J P Spano

Publications (28)103.55 Total impact

• Article: Added value of molecular targeted agents in oncology.

  J C Soria, J Y Blay, J P Spano, X Pivot, Y Coscas, D Khayat
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  ABSTRACT: The treatment of certain cancers has been revolutionised in recent years by the introduction of novel drugs designed to target specific molecular factors implicated in tumour growth. Notable examples include trastuzumab, a humanized monoclonal antibody (mAb) against human epidermal growth factor receptor (HER)-2 in women with HER2-positive breast cancer; rituximab, an anti-CD20 mAb in patients with non-Hodgkin's lymphoma; imatinib, a tyrosine kinase inhibitor in KIT-positive gastrointestinal stromal tumours and sunitinib, another tyrosine kinase inhibitor, in metastatic renal cell carcinoma. For regulatory reasons, new molecular targeted agents are first evaluated in advanced and metastatic disease, wherein they prolong survival. However, their most profound impact has been observed in the adjuvant setting, where they may contribute to curative therapy rather than mere palliation. Expansion in the use of molecular targeted therapies will have important cost implications for health care systems. Although expensive, on a monthly basis, molecular targeted therapies may not be more costly than treatments for other major chronic diseases, especially considering the contribution of cancer to the global disease burden, the associated socioeconomic costs and the long-term benefits of therapy. Nevertheless, the use of these agents must be optimised, in part using molecular biomarkers associated with drug response.
  Annals of Oncology 02/2011; 22(8):1703-16. · 6.43 Impact Factor
• Article: Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer--an expert review from the International Congress on Anti-Cancer Treatment (ICACT) 2009.

  R Adam, D G Haller, G Poston, J-L Raoul, J-P Spano, J Tabernero, E Van Cutsem
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  ABSTRACT: Metastatic colorectal cancer is a particularly frequent and severe cancer. Patients die mainly from metastatic disease; however, the survival of these patients has dramatically improved with the progress in chemotherapeutic regimens as new routes of administration and introduction of more potent cytotoxic agents administered in sequential 5-FU-folinic acid-irinotecan/5-FU-folinic acid-oxaliplatine strategies. Biologic therapies have been also developed targeting two different pathways, angiogenesis and the epidermal growth factor receptor. Their combination with chemotherapy leads to improved progression-free survival and overall survival in some cases as the addition of cetuximab in wild-type K-Ras tumors. The objectives of this expert conference were to review the different options, the available prognostic or predictive factors to optimally guide the treatment.
  Annals of Oncology 03/2010; 21(8):1579-84. · 6.43 Impact Factor
• Article: [Mechanisms of resistance to molecular targeted therapies in breast cancer: update and future].

  N Magné, C Chargari, R Conforti, R-A Toillon, O Bauduceau, L Védrine, D Khayat, J-P Spano
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  ABSTRACT: The importance of targeted therapies has been emphasized by clinical trials using antiangiogenic or HER2 inhibitors in breast cancer. First with trastuzumab, it was demonstrated that targeted therapies may improve outcome in patients with HER overexpressing breast cancer in metastatic or adjuvant settings. The emerging role for angiogenesis inhibitors has also been demonstrated with bevacizumab. Unfortunately, there is growing clinical and biological evidence that tumour cells may develop unexpected and complex mechanisms of resistance to those targeted therapies. This review outlines the mechanisms by which tumour cells may resist to new targeted agents. Most recent developments are also highlighted.
  Bulletin du cancer 02/2010; 97(3):385-95. · 0.67 Impact Factor
• Article: Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab.

  A Barbier, J Domont, N Magné, J-L Goldmard, C Genestie, C Hannoun, J-C Vaillant, A Bellanger, D Khayat, F Capron, J-P Spano
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  ABSTRACT: Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases. Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested. Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036). Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.
  Bulletin du cancer 02/2010; 97(2):E9-E15. · 0.67 Impact Factor
• Article: [Impact of radiotherapy on fertility in female patients].

