Construction and Evaluation of a Virtual Reality Laparoscopic Surgery Collaborative Training Platform: Taking Laparoscopic Cholecystectomy as an Example

Abstract Backgroud: Virtual reality (VR) technology represents the future of medical education due to its unique advantages, especially with the Covid-19 pandemic lasting. We developed a laparoscopic VR surgery collaborative training platform hoping to shed light on future medical education in China.Methods: We constructed a VR surgery training platform and designed surgery curriculum on laparoscopic cholecystectomy (LC). 36 first-year postgraduate students in China standardized training program for resident doctor (C-STRD) from the Third Xiangya Hospital of Central South University were enrolled for validation trials. In the Phase I trial, 12 students performed LC in the exploration mode. After training in the surgery learning mode, they performed LC again. The LC scores before and after training were compared. In the Phase II trial, another 12 students were randomly assigned to either the collaborative group or the control group. The former trained with a senior surgeon collaboratively in the surgery learning mode and then performed LC alone in the exploration mode. The latter trained in the surgery learning mode by themselves and performed LC in the exploration mode. The LC scores between groups were compared. The user experience (intention to use, skills improvement, usability, degree of enjoyment) were analyzed through questionnaires from the above 24 students. Interest in surgery learning of Phase I students was compared with 12 students who didn’t experience the VR platform.Results: In Phase I trial, the mean LC scores of the students were elevated from 56.83 to 61.17 (p=0.042) after learning in surgery learning mode. In Phase II trial, collaborative group students had higher scores than their rivals (67.17 vs 61.33, p=0.014). Most students have a positive users’ experience regarding the intention to use and skills improvement. Collaborative group students had higher evaluation regarding usability. Students who experienced the VR platform were significantly more interested in future surgery learning (3.60 vs 2.58, p <0.05).Conclusion: Our study constructed a VR platform for collaborative surgery training, which showed an excellent training effect. Medical students rated the platform highly, and their interest in learning increased.

Download Full-text

Limited Phase I Trial of Sequential High Dose Cytarabine and Clofarabine (HiDAC→CLOF) in Relapsed or Refractory Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v108.11.4565.4565 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4565-4565

Author(s):

Bayard L. Powell ◽

James Lovato ◽

Claire Kimbrough ◽

Susan Lyerly ◽

Sonya Galloway-Daniels ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Phase I ◽

Myeloid Leukemia ◽

Phase I Trial ◽

Phase Ii Trial ◽

Skin Toxicity ◽

High Dose ◽

High Dose Cytarabine ◽

Grade 3 ◽

Acute Myeloid

Abstract High dose cytarabine (HiDAC) is the most effective single agent for the treatment of acute myeloid leukemia (AML); clofarabine (CLOF) is also an active agent in AML. Preclinical data suggest synergy between cytarabine and clofarabine. We conducted a two step limited phase I trial of sequential HiDAC (2g/m2 over 3 hours) followed by CLOF (30 or 40 mg/m2 infused over 2 hours), each given daily for 5 days, in adults with AML in first or second relapse or refractory to initial induction chemotherapy. Patients with persistent leukemia on day 12–14 received a second course of HiDAC→CLOF; phase I toxicity evaluation was based on cycle 1 data only. Nine patients (6 men and 3 women) were treated. The median age was 55.5 years (range 29.2 – 68.1). All had relapsed AML; two had prior autologous stem cell transplant. The initial cohort of 3 patients received clofarabine 30 mg/m2 with one dose limiting toxicity (DLT); an additional 3 patients were treated in cohort 1. The second cohort was treated with CLOF 40 mg/m2, the target dose for a planned phase II trial of HiDAC→CLOF. Hematologic toxicities and infections were not considered DLT. In the first cohort (30 mg/m2; n = 6) there was 1 DLT - grade 4 skin rash in a patient who subsequently died on day 17 with sepsis-related multi-organ failure; 3 patients had reversible grade 3 elevations in AST/ALT, 1 had grade 3 skin toxicity. In cohort 2 (40 mg/m2 ; n = 3) there was no DLT; 1 patient had grade 3 AST/ALT; 2 had grade 3 skin. Three of nine patients received a second course of induction HiDACCLOF. Two of six patients in cohort 1 achieved complete remission (CR), 1/3 patients in cohort 2 achieved CRi(CRp). Two of three CR/CRi patients received one course and one received two courses of HiDAC→CLOF induction. Conclusion: HiDAC→CLOF was associated with transient elevation in AST/ALT (4/9) and skin rash (3/9; primarily extensive palmar/plantar); skin toxicity appeared especially prominent in patients with palmar/plantar toxicity during prior therapy with HiDAC. Toxicities (other than skin) were comparable to other salvage regimens for relapsed and refractory AML. This combination is active in relapsed AML with 3/9 CR/CRp. A phase II trial of HiDAC→CLOF is underway; prophylactic intravenous hydrocortisone has been incorporated in an attempt to decrease skin toxicity.

