Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution.

PURPOSE: The aim of our study was to evaluate the feasibility and the effectiveness of an intensified neoadjuvant protocol with the addition of weekly oxaliplatin in the preoperative strategy of rectal cancer treatment. PATIENTS AND METHODS: Patients with locally advanced rectal cancer received continous infusion 5-Fluorouracil (5-FU) 200 mg/m(2)/day in combination with weekly oxaliplatin at a dose of 50 mg/m(2). Doses of radiotherapy were 45 Gy to the whole pelvis plus 5.4-9 Gy to the tumour mass. The primary end-points of the study were evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response (pCR) and the rate of sphincter preservation for distal cancers. Secondary end-points were relapse-free and overall survival. RESULTS: From November 2006 to June 2009, 51 patients were enrolled into the study. Compliance with chemotherapy was 80%. The incidence of G3 diarrhoea and proctitis were 17.6% and 21.5%, respectively. Surgery was performed in 48 patients with 100% R0 resection. 76.4% of low-lying tumours underwent conservative treatment. Seventy-nine percent of patients were downstaged: T and N downstaging were observed in 71% and 75% of patients, respectively. A pCR was obtained in 11 (22.9%) patients. CONCLUSIONS: Intensification of neoadjuvant treatment for rectal cancer with the addition of weekly oxaliplatin is feasible, with remarkable rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. Phase III trials with a longer follow-up will establish whether this good outcome in terms of surrogate end-points will translate into better rates of disease-free and overall survival.

Comparison between intensified neoadjuvant treatment and standard preoperative chemoradiation for rectal cancer.

OBJECTIVES: The aim of the current study was to compare a neoadjuvant regimen containing oxaliplatin with standard preoperative treatment for rectal cancer. METHODS: From December 2006 to December 2007, 20 patients with rectal cancer were treated at our Institution with the weekly addition of oxaliplatin (50 mg/m(2)) to radiotherapy (50.4-54.0 Gy in 28-30 daily fractions) and continuous infusion of 5-fluorouracil (200 mg/m(2)). The results of the regimen were compared with a historical control group including 21 consecutive patients previously treated with standard 5-fluorouracil treatment from December 2004 to October 2006. RESULTS: Both the rate of sphincter preservation in low rectal cancer (91.7% vs 36.4%, P = 0.009) and the rate of downstaging (84.2% vs 47.6%, P = 0.023) were higher in the oxaliplatin group than in the control group. Pathological complete response was achieved in 8 patients (42.1%) in the oxaliplatin group and in 4 patients (19.0%) in the control group (P = 0.172). When ypT0-pT1 stages were analyzed together, the P value was 0.051. Acute toxicity was increased in the oxaliplatin group, with a higher incidence of G3 diarrhea and pelvic pain than in the control group (30.0% vs 14.3%, P = NS). CONCLUSIONS: Our data seem to correlate the addition of oxaliplatin to the standard treatment for rectal cancer with higher rates of sphincter preservation, down-staging and complete response. Toxicity is increased and requires careful monitoring. However, our results refer to a retrospective comparison of a small series of patients and need to be validated by the large, phase III randomized trial currently ongoing.

[Integrated multidisciplinary treatment of colorectal neoplasms]. / Trattamento multidisciplinare integrato delle neoplasie colo-rettali.

