Genitourinary Cancer

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SU_32_2322 - Maximum Tolerated Dose (MTD) Reached in a Phase I Dose Escalation Trial of Prostate Bed Stereotactic Body Radiation Therapy (PB-SBRT)

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Maximum Tolerated Dose (MTD) Reached in a Phase I Dose Escalation Trial of Prostate Bed Stereotactic Body Radiation Therapy (PB-SBRT)
S. Sampath1, B. Yuh2, P. Frankel3, A. Liu4, T. E. Schultheiss1, B. Del Vecchio5, T. Tsai1, and J. Y. C. Wong1,4; 1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 2Department of Surgery, City of Hope National Medical Center, Duarte, CA, 3Department of Information Sciences, City of Hope National Medical Center, Duarte, CA, 4City of Hope National Medical Center, Duarte, CA, 5Clinical Trials Office, City of Hope National Medical Center, Duarte, CA

Purpose/Objective(s):   To define the MTD from a phase I dose escalation trial using PB-SBRT and present final toxicity results.

Materials/Methods:   Postprostatectomy patients with non-metastatic, node-negative, prostate cancer with recurrent prostate-specific antigen (PSA) <2.0 were eligible.  Using a modified 3+3 (PMID 18182661), dose was escalated from 35 Gy (dose-level 1 [L1]), 40 Gy (L2), to 45 Gy (L3) in 5 fractions, given every other day.   A dose-limiting toxicity (DLT) was defined as CTCAE (version 4) grade 3 or higher gastrointestinal (GI) or genitourinary (GU) toxicity related to PB-SBRT within 90 days of treatment.  MTD was the highest dose where <33% of the patients experienced DLT.   A total of 15 patients were enrolled at the MTD.  PB-SBRT was delivered using volumetric arc intensity modulated radiation therapy with kilovoltage cone-beam computed tomography prior to each fraction.  Fiducial markers were placed in the prostate bed prior to simulation.  An air-filled rectal balloon was inserted for simulation and treatment.  Dose constraints to bladder and rectum were modeled after a previous prostate SBRT trial (PMID 21464418).

Results: A total of 26 patients completed treatment over a 4-year period.  Median follow-up times were 44 months, 31 months, and 18 months, on L1, L2, L3, respectively.  Toxicity data are listed in Table 1. No grade 3 or higher acute events (<90 days) were observed, and the MTD was 45 Gy.  Acute Grade 2 GI events were seen in 4 patients (proctitis n=2; hemorrhoids, n=2). Two patients had late grade 2 hemorrhoids.   Late grade 2 GU events were seen in 3 patients in L3 (urinary incontinence, n=1, ongoing; non-infective cystitis, n=2, both resolved).  There were 3 patients with grade 3 GU toxicity. Two patients had a late grade 3 ureteral stenosis, requiring stent placement.  The L2 patient had baseline grade 2 incontinence and elected for a urinary sphincter during follow-up.  The median pre-SBRT PSA was 0.42 (range 0.07-1.52).  The median time between surgery and SBRT was 21 months (range 9-97).  Positive margins were noted in 14 patients (L1, n=2; L2, n=4; L3, n=8). Androgen deprivation therapy (median 6 months) was given to 10 patients (L2, n=4; L3, n=6).   Biochemical control (PSA <0.2) is reported by dose level: L1, 0/3; L2, 6/8; and L3, 9/15.

Conclusion:   The MTD was 45 Gy in 5 fractions.  The 12% incidence of late grade 3 GU toxicity needs confirmation with future studies.  Given higher grade 2 GU events seen in L3 and similar levels of early biochemical control in L2, we recommend a phase II dose of 40 Gy in 5 fractions. Table 1. Toxicity results  
 

35 Gy ( n=3)

 

40 Gy (n=8)

 

45 Gy (n=15)

 

Acute

Late

Acute

Late

Acute

Late

 Highest GI toxicity

No.

No.

No.

No.

No.

No.

Grade  0

2

2

2

6

8

8

Grade 1

0

0

4

1

6

7

Grade 2

1

1

2

1

1

0

Grade 3

0

0

 

0

0

 

0

0

Highest GU toxicity

Grade 0

2

2

5

5

10

6

Grade 1

1

0

3

2

5

5

Grade 2

0

0

0

0

0

3

Grade 3

0

1

 

0

1

 

0

1

 

Author Disclosure: S. Sampath: None. B. Yuh: None. T.E. Schultheiss: Employee; Methodist Hospital of So Cal. B. Del Vecchio: None. T. Tsai: None. J.Y. Wong: Research Grant; Accuray Inc. Honoraria; Accuray Inc. Board Member; City of Hope Medical Group Medical Foundation.

Sagus Sampath, MD

Biography:
Sagus Sampath, MD, Associate Clinical Professor, Department of Radiation Oncology, City of Hope National Medical Center, Duarte CA
Dr. Sampath completed his residency at the University of Utah in 2010. After working at the University of New Mexico for 2 years, he joined City of Hope in 2012. He specializes in treating head/neck cancer, sarcoma, prostate, and thoracic malignancies. Dr. Sampath's research interests are exploring novel ways to incorporate SBRT in clinical practice across multiple disease sites, including prostate, head/neck, and lung cancer.

Presentation(s):

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SU_32_2322 - Maximum Tolerated Dose (MTD) Reached in a Phase I Dose Escalation Trial of Prostate Bed Stereotactic Body Radiation Therapy (PB-SBRT)



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