OSTEOGENIC SARCOMA (OSTEOSARCOMA) RESULTS OF THERAPY by fvo21223

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									VOL.      123,        No.      3



                       OSTEOGENIC                                  SARCOMA                                               (OSTEOSARCOMA):
                                                              RESULTS     OF                                           THERAPY*
                                                                               By      JUSTIN             J. S’rEIN,                      M.D.
                                                                                      LOS     ANGELES,            CALIFORNIA



B ETWEEN                     November              I, 1955        and June                                                                                                     IABLE           I
          30,          1973,46 patients              with       osteogenic                                                                                       AGE      DISTRIBUlION

sarcoma          (osteosarcoma)                   wi thou t evidence
of metastases              were admitted                  to the UCLA                                                                  Age          (Years)                                           No.           of Patients
Center        for Health             Sciences.           The follow-up
                                                                                                                                                   0-4                                                              None
is 100 per cent.                                                                                                                                   5-10                                                                    2
     The youngest               patient         was 5 years             of age                                                                11-20                                                                    29

and the oldest              73; the average                 age was 26.7                                                                      21-30                                                                        4

years      and the median                  age i6.o years;                29     or                                                           31-40                                                                        2
                                                                                                                                              41-50                                                                        4
60.3     per cent of the patients                         were between
                                                                                                                                              5I-60                                                                     3
ages I I and 20 (Table                      I).
                                                                                                                                              61-73                                                                        2
     There        were        26 males             and        20 females.
Thirty-five              patients           were          Caucasian,               6                                                                                                                                   46
Black,        and 5 Mexican                     American.             A peak
incidence          of osteosarcoma                    has been           noted
at about          i8 years         of age with a sharp                     drop                                   the 46 patients      as follows:     mild                                                             in         8;     mod-
above       this age in series ofpatients                           reported                                      erate   in 3; pathological       fracture                                                               in            I  with
in      Westminster,                Massachusetts                    General                                      minimal     trauma;     and I patient                                                                 had             a frac-
Hospital,             Mayo           Clinic,          and         Memorial                                        tune            of         his          femur                30       Tears               previously                           but
Hospital.            In many              reported             series,         the                                no       recent                  history                of        trauma.                   Trauma                        is not
highest       incidence           has been noted                in patients                                       considered                              as      an           etiological                          factor              in        the
between          I I and        20 years          of age.9                                                        causation                          of         osteosarcoma.                                 When                  trauma
     The average              time period              for the appear-                                            does            occur,                  it usually                    directs                attention                         to     a
ance of metastases                    calculated            from the on-                                          pre-existing                              tumor.
set of therapy               was 5.5 months.                    Of the pa-                                            Roentgenographic                     findings        of the        pni-
tients       who        developed            metastases,               87 per                                     mary         lesion     revealed         that     the lesions        were
cent had metastases                      within          a period         of 14                                   of the blastic             type      in i#{231},h-tic     type     in 17,
months          with       the majority                appearing             in 9                                 blastic        and lvtic in 14. There                  was evidence
months          or less time.             The        time of appear-                                              of local soft tissue               involvement             in 34 or 74
ance ofmetastases                    could       not be determined                                                per     cent      ofthe      patients         (Table      ii).
in I patient            because         he did not see a physi-                                                       i\iIcKenna           et al.’2     reported        the data       from
cian during            the last year of his life; in i pa-                                                        the      California           Tumor           Registry         from      i 2
 tient,     metastases              occurred            6 years         and 6                                     participating                                  hospitals                    from              1942              to         1969.
months         later      (this      patient         also had 3 other                                             There                 were              722          cases            of      primary                        malignant
pni mary                    malignancies-breast                                  carcinoma,                       bone                tumors                    during              that             period,                   represent-
cervix                        and
                      carcinoma,        malignant          mela-                                                  ing            an          incidence                         of       0.46            per            cent                 of        all
noma)    ; i patient         had      metastases         to the                                                    malignant                          tumors.                   They                 were           able           to make
lung 8 years        and 5 months           after   the initial                                                     a      personal                        study                of       367           cases                and              found
therapy;       another      patient        had    metastases                                                       that           the following                                t\’pes  of primary       malig-
3 years     and I I months          later.                                                                         nant            bone   tumors                                in decreasing      incidence
    A history       of trauma       was given        by 13 of                                                      accounted                              for      95          per cent      of all primary
   0   Presented            at the   Fifty-sixth     Annual        Meeting          of the    American         Radium          Society,        Maui,            Hawaii,         April        21-5,          1974.

