Systematic versus sentinel-lymph-node-driven axillary-lymph-node dissection in clinically node-negative patients with operable breast cancer. Results of the GF-GS01 randomized trial.

PURPOSE: Sentinel-lymph-node (SLN) resection seems to minimize systematic axillary-lymph-node dissection (sALND) side effects in operated breast cancer patients. We explored whether SLN resection achieves similar therapeutic outcomes as sALND but with fewer side effects. METHODS: A randomized, controlled, open-label trial with parallel-group design compared sALND restricted to cases with positive SLN biopsy (test arm, n = 774) versus SLN biopsy followed by sALND (control arm, n = 770). RESULTS: The five-year overall survivals in control and test arms were 96.42 and 95.64% (P = 0.2925). The estimated difference was nearly zero (precisely, - 0.79%, one-tailed 95% confidence interval (CI) limit - 2.44%). In a multivariate Cox model, the adjusted hazard ratio in the test arm was HR 0.81 (upper 95% CI limit 1.17). Advanced age (HR 1.05 per additional year, CI [1.03-1.08]), negative progesterone receptor (HR 2.17 [1.35-3.45]), SLN metastasis (HR 1.69 [1.03-2.79]), and only one SLN identification technique (HR 4.14 [1.21-14.18]) were associated with lower survival. Patients with ≥ 1 severe side effect at 1 month in control and test arms were 173/703 = 24.6% [21.5-28.0%] and 91/693 = 13.1% [10.7-15.9%] (P < 0.001). The estimated sensitivity of SLN biopsy (control arm) was 145/178 = 81.5% [74.8-86.7%]. CONCLUSIONS: Restricting ALND to cases with positive SLN biopsy does not affect the overall survival but reduces by 11.5% [7.5-15.6%] (P < 0.001) the risk of severe short-time side effects of sALND.

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer.

BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.

Sparse BSS from Poisson Measurements.

The problem of sparse Blind Source Separation (BSS) has been extensively studied when the noise is additive and Gaussian. This is however not the case when the measurements follow Poisson or shot noise statistics, which is customary with counting-based measurements. To that purpose, we introduce a novel sparse BSS algorithm coined pGMCA (poisson-Generalized Morphological Component Analysis) that specifically tackles the blind separation of sparse sources from measurements following Poisson statistics. The proposed algorithm builds upon Nesterov's smoothing technique to define a smooth approximation of sparse BSS, with a data fidelity term derived from the Poisson likelihood. This allows to design a block coordinate descent-based minimization procedure with a simple choice of the regularization parameter. Numerical experiments have been carried out that illustrate the robustness of the proposed method with respect to Poisson noise. The pGMCA algorithm has been further evaluated in a realistic astrophysical X-ray imaging setting.

Sparse spectral unmixing for activity estimation in γ-RAY spectrometry applied to environmental measurements.

This paper presents a sparse spectral unmixing algorithm for activity estimation of radionuclides in γ-ray spectrometry. The spectral unmixing method aims to decompose a measured spectrum into spectral signatures of radionuclides, which is sensitive to the choice of the spectral signatures. The sparsity of the solution is imposed to identify the active radionuclides. Experimental results on simulated and real spectra show that the proposed method yields significant improvement for estimating radioactivity at low statistics.

Spectral unmixing applied to fast identification of γ-emitting radionuclides using NaI(Tl) detectors.

Spectral unmixing was investigated for fast spectroscopic identification in γ-emitter mixtures at low-statistics in the case of measurements performed to prevent illegal nuclear material trafficking or for in situ environmental analysis following a radiological or nuclear accident. For that purpose, a multiplicative update algorithm based on full-spectrum analysis was tested in the case of a 3″x3″ NaI(Tl) detector. Automatic decision-making was addressed using Monte Carlo calculations of decision thresholds and detection limits. The first results obtained with a portable instrument equipped with a 3″x3″ NaI(Tl) detector designed for the control of food samples by non-expert users following a radiological or nuclear accident, are also presented.

Clinical implications of axillary sentinel lymph node 'micrometastases' in breast cancer.

