LESSONS-FROM-THE-BOSTON-EXPERIENCE by asafwewe

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									                     LESSONS FROM THE BOSTON EXPERIENCE
                           IN PROTON BEAM THERAPY1

                                         Michael Goitein, Ph.D.

                                            Harvard Medical School
                                                     &
                                                ProConsultants
                                Ankerstrasse 1, CH-5210 Windisch, Switzerland

                                             (michael @ goitein.ch)



The following is a summary of some of the lessons which I and my colleagues have drawn concerning
proton beam therapy from some 30 years experience at the Massachusetts General Hospital (MGH). My
comments cover both the years of pre-clinical and clinical experience at the Harvard Cyclotron Laboratory
(HCL) and the design and construction of a new proton medical facility. The work was a collaboration with
members of the HCL and the Massachusetts Eye and Ear Institute - and the clinical treatments discussed
here were all performed at the HCL. As I left the MGH over 2 years ago, these comments should not be
understood as my speaking for that institution – which I no longer can do.

While my experience, and the following comments, are in the field of proton beam therapy, many of the
following points are intended to be helpful in planning light-ion facilities, too.


CLINICAL EXPERIENCE AT THE HARVARD CYCLOTRON LABORATORY (1961-2001)
          HCL had a 160 MeV proton beam
               which penetrates only 160mm in H2O
               this was the reason that only a limited number of tumor sites were investigated
               this experience confirmed the need for a higher energy machine – which needs to
                penetrate circa 320mm in H2O (this figure being determined by the need to be able to
                deliver a lateral beam of protons in the pelvis reaching at least the contra-lateral pelvic
                wall)
          Kjellberg (neurosurgeon at MGH) used protons at HCL for pituitary ablation and AVM
           obliteration – similar work started about the same time (circa 1960) in Berkeley, USA and
           Uppsala, Sweden.
                 this gave protons an unwarranted reputation as being particularly suited for the treatment
                  of small targets (e.g. from one to a few centimeters in diameter)
                 a single high-dose fraction of radiation was used for the treatments
                 the suspension of proton program in Uppsala stimulated the invention of the gamma-
                  knife


1Presented at the workshop of the International school on “Physics and Industry” on the topic of “Particle
Accelerators and Detectors: from Physics to medicine”, Erice, Sicily, 15-17 April 2004.


                                                   - 1     -
          In circa 1974 Suit and Goitein and others from the MGH and Koehler, Schneider, Sisterson and
           others from the HCL initiated large-field conventionally-fractionated proton beam therapy at the
           HCL.
                 targets were general tumors– provided they could be reached with a beam of 160mm
                  penetration (for some clinical conclusions, see the presentation in this workshop by
                  Orecchia)
                 fraction sizes of typically from 1.8 to 2 GyE were used2 (except for ocular tumors where 5
                  fractions of 14 GyE were typically employed)
                 protons were only employed if it seemed as though an increase of 10% in effective dose
                  was possible
                 we found that protons were particularly well-suited for the treatment of large targets (i.e.
                  large compared to the anatomic compartment) as sparing of uninvolved tissues within the
                  body compartment is then much more critical than for small targets. In this relative sense,
                  the treatment of ocular melanomas involves large fields.
                 we consider that a move to a small number of high-dose fractions for anything other than
                  small tumors should be undertaken only with enormous caution – and judge that plans for
                  new facilities should not rely (e.g. for their business model) on the use of a small number
                  of fractions as this may well not work out in the future.
          The choice of tumor sites
                the HCL program had important successes for some rare tumors (e.g. chordoma and
                 chondrosarcoma of the skull base, ocular melanoma, para-nasal sinus tumors). These sites
                 came to our attention essentially by chance and not as the result of a planned program.
                 This suggests that, in choosing sites for investigation, one should not be too influenced by
                 a high frequency of occurrence.
                these rare sites eventually virtually saturated the treatment capacity at the HCL and this
                 fact, together with the limited penetration of the beam which excluded the majority of
                 human tumors from treatment at the HCL, explains in large part the current lack of long-
                 term clinical experience of the use of protons in the more common tumors.
          The operation at the HCL
               was labor intensive – suggesting the need for more efficient operation
               suggested the need for a proton gantry – the advantages of which are:
                          it allows treatment from any direction – yielding better dose distributions
                          it avoids the need for treatments with more than one position of the patient
                          the better immobilization of supine patients (as compared to seated patients) allows higher
                          precision
                          the supine position allows faster set-ups
               confirmed the undesirability of operating outside of a hospital environment
               confirmed the judgment that the quality of the treatment team is critical. That is, people
                are much more important than tools