   From         the    Radiation         Therapy     Division,          UCI.A        Center     for   Health       Sciences,           Los     Angeles,            California.
   Supported            by Grant         No. CA-oi       17      from    the    USPHS.


                                                                                                          607
6o8                                                                        Justin         J.     Stein                                                                      MARCH,        1975



                                      TABLE      II                                                   Twenty           (3.3      per      cent)          of     the     6oo osteo-
                               BONE      INVOLVED                                              sarcomas               reported           by         Dahlin            and Coven-
                                                                                               try4      originated              in bone             affected           by      Paget’s
                   Femur                                         28                            disease.         Three           of the 20 patients                    were long
                   Tibia                                           4                           time       survivors,                7 years,            7 years,            and        U
                   Humerus                                         3
                                                                                               years.        Sixteen            of their          patients          had osteo-
                   Mandible                                        3
                   Fibula                                          I                           sarcoma            which           arose        in previously                  irradi-
                   Ilium                                           2                           ated       bone.          None           of these             patients            lived
                   Sacrum                                          2                           more       than         3 years.            Eighty-three                (20.3         per
                   Frontal       bone                              I
                                                                                               cent)     of4o8           patients           who were followed                       and
                   Sphenoid                                        I
                                                                                               treated          before           January              i , i 960         survived
                   Maxilla                                         I
                                                                                               5 years,          and 62 (i7.                   per cent)            of 359 pa-
                                                                46                             tients      who were traced                       and treated               prior       to
                                                                                               J anuary           I, 1955          survived             for io years.
                                                                                                     McKenna               et al.’3 reported                   33 histologi-
                                                                                               cally     proven             cases of osteosarcoma                            arising
malignant          bone               tumors:              osteosarcoma,                       in patients            with osteitis               deformans              (Paget’s
chondrosarcoma,                   Ewing’s              sarcoma,           reticu-              disease).          The 33 cases                   accounted              for 6 per
lum      cell sarcoma,                 and        fibrosarcoma.                 The            cent      of the            cases        of osteosancomas                         diag-
reported       5 year              survival              for “localized”                       nosed        at Memorial                     Hospital.            They          found
tumors         was     given       as follows:             osteosarcoma,                       that      only                patients             with        osteosarcoma
8.9 per cent;                 Ewing’s              sarcoma             18.2       per          arising         in      bones           with        osteitis         deformans
cent;     chondrosarcoma                     62.2       per cent;          reticu-             survived            more          than        5 years           without              evi-
lum cell sarcoma                   42.9       per cent;             and fibro-                 dence         of       metastasis.                The         patients             were
sarcoma          30.8 per cent.                Multiple             myelomas                   treated         by surgery.                It has been stated                       that
were      not      considered              in their           report.        They              approximately                    0.2     per     cent        of the patients
found        that      54.8      per cent              were        male,        90.6           with      osteitis            deformans                 (Paget’s           disease)
per cent Caucasian,                     6.9 per cent Black,                      and           will develop               sarcomas.’5
2.5 per cent other                races. The authors                      recom-                    Lee8 has commented                             that       about          8o per
mended          standardization                    of the staging                and           cent       of patients                   with        osteosarcoma                     die
the      “up-dating”                of the             classification                of        usually         from         lung metastases                     and that              by
bone      tumors.                                                                              Jo months                after        diagnosis             of the        primary
     None       of the 46 patients                    in this series had                       lesion,        8o per cent                  of the metastases                        will
ever     received         radiation             therapy           to the area                  have occurred.
where       the osteosarcomas                      originated.            Irradi-                   He believes                that      since       the results              of im-
ation      has been given                   as one of the predis-                              mediate          surgery             have not been better                          than
posing        conditions            to the possible                    develop-                those       in patients                who have               had preopera-
ment       of osteosarcoma.                    Other           possible         pre-           tive radiation                 therapy           with delayed                 ampu-
disposing          conditions             are osteitis             deformans                   tation       in cases remaining                      free of metastases,
( Paget’s         disease),         fibrous          dysplasia,             osteo-             that the delay                   has cost no lives that might
chondroma,              and giant             cell tumor.                                      have      been saved.                  The trial of preoperative
     With       regard         to pre-existing                    pathology,                   radiation            therapy            followed            by delayed              am-
the 2 patients              who also had Paget’s                         disease               putation            was reported                    by Lee and                   Mac-
are deceased,              one 3 months                   after       the insti-               kenzie9         in     1964.      A total            of 187       patients            with
tution       of therapy             and the other                    patient          9        osteosarcoma              were so treated                         with         4!     (21.9
months         later.      One patient                 had fibrous              dys-           per cent)            5 year survivors.
plasia      with multiple               fractures            involving            the               Preoperative                   radiation             therapy              was        not
left     mandible             and         osteosarcoma.                    Death               recommended                 for patients     who had a funga-
occurred           in this        patient            i6 months                 after           tion of the             tumor    as a result    of the biopsy,
the diagnosis             of osteosarcoma                     was made.                        if a gross           pathological                  fracture            was     present,
VOL.      I3,    No.   3                              Osteogenic          Sarcoma        (Osteosarcoma)                                                                 609


