Feasibility of percutaneous radiofrequency ablation for pulmonary malignancies in the hands of the surgeon.

AIM: To assess the feasibility of percutaneous pulmonary radiofrequency ablation (RFA) executed by a single surgeon. MATERIALS AND METHODS: Between 2007 and 2010, 15 procedures were performed in 11 patients during 13 sessions. Sex, age, pulmonary localisation and tumor diameter are discussed. Metastatic lesions as well as pulmonary primitive malignancies were treated. For metastatic lesions, the primitive tumor was considered as completely treated. Surgery was refused because of impaired pulmonary function or due to patient's refusal. All interventions were carried out by a single thoracic surgeon under CT-guidance in the department of radiology. RESULTS: RFA was completed in all patients without perprocedural complications. There was no significant perioperative morbidity. Pneumothorax was the most frequent complication but none of the patients needed thoracic drainage. Hospital stay decreased progressively since the start of this series. Follow-up was complete. Most lesions were stable or diminishing in size. CONCLUSION: These early results show that pulmonary RFA is a safe and feasible technique in the hands of the surgeon. Longer follow-up and larger series will be welcome to confirm the results and position of this procedure which might become an important tool for the surgeon and not only for radiologists.

All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial.

BACKGROUND: This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC). METHODS: Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m(-2) (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m(-2) (750 if >or=65 years of age) twice daily, on days 1-14. Treatment was continued until progression or unacceptable toxicity. RESULTS: A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36-66), including complete response in 4%. The clinical benefit rate (response or stable disease for >or=6 months) was 63% (95% CI, 48-77). The median duration of response was 7.2 months (95% CI, 6.4-10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8-9.7) and median overall survival was 29.2 months (95% CI, 18.2-40.1). Treatment-related adverse events were manageable, the main grade 3-4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed. CONCLUSION: These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MBC.

A phase I-II trial of induction chemotherapy with carboplatin and fluorouracil in locally advanced head and neck squamous cell carcinoma: a report from the UCL-Oncology Group, Belgium.

Eighty-three patients (median age, 56 years and Karnofsky performance status greater than or equal to 70) were treated with carboplatin (Carbo) and fluorouracil (5Fu) for stage III and IV head and neck squamous cell carcinoma (HNSCC). 5Fu (1 g/m2/d) was administered from day 1 to 4 by continuous infusion. Carbo was given on day 1 and, in order to evaluate its maximum-tolerated dose (MTD), the dose level was progressively increased from 250 mg/m2 to 450 mg/m2. The effectiveness of this association and its potential role in local control were also evaluated. Three patients received Carbo at a dose of 250 mg/m2, 13 received 300 mg/m2, one received 330 mg/m2, 12 received 350 mg/m2, six received 375 mg/m2, 26 received 400 mg/m2, 18 received 420 mg/m2, and four received 450 mg/m2. Two (13 of 83) or three courses (64 of 83), repeated every 4 weeks, were administered. The overall (primary tumor and node) response and complete response (CR) rates were 33% and 14%, respectively. For primary tumor, the response rate (RR) was 57% with 32% CR and 18% pathologic complete response (PCR); the RR was higher for patients with oropharyngeal tumor (76%, P = .037) and for patients treated with Carbo greater than or equal to 350 mg/m2 (65%, P = .02); the tumor size (T1 + T2 v T3 + T4) was a good prognostic factor for RR (90% v 46%, P = .001), CR (65% v 20%, P less than .001), and PCR (45% v 8%, P less than .001). For nodes, the RR was 33% with 11% CR. Grade 3-4 neutropenia and thrombocytopenia were experienced by 17% and 28% of the patients treated with 420 mg/m2 of Carbo and by 50% of the patients treated with 450 mg/m2. The MTD can be fixed at 420 mg/m2 and the proposed dose at 400 mg/m2. Thirty-eight patients were treated with surgery plus radiotherapy, 33 with radiotherapy alone, and seven with surgery alone. The median follow-up is 12 months. The 18-month disease-free survival (DFS) is 78% for overall complete responders and 39% for the others (P = .04). There is no primary tumor recurrence among the 12 patients with a primary tumor PCR treated by radiotherapy alone for tumor control (median follow-up, 17.3 months). The association of Carbo-5Fu is a safe induction chemotherapy regimen for HNSCC. The proposed dose of Carbo for future treatment is 400 mg/m2.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical evidence for an engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation.

