Tuesday, August 30, 2016

Is there an optimal treatment schedule for high dose rate brachytherapy?

Protocols for high dose rate brachytherapy (HDR-BT) monotherapy vary. In recent years, practitioners have adopted various schedules for patient and physician convenience. Jawad et al. reported on the HDR-BT experience at William Beaumont Hospital. They treated 494 favorable risk patients using three different treatment schedules. Their definition of “favorable risk” was a Gleason score ≤7 and stage≤T2b and PSA≤15 ng/ml. The 3 treatment schedules they utilized, the number of patients who received each, and the relative biologically effective dose  (BED) were as follows:
  1. 38 Gy in 4 fractions (n=319) – 1.29 relative BED 
  2. 24 Gy in 2 fractions (n=79) – 1.00 relative BED 
  3. 27 Gy in 2 fractions (n=96) – 1.25 relative BED
Dose schedules #1 and #3 delivered much higher relative dose compared to dose schedule #2. The questions addressed by the study are whether the higher dose is justified by greater cancer control, and whether dose increased at the expense of increased side effects.

After 5.5 years median followup for schedule #1, 3.5 years for schedule #2, and 2.5 years for schedule #3, the toxicity outcomes were as follows:
  • No difference in clinical outcomes (cancer control) among the 3 treatment schedules.
  • Acute (appearing in less than 6 months) and chronic (appearing 6 months or more after treatment) grade ≥2 genitourinary (GU) and gastrointestinal (GI) side effects were similar for all treatment schedules.
  • Grade 2 acute GU toxicities:
o   Frequency/urgency: 14%
o   Dysuria (painful urination): 6%
o   Retention: 7%
o   Incontinence: 1.5%
o   Hematuria (blood in urine): 1.5%
  • ·      Grade 2 chronic GU toxicities:
o   Frequency/urgency: 20%
o   Dysuria (painful urination): 7%
o   Retention: 4% (Urethral stricture: 2%)
o   Incontinence: 2%
o   Hematuria (blood in urine): 7%
  • ·      There was minimal grade 3 GU toxicity
  • ·      Grade 2 acute GI toxicities:
o   Diarrhea: 1%
o   Rectal pain/tenesmus: <1%
o   Rectal bleeding: 0%
o   Proctitis: <1%
  • ·      Grade 2 chronic GI toxicities:
o   Diarrhea: 1%
o   Rectal pain/tenesmus: 0.5%
o   Rectal bleeding: 2%
o   Proctitis: 1%
  • ·      No Grade 3 or higher GI toxicity
  • ·      Time to maximal appearance of symptoms was similar across treatment schedules
  • ·      They did not report ED rates, which are typically low for HDR-BT.
Given the equivalence of cancer control and toxicity with treatment schedule, and the lack of any effect due to increasing the biologically equivalent dose, there seems to be little basis, other than cost and convenience, for choosing among these treatment schedules, at least with the available follow-up reported here.

Aspects of treatment scheduling that affect the convenience of HDR-BT are the number of implantations of the catheters, and the time frame in which the fractions are delivered.  William Beaumont Hospital uses a single implantation of catheters for all treatment schedules. Schedule #1 involves a longer (overnight) hospital stay because they wait for several hours between fractions for healthy tissue to recover. It also means that anesthesia must be administered over a longer period.

The California Endocurietherapy Center at UCLA has typically used a different protocol. They deliver 42 Gy in 6 fractions, with 3 fractions delivered one week and 3 fractions delivered a week later. This involves 2 overnight hospital stays, with anesthesia each time. Recently, they added a protocol where they deliver 27 Gy in 2 fractions (similar to schedule #3), but those fractions are still inserted a week apart. While this is certainly a cost reduction for the patient, who can now be treated as an outpatient, the patient is inconvenienced by having to go through the full procedure twice. It is a convenience for the treatment team that no longer has to attend the patient over an extended timeframe.

The William Beaumont Hospital experience demonstrates that HDR-BT treatment schedules can be constructed so as to lower costs and increase convenience for patients and doctors, without sacrificing cancer control or quality of life.

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