or if the patient   had                          a flexion     contracture                  Francis          etal.,’ in studying       the amputated
of the hip or knee.                                                                    specimens             in the femur,         frequently       found
       Because            of        8o   three        year    patients         re-     that     the       tumor     extended      through     the mar-
ported        by Lee and Mackenzie9                         who eventu-                row         cavity       for    a considerable         distance.
ally developed               metastases,            6o or 75 per cent                  They         reported            Jo        patients          with    osteosar-
did so within               5 months             of completing                 the     coma      of the femur         or tibia      treated    by pre-
preoperative              irradiation,            they       believe        that       operative       radiation         therapy          with   tissue
it would           be desirable               to wait           at least           5   doses     of 6,ooo      r to 12,000         r delivered      in
months         prior       to ablation.                                                to Jo treatments           followed       in i to 2 days by
     The      authors          presented             results        to show            amputation.                The        results         were    not   encourag-
that      the method              of adequate               megavoltage                ing     in that         of thepatients treated
                                                                                                                             10            during
radiation            therapy           and        elective          ablation           a 2 year      period,    only 3 were     considered        to
compares            favorably            with        immediate              sur-       be free of disease          at the end of i year,            2
gery.      They        do not believe                 anything          is lost        were    living      with   metastases,     and         were
by the           delay        in ablating               the      irradiated            dead.
tumor.                                                                                     A study        concerning          medullary           extension
     They       are of the opinion                     that      the whole             ofosteosancoma               with regard          to therapy         has
bone       must       be removed                in spite        of the ap-             been reported            by Lewis                            T
                                                                                                                                and Lotz.’#{176} wenty
pearance          of the tumor               being        confined           to a      cases        of osteosarcoma              of the long             bones
limited         area       because,         in their           experience,             representing          all amputation            specimens          from
the tumors             spread       widely         in the cancellous                   1959       to 1972      were      submitted           for study         at
portion        of the bone.                                                            the National            Cancer       Institute.         All the pa-
     Among         the 20 long-term                  survivors          of 5 on        tients       were free of metastatic                disease      at the
more        years         reported           by Lee             and       Mac-         time         of the        amputation.              No      cases       of
kenzie,9        there      were 7 patients                or 35 per cent               parosteal         osteosarcoma,               chondrosarcoma,
who had remained                     well from 5 to I I years                          or      primary        fibrosarcoma              of     bone       were
and who had radiation                          therapy          only,      with        included.
tumor        doses ranging              from 5,750            r in 33 days                 The correlation            between        the extent        of the
to     9,000       r in        76    days.                                             tumor      as noted        on the roentgenograms                    and
     Lee8 reported              that       of 21 patients                  with        on the gross          pathological          examination             was
chondrosarcoma                   treated          by preoperative                      good. There          were no local recurrences                  at the
radiation         therapy         and delayed              amputation,                 amputation            site    in the 20 cases.                It was
12 or 57 per            cent       were       alive      and well              or      noted     in 2 cases that            the transverse            micro-
more       years.       Lee8        commented                 that       “Our          scopic     sections        of the bone          within       i.o cm.
attitude        regarding           the osteosancoma                    group          of the gross           tumor       revealed        direct      micro-
may       be summed               up thus:            Success         is per-          scopic      extension          of the        tumor.         Sections
haps       too    euphemistic             a word         so long as we                 made     at 2.0 cm. from              the gross margin              and
are     treating        disseminated                disease        by local            beyond       revealed        no extension          of the tumor.
methods,            but we would                 measure           our suc-            There     were no “skip            areas.”      In the other           i8
cess-such             as it is-by           the number              of futile          cases,     multiple        microscopic           section       exami-
amputations             avoided,         and this was achieved                         nations       revealed        no microscopic              extension
in about         one-half         the cases.”                                          within       the      medullary          canal        beyond         the
     Allen       and      Stevens’            reported           their       ex-       gross       margin.
penience         using      preoperative              radiation           ther-            They        concluded        that    “no superiority           of
apy     in tumor         doses ranging               from 7,900            rads        disarticulation             or amputation             one    joint
to 10,000          rads     and      planned          delayed          ampu-           above        to transmedullary              amputation           has
tation.        Seven       patients          were       treated         and 3          been demonstrated                 in the literature.”
are alive          at        years.        Of 20 patients                  with            J enkin et al.7 reported            on 22 patients          less
osteosarcoma              of the femur               treated         by sun-           than      30    years     old with     the primary        site in
gery only,           only 2 were            alive      at       years.                 a limb        for which       the planned       management
6io                                                                                                     Justin           J.    Stein                                                                                  MARCH,        1975




