Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era

BACKGROUND:

Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone.

METHODS:

Demographics, clinicopathologic tumor characteristics, treatments, and outcomes of patients who underwent hepatic resection at 3 high‐volume centers from 1995 to 2010 were reviewed.

RESULTS:

In total, 39 patients underwent hepatectomy for metastatic GISTs, and 27 patients received postoperative TKI therapy. At a median follow‐up of 39.7 months, 23 patients (59%) experienced recurrence at a median of 18 months. The 1‐year, 2‐year, and 3‐year overall survival rates were 96.7%, 76.8%, and 67.9%, respectively. Median survival was not reached at 5 years. The rates of severe complication and mortality were 10.2% (4 patients) and 2.5% (1 patient), respectively. When controlling for confounders, postoperative TKI therapy was associated with improved survival (hazard ratio, 0.04; 95% confidence interval, 0.01‐0.50; P = .006), and extrahepatic disease was associated with worse survival (hazard ratio, 9.51; 95% confidence interval, 1.63‐55.7; P = .012).

CONCLUSIONS:

Overall survival after combination therapy exceeded previous reports for the treatment of metastatic GIST with hepatic resection or TKI therapy alone and was significantly enhanced by postoperative TKI therapy. The results from this study support findings that combination therapy for GIST liver metastases comprised of surgical resection and TKI therapy is more effective than surgery or TKI therapy alone. Cancer 2012;3571–3578. © 2011 American Cancer Society.     

Surgical treatment of locally advanced,non-metastatic,gastrointestinal stromal tumours after treatment with imatinib

Aims

Patients with locally advanced gastrointestinal stromal tumours (GISTs) have a high risk of tumour perforation, incomplete tumour resections and often require multivisceral resections. Long-term disease-free and overall survival is usually impaired in this group of patients. Induction therapy with imatinib followed by surgery seems to be beneficial in terms of improved surgical results and long-term outcome. We report on a large cohort of locally advanced GIST patients who have been treated in four centres in the Netherlands specialized in the treatment of sarcomas.

Methods

Between August 2001 and June 2011, 57 patients underwent surgery for locally advanced GISTs after imatinib treatment. Data of all patients were retrospectively collected. Endpoints were progression-free and overall survival.

Results

The patients underwent surgery after a median of 8 (range 1–55) months of imatinib treatment. Median tumour size before treatment was 12.2 (range 5.2–30) cm and reduced to 6.2 (range 1–20) cm before surgery. No tumour perforation occurred and a surgical complete (R0) resection was achieved in 48 (84%) patients. Five-year PFS and OS were 77% and 88%. Eight patients had recurrent/metastatic disease.

Conclusions

Imatinib in locally advanced GIST is feasible and enables a high complete resection rate without tumour rupture. The combination of imatinib and surgery in patients with locally advanced GIST seems to improve PFS and OS.     

Audit of a series of 40 gastrointestinal stromal tumour cases

AIMS: To analyze prognostic factors influencing survival and tumour recurrence after resection of gastrointestinal stromal tumours. METHODS: Forty patients who underwent surgery for a GIST at our institution were reviewed. Patients were classified on the basis of tumour size, mitotic rate and CD117 positivity. The overall survival and disease free survival were calculated using Kaplan-Meier method considering the extent of surgery comparing local tumour excisions with segmental organ resections. RESULTS: Tumours were localized in the oesophagus, stomach, duodenum, small bowel and large bowel and rectum. Sixty-five percent of the patients had an intermediate or high risk GIST according to tumour size and mitotic count. In 26/40 patients tumour resection was performed using segmental organ resection, in all other patients local tumour excision was carried out. The mean overall survival was 73 months. Disease free survival was significantly better after local tumour excision compared to segmental organ resection (73 months versus 53 months; p=0.05). Large tumour size (p=0.07) and high mitotic count (p=0.14) were negative prognostic factors for disease free survival, although statistical significance was not reached yet. CONCLUSION: Primary surgery remains the cornerstone in the treatment of primary and recurrent GIST. Risk adapted surgery is the most important factor to avoid early tumour recurrence. In case of small tumour size segmental organ resections can be avoided favouring local tumour excisions with a low risk of tumour recurrence.     

Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Long-term survival of patients with metastatic disease has only been observed in patients with completely resected disease. Recently, the tyrosine kinase inhibitor imatinib has been found to yield responses in the majority of patients with metastatic GIST suggesting improved resectability in responding patients. Combined treatment approaches including resective surgery after imatinib treatment in patients with advanced metastatic disease have rarely been explored. We report a series of 90 patients with metastatic GIST in whom treatment with imatinib enabled 12 patients with mostly recurrent and extensive disease to be considered for resection of residual disease. In 11 of these patients, complete resection could be achieved. Viable tumor cells were found in all but one resected specimens suggesting that despite favorable radiological or clinical responses, imatinib is unlikely to induce pathological complete responses. Until more mature data from prospective trials are available, these data suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST. Further trials investigating a combined surgical and pre/postoperative treatment with imatinib in patients with advanced metastatic GIST are warranted.     

Surgical options for localized and advanced gastrointestinal stromal tumors

The development of imitinab has led to a revolution in the management of gastrointestinal stromal tumors (GIST), but surgical resection remains the cornerstone of treatment for patients with localized disease. The principles to surgical treatment of GIST include careful handling of tissues to prevent tumor rupture and resection to negative margins without the need for wide excision. Minimally invasive techniques have proven equally efficacious provided appropriate oncologic resections are performed.     

Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours

AIMS: To analyse the prognostic factors of gastrointestinal stromal tumours (GIST) after a complete resection of the primary tumour. PATIENTS AND METHODS: Fifty-nine patients who underwent a complete initial resection of a GIST were studied. Peritumoral resections (PTR) were compared to segmental organ resections (SOR). Overall survival (OS) and the disease-free survival (DFS) were calculated using the Kaplan-Meier method. RESULTS: Primary sites were: stomach (25), small intestine (22), rectum (7), duodenum (5). Two patients had nodal involvement. The median follow-up was 45 months. Local DFS was significantly better after SOR compared to PTR (median 63 vs. 11 months, respectively, p<0.001). Univariate analysis for OS identified the grade (p=0.005) and size (p=0.02) as prognostic factors. Only a high histologic grade was an independent factor (p=0.02) in the multivariate analysis. Out of 49 patients who relapsed, the first recurrence was local only in 12, local and distant in 10 and distant only in 27; only one had a lymph node failure. Recurrences were accessible to curative surgery in 22 cases. OS of patients submitted to complete resection of their recurrence was significantly better than patients whose recurrence could not be resected (median 52 vs. 12 months, respectively, p<0.001). CONCLUSION: Complete surgery without rupture remains the mainstay of treatment in patients with localized, resectable disease. A peri-tumoral resection confers a high risk of local recurrence and should be avoided. Lymphadenectomy is not systematic. Grade is the main prognostic factor for OS and can be a decision marker for adjuvant treatment with Gleevec.     

Focal progression in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: a three-center-based study of 38 patients

BACKGROUND: This study aimed to investigate the outcome of patients with advanced gastrointestinal stromal tumors (GISTs) exhibiting focal disease progression during imatinib therapy, treated by surgical resection and imatinib continuation. METHODS: A consecutive series of 38 patients with metastatic GISTs who underwent treatment with imatinib at our centers during a defined period of time was evaluated. Patients were evaluated for demographics including tumor-related features, initial response, disease recurrence, and salvage treatment modalities, and were classified as having either focal or generalized progression upon presentation prior to salvage therapy. RESULTS: After a median follow-up of 31.8 months, 25 of the 38 (65.8%) patients had progressed. Nine (36%) patients were classified as having focal and 16 (64%) as having generalized progression. Salvage therapies were: surgical resection and imatinib dose escalation in patients exhibiting focal progression and imatinib dose escalation alone in the majority of patients exhibiting generalized progression. Focal progression was associated with prolonged progression-free survival (PFS) and overall survival (OS) after salvage therapy as compared with generalized progression (median PFS and OS, 11.3 months and not attained, versus 2.5 and 22.8 months, respectively). Six-month PFS was 89% and 39% in patients exhibiting focal and generalized progression, respectively. KIT mutation analysis of controlled and progressive lesions was performed in 4 patients with focal progression. Secondary KIT mutations affected progressive lesions, whereas nonprogressive lesions harbored the original mutations only. CONCLUSION: Patients with advanced GIST exhibiting focal disease progression during imatinib therapy may benefit from surgical resection and imatinib continuation. Imatinib resistance seems to be partial in these patients.     

Surgical interventions for focal progression of advanced gastrointestinal stromal tumors during imatinib therapy

Background Although imatinib has shown high activity in the majority of patients with advanced gastrointestinal stromal tumors (GIST), it has become clear that secondary resistance appears during chronic therapy. The aim of this study was to retrospectively analyze the safety and prognostic effects of surgical interventions for focal progression during imatinib treatment. Methods Between January 2002 and May 2005, 16 patients who had focal lesions of secondary-resistant GIST to imatinib treatment (male/female, 12 : 4; median age, 62 years) underwent surgical interventions such as resection, radiofrequency ablation, and their combination. Results Postoperative complications, including liver abscess, bile leak, wound infection, and ileus were mostly mild, and the patients recovered with conservative therapy. There was no hospital death. The median time to progression (TTP) of all patients was 5.5 months, and only one patient died of the disease; the others are alive after a median follow up of 12.4 months. Patients with complete resections of resistant lesions (n = 7) showed significantly better median TTP than those with incomplete resections (n = 9; P = 0.014). The impact of curability on focal lesions with secondary resistance was mainly significant in patients with tumors of stomach origin (P = 0.013), and a smaller number (P = 0.014) and smaller size (P = 0.018) of resistant lesions. Overall survival was 100% at 1 year and 75% at 2 years. Conclusion Our study indicates that surgical interventions in patients with GIST resistant to imatinib therapy are efficacious when complete resections are performed, when the lesions are of gastric origin, when the number of lesions is lower, and when the lesions are a smaller size.     

Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation.

Most gastrointestinal stromal tumors (GIST) have an activating mutation in either KIT or PDGFRA. Imatinib is a selective tyrosine kinase inhibitor and achieves a partial response or stable disease in about 80% of patients with metastatic GIST. It is now clear that some patients with GIST develop resistance to imatinib during chronic therapy. To identify the mechanism of resistance, we studied 31 patients with GIST who were treated with imatinib and then underwent surgical resection. There were 13 patients who were nonresistant to imatinib, 3 with primary resistance, and 15 with acquired resistance after initial benefit from the drug. There were no secondary mutations in KIT or PDGFRA in the nonresistant or primary resistance groups. In contrast, secondary mutations were found in 7 of 15 (46%) patients with acquired resistance, each of whom had a primary mutation in KIT exon 11. Most secondary mutations were located in KIT exon 17. KIT phosphorylation was heterogeneous and did not correlate with clinical response to imatinib or mutation status. That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies.     

胃肠间质瘤复发危险度的临床分析

目的:探讨不同临床病理因素对胃肠间质瘤(gastrointestinal stromal tumor,GIST)预后的影响,以期为GIST诊断和治疗以及预后判断提供依据。方法:回顾性分析2001年1月—2006年12月接受手术治疗的128例GIST患者的临床病理资料并进行随访,分析肿瘤原发部位、肿瘤大小、组织学类型、核分裂相、远处转移、甲磺酸伊马替尼等因素和GIST危险度与生存率之间的关系。结果:本组患者CD117表达阳性率为94.5%(121/128),CD34表达阳性率为72.7%(93/128)。按照Miettinen危险度分级标准,相同危险度的胃间质瘤与非胃间质瘤的生存率差异无统计学意义;而组织学类型与危险度分级相关(P=0.0282)。远处转移与GIST患者的生存率密切相关(P<0.0001)。甲磺酸伊马替尼治疗GIST可以明显提高中-高危险度GIST患者的生存率。结论:Miettinen危险度分级标准作为GIST的预后判定标准更为合理。组织学类型和远处转移可以作为评估GIST的重要因素,应在分级标准中予以体现。对中-高度危险的GIST患者,应建议口服甲磺酸伊马替尼治疗。     

Clinical Analysis of Diagnosis and Treatment of Gastrointestinal Stromal Tumors （Report of 96 Cases）

Objective To investigate the pathological diagnosis, surgical treatment and prognosis of gastrointestinal stromal tumors (GIST). Methods The clinicopathological data of 96 post-operative cases with GIST were analyzed retrospectively, and expression of immunohistochemical staining of CD117, CD34, SMA and S -100 was determined. Results Immunohistochemical positive staining showed: CD117, 79.1% (76/96); CD34, 58.3% (56/96); SMA, 35.4% (34/96); S-100, 9.3% (9/96). Twenty-three benign cases and 73 malignant cases were reported. The omentums were resected in 39 malignant cases. For the other 34 malignant cases the omentums were left intact. The recurrent and metastatic rates were 5.1% and 26.5%(P<0.05). The incisai section between the normal bowel and the tumor was >5cm in 46 cases, for the other 27 cases, the section was < 5cm. The recurrent and metastatic rates were 6.5% and 29.6%(P<0.05), respectively. The 5-year survival rates of benign and malignant GIST were 91.5% and 57.3%(P<0.05). Conclusion GIST were the most freuquent mesenchymal tumor seen in the gastrointestinal tract. The application of immunohistochemical markers CD117and CD34 are mutually beneficial for a final correct pathological diagnosis. The adaptation of a primary rational treatment, including the complete tumor resection and preventive omentectomy could reduce the recurrence of GIST.     

Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib – Analysis of prognostic factors (EORTC-STBSG collaborative study)

Background

Long-term complete remissions remain a rare exception in patients with metastatic gastrointestinal stromal tumors (GIST) treated with IM (imatinib). To date the therapeutic relevance of surgical resection of metastatic disease remains unknown except for the use in palliative intent.

Patients and methods

We analyzed overall survival (OS) and progression-free survival (PFS) in consecutive patients with metastatic GIST who underwent metastasectomy and received IM therapy (n = 239).

Results

Complete resection (R0+R1) was achieved in 177 patients. Median OS was 8.7 y for R0/R1 and 5.3 y in pts with R2 resection (p = 0.0001). In the group who were in remission at time of resection median OS was not reached in the R0/R1 surgery and 5.1 y in the R2-surgery (p = 0.0001). Median time to relapse/progression after resection of residual disease was not reached in the R0/R1 and 1.9 years in the R2 group of patients, who were resected in response. No difference in mPFS was seen in patients progressing at time of surgery. Conclusions: Our analysis implicates possible long-term survival in patients in whom surgical complete remission can be achieved. Incomplete resection, including debulking surgery does not seem to prolong survival. Despite the retrospective character and likely selection bias, this analysis may help in decision making for surgical approaches in metastatic GIST.     

Systemic treatment of patients with gastrointestinal stromal tumor: Current status and future opportunities

Imatinib mesylate is considered the standard first-line systemic treatment for patients with advanced gastrointestinal stromal tumor (GIST). Results from recent research have expanded the knowledge of tyrosine kinase inhibitors in management of GIST. In the setting of unresectable and metastatic GIST, long-term follow-up of the B2222 study showed that imatinib 400 and 600 mg/d produced objective responses in 68% of patients and clinical benefit in 84%; it also extended median survival from 19 months in historical controls to 57 months. The MetaGIST analysis in two large phase 3 trials consisting of more than 1600 patients with metastatic and/or unresectable GIST showed that imatinib 800 mg/d compared with the standard 400-mg/d dose conferred a progression-free survival advantage in patients with KIT exon 9 mutations but not in other subpopulations. The higher starting dose does not significantly improve overall survival. The BFR14 trial demonstrated that interrupting imatinib is associated with a high risk of rapid disease progression. For patients with imatinib-intolerant or imatinib-resistant GIST, sunitinib or a variety of investigational agents, including the next-generation kinase inhibitor nilotinib, may be viable options for achieving disease control. In the setting of primary localized GIST, function- sparing surgical resection is the standard treatment approach, but some patients may be at substantial risk of disease recurrence and metastasis depending on tumor size, mitotic count, and possibly other factors. Initial results from ACOSOG Z9001 indicate that adjuvant imatinib for 1 year prolongs recurrence-free survival following surgical resection of larger (at least 3 cm) KIT-expressing GIST. Other ongoing studies are further exploring the role of imatinib in both adjuvant and neoadjuvant therapy. Recent updates to clinical practice guidelines and recommendations now incorporate some of these new findings.     

Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors

The authors have previously reported that loss of heterozygosity (LOH) of the c-kit gene could be responsible for the gain in high proliferative activity in some gastrointestinal stromal tumors (GIST), resulting in enhanced metastatic potential. In the present study, an attempt was made to identify the factors that might predict the postoperative prognosis of patients with metastatic liver GIST. The clinicopathologic or genetic features of resected liver GIST in 14 patients who had undergone a hepatectomy for metachronous liver metastases and who had not received adjuvant imatinib treatment were examined. LOH of the c-kit gene was observed in seven of 12 metastatic liver GIST (58.3%), of which DNA suitable for testing could be extracted. Ten patients had recurrence after hepatectomy and four had none. The median post-recurrent disease-free survival (PRDFS) after hepatectomy was 27.5 months (range 8–104). The tumor-specific PRDFS was examined using clinicopathologic features, c-kit mutation and LOH of the c-kit gene. No single clinicopathologic or genetic finding was significantly associated with PRDFS. However, patients with 'Ki67 labeling index <5% and LOH(–)' had a significantly longer PRDFS than those with 'Ki67 ≥5% or LOH(+)' ( P =  0.032), and there was no correlation between the presence of LOH of the c-kit gene and the Ki67 labeling index. LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis. ( Cancer Sci 2007; 98: 1734–1739)     

Preoperative imatinib facilitates complete resection of locally advanced primary GIST by a less invasive procedure

Complete resection is the most effective therapy for gastrointestinal stromal tumors (GISTs). Complete resection of locally advanced primary GIST by less invasive procedure is usually difficult at initial diagnosis. Imatinib has been successful in treating locally advanced and metastatic GIST and this report shares the experiences in preoperative use of imatinib for patients with locally advanced primary GISTs. The procedure of treatment and completeness of resection were retrospectively accessed for locally advanced primary GIST. Disease-free survival (DFS) and overall survival (OS) after resection were analyzed. Thirteen patients were treated with imatinib preoperatively. All patients received surgical resection after a median imatinib treatment of 7 months when most tumors shrunk. All patients achieved R0 resection without tumor rupture. Two patients received an en-bloc multivisceral resection for the invasion of surrounding organs and 3 patients underwent Mile’s operation for a low rectal tumor. Eleven patients were disease-free. Median DFS or OS had not been reached, while 1- and 3-year DFS were estimated to be 92.3 and 76.9 %, respectively. 1- and 3-year OS were both estimated to be 100 %. Preoperative use of imatinib is useful in locally advanced primary GIST by downsizing the tumor in most patients and facilitating complete resection through less invasive procedures without tumor rupture.     

Surgery for hilar cholangiocarcinoma; a 10 year experience of a tertiary referral centre in the UK.

OBJECTIVE: To review the outcome of patients operated for hilar cholangiocarcinoma and analyse prognostic variables. PATIENTS AND METHODS: A prospectively collected database on patients with hilar cholangiocarcinoma, between 1992 and 2003, and relevant clinical notes were reviewed retrospectively. A total of 174 patients, 96 male, median age 63 years (27-86), were referred. Jaundice was the initial presentation in 167. RESULTS: ERCP was the initial interventional investigation at the referring centre in 150, of which only 30 were stented successfully. PTC and decompression was carried out on 120. In 17, combined PTC and ERCP were required for placement of stents. Seventy-two underwent laparotomy at which 27 had locally advanced disease. Forty-five had potentially curative resections. Extra hepatic bile duct resection was done in 14 patients of which four were R0 resections. Thirty-one had bile duct resection including partial hepatectomy with 19 R0 resections (P=0.042). Post-operative complications developed in 19 patients, and there were 4 30 day mortalities [hepatic insufficiency:/sepsis (n=3), thrombosis of the reconstructed portal vein (n=1)]. Among the patients with R0 resections, the cumulative survival rates at 1, 3, and 5 year; was 83, 58, 41%, respectively, and in those with R1 resections were 71, 24, 24%, respectively, (P=0.021). Overall survival was shorter in patients with positive perineural invasion (P=0.066: NS). There was no significant difference in survival between the node positive and negative group. Median survival of patients who underwent liver resection was longer than those with bile duct resection only (30 vs 24 months P=0.43: NS). CONCLUSIONS: ERCP was associated with a high failure rate in achieving pre-operative biliary decompression which was subsequently achieved by PTC. Clear histological margins were associated with improved survival and were better achieved by liver resection as compared to extra hepatic bile duct resection. Positive level I lymph nodes did not adversely impact survival.     

The role of surgery in the multidisciplinary management of patients with localized gastrointestinal stromal tumors

Surgical resection of localized gastrointestinal stromal tumors (GISTs) is associated with recurrence rates of approximately 50% at 5 years of follow-up. The introduction of tyrosine kinase inhibitors, such as imatinib, improved overall survival rates in advanced disease, while in the adjuvant setting, improved recurrence-free survival following resection of high-risk GIST. The demonstration of the clinical benefit of tyrosine kinase inhibitors in both the metastatic and adjuvant settings generated interest in neoadjuvant approaches for patients with operable locally advanced disease, particularly in difficult anatomic locations. The potential impact of tumor downsizing in areas such as the gastroesophageal junction, the duodenum or the rectum, on the extent of surgical resection and morbidity is real. The ongoing research regarding neoadjuvant therapy, the duration of adjuvant therapy and the optimal means by which to risk stratify patients with GIST continues to keep the treatment of this disease at the forefront of personalized cancer care.     

