endovascular stenting as the first step in the overall management of malignant superior vena cava...
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AJR:193, August 2009 549
exceeds 90%. It is common to observe 46% efficacy for RT in non–small cell lung carci-noma (NSCLC) and 62–80% for chemother-apy in patients with small cell lung carcino-ma (SCLC) [6, 7]. The use of chemotherapy and RT in combination is controversial and is currently under revision because of the many side effects and the low response rates (mean survival at 2 years = 5%) [7].
Placement of endovascular stents to man-age SVC syndrome and inferior vena cava syndrome has been used over the past 15 years as an additional tool for the palliative treatment of these patients [8–14]. To date, most of the patient series described in the lit-erature consider the use of stents to be a co-adjuvant treatment with RT or chemotherapy if there had been little or no response to RT or chemotherapy or if the clinical syndrome recurred after conventional treatment.
Earlier this decade, however, some investi-gators suggested that stents may be used as the
Endovascular Stenting as the First Step in the Overall Management of Malignant Superior Vena Cava Syndrome
Carlos Lanciego1
Cristina Pangua2
Jose Ignacio Chacón2
Javier Velasco1
Rafael Cuena Boy3
Antonio Viana4
Sara Cerezo5
Lorenzo García García1
Lanciego C, Pangua C, Chacón JI, et al.
1Interventional Radiology Unit, Department of Radiology, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Avda. de Barber 30, 45004 Toledo, Spain. Address correspondence to C. Lanciego ([email protected]).
2Servicio de Oncología Médica, Complejo Hospitalario de Toledo, Toledo, Spain.
3Unidad de Investigación-Estadística of the Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, Spain.
4Servicios de Oncología Médica del Hospital de Talavera, Toledo, Spain.
5Hospital La Mancha Centro-Alcázar de San Juán, Ciudad Real, Spain.
Vascular and Inter vent iona l Radiolog y • Or ig ina l Research
AJR 2009; 193:549–558
0361–803X/09/1932–549
© American Roentgen Ray Society
Superior vena cava (SVC) syndrome is caused by obstruction of the flow of venous blood from the up-per body into the right atrium. In
95% of the cases, the obstruction is due to an underlying malignant disease, usually ad-vanced-stage lung cancer. Obstruction of the SVC causes congestion and edema of the face and upper thorax [1, 2]. Other symptoms are often associated with the disorder such as dys-pnea, dysphagia, cognitive dysfunction, and se-vere headache. These symptoms result from cerebral venous hypertension that can arise due to blockage of the venous blood flow return.
The traditional treatment for SVC syn-drome has been radiation therapy (RT), che-motherapy, or both [3]. Bypass surgery, de-spite having been used in some centers until recently, is not justified because SVC syn-drome is not a terminal disease [4, 5].
Initial technical success using RT and che-motherapy to manage SVC syndrome rarely
Keywords: endovascular stenting, hemodynamics, lung cancer, oncologic imaging, stents, superior vena cava syndrome
DOI:10.2214/AJR.08.1904
Received October 3, 2008; accepted after revision January 15, 2009.
OBJECTIVE. Self-expandable metal stents were inserted in cancer patients with superior vena cava (SVC) syndrome to assess their effectiveness as a primary treatment for symptom relief.
SUBJECTS AND METHODS. Between January 1993 and June 2008, Wallstent pros-theses (n = 208) were inserted in 149 cancer patients (137 men, 12 women; median age, 65 years; age range, 44–84 years) diagnosed as having SVC syndrome. A single stent was suf-ficient to restore vessel patency in 102 patients, two stents in 36, three stents in 10, and four stents in one. Survival data were calculated using Kaplan-Meier curves and multivariate anal-ysis using the Cox regression method.
RESULTS. Complete resolution of symptoms was achieved in 123 patients within 72 hours, partial resolution in 22 patients, and no response in only four patients. At follow-up, 30 complications were noted: 16 obstructions, four cases of thrombosis, one partial stent mi-gration to the right atrium, two cases of incorrect stent placement, six stent “shortenings,” and one case in which stent expansion was insufficient. All complications except two were successfully resolved by repeat stenting or by angioplasty. The median symptom-free sur-vival was 6 months (range, 2 days–43 months). As of June 2008, eight patients were alive with patent stents.
CONCLUSION. The Wallstent vascular endoprosthesis is an effective initial treatment in patients with SVC syndrome of neoplastic origin: Morbidity and complications are mini-mal, and clinical relief of symptoms is very rapid. Because the clinical decision for subse-quent elective chemotherapy or radiation therapy is not prejudiced, stenting is a very effective initial step in the overall palliative treatment of patients with SVC syndrome.
