Metastatic Gastrointestinal Stromal Tumors Research Articles

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Monitoring advanced gastrointestinal stromal tumor with circulating tumor DNA.

This review explores the role of circulating tumor (ct)DNA as a biomarker for clinical decision-making and monitoring purposes in metastatic gastrointestinal stromal tumor (GIST) patients. We discuss key insights from recent clinical trials and anticipate the future perspectives of ctDNA profiling within the clinical landscape of GIST. The identification and molecular characterization of KIT/platelet-derived growth factor receptor alpha (PDGFRA) mutations from ctDNA in metastatic GIST is feasible and reliable. Such identification through ctDNA serves as a predictor of clinical outcomes to tyrosine-kinase inhibitors (TKIs) in metastatic patients. Additionally, conjoined ctDNA analysis from clinical trials reveal the evolving mutational landscapes and increase in intratumoral heterogeneity across treatment lines. Together, this data positions ctDNA determination as a valuable tool for monitoring disease progression and guiding therapy in metastatic patients. These collective efforts culminated in the initiation of a ctDNA-based randomized clinical trial in GIST, marking a significant milestone in integrating ctDNA testing into the clinical care of GIST patients. The dynamic field of ctDNA technologies is rapidly evolving and holds significant promise for research. Several trials have successfully validated the clinical utility of ctDNA in metastatic GIST, laying the foundations for its prospective integration into the routine clinical management of GIST patients.

Gastrointestinal stromal tumors : Where do we stand?

For more than 20 years gastrointestinal stromal tumors (GIST) have been aparadigm for atargeted treatment with tyrosine kinase inhibitors. Afundamental prerequisite for aneoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of ahereditary or syndromic predisposition must be considered because this results in consequences for the treatment and adifferent follow-up strategy.

Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries

Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

Safety outcomes of low versus high dose imatinib mesylate in patients with advanced, metastatic, or nonresectable gastrointestinal stromal tumors: A systematic review.

Gastrointestinal stromal tumors (GIST) are a rare cancer where tumors grow along the gastrointestinal tract. While treatment options aim towards surgical resection, some patients present with advanced metastatic and/or nonresectable diseases. The tyrosine kinase inhibitor imatinib mesylate is approved for this indication. However, dose escalation from 400 to 600 mg/d or 800 mg/d is allowed. The present study systematically evaluates the safety outcomes, particularly the incidence of grade ⩾ 3 adverse events (AEs) with low dose compared with high dose imatinib in these patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines were utilized to identify relevant studies through the PubMed, Cochrane Library, and Ovid databases and included randomized and non-randomized clinical trials comparing a low dose intervention of imatinib 400 mg/d with a high dose comparator of 600 or 800 mg/d in patients with histologically confirmed advanced metastatic and/or nonresectable GIST. Four studies were reviewed regarding study summaries and patient characteristics, patient demographics, and risk of bias, with a main emphasis on the evaluation of both efficacy outcomes and safety outcomes. Three of the four studies did not provide significant differences in response outcomes; however, all four studies reported a higher incidence of grade ⩾ 3 AEs in the high dose imatinib groups. Individual study reports of more high dose patients experiencing a grade ⩾ 3 event ranged from 0.6% to 19.8%, while combined low and high dose patient arms revealed a 17.1% difference favoring a high dose patient event. A sub-analysis of the three most frequently occurring categories, blood and lymphatic system disorders, gastrointestinal disorders, and general disorders and administration site conditions each revealed more high dose patients experiencing said category events compared to those low dose counterparts. Low dose imatinib provides clinically meaningful response and demonstrated better tolerability with less frequently reported reactions. This evidence supports further research into the maintenance of 400 mg/d for this patient population compared to a dose escalation.

Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence

We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers—GPX4, RBM4, TPM3, PFKFB2, and PGAM5—and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

Referral patterns of GIST patients: data from a nationwide study.