was by preoperative                                        radiation                     therapy             and              tients             received             roentgen                 therapy                   prior           to
selective delayed                                       amputation.                        The             mean               surgical                ablation              of       the       tumor.                  Thirteen
duration                      of         tumor                control                  by       radiation                     patients               survived               more             than                years           after
therapy                  was              3.6          months.                   The           tumor             re-          surgical               therapy.
curred      in all patients.                                                                                                         The           incidence              of primary     sarcoma         bone
    They      concluded        that      the palliation          ob-                                                          at      one          institution               between   and 1961         1941
tamed       was not adequate              to justify     delay     in                                                         was reported                      by Copeland’   as o.68 per cent.
amputation.          In their      total     experience        with                                                           He reported                      that early amputation      and oc-
the management             of 62 patients            with osteo-                                                              casionally                   radical            resection                   has          been         the
sarcoma        diagnosed       during        the years       1958-                                                            treatment          of choice       in 121 cases        of osteo-
I 970    and treated         by various          methods,        the                                                          lytic     osteosarcoma           with      a i6 per cent          5
S year             survival                      rate         was           not         greaten              than             year survival           rate and that cures have been
5 per           cent.              They         per   had       a     100                     cent recur-                     obtained        in 32 of 163 cases            (20 per cent)      of
rence            or failure      of local    control                                             within    6                  osteoblastic          osteosarcoma            by amputation
months             after    beginning     radiation                                               therapy.                    and in some            cases    by resection.        He was of
They            considered                            that          the      amount                of        mon-             the opinion          that     a permanent         cure has not
bidity             and              local              effects              of        the       radiation                     been       obtained          by    the    use     of radiation
therapy                 did         not         provide               adequate                  palliation                    therapy                only.
or justi f its use. Apparently,           osteosarcoma                                                                           Twenty-two                          osteosarcomas                            were        treated
in the Toronto       region    is a very lethal          dis-                                                                 by   Suit     and                      Lindberg’7                        with            radiation
ease. The tumor       registry    of the Hospital         for                                                                 therapy,                administered                        under            conditions                    of
Sick Children      in Toronto        reported       that    of                                                                tourniquet-induced                                   local            tissue              hypoxia.
18       children                    with               osteosarcoma                           diagnosed                      Thes’      concluded         that      the late reactions                of
at       that            hospital                      during               the         years           1924-                 normal        tissues      were so severe             after      i6,ooo
1958,           there              was          not         a single             5 year         survivor,                     rads,       that      this     treatment            method            was
regardless       of the treatment.                                                                                            not      considered          to be a clinically                    effec-
    Phillips      and Sheline’4              found       that      of 23                                                      tive     method         for the therapy               of osteosar-
patients        with      osteosarcoma              treated         with                                                      comas.
preoperative          radiation          therapy,           or 23 per                                                              The     average        5 year        survival       results        re-
cent       were   alive      at       years;      of 10 patients                                                              ported        from      7 series         totalling        926 cases
who had primary                 surgery,       I patient       (10    per                                                     treated       by surgery          only      was    19.8 per cent.
cent) survived    5 years.                                                                                                    The          average               5 year           survival               results           from              8
   They  compared     the size                                                   of     the       lesion            as        series          of 336             cases        treated               by        preoperative
noted        roentgenographically                  with     the true                                                          irradiation                    and      delayed                surgery               was          23.25

