- Email: [email protected]
Intensification of 111In-DTPA-octreotide scintigraphy by means of pretreatment with cold octreotide in small cell lung cancer
LUNG
ELSEVIER
Lung
Cancer
17 (1997)
231-238
Intensification of l1‘In-DTPA-octreotide scintigraphy by means of pretreatment with cold octreotide in small cell lung cancer E. Soresi a,*, G. Invernizzi a, R. Boffi a, M. Possa b, E. Bombardieri ‘, G. Petracca Ciavarella d, A. Liuzzi d a Department of Pneumology, Niguarda Hospital, Milan, Italy b Department of Nuclear Medicine, Niguarda Hospital, Milan, Italy ’ Department of Nuclear Medicine, National Cancer Institute, Milan, Italy ’ IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
Received 19 July 1996; received in revised form 2 December 1996; accepted 4 December 1996
Abstract Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced with “‘In-DTPA-octreotide scintigraphy. Although this technique is currently employed for staging and follow-up of neuroendocrine tumors of the gastrointestinal tract, its role in the clinical work-up of SCLC is at present under discussion. A better imaging contrast is desirable and recent reports suggest that this aim could be achieved by pretreatment with cold octreotide. Here we report on the results of “‘In-DTPA-octreotide scintigraphy in 12 SCLC patients carried out before and after octreotide treatment. The patients were treated for 7 days with octreotide 200 pug three times a day S.C. Uptake was studied at 5 h with whole body planar and SPET imagings. In all cases studied, pretreatment with octreotide was followed by enhancement of tumor imaging. In one patient a better contrast of the lesions was found at the parenchymal and mediastinal levels as well as at brain level. allowing a clear definition of otherwise questionable metastases. After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was observed in most cases, allowing a better imaging of liver metastases. The enhancement effect was confirmed by semiquantitative analysis of scintigraphic uptake. Taken together, our results seem to indicate that cold
* Corresponding
author.
0169-5002/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reserved. PII SO1 69-5002(97)00657-O
232
E. Soresi
et al. /Lung
Cancer
17 (1997)
231-238
octreotide enhancementcan improve i ’ ’ In-DTPA-octreotide imagingand optimize its clinical role in SCLC. 0 1997Elsevier ScienceIreland Ltd. Small cell lung cancer; Clinical assessment; “‘In-DTPA-octreotide scintigraphy; Somatostatinanalogs Keywords:
1. Introduction An accurate tumor staging is of the utmost importance in SCLC, since different therapeutic options are available for limited (LD) and extensive (ED) disease. Staging procedures should combine diagnostic accuracy, cost-containement, and minimal trouble to the patient [l]. The search for a protocol that encompassesas few clinical investigations as possible for an accurate staging is therefore a matter of great interest. The expression of somatostatin receptors in neuroendocrine tumors has led to a successful clinical use of labeled somatostatin analogs such as “‘In-DTPA-octreotide scintigraphy for carcinoids, insulinomas, gastrinomas, pituitary adenomas [2]. This technique can identify unkown tumor sites and very small lesions, undetectable by conventional staging [3,4]. Like other neuroendocrine tumors, SCLC also expressessomatostatin receptors that can be traced with “‘In-DTPAoctreotide scintigraphy [5]. With this technique in addition to lung and mediastinal SCLC lesions, distant lesions to bone, brain and lymph nodes can be visualised with high sensitivity [6-lo]. However, some limitations have been found in the specificity of this procedure and in its capability to locate tumor lesions in the sub-diaphragmatic area, due to the high background uptake in the liver, kidney and spleen [11,12]. Therefore, an improvement in imaging resolution is desirable. Recently it has been reported that pretreatment with cold octreotide can improve “‘In-DTPA-octreotide imaging in patients with carcinoids [13]. This effect was interpreted as due to the reduction in background activity. We reported a similar effect in a previous paper about a few SCLC cases[14]. Here we report an up-date of our experience on the enhancement of “‘In-DTPA-octreotide imaging in SCLC, along with a semiquantitative analysis of uptake ratios before and after treatment with cold octreotide.
