Neoadjuvant-intensified treatment for rectal cancer:Time to change?

AIM:To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer.METHODS:Between January 2007 and December 2011,80 patients with histologically confirmed rectal adenocarcinoma were enrolled.Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes.Patients received intensified combined modality treatment,consisting of neoadjuvant radiation therapy(50.4-54.0 Gy) and infusional chemotherapy(oxaliplatin 50 mg/m 2) on the first day of each week,plus five daily continuous infusions of fluorouracil(200 mg/m 2 per die) from the first day of radiation therapy until radiotherapy completion.Patients received five or six cycles of oxaliplatin based on performance status,clinical lymph node involvement,and potential risk of a non-sphincter-conserving surgical procedure.Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment;adjuvant chemotherapy treatment was left to the oncologist's discretion and was recommended in patients with positive lymph nodes.After treatment,all patients were monitored every three months for the first year and every six months for the subsequent years.RESULTS:Of the 80 patients enrolled,75 patients completed the programmed neoadjuvant radiochemotherapy treatment.All patients received the radiotherapy prescribed total dose;five patients suspended chemotherapy indefinitely because of chemotherapyrelated toxicity.At least five cycles of oxaliplatin were administered to 73 patients.Treatment was well tolerated with high compliance and a good level of toxicity.Most of the acute toxic effects observed were classified as grades 1-2.Proctitis grade 2 was the most common symptom(63.75%) and the earliest manifestation of acute toxicity.Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients(3.75%).Seventy-seven patients underwent surgery;low anterior resection was performed in 52 patients,Miles' surgery in 11 patients and total mesorectal excision in nine patients.Fifty patients showed tumor downsizing ≥ 50% pathological downstaging in 88.00% of tumors.Out of 75 patients surviving surgery,67 patients(89.33%) had some form of downstaging after preoperative treatment.A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response(stage ypT1ypN0) in six patients.An involvement of the radial margin was never present.During surgery,intra-abdominal metastases were found in only one patient(1.25%).Initially,45 patients required an abdominoperineal resection due to a tumor distal margin ≤ 5 cm from the anal verge.Of these patients,only seven of them underwent Miles' surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup.Fourteen patients received postoperative chemotherapy.In the full analysis of enrolled cohort,eight of the 80 patients died,with seven deaths related to rectal cancer and one to unrelated causes.Local recurrences were observed in seven patients(8.75%) and distant metastases in 17 cases(21.25%).The fiveyear rate of overall survival rate was 90.91%.Using a median follow-up time of 28.5 mo,the cumulative incidence of local recurrences was 8.75%,and the overall survival and disease-free survival rates were 90.00% and 70.00%,respectively.CONCLUSION:The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival,likely due to an increase in local tumor control.

An Analysis of the Global and Partial Voice Handicap Index in Patients with Early Glottic Carcinoma Treated with High Level of Irradiation

Background: This is a retrospective study on a group of patients with early glottic carcinoma, treated with curative radiotherapy. The aim of the study is to assess voice quality after treatment. We also evaluated local recurrence, overall survival, disease free survival and toxicity. Material and Methods: We examined a total of 36 patients, out of which 27 were smokers: 10 females/5 smokers;26 males/22 smokers. The sample was observed from January 2007 to July 2012 (average follow-up period: 33.5 months, range 12 - 76). Diagnosis of early glottic carcinoma was eight during the two-year period 2007/2008, nine during 2009/2010, eleven during year 2011 and eight during year 2012. All patients suffering from early glottic carcinoma, histopathologically confirmed, were classified as follows: 24 patients T1a, 3 patients T1b, 6 patients T2 and 3 patients had a carcinoma in situ. They were treated only with conventional radiotherapy. After the treatment (total dose 70 Gy), patients were asked to fill out the Voice Handicap Index (VHI) questionnaire, composed of 30 questions that covered physical, emotional and functional areas. Results: The global VHI was evidenced with good voice quality (62% of patients: VHI < 30;34% of patients: VHI 31 - 60). Vocal disability was mild in over 70% of patients within the physical area and over 80% within the emotional area. We observed two local recurrences, one occurred five years after the end of radiation therapy and one six months after. In terms of toxicity, we observed that acute reactions, such as dysphonia, dysphagia and erythema, were relatively limited. Conclusions: The VHI index suggests that radiotherapy produces acceptable functional results, with limited repercussion on life quality. In line with literature, our data confirmed good cure rates and larynx preservation (94.4%).