Preliminary report of the M. D. Anderson hospital randomized trial of neutron and photon irradiation...

Int. 1. Radiation Oncology Bid. Phys.. Vol. 7. pp. 1533-1540 F’rinted in Ihe U.S.A. All rights rawed.

03~3016/81/111~33-08102.00/0 cOpyr@ht01981 Per8monResrLtd.

??Original Contribution

PRELIMINARY REPORT OF THE M. D. ANDERSON HOSPITAL RANDOMIZED TRIAL OF NEUTRON AND PHOTON IRRADIATION FOR

LOCALLY ADVANCED CARCINOMA OF THE UTERINE CERVIX

PEDRO MORALES, M.D.,* DAVID H. HUSSEY, M.D.,? MOSHE H. MAOR, M.D.,$ ARTHUR D. HAMBERGER, M.D.,5

GILBERT H. FLETCHER, M.D.** AND J. TAYLOR WHARTON, M.D.??

The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, TX 77030

Between February 1977 and August 1979, 75 patients with locally advanced carcinoma of the uterine cervix were randomized to receive treatment with (a) a combination of 50-MeV neutrons and 25-MeV photons + intracavitary radium (mixed beam group) or (b) 25-MeV photons * intmcavitary radium (photon group). Tbe analysis of the total population revealed no difference between the mixed beam and photon groups with regard to local tumor control, frequency of major complications, or patient survival. There was a significant difference between the two groups with regard to tbe number of patients completing treatment with intracavitary radium. When the patients who completed treatment with intracavitary radium or an external beam boost are analyzed separately, tbe results with mixed beam irradiation are slightly better than those achieved with photon irradiation, although tbe difference is not statistically significant.

Fast neutrons, Uterine cervix cancer, Mixed beam, Cyclotron.

INTRODUCTION In March 1973, The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute initiated a series of pilot studies of fast neutron radiotherapy for locally advanced gynecological tumors. Three treatment schedules were evaluated in these studies: (1) 50-MeV,,, neutrons only, (2) 50-MeV,, neutrons following initial treatment with 25-MeV photons (neutron boost), and (3) combined 50-MeV,,, neutrons and 25-MeV photons (mixed beam). In the mixed beam schedule, patients were treated twice weekly with neutrons and three times weekly with photons. In a previous publication6 we reported that the best thera- peutic ratio in the pilot studies was achieved with the mixed beam technique. Furthermore, the local tumor control rate with mixed beam irradiation was superior to that achieved in a comparable group of patients treated

with photons during the same period, although no improvement in survival was detected.

As a result of the pilot study analysis, a prospective clinical trial* was initiated in January 1977. In this study, patients with locally advanced carcinoma of the uterine cervix were randomized to receive mixed beam or photon irradiation. All patients were evaluated in the 5th week for completion of treatment with intracavitary irradiation or an external beam boost using the randomized modality. This paper is a preliminary report of the randomized clinical trial. The results are analyzed in terms of local tumor control, complications, and patient survival.

Energy and dosage conventions The neutron treatments were given with the Texas

A&M variable energy cyclotron (TAMVEC), using a

*Fellow in Radiotherapy, Division of Radiotherapy. TProfessor of Radiotherapy, Division of Radiotherapy. $Assistant Professor of Radiotherapy, Division of Radiother-

apy. $Associate Professor of Radiotherapy, Division of Radiother-

apy. **Professor and Head, Division of Radiotherapy. TtProfessor of Gynecology, Department of Gynecology. Reprint requests to: David H. Hussey, M.D.

This investigation was supported in part by Public Health Research Grants CA 06294 and CA 12542 from the National Cancer Institute, Departments of Health, Education and Welfare.

Accepted for publication 9 July 198 1. *This study is part of a national cooperative clinical trial

being conducted under the direction of the Radiation Therapy Oncology Group.

1533

1534 Radiation Oncology 0 Biology 0 Physics November 198 1, Volume 7, Number 11

neutron beam produced by bombarding a thick beryllium target with 50-MeV deuterons (50-MeV,,,). The mean neutron energy of this beam is approximately 22 MeV. The photon treatments were delivered with 25-MeV photons using a betatron* or, less frequently, a linear accelerator.? Intracavitary irradiation was delivered with radium using a Fletcher-Suit afterloading applicator.

and significantly larger than that observed with 25-MeV photons. This is a significant disadvantage for fast neutron therapy, since critical normal structures 2-3 cm outside the treatment beam may receive as much as 30% of the central axis depth dose.

The neutron beam doses were determined by measure- ments with a tissue-equivalent ionization chamber immersed in tissue-equivalent liquid (p = 1.07 gm/cm3). The physical doses have been expressed in rad including both the neutron and gamma components (rad,,). The gamma dose for the 50-MeV d_Be neutron beam is approximately 10% of the total physical dose at 10 cm depth.

The mixed beam doses are reported in two ways: (1) the physical dose, with the neutron beam dose (rad,,) and photon beam dose (rad) listed separately, and (2) the total equivalent dose of the combined regimen (rad,). The equivalent doses (rad,,) were determined by multiplying the physical dose delivered with neutrons by a relative biological effectiveness (RBE) of 3.1 and adding this to the dose delivered with photons. The RBE of 3.1 was determined clinically by comparing the late effects of neutron irradiation twice weekly with the late effects of photon irradiation delivered in fractions of 200 rad five times weekly.*

lsodose curves for unfiltered 50-MeV,,,, neutrons are rounded because of forward-directed neutron emission from the target and secondary scatter within the patient. Because this constriction is unacceptable in many clinical situations, the 50-MeV,,, beam at TAMVEC has been flattened with polyethylene filters. This flattening produces a uniform distribution at depth, but results in approximately IO-15% greater dose off axis near the surface, a situation that could lead to high-dose effects in subcutaneous tissue.

Limitations of‘ajixed horizontal beam

Dosimetric properties

At TAMVEC the patients with gynecological tumors were treated in a standing position with a fixed horizontal beam. This is a significant disadvantage for neutron therapy because field shaping is compromised and patient diameters are greater in the standing position than they are in the supine or prone positions. Further- more, the intestines shift into the pelvis when patients are standing, leading to an increased risk of bowel complications. A compression device has been used to minimize these disadvantages by reducing the patient diameter and displacing the intestines out of the pelvis.

The 50-MeV,,,, neutron beam has skin-sparing and depth-dose properties similar to those of a photon beam generated by a 4-MeV linear accelerator.3 The surface dose is 43% of the maximum dose (D,,,), which occurs at 0.8 cm. A IO x 10 cm beam is attenuated to 50% of D,,, at a depth of 13.8 cm. The dosimetric properties of 25-MeV photons from a betatron* are far superior to those of 50-MeV,,,, neutrons. The surface dose with 25-MeV photons is 17% of D,,,, which occurs at 4.5 cm depth, and the beam is attenuated to 50% of D,,, at 24.3 cm.

METHODS AND MATERIALS

The poor penetration of 50-MeV,,,, neutrons is even more significant because neutrons are selectively absorbed in fat. For example, Bewley’ has calculated that fat absorbs approximately 18% more energy with 16-MeV,,, neutrons than muscle tissue because it has a greater hydrogen content. Tissue heterogeneity is proba- bly less important with 50-MeV,,,, neutrons because more energy is deposited by interactions with oxygen. Nevertheless, this factor could lead to increased subcutaneous fibrosis.

Between February 1977 and August 1979. 75 patients with locally advanced carcinoma of the uterine cervix were randomized to receive mixed beam or photon irradiation. There were 43 patients in the mixed beam group and 32 in the photon group. The size of the two groups differed because the randomization tables had been weighted in favor of the mixed beam group. Seventy-one patients presented with previously untreated squamous carcinoma of the cervix, one with adenocarcinoma of the cervix, and three with squamous carcinoma recurrent following radical hysterectomy.

Isodose distributions With fast neutrons, a significant dose of radiation is

delivered to tissues outside the geometrical edge of the treatment beam. The penumbral region with 50-MeV,_,,, neutrons is similar to that seen with kilovoltage X rays

The patients are listed by clinical stage in Table 1. The stage distribution of the mixed beam group was slightly more advanced than the stage distribution of the photon group since 5 I % of the patients treated with mixed beam irradiation presented with Stages IIIB, IVA, or recurrent tumors, compared to only 31% of those treated with photons. On the other hand, 34% of those treated with photons had hydronephrosis evident on intravenous pyelogram, compared to only 24% of those in the mixed beam group. Approximately one-fourth of the patients in each group had clinical evidence of pelvic lymph node metastasis.

