A Study of Patients Receiving High-Dose Rate Brachytherapy

A Pilot Study of High Dose Rate Brachytherapy in The Radiation Oncology Branch

Background:

• One standard way of giving radiation is to combine external beam treatments with internal brachytherapy treatments, which involve short-range radiation therapy that gives a high dose of radiation directly to a cancer or to the area where cancer cells were removed.
• Brachytherapy is done by placing hollow implant device(s) into the area to be treated and then moving a radiation source into each. The type of device depends on the type of cancer and the site to be treated. These devices can range from hollow applicators and needles to balloon-like equipment.

Objectives:

• To evaluate the quality of the brachytherapy procedure at the National Institutes of Health Radiation Oncology Branch.

Eligibility:

• Patients with cancer who could potentially benefit from high-dose brachytherapy as part of their treatment.

Design:

• In conjunction with their existing treatment, patients will be treated with high-dose brachytherapy as determined appropriate for their particular type of cancer and cancer history.
• Each treatment will take place in the Radiation Oncology Clinic.
• If the patient does not have implant devices, the clinic staff will insert them and check their placement through a computed tomography (CT) scan.
• The calculations to determine the appropriate brachytherapy dose will take a few hours; the brachytherapy treatment itself will take between 10 and 30 minutes.
• The number of brachytherapy treatments will vary according to the individual needs and requirements of each type of cancer and each patient.
• Patients will return to the Radiation Oncology Clinic for follow-up visits at 1, 3, 6, 9, and 12 months after the completion of radiation therapy. Follow-up evaluations will include a medical history and physical examination, assessment of any side effects of radiation therapy, and a repeat of any imaging (i.e., CT, magnetic resonance imaging (MRI), X-ray) that was done at baseline to evaluate the tumor response.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Esophageal Cancer; Prostate Cancer; Endometrial Cancer; Biliary Cancer
• Intervention / Treatment: Radiation: High Dose Radiation (HDR) Brachytherapy; Diagnostic test: MRI; Diagnostic test: CT; Diagnostic test: PET Scan

Detailed Description

BACKGROUND:

• High dose rate brachytherapy (HDR) is a challenging technique utilized in many malignancies in order to deliver a high dose of radiation therapy to a tumor in a conformal fashion with a rapid dose fall-off with the objective of sparing normal surrounding tissue
• HDR therapy has been targeted to particular subsites as an integral part of either definitive management or palliation for malignancy-related symptoms.

OBJECTIVES:

• The primary objective is to determine the quality of high dose rate brachytherapy implants performed in the radiation oncology branch. An implant will be adequate if 90% of the GTV receives 90% of the dose prescribed and 80% of the Gross Tumor Volume (GTV) receives 85% of the prescribed dose. An implant will be inadequate if the above dose limitations are not met.
• To evaluate local control and late toxicity rates following brachytherapy at the NCI ROB
• To increase the flow of oncology participants requiring brachytherapy to the National Cancer Institute (NCI) Radiation Oncology Branch (ROB), as these participants lend themselves to special study and have unique educational value for the purpose of educating nurses, medical students, residents, physicists, clinical fellows, and physicians.

ELIGIBILITY:

-Participants with cancer who could potentially benefit from the use of high dose rate brachytherapy as a component of their treatment.

DESIGN:

• Participants will undergo appropriate work-up and clinical evaluation to determine if high-dose brachytherapy would be beneficial in either primary treatment or palliation of their disease. Participants will be treated with high-dose brachytherapy appropriately sequenced with other modalities in their treatment regimen. This treatment will be administered in accordance with standard radiation oncology practice and per the ABS (American Brachytherapy Society) guidelines.
• The participants disease status and toxicity outcomes will be documented for a 12-month period at 3-months intervals.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

  1. Pathologically confirmed malignancy for which high-dose rate brachytherapy is appropriate as a component of their therapeutic regimen.
  2. Age greater than 18 years of age.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  4. Participant must have a primary medical or surgical oncologist in the community or at National Cancer Institute (NCI) who is willing to collaborate with the Radiation Oncology Branch (ROB) staff in the clinical management of the participant.
  5. Participants of childbearing or child- fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
  6. Site-specific inclusion criteria (any one or more of the following):

Gynecologic Cancers:

Endometrial cancer

• Participants at a higher risk of recurrence (because of either grade, myometrial invasion, lymphatic vascular space invasion, tumor size, lymph node status, tumor extension, presence or absence of surgical staging)
• Participants who have suffered a recurrence at the vaginal cuff
• Participants who are unable to undergo surgery and must have treatment for an inoperable primary endometrial cancer.

Cervical cancer

• Participants who are unable to undergo surgery and must have treatment for an inoperable primary cervical cancer.
• Participants with locally advanced cervical cancer in whom brachytherapy will be integrated as a boost to external beam radiation either in a palliative or curative setting (definitive or post-operative setting).

Lung cancer

• Participants with an endobronchial component causing symptoms
• Participants who cannot undergo resection because of poor lung function or distant lung metastasis

Breast cancer

• Infiltrating ductal carcinoma or ductal carcinoma in-situ (DCIS), stage T0, T1, and T2 less than or equal to 3.0 cm, N0 and M0,
• Participants benefiting from high dose radiation (HDR) as either as a boost or accelerated partial breast irradiation regimen.

Prostate Cancer

-Participants with localized prostate cancer (T1b-T3b) in whom brachytherapy will be integrated as a boost to external beam radiation or used as monotherapy for definitive management.

EXCLUSION CRITERIA:

1. Cognitively impaired participants who cannot give informed consent.
2. Participants currently receiving concurrent investigational chemotherapeutic agents.
3. Participants receiving concomitant chemotherapy administration in the 5 days preceding brachytherapy (except for gynecological cancer patients who may have received concurrent chemotherapy as a component of their treatment regimen)
4. Pregnant or breast-feeding females are excluded because of the potential mutagenic effects on a developing fetus or newborn.
5. Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the judgment of the Principal or Associate Investigator would compromise the participant s ability to tolerate this therapy or are likely to interfere with the study procedures or results.
6. Participants who are in the estimation of the PI, deemed unable or unlikely to adhere to protocol treatment.

7. Abnormal bleeding times or active anti-coagulation therapy.

   • platelets less than 100,000 per mm(3)
   • Prothrombin time (PT)/Partial thromboplastin time (PTT) greater than 1.5 the upper normal limit (UNL)
8. Any participant or tumor/anatomical factors that may prevent brachytherapy apparatus from being properly and safely inserted and positioned and from radiation therapy being administered per American Brachytherapy Society (ABS) guidelines.
9. Participants whose malignancy has one or more of the following site-specific criteria disqualifying them from the study:

1. Breast cancer:

• Participants inappropriate for standard breast conservation therapy (Multicentric disease, inability to achieve clear margins);
• male participants with breast cancer
• autoimmune disorders, including systemic lupus erythematosus (SLE), Scleroderma, etc.

• distant metastases;

  2. Prostate cancer:

• distant metastases
• lymph node metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1/Radiation Therapy; Radiation therapy given as high dose radiation (HDR) Brachytherapy.

