The value of oxaliplatin in the systemic treatment of locally advanced rectal cancer.

BACKGROUND: To evaluate, in a context of innovative multidisciplinary clinical practice, the efficacy of oxaliplatin in adjuvant administration (chemotherapy, CT) in relation to the total administered dose, in terms of prognosis with other clinical and therapeutic factors, in the heterogeneous model of locally advanced rectal cancer (LARC), which is characterized by a risk pattern of dominant systemic progression. METHODS: Observational-analytical, retrospective, unicentric, non-randomized study of two cohorts of patients receiving FOLFOX-4 induction CT in neoadjuvancy, radiochemotherapy and surgery, differing in that one cohort did not receive any adjuvant post-surgical treatment and the other one received adjuvant CT with FOLFOX-4 cycles. A total of 212 patients from the Radiotherapy Oncology Service at the University Hospital Gregorio Marañon were studied: the neoadjuvant CT treatment group with oxaliplatin consisted of 110 patients and adjuvant CT treatment group with oxaliplatin consisted of 102 patients. The median follow-up time for the whole study population was 72 months (6 years). RESULTS: The sociodemographic, clinical and diagnostic characteristics were very similar in both cohorts of patients, but with a pattern of therapeutic selection towards elements of adversity in pathological post-neoadjuvant staging. The dose of oxaliplatin in adjuvance (postoperative) superior to 6 cycles was positively associated with the locoregional control (LRC) at 5 years (P=0.012) and with the overall survival (OS) (P=0.048) at 5 years. In the responders to neoadjuvance with oxaliplatin [patients with tumor regression grade (TRG 3-4)], the dose of oxaliplatin greater than 5 cycles in adjuvance (postoperative) was positively associated with OS (P=0.06). And the dose of oxaliplatin in the range of 4-5 cycles in adjuvance (postoperative) was positively associated with distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the cohort of responding patients (P=0.015 and 0.004, respectively). CONCLUSIONS: The contribution of adjuvant oxaliplatin in the oncological evolution shows a favorable effect of LRC, DMFS, DFS and OS in the subgroups of patients that exhibit elements of response to neoadjuvant oxaliplatin (categories TRG 3-4, and pN0, downstaging T, downstaging N). Therefore, this neoadjuvant response profile with oxaliplatin, measured with highly reliable methodology (validated microscopic pathological response scales), defines a population of oxaliplatin-sensitive patients who benefits significantly from the administration of adjuvant oxaliplatin in sufficient cumulative doses (more of 5 cycles).

Neurological complications after gamma-knife radiosurgery for hypothalamic hamartoma.

BACKGROUND: The Gamma-knife technique is a safe and effective option for the treatment of hypothalamic hamartomas that produce epileptic seizures refractory to medical treatment and/or serious behavioral disorders. After this type of radiosurgery, an adequate symptomatic control is normally achieved, with notable decrease or even disappearance of the seizures. Radiological changes, such as a decrease in the size of the tumor or adjacent edema secondary to non-necrotizing radioinduced inflammatory reaction are unusual consequences. Side effects and neurological complications are also rare events. CASE PRESENTATION: This report describes an unusual case of complete radiological resolution of a hypothalamic hamartoma as well as neurological complications after Gamma-knife surgery (receiving 13 Gy to the 85% isodose line, 1 cm(3) of tumor volume) in a 8-year-old boy who suffered from severe refractory seizures. After radiosurgery, the patient experienced a notable improvement in his symptoms, achieving seizure cessation within 3 months. However, 4 months after the procedure he presented drowsiness, fever and decreased level of consciousness due to a direct effect on the hypothalamus with local and regional edema secondary to the radiosurgery that was performed. He was successfully treated with corticosteroids (with a total duration of 11 months), and twelve months after the surgery, complete disappearance of both the nodular lesion and the secondary edema was observed. The patient remains seizure-free in the last 16 months, with remarkable changes in his behavior. CONCLUSIONS: The present case shows that complete radiological resolution of a hypothalamic hamartoma after Gamma-knife technique is unusual but possible, without long-term neurological consequences. Nevertheless, despite its low incidence, if a patient presents neurological symptoms, primarily during the first year after intervention, possible complications of this type of surgery must be taken into account.

intraoperative radiation therapy part 2. Clinical results.

Intraoperative radiation therapy (IORT) has been used for over 30 years in Asia, Europe and America as a supplementary activity in the treatment of cancer patients with promising results. Modern IORT is carried out with electron beams (IOERT) produced by a linear accelerator generally used for external beam irradiation (EBRT) or a specialized mobile electron accelerator. HDR brachytherapy (HDR-IORT) has also been applied on selected locations. Retrospective analysis of clinical experiences in cancer sites such as operable pancreatic tumour, locally advanced/recurrent rectal cancer, head and neck carcinomas, sarcomas and cervical cancer are consistent with local tumour control promotion compared to similar clinical experiences without IORT. New emerging indications such as the treatment of breast cancer are presented. The IORT component of the therapeutical approach allows intensification of the total radiation dose without additional exposure of healthy tissues and improves dose-deposit homogeneity and precision. Results of the application of IORT on selected disease sites are presented with an analysis on future possibilities. To improve the methodology, clinical trials are required with multivariate analysis including patient, tumour and treatment characteristics, prospective evaluation of early and late toxicity, patterns of tumour recurrence and overall patient outcome.

Intraoperative radiation therapy first part: rationale and techniques.

Intraoperative radiotherapy (IORT) is a technique where a high, single-fraction radiation dose is delivered during a surgical procedure to macroscopic tumours or tumour beds with minimal exposure of surroundings tissues which are displaced and shielded during the procedure. In this paper, the rationale for and use of IORT, both with electron beams (IOERT) and high-dose-rate brachytherapy (HDR-IORT) are discussed. For most tumours, the likelihood of obtaining local control (LC) improves when increasing doses can be administered. In many clinical situations, however, the dose that can be delivered safely to the tumour target is limited by the risk of damaging normal tissues. Special consideration is therefore given on this paper to the relationship between dose, LC and possible complications. Criteria for patient's selection and evaluation and information on sequencing and techniques are presented as well as some considerations on the need for a proper programme on quality assurance and periodical reporting of data.