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Rectal cancers stages II–III are presenting many various clinical situations. Neoadjuvant chemoradiotherapy is a standard of care in many cases, and in association with TME surgery, local relapses are becoming uncommon. None of these neoadjuvant treatments have so far improved survival, and quality of life remains non-optimal after abdomino-perineal resection and quite often after anterior resection. To increase survival through sterilization of subclinical distant metastases, new induction chemotherapy is tested. In T4 tumors, radiation dose escalation should be able to further improve local control, and in elderly patients, reduction of nCRT toxicity may provide better compliance to TME surgery. A promising approach is the use of optimal neoadjuvant treatment in early tumors in order to achieve a clinical complete response and propose an organ preservation either after local excision or using a meticulous and prolonged watch and wait strategy. Well-conducted randomized trials will be necessary to modify the present standard of care.

This study aimed to determine the candidate genes and chromosomal imbalances capable of predicting occurrences of metastasis in patients with rectal cancer. Fresh frozen tumor tissues from 80 patients with rectal cancer were prospectively collected and analyzed using Affymetrix HG-U133 Plus 2.0 gene expression arrays and high-resolution Illumina single-nucleotide polymorphism (SNP) arrays. Endpoints of the study were metastasis-free survival (MFS) and cancer-specific survival (CSS). The median follow-up was 102 months (1–146). Deletions of 8p and 1p36-35 correlated with worse MFS (p = 0.005 and p = 0.01, respectively) and CSS (p = 0.001 and p = 0.01, respectively). Multivariate analysis identified 8p deletion as an independent prognostic factor for MFS (p = 0.04) and CSS (p = 0.003); 97 genes located on the 8p chromosome were significantly underexpressed in tumors with 8p deletion. This study shows for the first time in rectal cancer an independent correlation of 8p deletion with MFS and CSS and highlights potential new tumor suppressor genes.

Radiotherapy has been driven by constant technological advances since the discovery of X-rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonstrated by randomized trials in many different types of cancer (including breast, prostate and rectum) with a high level of scientific evidence. Such achievements, of major importance for the quality of life of patients, have been fostered during the past decade by linear accelerators with computer-assisted technology. More recently, these developments were augmented by proton and particle beam radiotherapy, usually combined with surgery and medical treatment in a multidisciplinary and personalized strategy against cancer. This article reviews the timeline of 100 years of radiotherapy with a focus on breakthroughs in the physics of radiotherapy and technology during the past two decades, and the associated clinical benefits.

Colorectal cancer survival has increased in recent years, however, the impact of these cancers and their treatment on long-term survivors has not been extensively investigated at the population level. This pilot study assessed the prevalence of late outcomes in long-term colorectal cancer survivors registered by two European population-based cancer registries (CRs) to determine the feasibility of using the approach on a wider basis in Europe. Long-term survivors diagnosed in 1990 and in 1997 in Cote d’Or (France) and Varese (Italy) CRs were surveyed. Questionnaires to general practitioners (GPs) and survivors investigated a wide range of outcomes. Information on stage at diagnosis, primary treatment, stoma inserted during main surgery, and vital status was available from a previous study. Logistic regression was used to identify associations of late outcomes with sex, age at survey, country, year of diagnosis, and site. Participation was 51.8% (45.2% of French and 56.6% of Italian cases identified). Of the 256 survivors available for analysis, 10% had bowel incontinence, about 70% had other bowel, gastrointestinal, or urination problems, 10% had second primary cancer, 4% had colorectal recurrence, and 10% had stoma. The proportion with stoma reduced by 65% in survivors diagnosed between 1990 and 1997, but no other outcomes reduced in prevalence with time. Most (67%) had optimal GP-assessed ECOG performance status. Around 80% were followed-up with liver imaging or colonoscopy. We identified non-trivial rates of bowel and bladder problems after colorectal treatment, but overall good levels of functioning. High-resolution studies of this kind must be population-based to provide data useful for public health provision. This pilot study encountered difficulties in contacting GPs and suffered from low compliance. However, it is the first to investigate late outcome trends after treatment for colorectal cancer.

Neoadjuvant treatment is becoming the standard for T3-4 (distal T2) rectal adenocarcinoma. Phase III ongoing clinical trials will yield the definition of optimal concurrent chemoradiotherapy protocol. Phase II trials will test new medical treatments (targeted biotherapy) and innovative radiation technique (contact radiotherapy). Most importantly, phase II and III trials will address the question of new strategies using neoadjuvant approach to improve conservative treatment and survival rates.

In rectal cancer, the problem of sphincter preservation is of increasing interest. This paper is a review of recent data regarding sphincter preservation. Randomized trials give the best evidence of any improvement in sphincter preservation. Such trials have been performed for T3 and T2 rectal cancers. For T2-3 rectal tumors immediate surgery after preoperative radiotherapy or the addition of chemotherapy to radiotherapy did not improve the chance of sphincter preservation. Only dose escalation with endocavitary contact x-ray and delayed surgery was able to achieve a 30% increase in sphincter preservation. Ongoing clinical research is exploring the role of preoperative chemoradiotherapy in early T2 (T3) rectal cancers combined with local excision. This approach is of special interest in elderly patients. Sphincter preservation is a very complex issue in rectal cancer requiring great clinical experience to select properly the patients to perform the optimal treatment.

To report our patient experience with squamous cell carcinoma of the anal margin and to evaluate the prognostic factors influencing outcome. Between 1980 and 2001, 26 patients with anal margin squamous cell carcinoma were treated in Lyon-Sud: 7 T1, 14 T2, 4 T3, and 1 T4 with 20 N0, 3 N1, and 3 N2. The anal canal was invaded in five patients. Treatment consisted of definitive external irradiation in 14 patients and adjuvant irradiation (after a local excision) in 12 patients. External irradiation was combined with chemotherapy in seven patients, brachytherapy in four patients, and both brachytherapy and chemotherapy in one patient. The local control rate was initially 61.4%, and it was 80.8% after salvage treatment. The 5-year overall and specific survival rates were 71 and 88.3%, respectively. Three factors correlated with specific survival: cell differentiation (P=0.038) and T (P=0.001) and N category (P=0.0005). A salvage abdominoperineal resection was successfully employed in five of seven local recurrences. Four grade 3 and two grade 4 toxicities were observed. Sphincter preservation was possible in 66% of alive patients. Our results confirm the dominating place of definitive irradiation and radiochemotherapy in the treatment of anal margin squamous cell carcinoma. The indications for abdominoperineal resection must be limited to local relapse. The prognosis of squamous cell carcinoma is correlated to T and N staging and cell differentiation.

Purpose. Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas.