Protons, photons and brachytherapy as the boost in locally advance prostate cancer

Reporter: Arpi Thukral, MD MPH
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 13 de mayo del 2011

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Presenter/Author: I.N. Kanchelli
Presenter's Affiliation: Russian Scientific Center for Roentgen-Radiology, Moscow, Russia

Background

  • Locally advanced prostate cancer is a serious health problem, and recurrence after treatment with conventional radiation therapy can leave patients and providers with few curative options.
  • Previous randomized trials have shown that dose escalation provides 10-20% improvement in biochemical progression free survival, but this has not yet translated to an overall survival benefit. (Kuban, 2008; Zeitman, 2005; Peeters, 2006)
  • While dose escalation in prostate cancer patients may increase the probability of local tumor control, it carries a risk of increased adverse effects to the volume of normal tissue treated in proximity to the tumor.
  • Many studies have examined different radiotherapy techniques to boost the prostate after pelvic radiation in which a lesser volume of normal tissue is irradiated. The organs of most concern are bladder and rectum and reduction of high-dose levels to these structures could result in decreased treatment-associated morbidity.
  • Proton therapy has been used for the treatment of prostate cancer at many proton centers in an effort to dose escalate while sparing normal tissues.
  • This study was performed to evaluate and compare toxicity associated with 3 different modalities of radiation therapy (protons, photons, and brachytherapy) used for boost treatment in locally advanced prostate cancer.

Materials and Methods

  • 259 patients with intermediate or high-risk prostate cancer were analyzed.
  • All patients received photon irradiation of the small pelvis with a dose of 44-46 Gy for 22-23 fractions with a 6-field technique.
  • The patients were then separated into 3 groups for boost treatment:
    • Group 1 (82 pts): proton boost irradiation (treated with 2 opposing lateral fields)
      • Patients were treated with:
      • X-ray positioning with free marker (endostate)
      • 220 MeV protons to a dose of 28.0-28.8 Gy(RBE) for 3-8 fractions 3.0-5.5 Gy(RBE)
        • Various proton fractionation schemes were used:
          • 3 Gy(RBE) x 8 (5 fractions/week)
          • 4 Gy(RBE) x5 (5 fractions/week)
          • 4 Gy(RBE) x5 (3 fractions/week)
          • 5.5 Gy(RBE) x 3 (3 f fractions/week)
    • Group 2 (121 pts): photon boost irradiation
      • 6-18 MV photons to a dose of 24-26 Gray for 12-13 fractions
    • Group 3 (56 patients): I125 brachytherapy boost to 110 Gy
      • Used a standard perineal brachytherapy implant method using TRUS
  • Groups 1 and 2 were formed by using random sampling, (included all patients) and group 3 included only patients with a low risk of infravesical obstruction.
    • Exclusion criteria for Group 3 (brachytherapy group): T3b-4 or N1, prior TURP, infravesical obstruction.
  • All patients received hormonal therapy for 3-6 months prior to and during radiation and 6 months after.

Results

  • No significant difference was seen in age of patients between the 3 groups.
  • Rate of grade 3-4 ACUTE GU toxicity based on RTOG criteria:
    • 0% for groups 1 and 2 vs. 7.1% for group 3 (p>0.05).
  • Rate of grade 3-4 LATE GU toxicity based on RTOG criteria:
    • 0% for groups 1 and 2 vs. 8.9% for group 3 (p>0.05).
  • Rate of grade 3-4 ACUTE GI toxicity based on RTOG criteria:
    • 0% for all groups
    • Grade 2 GI toxicity seen more often in photon boost group.
  • Rate of grade 3-4 LATE GI toxicity based on RTOG criteria:
    • 0% for all groups
    • Grade 2 GI toxicity seen less often in proton boost group (8.4% vs. 31.5% vs. 28.6% in groups 1,2,3 respectively, p<0.05).
  • Among the proton subgroups, increased grade 2 rectal toxicity was seen in the 4 Gy per fraction group: 67.4% vs. 36-41% in the other 3 Gy and 5 Gy proton subgroups (p<0.03). No other significant differences were seen among the proton subgroups.
  • Efficacy in terms of local control (LC) and overall survival (OS) was comparable among all 3 groups.
    • LC: 95-98% for all groups
    • 3 year OS: 88.5% vs. 83.0% vs. 96.3% in groups 1, 2 and 3 respectively (p>0.05)
    • 5 year OS: 75.1% vs. 71.8% vs. 96.3% in groups 1, 2 and 3 respectively (p>0.05)

Author's Conclusions

  • Radiation treatment for locally advanced prostate cancer to small pelvis followed by proton boost at 28Gy(RBE) was associated with the least amount of toxicity in this cohort, when compared to other radiation boost techniques.
  • On the other hand, the brachytherapy boost technique was associated with the most toxicity, even though patients at high risk for toxicity were excluded from this group.

Clinical Implications

  • The authors of this study have shown that LC and OS for prostate cancer boost radiation with proton, photon, or brachytherapy techniques are comparable at 5 years.
  • More importantly though, this study demonstrates an advantage to using proton radiation treatment for prostate boost therapy in terms of reducing GI and GU late-toxicity. Furthermore, brachytherapy boost was associated with an increased risk of toxicity compared to the other 2 groups, even despite patient selection for this group.
  • It is clear from the results of this study that, after pelvic radiation treatment, the addition of brachytherapy to boost the prostate can be highly toxic and should be avoided in clinical practice if possible.
  • However, the real question becomes whether or not the financial and logistical costs of proton therapy outweighs its potential small benefit over photon therapy in its use for boost in these patients.
  • With newer techniques of localizing and tracking the prostate, such as Calypso and image guided radiation therapy, photon beam boost may be comparable to protons in terms of normal tissue sparing. It is unclear whether a limited resource such as proton therapy should be used for this purpose, given its economical constraints.
  • However, one advantage of proton therapy that was not examined in this study, is that it may reduce likelihood of sexual dysfunction associated with prostate radiation, due to decreased radiation dose to the autonomic nerves in the sacral plexus.
  • Future work should focus on further dose escalation and possibly even hypofractionation using protons to exploit its tissue sparing benefit demonstrated in this study and previous work.

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