AIMS: The aim of this study was to determine, from a series of cases, the frequency and prognostic factors of invasion of non-sentinel lymph nodes when the axillary sentinel lymph node contains a metastasis < or =2 mm, and thereby select a population in which completion axillary dissection could be omitted. METHODS: Between July 1996 and July 2003, 62 patients, which axillary sentinel lymph node contained a metastasis < or =2 mm had an evaluation of the axillary non-sentinel lymph nodes. Eleven patients had also an evaluation of internal mammary lymph nodes. RESULTS: Eleven patients had axillary non-sentinel lymph node invasion: six by metastases < or =2 mm and five by macrometastases. When internal mammary lymph nodes were also concerned, nodal invasion apart from the axillary sentinel lymph node was seen in 14 patients. Vascular lymphatic invasion was the only factor, statistically significant, linked to non-sentinel lymph node invasion (p = 0.02). CONCLUSION: Whatever the size or method of histological detection (pN1mi or pN0(i+)), the presence of a metastasis < or =2 mm in the axillary sentinel lymph node leads us to carry out completion axillary dissection to optimize staging and loco-regional control of the disease.

Tagging sentinel lymph nodes: a study of 100 patients with breast cancer.

The aim of this study was to evaluate in breast cancer patients the feasibility of sentinel lymph node (SLN) identification and the sensitivity of this technique to detect node metastases. Between January and July 1997, SLNs were tracked with Evans Blue dye in 100 patients with breast cancer who then underwent complete level I/II axillary lymph node dissection (ALND). All SLNs were examined by haematoxylin-phloxin-saffron (HPS) staining and immunohistochemistry (IHC) of multiple sections. The findings for the SLNs were compared with results on ANLD. Axillary SLNs were identified in 83 patients (detection rate = 83%; 95% confidence interval (CI) 74-90%). Axillary SLNs were detected in 58/83 cases (70%) at level I only, and in 69/83 (83%) at levels including level I. Histologically positive axillary SLNs were found in 45% (37/83) of patients, including 2 patients with malignancy (micro-metastases) detected by IHC only. The sensitivity of axillary SLN to detect axillary lymph nodes metastases was 37/39 = 95% (95% CI 83-99%). SLNs of the internal mammary chain (IMC) were dissected for 33 tumours of the median or inner quadrants and detected in 26/33 = 79% of cases (95% CI 61-91%). In our experience, the overall sensitivity of SLN identification as a predictor of node (axillary or IMC) metastases was 41/43 = 95% (95% CI 84-99%), confirming the usefulness of the procedure.

Prognostic factors in chordoma: role of postoperative radiotherapy.

We have investigated prognostic factors for survival in a series of 26 patients with chordoma treated in Lyon, France, between 1979 and 1993. In this series, the median progression-free (PFS) and overall survival (OS) were 10 and 90 months, respectively. In univariate analysis, PFS, but not OS, was found significantly longer in males as compared to females (median: 19 versus 7 months, P = 0.05); and patients under 60 years of age had a longer PFS (median: 18 versus 6 months; P = 0.06) and OS (median: 108 versus 47+, P = 0.05) than older patients. A favourable prognostic subgroup including male patients under 60 years and a poor prognostic group including female patients and male over 60 years were thus defined (median PFS: 36 versus 6 months, P = 0.001; median OS: 108 versus 55+, P = 0.15). Primary treatment combining surgery and postoperative radiotherapy was associated with a longer PFS than surgery only (median: 36 versus 7 months, P = 0.002) in the whole series and in both prognostic subgroups.

Breast cancer prognostic significance of some modified urinary nucleosides.

The prognostic significance of six urinary modified nucleosides, 5-methylcytidine (5-MeCyd), 4-acetylcytidine (4-AcCyd), 1-methylinosine (1-MeIno), 1-methyladenosine (1-MeAdo), 7-methylguanosine (7-MeGua) and pseudouridine (psi-Urd) was evaluated in 68 breast cancer patients of the specialized cancer hospital of Lyon (France). Excretions of 1-MeIno and 1-MeAdo were significantly higher in patients hospitalized in the medical rather than surgical ward, reflecting more advanced disease, and also among patients who died within 5 years of follow-up as compared to those still alive. These results suggest an unfavourable prognostic significance of high urinary excretion of 1-MeIno and 1-MeAdo in breast cancer patients.

Angiosarcoma after conservative treatment and radiation therapy for adenocarcinoma of the breast.

Radio-induced angiosarcoma of the breast after conservative therapy for invasive adenocarcinoma is a very rare tumour. Between 1996 and 2000, four cases were operated in our Department of Surgical Oncology. After a review of the literature over the same period of time, natural history and treatment of radio-induced angiosarcomas of the breast were analysed.

