S. Montrone

A new nomogram for estimating survival in patients with brain metastases secondary to colorectal cancer

BACKGROUND The prognosis of brain metastases (BM) in colorectal cancer (CRC) is extremely poor, but the incidence is increasing. The performance of existing prognostic classifications such as recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) has never been evaluated in this specific setting. Moreover, the development of nomograms for estimating survival in such patients could be extremely helpful for treating physicians. PATIENTS AND METHODS Between 2000 and 2013, data from 227 patients with BM from CRC were collected at 8 Italian institutions. Overall survival (OS) was estimated with the Kaplan-Meier method and statistical comparison between curves was performed using the log-rank test. The discriminative ability for OS of RPA and GPA was assessed by the Harrell C-index from univariable Cox models. Putative prognostic factors for OS were also studied by multivariable Cox analysis, using the Harrell C index to evaluate the model discriminative ability. After a backward variable selection, a nomogram was developed to predict median survival time from individual patient- and tumor-related characteristics. The nomogram was externally validated on an independent series. RESULTS After a median follow-up of 59 months, fifty percent of patients were still at risk at 5 months. The C index was 0.594 and 0.607 for the RPA and GPA classifications, respectively. The C-index associated with the final multivariable Cox model used for developing the nomogram was 0.643; the favorable prognostic factors for survival were lower age (p=0.061), better Karnofsky performance status (p<0.001), supratentorial site of BM (p<0.001), and lower number of BM (p=0.035). The C index evaluated on the validation series was 0.733, even better than in the development series; also, the calibration of nomogram predictions was good. CONCLUSION The C-index associated to the nomogram model was slightly higher than that obtained for the RPA and GPA classifications. Most importantly, the very satisfactory results of nomogram validation on the external series, make us confident that our instrument may assist in prognostic assessment, treatment decision making, and enrollment into clinical trials.

Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Highlights • A large population based analysis to evaluate pathologic response according to time of surgery.• LARC patients were treated with modern techniques of radiotherapy and surgery.• The rate of pCR increased according to time interval from 12.6% to 31.1%.• The pCR increasing was 1.5% (about 0.2%/die) per each week of waiting.• Lengthening the interval (>13 weeks) significantly improved the pathological response.

Stereotactic body radiotherapy of bone metastases in oligometastatic disease: prognostic factors of oncologic outcomes.

Background To evaluate the safety of stereotactic body radiotherapy (SBRT) of bone metastases in oligometastatic disease and to investigate prognostic factors of local control (LC), progression/disease-free survival (PDFS), and overall survival (OS). Methods Eligibility criteria were number of metastates ≤5, controlled primary tumor without evidence of progression under systemic therapy, exclusion of surgery, and no previous radiotherapy of the lesion of interest. Oligometastatic status was classified into only bone (BOD) and outside bone disease (OBOD), whereas SBRT was delivered to bone lesions using 2 different schedules: 24 Gy/1 fraction or 27 Gy/3 fractions. A positron emission tomography study of the lesion of interest was performed at baseline and at 3 months after SBRT to evaluate metabolic response according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A Cox regression model was used for univariate and multivariate analysis. Results Between January 2010 and December 2013, 40 patients were enrolled. Only 1 patient experienced severe late toxicity (radiation-related fracture). Local control was longer among responders’ than nonresponders’ lesions (94.2% and 91.2% versus 63% and 35% at 1 and 2 years, respectively) (p = 0.004; hazard ratio = 9.958). The multivariate analysis of PDFS showed a significant correlation with planning target volume (PTV) size (p = 0.003) and oligometastatic status (p = 0.002). The multivariate analysis of OS confirmed a statistically significant value of the oligometastatic status (p = 0.002) and a significant trend for PTV size (p = 0.065). Conclusions Stereotactic body radiotherapy is safe with a low incidence of severe toxicity. Positron emission tomography response was a strong prognostic factor of LC whereas BOD status and small PTV size could identify a subset of oligometastatic patients at better prognosis.

Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early Versus Delayed Administration

Background/Aim: In patients with recurrent glioblastoma, the best timing to administer bevacizumab is not well addressed yet. In this study, we reported the results of a monocentric experience comparing the early use of bevacizumab (following the first GBM recurrence) with the delayed administration (following the second or even further GBM recurrences). Materials and Methods: This analysis included 129 glioblastoma patients with a median follow-up of 22.4 months (range=5.26-192 months). Results: The median time lapse from diagnosis of glioblastoma to disease recurrence was 11.6 months; 13.1 for patients treated with deferred administration of bevacizumab and 9.9 for patients with early administration (p=0.047). Bevacizumab progression-free survival with early and delayed use was 3.45 and 2.92 months, respectively (p=0.504). Survival time from the start of bevacizumab was 6.18 months in patients with early administration, and 6.47 in the delayed administration one (p=0.318). Conclusion: Delayed administration of bevacizumab can be considered in selected patients with less aggressive recurrent glioblastoma.

Adjuvant chemoradiotherapy (gemcitabine-based) in pancreatic adenocarcinoma: the Pisa University experience.

Introduction The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. Methods 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly). Results Median follow-up was 22.7 months (range 4-109). Gastrointestinal toxicity (G3), neutropenia (G3-G4) and cardiac toxicity (G2-G3) were observed in 2.4%, 10.6% and 1.6% of patients, respectively. OS at 12, 24 and 60 months was 79%, 55% and 31%, respectively (median 25 months). Two-year OS in patients with postoperative Karnofsky performance status (KPS) ≤70 and ≥80 was 37.1% and 62.3%, respectively (p<0.0001). OS was better in the group of patients with a postoperative CA 19-9 level ≤100 U/mL (p = 0.014). Median DFS was 17 months. Conclusions The combination of concomitant gemcitabine and radiotherapy in patients with radically resected PA was well tolerated and associated with a low incidence of local recurrences. Five-year OS was significantly influenced by postoperative KPS and CA 19-9 values.

Induction treatment with FOLFOXIRI + bevacizumab (BV) followed by chemo-radiotherapy (CRT) + BV and surgery in locally advanced rectal carcinoma (LARC): The phase II TRUST trial.

673 Background: Induction chemotherapy (CT) is a promising option in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer. Methods: Patients (pts) with LARC at < 12 cm from the anal verge, N+ or cT4 or high risk cT3 (MRI criteria) underwent 6 cycles of FOLFOXIRI + BV followed by CRT (50.4 Gy + 5FU 225 mg/m2/day or capecitabine 800 mg/m2/bid 5 days/week + BV 5 mg/kg on days 1, 15, 28). Surgery was planned 8 weeks after CRT. Primary endpoint is 2-year disease-free survival (DFS). Results: From April 2012 to April 2015 48 pts were enrolled. At now, 46 pts completed induction CT, 43 completed CRT and 39 underwent surgery (5 pts ongoing). Pts characteristics were: median age, 53 years (range 30-74); cT2/cT3/cT4, 4%/60%/36%; cN0/N+, 4%/96%. Main grade (G) 3/4 toxicities during induction were neutropenia (42%), febrile neutropenia (4.2%), diarrhea (12.5. Two pts did not complete induction: one died due to bowel perforation and sepsis and one discontinued CT after acute kidney injury. Re...