Lanciego et al. Endovascular Stenting to Manage SVC Syndrome
Vascular and Interventional RadiologyOriginal Research
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first-line therapeutic measure in all patients with SVC syndrome because stenting does not interfere with subsequent antitumor treat-ments. Also, the stent provides urgent relief of symptoms [15–17], the response is imme-diate and spectacular, and symptoms are al-leviated within 24–72 hours after placement. Further, if chemotherapy, RT, or both are the first-choice treatment of symptom relief, the protracted waiting time of 3–4 weeks to as-sess treatment effectiveness is eliminated.
We report our 15-year experience with the Wallstent endoprosthesis (Boston Scientif-ic) in the palliative management of SVC syn-drome of malignant origin. The database was prospective and undertaken jointly with the oncology departments at our institution and two other hospitals that work closely with our referral center unit. The objective of the data-base is to make stent placement available as an alternative to chemotherapy, RT, or surgery as the initial approach for the palliative relief of symptoms caused by SVC syndrome.
Subjects and MethodsAll procedures used in the study were in accord
with good clinical practice and were approved by our hospital’s clinical review board.
Between January 1993 and June 2008, 208 stents were implanted for the treatment of 149 cancer patients with SVC syndrome. The study group included 137 men and 12 women, all of whom had a clinical diagnosis of SVC syndrome confirmed by phlebocavography; the median age was 65 years (range, 44–84 years). The causes of SVC syndrome were mainly lung cancer: SCLC, also known as “oat cell carcinoma,” in 49 patients and NSCLC (epidermoid lung carcinoma or ade-nocarcinoma) in 78 patients. Mediastinal adenop-athy resulted from different tumors in 19 other pa-tients: sarcoma of the uterus in one, breast cancer in eight, esophageal carcinoma in one, larynx car-cinoma in two, cervical carcinoma in four, renal carcinoma in two, and carcinoma of the penis in one. There was one case of mesothelioma and two cases of double tumor (laryngeal and NSCLC) presenting together. The degree to which large thoracic veins were involved was highly variable; according to the classification of Stanford et al. [18], types I, II, III, and IV were noted in 14, 60, 41, and 34 cases, respectively.
Stent Placement TechniqueThe Wallstent insertion technique is well es-
tablished and well described in the literature. We highlight only the slight modifications to the tech-nique that we have introduced. We used a 9-French introducer (Super Arrow-Flex set, Arrow Interna-
tional) for the vein selected for the route of stent insertion. A hydrophilic 0.035-inch guidewire (Ra-diofocus, Terumo) was inserted and passed through the stenosis. We then used a 5-French catheter (Multipurpose catheter, AngioDynamics) followed by an Amplatz-type rigid guide (Amplatz-Super stiff, Boston Scientific) for the final placement of the Wallstent. No antibiotics were administered. Heparin was administered IV during the procedure as a single bolus of between 3,000 and 5,000 IU. After the deployment of the stent, the angiographic end point of success was when the vessel steno-sis was resolved; this change was accompanied, in most cases, by an evident decrease in the collateral venous network (Fig. 1).
Only 14 cases required balloon dilatation (Pow-erflex, Cordis) before stent placement and 43 cases
required dilatation after stent placement when the initially placed stent did not achieve a widening of > 50% of the vessel’s original diameter.
Wallstents were used in all cases and varied in length (3–8 cm) and diameter (10–16 mm). The most commonly used Wallstent was 6 cm × 14–16 mm (nominal length and diameter, respective-ly). For 75 prostheses, the easy system method of release was used and the uni system was used for the other 71 stents. Three prostheses initially designed for biliary use (shorter with a narrow-er bore) were inserted to treat complications that arose in two patients.
In 102 cases, only one stent was necessary to re-solve SVC syndrome, whereas 36 patients needed two stents, 10 needed three stents, and one patient needed four.
C
Fig. 1—68-year-old man with small cell carcinoma and severe stenosis of superior vena cava (SVC) with marked development of collateral veins. Patient had one Wallstent endoprosthesis (Boston Scientific) implanted in right innominate vein and SVC.A, Superior venacavogram shows stenosis of SVC and collateral network of veins that have developed in neck and via hemiazygos vein.B, Image shows placement of Wallstent (diameter, 16 mm; length, 6 cm). Scale: mm. C, Image shows use of angioplasty balloon to help achieve greater initial expansion of stent. Scale: mm. D, Final superior venacavogram obtained after right unilateral stent placement shows collateral venous network is no longer present and good angiographic results.
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Endovascular Stenting to Manage SVC Syndrome
Of the 208 stents inserted in our series of pa-tients, 182 were first-time placements and the re-maining 26 (nine immediate and 25 in follow-up) were second coaxial stents inserted to treat unex-pected complications.
All patients had an obstruction of > 75% of the vessel’s lumen; a significant network of collater-al veins was present in 135 of the 149 patients (91%). To ensure proper measurement and evalu-ation of the degree and extent of the stenosis as well as of the response after implantation, digi-tal subtraction equipment with associated mea-surement software was installed (Digitron 3D, Siemens Healthcare) for use in most but not all cases. Because this system was automated and computerized, routine pressure readings were not considered necessary.
Each patient gave informed consent before the procedure. In all cases the procedures were per-formed with the patient under local anesthesia without any sedatives. Blood pressure, ECG, and oxygen saturation were continuously monitored. Double venous access was achieved using the ba-silic vein for both phlebocavography and stent in-sertion. Access via the common femoral vein was needed in two cases. We were unable to recanalize the SVC in the course of the manipulations via the basilic vein at the level of the elbow flexure; in-stead, the femoral vein was used quite successfully using the “through-and-through” technique. This commonly used technique involves using a guide-wire that confers a degree of external rigidity to the vein to enable the stent, or the balloon in angio-plasty, to be introduced and to proceed through and beyond the stenosis. In the first few cases (n = 12) between 1993 and 1994, the stents were placed bi-laterally in the right and left brachiocephalic veins and involving the SVC. From 1995 onward, single stents were placed in the SVC and right innomi-nate vein or the SVC and left innominate vein ir-respective of whether the contra lateral venous axis was affected.
Table 1 summarizes the locations of stenoses, clinical data of the patients with respect to the number of stents and stent positioning, the cause of SVC syndrome, whether additional coadjuvant therapies were used, and the effectiveness of treat-ment in terms of patient survival.
Of the 43 patients who received treatment be-fore stenting, 24 had received chemotherapy, four, mediastinal RT; nine, chemotherapy and RT; and six, surgery for treatment of the neoplasia but not for SVC syndrome. The remaining 106 patients had not received any antitumor treatment to alle-viate SVC syndrome before stenting.
After the endovascular stenting procedure, all patients received their scheduled treatment of chemotherapy or RT or of palliative care alone for symptom relief.
TABLE 1: Characteristics of 149 Cancer Patients With Superior Vena Cava (SVC) Syndrome
Characteristic ValueSex (no. of patients)
F 12M 137
Age (y)Median 65Range 44–84
Cause of SVC syndrome (no. of patients)NSCLC 78SCLC 49Mediastinal adenopathy (no. of patients)
Double tumor (laryngeal and NSCLC) 2Other tumors 19Mesothelioma 1
Stanford classificationa (no. of patients)Type I 14Type II 60Type III 41Type IV 34
Stenosis location (no. of patients)SVC 72SVC and right innominate vein 15SVC and left innominate vein 13SVC and right and left innominate veins 49
Treatment before stent placement (no. of patients)None 106RT 4Chemotherapy 24Chemotherapy and RT 9Surgery 6
Treatment after stent placement (no. of patients)None 62RT 11Chemotherapy 44Chemotherapy and RT 32
Anticoagulant therapy (no. of patients)None 6Anticoagulation with coumarin derivatives 15Antiaggregation 146
Type of Wallstent endoprosthesisb (no. of patients)Easy 75Uni 71Others 3
No. of stents per patient (no. of patients)1 1022 363 104 1
Note—RT = radiation therapy, NSCLC = non–small cell lung carcinoma, SCLC = small cell lung carcinoma. aThe classification of SVC syndrome proposed by Stanford et al. [18] is as follows: type I, up to 90% SVC stenosis with patency of the azygos vein; type II, more than 90% SVC stenosis with a patent azygos vein flowing into the right atrium; type III, more than 90% SVC stenosis with reversal of azygos blood flow; and type IV, complete obstruction of the SVC and one or more of the major caval tributaries.
bBoston Scientific.
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Follow-Up and Evaluation of Symptom ResponsePatients underwent follow-up in the medical
oncology department of our hospital, the mem-bers of which were not involved in stent place-ment, thereby ensuring objectivity of assessment. Pulmonary insufficiency and severe cardiac or co-agulation abnormalities were considered the only contraindications.
All but six of the patients received anticoagulant treatment. Immediately after the procedure, the pa-tients were placed on a continuous infusion of hep-arin at full dosage for 1 week. Over the next 4–6 months, they received oral anticoagulant agents in the form of coumarin derivatives at weight-ad-justed doses to keep the international normalized ratio above 2; here, we refer to this treatment as the “classical treatment.” For patient safety and comfort this regimen was changed after the 15th patient to a modern oral antiaggregant treatment, which we describe here as the “current treatment,” with dipyridamole in place of the coumarin-type oral anticoagulants. Only five patients were main-tained in this second phase with the older “clas-sical” oral anticoagulant therapy schedule because of concomitant pathologies and the advisability of continuing with coumarin. They had been on cou-marin-type anticoagulants for protracted periods because of cardiac valve replacement.
Over the first 48- to 72-hour period after stent implantation, simple anteroposterior and later-al radiographs of the thorax were obtained to en-sure that the prosthesis was correctly positioned and had fully expanded. Another radiography ex-amination was performed for the same purpose on the seventh day after implantation. Usually phle-bocavography was not necessary during follow-up, but it was performed if signs and symptoms of SVC syndrome recurrence were detected because of possible reobstruction.
Vena cava patency was evaluated by monitoring symptom response. Five signs and symptoms were assessed: dyspnea; cervicofacial edema and ede-ma of the upper limbs; superficial–subcutaneous collateral venous network; jugular engorgement; and headache. Because most of these symptoms except jugular engorgement are either subjective (dyspnea and headache) or nonquantifiable or ob-jectively measurable signs (edema and collateral venous network), a simple scale or points score was devised to measure response: 0, no response; 1, partial response (incomplete disappearance of the sign or symptom); or 2, complete response (disappearance of the sign or symptom).
Not all of the patients had all five signs and symptoms. Some had only four or even three; the most variable were dyspnea and headache. Howev-er, evaluation of response to stenting was scored as the number of original symptoms that resolved af-
ter the procedure—for example, five of the original five symptoms present, four of four, and so on.
Response was assessed at intervals of 1, 2, 12, and 24 hours and up to 2–7 days after the proce-dure. During the first 7 days after stent placement, medications such as diuretics or corticosteroids were neither required nor administered as prophy-laxis; thus, the patients’ observed responses could not have been influenced by those drugs.
Statistical AnalysisDescription of the data were with means, SDs,
ranges, and percentages. The Kaplan-Meier meth-od and log-rank test were used to calculate and compare survival curves of groups as a function of the values of the following variables: patient sex, patient age, stenosis location, main complications such as thrombosis and obstruction, anticoagu-lant therapy, treatment before and after stenting, tumor type, other complications such as occlu-sion of the stent caused by tumor growth to cover the stent’s mesh, complications immediately after stenting such as stent shortening or partial migra-tion, number of stents per patient, type of Wall-stent, and type of angiography for SVC syndrome classification according to Stanford et al. [18]. A probability value of p < 0.05 was considered sig-nificant. Further, the association between survival and each of these variables was studied using the adjusted multivariate model of proportional risks (Cox’s regression) to calculate the adjusted hazard ratio and 95% CI.
The proportionality-of-hazards assumption was checked using diagnostic plots based on Schoen-feld residuals plots against time for each covari-able and using the comparisons of survival curves versus time between the groups formed as a func-tion of the values of the covariables. In the final model, we retrieved all the variables with statisti-cally significant coefficients and those that were not significant whose removal from the model pro-voked a clinically relevant change in the coeffi-cients of the variables that were significant. Anal-yses were performed with SPSS software (version 11.0, SPSS) for Microsoft Windows.
ResultsStent placement was successful in all pa-
tients. Clinical success was evident in 123 patients who showed partial disappearance of symptoms within 24 hours of the procedure and complete disappearance within 72 hours. Partial response (i.e., persistence of one or more signs or symptoms) was seen in 22 pa-tients and no resolution of signs and symp-toms caused by SVC syndrome in only four patients; however, even in the latter group of patients, at least one symptom improved.
After the procedure, 87 patients continued to receive scheduled antitumor treatment: 44 received chemotherapy; 11, mediastinal RT; and 32, RT and chemotherapy. The most used chemotherapy regimes were cisplatin plus etoposide and regimes based on anthra-cyclines. The radiation dose ranged between 4,000 and 5,000 Gy. The remaining 62 pa-tients received only support or maintenance for symptom relief.