  C Chargari, P Castadot, N Gillion, O Bauduceau, L Védrine, C Haie-Meder, J-P Spano, N Magné
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  ABSTRACT: Although insufficiently documented, the impact of radiation therapy on fertility should not be neglected in female patients. Toxicity on reproductive function is dual and is characterized by both mechanistic deleterious effects on the genital tract and partial or complete loss of ovarian function. Moreover, gonadic toxicity may be increased by the concurrent use of chemotherapy or surgical procedure. In some circumstances, ovarian transposition may be justified for young patients. But no compromise may be accepted in terms of carcinologic results. At least, the effect of low-doses of irradiation has not been demonstrated for extra-pelvic radiotherapy.
  Bulletin du cancer 09/2009; 96(10):1005-11. · 0.67 Impact Factor
• Article: [Colorectal cancers: prognostic and predictive factors of response to treatment].

  M-P Sablin, A Italiano, J-P Spano
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  ABSTRACT: For many years, 5-fluorouracil was the unique drug approved in the management of colorectal cancer. In the last decade, oxaliplatin, irinotecan, capecitabine and more recently targeted therapies as cetuximab and bevacizumab have been added to chemotherapy schedules. Prognosis and predictive factors are deeply needed to improve the management of the patients. To date, the TNM classification remains the only factor widely approved. But thanks to the progress of fundamental and translational research, it appears clearly that more clinical and molecular markers should be available soon to help the physician in the management of colorectal cancer.
  Bulletin du cancer 05/2009; 96(4):417-23. · 0.67 Impact Factor
• Article: [Prognostic and predictive factors in different malignant diseases].

  N Magné, J-P Spano
  Bulletin du cancer 05/2009; 96(4):349-50. · 0.67 Impact Factor
• Article: Management of hypertension in angiogenesis inhibitor-treated patients.

  H Izzedine, S Ederhy, F Goldwasser, J C Soria, G Milano, A Cohen, D Khayat, J P Spano
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  ABSTRACT: Hypertension (HTN) is one of the most frequent side-effects of systemic inhibition of vascular endothelial growth factor (VEGF) signaling. Its incidence and severity are dependent on the type of drugs, dose, and schedule used. The recognition of this side-effect is an important issue because poorly controlled HTN could lead to serious cardiovascular events. On another hand, HTN induced by anti-VEGF agents maybe a predictive factor of oncologic response. Knowledge of this clinical toxicity and/or therapeutic target or novel biomarker of drug activity can aid clinicians choosing the optimal and least toxic regimen suitable for an individual patient. A Medline search was carried out using the following criteria: (i) all Medline listings as of 1 January 2000 with abstracts, (ii) English language, and (iii) Humans. The following phrases were used to query the database: ('hypertension', OR 'blood pressure') AND ('anti-VEGF' OR 'VEGF inhibition' OR 'bevacizumab' OR 'sunitinib' OR 'sorafenib' OR 'VEGF Trap'). The references of each article identified were carefully reviewed for additional reference. Lifestyle modification should be encouraged. However, these nonpharmacologic strategies are not always suitable to patients with altered performance status related to metastatic cancer necessitating early drug intervention. Only one randomized study showed a beneficial effect of a calcium channel blocker use to prevent or minimize HTN secondary to antiangiogenic therapy. Nitrates looks as effective in controlling such side-effect. No clear recommendation for an antihypertensive agent can be made in this context because there is a lack of controlled studies addressing the subject. Blood pressure-lowering drugs should be individualized to the patient's clinical circumstances and angiogenic inhibitors should be withheld only from patients who experienced hypertensive crisis.
  Annals of Oncology 02/2009; 20(5):807-15. · 6.43 Impact Factor
• Article: Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer.

