Symptoms and General Pathology

All Conditions

Recurrence

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

The radioactive Iodine-125 seed can release low dose of irradiation persistently which kills tumors cell and causes less damage to normal tissue at the same time. The treatment was performed under CT monitoring. 3D-printing template includes information on the path of the implantation needle, characteristics of the surface of the therapy area of the patient, and positioning and orientation effects which can make the operation more accurate.

Radioactive Iodine-125 Seeds Implantation

Zhe Ji, M.D.

Junjie Wang, M.D. Ph.D

This study will observe the efficacy and toxicities of 3-dimensional printing noncoplanar template assisted CT guided radioactive iodine-125 seeds implantation in the treatment of patients with recurrent chest wall malignancies after external beam radiotherapy prospectively, and analyzes the influence of clinical and dosimetric factors on the outcomes.

Radioactive Iodine-125 seed brachytherapy is a conventional treatment in Peking University Third Hospital. Radioactive Iodine-125 seed brachytherapy is the implantation of Iodine-125 seed into tumors.The radioactive Iodine-125 seed can release low dose of irradiation persistently which kills tumors cell and causes less damage to normal tissue at the same time. This study will enroll the patients with recurrent chest wall malignancies after external beam radiotherapy (primary or metastasis) who underwent CT-guided radioactive iodine-125 seed implantation assisted by 3D-printing template from 2019 to 2021. The investigators evaluate the dose that covers 90% target volume(D90) and other parameters after the implantation. The efficacy and adverse events will be observed. Local control(LC) time and overall survival(OS) time are evaluated.

RISI in the Treatment of Recurrent Chest Wall Malignancies After EBRT

Safety and Efficacy of Three-dimensional Printing Template-assisted CT-guided Radioactive Iodine-125 Seeds Implantation in the Treatment of Recurrent Chest Wall Malignancies After External Beam Radiotherapy

De-identified individual participant data for all primary and secondary outcome measures will be made available.

The time from the date of seeds implantation to the date of recurrence of the implanted tumor or the date of last observation.

The adverse events are evaluated by the common terminology criteria for adverse events (CTCAE). The rate of each adverse event will be measured.

The time from the date of seeds implantation to the date of death from any cause or the date of last observation.

Peking University Third Hospital

Neoplasms

Musculoskeletal Diseases

Behaviors and Mental Disorders

Rare Diseases

Sarcoma

Bone Neoplasms

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Bone Diseases

Quality of Life

Soft Tissue Sarcoma

A patient with a tumor lesion of the chest wall undergoes СT scan with a step width of less than 1 mm, then engineers design an individual model to replace the defect. Using a 3D printer, a model is made based on the patient's anthropometric data.

The use of standard titanium plates to replace the chest defect. These plates must be modeled and modified using special equipment intraoperatively, based on the characteristics of the defect after resection.

Implants

Plates

Alexander Salkov

Aslan Valiev, PhD

Pavel Kononets, PhD

Teimuraz Charatishvili, PhD

Nikolay Petrochenko, PhD

A patient with a tumor lesion of the chest wall undergoes CT scan with a step width of less than 1 mm, then engineers design an individual model to replace the defect. Using a 3D printer, a model is made based on titanium alloy powder. Preoperative preparation takes an average of 14-21 days. The next stage is surgical treatment in the amount of resection of the chest wall with plastic defect with an individual titanium implant. In some cases, the titanium framework is separated from the pleural cavity by a polytetrafluoroethylene plate in order to seal and prevent the development of pulmonary hernias. The advantages of titanium individual prostheses include accurate matching of the implant to the size and characteristics of the defect, individual modeling allows you to repeat the anatomical features of the patient. This method helps to recreate the original shape of the chest, and most importantly, symmetrical, relatively healthy half. With the help of titanium, individualized prostheses are made based on 3D modeling, which will reduce the incidence of complications, accelerate rehabilitation and improve the quality of life of patients with tumor lesions of the chest wall. The postoperative period takes 15-30 days.

A patient with a tumor lesion of the chest wall undergoes CT scan with a step width of less than 1 mm, then engineers design an individual model to replace the defect. Using a 3D printer, a model is made based on the patient's anthropometric data.

