Unresectable Malignant Tumors Research Articles

Impact of Hepatoblastoma on Infectious Complications Following Pediatric Liver Transplantation.

Liver transplantation is the standard therapy for end-stage liver disease in pediatric patients with biliary atresia (BA), congenital and metabolic conditions, and for an unresectable malignant tumor like hepatoblastoma (HB). BA is the leading indication for pediatric liver transplantation, while HB is the most common childhood liver cancer. Despite improved outcomes through advanced surgical techniques and novel immunosuppression, pediatric liver transplantation (pLT) is complicated by post-transplant infections. A retrospective review was performed of pLT recipients at Cincinnati Children's Hospital Medical Center (CCHMC) and stratified patients by underlying disease to assess impact on post-transplant infectious events. BA patients were youngest at pLT (12.5 months; p < 0.001) compared to other disease cohorts (HB 30.8, other 43.7). All HB patients received organs from deceased donors. In the year following pLT, 93% of the patients experienced at least one infectious event (IE). HB patients had the highest mean number of IE across disease groups (5.5 IE/patient vs. BA 4.5, other 4.0; p = 0.055), with significantly more patients with fever and neutropenia (p < 0.001) and EBV infections (p = 0.012). HB patients were more likely to develop IE earlier after pLT than non-HB groups (p = 0.013), especially Clostridioides difficile (p < 0.01) and fever and neutropenia (p < 0.01). Despite having variable IE experiences, 1-and-5-year survival across disease groups were similar. IE were frequently observed in HB patients after pLT, possibly related to pre-and-postoperative chemotherapy and associated neutropenia. Underlying disease may help inform targeted infection-related patient management following pLT.

Effectiveness of palliative photodynamic therapy for unresectable biliary cancer. Systematic review and meta-analysis

A systematic review and meta-analysis was aimed to assess the effectiveness of palliative photodynamic therapy for unresectable malignant tumors of the biliary system in order to justify the feasibility of including photodynamic therapy (PDT) in the complex treatment of this category of patients. Publications in the databases PubMed Central, the bibliographic database of scientifi citations of the RSCI, and the Cochrane library were considered. Heterogeneity was assessed graphically using forest plots and statistically using tau2 and I2 statistics. A meta-analysis of 5-year survival revealed a statistically signifiantly longer pooled estimate of the survival period in groups where PDT was used – 339±161 days (95% CI 25-710; p &lt; 0.001) compared to groups where PDT was not used – 83±16 days (95% CI 33-100; p &lt; 0.001). Heterogeneity among studies was found to be statistically insignifiant (I2 = 29%, p = 0.23). A meta-analysis of the risk difference for adverse events revealed a statistically signifiantly lower risk (-0.2306; 95% CI -0.3917-0.0696; p = 0.005) of adverse events after PDT compared with the comparison group. Heterogeneity among studies was found to be statistically insignifiant (I2 = 0%, p = 0.35). There were no signifiant publication biases in either meta-analysis. The presented meta-analysis demonstrated that PDT may be the method of choice in the palliative complex treatment of patients with unresectable cholangicarcinomas, increasing the ˝ve-year survival of patients along with the absence of increased risks of postoperative complications in comparison with other methods of palliative surgical treatment.

FLASH Radiotherapy: Mechanisms of Biological Effects and the Therapeutic Potential in Cancer.

Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation therapy research, is an ultra-high dose rate treatment known for significantly reducing therapy time while effectively targeting tumors. This approach minimizes radiation side effects on at-risk organs and maximally protects surrounding healthy tissues. Despite decades of preclinical exploration and some notable achievements, the mechanisms behind FLASH effects remain debated. Standardization is still required for the type of FLASH-RT rays and dose patterns. This review addresses the current state of FLASH-RT research, summarizing the biological mechanisms behind the FLASH effect. Additionally, it examines the impact of FLASH-RT on immune cells, cytokines, and the tumor immune microenvironment. Lastly, this review will discuss beam characteristics, potential clinical applications, and the relevance and applicability of FLASH-RT in treating advanced cancers.

