Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Primary Liver Cancer

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Chlorotrianisene

Liver Extracts

Transarterial Chemoembolization will be given within 12 weeks and up to 3 staged procedures, depending on the architecture of the tumor vasculature.

Transarterial Chemoembolization

Dose is 45 Gy (15 Gy in 3 fractions) or 36 Gy(12 Gy in 3 fractions). Tumors should receive the higher dose unless normal tissue constraints cannot be met.

CyberKnife SBRT

Albert Koong, MD, PhD

Daniel Chang, MD

Nishita Kothary, MD

To compare the efficacy of Transarterial Chemoembolization (TACE) to CyberKnife stereotactic body radiotherapy in the treatment of patients with locally recurrent hepatocellular carcinoma (HCC) after TACE.

Hepatocellular carcinoma (HCC) is the third most deadly cancer in the world. It is primarily seen in areas where hepatitis is endemic, such as Asia, but other risk factors include alcoholic cirrhosis.

Surgical resection and/or transplantation remain the only curative options. However, more than 80% of patients present with unresectable disease. For these patients with unresectable tumors, a variety of treatment options are available, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), radioactive microspheres, microwave coagulation, laser-induced thermotherapy, and percutaneous alcohol injection, all of which have similar survival rates. Stereotactic body radiotherapy (SBRT) for unresectable HCC is a relatively new treatment option made available because of significant improvements in diagnostic imaging and radiation delivery techniques. Although follow-up is limited, results show encouraging local control rates. Some investigators have combined TACE with fractionated conventional radiotherapy as a means of intensifying local therapy, with evidence of efficacy.

TACE remains the dominant mode of local therapy for unresectable HCC. However, recurrence rates are high. Because SBRT is rapidly becoming an accepted local therapy for hepatic lesions, its role in treating HCC needs to be further defined. Moreover, once patients have recurred after initial TACE, it is unclear if additional TACE will be as effective or if another mode of local therapy such as SBRT would be preferable.

We propose to conduct a multicenter randomized study comparing TACE vs. SBRT using CyberKnife for locally recurrent HCC. Locally recurrent HCC will include lesions that persist, progress or recur minimum 3 months after initial TACE.

Transarterial Chemoembolization (TACE) vs. CyberKnife for Recurrent Hepatocellular Carcinoma (HCC)

International Randomized Study of Transarterial Chemoembolization Versus CyberKnife® for Recurrent Hepatocellular Carcinoma

Freedom from local progression at time T is defined as lack of local progression in the treated liver lesion in the set of patients alive and on study at time T and without distant progression up to time T.

Progression-free survival will be defined as subject alive and free from local progression, disease recurrence elsewhere in the liver, extrahepatic progression, or clinical deterioration unattributable to another underlying medical condition in the absence of clear radiographic findings of progressive disease.

Overall survival will be determined as a measure of time from diagnosis of initial recurrence until death from any cause.

Serum AFP levels will be measured at specific points during the study. The 2 endpoints to be analyzed are:

* Initial AFP levels
* AFP response - the percent decrease in serum AFP levels from the initial result to the eventual nadir after therapy

These endpoints will be correlated to the clinical endpoints (freedom from local progression, progression free-survival, and overall survival).

Stanford University

Accuray Incorporated

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Step 1: Pelvic Lymph Node Irradiation

Helical TomoTherapy (HT): 41.25 Gy in 15 fractions of 2.75 Gy each

Step 2: Treat boost volume to prostate and seminal vesicles

Acceptable treatment modalities:

CyberKnife SBRT: 19 Gy in 2 fractions of 9.5 Gy each with SBRT

Permanent prostate implant (PPI):

108 Gy for low dose rate PPI with I-125 90 Gy for low dose rate PPI with Pd-103 HDR brachytherapy: 15 Gy in one fraction for HDR

Helical TomoTherapy (HT)

Permanent Prostate Implant (PPI)

