Abstract Background To determine the timing of earliest, best and plateau response to neoadjuvant imatinib in patients with GIST. Materials and methods In this IRB-approved retrospective study, we ...included all 20 patients (10 women; mean age 61 years, range 30–83 years) with KIT-positive primary GIST who received neoadjuvant imatinib and underwent surgery between January 2001 and December 2012. Earliest (earliest time to partial response), best (percentage reduction in longest axial diameter LAD and volume correlated with RECIST 1.1 and volumetric criteria) and plateau (time point when there was <10% change in treatment response between two consecutive scans beyond best response) responses were analyzed on review of imaging. Results Median tumor size at baseline was 7.2 cm (range, 3.0–31.4 cm). Median duration of neoadjuvant imatinib was 32 weeks (IQR, 16–36 weeks). Partial response was noted in 16/20 patients (median interval = 16 weeks; IQR, 7–26 weeks); 4/20 had stable disease. Median time to earliest PR was 16 weeks (IQR, 7–26 weeks). At best response, median decrease in LAD and volume were 43% (IQR, 31–48%) and 83% (IQR, 63–87%), (median interval = 28 weeks; IQR, 18–37 weeks), at which point 10 tumors were resected. Plateau response (45% IQR, 35–45% LAD reduction) was noted in the remaining 10 patients (median interval = 34 weeks; IQR, 26–41 weeks) before resection. Tumor size, location or risk category did not correlate with best response or time to best response. Conclusion Best response to neoadjuvant imatinib was seen at 28 weeks irrespective of tumor size and location. Plateau response was seen at 34 weeks, beyond which further treatment may not be beneficial.
Background
Patients undergoing surgery for soft tissue sarcoma have high morbidity rates, particularly after preoperative radiation therapy (RT). An enhanced recovery after surgery (ERAS) programme ...may improve perioperative outcomes in abdominal surgery. This study reported outcomes of an ERAS programme tailored to patients with soft tissue sarcoma.
Methods
A prospective ERAS protocol was implemented in 2015 at a high‐volume sarcoma centre. Patients treated within the ERAS programme from 2015 to 2018 were case‐matched retrospectively with patients treated between 2012 and 2018 without use of the protocol, matched by surgical site, surgeon, sarcoma histology and preoperative RT treatment. Postoperative outcomes, specifically wound complications and duration of hospital stay, were reported.
Results
In total, 234 patients treated within the ERAS programme were matched with 237 who were not. The ERAS group had lower wound dehiscence rates overall (2 of 234 (0·9 per cent) versus 31 of 237 (13·1 per cent); P < 0·001), after preoperative RT (0 of 41 versus 11 of 51; P = 0·004) and after extremity sarcoma surgery (0 of 54 versus 6 of 56; P = 0·040) compared with the non‐ERAS group. Rates of postoperative ileus or obstruction were lower in the ERAS group (21 of 234 (9·9 per cent) versus 40 of 237 (16·9 per cent); P = 0·016) and in those with retroperitoneal sarcoma (4 of 36 versus 15 of 36; P = 0·007). Duration of hospital stay was shorter in the ERAS group (median 5 (range 0–36) versus 6 (0–67) days; P = 0·003).
Conclusion
Treatment within an ERAS protocol for patients with soft tissue sarcoma was associated with lower morbidity and shorter hospital stay.
Antecedentes
Los pacientes sometidos a cirugía por sarcoma de tejido blando (soft tissue sarcoma, STS) tienen altas tasas de morbilidad, particularmente después de la radioterapia preoperatoria (RT). El programa de recuperación intensificada después de la cirugía (enhanced recovery after surgery, ERAS) puede mejorar los resultados perioperatorios en la cirugía abdominal. Este estudio analizó los resultados de un programa ERAS diseñado para pacientes con STS.
Métodos
Se implementó un protocolo prospectivo ERAS en el año 2015 en un centro de alto volumen de sarcomas. Los pacientes en ERAS desde 2015 hasta 2018 fueron emparejados retrospectivamente con pacientes sin ERAS desde 2012 hasta 2018, según la localización quirúrgica, el cirujano, la histología del sarcoma y el tratamiento con RT preoperatoria. Se analizaron los resultados postoperatorios, específicamente las complicaciones de la herida y la duración de la estancia hospitalaria (length of stay, LOS).
Resultados
En total, 234 pacientes tratados con ERAS se compararon con 237 pacientes no tratados con ERAS. Los pacientes con ERAS tuvieron tasas globales más bajas de dehiscencia de la herida (2 (0,9%) versus 31 (13,1%), P < 0,001)), después de la RT preoperatoria (0 versus 11 (21,6%), P = 0,004)), y después de la cirugía de STS de extremidades (0 versus 6 (0,7%), P = 0,04)) en comparación con los pacientes no ERAS. Las tasas de íleo u obstrucción postoperatorias fueron más bajas en el grupo ERAS (21 (9,9%) versus 40 (16,9%), P = 0,02)) y en aquellos pacientes con sarcoma retroperitoneal (4 (11,1%) versus 15 (41,7%), P = 0,007)). La mediana (rango) de la LOS fue más corta en los pacientes con ERAS que fue de 5 (0‐36) días que en los pacientes sin ERAS que fue de 6 (0‐67) días (P = 0,003).
Conclusión
ERAS para pacientes con STS se asoció con una menor morbilidad y una estancia hospitalaria más corta.
An enhanced recovery after surgery (ERAS) protocol may diminish the adverse effects of postoperative wound complications associated with preoperative radiotherapy. Further studies validating these findings may lead to a consensus on treatment algorithms for patients with trunk and extremity soft tissue sarcoma. The results support the use of ERAS to minimize acute postoperative complications and reduce duration of hospital stay.
Organized care better
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Since the discovery that the KIT and PDGFRA receptor tyrosine kinases are the primary ...oncogenic drivers in the vast majority of GISTs, targeted therapy with tyrosine kinase inhibitors has been the mainstay of treatment for this disease. Using molecular profiling of tumor specimens, researchers also discovered that
and
mutations are non-random and occur in specific regions of the receptors, and furthermore, that particular genotypes predicted response or resistance to targeted therapy. Imatinib, the first tyrosine kinase inhibitor used to treat GIST, remains the first-line therapy in advanced GIST and the only therapy confirmed through clinical trials in the adjuvant or neoadjuvant setting for resectable disease. Resistance to imatinib is well described and is either primary or secondary. Primary resistance is associated with specific tumor genotypes, so genotyping of individual patient tumors helps guide decision-making into whether to offer imatinib and at what dose. Secondary resistance occurs due to the acquisition of secondary mutations during therapy. Currently, the main strategy to combat imatinib resistance is to switch to another tyrosine kinase inhibitor, because imatinib-resistant GIST is usually still oncogenically addicted to KIT/PDGFRA signaling. Surgery can also be used to combat resistant disease in select settings. Unfortunately, progression-free and overall survival remains dismal for patients who develop imatinib-resistant disease, and further research into alternative strategies is still needed.
A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, ...the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs.
A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves.
Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011).
This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Although cytoreductive surgery has been shown to be beneficial in carefully selected patients with metastatic gastrointestinal stromal tumours (GISTs) treated with tyrosine kinase ...inhibitors (TKIs), factors predictive of postoperative morbidity have not been investigated previously.
Methods
A surgical complexity score for GIST metastasectomy (GM‐SCS) composed of patient‐related and surgical factors was assigned retrospectively to patients with metastatic GIST treated with TKI therapy and surgery at two institutions between 2002 and 2014. The ability of clinicopathological factors and GM‐SCS to predict postoperative morbidity was assessed by means of a multivariable logistic regression model. Postoperative complications were categorized using the Clavien–Dindo classification.
Results
Some 400 operations on 323 patients with metastatic GIST on TKIs were included. Complications were observed following 110 operations (27·5 per cent) including 70 major complications (grade III–V) (17·5 per cent of 400 operations). Patients were divided into low (5 points or less; 100 patients, 25·0 per cent), intermediate (6–9 points; 191, 47·8 per cent) and high (at least 10 points; 109, 27·3 per cent) complexity scoring groups based on the GM‐SCS. An intermediate (odds ratio (OR) 2·88; P = 0·008) and high (OR 5·40; P < 0·001) GM‐SCS were independent predictors of overall complications, whereas only a high GM‐SCS was independently predictive of a major complication (OR 3·65; P = 0·018). Metastatic mitotic index was also an independent predictor of overall complications (OR 2·55; P = 0·047). GM‐SCS did not predict progression‐free or overall survival.
Conclusion
A gastrointestinal stromal tumour metastastectomy surgical complexity score can predict morbidity, which may help in preoperative risk stratification and optimal treatment planning.
May help treatment planning
Background
The duodenum is a rare site of primary gastrointestinal stromal tumor (GIST). Overall (OS) and disease-free survival (DFS) after limited resection (LR) versus pancreaticoduodenectomy (PD) ...were studied.
Methods
All patients who underwent surgery for primary, localized duodenal GIST between 2000 and 2011 were identified from four prospective institutional databases. OS and DFS were calculated by Kaplan–Meier method. Univariate analysis was performed.
Results
Eighty-four patients (median follow-up 42 months) underwent LR (
n
= 56, 67 %) or PD (
n
= 28, 33 %). Patients in the PD group had a larger median tumor size (7 cm vs. 5 cm,
p
= 0.024) and higher mitotic count (39 % vs. 19 % >5/50 high-power fields,
p
= 0.05). Complications were observed in five patients (9 %) in the LR group and ten patients (36 %) in the PD group. OS and DFS for the entire cohort were 89 % and 64 % at 5 years, respectively. No difference in outcome between LR and PD were observed. Eleven patients were treated with preoperative IM. A major RECIST response was obtained in nine (80 %), whereas two had stable disease. Twenty-three patients received postoperative Imatinib (IM). A trend toward a better OS in IM-treated patients could be detected only in the high-risk group.