Download Full-text

A phase I/II trial of erlotinib S-1 therapy in patients with non-small cell lung carcinoma: Thoracic Oncology Reseach Group (TORG) 0808/0913.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18099 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18099-e18099

Author(s):

Naoyuki Nogami ◽

Tetsu Shinkai ◽

Toshiyuki Kozuki ◽

Atsuko Ogino ◽

Yuka Kato ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Phase I Trial ◽

Phase Ii Trial ◽

Phase Ii Study ◽

Synergistic Effects ◽

Small Cell Lung Carcinoma ◽

Mrna Levels ◽

Cell Lung Carcinoma ◽

Basic Studies

e18099 Background: Gefitinib has been shown in basic studies to reduce the expression of thymidilate synthase, the target enzyme for the 5-FU-based chemotherapy, at the protein and mRNA levels, and synergistic effects of gefitinib used in combination with S-1 have been reported. Erlotinib also reduced TS expression and activity. The present studies were designed as study aimed at evaluating the efficacy and safety of erlotinib/ S-1 combination therapy as a 2nd/3rd-line therapy for recurrent/advanced NSCLC. Methods: Chemotherapy consisted of two 3-week cycles of erlotinib and S-1 treatment. Erlotinib was orally administered once daily at a dose of 150 mg/body, and patients received an oral dose of S-1 twice daily after meals from days 1 to 14 of each 21-day cycle. In phase I trial(TORG0808), the primary endpoint was to evaluate the DLT and the MTD for the following phase II study, and the secondary endpoint was to evaluate the antitumor activity and safety. Based on the phase I trial, we conducted a phase II trial (TORG0913) of this combination with pretreated EGFR negative NSCLC to determine the ORR. The secondary endpoints were PFS, disease control rate, OS, and safety. Results: 7 patients with good PS (0 or 1) and 10 patients with PS 0-2 participated in phase I and phase II trial. In phase I trial, the recommended doses for the phase II study were determined to be 150mg/body and 80mg/m2. The ORR was 67%, and 3/4 responders are EGFR positive patients. In phase II trial, the ORR was very low (only one patient).Myelosuppression was relatively mild, but Grade 3 or worse non-hematological toxicities including diarrhea, mucositis, and dermatitis were observed in 6 patients, which resulted in two treatment-related deaths. Data and Safety Monitoring Committee recommended the early termination, and the clinical trial was terminated due to adverse events. Conclusions: Phase I study showed the favorable efficacy and moderate safety profiles of this combination especially in EGFR positive patients, but less effective and too toxic in EGFR negative patients in phase II trial.

Download Full-text

Phase I trial results of PCK3145 in patients (pts) with castrate metastatic prostate cancer (PC)—The US experience

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4650 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4650-4650

Author(s):

S. F. Slovin ◽

L. Daigneault ◽

H. Dulude ◽

C. Panchal ◽

J. Richardson ◽

...

Keyword(s):

Phase I ◽

Tumor Invasion ◽

Metastatic Prostate Cancer ◽

Phase I Trial ◽

Seminal Fluid ◽

Phase Ii Trial ◽

Secretory Protein ◽

Invasion And Metastasis ◽

Dosing Schedule ◽

The Us

4650 Background: PCK3145 is a synthetic 15-mer peptide derived from the natural sequence of amino acids of Prostate Secretory Protein (PSCP94), a predominant protein found in seminal fluid. Its expression in PC is down-regulated in pts with metastatic disease and is believed to be a signal transduction inhibitor via multiple pathways in carcinogenesis. Recent data from a phase IIa trial in Great Britain demonstrated safety and suggested reduction in MMP-9 levels, an enzyme involved in angiogenesis, tumor invasion and metastasis. A phase I trial was performed to assess dosing and dosing schedule, pharmacokinetics, safety and impact on MMP-9 levels in pts with castrate metastatic PC who have failed multiple therapies including hormones and chemotherapy. Methods: Two cohorts of 10 pts received either 7.5 mg/m2 twice weekly or 15 mg/m2 weekly, respectively. Pts were treated for 4 weeks followed by a 2 week non-treatment period. Pts could receive addtional two-month cycles if PSAs and scans remained stable. MMP-9 levels, PSA, pharmacokinetics and imaging assessments were done at screening, and at weeks 2, 4 and 6. Results: Ten pts have been enrolled at each dose level. No adverse events were observed, however, declines in MMP-9 levels occurred in most pts by week #3 posttreatment. MMP-9 levels rose when drug was discontinued. Six pts were taken off study due to disease progression whereas 5 pts were discontinued due to rising PSAs. One pt at the 7.5 mg/m2 biweekly dosing schedule received 4 additional cycles with stable PSAs and scans with a PSA doubling time which increased from 4 months pretreatment to 8 months posttreatment. Conclusions: PCK3145 was well-tolerated without toxicity. While early, the weekly dosing schedule appears to result in greater declines in MMP-9 levels and will likely be used in a forthcoming phase II trial in chemotherapy naive pts. [Table: see text]