2GyE stands for “Gray-equivalent”. It is the physical dose multiplied by the radiobiological effectiveness
(RBE) which, for protons is taken to be 1.1. So, 1.1 GyE = (dose=1Gy) x (RBE=1.1)


                                                     - 2     -
NEW PROTON MEDICAL FACILITY (design/construction 1994-2000; first treatment 2001)

In circa 1990 the decision was made to design and build a new proton medical facility on the grounds of the
Massachusetts General Hospital. The reasons for this (in roughly their order of importance) were as follows:
                  a machine with higher energy that that of the HCL was needed
                  the facility needed to be hospital based
                  a gantry was judged to be necessary
                  a more efficient facility was needed
After a competitive bidding process, Ion Beam Applications (IBA) of Belgium was selected to provide the
equipment for the new facility.

A proton medical facility is large and relatively expensive (vs. a convention linac-based x-ray facility). This is
unfortunate in the sense that the difficulties of raising (and recovering) the funds and in the management
and construction of the facility (see ref [1]) detract from and obscure the really important aspect of the
problem which is, quite simply: how to make the best clinical use of protons. (This is in spite of the fact
that, in the end, the use of protons is probably not enormously more expensive than the use of high-
technology x-rays – see ref. [2]).

Top Level Specifications for a Proton Medical Facility
The following considerations formed the basis of the strategy for building the Northeast Proton Therapy Facility (NPTC) in
Boston. Our experience strongly confirmed their importance.

The specifications for a proton medical facility (see ref [3]) are extremely different from those for a
high energy physics facility – in two important ways:
       1. The most important (top-level) specifications are those relating to: safety, reliability and
          availability, ease of operation and ease of maintenance.
       2. The specifications are application driven. They must start with what is needed for the patient to
          be satisfactorily treated. The equipment requirements are then inferred from these specifications.
The design must also feature a thoughtful allocation between the capital equipment costs (cost of design,
construction and testing) and the running (or operating) costs. In the long term, the running costs are likely
to be dominant, so it is worth spending money up front to reduce the running costs.

In designing the equipment to meet the top level specifications mentioned above, a combination of clever
design and systematic analysis is required. The interaction between the equipment and the building
which houses it is much more complicated than in usual construction, so that the equipment/building
interface needs particular attention.

Safety
       A fatal failure must not occur more often than in circa 1 in 108 treatment field applications.3 This is a
       level of safety not unlike that required of a jumbo jet. To achieve it, a systematic analysis must be made
       and safe design strategies must be employed. It must be realized that safety is an issue at the level of the
       overall system - and not primarily the domain of any subsystem(s) (e.g. the control system).
                      The analysis should include a failure mode effects analysis (FMEA) – see ref [4]
3
    no fatality over 30 years for 50 machines, each delivering some 50,000 fields per year


                                                            - 3      -
                  design strategies (such as the requirements for redundancy) should be developed,
                   documented and followed.

Availability / Reliability
    Conventional linac-based radiation therapy machines operate with an availability (% of time machine is
    available during the period of scheduled operation) of  98%. A lower level of reliability is widely
    considered to be clinically unacceptable. This leads to the requirement that:
                 A proton medical facility should have each treatment room available 98% of the time.
                  This is usually taken to imply that a machine with 3 treatment rooms should have an
                  overall availability (all rooms available) at least 95% of the time.
                 scheduled down time for routine maintenance should not intrude upon a 2-shift,
                  5days/week; 52 weeks/year operation.                (A scheduled 4-weeks of preventative
                  maintenance time would be totally unacceptable in any conventional clinical facility.)
    Availability anti-correlates with safety. That is, for safety a machine should shut down on the
    slightest hint of malfunction. This clearly impacts negatively upon availability.

