MCC02961 Combined hypofractionated IMRT

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MCC-02961Combined hypo-fractionated IMRT HDR
for intermediate risk carcinoma of the prostate

• D Todor, N Dogan, D Arthur,
• M Fatyga, M Anscher
• M Hagan

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Intermediate Risk CAP

• NCCN Intermediate Risk Category
• T2b or T2c or
• Gleason score 7 or
• PSA 10-20 ng/ml
• Expectant management not considered reasonable
  for pt with gt10 yr LE
• 15 metastasis in 15 yr
• 11 die of prostate cancer (15yr data)
• Brachytherapy as mono-therapy or prostatectomy
  without PLN dissection are not recommended
• Johansson et
  al. JAMA 1997

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Intermediate Risk CAP

• Heterogeneous patient group including those with
  one or more of the following
• Likely peri-prostatic extension (20-60)
• PLN involvement (2-40)
• High parenchymal tumor burden (high number of bx
  cores )
• Evidence from series and trials favor
• Increased radiation dose
• Use of neo-adjuvant accompanying androgen
  ablation
• Treatment of PLN
• 
  Partin tables 2001

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Why use combined HDR hypo-fractionated IMRT ?

• Allows dose-escalation to the prostate with
  optimal rectal-sparing.
• IMRT component treats elective PLN basins while
  sparing bowel
• Hypo-fractionation allows simultaneous integrated
  boost of the prostate

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Why use combined HDR IMRT ?

• Rectal sparing
• Treatment of the anterior rectal wall adjacent ot
  the prostate to doses gt 72 Gy increases the risk
  for rectal bleeding.
• IMRT alone cannot treat the posterior prostate
  above 75 Gy without exceeding these levels of
  rectal dose.

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Treatment Design

• Goal was to provide
• minimum of 76 Gy to the prostate
• Treating 5mm peri-prostatic shell to 65Gy
• Prox SV to 65 Gy
• treating elective nodes to 50.4Gy
• Including high risk nodal basins, positive by
  EPLND (Scardino von Escenbach)
• using short-term androgen ablation for selected
  patients
• T2b, Gl 7 with PSA gt10

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Treatment Design

• IMRT component
• 70 Gy NTD1.8Gy to the prostate (63 Gy _at_ 2.25
  Gy/fx)
• 5mm peri-prostatic
• Proximal SV
• elective nodes to 50.4Gy _at_ 1.8Gy/fx
• Int iliac bifurcation to level of prostate apex
• Ext iliac bifurcation to 2.5cm sup to pubic
  tubercle
• HDR component
• 6 Gy, single fx (10.8 Gy NTD 1.8 Gy)
• Total 80.8 Gy NTD 1.8 Gy

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HDR dose heterogeneity

• 6Gy targeting of the PZ margin
• 80 of the PZ receives 9Gy
• Full thickness rectal wall is at 4Gy

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Final optimization for normal tissue sparing
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Clinical results to date

• 47 patients treated with this treatment paradigm
• Includes patients on MCC 02961 and its pilot

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HDR IMRT Early Response Data
Includes patients from MCC 02961 and pilot study
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Unanticipated results

• Rapid decrease in PSA
• Prostate atrophy equivalent to seeds

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Dose In-homogeneities in HDR Prostate Boost

• HDR Creates sub-volumes of high dose.
• In the LQ model dose in-homogeneities are
  amplified by the quadratic term, pronounced for
  prostate tumors.
• Prescription at the prostate periphery causes a
  significant sub-volume of the prostate to receive
  a high BED.
• We show the extent of this effect by calculating
  the Equivalent Uniform BED (ESD) under the
  condition of BED saturation.
• The peripheral dose prescription was 9Gy in 1Fx,
  corresponding to BED of 36Gy.

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Dose In-homogeneities in HDR Prostate Boost

• The ESD index saturates at 150 of the
  prescription BED (upper figure).
• More than 50 of the prostate volume is in the
  super-hot condition (lower figure).
• Conclusion a typical HDR boost treats more than
  50 of the prostate volume to greater than 150
  of the prescription dose.

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Conclusions I

• Single-fraction HDR boosted hypo-fractionated
  IMRT is a safe and effective treatment for
  intermediate risk prostate cancer.
• No relapses have been observed for 43 patients
  followed for a median of 45 months.
• No acute grade 3 toxicities were observed.
• The most significant late toxicity was erectile
  dysfunction, not resolved with sildenafil for 8
  of 43 patients.

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Conclusions II

• Biological response is consistent with the
  estimated NTD1.8Gy of 80.8 Gy.
• Early PSA decrease after protocol treatment is
  similar to that observed after interstitial
  brachytherapy.
• Prostate atrophy observed two years following
  protocol treatment is also similar to that
  observed following interstitial brachytherapy.

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