Neoplasms

All Conditions

Abdominal Neoplasms

Pelvic Neoplasms

Ahmed M. Morsy, MD

Badawy M. Ahmed, MD

Khalid M. Rezk, MD

Ameer M. Abuelgheet, MD

The aim of the study is to retrospectively review data about malignancies that arise primarily in the pelvis and/or in the pelvic organs, in pediatric cancer patients \& categorize the spectrum of these malignancies according to experience at South Egypt Cancer Institute which is the largest referral site in Upper Egypt.

Background:

The newborn and infant pelvis is not fully developed and the bladder, uterus, and ovaries are to a large degree intra-abdominal. The pelvis of the infant and child has different anatomic relationships than the adolescent or adult pelvis. Neoplasms of the pediatric pelvis constitute a unique group requiring highly specialized management in a setting staffed by pediatric surgical and radiation oncologists. The most common neoplasms are rhabdomyosarcomas of the bladder, prostate, and vagina; sacrococcygeal teratoma; and the germ cell tumors, including teratomas, endodermal sinus tumors, and the choriocarcinomas. Rapidly improving chemotherapy for all of these lesions has resulted in a changed role for the surgeon.

Patients \& Methods:

A hospital-based study, involving Pediatric cancer patients, those have been diagnosed with malignant tumors that primarily arising in the pelvis and/or arising from the pelvic organs, and may have an intra-abdominal extension, in the period from 2001 January till 2015 December, and received treatment at the pediatric oncology department, their medical reports will be retrospectively reviewed for data collection.

Spectrum of these malignancies will be categorized and recorded as specific disease entities, based on morphology \& the primary site of occurrence, their relative incidence will be calculated, and the treatment outcomes will be verified.

Malignant Pediatric Pelvic Tumors: A Retrospective Study

Malignant Pediatric Pelvi-abdominal Tumors: A Retrospective Study

Time from the date of initiation of treatment until death from any cause.

Time from the date of initiation of treatment until disease progression, or death for any reason.

Assiut University

Lecturer, Pediatric Oncology Department

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Lung Neoplasms

Breast Neoplasms

Breast Diseases

Skin Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

Patients with \> 1 cm tumor motion simulated using 4DCT with and without CPAP

Patients with heart abutting chest wall will be simulated using 4DCT with and without CPAP

Patient with liver metastases for SBRT or pancreatic tumors will be simulated using 4DCT with and without CPAP

Continuous positive airway pressure (CPAP)

Zvi Symon, MD

Hila Genesin, MsC

Jeffrey Goldstein, MD

Yaacov R Lawrence, MD

This is a clinical study on patients to compare the effects of CPAP on lung volume diaphragm motion, heart position and tumor motion compared to free breathing. Only patients with significant tumor motion of greater than 1 cm amplitude or unfavorable chest wall geometry (heart close to chest wall) identified on standard imaging and simulation will be candidates for the study. Patients will be re- simulated and planned for radiation treatments with CPAP. The radiation plans generated with and without CPAP will be compared to evaluate the impact of CPAP on tumor motion and dose delivered to adjacent critical structures such as the heart and lung.

Primary Objectives

* Evaluate effectiveness of CPAP to reproducibly reduce tumor and organ motion during radiation therapy treatments.
* Determine if CPAP allows for a reduction in normal tissue receiving radiation in chest and abdomen tumors and reduce heart exposure for patients receiving left breast irradiation.

Entry Criteria: This is a proof of concept and feasibility study. We propose to study 10 patients in each group for a total of thirty patients.

Eligibility criteria Group1. Lung tumors and nodules with tumor motion greater than 1 cm on standard imaging (n=10) Group2. Left sided breast tumors with unfavorable anatomy, viz heart abutting chest wall (n=10) Group3. Upper abdominal tumors: Liver and Pancreas with tumor motion greater than 1 cm. (n=10)

Pretreatment evaluations/management for patients meeting eligibility criteria CPAP All patients will be evaluated by a pulmonologist for their respiratory performances including physical examination, oxygen saturation and pulmonary function tests including DLCO that will serve for baseline measures. Then, adjustment session will be performed aiming to get adjusted to a CPAP device till the maximal tolerated pressure is not more than 16 cmH20 (TBD) for 30 minutes.

All patients must be able to tolerate CPAP and comply with daily treatment. 4D CT: CT simulation is the basis of conformal treatment planning \[24, 25\]. By using a slow acquisition time of 3 minutes the motion effects due to breathing can be captured and a 4D image generated. The tumor position can be imaged throughout the breathing cycle and a Maximum Intensity Projection (MIP) can be constructed and used in treatment planning. If there is no tumor motion the size of the MIP would equal the tumor size. The MIP size will increase with increasing tumor motion. The planning software allows us to calculate the MIP dimensions and volume. In addition total lung volumes and change in diaphragm position can be calculated (Figure 1). Radiation therapy planning parameters and volumetric analysis of tumor and normal tissue motion and position are calculated using available software and transferred to the Eclipse treatment planning system \[17\].

Treatment Planning:

The Eclipse treatment planning system will be used to generate and compare plans for treatment with and without CPAP.

Details of Intervention

Simulation All treatment planning and CPAP evaluation will be done in the radiation therapy department. Patients will be simulated on the Phillips 4D big bore CT simulator. The 4D scan which is done slowly over several minutes allows us to assess the full range of tumor motion throughout the respiratory cycle. An ITV is calculated which includes the actual tumor size with an expansion to account for the range of motion of the tumor by accounting for tumor location throughout the respiratory cycle (MIP) The MIP is the basis for the ITV and is the structure used for treatment planning. Patients recruited for the study will be re-simulated with the patient in the same position while undergoing CPAP treatment. ITV size and volume will be calculated for the tumor in in both the standard and CPAP studies and used for planning.

RPM: Diaphragm motion and respiratory cycle information will be obtained using the RPM for both the standard and the CPAP simulations. Differences in the respiratory wave cycle will be recorded \[17\].

The MIP/ITV images will be transferred to the Eclipse treatment planning system and using both the standard breathing and CPAP simulations treatment plans will be generated. Standard radiation plan evaluation parameters will be used and plans compared with respect to tumor coverage and normal tissue and normal tissue in the radiation field.

Radiation Plan:

Identical field arrangements will be generated for CPAP and non CPAP plans. Plans will be evaluated using standard radiation therapy planning parameters including: MIP or ITV, total lung volume, volume of GTV/CTV/PTV/ V20 and MLD.

Pre treatment Compare standard conformal radiation plans using Eclipse treatment planning system for each patient with and without CPAP.

RPM tracings with and without CPAP will be compared for all groups pre- treatment.

Evaluation of Continuous Positive Airway Pressure for Tumor Motion Management in Radiotherapy

Evaluation of CPAP (Continuous Positive Airway Pressure) in the Planning of Radiation Treatments for Lung, Upper Abdomen and Left Breast Cancers

Measurement of the Internal Target Volume in cc

Mean Lung dose, Mean Heart dose measured in Gy

Sheba Medical Center

Chairman Radiation Oncology

Symptoms and General Pathology

Wounds and Injuries

Behaviors and Mental Disorders

Rare Diseases

Hyperthermia

Sarcoma

Fever

Rhabdomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Myosarcoma

Body Temperature Changes

Stress Disorders, Traumatic

Heat Stress Disorders

Soft Tissue Sarcoma

Embryonal Sarcoma

Antineoplastic Agents

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Participants receive complete surgical tumor resection with no gross residual disease, followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) using Doxorubicin.

Participants receive debulking surgery followed by intra-operative radiation (IORT) in the form of brachytherapy to the gross residual pelvic tumor sites.

Participants have the option of returning for HIPEC 4 weeks (or more) after IORT, if active disease remains.

Resectable Intra-Abdominal/Pelvic Tumors Group: Participants receive peritonectomy, omentectomy, cytoreduction, (complete surgical tumor resection, no gross residual disease).

Unresectable Intra-Abdominal/Pelvic Tumors Group: Participants receive debulking surgery (90% resection) , with no more than 5mm thick residual implants, totaling no more than 2.5cm2 of residual tumor.

Abdominal Surgery

Dose Escalation: Heated Doxorubicin delivered by Hyperthermic Intraperitoneal Chemotherapy (HIPEC). After abdominal surgery two large bore catheters are placed in the peritoneal cavity through the incision. Starting dose of Doxorubicin is 15 mg/L of HIPEC perfusate.

Dose Expansion Starting Dose: MTD from Dose Escalation.

Standard dose brachytherapy delivered to the residual pelvic tumor sites.

Intra-Operative Radiation

Andrea Hayes-Jordan, MD

The goal of this clinical research study is to find the highest tolerable dose of heated doxorubicin that can be given to patients during surgery with abdominal tumors. The safety of this drug will also be studied.

Surgery and Study Drug Administration:

If participant is found to be eligible to take part in this study, surgery will be performed to try to remove as many tumors from participant's abdomen as possible. The surgery is not being performed specifically for this research study and would be performed as part of participant's standard of care treatment even if participant didn't take part in this study. Participant will be given a separate consent form to sign that explains the details and risks of the abdominal surgery in more detail.