Repeat liver resection for recurrent liver metastases from colorectal cancer.

AIMS: Numerous patients suffer from recurrence after resection of liver metastases from colorectal cancer. Recurrence is frequently restricted to the liver and repeat liver resection may offer a curative option in these patients. This study was conducted to clarify safety and effectiveness of this treatment and to identify prognostic factors of a favourable outcome after repeat hepatectomy. METHODS: Between January 1988 and March 2006 in our institution 811 patients underwent 841 liver resections for metastases from colorectal cancer. Among these, 94 patients underwent a repeat hepatectomy. Patients were identified from a prospective database and retrospectively reviewed. Results of different time periods were assessed and prognostic factors for a favourable outcome were determined. RESULTS: The perioperative morbidity and mortality was 24% (23 of 94) and 3% (3 of 94), respectively. The one-, three-, five- and ten-year survival for all patients in this series was 89%, 55%, 38% and 23%, respectively. In the univariate analysis, pT-stage of the primary, diameter of the largest metastases, surgical radicality, period of resection and distribution of metastases showed statistically significant influence on survival. The multivariate analysis revealed only pT-stage of the primary tumour, surgical radicality and period of resection as independent prognostic factors. CONCLUSIONS: Repeat hepatectomy is a safe and effective treatment for recurrent liver metastases from colorectal cancer. Perioperative risk and long-term survival were similar when compared to the results obtained during the initial resection. Achieving a curative resection is the most relevant prognostic factor for a favourable prognosis after repeat liver resection.     

甲磺酸伊马替尼治疗手术无法切除的晚期胃肠间质瘤

目的:探讨甲磺酸伊马替尼用于治疗晚期胃肠间质瘤的疗效及生存获益。方法:收集2004年9 月至2015年6 月天津医科大学肿瘤医院收治的无法手术切除的61例晚期胃肠间质瘤患者的临床资料,接受初始剂量400 mg/d 的口服甲磺酸伊马替尼治疗,定期随访,评价生存获益及药物不良反应。结果:61例患者开始接受治疗1 年后,治疗有效率为57.4%（35/ 61）,疾病控制率为88.5%（54/ 61）,Logic二元回归分析显示性别、年龄和腹盆腔多发病灶是影响治疗有效率的因素（P < 0.05）。 本组患者5 年累积生存率为53% ,Cox 回归模型分析提示腹盆腔的多发病灶是影响患者生存获益的重要因素（P < 0.05）。 除2 例患者出现出血,其余患者不良反应轻微。结论:甲磺酸伊马替尼显著改善晚期胃肠间质瘤的生存获益,可作为无法手术切除的晚期胃肠间质瘤的首选治疗。      

Surgical resection of residual disease in initially inoperable imatinib-resistant/intolerant gastrointestinal stromal tumor treated with sunitinib

Aim

Sunitinib malate therapy in inoperable and/or metastatic gastrointestinal stromal tumor (GIST) resistant to imatinib mesylate may facilitate surgical removal of residual disease. We explored this possibility in the course of treating patients as part of a treatment-use trial, the objective of which was to provide access to sunitinib treatment.

Methods

Four patients with inoperable and/or metastatic GIST resistant to imatinib who had responded to sunitinib therapy administered at a starting dose of 50 mg daily in 6-week cycles of 4 weeks on treatment followed by 2 weeks off underwent surgical removal of residual disease. Disease progression on or clinical response to treatment was defined based on Response Evaluation Criteria in Solid Tumors.

Results

In three of four cases it was possible to perform macroscopically complete resection of residual disease, resulting in surgical complete clinical responses, two with durations of 13 months. The fourth patient achieved a dramatic partial response to sunitinib that required emergency surgical resection of the necrotic tumor mass, with the partial response having been maintained for 15 months. In all cases, viable GIST cells were detected histologically in the resection specimens, and sunitinib treatment was resumed post-surgery. None of the patients experienced any postoperative complications during 13–16 months of follow-up.

Conclusions

Combining sunitinib treatment with surgical removal of residual disease may allow selected imatinib-resistant GIST patients who have shown a favorable response to sunitinib to achieve complete and sustained remission or durable control of previously progressive disease beyond that expected for sunitinib treatment alone.