External validation of a composite bio-humoral index in anal cancer patients undergoing concurrent chemoradiation.

BACKGROUND AND PURPOSE: A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation. MATERIALS AND METHODS: Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale. RESULTS: A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively. CONCLUSION: The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable.

Topical natural-origin polynucleotides in radiation-induced skin and mucosal toxicity.

Seventy to 90 percent of patients who have received radiation treatment struggle with radiation skin and mucosal toxicity. The inflicted damage to progenitor cells and local microcirculation makes it more likely that wounds, infections, and fibrosis may occur; lesions of variable severity often co-exist. Acute erythema, hyperpigmentation, and mild desquamation usually wane in weeks and require only minor treatment. Conversely, the management of persistent radiation dermatitis and telangiectasia remains unsatisfactory; chronic lesions may progress to tissue atrophy and disfiguring fibrosis.

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Weekly concomitant boost in adjuvant radiotherapy for patients with early breast cancer: preliminary results on feasibility.

AIMS AND BACKGROUND: Recent advances in the management of patients with breast cancer are focused toward the reduction of overall treatment time of radiotherapy by delivering a dose biologically equivalent to a standard schedule. The aim of the present study was to evaluate the feasibility and preliminary toxicity of a moderately hypofractionated whole breast irradiation schedule with the addition of a concomitant boost delivered to the tumor bed once-a-week in patients with early breast cancer submitted to conservative surgery. MATERIALS: We selected patients with pT1c and pT2 N0/N+ M0 carcinoma of the breast with negative surgical margins. The basic course consisted of 4600 cGy prescribed to the ICRU 50 reference point dose and delivered in 20 fractions, 4 times a week for 5 weeks. Once a week, immediately after whole breast irradiation, a concomitant photon boost of 120 cGy was delivered to the lumpectomy area. Overall, according to the linear-quadratic model, the schedule provides a biologically equivalent dose of 87 Gy for breast tumor (assuming alpha/beta = 4 Gy), of 66 Gy for acute responding normal tissues (assuming alpha/beta = 10 Gy), and 99 Gy for late responding normal tissues (assuming alpha/beta = 3 Gy). Biologically, the schedule compares favorably with the 6-week conventional regimen consisting of 50 Gy, 2 Gy/fraction, followed by a 10 Gy boost (BED(tumor), 90 Gy; BED(acute effects), 72 Gy, and BED(late effects), 100 Gy). RESULTS: From November 2004 to April 2007, we tested this radiotherapy schedule in 176 patients. All enrolled patients had achieved a minimum follow-up of 6 months and were considered in detail for the evaluation of feasibility. Three clinical examinations were performed by a group of independent physicians at treatment end, after 1 month and after 6 months. According to the RTOG/EORTC Toxicity Criteria, of the 176 assessable patients at the end of radiotherapy, 58% showed grade 0-1 skin toxicity, 30% grade 2 and 12% grade 3. At one month of follow-up, grade 0 toxicity was observed in 47% of cases, grade 1 in 46% and grade 2 in 7%. At 6 months, late (skin and subcutaneous tissue) toxicity was assessed with the following scores: grade 0 in 68%, grade 1 in 26% and grade 2 in 6% of the patients. At 6 months, cosmesis was excellent, good and fair in 71%, 24% and 5% of patients, respectively. CONCLUSIONS: The explored adjuvant schedule planned to intensify the radiotherapy course for patients with early breast cancer by adding a weekly concomitant boost appears to be feasible and provides low local toxicity and excellent to good short-term cosmetic results.