Surgical management of retroperitoneal sarcomas associated with external and intraoperative electron beam radiotherapy.

AIMS: To report outcomes of adults with retroperitoneal sarcoma (RS) treated by surgery, external beam radiotherapy (EBRT) and intraoperative electron beam radiotherapy (IORT). METHODS: From July 1988 to February 2001; 24 patients with primary and recurrent RS were diagnosed and treated. The median dose and energy of IORT delivered was 15 Gy/9meV. EBRT dose varies between 45-50 Gy. RESULTS: There were five primary and 19 recurrent tumours. One primary and five recurrent tumours underwent R0 resection. There were 12 liposarcomas and 19 grade I tumours; 13 patients developed local recurrence and three developed distant metastases.Twenty-two patients received IORT associated with EBRT: 11 developed recurrences. Six patients developed Neurotoxicity (4 grade II and 2 grade III). Disease free survival and overall survival at 5 years was 28 and 56% respectively. CONCLUSIONS: EBRT with IORT treatment is a promising technique for local control. Lower recurrence rates are associated with radical (R0) surgical procedures.

[Importance of local control of cancer after conservative therapy]. / L'importance du contrôle local en cancérologie après traitement conservateur.

The role of local control in the cure of solid tumors remains a matter of crucial importance particularly for the cases of conservative therapy. Arguments that higher local control rates would result in more cured patients is a subject of controversies for some tumors as breast cancer. For tumors with different natural history, the authors outlined the crucial role of local control to improve cure rate thank to surgery and radiotherapy.

[Unresolved questions in the indications for the conservative treatment of invasive cancer of the breast]. / Questions non résolues dans les indications du traitement conservateur du cancer invasif du sein.

The majority of patients with breast cancer can be treated by partial mastectomy and radiation therapy. The choice of the treatment involves the estimation of the risk for intramammary recurrence and the ability to achieve satisfactory cosmetic result. Patient selection in breast conserving therapy is dependent on clinical and histologic characteristics of the tumor, but many times the therapeutic decision is not easy. We present a review of the literature in order to try to resolve some controversed questions about breast conservation in relation to tumor size, margin status, tumor location, multicentricity, histologic subtype or presence of extensive intraductal component, age of patients and genetic factors.

[Role of surgery in the treatment of cancer. Surgical oncology]. / Place de la chirurgie dans le traitement du cancer. Chirurgie oncologique.

Surgical oncology requires an indispensable cultural and interdisciplinary approach of cancer. It needs a solid surgical formation combined with knowledges in biology, pathology, radiology, chemotherapy, and radiotherapy so oncologist surgeons are better able to define the limits of intervention according to the natural history of each type of tumors and the last modern therapeutic means.

[Cancer of the rectum: current trends in radiotherapy in conservative treatment]. / Cancer du rectum: perspectives nouvelles de la radiothérapie dans le traitement conservateur.

Conservative treatment of rectal cancer by intracavitary irradiation (Philips contact x-ray therapy followed or not by Iridium implant) is only applicable to tumours which are thought to have no lymphatic spread. A strict selection of cases is compulsory, especially with regard to the probability of lymph node involvement (degree of histological differentiation, degree of infiltration of the rectal wall, absence of palpable pararectal metastatic lymph nodes). After treatment, follow-up must be performed methodically. Moreover, in patients not older than 55, mesenteric and perirectal lymphadenectomy must be considered. At the Centre Léon Bérard (Lyon), 231 patients followed more than 5 years have been treated. The 5-year and 10-year survival rates are respectively 57 per cent and 74 per cent. The rate of local failure is 5.2 per cent. The rate of death from cancer at 5 and 10 years is 10 per cent. However intracavitary irradiation is only applicable in 10 to 15 per cent of rectal cancers. A new conservative approach has been worked out. It consists of preoperative external beam irradiation with Cobalt 60 (30 Gy in 12 days) followed 2 months later, according to the residual disease, either by radical surgery of Iridium implant. Applied to poor risk, patients this method can spare many of a permanent colostomy, without jeopardizing their chances of cure (27 cases, median age: 77 years).

[Pelvic exenteration for carcinoma of the uterine cervix (author's transl)]. / Les exentérations pelviennes dans le cancer du col utérin.