During the surgery, if it is decided that all of the tumors can be removed, the abdomen will be closed with a plastic tube left in place. Then, the abdominal wash will begin. During the wash, a pump that is connected to the plastic tube pushes the heated doxorubicin into the abdomen and then pulls it out to recirculate the doxorubicin. The heated doxorubicin will be recirculated in and out of the abdomen over 90 minutes while the surgeon gently presses on the abdomen to help the doxorubicin reach all areas in the abdomen. The plastic tube that the heated doxorubicin will be pumped through will stay in place after the surgery to drain the extra fluid. These are the same plastic tubes that would be present even if participant did not agree to take part in this study.

There is a chance that the surgeon may decide during the surgery that the abdominal wash will not be performed, for example if the disease has spread to or attached to certain organs. If this occurs, as many of the tumors will be removed as possible, followed by brachytherapy and the implantation of radioactive seeds. To perform brachytherapy, straws loaded with radioactive seeds will be inserted into the abdominal area. The radiation will then take place in the operating room over about 20 minutes. The straws will be removed before ending the surgery. Participant may be able to return for the abdominal wash procedure 4 weeks after the seeds have been implanted.

Pharmacokinetic Testing:

During participant's surgery, extra blood (about ½ teaspoon each time) and fluid from the abdominal area will be collected for pharmacokinetic (PK) testing when participant begins to receive the first infusion of the heated doxorubicin then 30, 60 and 90 minutes after the infusion has started, and again 24 hours after receiving the heated doxorubicin. The blood and fluid from the abdominal area will be collected through already placed catheters, so no additional needle sticks will be required. PK testing measures the amount of study drug in the body at different time points.

Length of Study:

Participant will remain on study for up to 6 months. Participant will be taken off study if the disease gets worse.

If the study doctor learns that the disease has come back or gotten worse at the 6 month follow-up visit, participant may be eligible to have the operation with heated doxorubicin wash repeated. If participant is eligible to have the surgery repeated, participant's active participation on this study will end and then participant will be given a new consent form to sign in order to be re-enrolled back onto this study.

Study Visits:

On Days 1-5, 11, and 14, (Day 1 being the day after surgery):

* Blood (about 1 teaspoon) will be drawn for routine tests.
* Participant will have a physical exam.

Follow-Up Visits:

About 1, 3, and 6 months after the surgery is complete, participant will have a follow-up visit and the following tests and procedures will be performed:

* Participant will have a physical exam.
* Blood (about 1-3 teaspoons) will be drawn for routine tests.
* Participant will have an ECHO to check your heart function.

It is recommended that participant has follow-up visits at MD Anderson at 3 and 6 months after surgery. In addition to blood draws (about 1-3 teaspoons each time), participant will have an MRI, CT, or PET-CT scan to check the status of the disease. These 3 and 6 month visits after surgery may be performed at participant's local doctor's office and/or laboratory.

This is an investigational study. Doxorubicin is FDA-approved and commercially available. The use of a heated doxorubicin wash during abdominal surgery in patients with tumors is investigational. The study doctor can explain how the study drug is designed to work.

Up to 28 patients will take part in this study. All will be enrolled at MD Anderson.

Study of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Intraoperative Brachytherapy for Unresectable or Refractory Pelvic and Abdominal Rhabdomyosarcoma and Undifferentiated Sarcomas in Children

A Phase I Study of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Intraoperative Brachytherapy for Unresectable or Refractory Pelvic and Abdominal Rhabdomyosarcoma and Undifferentiated Sarcomas in Children

MTD defined as the highest dose in which 1 or fewer patients in 6 treated experience a dose limiting toxicity (DLT).

Hematologic DLT defined as Grade IV neutropenia, anemia, or thrombocytopenia per Common Toxicity Criteria. Non-hematologic DLT is any Grade III or IV non-hematologic toxicity excluding Grade III nausea or vomiting, Grade III hepatic toxicity which returns to Grade I within two weeks of the HIPEC, or before hospital discharge, or Grade III fever occurring after the HIPEC per Common Toxicity Criteria.

Disease progression defined by radio graphically visible nodules greater than 1.5 cm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Malignant Pediatric Pelvic Tumors: A Retrospective Study	NCT02557256	Abdominal Neopl... Pelvic Neoplasm...		- 18 Years	Assiut University
Evaluation of Continuous Positive Airway Pressure for Tumor Motion Management in Radiotherapy	NCT02324530	Tumor Motion "Continuous Pos... Lung Cancer Breast Cancer Abdominal Tumor...	Continuous posi...	18 Years -	Sheba Medical Center
Study of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Intraoperative Brachytherapy for Unresectable or Refractory Pelvic and Abdominal Rhabdomyosarcoma and Undifferentiated Sarcomas in Children	NCT03111069	Malignant Neopl... Rhabdomyosarcom... Rhabdomyosarcom...	Abdominal Surge... Doxorubicin Intra-Operative...	1 Year - 6 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for abdominal tumors