Patients with locally advanced rectal cancer: predictive factors of pathological response and prognostic factors

In this retrospective study we analyzed the data of 119 consecutively patients affected by LARC, without evidence of distant metastases,treated in Pisa Universitary Hospital, between January 2008 and April 2014, with neoadjuvant RTCT. The primary endpoint of this retrospective analysis is to identify predictive factors of response to neoadjuvant RTCT, which could be used in the next future for treatment decision making. The second endpoint is to identify in this subset of patients the prognostic factors related to OS and DFS

Da tolerância à solidariedade: superação necessária ao exercício da cidadania, na construção de uma sociedade mais democrática

Esse artigo aborda a tolerância e a solidariedade, enquanto virtudes necessárias para o exercício da cidadania. Para tanto, parte-se da história da América Latina, que nos traz uma atualidade regada a injustiça e a violência, contexto este que compõe um sistema de dominação, vigente em nossa sociedade. Após algumas considerações sobre democracia e cidadania, argumenta-se sobre a tolerância e a solidariedade como virtudes imprescindíveis para a formação humana, quando se pretende uma participação social que prime pela luta na construção de uma sociedade para todos e todas, menos injusta e mais democrátic

Radiotherapy in the COVID-19 Pandemic Era

Background/Aim: In 2020, because of coronavirus pandemic, medical activities changed. The aim of this report is to compare the volumes of Pisa radiotherapy activities from March 9th to May 31st, 2020, with the same period in 2019. Patients and Methods: We analyzed the activity of our Unit to evaluate how logistics changes, related to the COVID-19 epidemic, impacted on volumes of radiotherapy (RT) activity and on the number of cases of COVID-19 infections observed in healthcare professionals and patients. Results: The total number of first-time visits between March-May 2020 was reduced by 18%, probably due to delays in diagnosis and histological tests as well as the temporary closure of the operating rooms. None of the healthcare professionals and only two patients contracted the infection. Conclusion: We were able to treat all patients referred to our hospital and we were able to reduce risk of infection for both our patients and healthcare staff, guaranteeing continuum of care for our oncological patien

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The impact of indeterminate pulmonary nodes at baseline ct staging in patiens affected by locally advanced rectal cancer and the possible role of liquid biopsy in their characterization

The aim of this monocentric retrospective study was to study the impact of indeterminate pulmonary nodules evidenced at initial chest CT scans in patients affected by locally advanced rectal cancer treated with neoadjuvant RTCT and the possible role of liquid biopsy in their characterization

PET based target volume delineation in hypofractionated radiotherapy in locally advanced NSCLC: A single institution experience

Background: Chemo-radiotherapy is the standard of care of locally advanced (stage III) unresectable non-small cell lung cancers (NSCLC). Concomitant chemo-radiotherapy reduces local failure compared to sequential schedules but distant failures remain common (about 40%). Conventional radiotherapy is given in 2Gy fractions over 6−7 weeks of treatment (total dose 60−70Gy) conditioning the patent’s quality of life. Stereotactic body radiotherapy (SBRT) is effective for the treatment of early stage NSCLCs not eligible for surgical resection. The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. We evaluated the feasibility of short course hypo fractionated radiotherapy with PET assisted visual-manual target delineation, given between chemotherapy cycles, in locally advanced NSCLCs. Methods: Patients, with a proven histological diagnosis of NSCLC, were enrolled if deem not resectable. Inclusion criteria were: maximum diameter of the primary tumor 1). All patient underwent 18FFDG PET-CT within 1 month from the beginning of the treatment and mean SUVmax was 12.6 (range 3.8–33.8). A total dose of 40 Gy was given in 5 fractions of 8Gy using volumetric modulated arch therapy and flattening filter free 6MV photon beams. Dose constraints from AAPM task group 101 were respected for organs at risk. Planning target volumes were delineated using the 18F-FDG uptake as reference and included the primary tumor and every clinically evident lymph node metastases. Platinum doublets were the preferred chemotherapy regimen (8 patients). Toxicity was evaluated according to CTCAE v4 and tumor response according to RECIST criteria 1.1 Results: From February 2014 to January 2015, 15 patients (11 males and 4 females) have been enrolled with a median age of 71 years (range 53−86). Performance status was 0 in 5 patients and 1 in the remaining. Eight were adenocarcinomas, 4 squamous cell carcinomas and 3 not otherwise specified NSCLCs. The median size of the primary tumor was 49mm (range 17−77; T1 13%, T2 13%, T3 27%, T4 47%). Five had N2, 3 N1 and 2 N3 lymph node metastases. Side effects were 7% of G1 esophagitis and 7% of G1 cough. Ten patients have been currently evaluated for response: partial responses 8 (80%) and stable disease 2 (20%), no local progression have been observed. Conclusions: Hypofractionated radiotherapy with PET-based target volume delineation is feasible with the current schedule in locally advanced NSCLCs with mediastinal spread and foresees promising results

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

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 â¥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/m2weekly). 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) â¤70 and â¥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 â¤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

Stereotactic Body Radiotherapy in Patients with Lung Oligometastases from Colorectal Cancer

AIM: To assess the role of stereotactic body radiotherapy (SBRT) in pulmonary metastases from colorectal cancer (CRC). PATIENTS AND METHODS: Thirty-three consecutive patients with pulmonary metastases from CRC who received SBRT were included in the analysis. The primary endpoints were local and systemic progression-free survival, a secondary endpoint was the safety profile of SBRT. RESULTS: A total of 56 lesions were treated with SBRT. A single nodule was treated in 15 patients, two in 13 and three in five. The radiotherapy dose and the adopted fractionations were 24-27 Gy as a single fraction for 40 lesions and 27-42 Gy in three fractions (2-3 times a week) for the other 16 lesions. After a median follow-up of 22.8 months (range=1.3-45.7 months), the median progression-free survival of the irradiated sites was 13.4 months. CONCLUSION: SBRT can be considered as local therapy in patients with lung metastases from CRC