The external beam treatments were delivered with conventional five-times-weekly fractionation using 200-

*Allis-Chalmers. tsagittaire.

Neutrons in treatment of the cervix 0 P. MORALES et al. 1535

Table I. Summary profile of the total patient population (February 1977-August 1979)

Mixed beam* Photons?

StageS No. (%) No. (%)

IIB * 7 (16) (22) IIIA 14 (33) 1: (47) IIIB 16 (37) 8 (25) IVA 3 (7) 2 (6) Recurrents 3 (7) 0

Abnormal IVP lo/43 (24) II/32 (34)

Regional metastasis** 1 l/40 (28) 8/31 (26)

*No. treated = 43; Mean age + 1 S.D. = 52 f 12 yr. tNo. treated = 32; Mean age + 1 S.D. = 48 2 14 yr. SMDAH staging system: Stage IIB = lateral parametrial

involvement, or massive involvement of the corpus (barrel- shaped); Stage IIIA = involvement of one pelvic wall or lower third of the vagina; Stage IIIB = involvement of both pelvic walls, or one pelvic wall and the lower third of the vagina; Stage IV = biopsy-proven rectal or bladder involvement (IVA), or distant metastasis (IV).

$Pelvic recurrence following radical hysterectomy for squamous carcinoma of the cervix.

**Regional node metastasis on lymphangiogram or at lymphadenectomy.

rad, fractions. The mixed beam treatments were given three times weekly with photons and twice weekly with neutrons. The neutron fraction size was 65 rad,,. This is equivalent to 200 rad with photons\ assuming an RBE of 3. I for this fraction size.

The aim was to deliver 4500-5000 rad, to the whole pelvis in 4’/2-5 weeks and re-evaluate the patient for completion of treatment using intracavitary radium (4000-5000 mg-hrs) or an external beam boost (IOOO- 2000 rad, in 1-2 weeks). In general, patients showing good regression of parametrial disease completed treatment with radium, whereas those with persistent disease at the pelvic sidewall completed treatment with an external beam boost. There was a significant difference between the two groups with regard to the number of patients completing treatment with intracavitary radium.

Only 16 of 43 patients (37%) in the mixed beam group completed treatment with intracavitary radium, compared to 23 of 32 patients (72%) in the photon group.

The treatment methods and tumor doses are listed in Table 2. For patients treated with external irradiation only, the average tumor dose was similar for both groups. For patients who completed treatment with intracavitary radium, the external beam doses were greater in the mixed beam group than in the photon group, but the intracavitary doses were lower in the mixed beam group. These differences may not be significant since the RBE of 3.1 for 50-MeV,,, neutrons is not clearly established, and the effective dose of the radium system is determined in part by the geometrical distribution of the sources. On the average, 39% of the total equivalent dose for the mixed beam patients was delivered with fast neutrons.

Two portal arrangements were employed for total pelvis irradiation with photons: (I ) a two-field technique using parallel-opposing 15 x 15 cm anterior and posterior portals, and (2) a four-field box technique using parallel- opposing I5 x 15 cm anterior and posterior portals and parallel-opposing I5 x 9 cm lateral portals. The four-field technique was usually employed if external beam doses of 5000 rad or greater were planned. The two-field technique was employed if lesser external beam doses were planned. or if the anterior-posterior extent of the tumor did not permit adequate coverage with lateral portals. Approximately half (I 5/32-47%) of the patients in the photon group were treated with the four-field box technique.

Similar portal arrangements were used for the mixed beam group, but a greater percentage of patients (35/43-81%) were treated with the four-field box technique because of the inferior depth-dose properties of 50-MeV,,,, neutrons. The two-field techique was employed only if the anterior-posterior extent of the tumor did not permit adequate coverage with lateral portals. The majority of patients treated with the mixed beam method were treated twice weekly with 16 x 16 cm anterior and posterior neutron portals, once weekly with 15 x 15 cm anterior and posterior photon portals, and twice weekly with parallel-opposing 15 x 9 cm lateral

Table 2. Summary of treatment received7

External beam only

External beam only

Mixed beam group Photon group

External beam + radium

Mixed beam group Photon group

Number of patients 27 9 16 23 Mean physical dose + 1 S.D.