extent        of the tumor             in 9 cases.          In these                                                          per        cent.           The         results              from           treatment                      by
cases,      the surgical         procedure          had been per-                                                             radiation                  therapy                  alone           is      less         than             by
formed         at distances          varying         from         to 15                                                       either    surgery     only or preoperative               irradia-
cm.     proximal         to the margin           of the lesion        as                                                      tion and delayed            surgery.
seen on the roentgenograms.                        In none of the                                                                 There     is apparently          very little     difference
cases was there             tumor       present       at the site of                                                          in the     chance     of survival         in osteosarcoma,
the amputation,              and later recurrence                at the                                                       whether       the primary          treatment       is immedi-
amputation            site was not noted.                                                                                     ate amputation          or ifpreopenative             radiation
     Weinfeld        and      Dudley’9         reported        the re-                                                        therapy               is given             followed             by         amputation                      in
stilts    of a study          of        patients        with osteo-                                                           approximately     6 months.
sarcoma          who were          treated        at the Massa-                                                                   The plan at the UCLA    Center   for Health
chusetts                  General                       Hospital                      between                1920             Sciences    has been  on an elective    basis   to
and        1960.              There               was   no uniform                          treatment                         give          preoperative                    megavoltage                          irradiation,
policy.            Lesions                      located    in the                        skull,    spine,                     6,ooo           to     7,000           nads         tumor             dose         at      the      rate
and        pelvis              which                  could          not         be     excised              were             of approximately                              900       rads             tumor            dose        per
treated                 by         radiation                    therapy.                    Only         2      pa-           week    to the                     whole            limb        or         bone           involved
VOL.             123,      No.    3                               Osteogenic                    Sarcoma                    (Osteosancoma)                                                                                                   6ii

                                                                                                       TABLE             III
                                                                      LONG-TERM                  SURVIVORS:                     OSTEOSARCOMA

           .              Age                 .   Symptoms
 Patient                                  Site                                        Therapy                                                           Comment                                                           Result
                        (Years)                    (Months)

I.        G.L.              i6        Sacrum         i8 mo.         Radiation          therapy                                Alive     and      free    of disease                                          4   years,      3 months

     .     A.S.             26        Mandible            3 mo.     Radiation    therapy,              surgery,               Alive     and      free    of disease                                      9 years,            8 months
                                                                    and chemotherapy

     3.    D.H.            6o         Femur         48 mo.          Radiation          therapy          and       hip         Alive     and      free    ofdisease                                      12       years,      6 months
                                                                    disarticulation

     4. L.O.               71         Femur               i mo.     Radiation          therapy                                Alive     and      free    of disease                                      4 years,            8 months

     5.    v.c.             i6        Femur               5 mo.     Radiation           therapy         and       re-         Alive     and      free    of disease                                      6 years,            6 months
                                                                    section

     6. 5.W.                19        Femur                 mo.     Radiation          therapy                                Alive     and      free    of disease                                     io       years

     7.    J.H.             14        Femur               I mo.     Radiation          therapy         and    hip             Alive     and      free ofdisease                                         I I years,           I month
                                                                    disarticulation

     8. J.S.                Ii        Femur               2 mo.     Radiation          therapy         and        hip          Free ofdisease        8 years,               months.       Dc-                8 years,              months
                                                                    disarticulation                                            veloped    metastases        to          lung.    Surgery.
                                                                                                                               Free of disease       now.

