Gastrointestinal Stromal Tumor (GIST)

Localized resectable GISTs can be cured with surgical resection, but no effective therapy had been established for patients with unresectable and/or metastatic GISTs and their prognosis was extremely poor before the advent of imatinib. Imatinib mesylate is an oral tyrosine-kinase inhibitor (TKI) with activity against KIT, PDGFRA, ABL, and DDR. The efficacy of imatinib was first shown in the pivotal B2222 trial and confirmed by two subsequent randomized phase III trials. The standard dose of imatinib was established as a 400mg once daily dose upfront high-dose imatinib treatment with a 800mg daily dose showed a higher efficacy in terms of progression-free survival (PFS) in patients with GISTs harboring KIT exon 9 mutations but also higher toxicity. The median time-to-progression (TTP) with imatinib was about 2 years in the extended follow-up results of the B2222 trial. Imatinib efficacy correlates with primary KIT mutations and patients with KIT exon 9 mutations had worse survival outcomes than those with KIT exon 11 mutations. Surgical resection is the mainstay of the treatment of localized GIST. However, in a proportion of patients, a high recurrence rate was observed, which prompted the investigation of the clinical efficacy of adjuvant imatinib treatment. The ACOSSOG Z9001 study showed that one year of adjuvant imatinib treatment after surgical resection in patients with a tumor size of 3cm of larger improved recurrence-free survival compared to placebo. This study was the first to demonstrate the efficacy of adjuvant imatinib treatment. Subsequently, SSG XVIII/AIO study showed that 3 years of adjuvant imatinib improved recurrence-free survival and overall survival compared to one year of adjuvant imatinib in High risk patients defined by modified NIH criteria. Based on this study in patients classified as high risk by the modified NIH criteria, 3 years adjuvant imatinib is the standard of care. However, given that a substantial proportion of such patients show disease recurrence, the PERSIST5 study recently showed that 5 years of imatinib treatment may further reduce the recurrence. In addition, clinical outcomes of the patients classified as high risk by the modified NIH criteria are heterogeneous, and some of these patients show particularly poor clinical outcomes. The investigators analyzed the clinical outcomes of 222 high risk GIST patients who received 3 years of adjuvant imatinib treatment following surgical resection. Among these, patients with tumor rupture defined by Nishida classification or those with a tumor size 10cm or larger and a mitotic index of 10/50HPFs or higher had poor clinical outcomes with a 5-year recurrence-free survival of 50%. In this study, the investigators aim to investigate the efficacy and safety of 5 years of adjuvant imatinib treatment in patients with tumor rupture defined by Nishida classification or those with a tumor size 10cm or larger and a mitotic index of 10/50HPFs or higher.

The purpose of this study is to examine the safety and efficacy of an abbreviated course of preoperative radiation, given over five days, for patients with soft tissue sarcoma of the extremity, trunk or retroperitoneum. This is in contrast to standard preoperative radiation, which is given over 25 days.

PRIMARY OBJECTIVE: I. To assess the feasibility and capability of gallium Ga 68-HA-DOTA-TATE (68Ga-DOTATATE) digital positron emission tomography (dPET)/ computed tomography (CT) imaging for soft tissue sarcomas. SECONDARY OBJECTIVES: I. To evaluate the clinical benefit of 68Ga-DOTATATE for a comprehensive assessment of soft tissue sarcomas (STS) using next-generation digital PET detector technology. II. To describe the perfusion and early tumor uptake kinetics of tumor targets at baseline and following conventional systemic therapy using both 68Ga-DOT AT A TE dPET/CT and 18F-FDG dPET/CT approaches. III. Using list-mode dPET acquisitions following standard 68Ga-DOTATATE dose administrations, imaging datasets will be retrospectively generated to simulate lower dose or faster image acquisition in order to define further the minimum 68Ga-DOTATATE dose and PET image acquisition times needed to maintain lesion detectability and PET quantification. V. To assess the feasibility for 68Ga-DOTATATE dPET/CT to identify and stratify STS patients with SSTR2-positive soft tissue sarcoma lesions for future therapy planning using 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) for patients with 68Ga-DOTATATE-avid sarcomas. VI. To assess the safety of 68Ga-DOTATATE in this patient population. OUTLINE: Patients receive gallium Ga 68-HA-DOTA-TATE intravenously (IV) and undergo dPET/CT over 60 minutes up to two weeks after starting standard chemotherapy. Beginning 24 hours after gallium Ga 68-HA-DOTA-TATE dPET/CT, patients also receive fludeoxyglucose F-18 IV and undergo dPET/CT over 60 minutes.

