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2010 1. J. Radiation Oncology 0 Biology 0 Physics
in the light of what we know about the physiology of
tumors, in particular their cell proliferation and oxygen
use under different conditions of O2 availability.
Experimental methods of altering oxygen delivery
Several different methods have been used to alter the
level of oxygenation in animal tumors to study its effect
on radiosensitivity. These may be divided into two broad
categories:
1. Alterations in the partial pressure of oxygen (POj
in the inspired gas. This may be accomplished either by
a change in the percentage of oxygen breathed from the
normal 2 l%, by a change in the pressure of the gas mixture
from the normal 1 atmosphere or by a combination of
the two. Obviously, this procedure alters the oxygen
transported by the blood, but compensatory mechanisms,
both rapid (cardiac output changes) and long term (altered
blood chemistry and hematocrit) must be considered in
the interpretation of results.
2. Alterationsin the concentrationofhemoglobin in the
bloodfrom the normal value of about 15 g/l00 ml (in the
mouse). Methods of achieving this include acute phle-
botomy, injection of red blood cells, plasma or dextran
solution, kidney irradiation (to suppress red blood cell
production through the erythropoetic system), red blood
cell destroying drugs such as phenylhydrazine and by ex-
ploiting the anemia which often accompanies the growth
of tumors to a large size. All of these procedures produce
an alteration in the oxygen carrying capacity of the blood
which varies linearly with hemoglobin content, but tissue
oxygenation depends not only on the amount of oxygen
in the arterial blood but also on tissue perfusion and tissue/
hemoglobin gas exchange. Perfusion varies inversely with
hematocrit in a nonlinear manner so that in anemia, for
example, increased perfusion compensates for the loss of
hemoglobin.6*5’ In addition the affinity of hemoglobin for
oxygen may be altered to promote oxygen release to the
tissue.3’*73Nevertheless, for several tissues optimum he-
matocrits have been shown at which the maximum oxygen
delivery is achieved2’,37*46V48and these vary with the level
of tissue activity. ‘7*2’
Eflect of reduced oxygen delivery on radiosensitivityof
animal tumors
As we have Seen oxygen delivery can be reduced by
lowering either the hematocrit or the oxygen tension in
the inspired gas. The effect of both procedures on tumor
radiosensitivity has been investigated and will be classified
as acute or chronic for the purpose of this analysis.
1. Acute reduction of oxygen delivery These are ma-
nipulations which were carried out a short time before
irradiation (within a few hours) so that there is insufficient
time for many adaptive mechanisms to compensate. As
part of a comprehensive investigation of the effects of ox-
ygen tension in the inspired air on radiosensitivity of the
RI-IT tumop it was clearly shown that an acute reduction
in the PO2 from normal caused a drop in arterial blood
PO2 which in turn increased tumor radioresistance.
November 1986. Volume 12, Number I I
Several studies have been carried out in which anemia
was induced immediately before radiation was given. In
two of these studies35.49no clear relationship was found
between anemia and tumor radioresistance, but in a recent
investigation in three mouse tumors acute anemia caused
a consistent increase in resistance to X rays.3o This indi-
cates that, at least in these tumors (EMT-6, KHT and
RIF- I), anemia induces a higher fraction of hypoxic cells.
Experiments where drugs are used to induce anemia25*6s
are difficult to classify as acute or chronic, but in each of
these studies where anemia was induced by injection of
phenylhydrazine 24 hrs before irradiation a pronounced
increase in the radiation resistance of mouse tumors was
observed. The conclusion that acute anemia causes ra-
dioresistance is, however, not consistent with all physio-
logical data. One study36 measured oxygenation directly
and found in a rat sarcoma that the optimum hematocrit
for oxygen availability was 30-35%, slightly below normal.
It remains to be seen whether this is a true difference
between these tumor systems of whether direct measure-
ment of oxygen tensions is a poor prediction of radio-
biological response.
2. Chronic reductions in oxygen delivery Under these
conditions tumors are exposed to low oxygen levels for
long enough to permit adaptive mechanisms to act to
restore tissue oxygenation. In one study6’ the effect of
chronic exposure to low oxygen levels (12%) on the sen-
sitivity of RI-IT tumors to X rays was investigated. Ra-
diosensitivity was the same as in mice which had been
exposed to normal air, but the experiment was compli-
cated by a gross adaptation in the form of greatly elevated
hemoglobin levels. so that any other adaptation would be
masked. These authors attempted to compensate for the
hemoglobin increase by phlebotomy, every 48 hrs, and
although more radio-resistant tumors resulted, it is diffi-
cult to assess the effect of the bleeding itself.
In a study of chronic anemia3’ tumors which were ini-
tially radioresistant when irradiation immediately fol-
lowed the acute loss of red blood cells, became progres-
sively more sensitive as the interval before irradiation was
increased until their response after 24-72 hrs was not dif-
ferent from tumors in animals that have never been ane-
mic. This adaptive mechanism occurred even though the
anemia persisted. Based on these results, a tumor in a
patient with low hemoglobin levels would seem fully
adapted to conditions of poor oxygen transport. However,
this conclusion is based on the assumption that the ex-
perimental anemia of 1-3 days duration is equivalent to
that seen in the cancer patient. One recent study56 has
looked at anemia of much longer duration. The effect of
the long term progressive anemia which follows kidney
irradiation in the mouse was described. CA NT tumors
in these anemic mice were actually more sensitive to X
rays than those in non-anemic controls, implying not only
that adaptation may have occurred, but that some other
process affects radiosensitivity beyond the l-3 day interval
investigated by others. 30It is dangerous, of course, to draw
conclusions from differences in results when the systems
 Anemia in radiotherapy 0 D. G. HIRST 2011

