Cécile Ortholan

Docetaxel-Based Chemotherapy in Elderly Patients (Age 75 and Older) with Castration-Resistant Prostate Cancer

BACKGROUND There are no data on the patterns of care and outcome of very elderly patients with castration-resistant prostate cancer (CRPC) treated with docetaxel. OBJECTIVE To assess the routine use of first-line docetaxel-based chemotherapy in CRPC patients aged >75 yr. DESIGN, SETTING, AND PARTICIPANTS We reviewed the clinical files of 175 patients aged > or =75 yr with CRPC treated with first-line docetaxel in nine French tertiary care cancer centres from 2000 to 2007. MEASUREMENTS Response rate, survival, and adverse events (AE). RESULTS AND LIMITATIONS Median age was 78 yr. Ninety-five patients (54%) received a standard 3-wk regimen (SR), and 80 patients (46%) received an adapted regimen (AR) delivered on a weekly schedule with various times for rest periods. Patients treated with an AR were older (>80 yr) and had poorer performance status (PS; > or =2) than patients treated with the SR. The prostate-specific antigen (PSA) response rates were not significantly different between the standard and adapted treatment groups (71% vs 68%, p=0.79). The median progression-free survival (PFS) was 7.4 mo. The median overall survival (OS) was 15 mo. The incidence of grade 3 or 4 AEs was 46% and was correlated with poor PS and the presence of visceral disease but not with the regimen. Early discontinuation of treatment because of toxicity occurred more frequently in the AR group than in the SR group (30% vs 8.4%, p=0.0005). In multivariate analysis, only PS and the presence of visceral disease were predictors of OS. CONCLUSIONS Docetaxel is active and feasible in elderly patients with good PS. The optimal treatment of frail patients with CRPC remains to be established. Geriatric tools should be used to more accurately detect elderly CRPC patients who are unfit for chemotherapy. Age by itself should not be used as a criterion to deny patients with CRPC a potentially effective chemotherapy.

Intensity-modulated radiotherapy in head and neck cancer: Results of the prospective study GORTEC 2004–03

BACKGROUND AND PURPOSE In 2003, the French Authority for Health (HAS) recommended the use of intensity modulated radiotherapy (IMRT) in prospective trial before its routine use. The Oncology and Radiotherapy Group for Head and Neck Cancer (GORTEC) proposed to evaluate prospectively acute and late toxicities, locoregional control and overall survival for patients treated for head and neck cancer (HNC) with IMRT and bilateral neck irradiation. MATERIALS AND METHODS Between 2002 and 2008, 208 patients with HNC were treated with IMRT in 8 centres. There were 38 nasopharynx, 117 oropharynx, 25 pharyngo-larynx, 24 oral cavity and 4 unknown primary (28.5% stage I-II and 71% Stage III-IV). Ninety-three patients (46%) had postoperative IMRT and 78 patients (37.5%) received concurrent chemotherapy. The doses were 70 Gy to the gross tumour, 66 Gy to the high-risk postoperative sites and 50 Gy to the subclinical disease. Toxicities were graded according to the RTOG-EORTC scales. RESULTS The median follow-up was 25.3 months (range: 0.4-72 months). There were 29 local-regional failures: 24 were in-field, three were marginal and one was out-field. The two-year loco-regional control and overall survival were 86% and 86.7%, respectively. At 18 months, grade ≥ 2 xerostomia was 16.1%. A mean dose to the spared parotid below 28 Gy led to significantly less grade ≥ 2 xerostomia (8.5% vs 24%) with a relative risk of 1.2 [95% CI: 1.02-1.41, p = 0.03]. Grade ≥ 2 xerostomia increased by approximately 3% per Gy of mean parotid dose up to 28, Gy then 7% per Gy above 33 Gy. CONCLUSIONS IMRT for HN cancer seems to reduce late toxicities without jeopardising local control and overall survival.

Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer.

