Seminars in Surgical Oncology 6:291-296 (1990)

Prognostic Indicators in Patients With

Pulmonary Metastases
JOEB. PUTNAM, JR., MD, AND JACK A. ROTH, MD
From the Department of Thoracic Surgery, The University of Texas M. D. Anderson Cancer
Center, Houston, Texas

Pulmonary metastases from different primary neoplasms have different

biological characteristics which may correlate with patient survival. Ob-
jective criteria to reliably select or exclude patients who would benefit
from resection of these metastases are not available; however, various
prognostic indicators have been studied for their correlation with post-
resection survival. Prognostic indicators differ among various tumor his-
tologies. Prognostic indicators identified preoperatively which may influ-
ence post-resection survival include age, sex, histology and location of the
primary tumor, tumor doubling time, disease free interval, the number of
nodules on preoperative roentgenographic studies, and the number of
metastases resected. Following surgery, resectability , and the number of
metastases resected may predict expected survival for patients meeting
certain criteria. No single criterion should be used to exclude patients from
surgery as resection will provide numerous patients with significant post-
resection survival.

KEYWORDS:tumor doubling time, disease free interval, survival

INTRODUCTION viewed as hopeless, as those individuals who can be

The identification of a pulmonary nodule on routine
screening chest roentgenograms suggests pulmonary me-
tastasis in patients with a controlled or treated primary
neoplasm. Some patients will die from metastases con-
fined solely to the lungs and may benefit from resection
of these metastases. The value of resecting a solitary
pulmonary metastasis was proven by Barney and
Churchill in 1939 [ 11 following a resection of a metasta-
sis from a patient with hypernephroma. Local control of
the primary tumor was also achieved and the patient
survived for 23 years following the procedure. Since
then resection of solitary and multiple pulmonary me-
tastases have been performed with long-term survival in
up to 40% of patients so treated.
Criteria for selection of patients with isolated pulmo-
nary metastases for resection have developed over the
past 10 years in an attempt to quantitate the biological
aggressiveness of the metastases and to identify patients
who would benefit from surgical resection [2-71. Pa-
tients with isolated pulmonary metastases should not be
successfully resected will usually have improved sur-
vival over those patients who are unresectable. Resected
metastases to the lungs may provide long-term survival
(>5 years) in one-third of patients with local control of
their neoplasm. Multiple and bilateral metastases may
likewise be resected with improved survival.
Various authors have reported good long-term survival
following resection of pulmonary metastases of various
tumor types. Analysis of prognostic indicators in groups
of patients with pulmonary metastases from heteroge-
nous tumors indicate that survival was enhanced in pa-
tients with a longer disease free interval [3,5],longer
tumor doubling time [2,5],fewer numbers of metastases
[5], resectability [5,6], and primary histology [3,4,7]. A
disadvantage of studying prognostic indicators of sur-
vival in patients’ pulmonary metastases from numerous
primary histologies is the wide variability in character-
Address reprint requests to Joe B. Putnam, Jr., M.D., Department of
Thoracic Surgery, The University of Texas M.D. Anderson Cancer
Center, 1515 Holcombe Blvd.lBox 109, Houston, Texas 77030.

0 1990 Wiley-Liss, Inc.