From 1953 to 1972, 149 patients at Centre Leon Bérard, were treated by pelvic exenteration for carcinoma of the cervix. A review of the literature and of our cases showed that the mortality rate varied between 12 and 38 per cent according to the authors. In our experience, the final cause of death has been essentially pelvic reccurences within 18 months of the operation. For Ketcham, the patients died principally from metastases. To illustrate these results, criteria for patient selection for pelvic exenteration are outlined, with some suggestions for operative and post-operative management. The pre-operative medical status, the roentgenographic studies and finally exploratory laparotomy eliminated all but a very small number of patients, 15 to 20 per cent. Pelvic exenteration is appreciably beneficial only for this small group. Indeed, the exenteration is acceptable only when it does not result in excessive mutilation disproportinate with the chances of survival. It is conceivable only as curative treatment requiring a radical loco-regional excision, not only for the involved viscerae but also for the pelvic lymph nodes.

[Resection of the thoracic wall in oncology]. / La résection de la paroi thoracique en cancérologie.

Based on our experience with 12 patients who underwent wide anterior chest wall resection in our institute, we attempt to define the indication of the different techniques for reconstruction by musculo-cutaneous flaps according to the extent of resection and location in the chest wall. The pectoralis major flaps are simple and important in the reconstruction of sternal defects; especially when dense retrosternal fibrosis has already developed after radiotherapy. The latissimus dorsi flaps are reliable and thick and suitable for coverage of major tissue loss. A new technique is also described for reconstruction of major anterolateral chest wall defects as well as sternal defects by a latissimus dorsi osteo-muscular flap. The external oblique musculo-cutaneous flaps are used to cover defects in the lateral chest wall below the 5th rib. Pedicled omental flaps are complementary flaps and can be used when muscle flaps are insufficient to replace significant tissue loss. Respiratory problems arising from paradoxical chest wall movement are temporary and may be encountered in the immediate post-operative period. Because of the development of fibrosis and of a better adaptation of the patient, this condition is well tolerated during the month following operation.

[Role of preoperative radiotherapy in preservation of the anal sphincter in cancer of the lower rectum]. / Rôle de la radiothérapie préopératoire dans la préservation anale pour les cancers du bas rectum.

Short term preoperative irradiation of rectal cancer (30 Gy in 12 days) followed by a two-month rest before surgery has proven to be more efficient than most usual protocols of radiotherapy. In a series of 136 tumors T2, T3 or T4, tumor-free specimens and Duke'A lesions were found at surgery in 17% and 36% respectively. Surgeons took advantage of the tumor regression and performed sphincter-saving surgery in 41 patients with T2, T3 or T4 tumors of the lower third of the rectum. Of 30 patients followed from 2 to 6 years, the disease-free survival rate is 86%. Only one local failure was observed and subsequently controlled by abdomino-perineal resection.

[Adjuvant therapy of breast cancer with tamoxifen and endometrial carcinoma]. / Traitement adjuvant du cancer du sein par tamoxifène et cancer de l'endomètre.

Twenty cases of endometrial carcinoma are reported, observed in women who had received long term tamoxifen treatment as adjuvant therapy for breast cancer. Furthermore, a specific study was carried out on an homogeneous group of 790 women with an operable breast cancer, 318 receiving tamoxifen as adjuvant treatment. Five endometrium carcinoma were observed in the group under tamoxifen versus none in the other group. From an analysis of these cases, authors will carry out a case control study to evaluate the relative risk of endometrial carcinoma for patients under tamoxifen. They underline the importance of gynecologic follow up procedures for all women receiving this endocrine therapy.

[Prognosis of operable breast cancers in women aged under forty years]. / Le pronostic des cancers du sein opérables des femmes de moins de 40 ans.

The present study is based on the data of a homogeneous series of 736 women with stage I and II operable breast cancer. The same methodology was used for treatment and follow-up. Eighty-seven patients were under 40 and 649 between 40 and 70 years ols. No statistical difference was noted between the distribution in these 2 groups regarding tumor size, the axillary or internal mammary nodal status or hormonal receptor levels. Small tumors were noted more frequently in the under 40 yr group. Overall survival was the same in both groups, independently of tumor size, axillary nodal status or hormonal receptors. Disease-free survival differed between the 2 groups: local relapse risk was 1.6 times higher for women under 40 yr, in relation to a higher frequency of conservative treatment in this group. No difference was noted for DFS in relation a tumor size, axillary nodal status of hormonal receptors.