  G Milano, M-C Etienne-Grimaldi, L Dahan, M Francoual, J-P Spano, D Benchimol, M Chazal, C Letoublon, T André, F-N Gilly, J-R Delpero, J-L Formento
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  ABSTRACT: In advanced colorectal cancer, K-Ras somatic mutations predict resistance to mAbs targeting epidermal growth factor receptor (EGFR). Relationships between K-Ras mutations and EGFR status have not been examined so far. We analyzed relationships between K-Ras mutations and EGFR tumoral status based on EGFR germinal polymorphisms, gene copy number and expression. Eighty colorectal tumors (stage 0-IV) and 39 normal mucosas were analyzed. K-Ras mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR-restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at positions -216G>T, -191C>A and 497Arg>Lys were analyzed (PCR-RFLP), along with CA repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy number (PCR amplification). EGFR expression was quantified by Scatchard binding assay. The number of EGFR high-affinity sites, dissociation constant (Kd), gene copy number, intron 1, -216G>T, -191C>A or 497Lys>Arg genotypes was not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene copy number. EGFR gene copy number in tumor and normal tissue was not correlated. The mean value of the tumor/normal mucosa gene copy number ratio was 1.16. Present data clearly show that EGFR status is independent of K-Ras mutations in colorectal tumors.
  Annals of Oncology 12/2008; 19(12):2033-8. · 6.43 Impact Factor
• Source

  Available from: PubMed Central

  Article: EGFR-targeting drugs in combination with cytotoxic agents: from bench to bedside, a contrasted reality.

  G Milano, J-P Spano, B Leyland-Jones
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  ABSTRACT: The clinical experience recently reported with epidermal growth factor receptor (EGFR)-targeting drugs confirms the synergistic interactions observed between these compounds and conventional cytotoxic agents, which were previously established at the preclinical stage. There are, however, examples of major gaps between the bench and the bedside. Particularly demonstrative is the failure of the tyrosine kinase inhibitors (TKIs) (gefitinib and erlotinib) combined with chemotherapy in pretreated nonsmall cell lung cancer patients. These discrepancies can be due to several factors such as the methodology used to evaluate TKI plus cytotoxic agent combinations in preclinical models and the insufficient consideration given to the importance of the drug sequences for the tested combinations. Recent advances in understanding the biologic basis of acquired resistance to these agents have great potential to improve their clinical effectiveness. The purpose of this review is to critically examine the experimental conditions of the preclinical background for anti-EGFR drug-cytotoxic agent combinations and to attempt to explain the gap between clinical observations and preclinical data.
  British Journal of Cancer 08/2008; 99(1):1-5. · 5.04 Impact Factor
• Article: Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer.

  M Bouchahda, T Macarulla, J P Spano, J B Bachet, G Lledo, T Andre, B Landi, J Tabernero, A Karaboué, J Domont, F Levi, P Rougier
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  ABSTRACT: Few data are available from clinical trials for elderly patients receiving cetuximab. The clinical data of consecutive patients aged > or =70 years given cetuximab for metastatic CRC were retrospectively captured from hospital pharmacy registries in seven centers. Fifty-six patients received cetuximab+/-with irinotecan. Median age was 76 years (70-84), 86% of patients were pretreated with fluoropyrimidines, irinotecan and oxaliplatin and 69.6% had documented resistance to irinotecan. Objective response rate was 21% (95% CI: 11-32%). The median progression-free survival was 4.4 months (95% CI: 3.0-5.7 months) and the median overall survival was 16.0 months (95% CI: 13.5-18.5 months). Skin rash occurred in 75% of the patients (11% grade 3) and diarrhea in 80% (20% grades 3-4). Tolerability of cetuximab was acceptable in elderly patients with pretreated metastatic CRC. Efficacy appeared similar to that observed in younger patients.
  Critical Reviews in Oncology/Hematology 04/2008; 67(3):255-62. · 4.41 Impact Factor
• Article: Identification of a functional EGF-R/p60c-src/STAT3 pathway in colorectal carcinoma: analysis of its long-term prognostic value.