     9. J.B.               ao         Tibia               I mo.     Radiation        therapy           and    mid             Alive     and      free    ofdisease.                                          8 years,        6 months
                                                                    thigh    amputation

so.        E.H.            ao         Tibia          ij     mo.     Radiation          therapy         and    mid              Had     primary          carcinoma         ofbreast,        pri-          8 years,    5 months,
                                                                    thigh       amputation                                    mary       carcinoma        of cervix,     and       pri-                  death  with  disease
                                                                                                                              mary       malignant        melanoma.        Lived
                                                                                                                              years,      5 months        free of disease          and
                                                                                                                              then         more     years    before  death       from
                                                                                                                              metastases         from osteosarcoma.

II.        M.B.            22         Mandible            6 mo.     Radiation                therapy          and             Lived     3 years, II months      free of dis-                             5 years,      II months,
                                                                    chemotherapy                                              ease.    Developed    metastases      to lungs                             death    with   disease
                                                                                                                              and died 5 years,      s I months      post  di-
                                                                                                                              agnosis.




and then to consider                      surgical       ablation          to 6                                         layed      amputation            is only a part ofthe               prob-
months          later.                                                                                                  lem.       Systemic          disease         requires        systemic
     Of the 46 patients                        admitted          with      “lo-                                         therapy.          It has been             amply        proven         that
calized”          disease,          there       have      been     i i long-                                            preoperative            irradiation          and delayed            abla-
term      survivors.             There         were no            year sun-                                             tion is just as effective                as immediate             ampu-
vivors        from         surgery           only.       There       were       3                                       tation.      If the end results             are to be improved
long-term            survivors           from radiation             therapy                                             from      the survival            of approximately                20 pen
only;        6 who            were         treated         by radiation                                                 cent     for        years,       then     planned         studies        in-
therapy         and surgery;                i treated       by radiation                                                volving         systemic          therapy         must       be insti-
therapy,           surgery,           and chemotherapy;                    and                                          tuted.               The          same            is      true            for            Ewing’s                    san-
 I who        had radiation                  therapy         and chemo-                                                 coma            where              local         surgery             or radiation                              then-
therapy          (Table         iii).                                                                                   apy           can      effectively                     control             the           local             disease
     When          patients            with       osteosarcoma              are                                         but     uniformly                         poor           results      have                         been     ob-
first seen after usually                       a very short          history                                            tamed       because                      local          measures         can                      cure local
averaging            2.5 months,               the local lesions            are                                         disease        but                      will            not      control                           systemic
usually        large.       Osteosarcoma                nepresen       ts sys-                                          disease.
temic       disease          and whether               the local lesion                                                         Encouraging                           results            have            been               reported
is treated           by immediate                 amputation             or by                                          following                 local     radiation                             therapy                     (6,000-
preoperative                irradiation             followed         by de-                                             7,000               nads)     followed        by                                drug               adjuvant
6i     2                                                                   Justin        J.     Stein                                                              MARCH,       1975




