Relationship between lymphoscintigraphy and clinical findings in lower limb lymphedema (LO): toward a comprehensive staging.

Although radionuclide lymphoscintigraphy (RNL) is widely used diagnostically for patients with lymphedema (LE), it has not been utilized for LE staging, which is still based upon clinical findings. The aim of this work is to establish whether the results of both conventional RNL and fusion imaging obtained from hybrid detectors may be used for a comprehensive clinicoimaging staging in LE. Radiolabeled nanocolloids (0.2 ml) were subcutaneously injected in 4,328 patients (23-78 years) with clinical lower limb LE and without venous disease. Patients were classified according to the ISL classification and had a minimal follow-up of 2 years. Images were taken 60 minutes after the injection as a whole body scanning and fusion images of functional SPET and anatomical CT. Clinical and RNL results were not in accordance, and a specific RNL staging was established. The association of clinical and functional staging yields a new method to grade LE patients, and this staging correlated with treatment efficacy. RNL is an important tool in lymphology, and its association with the clinical evaluation offers a new grading system which may be able to delineate patients with good prognosis, patients at risk for a complex decongestive physiotherapy (CDP) failure, and patients who may benefit from other therapeutic protocols.

[Pain and bone metastases]. / Douleur et métastases osseuses.

Average 20% of the cancer patients will have bone metastasis most of time painful and with variable clinical expressions. Due to animal models, the bone metastasis pain is better known and it explains the different treatments mechanisms. After a suitable evaluation of the pain, several therapeutic approaches can be suggested. In addition to the classical analgesics, several medications are known to be efficient in few indications like neuropathic pain. Besides a local surgery, an external radiotherapy or an interventional radiology treatment can often be useful along with a medical treatment. When there is a bone progression, the anti-cancer treatment by chemotherapy, hormonotherapy or targeted therapies must always be reviewed, because if efficient it could have an analgesic action.

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies.

PURPOSE: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography.

BACKGROUND: To study the longitudinal variations of plasma B-type natriuretic peptide (BNP) with reference to left ventricular ejection fraction (LVEF) during and after chemotherapy with cardiotoxic drugs. PATIENTS AND METHODS: We prospectively measured plasma BNP using an immunoradiometric assay in 12 anthracycline-treated breast cancer patients monitored for a mean time of 880+/-293 days (pilot group). Prior to each cycle and throughout the following year, LVEF and cardiac output were measured by radionuclide ventriculography. Anthracycline pharmacokinetics was studied during the first cycle. Relationships between serial observations were analysed with the general linear mixed effects model. Identical methods were subsequently applied to a test group of 67 anthracycline or trastuzumab-treated patients. RESULTS: Five out of 70 (6.33%) patients developed anthracycline-induced heart failure. BNP concentrations were found to be positively correlated to anthracycline cumulative dose and negatively to LVEF values. Variables entering the mixed models were cumulative anthracycline dose, time and cardiac output. CONCLUSION: An infra-clinical cardiotoxicity of anthracyclines as defined by BNP elevation is frequent but reversible. Patients who developed heart failure showed a continuous BNP increase and concentrations over 100 ng/ml.

Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells.

BACKGROUND: The sequence of the beta-subunit of human chorionic gonadotropin (hCGß) varies depending on whether hCGß is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGß can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGß encoded by type II genes (type II hCGß). METHODS: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGß dosing immunoassays and sequencing of CGB genes were performed. RESULTS: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGß derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGß. Placenta immunohistochemical studies confirmed that type II hCGß expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGß in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. CONCLUSION: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases.

One hundred and fourteen patients with painful bone metastases participated in this randomised, dose-controlled study of the efficacy and safety of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP), a systemically administered radiopharmaceutical. Fifty-five patients received single doses of 0.5 mCi/kg and 59 patients received single doses of 1.0 mCi/kg. Treatment with 153-Sm-EDTMP produced improvement from baseline in all patient-rated efficacy assessments, including degree of pain, level of daytime discomfort, quality of sleep and pain relief. During the first 4 weeks after dose administration, when the patients evaluated efficacy daily, there were statistically significant changes from baseline with the 1.0 mCi/kg dose but not with the 0.5 mCi/kg dose. The difference between doses in visual analogue pain scores was statistically significant at week 4 (P = 0.0476). Among subsets of patients examined, female patients with breast cancer receiving 1.0 mCi/kg had the most noticeable improvement. The physicians judged that approximately half of the patients in each dose group were experiencing some degree of pain relief by week 2. This value increased to 55% for the 0.5 mCi/kg group and 70% for the 1.0 mCi/kg group at week 4. More patients in the higher dose group (54%) than in the lower dose group (44%) completed the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with 153Sm-EDTMP treatment. Values for platelets and WBCs reached nadirs at 3 or 4 weeks with both doses and recovered by 8 weeks. Even at their lowest point, the values were generally higher than those associated with infectious or haemorrhagic complications. Myelotoxicity was no greater in female patients than in male patients. Long-term follow-up revealed longer survival among breast cancer patients who had received the higher dose than among those who had received the lower dose. The results suggest that the 1.0 mCi/kg dose of 153Sm-EDTMP is safe and effective for the treatment of painful bone metastases.

Prognostic factors in acquired aplastic anemia. A study of 352 cases.

The prognostic factors of short- and long-term survival have been studied in 352 patients with aplastic anemia of all grades of severity. This group was homogeneous with regard to the clinical and laboratory survey, and the treatment used [high-dose androgen therapy]. The "hierarchy" of the individual prognostic parameters has been established: current severe infection, granulocyte count, percentage of the nonmyeloid cells on the bone marrow slides, platelet count, reticulocyte count, 59Fe utilization, and stromal disorganization on the bone marrow biopsy specimen. As these parameters are interrelated, a multiparametric analysis enables us to define groups of patients with different short-term evolution and to derive a prognostic index from these data. The use of such an index, however, allows a correct prediction in only 73 per cent of the cases, better in the milder than in the more severe cases. It is possible that the short-term evolutive tendency (improvement or worsening during the first six weeks of therapy) may contribute supplementary information useful for prognosis and the choice of treatment. After the first three months critical period, the mortality rate no longer depends on the initial severity of the disease but exclusively on the clinical and hematologic improvement. Thus, comparing the hematologic data obtained initially and after three months of androgen therapy allows us to correctly predict the long-term evolution.

Significance of bone-marrow scintigraphy in aplastic anemia: concise communication.

Tc-99m colloid and In-111 transferrin were used in a semiquantitative scintigraphic study of bone-marrow activity in 76 patients with aplastic anemia, the majority of which were severe cases. The results are compared with other known prognostic parameters and with a predictive index formulated from a prior multi-parametric analysis performed in 352 cases. In 47 cases parallel abnormality of Tc and In uptakes was noted and was well correlated with other prognostic factors. Indium uptake is apparently a good indicator of the severity of aplasia; extension of active erythroid tissue, demonstrated with this method, is correlated with prognosis. In nine cases, excessive In uptake is explained by dyserythropoiesis associated with granulo- and thrombocytopenia (Fanconi's anemia in most cases). In 20 of our patients, TcSC uptake was excessive compared with that of In and with other prognostic factors. Statistically, this phenomenon carries an unfavorable prognosis but its physiological meaning remains to be defined.

Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

Radioimmunolymphoscintigraphy in the preoperative staging of primary breast cancer.

Thirty-one primary breast cancer patients were evaluated by radioimmunolymphoscintigraphy (RILS) and ex vivo scintigraphy (EVS) following subcutaneous injection of human monoclonal antibody In-111-LiLo-16.88. Lymph nodes (370) were assessed by EVS, pathology and immunohistochemistry. The positive predictive value (EVS) for antigen positive nodes, metastatic and hyperplastic, was 90% in stages O-IIB, and the sensitivity and specificity for all stages were 60% and 80% respectively. Four EVS positive nodes with follicular hyperplasia contained micrometastases. RILS and EVS correlate well by the Spearman Rank test (R=0.87). These results suggest RILS may be clinically useful and selectively limit the extent of the surgical procedure.

Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography.

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomography (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesion. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.

Positron emission tomography detection of breast cancer metastasis to the uterus.

BACKGROUND: We report the case of a patient presenting with moderate elevation of the tumor marker cancer antigen 15.3 during breast cancer follow-up. CASE: After a negative standard metastatic work-up, a positron emission tomography scan identified a localized central pelvic zone of uptake. Hysterectomy was performed, and pathology revealed a breast cancer metastasis within a previously known uterine leiomyoma. Positron emission tomography allowed assessment of soft tissues. CONCLUSION: With high sensitivity and specificity, positron emission tomography can be used to localize breast cancer metastases suspected by the presence of elevated serum tumor marker but not detected on standard metastatic workup.

Serum bFGF (basic fibroblast growth factor) and CA 15.3 in the monitoring of breast cancer patients.

BACKGROUND: Basic fibroblast growth factor (bFGF) is a potent angiogenetic factor which may influence breast cancer evolution. MATERIALS AND METHODS: Serum bFGF, (cut-off 10 pg/ml), was assayed in 166 breast cancer patients at all stages and compared with CA 15.3. RESULTS: In 99 pre-treatment (PT) sera, 39/99 (39.4%) were bFGF positive, 9/99 (9.1%) CA 15.3 positive (> 30 U/ml), and not correlated. No correlations were found between bFGF and age, menopausal status, TNM or pTNM, histology, SBR grading or steroid receptors. A postoperative decline in bFGF positivity, from 30.8 to 7.7% (n = 39), was observed. An abnormal CA 15.3 after primary treatment (n = 2/39) was of bad prognosis (P < 0.0001), whereas positive bFGF (n = 3/39) had no univariate prognostic value (median follow-up 5.5 years). During follow-up, positive bFGF was recorded in 6/92 (6.5%) disease-free patients (DFS), 13/15 (86.7%) regressions, 8/16 (50.0%) stable disease, and 46/67 (68.7%) progressive disease (significant differences between PT or DFS and post recurrence levels (P < 0.001), and between relapse before and after treatment (P = 0.002)). CONCLUSION: Serum bFGF is more often elevated before treatment or after relapse than in DFS, and rises under systemic treatments. Its pattern of variations does not add to CA 15.3 for breast cancer monitoring.

Evaluation by lymphoscintigraphy of the effect of a micronized flavonoid fraction (Daflon 500 mg) in the treatment of upper limb lymphedema.

Upper limb lymphedema after conventional treatment of breast cancer occurs in about 20% of all treated cases, even after conservative therapy. Women with mild to severe upper limb lymphedema expect a decongestive therapy, which usually associates physiotherapy and medical treatment. Upper limb lymphoscintigraphy using rhenium colloids labelled with technetium 99m can be used as a lymphatic functional test in order to evaluate the efficacy of a therapy. We report here the results of a pilot, open study carried out on 10 female patients, age ranging from 44 to 64 years, previously treated for a breast cancer. The average time delay for the occurrence [correction of occurence] of lymphedema was 17 +/- 7 months. All patients received 500 mg twice daily of a micronized flavonoid fraction (Daflon 500 mg) for 6 months. At the end of the study, all patients had a clinical improvement of symptoms and limb volume and the mean decrease in volume of the swollen limb reached 6.80%. Functional parameters (half-life, clearance and lymphatic speed of the colloid) assessed with scintigraphy were significantly improved. These preliminary results suggest that this therapy is effective for the treatment of lymphedemas.

Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer).