Neutrons 776 k 146 radnY 0 645 f 113 rad,, 0 Photons 4,047 + 4 15 rad 6,243 * 922 rad 3,073 f 373 rad 4,668 + 677 rad

Mean equivalent dose + 1 S.D.* 6,454 + 292 rad, 6,243 r 922 rad 5,072 * 653 rad, 4,668 t 677 rad Mean radium dose + 1 S.D. 0 0 4,586 * 1774 mg-hr 4,916 + 1,480 mg-hr

S.D. = Standard deviation. *Equivalent doses (rad,) were calculated by multiplying the neutron dose (rad,,) by an RBE of 3.1 and adding this to the dose

delivered with photons (rad).

.Lla~!~m.tsa~ sdnoJ% ureaq paxy pua uoloqd ay$ JOJ sampq-uou ag$ ]uasaJdaJ satin3 Ja!aK-ueldey aql uo sauq pue SMOJJB aqL ,'(8561 ‘poqlaw .ta!a&q purz uelde~)uogepdod [elo~ aql JOT saAJn3 laa!AJns (q) pu~‘suoy?~![dmo:, pue [OJIUO:, pool (e)le!Jenj~v ‘1 %J

'1 aJn8!d u! pallold ale saAJn3 IEA!AJns pue ‘uoyDgdmo3 ‘1o.11~03 1~01 le!JenlDv %.I! -A!AJllS aJaM (‘IE/61) Oh65 pue ‘suoyeyduro~ Jo[FXI.I pado -1aAap pgq (zc/z) s9 ‘~oJwo3 Jownl 1~301 paAay3e p~q

(z~/61) $&is ‘dnoJ% uoloqd aql ul 'aAge aJaM (EP/EZ) sfg pue‘suo!$eydruo3 JO~EUJ padolaaap peq (cp/p)o$6 ‘~OJIU~~JOLLI~~ 1e301 paAay3e peq uoy3!peJ~! weaq pax!lu

ql!M pawa4 swqw-J aql JO (EP/SZ) ~8s ‘s!s6p=e JO au+1 aql lv'(E aIqE~)II?A!AJns waged pu13'suo!~3~~d~1o3 JO huanbaJJ ‘~OJIUO~ IEDO[ 01 pJt?8aJ qym sdnoJ% uoloqd pw2 weaq pax!w aql uaawaq a3uaJaJ!p ou SI?M aJaqL

uoypdod ~IOI ayl$o sykpuy

P0loWl WeW P UBldBX

sllluow

PZ Zl

(a@ 16) =J’W’lld 0

Wd et) ueefl Pex!w ??08

lOJ$UO3 113301

001

.dnoJ% uoloqdaqlJoJ (sqwolu 6~-6 :a%ueJ) sqluour ~'pz pue dnoJ8 rueaq pax!m aql JOJ (Sq]UOUl 6E-6 :a%UKI) SqlUOlU (j’f7Z SBM S!S/(IEUE

JO all?p aql 01 i(deJaql UO!ll?!peJ JO IJElS aql LUOJJ It?AJa~U!

a%eJaAe aqL '0861 lCem u! paz@ue aJaM clep aqL

s.rmm

wvaq p2luoz!Joq paxyaql JO SIU!IXISUO:,OI anp waruu%~e lua!ledJoL]u!wawn aql ~oasne3aq uo!lt3pe~~! uoloqdJoJ ucql uoge!pe~J! uoJlnau JOT pa/(oldwa aJaM spwod JaLlJel Ic~~qSqs yeyod uoloqd

.alqeDyddr! IOU = 'V'N .LJa%Jns dq pa8enlss aJaM saJnl!ej p~o1 se pawI waged z$

.AJasJns Lq pa%alwsem aJnl!vj lwo~ se palsy wayed 14 Xuands%u$k?~s Hvam*

‘V’N c/z 210 El0 8/E 91101 SIIOI PI/9

L/9 LIS

‘V’N z/o 811 SIII

LIO

E/O El1

91/I PI/I

LII

E/Z E/Z

9116

luaJm3aa VA1 8111 VIII

811

SUOlOqd weaq pax!w SUWOqd weaqpax!yy SUWOqd weaqpax!,y ,a%3s P!U!l3

p2A!AJllS suoyqdwo3 [OJlUOD [I2307

0861 km S!Sd[WJV:((jL6[ ISIl8llV-LL61 AJanJqa~)ase~Sle~!U!l3~q S$IllSaJ dJW!UJ![aJd 'E a[qEl

I I J=V=“N ‘L aU”W’A ‘ 186 I -W’AoN 9ESI

Neutrons in treatment of the cervix ??P. MORALES et 01. 1537

Table 4. Major complications and possible contributing factors

Possible Treatment methods/complications contributing factors

Mixed beam + radium 2/16(13%) 1 uterosigmoid fistula (Rx colostomy) Deviated radium system I large bowel obstruction (Rx colostomy) Diverticuhtis; poor anatomy,

protruding source

Mixed beam alone 2/21(7%) I sigmoid perforation (Rx colostomy) None I small bowel obstruction (Rx by-pass) Previous cutaneous uterostomy

Photons + radium I /23 (4%) I sigmoid perforation (Rx colostomy) None

Photons alone l/9(11%) 1 tubo-ovarian abscess (Rx colostomy) None

There was no significant difference in the results obtained for the two groups when the data were analyzed by clinical stage because the number of patients in each category is small. However, the results achieved with photons were superior to those achieved with mixed beam irradiation for Stage IIlA tumors; the mixed beam results were slightly better than the photon results for Stages IIIB and IVA.

Six patients (8%) developed major complications-4 (9%) in the mixed beam group and 2 (6%) in the photon group. The major complications are listed in the Table 4 along with possible contributing factors. The only small bowel complication occurred in the mixed beam group. This may have been related to treatment technique since the intestines fall into the pelvis when patients are treated in a standing position.

Analysis by boost modality The patients who completed treatment with intracavi-

tary radium and those who received only external beam irradiation were analyzed separately because a significantly greater percentage of the photon patients completed treatment with intracavitary radium. The results for patients who completed treatment with intracavitary radium were superior to those obtained for patients treated entirely with external beam irradiation. This was equally true for the mixed beam and photon groups.

When the patients who completed treatment with intracavitary radium were analyzed, the local control rate with mixed beam irradiation (81%--13/16) was slightly better than that achieved in the photon group (65%-15/23) (Table 5). There was no improvement in survival (mixed beam: 63%, 10/16; photons: 70%, 16/23). however, because a greater number of patients in the mixed beam group developed distant metastasis with local tumor control. The current status of the patients treated with both external and intracavitary irradiation is listed in Table 6. Similar results were noted when the data were analyzed by actuarial methods (Fig. 2).

When the patients who were treated entirely with

Table 5. Preliminary results for patients treated with external irradiation only or external irradiation plus intracavitary

radium (February 1977-August 1979): Analysis May 1980

External beam only External + radium _

Mixed Mixed beam Photons beam Photons

Local control No. 12127 419 13/16 15/33 (%) (44) (44) (81) (65)

Complications No. 2127 ‘/9 2/16 l/23 (%) (7) (11) (13) (4)

Survival No. 13127 319 IO/16 16123 (%) (48) (33) (63) (70)

Table 6. Current status of patients treated with external beam and radium (February 1977-August 1979): Analysis May

1980

Mixed beam (16 pts)

Dead 6 Local failure (L.F.) 3

Distant metastasis (D.M.) S L.F.

Intercurrent disease

Alive N.E.D. from primary

treatment

3 1 N.A. N.A.

10 16

N.E.D. from surgical salvage

With local failure (L.F.)

7 (2ccomp)

N.A.

N.A. With distant metastasis

(D.M.) 3

Photons (23 pts)

7

(3ci.M.)

14 (1 ccomp)

2

N.A.

N.A.

N.E.D. = No evidence of disease; L.F. = Local failure; D.M. = Distant metastasis; camp = complications; N.A. = Not applicable.

