Proton therapy with concurrent chemotherapy for non-small-cell lung cancer: technique and early results

BackgroundProton therapy can deliver a more conformal dose distribution than photon radiation and may allow safe dose escalation in stage III lung cancer. Early outcomes are presented here for patients who received proton therapy with concurrent chemotherapy for non–small-cell lung cancer (NSCLC).Materials and MethodsNineteen patients with regionally advanced NSCLC were treated with concurrent chemotherapy (carboplatin and paclitaxel [n = 18]) and proton therapy from August 2008 to April 2010 either with (n = 7) or without (n = 12) induction chemotherapy. Eighteen patients had stage III NSCLC, and 1 patient had stage IIB disease. The median proton therapy dose was 74 cobalt gray equivalent (CGE) in 2 CGE fractions with 18 patients who received ≥70 CGE. Twelve patients also received selective nodal proton therapy to the adjacent uninvolved nodal regions, with a median dose of 40 CGE (range, 40-46 CGE). The patients were routinely evaluated for treatment-related toxicity and disease progression every 3 months, with a history, physical, and computed tomography or positron emission tomography–computed tomography.ResultsThe median follow-ups for living patients were 15 and 16 months (range, 7-26 months), respectively. Nonhematologic and hematologic acute grade 3+ toxicity (<90 days) developed in 1 and 4 patients, respectively. Two of 16 patients assessable for late toxicity (≥90 days) developed a significant grade 3+ nonhematologic late toxicity, whereas 1 patient developed a grade 3+ hematologic late toxicity. Local progression was the site of first relapse in one patient.ConclusionMediastinal proton therapy with concomitant chemotherapy was associated with acceptable toxicity. Although encouraging, longer follow-up with more patients is needed to confirm the long-term efficacy of this treatment.     

Positron Emission Tomography in oncology: Present and future of PET and PET/CT

PET is a crucial technique in molecular imaging, allowing in vivo assessment and localization of pathological processes, thanks to its ability to detect very small amounts of radioactive molecules. This is of particular interest in oncology where abnormal metabolism or synthesis in tumor cells but also various tumor characteristics can be studied using this nuclear medicine technique. FDG is currently the most widely used tracer, nowadays essential in the management of various malignancies, with large applications in diagnosis, initial assessment, therapy monitoring, and recurrence detection. The combination of anatomical information provided by PET/CT further increased its interest. Beyond its spread use in daily practice, future applications of PET will involve other tracers than FDG and develop research applications in humans as well as in small animals.     

Statin therapy in cardiovascular diseases other than atherosclerosis

Statins are drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, thereby blocking the synthesis of cholesterol. Since being discovered in Japan in the mid 1970s, statins have been widely used to lower low-density lipoprotein cholesterol. However, analysis of cardiovascular research has revealed other important effects beyond changes in lipid parameters, referred to as pleiotropic effects. This paper focuses on the effects of statins as anti-ischemic agents with improvement in endothelial function, along with studies on valvular aortic stenosis, atrial fibrillation, heart failure, peripheral arterial disease, and cancer. As the evolution of statin research continues, there appear to be new potential benefits from statins to be found in many facets of cardiovascular disease.     

IMMUNOLOGICAL STUDIES IN TWO CHILDREN WITH RECURRENT PAROTITIS

ABSTRACT. In two children with recurrent parotitis, labial salivary gland biopsies showed chronic sialoadenitis. Immunofluorescence studies disclosed deposits of immunoglobulins and complement in juxta-acinar small vessels. Case 1 had gluten enteropathy, IgA deficiency and high titres of antinuclear antibodies (ANA), and in vivo fixation of ANA to nuclei of different cells in lip, skin and jejunum was present. Case 2 showed deposition of IgM in the dermo-epidermal junction of the skin. These findings suggest that autoimmune reactivity and immune complexes may play a role in the pathogenesis of this disorder.     

The curative role of radiotherapy in adenocarcinoma of the prostate in patients under 55 years of age: a rare cancer network retrospective study.

To determine whether radiation therapy could be an acceptable alternative to surgery in young patients with adenocarcinoma of the prostate, we analysed the outcome of 39 patients aged under 55 with organ confined tumours who received external radiation therapy in a curative intent. Our results suggest that similar local control in younger and older patients can be expected from either external beam radiotherapy or radical prostatectomy.     

A phase I pharmacologic and pharmacogenetic trial of sequential 24-hour infusion of irinotecan followed by leucovorin and a 48-hour infusion of fluorouracil in adult patients with solid tumors.