Conclusions
Type of duodenal resection does not impact outcome. The choice should be determined by duodenal site of origin and tumor size. IM may be considered in cases at high risk of recurrence; in neoadjuvant setting, IM might facilitate resection and possibly increase the chance of preserving normal biliary and pancreatic anatomy.
The microsatellite instability (MSI) mutational pathway is critical to carcinogenesis in a small but significant proportion of colorectal cancers. While MSI is identified in most cancers in ...individuals with hereditary non-polyposis colorectal cancer, the majority of MSI tumors are found in individuals with sporadic disease. Colorectal cancers arising as a result of MSI have distinct clinicopathologic features distinguishing them from those with microsatellite stability. MSI colorectal cancers affect a larger percentage of women, are usually localized proximal to the splenic flexure, and have a higher incidence of synchronous and metachronous tumors. They are associated with a mucinous histology, tumor-infiltrating lymphocytes, a Crohn's-like inflammatory response, and a higher grade but lower stage. Overall survival is better in individuals with MSI. The benefit of chemotherapy in MSI colorectal cancers, with and without lymph node metastases, remains unclear.
The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). The standard of practice rapidly changed after the ...introduction of effective molecularly targeted therapy (such as imatinib and sunitinib) for GIST. Because of these changes, NCCN organized a multidisciplinary panel composed of experts in the fields of medical oncology, molecular diagnostics, pathology, radiation oncology, and surgery to discuss the optimal approach for the care of patients with GIST at all stages of the disease. The GIST Task Force is composed of NCCN faculty and other key experts from the United States, Europe, and Australia. The Task Force met for the first time in October 2003 and again in December 2006 with the purpose of expanding on the existing NCCN guidelines for gastrointestinal sarcomas and identifying areas of future research to optimize our understanding and treatment of GIST.
Major vascular resection performed at the time of pancreaticoduodenectomy (PD) for adenocarcinoma remains controversial. We analyzed all patients who underwent vascular resection (VR) at the time of ...PD for any histology at a single institution between 1990 and 2002. Preoperative imaging criteria for PD included the absence of tumor extension to the celiac axis or superior mesenteric artery (SMA). Tangential or segmental resection of the superior mesenteric or portal veins was performed when the tumor could not be separated from the vein. As a separate analysis, all patients who underwent PD with VR for pancreatic adenocarcinoma were compared to all patients who underwent standard PD for pancreatic adenocarcinoma. A total of 141 patients underwent VR with PD. Superior mesenteric-portal vein resections included tangential resection with vein patch (n
=
36), segmental resection with primary anastomosis (n
=
35), and segmental resection with autologous interposition graft (n
=
55). Hepatic arterial resections were performed in 10 patients, and resections of the anterior surface of the inferior vena cava were performed in 5 patients. PD was performed for pancreatic adenocarcinoma in 291 patients; standard PD was performed in 181 and VR in 110. Median survival was 23.4 months in the group that required VR and 26.5 months in the group that underwent standard PD (
P
=
0.177). A Cox proportional hazards model was constructed to analyze the effects of potential prognostic factors (VR, tumor size, T stage, N status, margin status) on survival. The need for VR had no impact on survival duration. In conclusion, properly selected patients with adenocarcinoma of the pancreatic head who require VR have a median survival of approximately 2 years, which does not differ from those who undergo standard PD and is superior to historical patients believed to have locally advanced disease treated nonoperatively.
A study was conducted to examine the effect of supplementation of rumen-protected choline chloride (RPC) on production performance and haemato-biochemical parameters of Kankrej cows. Twenty Kankrej ...cows were randomly allocated to two treatment groups: control (CON: fed basal diet without supplement) and treatment (RPC: basal diet supplemented with50 g/d/cow of RPC) from 4-weeks pre-partum through 8-weekspost-partum. Results showed that average body weights and dry matter intake were not affected (P<0.05) by the supplementation of RPC. There was significant (P<0.05)improvement in yields of milk (11.10 vs. 12.45 kg/d), FCM (10.93vs. 12.49 kg/d) and ECM (12.07 vs. 13.76 kg/d) with RPC supplementation when compared with cows fed on the control diet. The milk fat, SNF, total solids, protein and lactose contents did not differ (P>0.05) between the treatment groups. Supplementation of RPC improved feed efficiency in terms of kg of 4% FCM/kg of DMI and kg of ECM/kg of DMI in lactating cows. The higher (P<0.05) serum glucose concentration (65.72vs.62.05 mg/dL) was observed in RPC than the CON. Supplementation of RPC reduced (P<0.05) concentration of serum triglycerides (27.27 vs.31.38 mg/dL) as compared to the CON group. Other estimated blood metabolites were not influenced(P>0.05) by the supplementation of RPC. In conclusion, supplementation of 50 g/d rumen-protected choline during peripartum period improved milk production, feed efficiency and blood glucose in Kankrej cows.
PDF