Manufacturing takes place by 3D printing on a titanium alloy powder certified for the manufacture of medical implants. The technology used is a type of SLS (Selective Laser Sintering) -technology, layer-by-layer laser melting of metal-powder compositions. The printing process begins with dividing the digital 3D model of the product into layers with a thickness of 20 to 100 microns in order to create a 2D image of each layer of the product (section). The industry standard format is STL (Stereolithography) file. This file enters a special machine software, where the information is analyzed and compared with the technical capabilities of the machine. Based on the data obtained, a production cycle of construction is launched, consisting of many cycles of building individual layers of the product.

The cycle for constructing a layer (section) consists of typical operations:

* applying a layer of powder of a given thickness to the construction plate;
* scanning by a laser beam of the section of the product layer. The laser beam is a source of heat, under the influence of which the particles of the material are sintered along the profile of the section of the model;
* lowering the platform into the depth of the construction well by an amount corresponding to the thickness of the construction layer.

The process of building products takes place in the SLM (Selective Laser Melting) chamber of the machine, filled with an inert gas argon. After construction, the product is removed from the printer chamber and sent for heat treatment, annealing, to relieve internal stresses and improve mechanical properties. After annealing, the product is separated from the platform and undergoes finishing, which combines various types of machining. The final stages of the technological process are product cleaning and technical quality control.

Preoperative preparation takes an average of 14-21 days. The next stage is surgical treatment in the amount of resection of the chest wall with plastic defect with an individual titanium implant. In all cases, the titanium framework is separated from the pleural cavity by a synthetic polyester (Dacron) plate in order to seal and prevent the development of pulmonary hernias. The advantages of titanium individual implants include accurate matching of the implant to the size and characteristics of the defect, individual modeling allows you to repeat the anatomical features of the patient. This method helps to recreate the original shape of the chest, and most importantly, symmetrical, relatively healthy half. With the help of titanium, individualized prostheses are made based on 3D modeling, which will reduce the incidence of complications, accelerate rehabilitation and improve the quality of life of patients with tumor lesions of the chest wall. The postoperative period takes 15-30 days.

3D Printed Implants for the Defect Reconstruction in Patients With Chest Wall Tumors

The Use of Individual 3D-implants in the Reconstruction of the Chest Wall in Patients With the Tumor Lesions of the Chest Wall for the Treatment, Restoration, and Improved Quality of Life Compared to Reconstruction With Titanium Plates

Time after treatment during which no sign of cancer is found

Time after surgery till the end of hospitalization

Adverse Event Assessment and Serious Adverse Event Assessment according to CTCAE 5.0

Improvement on the Karnofsky scale by 10-30 points

Improvement on the Visual Analogue Scale by 3-5 points

Improvement on the Whatkins scale by 1-2 points

Blokhin's Russian Cancer Research Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

Pembrolizumab

Cyclophosphamide

Immunomodulating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

.Patients will be treated with pembrolizumab administered as an intravenous infusion at 200 mg in 21-day treatment cycles and oral cyclophosphamide (CTX) 50 mg per day in metronomic administration as a 21 days cycle

Patients will be treated with pembrolizumab administered as an intravenous infusion at 200 mg in 21-day treatment cycles and oral cyclophosphamide (CTX) 50 mg per day in metronomic administration as a 21 days cycle

Giuseppe Curigliano, MD PhD

Bruno Duso, MD

This is a Phase II single center, open-label, non-randomized study in patients with locally recurrent, inoperable, and/or metastatic inflammatory breast cancer with lymphangitic spread to the chest wall. Patients will be treated with pembrolizumab administered as an intravenous infusion at 200 mg in 21-day treatment cycles and oral cyclophosphamide (CTX) 50 mg per day in metronomic administration as a 21 days cycle Forty-six patients will be required for the study. Key inclusion criteria are PDL1 (≥1%) positive and/or tumor infiltrating lymphocyte positive (≥1%) locally advanced "chest wall" breast cancer (with or without distant metastases), who have been treated with chemotherapy or radiation therapy may be eligible for this study. Patients with cutaneous metastases only (with or without evidence of primary tumor) are eligible for the study. Key exclusion criteria included prior anti PD1 or anti CTLA-4 or other immune pathway-targeted therapy. Patients with autoimmune diseases and/or receiving drugs who interfere with the immune system will not be eligible.