Radiation: High Dose Radiation (HDR) Brachytherapy; Brachytherapy, the placement of a radioactive source close to a tumor, is a well-established part of the treatment of many malignancies, both for palliative and definitive applications. High dose brachytherapy is useful in many malignancies in order to deliver a high dose of radiation therapy to tumor in a conformal fashion with a rapid dose fall-off with the objective of sparing normal surrounding tissue.; Other Names: HDR Brachytherapy; Diagnostic test: MRI; When deemed necessary.; Other Names: Magnetic Resonance Imaging; Diagnostic test: CT; Obtained based on the sites of target, as clinical situation dictates and at each follow-up to determine local control.; Other Names: Computed Tomography; Diagnostic test: PET Scan; When deemed necessary.; Other Names: Positron Emission Tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had Adequate High-Quality Brachytherapy Implants Reported Per Strata (Four Body Sites) and Combined Overall	An implant is adequate if 90% of the Gross Tumor Volume (GTV) receives 90% of the dose prescribed and 80% of the Clinical Tumor Volume (CTV) receives 85% of the prescribed dose. An implant is inadequate if the above criteria is not met. A GTV only applies to certain disease sites such as gynecologic cancer that have not been removed by surgery and CTV applies to prostate or gynecologic cancer that have been removed surgically.	All participants were assessed 1 week after last dose of high dose radiation (HDR) brachytherapy, an average of 1 week (no range).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Prostate Participants With Local Control	Local control of the prostate is defined as Biochemical recurrence. Biochemical recurrence is a serum prostatic specific antigen (PSA) more than 2 ng/dL above the post brachytherapy nadir, measured by at least 2 PSA measurements separated by 1 month, and the National Comprehensive Cancer Network (NCCN) guidelines.	Assessed at 12 months after radiation
Number of Participants Accrued Who Received Brachytherapy Each Year	To help understand and increase the flow of participants receiving brachytherapy, the number of participants who received brachytherapy each year are reported.	Approximately 16 years
Number of Participants With Local Control Reported Per Strata (Body Sites) and Combined Overall	Local control is defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) of the treated site. In diseases where targets can be imaged, response will be measured using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria only for local sites. Complete Response is disappearance of the target lesion. Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of the target lesion taking into account the baseline sum LD. Stable Disease does not qualify for CR, PR, or progression. Progression is interval increase in the maximal dimension of the target lesion. Scoring of local control at each treated site will be based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria. Each site will be scored separately (Only for local sites) and the number of participants with CR, PR, SD will be determined.	Assessed at 12 months after radiation
Number of Grades 0-5 Late Toxicity Reported Per Strata (Body Sites) and Combined Overall	The Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Radiation Morbidity Scoring Scheme was used to score late toxicity following brachytherapy. Late toxicities are graded 0-5. Grade 0 is no symptoms. Grade 1 is mild/slight symptoms. Grade 2 is moderate. Grade 3 is severe. Grade 4 is severe/life-threatening. And Grade 5 is toxicity related to death.	Date treatment consent signed to date off study, approximately 159 months and 21 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria (CTC) v3.0	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria (CTC v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Assessed at 12 months after radiation
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Radiation Therapy Oncology Group (RTOG)	Here is the number of participants with serious and/or non-serious adverse events assessed by the RTOG. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Assessed at 12 months after radiation

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Deborah E Citrin, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van den Bergh AC, van de Steen-Banasik E, Beerman H, van Lent M. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000 Apr 22;355(9213):1404-11. doi: 10.1016/s0140-6736(00)02139-5.
• Kocak Z, Ozkan H, Adli M, Garipagaoglu M, Kurtman C, Cakmak A. Intraluminal brachytherapy with metallic stenting in the palliative treatment of malignant obstruction of the bile duct. Radiat Med. 2005 May;23(3):200-7.
• Perez CA, Grigsby PW, Castro-Vita H, Lockett MA. Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 1995 Jul 30;32(5):1275-88. doi: 10.1016/0360-3016(95)00220-S.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2009
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): July 24, 2025

Study Registration Dates

• First Submitted: June 17, 2009
• First Submitted That Met QC Criteria: June 17, 2009
• First Posted (Estimated): June 18, 2009

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Training; Cancer; Brachytherapy; Radiation; HDR
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Uterine Diseases; Genital Diseases, Female; Head and Neck Neoplasms; Biliary Tract Diseases; Esophageal Diseases; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Neoplasms; Prostatic Neoplasms; Biliary Tract Neoplasms; Esophageal Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Therapeutics; Diagnostic Techniques and Procedures; Diagnosis; Physical Phenomena; Tomography; Diagnostic Imaging; Radiotherapy; Radiography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Radiation; Magnetic Resonance Imaging; Brachytherapy; Tomography, X-Ray Computed; Positron-Emission Tomography
• Other Study ID Numbers: 090100; 09-C-0100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes