No outcome disparities in patients with diffuse large B-cell lymphoma and a low socioeconomic status

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Karin Boslooper, Mels Hoogendoorn, Eric N. van Roon, Robby E. Kibbelaar, Huib Storm, Sjoerd Hovenga, Gerhard Woolthuis, Bas P. van Rees, Bart Klijs, Nic J.G.M. Veeger, Hanneke C. Kluin-Nelemans, Geertruida H. de Bock
IntroductionIn patients with diffuse large B-cell lymphoma (DLBCL) socioeconomic status (SES) is associated with outcome in several population-based studies. The aim of this study was to further investigate the existence of disparities in treatment and survival.MethodsA population-based cohort study was performed including 343 consecutive patients with DLBCL, diagnosed between 2005 and 2012, in the North-west of the Netherlands. SES was based on the socioeconomic position within the Netherlands by use of postal code and categorized as low, intermediate or high. With multivariable logistic regression and Cox proportional hazard models the association between SES and respectively treatment and overall survival (OS) was evaluated.ResultsTwo-third of patients was positioned in low SES. Irrespective of SES an equal proportion of patients received standard immunochemotherapy. SES was not a significant risk indicator for OS (intermediate versus low SES: hazard ratio (HR) 1.31 (95%CI 0.78–2.18); high versus low SES: HR 0.83 (95%CI 0.48–1.46)). The mortality risk remained significantly increased with higher age, advanced performance status, elevated LDH and presence of comorbidity.ConclusionWithin the setting of free access to health care, in this cohort of patients with DLBCL no disparities in treatment and survival were seen in those with lower SES.



http://ift.tt/2oKZnj1

Nonalcoholic fatty liver disease and mortality among cancer survivors

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Justin C. Brown, Michael O. Harhay, Meera N. Harhay
BackgroundNonalcoholic fatty liver disease (NAFLD) may foster a tumor microenvironment that promotes cancer recurrence and progression. We examined the relationship between NAFLD and mortality among a sample of cancer survivors.MethodsUltrasonography was used to assess hepatic steatosis, and standardized algorithms were used to define NAFLD. Study endpoints included all-cause, cancer-specific, and cardiovascular-specific mortality.ResultsAmong 387 cancer survivors, 17.6% had NAFLD. During a median of 17.9 years of follow up, we observed 196 deaths from all causes. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of all-cause mortality [HR: 2.52, 95% CI: 1.47–4.34; P=0.001]. We observed 86 cancer-specific deaths. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of cancer-specific mortality [HR: 3.21, 95% CI: 1.46–7.07; P=0.004]. We observed 46 cardiovascular-specific deaths. In multivariable-adjusted regression models, NAFLD was not associated with an increased risk of cardiovascular-specific mortality [HR: 1.04, 95% CI: 0.30–3.64, P=0.951].ConclusionNAFLD is associated with an increased risk of all-cause and cancer-specific mortality among cancer survivors. This novel observation warrants replication. Evaluating the efficacy of interventions, such as lifestyle modification through weight loss and exercise, to improve NAFLD in this population may be considered.



http://ift.tt/2qkpJ8B

No outcome disparities in patients with diffuse large B-cell lymphoma and a low socioeconomic status

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Karin Boslooper, Mels Hoogendoorn, Eric N. van Roon, Robby E. Kibbelaar, Huib Storm, Sjoerd Hovenga, Gerhard Woolthuis, Bas P. van Rees, Bart Klijs, Nic J.G.M. Veeger, Hanneke C. Kluin-Nelemans, Geertruida H. de Bock
IntroductionIn patients with diffuse large B-cell lymphoma (DLBCL) socioeconomic status (SES) is associated with outcome in several population-based studies. The aim of this study was to further investigate the existence of disparities in treatment and survival.MethodsA population-based cohort study was performed including 343 consecutive patients with DLBCL, diagnosed between 2005 and 2012, in the North-west of the Netherlands. SES was based on the socioeconomic position within the Netherlands by use of postal code and categorized as low, intermediate or high. With multivariable logistic regression and Cox proportional hazard models the association between SES and respectively treatment and overall survival (OS) was evaluated.ResultsTwo-third of patients was positioned in low SES. Irrespective of SES an equal proportion of patients received standard immunochemotherapy. SES was not a significant risk indicator for OS (intermediate versus low SES: hazard ratio (HR) 1.31 (95%CI 0.78–2.18); high versus low SES: HR 0.83 (95%CI 0.48–1.46)). The mortality risk remained significantly increased with higher age, advanced performance status, elevated LDH and presence of comorbidity.ConclusionWithin the setting of free access to health care, in this cohort of patients with DLBCL no disparities in treatment and survival were seen in those with lower SES.



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Nonalcoholic fatty liver disease and mortality among cancer survivors

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Justin C. Brown, Michael O. Harhay, Meera N. Harhay
BackgroundNonalcoholic fatty liver disease (NAFLD) may foster a tumor microenvironment that promotes cancer recurrence and progression. We examined the relationship between NAFLD and mortality among a sample of cancer survivors.MethodsUltrasonography was used to assess hepatic steatosis, and standardized algorithms were used to define NAFLD. Study endpoints included all-cause, cancer-specific, and cardiovascular-specific mortality.ResultsAmong 387 cancer survivors, 17.6% had NAFLD. During a median of 17.9 years of follow up, we observed 196 deaths from all causes. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of all-cause mortality [HR: 2.52, 95% CI: 1.47–4.34; P=0.001]. We observed 86 cancer-specific deaths. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of cancer-specific mortality [HR: 3.21, 95% CI: 1.46–7.07; P=0.004]. We observed 46 cardiovascular-specific deaths. In multivariable-adjusted regression models, NAFLD was not associated with an increased risk of cardiovascular-specific mortality [HR: 1.04, 95% CI: 0.30–3.64, P=0.951].ConclusionNAFLD is associated with an increased risk of all-cause and cancer-specific mortality among cancer survivors. This novel observation warrants replication. Evaluating the efficacy of interventions, such as lifestyle modification through weight loss and exercise, to improve NAFLD in this population may be considered.