All patients were regularly monitored. After the intervention, the survival time averaged 6 months (range, 2 days–43 months) and all patients had improvement in at least one of their symptoms before stenting. Of the study group patients, 134 died as a result of the natu-ral history of the neoplasia, whereas eight were alive as of June 2008, still with their neoplasia but with clinical resolution of their SVC syn-drome symptoms as a result of continued pat-ency of the stents or, possibly, as a result of spontaneous increase in collateral blood flow. Seven patients were lost to follow-up.
Of the patients who died, three still had clinical evidence of SVC syndrome at the time of death, which was probably due to ob-struction of the stent. However, obstruction was not confirmed by radiologic imaging be-cause of the patient’s status before death.
The patients who were still alive as of June 2008 (n = 8) represent a median sur-vival time of 10.6 months (range, 15 days–36 months). Of the seven patients lost to follow-up, all had a good response to stenting up to the time of loss to follow-up (three in the third month and four in the sixth month after the procedure) and were without clinical evi-dence of SVC syndrome recurrence.
Symptom response was evaluated by clin-ical and nursing staff of the medical oncol-ogy department. The main findings were complete response in almost 80% and partial response in approximately 15% of patients with respect to jugular engorgement and col-lateral circulation within the first 72 hours af-ter stenting. Headache resolved completely in 70% of patients and partially in 30% within the first 24–48 hours after stent placement. Cervicofacial edema and edema of the up-per limbs, which affected 100% of the pa-tients, were the symptoms that responded best to the procedure. In all patients, those symptoms disappeared within 48–72 hours after implantation of the prosthesis. Dyspnea was the symptom that was most resistant and resolved completely in only 45% of patients, whereas partial remission was achieved in 60% of the patients.
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During follow-up of the 149 patients (Fig. 2), only 20 obstructions of the endoprostheses (16 complete or partial stent occlusions and four episodes of stent thrombosis) were de-tected. These data yield a primary patency of 86.6%. The stent in one patient partially mi-grated to the right atrium but did not result in any clinical consequences. In four patients, the stent was positioned poorly during place-ment, one with an excessive angle, and there were four episodes of shortening of the pros-thesis, two of which occurred in the same pa-tient. In another patient, the initial expansion of the stent was inadequate and did not re-solve until 2 months later.
All complications except two were re-solved by a second intervention (primary as-sisted patency = 93.3%). The cases of partial obstruction due to thrombosis (n = 2) were resolved by thrombolysis and balloon dila-tation. In another two patients, the throm-bosis was massive and poor clinical status precluded new repeat interventions; both pa-tients died over the next few days with flor-id SVC syndrome. Regarding the 16 cases of invasion of the stent or mesh by the tumor, 12 were complete and four were partial. All resolved with placement of a second coaxi-al prosthesis (Fig. 3). The six cases in which the stents were shortened or poorly posi-tioned were also easily relieved with coaxial prostheses. Table 2 summarizes these data.
Figure 4 summarizes the overall survival of the patients and the censored pattern. The median survival was 6 months after stenting (range, 2 days–43 months) during which the patients remained symptom-free. The natu-ral history of the neoplasia was responsible for the deaths of 134 patients, whereas eight were alive with patent stents as of June 2008, albeit with their disease.
The median survival was 7, 5, and 4 months, respectively, in patients with SCLC, NSCLC, and metastatic adenopathies (over-all, p = 0.0436). Subgroup comparisons in-
A
Fig. 2—65-year-old man with non–small cell lung carcinoma already treated on previous occasions (4 and 2 months earlier) with stents to resolve superior vena cava (SVC) syndrome. SVC syndrome recurred, probably from malfunction of prostheses. Scale: xxx. A, Superior venacavogram before de novo endovascular treatment show complete blockage of previous stents with incipient development of collateral venous network from azygos vein. B, Venacavogram obtained after placement of third vascular endoprosthesis shows Wallstent endoprosthesis (Boston Scientific) (diameter, 14 mm; length, 6 cm) implanted coaxially. Note immediate restoration of venous inflow and decrease in venous network.
B
C
Fig. 3—66-year-old man with occlusion of superior vena cava (SVC) due to non–small cell lung carcinoma. Although SVC occlusion was initially managed successfully for 6 months with stent placement, patient was readmitted because of reappearance of SVC syndrome.A, Superior venacavogram shows stenosis of vena cava due to partial obstruction of stent resulting from invasion by tumor (circle). Arrows indicate considerable collateral circulation.B, Image shows balloon angioplasty to reopen obstructed area. C, Image shows second coaxial Wallstent alongside first prosthesis. Scale: mm.D, Venacavogram after placement of second Wallstent. Note vessel reopening and resolution of vena cava stenosis.
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dicated significant differences only between the patients with adenopathies and those with NSCLC (p = 0.0076). In the patients with bi-lateral innominate venous stenosis (Fig. 5) or stenosis in both venous axes, the median sur-vival was 3.1 months, whereas in the patients with unilateral involvement, the median sur-vival reached 6 months (p = 0.0001).
The type of treatment administered before stenting was also a factor that significantly affected survival: The median survival was 2 months in patients who had undergone RT or surgery before stenting, 4 months in pa-tients who had undergone chemotherapy be-fore stenting, 5 months in those who had re-ceived chemotherapy and RT before stenting, and 6 months in those who did not receive any treatment before stenting. The log-rank test was significant (p = 0.0045), and the dif-ferences centered on the group who did not undergo treatment before stenting compared with the group who underwent chemothera-py (p = 0.0271) and on the group who did not undergo treatment compared with those who underwent surgery (p = 0.0008).
Treatment after stenting also significant-ly influenced survival. The median survival was 4 months for the patients who did not receive treatment after stenting or who un-derwent only RT after stent placement com-pared with 6 months for those who under-went chemotherapy and 7 months for those who underwent chemotherapy and RT. The overall difference in the survival curves was statistically significant (p = 0.0002).
In the 2 × 2 comparisons, statistical sig-nificance was reached between patients who did not receive treatment after stenting and those who underwent chemotherapy alone after stenting (p = 0.042) and those who un-derwent chemotherapy and RT after stent-ing (p = 0.0002). Statistical significance was also reached between patients who under-went RT alone after stenting and those who received chemotherapy alone after stenting (p = 0.0199) and those who underwent RT and chemotherapy after stenting (p = 0.0006). In patients in whom the stent became throm-bosed, survival was shortened to a median of 2 months compared with the group without thrombosis (p = 0.0331).
In the univariate analysis, no significant differences in survival were observed from the rest of the variables studied including patient sex; patient age; type of antithrom-botic treatment; complications, such as oc-clusions of the stent due to tumor growth across the stent mesh; immediate complica-
tions, such as stent shortening or partial mi-gration; number of stents used per patient; type of Wallstent; and type of angiography used to determine the Stanford classification of SVC syndrome.
In the multivariate analysis using the ad-justed model of proportional risk (Cox’s re-gression), the analysis of the Schoenfeld re-siduals plot versus time for each of the covariables and an examination of the cumu-lative survival curves led to the conclusion that the assumption of proportional hazards was not sustainable in the case of the covari-ate “type of tumor” (Table 3); as a conse-quence, tumor type was used as a stratifica-
tion factor, and a set of pooled coefficients was computed for the other covariates. Table 3 also contains the hazard ratios and 95% CIs of the variables that, with the indicated crite-ria in the Subjects and Methods section, were finally included in the model. As can be seen, the significant prejudicial effect was con-served with respect to survival time as was observed in the univariate analysis with re-spect to bilateral localization of the stenosis, stent thrombosis, and chemotherapy and sur-gery before stenting (in both cases compared with the no-previous-treatment group).
Treatment after stenting with RT and che-motherapy increased survival significantly
TABLE 2: Summary of Outcomes
Outcome Value
Symptom response (no. of patients)
Total 123
Partial 22
No response 4
Status (no. of patients)
Dead 134
Alive 8
Lost to follow-up 7
Symptom-free survival
Median (mo)
Patients who died 6
Patients who were alive as of June 2008 10.6
Range
Patients who died 2 d–43 mo
Patients who were alive as of June 2008 15 d–43 mo
PTA (no. of patients)
Before stent placement 14
After stent placement 43
Complications (no. of cases)
Stent occlusion 16
Partiala 4
Completea 12
Stent thrombosis 4
Treated with PTA and lysis 2
No treatment 2
Shorteninga 4
Migrationa 1
Incorrect positioninga 4
Insufficient expansiona 1
Stent patency (%)
Primary 86.6
Secondary 93.3
Note—PTA = percutaneous transluminal angioplasty.aResolved after placement of second coaxial prosthesis.