HDR brachytherapy

This is a phase I feasibility study to evaluate the feasibility of hypofractionated whole pelvis radiotherapy in 35 patients with biopsy-proven intermediate- to high-risk prostate cancer as defined by NCCN risk criteria. Patients will have \>15% risk of lymph node involvement as defined by the Roach equation 2/3(PSA)+10(Gleason Score-6). Day 0 of the study will be defined as the time of first LHRH/agonist/antagonist injection of hormone therapy. Radiation therapy should begin within 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection. Patients will be followed at 6 weeks and then every 3 months for the first 24 months after completion of radiotherapy in a similar schedule to usual standard of care. A history and physical, PSA, testosterone and EPIC-26 questionnaire will be collected at each visit. Any toxicity according to CTCAE v. 4.0 criteria will be documented. An interim analysis for evaluating acute toxicity (≤90 days) will be performed after the first follow-up visit of the20th patient enrolled on protocol. The trial will be terminated if \>30% acute grade 2 or \>5% grade 3 or greater toxicity is observed as a result of radiation treatment by CTCAE v. 4.0 criteria. Grade 2 toxicity is defined as a minimal, local or noninvasive intervention. Grade 3 toxicity is defined as a severe or medically significant but not immediately life-threatening event requiring hospitalization or prolongation of hospitalization. Previous studies have demonstrated approximately 30% and 5% incidence of Grade 2 and Grade 3 or greater toxicity, respectively, with conventionally fractionated radiotherapy followed by brachytherapy.

Hypofractionated Whole Pelvic Radiotherapy of the Prostate

Phase I Feasibility Study of Accelerated Hypofractionated Whole Pelvic Radiotherapy for Patients With Intermediate-High Risk Prostate Cancer

Acute G3 or greater genitourinary or gastrointestinal toxicity as measured by CTCAE v.4

G3 or greater genitourinary or gastrointestinal toxicity as measured by CTCAE v.4

Albert J. Chang

Assistant Professor

Rachelle Lanciano, MD

Michael Good, RN

Shilecion Cooper, RN

Stereotactic body radiation therapy (SBRT) has been employed in the treatment of prostate cancer. Multiple single institution experiences suggest high biochemical control rates with acceptable toxicity in low risk prostate cancer but efficacy data in unfavorable type prostate cancer is less convincing. CyberKnife-SBRT (CK-SBRT) can be used to escalate radiation dose delivery to the prostate while sparing normal tissue.

The optimal radiation schedule for the curative treatment of prostate cancer remains unknown. Prostate cancer patients receiving radiation therapy are typically treated 5 days per week for 8-9 weeks. Recent data suggest that large radiation fraction sizes are radio-biologically favorable over lower fraction sizes in prostate cancer radiotherapy. The sensitivity of a tumor or normal tissue to fraction size of radiation can be approximated by the alpha-beta ratio. It has been suggested that the alpha/beta ratio for prostate cancer is actually as low as 1.5 implying that the current radiation therapy paradigm for prostate cancer treatment might be fundamentally flawed, as high fraction sizes would be expected to damage tumor more readily.

Typical prostate SBRT doses do not appear to have similar efficacy in higher risk prostate cancer suggesting even higher doses are required. Many techniques including dose escalated external beam radiation therapy (EBRT), proton therapy (PT) and brachytherapy have been employed to increase dose to the prostate. Data from the ASCEND-RT trial utilizing low dose rate brachytherapy boost showed a dramatic 21% improvement in biochemical control at 9 years favoring brachytherapy boost compared to conventional dose escalated EBRT radiation therapy. However, no corresponding benefit was identified in overall survival, incidence of bone metastases or prostate cancer specific mortality while a 3 fold increase in late urinary toxicity was noted.

SBRT is well tolerated with minimal acute and late side effects. In this protocol, CK-SBRT will be used to target the microscopic and gross disease in the prostate, seminal vesicles. An escalated dose of 40 Gy in 5 fractions will be delivered to the entire target volume while any nodules visible within the prostate gland on endorectal MRI will receive 50 Gy in 5 fractions.