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The effect of endorectal balloon on anorectal dose during postoperative volumetric arc radiotherapy of prostate cancer

To evaluate the impact of endorectal balloon (ERB) on anorectal dose during postoperative VMAT of prostate cancer.

http://ift.tt/2phs0Db

Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy

To investigate whether radiotherapy (RT) dose escalation would improve treatment outcomes without increasing severe toxicity in locally advanced pancreatic cancer patients.

http://ift.tt/2qjEuJ2

Regional susceptibility to dose-dependent white matter damage after brain radiotherapy

Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose–response across white matter tracts using diffusion tensor imaging (DTI).

http://ift.tt/2phnzrU

Dermatoses réactionnelles rares après radiothérapie : une série de cas avec cancer du sein

Publication date: Available online 29 April 2017
Source:Cancer/Radiothérapie
Author(s): C. Dalmasso, É. Tournier, B. de Lafontan, A. Modesto, F. Dalenc, É. Chantalat, L. Gladieff, E. Jouve, C. Livideanu, F. Izar, V. Sibaud
La toxicité cutanée de la radiothérapie est maintenant bien individualisée, que ce soient les effets aigus (radiodermites aiguës) ou chroniques (radiodermites chroniques, carcinomes cutanés secondaires, séquelles esthétiques). Beaucoup plus exceptionnellement, la radiothérapie peut aussi induire, par réaction isomorphique ou phénomène de Koebner, certaines dermatoses spécifiques. Nous rapportons ici cinq nouvelles observations de ces complications inhabituelles de la radiothérapie, survenues dans des délais très variables après la fin d'une irradiation mammaire et restant strictement localisées dans le territoire initialement irradié (mastocytose cutanée, syndromes de Sweet, lichen plan et vitiligo segmentaires). Ces cas soulignent la nécessité de réaliser un examen histologique systématique devant toute lésion cutanée atypique apparaissant après une radiothérapie, même longtemps après.Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.



http://ift.tt/2phtMnS

Intelligence artificielle appliquée à la radiothérapie

Publication date: Available online 29 April 2017
Source:Cancer/Radiothérapie
Author(s): J.-E. Bibault, A. Burgun, P. Giraud




http://ift.tt/2oWp8ZM

Dermatoses réactionnelles rares après radiothérapie : une série de cas avec cancer du sein

Publication date: Available online 29 April 2017
Source:Cancer/Radiothérapie
Author(s): C. Dalmasso, É. Tournier, B. de Lafontan, A. Modesto, F. Dalenc, É. Chantalat, L. Gladieff, E. Jouve, C. Livideanu, F. Izar, V. Sibaud
La toxicité cutanée de la radiothérapie est maintenant bien individualisée, que ce soient les effets aigus (radiodermites aiguës) ou chroniques (radiodermites chroniques, carcinomes cutanés secondaires, séquelles esthétiques). Beaucoup plus exceptionnellement, la radiothérapie peut aussi induire, par réaction isomorphique ou phénomène de Koebner, certaines dermatoses spécifiques. Nous rapportons ici cinq nouvelles observations de ces complications inhabituelles de la radiothérapie, survenues dans des délais très variables après la fin d'une irradiation mammaire et restant strictement localisées dans le territoire initialement irradié (mastocytose cutanée, syndromes de Sweet, lichen plan et vitiligo segmentaires). Ces cas soulignent la nécessité de réaliser un examen histologique systématique devant toute lésion cutanée atypique apparaissant après une radiothérapie, même longtemps après.Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.



from Cancer via ola Kala on Inoreader http://ift.tt/2phtMnS
via IFTTT

Intelligence artificielle appliquée à la radiothérapie

Publication date: Available online 29 April 2017
Source:Cancer/Radiothérapie
Author(s): J.-E. Bibault, A. Burgun, P. Giraud




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Treatment of cutaneous metastases of breast cancer with electrochemotherapy: what is the magnitude of clinical benefit?

http://ift.tt/2ph5WbU

Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503)

Abstract

Purpose

Tools to estimate survival, such as ePrognosis (http://ift.tt/2qisI1w), were developed for general, not cancer, populations. In older patients with breast cancer, accurate overall survival estimates would facilitate discussions about adjuvant therapies.

Methods

Secondary analyses were performed of data from two parallel breast cancer studies (CALGB/Alliance 49907/NCT000224102 and CALGB/Alliance 369901/NCT00068328). We included patients (n = 971) who were age 70 years and older with complete baseline quality of life data (194 from 49907; 777 from 369901). Estimated versus observed all-cause two-year mortality rates were compared. ePrognosis score was calculated based on age, sex, and daily function (derived from EORTC QLQ-C30). ePrognosis scores range from 0 to 10, with higher scores indicating worse prognosis based on mortality of community-dwelling elders and were categorized into three groups (0–2, 3–6, 7–10). Observed mortality rates were estimated using Kaplan–Meier methods.

Results

Patient mean age was 75.8 years (range 70–91) and 73% had stage I–IIA disease. Most patients were classified by ePrognosis as good prognosis (n = 562, 58% 0–2) and few (n = 18, 2% 7–10) poor prognosis. Two-year observed mortality rates were significantly lower than ePrognosis estimates for patients scoring 0–2 (2% vs 5%, p = 0.001) and 3–6 (8% vs 12%, p = 0.01). The same trend was seen with scores of 7–10 (23% vs 36%, p = 0.25).

Conclusions

ePrognosis tool only modestly overestimates mortality rate in older breast cancer patients enrolled in two cooperative group studies. This tool, which estimates non-cancer mortality risk based on readily available clinical information may inform adjuvant therapy decisions but should be validated in non-clinical trial populations.

http://ift.tt/2oIXO5e

Breast cancer subtype distribution is different in normal weight, overweight, and obese women

Abstract

Purpose

Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women.

Methods

A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18–24.9), overweight (BMI = 25–29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared.

Results

Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008).

Conclusions

We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.

http://ift.tt/2oTep1y

Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing

Abstract

Purpose

Liquid biopsy using digital PCR (dPCR) has been widely used for the screening of ESR1 mutations, since they are frequently identified in the hotspot. However, dPCR is limited to the known mutations. Therefore, we aimed to analyze the utility of next-generation sequencing (NGS) to discover novel ESR1 mutations.

Methods

Whole exon sequencing of the ESR1 gene using NGS was performed in 16 primary and 47 recurrent tumor samples and 38 plasma samples from hormone receptor-positive metastatic breast cancer patients. Functional analyses were then performed for the novel mutations we detected.

Results

We identified no mutations in primary tumors and six mutations in five recurrent tumors, including three types of known mutations (Y537C, Y537N, and D538G) and two novel mutations (E279V and G557R). We also identified seven mutations in five plasma samples, including three types of known mutations (S463P, Y537S, and D538G) and one mutation not reported in COSMIC database (L536H). All nine patients with ESR1 mutations were treated with aromatase inhibitors (AIs) prior to sampling, and the mutations were frequently detected in patients who received AI treatments in the metastatic setting. Among the three novel mutations (E279V, L536H, and G557R), L536H, but not E279V and G557R, showed ligand-independent activity. All three mutant proteins showed nuclear localization and had no relation with non-genomic ER pathways.