    Strategies to keep availability high while keeping the system safe need to be adopted. For
    example:
                the system design should require fail-safe operation of all components (that is, any
                 component’s failure will leave the system in a safe condition).
                reliance on a single component to measure or assure a safety-critical function is generally
                 not safe and generally should not be permitted (although this may be acceptable for some
                 enormously reliable components – such as strong mechanical structures)
                the use of two independent components to measure a safety-critical function together
                 with the requirement that they agree with one another increases safety substantially, but
                 may reduce availability unacceptably (depending on the expected failure rate of the
                 components)
                the use of three independent components to measure a safety-critical function and the use
                 of majority logic – i.e. the requirement that at least two of the three agree with one
                 another - will likely maintain safety, and is likely to result in acceptable availability.
    It should not be forgotten that the availability of the other parts of the facility (e.g. of the building with
    its electrical and other utilities) impacts overall availability too.

Operability
    Ideally, a proton medical facility should feature push-button operation. Ease of operation is
    important for the following reasons:
                 it reduces operating costs (full-time operators are not required)
                 it may increase reliability by reducing or eliminating operator error

Maintainability
    Availability is high when failures are infrequent and, when they occur, can be quickly repaired. That is,
    one would like a long meant time between failures (MTBF), and a short mean time to repair (MTTR).
    These are necessary to maintain availability at the required level. A maintainability and reliability
    analysis should be performed on the proton medical facility design to increase the chances that its
    operation will be satisfactory.

    Some features which support a high level of maintainability are:


                                                    - 4     -
                   modular components
                   easily swappable sub-assemblies
                   good diagnostics
                   a good supply of spare parts (in part based on the reliability and maintainability analysis)
                   components available from (preferably, several) commercial sources wherever possible
                   a strong preventative maintenance (PM) program

Other Specifications for a Proton Medical Facility

Extensibility
    Technology changes rapidly. The proton medical facility should, to the extent possible, be designed so
    as to allow the addition of new features and the modification of existing ones.

General vs. Special Purpose facility
    A decision has to be made as to whether to build: a facility to treat general tumors at all sites; or a special
    purpose facility focused on one or a few types of treatment. Given the relative youth of the field, I tend
    towards the former approach. However, special purpose machines are conceivable.

Intensity Modulated Proton Therapy (IMPT)
    It is widely accepted that any proton medical facility built in the future will have to provide an intensity
    modulated proton therapy capability. This implies:
                  some form of beam scanning
                  the need to make provision for organ motion through repainting (even if organ tracking is
                   implemented)

Field Size and Geometry
    Experience has indicated that protons are the more advantageous the larger the tumor (relative to the
    relevant body compartment – which is often the entire body cross-section). Also, the history of
    conventional x-ray therapy has seen the provision of increasingly large field sizes; 400mmm x 400mm at
    isocenter is now usual. There is no reason to think that, for general cancer therapy, proton field
    sizes should be much smaller than for x-ray therapy.

    The development of a parallel beam of protons (e.g. at PSI) – in which the virtual particle source is at
    infinity – provides some quite advantageous fields with minimal junction problems (e.g. for treatment of
    the cerebral-spinal axis in childhood meningiomas). This Cartesian geometry should be seriously
    considered – or alternative means of abutting fields must be provided.

PROJECT REVIEW

The conduct of any project involves a few obvious steps:
      determination and documentation of how the project will be conducted
      determination and documentation of what it is that one wishes to make
      determination and documentation of how the system will be designed, built and tested
      determination and documentation of how changes to the system are to be made during the course of
       the project (e.g. change board review, configuration control, etc.)
      design, construction and testing of the system (with documentation of each step)



                                                     - 5     -
Internal review - QA
To ensure that the above steps are properly carried out, it is essential to institute a program of Quality
Assurance which should be the responsibility of someone not directly involved in the design, construction
and testing of the system.

External review
It has been our experience that frequent external reviews, starting very early in the design process,
continuing throughout it, and extending to the final safety and operation review, are extremely valuable.




                                             REFERENCES

   1. Goitein M and Jermann M. The relative costs of proton and x-ray radiation therapy. Clinical
      Oncology 2003 15: S37-S50.
   2. Goitein, M. The technology of hadrontherapy: the context within which technical choices are made.
      in: Advances in Hadrontherapy; eds. Amaldi, Larsson and Lemoigne; Elsevier, 1997.
   3. Gall, K. et al. State of the Art? New proton medical facilities for the Massachusetts General
      Hospital and the University of California Davis Medical Center. Nucl. Instr. Meth. in Phys. Res.
      B79: 881-4, 1993.
   4. Failure Mode and Effects Analysis (FMEA): A Guide for Continuous Improvement for the
      Semiconductor Equipment Industry. SEMATECH Technology Transfer #92020963B-ENG




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