To assess the activity of a purified, micronized, flavonoidic fraction (Dios; Daflon 500 mg*) on upper limb lymphedema occurring after breast cancer therapy, a monocenter, randomized, double-blind, parallel group vs placebo (Plac) trial was carried out. One hundred and four women with lymphedema were included; 94 completed the study (46 Dios, 48 Plac). A subset of 24 patients with more severe lymphedema (10 Dios, 14 Plac) was subjected to a separate analysis. Treatment consisting of Dios or Plac was given two tablets daily over a six-month period. A radionuclide lymphoscintigraphy using technetium-99m was performed at inclusion and at the end of the treatment. The upper limb volume was measured every two months. In the overall population the evolution of parameters was not different between Dios and Plac. In the 24 patients with a more severe lymphedema, the lymphoscintigraphic parameters (m +/- sd) were as follows: lymphatic migration speed was significantly improved by Dios in comparison with Plac (delta Speed cm/minute: 0.84 +/- 0.6 vs 0.14 +/- 0.26, P = 0.005). The half-life of the colloidal compound was significantly improved over time in the Dios group (delta half-life = 10.3 +/- 13.07 minute, P = 0.034) but not in the Plac group (delta half-life = 0.53 +/- 15.51 minute, P = 0.086). The change over time of colloidal clearance was close to significance in the Dios group (delta clearance microL/minute: 2.18 +/- 3.10, P = 0.054) but not in the Plac group (0.11 +/- 2.26, P = 0.86). No significant difference was found for evolution of lymphedema volume, despite a tendency in favor of Dios. This can be related to wide distribution of volume values and small numbers of patients. In conclusion, these results suggest a beneficial therapeutic activity of Dios at the usual dose of two tablets/day in patients affected with more severe lymphedema. The clear improvement of the lymphatic speed illustrates its known lymphokinetic activity. Further studies with a higher dosage could confirm the beneficial activity of this drug in secondary lymphedema.

[Treatment of postoperative lymphedema of the upper limb]. / Traitement du lymphoedème séquellaire du membre supérieur.

In breast cancer the overall incidence of post-therapeutic lymphedemas of the arm remains at 20% despite the use of new conservative treatments. Patients suffering from pains and heaviness require additional treatment for their swollen arm. One hundred and seventy-nine women with a post therapeutic edema of the upper limb have been treated in a special medical unit where medical and physiotherapeutic care were given as an intensive treatment for 4 weeks. More than 80% of good results were obtained with a median decrease in volume of swelling of 45%. The duration of the clinical improvement during the 6 months following the intensive first treatment was excellent for 76% of all improved cases. Treatment failure occurred in 16.2% of upper limb swelling mostly in relation to a recurrence of the disease (81%). 84.3% of cases undergoing a second intensive treatment 6 months later displayed a new decrease in volume and a new real clinical improvement. Small post therapeutic lymphedemas must be treated as soon as possible to avoid more serious delayed disorders.

[Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials]. / Réponse des métastases osseuses aux thérapeutiques médicales: définition des critères d'évaluation et essai de classification.

Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

Efficacy of BN165 (Ginkor Fort) in breast cancer related upper limb lymphedema: a preliminary study.

The purpose of this study was to determine whether BN165 (Ginkor Fort), which has been reported to alleviate symptoms of venous insufficiency, has a beneficial effect on lymphatic function or lymphedema symptoms. Using a 3-arm, double-blind, placebo-controlled design in 48 patients with upper extremity lymphedema secondary to breast cancer treatment, improvement in symptoms and signs as well as lymphoscintigraphic kinetic parameters (radiocolloid half-life and lymphatic migration speed) was assessed in response to treatment. A statistically significant effect on limb heaviness was noted. Lymphatic migration speed also demonstrated a significant increase at a dose of 2 active capsules per day but not at the 3 capsules per day dose, but lymphatic migration speed also improved in the placebo group. These findings in mechanical lymphatic insufficiency in breast cancer-related lymphedemas can be compared to the previously published clinical amelioration by BN165 of the subjective symptoms (heavy limbs) of dynamic lymphatic insufficiency in patients with venous insufficiency. Further studies are needed to define the possible role of BN165 in treating patients with lymphedema.