Seventy autologous peripheral blood stem cell transplants (APBSCT) performed in 61 cancer patients were retrospectively analyzed. Patients were heterogenous with regard to malignancy, conditioning regimens and use of growth factors after transplantation. Six patients developed a non-infectious fever, fluid retention and pulmonary interstitial infiltrates during the early phase of neutrophil recovery. Diarrhea was observed in four of these patients and cutaneous rash in three. The clinical condition improved spontaneously in one patient, and within 48 h after steroid therapy in four. One patient died from multiple organ failure. Age, sex (all patients were female; P = 0.07), and time to platelet recovery did not distinguish the six courses complicated by the hypothetical engraftment syndrome (ES) from the other 64 courses taken as controls. However, neutrophil recovery > 0.5 x 10(9)/l occurred earlier (P = 0.01), and the neutrophil count increment during the early phase of recovery was steeper in ES patients (P = 0.003). ES was also associated with infusion of a high number of CD34+ progenitors (P = 0.03) and conditioning with busulfan (P = 0.03). Although all ES patients received G-CSF after transplantation, an association of ES with G-CSF use could not be demonstrated, possibly because of the small number of courses not supported by G-CSF. However, in one patient, ES did not recur after a second transplant unsupported by growth factors. Our study supports the idea of an engraftment syndrome associated with an early and steep neutrophil recovery after APBSCT.

Experience of the Belgian Society of Medical Oncology with single-administration 5 g/m2 ifosfamide with mesna as second- or third-line therapy in advanced breast cancer.

In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits.

Improvement of hematological and general tolerance to CMF by high-dose medroxyprogesterone acetate (HD-MPA) adjuvant treatment for primary node positive breast cancer (analysis of 100 patients).

In a prospective randomized trial comparing CMF to CMF + HD-MPA for primary node positive breast cancer patients, the authors evidenced clear improvement of hematological tolerance (especially of WBC - granulocytes counts) to chemotherapy in the group receiving also hormonotherapy. The design of the trial allowed to give the patients overall high doses of CMF therapy in both arms; in the group receiving HD-MPA significantly higher doses of CMF could be administered (96.3-97.8% for CMF + HD-MPA treated patients vs 89.7-91.1% for CMF alone treated patients). The menopausal status did not influence the results.

Oral versus intramuscular high-dose medroxyprogesterone acetate (HD-MPA) in advanced breast cancer. A randomized study of the Belgian Society of Medical Oncology.

Ninety postmenopausal women with advanced breast cancer were randomly assigned to be treated with HD-MPA administered either by oral route (daily dose 900 mg) or by intramuscular injections (1 g IM daily X 5 q w during 4 consecutive weeks followed by maintenance with 1 g twice weekly). Among 78 evaluable cases, most heavily pretreated, remissions, lasting for a median duration of 11 months, were more frequent on oral (8/37 = 22%) than on IM therapy (5/41 = 12%). In both arms, high estrogen receptor levels and various clinical factors were associated with higher response rates i.e., age greater than 60, Karnofsky greater than 70, light prior systemic treatment. Side-effects, consisting mainly of weight gain, hypertension and tremor occurred with equal frequency on oral or IM treatment. Five patients complained of pain at the sites of IM injections. Thus, we recommended that, whenever possible, the oral route should be preferred. During the same study, in 20 patients (11 on oral and 9 on IM therapy), blood was drawn at 0, 30, and 60 days of treatment for the assessment of MPA and hormone levels. In both arms, at 60 days, comparable levels of circulating MPA were obtained, with a very significant drop of cortisol, androstenedione, and estrone. These endocrine results, together with our clinical data, indicate that HD-MPA therapy is active on estrogen-dependent tumors with the same specificity as that of other modalities aiming to suppress the adrenal function. Its antineoplastic action in humans could be ascribed at least in part to its suppressive action on the adrenals, resulting in a severe estrogenic deprivation in postmenopausal women.