1538 Radiation Oncology 0 Biology ??Physics November 198 1, Volume 7, Number 11

1 \ Local Control

‘i 60

z ii n 40 t

II 1 I II 1 1

t

1 L,

Complications

Months Kaplan b. Meler Method

s Mlxed Beam + Radium (16 pts)

o Photons + Radium (23 pts)

,j: 12 24 36

Months Kaplan 6 Meier Method

Fig. 2. Actuarial (a) local control and complications, and (b) survival curves for the patients who completed treatment with intracavitary radium (Kaplan and Meier method, 1958).4 The arrows and lines on the Kaplan-Meier curves represent the non-failures for the photon and mixed beam groups respectively.

external beam irradiation were analyzed, the local control rates in the mixed beam and photon groups were identical (mixed beam: 44% l2/27; photons: 44% 4/9) (Table 5). The survival rate for the mixed beam group (48%. 13/27), however, was greater than that observed for the photon group (3/9). The current status of these patients is listed in Table 7. When actuarial local control, complication, and survival curves were plotted (Fig. 3), the results with the mixed beam irradiation were superior to those achieved with the photon beam. However, the difference may not be significant because of the small number of patients in the photon group.

DISCUSSION In a previous publication,6 we reported that the local

control rate in the mixed beam pilot study was superior to that achieved in a comparable group of patients treated during the same period with photons alone, although there was no improvement in survival because of a difference in the number dying from metastatic or intercurrent disease. The preliminary analysis of the randomized trial, however, fails to show an advantage with either treatment modality since the results for the mixed beam and photon groups are almost identical in terms of local tumor control, complications, and patient survival (Fig. I).

A similar experience was noted in a clinical trial performed in the 1960’s at M. D. Anderson Hospital that used intra-arterial Sfluorouracil infusion and photon irradiation to treat locally advanced gynecological tumors. The initial clinical impressions in a pilot study indicated an unusually rapid regression with combined

Table 7. Current status of patients treated with external irradiation only (February 1977-August 1979):

Analysis May 1980

Mixed beam (27 pts)

Photons (9 pts)

Dead 14 Local failure (L.F.) 12

(2 C D.M.) Distant metastasis

(D.M.) S L.F. I Intercurrent disease I

(I C camp)

Alive 13 N.E.D. from primary

treatment (I EEZmp)

N.E.D. from surgical salvage I

With local failure (L.F.) 2

With distant metastasis (D.M.) N.A.

7 5

(2 T D.M.)

N.A

(I C camp)

3

2

N.A.

N.A.

1

N.E.D. = No evidence of disease; L.F. = Local failure; D.M. = Distant metastasis; camp = complications; N.A. = Not applicable.

Neutrons in treatment of the cervix 0 P. MORALES et al. 1539

?? Mixed Beam Only (27 pts) o Photon8 Only (B pto 1

Local Control

1 Complications

2o I

12 24 36 Months

Kaplan ll Meier Method

80

?? Mixed Beam Only (27

o Photono Only (0 pts) pte)

t

0’ . I I I I I I

12 24 36 Months

Kaplan 6 Meler Method

Fig. 3. Actuarial (a) local control and complications, and (b) survival curves for patients treated with external irradiation only (Kaplan and Meier method, 1958).4 The arrows and lines on the Kaplan-Meier curves represent the non-failures for the photon and mixed beam groups respectively.

treatment. A subsequent randomized clinical trial, however, showed no increase in effectiveness as compared to that obtained with photon irradiation alone.’

One drawback of the present study is the discrepancy in the two treatment arms in the number of patients completing treatment with radium. Whereas, 72% of the

patients in the photon group completed treatment with intracavitary radium, only 37% of the patients in the mixed beam group completed treatment with radium. This difference could be a result of any or all of the following:

