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Filippo de Braud

Publications and source records attributed to Filippo de Braud.

At least 19 recordsLinked to original sources
PubMed2007

Oligometastatic non-small cell lung cancer: a multidisciplinary approach in the positron emission tomographic scan era.

BACKGROUND: We have assessed the survival rate of patients with non-small cell lung cancer and synchronous hematogenous solitary metastasis identified with complete staging workup, including total body [18F]fluorodeoxyglucose positron emission tomography scan, and treated with a multidisciplinary approach. METHODS: We examined the database of all patients who underwent surgery for primary non-small cell lung cancer in our institute. The criteria required for inclusion in this analysis were diagnosis of non-small cell lung cancer with synchronous hematogenous solitary metastasis by staging workup with total body computed tomography scan and brain magnetic resonance if indicated, total body positron emission tomography scan, radical surgery for the primary tumors, local treatment of the solitary metastasis, and systemic chemotherapy administration. RESULTS: We analyzed the data from 1,509 patients treated from January 2000 to December 2005: 10 patients (0.7%) satisfied the selection criteria. The median overall survival was 26 months, and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median follow-up of 30 months. Four patients were tumor progression-free after 9, 18, 23, and 32 months from the start of their treatment. CONCLUSIONS: The presentation of non-small cell lung cancer with a synchronous hematogenous solitary metastasis identified by [18F]fluorodeoxyglucose positron emission tomography containing complete staging workup is extremely rare. This subset of patients can achieve long-term survival after a multidisciplinary treatment approach.

Adult↗
PubMed2006

A proper schedule of weekly paclitaxel and gemcitabine combination is highly active and very well tolerated in NSCLC patients.

BACKGROUND: In a previous phase I dose-escalation study, we showed a weekly administration of paclitaxel (TAX) and gemcitabine (GEM) to be active and very well tolerated in non-small-cell lung cancer (NSCLC) patients, with the lack of interaction between drugs. The dose of GEM 1500 mg/m(2) and TAX 100 mg/m(2) was selected for phase II studies due to its predictable kinetic behaviour and less severe thrombocytopenia. PATIENTS AND METHODS: Fifty-four chemo-naïve patients with advanced NSCLC (53 patients: stage IV) received TAX (100mg/m(2) i.v. infusion over 1h) followed by GEM 1500 mg/m(2) over 30 min) on days 1, 8, 15 and 21 of a 28-day cycle. RESULTS: The objective response rate was 46% (95% CI 32-61), median OS of 10.4 ms (95% CI 6.5-4.3), and a 1-year survival rate of 53%. Grades 3 and 4 haematological toxicity consisted of non-febrile neutropenia and thrombocytopenia in 13 and 4% of the cycles, respectively. Grade 3 non-haematological toxicities were observed in three patients (asthenia, diarrhoea and neuropathy), and were always reversible. CONCLUSIONS: This weekly schedule of TAX and GEM is highly active in chemo-naïve NSCLC patients and confirms the low toxicity profile already observed in a previous phase I study.

Adult↗
PubMed2005

Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production.

Yondelis (Trabectedin) is a novel antitumor agent of marine origin extracted from the tunicate Ecteinascidia turbinata. This original compound is active against several human tumors including sarcoma and ovarian and breast adenocarcinoma, as evidenced in phase II clinical trials in advanced multitreated patients. Yondelis is a DNA minor groove binder that blocks cell cycle and interferes with inducible gene transcription in a selective manner. In this study, we investigated the immunomodulatory properties of Yondelis on leukocytes. Human blood monocytes were highly susceptible in vitro to its cytotoxic effect and underwent apoptosis at pharmacologically relevant concentrations (5 nmol/L), whereas lymphocytes were up to 5-fold less sensitive. Macrophages differentiated in vitro with macrophage colony-stimulating factor and tumor-associated macrophages (TAM), isolated from patients with ovarian cancer, were also susceptible. At subcytotoxic concentrations, Yondelis inhibited the in vitro differentiation of monocytes to macrophages. In tumor-treated patients, drug infusion caused a selective decrease of monocyte counts and of ex vivo macrophage differentiation. The in vitro production of two proinflammatory mediators, CCL2 and IL-6, was markedly reduced by Yondelis in monocytes, macrophages, TAM, and freshly isolated ovarian tumor cells. The chemokine CCL2 is the major determinant of monocyte recruitment at tumor sites, whereas IL-6 is a growth factor for ovarian tumors. In view of the protumor activity of TAM and of the strong association between chronic inflammation and cancer progression, the inhibitory effect of Yondelis on macrophage viability, differentiation, and cytokine production is likely to contribute to the antitumor activity of this agent in inflammation-associated human tumors.