292 Putnam and Roth

istics of metastases. Patients with pulmonary metastases SURVIVAL ANALYSIS

from the same tumor histology will provide more precise Significant differences in patient survival based on
information on the value of prognostic indicators for sur- various prognostic indicators may be evaluated using
vival following resection of these metastases. various statistical methods. Survival is calculated from
Surgical procedures for resection include single thora- the time the surgical procedure is performed to assess the
cotomy, staged bilateral thoracotomy, or median sternot- influence of resection on survival. Survival and disease
omy. These procedures in reported series have almost no free interval curves may be estimated using the method
mortality and minimal morbidity [ 8,9]. The procedure of Kaplan and Meier [ 121. Patients may be stratified into
chosen does not influence patient survival in those indi- two or more groups (those patients meeting a specific
viduals resected of all disease. Patients with pulmonary objective criteria and all others, etc.) to evaluate differ-
metastases may also undergo multiple procedures for re- ences in survival. Comparisons between groups (univari-
resection of metastases; again, with improved survival in ate analysis) may be made using the generalized Wil-
those patients having a complete resection [lo]. coxon test of Gehan [ 131. Thomas’s exact text [ 141 may
be used when the sample sizes are small or if few failures
RESECTION OF PULMONARY METASTASES are present. To determine the relative effect of various
Various guidelines [7,11] have been proposed to select prognostic indicators, Cox’s proportional hazards model
those patients who should be considered as candidates [ 151 would be used. Univariate analysis will identify the
for surgical resection of their pulmonary metastases. most important prognostic indicators. Combining two or
These guidelines for resection include 1) presence of more indicators may provide additional prognostic value.
parenchymal nodules or changes in the lung consistent
with metastases, 2) control of the patient’s primary tu- AGE AND SEX
mor, 3) potential for complete resection, 4) sufficient Age or sex do not usually influence post-thoracotomy
pulmonary parenchymal reserve following resection, and survival. Only one study [16] demonstrated a survival
5 ) absence of uncontrolled extrathoracic metastases. advantage of male patients with pulmonary metastases
A wide range of patients fall within these guidelines from osteogenic sarcoma. Survival depends on other fac-
and further criteria may better select those individuals tors, including the nature of the underlying primary neo-
who will have improved survival following surgical re- plasm and the “aggressiveness” of the pulmonary me-
section. Some patients will not benefit from surgery be- tastases. Generally, age or sex should not be considered
cause of extensive disease, a short disease free interval prognostic factors.
between control of their primary tumor and identification
of pulmonary metastases, and rapid metastatic growth.
Biological characteristics differ with the tumor histol- LOCATION AND STAGE OF PRIMARY TUMOR
ogy. Prognostic indicators may be used to identify those If the primary tumor is locally controlled, then post-
patients who are most likely to have improved survival thoracotomy survival is not usually influenced by the
following resection of pulmonary metastases. Predictors specific anatomic location of the primary tumor (e.g.,
for improved survival have been studied retrospectively extremity vs. retroperitoneal for soft tissue sarcomas).
for various tumor types to identify selected patients who Post-resection survival in patients with more advanced
will benefit from pulmonary metastasectomy. stage primary neoplasms did not differ from those pa-
tients with earlier stage disease except for those patients
PROGNOSTIC INDICATORS with negative nodes at primary surgery for breast carci-
noma [ 171. A negative nodal status predicted improved
Various prognostic indicators have been studied to as-
post-resection survival for patients with breast cancer.
sess their influence singularly and in combination on
Location of the primary tumor and stage was not a sig-
post-resection survival in patients with pulmonary me-
nificant predictor of post-resection survival for colorectal
tastases (Table I). Factors that can be examined preop-
carcinoma. However, one study [18] did show signifi-
eratively include age, sex, histology, grade and location
cantly better post-thoracotomy survival in patients with
of the primary tumor, stage of primary tumor, disease
Dukes’ stage A (5 year survival 37.5%) compared to
free survival, number of nodules on preoperative radio-
Dukes’ C patients (5 year survival 15%).
logical studies, unilateral or bilateral metastases, tumor
doubling time, and synchronous or metachronous me-
tastases. Prognostic indicators which can be assessed DISEASE FREE INTERVAL
post-operatively include resectability , technique of re- The initial disease free interval (DFI) extends from
section, nodal spread, number of metastases and loca- resection of the primary tumor until pulmonary me-
tion, and re-resection. tastases are detected. A short disease free interval may
 Prognostic Indicators For Lung Metastases 293

TABLE I. Prognostic Indicators Associated With Better Post-ResectionSurvival for Various Tumor Histologies
(Univariate Analysis)*

Stage of nodules 5 year

Tumor Location METS DFI Median survival
Tumor IREF] N Age Sex grade primary Primary CT TOMO resected TDT RESECT (mo) survival (%)

Breast
[17] 50 Neg NS >18 13 12
nodes
Colorectal
[I91 66 NS NS NS NS NS 1" >24b 42 38
[18] 35 +c NS" NS 22
[21] 27 NSd NSaZd 27 9
[20] 27 NS NS NS NS NS NS" + >24 35 21
[22] 62 NS NS NS NS 1a.e NS 24 42
Osteogenic sarcoma
[ l l ] 38 NS NS NS 54 NS + NS
[16] 39 NS Male NS <4 <6 + NS 20 38'
[23] 38 NS NS NS s3 54 NS + >6 26 40
[24] 27 1 >12 28 47 (@3 yr)
[25] 32 NS + NS 24 32
[26] 20 NS NS NS + NS 37
Soft tissue sarcomas
[ll] 67 NS NS NS 14 >20d t >I2
[27] 67 NS NS NS s4 <16 >20d + >12 18 10
[28] 63 NS NS NS NS 55 53 NS NS + >I2 20.3 27
[29] 28 NS NS 35g
Ewing's sarcoma
[31] 19 s4 + NS 28h 15h.i
Melanoma
[32] 31 NSJ NS NS NS NS 13.0 78
[33] 47 + NS 19.0 25'
[34] 17 NS NS 16.5 11.1
Renal
[301 44 NS NS NS NS NSk ~NS >24 33 21
1351 39 NS" + NS 36 32.7
*REF, reference; CT, computerized tomography; TOMO, full lung linear tomograms; METS, metastases; TDT, tumor doubling time; RESECT,
resectability; DFI, disease free interval between control of primary tumor and identification of pulmonary metastases; NS, not significant.
"Solitary vs. multiple.
bBorderline significance (P = 0. I).
'Dukes' A had better survival than Dukes' C.
dP values not presented.
"Patients with metastasis <3 cm had better survival.
'Addition of adjuvant therapy did not influence survival.
gEstimated.
hResectable patients only.
'Metastases occurring after primary chemotherapy were associated with better survival than patients with pulmonary metastases developing
during primary chemotherapy.
'Nodal status was not significant.
kPatients with largest metastasis resected 2 3 cm (n = 11) had better survival.

