Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant treatment for rectal cancer

Abstract. Background: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). Patients and Methods: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. Results: A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). Conclusion: Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our result

number of mediastinal lymph nodes as a prognostic factor in pn2 non small cell lung cancer a single centre experience and review of the literature

Lung cancer is one of the most common cause of cancer-related death for men and women in the world. The prevalent histology is non-small cell lung carcinoma (NSCLC), including squamous cell carcinoma, adenocarcinoma and large cell carcinoma (Moretti et al., 2009), with a 5year survival rate of 67% (stage IA) to <5% (stage IV) (End, 2006). Currently the most important predictor of survival in lung cancer is the stage (TNM) (Kligerman and Abbot, 2010; Goldstraw, 2009). Despite the new staging system (Kligerman and Abbot, 2010), stage III NSCLC remains a very heterogeneous disease , with a 5-year survival rate ranging from 35% to 5%. There are two major treatment targets for of patients with stage III : locoregional control and control of micrometastases, preventing distant metastatic disease (Penland et al., 2004; Bradley et al., 2005). The standard of care is represented by multimodality treatment, comprehending surgery for resectable disease, perioperative chemotherapy and radiation therapy (RT) for patients with pathological (p) N2 disease (Okamoto, 2008). In current TNM classification system, N category is defined exclusively by anatomic nodal location, though number of lymph nodes confirmed to be a fundamental prognostic factor as in other type of tumours. In our study, we assessed, in patients with stage III N2 category NSCLC disease, the prognostic value of the number of lymph nodes after multimodality treatment

Relationship between severe obesity and gut inflammation in children: what's next?

Background: Preliminary evidence suggests an association between obesity and gut inflammation. Aims: To evaluate the frequency of glucose abnormalities and their correlation with systemic and intestinal inflammation in severely obese children. Patients and Methods: Thirty-four children (25 males; median age 10.8 ± 3.4 yrs) with severe obesity (BMI >95%) were screened for diabetes with oral glucose tolerance test (OGTT), systemic inflammation with C-reactive protein (CRP) and gut inflammation with rectal nitric oxide (NO) and faecal calprotectin. Results: BMI ranged from 23 to 44 kg/m2, and BMI z-score between 2.08 e 4.93 (median 2.69 ± 0.53). Glucose abnormalities were documented in 71% of patients: type 2 diabetes in 29%, impaired fasting glucose (IFG) in 58%, and impaired glucose tolerance (IGT) in 37.5%. Thirty-one patients (91%) were hyperinsulinemic. CRP was increased in 73.5% with a correlation between BMI z-score and CRP (p 0.03). Faecal calprotectin was increased in 47% patients (mean 77 ± 68), and in 50% of children with abnormal glucose metabolism (mean 76 ± 68 ìg/g), with a correlation with increasing BMI z-score. NO was pathological in 88%, and in 87.5% of glucose impairment (mean 6.8 ± 5 ìM). Conclusions: In this study, the prevalence of glucose abnormalities in obese children is higher than in other series; furthermore, a correlation is present between markers of systemic and intestinal inflammation and glucose abnormalities

Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4 production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Chemoradiation as definitive treatment for primary squamous cell cancer of the rectum

In this report, we present a case of advanced squamous cell cancer located in the rectum of a 78-year-old woman treated with chemoradiation with curative intent. The patient showed a complete clinical response to chemoradiation; multiple biopsies were performed at the site of the previous mass 5 mo after the end of treatment and histological examination showed no residual tumour in the specimens. Surgical intervention was avoided and the patient was free of disease 12 mo after the diagnosis of cancer. Primary chemoradiation should be considered as the treatment of choice for this rare malignancy

Pulsed-Dose Rate Brachytherapy for the Treatment of Endometrial Cancer

Abstract Endometrial cancer (EC) is the most frequent gynecologic malignancy. The aim of this review is to outline clinical practice recommendations, to suggest a technical solution, and to advise doses selection for pulsed-dose rate (PDR) brachytherapy in EC. Electronic bibliographic databases, including PubMed, clinicaltrials.gov, and the American Society of Clinical Oncology (ASCO) Meeting Library, were searched for articles in English. Clinical guidelines and systematic reviews were also considered. The appropriate therapeutic approach should consider risk factors for tumor relapse and PDR brachytherapy and have a convincing role in this multidisciplinary scenario. Performing PDR brachytherapy in EC requires robust training and experience