In this retrospective study, the modality and advantages of the multidisciplinary diagnostic work-up and therapy regarding colorectal neoplasm were analysed. Over the period 2004-2008, 63 patients underwent multidisciplinary treatment for colorectal cancer. All patients underwent surgery (laparoscopic/open). Exeresis was supplemented by adjuvant chemotherapy in those cases beyond IIA stage; all cases of extraperitoneal rectal and anal canal neoplasms plus one case of carcinoma of the transverse colon, initially inoperable, underwent neoadjuvant radiotherapy plus chemotherapy. The treatment was initiated approximately 3 weeks after the diagnosis. Fifty-four percent of patients with colonic and upper rectal neoplasms were given adjuvant chemotherapy, starting around 4 weeks after surgery. Exeresis was performed in those patients with extraperitoneal rectal and anal canal neoplasms (12.7%) about 6-8 weeks after they had completed neoadjuvant therapy. At the end of the treatment, 76% of the overall total numbers of patients were in good condition (follow-up 4-50 months). The remaining 24% suffered recurrences about 13 months after the treatment for colonic and upper rectal neoplasm, and 8 1/2 months after treatment for extraperitoneal rectal/anal canal neoplasms. Seventy-five percent of the recurring cases underwent treatment again, with 50% success; the others are still undergoing treatment. The best therapeutic results were obtained by programmed integration of the various diagnostic-therapeutic steps according to an algorithm which we elaborated to evaluate all types of neoplasm at any stage of illness.

Radiotherapy and chemotherapy in the conservative treatment of anal canal carcinoma.

AIM: To evaluate the feasibility of conformal radiotherapy and concurrent chemotherapy in patients with anal canal carcinoma. PATIENTS AND METHODS: Between 1990 and 2006, 83 patients affected by anal canal carcinoma were treated at the Radiotherapy Department of "La Sapienza" University of Rome. In all patients, a daily dose of 1.8 Gy, five times per week, was given for a total dose of 45 Gy for the whole pelvis (CTV1) and of 55-60 Gy for the tumor bed (CTV2). In 63 patients, chemotherapy consisted of two cycles of 5-fluorouracil (5-FU) and mitomycinC (MMC) or cisplatin delivery during the first and last week of radiotherapy. RESULTS: The median follow-up time for all patients was 56.2 months. Treatment response was considered complete in 53 patients (63.8%) and partial in 30 patients (36.1%). Local tumor relapse was observed in 13 patients (15.6%). The probability of overall survival for all patients at 5 years was 75%: 39% in patients who underwent radiotherapy alone and 85% in patients who underwent radiochemotherapy (p=0.0013). Concerning acute toxicity, 9 patients developed grade 1 skin toxicity (10.8%), 35 grade 2 (42.1%), 26 grade 3 (31.3%) and 3 grade 4 (3.6%); eleven patients had grade 2 diarrhea (14.5%) and 2 grade 3 diarrhea (2.4%). CONCLUSION: This analysis suggests that the treatment scheme employed was effective for anal sphincter preservation and local control.

Prognostic implication of clinical and pathologic features in patients with glioblastoma multiforme treated with concomitant radiation plus temozolomide.

AIMS AND BACKGROUND: Glioblastoma multiforme is the most common and most malignant primary brain tumor in adults. The current standard of care for glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy plus temozolomide, given concomitantly with and after radiotherapy. This report is a prospective observational study of 43 cases treated in the Department of Radiotherapy, University of Rome La Sapienza, Italy. We examine the relationship between pathologic features and objective response rate in adult patients treated with concomitant radiation plus temozolomide to identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance. METHODS: Forty-three consecutive patients (24 males and 19 females), ages 15-77 years (median, 57) with newly diagnosed glioblastoma multiforme, were included in this trial between 2002 and 2004 at our department. All patients were treated with surgery (complete resection in 81%, incomplete in 19%) followed by concurrent temozolomide (75 mg/m2/day) and radiotherapy (median tumor dose, 60 Gy), followed by temozolomide, 200 mg/m2/day for 5 consecutive days every 28 days. Neurologic evaluations were performed monthly and cranial magnetic resonance bimonthly. We analyzed age, clinical manifestations at diagnosis, seizures, Karnofsky performance score, tumor location, extent of resection, proliferation index (Ki-67 expression), p53, platelet-derived growth factor and epidermal growth factor receptor immunohistochemical expression as prognostic factors in the patients. The Kaplan-Meier statistical method and logrank test were used to assess correlation with survival. RESULTS: Fourteen patients (32%) manifested clinical and neuroradiographic evidence of tumor progression within 6 months of surgery. In contrast, 5 patients (12%) showed no disease progression for 18 months from the beginning of treatment. Median overall survival was 19 months. Multivariate analysis revealed that an age of 60 years or older (P <0.03), a postoperative performance score < or =70 (P = 0.04), the nontotal tumor resection (P= 0.03), tumor size >4 cm (P = 0.01) and proliferation index overexpression (P = 0.001) were associated with the worst prognosis. p53, PDGF and EGFR overexpression were not significant prognostic factors associated with survival. CONCLUSIONS: The results suggest that analysis of prognostic markers in glioblastoma multiforme is complex. In addition to previously recognized prognostic variables such as age and Karnofsky performance score, tumor size, total resection and proliferation index overexpression were identified as predictors of survival in a series of patients with glioblastoma multiforme.