REDUCED CORD RADIUS MODEL

ANEMIA ADAPTATION RETRANSFUSION ADAPTATION

by cell death and with red blood cells by cell

shrinkage of cord . proliferation

5 mins 5 mine 6-24 hrs

INCREASED OXYGEN AVAILABILITY MODEL

ANEMIA ADAPTATION RETRANSFUSION ADAPTATION

by increased with red blood cells by reduction in

2.3-DPG 2,3-DPG

5 mlns 24-46 hrs 5 mins 6-24 hrs

Fig. 1. A diagrammatic representation of a tumor blood vessel surrounded by its dependent volume of tumor cells.
The effects on this model of anemia and subsequent transfusion with red blood cells are shown for two independent
mechanisms of tumor adaptation, one or both of which may be important in determining the radiobiological
hypoxic fraction. Radiobiologically hypoxic cells are depicted by shading.

used are not the same, but speaking with some confidence,
adaptation to anemia probably occurs and tends to bring
the tumor radiosensitivity back to that in non-anemic
hosts.
Adaptation to anemia can occur at several levels within
the body. These have been discussed in some detail pre-
viously30 where several possible mechanisms were shown
to have a time scale inconsistent with the restoration of
tumor radiosensitivity described here. Two likely mech-
anisms remain (Fig. 1). Histological examination of tu-
mors in animals exposed to low oxygen tension for several
days has shown that the thickness of the “cords”* which
can be supported by blood vessels is less than in animals
breathing normal air,*67adaptation is therefore simply the
shrinkage of these “cords.*’ This explanation has been
proposed previously’4T62 to explain animal and clinical
data. It could be argued, however, that complete recovery
to a normal hypoxic fraction would not be expected with
this model because of geometric considerations, which
would predict a slightly higher hypoxic fraction in
shrunken “cords.” An increase in the red blood cell 2,3-
diphosphoglycerate (2,3-DPG) concentration (see appen-
dix) has also been noted’j2 in mice exposed to low oxygen
tension. It was also shown that this had, as would be ex-
pected, increased the Pw, therefore promoting the un-
loading of oxygen in the tissues.
3. Restoration of oxygen delivery levels before irradia-
tion. Whatever the mechanisms which contribute to ad-
aptation of the tumor to lowered oxygen delivery, most
available data indicate that any increase in tumor hypoxic
fraction induced by reduced oxygen availability is only
transient. It follows that this adaptation may be exploitable
therapeutically. If tumors are allowed to adapt to condi-
tions where oxygen transport is poor, and normal con-
ditions are restored immediately before irradiation, their
previously hypoxic cells should become oxygenated. This
hypothesis has been tested using a retransfusion tech-
nique. 25*27Hemoglobin levels of previously anemic, tu-
mor-bearing mice were restored before irradiation and a
change in radiosensitivity was obtained which was con-
sistent in each case with a reduction in hypoxic fraction
by about 50%. Using the same strategy but different pro-
cedures, Siemann et a1.62obtained a similar sensitization
with tumors in mice which had been adapted to breathing
a low oxygen tension but were placed in normal air during
irradiation. An exciting aspect of this study was that the
effect could be repeated for 7 fractions of radiation and