Palmar fasciitis and arthritis: association with endometrial adenocarcinoma.

A 74-year-old woman was referred because of rheumatic symptoms consisting of pain, swelling of the hands, contracture and flexion of the fingers and severe palmar erythrosis. One year earlier she had undergone a total abdominal hysterectomy (TAH) for uterine adenocarcinoma. A paraneoplastic syndrome with palmar fasciitis and arthritis was then suspected and an evolutive peritoneal carcinomatosis was confirmed by abdominal CT scan. The patient was first treated with hormonal therapy (progestagen) and then with chemotherapy. This, associated with calcitonin, corticosteroids and physiotherapy, allowed a temporary recovery, but the patient died 10 months later from progressive peritoneal carcinomatosis.

Adriamycin cardiotoxicity. Prognostic value of the systolic time intervals.

The aim of this study was to detect the cardiotoxicity of Adriamycin (ADM) by the evolution of the systolic time intervals (STI). The PEP/LVET ratio represents an easy and reproducible index of myocardial function. The more important this increase, the greater the risk of developing heart failure. A significant correlation exists between the variation of this ratio and the total administered dose, but the correlation coefficient is low. A heart failure may appear for doses of ADM under 500 mg/m2 but it is preceded by an increase of the index. In the absence of a significant modification, the generally admitted maximum dose of 550 mg/m2 may be exceeded. In case of a ratio increase in excess of 0.08 it will be necessary to balance the potential benefits of treatment with the hazards of cardiac failure. The PEP/LVET ratio allows proceeding with the cytostatic treatment in increased security by selecting the patients at high risk for cardiac failure.

[A case of post-mastectomy lymphangiosarcoma]. / A propos d'un cas de lymphangiosarcome post-mammectomie.

Postmastectomy lymphedema and lymphangiosarcoma. A case of 73-year-old woman with postmastectomy lymphedema of the right arm and subsequent lymphangiosarcoma is reported. The diagnosis has been confirmed immunohistologically. The patient had to undergo an amputation of the arm. Presently this treatment offers the greatest chance for survival.

[Soft-tissue sarcomas. Review of 47 patients treated in 10 years in the same institute]. / Les sarcomes des tissus mous. Revue de 47 patients traités en 10 ans dans une même institution.

We have retrospectively examined the records of 47 patients treated in our department between 1977 and 1987 for soft tissue sarcoma of the extremities trunk, head or retroperitoneal space. We also reanalyze the histologic slides of 38 patients with respect to grade and necrosis. Surgery was performed for cure intent in 31 patients. Of these, 20 with a tumor of the extremities, trunk, or head underwent adjuvant radiotherapy. The patients with a high-grade sarcoma also received adjuvant chemotherapy. Local control was achieved in 95% of these 20 patients. These results compare favorably with other reported series. Out of the 8 patients with a tumor of the retroperitoneum, only one is alive without evidence of disease. The histological studies confirmed the relationship between grade and necrosis.

Coronary artery spasm induced by 5-fluorouracil.

We report a case of coronary artery spasm induced by 5-fluorouracil. The symptoms occurred during continuous intravenous infusion of the drug, and a coronary spasm was visualized at angiography.

[Ascitic fluid: the value of various biological tests in the differential diagnosis between cirrhotic and neoplastic ascites]. / Le liquide d'ascite: intérêt de divers tests biologiques dans le diagnostic différentiel entre ascite cirrhotique et néoplasique.

The authors have analyzed sixty cases of ascites including twenty of neoplastic origin and thirty-six of cirrhotic origin in order to evaluate the usefulness of several laboratory tests for the differential diagnosis of ascites. The tests which gave more than 85% diagnostic accuracy were ascitic fluid concentrations of fibronectin and total protein, serum-ascites gradients of albumin and total protein concentrations, ascitic fluid concentrations of albumin and cholesterol. The last three tests gave a diagnostic accuracy of more than 92% at discriminant levels of 3.8 gr/dl, 1.6 gr/dl and 60 mg/dl, respectively. For these six tests, neoplastic ascites due to liver metastasis had values intermediate between cirrhotic ascites and neoplastic ascites due to peritoneal carcinomatosis. A serum-ascites albumin gradient of more than 1.1 gr/dl was indicative of portal hypertension in cirrhotic patients; the total protein serum-ascites gradient had a better diagnostic accuracy. Flow cytometry had less diagnostic accuracy than cytology; moreover, all cases with abnormal flow cytometry were already recognized by cytology.

[Serum level of neuron-specific enolase: value as tumor marker of microcellular bronchial cancer]. / Dosage sérique de la neurone spécifique énolase: intérêt comme marqueur tumoral du cancer microcellulaire bronchique.

This study analyses retrospectively the plasma level of neuron-specific enolase (NSE) performed in 236 patients presenting for the diagnosis of a bronchopulmonary disease. Taking a cut off on 15 micrograms/L, 61 (64%) of the 95 patients sharing a small cell lung cancer (SCLC) (45% of those with a limited disease and 90% with an extensive disease) but 8 (13%) of 60 with a non small cell lung cancer patients and 0% of those with a benign bronchopulmonary disease showed an abnormal value of NSE. Therefore in this group of patients, the diagnosis of SCLC could be assessed with a sensitivity of 64% and a specificity of 94% in patients with an NSE plasma level above 15 micrograms/L. In addition, the interest of sequential dosages of NSE for the monitoring of SCLC patients is also stressed.

Carboplatin in combination with etoposide in inoperable non-small-cell lung cancer (NSCLC).

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.

Adjuvant treatment with high dose medroxyprogesterone acetate in node-negative early breast cancer. A 3-year interim report on a randomized trial (I).

After initial surgery, 240 pre-, peri- or postmenopausal patients with early node-negative breast carcinoma were randomized to receive either no hormone therapy or adjuvant therapy with medroxyprogesterone acetate at high dosage (HD-MPA; 500 mg IM per day times 28 or 500 mg intramuscularly (i.m.) 5 days a week for 5 weeks then 500 mg i.m. twice weekly for the 5 following months. After a median follow-up time of 3 years, relapse-free survival and overall survival appeared significantly improved in the HD-MPA arm. Side effects were tolerable.

Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: a dose escalation study of carboplatin. UCL Clinical Oncology Group.

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial.

The authors updated their report on a randomized trial initiated in 1982 comparing, in early breast cancer, high-dose IM Medroxyprogesterone acetate (HD-MPA) adjuvant hormonotherapy during 6 months with no hormonotherapy; node-positive patients also received 6 courses of IV CMF (day 1, day 8; q.4 weeks). 246 node-negative (NN) and 270 node-positive (NP) patients had been followed for a median duration of 13 years. Previous results were confirmed in this analysis on mature data. In NN patients, relapse-free survival (RFS) was improved in the adjuvant hormonotherapy arm, regardless of age while overall survival (OAS) was also increased in younger (less then 50 years) patients. In the whole group of NP patients, no difference was seen regarding RFS or OAS. However, an age-dependant opposite effect was observed: younger patients (< 50) experienced a worse and significant outcome of relapse-free and overall survivals when receiving adjuvant HD-MPA while older patients (> or = 50) enjoyed a significant improvement of their relapse-free survival. For both NN and NP patients, differences in overall survivals observed in older women with a shorter follow-up, were no longer detected.