The safety and short-term efficacy of selective internal radiation therapy combined with systemic treatment for unresectable malignant hepatic tumors in Chinese patients.

e16247 Background: There are many systemic treatment options for patients with unresectable malignant hepatic tumors. In China, selective internal radiation therapy (SIRT) with yttrium-90 (Y90) resin microspheres was approved until 2022. The aim of this retrospective study was to investigate the safety and short-term efficacy of SIRT with Y90 resin microspheres followed by systemic treatment in Chinese patients. Methods: The study analyzed patients who received SIRT with Y90 combined with systemic treatment at our center between June 2022 and October 2023. The study's primary endpoint was to determine the objective response rate (ORR), while safety was the secondary endpoint. Response was measured based on modified Response Evaluation Criteria in Solid Tumors criteria (mRECIST) up to 90 days after the initial therapy. Safety was evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Results: 21 patients wereincluded, of whom 22 times of SIRT were performed. 18 patients had HCC, and 3 had mCRC.The baseline characteristics of the patients are shown in Table. The median age was 54 years (IQR, 48-59 years) and 90.5% of patients were male. According to Eastern Cooperative Oncology Group performance status, grade 0 and grade 1 were 81% and 19%, respectively, whereas Child-Pugh A represented 90.5% of cases. The proportion of patients with hepatitis B virus infection was 95.2%. Thirteen (61.9%) patients received different treatments before SIRT. The median number of tumors was 2.5 (IQR, 1-4.3), whereas the median diameter of the largest lesion was 100.4 mm (IQR, 68.3-127.7 mm). PVTT was classified as follows: Vp1 (n = 3), Vp2 (n = 2), Vp3 (n = 2) and Vp4 (n = 1). Median AFP was 33.2 ng/mL (IQR, 5.9-401 ng/mL). The median total radiation activity administered was 1.4 GBq (IQR, 0.9-2.7 GBq) and the median target tissue dose was 205 Gy (IQR, 155-242 Gy). Nine (43%) patients were downstaged to surgery. Four (19%) patients had a complete response, fifteen (71.4%) had a partial response and two (9.5%) had a progressive disease. ORR and disease control rate were 90.5% and 90.5%, respectively. None of the patients experienced grade 3 and higher adverse events. The most common treatment-related adverse events were fever and abdominal pain, which required no special treatment. Conclusions: SIRT with Y90 resin microspheres combined with systemic treatment is safe and effective in patients with unresectable malignant hepatic tumors, which resulted in encouraging ORR (90.5%) and a downstaging rate (43%). Clinical trial information: ChiCTR2300077524. [Table: see text]

Phase I dose escalation study and pilot efficacy analysis of LXI-15029, a novel mTOR dual inhibitor, in Chinese subjects with advanced malignant solid tumors

BackgroundThe mammalian target of rapamycin (mTOR) kinase, a central component of the PI3K/AKT/mTOR pathway, plays a critical role in tumor biology as an attractive therapeutic target. We conducted this first-in-human study to investigate the safety, pharmacokinetics (PK), and pilot efficacy of LXI-15029, an mTORC1/2 dual inhibitor, in Chinese patients with advanced malignant solid tumors.MethodsEligible patients with advanced, unresectable malignant solid tumors after failure of routine therapy or with no standard treatment were enrolled to receive ascending doses (10, 20, 40, 60, 80, 110, and 150 mg) of oral LXI-15029 twice daily (BID) (3 + 3 dose-escalation pattern) until disease progression or intolerable adverse events (AEs). The primary endpoints were safety and tolerability.ResultsBetween June 2017 and July 2021, a total of 24 patients were enrolled. LXI-15029 was well tolerated at all doses. Only one dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in the 150 mg group, and the maximum tolerated dose was 110 mg BID. The most common treatment-related AEs were leukocytopenia (41.7%), increased alanine aminotransferase (20.8%), increased aspartate aminotransferase (20.8%), prolonged electrocardiogram QT interval (20.8%), and hypertriglyceridemia (20.8%). No other serious treatment-related AEs were reported. LXI-15029 was absorbed rapidly after oral administration. The increases in the peak concentration and the area under the curve were greater than dose proportionality over the dose range. Eight patients had stable disease. The disease control rate was 40.0% (8/20; 95% CI 21.7–60.6). In evaluable patients, the median progression-free survival was 29 days (range 29–141).ConclusionsLXI-15029 demonstrated reasonable safety and tolerability profiles and encouraging preliminary antitumor activity in Chinese patients with advanced malignant solid tumors, which warranted further validation in phase II trials.Trial registrationNCT03125746(24/04/2017),http://ClinicalTrials.gov/show/NCT03125746

In vivo total or partial hepatectomy followed by ex vivo liver resection and autotransplantation for malignant tumors: a single center experience.

Ex vivo liver resection and autotransplantation (ELRAT) may provide an opportunity for R0 resection of conventionally unresectable hepatobiliary cancers and hepatic metastases. To date, few studies of the surgery for malignant tumors have been conducted and there are no known reports of in vivo partial hepatectomy followed by ELRAT (IPH-ELRAT) for malignant tumors. Between December 2021 and November 2022, ten patients with malignant hepatobiliary primary cancers or hepatic metastases underwent ELRAT at our institution. We shared the surgical skills and postoperative prognoses of these patients were assessed. The types of tumors were biliary tract cancer (BTC, n=8), hepatic metastasis of colonic carcinoma (n=1), and hepatic metastasis of small-bowel stromal tumor (n=1). Five patients underwent in vivo total hepatectomy followed by ex vivo liver resection and autotransplantation (ITH-ELRAT), The other five received in vivo partial hepatectomy followed by ex vivo liver resection and autotransplantation (IPH-ELRAT). Four patients underwent inferior vena cava replacement using artificial blood vessels. The survival rate of all ten patients one month after surgery was 100%. Nine patients (90%) are currently alive, with a median follow-up of 8.5 months (range 6-16.5 months). To date, seven of the nine surviving patients have had no cancer recurrence, including six with BTC. We report the world first five cases that received IPH-ELRAT for malignancies. We also demonstrated relatively favorable outcomes in patients who underwent ELRAT. ELRAT may be a recommendable surgical option for selected patients with conventionally unresectable hepatobiliary malignant tumors.

Abstract 5484: Synergistic antitumor activity of nab-sirolimus in combination with KRAS inhibitors (KRASis) sotorasib and adagrasib in KRAS G12C NSCLC and bladder cancer xenografts

Abstract KRAS is frequently mutated in non-small cell lung cancer (NSCLC) and other tumor types, with KRAS G12C mutation representing ~12% of patients with NSCLC. Sotorasib (sot) is approved and adagrasib (ada) is under review for the treatment of KRAS G12C NSCLC. Mutations in KRAS may lead to mTORC1 activation, and mTOR may contribute to adaptive resistance to KRASis. nab-Sirolimus (nab-S) is a novel albumin-bound nanoparticle form of the mTOR inhibitor sirolimus approved for the treatment of locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors. This study investigated the antitumor activity of nab-s in combination with KRASis in KRAS G12C NSCLC and bladder xenograft models. Athymic mice bearing subcutaneous KRAS G12C- and STK11-mutant NCI-H2030 and NCI-H2122 NSCLC and KRAS G12C and PTEN-null UMUC3 bladder cancer were treated for 6 weeks with nab-s IV at 15 mg/kg/wk, sot or ada (for NCI-H2122 and UMUC3) orally at 30 mg/kg/d alone or in combination. Tumor samples were harvested for analysis of tumor drug levels and biomarkers. In all 3 models tested, single-agent (SA) nab-s or KRASis overall showed modest tumor growth suppression. In contrast, nab-s in combination with either sot or ada showed greater tumor growth inhibition and a higher meaningful tumor regression rate vs SA (Table). There was no significant difference in antitumor activity between combinations of nab-s with either sot or ada. High trough intertumoral sirolimus levels were observed in groups treated with nab-s alone or in combination with KRASis, indicating sustained presence of sirolimus in the tumor. nab-S in combination with either sot or ada showed synergistic antitumor activity compared to the SA. A multicenter, single-arm, open-label Phase 1/2 clinical study is planned to determine the recommended Phase 2 dose, safety, tolerability, and efficacy for the combination of ada and nab-s in patients with KRAS G12C tumors. Changes in TGI and Tumor Regression Tumor Model Combination Treatment TGI vs Single Agent (%) P Value vs Single Agent for Tumor Growth Curve (ANOVA) Tumor Regression Over 30% P Value vs Single Agents for Rate of Tumor Regression Over 30% (Chi-Square) vs nab-S vs KRASi vs nab-S vs KRASi NCI-H2030 nab-S + Sotorasib 129 111 0.01 0.001 3/6 0.03 NCI-H2122 nab-S + Sotorasib 112 106 0.001 &amp;lt;0.001 8/10 &amp;lt;0.001 nab-S + Adagrasib 101 100 0.001 &amp;lt;0.001 4/10 0.03 UMUC3 nab-S + Sotorasib 107 105 &amp;lt;0.001 &amp;lt;0.001 6/6 &amp;lt;0.001 nab-S + Adagrasib 107 107 &amp;lt;0.001 0.04 6/6 0.001 ANOVA, analysis of variance; KRASi, KRAS inhibitor; nab-s, nab-sirolimus; TGI, tumor growth inhibition. Citation Format: Shihe Hou, Andrew Kwon, Jorge Nieva, Neil Desai. Synergistic antitumor activity of nab-sirolimus in combination with KRAS inhibitors (KRASis) sotorasib and adagrasib in KRAS G12C NSCLC and bladder cancer xenografts. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5484.

Characteristic cerebrospinal fluid findings in immune checkpoint inhibitor-related peripheral neuropathy: A case report

Although immune checkpoint inhibitors (ICIs) are widely used to treat unresectable malignant tumors, they can cause undesirable side effects called immune-related adverse events, including neurological toxicities. Here, we describe a case of ICI-related peripheral neuropathy (irPN) with characteristic cerebrospinal fluid (CSF) findings. In addition to pleocytosis and increased protein levels, the present case showed increased levels of CSF soluble interleukin-2 receptor (sIL-2R), IL-6, and IL-10, suggesting activated T cell-related autoimmunity. We believe that CSF cytokines and sIL-2R could be novel biomarkers of irPN.

Gastric cancer and genomics: review of literature

Gastric cancer (GC) is a major health concern in many countries. GC is a heterogeneous disease stratified by histopathological differences. However, these variations are not used to determine GC management. Next-generation sequencing (NGS) technologies have become widely used, and cancer genomic analysis has recently revealed the relationships between various malignant tumors and genomic information. In 2014, studies using whole-exome sequencing (WES) and whole-genome sequencing (WGS) for GC revealed the entire structure of GC genomics. Genomics with NGS has been used to identify new therapeutic targets for GC. Moreover, personalized medicine to provide specific therapy for targets based on multiplex gene panel testing of tumor tissues has become of clinical use. Recently, immune checkpoint inhibitors (ICIs) have been used for GC treatment; however, their response rates are limited. To predict the anti-tumor effects of ICIs for GC and to select patients suitable for ICI treatment, genomics also provides informative data not only of tumors but also of tumor microenvironments, such as tumor-infiltrating lymphocytes. In therapeutic strategies for unresectable or recurrent malignant tumors, the target is not only the primary lesion but also metastatic lesions, and metastatic lesions are often resistant to chemotherapy. Unlike colorectal carcinoma, there is a heterogeneous status of genetic variants between the primary and metastatic lesions in GC. Liquid biopsy analysis is also helpful for predicting the genomic status of both primary and metastatic lesions. Genomics has become an indispensable tool for GC treatment and is expected to be further developed in the future.

Novel Insights on Lipid Metabolism Alterations in Drug Resistance in Cancer

Chemotherapy is one of the primary treatments for most human cancers. Despite great progress in cancer therapeutics, chemotherapy continues to be important for improving the survival of cancer patients, especially for those who has unresectable metastatic tumors or fail to respond to immunotherapy. However, intrinsic or acquired chemoresistance results in tumor recurrence, which remains a major obstacle in anti-cancer treatment. The high prevalence of chemoresistant cancer makes it urgent to deepen our understanding on chemoresistance mechanisms and to develop novel therapeutic strategies. Multiple mechanisms, including drug efflux, enhanced DNA damage reparability, increased detoxifying enzymes levels, presence of cancer stem cells (CSCs), epithelial mesenchymal transition (EMT), autophagy, ferroptosis and resistance to apoptosis, underlie the development of chemoresistance. Recently, accumulating evidence suggests that lipid metabolism alteration is closely related to drug resistance in tumor. Targeting lipid metabolism in combination with traditional chemotherapeutic drugs is a promising strategy to overcome drug resistance. Therefore, this review compiles the current knowledge about aberrant lipid metabolism in chemoresistant cancer, mainly focusing on aberrant fatty acid metabolism, and presents novel therapeutic strategies targeting altered lipid metabolism to overcome chemoresistance in cancer.

Hypothyroidism and hypopituitarism as immune-related adverse events due to lenvatinib plus pembrolizumab therapy in the immediate postoperative period after laparoscopic hepatectomy for liver metastases from gastric cancer: a case report

BackgroundImmune checkpoint inhibitors (ICIs) are emerging agents used for the treatment of various malignant tumors. As ICIs are generally used for unresectable malignant tumors, there have been only a few reports of patients who underwent surgery after receiving these drugs. Therefore, it remains unclear how immune-related adverse events (irAEs) affect the postoperative course. Here, we report a patient with advanced gastric cancer who underwent laparoscopic hepatectomy for liver metastases after an objective response with lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism as irAEs in the immediate postoperative period.Case presentationA 73-year-old man had undergone total gastrectomy for pT4aN2M0 gastric cancer followed by adjuvant chemotherapy with S-1 and docetaxel, and developed liver metastases in segments 6 and 7. He was enrolled in phase 2 clinical trial of lenvatinib plus pembrolizumab. He continuously achieved a partial response with the study treatment, and the liver metastases were decreased in size on imaging. The tumors were judged to be resectable and the patient underwent laparoscopic partial hepatectomy for segments 6 and 7. From the 1st postoperative day, the patient continuously presented with fever and general fatigue, and his fasting blood glucose level remained slightly lower than that before the surgery. On the 4th postoperative day, laboratory examination revealed hypothyroidism and hypopituitarism, which were suspected to be irAE caused by lenvatinib plus pembrolizumab after surgery. He received hydrocortisone first, followed by levothyroxine after adrenal insufficiency was recovered. Subsequently, his fever, general fatigue, and any abnormality regarding fasting blood glucose level resolved, and he was discharged on the 12th postoperative day. After discharge, his laboratory data for thyroid and pituitary function remained stable while receiving hydrocortisone and levothyroxine without recurrence of gastric cancer.ConclusionWe present a case of laparoscopic hepatectomy after receiving lenvatinib plus pembrolizumab and developed hypothyroidism and hypopituitarism after surgery. Regarding surgery after ICI therapy, it is important to recognize that irAEs might occur in the postoperative period.

An Auto-Contouring Method for Kidney Using a Novel Semi-Supervised Leaning Extreme Learning Machine Method

Background: Adaptive radiation therapy planning requires contour segmentation of dangerous organs in medical images. However, manual contour rendering is the most time-consuming and laborious work in radiotherap planning. In order to solve this problem, we propose a novel semi-supervised leaning extreme learning machine (SSL-ELM) method to realize abdominal Magnetic Resonance Imaging (MRI) guided Adaptive Radiation Therapy (MR-ART) automatic contour rendering. Method/Material: Our algorithm is based on the assumption that data within the same class are close to each other. We use this heuristic method to improve the ELM algorithm. The experimental results show that our proposed method outperforms existing classification algorithms. We used a data set of eight patients with unresectable abdominal malignant tumors recruited by professionals approved by the Cleveland Medical Center Institution Review Board. Each group included MRI and airborne T1MRI with randomly selected treatment phases. Each MRI consisted of 16 slices with a resolution of 370×370 pixels. Manual and automatic contours of the kidney were compared using Dice similarity index (DSI). Results: The proposed SSL-ELM algorithm has better performance than most classification algorithms, and the experimental results also show that the DSI values are above 0.87, with some samples reaching 0.99.

Debulking surgery for malignant tumors: the current status, evidence and future perspectives.

Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.

Clinical Usefulness of a Modified Mohs' Technique and Topical Application of Zinc Oxide Powder for Treating Skin Infiltration Caused by Unresectable Malignant Tumors.

Background: Infiltrative lesions of the skin caused by unresectable malignant tumors reduce the quality of life of patients significantly due to the presence of bleeding, exudate, pain, and/or malodor.Objective: We compared the efficacy of a modified Mohs' technique and topical application of a starch powder containing zinc oxide as palliative treatments for skin lesions caused by unresectable tumors in our hospital.Design: This is a retrospective study.Settings/Subjects: This study included nine patients who were treated for skin-infiltrating lesions caused by unresectable malignant tumors at our hospital in Japan from April 2008 to December 2019.Measurements: Mohs' paste or zinc oxide powder (50%) was applied to the infiltrative skin lesions. Arterial embolization was performed before the application of the Mohs' paste for patients at risk for arterial hemorrhage. Patients were evaluated for pain, tumor size, bleeding, wound exudate, and malodor.Results: Both treatments were useful for alleviating symptoms, such as tumor size, local bleeding, malodor, and exudate in patients with unresectable malignant tumors. Pain was reduced in patients treated with Mohs' paste for 1 hour as compared with those treated for 24 hours.Conclusions: Effective management of skin infiltrative lesions can be achieved by using a modified Mohs' technique, topical application of starch powder containing zinc oxide, and arterial embolization to reduce the vascularization of the tumors.

Applications of Recombinant Adenovirus-p53 Gene Therapy for Cancers in the Clinic in China.

Suppression of TP53 function is nearly ubiquitous in human cancers, and a significant fraction of cancers have mutations in the TP53 gene itself. Therefore, the wild-type TP53 gene has become an important target gene for transformation research of cancer gene therapy. In 2003, the first anti-tumor gene therapy drug rAd-p53 (recombinant human p53 adenovirus), trade name Gendicine™, was approved by the China Food and Drug Administration (CFDA) for treatment of head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy. The recombinant human TP53 gene is delivered into cancer cells by an adenovirus vector constructed to express the functional p53 protein. Although the only currently approved used of Gendicine is in combination with radiotherapy for treatment of HNSCC, clinical studies have been carried out for more than 20 other applications of Gendicine in treating cancer, including treatment of advanced lung cancer, advanced liver cancer, malignant gynecological tumors, and soft tissue sarcomas. Currently more than 30,000 patients have been treated with Gendicine. This review provides an overview of the clinical applications of Gendicine in China. We summarize a total of 48 studies with 2,561 patients with solid tumors, including 34 controlled clinical studies and 14 open clinical studies, i.e., clinical studies without a control group. There are 11 studies for head and neck cancer, 10 for liver cancer, 6 for malignant gynecological tumors, 4 for non-small cell lung cancer, 4 for soft tissue sarcoma, 4 for malignant effusion, 2 for gastrointestinal tumors, and 7 for other types of cancer. In all the reported clinical studies, the most common side effect was self-limited fever. Intratumoral injection and intra-arterial infusion were the most common routes of administration. Overall, Gendicine combined with chemotherapy, radiotherapy, or other conventional treatment regimens demonstrated significantly higher response rates compared to standard therapies alone. Some of the published studies also showed that Gendicine combination regimens demonstrated longer progression-free survival times than conventional treatments alone. To date, Gendicine has been clinically used in China for treatment of cancers other than HNSCC for more than ten years, mainly for patients with advanced or unresectable malignant tumors. However, the establishment of standard treatment regimens using TP53 gene therapy is still needed in order to advance its use in clinical practice.

Gastrointestinal Stromal Tumors of the Small Intestine: Progress in Diagnosis and Treatment Research.

In recent years, the diagnosis and treatment of gastrointestinal stromal tumors (GISTs) of the small intestine have been a hot topic due to their rarity and non-specific clinical manifestations. With the development of gene and imaging technology, surgery, and molecular targeted drugs, the diagnosis and treatment of GISTs have achieved great success. For a long time, radical resection was prioritized to treat GISTs of the small intestine. At present, preoperative tumor staging is a novel treatment for unresectable malignant tumors. In addition, karyokinesis exponent is the sole independent predictor of progression-free survival of GISTs. The DNA, miRNA, and protein of exosomes have also been found to be biomarkers with prognostic implications. The research on the treatment of GISTs has become a focus in the era of precision medicine, ushering in the use of standardized, normalized, and individualized treatment.

Factors related to poor dietary intake after gastrojejunal bypass surgery for unresectable malignant tumor

Factors related to poor dietary intake after gastrojejunal bypass surgery for unresectable malignant tumor

III–3 Low-Intensity Pulsed Ultrasound (LIPUS) for the Treatment of Massive Osteonecrosis Following Carbon Ion Radiotherapy for Malignant Bone Tumor

Objective: Carbon ion radiotherapy (CIR) can be applied for unresectable malignant bone tumors, especially arising from the pelvis and spine. The most serious adverse effect of CIR is a massive osteonecrosis of healthy bone surrounding the tumor. We applied LIPUS therapy in 2 cases and report here their clinical courses. Materials and Methods: Two cases with the pelvic sarcoma were treated by CIR. Thirteen year-old-male had a metastasis of osteosarcoma at the acetabulum. Seventy three year-old-male had a chondrosarcoma in the pubis, acetabulum and iliac bone. Results: Malignant tumors were controlled by CIR only and at present, we find no evidence of disease. Both cases complained of severe hip pain after CIR due to osteonecrosis of the acetabulum. Their pains were well improved at 1 month after LIPUS therapy. Destruction of the hip joint was not observed at the final follow-up. Discussion: Until now, positive effect of LIPUS have been reported on osteonecrosis of knee, hip joint and jaw bone. However, there have been, to our knowledge, no report on applying LIPUS for these difficult conditions. LIPUS therapy seems beneficial for pain relief and bone regeneration for massive osteonecrosis after CIR.

First-in-Human Phase I Study of a Non-Woven Fabric Bioabsorbable Spacer Combined with Particle Therapy Against Abdominal or Pelvic Sarcomas

Surgical spacer placement (SSP) is useful in particle therapy (PT) for patients with abdominal or pelvic tumors located adjacent to normal organs. We developed a non-woven fabric bioabsorbable spacer made of polyglycolic acid sutures that degrades via hydrolysis. We then conducted this first-in-human phase I study of the combination of SSP and PT using the PGA spacer and we termed space-modulated particle therapy (SMPT). This study aimed to evaluate the safety and efficacy of SMPT in patients with unresectable malignant tumor located adjacent to normal organs. The eligibility criteria included histologically proven malignant abdominal or pelvic tumor adjacent to the intestines, no metastasis, and no previous radiotherapy. Periodic computed tomography (CT) images were obtained before SSP and before, during, and after PT until the spacer disappeared. Treatment planning was performed for each CT image set until the end of PT, and doses for the planning target volume (PTV) and organs at risk were analyzed. The thickness and volume of the PGA spacer were measured in each CT image set. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events v4.0. Five patients were enrolled in this study. All patients received 70.4 Gy (RBE) of irradiation. V95% of the PTV before SSP, at the beginning of PT, and at the end of PT was 82.1±11.3%, 98.1±1.1%, and 97.1±0.8%, respectively. The PGA spacers maintained enough thickness (≥ 1 cm) until the end of PT and disappeared within 8 months after SSP in all patients. No grade ≥3 acute adverse events were observed. The SMPT is feasible and useful for abdominal or pelvic tumors adjacent to the intestines. This method may be applicable to unresectable tumors located adjacent to normal organs and may expand the indications of particle therapy.

Irreversible electroporation ablation of end-stage metastatic retroperitoneal lesions: Report on three cases and literature review.

Metastatic retroperitoneal tumors constitute an end-stage disease with poor prognosis that represents a heavy global health burden. The present study aimed to explore the efficacy of irreversible electroporation ablation (IRE) therapy in patients with end-stage retroperitoneal tumors. Between April 2016 and September 2017, three patients with unresectable retroperitoneal malignant tumors were enrolled. Among these cases, ultrasound (US)-guided IRE was palliatively performed for targeting 3 tumors (1 tumor per patient) located around the abdominal aorta. Post-treatment contrast-enhanced US (CEUS) and contrast-enhanced computed tomography (CECT) scans were subsequently performed to evaluate the area adjacent to the ablation zone and determine the prognosis. During the follow-up, the cases experienced a reduction of pain (mean score of 5.8 decreased to 2.2, based on the visual analogue scale), and had an overall survival rate ranging from 2 to 11 months. Case 1 remained alive at the time of submission of this study, but case 2 died within 2 months and case 3 within 11 months due to liver metastases of the primary tumor. At the 3-week follow-up, the CEUS image for case 1 exhibited a contrast defect with a sufficient ablation margin, in accordance with the CECT at 1.5 months following IRE, exhibiting complete tumor necrosis without contrast enhancement. Overall, these results suggest that US-guided percutaneous IRE may be effective in the treatment of end-stage retroperitoneal tumors. However, further studies are required to substantiate the conclusions of the present study. The present clinical trial was registered at clinicaltrials.gov (ID: NCT02822066) on June 20th, 2016.