PURPOSE: In preclinical studies, sequential exposure to irinotecan (CPT-11) then fluorouracil (5-FU) is superior to concurrent exposure or the reverse sequence; a 24-hour infusion of CPT-11 may be better tolerated than shorter infusions. EXPERIMENTAL DESIGN: CPT-11 was first given at four levels (70-140 mg/m(2)/24 hours), followed by leucovorin 500 mg/m(2)/0.5 hours and 5-FU 2,000 mg/m(2)/48 hours on days 1 and 15 of a 4-week cycle. 5-FU was then increased in three cohorts up to 3,900 mg/m(2)/48 hours. RESULTS: Two patients had dose-limiting toxicity during cycle 1 at 140/3,900 of CPT-11/5-FU (2-week delay for neutrophil recovery; grade 3 nausea despite antiemetics); one of six patients at 140/3,120 had dose-limiting toxicity (grade 3 diarrhea, grade 4 neutropenia). Four of 22 patients with colorectal cancer had partial responses, two of which had prior bolus CPT-11/5-FU. The mean 5-FU plasma concentration was 5.1 micromol/L at 3,900 mg/m(2)/48 hours. The end of infusion CPT-11 plasma concentration averaged 519 nmol/L at 140 mg/m(2)/24 hours. Patients with UDP-glucuronosyltransferase (UGT1A1; TA)6/6 promoter genotype had a lower ratio of free to glucuronide form of SN-38 than in patients with >/=1 (TA)7 allele. Thymidylate synthase genotypes for the 28-base promoter repeat were 2/2 (13%), 2/3 (74%), 3/3 (13%); all four responders had a 2/3 genotype. CONCLUSIONS: Doses (mg/m(2)) of CPT-11 140/24 hours, leucovorin 500/0.5 hours and 5-FU 3,120/48 hours were well tolerated.     

Lupane-triterpenes from the leaves ofBrassaiopsis glomerulata

Three known lupane-triterpenes, 3alpha-hydroxy-lup-20(29)-en-23,28-dioic acid (1), 3a-hydroxylup-20(29)-en-23,28-dioic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (acankoreoside A, 2) and 3alpha,11alpha-dihydroxy-23-oxo-lup-20(29)-en-28-oic acid (3) were isolated from the leaves of Brassaiopsis glomerulata (Blume) Regel, a species of Araliaceae family growing in Vietnam. Their structures were determined on the basis of spectroscopic data.     

Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC)

Focal non-epidermolytic palmoplantar keratoderma (PPK or palmoplantar ectodermal dysplasia type III) is associated with oesophageal cancer in three families: two large pedigrees located in Liverpool, UK and in the midwestern American states and one smaller family from Germany. In these families, the PPK is inherited as autosomal dominant and has a late onset, usually manifesting between 7 and 8 years of age. The disease is characterised by thickening of the pressure areas of the soles, but is not restricted to the feet and also presents with oral leukokeratosis and follicular hyperkeratosis. The disease locus [previously termed the "tylosis oesophageal cancer gene' (TOC) locus] has been mapped to 17q23-qter by linkage analysis. This region is located telomeric to the keratin 16 gene, in which mutations have been identified in focal PPK families who show no increased cancer risk. We describe the close mapping of this locus to the interval between AFMb054zf9 and D17S1603 using haplotype analysis of additional Genethon markers in the region and show that although the American family is unlikely to be related to either of the other two, the UK and German pedigrees may share a common descent. This work provides a basis for positional cloning and candidate gene analysis in order to identify a gene that may be involved in familial oesophageal cancer.      

Resistance of CD1d-/- mice to ultraviolet-induced skin cancer is associated with increased apoptosis

Inhibition of p53-induced epidermal apoptosis, generation of p53 mutations, and suppressor T cells are the critical events responsible for the induction and development of UV-induced skin cancers. Recently, we demonstrated that CD1d knockout mice were resistant to UV-induced immunosuppression, prompting us to further address the role of CD1d in regulating UV carcinogenesis. We, therefore, investigated the response of wild-type (WT) and CD1d-/- mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d-/- mice developed skin tumors. Surprisingly, keratinocytes and fibroblasts from CD1d-/- mice were more sensitive to UV-induced apoptosis and persisted longer than cells derived from WT mice. In addition, epidermis and dermis taken from chronically UV-irradiated CD1d-/- mice harbored significantly fewer p53 mutations than WT mice. Our findings identify an unexpected and novel function for CD1d as a critical molecule regulating UV carcinogenesis, by inhibiting apoptosis to prevent elimination of potentially malignant keratinocytes and fibroblasts.