The role of the interaction between tumor cells and inflammatory cells in nonsmall cell lung carcinoma (NSCLC) is unclear. In this study, the authors assessed the prognostic impact of intratumoral cluster of differentiation 66b (carcinoembryonic antigen‐related cell adhesion molecule 8 [CD66b])‐positive neutrophils and of the intratumoral CD66b‐positive neutrophil‐to‐cluster of differentiation 8 (cell surface antigen T8 [CD8])‐positive lymphocytes (the CD66b‐positive neutrophil‐to‐CD8‐positive lymphocyte ratio [iNTR]) in patients with resectable NSCLC.

MicroRNAs and lung cancer: new oncogenes and tumor suppressors, new prognostic factors and potential therapeutic targets.

MicroRNAs (miRNAs) are small non-protein-coding RNA that negatively control mRNA expression at a post-transcriptional level. They regulate various cellular functions and bioinformatic data suggest that they collectively control about 30% of human mRNAs. MiRNAs have been recently implicated in several carcinogenic processes, where they can act either as oncogenes or as tumor suppressors. This is the case in lung cancer, i.e. the leading cause of cancer deaths in Western countries, in which about 40-45 miRNAs have been found to be aberrantly expressed, thereby constituting a specific miRNA signature. Some of these miRNAs can play an important role in lung carcinogenesis. Indeed, some transcripts of the let-7 family that are significantly down-regulated in lung tumors have been identified as tumor suppressors through their ability to control several oncogenic pathways, including the RAS pathway. Identification of a growing number of other potential oncogenic or tumor suppressor miRNAs in lung cancers is in constant progress. Recent evidence supports the use of specific miRNA signatures to predict clinical outcome. This review aims to report the current knowledge about the role of miRNAs in lung cancer carcinogenesis, their potential for improving diagnosis and prognosis and their impact on future therapeutic strategies.

Role of Radiotherapy With Surgery for T3 and Resectable T4 Rectal Cancer: Evidence From Randomized Trials

PurposeThe main treatment for resectable rectal cancer T2–T4 N0–N2 M0 is surgery. The benefit of preoperative or postoperative radiation therapy can be analyzed in terms of improvement of local control, sphincter preservation, and survival weighted against increased toxicity.MethodsOnly randomized trials can provide strong evidence of a positive cost-benefit ratio of such combined approach. The most recent trials were reviewed.ResultsThree randomized trials, including the latest German CAO-ARO trial, have demonstrated the superiority of preoperative radiotherapy with or without chemotherapy (vs. postoperative) in terms of local control and toxicity. The Ducth TME trial showed that even with modern standard surgery, preoperative radiotherapy improved local control. Preoperative irradiation using a high dose in a small volume and a long interval before surgery may improve sphincter preservation (Lyon trials). Concurrent chemoradiation (FFCD 9203, EORTC 22921, did not significantly improve sphincter preservation or survival but significantly reduced the local recurrence rate.ConclusionsIn 2005 examination of randomized trials provides evidence for the benefit of preoperative chemoradiation in improving local control and probably sphincter preservation in rectal cancer. Randomized trials should be designed to further demonstrate improved sphincter preservation and to increase survival using adjuvant medical treatments.

Can we increase the chance of sphincter saving surgery in rectal cancer with neoadjuvant treatments: Lessons from a systematic review of recent randomized trials

PURPOSE A common hypothesis is that neo-adjuvant treatment in rectal cancer, is able to increase sphincter saving surgery. This review studies data relevant to this question. STUDY SELECTION A total of 17 randomized trials were analysed. RESULTS Since 1976, the rate of sphincter saving surgery increased from 20% to 75%. In none of the 17 trials it was possible to demonstrate a significant benefit of the neo-adjuvant regimens on the rate of sphincter saving surgery. There was a reduction in the risk of 5-year local recurrence partly due to these neo-adjuvant treatments. These neo-adjuvant regimens had no significant impact on the overall 5-year survival. CONCLUSIONS None of the neo-adjuvant treatments tested was able to demonstrate an increase in the rate of sphincter saving surgery. The improvement in conservative surgery is mainly due to technical changes in surgery. Organ preservation after complete clinical response appears as an interesting hypothesis to test.

Overexpression of carbonic anhydrase XII in tissues from resectable non-small cell lung cancers is a biomarker of good prognosis

The pattern of protein expression in tumors is under the influence of nutrient stress, hypoxia and low pH, which determines the survival of neoplastic cells and the development of tumors. Carbonic anhydrase XII (CAXII) is a transmembrane enzyme that catalyzes the reversible hydration of cell‐generated carbon dioxide into protons and bicarbonate. Hypoxic conditions activate its transcription and translation and enhanced expression is often present in several types of tumors. The aim of our study was to assess the prognostic significance of CAXII tumor tissues expression in patients with NSCLC. Five hundred fifty‐five tumors were immunostained for CAXII on tissue microarrays (TMA) and the results were correlated with clinicopathological parameters and outcome of patients. CAXII overexpression was present in 105/555 (19%) cases and was associated with tumors of lower grade (p = 0.015) and histological type (p < 0.001), being significantly higher in squamous cell carcinoma. High CAXII expression correlated with better overall and disease‐specific survival of patients with resectable NSCLC in univariate (p < 0.001) and multivariate survival analyses (p < 0.001). In conclusion, this is the first study demonstrating that a high CAXII tumor tissue expression evaluated on TMAs is related to a better outcome in a large series of patients with resectable NSCLC.

Correlation in Rectal Cancer Between Clinical Tumor Response After Neoadjuvant Radiotherapy and Sphincter or Organ Preservation: 10-Year Results of the Lyon R 96-02 Randomized Trial

PURPOSE To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial. METHODS AND MATERIALS A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months. RESULTS The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥ 50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR ≥ 50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥ 50%, and 77% for patients with CR <50% (p = 0.014). CONCLUSION In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.

Head and Neck Squamous Cell Carcinoma in Patients Aged ‡80 Years Patterns of Care and Survival

Scarce data exist concerning the outcome of very elderly patients with head and neck squamous cell carcinoma (HNSCC).

Contact X-ray Therapy for Rectal Cancer: Experience in Centre Antoine-Lacassagne, Nice, 2002–2006

PURPOSE To report the results of using contact X-ray (CXR), which has been used in the Centre-Lacassagne since 2002 for rectal cancer. METHODS AND MATERIALS A total of 44 patients were treated between 2002 and 2006 using four distinct clinical approaches. Patients with Stage T1N0 tumors were treated with transanal local excision (TLE) and adjuvant CXR (45 Gy in three fractions) (n = 7). The 11 inoperable (or who had refused surgery) patients with Stage T2-T3 disease were treated with CXR plus external beam radiotherapy (EBRT). Those with Stage T3N0-N2 tumors were treated with preoperative CXR plus EBRT (with or without concurrent chemotherapy) followed by surgery (n = 21). Finally, the patients with Stage T2 disease were treated with CXR plus EBRT followed by TLE (n = 5). RESULTS The median follow-up was 25 months. In the 7 patients who underwent TLE first, no local failure was observed, and their anorectal function was good. Of the 11 inoperable patients who underwent CXR plus EBRT alone, 10 achieved local control. In the third group (preoperative CXR plus EBRT), anterior resection was performed in 16 of 21 patients. Complete sterilization of the operative specimen was seen in 4 cases (19%). No local recurrence occurred. Finally, of the 5 patients treated with CXR plus EBRT followed by TLE, a complete or near complete clinical response was observed in all. TLE with a R0 resection margin was performed in all cases. The rectum was preserved with good function in all 5 patients. CONCLUSION These early results have confirmed that CXR combined with surgery (or alone with EBRT) can play a major role in the conservative and curative treatment of rectal cancer.