This study compares the characteristics, referral and treatment patterns and overall survival (OS) of gastrointestinal stromal tumor (GIST) patients treated in reference and non-reference centers in the Netherlands. This retrospective cohort study on patients diagnosed between 2016 and 2019, utilises data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database. Patients were categorized into two groups: patients diagnosed in or referred to reference centers and patients diagnosed in non-reference centers without referral. This study included 1,550 GIST patients with a median age of 67.0 in reference and 68.0 years in non-reference centers. Eighty-seven per cent of patients were diagnosed in non-reference centers, of which 36.5% (493/1,352) were referred to a reference center. Referral rates were higher for high-risk (62.2% [74/119]) and metastatic patients (67.2% [90/134]). Mutation analysis was performed in 96.9% and 87.6% of these cases in reference and in non-reference centers (p < 0.01), respectively. Systemic therapy was given in reference centers versus non-reference in 89.5% versus 82.0% (p < 0.01) of high-risk and in 94.1% versus 65.9% (p < 0.01) of metastatic patients, respectively. The proportion of positive resection margins and tumor rupture did not differ between reference and non-reference centers. Median OS was not reached. A substantial amount of metastatic GIST patients in non-reference centers did not receive systemic treatment. This might be due to valid reasons. However, optimisation of the referral strategy of GIST patients in the Netherlands could benefit patients. Further research is needed to explore reasons for not starting systemic treatment in metastatic GIST patients.

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumours

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumours

Cytoreductive surgery in patients with recurrent or metastatic gastrointestinal stromal tumors sensitive to imatinib: a retrospective analysis of two Russian cancer centers.

The role of cytoreductive surgery for patients with recurrent or metastatic gastrointestinal stromal tumors (mGISTs) responding to imatinib (IM) has not yet been established. We carried out a retrospective analysis of the outcomes of patients with mGISTs in two Russian cancer centers. We compared two cohorts: treated (Group S) or not treated with surgery (Group NS) after a partial response (PR) or stable disease (SD) while on IM. A total 44 patients treated by IM as first line treatment were included in our analysis. Prognostically similar patients only sensitive to IM cases with hepatic or peritoneal metastases as well as durable response to IM lasting more than 12 months were included in a control arm. Patients in Group NS received only IM until disease progression. Patients in Group S were treated additionally with metastasectomy after having response or SD on IM. The baseline characteristics were similar between the groups with several trends: a higher proportion of patients achieved a PR in Group S (87% vs. 55%, P=0.165), and greater number of patients had peritoneal metastases in Group NS (45% vs. 27%, P=0.759). The median time to surgery from the initiation of IM was 8 months. Progression-free survival (PFS) and overall survival (OS) were significantly longer in Group S than Group NS: the median PFS was 78 vs. 35 months (P=0.088); the median OS was 141 vs. 80 months (P=0.154). The surgical resection of residual lesions after disease control with IM is likely to be beneficial to patients with mGISTs.

Retracted: Might Patients with Metastatic Gastrointestinal Stromal Tumors Benefit from Operative Management? A Population-Based Retrospective Study.

[This retracts the article DOI: 10.1155/2022/9432410.].

Recent advances for treatment of upper gastrointestinal malignancy.

Recent prospective trials for esophageal cancer, gastric cancer, and gastrointestinal stromal tumor (GIST)are encouraging. This manuscript reviews selected recently published studies. Not surprisingly, immunotherapy dominates the current clinical trial landscape. However, targeted biologic therapies and standard chemotherapy remain critical to the treatment of gastric and esophageal cancer while imatinib remains the backbone for advanced or metastatic GISTs. For all three cancers, surgical resection remains important when intent of treatment is potential cure.

Sunitinib-induced hyperammonemic encephalopathy in metastatic gastrointestinal stromal tumors: A case report

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.

Liver resection for metastatic GIST tumor improves survival in the era of tyrosine kinase inhibitors: a systematic review and meta-analysis.