Platelet-derived growth factor receptor α (PDGFRα) is expressed on soft tissue sarcoma (STS) where it could act as a potential therapeutic target. Olaratumab is a PDGFRα-targeted antibody that has the potential to act as the targeting moiety for both imaging and therapeutic radioisotopes. Olaratumab's demonstrated safety profile and its ability to target PDGFRα on STS cell surfaces and be rapidly internalised, make it a promising candidate for use as a radionuclide targeting agent in STS. 89Zr-TLX300-CDx is being developed for PDGFRα molecular imaging with positron emission tomography (PET) in STS. The aim of this study is to provide proof-of-concept tumour targeting of 89Zr-TLX300-CDx and assess the safety and radiation dosimetry of radiolabelled olaratumab. This study will inform future development of olaratumab as a therapeutic radiopharmaceutical agent in STS. SCHEDULE OF ASSESSMENTS Part A and B: IMAGING: 1 single injection of 89Zr-TLX300-CDx on Day 1 and whole-body imaging at 6 days ± 1 day post-injection Blood Collection for PHARMACOKINETICS: Pre-injection, 4h ± 0.5h and 6 days ± 1 day post-injection. OPTIONAL: Imaging at 4h ± 0.5h post-injection. Part C: IMAGING: 1 single injection of 89Zr-TLX300-CDx on Day 1, whole-body imaging at 24h ± 4h post-injection, whole-body imaging at 4 days ± 1 post-injection and whole-body imaging at 7 days ± 1 day post-injection Blood collection for PHARMACOKINECTCS: Pre-injection, 4h ± 0.5h, 24h ± 4h, 4 days ± 1 day and 7 days ± 1 day post-injection. OPTIONAL: Dynamic imaging 15 min ± 2 min post-injection at selected sites (extended field-of-view scanner is available), imaging at 4h ± 0.5h post-injection and imaging at 7h ± 1hpost-injection

The goal of this clinical trial is to learn if a new type of scan, FAPI-PET/CT, can help find metastases of gastric cancer. We want to know how well this scan works for this purpose and whether it is less burdensome for patients compared to the methods we currently use to find metastases. The main questions it aims to answer are: * In how many patients can FAPI-PET/CT find metastases, which leads to a change in their treatment plan as decided by their medical team, such as avoiding unnecessary surgeries and changing from treatment meant to cure the disease to treatment focused on comfort (palliative treatment)? * In how many patients does FAPI-PET/CT change the diagnostic process as decided by their medical team, like more biopsies or imaging, or changing the type (extent) of surgery needed? Apart from the usual care gastric cancer patients receive, participants will: * Undergo one additional scan, which will take approximately 2 hours in total (excluding travel time) * Complete a number of questionnaires, which will take approximately 4 hours in total

9 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with advanced bone and soft tissue tumors.

Primary Objective 1. To evaluate tumour ablation in tumours and/or tumour segments following one or more treatments with tigilanol tiglate; and 2. To evaluate the effect of tigilanol tiglate on overall disease control (not limited to injected tumours) (Stage 2 only). Secondary Objective 1. To assess the safety and tolerability of intratumoural injections with tigilanol tiglate; and 2. To evaluate systemic exposure through pharmacokinetic (PK) assessment after a single intratumoural injection of tigilanol tiglate. Exploratory Objectives 1. To evaluate the microenvironment of injected tumours +/- non-injected tumours; 2. To evaluate the degree of immune response elicited with intratumoural tigilanol tiglate; 3. To evaluate local recurrence rate; 4. To evaluate Progression Free Survival (PFS) (Stage 2 only); and 5. To evaluate metabolites after a single intratumoural injection of tigilanol tiglate (Stage 2 only).

There is a lack of high-quality evidence on the efficacy and safety of laparoscopic resection of gastric GIST over 5cm. A multicenter, prospective cohort study was conducted to evaluate the clinical efficacy of laparoscopic resection of 5cm or larger gastric gastrointestinal stromal tumors (GIST) compared to laparoscopic resection of GIST of less than 5cm. The primary evaluation parameter is overall postoperative morbidity.

Patients with peritoneal metastases from colorectal and appendix cancer are treated with cytoreductive surgery and HIPEC. However, several patients are considered unresectable due to the inability to remove all the cancer safely. Repeated (Iterative) intra-peritoneal chemotherapy delivered via HIPEC laparoscopically has been shown to have favorable outcomes with a potential increase in sensitivity to immunotherapy . Such procedures often use chemotherapy that is not tailored to the patients cancer. In this study, patients with unresectable colorectal and appendiceal peritoneal metastases will undergo MRT on tissue biopsies to determine optimal chemotherapy regimen to be delivered intraperitoneally. For patients with unresectable disease, iterative HIPEC (IHIPEC) will be administered starting three weeks after the laparoscopy. (IHIPEC refers to HIPEC followed by systemic chemotherapy repeated 3 times with approximately 6 weeks in between each HIPEC.)

Primary Objective: 1. Part A. Determine the safety, maximum tolerated dose and/or recommended phase 2 dose of adoptively transferred T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells in combination with cyclophosphamide in patients with advanced/metastatic soft tissue or bone sarcomas 2. Part B. Characterize the safety and tolerability and assess preliminary efficacy of attIL12-armed T cells in combination with cyclophosphamide by evaluating the 4-month disease control rate (DCR4 months) in patients with recurrent unresectable osteosarcoma Secondary Objectives: 1\. Evaluate the anti-tumor efficacy achieved following adoptive transfer of T cellmembrane-anchored tumor targeted IL12 (attIL12)-T cells in combination with cyclophosphamide in patients with advanced/metastatic soft tissue or bone sarcomas Exploratory Objectives: 1. Characterize the immune response following adoptive transfer of T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells in paired in pre-treatment and on-treatment tumor specimens and peripheral blood samples 2. Assess FoxP3/CD33/CD8/IFNg expression in pre-treatment and on-treatment tumor specimens and correlate with clinical benefit/anti-tumor response 3. Determine changes in cell surface vimentin (CSV)-positive circulating tumor cells (CTCs) in peripheral blood before and after adoptive transfer of T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells and correlate with clinical benefit/anti-tumor response