Download Full-text

Phase I study of SIR-sphere plus sorafenib as first-line treatment in patients with nonresectable hepatocellular carcinoma: The Asia-Pacific Hepatocellular Carcinoma Trials Group protocol 05 (AHCC05)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15538 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15538-e15538 ◽

Cited By ~ 1

Author(s):

P. K. Chow ◽

D. Poon ◽

S. Choo ◽

H. Lai ◽

A. Goh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase I ◽

Phase Ii ◽

Phase I Trial ◽

Phase Ii Trial ◽

Asia Pacific ◽

Tumour Regression ◽

Sorafenib Therapy ◽

Radio Therapy ◽

Grade 3

e15538 Background: Sorafenib has been shown to significantly prolong survival in patients with nonresectable hepatocellular carcinoma (HCC) without however significant tumour regression. The addition of radio-ablative therapy could confer additional survival benefit. This phase I trial was carried out to ascertain the toxicities and safety of this combination and was designed as a prelude to a phase II trial. Methods: Eligible patients were administered SIR-sphere (max dose 3 GBq) and subsequently given Sorafenib therapy (400mg bd) either 14 days (Cohort 1: first 3 patients) or 11 days (Cohort 2: subsequent patients) later. Assessment was carried out for 30 days after commencement of Sorafenib. Results: 10 patients were recruited into this phase I trial. The second patient became ineligible for sorafenib therapy after SIR-sphere due to pulmonary bleeding not related to radio-therapy and was excluded from assessment. The characteristics of the patients are in the Table. At the end of the study period, there was no adverse events (AE) of grade 3 or 4 for Cohort 1 and 3 for Cohort 2. The only serious adverse event (SAE) recorded was from Cohort 2. Conclusions: Starting sorafenib 14 days after SIR-sphere therapy is associated fewer AEs and SAEs. The phase II trial has commenced withsorafenib starting 14 days after SIR-sphere. [Table: see text] [Table: see text]

Download Full-text

Phase I cancer clinical trials†

Neuro-Oncology Practice ◽

10.1093/nop/npw014 ◽

2016 ◽

Vol 4 (1) ◽

pp. 67-72 ◽

Cited By ~ 1

Author(s):

Juan R. Cabrera ◽

Jennie W. Taylor ◽

Annette M. Molinaro

Keyword(s):

Phase I ◽

Phase I Trial ◽

Phase Ii Trial ◽

Maximum Tolerated Dose ◽

Cancer Clinical Trials ◽

Dose Estimation ◽

Time To Event ◽

Timely Manner ◽

Continual Reassessment Method ◽

Continual Reassessment

Abstract An efficient phase I trial is a crucial step in developing a new drug in a safe and timely manner. The main objective of a phase I trial is to determine the maximum tolerated dose in order to recommend the dose for a phase II trial. There are many designs that are implemented in phase I trials. Rule-based designs such as the traditional 3 + 3 method and rolling six design are easy to implement and assess for safety using a conservative approach. Model-based designs such as the continual reassessment method and the time-to-event continual reassessment method use mathematical models to increase the precision of dose estimation. The advantages and shortcomings of these designs, along with other designs, are reviewed.