  A Tadlaoui Hbibi, C Lagorce, P Wind, J P Spano, G Des Guetz, G Milano, R Benamouzig, O Rixe, J-F Morere, J-L Breau, A Martin, R Fagard
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  ABSTRACT: The Epidermal Growth Factor-Receptor (EGF-R) is frequently overexpressed in colorectal carcinoma (CRC) and patients can benefit from anti-EGF-R therapy. Yet, the relationship, within tumours, between EGF-R and the activity of downstream effectors such as the non-receptor tyrosine kinase p60c-src and the signal transducer and activator of transcription 3 (STAT3) has not been extensively analyzed. We evaluated EGF-R, tyrosine 416-phosphorylated p60c-src (P-p60c-src), STAT3 and tyrosine 705-phosphorylated STAT3 (P-STAT3) on Tissue Micro Array (TMA) from 126 patients with CRC. Composite immunohistochemistry scores based on the intensity of labelling and the percentage of positive cells were determined on TMA for EGF-R, P-p60c-src, STAT3 and P- STAT3. A high score was found in 56%, 61%, 62% and 27% of the cases for EGF-R, P-p60c-src, STAT3 and P-STAT3 respectively. There was a significant correlation between EGF-R and P-p60c-src (p=0.006) and between P-p60c-src and P-STAT3 (p=0.0009). STAT3 was significantly correlated with vascular emboli (p=0.03) and perineural invasion (p=0.02). The correlations between EGF-R, P-p60-src and P-STAT3 and some stage-related pathological features point to a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within CRC tumours.
  Cancer biomarkers: section A of Disease markers 02/2008; 4(2):83-91. · 1.08 Impact Factor
• Article: [A rare cause of lung and peritoneal calcifications].

  B Miled, G Des-Guetz, J M Brechot, J L Breau, J P Spano, P Y Brillet
  Revue des Maladies Respiratoires 12/2007; 24(9):1155-6. · 0.59 Impact Factor
• Article: FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study.

  J Taïeb, T Lecomte, T Aparicio, A Asnacios, T Mansourbakht, P Artru, D Fallik, J P Spano, B Landi, G Lledo, J Desrame
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  ABSTRACT: The purpose of the study was to prospectively evaluate the efficacy and tolerability of the FOLFIRI.3 regimen in patients with unresectable pancreatic adenocarcinoma. Chemotherapy-naive patients with histologically proven advanced pancreatic adenocarcinoma were treated with the FOLFIRI.3 regimen, consisting of irinotecan 90 mg/m(2) as a 60-min infusion on day 1, leucovorin 400 mg/m(2) as a 2-h infusion on day 1, followed by 5-fluorouracil (5-FU) 2000 mg/m(2) as a 46-h infusion and irinotecan 90 mg/m(2), repeated on day 3, at the end of the 5-FU infusion, every 2 weeks. Forty patients were enrolled, of whom 29 (73%) had metastatic disease. A total of 441 cycles were delivered (1-53). Grade 3-4 neutropenia occurred in 35% of the patients, accompanied by fever in two cases. Other relevant grade 3-4 toxic effects were nausea-vomiting (27%) and diarrhea (25%). Grade 2 alopecia occurred in 48% of the patients. There were no treatment-related deaths. The confirmed response rate was 37.5%. Stable disease was observed in 27.5% of the patients. The median progression-free and overall survivals were 5.6 months and 12.1 months, respectively. The 1-year survival rate was 51%. The FOLFIRI.3 regimen seems to be active on advanced pancreatic cancer and to have a manageable toxicity profile. The lack of cross-resistance between FOLFIRI.3 and gemcitabine-based regimens allows efficient second-line therapies.
  Annals of Oncology 04/2007; 18(3):498-503. · 6.43 Impact Factor
• Article: EGFR in colorectal cancer: more than a simple receptor.