2. Materials and methods During the period between April and November 1994 we studied 12 male patients with histologically proven SCLC with an age range of 52-72 years. Four patients were at initial staging and eight at re-staging after chemotherapy f radiotherapy. Demographic and clinical details are shown in Table 1. For conventional staging, patients were submitted to chest X-ray, evaluation of serum neuron-specific enolase, tissue polypeptide antigen and carcino-embryonic antigen, fiberoptic bron-
E. Soresi et al. /Lung
Cancer
17 (1997)
231-238
233
choscopy, bone scintigraphy, thoraco-adbominal CT scan or thoracic CT scan plus adbominal ultrasound, and brain CT scan if needed. Patients received a basal “‘In-DTPA-octreotide scintigraphy (Octreoscan, Mallinckrodt Medical, The Nederlands) followed by a 7-day treatment with octreotide S.C. (Sandostatin, Sandoz, scintigraphy was Switzerland; 200 ,ug 3 times/day). A repeat “‘In-DTPA-octreotide carried out on day 8. Planar scintigraphy was carried out 5 h after i.v. injection of 110-130 mBq of ’ ’ ’ In-DTPA-octreotide. A semiquantitative evaluation of “‘In-DTPA-octreotide uptake was recorded by means of region-of-interest (ROI) technique. ROI were drawn on the lung tumor, on a homogeneous area of the controlateral lung and on a homogeneous area of the liver. Background and liver ROI were created with the same size of the tumor lesion. This method was applied by all participant centers. Anterior and posterior views were recorded for whole body imaging, followed by chest planar images. Local ethics committee agreement on this study and patients’ informed consent were obtained.
3. Results Basal I1‘In-DTPA-octreotide scintigraphy demonstrated lung and mediastinal SCLC lesions in all patients studied, concordant with chest X-ray and CT scan. Correct identification was possible also for three liver, two brain, one bone and one lymph-node lesions, while an adrenal lesion could not be detected. After treatment with octreotide, overall scintigraphic appearance was improved in most cases, as shown by uptake ratio analysis of ROI (Table 2). An improvement of lesion/lung ROI uptake ratio was recorded in 8 out of 12 cases, while no difference was observed in two cases and a decrease was observed in two additional cases. Lesion/liver ROI uptake ratios were improved in 9 out of 12 cases, while a decrease Table 1 Demographic
and clinical
data
of the patients
studied
Patients
Age
Sex
P.S.”
Staging
TNM
1 2 3 4 5 6 7 8 9 10 11 12
58 65 68 57 55 70 52 55 70 72 62 65
M M M M M M M M M M M M
2 1 2 0 2 3 2 0 1 2 1 1
Restaging Restaging Restaging Restaging Restaging Restaging Restaging Restaging Staging Staging Staging Staging
T4,N2,MO T4,N2,MO TZ,Nl.MO T2,N3.M0 T2,N3,MO T3,N2,M T3,N2,M T3,Nl,MO T3,N2,M T3,N2.M T3,N2,M T4,N2,M
d Performance
status
(Zubrod
scale).
+ + + + + +
234
E. Soresi et al. /Lung
Table 2 Octreotide-enhanced
“‘In-DTPA-octreotide
Patients
Uptake
ratio
Lesion/lung
1 2 3 4 5 6 7 8 9 10 11 12 Mean
(S.D.)
* P = 0.026,
before
Cancer
scintigraphy and after
17 (1997)
231-238
in SCLC
octreotide
ratio
treatment Lesion/liver
ratio
Before
After
Before
After
1.76 1.12 1.80 2.11 1.59 1.80 2.04 1.44 2.50 1.80 2.50 1.50 1.83 (0.41)
1.76 1.60 1.90 2.19 1.89 1.78 1.70 1 .I2 2.90 2.00 2.90 1.50 I .98* (0.46)
0.71 0.49 0.69 0.56 0.77 0.55 0.69 0.83 0.63 0.57 1.01 0.57 0.67 (0.14)
0.84 0.33 0.72 0.79 0.73 0.89 1.05 0.86 0.81 0.79 1.10 0.55 0.78**
** P = 0.039 (as compared
to basal
values,
paired
Student’s
(0.20)
f-test).
was observed in three cases. Comparisons of the means showed a statistically significant improvement after octreotide treatment for both kinds of uptake ratios. An example of imaging improvement is reported in Fig. 1, that shows a better contrast of the lesions at the parenchymal and mediastinal levels, and at brain level where a questionable metastasis could be clarified after octreotide treatment. Similarly, brain lesions were enhanced in another case (Fig. 2). After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was also observed in most cases, as shown in Fig. 3, where an imaging improvement is evident also for the lung lesion. Octreotide treatment was well tolerated, without important side-effects, with the exception of transitory diarrhoea in some cases, easily controlled with pancreatic extracts.