Download Full-text

Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with advanced sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.5.2111 ◽

1997 ◽

Vol 15 (5) ◽

pp. 2111-2117 ◽

Cited By ~ 28

Author(s):

E S Casper ◽

G K Schwartz ◽

A Sugarman ◽

D Leung ◽

M F Brennan

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Phase I ◽

Phase I Trial ◽

Phase Ii Trial ◽

Dose Intensity ◽

Maximum Tolerated Dose ◽

Advanced Soft Tissue Sarcoma ◽

Stimulating Factor ◽

Specific Phase

PURPOSE To define the maximum-tolerated dose (MTD) of liposome-encapsulated doxorubicin (LED) when used every 2 weeks with granulocyte colony-stimulating factor (G-CSF) in patients with advanced soft tissue sarcoma. PATIENTS AND METHODS Doxorubicin encapsulated in egg phosphatidylcholine/cholesterol liposomes was given to patients with sarcoma in a disease-specific phase I trial. The initial dose was 75 mg/m2 with G-CSF 5 micrograms/kg. The MTD was defined as the highest dose that could be given every 2 weeks. RESULTS Twenty-nine patients participated in this study. Major toxicities included myelosuppression, nausea and vomiting, fatigue, and mucositis. Eight patients were hospitalized for nadir fever. No cardiotoxicity was seen. The MTD was LED 105 mg/m2 with G-CSF 5 micrograms/kg. LED 120 mg/m2 resulted in tolerable, albeit prominent, acute toxicity, but did not permit recycling of therapy on day 15. Among 26 patients with soft tissue sarcoma, 23 had measurable disease, of whom three achieved a partial response (13%; 95% confidence interval, 2% to 34%). CONCLUSION LED can be administered every 2 weeks at a dose of 105 mg/m2 with G-CSF support, which provides a dose-intensity of 52.5 mg/m2/wk. To exceed this intensity, the dose of LED that would have to be administered every 3 weeks would be greater than 157.5 mg/m2. A formal phase II trial is needed to estimate better the true response rate.

Download Full-text

Establishment of A Piglet Model for Peritoneal Metastasis of Ovarian Cancer

10.21203/rs.3.rs-806069/v1 ◽

2021 ◽

Author(s):

Eun Ji Lee ◽

Soo Jin Park ◽

Aeran Seol ◽

Hyunji Lim ◽

Jaehee Mun ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase I ◽

Phase Ii ◽

Peritoneal Metastasis ◽

Phase I Trial ◽

Phase Ii Trial ◽

Peritoneal Cancer Index ◽

Time Frame ◽

Ovarian Cancer Cells ◽

Peritoneal Cancer

Abstract Background: A piglet model for peritoneal metastasis (PM) of ovarian cancer was developed. It will contribute to the establishment of innovative chemotherapeutical and surgical strategies without any limitation of rodent models.Methods: A total of 12 four- to five-week-old piglets of 7 to 8 kg were used. Two phases of ovarian cancer cell injections were performed with a laparoscopic surgery. In phase I trial, 5.0×106 SK-OV-3 cells in 0.1 ml suspension were inoculated into the omentum, peritoneum, and uterine horns of two piglets twice with a one-week interval. In the phase II trial, 5.0×106 SNU-008 cells in 0.1 ml suspension were injected only into uterine horns with the same time frame because tumor implantation after inoculation of SK-OV-3 cells was not observed at the omentum or peritoneum in the phase I trial. Modified peritoneal cancer index (PCI) score was used to monitor tumorigenesis up to four weeks after inoculation. Tumor tissues disseminated in the peritoneum at four weeks after injection were used for histological examination with hematoxylin and eosin (H&E) and paired-box gene 8 (PAX-8) staining.Results: In the phase I trial, two piglets showed PM with modified PCI scores of 5 and 4 at three weeks after the first inoculation, which increased to 14 and 15 after four weeks, respectively. In the phase II trial, PM was detected in eight of ten piglets, which showed modified PCI scores of 6 to 12 at four weeks after the first inoculation. The overall incidence of PM from the total of 12 piglets after inoculation was 75%. Metastatic tumors were confirmed by immunohistochemical H&E and PAX-8 staining. Conclusions: This study provides strong evidence that piglets can be employed as a model for PM by inoculating ovarian cancer cells form humans. Using two cell lines the PM rate is 75%.

Download Full-text

Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.9.1969 ◽

1994 ◽

Vol 12 (9) ◽

pp. 1969-1973 ◽

Cited By ~ 3

Author(s):

P D Sadowitz ◽

R Dubowy ◽

A Souid ◽

B H Pollock ◽

H Weinstein ◽

...

Keyword(s):

Acute Leukemia ◽

Phase I ◽

Continuous Infusion ◽

Phase I Study ◽

Phase I Trial ◽

Phase Ii Trial ◽

Fixed Dose ◽

Life Threatening ◽

Pediatric Oncology Group ◽

Grade Iii

PURPOSE The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. PATIENTS AND METHODS From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). CONCLUSION In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.

Download Full-text