indicate a poorer prognosis following resection as these sarcoma in two [23,24] of six studies demonstrated a
metastases may be multiple and rapidly growing. survival advantage with a DFI of >6 months [23] or > 12
In patients with breast carcinoma 1171 a DFI of >18 months 1241 in contrast to other studies which demon-
months was associated with a prolonged post-resection strated no such advantage [11,16,25,26]. In soft tissue
survival. Two of four studies of colorectal carcinoma sarcomas, a DFI of > 12 months [I 1,27,28] was usually
[19,20] demonstrated a survival advantage in those pa- associated with a better post-resection survival. One
tients with a DFI greater than 24 months. However, two study did not observe any survival advantage [29].
studies demonstrated no survival advantage [ 18,211. One One study of patients with metastatic renal cell carci-
additional study did not evaluate DFI [22]. noma demonstrated longer post-resection survival in
Patients with pulmonary metastases from osteogenic those patients with a DFI of >24 months [30]. Evalua-
294 Putnam and Roth
tion of patients with Ewing’s sarcoma [311, melanoma
[32-341, or renal carcinoma [35] did not reveal differ-
ences in survival based on DFI.
UNILATERAL OR BILATERAL DISEASE
Unilateral or bilateral pulmonary metastases per se do
not influence post-resection survival [23,27]. The num-
ber of nodules is a more precise prognostic indicator than
unilaterality or bilaterality .
NUMBER OF NODULES ON PREOPERATIVE
ROENTGENOGRAPHIC STUDIES
Computerized tomography has replaced linear tomo-
grams as the examination of choice in patients with sus-
pected pulmonary metastases. CT scans of the chest pro-
vide a sensitive and specific study for patients with pul-
monary metastases [36,37]. CT scans of the chest are
quite sensitive and will identify smaller nodules (7.6
mm) earlier than conventional linear tomography. These
nodules may or may not be metastases. Theoretically,
earlier detection and treatment of metastases could im-
prove survival. However, in one study which detected
occult metastases during median sternotomy with bilat-
eral lung exploration, survival was not improved over
patients having a single thoracotomy, even though a sig-
nificant percentage of these patients would be expected
to have occult metastases [9].
In patients with osteogenic or soft tissue sarcomas,
better post-resection survival was found in patients with
fewer number of nodules identified on preoperative full
lung linear tomograms or CT scans of the chest. CT
scans are more sensitive and better survival was noted in
those patients with <4 nodules identified on CT scans
with osteogenic sarcoma [16], and those with G.5 nod-
ules in soft tissue sarcomas [28]. Full lung tomograms
(FLT) were performed in several studies. Patients with
<4 metastases identified on FLT in osteogenic sarcoma
[11,23] or G4 nodules on FLT in soft tissue sarcomas
[ 11,27,28] had better post-resection survival than those
individuals with more nodules.
NUMBER OF METASTASES RESECTED
Usually, the fewer the number of pulmonary me-
tastases at the time of resection the better the post-
resection survival. Patients with pulmonary metastases
from colorectal carcinoma usually have only one or two
metastases. Patients with only one metastasis identified
and resected [19,22] had a better survival than those
patients with more than one metastasis although this was
not consistent in all studies [18,20,21]. Patients with <5
1231 or <4 [24] metastases resected from patients with
osteogenic sarcoma or < 16 metastases in soft tissue sar-
comas [27] had a better post-resection survival than pa-
tients with more metastases resected.
Post-resection survival following complete resection
in patients with pulmonary metastases from renal cell
carcinoma [30,35], melanoma 132-341, osteogenic sar-
coma [25], or soft tissue sarcoma [28,29] was not influ-
enced by the number of metastases resected.
TUMOR DOUBLING TIME
Tumor doubling time (TDT) has been analyzed for
multiple tumor types and is based on original observa-
tions by Collins et al. 1381 as calculated by Joseph et al.
[39,40]. The tumor doubling time is calculated by mea-
suring the same nodule on similar studies (for example
serial chest roentgenograms) which are separated by a
minimum of 10-14 days. Tumor doubling time can be
easily calculated by plotting changing diameters of pul-
monary metastases on semilogarithmic paper; however,
graphical error may be present. A mathematical formula
may be used to calculate more precisely the tumor dou-
bling time and minimize graphical error.
M1 (Measurement 1) = S
M2 (Measurement 2) = M
T = Number of days between measurements
Tumor doubling time= T [In ?43 * In (M/S)]
= 0.231 * T/ln (M/S)
Initially pulmonary metastases grow exponentially
(rapid TDT), and with increased size, the growth rate
may diminish (slower TDT). This growth may be ex-
pressed by “Gompertzian” kinetics [41,42], which con-
siders this gradual diminution in TDT with time and
increased size of the metastasis. Whether the growth rate
is linear, exponential, or Gompertzian may be difficult to
discern for groups of patients. The growth rate measured
over a few weeks represents a brief period in the lifetime
of the metastasis. Although it is assumed this growth rate
is linear, this may not always be correct.
TDT is not a significant predictor of post-resection
survival in patients with pulmonary metastases from os-
teogenic sarcoma [ 11,231. TDT of >20 days in patients
with soft tissue sarcomas did predict better post-thora-
cotomy survival than those patients with more rapid tu-
mor doubling times. One study of patients with soft tis-
sue sarcomas [28] failed to find any correlation between
TDT and post-resection survival.
All metastases do not grow at the same rate. In general
metastases from the same primary grow at similar rates
although differing growth rates between tumor nodules
may reflect heterogeneity of metastases from the pri-
mary. The tumor doubling time may indirectly reveal the
underlying biological nature of the metastases and as
such influence the patient’s post-resection survival.
CHOICE OF RESECTION
Patients with bilateral metastases may be safely ex-
plored with either a median sternotomy or staged bilat-

eral thoracotomies. Either approach is safe and post-
resection survival is similar. We advocate a median ster-
notomy for the initial exploration in patients with
unilateral or bilateral nodules. Prior evaluation of pa-
tients with osteogenic or soft tissue sarcomas with uni-
lateral pulmonary nodules demonstrated bilateral spread
in 38%-60% of patients [8,9].
Numbers of nodules, presence of unilateral or bilateral
nodules, location, and the size of various nodules can be
identified, and if required, resected through a median
stemotomy. Mediastinal lymph nodes can also be exam-
ined for potentially rare involvement from pulmonary
metastases [27]. In this manner, a complete exploration
and resection of all abnormal areas may be accom-
plished. All lobes may be resected through a median
sternotomy; however, a left lower lobectomy may be
difficult and a left thoracotomy may provide better ex-
posure for a complete resection. Every effort should be
made to completely resect all nodules with a margin of
normal tissue. Nodules should not be “shelled out” as
viable tumor cells remain on the periphery of the resected
area. Often the decision as adequacy of margin is the
surgeon’s alone as lung parenchyma may become dis-
torted around the nodule after resection giving the false
illusion of a “positive” or “close” margin.
MULTIVARIATE ANALYSIS OF
PROGNOSTIC FACTORS
Combining separate prognostic variables together may
enhance the predictive value for post-resection survival.
Meyer et al. [16] found significant differences in post-
resection survival in patients with pulmonary metastases
from osteogenic sarcoma. Male patients with five or
fewer nodules detected either radiologically or during
surgery had a median survival of 560 days as compared
to women with more than 5 nodules, who had a median
survival of only 128 days. Putnam et al. [23] however
found that in patients with pulmonary metastases from
osteogenic sarcoma that the number of nodules on pre-
operative tomograms, and the disease free interval (the
two best predictors of post-thoracotomy survival) had no
significant increase in predictive ability when combined
as compared to either alone. Jablons et al. [28] examined
the disease free interval, sex, resectability , and truncal
location in patients with pulmonary metastases from
soft tissue sarcomas as a single prognostic indicator
and found it to be the best predictor of post-thoracot-
omy survival. Putnam et al. [27] examined DFI > 12
months, TDT > 20 days, S 4 nodules on preoperative
full lung tomograms as a single prognostic indicator in
patients with pulmonary metastases from soft tissue sar-
comas and found that it was the best predictor of post-
thoracotomy survival. Roth et al. [ 1I] found that in os-
teogenic sarcoma, no combination of prognostic indica-
tors added any significant increase in predictive ability
Prognostic Indicators For Lung Metastases 295
compared to soft tissue sarcoma metastases where TDT,
number of metastases on preoperative full lung tomo-
grams, and disease free interval, combined, gave a better
predictive ability than any single factor or pair of factors.
Use of multivariate analysis may allow more accurate
prediction of post-resection survival and allow better pa-
tient selection.
RESECTABILITY
Resectability is the major factor which correlated with
improved post-thoracotomy survival for patients with
pulmonary metastases. Only two studies [melanoma
[32], renal cell carcinoma [30]] suggested that a com-
plete resection was NOT associated with better post-
thoracotomy survival. If pulmonary metastases cannot be
completely removed, the post-thoracotomy survival is
shortened for patients with most tumors in comparison to
those individuals completely resected.
Pulmonary metastases may recur in the lungs follow-
ing resection. Resection of new pulmonary metastases in
soft tissue sarcoma patients will provide the patient with
enhanced survival over unresectable patients despite re-
recurrence in the lungs [lo].
NODAL OR ENDOBRONCHIAL METASTASES
Involvement of mediastinal lymph nodes from pulmo-
nary metastases is rare [27]. When mediastinal lymph
node involvement does occur in soft tissue sarcoma pa-
tients [28] survival is significantly worse (5 months)
compared to those patients without nodal metastases (3 1
months). Endobronchial metastases in patients with adult
soft tissue sarcomas have a short post-resection survival.
Seven of 11 patients with endobronchial metastases lived
6 months or less [43].
CONCLUSIONS
Patients with pulmonary metastases may be catego-
rized by various prognostic indicators to define the bio-
logical nature of the metastases, to predict post-resection
survival, and to assist the clinician in selecting patients
who will benefit from surgery. No single criterion will
predict which patients will have enhanced long-term sur-
vival following resection, although patients who can be
completely resected of all pulmonary metastases tend to
have improved post-thoracotomy survival regardless of
tumor histology. Prognostic factors are heterogeneous
among different tumor histologies. Factors predictive for
one type of tumor are frequently not predictive for an-
other. Various prognostic indicators used together may
be better than any single prognostic indicator. Multivari-
ate analyses of combinations of prognostic indicators in
patients with osteogenic or soft tissue sarcomas may be
helpful in deciding which patients would not benefit
from surgery and should be offered other therapy. The
2% Putnam and Roth