Fig. 1. Top: basal (left side) and octreotide-enhanced (right side) “‘In-DTPA-octreotide scintigraphy of the thorax and upper abdomen in patient 11, showing an improved contrast of mediastinic and parenchymal lung lesions (arrows) after octreotide conditioning. Bottom: basal (left side) and octreotideenhanced (right side) scintigraphy of the brain in the same patient, showing an better constrast of a metastatic lesion (arrows) after enhancement. Fig. 2. “‘In-DTPA-octreotide scintigraphy in patient 10 showing a clear cut enhancement of a brain lesion after octreotide pre-treatment (right arrow) as compared to basal imaging (left arrow).
E. Soresi et al. /Lung Cancer 17 (1997) 231-238
235
236
E. Soresi
et al. /Lung
Cancer
17 (1997)
231-238
Fig. 3. “‘In-DTPA-octreotide scintigraphy showing a marked enhancement of lung lesion and a concomitant decrease in subdiaphragmatic uptake after octreotide pretreatment in patient 9 (top: front-view; bottom: back-view; left side: basal; right side: after octreotide pretreatment).
4. Discussion SCLC is characterized by high aggressiveness and early dissemination. Multiple distant lesions are frequently observed and clinical experience suggests that hidden metastases are frequently present at basal staging in patients initially classified as LD. Thus SCLC staging should be as exhaustive as possible, encompassing several instrumental investigations such as chest X-ray, fiberoptic bronchoscopy, chest CT scan, bone scintigraphy, selective bone X-ray, abdominal ultrasound and CT scan, bone marrow biopsy, and brain CT scan. Therefore any improvement in the clinical applications of whole-body somatostatin-receptor scintigraphy would be welcome. The present data point to a real improvement in imaging after treatment with cold octreotide, as supported by the semiquantitative analysis with ROI evaluation. Our data are confirmed by a recent report by Kalkner et al. on a large series of carcinoid tumors [15]. The effect of this conditioning could be explained by different mechanisms such as (1) a decrease of background uptake in normal tissues effected by means of physiological receptor saturation, (2) an increase in labelled octreotide availability to tumor cell receptors because of the saturation of normal tissue receptors, and (3) a persisting internalization of labelled octreotide in tumor
E. Soresi
et al. /Lung
Cancer
17 (1997)
231-238
231
cell, as recently reported [ 161. The usefulness of cold-octreotide ‘enhanced’ scintigraphy is shown by the better imaging of lung and mediastinal lesions as well as by distant lesions in the brain, but also in the sub-diaphragmatic area, that is regarded generally as a difficult site of imaging [12]. We have not done dosage titration studies with cold octreotide, but theoretically better results might be achieved by changing the regimen. scintigraphy has a questionable Due to its low specificity, ” ‘In-DTPA-octreotide role in primary staging in SCLC, even though it can provide integrative informations on the extent of the disease [17,18]. Additional administration of cold octreotide might sometimes provide better images with octreotide scintigraphy. In doubtful cases of tumor staging cold octreotide administration might be justified. In addition, the high sensitivity of this technique can be particularly helpful at re-staging and at follow-up, e.g. to confirm complete remission as evaluated by conventional re-staging. With reference to this point, we are carrying out a pilot study with “‘In-DTPA-octreotide scintigraphy to verify complete remission in SCLC after chemo/radiotherapy. Preliminary data on five patients indicate concordance with conventional restaging in three cases, while anticipatory results were obtained with enhanced “‘In-DTPA-octreotide scintigraphy in the other two patients, with the early demonstration of local recurrences and of hepatic lesions, respectively (unpublished data).