CyberKnife Dose Escalation Prostate Cancer Trial

CyberKnife Dose Escalation for Unfavorable and High-risk Prostate Cancer

Genitourinary or Bowel Toxicity as a result of radiation therapy will be reported using

Time in months from completion of SBRT to biochemical failure

time in months from SBRT completion to local failure

time in months from SBRT completion to distant failure

time in months from the date that the patient is determined to be free of disease to the date of known disease recurrence for any measure of disease.

time in months from completion of SBRT to death due to prostate cancer, other causes with active malignancy, or complications from treatment.

ime in months from SBRT completion until death

Crozer-Keystone Health System

Principal Investigator

Neoplasm Metastasis

Colorectal Neoplasms

Neoplasms, Second Primary

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Dose is 45 Gy (15 Gy in 3 fractions) and delivered over 5 to 10 days.

Xavier Mirabel, MD

This prospective, multicenter study is intended to establish the efficacy and toxicity of treating unresectable colorectal liver metastases with accurately administered radiation using the CyberKnife stereotactic radiosurgery system.

Colorectal cancer is the fourth most commonly diagnosed malignant disease worldwide, with an estimated 1,023,000 new cases and 529,000 deaths each year. The liver is the most frequent site of metastatic spread from colorectal cancer, 25% of colorectal cancer patients will have liver metastases at the time of initial colorectal resection and more than 50% of colorectal cancer patients will develop liver metastases during the course of the disease.

The current standard of care and only potential curative therapy for colorectal liver metastases is liver resection of the metastatic lesions. Surgical resection provides long term survival in patients with colorectal carcinoma (CRC) liver metastases. In a report of 1001 patients with metastatic colorectal cancer from Memorial Sloan-Kettering Cancer Center in NY, USA, surgical resection of liver metastases resulted in 3- and 5-year survival rates of 37% and 22%, respectively. Advances in pre- and intra-operative imaging and chemotherapy during recent years have increased overall survival up to 60% at 5 years after liver resection. However, 80-90% of liver metastases are unresectable at the time of diagnosis usually due to tumor location, multifocality, inadequate functional hepatic reserve or the patient's overall condition. For those patients, harboring unresectable liver metastases, alternative treatment approaches include neoadjuvant chemotherapy, local ablation therapy and stereotactic radiation therapy.

The recent availability of neoadjuvant chemotherapeutic agents has increased the response rates and doubled the median overall survival time for metastatic colorectal cancer from 10 to 20 months. Recent studies have demonstrated that neoadjuvant therapy allows 12.5% of patients with unresectable CRC liver metastases to be significantly downstaged and eligible for hepatic resection.

For unresectable CRC liver metastases, local ablative therapies are widely applied. Local ablative treatment refers to a variety of intervention techniques that specifically target tumors to directly destroy them. Numerous methods of ablation have been developed including cryoablation, percutaneous ethanol injection, radiofrequency ablation (RFA) and stereotactic radiation therapy. The most widely employed non-radiation based local ablative treatment is RFA which induces thermal ablation by passing high-frequency alternating current through the tumor utilizing electrodes that are placed within the tumor and surrounding tissue. RFA can be applied percutaneously under ultrasonic guidance or directly during laparoscopy or open laparotomy. Local recurrence rates of 44.4% at 18 months were reported by Solbiati et al. for CRC liver metastases with a median diameter of 2.6 cm. For tumors greater than 4 cm the local recurrence rate was 68%. RFA has an overall 3-year survival rate of 28-46% and a 5-year survival rate of 25%. However, patients with advanced hepatic decompensation, large tumors (3 to 5 cm), or multifocal tumors are generally considered poor candidates for RFA.

Conventional radiation therapy has been shown useful for palliation of hepatic capsular pain, but historically it has played a minor role in the treatment of patients with unresectable liver metastases. This can be attributed chiefly to the low tolerance of the whole liver to radiation. The liver was thought to be a relatively radiosensitive organ and with whole liver irradiation, it was difficult to achieve the radiation doses necessary to eradicate gross tumors without causing radiation induced liver disease. Partial liver irradiation has shown some promise. Limiting irradiation to only one-third of the liver through three-dimensional (3D) conformal radiotherapy techniques, including intensity modulated radiotherapy (IMRT), several studies have shown that partial liver irradiation is safe with doses up to 50-72.6 Gy. However, further dose escalation with conventional radiation therapy techniques risks injury to adjacent abdominal organs.

