Medical Archive

Hall C24 Retreatment after Radiotherapy: The possibilities and the Perils

1 Three major reasons for second cancers

    1. Continued lifestyle – smokng, alcohol
    2. Genetic predisposition
    3. Treatment-related
      • à in the case of RT, most 2nd cancers not only occur within or close to the Tx field, but also occur in remote locations (lung)

    2 Factors related with reRT

    • Initial RT – dose, volume, and extent
    • Chemotherapy in the initial Tx
    • Time interval
    • The tissues and organs involved
    • Highly conformal tech – SRS, SBRT, brachy
    • Alternative options

    3 Early and late responding tissues

    • Early responding tissue
      • Self-renewing and rapidly proliferating cellsSurviving stem cells à partly or completely restoredTolerate reRT to almost full dose, provided sufficient time is allowed
    • Late responding tissue
      • Not have ability to recover from the initial damage
      • Some slowly proliferating tissues – partial proliferating and functional recovery à take months and some residual damage

    4 Preclinical data

    Rodent skin

    • Quick recover  – slower with increased initial dose

    Rodent hind limb deformation

    • Representing late subQ fibrosis
    • Much poorer retreatment tolerance

    Monkey – spinal cord

    • 44Gy/22fx à 1~3 yr à 57.2~66Gy
    • 4/45 developed myeloparesis

    5 Clinical studies

    Spinal cord

      • A major dose-limiting organIncidence of myelopathy in conventional 2Gy/fx
        • <1% for 50-55Gy / ~5% for 55-60Gy
        Substantial recovery in reirradiation
        • Initial Tx – not exceed 90% of acceptable BED1 year or more time interval
        Important threshold of a cumulative BED – 130-135% of acceptable BED (a/b=3)
        • Not possible to suggest more detailed recommendations concerning the optimal dose and fx size
        SBRT for salvage Tx
        • Nelson, Sahgal – prior RT of spinal mets24 Gy / 3 fx without unacceptable toxicity

    Brain

    • No animal data
    • Recurrent glioma study (Mayer and Sminia)
      • Cumulative BED > 100Gy à normal brain tissue necrosis
      • In most cases, initial RT – 60Gy in 2Gy/fx
      • a/b=2, BED 2Gy equivalent
    • time interval: no correlation between initial and re-irradiation (LINAC vs. GKS)
    • RTOG 9005
      • 156 pt with recurrent brain tumor and brain mets
      • reRT with single fx SRS à 24Gy (<=20mm), 18 Gy (21-30mm), 15 Gy (31-40mm)greater risk of local progression in recurrent brain tumor and LINAC

    Head and neck

    • Locoregional progression -> major pattern of failure
    • Radical reRT 50-60Gy +/- surgery -> improve LRC and (possibly) survival
    • IMRT (Sulman)
      • Less treatment-related morbidity than conventional tech
      • Median time interval 4y, median lifetime dose 116.1Gy

    Rectum

    • Local recur 10~15%
    • Mohiuddin et al.
      • 103 pt who underwent reRT with concurrent 5-FU
      • Overall survival poor, substantial incidence of early and late complications
      • Wide range of dose

    Bone mets

    • Chow et al
      • Patients who respond to the 1st Tx usually respond to subsequent Tx
      • Limited evidence – small proportion of initial nonresponder would respond to reirradiation
    • No agreement of optimal schedule
      • Single Fx 4 or 8 Gy ~ 35 Gy in 4 fx
    • Pain relief mechanism
      • Appears to be independent of the size reduction
        • Rapid onset of pain relief – absence of dose response
      • Limited life expectancy  – short course vs. multiple fx

    Breast

    • Harms
      • reRT with electron, continuous LDR or pulsed dose rate brachy
        • chest wall – high dose / deep organ can be spared
      • electron reRT  vs.  brachy
        • CR 41-70% vs 79-82%
      • protracted irradiation schedule of CLDR/PDR brachytherapy -> result in improved therapeutic ratio
    • Hyperthermia
      • Vernon
        • RT vs. RT+hyperthermia
          • The greatest advantage: previously treated area recur + lower dose reRT
          • CR rate doubled

    Lung

    • Okamoto
      • Small 34 pt
      • Initial 30-80Gy à reRT 10-70Gy
      • Symptomatic benefit, but substantial toxicity
      • Most patients expired before serious fibrosis
    • Proton or SBRT

    Recurrent vaginal mets

    • Recur or persistent disease after a full course or RT
      • Surgery: best option -> 5y survival 60%
      • reRT: when op is not possible
        • local control, survival poor, significant complications
    • china data
      • early detection, small volume à brachy in most cases