References [I]
[2]
[3] [4]
[5] [6] [7]
[S] [9]
[lo]
Richardson GE, Venzon DJ, Edison M, Brown M, Frame JN, Idhe DC, Johnson BE. Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs. Arch Intern Med 1993; 153: 329-337. Krenning EP, Kwekkeboom DJ, Dejong M, Visser TJ, Reubi JC, Bakker WH, Kooij PPM, Lamberts SWJ. Essentials of peptide receptor scintigraphy with emphasis on the somatostatin analogue octreotide. Sem Oncol 1994; 21(Suppl 13): 6-14. Carnaille B, Nocaudie M, Pattou F. Huglo D, Deveaux M, Marchandise X, Proye C. Scintiscans and carcinoid tumors. Surgery 1994; 116: 1118-1122. Woltering EA, Barrie R, Odorisio TM, Odorisio MS, Nance R, Cook DM. Detection of occult gastrinomas with “?-labeled lanreotide and intraoperative gamma detection. Surgery 1994; 116: 1139-1147. Lamberts SWJ, Bakker WH. Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 1990; 323: 124661249. Kwekkeboom DJ, Kho GS, Lamberts SWJ, Reubi JC, Laissue JA, Krenning EP. The value of octreotide scintigraphy in patients with lung cancer. Eur J Nucl Med 1994; 21: 110661113. Kwekkeboom DJ. Krenning EP, Bakker WH, Oei HY, Splinter TAW, Kho GS, Lamberts SWJ. Radioiodinated somatostatin analog scintigraphy in small cell lung cancer. J Nucl Med 1991; 32: 1845-1848. Lamberts SWJ, Reubi JC, Krenning EP. Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors. Acta Oncol 1993; 32: 167-170. Bombardieri E. Crippa F, Cataldo I, Chiti A, Seregni E, Soresi E, Boffi R, Invernizzi G, Buraggi CL. Somatostatin receptor imaging of small cell lung cancer (SCLC) by means of “‘In-DTPA-octreotide scintigraphy. Em J Cancer 1995; 31A: 1844188. Obyrne KJ. Ennis JT, Freyne PJ, Clancy LJ, Prichard JS, Carney DN. Scintigraphic imaging of small-cell lung cancer with [In-l I llpentetreotide, a radiolabelled somatostatin analogue. Br J Cancer 1994; 69: 762-766.
238 [ll]
[12] [13] [14]
[15]
[16]
[17] [18]
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et al. /Lung
Cancer
17 (1997)
231-238
Crippa F, Bombardieri E, Chiti A, Soresi E, Boffi R, Buraggi GL. “‘In-0ctreotide uptake in granulomatous lesion and tumor in a patient with small cell lung cancer. J Nucl Biol Med 1994; 37: 576-578. Stokkel MPM, Pauwels EKJ. Octreotide scintigraphy for small cell lung carcinoma-past, present or future. Eur J Nucl Med 1994; 21: 1276-1278. Dorr U. Improved visualization of carcinoid liver metastases by Indium-11 I-pentetreotide scintigraphy following treatment with cold somatostatin analogue. Eur J Nucl Med 1993; 20: 431-433. Soresi E, Bombardieri E, Chiti A, Boffi R, Invernizzi G, Crippa F, Maffioli L. Indium-1 1 I-DTPAOctreotide scintigraphy modulation by treatment with unlabelled somatostatin analogue in smallcell lung cancer. Tumori 1995; 81: 125-127. Kalkner KM, Janson ET, Nilsson S, Carlsson S, Oberg K, Westlin JE. Somatostatin receptor scintigraphy in patients with carcinoid tumors-comparison between radioligand uptake and tumor markers. Cancer Res 1995; 55: S5801-S5804. Hofland LJ, Vankoetsveld PM, Waaijers M, Zuyderwijk J, Breeman WAP, Lamberts SWJ. Internalization of the radioiodinated somatostatin analog [I-125-tyr(3)loctreotide by mouse and human pituitary tumor cells-increase by unlabeled octreotide. Endocrinology 1995; 136: 36983706. Reubi JC. The clinical relevance of somatostatin receptor imaging. Eur J Endocrinol 1994; 131: 575-576. Lamberts SWJ, Vanderlely AJ, Deherder WW, Hofland LJ. Drug therapy-octreotide. N Engl J Med 1996; 334: 2466254.