chemotherapy                  for Ewing’s sarcoma       (actino-                                  The       plan      for therapy        after      biopsy     has
mvcin       D,             adniamycin,    vincnistine,         and                            been        to give          preoperative          megavoltage
cyclophosphamide)              by Rosen       et al.’8 Ewing’s                                radiation           therapy,         6,ooo     to 7,000        rads
sarcoma          of bone     must     be considered           as a                            tumor        dose at the rate of 900 nads per week
disease       with early systemic           spread.     Investi-                              to the whole              limb     or bone       involved       and
gations        are in progress         combining         chemo-                               then      to consider           surgical     ablation          to 6
therapy         with other      methods        of therapy        for                          months          later,     if metastases         have      not oc-
osteosarcoma.            Hopefully,       effective      chemo-                               cunred.
therapeutic           drug      combinations            will      be                               The average               duration            of symptoms                   was
found       since   the present        20 per cent        5 year                              2.5    months,          and the average                   time period              for
survival            rate    obtained          by      the    use      of surgery              the      appearance               of metastases                    calculated
alone     on when     combined                     with preoperative                          from the onset                 of therapy             was 5.5 months.
radiation     therapy      is not                  adequate     for this                      Eighty-seven                  per       cent          had         metastases
disease.                                                                                      within       a period         of 14 months                 after      diagnosis
       Multi-drug              adjuvant            chemotherapy                     at        with the majority                    appearing              usually         in the
the M. D. Anderson                  Hospital        using      cyclo-                         lungs      in 9 months               or less.
phosphamide,       oncovin,             phenylalanine            mus-                              There       have been i i long-term                            survivors.
tand and adniamycin                 following        amputation                               There        were         no        year       survivors             from        sun-
has given    encouraging               results.     Prior     to ad-                          gery     only. There             were 3 long-term                    survivors
juvant      chemotherapy,              the survival          rate in                          from       radiation            therapy           only;         6 who were
33 children         with       osteosarcoma            was 6 per                              treated         by radiation               therapy            and surgery;
 cent.   Eighteen         patients        have     been     treated                            I treated           by surgery,                radiation              therapy,
 with multi-drug           therapy        following       amputa-                             and chemotherapy;                        and i who had radia-
 tion  and 8 have developed                   metastases,         3 to                        tion     therapy           and chemotherapy.
 I 2 months        from       the time          of amputation.                                     It is believed                   that        maximum                  results
 Ten of the patients               on 5 per cent still re-                                    which        can be obtained                    from surgery                 alone
 main    free of disease            20 months           or longer.                            or from preoperative                      radiation            therapy          plus
Studies             are    continuing           and         further       studies             ablative          surgery          have        been         achieved,            and
with    the multi-drug                        therapy           plus metho-                   the results            are approximately                         20 pen         cent
trexate    and citrovonum                          factor         rescue may                  5 year         survivals.            Since        osteosarcoma                   is a
give       improved             results.3”8                                                   systemic           disease         and       because            of the brief
     Marcove         et al.,” in a preliminary                      report                    period        of      symptoms                and        rapid         onset         of
concerning           the use of vaccine                   in patients                         metastases              following           therapy,             any further
with       osteosancoma,               made         the       following                       improvement                 in survival           statistics          will have
comment         : “Twenty-one                patients          wi th os-                      to be the            result        of additional                 therapy           di-
teogenic       sarcoma         of the long bones                  treated                     rected       to the prevention                    of systemic              spread
by a lysed             cell vaccine,             in addition               to                 of     the disease.              There          are some                cases        of
routine       amputation,             appear       to have          an en-                    osteosarcoma                 which      represent             localized           dis-
counaging          response          to vaccine            treatment,                         ease,     possibly           5 to I 5 per cent,                  but there            is
compared          with both the whole                    cell vaccine                         no method                to determine                which          ones        they
and the control             series.”       Their      data       suggest                      are at the present                    time prior              to the initia-
that     there      is clinical        evidence         of immuno-                            tion of therapy.
logic manipulation                of a human             tumor.
                                                                                              Departmen          t of Radiological              Sciences
                                   SUMMARY                                                    The Center           for the Health              Sciences
                                                                                              University         of   California,        Los      Angeles
    Between      November         i, 1955    and June 30,                                     Los Angeles,            California       90024
I 973,    46 patients       with osteosancoma          with-
out    evidence      of metastases        were   admitted                                           The     author     wishes   to express    his appreci-
to the UCLA            Center     for Health     Sciences.                                    ation        to  Frederick      C. David     and Brien        L.
The follow-up          was 100 per cent.                                                      Hensley,         senior    UCLA     medical   students,      for
VOL.      123,      No.      3                                            Osteogenic                      Sarcoma                  (Osteosarcoma)                                                                                       613


their            assistance          in                    the   detailed     medical                                        II.      MARCOVE,                R. C., MIKE,     V., HAJEK,   J. V.,
                                                                                                                                         LEVIN,             A. G., and HUTTER,     R. V. P. Osteo-
study             and       follow-up                         of the patients         re-
                                                                                                                                         genic         sarcoma                under          age of twenty-one.                               7.
ported             in this      study.                                                                                                   Bone & Joint Surg., 1970,                                52,      411-423.

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