use of prognostic indicators to select patients who will 21. Goya T, Miyazawa N, Kondo H, et al: Surgical resection of
pulmonary metastases from colorectal cancer: Ten year follow-
benefit from surgery remains inexact and should be used up. Cancer 64:1418-1421, 1989.
in addition to the clinical information available. Never- 22. Wilking N, Petrelli NJ, Herrera L, et al: Surgical resection of
theless, careful use of prognostic indicators for a tumor pulmonary metastases from colorectal adenocarcinoma. Dis Co-
lon Rectum 28562-564, 1985.
type may facilitate selection of patients for investiga- 23. Putnam JB, Roth JA, Wesley MN, et al: Survival following ag-
tional therapies. Further and more detailed analyses of gressive resection of pulmonary metastases from osteogenic sar-
prognostic factors from larger populations of patients coma: Analysis of prognostic factors. Ann Thorac Surg 36:516-
523, 1983.
with single tumor histologies will assist in better defining 24. Pastorino U , Valente M, Gasparini M, et al: Lung resection as
the value of prognostic indicators to select for or exclude salvage treatment for metastatic osteosarcoma. Tumori 74:201-
patients from surgical resection. 206, 1988.
25. Goorin AM, Delorey MJ, Lack EE, et al: Prognostic significance
REFERENCES of complete surgical resection of pulmonary metastases in patients
with osteogenic sarcoma: Analysis of 32 patients. J Clin Oncol
1 . Barney JD, Churchill W: Adenocarcinoma of the ludney with 2:425-431, 1984.
metastasis to the lung cured by nephrectomy and lobectomy. J 26. Belli L, Scholl S, Livartowski A, et al: Resection of pulmonary
Urol 42:269-276, 1939. metastases in osteosarcoma: A retrospective analysis of 44 pa-
L. Takita H, Merrin C, Didolkar MS, et al: The surgical manage- tients. Cancer 63:25462550, 1989.
ment of multiple lung metastases. Ann Thorac Surg 24:359-364, 27. Putnam JB Jr, Roth JA, Wesley MN, et al: Analysis of prognostic
1977. factors in patients undergoing resection of pulmonary metastases
3. Morrow CE, Vassilopoulos PP, Grange TB: Surgical resection for from soft tissue sarcomas. J Thorac Cardiovasc Surg 87:26&267,
metastatic neoplasms of the lung: Experience at the University of 1984.
Minnesota Hospitals. Cancer 45:2981-2985, 1980. 28. Jablons D, Steinberg SM, Roth JA, et al: Metastasectomy for soft
4. McCormack PM, Martini N: The changing role of surgery for tissue sarcoma. Further evidence for efficacy and prognostic in-
pulmonary metastases. Ann Thorac Surg 28:139-142, 1979. dicators. J Thorac Cardiovasc Surg 97:695-705, 1989.
5. Takita H, Edgerton F, Karakousis C, et al: Surgical management 29. Pastorino U, Valente M, Gasparini M, et al: Lung resection for
of metastases to the lung. Surg Gyn Obstet 152:191-194, 1981. metastatic sarcomas: Total survival from primary treatment. J
6. Wright JO, Brandt B, Ehrenhaft JL: Results of pulmonary resec- Surg Oncol 40:275-280, 1989.
tion for metastatic lesions. J Thorac Cardiovasc Surg 83:94-99, 30. Jett JR, Hollinger CG, Zinsmeister AR, Pairolero PC: Pulmonary
1982. resection of metastatic renal cell carcinoma. Chest 84442-445,
7 . Mountain CF, McMurtrey MJ, Hermes KE: Surgery for pulmo- 1983.
nary metastasis: A 20-year experience. Ann Thorac Surg 38:323- 3 1. Lanza LA, Miser JS, Pass HI, Roth JA: The role of resection in
330, 1984. the treatment of pulmonary metastases from Ewing’s sarcoma. J
8. Johnston MR: Median sternotomy for resection of pulmonary me- Thorac Cardiovasc Surg 94:181-187, 1987.
tastases. J Thorac Cardiovasc Surg 85:516-522, 1983. 32. Pogrebniak HW, Stovroff M, Roth JA, Pass HI: Resection of