ELSEVIER
Lung
Cancer
17 (1997)
231-238
Intensification of l1‘In-DTPA-octreotide scintigraphy by means of pretreatment with cold octreotide in small cell lung cancer E. Soresi a,*, G. Invernizzi a, R. Boffi a, M. Possa b, E. Bombardieri ‘, G. Petracca Ciavarella d, A. Liuzzi d a Department of Pneumology, Niguarda Hospital, Milan, Italy b Department of Nuclear Medicine, Niguarda Hospital, Milan, Italy ’ Department of Nuclear Medicine, National Cancer Institute, Milan, Italy ’ IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
Received 19 July 1996; received in revised form 2 December 1996; accepted 4 December 1996
Abstract Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced with “‘In-DTPA-octreotide scintigraphy. Although this technique is currently employed for staging and follow-up of neuroendocrine tumors of the gastrointestinal tract, its role in the clinical work-up of SCLC is at present under discussion. A better imaging contrast is desirable and recent reports suggest that this aim could be achieved by pretreatment with cold octreotide. Here we report on the results of “‘In-DTPA-octreotide scintigraphy in 12 SCLC patients carried out before and after octreotide treatment. The patients were treated for 7 days with octreotide 200 pug three times a day S.C. Uptake was studied at 5 h with whole body planar and SPET imagings. In all cases studied, pretreatment with octreotide was followed by enhancement of tumor imaging. In one patient a better contrast of the lesions was found at the parenchymal and mediastinal levels as well as at brain level. allowing a clear definition of otherwise questionable metastases. After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was observed in most cases, allowing a better imaging of liver metastases. The enhancement effect was confirmed by semiquantitative analysis of scintigraphic uptake. Taken together, our results seem to indicate that cold
* Corresponding
author.
0169-5002/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reserved. PII SO1 69-5002(97)00657-O
232
E. Soresi
et al. /Lung
Cancer
17 (1997)
231-238
octreotide enhancementcan improve i ’ ’ In-DTPA-octreotide imagingand optimize its clinical role in SCLC. 0 1997Elsevier ScienceIreland Ltd. Small cell lung cancer; Clinical assessment; “‘In-DTPA-octreotide scintigraphy; Somatostatinanalogs Keywords:
1. Introduction An accurate tumor staging is of the utmost importance in SCLC, since different therapeutic options are available for limited (LD) and extensive (ED) disease. Staging procedures should combine diagnostic accuracy, cost-containement, and minimal trouble to the patient [l]. The search for a protocol that encompassesas few clinical investigations as possible for an accurate staging is therefore a matter of great interest. The expression of somatostatin receptors in neuroendocrine tumors has led to a successful clinical use of labeled somatostatin analogs such as “‘In-DTPA-octreotide scintigraphy for carcinoids, insulinomas, gastrinomas, pituitary adenomas [2]. This technique can identify unkown tumor sites and very small lesions, undetectable by conventional staging [3,4]. Like other neuroendocrine tumors, SCLC also expressessomatostatin receptors that can be traced with “‘In-DTPAoctreotide scintigraphy [5]. With this technique in addition to lung and mediastinal SCLC lesions, distant lesions to bone, brain and lymph nodes can be visualised with high sensitivity [6-lo]. However, some limitations have been found in the specificity of this procedure and in its capability to locate tumor lesions in the sub-diaphragmatic area, due to the high background uptake in the liver, kidney and spleen [11,12]. Therefore, an improvement in imaging resolution is desirable. Recently it has been reported that pretreatment with cold octreotide can improve “‘In-DTPA-octreotide imaging in patients with carcinoids [13]. This effect was interpreted as due to the reduction in background activity. We reported a similar effect in a previous paper about a few SCLC cases[14]. Here we report an up-date of our experience on the enhancement of “‘In-DTPA-octreotide imaging in SCLC, along with a semiquantitative analysis of uptake ratios before and after treatment with cold octreotide.
