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

Pattern of care for re-irradiation in locally recurrent rectal cancer: a national survey on behalf of the AIRO gastrointestinal tumors study group

PurposeRadical resection (R0) represents the best curative treatment for local recurrence (LR) rectal cancer. Re-irradiation (re-RT) can increase the rate of R0 resection. Currently, there is a lack of guidelines on Re-RT for LR rectal cancer. The Italian Association of Radiation and clinical oncology for gastrointestinal tumors (AIRO-GI) study group released a national survey to investigate the current clinical practice of external beam radiation therapy in these patients.Material and methodsIn February 2021, the survey was designed and distributed to members of the GI working group. The questionnaire consisted of 40 questions regarding center characteristics, clinical indications, doses, and treatment techniques of re-RT for LR rectal cancer.ResultsA total of 37 questionnaires were collected. Re-RT was reported as an option for neoadjuvant treatment in resectable and unresectable disease by 55% and 75% of respondents, respectively. Long-course treatment with 30-40 Gy (1.8-2 Gy/die, 1.2 Gy bid) and hypofractionated regimen of 30-35 Gy in 5 fractions were used in most centers. A total dose of 90-100 Gy as EqD2 dose (& alpha;/& beta; = 5 Gy) was delivered by 46% of the respondents considering the previous treatment. Modern conformal techniques and daily image-guided radiation therapy protocols were used in 94% of centers.ConclusionOur survey showed that re-RT treatment is performed with advanced technology that allow a good management of LR rectal cancer. Significant variations were observed in terms of dose and fractionation, highlighting the need for a consensus on a common treatment strategy that could be validated in prospective studies

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

Studio multicentrico di fase II di chemioterapia sequenziale con irinotecano (CPT-11) + capecitabina seguita da oxaliplatino (LOHP) + capecitabina, nel paziente anziano affetto da carcinoma colorettale metastatico.

I pazienti anziani affetti da carcinoma colorettale metastatico sono spesso sottoposti ad un inadeguato trattamento chemioterapico per il timore che sviluppino eccessive tossicita'-trattamento correlate. In realta', esiste una percentuale di pazienti anziani che, per le loro caratteristiche fisiche e psico-sociali, puo' tollerare trattamenti chemioterapici uguali o simili a quelli offerti ai pazienti più giovani. Questo studio di fase II si propone appunto di valutare tollerabilita' ed attività di uno schema di chemioterapia sequenziale che utilizzi tutti e tre i farmaci cardine della terapia del carcinoma colorettale metastatico: Le fluoropirimidine, l'irinotecano e l'oxaliplatino. Lo studio prevede la somministrazione di capecitabina+irinotecano, seguita dalla somministrazione di capecitabina+ oxaliplatino

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

Radiation-induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? "A narrative review"

Radiation therapy is one of the cornerstones in the treatment of head and neck squamous cell carcinomas (HNSCC), alone or in combination with chemotherapy or surgery. Technological advances which occurred over the last few decades have increased the efficacy of radiotherapy (RT), particularly, intensity-modulated RT (IMRT). IMRT can deliver treatments on complex tumoral targets with dose escalation while sparing organs at risk; anyway IMRT deposits dose in unpredictable patterns outside of the target volume with the purpose of improving conformality. Radiation-induced nausea and vomiting (RINV) is a frequent albeit neglected side effect of RT that can lead to delays in treatment with serious consequences on cure rates. According to several guidelines (MASCC 2016, NCCN 2018), RT for HNSCC has traditionally been regarded as a low emetic risk treatment. Nevertheless, several works suggest that IMRT could increase RINV. Further studies are needed to define the exact incidence and the detailed pathophysiology of RINV in patients with HNSCC treated with state of art IMRT techniques, with and without concurrent chemotherapy