Beyond D'Amico risk classes for predicting recurrence after external beam radiotherapy for prostate cancer: the Candiolo classifier.

BACKGROUND: The aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D'Amico risk classification. METHODS: Two thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables' combinations were combined to classify patients into five different "Candiolo" risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D'Amico risk grouping performances. RESULTS: The Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D'Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively. CONCLUSIONS: Our classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D'Amico risk classes.

Patterns of practice in the radiation therapy management of rectal cancer: survey of the Interregional Group Piedmont, Valle d'Aosta and Liguria of the "Associazione Italiana di Radioterapia Oncologica (AIRO)".

AIMS AND BACKGROUND: To report the survey about the main aspects on the use of radiotherapy for the treatment of rectal cancer in Piedmont and Liguria. METHODS AND STUDY DESIGN: Sixteen centers (11 from Piedmont and 5 from Liguria) received and answered by email a questionnaire data base about clinical and technical aspects of the treatment of rectal cancer. All data were incorporated in a single data base and analyzed. RESULTS: Data regarding 593 patients who received radiotherapy for rectal cancer during the year 2009 were collected and analyzed. Staging consisted in colonoscopy, thoracic and abdominal CT, pelvic MRI and endoscopic ultrasound. PET/CT was employed to complete staging and in the treatment planning in 12/16 centers (75%). Neoadjuvant radiotherapy was employed more frequently than adjuvant radiotherapy (50% vs 36.4%), using typically a total dose of 45 Gy with 1.8 Gy/fraction. Concurrent chemoradiation with 5-fluorouracil or capecitabine was mainly employed in neoadjuvant and adjuvant settings, whereas oxaliplatin alone or in combination with 5-FU or capecitabine and leucovorin was commonly employed as the adjuvant agent. The median interval from neoadjuvant treatment to surgery was 7 weeks after long-course radiotherapy and 8 days after short-course radiotherapy. The pelvic total dose of 45 Gy in the adjuvant setting was the same in all the centers. Doses higher than 45 Gy were employed with a radical intent or in case of positive surgical margins. Hypofractionated regimens (2.5, 3 Gy to a total dose of 35-30 Gy) were used in the palliative setting. No relevant differences were observed in target volume definition and patient setup. Twenty-six patients (4.4%) developed grade 3 acute toxicity. Follow-up was scheduled in a similar way in all the centers. CONCLUSIONS: No relevant differences were found among the centers involved in the survey. The approach can help clinicians to address important clinical questions and to improve consistency and homogeneity of treatments.

Radiotherapy alone or with concomitant daily low-dose carboplatin in locally advanced, unresectable head and neck cancer: definitive results of a phase III study with a follow-up period of up to ten years.

AIM AND BACKGROUND: Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial. MATERIALS AND METHODS: From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin. RESULTS: The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II (21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs. 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04). CONCLUSIONS: Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.

Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design.

PURPOSE: To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer. PATIENTS AND METHODS: Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS: The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue. CONCLUSION: Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability.