68Ga-NODAGA-Exendin-4 PET/CT Findings in a Case of Metastatic Insulinoma With Refractory Hypoglycemia Controlled by 90Y Transarterial Radioembolization.

ABSTRACT: Metastatic insulinomas can cause recurrent hypoglycemia requiring continuous IV glucose infusion. Various medical and chemotherapeutic treatment options are used to reduce the patient's risk of death due to hypoglycemia. Treatment-resistant hepatic metastatic insulinomas may benefit clinically from 90Y transarterial radioembolization therapy. In this case, we present a case of liver metastatic insulinoma that achieved clinical improvement after 2 cycles of 90Y microspheres transarterial radioembolization, and the presence of active metastases was demonstrated with 68Ga-NODAGA-exendin-4 PET/CT imaging.

Radiochemotherapy in Pancreatic Cancer.

Despite the advancements made in oncology in recent years, the treatment of pancreatic cancer remains a challenge. Five-year survival rates for this cancer do not exceed 10%. Among the reasons contributing to poor treatment outcomes are the oligosymptomatic course of the tumor, diagnostic difficulties due to the anatomical location of the organ, and the unique biological features of pancreatic cancer. The mainstay of treatment for resectable cancer is surgery and adjuvant chemotherapy. For unresectable and metastatic cancers, chemotherapy remains the primary method of treatment. At the same time, for about thirty years, there have been attempts to improve treatment outcomes by using radiotherapy combined with systemic treatment. Unlike chemotherapy, radiotherapy has no established place in the treatment of pancreatic cancer. This paper addresses the topic of radiotherapy in pancreatic cancer as a valuable method that can improve treatment outcomes alongside chemotherapy.

14-3-3σ downregulation sensitizes pancreatic cancer to carbon ions by suppressing the homologous recombination repair pathway.

This study explored the role of 14-3-3σ in carbon ion-irradiated pancreatic adenocarcinoma (PAAD) cells and xenografts and clarified the underlying mechanism. The clinical significance of 14-3-3σ in patients with PAAD was explored using publicly available databases. 14-3-3σ was silenced or overexpressed and combined with carbon ions to measure cell proliferation, cell cycle, and DNA damage repair. Immunoblotting and immunofluorescence (IF) assays were used to determine the underlying mechanisms of 14-3-3σ toward carbon ion radioresistance. We used the BALB/c mice to evaluate the biological behavior of 14-3-3σ in combination with carbon ions. Bioinformatic analysis revealed that PAAD expressed higher 14-3-3σ than normal pancreatic tissues; its overexpression was related to invasive clinicopathological features and a worse prognosis. Knockdown or overexpression of 14-3-3σ demonstrated that 14-3-3σ promoted the survival of PAAD cells after carbon ion irradiation. And 14-3-3σ was upregulated in PAAD cells during DNA damage (carbon ion irradiation, DNA damaging agent) and promotes cell recovery. We found that 14-3-3σ resulted in carbon ion radioresistance by promoting RPA2 and RAD51 accumulation in the nucleus in PAAD cells, thereby increasing homologous recombination repair (HRR) efficiency. Blocking the HR pathway consistently reduced 14-3-3σ overexpression-induced carbon ion radioresistance in PAAD cells. The enhanced radiosensitivity of 14-3-3σ depletion on carbon ion irradiation was also demonstrated in vivo. Altogether, 14-3-3σ functions in tumor progression and can be a potential target for developing biomarkers and treatment strategies for PAAD along with incorporating carbon ion irradiation.

Triple Blockade of Oncogenic RAS Signaling Using KRAS and MEK Inhibitors in Combination with Irradiation in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of human malignancies and carries an exceptionally poor prognosis. It is mostly driven by multiple oncogenic alterations, with the highest mutation frequency being observed in the KRAS gene, which is a key oncogenic driver of tumorogenesis and malignant progression in PDAC. However, KRAS remained undruggable for decades until the emergence of G12C mutation specific KRAS inhibitors. Despite this development, this therapeutic approach to target KRAS directly is not routinely used for PDAC patients, with the reasons being the rare presence of G12C mutation in PDAC with only 1-2% of occurring cases, modest therapeutic efficacy, activation of compensatory pathways leading to cell resistance, and absence of effective KRASG12D or pan-KRAS inhibitors. Additionally, indirect approaches to targeting KRAS through upstream and downstream regulators or effectors were also found to be either ineffective or known to cause major toxicities. For this reason, new and more effective treatment strategies that combine different therapeutic modalities aiming at achieving synergism and minimizing intrinsic or adaptive resistance mechanisms are required. In the current work presented here, pancreatic cancer cell lines with oncogenic KRAS G12C, G12D, or wild-type KRAS were treated with specific KRAS or SOS1/2 inhibitors, and therapeutic synergisms with concomitant MEK inhibition and irradiation were systematically evaluated by means of cell viability, 2D-clonogenic, 3D-anchorage independent soft agar, and bioluminescent ATP assays. Underlying pathophysiological mechanisms were examined by using Western blot analyses, apoptosis assay, and RAS activation assay.

Gastroscopic observation and dose-volume histogram parameter study on gastrointestinal mucous injury for pancreatic cancer treated with TOMO.

To explore the relationships between gastrointestinal radiation injuries of pancreatic cancer patients treated with TOMO and dose-volume histogram parameters prospectively. Seventy patients with pancreatic cancer who underwent TOMO were enrolled in this prospective study from February 2015 to May 2020. The clinical and dose-volume histogram parameters of the patients were collected. The optimal dose parameters for gastrointestinal radiation ulcers were confirmed based on the receiver operating characteristic curve (ROC) and the area below the ROC curve. Acute gastrointestinal tract toxic and side effect and injury grading correlation analyzed by Kruskal-Wallis rank sum test. Gastrointestinal injury often occurs during radiotherapy for pancreatic cancer, as observed using gastroscopy. The main adverse reactions were radioactive gastrointestinal inflammation (58.5%), radioactive gastrointestinal ulcers (41.4%), active bleeding (10%), newly-developed gastric retention (8.6%), and gastric varices (5.7%). As for the stomach, Dmean and V10 were related to radiation ulcer injury. ROC curve indicated that for stomach a Dmean of 13.39 Gy (area under ROC curves = 0.74, P = .048) and a V10 of 72.21% (area = 0.74, P = .048) was the tolerated dose for the injury of stomach radiation ulcer. As for duodenum, aV20 and aV25 are related to radiation ulcer injury. ROC curve indicated that aV20 of 22.82 cm3 (area = 0.68, P = .025) and aV25 of 32.04 cm3 (area = 0.66, P < .047) was the tolerated dose for the injury of duodenum radiation ulcer. The acute gastrointestinal tract toxic and side effects have no significant correlation with injury grading under gastroscope. Dmean > 13.39 Gy and V10 > 72.21% were the key dosimetric indices for predicting radiation-induced gastric ulcer, and aV20 > 22.82 cm3 and aV25 > 32.04 cm3 were for duodenal. Gastrointestinal reactions cannot be used as an overall basis for the diagnosis of gastrointestinal injury, and gastroscopy is recommended as a review item after radiotherapy.

Escalated-dose radiotherapy for unresected locally advanced pancreatic cancer: Patterns of care and survival in the United States.

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes. METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively. RESULTS: Among the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas-directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p < 0.001) and treatment between 2016 and 2019 (aOR 2.54, p < 0.001) were associated with greater receipt of EDR, whereas use of chemotherapy (aOR 0.60, p < 0.001) was associated with less receipt. Median OS estimates for EDR and CDR were 14.5 months and 13.0 months (p < 0.0001), respectively. For radiation therapy subset patients with available survival data (n = 13,579), multivariable Cox regression correlated EDR (adjusted hazard ratio 0.85, 95% confidence interval 0.80-0.91; p < 0.001) with longer OS versus CDR. DISCUSSION AND CONCLUSIONS: Utilization of EDR has increased since 2016, but overall utilization of RT for LAPC has remained at less than one in five patients for almost two decades. These real-world results additionally provide an estimate of effect size of EDR for future prospective trials.

TLK1 Inhibition Enhances the Anticancer Effect of Deep UV Irradiation Through CHK1 Activation.

BACKGROUND/AIM: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells. MATERIALS AND METHODS: Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks. RESULTS: DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups. CONCLUSION: TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.

Inhibition of ribonucleotide reductase subunit M2 enhances the radiosensitivity of metastatic pancreatic neuroendocrine tumor.

Ribonucleotide Reductase (RNR) is a rate-limiting enzyme in the production of deoxyribonucleoside triphosphates (dNTPs), which are essential substrates for DNA repair after radiation damage. We explored the radiosensitization property of RNR and investigated a selective RRM2 inhibitor, 3-AP, as a radiosensitizer in the treatment of metastatic pNETs. We investigated the role of RNR subunit, RRM2, in pancreatic neuroendocrine (pNET) cells and responses to radiation in vitro. We also evaluated the selective RRM2 subunit inhibitor, 3-AP, as a radiosensitizer to treat pNET metastases in vivo. Knockdown of RNR subunits demonstrated that RRM1 and RRM2 subunits, but not p53R3, play significant roles in cell proliferation. RRM2 inhibition activated DDR pathways through phosphorylation of ATM and DNA-PK protein kinases but not ATR. RRM2 inhibition also induced Chk1 and Chk2 phosphorylation, resulting in G1/S phase cell cycle arrest. RRM2 inhibition sensitized pNET cells to radiotherapy and induced apoptosis in vitro. In vivo, we utilized pNET subcutaneous and lung metastasis models to examine the rationale for RNR-targeted therapy and 3-AP as a radiosensitizer in treating pNETs. Combination treatment significantly increased apoptosis of BON (human pNET) xenografts and significantly reduced the burden of lung metastases. Together, our results demonstrate that selective RRM2 inhibition induced radiosensitivity of metastatic pNETs both in vitro and in vivo. Therefore, treatment with the selective RRM2 inhibitor, 3-AP, is a promising radiosensitizer in the therapeutic armamentarium for metastatic pNETs.

Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.

Early outcomes of MR-guided SBRT for patients with recurrent pancreatic adenocarcinoma.

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC. METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5. RESULTS: Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted. CONCLUSIONS: This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated. TRIAL REGISTRATION: Jefferson IRB#20976, approved 2/17/21.

Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[177Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from 177Lu. The objective of this work was to explore how postinfusion [177Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [177Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients' health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1-9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation (P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management.

CBCT-DRRs superior to CT-DRRs for target-tracking applications for pancreatic SBRT.

Objective.In current radiograph-based intra-fraction markerless target-tracking, digitally reconstructed radiographs (DRRs) from planning CTs (CT-DRRs) are often used to train deep learning models that extract information from the intra-fraction radiographs acquired during treatment. Traditional DRR algorithms were designed for patient alignment (i.e.bone matching) and may not replicate the radiographic image quality of intra-fraction radiographs at treatment. Hypothetically, generating DRRs from pre-treatment Cone-Beam CTs (CBCT-DRRs) with DRR algorithms incorporating physical modelling of on-board-imagers (OBIs) could improve the similarity between intra-fraction radiographs and DRRs by eliminating inter-fraction variation and reducing image-quality mismatches between radiographs and DRRs. In this study, we test the two hypotheses that intra-fraction radiographs are more similar to CBCT-DRRs than CT-DRRs, and that intra-fraction radiographs are more similar to DRRs from algorithms incorporating physical models of OBI components than DRRs from algorithms omitting these models.Approach.DRRs were generated from CBCT and CT image sets collected from 20 patients undergoing pancreas stereotactic body radiotherapy. CBCT-DRRs and CT-DRRs were generated replicating the treatment position of patients and the OBI geometry during intra-fraction radiograph acquisition. To investigate whether the modelling of physical OBI components influenced radiograph-DRR similarity, four DRR algorithms were applied for the generation of CBCT-DRRs and CT-DRRs, incorporating and omitting different combinations of OBI component models. The four DRR algorithms were: a traditional DRR algorithm, a DRR algorithm with source-spectrum modelling, a DRR algorithm with source-spectrum and detector modelling, and a DRR algorithm with source-spectrum, detector and patient material modelling. Similarity between radiographs and matched DRRs was quantified using Pearson's correlation and Czekanowski's index, calculated on a per-image basis. Distributions of correlations and indexes were compared to test each of the hypotheses. Distribution differences were determined to be statistically significant when Wilcoxon's signed rank test and the Kolmogorov-Smirnov two sample test returnedp≤ 0.05 for both tests.Main results.Intra-fraction radiographs were more similar to CBCT-DRRs than CT-DRRs for both metrics across all algorithms, with allp≤ 0.007. Source-spectrum modelling improved radiograph-DRR similarity for both metrics, with allp< 10-6. OBI detector modelling and patient material modelling did not influence radiograph-DRR similarity for either metric.Significance.Generating DRRs from pre-treatment CBCT-DRRs is feasible, and incorporating CBCT-DRRs into markerless target-tracking methods may promote improved target-tracking accuracies. Incorporating source-spectrum modelling into a treatment planning system's DRR algorithms may reinforce the safe treatment of cancer patients by aiding in patient alignment.

Impact of data transfer between treatment planning systems on dosimetric parameters.

PURPOSE: In radiotherapy it is often necessary to transfer a patient's DICOM (Digital Imaging and COmmunications in Medicine) dataset from one system to another for re-treatment, plan-summation or registration purposes. The aim of the study is to evaluate effects of dataset transfer between treatment planning systems. MATERIALS AND METHODS: Twenty-five patients treated in a 0.35T MR-Linac (MRidian, ViewRay) for locally-advanced pancreatic cancer were enrolled. For each patient, a nominal dose distribution was optimized on the planning MRI. Each plan was daily re-optimized if needed to match the anatomy and exported from MRIdian-TPS (ViewRay Inc.) to Eclipse-TPS (Siemens-Varian). A comparison between the two TPSs was performed considering the PTV and OARs volumes (cc), as well as dose coverages and clinical constraints. RESULTS: From the twenty-five enrolled patients, 139 plans were included in the data comparison. The median values of percentage PTV volume variation are 10.8 % for each fraction, while percentage differences of PTV coverage have a mean value of -1.4 %. The median values of the percentage OARs volume variation are 16.0 %, 7.0 %, 10.4 % and 8.5 % for duodenum, stomach, small and large bowel, respectively. The percentage variations of the dose constraints are 41.0 %, 52.7 % and 49.8 % for duodenum, stomach and small bowel, respectively. CONCLUSIONS: This study has demonstrated a non-negligible variation in size and dosimetric parameters when datasets are transferred between TPSs. Such variations should be clinically considered. Investigations are focused on DICOM structure algorithm employed by the TPSs during the transfer to understand the cause of such variations.

RAS-RAF-miR-296-3p signaling axis increases Rad18 expression to augment radioresistance in pancreatic and thyroid cancers.

Oncogenic RAS and RAF signaling has been implicated in contributing to radioresistance in pancreatic and thyroid cancers. In this study, we sought to better clarify molecular mechanisms contributing to this effect. We discovered that miRNA 296-3p (miR-296-3p) is significantly correlated with radiosensitivity in a panel of pancreatic cancer cells, and miR-296-3p is highly expressed in normal cells, but low in cancer cell lines. Elevated expression of miR-296-3p increases radiosensitization while decreasing the expression of the DNA repair enzyme RAD18 in both pancreatic and thyroid cancer cells. RAD18 is overexpressed in both pancreatic and thyroid tumors compared to matched normal controls, and high expression of RAD18 in tumors is associated with poor prognostic features. Modulating the expression of mutant KRAS in pancreatic cancer cells or mutant BRAF in thyroid cancer cells demonstrates a tight regulation of RAD18 expression in both cancer types. Depletion of RAD18 results in DNA damage and radiation-induced cell death. Importantly, RAD18 depletion in combination with radiotherapy results in marked and sustained tumor regression in KRAS mutant pancreatic cancer orthotopic tumors and BRAF mutant thyroid heterotopic tumors. Overall, our findings identify a novel coordinated RAS/RAF-miR-296-3p-RAD18 signaling network in pancreatic and thyroid cancer cells, which leads to enhanced radioresistance.

The efficacy of coaxial percutaneous iodine-125 seed implantation combined with arterial infusion chemotherapy for advanced pancreatic cancer: a randomized clinical trial.

BACKGROUND: This study aimed to evaluate the clinical efficacy of coaxial percutaneous Iodine-125 (125I) seed implantation in combination with arterial infusion chemotherapy for the treatment of advanced pancreatic cancer (PC) through a randomized controlled trial. METHODS: A total of 101 patients with advanced PC were randomized into two groups: control group treated with systemic intravenous chemotherapy and experimental group that received 125I seed implantation in combination with arterial infusion chemotherapy. Outcomes, including tumor control, abdominal pain relief, and survival time were compared between these two groups (Trial Registration No. KYKT2018-65). RESULTS: Pretreatment abdominal pain scores were comparable between the two groups, whereas the abdominal pain scores at 1- and 3-month post-treatment were significantly lower in the control group than those in the experimental group (1-month: 3.74 ± 1.54 vs. 4.48 ± 1.46, p = .015; 3-month: 3.64 ± 2.21 vs. 5.40 ± 1.56, p < .001). At 3-month post-treatment, computed tomography (CT) scan revealed a significantly higher disease control rate in the experimental group than that in the control group (94.0% vs. 74.5%, p = .007). The median survival time in the experimental group was significantly longer than that in the control group (15-month vs. 9-month, p < .001). CONCLUSION: The combination of coaxial percutaneous 125I seed implantation with arterial infusion chemotherapy could significantly alleviate abdominal pain, improve tumor control rates, and prolong survival time in patients with advanced PC.

Neoadjuvant Peptide Receptor Radionuclide Therapy in a Rare Case of Pediatric Primary Hepatic Gastrinoma.

ABSTRACT: Gastrinomas with predilection for the adult male population are located in the gastrinoma triangle (>90%). Primary hepatic gastrinoma especially in pediatric population is very rare. Peptide receptor radionuclide therapy has shown benefit in metastatic gastroenteropancreatic neuroendocrine tumors (NETs) with an increasing interest in expanding its role as neoadjuvant treatment modality to improve the surgical candidature in inoperable NETs. There is currently no literature supporting its role in the pediatric NET patients. We present a rare case of a young boy with primary hepatic gastrinoma where 177Lu-based peptide receptor radionuclide therapy in the neoadjuvant setting contributed to his final disease-free status.

Evaluation of the availability of single-position treatment with a rotating gantry and the validity of deformable image registration dose assessment for pancreatic cancer carbon-ion radiotherapy.

BACKGROUND: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. MATERIAL AND METHODS: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. RESULTS: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc. CONCLUSION: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.

Feasibility estimation of injected hydrodissection before definitive radiotherapy of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.