Conclusions

Although the molecular mechanisms of the E279V and G557R mutations remain unclear, our data suggest the utility of NGS as a liquid biopsy for metastatic breast cancer patients and the potential to identify novel ESR1 mutations.

http://ift.tt/2oTkHy7

Reply to Munhoz et al.

http://ift.tt/2phh0pl

Breast cancer screening in patients with cancers other than breast

Abstract

Background

Screening mammography can detect early breast cancers and reduce subsequent cancer mortality. However, there is a lack of consensus as to when to discontinue screening. The absence of clear-cut guidelines on when not to screen means that many patients with advanced malignancies continue screening despite unclear benefit.

Methods

We performed a retrospective cohort study of female patients diagnosed with a non-breast malignancy to explore the incidence and effects of screening mammography. Female patients diagnosed with a non-breast malignancy stage II or higher between 2007 and 2012 were identified through the Vermont Cancer Registry and cross-referenced with mammography screening logs from January 1, 2007 to September 30, 2014. Additional data were collected through chart review, in May 2016.

Results

Twenty-six percent of women (398/1501) with a stage II or greater cancer (other than breast) diagnosed between 2007 and 2012 had a screening mammogram within the first 5 years of their diagnosis. Of these 398 women, 193 (48.5%) were alive without cancer, 132 (33.2%) had died, and 73 (18.3%) were alive with cancer at the time of chart review. Of those who died, 84 (63.6%) had a stage III or IV cancer. Eighteen (4.5%) had a breast biopsy following a screening mammogram suspicious for cancer, resulting in 13 (3.3%) benign diagnoses and 5 (1.3%) breast cancer diagnoses. No patient died of breast cancer.

Conclusions

Except for highly curable cancers, female patients diagnosed with an advanced non-breast malignancy experienced mortality that outweighs a breast cancer mortality benefit from screening mammography as estimated from prior studies.

http://ift.tt/2oTkOcV

Evaluation of changes to foot shape in females 5 years after mastectomy: a case–control study

Abstract

Purpose

The aim of this study was to evaluate changes in foot shape of women 5 years after undergoing breast amputation.

Methods

Evaluation of foot shape was performed using a non-invasive device for computer analysis of the plantar surface of the foot. Obtained results were compared between feet on the healthy breast side (F1) and on the amputated breast side (F2).

Results

128 women aged 63.60 ± 8.83, 5–6 years after breast amputation were enrolled in this case–control study. Weight bearing on the lower extremity on the amputated breast side (F1) compared with the healthy breast side (F2) showed statistically significant differences (p < 0.01). Patients put more weight onto the healthy breast side. No statistically significant difference was found with regard to F1 and F2 foot length (p = 0.4239), as well as BETA (p = 0.4470) and GAMMA (p = 0.4566) angles. Highly statistically significant differences were noted with respect to foot width, ALPHA angle, and Sztriter–Godunov index—higher values were observed on the healthy breast side (p < 0.001). Highly statistically significant differences were also noted while comparing Clark's angles, higher values being observed on the operated breast side (p < 0.001).

Conclusions

Differences in foot shape on the healthy breast side and amputated breast side constitute a long-term negative consequence of mastectomy, and can be caused by unbalanced weight put on feet on the healthy breast side compared to the amputated breast side.

http://ift.tt/2phgYOf

Identifying socio-demographic and clinical characteristics associated with medication beliefs about aromatase inhibitors among postmenopausal women with breast cancer

Abstract

Purpose

Non-adherence/persistence to adjuvant endocrine therapy can negatively impact survival. Beliefs about medicines are known to affect adherence. This study aims to identify socio-demographic and clinical characteristics associated with medication beliefs among women taking aromatase inhibitors (AIs).

Methods

Women completed an online survey on beliefs about AI therapy [Beliefs about Medicines Questionnaire (BMQ)], beliefs about breast cancer [Assessment of Survivor Concerns scale (ASC)], and depression [Personal Health Questionnaire depression scale (PHQ-8)]. Socio-demographic and clinical characteristics were collected. Bivariate analyses and linear regression models were performed to investigate relationships between variables.

Results

A total of 224 women reported currently taking AI therapy and were included in the analysis. Significantly higher concern beliefs were found among women who had at least mild depression, experienced side effects from AIs, and previously stopped therapy with another AI. Significant correlations were found between concern and necessity beliefs and cancer and health worry. Women age 70 and older displayed less fear of cancer recurrence and health worry, and a trend towards lower necessity and concern beliefs. No differences were found for other variables. In the regression model, greater necessity beliefs were found with increases in the number of current prescription medications (B = 1.06, 95% CI 0.31–1.81, p = 0.006) and shorter duration of current AI therapy (B = −0.65, 95% CI −1.23 to −0.07, p = 0.029), whereas greater concern beliefs were associated with higher depression scores (B = 1.19, 95% CI 0.35–2.03, p = 0.006).

Conclusions

Medication necessity and concern beliefs were associated with a definable subset of patients who may be at higher risk for non-persistence.

http://ift.tt/2oT8DwY

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database

Abstract

Purpose

The Oncotype DX^® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases.

Methods

In this population-based study, BC cases in SEER registries (diagnosed 2004–2013) were linked to RS results from assays performed by Genomic Health (2004–2014). The primary analysis included only patients (diagnosed 2004–2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method.

Results

The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4–99.6) for those with micrometastases to 92.8% (95% CI 73.4–98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18–30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001).

Conclusions

Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

http://ift.tt/2qiAJmY

Oncoplastic surgery with omental flap reconstruction: a study of 200 cases

http://ift.tt/2phdsDC

Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients

Abstract

Purpose

Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing.

Methods

We tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma.

Results

Across the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene.

Conclusions

Among women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing.

http://ift.tt/2oIVOKt

Effects of hormone receptor status on the durable response of trastuzumab-based therapy in metastatic breast cancer

Abstract

Purpose

Trastuzumab-based treatment is the standard care for patients with HER2+ metastatic breast cancer (MBC). About 10% of HER2+ MBC showed a long-term durable response (progression-free survival, PFS > 3 years) to trastuzumab-based therapy. The aim of this study is to identify clinico-pathologic factors for a durable response to trastuzumab-based therapy in HER2-positive MBC.

Methods

In the Yonsei Breast Cancer MBC Database, we identified 1218 MBC patients who were diagnosed from 2006 to 2015. Among them, 294 had HER2+ disease, and 153 received trastuzumab plus taxane chemotherapy as first-line treatment. Clinico-pathologic factors, such as hormone receptor (HR) status and metastatic sites, were reviewed. To evaluate a durable response, landmark analysis was performed.

Results

The median follow-up time was 28 months (95% CI 4.4–83.0 months). Of 153 HER2+ patients, there were 73 HR- patients (47.7%), and bone was the most common metastatic site. The median PFS and overall survival (OS) were 12 and 39 months, respectively. HR- patients showed a tendency toward longer PFS (median, 13 vs. 11 months, P = 0.160) compared with HR+ patients. Patients with non-visceral metastases had longer median PFS and OS than those with visceral disease (median PFS, 15 vs. 11 months, P = 0.012; median OS, 75 vs. 34 months, P = 0.03). Landmark analysis at 9 months suggested that the PFS of HR- patients was significantly longer than that of HR+ patients (median, 19 vs. 9 months, P = 0.008).