  M Francoual, M-C Etienne-Grimaldi, J-L Formento, D Benchimol, A Bourgeon, M Chazal, C Letoublon, T André, N Gilly, J-R Delpero, P Lasser, J-P Spano, G Milano
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  ABSTRACT: Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR). The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon-colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis). A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue. These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.
  Annals of Oncology 07/2006; 17(6):962-7. · 6.43 Impact Factor
• Article: Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

  F Andre, N Cabioglu, H Assi, J C Sabourin, S Delaloge, A Sahin, K Broglio, J P Spano, C Combadiere, C Bucana, J C Soria, M Cristofanilli
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  ABSTRACT: Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. Primary tumors were obtained from 142 patients with axillary node-positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the 'seed and soil' theory.
  Annals of Oncology 07/2006; 17(6):945-51. · 6.43 Impact Factor
• Article: Molecularly targeted agents: their promise as cancer chemopreventive interventions.

  A Thiery-Vuillemin, T Nguyen, X Pivot, J P Spano, A Dufresnne, J C Soria
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  ABSTRACT: Molecular medicine has fully entered in to the oncology arena. The development of targeted therapies is one of the major ongoing efforts in cancer treatment. Targeted therapy refers to treatment strategies directed against molecular targets considered to be involved in neoplastic transformation. Such molecularly targeted agents (MTA) are currently under study in all treatment settings including that of chemoprevention, defined as the use of natural or synthetic agents to interrupt the carcinogenic process, to nip tumours in the bud. This review article aims to provide a general overview of the potential use of some of these MTA in the chemoprevention setting.
  European Journal of Cancer 10/2005; 41(13):2003-15. · 5.54 Impact Factor
• Article: Molecular prognostic factors in resectable non-small cell lung cancer.

  P Vielh, J-P Spano, J Grenier, T Le Chevalier, J-C Soria
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  ABSTRACT: Lung cancer retains the leading position in cancer-related deaths in the western countries. Non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancers, and complete surgical resection of primary tumors in early-stage disease is the only potentially curative treatment. One area of intense research on early-stage NSCLC is the identification of molecular markers to complement TNM staging to fully assess the prognosis of patients and to define innovative strategies. Numerous prognostic factors have been identified in patients with early-stage NSCLC that might enable classification of such patients into different subsets corresponding to different risks of recurrence following complete resection. Most of the markers are proteins that can be detected by immunohistochemistry assays based on the antigen-antibody reaction. The present review aims at providing a panorama on classical as well as new prognostic markers. Of special interest are some molecular factors, already or currently tested from a prognostic point of view, that might also become good candidates for predicting treatment efficacy.
  Critical Reviews in Oncology/Hematology 04/2005; 53(3):193-7. · 4.41 Impact Factor
• Article: Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives.

  J P Spano, R Fagard, J-C Soria, O Rixe, D Khayat, G Milano
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  ABSTRACT: Epidermal growth factor receptor (EGFR) belongs to a family of receptors known as the ErbB family (ErbB tyrosine kinase receptors) which comprises four proteins encoded by the c-erbB proto-oncogene. EGFR is known to activate a cascade of multiple signaling pathways that facilitate tumor growth process. EGFR has been shown to be overexpressed in colorectal cancer patient populations but its prognostic value in colorectal cancer progression remains unclear. The development of a panel of EGFR inhibitors could reduce the proliferation of tumor cells when used alone or in combination with cytotoxic drugs or radiation. This review focuses on the potential role of EGFR signaling in the survival of colorectal tumor cells and the possible modulation of such signaling pathways by EGFR inhibitors so as to increase tumor control or render tumor cells more sensitive to conventional therapy.
  Annals of Oncology 03/2005; 16(2):189-94. · 6.43 Impact Factor
• Article: Impact of EGFR expression on colorectal cancer patient prognosis and survival.

  J-P Spano, C Lagorce, D Atlan, G Milano, J Domont, R Benamouzig, A Attar, J Benichou, A Martin, J-F Morere, M Raphael, F Penault-Llorca, J-L Breau, R Fagard, D Khayat, P Wind
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  ABSTRACT: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.
  Annals of Oncology 02/2005; 16(1):102-8. · 6.43 Impact Factor