still produce sensitization.
The amount of sensitization seen in these studies where
retransfusion with red blood cells was carried out in the
24 hr period before irradiation25*27 was not large. This is
rather disappointing as we might reasonably expect to

* The term “cord” will be used to describe the functional unit is often portrayed in tumor models, may be histologically rec-
of a blood vessel and its dependent tumor cell volume72 although ognizable in only a few tumor types.
it should be emphasized that a structural unit of this kind, as it
2012 1. J. Radiation Oncology 0 Biology 0 Physics November 1986, Volume 12, Number I1

eliminate most of the cells in these tumors which are hyp
oxic as a result of the limited oxygen diffusion range from
blood vessels. However, we have recently established that
for one mouse tumor (RIF-1) the ability to sensitize is
critically dependent on the interval between retransfUsion
of the anemic mice with red blood cells and irradiation
of their tumors. Figure 2 shows that while considerable
sensitization can be obtained when the transfusion im-
mediately precedes the irradiation the effect is rapidly lost
so that by 24 hrs sensitivity is not different ftom that of
tumors in control animals with no history of anemia and
transfusion. The result implies that tumors will also adapt
to an improvement in their oxygenation just as they do
to the reduced oxygen supply of anemia. The mechanism
anemia and its correction might affect the response of
human tumors to clinical multifraction radiotherapy for
comparison with the available clinical data.
The anemic cancer patient
1. Should anemic patients’tumors be more radioresis-
tant?On the basis of the available data from anemic an-
imals we would not expect tumors in anemic patients to
be significantly more resistant to radiation than those in
patients with normal hemoglobin levels30*56because they
should have adapted to conditions of low oxygen delivery.
However, most clinical studies have indicated that better
tumor control can be achieved in those patients with
higher hemoglobin levels. 18,26.50,57,59,74 Surprisingly, this

of this adaptation is not known, but it is possible that the
tumor cells respond to increased oxygen levels by more
rapid proliferation28S66so pushing cells once again beyond
the diffusion distance of the available oxygen supply, or
that 2,3-DPG levels fall when oxygenation is restored.
The results of these animal studies emphasize the com-
plexity of the relationship betweeen the oxygen transport
characteristics of the blood and the sensitivity of tumors,
even to single radiation doses. They should, however, al-
low some prediction to be made about the way in which
applied in one trial with head and neck tumors” even
when the “low hemoglobin” group had levels well within
the normal range, implying perhaps that hemoglobin lev-
els which are perfectly adequate for supplying the normal
metabolic requirements of tissues do not optimally oxy-
genate tumors. An alternative explanation for these effects
is that radioresistance is not a direct consequence of ane-
mia but that certain tumors may have vascular properties
which tend to cause both severe blood loss and radiore-
sistance.14 This has yet to be investigated and would be

50

t
::
0
4o
4’ 30
I
z 20
RIF- 1 (leg) RIF- 1 (flank)

IO40 24
02 6 24 48 02 6 24 48

HOURS

Fig. 2. The effect of a single dose of 20 Gy X rays on RIF-I tumor cell survival in C3H/Km mice following various
hemotacrit manipulations. (0 and cross-hatched areas) non-anemic control mice given 20 Gy only; (irradiated
whole body at a dose rate of 2.85 Gy/min; tumor excised immediately after irradiation.“) (0) mice irradiated
immediately after induction of anemia;W (m) mice irradiated 24 hrs post anemia: (A) mice irradiated at different
times after red blood cell transfusion (0.5 ml i.v. obtained from syngeneic donors) to restore hematocrit to normal.
Hematocrits measured during this experiment are shown in the upper panels. Data points are geometric means
f 1 s.e. from 4-9 separate determinations obtained in 3 independent experiments.
 Anemia in radiotherapy 0 D. G. HIRST
difficult to test, but it does Seem likely that we can elim-
inate an association between metastasis and anemia, at
least for cervix carcinoma.”
It should be emphasized that neither of the animal
studies where “chronic” anemia was investigated30.56
would have predicted the clinical results so the theory of
a common denominator may have some merit. Whatever
the mechanism underlying the clinical association be-
tween hemoglobin levels and radiosensitivity, the systems
that have been used in animals do not adequately model
the complexity of the clinical situation. They should,
however, permit an understanding of underlying princi-
ples to be gained.
2. Should blood transfusion be given to anemic patients
before radiotherapy? It is considered to be good clinical
practice to transfuse the severely anemic cancer patient
before treatment. This improves the general well being of
the patient and helps them to withstand the rigors of ther-
apy, irrespective of any benefits from a more radiosensitive
tumor. A more difficult question is whether patients with
hemoglobin levels at the lower end of the normal range
should be transfused with red blood cells to boost their
levels before radiotherapy. This has been tested directly
in one clinical trial” in which those cancer patients whose
hemoglobin levels were maintained above 12.5g% showed
a significantly lower recurrence rate after radiotherapy
than those with levels between 10 and 12%. This rela-
tionship, it should be noted, held only for the more ad-
vanced Stages, IIB and III (for review see Bush’). Another
study, also involving patients with carcinoma of the cervix,
looked at the influence of anemia and blood transfusion
in a trial of radiotherapy given in hyperbaric oxygen.14
Hemoglobin levels did not influence the validity of the
trial nor was there an overall difference in local tumor
control between those patients who were classed as slightly
anemic (lo-12g%) before treatment and those classed as
non-anemic (> 12g%). The striking result from this study,
however, was seen in the severely anemic/transfused pa-
tients treated in hyperbaric oxygen. This group showed
the highest tumor control rate. Possible explanations for
this will be discussed later.
What can be predicted from animal studies? The re-
duction in the hypoxic fraction resulting from transfusion
of red blood cells in the tumors of anemic mice is transient
(Fig. 2). The duration of any benefit therefore must depend
on how quickly the tumor adapts. It has been shown that
the rate of tumor cell proliferation is highly dependent
on the level of oxygenation and the position of tumor
cells in relation to their supplying blood vessels.28*66It is
reasonable to expect therefore that the tumor cells which
are abruptly exposed to higher oxygen levels, as following
blood transfusion in anemic mice, will begin to proliferate
more rapidly and will once again outgrow their oxygen
supply, thereby restoring the proportion of hypoxic cells.
In the mouSe this process must begin within 2 hrs and be
complete in 24 hr (Fig. 2) in the absence of radiation.
However, a more slowly proliferating human cervical car-
cinoma during a course of radiotherapy may adapt much
9013
more slowly to the blood transfusion. The rate at which
expansion of tumor “cords” occurs after irradiation is
dependent on many factors. These include the fraction
of cells surviving the radiation dose, the number of cell
divisions of which they are capable, the cycle time of these
survivors and the rate at which dead cells are removed
