrointestinal stromal tumor was locally advanced, imatinib mesylate therapy was administrated with 400 mg per day for a year. The abdominopelvic computed tomography demonstrated tumoral shrinkage and central necrosis (Fig. 4). The patient was operated on in the lithotomy position with an abdominal and transvaginal approach. An en bloc resection of the tumor and the posterior wall of the vagina was performed with an intact capsula (Fig. 5). No resulting defect in the rectal mucosa or the anal sphincter was observed. Vaginal layers were closed vertically. Microscopic examination revealed a mitotic rate of 5 in 50 high-power fields. The necrosis was observed in 98 % of the cells. The resection margins were safe. The postoperative course was uneventful. The patient did not develop impaired anal sphincter function and fecal incontinence. Imatinib mesylate therapy was being prescribed. No recurrence has been observed yet after 36 months.
1
Department of Surgery, Jendouba’s Hospital, University of Medicine El Manar, Tunis, Tunisia
Second Case Report
2
Department of Surgery, Charles Nicolle Hospital, University of Medicine El Manar, Tunis, Tunisia
3
5, rue Arif Ben Mohamed Salah, cité Essedik, 2042 Tunis, Tunisia
A 29-year-old man, with no medical history, presented with abdominal pain. Computed tomography revealed the existence of two cystic masses in the pelvis and in hepatic
J Gastrointest Canc Fig 1 Pelvic computed tomographies revealing a large tumor of the pelvis with a central necrosis
segments VI and VII (Fig. 6). Percutaneous biopsy was not carried out since it was thought to be risky and there was no sufficient tissular component to give an accurate diagnosis. A laparotomy was then performed. It showed a locally advanced tumor of the mesentery involving the posterior wall of the bladder and a small intestine loop located at 20 cm from the duodeno-jejunal junction. An en bloc resection was carried out without infraction of the capsula. Suture of the bladder and intestine anastomosis were performed. The postoperative course was uneventful. The histopathological exam concluded to a gastrointestinal stromal tumor 15 cm in diameter and 1 mitosis in 50 high-power fields. The patient received Glivec® 400 mg per day during only 6 months for financial problems. Thus, a resection of segments VI and VII was done. The medical treatment was given postoperatively for only 6 months since the patient has been lost to follow-up for 30 months. After that, he complained from a mass in the right upper part of the abdomen. This mass corresponded to a hepatic relapse. A tumorectomy was carried out with uneventful outcomes. No relapse was diagnosed after a follow-up of 12 months. The patient is still receiving Glivec® 400 mg per day.
Fig 2 Pelvic magnetic resonance showing the adherence of the tumor to the rectum (red arrow) and the bladder (green arrow)
Discussion These cases focused on treatment planning, resection strategy, and perioperative molecular targeted therapy success for locally advanced gastrointestinal stromal tumor of the spatium rectovaginale and metastatic intestinal gastrointestinal stromal tumor. The particularities of our first report were a downstaging of a locally advanced tumor allowing a curative resection in one hand and a minimally invasive approach in the other hand. As for the second case, a first resection of the liver metastases was done in order to make the diagnosis. A reresection of hepatic relapse was performed with a twelve months disease-free survival. These reports suggest the utility of an aggressive approach toward locally advanced and metastatic gastrointestinal stromal tumors. The resection of a locally advanced tumor is still challenging because of the need for invasive surgery and the risk of incomplete tumor removal. For our first patient, the location of this large gastrointestinal stromal tumor in the spatium rectovaginale needed treatment planning in order to achieve complete excision without pseudocapsule rupture or anal dysfunction. A downsizing of the tumor is mandatory by means of perioperative imatinib [4–9]. A fine needle biopsy is recommended for the diagnosis of the gastrointestinal stromal tumor before neoadjuvant imatinib administration [10]. It
Fig 3 Computed tomography-guided biopsy of the tumor
J Gastrointest Canc Fig 4 Computed tomographies 1 year after the beginning of imatinib concluding to a reduction of the tumor size (arrow: rectum)
Fig 5 Preoperative views showing the tumor before and after en bloc excision
has a sensitivity of 80 % [11]. Computed tomography represents the standard method allowing therapy response assessment [12]. Since procedures on the lower rectum may lead to fecal incontinence as a consequence of dissection down to the levator ani muscles, less invasive procedures should be attempted [13] as in our first case. The transvaginal approach is efficient for large tumors [13]. It allows to achieve surgery goals of histologically negative margins [4, 5] and absence of capsule rupture. This rupture constitutes a major prognostic factor since it reduces the disease-free and overall survival [14]. Almost all patients develop abdominal metastases after rupture of a gastrointestinal stromal tumor [15]. The risk of recurrence depends also on the size of the tumor, its location, and the mitotic count [16]. For our first patient, the risk was
about 71 %. This high relapse risk recommends the adjuvant therapy based on imatinib in cases of positive margins, capsule rupture, tumor size greater than 10 cm, and/or more than 5 mitoses per 50 high-power fields [4–6, 15]. Our first patient had two pejorative prognostic factors: the size of the tumor and the number of mutations. The optimal duration of imatinib administration in adjuvant therapy has not yet been determined [17]. Our second patient had a metastatic gastrointestinal stromal tumor. Laparotomy allowed the positive diagnosis since the percutaneous biopsy was judged risky and not beneficial for accurate diagnosis. Our attitude is in accordance with the recommendations of the European Sarcoma Network Working Group [18]. The treatment for metastatic gastrointestinal
Fig 6 Computed tomographies showing cystic tumors in the pelvis and the liver
J Gastrointest Canc
stromal tumor is challenging. Recommendations are in favor of medical treatment [17, 18], but complete excision of the metastatic tumor is related with a good prognosis [19–21] as for our second patient.
9.
10.
Conclusion
11.
Treatment planning is mandatory in order to achieve successful treatment toward gastrointestinal stromal tumors with aggressive behavior.
12.
Conflict of Interest The authors declare that they have no conflict of interest.
13.
14.
References 1.
Furihata M, Fujimori T, Imura J, et al. Malignant stromal tumor, so called “gastrointestinal stromal tumor”, with rhabdomyomatous differentiation occurring in the gallbladder. Pathol Res Pract. 2005;201:609–13. doi:10.1016/j.prp.2005.04.011. 2. Krska Z, Peskova M, Povysil C, Horejs J, Sedlackova E, Kudrnova Z. GIST of pancreas. Prague Med Rep. 2005;106:201–8. 3. Reith JD, Goldblum JR, Lyles RH, Weiss SW. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol. 2000;13:577–85. 4. Casali PG, Blay JY. Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v98–102. doi:10.1093/annonc/mdq208. 5. Demetri GD, von Mehren M, Antonescu CR, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw. 2010;8 Suppl 2: S1–41. quiz S42–4. 6. Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebocontrolled trial. Lancet. 2009;373:1097–104. doi:10.1016/S01406736(09)60500-6. 7. Eisenberg BL, Harris J, Blanke CD, et al. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009;99:42–7. doi:10.1002/jso.21160. 8. Fiore M, Palassini E, Fumagalli E, et al. Preoperative imatinib mesylate for unresectable or locally advanced primary gastrointestinal
15.
16.
17.
18.
19.
20.
21.
stromal tumors (GIST). Eur J Surg Oncol. 2009;35:739–45. doi:10. 1016/j.ejso.2008.11.005. Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–6. Chaudhry UI, DeMatteo RP. Advances in the surgical management of gastrointestinal stromal tumor. Adv Surg. 2011;45:197–209. Sepe PS, Moparty B, Pitman MB, Saltzman JR, Brugge WR. EUSguided FNA for the diagnosis of GI stromal cell tumors: sensitivity and cytologic yield. Gastrointest Endosc. 2009;70(2):254–61. doi: 10.1016/j.gie.2008.11.038. Kalkmanna J, Zeileb M, Antochc G, et al. Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group. Cancer Imaging. 2012;12:126–35. doi:10.1102/ 1470-7330.2012.0013. Hara M, Takayama S, Arakawa A, Sato M, Nagasaki T, Takeyama H. Transvaginal resection of a rectal gastrointestinal stromal tumor. Surg Today. 2012;42:909–12. doi:10.1007/s00595-012-0215-8. Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. 1992;215(1):68–77. Hohenberger P, Ronellenfitsch U, Oladeji O, et al. Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. Br J Surg. 2010;97(12):1854–9. doi:10.1002/bjs.7222. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70– 83. Von Mehren M, Lor Randall R, Robert SB, et al. Soft tissue sarcoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2014;12:473–83. The ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Supplement 3):iii21–6. doi:10.1093/annonc/ mdu255. Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24: 2325–31. Wang D, Zhang Q, Blanke CD, et al. Phase II trial of neoadjuvant/ adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132. Ann Surg Oncol. 2012;19:1074–80. doi:10. 1245/s10434-011-2190-5. Mussi C, Ronellenfitsch U, Jakob J, et al. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21:403–8. doi:10.1093/annonc/mdp310.
