NEJM cartoon regarding radium and prostate cancer

Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer Death

"Using low-dose CT screening for lung cancer prevents the greatest number of deaths (and gives the lowest proportion of false-positives) among those at highest risk, according to a New England Journal of Medicine study. CT screening was previously shown to reduce such deaths by 20% compared with radiography, and researchers stratified over 25,000 CT-screened patients into risk quintiles to examine whether the benefits of screening varied according to risk levels. The quintiles ranged from 0.15% to more than 2% in 5-year risk for lung cancer mortality. They found that percentage death reduction was constant across all quintiles, however, the number of deaths prevented was highest among those in the top three risk quintiles (77) versus those in the bottom two (11). Similarly, the number needed to screen to prevent one lung cancer death was 208 for those in the top three quintiles, compared with 302 for the entire group. The proportion of false-positive results also declined significantly with increasing risk quintile. " ref NEJM

The Influence of Prostate Volume on Outcome After High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer

this brachy article writen by dudes from Mount Vernon.

Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition

EBRT is confined to normal tissue tols. in this study, the authors combined a virus that targets cancer cells and kills them. they linked the virus with an isotope that together with teh replicating virus, drives the uptake of therapeutic radioisotopes. This approach involves infecting cancer cells with viruses that mediate tumour-specific radioisotope uptake to deliver selective, highly conformal escalation of local dose delivery. THey also used a DNA damage blocker to stop the cancer cells using a repair pathway if they were infected with the radiovirus. together with EBRT, the dose is taken up by the isotope which is inside the cancer cell- dose escalation to just the cells that are infected with the virus ---> cancer cells authours conc "We have shown that combining NIS-expressing oncolytic measles virus, radioiodide, EBRT and Chk1 inhibition yields impressive in vitro and in vivo activities. Clinical translation of this approach represents an attractive way of delivering highly conformal radiation boosts to improve tumour control without increasing normal tissue toxicity." the combination was tested in cell cultures of head and neck cancer and colorectal carcinoma, and was found to deliver more radiation to the cancer cells than using any of the four treatments separately. ref Ouchefeu Y, Khan A, Borst G, Zaidi SH, McLaughlin M, Roulstone V, et al. Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition. Radiother Oncol2013, doi:10.1016/j.radonc.2013.05.036.

Treatment Consequences in Adults Who Survive Childhood Cancer

mean age was 4-5yr old, most had ALL. median age of this cohort was only 32 years, these data are concerning and may indicate a pattern of accelerated or premature aging. Authors wanted to see effects of screening on the adults who were survivors of childhood cancer. They found >20% increase in heart/lung and neuroendocrine abnormalities compared to standard age control. Ninety-eight percent of our cohort had 1 or more chronic health conditions, survivor of leukemias who were treated with 24-Gy cranial irradiation demonstrated reduced cognitive status and memory on formal neuropsychological testing. Authors show that even though this radiation does not affect the patietns chance of finding a job and living etc (from a cognitive point of view), there seems to be an increase risk of developing dementia at an earlier age, thus screening these patient for affects upon mental status might be needed "Exposure-specific, risk-based screening resulted in identification and referral for treatment of some conditions that are amenable to remediation" study has selection bias as only 60% contacted consented to study. Also differing treatment regimes used when the child was treated maybe different then compared to now thus one maynot be able to guide future interventions. Survivors of childhood cancer are at much greater risk of heart, lung, mental disabilities which can start to be see, (via screening) at an early age in adulthood (30). Thus the health care system needs to be aware of this population of patients and prospectively treat these patients before any conditions get worse (stroke etc). ref Hudson MM et al. Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 2013 Jun 12; 309:2371 - See more at: http://www.jwatch.org/na31363/2013/07/02/treatment-consequences-adults-who-survive-childhood-cancer#sthash.aPk2tfgD.dpuf

Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer

study shows affect of changes in weight in adulthood. PLus confirms extra risk (3x) if patient is overweight and a reduction of risk if patient loses weight or maintains steady BMI. They found simular result between both the classical oestrogen driven type I and the more aggresive type II endometrial ca. Authors suggest weight loss changes inflammatory cytokines and hormones. Study used case-control, and retroespective questionnaire, thus bias from women 'estimating' weight over time, and also used the BMI scale which isnt that great a measure of fat/weight/lean body mass etc. Also all other studies used a differing definition of 'weight cycling' thus one cant not compare between studies with ease. overall, weight cycling in adulthood, which results is changes in fat distribution may increase risk of endo cancer (both types), the patient who doesnt cycle weight/bmi is still at a risk, but if patient drops BMI/or maintains simular BMI when she was 20year old have less risk C.M. Nagle, L. Marquart, C.J. Bain, S. O’Brien, P.H. Lahmann, M. Quinn, M.K. Oehler, A. Obermair, A.B. Spurdle, P.M. Webb. Australian National Endometrial Cancer Study Group, Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer, European Journal of Cancer, Volume 49, Issue 12, August 2013, Pages 2717-2726,

HPV goes up, HPV goes down, and America struggles with the vaccine’s image problem

discussion about HPV vaccine uptake

Adjuvant therapy for resectable pancreatic adenocarcinoma: Review of the current treatment approaches and future directions

Less than one out of five patients have resectable disease at the time of initial diagnosis. Nearly 90% are adenocarcinomas (PDAC) arising from the exocrine ductal system. has a very low prognosis, around 3% at 5 yrs. Even if resectable and even with R0 margins, there is high propensaty of recurrance and metastasis in the liver and at the tumor bed. post resection treatment strategies aim to control both micro-metastatic disease as well as loco-regional recurrence. treatments? various trials in the past have compared adjuvant RT and 5-FU to resected pancreatic adeno ca, most have reported mixed results, low accural in patient numbers and differing RT percriptions (i.e. split courses) multicenter trial (ESPAC-1; n = 289) examined the role of both adjuvant chemo (5FU/leucovorin) and CRT (split course 20gy 10# x2). Patients who received CHT [5FU/leucovorin (LCV)] had a significantly improved median OS over no treatment arm (20.1 vs 15.5 mo, respectively; p = 0.009). Surprisingly enough, patients on the CRT arm had a trend towards worse outcome (median OS: 15.9 vs 17.9 mo, respectively; p = 0.05). however this study like most others in the past regarding pancretic trials was criticized because of the suboptimal delivery and dosing of RT that potentially negated any survival benefit conferred by CRT with longer time-to-treatment in the CRT group and inclusion of R1 patients based on other small trials, it has become that adjuvant chemo alone should be the standard of care for either R0 or R1 resections and CRT might only be considered for patients with unfavorable profile. a german trial with gemcitabine compared adjuvant GEM administered for six cycles with observation alone in 368 patients with completely resected PDAC.>>>>> Patients receiving GEM had a near doubling of median disease-free survival (DFS) (13.4 vs 6.9 mo, respectively; p < 0.001), and improved median OS (22.8 vs 20.2 mo, p = 0.005) thus establishing its pivotal role in the management of patients in the AS European Study Group for Pancreatic Cancer (ESPAC) investigators proceeded with another study (ESPAC-3v2) that compared GEM vs 5-FU in the AS without RT. >>>>>> Results showed no differences in DFS and OS between patients receiving GEM and those receiving 5FU (23.6 vs 23.0 mo, respectively), with more grade 3/4 thrombocytopenia observed in patients on the GEM arm and more grade 3/4 stomatitis and diarrhea in patients on the 5FU arm. many other combination of drug have been used but the current best results have been consistency observed when using GEM/5FU In the metastatic setting FOLFIRINOX. A combination of 5FU/Irinotecan and oxaliplatin, was associated with a survival advantage over GEM (11.1 vs 6.8 mo, p < 0.001), offering patients with advanced disease and good performance status . Nab-paclitaxel in a phase II study, showed increased delivery of GEM in the tumor, elimination of PDAC stroma and association with anti-tumor activity. Preliminary reports showed a clear benefit of the combination therapy associated with significantly higher response rate (23% vs 7%), significantly longer median OS (8.5 vs 6.7 mo) and PFS (5.5 vs 3.7 mo) with an acceptable toxicity profile for the setting. This may offer a viable alternative to the above FOLFIRINOX. many other targeted therapies have been studied with little postive results, cetuximab, trastuzumab combinations, Hedgehog inhibitors, VEGF 1,2,3 inhibitors all with Gemcitabine have shown nohting. The used of immunotherapy such as Hyperacute immunotherapy approach (Algenpantucel-L) combined with AT has been tested in the AS demonstrating survival benefit. biomarkers CA19.9 most rountinely used can not be used to govern who will gain most from adjuvant therapy. levels of Human equilibrative nucleoside transport protein 1 (hENT1) alters resistance and predict sensitivity to the treatment. C-X-C chemokine receptor type 4 (CXCR-4) is an independent negative prognostic factor and a predictor of distant relapse suggesting that anti-CXCR4 targeting therapies could be a promising approach in combination with cytotoxic chemotherapy in the AS. concluesion- The optimal adjuvant treatment for PDAC patients remains elusive and there is no worldwide consensus. other directions deserving further evaluation include the role of pre- and perioperative approach Emerging evidence suggests that poor prognosis should at least in part be accounted for by the failure to destroy cancer stem cells (CSC) which may lead to chemo resistance.>>>>argeting signaling pathways that will intercept CSC growth is giving rise to a whole new era of anticancer treatment, albeit questions regarding fundamental cell functions still remain. Ref G. Antoniou, P. Kountourakis, K. Papadimitriou, V. Vassiliou, D. Papamichael, Adjuvant therapy for resectable pancreatic adenocarcinoma: Review of the current treatment approaches and future directions, Cancer Treatment Reviews, Available online 26 June 2013, ISSN 0305-7372, http://dx.doi.org/10.1016/j.ctrv.2013.05.008. (http://www.sciencedirect.com/science/article/pii/S0305737213001229)