Antineoplastic Agents, Alkylating↗
PubMed2005

Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study.

PURPOSE: To evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA-IIIB non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. RESULTS: From February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). CONCLUSION: In this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC.

Antineoplastic Agents↗
PubMed2005

Extended pneumonectomy with partial resection of the left atrium, without cardiopulmonary bypass, for lung cancer.

BACKGROUND: Extended pneumonectomy with partial resection of the left atrium for lung cancer is not frequently performed; therefore, its results remain controversial. The present study analyzed a single center's experience with this extended surgery, highlighting the surgery's technical aspects, postoperative outcomes, and oncologic results. METHODS: From November 1996 to December 2003, 15 patients underwent extended pneumonectomy with partial resection of the left atrium for lung cancer, without cardiopulmonary bypass. RESULTS: Of the 15 patients (median age of 63 years, range 35 to 74 years), 11 were men (73%) and 4 were women. Six patients (40%) underwent preoperative invasive mediastinal staging. Nine patients (60%) underwent induction chemotherapy. Nine patients (60%) underwent right pneumonectomy. Pathologic analysis of the specimens identified 8 patients (53%) with N2 disease, 5 patients (33%) with N1 disease, and 2 patients with N0 disease. The T status was T4 in 10 patients, pT3 in 3 patients, and T0 in the remaining 2 patients. The were 10 squamous cell carcinomas (60%), 2 adenocarcinomas, 1 adenosquamous carcinoma, 1 mucoepidermoid carcinoma, and 1 atypical carcinoid tumor. The median intensive care unit and hospital stay were 1 day and 6.4 days, respectively. There were only two (15.3%) minor postoperative complications (atrial arrhythmias), which were successfully treated medically. There was no postoperative mortality. At completion of the study, 9 patients (60%) were still alive, with 8 showing no evidence of disease. The remaining 6 patients died because of systemic recurrences. The 3-year probability of survival was 39%. CONCLUSIONS: Extended pneumonectomy with partial resection of the left atrium for advanced lung cancer is a feasible procedure, with low postoperative morbidity and mortality. In fact, it can lead to excellent local control of the disease, if not to a permanent cure in select patients.

Adenocarcinoma↗
PubMed2005

Gastric cancer.

Gastric cancer is one of the most common cancers and one of the most frequent causes of cancer-related deaths. The incidence, diagnostic studies, and therapeutic options have undergone important changes in the last decades, but the prognosis for gastric cancer patients remains poor, especially in more advanced stages. Surgery is the mainstay of treatment of this disease, even if it is associated with a high rate of locoregional and distant recurrence. There is ongoing debate regarding the role of adjuvant treatment In advanced disease, palliation of symptoms, rather than cure, is the primary goal of patient management. Several combination therapies have been developed and have been examined in phase III trials; however, in most cases, they have failed to demonstrate a survival advantage over the reference arm. This review summarizes the most important recommendations for the management of patients with gastric cancer.

Combined Modality Therapy↗
PubMed2005

Cancer of the prostate.