Differences in the clinical material assigned to each treatment arm. If the patients assigned to the mixed beam group had more advanced cancers, on the average, than did those in the photon group, fewer would be suitable for completion of treatment with intracavitary radium. This explanation pertained to some extent, since 5 1% (22/43) of the mixed beam patients and only 3 I% (10/32) of the photon patients had Stages 1 IIB, IVA. or recurrent tumors. However, there was also a difference in the number completing treatment with radium within each stage category. Differences in tumor regression with photon and mixed beam irradiation. If photons produced more rapid regression of parametrial disease than did mixed beam irradiation, a greater percentage would become eligible for intracavitary irradiation. This seems to be an unlikely explanation, however, since no differences in regression rates have been noted following mixed beam and photon irradiation for tumors of other sites.’ Differences in criteria used to decide whether a patient was suitable for completion of treatment with radium. The same team of radiotherapists usually evaluated the mixed beam and photon patients for the completion of treatment with radium. but this was not always the case. Although we were not aware of any differences in evaluation criteria, it is possible that we relied more on external beam irradiation in the mixed beam group.

In interpreting the results of the randomized clinical trial, one must keep in mind the dosimetric and technical disadvantages of fast neutron therapy at TAMVEC. Although the skin-sparing and depth-dose properties of the 50-MeV,,,, neutron beam are superior to those that can be achieved with 6oCo gamma rays, they are distinctly inferior to the skin-sparing and depth-dose properties of conventional 25-MeV X rays. Furthermore, the added constraint of a fixed horizontal beam repre- sents a considerable disadvantage for pelvic irradiation since the intestines fall into the pelvis when patients are standing.

A 42-MeV r_-Be cyclotron is presently being installed at M. D. Anderson Hospital in order to continue the fast neutron therapy program. This machine will produce a neutron beam with a penetration similar to that of the TAMVEC beam, so that the dosimetric properties will still be significantly inferior to those which can be achieved with 25-MeV X rays. Many of the technical problems will be diminished, however, since this machine will possess isocentric capabilities enabling the treatment of patients in a supine or prone position.

1540 Radiation Oncology 0 Biology 0 Physics November 198 1, Volume 7, Number 11

REFERENCES Bewley, D.K.: Fast neutron beams for therapy. Curr. Top. Radiat. Res. 6: 251-292, 1970. Hussey, D.H., Fletcher, G.H., Caderao, J.B.: A preliminary report of the MDAH-TAMVEC neutron therapy pilot study. In Proceedings from the 5th International Congress of Radiation Research. New York, Academic Press, Inc. 1975,~~. 1106-1117. Hussey, D.H., Peters, L.J., Sampiere, V.A., Fletcher, G.H.: Radiotherapy with combined 50 MeV,_,, neutrons and 25 MV photons for locally advanced gynecologic and prostatic tumors. 1st International Meeting on Radio-Oncology, Baden (Vienna), Austria, 18-20 May, 1978. In Progress in RadbOncology, K.-H. Karcher, H.D. Kogelnik, H.-J. Meyer (Eds.). Stuttgart, Georg Thieme Verlag. 1980, pp. 3243. Kaplan, E.L., Meier, P.: Nonparametric estimations from incomplete observation. Am. Stat. Assoc. J. 53: 4577480, 1958.

5.

6.

7.

Maor, M.H., Hussey, D.H., Fletcher, G.H., Jesse, R.H.: Fast neutron therapy for locally advanced head and neck tumors. Int. J. Radiat. Oncol. Biol. Phys. 7: 155-163, 1981.

Peters, L.J., Hussey, D.H., Fletcher, G.H., Baumann, P.A., Olson, M.H.: Preliminary report of the M. D. Anderson study of neutron therapy for locally advanced gynecological tumors. In High-LET Radiations in Clinical Radiotherapy. Proceedings of the 3rd Meeting on Fundamental and Practi- cal Aspects of the Application of Fast Neutrons and Other High-LET Particles in Clinical Radiotherapy, The Hague, The Netherlands, 13-l 5 September 1978. G.W. Barendsen, J.J. Broerse, K. Breur (Eds.). Supplement to Eur. J. Cancer London, Pergamon Press. 1979, pp 3-l 0.

Smith, J.P., Rutledge, F.N., Delclos, L.: The postoperative treatment of early cancer of the ovary: A random trial between postoperative irradiation and chemotherapy. Nat. Cancer Inst. Monog. 42: 49-l 53, 1975.

Preliminary report of the M. D. Anderson hospital randomized trial of neutron and photon irradiation...

Documents

Transcript of Preliminary report of the M. D. Anderson hospital randomized trial of neutron and photon irradiation...