2. Materials and methods During the period between April and November 1994 we studied 12 male patients with histologically proven SCLC with an age range of 52-72 years. Four patients were at initial staging and eight at re-staging after chemotherapy f radiotherapy. Demographic and clinical details are shown in Table 1. For conventional staging, patients were submitted to chest X-ray, evaluation of serum neuron-specific enolase, tissue polypeptide antigen and carcino-embryonic antigen, fiberoptic bron-
E. Soresi et al. /Lung
Cancer
17 (1997)
231-238
233
choscopy, bone scintigraphy, thoraco-adbominal CT scan or thoracic CT scan plus adbominal ultrasound, and brain CT scan if needed. Patients received a basal “‘In-DTPA-octreotide scintigraphy (Octreoscan, Mallinckrodt Medical, The Nederlands) followed by a 7-day treatment with octreotide S.C. (Sandostatin, Sandoz, scintigraphy was Switzerland; 200 ,ug 3 times/day). A repeat “‘In-DTPA-octreotide carried out on day 8. Planar scintigraphy was carried out 5 h after i.v. injection of 110-130 mBq of ’ ’ ’ In-DTPA-octreotide. A semiquantitative evaluation of “‘In-DTPA-octreotide uptake was recorded by means of region-of-interest (ROI) technique. ROI were drawn on the lung tumor, on a homogeneous area of the controlateral lung and on a homogeneous area of the liver. Background and liver ROI were created with the same size of the tumor lesion. This method was applied by all participant centers. Anterior and posterior views were recorded for whole body imaging, followed by chest planar images. Local ethics committee agreement on this study and patients’ informed consent were obtained.
3. Results Basal I1‘In-DTPA-octreotide scintigraphy demonstrated lung and mediastinal SCLC lesions in all patients studied, concordant with chest X-ray and CT scan. Correct identification was possible also for three liver, two brain, one bone and one lymph-node lesions, while an adrenal lesion could not be detected. After treatment with octreotide, overall scintigraphic appearance was improved in most cases, as shown by uptake ratio analysis of ROI (Table 2). An improvement of lesion/lung ROI uptake ratio was recorded in 8 out of 12 cases, while no difference was observed in two cases and a decrease was observed in two additional cases. Lesion/liver ROI uptake ratios were improved in 9 out of 12 cases, while a decrease Table 1 Demographic
and clinical
data
of the patients
studied
Patients
Age
Sex
P.S.”
Staging
TNM
1 2 3 4 5 6 7 8 9 10 11 12
58 65 68 57 55 70 52 55 70 72 62 65
M M M M M M M M M M M M
2 1 2 0 2 3 2 0 1 2 1 1
Restaging Restaging Restaging Restaging Restaging Restaging Restaging Restaging Staging Staging Staging Staging
T4,N2,MO T4,N2,MO TZ,Nl.MO T2,N3.M0 T2,N3,MO T3,N2,M T3,N2,M T3,Nl,MO T3,N2,M T3,N2.M T3,N2,M T4,N2,M
d Performance
status
(Zubrod
scale).
+ + + + + +
234
E. Soresi et al. /Lung
Table 2 Octreotide-enhanced
“‘In-DTPA-octreotide
Patients
Uptake
ratio
Lesion/lung
1 2 3 4 5 6 7 8 9 10 11 12 Mean
(S.D.)
* P = 0.026,
before
Cancer
scintigraphy and after
17 (1997)
231-238
in SCLC
octreotide
ratio
treatment Lesion/liver
ratio
Before
After
Before
After
1.76 1.12 1.80 2.11 1.59 1.80 2.04 1.44 2.50 1.80 2.50 1.50 1.83 (0.41)
1.76 1.60 1.90 2.19 1.89 1.78 1.70 1 .I2 2.90 2.00 2.90 1.50 I .98* (0.46)
0.71 0.49 0.69 0.56 0.77 0.55 0.69 0.83 0.63 0.57 1.01 0.57 0.67 (0.14)
0.84 0.33 0.72 0.79 0.73 0.89 1.05 0.86 0.81 0.79 1.10 0.55 0.78**
** P = 0.039 (as compared
to basal
values,
paired
Student’s
(0.20)
f-test).
was observed in three cases. Comparisons of the means showed a statistically significant improvement after octreotide treatment for both kinds of uptake ratios. An example of imaging improvement is reported in Fig. 1, that shows a better contrast of the lesions at the parenchymal and mediastinal levels, and at brain level where a questionable metastasis could be clarified after octreotide treatment. Similarly, brain lesions were enhanced in another case (Fig. 2). After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was also observed in most cases, as shown in Fig. 3, where an imaging improvement is evident also for the lung lesion. Octreotide treatment was well tolerated, without important side-effects, with the exception of transitory diarrhoea in some cases, easily controlled with pancreatic extracts.
Fig. 1. Top: basal (left side) and octreotide-enhanced (right side) “‘In-DTPA-octreotide scintigraphy of the thorax and upper abdomen in patient 11, showing an improved contrast of mediastinic and parenchymal lung lesions (arrows) after octreotide conditioning. Bottom: basal (left side) and octreotideenhanced (right side) scintigraphy of the brain in the same patient, showing an better constrast of a metastatic lesion (arrows) after enhancement. Fig. 2. “‘In-DTPA-octreotide scintigraphy in patient 10 showing a clear cut enhancement of a brain lesion after octreotide pre-treatment (right arrow) as compared to basal imaging (left arrow).
E. Soresi et al. /Lung Cancer 17 (1997) 231-238
235
236
E. Soresi
et al. /Lung
Cancer
17 (1997)
231-238
Fig. 3. “‘In-DTPA-octreotide scintigraphy showing a marked enhancement of lung lesion and a concomitant decrease in subdiaphragmatic uptake after octreotide pretreatment in patient 9 (top: front-view; bottom: back-view; left side: basal; right side: after octreotide pretreatment).
4. Discussion SCLC is characterized by high aggressiveness and early dissemination. Multiple distant lesions are frequently observed and clinical experience suggests that hidden metastases are frequently present at basal staging in patients initially classified as LD. Thus SCLC staging should be as exhaustive as possible, encompassing several instrumental investigations such as chest X-ray, fiberoptic bronchoscopy, chest CT scan, bone scintigraphy, selective bone X-ray, abdominal ultrasound and CT scan, bone marrow biopsy, and brain CT scan. Therefore any improvement in the clinical applications of whole-body somatostatin-receptor scintigraphy would be welcome. The present data point to a real improvement in imaging after treatment with cold octreotide, as supported by the semiquantitative analysis with ROI evaluation. Our data are confirmed by a recent report by Kalkner et al. on a large series of carcinoid tumors [15]. The effect of this conditioning could be explained by different mechanisms such as (1) a decrease of background uptake in normal tissues effected by means of physiological receptor saturation, (2) an increase in labelled octreotide availability to tumor cell receptors because of the saturation of normal tissue receptors, and (3) a persisting internalization of labelled octreotide in tumor
E. Soresi
et al. /Lung
Cancer
17 (1997)
231-238
231
cell, as recently reported [ 161. The usefulness of cold-octreotide ‘enhanced’ scintigraphy is shown by the better imaging of lung and mediastinal lesions as well as by distant lesions in the brain, but also in the sub-diaphragmatic area, that is regarded generally as a difficult site of imaging [12]. We have not done dosage titration studies with cold octreotide, but theoretically better results might be achieved by changing the regimen. scintigraphy has a questionable Due to its low specificity, ” ‘In-DTPA-octreotide role in primary staging in SCLC, even though it can provide integrative informations on the extent of the disease [17,18]. Additional administration of cold octreotide might sometimes provide better images with octreotide scintigraphy. In doubtful cases of tumor staging cold octreotide administration might be justified. In addition, the high sensitivity of this technique can be particularly helpful at re-staging and at follow-up, e.g. to confirm complete remission as evaluated by conventional re-staging. With reference to this point, we are carrying out a pilot study with “‘In-DTPA-octreotide scintigraphy to verify complete remission in SCLC after chemo/radiotherapy. Preliminary data on five patients indicate concordance with conventional restaging in three cases, while anticipatory results were obtained with enhanced “‘In-DTPA-octreotide scintigraphy in the other two patients, with the early demonstration of local recurrences and of hepatic lesions, respectively (unpublished data).
References [I]
[2]
[3] [4]
[5] [6] [7]
[S] [9]
[lo]
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