Prostate carcinoma, with about 190,000 new cases occurring each year (15% of all cancers in men), is the most frequent cancer among men in northern and western Europe. Causes of the disease are essentially unknown, although hormonal factors are involved, and diet may exert an indirect influence; some genes, potentially involved in hereditary prostate cancer (HPC) have been identified. A suspect of prostate cancer may derive from elevated serum prostate-specific antigen (PSA) values and/or a suspicious digital rectal examination (DRE) finding. For a definitive diagnosis, however, a positive prostate biopsy is requested. Treatment strategy is defined according to initial PSA stage, and grade of the disease and age and general conditions of the patient. In localized disease, watchful waiting is indicated as primary option in patients with well or moderately differentiated tumours and a life expectancy <10 years, while radical prostatectomy and radiotherapy (with or without hormone-therapy) could be appropriate choices in the remaining cases. Hormone-therapy is the treatment of choice, combined with radiotherapy, for locally advanced or bulky disease and is effective, but not curative, in 80-85% of the cases of advanced disease. Patients who develop a hormone-refractory prostate cancer disease (HRPC) have to be evaluated for chemotherapy because of the recent demonstration of improved overall survival (2-2.5 months) and quality of life with docetaxel in more than 1,600 cases.

Antineoplastic Protocols↗
PubMed2004

Modulation of epidermal growth factor receptor status by chemotherapy in patients with locally advanced non-small-cell lung cancer is rare.

PURPOSE: To determine whether epidermal growth factor receptor (EGFR) expression in non-small-cell lung cancer (NSCLC) is modulated by chemotherapy and to assess the agreement of EGFR status between mediastinal nodes and the primary tumor after chemotherapy. PATIENTS AND METHODS: Patients with NSCLC stage IIIa/b pN2/3 confirmed by mediastinoscopy or mediastinostomy were treated with at least three cycles of chemotherapy before undergoing surgery. EGFR expression was evaluated on mediastinal nodes at the time of initial diagnosis and on both the primary tumor and residual metastatic nodes after treatment. RESULTS: EGFR expression determined on 138 of 164 patients who underwent mediastinoscopy or mediastinostomy was 0 (22 patients), 1+ (27 patients), 2+ (28 patients), and 3+ (61 patients). Fifty-four patients of 164 received chemotherapy followed by surgery. Of the 89 of 138 patients with EGFR score of 2+/3+ at the time of diagnosis, 34 patients underwent surgery after induction chemotherapy. None changed to zero EGFR immunoreactivity, with 29 patients (88%) maintaining a score of 2+/3+. Of the 22 of 138 patients with no EGFR expression at the time of diagnosis, six underwent surgical resection after induction chemotherapy. Of these six patients, four changed their EGFR expression from an EGFR score of 0 to 2+/3+. After treatment, the agreement of EGFR status between tumor and nodes in the subgroup of patients with EGFR score 2+/3+ was 89% to 92%. CONCLUSION: Our data suggest a very good agreement of EGFR status before and after chemotherapy in EGFR-positive NSCLC. Induction chemotherapy can induce EGFR expression in occasional EGFR-negative tumors.

Adolescent↗
PubMed2004

Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopasual patients.

BACKGROUND: Aging remains one of the single greatest risk factors for the development of new breast carcinoma. The aim of the study was to evaluate the relation between biologic features at first diagnosis of breast carcinoma and treatment choice for postmenopausal women > or = 50 years to optimize treatment in the elderly. METHODS: The sample included 2999 consecutive postmenopausal patients referred for surgery at the European Institute of Oncology (Milan, Italy) from April 1997 to February 2002. The patients were grouped according to age: young postmenopausal (YPM; 50-64 years, n = 2052), older postmenopausal (OPM; 65-74, n = 801), and elderly postmenopausal (EPM; > or = 75, n = 146). RESULTS: EPM patients referred to surgery had larger tumors compared with YPM patients (pT4: 6.7% vs. 2.4%) as well as greater lymph node involvement (lymph node positive: 62.5% vs. 51.3%). EPM patients showed a higher degree of estrogen and progesterone receptor expression (P < 0.01), less peritumoral vascular invasion (P < 0.01), and less HER-2/neu expression (P < 0.01) than YPM patients. Comorbidities were more often recorded for elderly patients (72% EPM vs. 45% YPM; P < 0.001), did not influence surgical choices, and were similar across groups (breast conservation: 73.9%, 76.9%, and 72.9%, respectively). No systemic therapy (either chemotherapy or endocrine therapy) was recommended for 19.1% of the EPM compared with 5.4% and 4.7% of the two other groups. CONCLUSIONS: In spite of larger tumor size at presentation, older patients had tumors with more favorable biologic characteristics, when compared with younger postmenopausal patients. Reluctance to prescribe systemic treatments was due to the complexity of evaluation for these patients. Taking into account the data from the current study and given the climate of uncertainty regarding optimal treatment, the authors decided to individualize care on the basis of biologic characteristics, comorbidity, social support, functional status, and patient preferences. Trials of tailored adjuvant therapy should be a health care priority.

Aged↗
PubMed2004

Optimization of the schedule of gemcitabine-cisplatin combination as induction regimen for patients with biopsy-proven stage IIIa N2 - stage IIIb non-small-cell lung cancer: a prospective phase-II study.

Aim of this study was to define the optimal schedule of gemcitabine (GCB)\cisplatin (CDDP) combination as induction chemotherapy (CHT) in patients with stage IIIa pN2-IIIb non - small-cell lung cancer (NSCLC). Fifty patients with mediastinoscopically-proven stage-IIIa pN2 -IIIb NSCLC were treated with 3 cycles of induction CHT followed by surgery (if staged IIIa) and three-time-daily accelerated radiotherapy. Chemotherapy initially consisted of 3 courses of CDDP 100 mg\m(2) d1 plus GCB 1000 mg\m(2) dd 1,8,15 repeated every 4 weeks, than was modified in CDDP 80 mg\m(2) d1 plus GCB 1250 mg\m(2) dd 1,8 repeated every 3 weeks. Twenty-nine four-week scheduled treatment cycles were firstly administered to 10 patients (pts): treatment-related toxicity, mainly hematological, caused a dose-reduction or treatment omission on day 15 in 65% of cycles. After the protocol was amended, 119 three-week scheduled treatment cycles were administered to 40 pts. Treatment-related toxicity of the new schedule caused a dose-reduction or treatment omission in only 10% of cycles, no patients requiring chemotherapy discontinuation. Thirty-seven out of fifty patients (74%, 95% CI: 60-85%) achieved a partial response, 7 had stable disease and 6 had disease progression. Similar activity was seen with both schedules. One nodal pathological complete remission was observed among the 24 pts who underwent surgery. At present, with a median follow-up of 13 months (mos), 2-year (y) survival of all the 50 pts and of the 24 pts staged IIIa who underwent surgery is estimated as 37% (95% CI: 24-58%) and 47% (95%CI: 27-80%), respectively. When given as induction chemotherapy, a three-week schedule of CDDP plus GCB combination appeared to be effective, with lower toxicity and better compliance than a four-week schedule.

Adult↗
PubMed2004

Colon cancer.

Colon cancer is one of the leading tumours in the world and is considered among the big killers, together with lung, prostate and breast cancer. In the recent years very important advances occurred in the field of treatment of this frequent disease: adjuvant chemotherapy was demonstrated to be effective, chiefly in stage III patients, and surgery was optimized in order to achieve the best results with a low morbidity. Several new target-oriented drugs are under evaluation and some of them (cetuximab and bevacizumab) have already exhibited a good activity/efficacy, mainly in combination with chemotherapy. The development of updated recommendations for the best management of these patients is crucial in order to obtain the best results, not only in clinical research but also in everyday practice. This report summarizes the most important achievements in this field and provides the readers useful suggestions for their professional practice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?