Chemoradiation as definitive treatment for primary squamous cell cancer of the rectum.

In this report, we present a case of advanced squamous cell cancer located in the rectum of a 78-year-old woman treated with chemoradiation with curative intent. The patient showed a complete clinical response to chemoradiation; multiple biopsies were performed at the site of the previous mass 5 mo after the end of treatment and histological examination showed no residual tumour in the specimens. Surgical intervention was avoided and the patient was free of disease 12 mo after the diagnosis of cancer. Primary chemoradiation should be considered as the treatment of choice for this rare malignancy.

Irradiated fields spared Stevens-Johnson syndrome in a patient undergoing radiotherapy for bone metastases.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe, rare, and life-threatening adverse reactions to medications. Their incidence is approximately two patients per million population per year. Several cases have been reported in the literature in which SJS and TEN have occurred in patients with a neoplasm undergoing radiation therapy and who are taking an anticonvulsant. We report a case of SJS-TEN that developed in a 51-year-old woman with nonresectable non-small-cell lung cancer during treatment with phenobarbital plus radiation therapy for bone metastases but in whom the irradiated areas did not exhibit the SJS skin reaction. To our knowledge, no similar cases have been reported in the literature.

Radiotherapy and sequential temozolomide compared with radiotherapy with concomitant and sequential temozolomide in the treatment of newly diagnosed glioblastoma multiforme.

Our objective was to determine and compare effects of sequential temozolomide vs. concomitant plus sequential temozolomide with conventional radiotherapy, in patients with newly diagnosed glioblastoma multiforme, comparing two independent trials. Sixty-four patients were treated on two consecutive separate phase II studies that used identical eligibility criteria and the same radiotherapy (60 Gy, 2 Gy/day, after surgery) and adjuvant temozolomide (200 mg/m/day for 5 days/28 days until progression), but differed in the absence or presence of a concomitant treatment with temozolomide (75 mg/m/day) during radiotherapy. In the first protocol (1999-2002), 21 patients (median age of 64 years) received radiotherapy alone and sequential temozolomide; in the succeeding protocol (2002-2004), 43 patients (median age of 61 years) with similar characteristics received radiotherapy with concomitant and sequential temozolomide. Median number of adjuvant cycles was five in both trials. Median survival was similar in both studies (18 vs. 17.4 months); overall survival rates at 6, 12, 18 and 24 months of all the population were 89, 69, 45 and 24%. No statistically significant differences were found among prognostic factors considered. Hematologic toxicities were mild and similar, with grade 3-4 neutropenia in 5-7% and grade 3-4 thrombocytopenia in 7-10% of patients in the sequential phases, and grade 3-4 thrombocytopenia in 7% in the concomitant phase of temozolomide. We confirmed that temozolomide combined with radiotherapy is well tolerated and provides a survival advantage compared with historical data using radiotherapy alone. Nevertheless, a concomitant use of temozolomide during radiotherapy does not seem to improve survival, although it does not increase toxicity.