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relative to the group who did not receive treat-ment after stenting, as indicated by the Kaplan-Meier analysis. Statistically signifi-cant effects that were not detected by Kaplan-Meier analysis were also observed, such as the case of previous RT with an increase in the risk compared with no previous therapy and, in the case of males, a greater risk than the females. The effect of chemotherapy after stenting that was detected in the univariate analysis did not appear in the Cox model analysis. Similarly, the effects of patient age and the presence of stent obstruction contin-ued being nonsignificant. Other factors not
retained in the final model were immediate complications such as shortenings type, par-tial migration, number of stents per patient, type of Wallstent, and type of angiography used to determine the Stanford type classifi-cation of SVC syndrome.
DiscussionVena cava syndrome generally occurs be-
cause the vein is being compressed by adja-cent tumor masses. It is less frequent for a tu-mor to invade the vena cava, although this can occur at advanced stages of the disease [19]. Vena cava syndrome is a highly stress-
ful additional complication for patients whose life expectancy is already severely curtailed.
Lung cancer is the most frequent cause of vena cava syndrome and is responsible for more than 70% of the cases. RT and che-motherapy are the standard forms of treat-ment, and the combination of the two recent-ly was proposed. Symptom improvement of 75–90% has been observed by some investi-gators, whereas others have obtained results that are less hopeful (46% success with RT for NSCLC and 62–80% success with che-motherapy for SCLC) [6, 7]. Conventional therapies take between 2 and 4 weeks to be-gin to show any degree of effectiveness [3, 7, 15]. Further, vena cava syndrome recurs in 20–50% of patients, and at that stage of dis-ease, only symptom treatment is possible.
Some investigators propose more aggressive RT (8 Gy three times a week for 3 weeks) and have achieved responses of up to 90% [20]. However, one needs to account for the many complications of high-dose RT. These com-plications include tumor necrosis with con-comitant fever and bleeding and perforation of the SVC. Other debilitating effects include nausea, vomiting, anorexia, skin irritation,
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Fig. 4—Kaplan-Meier curves.A, Stent patency.B, Patient survival.C, Survival of patients who underwent coadjuvant therapies after stenting. RT = radiation therapy.D, Survival according to tumor type. NSCLC = non–small cell lung carcinoma, SCLC = small cell lung carcinoma.E, Survival of patients who underwent coadjuvant therapies before stenting. RT = radiation therapy.
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and esophagitis. These negative effects on the quality of life for a patient whose life expectan-cy is only on the order of approximately 6 months may be considered unacceptable and counterproductive. Also, RT can induce fibrotic changes that further constrict the vessels. A sec-ondary effect of radiation fibrosis is that collat-erals do not develop in this scarred tissue [21]. This is not surprising because RT cannot easily discriminate between tumor and adjacent nor-mal tissue [15].
The deployment of endovascular stents emerged during the early 1990s as a promis-ing new therapy [22–29]. Although there do not appear to be doubts regarding the ben-efits that these endovascular prostheses of-fer patients in terms of symptom relief, de-bate continues as to whether the stent should be used as the initial treatment of choice—
that is, before implementing RT or chemo-therapy. Also being debated is if a stent is an option only when obstruction recurs or if it can be used subsequent to the failure of RT and chemotherapy. There are two opposing views, each acquiring more adherents. Be-ginning earlier this decade, several authors of case series advocated stents as the initial treatment of SVC syndrome [16, 17, 30, 31]. Systematic reviews of the results of the dif-ferent therapeutic options of SVC syndrome related to lung cancer have reported a high-er effectiveness for stenting compared with chemotherapy, RT, or steroid treatment [32]. However, the classic views of other investi-gators persist [33, 34]. The recommenda-tions are for initial insertion of stents for symptomatic SVC syndrome in NSCLC, but stent insertion is not recommended initially
in symptomatic SVC syndrome caused by other malignancies such as SCLC and meta-static adenopathies of other tumors. More re-strictively [34], stenting has been used only to alleviate urgent symptoms and in more an-ecdotal cases such as mesothelioma.
Over a period of 15 years, we implanted 208 stents in 149 cancer patients. Our results in terms of technical and clinical success are en-couraging. Immediate and late complications were minimal and were easily resolved with re-peat stenting (primary stent patency = 86.6%, primary assisted patency = 93.3%). These out-comes are similar to those of other published series. Patient survival after stenting is cur-rently approximately 6 months, as observed in other published studies [15–17, 30–36]. Curi-ously, median life expectancy among patients with obstruction of the SVC is approximately 6 months, but estimates vary widely depend-ing on the underlying malignant condition and this figure does not appear to differ significant-ly from survival among patients with the same tumor type and disease stage but who do not have obstruction of the SVC [34].
The innovative approach of our study was to collect and analyze the results of an ex-tended series of patients with malignant SVC syndrome who had a stent inserted indepen-dent of whether they had received prior treat-ment and who had completed long-term fol-low-up in which other factors that could have had a confounding effect on the outcomes (e.g., the use of a stent as the first-choice therapeutic tool) were collected.
Deployment of a stent as the first step nei-ther influenced the decision of the oncologist to continue with the scheduled coadjuvant therapies (chemotherapy, RT, or chemother-apy and RT) nor affected the survival rate. Other factors such as bilateral involvement of the innominate veins and the SVC, male sex, certain tumor types, and having under-gone surgery, chemotherapy, or RT before stenting do appear to negatively impact sur-vival, whereas RT and chemotherapy treat-ment after stenting decreases the mortali-ty hazard and is the only factor that had a significant positive effect on survival in our study. However, these findings could be as-sociated more with the advanced stage of the disease and, thus, the poorer prognosis than with the stent treatment per se.
The innovative approach of stenting de novo appeared for the first time in an article in 1997 by Nicholson et al. [15]. Those inves-tigators compared the results obtained in 76 SVC syndrome patients treated with stents
C
Fig. 5—57-year-old man with type IV obstruction (Stanford classification) of superior vena cava (SVC) caused by metastatic adenopathies from laryngeal carcinoma.A–D, Despite patient’s preterminal clinical status (patient died 1.5 months after these images were obtained) and with difficult approach because SVC could be visualized only with difficulty, there was intent to open one of brachiocephalic trunk veins. Procedure was successful, and although aperture of stent was small, symptoms were effectively alleviated. Scale in C and D is mm.
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(with or without associated RT) versus those in 25 retrospective cases treated only with RT. They concluded that stenting provided faster relief of symptoms and resulted in sig-nificantly greater improvement in the SVC obstruction score than RT (p < 0.001).
The option of conducting randomized pro-spective comparative studies is very limited. To our knowledge, only two small retrospec-tive studies [15, 35] in which the use of endo-vascular stents was compared with RT have been reported. We agree with Dyet et al. [24] and Irving et al. [11] who concluded that this procedure incurs a very marginal increase in the overall cost of management of these can-cer patients.
With respect to other technical issues, we believe (and our view is supported by many other authors) that it is necessary to open only one venous axis to insert the stent for SVC syndrome to be completely reversed. As we proposed since the third year of our commit-ment to the use of stents in 1992, we observed
that inserting stents bilaterally is not neces-sary. We are in complete agreement with Din-kel et al. [36] and with others [15, 16, 31] that unilateral placement is preferable in patients with SVC syndrome because it was as clin-ically effective as bilateral placement while offering lower cost, easier placement, and low rates of complications and recurrence.
Anticoagulation therapy is often prescribed for patients with SVC syndrome after stent-ing, although its effectiveness has never been clearly proven. The stent is highly thrombo-genic in the first month until neoendothelium covers the endovascular surfaces. We believe that anticoagulation therapy is mandatory es-pecially during the period immediately after stent placement. We and other investigators [16, 37, 38] use only oral antiplatelet thera-py (aspirin, ticlopidine, or similar) for main-tenance after complete heparinization for the first 3 or 4 days after stent placement. Our re-sults indicated that this more modern therapy does not significantly differ from the classi-
cal therapy we had used in 15 of our early pa-tients. The question of the appropriate anti-thrombotic preventive strategy remains to be resolved as well.
In conclusion, our experience over more than 15 years has shown the effectiveness of vascular stenting in the management of SVC syndrome in cancer patients. Palliation of symptoms, together with more general im-provement of quality of life, is the major goal in the overall management of lung cancer pa-tients experiencing a highly stressful addition-al complication such as SVC syndrome. The syndrome requires effective fast-acting treat-ment, and percutaneous implantation of vascu-lar endoprostheses is fully justified in patients with a terminal illness irrespective of their life expectancy because of the rapid disappearance of clinical symptoms. The Wallstent endopros-thesis can be rapidly and safely introduced and, above all, does not interfere in any way with subsequent scheduled neoadjuvant oncol-ogy treatment. We believe that stenting should be considered the first treatment option for pa-tients with this clinical condition.
AcknowledgmentsWe thank the nursing and auxiliary staff of
the interventional radiology unit and oncolo-gy departments of the three hospitals involved in this study. Without their constant help and dedication to patient care over a protracted pe-riod, this report would not have been possible. Editorial assistance was provided by Peter R. Turner of t-SciMed (Reus, Spain).
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