Survival for gastrointestinal stromal tumor (GIST) has been increasing over the years after the introduction of tyrosine kinase inhibitors. However, the role of metastasectomy for GIST is still controversial. Patients are currently treated with imatinib or sunitinib in case of imatinib failures as optimal medical therapy for metastatic GIST. The Pubmed, EMBASE, and Cochrane Library were systematically searched. Overall survival following liver resection ± tyrosine kinase inhibitor treatment for metastatic GIST was compared to treatment with tyrosine kinase inhibitors alone. Eleven studies including both randomized control trials and retrospective cohort studies were included in the final analysis with a total of 988 patients. Seven studies encompassed data on 556 patients with isolated liver metastases (219 surgery ± drug groups and 337 drug-only groups) were included. Overall survival was significantly improved in patients undergoing liver resection ± drug therapy in comparison to drug therapy alone. [HR (95%CI) = 2.10 (1.58, 2.79); p<0.00001]. Subgroup analysis showed that patients also had improved progression free survival based on 4 studies. [HR (95%CI) = 1.92 (1.43, 2.56); p<0.00001]. In case of concurrent liver and peritoneal metastases, patients showed improved overall survival with aggressive surgical approaches based on 10 studies. [HR (95%CI) = 1.90 (1.56, 2.31); p<0.00001]. This meta-analysis found that liver resection for patients with metastatic GIST regardless of peritoneal metastases improved progression free and overall survival in conjunction with tyrosine kinase inhibitors as compared with medical therapy alone. Furthermore, liver resections did not have any immediate detrimental impact on survival in the group of patients selected.

Comparative MIP sensor technique: photopolymerization or thermal polymerization for the sensitive determinationof anticancer drug Regorafenib in different matrixes.

Regorafenib (REG) is a diphenylurea derivative oral multikinase inhibitor. It plays an important role in the treatment of colorectal cancer, metastatic gastrointestinal stromal tumors, and hepatocellular carcinoma. Molecularly imprinted polymer (MIP) based glassy carbon electrodes (GCE) were fabricated using photopolymerization (PP) and thermal polymerization (TP) methods. The characterizations of the proposed sensors were investigated by electrochemical techniques, Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Several parameters were studied in detail for the optimum conditions of MIP-based sensors, such as dropping volume, photopolymerization and thermal polymerization durations, removal medium and time, and rebinding time. Both sensors' analytical validation and electroanalytical performance comparison were made in different REG concentrations ranging between 0.1 nM and 2.5 nM in standard solution and commercial human serum samples. The limit of detection (LOD) of PP-REG@MIP/GCE and TP-REG@MIP/GCE were 9.13 × 10-12 M and 1.44 × 10-11 M in standard solutions and 2.04 × 10-11 M and 2.02 × 10-11 M in serum samples, respectively. The applicability of the proposed sensors was tested using commercial human serum samples and pharmaceutical form of REG with high recovery values (PP-REG@MIP/GCE and TP REG@MIP/GCE sensors, 99.56-101.59%, respectively). The selectivity of the sensor for REGwas investigatedin the presence of similar molecules: Sorafenib, Sunitinib, Nilotinib, and Imatinib. The developed techniques and sensors checked the possible biological compounds and ions' effects and storage stability.

Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades.

Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by KIT or PDGFRA mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018. The primary objective was to describe the clinical and biological profiles as well as the treatment modalities of patients with metastatic GIST in a real-life setting, including access to clinical trials and LR procedures in the metastatic setting. Secondary objectives were to assess (1) patients' outcome in terms of time to next treatment (TNT) for each line of systemic treatment, (2) patients' overall survival (OS), (3) evolution of patients' treatment modalities and OS according to treatment access: <2002 (pre-imatinib approval), 2002-2006 (pre-sunitinib approval), 2006-2014 (pre-regorafenib approval), post 2014, and (4) the impact of clinical trials and LR procedures on TNT and OS in the metastatic setting. 1038 patients with a diagnosis of GIST made in one of the three participating centers between 1990 and 2018 were included in the national prospective database. Among them, 492 patients presented metastasis, either synchronous or metachronous. The median number of therapy lines in the metastatic setting was 3 (range 0-15). More than half of the patients (55%) participated in a clinical trial during the course of their metastatic disease and half (51%) underwent additional LR procedures on metastatic sites. The median OS in the metastatic setting was 83.4 months (95%CI [72.7; 97.9]). The median TNT was 26.7 months (95%CI [23.4; 32.3]) in first-line, 10.2 months (95%CI [8.6; 11.8]) in second line, 6.7 months (95%CI [5.3; 8.5]) in third line, and 5.5 months (95%CI [4.3; 6.7]) in fourth line, respectively. There was no statistical difference in OS in the metastatic setting between the four therapeutic periods (log rank, p = 0.18). In multivariate analysis, age, AFIP Miettinen classification, mutational status, surgery of the primary tumor, participation in a clinical trial in the first line and LR procedure to metastatic sites were associated with longer TNT in the first line, whereas age, mitotic index, mutational status, surgery of the primary tumor and LR procedure to metastatic sites were associated with longer OS. This real-life study advocates for early reference of metastatic GIST patients to expert centers to orchestrate the best access to future innovative clinical trials together with LR strategies and further improve GIST patients' survival.

Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Surgical treatment is recommended for the majority of localised GIST, while systemic treatment is the cornerstone of management for metastatic or unresectable disease. While a three-year regimen of imatinib is the standard of care in the adjuvant setting, there is no precise recommendation for the duration of neoadjuvant treatment, where imatinib is usually given between 4 and 12 months. Continuous treatment with imatinib at a dose of 400 mg once per day is recommended for most patients with unresectable or metastatic GIST in the first line. An exception is represented by patients with tumours harbouring the imatinib-insensitive PDGFRA D842V mutation who would be better treated with avapritinib. Targeted therapies are also recommended in the presence of NTRK rearrangements and BRAF mutations, although limited data are available. While an increase in the dose of imatinib to 800 mg is an option for the second line, sunitinib is usually considered the standard of care. Similar outcomes were reported for ripretinib in patients with tumours harbouring KIT exon 11 mutation, with significantly fewer side effects. Regorafenib and ripretinib are the standards of care in the third and fourth lines, respectively. The recent development of various systemic treatment options allows for a more personalised approach based on the molecular profile of the GIST, patient characteristics, and the profile of medications' adverse events. A multidisciplinary approach is paramount since combining systemic treatment with locoregional treatment options and supportive care is vital for long-term survival.

Cytoreductive surgery for metastatic gastrointestinal stromal tumors treated with ripretinib: A single-center experience

BackgroundCytoreductive surgery (CRS) has been advocated as an additional treatment with survival benefits for advanced gastrointestinal stromal tumor (GIST), especially in patients with responsive disease or focal progression after treatment with imatinib. Ripretinib is a fourth-line therapy for advanced GIST. This single-center pilot study investigated the short-term safety and efficacy of CRS after treatment with ripretinib in selected patients with recurrent or metastatic GIST. MethodsMedical records of patients with recurrent or metastatic GIST who underwent CRS after ripretinib in the First Affiliated Hospital of Sun Yat-sen University between June 1st, 2020 and June 1st, 2022 were retrospectively reviewed. Patients’ clinicopathological characteristics, preoperative treatment and general condition, surgical information, and postoperative management were recorded. ResultsThis study included 7 patients who underwent CRS after ripretinib. Radiographic response to ripretinib included partial response (n ​= ​1), stable disease (n ​= ​5), and progressive disease (n ​= ​1). The cumulative size of targeted lesions shrank by 4.8%–45.3% in 5 patients. R0/R1 resection was achieved in 6 (85.7%) patients. Postoperative complications (IId) were reported in 2 (28.6%) patients. There were no delayed post-operative complications. Median follow-up was 11.8 months. Median time-to-progression and median post-operative progression-free survival were not reached. Four patients who did not progress before surgery had no evidence of disease. ConclusionRipretinib combined with CRS is safe and effective in select patients with advanced GIST despite extensive prior therapy.