Conclusions

Among patients with HER2+ MBC, HR status is a possible predictive biomarker of a durable response to trastuzumab-based therapy.

http://ift.tt/2oTjNS0

Effective treatment of intractable cutaneous metastases of breast cancer with electrochemotherapy: a useful contributor to cutaneous disease control

http://ift.tt/2phdqLU

Lymphatico-venous anastomosis as treatment for breast cancer-related lymphedema: a prospective study on quality of life

Abstract

Purpose

Lymphedema is a chronic and disabling sequel of breast cancer treatment that can be treated by lymphatico-venous anastomosis (LVA). Artificial connections between the venous and lymphatic system are performed supermicrosurgically. This prospective study analyses the effect of LVA on quality of life.

Methods

A prospective study was performed between November 2015 and July 2016 on consecutive patients in the Maastricht University Medical Centre. Quality of life was considered as the primary outcome, and the Lymphedema International Classification of Functioning (Lymph-ICF) questionnaire was used. Discontinuation of compressive stockings and arm volume, using the Upper Extremity Lymphedema index (UEL-index), were the secondary outcomes.

Results

Twenty women with early-stage breast cancer-related lymphedema (BCRL) were included. The mean age was 55.9 ± 4 years and the median BMI was 25.1 [21–30] kg/m². The mean follow-up was 7.8 ± 1.5 months. Statistically significant improvement in quality of life was achieved in the total score and for all the quality of life domains after one year of follow-up (p < 0.05). The discontinuation rate in compressive stockings use was 85%. The difference in mean relative volume did not show a statistically significant decrease.

Conclusions

LVA for early-stage BCRL resulted in a significant improvement in quality of life and a high rate in stocking discontinuation.

http://ift.tt/2oTfExH

The impact of mastectomy type on the Female Sexual Function Index (FSFI), satisfaction with appearance, and the reconstructed breast’s role in intimacy

Abstract

Background

As mastectomy rates increase and overall survival for early breast cancer improves, a better understanding of the long-term consequences of mastectomy is needed. We sought to explore the correlation of specific mastectomy type with the Female Sexual Function Index (FSFI), body image satisfaction, and the reconstructed breast's role in intimacy.

Methods

This study is a secondary analysis of a cross-sectional survey including a retrospective chart review. Patients at least one year from primary surgery were invited to complete the survey between 2012 and 2014. Baseline characteristics and survey responses were compared between three mastectomy groups: total/modified radical (TMRM), skin-sparing (SSM), and nipple-sparing (NSM). All patients underwent reconstruction.

Results

Of 453 invited, 268 (59%) completed the survey. Sixty underwent mastectomy with reconstruction: 16 (27%) TMRM, 36 (60%) SSM, and 8 (13%) NSM. There were no significant differences in median total FSFI scores between groups, yet median FSFI scores for the NSM group indicated sexual dysfunction. After adjusting for receipt of chemotherapy and/or radiation, NSM had the lowest median desire score. There was a trend for the NSM group to be the least satisfied with postoperative appearance, but also more likely to report that the chest was "often" caressed during intimacy. However, nearly 40% of the NSM group reported that caress of the reconstructed breast was unpleasant.

Conclusion

NSM offers patients the greatest opportunity for preservation of their native skin envelope and potentially enhanced cosmetic outcome, but our results did not demonstrate superior sexual function or body image outcomes in this group. By highlighting surgical consequences of mastectomy preoperatively, surgeons may better set realistic patient expectations regarding both aesthetic and functional outcomes after breast cancer surgery. With clearer expectations, patients will have a better opportunity for improved surgical decision-making.

http://ift.tt/2phajng

Estrogen–progestin use and breast cancer characteristics in lean and overweight postmenopausal women

Abstract

Purpose

Breast cancer associated with estrogen–progestin (EP) therapy may have more favorable characteristics than cancer in never users, but results are conflicting. It is not well known either whether Body Mass Index (BMI) modifies this association. We investigated breast cancer characteristics in EP users for lean (BMI < 25 kg/m²) and overweight women (BMI ≥ 25 kg/m²).

Methods

The Icelandic Cancer Detection Clinic cohort, with information on breast cancer risk factors for 90% of Icelandic women, was linked with the population-based Icelandic Cancer Registry. A total of 781 women with invasive breast cancer diagnosed 51 years or older were matched with 7761 controls from the cohort. Conditional logistic regression was used for estimating adjusted odds ratios (OR) and 95% confidence intervals (CI) according to tumor characteristics, stratified by BMI. Polytomous logistic regression was applied in a case-only analysis for testing whether the risk associated with EP use differed according to tumor characteristics.

Results

Ever EP users had a twofold higher risk of breast cancer compared with never users (OR 2.05, 95% CI 1.71–2.45). In lean women, EP use was significantly less likely to be associated with grade 2 or 3 tumors than grade 1 tumors, contrary to overweight women for whom risk was increased irrespective of grade. EP use in overweight women was associated with a higher risk of lobular than ductal cancer (OR 2.75, 95% CI 1.29–5.87).

Conclusion

Among lean EP users, tumor characteristics were more favorable than among never users. This effect was not observed for overweight women.

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Scalp cooling with adjuvant/neoadjuvant chemotherapy for breast cancer and the risk of scalp metastases: systematic review and meta-analysis

Abstract

Purpose

The risk of scalp metastases in patients using scalp cooling for preservation of hair during chemotherapy has been a concern but is poorly described.

Methods

A systematic review and meta-analysis of longitudinal studies was undertaken to evaluate the effect of scalp cooling versus no scalp cooling on the risk of scalp metastasis in patients treated for breast cancer with chemotherapy. Electronic databases, journal specific, and hand searches of articles identified were searched. Patients were matched based on disease, treatment, lack of metastatic disease, and sex.

Results

A total of 24 full-text articles were identified for review. Of these articles, ten quantified the incidence of scalp metastasis with scalp cooling over time. For scalp cooling, 1959 patients were evaluated over an estimated mean time frame of 43.1 months. For no scalp cooling, 1238 patients were evaluated over an estimated mean time frame of 87.4 months. The incidence rate of scalp metastasis in the scalp cooling group versus the no scalp cooling group was 0.61% (95% CI 0.32–1.1%) versus 0.41% (95% CI 0.13–0.94%); P = 0.43.