9. Roth JA, Pass HI, Wesley MN, et al: Comparison of median pulmonary metastases from malignant melanoma: Results of a
sternotomy and thoracotomy for resection of pulmonary me- 16-year experience. Ann Thorac Surg 46:20-23, 1988.
tastases in patients with adult soft-tissue sarcomas. Ann Thorac 33. Wong JH, Euhus DM, Morton DL: Surgical resection for meta-
Surg 42:134-138, 1986. static melanoma to the lung. Arch Surg 123:1091-1095, 1988.
10. Rizzoni WE, Pass HI, Wesley MN, et al: Resection of recurrent 34. Thayer JO, Overholt RH: Metastatic melanoma to the lung: Long
pulmonary metastases in patients with soft-tissue sarcomas. Arch term results of surgical excision. Am J Surg 149558-562, 1985.
Surg 121:1248-1252, 1986. 35. Schott G, Weissmuller J, Vecera E: Methods and prognosis of the
1 1 . Roth JA, Putnam JB, Wesley MN, Rosenberg SA: Differing de- extirpation of pulmonary metastases following tumor nephrecto-
terminants of prognosis following resection of pulmonary me- my. Urol Int 43:272-274, 1988.
tastases from osteogenic and soft tissue sarcoma patients. Cancer 36. Chang AE, Schange EG, Conkle DM, et al: Evaluation of com-
55~1361-1366, 1985. puted tomography in the detection of pulmonary metastases: a
12. Kaplan EL, Meier P: Nonparametric estimation from incomplete prospective study. Cancer 43:913-916, 1979.
observations. J Am Stat Assoc 53:457-481, 1958. 37. Pass HI, Dwyer A, Makuch R, Roth JA: Detection of pulmonary
13. Gehan EA: A generalized Wilcoxon test for comparing arbitrarily metastases in patients with osteogenic and soft-tissue sarcomas:
singly-censored samples. Biometrika 52:203-223, 1965. The superiority of CT scans compared with conventional linear
14. Thomas DG: Exact and asymptotic methods for the combination tomograms using dynamic analysis. J Clin Oncol 3(9):1261-
of 2 x 2 tables. Comput Biomed Res 8 : 4 2 U 6 , 1975. 1265, 1985.
15. Cox DR: Regression models and life-tables. J R Stat Soc B 38. Collins VP, Loeffler RK, Tivey H: Observations on growth rates
34:187-220, 1972. of human tumors. Am J Radio1 76:988-1000, 1956.
16. Meyer WH, Schell MJ, Jumar PM, et al: Thoracotomy for pul- 39. Joseph WL, Morton DL, Adkins RC: Prognostic significance of
monary metastatic osteosarcoma. An analysis of prognostic indi- tumor doubling time in evaluating operability in pulmonary met-
cators of survival. Cancer 59:374-379, 1987. astatic disease. J Thorac Cardiovasc Surg 61:23-32, 1971.
17. Schlappack OK, Baur M, Steger G, et al: The clinical course of 40. Joseph WL, Morton DL, Adkins PC: Variation in tumor doubling
lung metastases from breast cancer. Klin Wochenschr 66:79CL time in patients with pulmonary metastatic disease. J Surg Oncol
795, 1988. 3:143-149, 1971.
18. McCormack PM, Attiyeh FF: Resected pulmonary metastases 4 1 . Gompertz B: On the nature of the function expressive of the law
from colorectal cancer. Dis Colon Rectum 22:553-556, 1979. of human mortality, and on a new mode of determining the value
19. Brister SJ, DeVarennes B, Gordon PH, et al: Contemporary op- of life contingencies. Philos Trans pp. 513-585, 1825.
erative management of pulmonary metastases of colorectal origin. 42. Laird AK: Dynamics of tumor growth. Br J Cancer 18:49@502,
Dis Colon Rectum 31:786-792, 1988. 1960.
20. Manse1 KJ, Zinsmeister AR, Pairolero PC, Jen JR: Pulmonary 43. Udelsman R, Roth JA, Lees D, et al: Endobronchial metastases
resection of metastatic colorectal adenocarcinoma. Chest 1 :109- from soft tissue sarcoma. J Surg Oncol 32:145-149, 1986.
112, 1986.