Stereotactic Body Radiation Therapy (SBRT) has emerged as a novel approach for the local ablation of liver metastases. SBRT provides a conformal isodose distribution with a steep radiation dose gradient allowing much higher doses of radiation than conventional radiation therapy and conformal radiotherapy techniques to be delivered safely with high precision to focal liver metastases while minimizing the radiation dose to normal liver and adjacent organs. To achieve this, precise localization of the target during treatment is required which necessitates accounting for tumor motion. SBRT technology utilizes a number of techniques to accommodate for tumor and respiratory motion including motion-restrictive techniques such as frames and abdominal compression, as well as motion-compensating techniques such as active breathing control and tumor tracking. The motion-restrictive techniques can be difficult for some patients to withstand, limiting those patients from being able to receive treatment. The motion-restrictive techniques can also necessitate the use of wide margins. Rusthoven et al. found a gross tumor volume (GTV) to planning target volume (PTV) expansion of up to 15 mm necessary in the craniocaudal direction. Wide margins can result in irradiation of a substantial volume of normal liver, potentially increasing the risk of radiation-induced injury. Some studies suggest the motion-compensating approach of active breathing control can aid in reducing the margins required by motion-restrictive approaches, however, Korreman et al. suggest those reductions may only be applicable with the use of image-guidance between and within sessions.

The CyberKnife robotic radiosurgery system (Accuray Incorporated, Sunnyvale, CA) an advanced platform to deliver SBRT, provides a therapeutic solution to this problem by continuously tracking the tumor during treatment while it accounts for organ motion due to respiratory movement, using the Synchrony respiratory tracking system (Accuray Incorporated, Sunnyvale, CA). Utilizing continuous tumor tracking, margin expansion to account for motion uncertainty can be reduced, having the potential to make this a safe and effective treatment. The frameless nature of the CyberKnife and its continuous image guidance system eliminates the need of motion-restriction techniques increasing the comfort and availability of the treatment to patients.

CyberKnife® for Hepatic Metastases From Colorectal Cancer

International, Phase II Study of CyberKnife® for Hepatic Metastases From Colorectal Cancer

Local hepatic control (non progression: complete response, partial response or stable disease) will be assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Local recurrence-free survival time is calculated as the time between the date of first treatment session and the date of the first local recurrence. Patients alive who never experienced local recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than local recurrence at the time of analysis are censored at the date of death.

Recurrence-free survival time is calculated as the time between the date of first treatment session and the date of a local or distant recurrence or death from progression whichever comes first. Patients alive who never experienced recurrence at the time of analysis are censored at the date of the last follow-up visit. Patients who die from causes other than cancer are censored at the date of death.

Overall survival time is calculated as the time between the date of first treatment session and the date of death, whatever the cause. Patients alive at the time of analysis are censored at the date of the last follow-up visit.

The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used for toxicity assessment.

* European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) measures the quality of life for patients with cancer (for all participating sites).
* Quality of Life Questionnaire-Liver Metastases Colorectal (QLQ-LMC21) is a specific module developed by the EORTC for patients with colorectal liver metastases (for sites in the United Kingdom, The Netherlands, Germany, France, and Belgium (French speaking part)).

The PERCIST response criteria will be applied to patients who have tumor characteristics measured by a PET-Scan. The association of response according to RECIST 1.1 and PERCIST will be evaluated with Spearman's correlation coefficient and the kappa statistic.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Transarterial Chemoembolization (TACE) vs. CyberKnife for Recurrent Hepatocellular Carcinoma (HCC)	NCT01318200	Recurrent Hepat...	Transarterial C... CyberKnife SBRT	18 Years -	Accuray Incorporated
Hypofractionated Whole Pelvic Radiotherapy of the Prostate	NCT02546427	Prostate Cancer	Helical TomoThe... CyberKnife SBRT Permanent Prost... HDR brachythera...	18 Years -	University of California, San Francisco
CyberKnife Dose Escalation Prostate Cancer Trial	NCT03822494	Prostate Cancer Prostate Adenoc... Prostate Neopla...	CyberKnife SBRT	18 Years -	Crozer-Keystone Health System
CyberKnife® for Hepatic Metastases From Colorectal Cancer	NCT01318447	Colorectal Live...	CyberKnife SBRT	18 Years -	Accuray Incorporated

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