Conclusion

The incidence of scalp metastases was low regardless of scalp cooling. This analysis suggests that scalp cooling does not increase the incidence of scalp metastases.

http://ift.tt/2ph06qU

Mutational studies on single circulating tumor cells isolated from the blood of inflammatory breast cancer patients

Abstract

Purpose

The molecular characterization of circulating tumor cells (CTCs) is critical to identify the key drivers of cancer metastasis and devising therapeutic approaches, particularly for inflammatory breast cancer (IBC) which is usually diagnosed at advance stages and progresses rapidly.

Methods

Genomic alterations in tumor tissue samples were studied using Foundation One™. Single CTCs were isolated using CellSearch followed by single-cell isolation by DEPArray™. Samples with 20 or more CTCs were chosen to isolate single CTCs using the DEPArray™.

Results

Genomic alterations were studied in primary tumor or metastatic sites from 32 IBC patients. Genes with high-frequency mutations were as follows: TP53 (69%), RB1 (16%), PIK3CA (13%), and also ErbB2 (3%). At least once during treatment, CTCs were detected in 26 patients with metastatic IBC, in two patients with locally advanced IBC, and four patients had no detectable CTCs. Per 7.5 mL of blood, fifteen patients (47%) had ≥20 CTCs and six of them were chosen at random to isolate single CTCs. These cells were tested for the presence of TP53, RB1, PIK3CA, and/or ErbB2 mutations previously found in matching tissue biopsies. The isolated CTCs showed the same mutations as primary or metastatic tumor samples. Intra-patient CTC heterogeneity was found by the presence of different CTC subclones, with some CTCs harboring different combinations of mutated and wild-type genes.

Conclusions

Our results indicate that CTCs could represent a non-invasive source of cancer cells from which to determine genetic markers as the disease progresses and identify potential therapeutic targets in IBC patients.

http://ift.tt/2oTdwWA

Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials

Abstract

Purpose

The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2− patients who do not achieve a pathological complete response.

Methods

Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2− patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.

Results

StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the high vs low StrTIL group (64 vs. 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (−41%) was observed for high StrTIL cases treated with chemotherapy.

Conclusions

This hypothesis-generating study suggests that in HR+/HER2− breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.

http://ift.tt/2ph6ONJ

Identification of frequent somatic mutations in inflammatory breast cancer

Abstract

Purpose

Inflammatory breast cancer is an aggressive form of breast cancer that shows distinct clinical features from non-inflammatory breast cancer. Genomic understanding of inflammatory breast cancer will shed light on biological targets for this disease. Our objective was to identify targeted hotspot mutations using multiplex genome sequencing in inflammatory breast cancer and compare the findings with those for patients with non-inflammatory breast cancer to further recognize novel targets.

Methods

We studied 400 patients with metastatic breast cancer who had somatic hotspot mutation testing using a 46- or 50-gene multiplex platform from March 2012 to December 2014. Among this population, 24 patients had inflammatory breast cancer and 376 patients had non-inflammatory breast cancer. We tested a total of 26 samples from 24 patients with inflammatory breast cancer.

Results

The average number of mutations per patient was higher in inflammatory breast cancer than in non-inflammatory breast cancer (1.23 vs. 0.65, respectively). Identified somatic mutations in inflammatory breast cancer were TP53 (n = 18, 75%), PIK3CA (n = 10, 41.7%), and ERBB2 (n = 4, 16.7%). TP53 and ERBB2 mutations were significantly more prevalent in inflammatory breast cancer than in non-inflammatory breast cancer (P < 0.01). All patients with ERBB2 mutations had hormone receptor (HR)+ primary tumors.

Conclusions

TP53, PIK3CA, and ERBB2 were detected as three major somatic mutations in metastatic inflammatory breast cancer patients. While the inflammatory breast cancer TP53 and PIK3CA mutations mirrored previously reported data for metastatic non-inflammatory breast cancer, this is the first report of higher frequency of ERBB2 mutation in inflammatory breast cancer, especially in the HR+ subtype. Once validated in a larger cohort of inflammatory breast cancer patients, this novel finding could lead to development of treatments for HR+ inflammatory breast cancer.

http://ift.tt/2oTpvDG

The effect of population-based mammography screening in Dutch municipalities on breast cancer mortality: 20 years of follow-up

Abstract

Long-term follow-up data on the effects of screening are scarce and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long-term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N=431) and age of death (40-79) in the Netherlands. Breast cancer mortality trends were analysed by defining the municipality-specific calendar year of introduction of screening as year 0. Additionally, log-linear Poisson regression was used to estimate the turning point in the trend after year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55-74 and by 34% in women aged 75-79, compared to year 0. A similar and significant decrease was present in municipalities that started early (1987-1992) and late (1995-1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55-74 and 75-79 the turning point in the trend in breast cancer mortality was estimated in year 2 and 6 after the introduction of screening respectively, after which mortality decreased significantly by 1.9% and 2.6% annually.

These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55-79, irrespective of time of implementation. This article is protected by copyright. All rights reserved.

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Letter to the Editor in response to Herweijer E., Sundström K., Ploner A., Uhnoo I., Sparén P. and Arnheim-Dahlström L. (2016), Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study. Int. J. Cancer, 138: 2867–2874. doi:10.1002/ijc.30035

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The effect of population-based mammography screening in Dutch municipalities on breast cancer mortality: 20 years of follow-up

Abstract

Long-term follow-up data on the effects of screening are scarce and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long-term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N=431) and age of death (40-79) in the Netherlands. Breast cancer mortality trends were analysed by defining the municipality-specific calendar year of introduction of screening as year 0. Additionally, log-linear Poisson regression was used to estimate the turning point in the trend after year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55-74 and by 34% in women aged 75-79, compared to year 0. A similar and significant decrease was present in municipalities that started early (1987-1992) and late (1995-1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55-74 and 75-79 the turning point in the trend in breast cancer mortality was estimated in year 2 and 6 after the introduction of screening respectively, after which mortality decreased significantly by 1.9% and 2.6% annually.

These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55-79, irrespective of time of implementation. This article is protected by copyright. All rights reserved.

http://ift.tt/2oJoKlc

Letter to the Editor in response to Herweijer E., Sundström K., Ploner A., Uhnoo I., Sparén P. and Arnheim-Dahlström L. (2016), Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study. Int. J. Cancer, 138: 2867–2874. doi:10.1002/ijc.30035

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Progress and challenges in the treatment of small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is a very aggressive malignancy characterized by high cellular proliferation and early metastatic spread. In fact, although SCLC is a chemosensitive and radiosensitive disease, the initial responsiveness to chemotherapy is usually followed by development of resistance and the prognosis remains poor with a median survival of less than 12 months in patients with extensive disease (ED-SCLC). Furthermore, no significant progress has been made over the last years, with no newly approved drug. For all these reasons, SCLC represents for the oncologists a major challenge and an exciting field of clinical research. In this review, we analyze the most promising advances in development for SCLC with a special focus on antiangiogenic treatments, immunotherapy, novel chemotherapeutic and targeted agents.

http://ift.tt/2pIPu5C

Progress and challenges in the treatment of small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is a very aggressive malignancy characterized by high cellular proliferation and early metastatic spread. In fact, although SCLC is a chemosensitive and radiosensitive disease, the initial responsiveness to chemotherapy is usually followed by development of resistance and the prognosis remains poor with a median survival of less than 12 months in patients with extensive disease (ED-SCLC). Furthermore, no significant progress has been made over the last years, with no newly approved drug. For all these reasons, SCLC represents for the oncologists a major challenge and an exciting field of clinical research. In this review, we analyze the most promising advances in development for SCLC with a special focus on antiangiogenic treatments, immunotherapy, novel chemotherapeutic and targeted agents.

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Major and ancillary magnetic resonance features of LI-RADS to assess HCC: an overview and update

Abstract

Liver Imaging Reporting and Data System (LI-RADS) is a system for interpreting and reporting of imaging features on multidetector computed tomography (MDCT) and magnetic resonance (MR) studies in patients at risk for hepatocellular carcinoma (HCC). American College of Radiology (ACR) sustained the spread of LI-RADS to homogenizing the interpreting and reporting data of HCC patients. Diagnosis of HCC is due to the presence of major imaging features. Major features are imaging data used to categorize LI-RADS-3, LI-RADS-4, and LI-RADS-5 and include arterial-phase hyperenhancement, tumor diameter, washout appearance, capsule appearance and threshold growth. Ancillary are features that can be used to modify the LI-RADS classification. Ancillary features supporting malignancy (diffusion restriction, moderate T2 hyperintensity, T1 hypointensity on hapatospecifc phase) can be used to upgrade category by one or more categories, but not beyond LI-RADS-4. Our purpose is reporting an overview and update of major and ancillary MR imaging features in assessment of HCC.

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Major and ancillary magnetic resonance features of LI-RADS to assess HCC: an overview and update

Abstract

Liver Imaging Reporting and Data System (LI-RADS) is a system for interpreting and reporting of imaging features on multidetector computed tomography (MDCT) and magnetic resonance (MR) studies in patients at risk for hepatocellular carcinoma (HCC). American College of Radiology (ACR) sustained the spread of LI-RADS to homogenizing the interpreting and reporting data of HCC patients. Diagnosis of HCC is due to the presence of major imaging features. Major features are imaging data used to categorize LI-RADS-3, LI-RADS-4, and LI-RADS-5 and include arterial-phase hyperenhancement, tumor diameter, washout appearance, capsule appearance and threshold growth. Ancillary are features that can be used to modify the LI-RADS classification. Ancillary features supporting malignancy (diffusion restriction, moderate T2 hyperintensity, T1 hypointensity on hapatospecifc phase) can be used to upgrade category by one or more categories, but not beyond LI-RADS-4. Our purpose is reporting an overview and update of major and ancillary MR imaging features in assessment of HCC.

http://ift.tt/2pvC1go

Dose tracking assessment for image-guided radiotherapy of the prostate bed and the impact on clinical workflow

The cumulative dose was compared with the planned dose among fourteen patients undergoing image-guided, intensity-modulated radiotherapy of the prostate bed. Moreover, we investigated the feasibility of adding...

http://ift.tt/2qidWHS

Does age really matter? Radiotherapy in elderly patients with glioblastoma, the Munich experience

Glioblastoma is usually diagnosed around the age of 60–70 years. Patients older than 65 years are frequently described as "elderly". Several trials with monotherapy have established treatment regimens that off...

http://ift.tt/2oIDUHL

Dose tracking assessment for image-guided radiotherapy of the prostate bed and the impact on clinical workflow

The cumulative dose was compared with the planned dose among fourteen patients undergoing image-guided, intensity-modulated radiotherapy of the prostate bed. Moreover, we investigated the feasibility of adding...

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Does age really matter? Radiotherapy in elderly patients with glioblastoma, the Munich experience

Glioblastoma is usually diagnosed around the age of 60–70 years. Patients older than 65 years are frequently described as "elderly". Several trials with monotherapy have established treatment regimens that off...

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Clonal chromosomal aberrations in philadelphia negative cells such as monosomy 7 and trisomy 8 may persist for years with no impact on the long term outcome in patients with chronic myeloid leukemia

Publication date: Available online 28 April 2017
Source:Cancer Genetics
Author(s): Ewa M. Wasilewska, Barbara Panasiuk, Michał Gniot, Anna Sawicka, Katarzyna Kozlowska, Krzysztof Lewandowski, Janusz Kłoczko, Alina T. Midro
The appearance of clonal chromosomal aberrations in Philadelphia negative cells (CCA/Ph-) during the treatment of chronic myeloid leukemia (CML) was recently confirmed. Importance of these findings has not been clearly defined. We present data on the time of appearance, persistence, size of the CCA/Ph- clone in terms of drugs used and hematological, cytogenetic and molecular response rates. The focus was on the peripheral blood cytopenias and myelodysplastic changes in the bone marrow microscopic evaluation. In 5 out of 155 (3,2%) CML patients, the persistent presence (up to nine years) of CCA/Ph- was found (monosomy 7 and trisomy 8 in unrelated clones in two patients treated with tyrosine kinase inhibitors; trisomy 8 in two patients on imatinib; trisomy 21 in one patient on interferon alfa treatment). Aberrations were present in median 24% Ph- cells in 3 to 15 subsequent analyses at different cytogenetic and molecular response time points. No evident myelodysplastic changes nor transformation to MDS/AML occurred in patients with CCA/Ph-. All the patients achieved major molecular response (MMR). It seems that CCA/Ph- presence does not affect the long term outcome in patients with chronic myeloid leukemia. Further complex monitoring of the CML patients with CCA/Ph- is still needed.



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Erratum to: Entangling Relation of Micro RNA-let7, miRNA-200 and miRNA-125 with Various Cancers

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Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer

Abstract

Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m²/week, loading dose: 400 mg/m²), gemcitabine (1000 mg/m² on day 1 and 8), and capecitabine (1300 mg/m²/day on days 1–14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24–40) and 54 (43–67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.

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Erratum to: Entangling Relation of Micro RNA-let7, miRNA-200 and miRNA-125 with Various Cancers

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Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer

Abstract

Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m²/week, loading dose: 400 mg/m²), gemcitabine (1000 mg/m² on day 1 and 8), and capecitabine (1300 mg/m²/day on days 1–14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24–40) and 54 (43–67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.

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n-Hexane intoxication in a Chinese medicine pharmaceutical plant: a case report

n-Hexane is a well-known neurotoxicant. Polyneuropathy due to occupational n-hexane exposure has been reported worldwide, however, our case is the first report in the Chinese herb indu...

http://ift.tt/2oIlAOK

The survival and prognosticators of peritoneal cytology-positive gastric cancer patients who received upfront gastrectomy and subsequent S-1 chemotherapy

Abstract

Background

Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival.

Methods

Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors.

Results

The median OS was 22.3 months (95% confidence interval 18.7–31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0–N3a (pN0–N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0–N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007).

Conclusions

The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

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The survival and prognosticators of peritoneal cytology-positive gastric cancer patients who received upfront gastrectomy and subsequent S-1 chemotherapy

Abstract

Background

Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival.

Methods

Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors.

Results

The median OS was 22.3 months (95% confidence interval 18.7–31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0–N3a (pN0–N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0–N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007).

Conclusions

The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

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Panniculus morbidus: obesity-related abdominal wall lymphoedema

A 52-year-old female patient presented with a massive abdominal wall swelling that adversely affected her lifestyle. Imaging revealed significant subcutaneous oedema and the presence of grossly distended veins. Subsequently, she underwent a 'toilet' panniculectomy and abdominoplasty. We describe the surgical technique used to retract the lymphoedematous tissue facilitating excisional surgery, and discuss the pathophysiology of this condition and the possible contribution of venous obstruction to the development of subcutaneous oedema.

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A case of fulminant necrotising fasciitis

Description

A 57-year-old man presented to the emergency department with fever, chills and a wound on his left foot since 2 weeks. He had no previous medical history. Despite receiving flucloxacillin, the wound was neglected and became necrotic with skin discoloration and a purulent, foul-smelling discharge. The leg developed functional impairment with severe claudication pain. All digits were pale, cold and numb (figure 1A, B). Biochemistry showed high infection parameters and hyperlactaemia as a sign of hypoperfusion. Hyperglycaemia revealed de novo diabetes. X-rays of the left lower extremity showed subcutaneous air (figure 2A–C).

Figure 1

(A,B) The extension of necrotising fasciitis of the left lower extremity.

Figure 2

X-rays of the foot (A) and knee (B and C) showing subcutaneous air (arrows), which is typical of necrotising fasciitis.

Patient underwent immediate left transfemoral amputation. Postoperatively he was...

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Scalp vein sign: a forgotten clinical clue?

Description

A 72-year-old man presented for general health check. He was asymptomatic except for hard of hearing and uses hearing aid for the last 4 years. Clinical examination revealed very prominent tortuous superficial temporal veins bilaterally, more on the left side (figure 1) with no bruit and a warm non-tender skull on palpation. Serum chemistries showed significantly elevated alkaline phosphatase 1520 U/L (normal, 45–140 U/L) with normal liver, kidney and haematological parameters. Serum calcium, phosphorus, 25-hydroxy vitamin D and parathyroid hormone levels were normal. Skull radiograph showed moth-eaten appearance suggestive of Pagetoid bone (figure 2). With this clinico-biochemical picture in an otherwise asymptomatic individual, Paget's disease of bone was strongly considered. It was confirmed by significant uptake of technetium-methylene diphosphonate (MDP) in skull and right hemipelvis. He was managed with intravenous zoledronic acid, calcium and vitamin D supplementation. Serum alkaline phosphatase normalised at 6 months follow-up, though hearing and scalp vein...

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High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin lymphoma

Abstract

A new immunological investigation was carried out to study the association between non-Hodgkin lymphoma and Simian virus 40 (SV40). To this end, a new indirect ELISA was employed with two mimotopes from SV40 large T antigen (Tag), the viral oncoprotein, to analyse for specific reactions to antibodies in sera from non-Hodgkin lymphoma patients and controls, represented by healthy subjects (HS) and breast carcinoma (BC) patients. This study allowed us to assay a new sera collection from non-Hodgkin lymphoma patients (NHL, n = 254). To verify the association between NHL and SV40 Tag, two totally independent cohorts were analysed: NHL1 n = 150 and NHL2 n = 104. The epidemiological survey included sera from HS1, n = 150; HS2, n = 104 and BC, n = 78. This new indirect ELISA revealed that antibodies against SV40 Tag mimotopes are detectable in NHL1 and NHL2 sera with a prevalence of 37 and 36%, respectively. The prevalence of SV40-antibodies detected in both NHL1 and NHL2 cohorts differs statistically from controls, at 19% for HS1 (p < 0.01), HS2 (p < 0.05) and BC patients (p < 0.05). This study, carried out with an immunological assay with specific Tag oncoprotein mimotopes of Simian virus 40, reports the presence of IgG antibodies against the large Tumour antigen in non-Hodgkin lymphomas for the first time. Our immunological data with two independent NHL cohorts show a statistically significant association between Simian virus 40 Tag and non-Hodgkin lymphoma. These results suggest that SV40-positive non-Hodgkin lymphomas could be treated differently from those tested SV40-negative.

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The Relationship Between Infant Facial Expressions and Food Acceptance

Abstract

Purpose of Review

To highlight the range of methodological approaches used to objectively measure hedonic responses to taste stimuli during the first year of life and how these behavioral responses change with experience. Challenges inherent to this type of research are discussed.

Recent Findings

Although newborns display characteristic orofacial reactivity to four of the five basic tastes, the facial expressions made and the amount of food consumed can be modified by experience: children learn to like what they are fed. In some cases, changes in facial responses are concordant with infant consumption, whereas in other cases facial reactivity follows changes in intake.

Summary

Together with ingestive measurements, precise and objective measurements of orofacial reactivity provide an understanding of how early experiences shift the hedonic tone of the taste of foods, the foundation of dietary preferences.

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Role of Nutrition to Promote Healthy Brain Aging and Reduce Risk of Alzheimer’s Disease

Abstract

Purpose of Review

Alzheimer's disease (AD) is the most common form of dementia worldwide, with the disease burden expected to rise as the population ages.

Recent Findings

No pharmacological therapy is currently available to cure or prevent AD. Nonetheless, recent research suggests that nutritional and lifestyle modifications might help delay or even prevent the onset of AD, especially when instituted prior to substantial neuronal loss.

Summary

This article reviews proposed nutritional interventions for AD prevention that focus on adopting dietary patterns and improvement of macro- and micronutrient distribution or intakes, improvement of insulin resistance, correction of dyslipidemia, and reduction of oxidative stress.

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3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer

Publication date: July 2017
Source:European Journal of Cancer, Volume 79
Author(s): Manfred P. Lutz, John R. Zalcberg, Michel Ducreux, Daniela Aust, Marco J. Bruno, Markus W. Büchler, Jean-Robert Delpero, Beat Gloor, Rob Glynne-Jones, Werner Hartwig, Florence Huguet, Pierre Laurent-Puig, Florian Lordick, Patrick Maisonneuve, Julia Mayerle, Marc Martignoni, John Neoptolemos, Andrew D. Rhim, Bruno M. Schmied, Thomas Seufferlein, Jens Werner, Jean-Luc van Laethem, Florian Otto
The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations.It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases).The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate.The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment.