This is a Phase II single center, open-label, non-randomized study in patients with locally recurrent, inoperable, and/or metastatic inflammatory breast cancer with lymphangitic spread to the chest wall. Patients will be treated with pembrolizumab administered as an intravenous infusion at 200 mg in 21-day treatment cycles and oral cyclophosphamide (CTX) 50 mg per day in metronomic administration as a 21 days cycle. Forty-six patients will be required for the study. The study will be open to participants with histologically confirmed, inoperable, locally recurrent and/or metastatic breast cancer (mBC) with lymphangitic spread to the chest wall (chest wall disease), which had received one or more prior cytotoxic treatment. Key exclusion criteria consist of prior anti-PD1, anti-CTLA-4 or other immune pathway-targeted therapy. Patients with autoimmune diseases and/or receiving drugs who interfere with the immune system will not be eligible. Patients will be monitored carefully for the development of adverse experiences and will be monitored for clinical and/or radiographic evidence of disease progression according to usual standards of clinical practice. Adverse experiences will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. For individual patients that experience dose-limiting toxicities, criteria for dose modification of pembrolizumab and CTX are outlined in details in the protocol. Treatment with pembrolizumab and metronomic chemotherapy will continue until documented disease progression, unacceptable adverse events (as reported by the site), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, completion of 24 months of treatment with pembrolizumab, or administrative reasons requiring the cessation of treatment. Subjects who attain complete response (CR) confirmed by central radiology review may consider stopping trial treatment after receiving at least 24 weeks of treatment. Subjects who discontinue treatment after 24 months of therapy for reasons other than disease progression or intolerability or who discontinue treatment after attaining a CR may be eligible for up to one year of retreatment after they have experienced radiographic disease progression. The decision to retreat will be at the discretion of the Investigator, only if no cancer treatment was administered since the last dose of pembrolizumab, the subject still meets the safety parameters listed in the Inclusion/Exclusion criteria and the trial remains open.

Primary Objective: assessment of the efficacy of pembrolizumab and metronomic cyclophosphamide according to immune-related RECIST (irRECIST) criteria in patients with chest wall breast cancer. Primary endpoint will be objective response (confirmed CR or PR as best overall response) based on irRECIST criteria and also based on evaluable disease.

Secondary objectives: duration of response (DoR); time to progression (TTP); progression-free survival (PFS); overall survival (OS).

Exploratory Objectives: responses according to levels of PD-L1, measured by immunohistochemistry IHC in unresectable locoregional lesion. Responses according to levels of tumor infiltrating lymphocytes. Responses according to ER status. Responses according to FISH ratio and HER2 copy number. Tumor dynamics during the disease course as well as emergence of new clones (i.e.: resistance mechanisms) by determination of circulating tumor DNA (ctDNA). Sequencing of material from tumor biopsies to determine molecular profiles of responders and non-responders. Evaluation of efficacy by immune-related RECIST (irRECIST) (i.e.: irORR, irDoR, irPFS, irDCR). Through analysis of peripheral blood transcriptome in patients treated with pembrolizumab and cyclophosphamide therapy (P and CTX) combination therapy the investigators aim at:

1. Defining baseline peripheral blood gene signatures associated with treatment responsiveness (pre-treatment biomarkers);
2. Defining molecular perturbations associated with the administration P and CTX combination therapy and their relationship with immune-related adverse events (post-treatment predictive biomarkers) and clinical outcome.

Phase II single center, open-label, non-randomized study

Pembrolizumab and Oral Metronomic Cyclophosphamide in Patients With Chest Wall Breast Cancer

Combination of Pembrolizumab With Oral Metronomic Cyclophosphamide in Patients With Chest Wall Breast Cancer (PERICLES): A Phase II Study

Sharing of data will de decided if opportunity of collaborations will emerge

Confirmed CR or PR as best overall response based on irRECIST criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
RISI in the Treatment of Recurrent Chest Wall Malignancies After EBRT	NCT04077710	Chest Wall Tumo...	Radioactive Iod...	18 Years - 80 Years	Peking University Third Hospital
3D Printed Implants for the Defect Reconstruction in Patients With Chest Wall Tumors	NCT05057143	Tumor of Bone Chest Wall Tumo... Chest Wall Sarc... Sarcoma of Bone Surgery Implant Site Re...	Implants Plates	18 Years -	Blokhin's Russian Cancer Research Center
RISI in the Treatment of Recurrent Chest Wall Malignancies After EBRT	NCT04077710	Chest Wall Tumo...	Radioactive Iod...	18 Years - 80 Years	Peking University Third Hospital
Pembrolizumab and Oral Metronomic Cyclophosphamide in Patients With Chest Wall Breast Cancer	NCT03971045	Breast Cancer Chest Wall Tumo...	Pembrolizumab	18 Years -	European Institute of Oncology

Spots Global Cancer Trial Database for chest wall tumor