from the tumor “cord.” With so many parameters af-
fecting the rate of “cord” expansion, it is all but impossible
to predict whether it will occur rapidly enough in a given
tumor during a given course of radiotherapy to cancel out
the oxygenating effect of retransfusion in a previously
anemic patient. However, the turnover time of human
tumor cells is much longer than in the mouse.‘1.63 There-
fore, in the absence of cell killing by radiation the adap-
tation time, if it is dependent on cell proliferation, will
be at least several days. The introduction of cell killing
by radiation should prolong this. It is not unreasonable,
therefore, to expect that daily doses of 200 cGy should
kill sufficient cells to delay “cord” enlargement in the hu-
man tumor for the effect of red blood cell transfusion to
be seen. This should be tested using fractionated irradia-
tion in a mouse model, preferably one of the few slow
growing mouse tumors.
Although recent experiments (Fig. 2) in mice led to the
conclusion that changes at the cell population level are
important in tumor adaptation to changes in oxygen
availability, biochemical and rheological changes in the
blood should not be ignored. It has been calculated that
up to half of the oxygen deficit in anemic patients may
be compensated for by a 2,3-DPG mediated reduction in
hemoglobin affinity for oxygen (see appendix).73 It has
also been suggested that increased levels of 2,3-DPG may
affect the adaptation of tumors to low inspired oxygen
tensions62 and anemia3’ so it is not unlikely that a reduc-
tion in 2,3-DPG will follow hematocrit restoration, per-
haps accelerating the loss of tumor radiosensitivity. We
know of no data in man showing a loss of 2,3-DPG under
these conditions, but it has been clearly shown that 2,3-
DPG levels return to normal within 3 days when altitude
acclimatized subjects return to sea level.” If a similar loss
occurs after anemic cancer patients are transfused with
red blood cells this effect would accelerate the loss of ra-
diosensitivity. The complexity of these adaptive mecha-
nisms must contribute to the difficulty of predicting the
importance of hemoglobin levels and transfusion in clin-
ical radiotherapy from animal models. Some useful in-
formation about the possible importance of these effects
could be assesed by measuring 2,3-DPG and Pso values
in transfused, previously anemic patients, and from fur-
ther studies of the effect of hemoglobin affinity on the
radiosensitivity of tumors in animals.
3. Is the effectiveness of hyperbaric oxygen increased
in anemia? A way of avoiding the complexities of tumor
adaptation to attempts to oxygenate them would, of
course, be to use a procedure which exposes tumors which
are already adapted to anemia to restored oxygen delivery
only at the time of irradiation. The transient application
of raised oxygen tension is an old strategy in the form of
2014 I. J. Radiation Oncology 0 Biology 0 Physics
hyperbaric oxygen (HBO), but recently its ability to sen-
sitize tumors to radiation therapy in transfused anemic
patients has been compared with its effects in patients
with normal hemoglobin levels.14 In this MRC trial pa-
tients who had been anemic and were transfused before
treatment showed a dramatic response when their radio-
therapy was given in HBO; a control group of anemic
transfused patients irradiated in air had a poorer outcome.
Some sensitization by HBO was also seen in the non-
anemic patients, but it was less pronounced. The effec-
tiveness of HBO in anemia has led one group (Sealy, writ-
ten communication, February, 1985) to induce anemia
deliberately in some cancer patients several days before
commencing radiotherapy with HBO and to restore the
hemoglobin level shortly before the first dose. The effec-
tiveness of this strategy will not be known for some time.
Why should tumors in transfused, anemic patients be
so sensitized? We must assume that some residual effect
of the anemia/transfusion procedure combines with the
HBO to give benefit; this might be either at the level of
the tumor “cords” or blood biochemistry, It has already
been suggested that the only long lived consequence of
prior anemia after retransfusion will be the reduced di-
ameter of tumor “cords” which have been speculated to
persist for several days after the beginning of fractionated
irradiation, The idea that the effectiveness of HBO is in-
creased under conditions where some shrinkage of tumor
“cords” has occurred is supported by the observation that
the effectiveness of HBO is increased through fractionated
irradiation32*64 when cell killing will cause a reduction in
diameter. A preexisting anemia should have created nar-
row cords which will be present from the beginning of
radiotherapy and not only, as in the non-anemic patient,
after sufficient cell killing has already occurred. It has al-
ready been suggested that HBO may be especially effective
in the anemic patient,15 even without blood transfusion.
Hyperbaric oxygen increases the oxygen transported in
the blood mainly in simple solution giving a 25% increase
in total transport at 3 ATM. This increase should permit
PO;! to be maintained longer as blood passes along the
vascular network within the tissues so reaching cells at a
greater radial distance from the blood vessel. Nevertheless,
there will probably still be cells located in the most un-
favorable position at the perimeter of the tumor “cords”
and at the venous end of capillaries which receive little
or no extra oxygen because of the known ability of tumor
cells to increase their oxygen use in response to an increase
in the oxygen supply. 22Thus, these cells may not be fully
sensitized by HBO alone. The transfused, anemic patient
should, however, have cords of reduced diameter for at
least part of a course of radiotherapy so that these most
difficult to oxygenate cells can be sensitized. How effective
is HBO at oxygenating tumors? In one elegant study4’ the
effect of hyperbaric oxygen breathing in the Hb/02 sat-
uration in individual red blood cells in rat tumors was
measured. At 3 ATM of pure 02, the pressure most widely
November 1986. Volume 12. Number I I
used clinically, only 0.2% of the measured values were
equivalent to oxygen tensions at which radiosensitivity is
reduced by 50% compared with 16% of the values in air.
However, from logarithmic cell survival curves we know
that the ability to sensitize the last few hypoxic cells has
as big an impact on tumor curability as sensitizing the
first 10’or 10 hypoxic cells which probably exist in many
human tumors. This view is supported by radiobiological
studies in which the effects of hyperbaric oxygen on the
sensitivity of mouse tumors to single doses of radiation
is generally modest. 42V64 It is not difficult to understand,
then, how the addition of a procedure such as transfusion
of the anemic patient which alone does not sensitize
enough cells to give a clear benefit could however help to
eradicate the last few cells which with HBO alone could
survive to regrow the tumor.
4. Is there a better transfusion medium that red blood
cells? Recent interest in the use of perfluorochemical
emulsions to transport oxygen to hypoxic tumor tissues
has led to many investigations in mouse tumor systems.
While the commercially available formulation Fluosol-
DA (20%) clearly has the ability to sensitize hypoxic cells
in many tumors to radiation,23,34*424*s2-55*69-7’ recent in-
vestigations suggested that it is more effective given as a
transfusion to the anemic animal prior to irradiation of
its tumor.24 It has the advantage that tumor adaptation
to increased oxygen delivery should not occur because
Fluosol-DA (20%) is effective only when oxygen is
breathed at higher than normal tensions (at least 1 at-
mosphere) and the tumor is exposed to these levels only
at the time of irradiation. Another method by which the
effectiveness of Fluosol-DA (20%) treatment can be in-
creased is by combining it with HBO. It was recently
shown that a dramatic reduction in hypoxic fraction can
be achieved using this combination.42 Thus Fluosol-DA
(20%) could be a superior transfusion medium to red
blood cells for the anemic cancer patient who is to receive
a course of radiotherapy.
In this analysis of the clinical value of blood transfusion
to the anemic cancer patient, no consideration has yet
been given to possible deleterious effects. The risk of in-
fection from contaminated blood has been well publicized
recently, but assuming that this problem will be controlled,
are there any other considerations? It is obvious that the
oxygen transporting properties of donor red cells should
be optimized particularly with regard to organic phosphate
levels3 but perhaps more serious are concerns that blood
transfusion per se may be prejudicial to the control of