Hypofractionated radiotherapy combined with cetuximab in vulnerable elderly patients with locally advanced head and neck squamous cell carcinoma

This study was designed to evaluate the objective response after hypofractionated radiotherapy (HFRT) combined with cetuximab (HFBRT) in vulnerable elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Vulnerable elderly patients with histologically proven HNSCC received HFRT (total dose 60&nbsp;Gy, 3&nbsp;Gy/fraction) with concurrent cetuximab (250&nbsp;mg/m2 with a loading dose of 400&nbsp;mg/m2 1&nbsp;week before HFRT). Elderly patients were categorized as vulnerable based on mini-cog test and adult comorbidity evaluation-27 score. All patients completed the programmed HFRT and two patients received the planned cetuximab infusion. Severe acute toxicity, observed in four patients, was gastrointestinal (oral mucositis in four cases; nausea/vomiting in one case) and dermatological (acneiform eruption in three cases; radiation dermatitis in one case). Three serious adverse events were recorded in three out of six patients Overall, three patients had a partial response and three patients had progression disease 3&nbsp;months after the end of the treatment. No complete response was observed. HFBRT seems to be not a safer alternative approach for vulnerable elderly patients with locally advanced HNSCC. Further prospective trials are needed to define better tumor control with less incidence of toxic effects in vulnerable elderly HNSCC patients

Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution

The aim of our study was to evaluate the feasibility and the effectiveness of an intensified neoadjuvant protocol with the addition of weekly oxaliplatin in the preoperative strategy of rectal cancer treatment. Patients with locally advanced rectal cancer received continous infusion 5-Fluorouracil (5-FU) 200 mg/m(2)/day in combination with weekly oxaliplatin at a dose of 50 mg/m(2). Doses of radiotherapy were 45 Gy to the whole pelvis plus 5.4-9 Gy to the tumour mass. The primary end-points of the study were evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response (pCR) and the rate of sphincter preservation for distal cancers. Secondary end-points were relapse-free and overall survival. From November 2006 to June 2009, 51 patients were enrolled into the study. Compliance with chemotherapy was 80%. The incidence of G3 diarrhoea and proctitis were 17.6% and 21.5%, respectively. Surgery was performed in 48 patients with 100% R0 resection. 76.4% of low-lying tumours underwent conservative treatment. Seventy-nine percent of patients were downstaged: T and N downstaging were observed in 71% and 75% of patients, respectively. A pCR was obtained in 11 (22.9%) patients. Intensification of neoadjuvant treatment for rectal cancer with the addition of weekly oxaliplatin is feasible, with remarkable rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. Phase III trials with a longer follow-up will establish whether this good outcome in terms of surrogate end-points will translate into better rates of disease-free and overall survival

Intensified Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer in Elderly Patients: Toxicity, Disease Control, and Survival Outcomes

INTRODUCTION: We report the treatment compliance, toxicity rates, and long-term clinical outcomes of elderly patients who received intensified neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We identified a retrospective cohort of patients aged ≥ 70 years with LARC who received intensified neoadjuvant CRT, followed by surgery and adjuvant chemotherapy, from 2007 to 2014. Intensified neoadjuvant CRT consisted of radiotherapy (total dose, 50.4/54 Gy) with concomitant oxaliplatin (50 mg/m2/wk) and 5-fluorouracil (200 mg/m2 in 5 daily continuous infusion). RESULTS: A total of 26 patients were included. All patients completed the programmed CRT. Severe acute toxicity was recorded in 19.2% of cases. Conservative surgery was performed in 16 patients, and a pathologic complete response was achieved in 19.2%. Overall, 26.9% of the patients died. The 5-year overall survival and disease-free survival rates were 70.6% and 65.5%, respectively. CONCLUSIONS: Intensified neoadjuvant CRT is an efficacious and safe treatment option for LARC in elderly patients