BACKGROUND: Patients receiving chemotherapy for lung cancer usually modify their lung function during treatment with increases in forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) and decreases in lung diffusion for carbon monoxide (DLCO). This prospective study was designed to evaluate functional changes in forced expiratory volume in 1 second, forced vital capacity, and DLCO after three courses of induction chemotherapy with cisplatinum and gemcitabine in stage IIIa lung cancer patients and to assess their impact on respiratory complications after lung resection. METHODS: From March 1998 to January 2001, 30 consecutive patients with N2 nonsmall cell lung cancer had surgical resection after neoadjuvant treatment. Pre-chemotherapy and postchemotherapy results of standard respiratory function tests and DLCO were compared in patients with and without postoperative respiratory complications. RESULTS: All 30 patients completed the chemotherapy protocol without respiratory complications. Significant improvements (p < 0.05) were recorded after chemotherapy in transition dyspnea score, PaO(2) (mean value from 79.8 to 86.4 mm Hg), forced expiratory volume in 1 second % (from 78.1% to 87.5%) and forced vital capacity % (from 88.1% to 103.3%). Lung diffusion for carbon monoxide was significantly impaired after chemotherapy (from 74.1% to 65.7%; p = 0.0006), as well as DLCO adjusted for alveolar volume (from 92.8% to 77.4%; p < 0.0001). One patient died after surgery and 4 patients (13.3%) experienced postoperative respiratory complications. Compared with patients without complications, these 4 patients had higher mean increase in FEV(1) after chemotherapy (+26.8% vs + 6.7%; p = 0.025), but greater mean decrease in DLCO/Va (-27.8% vs -13.6%; p = 0.03). Impact of change in DLCO on postoperative respiratory complications was not confirmed by multiple logistic regression analysis (p = 0.16). CONCLUSIONS: In lung cancer patients, forced expiratory volume in 1 second and forced vital capacity assessed after neoadjuvant chemotherapy are not reliable indicators of the likelihood of respiratory complications after surgery. The risk of respiratory complication may be directly linked to loss of DLCO/Va. Lung diffusion for carbon monoxide assessed after neoadjuvant chemotherapy is probably the most sensitive risk indicator of respiratory complications after surgery. We recommend that DLCO studies be performed before and after chemotherapy in lung cancer patients undergoing induction therapy.

Carbon Monoxide↗
PubMed2004

Cancer of pancreas.

Cancer of the pancreas is the tenth most frequent cancer in Europe, accounting for some 3% of cancer in both sex. Smoking has been clearly established as a major risk factor affecting the carcinogenesis of pancreatic carcinoma. Diet has also been associated with pancreatic cancer, although no conclusive data are yet available. Different genetic alterations have been observed in pancreatic neoplasms. Typical symptoms of pancreatic cancer are: jaundice, abdominal pain and weight loss. The prognosis of pancreatic carcinoma depends mainly on radical surgery and the presence of negative resection margins, as well as on the biological tumour stage, which also influences the treatment strategy. The treatment of pancreatic cancer is undertaken with two aims. Radical surgery is indicated for patients with early stage of disease, mainly stage I and partially II. In all other cases, the aim of treatment is the palliation of different very distressing symptoms related to this neoplasm.

Follow-Up Studies↗
PubMed2003

Malignant melanoma.

In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk factors. The change over a period of months is the main sign of a skin lesion turned into a melanoma. The ABCDE scheme for early detection of melanoma is commonly accepted. A new staging classification will be published in the next AJCC/UICC Cancer Staging System Manual in 2002. The clinical course of melanoma is determined by its dissemination and depends on thickness, ulceration, localisation, gender and histology of the primary tumour. Tumour stage at diagnosis remains the major prognostic factor. Surgery is the standard treatment option for operable local-regional disease. Sentinel node biopsy represents a promising experimental approach in the clinical detection and early treatment of occult lymph node involvement. For metastatic inoperable patients systemic chemotherapy can be attempted, while radiation therapy has to be considered as palliative treatment. No studies concerning frequency of follow-up are currently available, but common procedures may be performed.

Female↗