some tumors possibly through inhibition of immune re-
sponses.4~8*20
Whatever strategy is to be used against hypoxic cells in
tumors, guard must be taken against adopting too simple
a model when considering its effectiveness. The most ac-
curate model of hypoxic fraction will be one which in-
corporates the concept of a dynamic, constantly changing
tumor cell population where the degree of hypoxia at any
 Anemia in radiotherapy 0 D. G. HIRST
one time will be determined by the balance between ox-
ygen consumption and oxygen supply. Obviously, if tu-
mor cells died rapidly at an oxygen tension above that at
which reduced radiosensitivity is seen, viable hypoxic cells
would not exist in tumors. We know, of course, that this
is not the case and that tumor cells can survive at low
oxygen tensions for many hours.5~‘3 It is often supposed
that hypoxic fraction is determined by some aspect of the
vasculature, but in fact it may simply reflect a particular
tumor’s cells ability to survive under hypoxic conditions.
Both duration and severity of hypoxia will be important
in determining survival. In the “cord” model, the two will
be interdependent as hypoxia will become more severe
the longer and hence further a given tumor cell can mi-
grate away from its blood ~upply.*~.~~As oxygen supply
is altered, a transient change in hypoxic fraction will occur
until the balance is restored by changes in the rates of two
opposing phenomena within the tumor, cell death on the
one hand and cell proliferation on the other. This view
of hypoxia is not new; it is indeed likely that Thomlinson
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APPENDIX
The importance of 2,3_diphosphoglycerate to the anemic
cancer patient
It has been known for some time that 2,3-diphosphog-
lycerate (2,3-DPG), a product of glucose metabolism,
modifies the affinity of hemoglobin for oxygen by pro-
ducing a conformational change in the hemoglobin tet-
ramer.‘,” With increasing concentration of 2,3-DPG in
the red blood cell the oxygen/hemoglobin dissociation
curve moves to the right so that the Pw (the oxygen tension
at which the hemoglobin is 50% saturated) increases. This
is a powerful mechanism capable of increasing the PSO
from a normal value of 28 mmHg to as high as 36 mmHg,
a change which has the effect of approximately doubling
the amount of oxygen released by the blood as it passes
through the tissues. It has been known for some time that
this intraerythrocytic adaptation is probably the most im-
portant means by which tissue oxygenation is maintained
in anemia so avoiding the necessity for a large increase
in cardiac output.3’,73 It is also common to find elevated
2,3-DPG levels in anemic cancer patients before treat-
‘017
chemical emulsion as an adjuvant to radiation therapy in
mice. Cancer Res. 44: 4285-4288, 1984.
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of some human lung cancers and the possible implications
for radiotherapy. Br. J. Cancer 9: 539-549, 1955.
73. Torrance, J.D., Jacobs, P., Restrepo, A., Eschbach, J., Len-
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N. Engl. J. Med. 283: 165-169, 1970.
74. Vigario, G., Kurohara, S.S., George, F.W.: Association of
hemoglobin levels before and during radiotherapy with
prognosis in uterine cervix cancer. Radiology 106:649-652,
1973.
ment, particularly those with leukemia and lymphomai6
and in some childhood malignancies.‘9 This recent study”
also reported an important difference in the blood chem-
istry between the cancer patient presenting with anemia
before treatment and the patient who becomes anemic as
a result of therapy. A normal correlation between 2,3-
DPG levels and PSo, whereby a concomitant rise in PSO
should occur when 2,3-DPG concentration increases, was
often not found in the latter group, implying some red
cell abnormality. Thus, while some anemic cancer patients
compensate well for their anemia by changes in blood
chemistry others, particular-y those who have received
chemotherapy within one day of blood transfusion, do
not.” Currently measurements of 2,3-DPG and PSOare
not part of the routine blood work up for the cancer pa-
tient. It would seem desirable to have this information as
an aid to determining the need for blood transfusion and
whether the normal compensatory physiological mecha-
nisms are functioning adequately in a given patient.