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Are There Sensitive Periods for Food Acceptance in Infancy?

Abstract

Purpose of Review

A sensitive period in development is one in which it is easier for learning to take place; the behaviour can however still be learned at a later stage, but with more difficulty. This is in contrast to a critical period, a time at which a behaviour must be learned, and if this window of opportunity is missed, then the behaviour can never be acquired. Both might determine food acceptance in childhood.

Recent Findings

There is evidence to support the idea of a sensitive period for the introduction of tastes, a critical period for the introduction of textures and for the development of oral motor function, and a possible critical period for the introduction of new foods but only in children where there is an innate disposition to develop early and extreme disgust responses.

Summary

There are both sensitive and critical periods in the acquisition of food preferences.

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Are There Sensitive Periods for Food Acceptance in Infancy?

Abstract

Purpose of Review

A sensitive period in development is one in which it is easier for learning to take place; the behaviour can however still be learned at a later stage, but with more difficulty. This is in contrast to a critical period, a time at which a behaviour must be learned, and if this window of opportunity is missed, then the behaviour can never be acquired. Both might determine food acceptance in childhood.

Recent Findings

There is evidence to support the idea of a sensitive period for the introduction of tastes, a critical period for the introduction of textures and for the development of oral motor function, and a possible critical period for the introduction of new foods but only in children where there is an innate disposition to develop early and extreme disgust responses.

Summary

There are both sensitive and critical periods in the acquisition of food preferences.

http://ift.tt/2qpkGTJ

A Systematic Review of Methods for Increasing Vegetable Consumption in Early Childhood

Abstract

Purpose of Review

This study aims to synthesise the body of research investigating methods for increasing vegetable consumption in 2- to 5-year-old children, while offering advice for practitioners.

Recent Findings

Repeated exposure is a well-supported method for increasing vegetable consumption in early childhood and may be enhanced with the inclusion of non-food rewards to incentivise tasting. Peer models appear particularly effective for increasing 2–5-year-olds' vegetable consumption. There is little evidence for the effectiveness of food adaptations (e.g. flavour-nutrient learning) for increasing general vegetable intake among this age group, although they show some promise with bitter vegetables.

Summary

This review suggests that practitioners may want to focus their advice to parents around strategies such as repeated exposure, as well as the potential benefits of modelling and incentivising tasting with non-food rewards. Intervention duration varies greatly, and considerations need to be made for how this impacts on success.

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The Relationship Between Infant Facial Expressions and Food Acceptance

Abstract

Purpose of Review

To highlight the range of methodological approaches used to objectively measure hedonic responses to taste stimuli during the first year of life and how these behavioral responses change with experience. Challenges inherent to this type of research are discussed.

Recent Findings

Although newborns display characteristic orofacial reactivity to four of the five basic tastes, the facial expressions made and the amount of food consumed can be modified by experience: children learn to like what they are fed. In some cases, changes in facial responses are concordant with infant consumption, whereas in other cases facial reactivity follows changes in intake.

Summary

Together with ingestive measurements, precise and objective measurements of orofacial reactivity provide an understanding of how early experiences shift the hedonic tone of the taste of foods, the foundation of dietary preferences.

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Role of Nutrition to Promote Healthy Brain Aging and Reduce Risk of Alzheimer’s Disease

Abstract

Purpose of Review

Alzheimer's disease (AD) is the most common form of dementia worldwide, with the disease burden expected to rise as the population ages.

Recent Findings

No pharmacological therapy is currently available to cure or prevent AD. Nonetheless, recent research suggests that nutritional and lifestyle modifications might help delay or even prevent the onset of AD, especially when instituted prior to substantial neuronal loss.

Summary

This article reviews proposed nutritional interventions for AD prevention that focus on adopting dietary patterns and improvement of macro- and micronutrient distribution or intakes, improvement of insulin resistance, correction of dyslipidemia, and reduction of oxidative stress.

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via IFTTT

A Systematic Review of Methods for Increasing Vegetable Consumption in Early Childhood

Abstract

Purpose of Review

This study aims to synthesise the body of research investigating methods for increasing vegetable consumption in 2- to 5-year-old children, while offering advice for practitioners.

Recent Findings

Repeated exposure is a well-supported method for increasing vegetable consumption in early childhood and may be enhanced with the inclusion of non-food rewards to incentivise tasting. Peer models appear particularly effective for increasing 2–5-year-olds' vegetable consumption. There is little evidence for the effectiveness of food adaptations (e.g. flavour-nutrient learning) for increasing general vegetable intake among this age group, although they show some promise with bitter vegetables.

Summary

This review suggests that practitioners may want to focus their advice to parents around strategies such as repeated exposure, as well as the potential benefits of modelling and incentivising tasting with non-food rewards. Intervention duration varies greatly, and considerations need to be made for how this impacts on success.

http://ift.tt/2qppzwb

Baby-Led Weaning: The Evidence to Date

Abstract

Purpose of Review

Infants are traditionally introduced to solid foods using spoon-feeding of specially prepared infant foods.

Recent Findings

However, over the last 10–15 years, an alternative approach termed 'baby-led weaning' has grown in popularity. This approach involves allowing infants to self-feed family foods, encouraging the infant to set the pace and intake of the meal. Proponents of the approach believe it promotes healthy eating behaviour and weight gain trajectories, and evidence is starting to build surrounding the method. This review brings together all empirical evidence to date examining behaviours associated with the approach, its outcomes and confounding factors.

Summary

Overall, although there is limited evidence suggesting that a baby-led approach may encourage positive outcomes, limitations of the data leave these conclusions weak. Further research is needed, particularly to explore pathways to impact and understand the approach in different contexts and populations.

from Cancer via ola Kala on Inoreader http://ift.tt/2qpfMX0
via IFTTT

Baby-Led Weaning: The Evidence to Date

Abstract

Purpose of Review

Infants are traditionally introduced to solid foods using spoon-feeding of specially prepared infant foods.

Recent Findings

However, over the last 10–15 years, an alternative approach termed 'baby-led weaning' has grown in popularity. This approach involves allowing infants to self-feed family foods, encouraging the infant to set the pace and intake of the meal. Proponents of the approach believe it promotes healthy eating behaviour and weight gain trajectories, and evidence is starting to build surrounding the method. This review brings together all empirical evidence to date examining behaviours associated with the approach, its outcomes and confounding factors.

Summary

Overall, although there is limited evidence suggesting that a baby-led approach may encourage positive outcomes, limitations of the data leave these conclusions weak. Further research is needed, particularly to explore pathways to impact and understand the approach in different contexts and populations.

http://ift.tt/2qpfMX0

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

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