Gastrointestinal Stromal Tumor (GIST)

&#x0D; &#x0D; &#x0D; Gastrointestinal stromal tumor (GIST) are the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine. Although the exact prevalence of GIST is not known, GIST was recognized as tumor it's arise from interstitial cells of Cajal. Most of the GISTs driven by a KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation. Histologically, GISTs look like spindle cell tumors most of the time, but they can be epitheoid or mixed type. Clinically, patients with small GISTs remain asymptomatic. In another case, patients with larger GISTs present with various symptoms depending on the location of the GISTs. Most of GISTs are located in the stomach or small bowel. But, they can involve almost any segment of the gastrointestinal tract from distal esophagus to anus. Diagnosis is suspected on imaging and endoscopic studies, and confirmed by tissue acquisition with immunohistochemical staining. The various endoscopic modalities of resection are increasingly tried. Surgical resection is the treatment of choice. In management of larger GISTs, tyrosine kinase inhibitors are extremly useful. Treatment options for metastatic GISTs also include radiotherapy, chemotherapy, hepatic artery embolization, chemoembolization, and radiofrequency ablation.&#x0D; &#x0D; &#x0D;

Applicability of fluorescamine as a fluorogenic reagent for highly sensitive fluorimetric analysis of the tyrosine kinase inhibitor (avapritinib) in pharmaceuticals and biological samples.

Avapritinib (AVP) was the first precision drug to be approved by the US Food and Drug Administration (FDA) in 2020 for patients suffering from metastatic gastrointestinal stromal tumors (GISTs) and progressive systemic mastocytosis. The analysis of AVP in pharmaceutical tablets and human plasma was then carried out using a fast, efficient, sensitive, and simple fluorimetric method using a fluorescamine reagent. The procedure is based on the interaction between fluorescamine as a fluorogenic reagent and the primary aliphatic amine moiety in AVP using borate buffer solution at pH8.8. The produced fluorescence was measured at 465 nm (Excitation at 395 nm). The calibration graph's linearity range was discovered to be 45.00-500.0ng mL-1 . Utilizing the International Council for Harmonization (ICH) and US-FDA recommendations, the research technique was validated and bioanalytically validated. The proposed approach was effectively employed for determining the stated pharmaceuticals in plasma with a high percentage of recovery ranging from 96.87 to 98.09 and pharmaceutical formulations with a percentage of recovery equal to 102.11% ± 1.05%. In addition, the study was extended to a pharmacokinetic study of AVP with 20 human volunteers as a step for AVP management in therapeutic cancer centers.

Cytoreductive surgery offers prognostic benefits in metastatic gastrointestinal stromal tumors with generalized progression following imatinib therapy: a single institute retrospective study

BackgroundGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Distant metastasis has been detected in approximately 50% of GIST patients at the first diagnosis. The surgical strategy for metastatic GIST with generalized progression (GP) after imatinib therapy remains unclear.MethodsWe recruited 15 patients with imatinib-resistant metastatic GIST. They received cytoreductive surgery (CRS) for tumor rupture, intestinal obstruction and gastrointestinal bleeding. We collected clinical, pathological and prognostic data for analyses.ResultsOS and PFS after R0/1 CRS were 56.88 ± 3.47 and 26.7 ± 4.12 months, respectively, when compared with 26 ± 5.35 and 5 ± 2.78 months after R2 CRS (P = 0.002 and P < 0.001, respectively). The OS of patients from the initiation of imatinib in the R0/1 group was 133.90 ± 15.40 months when compared with 59.80 ± 10.98 months in the R2 CRS group. There were two significant grade III complications after 15 operations (13.3%). No patient underwent reoperation. In addition, no perioperative death occurred.ConclusionsR0/1 CRS is highly probable to provide prognostic benefits for patients with metastatic GIST who experience GP following imatinib treatment. An aggressive surgical strategy for achieving R0/1 CRS can be deemed safe. If applicable, R0/1 CRS should be carefully considered in imatinib-treated patients with GP metastatic GIST.